Cerebral Hemorrhages 167 S

SURGERY – PROCEDURES, COMPLICATIONS, AND RESULTS

NEUROVASCULAR SURGICAL DISEASES

A CASE-BASED APPROACH

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SURGERY – PROCEDURES, COMPLICATIONS, AND RESULTS

NEUROVASCULAR SURGICAL DISEASES

A CASE-BASED APPROACH

RENATO GALZIO, MD AND SABINO LUZZI, MD, PHD EDITORS

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ISBN: 978-1-53618-175-3 Names: Galzio, Renato, editor. | Luzzi, Sabino, editor. Title: Neurovascular surgical diseases : a case-based approach / Renato Galzio, editor, Sabino Luzzi, editor. Description: New York : Nova Science Publishers, [2020] | Series: Surgery - procedures, complications, and results | Includes bibliographical references and index. | Identifiers: LCCN 2020028345 (print) | LCCN 2020028346 (ebook) | ISBN 9781536181753 (hardcover) | ISBN 9781536182644 (adobe pdf) Subjects: LCSH: Nervous system--Blood-vessels--Surgery. Classification: LCC RD594.2 .N52 2020 (print) | LCC RD594.2 (ebook) | DDC 617.4/8--dc23 LC record available at https://lccn.loc.gov/2020028345 LC ebook record available at https://lccn.loc.gov/2020028346

Published by Nova Science Publishers, Inc. † New York

CONTENTS

Preface ix Section I: Anatomical Overview of Skull Base and Cerebral Vasculature 1 Chapter 1 Microsurgical Anatomy of the Cranial Base 3 S. Luzzi, A. Giotta Lucifero, M. Del Maestro, C. Gragnaniello and R. Galzio Chapter 2 Vascular Anatomy of the Cranial Anterior Circulation 21 S. Luzzi, A. Giotta Lucifero, M. Del Maestro, M. Nuñez and R. Galzio Chapter 3 Vascular Anatomy of the Cranial Posterior Circulation 43 S. Luzzi, A. Giotta Lucifero, M. Del Maestro, M. Nuñez and R. Galzio Chapter 4 Vascular Anatomy of the Spinal Cord 63 B. Del Sette, A. Consoli, R. Russo and G. Rodesch

Section II: Diagnosis, Preoperative Evaluation and Surgical Planning 79 Chapter 5 Intracranial Aneurysms 81 S. Luzzi, A. Giotta Lucifero, M. Del Maestro, C. Gragnaniello and R. Galzio Chapter 6 Brain Arteriovenous Malformations 107 M. Cenzato and D. Boeris Chapter 7 Spinal Arteriovenous Malformations 127 D. Boeris and M. Cenzato Chapter 8 Brain and Spinal Cord Cavernous Malformations 137 M. Fontanella, L. Zanin, A. Fiorindi, G. Spena, F. Nicolosi, F. Belotti, P. Panciani, L. De Maria, G. Saraceno, C. Cornali and F. Doglietto Chapter 9 Cranial and Spinal Dural Arteriovenous Fistulas 149 G. Baltsavias vi Contents

Chapter 10 Cerebral Hemorrhages 167 S. Luzzi, A. Giotta Lucifero, M. Del Maestro and R. Galzio Chapter 11 Principles of Neuroanesthesia 187 M. Seveso and D. Caldiroli Chapter 12 Intraoperative Neurophysiological Monitoring in Neurovascular Surgery 209 S. Luzzi, G. Mezzini, M. Del Maestro, A. Giotta Lucifero and R. Galzio Chapter 13 Intraoperative Evaluation of Cerebral Blood Flow 227 A. Pasqualin, P. Meneghelli, F. Cozzi and A. Musumeci

Section III: Case-Based Surgical Approaches 237 Chapter 14 Pterional Approach 239 S. Luzzi, M. Del Maestro, A. Giotta Lucifero and R. Galzio Chapter 15 Trans-Eyebrow Keyhole Approach 255 G. Esposito and L. Regli Chapter 16 Cranio-Orbito-Zygomatic Approach 263 S. Luzzi, A. Giotta Lucifero, M. Del Maestro and R. Galzio Chapter 17 Interhemispheric Approach 281 S. Anetsberger, P. Gonzalez- Lopez, Y. Elsawaf, S. Luzzi and S. K. Elbabaa Chapter 18 Subtemporal Approach 297 L. Silveira, J. Muse, S. Luzzi, R. Galzio and C. Gragnaniello Chapter 19 Retrosigmoid Approach 317 F. Cofano, F. Vincitorio, F. Zenga and D. Garbossa Chapter 20 Far Lateral Approach 329 S. Luzzi, A. Giotta Lucifero, M. Del Maestro, C. Gragnaniello and R. Galzio Chapter 21 Combined Petrosal Approach 349 D. T. Di Carlo, T. Passeri, P. Di Russo, K. Watanabe, A. L. Bernat and S. Froelich Chapter 22 Approaches for Brain and Spinal Cord Arteriovenous Malformations 359 R. Messina, G. Cirrottola, N. Bruno and F. Signorelli Chapter 23 Approaches for Brain and Spinal Cord Cavernous Malformations 375 M. Del Maestro, S. Luzzi, G. Mezzini, A. Giotta Lucifero and R. Galzio Chapter 24 Approaches for Brain and Spinal Cord Dural Arteriovenous Fistulas 395 S. Paolini, C. Mancarella, R. Severino and V. Esposito Contents vii

Section IV: Miscellaneous 405 Chapter 25 Endoscope-Assisted Microneurosurgery for Intracranial Aneurysms 407 M. Del Maestro, S. Luzzi, A. Giotta Lucifero, A. Rampini and R. Galzio Chapter 26 Surgical Management of Giant Intracranial Aneurysms 423 S. Luzzi, A. Giotta Lucifero, M. Del Maestro and R. Galzio Chapter 27 Revascularization Techniques for Complex Intracranial Aneurysms 441 L. Berra and A. Santoro Chapter 28 Endovascular Treatments for Intracranial Aneurysms and Dural Arteriovenous Fistulas 449 S. Mangiafico, F. Capasso, S. Vidale, F. Incandela and A. Laiso Chapter 29 Preoperative Embolization of Brain Arteriovenous Malformation 463 S. Luzzi, M. Del Maestro, A. Giotta Lucifero and R. Galzio Chapter 30 Radiosurgery for Brain and Spinal Cord Arteriovenous and Cavernous Malformations 483 B. C. Bono, I. Zaed, L. Attuati and P. Picozzi Chapter 31 Intraoperative Indocyanine Green and Fluorescein Videoangiography of Brain and Spinal Cord Vascular Lesions 503 F. Acerbi, I. G. Vetrano, G. Faragò and P. Ferroli About the Editors 521 Index 523

PREFACE

Neurosurgery is one of the most exciting and important fields in medicine today. Advances in technology and a better understanding of the diseases have revolutionized the field. The innumerable problems that neurosurgeons deal with are a significant cause of morbidity in productive citizens everywhere. Neurovascular disease of neurosurgical interest such as intracranial aneurysms, brain and spinal cord AVMs and cavernous angiomas, cranial and spinal dural arteriovenous fistulas, as well as spontaneous cerebral hemorrhages. The management of these diseases requires a multidisciplinary approach where neurosurgeons work in close contact with neuroradiologist, neurologists, neuro-intensivists, neuro-physiologists in Centres of excellence. This book reports all the background of these pathologies together with an accurate description of the surgical approaches together with all the up to date surgical instruments, microscopes, radio-surgery and intraoperative monitorings. Nowdays it has become difficult to teach the youngest generation of surgeons how to surgically treat an aneurysm or an AVM: quite a number of patients are treated via endovascular management and other ones with a gamma knife. Very few Centres have enough volume of vascular patients to have a good hand on surgical learning curve. The experience of the senior authors and of some other dedicated surgeons reported in this book is extremely valuable for the training of our younger colleagues Furthermore, the description of the most common surgical approaches together with a case by case discussion is also important I thank Prof Galzio and his youngest co-workers for this important contribution to the neurosurgical literature

Franco Servadei Prof. of Neurosurgery, Humanitas University, Milano Past President Italian Neurosurgical Society

SECTION I: ANATOMICAL OVERVIEW OF SKULL BASE AND CEREBRAL VASCULATURE

Chapter 1

MICROSURGICAL ANATOMY OF THE CRANIAL BASE

S. Luzzi1,2,, MD, PhD, A. Giotta Lucifero1, MD, M. Del Maestro2,3, MD, C. Gragnaniello4, MD, PhD and R. Galzio1,2, MD 1Neurosurgery Unit, Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy 2Neurosurgery Unit, Department of Surgical Sciences, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy 3PhD School in Experimental Medicine, Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy 4Department of Neurological Surgery, University of Illinois at Chicago, Chicago, Il, US

ABSTRACT

A thorough knowledge of both the endocranial and exocranial anatomy of the skull base is imperative to safely and effectively perform the various transcranial surgical approaches to neurovascular pathologies. This chapter provides a description of the anatomy based on the classical division of the skull base into anterior, middle, and posterior fossae.

Keywords: anterior skull base, foramen magnum, jugular foramen, middle skull base, posterior skull base, skull base

1. OVERVIEW

The skull is composed of the splanchnocranium, or the facial skeleton, and the neurocranium, which surrounds the cerebral structures. The neurocranium is divided further

 Corresponding Author’s Email: [email protected]. 4 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al. into the calvaria and the cranial base by a plane passing through the glabella to the external occipital protuberance. The calvaria is formed by the frontal, parietal, temporal, and occipital bones and part of the greater sphenoid wings. The cranial base is composed of the frontal, ethmoid, temporal, and occipital bones, all of which join with the sphenoid bone in the center of the skull base. The cranial base has an exocranial and endocranial surface, which are connected by channels and foramina traversed by nerves, arteries, and veins. The endocranial surface is classically divided into the anterior, middle and posterior fossae. The exocranial surface borders the orbit, nasal cavity, nasopharynx, and the infratemporal, pterygopalatine, and mandibular fossae.The distinction of median, paramedian, and lateral corridors is a useful concept to understand the three-dimensional anatomy of the skull base and is relevant for the execution of surgical approaches to skull base pathology.

2. ANTERIOR SKULL BASE

2.1. Endocranial Surface

The anterior skull base is composed of the frontal, ethmoid, and sphenoid bones which articulate at the frontoethmoidal, sphenoethmoidal, and sphenofrontal sutures. The frontal bone forms the roof of the orbit and is immediately beneath the rectus gyri and orbital cortex. The ethmoid bone articulates in the midline with the frontal bone. The posterior portion of the endocranial surface of the anterior skull base is completed posteriorly by the lesser sphenoid wings, anterior clinoid processes, and the planum and jugum sphenoidale. The central corridor is formed by the frontal crest of the frontal bone, crista galli, and cribriform plate of the ethmoid bone, and the planum and jugum sphenoidale. The crista galli serves as a point of attachment for the falx cerebri and the superior and inferior sagittal sinuses. The cribriform plate transmits the olfactory fila. Between the crista galli and the cribriform plate, the foramen cecum may rarely transmit the persistent anterior nasal emissary vein, when present. The planum and jugum sphenoidale form the roof of the sphenoid sinus. The paramedian corridor is formed by the fovea ethmoidalis of the frontal bone, which is the roof of the ethmoid air cells. Here, the anterior and posterior ethmoidal foramina give passage to the anterior and posterior ethmoidal arteries and nerves, respectively. The lateral corridor is composed of the orbital plates of the frontal bone anteriorly and the lesser sphenoid wings posteriorly; the medial portion of the lesser sphenoid wing forms the anterior clinoid processes. On the endocranial surface, the anterior and middle skull base are separated by the sphenoid ridges laterally, the anterior clinoid processes in the paramedian region, and the jugum sphenoidale in the midline.

2.2. Exocranial Surface

The exocranial surface is composed mainly of the frontal, ethmoid, and sphenoid bones. The frontal and the ethmoid bones constitute the anterior two-thirds of the roof of the nasal Microsurgical Anatomy of the Cranial Base 5 cavity; the sphenoethmoidal recess comprises the posterior third. The lateral plates of the ethmoid bone separate the nasal cavity from the orbits, while the perpendicular plate attaches to the vomer and contributes to formation of the upper portion of the nasal septum, which divides the nasal cavity in the midline. The conventional division between the anterior and middle skull base on the exocranial surface corresponds to a line drawn at the level of the pterygomaxillary fissures going down to the posterior edges of the alveolar processes of the maxillae; in the paramedian corridor, the line follows the inferior border of the choanae to end at the level of the posterior nasal spine.

3. MIDDLE SKULL BASE

3.1. Endocranial Surface

The middle skull base is composed of the sphenoid and temporal bones, which articulate at the sphenopetrosal and sphenosquamosal sutures. The median corridor is formed, from anterior to posterior, by the chiasmatic sulcus on the superior aspect of the body of the sphenoid bone, tuberculum sellae, sella turcica, and dorsum sellae. At the lateral ends of the chiasmatic sulcus, the optic canals transmit the optic nerves and the ophthalmic arteries from the intracranial space to the orbits. The anterior and posterior limbs of the chiasmatic sulcus are also referred to as the jugum sphenoidale and tuberculum sellae, respectively. The sella turcica is a deep rounded depression in the sphenoid body containing the pituitary gland. The sella is delineated posteriorly by the dorsum sellae, the lateral and uppermost parts of which are known as the posterior clinoid processes. Anteriorly, the paramedian corridor involves the lateral aspect of the body of the sphenoid bone, which is the root of the lesser and greater sphenoid wings; posteriorly, it is comprised of the foramen lacerum. The carotid sulcus of the sphenoid bone is also within the paramedian corridor and extends from the petrolingual ligament forward to the paraclinoid region. The foramen lacerum is formed by the union between the petrous apex, the uppermost part of the petroclival fissure, and the lateral aspects of the dorsum sellae. The greater superficial petrosal nerve joins the deep petrosal nerve from the sympathetic plexus around the petrous internal carotid artery to form the vidian nerve at the level of the foramen lacerum. Meningeal branches from the ascending pharyngeal artery pass through the foramen lacerum, along with emissary veins connecting the cavernous sinus, inferior petrosal sinus, and basilar plexus to the pterygoid plexus. In the parasellar region, the roof of the cavernous sinus is formed by the anterior clinoid process anteriorly and the oculomotor triangle posteriorly. The lingula of the sphenoid bone provides a site of attachment for the petrolingual ligament, which marks the border between the lacerum and cavernous segments of the internal carotid artery. The lateral corridor is composed of the lesser and greater sphenoid wings and the squamous and petrous parts of the temporal bone, forming the temporal fossae on both sides. The optic strut separates the optic canal from the superior orbital fissure and is the root of the lesser sphenoid wing on the lateral surface of the body of the sphenoid bone. The stout root of the greater sphenoid wing originates from the inferior part of the lateral sphenoid body and forms a large part of the temporal fossa floor. The superior orbital fissure lies between the lesser and greater sphenoid wings and is located lateral to the optic canal at the orbital apex. The superior 6 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al. orbital fissure transmits the first trigeminal division, the oculomotor, trochlear, and abducens nerves, and the inferior ophthalmic veins. The lateral corridor involves the foramen rotundum, foramen ovale, foramen spinosum, and occasionally the foramen of Vesalius, when present. The foramen rotundum is separated from the superior orbital fissure by the maxillary strut and transmits the second trigeminal division. The foramen ovale transmits the third trigeminal division, the motor trigeminal branch, the lesser superficial petrosal nerve, and in most cases, the accessory meningeal artery. The foramen spinosum is the most lateral of the three foramina and gives passage to the middle meningeal artery and spinosum nerve (branch of V3). The foramen spinosum is an important landmark for orientation during the middle fossa surgical approach. The foramen of Vesalius is medial to the foramen ovale when present; it transmits a vein connecting the pterygoid venous plexus and the cavernous sinus and may contain the accessory meningeal artery in some cases. The most lateral part of the middle skull base is composed of the superior surface of the petrous and squamosal parts of the temporal bone. On the petrous apex, the trigeminal impression forms the floor of Meckel’s cave, which contains the Gasserian ganglion. Posterolaterally, the arcuate eminence overlies the superior semicircular canal. Lateral to the arcuate eminence, the tegmen tympani separates the middle fossa from the middle ear. The border between the middle and posterior skull base is given by a line traced along the posterior-superior edge of the petrous part of the temporal bone laterally, and the posterior clinoid processes and dorsum sellae.

3.2. Exocranial Surface

The exocranial surface of the middle skull base borders with the pterygopalatine, infratemporal, and mandibular fossae and the parapharyngeal space. The median corridor is mainly composed of the inferior aspect of the body of the sphenoid bone. The paramedian corridor is constituted by the pterygoid process of the sphenoid bone, which branches into medial and lateral pterygoid plates. Between the medial and lateral pterygoid plates, the pterygoid (scaphoid) fossa is beneath the floor of the paramedian middle skull base. In the sagittal plane, the length of the pterygoid process marks the anterior-posterior limits of the cavernous sinus. Lateral to the pterygoid fossa, the infratemporal fossa forms the anterior part of the lateral corridor and the mandibular fossa constitutes the posterior part. The pterygopalatine fossa lies between the pterygoid process of the sphenoid bone posteriorly and the posterior wall of the maxillary sinus anteriorly. The medial boundary is the lateral pterygoid plate. Laterally, it opens into the infratemporal fossa through the pterygomaxillary fissure. The vidian canal, which transmits the vidian nerve and artery opens into the pterygopalatine fossa. The infratemporal fossa is bounded superiorly by the infratemporal crest of the sphenoid bone, anteriorly by the pterygomaxillary fissure, and posteriorly by the tympanic part of the temporal bone and the styloid process. Superiorly, the infratemporal fossa communicates with the temporal fossa; inferiorly, it blends into the parapharyngeal space. The mandibular fossa includes the mandibular condyle and is roofed by the tympanic and squamosal parts of the temporal bone. The squamotympanic fissure, along which the chorda tympani nerve passes, divides the mandibular fossa into an anterior and posterior part. Microsurgical Anatomy of the Cranial Base 7

The parapharyngeal space is shaped like an inverted pyramid with the base formed by the greater wing of the sphenoid bone and the apex formed by the hyoid bone. The medial wall is formed by the superior pharyngeal constrictor muscle; the medial pterygoid muscle, ramus of the mandible, deep lobe of the parotid gland, and posterior belly of the digastric form the lateral wall. Posteriorly, the space is bounded by an extension of the prevertebral fascia. The parapharyngeal space is divided by the styloid diaphragm into prestyloid and retrostyloid compartments; the parapharyngeal internal carotid artery courses within the retrostyloid space. The foramen rotundum opens into the pterygopalatine fossa; the foramen ovale and foramen spinosum into the infratemporal fossa; and the jugular foramen into the parapharyngeal space. The border between the middle and posterior skull base is traced by a line drawn oblique medially and forward passing through the mastoid tip, stylomastoid foramen, external orifice of the carotid canal, and foramen lacerum. In the midline, the border is delineated by a line passing along the posterior border of the vomer–sphenoid junction.

4. POSTERIOR SKULL BASE

4.1. Endocranial Surface

The posterior skull base is formed by the sphenoid, temporal, and occipital bones, which articulate at the spheno-occipital, temporomastoid, occipitomastoid and petro-occipital (petroclival) sutures. The median corridor involves the clivus and the foramen magnum. The anatomical boundaries of the clivus are the dorsum sellae of the sphenoid bone superiorly, the petroclival sutures laterally, and the anterior border of the foramen magnum inferiorly. The most caudal point of the clivus, which corresponds to the most anterior part of the foramen magnum in the midline, is referred as the basion. The basilar part of the occipital bone forms the lower two- thirds of the clivus; the posterior surface of the sphenoid body (dorsum sellae) forms the upper third. The basilar part of the occipital bone and the sphenoid body articulate at the spheno- occipital synchondrosis. In adults, the division between the two bones is not appreciable due to the fact that physiological closure of the spheno-occipital synchondrosis is well underway by the age of 15 years, and complete by 17 years (Bassed, Briggs, and Drummer 2010). On a sagittal view, the basilar (or clival) part of the occipital bone is oriented anteriorly and superiorly at a 45° angle. When viewed from behind, the clivus is concave from side to side; the central concavity is known as the central clival depression. This region is very difficult to reach surgically at the midclivus level (Abdel Aziz et al. 2000; Luzzi S 2019). The conventional border between the upper and middle clivus coincides with a horizontal line traced at the level of the petrous apex; a line passing through the glossopharyngeal notch of the jugular foramen delineates the middle and lower clivus (Funaki et al. 2013). Intradurally, the same limits are given by the exit point of the abducens nerve through the dura, located 3.4 millimeters below the posterior-superior border of the petrous part of the temporal bone, and the entry point of the glossopharyngeal nerve in the jugular foramen, respectively (Funaki et al. 2013).

8 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

The foramen magnum is bounded by the basilar, lateral, and squamosal parts of the occipital bone. The anterior border is formed by the inferior third of the clivus; the lateral limits are formed by the jugular tubercles, which are thought to be the result of the fusion between the basilar and lateral (condylar) parts of the occipital bone. The posterior border is formed by the most caudal aspect of the squamosal part of the occipital bone. The opisthion is the most posterior point of the foramen magnum in the midline. The structures passing through the foramen magnum are the upper cervical spinal cord, spinal accessory nerves, vertebral arteries, and anterior and posterior spinal arteries. The paramedian corridor involves the superior half of the petro-occipital suture and the jugular tubercle. Inferior to the jugular tubercle lies the inner orifice of the hypoglossal canal. The petro-occipital sutures are oriented posteriorly and laterally and course from the foramen lacerum to the jugular foramen. The jugular tubercle is a bony prominence connecting the basal and lateral parts of the occipital bone. It is located 5 mm above and anterior the hypoglossal canal and 8 mm medial to the medial edge of the jugular foramen (Wen et al. 1997; Rhoton 2000; de Oliveira, Rhoton, and Peace 1985; Mintelis et al. 2006). Its average length, width, and thickness (amount of medial bulging measured at the level of the hypoglossal canal) measure 16.5, 11.5, and 0.61 mm on average, respectively (Mintelis et al. 2006; S. Luzzi, Del Maestro, Elia, et al. 2019). The hypoglossal canal is located in the jugular process of the lateral part of the occipital bone. It is oriented anteriorly, laterally, and superiorly, forming an angle with the sagittal plane ranging between 45° and 49° (Naderi et al. 2005; Muthukumar et al. 2005; de Oliveira, Rhoton, and Peace 1985). It opens laterally into the interval between the jugular foramen and carotid canal. The hypoglossal canal is also referred as the anterior condylar canal and transmits the hypoglossal nerve. The lateral corridor involves the caudal half of the petro-occipital suture, the jugular foramen, the posterior aspect of the petrous bone including the internal auditory canal, and the sulcus of the sigmoid sinus. At the inferior limit of the petro-occipital suture, the lateral part of the occipital bone, and the petrous part of the temporal bone form the jugular foramen. The notch on the jugular process of the occipital bone forms the posterior border of the jugular foramen; the anterior border is formed by the jugular fossa of the petrous part of temporal bone (Williams 1995; Rhoton 2000). The jugular foramen transmits the inferior petrosal sinus, sigmoid sinus, and glossopharyngeal, vagus, and accessory nerves. The posterior surface of the petrous bone and the squamosal part of the occipital bone form the posterolateral skull base. On the posterior surface of the petrous bone, the internal auditory canal is located 5 mm above the jugular foramen, and transmits the facial and vestibulocochlear nerves and the labyrinthine artery which arises from the anterior inferior cerebellar artery (de Oliveira, Rhoton, and Peace 1985; Wen et al. 1997). The sulcus of the sigmoid sinus runs lateral to medial from the astèrion to the jugular foramen. The astèrion is a craniometric point corresponding to the site where the lambdoid (parieto-occipital), parietomastoid, and occipitomastoid sutures meet. It overlies the point where the transverse sinus turns sharply inferiorly into the sigmoid sinus.

Microsurgical Anatomy of the Cranial Base 9

Figure 1. (A) Endocranial surface of the skull base. The border between the anterior and middle skull base is marked, from lateral to medial, by the sphenoid ridges, the anterior clinoid processes, and the jugum sphenoidale in the midline (dotted line). The middle and posterior skull base are separated by a line along the posterosuperior edge of the petrous ridges laterally and the posterior clinoid processes and dorsum sellae in the medially (pointed line). (B) Exocranial surface of the skull base. The anterior and middle skull base are separated by a transverse line extending through the pterygomaxillary fissures and the posterior edges of the alveolar processes of the maxillae laterally, the inferior border of the choanae in the paramedian corridor, and the posterior nasal spine in the midline (dotted line). The border between the middle and posterior skull base is marked by the mastoid tip, stylomastoid foramen, external orifice of the carotid canal, foramen lacerum, and the vomer–sphenoid junction in the midline (pointed line).

4.2. Exocranial Surface

In the midline, the outer surface of the clivus is convex-shaped. Its transnasal frontal view is widely limited by the pterygoid processes of the sphenoid bone. The lower clivus is wider than the upper and mainly consists of the exocranial surface of the basioccipital bone. In the midline, at an average distance of 1 cm from the basion, the superior constrictor muscle of the pharynx attaches to the pharyngeal tubercle. The paramedian corridor involves the exocranial part of the petroclival fissure and the occipital condyle. When viewed from outside the cranium, the petroclival fissure appears as a deep cleft filled with a fibrocartilaginous tissue remnant of the primitive chondrocranium along which the inferior petroclival vein passes. The condyle is exocranial, generally oval in shape, convex downward and outward, and articulates with the superior articular facet of the atlas, which conversely, is concave upward and inward. The condyles are located along the anterior half of the edge of the foramen magnum and extend forward and medially from three to one and nine to eleven o'clock (Naderi et al. 2005; Guidotti 1984; Olivier 1975; Bozbuga et al. 1999). The supracondylar fossa is a small depression lying posterior to the condyle that corresponds to the location of the jugular tubercle on the endocranial side. The posterior condylar vein runs within the posterior condylar canal of the supracondylar fossa.

10 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

Figure 2. (A) The endocranial surface of the anterior skull base is divided into medial, paramedian, and lateral corridors. The central corridor (light blue) is composed of the frontal crest of the frontal bone, crista galli and cribriform plate of the ethmoid bone, and planum and jugum sphenoidale. The paramedian corridor (yellow) involves the fovea ethmoidalis. The lateral corridor (black) is composed of the orbital plates of the frontal bone anteriorly and the lesser sphenoid wings laterally. The boundary between the anterior and middle skull base is delineated by the dotted line. (B) The exocranial surface of the anterior skull base is composed in the midline (light blue) by the frontal, ethmoid and sphenoid bones. The perpendicular plate of the ethmoid bone, joined to the vomer, forms the upper part of the nasal septum. The lateral plates of the ethmoid bone are in the paramedian region (yellow) and divide the nasal cavity from the orbits. The lateral corridor (black) is composed of the orbital plates of the frontal bone and the lesser sphenoid wings. CG: crista galli, CP: cribriform plate, EB: ethmoid bone, FB: frontal bone, FC: frontal crest, FE: fovea ethmoidalis, JS: jugum sphenoidale, Lp: lateral plates, LSW: lesser sphenoid wings, OP: orbital plates, P: planum, Pp: perpendicular plate, SB: sphenoid bone.

The exocranial posterolateral skull base is formed by the styloid, mastoid, and petrous parts of the temporal bone and the squamosal part of the occipital bone. The styloid process is the cranial point of attachment for the muscles of the styloid diaphragm. Posterior to the styloid process, the stylomastoid foramen transmits the facial nerve at its exit from the Fallopian canal. On the inferior exocranial surface of the petrous part of the temporal bone, the external orifice of the carotid canal is located anterior and medial to the jugular foramen. The jugular foramen and hypoglossal canal open into the parapharyngeal space. The mastoid part of the temporal bone forms the posterior border of the external acoustic meatus. The mastoid process is lateral to the styloid process, grooved by the occipital artery, and contains the mastoid emissary foramen for the mastoid emissary vein. The mastoid notch is the cranial point of attachment for the sternocleidomastoid and digastric muscles.

5. DISCUSSION

Thorough knowledge of skull base anatomy is the starting point for the treatment of all surgical neurovascular pathologies, ranging from intracranial aneurysms to arteriovenous malformations and arteriovenous fistulas (Ciappetta, Luzzi, et al. 2009; Ciappetta, Occhiogrosso, et al. 2009; De Tommasi et al. 2006; Del Maestro et al. 2018; Gallieni et al. 2018; S. Luzzi, Del Maestro, et al. 2018; S. Luzzi, Del Maestro, and Galzio 2019; S. Luzzi, Microsurgical Anatomy of the Cranial Base 11

Elia, Del Maestro, Morotti, et al. 2019; S. Luzzi, Gallieni, et al. 2018; Ricci et al. 2017; S. Luzzi et al. 2020). Infratentorial cavernous hemangiomas may also require skull base approaches. Anterolateral approaches, including the pterional, supraorbital, orbitopterional, and cranio- orbitozygomatic, are directed through the anterior and middle skull base, whereas posterior and posterolateral approaches are useful for vascular lesions involving the posterior skull base. Execution of the pterional approach, a workhorse for most anterior circulation aneurysms, requires a precise knowledge of surgical landmarks and the anatomical relationships between the sphenoid, frontal, and temporal bones within the anterior and middle fossae. The key difference between the pterional and frontotemporal approaches is the wide drilling of the lesser sphenoid wing that the latter involves in order to fully expose the sphenoidal compartment of the sylvian fissure, which is mandatory to avoid excessive brain retraction, and gain access to both the anterior and posterior circulation (Yaşargil 1984). The mastery of the relationships between the anterior clinoid process, lesser sphenoid wing, internal carotid artery, and optic nerve is also essential to properly perform anterior clinoidectomy, which is a condictio sine qua non to expose aneurysms involving the clinoid and ophthalmic segments of the internal carotid artery. Surgical routes directed across the anterior skull base are often also used to treat posterior circulation aneurysms; for example, basilar tip and superior cerebellar artery aneurysms can be accessed via the cranio-orbitozygomatic approach. In this approach, an intradural transcavernous posterior clinoidectomy is performed to effectively expose basilar tip aneurysms occurring in low-riding basilar artery bifurcations, which requires detailed anatomical knowledge of upper clivus region anatomy. The same anterior skull base approaches are frequently employed in the treatment of arteriovenous malformations involving the frontobasal area and sylvian fissure. Middle skull base approaches are generally directed toward basilar tip and midbasilar trunk aneurysms, but also temporobasal and temporomesial arteriovenous malformations. Midbrain cavernous angiomas posterior to the lateral mesencephalic sulcus are generally approached via a subtemporal transtentorial route, as are basilar tip aneurysms (Drake’s approach) (Drake 1961, 1999). Middle skull base approaches also provide a direct route to the anterolateral pons, lower basilar artery, and therefore the posterior skull base, via the subtemporal transanterior petrosal route described by Kawase in 1985 (Kawase et al. 1985). Posterior petrosal or combined petrosal presigmoid approaches are generally employed for the surgical exposure of aneurysms involving the midbasilar trunk (Al-Mefty, Fox, and Smith 1988). The far lateral approach is the mainstay for surgery of the posterolateral skull base. Since its first description by Heros in 1986 (Heros 1986), it has been routinely employed for aneurysms of the anterior medullary segments of the vertebral artery, anterior and lateral medullary segments of the posterior inferior cerebellar artery, and the vertebrobasilar junction. Thorough knowledge of the relationships between the occipital condyle, hypoglossal canal, jugular tubercle, lower clivus, and anterior border of the foramen magnum is essential to tailor the approach. For example, a supracondylar or transcondylar extension of the far lateral approach can be carried out to widen the exposure of proximal aneurysms located anterior to the jugular tubercle (Wen et al. 1997; Ciappetta, Occhiogrosso, et al. 2009; S. Luzzi, Gallieni, et al. 2018; Ciappetta, Luzzi, et al. 2009).

12 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

Figure 3. Endocranial surface of the middle skull base. (A) The median corridor (light blue) involves, from anterior to posterior, the chiasmatic sulcus, tuberculum sellae, sella turcica, and dorsum sellae; the posterior clinoid processes comprise the superolateral parts of the dorsum sellae. The openings of the optic canals are located at the lateral ends of the chiasmatic sulcus. The paramedian region (yellow) is composed of the root of the lesser and greater sphenoid wings and the anterior clinoid processes anteriorly, and the foramen lacerum posteriorly. This region contains the carotid sulcus, which contains the cavernous segment of the internal carotid artery above the petrolingual ligament. The petrolingual ligament marks the border between the lacerum and cavernous segments of the internal carotid artery and attaches to the lingula of the sphenoid bone. Boundaries between anterior and middle (dotted line), and middle and posterior skull base (pointed line). (B) The lateral region (black) is composed of the lesser and greater sphenoid wings and the superior orbital fissure in between. In the lateral corridor, the squamous and petrous parts of the temporal bone form the temporal fossa, which contains the foramen rotundum, foramen ovale, foramen spinosum, and occasionally the foramen of Vesalius, when present. The most lateral portion is composed of the superior surface of the petrous part of the temporal bone. At the petrous apex, the trigeminal impression houses Meckel’s cave, which contains the Gasserian ganglion. Laterally, the arcuate eminence overlies the superior semicircular canal; the tegmen tympani separates the middle skull base from the middle ear. (C) The optic strut is the root of the lesser sphenoid wing and located on the lateral surface of the body of the sphenoid bone; it separates the optic canal from the superior orbital fissure. (D) The maxillary strut separates the foramen rotundum from the superior orbital fissure. (E) The median or sellar (light blue), paramedian or parasellar (yellow), and lateral (black) corridors of the middle skull base. The lateral region is formed by the sphenoid bone and squamous and petrous part of the temporal bone, which articulate at the sphenopetrosal and sphenosquamosal sutures. (F) Exocranial surface of the middle skull base. The median corridor (light blue) involves the inferior side of the body of the sphenoid bone. The paramedian corridor (yellow) is composed of the pterygoid process of the sphenoid bone, which branches into medial and lateral pterygoid plates; the pterygoid fossa is located between the plates. The lateral corridor (black) is comprised of the infratemporal fossa anteriorly and the mandibular fossa posteriorly. The exocranial surface of the middle skull base also borders the parapharyngeal space. The boundaries between the anterior and middle skull base and the middle and posterior skull base are delineated by dotted and pointed lines, respectively. AC: anterior clinoid, AE: arcuate eminence, CS: carotid sulcus, Cs: chiasmatic sulcus, DS: dorsum sellae, FL: foramen lacerum, FO: foramen ovale, FR: foramen rotundum, FS: foramen spinosum, FV: foramen of Vesalius, GSW: greater sphenoid wing, ITF: infratemporal fossa, JS: jugum sphenoidale, LWS: less sphenoid wing, MF: mandibular fossa, OC: optic canal, Os: optic strut, P: planum, PC: posterior clinoid, Pf: pterygoid fossa, PL: petrolingual ligament, PP: pterygoid process, PPS: parapharyngeal space, pT: petrous part of temporal bone, S: sella, SB: sphenoid body, SOF: superior orbital fissure, Sps: sphenopetrosal suture, Sss: sphenosquamosal suture, sT: squamous and petrous part of temporal bone, TF: temporal fossa, TI: trigeminal impression, TS: tuberculum sellae, Tt tegmen tympani. Microsurgical Anatomy of the Cranial Base 13

Figure 4. (A) Endocranial surface of the posterior skull base. The central corridor (light blue) includes the clivus and the foramen magnum. In the midline, the most anterior point of the foramen magnum on the clival part of the occipital bone is the basion; the most posterior point is the opisthion, located at the most caudal aspect of the squamosal part of the occipital bone. In the paramedian region (yellow) lie the jugular tubercle and the hypoglossal canal. The lateral corridor (black) contains the jugular foramen, bordered by the notch of the jugular process of the occipital bone and the jugular fossa of the petrous part of the temporal bone. On the posterior surface of the petrous bone, the internal auditory canal is located above the jugular foramen. The sulcus of the transverse and sigmoid sinuses courses lateral to medial toward the jugular foramen along the surface of the squamous part of the temporal bone. The boundary between the middle and posterior skull base is delineated by a pointed line. (B) Exocranial surface of the posterior skull base. The midline corridor (light blue) is occupied by the clivus and foramen magnum. The paramedian corridor (yellow) involves the occipital condyles. The condyles are oval shaped, articulate with the superior articular facet of the atlas, and oriented anteriorly and medially from three to one and nine to eleven o'clock. The exocranial posterolateral skull base (black) is formed by the styloid, mastoid, and petrous parts of the temporal bone, and the squamosal part of the occipital bone. Anteromedially it contains the external orifice of the carotid canal; posterior to this lie the jugular foramen and hypoglossal canal, which open into the parapharyngeal space. Posterior to the styloid process is the opening of the stylomastoid foramen. The mastoid process constitutes the posterior border of the external acoustic meatus. The boundary between the middle and posterior skull base is delineated by a pointed line. B: basion, C: clivus, CC: carotid canal, EAM: external acoustic meatus, FM: foramen magnum, HC: hypoglossal canal, IAC: internal auditory canal, JF: jugular foramen, JT: jugular tuberculum, MP: mastoid process, O: opisthion, OC: occipital condyle, SMF: stylomastoid foramen, SP: styloid process, sSS sulcus of sigmoid sinus, sTS: sulcus of transverse sinus.

The median suboccipital approach, which is a pure transoccipital route performed through the inferior aspect of the squamous part of the occipital bone and the posterior border of the foramen magnum, is commonly employed for the treatment of aneurysms involving the lateral medullary segment of the vertebral artery and the distal segment of the posterior inferior cerebellar artery. Certain median vermian or paramedian hemispheric cerebellar arteriovenous malformations are also treated by this approach. Endoscopic approaches have achieved good results for most but not all neurosurgical pathologies (Arnaout et al. 2019; S. Luzzi, Del Maestro, Elia, et al. 2019; S. Luzzi, Del Maestro, Trovarelli, et al. 2019; S. Luzzi, Zoia, et al. 2019; Zoia et al. 2019; Gardner et al. 2015; Heiferman et al. 2015). Despite the advent and implementation of stereotactic neuronavigation, one of the recent tremendous neurosurgical advancements (Bellantoni et al. 2019; Cheng, Shetty, and Sekhar 2018; De Tommasi et al. 2008; De Tommasi et al. 2007; Guastamacchia et al. 2007; Sabino Luzzi, Crovace, et al. 2019; S. Luzzi, Crovace, et al. 2018; S. Luzzi, Elia, Del Maestro, Elbabaa, et al. 2019; S. Luzzi, Giotta Lucifero, et al. 2019; Palumbo et al. 2019; Palumbo et al. 2018; 14 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

Raysi Dehcordi et al. 2017; Spena et al. 2019; Zoia et al. 2018; Bongetta et al. 2019; Millimaggi et al. 2018; Antonosante et al. 2020; Campanella et al. 2020; Zoia et al. 2020; Elsawaf et al. 2020), detailed knowledge of skull base anatomy remains mandatory for the planning and execution of surgical skull base approaches used in the treatment of vascular diseases affecting the central nervous system.

CONCLUSION

Thorough knowledge of cranial base anatomy is paramount for planning and executing the surgical skull base approaches commonly employed in the treatment of most intracranial neurovascular diseases.

REFERENCES

Abdel Aziz, K. M., A. Sanan, H. R. van Loveren, J. M. Tew, Jr., J. T. Keller, and M. L. Pensak. 2000. “Petroclival meningiomas: predictive parameters for transpetrosal approaches.” Neurosurgery 47 (1): 139-50; discussion 150-2. https://www.ncbi.nlm.nih.gov/pubmed/ 10917357. Al-Mefty, O, J L Fox, and R R Smith. 1988. “Petrosal approach for petroclival meningiomas.” Neurosurgery 22: 510-7. Antonosante, A., L. Brandolini, M. d'Angelo, E. Benedetti, V. Castelli, M. D. Maestro, S. Luzzi, A. Giordano, A. Cimini, and M. Allegretti. 2020. “Autocrine CXCL8-dependent invasiveness triggers modulation of actin cytoskeletal network and cell dynamics.” Aging (Albany NY) 12 (2): 1928-1951. https://doi.org/10.18632/aging.102733. https://www. ncbi.nlm.nih.gov/pubmed/31986121. Arnaout, M. M., S. Luzzi, R. Galzio, and K. Aziz. 2019. “Supraorbital keyhole approach: Pure endoscopic and endoscope-assisted perspective.” Clin Neurol Neurosurg 189: 105623. https://doi.org/10.1016/j.clineuro.2019.105623. https://www.ncbi.nlm.nih.gov/pubmed/ 31805490. Bassed, R. B., C. Briggs, and O. H. Drummer. 2010. “Analysis of time of closure of the spheno- occipital synchondrosis using computed tomography.” Forensic Sci Int 200 (1-3): 161-4. https://doi.org/10.1016/j.forsciint.2010.04.009. https://www.ncbi.nlm.nih.gov/pubmed/ 20451338. Bellantoni, G., F. Guerrini, M. Del Maestro, R. Galzio, and S. Luzzi. 2019. “Simple schwannomatosis or an incomplete Coffin-Siris? Report of a particular case.” eNeurologicalSci 14: 31-33. https://doi.org/10.1016/j.ensci.2018.11.021. https://www. ncbi.nlm.nih.gov/pubmed/30555950. Bongetta, D., C. Zoia, S. Luzzi, M. D. Maestro, A. Peri, G. Bichisao, D. Sportiello, I. Canavero, A. Pietrabissa, and R. J. Galzio. 2019. “Neurosurgical issues of bariatric surgery: A systematic review of the literature and principles of diagnosis and treatment.” Clin Neurol Neurosurg 176: 34-40. https://doi.org/10.1016/j.clineuro.2018.11.009. https://www.ncbi. nlm.nih.gov/pubmed/30500756. Microsurgical Anatomy of the Cranial Base 15

Bozbuga, M., A. Ozturk, B. Bayraktar, Z. Ari, K. Sahinoglu, G. Polat, and I. Gurel. 1999. “Surgical anatomy and morphometric analysis of the occipital condyles and foramen magnum.” Okajimas Folia Anat Jpn 75 (6): 329-34. https://doi.org/10.2535/ ofaj1936.75.6_329. https://www.ncbi.nlm.nih.gov/pubmed/10217952. Campanella, R., L. Guarnaccia, C. Cordiglieri, E. Trombetta, M. Caroli, G. Carrabba, N. La Verde, P. Rampini, C. Gaudino, A. Costa, S. Luzzi, G. Mantovani, M. Locatelli, L. Riboni, S. E. Navone, and G. Marfia. 2020. “Tumor-Educated Platelets and Angiogenesis in Glioblastoma: Another Brick in the Wall for Novel Prognostic and Targetable Biomarkers, Changing the Vision from a Localized Tumor to a Systemic Pathology.” Cells 9 (2). https://doi.org/10.3390/cells9020294. https://www.ncbi.nlm.nih.gov/pubmed/31991805. Cheng, C. Y., R. Shetty, and L. N. Sekhar. 2018. “Microsurgical Resection of a Large Intraventricular Trigonal Tumor: 3-Dimensional Operative Video.” Oper Neurosurg (Hagerstown) 15 (6): E92-E93. https://doi.org/10.1093/ons/opy068. https://www.ncbi. nlm.nih.gov/pubmed/29618124. Ciappetta, P., S. Luzzi, R. De Blasi, and P. I. D'Urso. 2009. “Extracranial aneurysms of the posterior inferior cerebellar artery. Literature review and report of a new case.” J Neurosurg Sci 53 (4): 147-51. https://www.ncbi.nlm.nih.gov/pubmed/20220739. Ciappetta, P., G. Occhiogrosso, S. Luzzi, P. I. D'Urso, and A. P. Garribba. 2009. “Jugular tubercle and vertebral artery/posterior inferior cerebellar artery anatomic relationship: a 3- dimensional angiography computed tomography anthropometric study.” Neurosurgery 64 (5 Suppl 2): 429-36; discussion 436. https://doi.org/10.1227/01.NEU.000033 7573.17073.9F. https://www.ncbi.nlm.nih.gov/pubmed/19404121. de Oliveira, E., A. L. Rhoton, Jr., and D. Peace. 1985. “Microsurgical anatomy of the region of the foramen magnum.” Surg Neurol 24 (3): 293-352. https://www.ncbi.nlm.nih.gov/ pubmed/4023912. De Tommasi, A., C. De Tommasi, E. Lauta, S. Luzzi, A. Cimmino, and P. Ciappetta. 2006. “Pre-operative subarachnoid haemorrhage in a patient with spinal tumour.” Cephalalgia 26 (7): 887-90. https://doi.org/10.1111/j.1468-2982.2006.01122.x. https://www.ncbi.nlm. nih.gov/pubmed/16776708. De Tommasi, A., S. Luzzi, P. I. D'Urso, C. De Tommasi, N. Resta, and P. Ciappetta. 2008. “Molecular genetic analysis in a case of ganglioglioma: identification of a new mutation.” Neurosurgery 63 (5): 976-80; discussion 980. https://doi.org/10.1227/01.NEU. 0000327699.93146.CD. https://www.ncbi.nlm.nih.gov/pubmed/19005389. De Tommasi, A., G. Occhiogrosso, C. De Tommasi, S. Luzzi, A. Cimmino, and P. Ciappetta. 2007. “A polycystic variant of a primary intracranial leptomeningeal astrocytoma: case report and literature review.” World J Surg Oncol 5: 72. https://doi.org/10.1186/1477- 7819-5-72. https://www.ncbi.nlm.nih.gov/pubmed/17587463. Del Maestro, M., S. Luzzi, M. Gallieni, D. Trovarelli, A. V. Giordano, M. Gallucci, A. Ricci, and R. Galzio. 2018. “Surgical Treatment of Arteriovenous Malformations: Role of Preoperative Staged Embolization.” Acta Neurochir Suppl 129: 109-113. https://doi.org/ 10.1007/978-3-319-73739-3_16. https://www.ncbi.nlm.nih.gov/pubmed/30171322. Drake, C. G. 1961. “Bleeding aneurysms of the basilar artery. Direct surgical management in four cases.” J Neurosurg 18: 230-8. https://doi.org/10.3171/jns.1961.18.2.0230. https://www.ncbi.nlm.nih.gov/pubmed/13724254. 16 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

---. 1999. “Bleeding aneurysms of the basilar artery. Direct surgical management in four cases. 1961.” Can J Neurol Sci 26 (4): 335-40. https://doi.org/10.1017/s0317167100000524. https://www.ncbi.nlm.nih.gov/pubmed/10563224. Elsawaf, Y., S. Anetsberger, S. Luzzi, and S. K. Elbabaa. 2020. “Early Decompressive Craniectomy as Management for Severe TBI in the Pediatric Population: A Comprehensive Literature Review.” World Neurosurg. https://doi.org/10.1016/j.wneu.2020.02.065. https://www.ncbi.nlm.nih.gov/pubmed/32084616. Funaki, T., T. Matsushima, M. Peris-Celda, R. J. Valentine, W. Joo, and A. L. Rhoton, Jr. 2013. “Focal transnasal approach to the upper, middle, and lower clivus.” Neurosurgery 73 (2 Suppl Operative): ons155-90; discussion ons190-1. https://doi.org/10.1227/01.neu. 0000431469.82215.93. https://www.ncbi.nlm.nih.gov/pubmed/24056315. Gallieni, M., M. Del Maestro, S. Luzzi, D. Trovarelli, A. Ricci, and R. Galzio. 2018. “Endoscope-Assisted Microneurosurgery for Intracranial Aneurysms: Operative Technique, Reliability, and Feasibility Based on 14 Years of Personal Experience.” Acta Neurochir Suppl 129: 19-24. https://doi.org/10.1007/978-3-319-73739-3_3. https://www. ncbi.nlm.nih.gov/pubmed/30171309. Gardner, P. A., F. Vaz-Guimaraes, B. Jankowitz, M. Koutourousiou, J. C. Fernandez-Miranda, E. W. Wang, and C. H. Snyderman. 2015. “Endoscopic Endonasal Clipping of Intracranial Aneurysms: Surgical Technique and Results.” World Neurosurg 84 (5): 1380- 93. https://doi.org/10.1016/j.wneu.2015.06.032. https://www.ncbi.nlm.nih.gov/pubmed/ 26117084. Guastamacchia, E., V. Triggiani, E. Tafaro, A. De Tommasi, C. De Tommasi, S. Luzzi, C. Sabba, F. Resta, M. R. Terreni, and M. Losa. 2007. “Evolution of a prolactin-secreting pituitary microadenoma into a fatal carcinoma: a case report.” Minerva Endocrinol 32 (3): 231-6. https://www.ncbi.nlm.nih.gov/pubmed/17912159. Guidotti, A. 1984. “Morphometrical considerations on occipital condyles.” Anthropologischer Anzeiger; Bericht über die biologisch-anthropologische Literatur 42 (2): 117--9. http://www.ncbi.nlm.nih.gov/pubmed/6465869. Heiferman, D. M., A. Somasundaram, A. J. Alvarado, A. M. Zanation, A. L. Pittman, and A. V. Germanwala. 2015. “The endonasal approach for treatment of cerebral aneurysms: A critical review of the literature.” Clin Neurol Neurosurg 134: 91-7. https://doi.org/10.1016/j.clineuro.2015.04.018. https://www.ncbi.nlm.nih.gov/pubmed/ 25974398. Heros, R. C. 1986. “Lateral suboccipital approach for vertebral and vertebrobasilar artery lesions.” J Neurosurg 64 (4): 559-62. https://doi.org/10.3171/jns.1986.64.4.0559. https://www.ncbi.nlm.nih.gov/pubmed/3950739. Kawase, T., S. Toya, R. Shiobara, and T. Mine. 1985. “Transpetrosal approach for aneurysms of the lower basilar artery.” J Neurosurg 63 (6): 857-61. https://doi.org/10. 3171/jns.1985.63.6.0857. https://www.ncbi.nlm.nih.gov/pubmed/4056899. Luzzi S, Del Maestro M, Elia A, Vincitorio F, Di Perna G, Zenga F, Garbossa D, Elbabaa S, Galzio R 2019. “Morphometric and Radiomorphometric Study of the Correlation Between the Foramen Magnum Region and the Anterior and Posterolateral Approaches to Ventral Intradural Lesions.” Turkish Neurosurgery In Press. https://doi.org/10.5137/1019- 5149.JTN.26052-19.2. Luzzi, S., A. M. Crovace, L. Lacitignola, V. Valentini, E. Francioso, G. Rossi, G. Invernici, R. J. Galzio, and A. Crovace. 2018. “Engraftment, neuroglial transdifferentiation and Microsurgical Anatomy of the Cranial Base 17

behavioral recovery after complete spinal cord transection in rats.” Surg Neurol Int 9: 19. https://doi.org/10.4103/sni.sni_369_17. https://www.ncbi.nlm.nih.gov/pubmed/29497572. Luzzi, S., M. Del Maestro, D. Bongetta, C. Zoia, A. V. Giordano, D. Trovarelli, S. Raysi Dehcordi, and R. J. Galzio. 2018. “Onyx Embolization Before the Surgical Treatment of Grade III Spetzler-Martin Brain Arteriovenous Malformations: Single-Center Experience and Technical Nuances.” World Neurosurg 116: e340-e353. https://doi.org/10.1016/ j.wneu.2018.04.203. https://www.ncbi.nlm.nih.gov/pubmed/29751183. Luzzi, S., M. Del Maestro, S. K. Elbabaa, and R. Galzio. 2020. “Letter to the Editor Regarding “One and Done: Multimodal Treatment of Pediatric Cerebral Arteriovenous Malformations in a Single Anesthesia Event”.” World Neurosurg 134: 660. https://doi.org/ 10.1016/j.wneu.2019.09.166. https://www.ncbi.nlm.nih.gov/pubmed/32059273. Luzzi, S., M. Del Maestro, A. Elia, F. Vincitorio, G. Di Perna, F. Zenga, D. Garbossa, S. Elbabaa, and R. Galzio. 2019. “Morphometric and Radiomorphometric Study of the Correlation Between the Foramen Magnum Region and the Anterior and Posterolateral Approaches to Ventral Intradural Lesions.” Turk Neurosurg. https://doi.org/ 10.5137/1019-5149.JTN.26052-19.2. https://www.ncbi.nlm.nih.gov/pubmed/31452176. Luzzi, S., M. Del Maestro, and R. Galzio. 2019. “Letter to the Editor. Preoperative embolization of brain arteriovenous malformations.” J Neurosurg: 1-2. https://doi.org/10.3171/ 2019.6.JNS191541. https://www.ncbi.nlm.nih.gov/pubmed/31812150. https://thejns.org/view/journals/j-neurosurg/aop/article-10.3171-2019.6.JNS191541/article- 10.3171-2019.6.JNS191541.xml. Luzzi, S., M. Del Maestro, D. Trovarelli, D. De Paulis, S. R. Dechordi, H. Di Vitantonio, V. Di Norcia, D. F. Millimaggi, A. Ricci, and R. J. Galzio. 2019. “Endoscope-Assisted Microneurosurgery for Neurovascular Compression Syndromes: Basic Principles, Methodology, and Technical Notes.” Asian J Neurosurg 14 (1): 193-200. https://doi.org/ 10.4103/ajns.AJNS_279_17. https://www.ncbi.nlm.nih.gov/pubmed/30937034. Luzzi, S., A. Elia, M. Del Maestro, S. K. Elbabaa, S. Carnevale, F. Guerrini, M. Caulo, P. Morbini, and R. Galzio. 2019. “Dysembryoplastic Neuroepithelial Tumors: What You Need to Know.” World Neurosurg 127: 255-265. https://doi.org/10.1016/j.wneu. 2019.04.056. https://www.ncbi.nlm.nih.gov/pubmed/30981794. Luzzi, S., A. Elia, M. Del Maestro, A. Morotti, S. K. Elbabaa, A. Cavallini, and R. Galzio. 2019. “Indication, Timing, and Surgical Treatment of Spontaneous Intracerebral Hemorrhage: Systematic Review and Proposal of a Management Algorithm.” World Neurosurg. https://doi.org/10.1016/j.wneu.2019.01.016. https://www.ncbi.nlm.nih.gov/ pubmed/30677572. Luzzi, S., M. Gallieni, M. Del Maestro, D. Trovarelli, A. Ricci, and R. Galzio. 2018. “Giant and Very Large Intracranial Aneurysms: Surgical Strategies and Special Issues.” Acta Neurochir Suppl 129: 25-31. https://doi.org/10.1007/978-3-319-73739-3_4. https://www. ncbi.nlm.nih.gov/pubmed/30171310. Luzzi, S., A. Giotta Lucifero, M. Del Maestro, G. Marfia, S. E. Navone, M. Baldoncini, M. Nunez, A. Campero, S. K. Elbabaa, and R. Galzio. 2019. “Anterolateral Approach for Retrostyloid Superior Parapharyngeal Space Schwannomas Involving the Jugular Foramen Area: A 20-Year Experience.” World Neurosurg. https://doi.org/10.1016/j.wneu. 2019.09.006. https://www.ncbi.nlm.nih.gov/pubmed/31520759. Luzzi, S., C. Zoia, A. D. Rampini, A. Elia, M. Del Maestro, S. Carnevale, P. Morbini, and R. Galzio. 2019. “Lateral Transorbital Neuroendoscopic Approach for Intraconal 18 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

Meningioma of the Orbital Apex: Technical Nuances and Literature Review.” World Neurosurg 131: 10-17. https://doi.org/10.1016/j.wneu.2019.07.152. https://www.ncbi. nlm.nih.gov/pubmed/31356977. Luzzi, Sabino, Alberto Maria Crovace, Mattia Del Maestro, Alice Giotta Lucifero, Samer K. Elbabaa, Benedetta Cinque, Paola Palumbo, Francesca Lombardi, Annamaria Cimini, Maria Grazia Cifone, Antonio Crovace, and Renato Galzio. 2019. “The cell-based approach in neurosurgery: ongoing trends and future perspectives.” Heliyon 5 (11). https://doi.org/10.1016/j.heliyon.2019.e02818. Millimaggi, D. F., V. D. Norcia, S. Luzzi, T. Alfiero, R. J. Galzio, and A. Ricci. 2018. “Minimally Invasive Transforaminal Lumbar Interbody Fusion with Percutaneous Bilateral Pedicle Screw Fixation for Lumbosacral Spine Degenerative Diseases. A Retrospective Database of 40 Consecutive Cases and Literature Review.” Turk Neurosurg 28 (3): 454-461. https://doi.org/10.5137/1019-5149.JTN.19479-16.0. https://www.ncbi. nlm.nih.gov/pubmed/28481388. Mintelis, A., T. Sameshima, K. R. Bulsara, L. Gray, A. H. Friedman, and T. Fukushima. 2006. “Jugular tubercle: Morphometric analysis and surgical significance.” J Neurosurg 105 (5): 753-7. https://doi.org/10.3171/jns.2006.105.5.753. https://www.ncbi.nlm.nih.gov/ pubmed/17121139. Muthukumar, N., R. Swaminathan, G. Venkatesh, and S. P. Bhanumathy. 2005. “A morphometric analysis of the foramen magnum region as it relates to the transcondylar approach.” Acta Neurochir (Wien) 147 (8): 889-95. https://doi.org/10.1007/s00701-005- 0555-x. https://www.ncbi.nlm.nih.gov/pubmed/15924208. Naderi, S., E. Korman, G. Citak, M. Guvencer, C. Arman, M. Senoglu, S. Tetik, and M. N. Arda. 2005. “Morphometric analysis of human occipital condyle.” Clin Neurol Neurosurg 107 (3): 191-9. https://doi.org/10.1016/j.clineuro.2004.07.014. https://www.ncbi.nlm.nih. gov/pubmed/15823674. Olivier, G. 1975. “Biometry of the human occipital bone.” J Anat 120 (Pt 3): 507-18. https://www.ncbi.nlm.nih.gov/pubmed/1213952. Palumbo, P., F. Lombardi, F. R. Augello, I. Giusti, S. Luzzi, V. Dolo, M. G. Cifone, and B. Cinque. 2019. “NOS2 inhibitor 1400W Induces Autophagic Flux and Influences Extracellular Vesicle Profile in Human Glioblastoma U87MG Cell Line.” Int J Mol Sci 20 (12). https://doi.org/10.3390/ijms20123010. https://www.ncbi.nlm.nih.gov/pubmed/ 31226744. Palumbo, P., F. Lombardi, G. Siragusa, S. R. Dehcordi, S. Luzzi, A. Cimini, M. G. Cifone, and B. Cinque. 2018. “Involvement of NOS2 Activity on Human Glioma Cell Growth, Clonogenic Potential, and Neurosphere Generation.” Int J Mol Sci 19 (9). https://doi.org/10.3390/ijms19092801. https://www.ncbi.nlm.nih.gov/pubmed/30227679. Raysi Dehcordi, S., A. Ricci, H. Di Vitantonio, D. De Paulis, S. Luzzi, P. Palumbo, B. Cinque, D. Tempesta, G. Coletti, G. Cipolloni, M. G. Cifone, and R. Galzio. 2017. “Stemness Marker Detection in the Periphery of Glioblastoma and Ability of Glioblastoma to Generate Glioma Stem Cells: Clinical Correlations.” World Neurosurg 105: 895- 905. https://doi.org/10.1016/j.wneu.2017.05.099. https://www.ncbi.nlm.nih.gov/pubmed/ 28559081. Rhoton, A. L., Jr. 2000. “The foramen magnum.” Neurosurgery 47 (3 Suppl): S155-93. https://www.ncbi.nlm.nih.gov/pubmed/10983308. Microsurgical Anatomy of the Cranial Base 19

Ricci, A., H. Di Vitantonio, D. De Paulis, M. Del Maestro, S. D. Raysi, D. Murrone, S. Luzzi, and R. J. Galzio. 2017. “Cortical aneurysms of the middle cerebral artery: A review of the literature.” Surg Neurol Int 8: 117. https://doi.org/10.4103/sni.sni_50_17. https://www. ncbi.nlm.nih.gov/pubmed/28680736. Spena, G., E. Roca, F. Guerrini, P. P. Panciani, L. Stanzani, A. Salmaggi, S. Luzzi, and M. Fontanella. 2019. “Risk factors for intraoperative stimulation-related seizures during awake surgery: an analysis of 109 consecutive patients.” J Neurooncol. https://doi.org/10.1007/s11060-019-03295-9. https://www.ncbi.nlm.nih.gov/pubmed/ 31552589. Wen, H. T., A. L. Rhoton, Jr., T. Katsuta, and E. de Oliveira. 1997. “Microsurgical anatomy of the transcondylar, supracondylar, and paracondylar extensions of the far-lateral approach.” J Neurosurg 87 (4): 555-85. https://doi.org/10.3171/jns.1997.87.4.0555. https://www.ncbi. nlm.nih.gov/pubmed/9322846. Williams, P. L. 1995. “Gray's anatomy.” Nervous System: 1240-1243. https://ci.nii.ac.jp/ naid/10010326773/en/. Yaşargil, M.G. 1984. Microneurosurgery. Vol. v. 1: Thieme. Zoia, C., D. Bongetta, G. Dorelli, S. Luzzi, M. D. Maestro, and R. J. Galzio. 2019. “Transnasal endoscopic removal of a retrochiasmatic cavernoma: A case report and review of literature.” Surg Neurol Int 10: 76. https://doi.org/10.25259/SNI-132-2019. https://www. ncbi.nlm.nih.gov/pubmed/31528414. Zoia, C., D. Bongetta, F. Guerrini, C. Alicino, A. Cattalani, S. Bianchini, R. J. Galzio, and S. Luzzi. 2018. “Outcome of elderly patients undergoing intracranial meningioma resection: a single center experience.” J Neurosurg Sci. https://doi.org/10.23736/S0390- 5616.18.04333-3. https://www.ncbi.nlm.nih.gov/pubmed/29808631. Zoia, C., F. Lombardi, M. R. Fiore, A. Montalbetti, A. Iannalfi, M. Sansone, D. Bongetta, F. Valvo, M. Del Maestro, S. Luzzi, and R. J. Galzio. 2020. “Sacral solitary fibrous tumour: surgery and hadrontherapy, a combined treatment strategy.” Rep Pract Oncol Radiother 25 (2): 241-244. https://doi.org/10.1016/j.rpor.2020.01.008. https://www.ncbi.nlm.nih. gov/pubmed/32025222.

Chapter 2

VASCULAR ANATOMY OF THE CRANIAL ANTERIOR CIRCULATION

S. Luzzi1,2,, MD, PhD, A. Giotta Lucifero1, MD, M. Del Maestro2,3, MD, M. Nuñez4, MD and R. Galzio1,2, MD 1Neurosurgery Unit, Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy 2Neurosurgery Unit, Department of Surgical Sciences, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy 3PhD School in Experimental Medicine, Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy 4Department of Neurosurgery, Hospital El Cruce, Buenos Aires, Argentina

ABSTRACT

Treatment of central nervous system vascular pathology requires detailed knowledge of vascular anatomy. This chapter describes the vasculature of the anterior cerebral circulation from a surgical perspective. Synoptic tables are used to present arterial segments, branches, and vascular supply.

Keywords: anterior cerebral artery, anterior communicating artery, external carotid artery, internal carotid artery, middle cerebral artery, perforating arteries

1. INTERNAL CAROTID ARTERY

The internal carotid artery (ICA) arises in the neck from the common carotid artery at the level of Farabeuf’s triangle, which is delineated by the internal jugular vein (IJV) posteriorly, the thyrolinguofacial venous trunk anteriorly, and the hypoglossal nerve superiorly. Classically, the ICA is noted to originate at the level of the superior border of the thyroid cartilage, but in

 Corresponding Author’s Email: [email protected]. 22 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al. fact the site of origin varies largely (Al-Rafiah et al. 2011). The ICA ascends toward the external orifice of the carotid canal, initially superficial to the external carotid artery (ECA), then turning medially and passing posterior to the ECA. Before entering the skull base, the ICA passes through the parapharyngeal space which is divided into pre- and post-styloid compartments and bordered laterally by the posterior belly of the digastric muscle (S. Luzzi, Giotta Lucifero, et al. 2019). The cervical ICA has no branches. Inside the temporal bone, the ICA has three well- defined segments, namely, the posterior vertical, horizontal, and anterior vertical segments. The posterior genu lies between the posterior vertical and horizontal segments, whereas the anterior genu is located between the horizontal and anterior vertical segments. The posterior vertical segment gives rise to the caroticotympanic artery. The horizontal segment is cushioned by a venous plexus and the distal segment runs inferior to the third trigeminal division lying within Meckel’s cave. This area corresponds to the foramen lacerum, which is formed by the union between the petrous apex, the lateral aspect of the dorsum sellae, and the sphenoid body. Above the foramen lacerum, the petrolingual ligament, lying between the petrous apex and the lingual process of the sphenoid bone, envelopes the anterior genu, fixes the ICA to the carotid sulcus on the lateral aspect of the body of the sphenoid bone, and marks the caudal limit of the carotid sulcus itself. The carotid sulcus, where the ICA runs superiorly, is located within the cavernous sinus; this is where the cavernous ICA segment begins. The cavernous ICA makes a vertical posterior bend, then has a horizontal forward segment and a horizontal anterior bend, the uppermost part of which passes medial to the anterior clinoid process, and pierces the roof of the cavernous sinus (Rhoton 2002b). The so-called clinoid segment of the ICA is comprised between the proximal and distal dural rings that define the limit of the carotid collar (Rhoton 2002a; Seoane, Rhoton, and de Oliveira 1998). The clinoid segment is bounded medially by the carotid sulcus, anteriorly by the optic strut, and medially by the anterior clinoid process. The distal dural ring is tightly adherent to the anterior and lateral aspect of the clinoid segment, but not the medial and posterior aspect. This posteromedial area around the distal clinoid segment is known as the carotid cave; aneurysms of the carotid cave hemorrhage into the subarachnoid space (Joo et al. 2012; Rhoton 2002a; Seoane, Rhoton, and de Oliveira 1998). Not infrequently, the superior hypophyseal artery arises from the carotid cave. The cavernous segment gives rise to the meningohypophyseal artery, the inferolateral trunk, and the capsular arteries. Above the level of the anterior clinoid process, the supraclinoid ICA ascends superiorly, posteriorly, and laterally toward the lateral aspect of the optic chiasm, then up to the anterior perforated substance where it bifurcates into the anterior and middle cerebral arteries (Figure 1 A). From proximal to distal, the supraclinoid ICA gives rise to the ophthalmic artery (OphA), posterior communicating artery (PCoA), and anterior choroidal artery (AChA), which mark the ophthalmic, posterior communicating, and choroidal segments of the ICA. The ophthalmic is the longest segment, whereas the posterior communicating is the shortest one (Rhoton 2002b). The OphA emerges from the ventral aspect of the supraclinoid ICA just inferior to the optic nerve and the anterior clinoid. An anterior clinoidectomy is generally necessary to expose the OphA. The PCoA and AChA arise from the back wall of the ICA, along with the superior hypophyseal perforating arteries arising specifically from the back wall of the ophthalmic segment. The largest of these arteries is referred to as the superior hypophyseal artery (Gibo, Lenkey, and Rhoton 1981; Rhoton 2002b). The PCoA arises from the posteromedial aspect of the backwall of the ICA; its diameter may be as large as that of the posterior cerebral artery in cases of persistent fetal PCoA. The AChA also arises from the posteromedial aspect of the ICA and courses posteriorly toward the lateral aspect of the lateral Vascular Anatomy of the Cranial Anterior Circulation 23 geniculate body. The first AChA segment, coursing parallel to the optic tract within the crural cistern, is known as the cisternal segment, which is delineated anterolaterally by the uncus and posteromedially by the cerebral peduncle. The lateral geniculate body marks the transition from the cisternal to the plexal segment of the AChA, which turns abruptly from medial to lateral to reach the inferior choroidal point (Frigeri et al. 2014; Rhoton, Fujii, and Fradd 1979; Tubbs et al. 2010; Wen et al. 1999; Fujii, Lenkey, and Rhoton 1980). Along its course, the AChA gives rise to important branches to the optic tract, uncus, cerebral peduncle, temporal horn, lateral geniculate body, hippocampus, dentate gyrus and fornix, and anterior perforated substance (Rhoton, Fujii, and Fradd 1979; Tubbs et al. 2010; Fujii, Lenkey, and Rhoton 1980). Within the temporal horn of the lateral ventricle, the plexal segment of the AChA widely anastomoses with the lateral posterior choroidal artery to form a dense arterial plexus supplying the choroid plexus.

Figure 1. (A) Supraclinoid segment of the internal carotid artery; (B) Anterior cerebral and callosomarginal arteries; (C) Anterior part of the circle of Willis; (D) Course of the anterior cerebral artery along the genu of the corpus callosum; (E, F) Distal segment of the anterior cerebral artery; (G-I) pericallosal artery.

Over the years, several ICA segment classifications have been proposed; some of these have considerable importance from a surgical standpoint (Perlmutter and Rhoton 1976; Lasjaunias and Santoyo-Vazquez 1984; Bouthillier, van Loveren, and Keller 1996; Ziyal et al. 2005; Labib et al. 2014). The extremely detailed seven-segment classification by Bouthillier and colleagues probably conforms best to the needs of most surgeons (Bouthillier, van Loveren, and Keller 1996). Table 1 summarizes the main ICA segment classification schemes and highlights the differences between them (Table 1).

Table 1. Main Internal Carotid Artery Segment Classification Schemes

Segment Nomenclature Cavernous Supraclinoid Cervical Petrous Lacerum Paraclival Parasellar Vertical Horizontal Clinoid Ophthalmic Communicating Cavernous Cavernous Authors Distal Anatomic Border External orifice Superior edge of Primitive Distal Foramen Petrolingual Proximal Trigeminal of the carotid the petroclival maxillary dural PCoA ICA bifurcation lacerum ligament dural ring artery canal fissure artery ring Perlmutter et al. 1976 (Perlmutter and Cervical Petrous Cavernous Supraclinoid Rhoton 1976) Lasjaunias et al. 1984 (Lasjaunias and Vertical Horizontal Cervical Petrous Clinoid Cisternal Santoyo-Vazquez Cavernous Cavernous 1984) Bouthillier et al. 1996 (Bouthillier, van C1 C2 C3 C4 C5 C6 C7 Loveren, and Keller 1996) Ziyal et al. 2005 (Ziyal Cervical Petrous Cavernous Clinoid Cisternal et al. 2005) Labib et al. 2014 Parapharyngeal Petrous Paraclival Parasellar Paraclinoid Intradural (Labib et al. 2014)

Vascular Anatomy of the Cranial Anterior Circulation 25

Table 2. Collateral Branches of The ICA Segments and Vascular Supply

ICA segment Collateral Branches Vascular Supply C1 Cervical C2 Petrous Caroticotympanic artery Tympanic cavity Upper part of the pharynx and the C3 Lacerum Vidian artery (45% of cases) auditory tube CN III and IV, roof of cavernous sinus, Medial tentorial artery medial third of tentorium, and posterior (Bernasconi-Cassinari) attachment of the falx cerebri Lateral tentorial artery Lateral third of tentorium CN VI into Dorello’s canal, dura of Meningohypophyseal Dorsal meningeal artery dorsum sellae trunk Inferior hypophyseal Pituitary gland artery Dura over posterior clinoid, dorsum Medial clival artery sellae, and medial wall of cavernous C4 Cavernous sinus CNs III and IV, roof of cavernous sinus, Superior division medial third of tentorium, and posterior attachment of the falx cerebri CNs III, IV, VI and cavernous sinus dura Inferolateral trunk Anterior division around superior orbital fissure, V2, dura around foramen rotundum V1, V3, CN VII and dura around Posterior division gasserian ganglion Capsular arteries Dura of sellar floor C5 Clinoid Central retinal artery Inner retinal layers Lacrimal artery Lacrimal gland, eyelids and conjunctiva Posterior ciliary arteries Posterior uveal tract Muscular branches Extraocular muscles Supraorbital artery Muscles and skin of the forehead Ophthalmic artery Anterior and middle ethmoidal sinuses; Anterior Ethmoidal artery dura of the anterior cranial fossa C6 Ophthalmic Posterior ethmoidal sinuses; dura of the Posterior Ethmoidal artery anterior cranial fossa Medial palpebral arteries Eyelid Superior hypophyseal arteries (n. 4 on average). The largest of the branches is often referred to as Infundibulum of the pituitary gland, the superior hypophyseal artery (Gibo, Lenkey, and optic nerve, chiasm, floor of the third Rhoton 1981; Tubbs et al. 2007; Fujii, Lenkey, and ventricle Rhoton 1980) Perforating arteries (n. 4- 16, inconstant) (Rhoton Posterior 2002b; Rosner et al. 1984) Contribution to the posterior limb of the Communicating Premammillary artery internal capsule artery (anterior thalamoperforating artery) C7 Choroid plexus of the lateral ventricle Communicating and third ventricle; optic chiasm and Anterior Choroidal artery (Frigeri et al. 2014; optic tract; posterior limb of the internal Rhoton, Fujii, and Fradd 1979; Tubbs et al. 2010; capsule; lateral geniculate body; globus Wen et al. 1999; Fujii, Lenkey, and Rhoton 1980) pallidus; tail of the caudate nucleus; hippocampus; amygdala; substantia nigra; red nucleus; crus cerebri CN: cranial nerve.

26 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

Table 2 describes the collateral branches arising from the different ICA segments according to the Bouthillier classification (Bouthillier, van Loveren, and Keller 1996) (Table 2).

2. ANTERIOR CEREBRAL ARTERY

The anterior cerebral artery (ACA) is the smallest branch of the ICA bifurcation. Like the middle cerebral artery (MCA), the ACA originates below the anterior perforated substance then courses medially to pass above the chiasm or optic nerve and below the lateral olfactory stria to reach the basal aspect of the interhemispheric fissure where it joins the anterior communicating artery (ACoA). From this point, the ACA turns abruptly upward within the interhemispheric fissure until the subcallosal area where it courses inside the callosal sulcus following the profile of the rostrum, genu, body and splenium of the corpus callosum until it joins the distal posterior cerebral artery (PCA); the ACA and PCA are widely anastomosed above the splenium of the corpus callosum. The average ACA length and diameter at the origin are 12.7 mm and 2.5 mm, respectively (Perlmutter and Rhoton 1976; Rhoton 2002b). However, the two ACAs are seldom equal in length and diameter. In case of hypoplastic ACA, the ACoA is of larger diameter to compensate. The ACA is classically divided into five segments, from A1 to A5. The ACoA marks the limit between the A1 and A2 segments. If an A1 segment is shorter than the contralateral one, an unavoidable twist of the ACoA occurs on the axial plane, this being the main reason why the ACoA is often better seen on oblique angiographic projections. All together, the A2 to A5 segments are also referred to as the pericallosal artery because of the intimate relationship existing between the distal ACA and the corpus callosum (Figure 1 B-I). With the exception of its posterior portion, the pericallosal artery is located below the free margin of the falx, this aspect being paramount for orientation during surgery of pericallosal artery aneurysms. Within the interhemispheric fissure, the left pericallosal artery courses above the right one in most cases (Perlmutter and Rhoton 1978). During its complex course, the ACA gives rise to a series of medial lenticulostriate arteries, the most medial one of which is also known as the recurrent artery of Heubner (Perlmutter and Rhoton 1976; Rosner et al. 1984), as well as eight cortical branches by means of which, apart from the caudate nucleus and the anterior limb of the internal capsule, the ACA vascularizes the medial part of the orbital gyri, gyrus rectus, olfactory bulb and tract, superior frontal gyrus, and the superior parts of the precentral, central, and postcentral gyri (Perlmutter and Rhoton 1976, 1978; Rhoton 2002b). The strip of lateral cortex vascularized by the ACA is wider anteriorly and narrower progressively posteriorly. Not infrequently, the ACA ends in the callosomarginal artery, the largest branch from the A3 segment running inside the cingulate sulcus, which is related to the cingulate gyrus (Perlmutter and Rhoton 1978). This pattern is responsible for the angiographic “bull nose” appearance of the ACA (Osborn 1999). Table 3 presents a detailed description of the ACA segments, along with their limits, collateral branches, and vascular supply (Table 3).

Vascular Anatomy of the Cranial Anterior Circulation 27

Table 3. Segments, Collateral and Terminal Branches, And Vascular Supply of The Anterior Cerebral Artery

Distal Collateral and Anterior Cerebral Artery Segment Anatomical Vascular Supply Terminal Branches Border Medial lenticulostriate Proximal A1 Anterior arteries (n. 8 on Caudate nucleus; anterior (precommunicating) (precommunicating, Communicating average (Rosner et al. limb of the internal capsule (Rhoton 2002b) or horizontal) artery 1984)) Recurrent artery of Heubner* (Perlmutter Internal capsule and Rhoton 1976; Callosomarginal Rosner et al. 1984) A2 (infracallosal) artery Inferomedial surface of the Orbitofrontal artery frontal lobe; gyrus rectus Frontopolar artery Frontal pole Anterior third Distal (post of the mesial communicating) AIFA aspect of the (Rhoton 2002b) superior frontal gyrus Middle third Calloso Medial of the mesial A3 (pericallosal) Paracentral artery marginal frontal MIFA aspect of the artery arteries superior frontal gyrus Posterior third of the mesial PIFA aspect of the superior frontal gyrus Inferior parietal Cingulate Paracentral A4 (pericallosal) Paracentral artery artery branches lobule Superior half of the Anastomosis with Superior parietal artery precuneus A5 (postcallosal) posterior cerebral Superior half of the artery branches Inferior parietal artery precuneus *The recurrent artery may arise from A1, A2, or the A1-A2 junction (Perlmutter and Rhoton 1976; Rosner et al. 1984); AIFA: anterior internal frontal artery; MIFA: middle internal frontal artery; PIFA: posterior internal frontal artery.

3. MIDDLE CEREBRAL ARTERY

Like the ACA, the MCA arises from the ICA below the anterior perforated substance and courses laterally behind the sphenoid ridge to reach the limen insula where it turns abruptly upward making a genu that is very well defined on an anterior-posterior angiographic view (Figure 1 A-E). The MCA has a bifurcation (78%), trifurcation (12%), or rarely, a quadrifurcation (10%) point located proximal to the genu of the M1 segment in more than 90% of cases (Rhoton 2002b; Gibo et al. 1981). Bifurcation further divides the M1 segment into prebifurcation and postbifurcation segments, the latter of which has a superior and inferior trunk. Arteries arising from the prebifurcation segment other than perforating arteries are generally cortical and called early branches. Regarding size of the postbifurcation segment 28 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al. trunks, equal size, inferior trunk dominant, and superior trunk dominant has been reported in 18%, 32%, and 28% of hemispheres, respectively (Rhoton 2002b; Gibo et al. 1981). Nearly half of MCAs send early branches directed to the temporal lobe in more than 90% of cases (Gibo et al. 1981). Uncal and temporopolar arteries, and the anterior temporal artery, which is an important landmark for orientation during surgery of MCA aneurysms, are examples of early cortical branches (Lawton 2011). Ascending along the insular cortex, the MCA trunks reach the circular sulcus of the insula and the operculum of the frontal, temporal, and parietal lobes before supplying a wide cortical area consisting of most of the lateral surface and some of the basal surface of the hemisphere. Classically, the cortex supplied by the MCA is divided into 12 areas: orbitofrontal, prefrontal, precentral, central, anterior parietal, posterior parietal, angular, temporo-occipital, posterior temporal, middle temporal, anterior temporal, and temporopolar (Rhoton 2002b; Gibo et al. 1981). This scheme follows a clockwise order around the sylvian fissure starting at 8 o’clock. Each cortical area is generally supplied by a single stem artery. The posterior temporal stem artery supplying the angular gyrus is called the angular artery; this particular artery always has a diameter 1.4 mm, the critical size required for long-term bypass patency, and is widely used as the recipient vessel in most cerebral vascular bypasses to the MCA (Chater et al. 1976). Table 3 describes the segments of the MCA as well as their limits, collateral branches, and vascular supply (Table 4).

Table 4. Segments, Collateral and Terminal Branches, And Vascular Supply of The Middle Cerebral Artery

Middle Distal Cerebral Artery Anatomical Collateral and Terminal Branches Vascular Supply Segment Border Lateral lenticulostriate Caudate, putamen, globus arteries (n. 10 on pallidus, superior half of the average (Gibo et al. internal capsule, and corona 1981; Rosner et al. Superior surface radiata 1984)) Insular arteries (n. 1-6 in 55% (Ture et al. Limen insulae M1 Limen insula 2000)) (sphenoidal)* Uncal arteries Uncal region Polar and anterolateral Temporopolar arteries portions of the temporal Inferior surface lobe Anterior third of the Anterior temporal artery superior, middle, and inferior temporal gyri Superior Insular arteries (n. >10 Insular cortex, extreme branches 90% (Ture et al. 2000)) capsule Orbitofrontal artery (origin from M1 is rare. In most cases, it arises Inferomedial surface of the Superior from the A2 segment of frontal lobe; gyrus rectus Circular sulcus of and M2 (insular)* the anterior cerebral the insula inferior Anterior artery) trunk** branches Operculofrontal artery Frontal opercular area Superior part of the precentral gyrus and the Central sulcus artery inferior one-half of the postcentral gyrus Vascular Anatomy of the Cranial Anterior Circulation 29

Middle Distal Cerebral Artery Anatomical Collateral and Terminal Branches Vascular Supply Segment Border Posterior part of the Posterior superior and inferior parietal Posterior parietal artery branches lobules; supramarginal gyrus Angular gyrus, supramarginal gyrus, Angular artery posterior superior temporal gyrus, parietooccipital

sulcus Middle and posterior third Posterior temporal of the superior, middle and artery inferior temporal gyri Cortical surface of Superior or inferior M3 (opercular) Insular arteries (n. 1-2 in 25% (Ture et al. 2000)) the sylvian fissure periinsular sulcus MCA territory: 12 areas, namely, orbitofrontal, prefrontal, precentral, central, anterior parietal, Terminal posterior parietal, angular, M4 (cortical) territories on the Cortical branches temporo-occipital, posterior lateral convexity temporal, middle temporal, anterior temporal, and temporopolar (Rhoton 2002b; Gibo et al. 1981) *The middle cerebral artery bifurcation into superior and inferior trunks may located be at M1, M2, or the M1-M2 junction. A trifurcation, with superior, middle, and inferior trunks, is present in approximately 30% of cases, whereas a quadrifurcation is rare; ** Superior and inferior trunks are seldom symmetrical and equal in size; MCA: middle cerebral artery.

4. ANTERIOR COMMUNICATING ARTERY

The ACoA establishes the vascular connection between the left and right ICA systems in the midline; crossing blood flow is perfectly balanced in cases of equally sized A1 segments. On par with the ICAs, PCoAs and A1 segments of the ACA, the ACoA contributes to form the anterior part of the polygon of Willis (Figure 1 C). Mean ACoA diameter and length are 1.5 mm and 4 mm, respectively (Perlmutter and Rhoton 1976). Larger ACoAs are generally associated with significant diameter differences between left and right A1s. The ACoA gives rise to three important groups of perforating arteries: the subcallosal, hypothalamic, and chiasmatic (Serizawa, Saeki, and Yamaura 1997). Within the anterior circulation, the ACoA is among the sites having a high frequency of anatomical variation. Serizawa and colleagues reported the main types and relative frequency of these variations as follows: plexiform (33%), dimple (33%), fenestration (21%), duplication (18%), string (18%), fusion (12%), median artery of the corpus callosum (6%), and azygous anterior cerebral artery (3%) (Serizawa, Saeki, and Yamaura 1997). Despite its small average length and diameter, the ACoA has considerable importance from a functional standpoint in pathologic conditions because it allows blood flow to the contralateral hemisphere in cases of ICA occlusion. The balloon test occlusion routinely performed in clinical practice for ICA aneurysms and various occlusive ICA pathologies is aimed to assess the functional role of the ACoA, which may vary case-by-case. The origin of the ACoA is a common site of aneurysms. 30 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

5. PERFORATING ARTERIES

Perforating arteries of the anterior circulation supply the striatum, thalamus, and basal ganglia. They also serve as feeders in deep-seated arteriovenous malformations. During clipping or endovascular embolization of aneurysms, preservation of the perforating arteries is fundamental. Perforating arteries related to the anterior circulation arise from the ICA, PCoA, ACA, MCA, and ACoA.

Figure 2. (A) Circle of Willis; (C-E) Origin and course of the middle cerebral artery within the Sylvian fissure; (F) Lateral lenticulostriate perforating arteries arising from the M1 segment of the middle cerebral artery supply the internal capsule and basal ganglia. A1, A2, A3, A4, and A5: segments of the anterior cerebral artery; ACoA: anterior communicating artery; AIFA: anterior inferior frontal artery; Ant. perf.: anterior perforated substance; R, G, B, S: rostrum, genu, body and splenium of the corpus callosum; BA: basilar artery; Cma: callosomarginal artery; Dist. ACA: distal anterior cerebral artery; F1: superior frontal gyrus; Fronto-polar: fronto-polar artery; ICA: internal carotid artery; MIFA: middle inferior frontal artery; Orb fr: orbitofrontal artery; P1, P2: segments of the posterior cerebral artery; PCoA: posterior communicating artery; PIFA: posterior inferior frontal artery; Rec. A: recurrent artery of Heubner; MCA: middle cerebral artery; M2 f: M2 frontal trunk; M2 t: M2 temporal trunk; PCA: posterior cerebral artery; SCA: superior cerebellar artery.

The lateral lenticulostriate arteries arise in all cases from the entire prebifurcation M1 segment of the MCA and also from the postbifurcation segment in half of cases (Rhoton 2002b; Gibo et al. 1981). In more than 70% of cases, the lenticulostriate arteries are located less than 5 mm from the bifurcation. The M2 segment rarely has perforating arteries (Rosner et al. 1984) (Figure 2 F). The earlier the bifurcation, the greater the number of postbifurcation branches, and vice versa. No branches arise from the postbifurcation segment if the bifurcation point is located more than 2.5 cm from the origin of the MCA (Rhoton 2002b; Gibo et al. 1981). This data is important for the assessment of the risk of perforating artery occlusion during surgery for MCA bifurcation aneurysms. Table 4 summarizes the main groups and the vascular supply of the perforating arteries of the anterior circulation, according to their origin from the parent artery (Table 5).

Vascular Anatomy of the Cranial Anterior Circulation 31

Table 5. Perforating Arteries of The Anterior Circulation

Parent Perforating Arteries Vascular Supply Vessel Superior hypophyseal arteries (n. 4 an average). The largest of the branches is Infundibulum of the pituitary gland, often referred to as the superior C6 Ophthalmic optic nerve, chiasm, floor of the third hypophyseal artery (Gibo, Lenkey, and ventricle Rhoton 1981; Tubbs et al. 2007; Fujii, Lenkey, and Rhoton 1980) Perforating arteries (n. 4-16, inconstant) (Rhoton 2002b) Contribution to the posterior limb of the C7 Communicating PCoA Premammillary artery (anterior internal capsule ICA thalamoperforating artery) Choroidal branches (n. 4, range 1–9) (Rosner et al. 1984; Rhoton 2002b) (from the choroidal C4 segment according to the Perlmutter Anterior perforated substance classification (Perlmutter and Rhoton 1976)) Posterior limb of the internal capsule; AChA (n. 9 branches on average) (Frigeri et al. 2014; Rhoton, lateral geniculate body; globus pallidus; Fujii, and Fradd 1979; Tubbs et al. 2010; Wen et al. 1999; Fujii, tail of the caudate nucleus; Lenkey, and Rhoton 1980) hippocampus; amygdala; substantia nigra; red nucleus; crus cerebri A1 (precommunicating Medial lenticulostriate arteries Caudate nucleus; anterior limb of the or horizontal) (n. 8 on average (Rosner et al. 1984)) internal capsule ACA Recurrent artery of Heubner* A2 (infracallosal) (Perlmutter and Rhoton 1976; Rosner et Internal capsule al. 1984) Lateral lenticulostriate arteries (n. 10 on Caudate, putamen, globus pallidus, MCA M1 (sphenoidal) average (Gibo et al. 1981; Rosner et al. superior half of the internal capsule, and 1984)) corona radiata Subcallosal (Serizawa, Saeki, and Yamaura 1997) Subcallosal area, septal nuclei ACoA Hypothalamic (Serizawa, Saeki, and Yamaura 1997) Hypothalamus Chiasmatic (Serizawa, Saeki, and Yamaura 1997) Optic chiasm ICA: internal carotid artery; ACA: anterior cerebral artery; MCA: middle cerebral artery; ACoA: anterior communicating artery; AChA: anterior choroidal artery.

6. EXTERNAL CAROTID ARTERY

The ECA is a branch of the common carotid artery. It provides the vascular supply for much of the face, head, and neck and most of the meninges. It has a role in several vascular pathological conditions, including arteriovenous fistulas and arteriovenous malformations. Most cerebral vascular bypasses are extracranial to intracranial and involve branches from the ECA. Table 4 reports the main branches of the ECA and their vascular supply (Table 6).

7. VEINS

The complex venous system of the head and neck is a tributary of the internal and external jugular veins. The internal jugular venous system involves the cerebral and facial system; the former is further composed of superficial and deep venous systems that drain into the dural sinuses. Table 6 describes the general arrangement of the head and neck venous system (Table 7).

Table 6. Collateral and Terminal Branches, And Vascular Supply of the External Carotid Artery

Collateral and Terminal Branches Vascular Supply Infrahyoid branch Muscles attached onto the hyoid bone Sternocleidomastoid branch Sternocleidomastoid muscle Superior thyroid artery Superior laryngeal artery Muscles, mucous membrane, and glands of the larynx Cricothyroid artery Larynx Superior branches Pharyngeal trunk Middle branches Pharyngeal submucosal spaces Inferior pharyngeal branches Ascending pharyngeal artery Hypoglossal branch Meninges of the posterior fossa; CN XII (Lasjaunias and Moret 1976; Hacein- Meninges of the posterior fossa and jugular foramen; Bey et al. 2002; Cavalcanti et al. Jugular branch CN IX, X, and XI 2009; Martins et al. 2005) Neuromeningeal trunk Caroticotympanic branch of the internal carotid artery; Inferior tympanic branch CN XI Musculospinal artery CN XI; superior sympathetic ganglion Deep lingual artery Lingual artery Genioglossus muscle Sublingual artery Ascending palatine artery Tonsillar branch Cervical Submental artery Glandular branches Facial artery Mimic muscles Inferior labial artery Superior labial artery Facial Lateral nasal branch Angular artery Digastric, stylohyoid, splenius, and longus capitis Muscular branches muscles Occipital artery Sternocleidomastoid branch Sternocleidomastoid muscles (Lasjaunias, Theron, and Moret Auricular branch Skin of the back of the ear; mastoid air cells 1978; Martins et al. 2005) Meningeal branch Meninges of the posterior fossa Trapezius muscle Descending branches

Collateral and Terminal Branches Vascular Supply Posterior auricular artery(Martins et Stylomastoid artery Tympanic cavity, the tympanic antrum and mastoid al. 2005) cells, and the semicircular canals; CN VII Maxillary artery* Mandibular segment Deep auricular artery Tympanic membrane Anterior tympanic artery Middle ear Middle meningeal artery Meninges of the middle fossa Inferior alveolar artery Pulp of the teeth; chin; mylohyoid muscle Accessory meningeal artery Meninges of the middle fossa Pterygoid segment Masseteric artery Masseter muscle Pterygoid branches Lateral and medial pterygoid muscle Deep temporal arteries Temporalis muscle; periosteum of the temporal fossa Buccal artery Cheek; buccinator muscle Pterygomaxillary segment Sphenopalatine artery Mucosa of the nasal cavity Descending palatine artery Mucosa of hard and soft palate Collateral and Terminal Branches Vascular Supply Infraorbital artery Inferior rectus and inferior oblique muscles; Mucosa of the maxillary sinus Posterior superior alveolar artery Molar and premolar teeth; mucosa of the alveolar process of the maxilla Artery of the pterygoid canal Upper part of the pharynx; auditory tube Pharyngeal branch Middle and lower pharynx Alveolar arteries Mucosa of the alveolar process of the maxilla Superficial temporal artery* Frontal branch Pericranium, skin and muscles of the forehead Parietal branch Superficial layer of the temporalis fascia; skin of the parietal region CN: cranial nerve; *Maxillary and superficial temporal are considered terminal branches of the external carotid artery.

Table 7. General Arrangement of The Head and Neck Venous System

External Jugular Vein System Superficial temporal (anterior auricular) Retromandibular Maxillary (pterygoid plexus) Posterior auricular External jugular vein Transverse cervical Suprascapular Anterior jugular Internal Jugular Vein System Superior ophthalmic vein Cavernous Superior Dural sinus petrosal sinuses Inferior ophthalmic vein (anterior sinus Basilar Breschet's veins Superficial Middle cerebral and Spheno Inferior plexus (Extradural neural axis compartment)(Parkinson 2000) vein (superficial Sylvian vein) posterior parietal petrosal deep middle cerebral vein cavernous sinus sinus Superficial (deep Sylvian vein) sinuses) Cerebral Venous Superior cerebral veins system system Middle cerebral veins Superior sagittal Trolard vein (superior anastomotic) Transverse Sigmoid Jugular sinus Labbé vein (inferior anastomotic) sinus sinus bulb Internal Torcular Inferior cerebral veins jugular Herophili Superior thalamostriate vein Internal cerebral vein Deep Septal vein vein Vein of Straight Venous Occipital Basal vein of Rosenthal Galen sinus Marginal sinus system sinus Inferior sagittal sinus Deep Facial vein Inferior Labial vein Superior Labial vein Facial vein Angular vein Facial Supraorbital vein system Frontal vein Middle thyroid vein Superior thyroid vein Pharyngeal veins Lingual veins

Vascular Anatomy of the Cranial Anterior Circulation 35

DISCUSSION

Thorough knowledge of the vascular anatomy of the head and neck is a condictio sine qua non to deal with all neurovascular pathologies. Among these, aneurysms and arteriovenous malformations and fistulas hold the greatest interest for neurosurgeons and interventional neuroradiologists (Ciappetta, Luzzi, et al. 2009; Ciappetta, Occhiogrosso, et al. 2009; De Tommasi, De Tommasi, et al. 2006; Del Maestro et al. 2018; Gallieni et al. 2018; S. Luzzi, Del Maestro, et al. 2018; S. Luzzi, Del Maestro, and Galzio 2019; S. Luzzi, Elia, Del Maestro, Morotti, et al. 2019; S. Luzzi, Gallieni, et al. 2018; Ricci et al. 2017; S. Luzzi et al. 2020). Identification of the segments of the ICA, ACA, and MCA is achieved by means of specific landmarks and necessary to plan surgical approaches. For example, paraclinoid and carotid cave aneurysms are considered challenging because of the need for anterior clinoidectomy, opening of the distal dural ring and, therefore, a transcavernous approach. An endoscopic route has also recently been reported for these aneurysms, which are located between the proximal and distal dural ring (Gardner et al. 2015; Szentirmai et al. 2016). Their precise localization on angiography is obviously essential in the choice of approach, which in the future may become primarily endoscopic, on par with other pathologies (Arnaout et al. 2019; S. Luzzi, Del Maestro, Elia, et al. 2019; S. Luzzi, Del Maestro, Trovarelli, et al. 2019; S. Luzzi, Zoia, et al. 2019; Zoia et al. 2019). Despite the tremendous recent advances in all fields of neurosurgery (Bellantoni et al. 2019; Cheng, Shetty, and Sekhar 2018; De Tommasi et al. 2008; De Tommasi et al. 2007; Guastamacchia et al. 2007; Sabino Luzzi, Crovace, et al. 2019; S. Luzzi, Crovace, et al. 2018; S. Luzzi, Elia, Del Maestro, Elbabaa, et al. 2019; S. Luzzi, Giotta Lucifero, et al. 2019; Palumbo et al. 2019; Palumbo et al. 2018; Raysi Dehcordi et al. 2017; Spena et al. 2019; Zoia et al. 2018; Bongetta et al. 2019; Ciappetta et al. 2008; De Tommasi, Cascardi, et al. 2006; Millimaggi et al. 2018; Antonosante et al. 2020; Campanella et al. 2020; Zoia et al. 2020; Elsawaf et al. 2020), thorough knowledge of brain and vascular anatomy retains a primary role in the treatment of all central nervous system pathology and is essential for the endovascular treatment of neurovascular disease.

CONCLUSION

The internal and external carotid arteries provide arterial vascularization of the anterior circulation of the head and neck. They are widely anastomosed at different sites. The ACoA is the main physiologic functional anastomosis between the left and right ICA systems. The anterior cerebral circulation involves a large number of perforating arteries arising from the ICA, PCoA, AChA, ACA, ACoA, and MCA that provide vascular supply to the striatum, thalamus, and basal ganglia. The ECA supplies the soft tissues of the face, head and neck, and also the meninges. Venous outflow of the head is primarily a tributary of the internal jugular vein and composed of superficial and deep venous systems, both draining into the dural sinuses.

36 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

REFERENCES

Al-Rafiah, A., E. L-Haggagy AA, I. H. Aal, and A. I. Zaki. 2011. "Anatomical study of the carotid bifurcation and origin variations of the ascending pharyngeal and superior thyroid arteries." Folia Morphol (Warsz) 70 (1): 47-55. https://www.ncbi.nlm.nih.gov/pubmed/ 21604253. Antonosante, A., L. Brandolini, M. d'Angelo, E. Benedetti, V. Castelli, M. D. Maestro, S. Luzzi, A. Giordano, A. Cimini, and M. Allegretti. 2020. "Autocrine CXCL8-dependent invasiveness triggers modulation of actin cytoskeletal network and cell dynamics." Aging (Albany NY) 12 (2): 1928-1951. https://doi.org/10.18632/aging.102733. https://www.ncbi. nlm.nih.gov/pubmed/31986121. Arnaout, M. M., S. Luzzi, R. Galzio, and K. Aziz. 2019. "Supraorbital keyhole approach: Pure endoscopic and endoscope-assisted perspective." Clin Neurol Neurosurg 189: 105623. https://doi.org/10.1016/j.clineuro.2019.105623. https://www.ncbi.nlm.nih.gov/pubmed/ 31805490. Bellantoni, G., F. Guerrini, M. Del Maestro, R. Galzio, and S. Luzzi. 2019. "Simple schwannomatosis or an incomplete Coffin-Siris? Report of a particular case." e Neurological Sci 14: 31-33. https://doi.org/10.1016/j.ensci.2018.11.021. https://www.ncbi. nlm.nih.gov/pubmed/30555950. Bongetta, D., C. Zoia, S. Luzzi, M. D. Maestro, A. Peri, G. Bichisao, D. Sportiello, I. Canavero, A. Pietrabissa, and R. J. Galzio. 2019. "Neurosurgical issues of bariatric surgery: A systematic review of the literature and principles of diagnosis and treatment." Clin Neurol Neurosurg 176: 34-40. https://doi.org/10.1016/j.clineuro.2018.11.009. https://www.ncbi. nlm.nih.gov/pubmed/30500756. Bouthillier, A., H. R. van Loveren, and J. T. Keller. 1996. "Segments of the internal carotid artery: a new classification." Neurosurgery 38 (3): 425-32; discussion 432- 3. https://doi.org/10.1097/00006123-199603000-00001. https://www.ncbi.nlm.nih.gov/ pubmed/8837792. Campanella, R., L. Guarnaccia, C. Cordiglieri, E. Trombetta, M. Caroli, G. Carrabba, N. La Verde, P. Rampini, C. Gaudino, A. Costa, S. Luzzi, G. Mantovani, M. Locatelli, L. Riboni, S. E. Navone, and G. Marfia. 2020. "Tumor-Educated Platelets and Angiogenesis in Glioblastoma: Another Brick in the Wall for Novel Prognostic and Targetable Biomarkers, Changing the Vision from a Localized Tumor to a Systemic Pathology." Cells 9 (2). https://doi.org/10.3390/cells9020294. https://www.ncbi.nlm.nih.gov/pubmed/31991805. Cavalcanti, D. D., C. V. Reis, R. Hanel, S. Safavi-Abbasi, P. Deshmukh, R. F. Spetzler, and M. C. Preul. 2009. "The ascending pharyngeal artery and its relevance for neurosurgical and endovascular procedures." Neurosurgery 65 (6 Suppl): 114-20; discussion 120. https://doi.org/10.1227/01.NEU.0000339172.78949.5B. https://www.ncbi.nlm.nih.gov/ pubmed/19934985. Chater, N., R. Spetzler, K. Tonnemacher, and C. B. Wilson. 1976. "Microvascular bypass surgery. Part 1: anatomical studies." J Neurosurg 44 (6): 712-4. https://doi.org/ 10.3171/jns.1976.44.6.0712. https://www.ncbi.nlm.nih.gov/pubmed/1271091. Cheng, C. Y., R. Shetty, and L. N. Sekhar. 2018. "Microsurgical Resection of a Large Intraventricular Trigonal Tumor: 3-Dimensional Operative Video." Oper Neurosurg Vascular Anatomy of the Cranial Anterior Circulation 37

(Hagerstown) 15 (6): E92-E93. https://doi.org/10.1093/ons/opy068. https://www.ncbi. nlm.nih.gov/pubmed/29618124. Ciappetta, P., I. D'Urso P, S. Luzzi, G. Ingravallo, A. Cimmino, and L. Resta. 2008. "Cystic dilation of the ventriculus terminalis in adults." J Neurosurg Spine 8 (1): 92-9. https://doi.org/10.3171/SPI-08/01/092. https://www.ncbi.nlm.nih.gov/pubmed/18173354. Ciappetta, P., S. Luzzi, R. De Blasi, and P. I. D'Urso. 2009. "Extracranial aneurysms of the posterior inferior cerebellar artery. Literature review and report of a new case." J Neurosurg Sci 53 (4): 147-51. https://www.ncbi.nlm.nih.gov/pubmed/20220739. Ciappetta, P., G. Occhiogrosso, S. Luzzi, P. I. D'Urso, and A. P. Garribba. 2009. "Jugular tubercle and vertebral artery/posterior inferior cerebellar artery anatomic relationship: a 3- dimensional angiography computed tomography anthropometric study." Neurosurgery 64 (5 Suppl 2): 429-36; discussion 436. https://doi.org/10.1227/01.NEU.0000337573. 17073.9F. https://www.ncbi.nlm.nih.gov/pubmed/19404121. De Tommasi, A., P. Cascardi, C. De Tommasi, S. Luzzi, and P. Ciappetta. 2006. "Emergency surgery in a severe penetrating skull base injury by a screwdriver: case report and literature review." World J Emerg Surg 1: 36. https://doi.org/10.1186/1749-7922-1-36. https://www. ncbi.nlm.nih.gov/pubmed/17169147. De Tommasi, A., C. De Tommasi, E. Lauta, S. Luzzi, A. Cimmino, and P. Ciappetta. 2006. "Pre-operative subarachnoid haemorrhage in a patient with spinal tumour." Cephalalgia 26 (7): 887-90. https://doi.org/10.1111/j.1468-2982.2006.01122.x. https://www.ncbi.nlm. nih.gov/pubmed/16776708. De Tommasi, A., S. Luzzi, P. I. D'Urso, C. De Tommasi, N. Resta, and P. Ciappetta. 2008. "Molecular genetic analysis in a case of ganglioglioma: identification of a new mutation." Neurosurgery 63 (5): 976-80; discussion 980. https://doi.org/10.1227/01.NEU. 0000327699.93146.CD. https://www.ncbi.nlm.nih.gov/pubmed/19005389. De Tommasi, A., G. Occhiogrosso, C. De Tommasi, S. Luzzi, A. Cimmino, and P. Ciappetta. 2007. "A polycystic variant of a primary intracranial leptomeningeal astrocytoma: case report and literature review." World J Surg Oncol 5: 72. https://doi.org/10.1186/1477- 7819-5-72. https://www.ncbi.nlm.nih.gov/pubmed/17587463. Del Maestro, M., S. Luzzi, M. Gallieni, D. Trovarelli, A. V. Giordano, M. Gallucci, A. Ricci, and R. Galzio. 2018. "Surgical Treatment of Arteriovenous Malformations: Role of Preoperative Staged Embolization." Acta Neurochir Suppl 129: 109-113. https://doi.org/ 10.1007/978-3-319-73739-3_16. https://www.ncbi.nlm.nih.gov/pubmed/30171322. Elsawaf, Y., S. Anetsberger, S. Luzzi, and S. K. Elbabaa. 2020. "Early Decompressive Craniectomy as Management for Severe TBI in the Pediatric Population: A Comprehensive Literature Review." World Neurosurg. https://doi.org/10.1016/j.wneu.2020.02.065. https://www.ncbi.nlm.nih.gov/pubmed/32084616. Frigeri, T., A. Rhoton, E. Paglioli, and N. Azambuja. 2014. "Cortical projection of the inferior choroidal point as a reliable landmark to place the corticectomy and reach the temporal horn through a middle temporal gyrus approach." Arq Neuropsiquiatr 72 (10): 777- 81. https://doi.org/10.1590/0004-282x20140165. https://www.ncbi.nlm.nih.gov/pubmed/ 25337730. Fujii, K., C. Lenkey, and A. L. Rhoton, Jr. 1980. "Microsurgical anatomy of the choroidal arteries: lateral and third ventricles." J Neurosurg 52 (2): 165-88. https://doi.org/ 10.3171/jns.1980.52.2.0165. https://www.ncbi.nlm.nih.gov/pubmed/7351556. 38 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

Gallieni, M., M. Del Maestro, S. Luzzi, D. Trovarelli, A. Ricci, and R. Galzio. 2018. "Endoscope-Assisted Microneurosurgery for Intracranial Aneurysms: Operative Technique, Reliability, and Feasibility Based on 14 Years of Personal Experience." Acta Neurochir Suppl 129: 19-24. https://doi.org/10.1007/978-3-319-73739-3_3. https://www. ncbi.nlm.nih.gov/pubmed/30171309. Gardner, P. A., F. Vaz-Guimaraes, B. Jankowitz, M. Koutourousiou, J. C. Fernandez-Miranda, E. W. Wang, and C. H. Snyderman. 2015. "Endoscopic Endonasal Clipping of Intracranial Aneurysms: Surgical Technique and Results." World Neurosurg 84 (5): 1380- 93. https://doi.org/10.1016/j.wneu.2015.06.032. https://www.ncbi.nlm.nih.gov/pubmed/ 26117084. Gibo, H., C. C. Carver, A. L. Rhoton, Jr., C. Lenkey, and R. J. Mitchell. 1981. "Microsurgical anatomy of the middle cerebral artery." J Neurosurg 54 (2): 151-69. https://doi.org/ 10.3171/jns.1981.54.2.0151. https://www.ncbi.nlm.nih.gov/pubmed/7452329. Gibo, H., C. Lenkey, and A. L. Rhoton, Jr. 1981. "Microsurgical anatomy of the supraclinoid portion of the internal carotid artery." J Neurosurg 55 (4): 560-74. https://doi.org/ 10.3171/jns.1981.55.4.0560. https://www.ncbi.nlm.nih.gov/pubmed/7277004. Guastamacchia, E., V. Triggiani, E. Tafaro, A. De Tommasi, C. De Tommasi, S. Luzzi, C. Sabba, F. Resta, M. R. Terreni, and M. Losa. 2007. "Evolution of a prolactin-secreting pituitary microadenoma into a fatal carcinoma: a case report." Minerva Endocrinol 32 (3): 231-6. https://www.ncbi.nlm.nih.gov/pubmed/17912159. Hacein-Bey, L., D. L. Daniels, J. L. Ulmer, L. P. Mark, M. M. Smith, J. M. Strottmann, D. Brown, G. A. Meyer, and P. A. Wackym. 2002. "The ascending pharyngeal artery: branches, anastomoses, and clinical significance." AJNR Am J Neuroradiol 23 (7): 1246- 56. https://www.ncbi.nlm.nih.gov/pubmed/12169487. Joo, W., T. Funaki, F. Yoshioka, and A. L. Rhoton, Jr. 2012. "Microsurgical anatomy of the carotid cave." Neurosurgery 70 (2 Suppl Operative): 300-11; discussion 311-2. https://doi.org/10.1227/NEU.0b013e3182431767. https://www.ncbi.nlm.nih.gov/pubmed/ 22113241. Labib, M. A., D. M. Prevedello, R. Carrau, E. E. Kerr, C. Naudy, H. Abou Al-Shaar, M. Corsten, and A. Kassam. 2014. "A road map to the internal carotid artery in expanded endoscopic endonasal approaches to the ventral cranial base." Neurosurgery 10 Suppl 3: 448-71; discussion 471. https://doi.org/10.1227/NEU.0000000000000362. https://www. ncbi.nlm.nih.gov/pubmed/24717685. Lasjaunias, P., and J. Moret. 1976. "The ascending pharyngeal artery: normal and pathological radioanatomy." Neuroradiology 11 (2): 77-82. https://doi.org/10.1007/bf00345017. https://www.ncbi.nlm.nih.gov/pubmed/1084963. Lasjaunias, P., and A. Santoyo-Vazquez. 1984. "Segmental agenesis of the internal carotid artery: angiographic aspects with embryological discussion." Anat Clin 6 (2): 133-41. https://doi.org/10.1007/bf01773165. https://www.ncbi.nlm.nih.gov/pubmed/6498000. Lasjaunias, P., J. Theron, and J. Moret. 1978. "The occipital artery. Anatomy--normal arteriographic aspects--embryological significance." Neuroradiology 15 (1): 31-7. https://doi.org/10.1007/bf00327443. https://www.ncbi.nlm.nih.gov/pubmed/643171. Lawton, M.T. 2011. Seven Aneurysms: Tenets and Techniques for Clipping. Thieme. Luzzi, S., A. M. Crovace, L. Lacitignola, V. Valentini, E. Francioso, G. Rossi, G. Invernici, R. J. Galzio, and A. Crovace. 2018. "Engraftment, neuroglial transdifferentiation and Vascular Anatomy of the Cranial Anterior Circulation 39

behavioral recovery after complete spinal cord transection in rats." Surg Neurol Int 9: 19. https://doi.org/10.4103/sni.sni_369_17. https://www.ncbi.nlm.nih.gov/pubmed/29497572. Luzzi, S., M. Del Maestro, D. Bongetta, C. Zoia, A. V. Giordano, D. Trovarelli, S. Raysi Dehcordi, and R. J. Galzio. 2018. "Onyx Embolization Before the Surgical Treatment of Grade III Spetzler-Martin Brain Arteriovenous Malformations: Single-Center Experience and Technical Nuances." World Neurosurg 116: e340-e353. https://doi.org/10.1016/ j.wneu.2018.04.203. https://www.ncbi.nlm.nih.gov/pubmed/29751183. Luzzi, S., M. Del Maestro, S. K. Elbabaa, and R. Galzio. 2020. "Letter to the Editor Regarding "One and Done: Multimodal Treatment of Pediatric Cerebral Arteriovenous Malformations in a Single Anesthesia Event." World Neurosurg 134: 660. https://doi.org/10.1016/j. wneu.2019.09.166. https://www.ncbi.nlm.nih.gov/pubmed/32059273. Luzzi, S., M. Del Maestro, A. Elia, F. Vincitorio, G. Di Perna, F. Zenga, D. Garbossa, S. Elbabaa, and R. Galzio. 2019. "Morphometric and Radiomorphometric Study of the Correlation Between the Foramen Magnum Region and the Anterior and Posterolateral Approaches to Ventral Intradural Lesions." Turk Neurosurg. https://doi.org/10.5137/1019- 5149.JTN.26052-19.2. https://www.ncbi.nlm.nih.gov/pubmed/31452176. Luzzi, S., M. Del Maestro, and R. Galzio. 2019. "Letter to the Editor. Preoperative embolization of brain arteriovenous malformations." J Neurosurg: 1-2. https://doi.org/10.3171/ 2019.6.JNS191541. https://www.ncbi.nlm.nih.gov/pubmed/31812150. https://thejns.org/ view/journals/j-neurosurg/aop/article-10.3171-2019.6.JNS191541/article-10.3171-2019. 6.JNS191541.xml. Luzzi, S., M. Del Maestro, D. Trovarelli, D. De Paulis, S. R. Dechordi, H. Di Vitantonio, V. Di Norcia, D. F. Millimaggi, A. Ricci, and R. J. Galzio. 2019. "Endoscope-Assisted Microneurosurgery for Neurovascular Compression Syndromes: Basic Principles, Methodology, and Technical Notes." Asian J Neurosurg 14 (1): 193-200. https://doi.org/ 10.4103/ajns.AJNS_279_17. https://www.ncbi.nlm.nih.gov/pubmed/30937034. Luzzi, S., A. Elia, M. Del Maestro, S. K. Elbabaa, S. Carnevale, F. Guerrini, M. Caulo, P. Morbini, and R. Galzio. 2019. "Dysembryoplastic Neuroepithelial Tumors: What You Need to Know." World Neurosurg 127: 255-265. https://doi.org/10.1016/j.wneu. 2019.04.056. https://www.ncbi.nlm.nih.gov/pubmed/30981794. Luzzi, S., A. Elia, M. Del Maestro, A. Morotti, S. K. Elbabaa, A. Cavallini, and R. Galzio. 2019. "Indication, Timing, and Surgical Treatment of Spontaneous Intracerebral Hemorrhage: Systematic Review and Proposal of a Management Algorithm." World Neurosurg. https://doi.org/10.1016/j.wneu.2019.01.016. https://www.ncbi.nlm.nih.gov/ pubmed/30677572. Luzzi, S., M. Gallieni, M. Del Maestro, D. Trovarelli, A. Ricci, and R. Galzio. 2018. "Giant and Very Large Intracranial Aneurysms: Surgical Strategies and Special Issues." Acta Neurochir Suppl 129: 25-31. https://doi.org/10.1007/978-3-319-73739-3_4. https://www. ncbi.nlm.nih.gov/pubmed/30171310. Luzzi, S., A. Giotta Lucifero, M. Del Maestro, G. Marfia, S. E. Navone, M. Baldoncini, M. Nunez, A. Campero, S. K. Elbabaa, and R. Galzio. 2019. "Anterolateral Approach for Retrostyloid Superior Parapharyngeal Space Schwannomas Involving the Jugular Foramen Area: A 20-Year Experience." World Neurosurg. https://doi.org/10.1016/j.wneu.2019. 09.006. https://www.ncbi.nlm.nih.gov/pubmed/31520759. Luzzi, S., C. Zoia, A. D. Rampini, A. Elia, M. Del Maestro, S. Carnevale, P. Morbini, and R. Galzio. 2019. "Lateral Transorbital Neuroendoscopic Approach for Intraconal 40 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

Meningioma of the Orbital Apex: Technical Nuances and Literature Review." World Neurosurg 131: 10-17. https://doi.org/10.1016/j.wneu.2019.07.152. https://www.ncbi. nlm.nih.gov/pubmed/31356977. Luzzi, Sabino, Alberto Maria Crovace, Mattia Del Maestro, Alice Giotta Lucifero, Samer K. Elbabaa, Benedetta Cinque, Paola Palumbo, Francesca Lombardi, Annamaria Cimini, Maria Grazia Cifone, Antonio Crovace, and Renato Galzio. 2019. "The cell-based approach in neurosurgery: ongoing trends and future perspectives." Heliyon 5 (11). https://doi.org/10.1016/j.heliyon.2019.e02818. Martins, C., A. Yasuda, A. Campero, A. J. Ulm, N. Tanriover, and A. Rhoton, Jr. 2005. "Microsurgical anatomy of the dural arteries." Neurosurgery 56 (2 Suppl): 211-51; discussion 211-51. https://doi.org/10.1227/01.neu.0000144823.94402.3d. https://www. ncbi.nlm.nih.gov/pubmed/15794820. Millimaggi, D. F., V. D. Norcia, S. Luzzi, T. Alfiero, R. J. Galzio, and A. Ricci. 2018. "Minimally Invasive Transforaminal Lumbar Interbody Fusion with Percutaneous Bilateral Pedicle Screw Fixation for Lumbosacral Spine Degenerative Diseases. A Retrospective Database of 40 Consecutive Cases and Literature Review." Turk Neurosurg 28 (3): 454-461. https://doi.org/10.5137/1019-5149.JTN.19479-16.0. https://www.ncbi. nlm.nih.gov/pubmed/28481388. Osborn, Anne G. 1999. Diagnostic cerebral angiography. Lippincott Williams & Wilkins. Palumbo, P., F. Lombardi, F. R. Augello, I. Giusti, S. Luzzi, V. Dolo, M. G. Cifone, and B. Cinque. 2019. "NOS2 inhibitor 1400W Induces Autophagic Flux and Influences Extracellular Vesicle Profile in Human Glioblastoma U87MG Cell Line." Int J Mol Sci 20 (12). https://doi.org/10.3390/ijms20123010. https://www.ncbi.nlm.nih.gov/pubmed/ 31226744. Palumbo, P., F. Lombardi, G. Siragusa, S. R. Dehcordi, S. Luzzi, A. Cimini, M. G. Cifone, and B. Cinque. 2018. "Involvement of NOS2 Activity on Human Glioma Cell Growth, Clonogenic Potential, and Neurosphere Generation." Int J Mol Sci 19 (9). https://doi.org/10.3390/ijms19092801. https://www.ncbi.nlm.nih.gov/pubmed/30227679. Parkinson, D. 2000. "Extradural neural axis compartment." J Neurosurg 92 (4): 585- 8. https://doi.org/10.3171/jns.2000.92.4.0585. https://www.ncbi.nlm.nih.gov/pubmed/107 61646. Perlmutter, D., and A. L. Rhoton, Jr. 1976. "Microsurgical anatomy of the anterior cerebral- anterior communicating-recurrent artery complex." J Neurosurg 45 (3): 259- 72. https://doi.org/10.3171/jns.1976.45.3.0259. https://www.ncbi.nlm.nih.gov/pubmed/ 948013. ---. 1978. "Microsurgical anatomy of the distal anterior cerebral artery." J Neurosurg 49 (2): 204-28. https://doi.org/10.3171/jns.1978.49.2.0204. https://www.ncbi.nlm.nih.gov/ pubmed/671075. Raysi Dehcordi, S., A. Ricci, H. Di Vitantonio, D. De Paulis, S. Luzzi, P. Palumbo, B. Cinque, D. Tempesta, G. Coletti, G. Cipolloni, M. G. Cifone, and R. Galzio. 2017. "Stemness Marker Detection in the Periphery of Glioblastoma and Ability of Glioblastoma to Generate Glioma Stem Cells: Clinical Correlations." World Neurosurg 105: 895- 905. https://doi.org/10.1016/j.wneu.2017.05.099. https://www.ncbi.nlm.nih.gov/pubmed/ 28559081. Vascular Anatomy of the Cranial Anterior Circulation 41

Rhoton, A. L., Jr. 2002a. "The cavernous sinus, the cavernous venous plexus, and the carotid collar." Neurosurgery 51 (4 Suppl): S375-410. https://www.ncbi.nlm.nih.gov/pubmed/ 12234454. ---. 2002b. "The supratentorial arteries." Neurosurgery 51 (4 Suppl): S53-120. https://www.ncbi.nlm.nih.gov/pubmed/12234447. Rhoton, A. L., Jr., K. Fujii, and B. Fradd. 1979. "Microsurgical anatomy of the anterior choroidal artery." Surg Neurol 12 (2): 171-87. https://www.ncbi.nlm.nih.gov/pubmed/ 515913. Ricci, A., H. Di Vitantonio, D. De Paulis, M. Del Maestro, S. D. Raysi, D. Murrone, S. Luzzi, and R. J. Galzio. 2017. "Cortical aneurysms of the middle cerebral artery: A review of the literature." Surg Neurol Int 8: 117. https://doi.org/10.4103/sni.sni_50_17. https://www. ncbi.nlm.nih.gov/pubmed/28680736. Rosner, S. S., A. L. Rhoton, Jr., M. Ono, and M. Barry. 1984. "Microsurgical anatomy of the anterior perforating arteries." J Neurosurg 61 (3): 468-85. https://doi.org/10.3171/ jns.1984.61.3.0468. https://www.ncbi.nlm.nih.gov/pubmed/6747683. Seoane, E., A. L. Rhoton, Jr., and E. de Oliveira. 1998. "Microsurgical anatomy of the dural collar (carotid collar) and rings around the clinoid segment of the internal carotid artery." Neurosurgery 42 (4): 869-84; discussion 884-6. https://doi.org/10.1097/00006123- 199804000-00108. https://www.ncbi.nlm.nih.gov/pubmed/9574652. Serizawa, T., N. Saeki, and A. Yamaura. 1997. "Microsurgical anatomy and clinical significance of the anterior communicating artery and its perforating branches." Neurosurgery 40 (6): 1211-6; discussion 1216-8. https://doi.org/10.1097/00006123- 199706000-00019. https://www.ncbi.nlm.nih.gov/pubmed/9179894. Spena, G., E. Roca, F. Guerrini, P. P. Panciani, L. Stanzani, A. Salmaggi, S. Luzzi, and M. Fontanella. 2019. "Risk factors for intraoperative stimulation-related seizures during awake surgery: an analysis of 109 consecutive patients." J Neurooncol. https://doi.org/ 10.1007/s11060-019-03295-9. https://www.ncbi.nlm.nih.gov/pubmed/31552589. Szentirmai, O., Y. Hong, L. Mascarenhas, A. A. Salek, P. E. Stieg, V. K. Anand, A. A. Cohen- Gadol, and T. H. Schwartz. 2016. "Endoscopic endonasal clip ligation of cerebral aneurysms: an anatomical feasibility study and future directions." J Neurosurg 124 (2): 463-8. https://doi.org/10.3171/2015.1.JNS142650. https://www.ncbi.nlm.nih.gov/ pubmed/26230466. Tubbs, R. S., A. Hansasuta, M. Loukas, R. G. Louis, Jr., M. M. Shoja, E. G. Salter, and W. J. Oakes. 2007. "Branches of the petrous and cavernous segments of the internal carotid artery." Clin Anat 20 (6): 596-601. https://doi.org/10.1002/ca.20434. https://www.ncbi. nlm.nih.gov/pubmed/17072872. Tubbs, R. S., J. H. Miller, A. A. Cohen-Gadol, and D. D. Spencer. 2010. "Intraoperative anatomic landmarks for resection of the amygdala during medial temporal lobe surgery." Neurosurgery 66 (5): 974-7. https://doi.org/10.1227/01.NEU.0000368105.64548.71. https://www.ncbi.nlm.nih.gov/pubmed/20404703. Ture, U., M. G. Yasargil, O. Al-Mefty, and D. C. Yasargil. 2000. "Arteries of the insula." J Neurosurg 92 (4): 676-87. https://doi.org/10.3171/jns.2000.92.4.0676. https://www.ncbi. nlm.nih.gov/pubmed/10761659. Wen, H. T., A. L. Rhoton, Jr., E. de Oliveira, A. C. Cardoso, H. Tedeschi, M. Baccanelli, and R. Marino, Jr. 1999. "Microsurgical anatomy of the temporal lobe: part 1: mesial temporal lobe anatomy and its vascular relationships as applied to amygdalohippocampectomy." 42 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

Neurosurgery 45 (3): 549-91; discussion 591-2. https://doi.org/10.1097/00006123- 199909000-00028. https://www.ncbi.nlm.nih.gov/pubmed/10493377. Ziyal, I. M., T. Ozgen, L. N. Sekhar, O. E. Ozcan, and S. Cekirge. 2005. "Proposed classification of segments of the internal carotid artery: anatomical study with angiographical interpretation." Neurol Med Chir (Tokyo) 45 (4): 184-90; discussion 190- 1. https://doi.org/10.2176/nmc.45.184. https://www.ncbi.nlm.nih.gov/pubmed/15849455. Zoia, C., D. Bongetta, G. Dorelli, S. Luzzi, M. D. Maestro, and R. J. Galzio. 2019. "Transnasal endoscopic removal of a retrochiasmatic cavernoma: A case report and review of literature." Surg Neurol Int 10: 76. https://doi.org/10.25259/SNI-132-2019. https://www. ncbi.nlm.nih.gov/pubmed/31528414. Zoia, C., D. Bongetta, F. Guerrini, C. Alicino, A. Cattalani, S. Bianchini, R. J. Galzio, and S. Luzzi. 2018. "Outcome of elderly patients undergoing intracranial meningioma resection: a single center experience." J Neurosurg Sci. https://doi.org/10.23736/S0390-5616. 18.04333-3. https://www.ncbi.nlm.nih.gov/pubmed/29808631. Zoia, C., F. Lombardi, M. R. Fiore, A. Montalbetti, A. Iannalfi, M. Sansone, D. Bongetta, F. Valvo, M. Del Maestro, S. Luzzi, and R. J. Galzio. 2020. "Sacral solitary fibrous tumour: surgery and hadrontherapy, a combined treatment strategy." Rep Pract Oncol Radiother 25 (2): 241-244. https://doi.org/10.1016/j.rpor.2020.01.008. https://www.ncbi.nlm.nih.gov/ pubmed/32025222.

Chapter 3

VASCULAR ANATOMY OF THE CRANIAL POSTERIOR CIRCULATION

S. Luzzi1,2,*, MD, PhD, A. Giotta Lucifero1, MD, M. Del Maestro2,3, MD, M. Nuñez4, MD and R. Galzio1,2, MD 1Neurosurgery Unit, Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy 2Neurosurgery Unit, Department of Surgical Sciences, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy 3PhD School in Experimental Medicine, Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy 4Department of Neurosurgery, Hospital El Cruce, Buenos Aires, Argentina

ABSTRACT

The posterior skull base is frequently involved in a variety of central nervous system vascular pathologies. Knowledge of the vascular anatomy of the posterior fossa and the posterolateral neck region is of utmost importance for the planning and execution of surgical approaches to this region. This chapter describes the posterior cerebral circulation vasculature from a surgical perspective, focusing on the anatomical basis of approaches used for the treatment of infratentorial aneurysms and arteriovenous malformations. The occipital artery of the extracranial circulation is considered in this chapter as it frequently serves as the main feeder in posterior fossa arteriovenous fistulas and as the donor vessel in cerebral bypass procedures.

Keywords: anterior inferior cerebellar artery, basilar artery, posterior cerebral artery, posterior inferior cerebellar artery, superior cerebellar artery, vertebral artery

* Corresponding Author’s Email: [email protected]. 44 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

1. VERTEBRAL ARTERY

The vertebral artery (VA) has four segments. The first three are extradural and the fourth is intradural. The V1 segment arises from the subclavian artery within the triangle of the VA, which is delineated by the longus colli, the anterior scalene, and the first part of the subclavian artery (Bruneau, Cornelius, and George 2006b). The V1 segment ascends to the most caudal of the transverse foramina of the subaxial cervical vertebrae, generally C6. At this point, the V2 segment begins and ascends from C6 to the C1 transverse foramen. After exiting the C2 transverse foramen, the vertebral artery courses laterally to reach the transverse foramen of the atlas (Russo et al. 2011). The V3 segment is comprised of the portion of the artery between the C1 transverse foramen and the dural entry point. This segment runs above the posterior arch of the atlas, generally into the “J-groove” (Wanibuchi et al. 2009) behind the lateral mass of C1 and atlanto-occipital joint. On an axial plane, the V3 segment forms a posterior convex curve. Not infrequently, the artery is contained within a complete or incomplete bony canal rather than a groove on the posterior arch of the atlas (de Oliveira, Rhoton, and Peace 1985, Gupta 2008, Rhoton 2000b, Bruneau, Cornelius, and George 2006a, Wen et al. 1997). The V3 segment, vertebral venous plexus, and C1 nerve root course within the superior suboccipital triangle. The superior suboccipital triangle is bordered by the rectus capitis superior major superomedially, the obliquus capitis superior superolaterally, and the obliquus capitis inferior inferolaterally.

Figure 1. (A-I) Extradural segment of the vertebral artery. Vascular Anatomy of the Cranial Posterior Circulation 45

Table 1. Segments, Collateral and Terminal Branches, And Vascular Supply of The Vertebral Artery

Distal Anatomic VA Segment Subsegment Collateral and Terminal Branches Vascular Supply Border C6 transverse V1 process (Hong et al. 2008) Lateral spinal branches Transverse (Lateral spinal artery (P. Lasjaunias et Spinal cord V2 foramen of the al. 1985)) atlas Deep cervical Vertical Muscular branches musculature portion Dura of the Horizontal Extradural foramen magnum Posterior meningeal artery Posterior fossa dura portion (Bruneau, Restiform body, Cornelius, and gracile and cuneate George 2006a, V3 tubercles, Rhoton 2000b, accessory nerve, Wen et al. 1997, Oblique Posterior spinal artery choroid plexus, de Oliveira, portion superficial part of Rhoton, and Peace the dorsal half of the 1985) cervical spinal cord Perforating arteries (Lister et al. 1982, PICA (5-20% of T. Matsushima, Medulla cases extradural Rhoton, and origin) (Fine, Lenkey 1982) Cardoso, and Choroidal arteries Rhoton 1999, de (Lister et al. 1982, Lateral Choroid plexus of Oliveira, Rhoton, T. Matsushima, medullary the fourth ventricle and Peace 1985) Rhoton, and Ponto-medullary segment Intradural V4 (P1-P5 segments) Lenkey 1982) sulcus (T. Matsushima, Cortical arteries Rhoton, and (Lister et al. 1982, Vermis, tonsils, Lenkey 1982) T. Matsushima, hemisphere of the Rhoton, and suboccipital surface Lenkey 1982) Anterior medullary Anterior spinal artery Cervical spinal cord segment PICA: Posterior Inferior Cerebellar Artery.

The C1 nerve root passes beneath the artery and above the posterior arch of the atlas. During their course through the superior suboccipital triangle, all the neurovascular structures are located behind the posterior atlanto-occipital membrane, which forms the floor of the suboccipital triangle, and in front of a thick fibrofatty layer that closes the triangle posteriorly and forms its roof (de Oliveira, Rhoton, and Peace 1985, Campero A 2011, Tubbs et al. 2005). The superior suboccipital triangle is covered by the semispinalis capitis (Figure 1). The posterior atlanto-occipital membrane may form a funnel-shaped dense ring around the vertebral artery just before its dural entry point. The V3 segment gives rise to several branches: the posterior meningeal artery, posterior spinal artery, and deep cervical branches. The posterior meningeal artery ascends through the foramen magnum to the dura covering the posterior and lateral portion of the posterior fossa, posterior aspects of the tentorium, and the falx cerebri. It anastomoses with meningeal branches of the occipital and ascending pharyngeal arteries. The posterior spinal artery anastomoses with the lateral spinal artery and supplies the restiform 46 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al. body, gracile and cuneate tubercles, accessory nerve, choroid plexus, and superficial portion of the dorsal half of the cervical spinal cord (P. Lasjaunias et al. 1985). The deep cervical branches are directed to the deep suboccipital muscles where they anastomose with deep cervical arteries from the costocervical trunk of the subclavian artery. Extradural origin of the posterior inferior cerebellar artery (PICA) from the V3 segment has been reported in 5%–20% of cases (Yaşargil 1984, Fine, Cardoso, and Rhoton 1999, de Oliveira, Rhoton, and Peace 1985). Rarely, the posterior meningeal artery may arise intradurally from the V4 segment. The most lateral part of the vertebral artery is medial to the rectus capitals lateralis (Ulm et al. 2010). Youssef et al. provided histological confirmation of the existence of a thin distinct membrane surrounding the V3 segment of the vertebral artery and its venous plexus (Youssef et al. 2010). Based on this finding, they suggested an interfascial technique for VA exposure in the suboccipital triangle, following the natural tissue planes between the deep suboccipital fascia, posterior atlanto- occipital membrane, common periosteal sheath covering the VA, vertebral venous plexus, and the periosteal plane of the C1 and C2 laminae. The V4 segment is intradural and generally divided by the preolivary sulcus into lateral and anterior meduallary segments. The lateral medullary segment passess above the C1 nerve rootlets and ascends forward, anterior to the dentate ligament and spinal accessory nerve (Figure 2 A). The anterior medullary segment courses in front of or between the hypoglossal rootlets, crosses the pyramid, and joins the contralateral VA in the midline at the level of the pontomedullary sulcus to give rise to the basilar artery (BA). The anterior medullary segment faces the occipital condyle, hypoglossal canal, and jugular tubercle (Campero A 2011) and gives rise to the anterior spinal artery supplying the cervical spinal cord. The lateral medullary segment gives rise to the PICA in approximately 80% of cases (Fine, Cardoso, and Rhoton 1999, Rhoton 2000a). Table 1 presents the segments, collateral and terminal branches, and vascular supply of the VA (Table1).

1.1. Posterior Inferior Cerebellar Artery

The PICA arises from the VA, generally from the proximal segment, although variations are possible. Lister and colleagues identified five segments of the PICA: anterior medullary, lateral medullary, tonsillomedullary, telovelotonsillar, and cortical (Lister et al. 1982). Perforating branches from the PICA supply the medulla and the cerebellum, it follows that PICA occlusion causes catastrophic sequelae. The PICA has the highest frequency of variation among the infratentorial arteries. Along its complex and tortuous course, the PICA crosses the rootlets of the hypoglossal, glossopharyngeal, vagus, and accessory nerves before entering the cerebellomedullary fissure (Figure 2 B). Although uncommon, intracranial aneurysms may develop along the proximal and distal segments of the PICA, these aneurysms are often complex in nature. Very frequently, branches of the PICA are feeders of infratentorial arteriovenous malformations. The site of origin of the PICA and its anatomical relationship with the lower cranial nerves largely determines the choice of approach in proximal VA-PICA aneurysms. The VA occasionally terminates in a PICA, this can occur regardless of extradural or intradural VA origin. Table 2 presents the PICA segments according to the classification of Lister et al. (Lister et al. 1982) along with its collateral branches and vascular supply (Table 2).

Vascular Anatomy of the Cranial Posterior Circulation 47

Table 2. PICA Segments according to Lister et al. (Lister et al. 1982), Collateral and Terminal Branches, and Vascular Supply

PICA Segment Distal Anatomic Collateral and Terminal Branches Vascular Supply (Lister Et Al. 1982) Border Most prominent part of Perforating branches Anterior medullary Anterior medulla the olive (n. 1 on average) (Lister et al. 1982) Perforating branches Lateral medullary Retro-olivary sulcus Lateral medulla (n. 2 on average) (Lister et al. 1982) Tonsillomedullary Perforating branches Caudal half of the tonsil Posterior medulla (caudal loop) (n. 4 on average) (Lister et al. 1982) Posterior end of the Tela choroidea, choroid Telovelotonsillar cerebellomedullary Choroidal arteries plexus of the fourth (cranial loop) fissure ventricle Median Vermis Paramedian vermian Tonsillar Tonsil Terminal cortical Cortical Medial hemispheric branches Intermediate Cerebellar hemisphere, Hemispheric dentate nucleus Lateral hemispheric PICA: Posterior Inferior Cerebellar Artery.

Figure 2. Intradural segment of the vertebral artery (A) and PICA (B): anterior medullary (green), lateral medullary (orange), tonsillomedullary (blue) and telovelotonsillar segments (yellow) of the PICA.

2. BASILAR ARTERY

The BA arises from the union of both VAs at the level of the pontomedullary sulcus. It ascends along the pons within the basilar sulcus to reach the pontomesencephalic sulcus, where it bifurcates into the paired posterior cerebral arteries. (Figure 3 A-F). The bifurcation point is also known as the basilar tip, which may be located at, above, or below the level of the superior 48 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al. border of the dorsum sellae. Cases of basilar tip location above or below the dorsum sellae are referred to as high- or low-riding, respectively. In 16% of cases, the BA has a widening at the level of the bifurcation, which is responsible for a cobra-like appearance on angiograms (Saeki and Rhoton 1977, Zeal and Rhoton 1978). The BA gives rise to the anterior inferior cerebellar artery (AICA), pontine arteries, and superior cerebellar artery (SCA). Table 3 presents the branches from the BA and their vascular supply (Table 3).

Figure 3. (A-I) Posterior cerebral circulation. A1: A1 segment of the anterior cerebral artery, Acc. N: accessory nerve, AChA: anterior choroidal artery, ACoA: anterior communicating artery, AICA: anterior inferior cerebellar artery, BA: basilar artery, C1: atlas, C2 N: C2 nerve, Calc. A: calcarine artery, cist. M: cisterna magna, FM: foramen magnum, ICA: internal carotid artery, Inf. temp. A: inferior temporal arteries, IX-X-XI: glossopharyngeal, vagus and accessory nerves, LC: lateral condyle, Med: medulla, OB: occipital bone, OC: occipital condyle, P1, P2, P3: segments of the posterior cerebral artery, PCoA: posterior communicating artery, perf. pont.: perforating pontine arteries, PICA: posterior inferior cerebellar artery, Rect. Post. M: rectus posterior major, S: splenium of the corpus callosum, SCA: superior cerebellar artery, SOM: superior oblique muscle, T: tentorium, V3 v, h, o: vertical, horizontal, and oblique segments of the vertebral artery, VA: vertebral artery, VII-VIII: facial-vestibulocochlear nerve, XII: hypoglossal nerve.

2.1. Anterior Inferior Cerebellar Artery

The AICA arises from the BA at the level of the origin of the abducens nerve. It courses superiorly along the convex surface of the pons to reach the cerebellopontine angle where, generally, at the level of the vestibulocochlear nerves and near the internal acoustic meatus, it bifurcates into rostral and caudal trunks (Figure 3 C, D). The bifurcation can be found in the premeatal, meatal, or postmeatal area. During its course, the AICA gives rise to the nerve- related arteries directed to the 7th through 11th cranial nerves within the cerebellopontine angle Vascular Anatomy of the Cranial Posterior Circulation 49 as well as recurrent perforating branches to the brainstem (Rhoton 2000a, Martin et al. 1980) (Table 3).

Table 3. Collateral and Terminal Branches and Vascular Supply of the Basilar Artery

Collateral and Terminal Branches of the BA Vascular Supply Anterior pontomesencephalic Direct and recurrent Tegmentum, interpeduncular fossa, cerebral peduncle, segment (circumflex) superior and middle cerebellar peduncles, collicular region Lateral pontomesencephalic perforating arteries segment Marginal branch Petrosal surface of the cerebellum SCA Hemispheric surface of the cerebellum, dentate and deep Cerebellomesencephalic segment cerebellar nuclei, vermis, inferior colliculi, superior medullary velum Tentorial surface of the cerebellum, vermis, upper part of Hemispheric and Cortical segment the petrosal surface, superior part of the suboccipital vermian branches surface Perforating pontine arteries Pons Anterior pontine segment Abducens nerve Lateral pontine Labyrinthine artery Facial and vestibulocochlear nerves, labyrinth segment Brainstem, middle cerebellar peduncle, glossopharyngeal Nerve- Recurrent perforating (premeatal, meatal, and vagus nerves, choroid plexus protruding from the related arteries AICA and postmeatal) foramen of Luschka arteries (Rhoton 2000a, Subarcuate artery Subarcuate fossa Martin et al. 1980) Flocculopeduncular segment Middle cerebellar peduncle Cortical segment Petrosal surface of the cerebellum BA: Basilar Artery, SCA: Superior Cerebellar Artery, AICA: Anterior Inferior Cerebellar Artery.

2.2. Perforating Pontine Arteries

Perforating pontine arteries are a series of tiny vessels emerging directly from the BA directed into the brainstem. In contrast to the recurrent perforating branches from the AICA, these arteries have an orientation that is perpendicular to the surface of the pons, which they pierce as medullary vessels (Figure 3 E).

2.3. Superior Cerebellar Artery

The SCA arises from the BA immediately below the oculomotor nerve. In approximately 7% of cases, it is duplicated (Hardy, Peace, and Rhoton 1980). The SCA courses posterolaterally below the trochlear nerve and above the trigeminal nerve to reach the cerebellomesencephalic fissure. Its cortical segments are directed to a large part of the infratentorial surface of the cerebellum along with the vermis. The SCA has four segments: anterior and lateral pontomesencephalic, cerebellomesencephalic, and cortical (Figure 3 E, F). The SCA gives off a series of direct and circumflex perforating arteries, mainly from its first two segments, which are directed to the interpeduncular fossa, cerebral peduncle, superior and middle cerebellar peduncles, and collicular region (Table 3).

50 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

3. POSTERIOR CEREBRAL ARTERY

Table 4. Segments, Collateral and Terminal Branches, And Vascular Supply of the Posterior Cerebral Artery

Distal Vascular Supply PCA Segment Anatomic Collateral and Terminal Branches

Border Posterior perforated substance, mamillary bodies, anterior and part of the posterior thalamus, hypothalamus, subthalamus, Thalamoperforating arteries (direct, medial part of the upper midbrain, short, and long circumflex, n. 4 on substantia nigra, red nucleus, oculomotor average (Zeal and Rhoton 1978), and trochlear nuclei, oculomotor nerve, P1 (interpeduncular thalamoperforating artery is the major Junction with mesencephalic reticular formation, segment, 25 mm on branch) the PComA pretectum, rostromedial floor of the fourth average) ventricle, posterior portion of the internal capsule (Zeal and Rhoton 1978) Branch to the quadrigeminal plate Superior and inferior colliculi Branches to the cerebral peduncle and Cerebral peduncle, mesencephalic mesencephalic tegmentum tegmentum Geniculate bodies, cerebral peduncle Circumflex branches (short and long) (short), quadrigeminal colliculi, tegmentum, pulvinar (long) P2A (crural or Choroid plexus of the third ventricle, peduncular choroidal fissure, foramen of Monro, segment, 25 mm MPChAs (range 1-3 (Zeal and Rhoton choroid plexus of the lateral ventricle, on average) Posterior edge 1978, Fujii, Lenkey, and Rhoton 1980)) cerebral peduncle, tegmentum, geniculate (Saeki and of the midbrain bodies, quadrigeminal colliculi, pulvinar, Rhoton 1977, pineal gland, medial thalamus. Zeal and Rhoton Corticospinal and corticobulbar tracts, 1978, Rhoton Peduncular Perforating Arteries substantia nigra, red nucleus 2002) P2 Thalamogeniculate Arteries (n. 3 on Geniculate bodies, posterior limb of the P2P (ambient or average (Zeal and Rhoton 1978)) internal capsule, optic tract lateral mesencephalic segment, 25 mm Lateral part of Choroid plexus of the temporal horn and on average) the atrium of the lateral ventricle, cerebral (Saeki and quadrigeminal LPChAs (range 1-9 (Fujii, Lenkey, and peduncle, posterior commissure, fornix, Rhoton 1977, cistern Rhoton 1980)) lateral geniculate body, pulvinar, Zeal and Rhoton dorsomedial thalamic nucleus, body of the 1978, Rhoton caudate nucleus. 2002) Uncus, anterior parahippocampal gyrus, Hippocampal hippocampal formation, the dentate gyrus. Inferior Anterior temporal arteries Temporal P3 (quadrigeminal Middle temporal arteries Arteries Inferior surface of the temporal lobe segment, 20 mm on Posterior temporal arteries Anterior limit average) (Saeki and Common temporal arteries of the calcarine Rhoton 1977, Zeal Calcarine artery (terminal branch, fissure Visual cortex and Rhoton 1978, courses within the calcarine fissure) Rhoton 2002) Splenial branches Splenium of the corpus callosum Parieto-occipital artery (terminal branch, courses within the parieto- occipital fissure) Posterior parasagittal region, cuneus, Parieto- precuneus, lateral occipital gyrus P4 occipital Parieto-occipital branches cortical surface PCA: Posterior Cerebral Artery, PComA: Posterior Communicating Artery, MPChA: Medial Posterior Choroidal Artery, LPChA: Lateral Posterior Choroidal Artery.

The posterior cerebral artery (PCA) arises from the BA below the posterior perforated substance. Classically, the junction with the posterior communicating artery (PComA) divides its proximal portion into proximal P1 and distal P2 segments. The posterior edge of the Vascular Anatomy of the Cranial Posterior Circulation 51 midbrain marks the boundary between the P2 and P3 segments, the most distal P4 segment is directed mainly to the parieto-occipital and visual cortices. A PComA diameter greater than the PCA diameter indicates the PComA embyologically arose from the internal carotid artery (ICA), in this case, the posterior circulation is referred to as fetal type. The P1, P2, P3 and P4 segments course through the interpeduncular, crural, ambient, and quadrigeminal cisterns, respectively (Figure 3 F, H). During its course, the PCA gives off three types of branches: perforating, choroidal, and cortical. Table 4 presents the segments, collateral branches, and vascular supply of the PCA (Table 4).

4. PERFORATING ARTERIES

Table 5. Perforating Arteries of the Posterior Circulation

Parent Collateral Perforating Segment Subsegment Vascular Supply Vessel Branch Arteries Posterior perforated substance, mamillary bodies, anterior and part of Thalamoperforating the posterior thalamus, hypothalamus, (direct, short and subthalamus, medial part of the upper long circumflex, n. 4 midbrain, substantia nigra, red nucleus, on average (Zeal and P1 oculomotor and trochlear nuclei, Rhoton 1978), oculomotor nerve, mesencephalic thalamoperforating reticular formation, pretectum, artery is the major rostromedial floor of the fourth PCA branch) ventricle, posterior portion of the internal capsule (Zeal and Rhoton 1978) Geniculate bodies, cerebral peduncle Circumflex branches P2A (short), quadrigeminal colliculi, (short and long tegmentum, pulvinar (long) Thalamogeniculate arteries (n. 3 on Geniculate bodies, posterior limb of the P2P average (Zeal and internal capsule, optic tract Rhoton 1978)) Peduncular Corticospinal and corticobulbar tracts,

Perforating substantia nigra, red nucleus Anterior Tegmentum, interpeduncular fossa, pontomesencephalic Direct and recurrent SCA cerebral peduncle, superior and middle Lateral (circumflex) cerebellar peduncles, collicular region pontomesencephalic BA Perforating pontine arteries Direct Pons Lateral pontine Brainstem, middle cerebellar peduncle, segment (premeatal, Recurrent perforating glossopharyngeal and vagus nerves, AICA meatal, and arteries choroid plexus protruding from the postmeatal) foramen of Luschka n. 4 (average) (Lister Anterior et al. 1982, T. Anterior medulla medullary Matsushima, Rhoton, and Lenkey 1982) VA PICA Lateral n. 2 (average) Lateral medulla medullary (Lister et al. 1982) Tonsillome- n. 4 (average) dullary Posterior medulla (Lister et al. 1982) (caudal loop) PCA: Posterior Cerebral Artery, BA: Basilar Artery, VA: Vertebral Artery, SCA: Superior Cerebellar Artery, AICA: Anterior Inferior Cerebellar Artery, PICA: Posterior Inferior Cerebellar Artery.

52 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

Perforating arteries of the posterior circulation supply the brainstem, posterior perforated substance, thalamus, hypothalamus, subthalamus, posterior portion of the internal capsule, substantia nigra, red nucleus, and reticular formation (Lister et al. 1982, T. Matsushima, Rhoton, and Lenkey 1982). They arise from the PCA, BA, SCA, AICA and PICA. Occlusion of the perforating arteries of the posterior circulation is often not compatible with life. Their preservertion is therefore imperative during surgery of posterior circulation aneurysms and infratentorial arteriovenous malformations. Table 5 summarizes the perforating arteries of the posterior fossa, along with their vascular supply (Table 5).

5. OCCIPITAL ARTERY

The occipital artery (OA) arises from the back wall of the external carotid artery (ECA) at the level of the angle of the jaw within the retrostyloid space of the maxillopharyngeal region. Its origin is located below the level of the posterior belly of the digastric before the point where the ECA pierces the styloid diaphragm (Bejjani et al. 1998). The OA has three well defined segments: ascending cervical, cervico-occipital (or horizontal), and ascending occipital (Martins et al. 2005). The ascending cervical segment is located within the retrosyloid space and is covered by the posterior belly of the digastric and stylohyoid. It runs posteriorly and superiorly lateral to the ICA, internal jugular vein, and lower cranial nerves. The cervico-occipital segment is located in the mastoid region between the transverse process of C1 and the mastoid tip. Here, the OA courses along a groove in the temporal bone that is medial to the deeper digastric groove which is located adjacent to the posterior belly of the digastric. This segment courses posteriorly between the rectus capitis lateralis medially, and the digastric, splenius capitis, and sternocleidomastoid laterally. Moving posteriorly, it passes above the obliquus capitis superior of the suboccipital triangle and beneath the longissimus capitis in most cases. The ascending occipital segment courses posteriorly and superiorly toward the vertex of the skull, becoming superficial at the level of the superior nuchal line of the occipital squama. Here, it pierces the semispinalis capitis and continues towards the occipital scalp. During its course, the OA gives off four types of branches destined for the skin, facial nerve, posterior neck muscles, and posterior fossa dura. The stylomastoid artery, arising from the cervico-occipital segment, supplies the facial nerve at its exit through the stylomastoid foramen and the dura adjacent to the stylomastoid foramen, tympanic cavity, and endolymphatic duct and sac. In case of hypoplasia or occlusion of the OA, branches of the ascending pharyngeal, posterior auricular, or vertebral artery may provide blood flow to the regions typically supplied by the OA. (P Lasjaunias, Théron, and Moret 1978).

6. VEINS

The veins of the posterior fossa have been elegantly classified by Rhoton and colleagues (K. Matsushima et al. 2016, T. Matsushima et al. 1983, T. Matsushima, Rhoton, and Lenkey 1982, Rhoton 2000c). These veins are categorized into four different groups based on area of Vascular Anatomy of the Cranial Posterior Circulation 53 drainage: superficial, deep, brainstem, and bridging veins. Each group is further classified according to topography of the venous outflow. The posterior fossa venous outflow is ultimately through the bridging veins, which in turn collect into three groups: galenic, petrosal, and tentorial. Table 6 summarizes the classification of the venous pathways of the infratentorial space according to Rhoton and colleagues (K. Matsushima et al. 2016, T. Matsushima et al. 1983, T. Matsushima, Rhoton, and Lenkey 1982, Rhoton 2000c) (Table 6).

Table 6. Venous Pathways of the Infratentorial Space

Main Group Subgroup Superior vermian veins Tentorial surface Superior hemispheric veins Inferior vermian veins Superficial Veins Inferior hemispheric veins Suboccipital surface Retrotonsillar veins Medial and lateral tonsillar veins Petrosal surface Anterior hemispheric veins Vein of superior cerebellar peduncle Cerebellomesencephalic Vein of cerebellomesencephalic fissure fissure Pontotrigeminal vein Tectal veins Vein of cerebellomedullary fissure Deep Veins Vein of inferior cerebellar peduncle Cerebellomedullary fissure Supratonsillar veins Choroidal veins Vein of cerebellopontine fissure Cerebellopontine fissure Vein of middle cerebellar peduncle Median anterior pontomesencephalic vein Midline Median anterior medullary vein Lateral anterior pontomesencephalic vein Longitudinal veins Anterolateral Lateral anterior medullary vein Lateral mesencephalic vein Lateral Lateral medullary and retro-olivary veins Veins of the Brainstem Peduncular vein Posterior communicating vein Vein of pontomesencephalic sulcus Transverse Veins Transverse pontine veins Vein of pontomedullary sulcus Transverse medullary vein Galenic group (to vein of Galen) Bridging Veins (Major Tentorial group (to torcula and tentorial sinuses) Draining Groups) Petrosal group (to petrosal sinuses) Other bridging veins

7. DISCUSSION

The infratentorial compartment is frequently involved in a variety of neurovascular pathologies ranging from aneurysms to arteriovenous malformations and arteriovenous fistulas. The surgical and endovascular management of these lesions is dependent on a thorough knowledge of neurovascular anatomy (Ciappetta, Luzzi, et al. 2009, Ciappetta, Occhiogrosso, et al. 2009, De Tommasi, De Tommasi, et al. 2006, Del Maestro et al. 2018, Gallieni et al. 2018, S. Luzzi, Del Maestro, et al. 2018, S. Luzzi, Del Maestro, and Galzio 2019, S. Luzzi, Elia, Del Maestro, Morotti, et al. 2019, S. Luzzi, Gallieni, et al. 2018, Luzzi S 2019, Ricci et 54 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al. al. 2017, S. Luzzi et al. 2020). Planning the approach to VA and PICA aneurysms requires precise localization of the lesion along the different arterial segments. Surgical risk is primarily related to occlusion of perforating arteries and evaluated based on anatomic localization. Brainstem and cerebellar infarcts are often deadly, in contrast to those that occur in the supratentorial space. A classic example comes from the occlusion of thalamoperforating arteries during surgical or endovascular treatment of basilar tip aneurysms. As in many other pathologies affecting the skull base (Arnaout et al. 2019, S. Luzzi, Del Maestro, Elia, et al. 2019, S. Luzzi, Del Maestro, Trovarelli, et al. 2019, S. Luzzi, Zoia, et al. 2019, Zoia et al. 2019), endoscopic surgical treatment of posterior fossa aneurysms has been suggested. An endoscopic transnasal transclival approach to vertebrobasilar junction aneurysms has been recently proposed because of their midline localization and the morbidity associated with conventional posterolateral skull base approaches (Gardner et al. 2015, Szentirmai et al. 2016). Nevertheless, the endoscopic approach currently remains unproven. In the near future, the biotechnological revolution that has already occurred in most other neurosurgical fields (Bellantoni et al. 2019, Cheng, Shetty, and Sekhar 2018, De Tommasi et al. 2008, De Tommasi et al. 2007, Guastamacchia et al. 2007, Sabino Luzzi, Crovace, et al. 2019, S. Luzzi, Crovace, et al. 2018, S. Luzzi, Elia, Del Maestro, Elbabaa, et al. 2019, S. Luzzi, Giotta Lucifero, et al. 2019, Palumbo et al. 2019, Palumbo et al. 2018, Raysi Dehcordi et al. 2017, Spena et al. 2019, Zoia et al. 2018, Bongetta et al. 2019, Ciappetta et al. 2008, De Tommasi, Cascardi, et al. 2006, Millimaggi et al. 2018, Antonosante et al. 2020, Campanella et al. 2020, Zoia et al. 2020, Elsawaf et al. 2020) will likely lead to further refinements in endoscopic techniques and instrumentation, thus pushing neuroendoscopy beyond its limits. Regardless, the knowledge of vascular and skull base anatomy will remain essential in treating all forms of central nervous system vascular pathology.

CONCLUSION

The VA, BA, and PCA are the main arteries of the posterior cerebral circulation. They supply the infratentorial space via the PICA, AICA, and SCA, and portions of the temporal, occipital, and parietal lobes via branches arising from the PCA. In the case of fetal type circulation, the PCoA diameter is larger than the PCA diameter, indicating that the supratentorial PCA is primarily embryologically derived from the ICA. All arteries of the posterior circulation have associated perforating arteries that arise from the main segment or branches that are destined for the brainstem and cerebellum. The occipital artery may serve as the main feeder of posterior fossa arteriovenous fistulas and as well as the donor vessel in cerebral vascular bypass procedures. Venous outflow of the posterior circulation is primarily or secondarily via the dural sinuses, tributaries of the internal jugular vein. Arterial and venous infarcts of the posterior cerebral circulation are deadly in most cases. Thorough knowledge of the vascular anatomy of the posterior cerebral circulation is essential to deal with all forms of neurovascular disease.

Vascular Anatomy of the Cranial Posterior Circulation 55

REFERENCES

Antonosante, A., L. Brandolini, M. d’Angelo, E. Benedetti, V. Castelli, M. D. Maestro, S. Luzzi, A. Giordano, A. Cimini, and M. Allegretti. 2020. “Autocrine CXCL8-dependent invasiveness triggers modulation of actin cytoskeletal network and cell dynamics.” Aging (Albany NY) 12 (2): 1928-1951. https://doi.org/10.18632/aging.102733. https://www. ncbi.nlm.nih.gov/pubmed/31986121. Arnaout, M. M., S. Luzzi, R. Galzio, and K. Aziz. 2019. “Supraorbital keyhole approach: Pure endoscopic and endoscope-assisted perspective.” Clin Neurol Neurosurg 189: 105623. https://doi.org/10.1016/j.clineuro.2019.105623. https://www.ncbi.nlm.nih.gov/pubmed/ 31805490. Bejjani, G. K., B. Sullivan, E. Salas-Lopez, J. Abello, D. C. Wright, A. Jurjus, and L. N. Sekhar. 1998. “Surgical anatomy of the infratemporal fossa: the styloid diaphragm revisited.” Neurosurgery 43: 842-52, discussion 852-3. Bellantoni, G., F. Guerrini, M. Del Maestro, R. Galzio, and S. Luzzi. 2019. “Simple schwannomatosis or an incomplete Coffin-Siris? Report of a particular case.” eNeurologicalSci 14: 31-33. https://doi.org/10.1016/j.ensci.2018.11.021. https://www. ncbi.nlm.nih.gov/pubmed/30555950. Bongetta, D., C. Zoia, S. Luzzi, M. D. Maestro, A. Peri, G. Bichisao, D. Sportiello, I. Canavero, A. Pietrabissa, and R. J. Galzio. 2019. “Neurosurgical issues of bariatric surgery: A systematic review of the literature and principles of diagnosis and treatment.” Clin Neurol Neurosurg 176: 34-40. https://doi.org/10.1016/j.clineuro.2018.11.009. https://www.ncbi. nlm.nih.gov/pubmed/30500756. Bruneau, M., J. F. Cornelius, and B. George. 2006a. “Antero-lateral approach to the V3 segment of the vertebral artery.” Neurosurgery 58 (1 Suppl): ONS29-35, discussion ONS29-35. https://doi.org/10.1227/01.neu.0000193930.74183.42. https://www.ncbi.nlm. nih.gov/pubmed/16479626. ––––– . 2006b. “Anterolateral approach to the V1 segment of the vertebral artery.” Neurosurgery 58 (4 Suppl 2): ONS-215-9, discussion ONS-219. https://doi.org/10.1227/ 01.NEU.0000204650.35289.3E. https://www.ncbi.nlm.nih.gov/pubmed/16582643. Campanella, R., L. Guarnaccia, C. Cordiglieri, E. Trombetta, M. Caroli, G. Carrabba, N. La Verde, P. Rampini, C. Gaudino, A. Costa, S. Luzzi, G. Mantovani, M. Locatelli, L. Riboni, S. E. Navone, and G. Marfia. 2020. “Tumor-Educated Platelets and Angiogenesis in Glioblastoma: Another Brick in the Wall for Novel Prognostic and Targetable Biomarkers, Changing the Vision from a Localized Tumor to a Systemic Pathology.” Cells 9 (2). https://doi.org/10.3390/cells9020294. https://www.ncbi.nlm.nih.gov/pubmed/31991805. Campero A., Rubio P. A., Rhoton A. L. 2011. “Anatomy of the vertebral artery.” In Pathology and Surgery around the Vertebral Artery, edited by Bruneau M George B, Spetzler RF, eds, 29–40. Paris: Springer-Verlag France. Cheng, C. Y., R. Shetty, and L. N. Sekhar. 2018. “Microsurgical Resection of a Large Intraventricular Trigonal Tumor: 3-Dimensional Operative Video.” Oper Neurosurg (Hagerstown) 15 (6): E92-E93. https://doi.org/10.1093/ons/opy068. https://www.ncbi. nlm.nih.gov/pubmed/29618124. 56 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

Ciappetta, P., I. D’Urso P, S. Luzzi, G. Ingravallo, A. Cimmino, and L. Resta. 2008. “Cystic dilation of the ventriculus terminalis in adults.” J Neurosurg Spine 8 (1): 92-9. https://doi.org/10.3171/SPI-08/01/092. https://www.ncbi.nlm.nih.gov/pubmed/18173354. Ciappetta, P., S. Luzzi, R. De Blasi, and P. I. D’Urso. 2009. “Extracranial aneurysms of the posterior inferior cerebellar artery. Literature review and report of a new case.” J Neurosurg Sci 53 (4): 147-51. https://www.ncbi.nlm.nih.gov/pubmed/20220739. Ciappetta, P., G. Occhiogrosso, S. Luzzi, P. I. D’Urso, and A. P. Garribba. 2009. “Jugular tubercle and vertebral artery/posterior inferior cerebellar artery anatomic relationship: a 3- dimensional angiography computed tomography anthropometric study.” Neurosurgery 64 (5 Suppl 2): 429-36, discussion 436. https://doi.org/10.1227/01.NEU.0000337573. 17073.9F. https://www.ncbi.nlm.nih.gov/pubmed/19404121. de Oliveira, E., A. L. Rhoton, Jr., and D. Peace. 1985. “Microsurgical anatomy of the region of the foramen magnum.” Surg Neurol 24 (3): 293-352. https://www.ncbi.nlm.nih.gov/ pubmed/4023912. De Tommasi, A., P. Cascardi, C. De Tommasi, S. Luzzi, and P. Ciappetta. 2006. “Emergency surgery in a severe penetrating skull base injury by a screwdriver: case report and literature review.” World J Emerg Surg 1: 36. https://doi.org/10.1186/1749-7922-1-36. https://www. ncbi.nlm.nih.gov/pubmed/17169147. De Tommasi, A., C. De Tommasi, E. Lauta, S. Luzzi, A. Cimmino, and P. Ciappetta. 2006. “Pre-operative subarachnoid haemorrhage in a patient with spinal tumour.” Cephalalgia 26 (7): 887-90. https://doi.org/10.1111/j.1468-2982.2006.01122.x. https://www.ncbi.nlm. nih.gov/pubmed/16776708. De Tommasi, A., S. Luzzi, P. I. D’Urso, C. De Tommasi, N. Resta, and P. Ciappetta. 2008. “Molecular genetic analysis in a case of ganglioglioma: identification of a new mutation.” Neurosurgery 63 (5): 976-80, discussion 980. https://doi.org/10.1227/01.NEU. 0000327699.93146.CD. https://www.ncbi.nlm.nih.gov/pubmed/19005389. De Tommasi, A., G. Occhiogrosso, C. De Tommasi, S. Luzzi, A. Cimmino, and P. Ciappetta. 2007. “A polycystic variant of a primary intracranial leptomeningeal astrocytoma: case report and literature review.” World J Surg Oncol 5: 72. https://doi.org/10.1186/1477- 7819-5-72. https://www.ncbi.nlm.nih.gov/pubmed/17587463. Del Maestro, M., S. Luzzi, M. Gallieni, D. Trovarelli, A. V. Giordano, M. Gallucci, A. Ricci, and R. Galzio. 2018. “Surgical Treatment of Arteriovenous Malformations: Role of Preoperative Staged Embolization.” Acta Neurochir Suppl 129: 109-113. https://doi.org/ 10.1007/978-3-319-73739-3_16. https://www.ncbi.nlm.nih.gov/pubmed/30171322. Elsawaf, Y., S. Anetsberger, S. Luzzi, and S. K. Elbabaa. 2020. “Early Decompressive Craniectomy as Management for Severe TBI in the Pediatric Population: A Comprehensive Literature Review.” World Neurosurg. https://doi.org/10.1016/j.wneu.2020.02.065. https://www.ncbi.nlm.nih.gov/pubmed/32084616. Fine, A. D., A. Cardoso, and A. L. Rhoton, Jr. 1999. “Microsurgical anatomy of the extracranial-extradural origin of the posterior inferior cerebellar artery.” J Neurosurg 91 (4): 645-52. https://doi.org/10.3171/jns.1999.91.4.0645. https://www.ncbi.nlm.nih.gov/ pubmed/10507387. Fujii, K., C. Lenkey, and A. L. Rhoton, Jr. 1980. “Microsurgical anatomy of the choroidal arteries: lateral and third ventricles.” J Neurosurg 52 (2): 165-88. https://doi.org/ 10.3171/jns.1980.52.2.0165. https://www.ncbi.nlm.nih.gov/pubmed/7351556. Vascular Anatomy of the Cranial Posterior Circulation 57

Gallieni, M., M. Del Maestro, S. Luzzi, D. Trovarelli, A. Ricci, and R. Galzio. 2018. “Endoscope-Assisted Microneurosurgery for Intracranial Aneurysms: Operative Technique, Reliability, and Feasibility Based on 14 Years of Personal Experience.” Acta Neurochir Suppl 129: 19-24. https://doi.org/10.1007/978-3-319-73739-3_3. https://www. ncbi.nlm.nih.gov/pubmed/30171309. Gardner, P. A., F. Vaz-Guimaraes, B. Jankowitz, M. Koutourousiou, J. C. Fernandez-Miranda, E. W. Wang, and C. H. Snyderman. 2015. “Endoscopic Endonasal Clipping of Intracranial Aneurysms: Surgical Technique and Results.” World Neurosurg 84 (5): 1380- 93. https://doi.org/10.1016/j.wneu.2015.06.032. https://www.ncbi.nlm.nih.gov/pubmed/ 26117084. Guastamacchia, E., V. Triggiani, E. Tafaro, A. De Tommasi, C. De Tommasi, S. Luzzi, C. Sabba, F. Resta, M. R. Terreni, and M. Losa. 2007. “Evolution of a prolactin-secreting pituitary microadenoma into a fatal carcinoma: a case report.” Minerva Endocrinol 32 (3): 231-6. https://www.ncbi.nlm.nih.gov/pubmed/17912159. Gupta, T. 2008. “Quantitative anatomy of vertebral artery groove on the posterior arch of atlas in relation to spinal surgical procedures.” Surg Radiol Anat 30 (3): 239-42. https://doi.org/10.1007/s00276-008-0313-x. https://www.ncbi.nlm.nih.gov/pubmed/1825 3689. Hardy, D. G., D. A. Peace, and A. L. Rhoton, Jr. 1980. “Microsurgical anatomy of the superior cerebellar artery.” Neurosurgery 6 (1): 10-28. https://doi.org/10.1227/00006123- 198001000-00002. https://www.ncbi.nlm.nih.gov/pubmed/7354893. Hong, J. T., D. K. Park, M. J. Lee, S. W. Kim, and H. S. An. 2008. “Anatomical variations of the vertebral artery segment in the lower cervical spine: analysis by three-dimensional computed tomography angiography.” Spine (Phila Pa 1976) 33 (22): 2422-6. https://doi.org/10.1097/BRS.0b013e31818938d1. https://www.ncbi.nlm.nih.gov/pubmed/ 18923317. Lasjaunias, P, J Théron, and J Moret. 1978. “The occipital artery. Anatomy--normal arteriographic aspects--embryological significance.” Neuroradiology 15: 31-7. Lasjaunias, P., B. Vallee, H. Person, K. Ter Brugge, and M. Chiu. 1985. “The lateral spinal artery of the upper cervical spinal cord. Anatomy, normal variations, and angiographic aspects.” J Neurosurg 63 (2): 235-41. https://doi.org/10.3171/jns.1985.63.2.0235. https://www.ncbi.nlm.nih.gov/pubmed/4020445. Lister, J. R., A. L. Rhoton, Jr., T. Matsushima, and D. A. Peace. 1982. “Microsurgical anatomy of the posterior inferior cerebellar artery.” Neurosurgery 10 (2): 170-99. https://www.ncbi. nlm.nih.gov/pubmed/7070615. Luzzi S, Del Maestro M, Elbabaa S. K, Galzio R. 2019. “Letter to the Editor Regarding The “One and Done” Approach in the Combined Endovascular Surgical Treatment of Pediatric Cerebral Arteriovenous Malformations.” World Neurosurg. Luzzi, S., A. M. Crovace, L. Lacitignola, V. Valentini, E. Francioso, G. Rossi, G. Invernici, R. J. Galzio, and A. Crovace. 2018. “Engraftment, neuroglial transdifferentiation and behavioral recovery after complete spinal cord transection in rats.” Surg Neurol Int 9: 19. https://doi.org/10.4103/sni.sni_369_17. https://www.ncbi.nlm.nih.gov/pubmed/29497572. Luzzi, S., M. Del Maestro, D. Bongetta, C. Zoia, A. V. Giordano, D. Trovarelli, S. Raysi Dehcordi, and R. J. Galzio. 2018. “Onyx Embolization Before the Surgical Treatment of Grade III Spetzler-Martin Brain Arteriovenous Malformations: Single-Center Experience 58 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

and Technical Nuances.” World Neurosurg 116: e340-e353. https://doi.org/10.1016/j. wneu.2018.04.203. https://www.ncbi.nlm.nih.gov/pubmed/29751183. Luzzi, S., M. Del Maestro, S. K. Elbabaa, and R. Galzio. 2020. “Letter to the Editor Regarding “One and Done: Multimodal Treatment of Pediatric Cerebral Arteriovenous Malformations in a Single Anesthesia Event”.” World Neurosurg 134: 660. https://doi.org/ 10.1016/j.wneu.2019.09.166. https://www.ncbi.nlm.nih.gov/pubmed/32059273. Luzzi, S., M. Del Maestro, A. Elia, F. Vincitorio, G. Di Perna, F. Zenga, D. Garbossa, S. Elbabaa, and R. Galzio. 2019. “Morphometric and Radiomorphometric Study of the Correlation Between the Foramen Magnum Region and the Anterior and Posterolateral Approaches to Ventral Intradural Lesions.” Turk Neurosurg. https://doi.org/10.5137/1019- 5149.JTN.26052-19.2. https://www.ncbi.nlm.nih.gov/pubmed/31452176. Luzzi, S., M. Del Maestro, and R. Galzio. 2019. “Letter to the Editor. Preoperative embolization of brain arteriovenous malformations.” J Neurosurg: 1-2. https://doi.org/10.3171/ 2019.6.JNS191541. https://www.ncbi.nlm.nih.gov/pubmed/31812150 https://thejns.org/ view/journals/j-neurosurg/aop/article-10.3171-2019.6.JNS191541/article-10.3171-2019. 6.JNS191541.xml. Luzzi, S., M. Del Maestro, D. Trovarelli, D. De Paulis, S. R. Dechordi, H. Di Vitantonio, V. Di Norcia, D. F. Millimaggi, A. Ricci, and R. J. Galzio. 2019. “Endoscope-Assisted Microneurosurgery for Neurovascular Compression Syndromes: Basic Principles, Methodology, and Technical Notes.” Asian J Neurosurg 14 (1): 193-200. https://doi.org/10.4103/ajns.AJNS_279_17. https://www.ncbi.nlm.nih.gov/pubmed/30937 034. Luzzi, S., A. Elia, M. Del Maestro, S. K. Elbabaa, S. Carnevale, F. Guerrini, M. Caulo, P. Morbini, and R. Galzio. 2019. “Dysembryoplastic Neuroepithelial Tumors: What You Need to Know.” World Neurosurg 127: 255-265. https://doi.org/10.1016/j.wneu. 2019.04.056. https://www.ncbi.nlm.nih.gov/pubmed/30981794. Luzzi, S., A. Elia, M. Del Maestro, A. Morotti, S. K. Elbabaa, A. Cavallini, and R. Galzio. 2019. “Indication, Timing, and Surgical Treatment of Spontaneous Intracerebral Hemorrhage: Systematic Review and Proposal of a Management Algorithm.” World Neurosurg. https://doi.org/10.1016/j.wneu.2019.01.016. https://www.ncbi.nlm.nih.gov/ pubmed/30677572. Luzzi, S., M. Gallieni, M. Del Maestro, D. Trovarelli, A. Ricci, and R. Galzio. 2018. “Giant and Very Large Intracranial Aneurysms: Surgical Strategies and Special Issues.” Acta Neurochir Suppl 129: 25-31. https://doi.org/10.1007/978-3-319-73739-3_4. https://www. ncbi.nlm.nih.gov/pubmed/30171310. Luzzi, S., A. Giotta Lucifero, M. Del Maestro, G. Marfia, S. E. Navone, M. Baldoncini, M. Nunez, A. Campero, S. K. Elbabaa, and R. Galzio. 2019. “Anterolateral Approach for Retrostyloid Superior Parapharyngeal Space Schwannomas Involving the Jugular Foramen Area: A 20-Year Experience.” World Neurosurg. https://doi.org/10.1016/j.wneu.2019. 09.006. https://www.ncbi.nlm.nih.gov/pubmed/31520759. Luzzi, S., C. Zoia, A. D. Rampini, A. Elia, M. Del Maestro, S. Carnevale, P. Morbini, and R. Galzio. 2019. “Lateral Transorbital Neuroendoscopic Approach for Intraconal Meningioma of the Orbital Apex: Technical Nuances and Literature Review.” World Neurosurg 131: 10-17. https://doi.org/10.1016/j.wneu.2019.07.152. https://www.ncbi. nlm.nih.gov/pubmed/31356977. Vascular Anatomy of the Cranial Posterior Circulation 59

Luzzi, Sabino, Alberto Maria Crovace, Mattia Del Maestro, Alice Giotta Lucifero, Samer K. Elbabaa, Benedetta Cinque, Paola Palumbo, Francesca Lombardi, Annamaria Cimini, Maria Grazia Cifone, Antonio Crovace, and Renato Galzio. 2019. “The cell-based approach in neurosurgery: ongoing trends and future perspectives.” Heliyon 5 (11). https://doi.org/10.1016/j.heliyon.2019.e02818. Martin, R. G., J. L. Grant, D. Peace, C. Theiss, and A. L. Rhoton, Jr. 1980. “Microsurgical relationships of the anterior inferior cerebellar artery and the facial-vestibulocochlear nerve complex.” Neurosurgery 6 (5): 483-507. https://doi.org/10.1227/00006123-198005000- 00001. https://www.ncbi.nlm.nih.gov/pubmed/6251396. Martins, C., A. Yasuda, A. Campero, A. J. Ulm, N. Tanriover, and A. Rhoton, Jr. 2005. “Microsurgical anatomy of the dural arteries.” Neurosurgery 56 (2 Suppl): 211-51, discussion 211-51. https://doi.org/10.1227/01.neu.0000144823.94402.3d. https://www. ncbi.nlm.nih.gov/pubmed/15794820. Matsushima, K., K. Yagmurlu, M. Kohno, and A. L. Rhoton, Jr. 2016. “Anatomy and approaches along the cerebellar-brainstem fissures.” J Neurosurg 124 (1): 248- 63. https://doi.org/10.3171/2015.2.JNS142707. https://www.ncbi.nlm.nih.gov/pubmed/ 26274986. Matsushima, T., A. L. Rhoton, Jr., E. de Oliveira, and D. Peace. 1983. “Microsurgical anatomy of the veins of the posterior fossa.” J Neurosurg 59 (1): 63- 105. https://doi.org/10.3171/jns.1983.59.1.0063. https://www.ncbi.nlm.nih.gov/pubmed/ 6602865. Matsushima, T., A. L. Rhoton, Jr., and C. Lenkey. 1982. “Microsurgery of the fourth ventricle: Part 1. Microsurgical anatomy.” Neurosurgery 11 (5): 631-67. https://doi.org/ 10.1227/00006123-198211000-00008. https://www.ncbi.nlm.nih.gov/pubmed/7155330. Millimaggi, D. F., V. D. Norcia, S. Luzzi, T. Alfiero, R. J. Galzio, and A. Ricci. 2018. “Minimally Invasive Transforaminal Lumbar Interbody Fusion with Percutaneous Bilateral Pedicle Screw Fixation for Lumbosacral Spine Degenerative Diseases. A Retrospective Database of 40 Consecutive Cases and Literature Review.” Turk Neurosurg 28 (3): 454-461. https://doi.org/10.5137/1019-5149.JTN.19479-16.0. https://www.ncbi. nlm.nih.gov/pubmed/28481388. Palumbo, P., F. Lombardi, F. R. Augello, I. Giusti, S. Luzzi, V. Dolo, M. G. Cifone, and B. Cinque. 2019. “NOS2 inhibitor 1400W Induces Autophagic Flux and Influences Extracellular Vesicle Profile in Human Glioblastoma U87MG Cell Line.” Int J Mol Sci 20 (12). https://doi.org/10.3390/ijms20123010. https://www.ncbi.nlm.nih.gov/pubmed/ 31226744. Palumbo, P., F. Lombardi, G. Siragusa, S. R. Dehcordi, S. Luzzi, A. Cimini, M. G. Cifone, and B. Cinque. 2018. “Involvement of NOS2 Activity on Human Glioma Cell Growth, Clonogenic Potential, and Neurosphere Generation.” Int J Mol Sci 19 (9). https://doi.org/10.3390/ijms19092801. https://www.ncbi.nlm.nih.gov/pubmed/30227679. Raysi Dehcordi, S., A. Ricci, H. Di Vitantonio, D. De Paulis, S. Luzzi, P. Palumbo, B. Cinque, D. Tempesta, G. Coletti, G. Cipolloni, M. G. Cifone, and R. Galzio. 2017. “Stemness Marker Detection in the Periphery of Glioblastoma and Ability of Glioblastoma to Generate Glioma Stem Cells: Clinical Correlations.” World Neurosurg 105: 895- 905. https://doi.org/10.1016/j.wneu.2017.05.099. https://www.ncbi.nlm.nih.gov/pubmed/ 28559081. 60 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

Rhoton, A. L., Jr. 2000a. “The cerebellar arteries.” Neurosurgery 47 (3 Suppl): S29- 68. https://doi.org/10.1097/00006123-200009001-00010. https://www.ncbi.nlm.nih.gov/ pubmed/10983304. ––––– . 2000b. “The foramen magnum.” Neurosurgery 47 (3 Suppl): S155- 93. https://doi.org/10.1097/00006123-200009001-00017. https://www.ncbi.nlm.nih.gov/ pubmed/10983308. ––––– . 2000c. “The posterior fossa veins.” Neurosurgery 47 (3 Suppl): S69- 92. https://doi.org/10.1097/00006123-200009001-00012. https://www.ncbi.nlm.nih.gov/ pubmed/10983305. ––––– . 2002. “The supratentorial arteries.” Neurosurgery 51 (4 Suppl): S53-120. https://www.ncbi.nlm.nih.gov/pubmed/12234447. Ricci, A., H. Di Vitantonio, D. De Paulis, M. Del Maestro, S. D. Raysi, D. Murrone, S. Luzzi, and R. J. Galzio. 2017. “Cortical aneurysms of the middle cerebral artery: A review of the literature.” Surg Neurol Int 8: 117. https://doi.org/10.4103/sni.sni_50_17. https://www. ncbi.nlm.nih.gov/pubmed/28680736. Russo, V. M., F. Graziano, M. Peris-Celda, A. Russo, and A. J. Ulm. 2011. “The V(2) segment of the vertebral artery: anatomical considerations and surgical implications.” J Neurosurg Spine 15 (6): 610-9. https://doi.org/10.3171/2011.7.SPINE1132. https://www.ncbi. nlm.nih.gov/pubmed/21905775. Saeki, N., and A. L. Rhoton, Jr. 1977. “Microsurgical anatomy of the upper basilar artery and the posterior circle of Willis.” J Neurosurg 46 (5): 563-78. https://doi.org/ 10.3171/jns.1977.46.5.0563. https://www.ncbi.nlm.nih.gov/pubmed/845644. Spena, G., E. Roca, F. Guerrini, P. P. Panciani, L. Stanzani, A. Salmaggi, S. Luzzi, and M. Fontanella. 2019. “Risk factors for intraoperative stimulation-related seizures during awake surgery: an analysis of 109 consecutive patients.” J Neurooncol. https://doi.org/10.1007/s11060-019-03295-9. https://www.ncbi.nlm.nih.gov/pubmed/ 31552589. Szentirmai, O., Y. Hong, L. Mascarenhas, A. A. Salek, P. E. Stieg, V. K. Anand, A. A. Cohen- Gadol, and T. H. Schwartz. 2016. “Endoscopic endonasal clip ligation of cerebral aneurysms: an anatomical feasibility study and future directions.” J Neurosurg 124 (2): 463-8. https://doi.org/10.3171/2015.1.JNS142650. https://www.ncbi.nlm.nih.gov/ pubmed/26230466. Tubbs, R. S., E. G. Salter, J. C. Wellons, 3rd, J. P. Blount, and W. J. Oakes. 2005. “The triangle of the vertebral artery.” Neurosurgery 56 (2 Suppl): 252-5, discussion 252- 5. https://doi.org/10.1227/01.neu.0000156797.07395.15. https://www.ncbi.nlm.nih.gov/ pubmed/15794821. Ulm, A. J., M. Quiroga, A. Russo, V. M. Russo, F. Graziano, A. Velasquez, and E. Albanese. 2010. “Normal anatomical variations of the V(3) segment of the vertebral artery: surgical implications.” J Neurosurg Spine 13 (4): 451-60. https://doi.org/10.3171/2010.4. SPINE09824. https://www.ncbi.nlm.nih.gov/pubmed/20887142. Wanibuchi, M., T. Fukushima, F. Zenga, and A. H. Friedman. 2009. “Simple identification of the third segment of the extracranial vertebral artery by extreme lateral inferior transcondylar-transtubercular exposure (ELITE).” Acta Neurochir (Wien) 151 (11): 1499- 503. https://doi.org/10.1007/s00701-009-0360-z. https://www.ncbi.nlm.nih.gov/pubmed/ 19657583. Vascular Anatomy of the Cranial Posterior Circulation 61

Wen, H. T., A. L. Rhoton, Jr., T. Katsuta, and E. de Oliveira. 1997. “Microsurgical anatomy of the transcondylar, supracondylar, and paracondylar extensions of the far-lateral approach.” J Neurosurg 87 (4): 555-85. https://doi.org/10.3171/jns.1997.87.4.0555. https://www. ncbi.nlm.nih.gov/pubmed/9322846. Yaşargil, M. G. 1984. Microneurosurgery. Vol. v. 1: Thieme. Youssef, A. S., J. S. Uribe, E. Ramos, R. Janjua, L. B. Thomas, and H. van Loveren. 2010. “Interfascial technique for vertebral artery exposure in the suboccipital triangle: the road map.” Neurosurgery 67 (2 Suppl Operative): 355-61. https://doi.org/10.1227/ NEU.0b013e3181f741f7. https://www.ncbi.nlm.nih.gov/pubmed/21099558. Zeal, A. A., and A. L. Rhoton, Jr. 1978. “Microsurgical anatomy of the posterior cerebral artery.” J Neurosurg 48 (4): 534-59. https://doi.org/10.3171/jns.1978.48.4.0534. https://www.ncbi.nlm.nih.gov/pubmed/632878. Zoia, C., D. Bongetta, G. Dorelli, S. Luzzi, M. D. Maestro, and R. J. Galzio. 2019. “Transnasal endoscopic removal of a retrochiasmatic cavernoma: A case report and review of literature.” Surg Neurol Int 10: 76. https://doi.org/10.25259/SNI-132-2019. https://www. ncbi.nlm.nih.gov/pubmed/31528414. Zoia, C., D. Bongetta, F. Guerrini, C. Alicino, A. Cattalani, S. Bianchini, R. J. Galzio, and S. Luzzi. 2018. “Outcome of elderly patients undergoing intracranial meningioma resection: a single center experience.” J Neurosurg Sci. https://doi.org/10.23736/S0390- 5616.18.04333-3. https://www.ncbi.nlm.nih.gov/pubmed/29808631. Zoia, C., F. Lombardi, M. R. Fiore, A. Montalbetti, A. Iannalfi, M. Sansone, D. Bongetta, F. Valvo, M. Del Maestro, S. Luzzi, and R. J. Galzio. 2020. “Sacral solitary fibrous tumour: surgery and hadrontherapy, a combined treatment strategy.” Rep Pract Oncol Radiother 25 (2): 241-244. https://doi.org/10.1016/j.rpor.2020.01.008. https://www.ncbi.nlm.nih. gov/pubmed/32025222.

Chapter 4

VASCULAR ANATOMY OF THE SPINAL CORD

B. Del Sette1,*, A. Consoli2, R. Russo2 and G. Rodesch2, PhD 1Ospedale Maggiore della Carità di Novara, Novara, Italy 2Department of Diagnostic and Therapeutic Neuroradiology, Hôpital Foch, Suresnes, France

ABSTRACT

The three-dimensional vascular anatomy of the spinal cord is intricate and attractive to understand. An appropriate knowledge of the vessels anatomy, as well as its embryological development, is the basis for the comprehension of the medullary vascular pathologies. In this chapter, we report an exhaustive description of the intrinsic and extrinsic spinal cord vascularization of the arterial and venous system. We indicate the most appropriate angiographic approach to reveal cervical, thoracic and lumbar spinal cord vasculature, focusing on the pathophysiological and clinical aspects.

INTRODUCTION

Normal anatomy, physiology and pathological conditions affecting the vascular system of the spinal cord are better defined through the comprehension of embryological development of such structures, allowing more precise diagnostic methods, more appropriate therapeutic procedures and achieving better outcomes. Understanding vascular spinal cord pathologies relies on a deep knowledge of vessel anatomy as well as clinical manifestations, highlighting the importance of a multidisciplinary approach of the disease.

* Corresponding Author’s Email: [email protected]. 64 B. Del Sette, A. Consoli, R. Russo et al.

1. EMBRYOLOGY

During the third week of embryological growth 31 somites develop. These mesodermic structures are located on both sides of the neural tube and notochord; they compose consecutive embryological units along the anteroposterior axis of the embryo. Segmentation leads to development of segments called metameres. Each somite then receives a couple of segmental arteries, from the rostral and caudal ends of the embryo, which arise from the dorsal aorta. Each segmental artery takes in charge the vascularization of the ipsilateral tissues that will develop from the corresponding metamere (P. Lasjaunias 2001) (eg. Muscles, skin, bones, nerves and spinal cord). A metameric disposition of the vascular structure is thus achieved. Metameric arteries are the structures underlying the development of the vertebral vascular system. Conventionally, each metameric artery is named after the nerve that accompanies it inside the transverse foramen. At each level these arteries anastomose with the caudal and rostral metameric arteries, in the extra spinal and extradural space, developing also anastomoses that cross the midline. These anastomoses give rise to multi-metameric longitudinal extra spinal common trunks. During embryogenesis the peripheral nervous system develops before the central nervous system. The neural crest (which will form the peripheral nervous system) receives a dorsomedial branch of the ipsilateral segmental artery. The development of the two terminations of a spinal nerve has two goals: to orientate the dorsomedial artery towards the neural tube (central termination) and stimulate vascularization of the distal segment (peripheral termination). There is a direct relationship between nerves and arteries: from each artery to the cord there is a coupled nerve root that runs along the same route. It is safe to say that, if the point where nerve roots reach the spinal cord is the corresponding spinal myelomeric level, the point where radicular arteries reach the spinal cord identifies the origin of the nerve root and therefore its myelomeric origin (eg. a spinal artery that arises at Th10 will reach the spinal cord at Th10 alongside the nerve root of Th10 at the same myelomere). A dysregulation of vascular development during this stage will lead to an affection of the whole metamere, including the tissues derived from the same segment (Cobb syndrome or spinal arteriovenous metameric syndrome). Growth differences between spine and cord will modify the axial correspondence between the central myelomere and other somitic deriving tissues of the same level. This explains the oblique route of the nerve roots, and therefore of the radicular arteries following them. This obliquity is much more evident in the lower segments. Dorsomedial arterial branches anastomose one with another longitudinally with the caudal and rostral homologues, giving rise to two symmetrical ventral longitudinal arteries which vascularize the neural tube. Meanwhile a capillary network starts developing, which envelops the surface of the neural tube, with secondary flow induced definition of two longitudinal axes on the posterior surface. Between the fourth and sixth embryological week a classic and definitive anatomical disposition is achieved, with a distinct craniocaudal pattern.

 The two ventral longitudinal vessels migrate to the midline and fuse together in a single ventral longitudinal axis: the anterior spinal artery; duplications or fenestrations of this artery are consequences of an incomplete (or lack of) fusion along the midline. Each Vascular Anatomy of the Spinal Cord 65

unfused segment will perfuse the corresponding ipsilateral part of the spinal cord (Figure 1).

Figure 1. (A) Injection of right cervical artery with visualization of a duplication of the anterior spinal artery due to lack of fusion of ventral longitudinal arteries during embryological development, (B) injection of an anatomical sample shows two separate arterial ventral axis where lack of fusion occurred (courtesy of Philippe Mercier).

 During the first month of intrauterine life the intrinsic vascularization of the cord starts developing. During this phase sulcal arteries start to appear on the dorsal surface of the ventral longitudinal axis. After fusion of the central axis these arteries remain lateralized, therefore each sulcal artery feeds the ipsilateral half of the spinal cord. Proximal fusions of these arteries, with development of a common trunk, are extremely rare.  Arteries that follow dorsal roots will help develop a superficial network, mainly located on the posterior surface of the cord: the pial network. The same kind of arteries, located ventrally, will contribute to the vascularization of the anterior pial network.  Secondly, after development of the sulcal network, on the posterior surface of the cord, two longitudinal paramedian arteries will develop, with a tortuous course and not well- defined at the beginning, which correspond to the dominant flow inside the pial network (they are not embryonic vessels like the ventral artery): these will later develop into posterior or posterolateral spinal arteries.  Fusion and the desegmentation process lead to regression of some radicular branches of both the anterior and posterior network. Usually 4-8 anterior radicular and 10-20 posterior radicular branches will remain. This regression is predominant in the very caudal part of the cord, where only one radiculomedullary artery persists (artery of the lumbar enlargement, or artery of Adamkiewicz). This artery perfuses a large territory, comprising the lower thoracic, lumbar and sacral myelomeres. Persisting ventral radicular arteries represent radiculomedullary contributors to the anterior spinal axis, while persisting dorsal radiculopial arteries represent contributors to the posterior pial network. Axial disposition will gradually disappear while a longitudinal truncal 66 B. Del Sette, A. Consoli, R. Russo et al.

distribution of the arteries will develop. Residues of segmental arteries will vascularize nerves, bones or dura mater.

Extra spinal arteries undergo few modifications: intercostal and lumbar arteries share the same characteristics. Longitudinal intersegmental anastomosis will develop outside the spinal canal.

 At the cervical level vertebral arteries arise from extraspinal longitudinal anastomosis, specifically from the persistence and fusion of 6 intersegmental anastomoses between segmental cervical arteries; nevertheless, the transdural segment of the vertebral artery arises from a true segmental vessel: the proatlantal artery (Gailloud 2014).  The ascending cervical artery is formed and vascularizes C3 and C4 nerves.  At the thoracic and lumbar level the superior intercostal trunk is developed, which can harbor numerous multimetameric variants.  At the sacral level these anastomoses give rise to the lateral sacral arteries which originate from the internal iliac arteries, while the caudal portion of the dorsal aorta regresses and becomes the median sacral artery.

2. VASCULAR ANATOMY

We can identify three different types of radicular arteries: pure radicular, radiculopial and radiculomedullary. They can arise from a common trunk or each separately. Each of the 62 radicular arteries (31 left and 31 right) belongs to one of these subtypes. There is only one segmental artery for each nerve, which divides in a ventral and dorsal branch. Radicular arteries follow trajectories that have characteristic features in angiographic acquisitions on the anteroposterior view: they present an ascending course, following the route of the nerve roots and their obliquity may vary according to the level of origin (almost horizontal at the upper cervical level and almost vertical at the lower lumbar level). All radicular arteries have two fixed points: the transverse foramen and the origin of the nerve root from the spinal cord. Radicular arteries are present at each level alongside a spinal nerve (only C1 can be absent). These arteries represent the smallest contribution of the segmental embryonic system to the neural crest derivates. A focal narrowing of the vessel is frequently observed when these arteries enter the dura mater. One describes thus:

 Pure radicular arteries - (which vascularize only the nerve without contribution to the cord vasculature) are usually small and rarely visible at DSA examinations; pathological enlarged radicular arteries may be witnessed if a vascular lesion is present along the route of the nerve.  Radiculopial arteries - these are the arteries that reach the surface of the spinal cord and can be ventral or, more often, dorsal. They follow the corresponding nerve root and reach the ventral or dorsal surface of the cord, contributing to the ventral or dorsal pial network but not participating in the anterior spinal vascular axis; their vascular contribution is monosegmental and they anastomose with pial branches of the anterior Vascular Anatomy of the Spinal Cord 67

spinal artery through circumferential coronal vessels and through the lumbar basket, which connects anterior and posterior circulation (Figure 2).

Figure 2. Injection of anterior spinal artery (*) with reflux at the level of the basket (**) inside the left and right posterior spinal arteries and visualization of the caudal continuity of the anterior spinal artery below the basket: the artery of filum terminalis (arrow).

 Posterolateral medullary arteries represent a preferential arterial flow along the pial network, which is variable. They are not vessels with a proper embryological origin.  Radiculomedullary arteries - these arteries contribute to segmental and longitudinal vascularization and supply more than one segment of the spinal cord. Radiculomedullary arteries are the only vascular supply to the anterior spinal axis: they behave as radicular arteries along their proximal tract where they feed the corresponding segment of the nerve root. They follow the ventral surface of the nerve root and reach the ventral surface of the cord where they can give rise to pial branches that contribute to the anterior spinal network. Finally, they reach the ventral sulcus where they divide into an ascending and descending branch, which anastomose along the midline with the corresponding arteries above and below to form the anterior spinal artery. Radiculomedullary arteries are variable in number and location in each subject. Two radiculomedullary arteries are of relevance: the artery of the cervical enlargement and the artery of the lumbar enlargement. In 30-50 per cent of subjects, the artery of the lumbar enlargement, or artery of Adamkiewicz (N’Da H et al. 2016), contributes also greatly to the posterior pial network of the cord via pial collaterals. The origin of this vessel is extremely variable: in 75% of cases it arises between Th9 and Th12 usually from the left side. If its origin is above Th8 or below Th12 there is another associated radiculomedullary artery which arises caudally or cranially respectively. 68 B. Del Sette, A. Consoli, R. Russo et al.

2.1. Extrinsic Vascularization

There are two predominant dispositions in the spinal cord: longitudinal and transversal. Each of these systems receive different afferent arteries; the longitudinal ventral system receives radiculo-medullary arteries while the transverse and posterolateral longitudinal systems receive radiculopial arteries. Although the ventral spinal axis can be considered as an anatomical continuity of dominant radiculomedullary branches, it is also different since it represents the persistence of two different embryonic systems: the ventral longitudinal arteries and the axial segmental arteries.

Figure 3. Selective injection inside the left L1 lumbar artery: visualization of a radiculomedullary artery, with a cranial branch which anastomoses with the caudal branch of a radiculomedullary artery above (*), which is visualized by reflux. Due to the presence of these anastomoses the continuity of the anterior spinal axis is created.

 Anterior spinal artery (longitudinal ventral system) - The ventral spinal artery is described as a single continuous axis, which is formed below the vertebrobasilar junction up to the filum terminalis; it can be discontinuous, especially at the thoracic level, harbor irregular caliber or unfused segments, especially at the cervical level below the vertebrobasilar junction. This artery runs in the subpial space, superficially along the ventral sulcus, in strict connection with ventral spinal veins. Morphology of the radiculomedullary junction varies in each spinal cord segment. A “Y shape” is typical of the cervical region (Figure 3) while in the thoracolumbar level a “hairpin” shape is typical. At the end of the conus, the anterior spinal artery anastomoses with branches of the posterior pial network, giving rise to the basket: caudal continuity of the anterior spinal artery is the artery of filum terminalis. Any lesion vascularized by the distality of the anterior spinal artery below the conus can only be located on the Vascular Anatomy of the Spinal Cord 69

filum. On the other hand, it is not possible to observe vascular lesions of the cauda equina (Namba 2016) fed by the artery of filum terminalis since all vascular lesions of the cauda are vascularized by radicular branches. Likewise, a vascular lesion fed by the arteries arising from the basket or by lumbar or sacral branches can only be radicular.  Pial network (posterolateral longitudinal system) - The spinal cord is enveloped in a plexiform vascular network which is the pial network. This structure is more represented on the posterior surface of the cord: the dorsal surface is indeed covered by an extensive vascular network; among this network it is possible to recognize two dominant longitudinal vessels: the posterior spinal arteries. Other types of vascular dispositions can be described: medial (with presence of a median dorsal accessory artery) or lateral, mainly at the cervical level as the lateral spinal artery. The junction with the vertebral system shows the links between the postero -inferior cerebellar artery (PICA), the transdural segment of the vertebral artery and the dorsolateral vasculature of the cord. Depending on the origin of PICA, the pial spinal vasculature can arise from the vertebral artery (if the PICA originates distally) or from the proximal part of the PICA itself. In most cases this dominant cervical dorsal network runs anteriorly to the dorsal roots and represents the lateral spinal artery which contributes to the pial network, following the origin of the accessory nerve. More caudally this vessel runs dorsally to the dorsal roots until C4 level where it connects with the posterior pial network. The lateral spinal artery vascularizes the posterior columns.  Radiculopial arteries contribute to the constitution of a posterior pial network along the whole cord while contribution of anterior radiculopial arteries is rare. When radiculopial arteries reach the cord they show the typical “hairpin” curve shape: the curve is sharper the lower these arteries are located. Sometimes, posterolateral spinal arteries of the right and left side originate from a single common radiculopial trunk.  At the caudal portion of the cord, two dorsolateral arteries anastomose with the ventral axis, forming the basket, which has a characteristic tripod shape at angiographic imaging (Figure 3).

The pial network can be subdivided in three sectors, dorsal, lateral and ventral, wich anastomose on the axial plane:

 The dorsal pial network crosses the midline. It vascularizes the dorsal surface of the cord bilaterally and gives rise to perforating arteries of small caliber which penetrate the posterior columns.  The lateral pial network is found between the dorsal and ventral nerve roots; it receives small pial branches from radiculopial and radiculomedullary arteries and forms axial dorsoventral anastomosis.  Amongst the pial network there can also be some short longitudinal anastomoses, although these are rarely functionally effective to support a true lateral longitudinal network.  The ventral pial network is vascularized by ventral radiculopial branches and collateral pial branches of the radiculo-medullary arteries.

70 B. Del Sette, A. Consoli, R. Russo et al.

The pial network, which covers the whole spinal cord, is, nevertheless, not a system capable of supporting a sufficient collateral flow to the cord in case of spinal artery occlusion.

2.2. Intrinsic Vascularization

Intrinsic vascularization of the spinal cord includes ventrally the sulcal arteries, arising from the anterior spinal axis, and dorsally the radial perforating arteries, which arise from the circumferential pial network. Although these perforating arteries are located on an axial place, longitudinal extrinsic or intrinsic anastomoses do exist.

Figure 4. Cone-Beam CT after selective injection of a common supreme intercostal trunk of Lazorthes type: sagittal (a) and axial (b) views. A: note the intersulcal longitudinal anastomosis in the depth of the ventral sulcus (thick arrow), linking sulcal arteries (enlarged because of an AVM, not shown). The posterior spinal network is well seen (double arrows) with its perforating arteries penetrating into the posterior funiculi (*). B: visualization of two sulcal arteries (arrow) which are lateralized in the ventral sulcus before penetrating the spinal cord; visualization of the posterior pial network (*) which covers the posterior columns, which is connected with corresponding pial arteries of the anterior spinal axis through the vasa corona (arrowheads). From this pial network arise the centripetal perforating arteries, which contribute to the intrinsic vascularization of the cord (small arrows). Transmedullary arterial anastomosis between centripetal and centrifugal arteries can be seen (**).

 Sulcal arteries - they arise from the anterior spinal axis. During embryogenesis they arise from the dorsal surface of each ventral longitudinal axis; after fusion at the midline they remain lateralized: they vascularize the ventral left or right half of the cord. If no fusion occurs, each separated axis will give rise to its sulcal artery, which vascularizes its half of the spinal cord (Figure 4). Some common bilateral trunks can be exceptionally found; there are no anastomoses crossing the midline. Before penetrating the spinal cord, sulcal arteries will run on the ventral sulcus at a subpial level and can give ascending and descending branches, which anastomose cranially and caudally with the upper and lower sulcal arteries of the same side. Inside the cord, Vascular Anatomy of the Spinal Cord 71

sulcal arteries bifurcate inside the grey matter, where they generate the centrifugal system of Adamkiewicz. The density of the sulcal arteries is related to the density and activity of the grey matter. Therefore, at each spinal level their role varies: at the cervical and lumbar enlargement, sulcal arteries feed approximately 50% of the cord section, while at the thoracic level they feed up to 15-20% of it. Nevertheless, at the thoracic level, there is a higher concentration of pial and intramedullary anastomosis, suggesting an overlap or a more effective arterial equilibrium between pial and ventral feeders. Radiculomedullary arteries fix the spinal cord inside the spinal canal, while sulcal arteries fix the anterior spinal arterial axis to the cord. During postnatal growth of the spinal cord and vertebral column, the ventral spinal artery applies traction on the sulcal arteries; even if the vascular supply of sulcal arteries is mostly on the axial plane, they present an ascending oblique route on the ventral sulcus before penetrating the cord, prolonging the ascending route of the radiculomedullary arteries. This disposition is acquired after birth, while during fetal life sulcal arteries present exclusively an axial orientation.  Radial perforating arteries - They arise from the pial network and they form the centripetal system of Adamkiewicz. They penetrate inside the white matter, where they divide into numerous small caliber branches mostly on the axial plane but also on the longitudinal one. Other blood vessels follow the nervous fibers of the dorsal root, reaching the posterior horns of the grey matter. This disposition is more often witnessed in the posterior columns but it can be seen also in lateral and ventral columns.  Intrinsic anastomosis - There are two main different types of anastomosis, axial and longitudinal: ˗ Axial anastomoses can be sulco-ventro-lateral or sulco-dorso-lateral and are both more common at thoracic level ˗ Longitudinal anastomoses ˗ Other anastomoses can involve sulcal and radial arteries on the axial plane, marginally to the grey matter. Some precapillary anastomoses have been described. They can be 2 or 3 times bigger than medullary capillaries. All this vascular disposition forms an uninterrupted network of blood vessels inside the cord, inside both grey and white matter. These arteries are considered to be terminal arteries. Nevertheless, in arteriovenous malformation of the spinal cord, blood flow due to shunt can keep patent wide intrinsic anastomosis; communication between normal and pathological blood vessels is possible: an intramedullary arteriovenous malformation is therefore formed by abnormal vessels but also normal intrinsic vessels, dilated due to the shunt. Morbidity reported after surgical or endovascular complete treatments can be explained by specific iatrogenic alterations of normal intrinsic vascularization of the spinal cord.

Although there are fewer sulcal arteries at the thoracic level compared to cervical and lumbar enlargements, blood supply to this area is sufficient for the amount of grey matter found at this level. Yoss (Peterman, Yoss, and Corbin 1958) described the effects of the occlusion of a ventral spinal artery in a primate, which led to severe ischemia of the anterolateral two thirds 72 B. Del Sette, A. Consoli, R. Russo et al. of the spinal cord at the entry point of this artery inside the cord and also cranially and caudally. Studying the spinal cord tissue response to anoxia, Gelfan (Gelfan and Tarlov 1955) described a lower resistance to this pathological condition in motor neurons. Krogh (Krogh 1950) demonstrated, in experimental studies on rabbits, that peripheral motor neurons located in the anterior horns were more resistant to anoxia if compared to the more central ones. In these types of cells, located in a watershed area, resistance to anoxia does not appear to be related to the number of feeding vessels. The neuron cell is the functional unit of the spinal cord grey matter, around which the blood vessels will develop. Cellular resistance to anoxia is therefore unrelated to the number of feeding vessels and the recovery after the lack of oxygen seems to be related to the sensitivity of the tissue to the cellular anoxia. Different animal species reacts differently to hypoxia of the central nervous system and therefore experimental animal studies cannot be directly compared to human physiopathology. The characteristics of blood supply and extension of the vascular territory of the anterior spinal artery on the spinal cord resemble the characteristics of the internal carotid artery for cerebral hemispheres. Anterior spinal artery syndrome is rarely described at cervical level, because, at this level, most of the time the ventral axis is duplicated and vascular feeders are often located on multiple consecutive metamers. This syndrome can be complete at cervical levels if the axes are fused together; if occlusion of only one axis occurs this will give rise to an incomplete syndrome of Brown-Séquard. Precise anatomical knowledge and good qualitative angiographic exams lead to a better understanding of spinal arterial pathologies. From a practical point of view: Study of the cervical spinal cord vascularization must always include:

 Injection of the two vertebral arteries.  Injection of the cervical arteries (ascending and deep) bilaterally.

The aim of the exam is to verify the continuity and aspect of the anterior spinal axis(Chen and Gailloud 2011). At the vertebrobasilar junction, the anterior spinal axis often arises from the vertebral artery on the side of the dominating PICA; if there is no dominant configuration of PICA, it may arise symmetrically by both vertebral arteries; this arterial segment can anastomose at midline with other radiculomedullary arteries, such as the artery of the cervical enlargement. The posterior cervical arterial pial network is constituted, in its cranial part, by the lateral spinal artery, which arises directly from the vertebral artery or the PICA (depending on the origin of the PICA). This artery anastomoses with other radiculopial arteries which arise more caudally from cervical or vertebral arteries. If there are no pathological vascular malformations, the lateral spinal artery has a small calibre and it is rarely seen on DSA. Study of the thoracic spinal cord has to be performed by selective catheterization of intercostal arteries. All vessels feeding the pathological segment must be catheterized on both sides, to visualize the potential origin of each radiculopial and radiculomedullary arteries. Radiculomedullary arteries anastomose on the midline (upper caudal branch and lower cranial branch) and this anastomosis contributes directly to the continuity of the anterior spinal axis. Radiculopial arteries are thinner and lateralized; the same longitudinal disposition of these pial vessels is found on the posterior surface of the spinal cord: the posterior anastomosis between the two pial axes, left and right, will contribute to the development of the posterior pial network. Their curved “hairpin” shape is tighter where these arteries reach the surface of the spinal cord, Vascular Anatomy of the Spinal Cord 73 and sharper than the homologous radiculomedullary anastomosis, therefore easily recognizable. Study of the lumbar spinal cord and conus medullaris must be performed by catheterization of the lower intercostal arteries and iliolumbar arteries, up to the lateral sacral arteries. It is important to visualize the lumbar basket which surrounds the conus medullaris, and helps to recognize the anastomosis between radiculomedullary arteries, radiculopial arteries and the artery of filum terminalis (which represents the continuity of the anterior spinal artery). Injection of the radiculomedullary artery of the lumbar enlargement (artery of Adamkiewicz) helps visualize the basket. Good quality injection will help to depict properly some arterial branches for the cauda equina. If no basket is visualized by injection of the intercostal arteries, the iliolumbar arteries must be checked, since some radiculomedullary arteries may have lower origin.

3. SPINAL CORD VEINS

Study and comprehension of spinal vascular malformations, have led to a better understanding of venous vascular anatomy of the spinal cord and to a better comprehension of their role in physiopathology of the symptoms related to these malformations.

3.1. Intrinsic Spinal Cord Veins

The intrinsic spinal cord venous system consists in a large venous capillary network which is located inside the spinal cord itself, and anastomoses symmetrically on the axial plane. A ventral (anterior) dominance, like that described for the arterial system, is partially encountered at the thoracolumbar level. Dorsal dominance is witnessed at the thoracic level (Chen, Ethiati, and Gailloud 2012). If a large intrinsic anastomotic network is thus seen predominant at the thoracic level, it can be present along the whole spinal cord. Axial anastomoses connect sulcal veins and radial ventro –dorso -lateral and ventro –dorso -medial veins. Longitudinal anastomoses are also present, inside both grey and white matters. The importance of these anastomoses explains the extension of spinal cord alteration over multiple myelomeres even in the presence of small and focal arterio-venous lesions: venous congestion can therefore propagate over multiple adjacent levels. Transmedullary veins have also been described; they are orientated on an oblique pattern, having large caliber, up to 700 microns of diameter at thoracic level. Similar venous structures have been reported at cerebral level: the transcerebral veins, which have an important role in balancing pressure and CSF reabsorption rate. It is still difficult to assess a precise analogy between these two structures: transmedullary veins are anastomotic veins, (Gregg and Gailloud 2015) but they do not receive venous collectors from the deep spinal cord structures, while transcerebral veins function as a bridge between sub ependymal and subpial systems. Transcerebral veins take part in the constitution of developmental venous anomalies (DVA), but these kinds of anomalies are not seen at the spinal level. Intrinsic veins can still participate in the constitution of a pathological intramedullary nidus and, therefore, it can be supposed that 74 B. Del Sette, A. Consoli, R. Russo et al. a nidus is composed by some abnormal vessels as well as normal dilated vessels that can be represented by dilated intrinsic nutritional arteries or by congested intrinsic venules. What has been described in patients with evolutive vascular lesions as “capillary neovascularization” can correspond to:

 either a dilated and congested intrinsic network.  or an intrinsic vascularization of de novo formation, due to repeated ischemic damage and hypoxia related to chronic venous congestion.

Complication rates described after surgical curative treatment of intradural arteriovenous malformations are probably related to iatrogenic damage of these normal vessels that constitute part of the malformation and are not easily recognized.

3.2. Extrinsic Medullary Veins

They include the venous pial network, the longitudinal collectors and radicular veins (Figure 5). The venous pial network consists of the longitudinal venous disposition that connects intrinsic perforating veins as large lateral and dorsoventral anastomoses; ventral sulcal and dorsal veins drain the venous blood from grey matter territories. Some pial collectors join together and compose common trunks, which are more present than their arterial homologues, especially on the ventral side. Laterally, the presence of short intersegmental channels represents the communications between adjacent radial collectors, which are not developed enough to create a functional longitudinal venous network. Longitudinal collectors can be divided into two main systems: one ventral and the other dorsal. Along the midline, in most cases, at cervical and lumbar levels, there is only one collector, while at thoracic level up to three different collectors have been described. Association between the number of transmedullary anastomoses and longitudinal collectors at this level can explain the tendency of congestion and venous stasis. Lazorthes (Lazorthes 1949) described a fragility in thoracic spinal cord vascular disposition which appears to be more connected to a venous anatomical organization rather than to an arterial one: the thoracic venous draining system seems to have a bipolar disposition, which collects cranially the venous drainage of the cervical level, while caudally that of lumbar level, with convergent aspect in both cases. This particular feature of structural anatomy of the thoracic venous draining system, can develop a natural obstacle to blood drainage in case of pathologies which affect thoracolumbar radicular veins. Dural fistulae which drain into longitudinal veins, can worsen the functionality of this anatomical disposition, leading to retrograde venous congestion, with reflux into radial veins. Intracranial dural shunts, drained caudally into medullary veins, can be confronted to the convergent system of the thoracic level. Symptoms related to these spinal cord pathologies can be linked to this kind of anatomical configuration.

Vascular Anatomy of the Spinal Cord 75

Figure 5. Injection of an anatomical sample showing the dorsal venous pial network on the surface of the cord. Multiple radicular veins (*) can be seen merging into a larger dorsal longitudinal collector (**) (courtesy of Philippe Mercier).

A slow flow in these lesions can develop irreversible haemodynamic conditions that can lead to stasis and even venous thrombosis, even after complete occlusion of the shunt. Necrotizing myelopathy of Foix and Alajouanine can represent the final stage of a venous myelopathy. At cervical level, the cranial venous anastomoses of the spinal cord venous system create a favorable configuration for the venous drainage. Ventral spinal veins are located in the subpial space, while dorsal ones are located in the subarachnoid space. Moderate congestion of the ventral veins due to an arteriovenous shunt can be observed on MR as signal hyperintensity due to spinal cord suffering, even if no venous dilatation is visible, with the congested vein that is “trapped” in the subpial space. Dorsal subarachnoid veins, on the contrary, can dilate more rapidly and evidently with higher chance of rupture due to venous hypertension. Some cases of subarachnoid haemorrhage in spinal vascular malformations are secondary to rupture of the posterior subarachnoid veins, since anterior subpial veins rupture is more often linked to haematomyelia.

3.3. Radicular Veins

Dorsal and ventral radicular veins are often seen as the venous draining system is balanced on the anterior and posterior surface. A thoracolumbar enlargement vein is commonly described during angiographic examinations, after adequate injection of the radiculomedullary artery of the lumbar enlargement (artery of Adamkiewicz). In most cases, visualization of the anterior venous axis is inconstant and variable. The exit point of the radicular vein is nearly localized on the point of the dural penetration of the artery. Phlebogram quality depends on the supplied territory of the injected artery. 76 B. Del Sette, A. Consoli, R. Russo et al.

As it has been described for radicular arteries, it is possible to observe pure radicular veins: these veins travel along nerve roots only in 60% of cases; in the other 40%, veins enter the dura mater through a different foramen, between two different nerve roots, and do not follow a segmental disposition. Transdural portion of the radicular vein can have an extension of up to 1cm; at the dural entry point, a narrowing of the vessel can always be seen. This has been considered as an anti- reflux system, which protects the spinal cord from intraabdominal pressure alterations. Although interesting, this theory cannot be completely confirmed, since phlebographies have allowed visualization of radicular veins.

3.4. The Spinal and Extraspinal Venous System

Epidural venous channels of the spine can be compared to those at the skull base with whom they anastomose. Epidural dorsal veins have small calibre; the ventral plexus is connected to the bone and drains mainly the vertebral body. Different factors can influence blood flow inside this venous system: gravity, position, variations in thoracic and intraabdominal pressure. Intracranial dural sinus pressure can range from 10 cmH2O (in supine position) to negative pressure (in orthostatism); moreover, venous flow characteristics at the spinal cord level are different depending on the position (above or below the heart). The respiratory cycle also has an important role in aiding the caudal venous drainage, generating negative pressure and promoting a central flow during inspiration. It is therefore also possible to hypothesize that at thoracolumbar level arterial blood flow depends on cardiac rhythm, while venous flow is connected to the respiratory cycle. Extradural venous channels are arranged in a hexagonal shape and anastomose along the midline with rostral and caudal systems. They form a continuous system from the sacrum to the skull base. Extradural veins drain equally the bony borders of the spinal canal: ventral and dorsal veins collect venous blood from vertebrae and join the extradural venous system which lacks valves. Radicular veins can travel alongside the nerve roots, but do not present the typical metameric distribution as seen in the arterial system. They usually join the perinervous foraminal venous plexus, but can also reach venous lacunae which drain into the extradural longitudinal ventral plexus. The relationship between cerebral spinal fluid circulation and the venous spinal system is not completely clear, although a process of liquor reabsorption at spinal level has been described.

REFERENCES

Chen, J., T. Ethiati, and P. Gailloud. 2012. “Flat panel catheter angiotomography of the spinal venous system: an enhanced venous phase for spinal digital subtraction angiography.” AJNR Am J Neuroradiol 33 (10): 1875-81. https://doi.org/10.3174/ajnr.A3111. https://www.ncbi.nlm.nih.gov/pubmed/22723065. Vascular Anatomy of the Spinal Cord 77

Chen, J., and P. Gailloud. 2011. “Safety of spinal angiography: complication rate analysis in 302 diagnostic angiograms.” Neurology 77 (13): 1235-40. https://doi.org/10.1212/ WNL.0b013e3182302068. https://www.ncbi.nlm.nih.gov/pubmed/21917768. Gailloud, P. 2014. “The supreme intercostal artery includes the last cervical intersegmental artery (C7) - angiographic validation of the intersegmental nomenclature proposed by Dorcas Padget in 1954.” Anat Rec (Hoboken) 297 (5): 810-8. https://doi.org/10.1002/ ar.22893. https://www.ncbi.nlm.nih.gov/pubmed/24610867. Gelfan, S., and I. M. Tarlov. 1955. “Differential vulnerability of spinal cord structures to anoxia.” J Neurophysiol 18 (2): 170-88. https://doi.org/10.1152/jn.1955.18.2.170. https://www.ncbi.nlm.nih.gov/pubmed/14354454. Gregg, L., and P. Gailloud. 2015. “Transmedullary Venous Anastomoses: Anatomy and Angiographic Visualization Using Flat Panel Catheter Angiotomography.” AJNR Am J Neuroradiol 36 (7): 1381-8. https://doi.org/10.3174/ajnr.A4302. https://www.ncbi.nlm. nih.gov/pubmed/25953764. Krogh, E. 1950. “The effect of acute hypoxia on the motor cells of the spinal cord.” Acta Physiol Scand 20 (4): 263-92. https://doi.org/10.1111/j.1748-1716.1950.tb00704.x. https://www.ncbi.nlm.nih.gov/pubmed/15425355. Lasjaunias, P., A. Berenstein, K. Ter Brugge. 2001. Surgical Neuroangiography. Clinical Vascular Anatomy and Variations. edited by A. Berenstein P. Lasjaunias, K. Ter Brugge. Berlin Heidelberg: Springer-Verlag. Lazorthes, Guy, René Leriche. 1949. Le Système Neurovasculaire: étude Anatomique, Physiologique, Pathologique Et Chirurgicale [The Neurovascular System: Anatomical, Physiological, Pathological And Surgical Study]. . Paris: Masson. N’Da H, A., L. Chenin, C. Capel, E. Havet, D. Le Gars, and J. Peltier. 2016. “Microsurgical anatomy of the Adamkiewicz artery-anterior spinal artery junction.” Surg Radiol Anat 38 (5): 563-7. https://doi.org/10.1007/s00276-015-1596-3. https://www.ncbi.nlm.nih.gov/ pubmed/26627692. Namba, K. 2016. “Vascular Anatomy of the Cauda Equina and Its Implication on the Vascular Lesions in the Caudal Spinal Structure.” Neurol Med Chir (Tokyo) 56 (6): 310- 6. https://doi.org/10.2176/nmc.ra.2016-0006. https://www.ncbi.nlm.nih.gov/pubmed/ 27021641. Peterman, A. F., R. E. Yoss, and K. B. Corbin. 1958. “The syndrome of occlusion of the anterior spinal artery.” Proc Staff Meet Mayo Clin 33 (2): 31-7. https://www.ncbi.nlm.nih. gov/pubmed/13505884.

SECTION II: DIAGNOSIS, PREOPERATIVE EVALUATION AND SURGICAL PLANNING

Chapter 5

INTRACRANIAL ANEURYSMS

ABSTRACT

Intracranial aneurysm is a cerebrovascular disease characterized by local pathological enlargement of cerebral arteries. Many risk factors are involved in the pathogenesis, but the precise mechanisms underlying formation, progression, and rupture remain unclear. This chapter provides a comprehensive overview of the epidemiology, pathophysiology, classification systems, and diagnostic management based on current evidence in literature. Special regard is dedicated to histological and angioarchitectural features, natural history, rupture predictor signs, and risk stratification for intracranial aneurysms. Clinical characteristics of subarachnoid hemorrhage and the best diagnostic techniques are presented in order to improve patient evaluation and choice of successful treatment strategy.

Keywords: intracranial aneurysm, subarachnoid hemorrhage, inflammation, endothelial disfunction, wall shear stress

 Corresponding Author’s Email: [email protected]. 82 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

1. OVERVIEW

Intracranial aneurysms are the most common vascular abnormalities in adulthood characterized by focal enlargment of the arterial walls, with structural deterioration of the internal elastic lamina and disruption of the tunica media. Aneurysms are usually an incidental finding in postmortem autopsy series as 1%–6% of the population harboring an aneurysm, with a prevalence of 3.2% (Juvela 2011). Thin-walled regions of aneurysms are susceptible to rupture, leading to subarachnoid hemorrhage (SAH), severe clinical conditions, and are lethal in 65% of cases (Wiebers et al. 2003). SAH has an incidence of 6–8 per 100,000 person years, peaking in the sixth decade (Johnston, Selvin, and Gress 1998), and accounts more than 25% of stroke victims. The pathophysiology of this devastating cerebrovascular disease is closely related to molecular, hemodynamic, and genetic factors resulting in degradation of the integrity and bulge of the arterial wall. Recent studies based on histological findings clarified the essential role of endothelial dysfunction and inflammatory cascades underlying aneurysm formation, growth, and rupture; however, the exact mechanism(s) remain obscure. Despite tremendous technical development in neurovascular surgery techniques (Ciappetta, Luzzi, et al. 2009; Ciappetta, Occhiogrosso, et al. 2009; Del Maestro et al. 2018; Gallieni et al. 2018; S. Luzzi, Del Maestro, et al. 2018; S. Luzzi, Del Maestro, and Galzio 2019; S. Luzzi, Elia, Del Maestro, Morotti, et al. 2019; S. Luzzi, Gallieni, et al. 2018; Ricci et al. 2017; De Tommasi, De Tommasi, et al. 2006; S. Luzzi et al. 2020) involving the knowledge of the pathogenic pathways, morphological classification criteria, improvement in diagnostic techniques, and stratification of pre-operative risk, the mortality, and morbidity of aneurysmal SAH remains high.

2. GENETICS

In recent years, many clinical trials have shown an increased incidence of hereditary aneurysms associated with a large number of genetic conditions. A positive family history is the greatest risk factor. Patients with a relative with an aneurysm have 4% risk; the risk increases to 10% with two or more affected first-degree family members (Johnston, Selvin, and Gress 1998; Korja, Lehto, and Juvela 2014). Genome-wide linkage studies have demonstrated the role of several chromosomal loci involved in familial aneurysm occurrence. In particular, one major documented association is among the cyclin-dependent kinase inhibitor 2B, antisense inhibitor gene on chromosome 9, SOX17 transcription regulator gene on chromosome 8, and endothelin receptor A gene (Alg et al. 2013). The association is logically explained by the role of endothelin-1 in vasoconstriction (Caranci et al. 2013). Moreover, the T786C polymorphism of the endothelial nitric oxide synthase (NOS) gene is closely linked because it is responsible for normal function of nitric oxide, a vasoprotective molecule (Marchese et al. 2010). Regarding the transcriptor gene of interleukin (IL)-6, a pro-inflammatory cytokine, two polymorphisms have been studied: G572C increased the risk, while G174C seems to be protective (Sun, Zhang, and Zhao 2008; Liu et al. 2012). Recently, a polymorphism of the TP53 gene has been found to increase susceptibility to aneurysm occurrence (Li et al. 2012). Two clinical studies have highlighted the different biological characteristics of hereditary and sporadic aneurysms: the Familial Intracranial Aneurysm (Broderick et al. 2005), an Intracranial Aneurysms 83 international multicenter trial aimed at identifying genetic issues, and the International Study of Unruptured Intracranial Aneurysms (International Study of Unruptured Intracranial Aneurysms 1998), which is based on demographic data and aneurysm site, size, and features. Results revealed that familial aneurysms are larger, more likely to be multiple, and more frequently located in the middle cerebral artery [MCA] (Bromberg et al. 1995), unlike the sporadic ones, which are typically found in the posterior communicating artery (Mackey et al. 2012). Additionally, aneurysm diagnosis in patients with a positive family history usually occurs in the fifth decade and at a younger age in successive generations, suggesting a genetic mechanism of anticipation (Bromberg et al. 1995) different from the sixth decade for sporadic cases (Kassell et al. 1990). Therefore, it is imperative that patients with two affected first-degree relatives undergo early neuroimaging screening. Beyond the familiar occurrence, other heritable genetic diseases are associated with aneurysm formation, including adult polycystic kidney disease (Rinkel et al. 1998). Adult polycystic kidney disease predisposes to a 40% risk of aneurysm in 10%–30% of multiple cases (Masoumi et al. 2008). Ehlers-Danlos syndrome type IV is a rare inherited connective tissue disorder caused by mutation of COL3A1, which codes for type III procollagen, causing abnormal synthesis of collagen type III, fragility of vessel walls, and aneurysm development (Grassl et al. 1979). Floating-Harbor syndrome is due to mutation of SRCAP, a gene that encodes SNF2-related chromatin-remodeling ATPase protein which plays a key role in the growth process of endothelial cells and vascular repair (Menzies et al. 2019). Furthermore, less common hereditary conditions seem to be implied in the pathogenesis of aneurysms, including Marfan syndrome (Finney, Roberts, and Anderson 1976), neurofibromatosis type I (Morooka and Waga 1983), pseudoxanthoma elasticum (Munyer and Margulis 1981), hereditary hemorrhagic telangiectasia (Roman et al. 1978), and 1-antitrypsin deficiency (Schievink et al. 1996).

3. RISK FACTORS

Several patient-related risk factors have been detected in the occurrence of acquired brain aneurysms, of which old age, hypertension, female sex, and cigarette smoking are the most revelant. An age over 55 years and high blood pressure, in conjunction with hypercholesterolemia, atherosclerosis, or ischemic heart disease, create a pro-inflammatory setting and chronic hemodynamic stress of the vascular wall that greatly predisposes to formation and evolution of an aneurysm. Unruptured aneurysms are more common in females (3:1 females:males), especially in the postmenopausal period, due to the protective role of estrogen against inflammatory reactions and reduction of leukocytes in cerebral vessels. Active cigarette smoking promotes endothelial disfunction, increasing reactive oxygen species (ROS) and inflammatory cells and resulting in progressive artery wall damage. In addition, alcohol consumption, drug abuse (Oyesiku et al. 1993), and oral contraceptives also contribute to insult to the arterial wall. Recent prospective studies have compared the location of aneurysms and different risk factors, highlighting that aneurysms sited at the anterior communicating artery and MCA are more frequent in patients over 55 years-old; those localized at the posterior communicating artery are not common in males, and those at the basilar artery are not related to alcohol abuse. 84 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

4. PATHOGENESIS

4.1. Hemodynamic Stress and Endothelial Dysfunction

The pathogenic pathways underlying aneurysm development begin with disruption of the physiological homeostatic balance between hemodynamic stress and structural integrity of the vascular wall. High wall shear stress (WSS) due to the impingement of blood flow loaded mainly on arterial bifurcation sites triggers aneurysm formation (Sforza, Putman, and Cebral 2009). In response to WSS, endothelial cells are subject to functional and morphological modifications, with inversion of the ratio between synthesis and degradation of protein in the extracellular matrix, shape elongation, decrease of cellular components, and consequently, loss of mechanical strength properties of vascular walls (Sakamoto et al. 2010; Szymanski et al. 2008). Endothelial dysfunction induced by hemodynamic stress is followed by inflammatory cascade activation and abnormal remodeling of arterial walls.

4.2. Role of Inflammation

Over the last decade, experimental molecular advances in all fields of neurosurgery (Bellantoni et al. 2019; Cheng, Shetty, and Sekhar 2018; De Tommasi et al. 2008; De Tommasi et al. 2007; Guastamacchia et al. 2007; Sabino Luzzi, Crovace, et al. 2019; S. Luzzi, Crovace, et al. 2018; S. Luzzi, Elia, Del Maestro, Elbabaa, et al. 2019; S. Luzzi, Giotta Lucifero, et al. 2019; Palumbo et al. 2019; Palumbo et al. 2018; Raysi Dehcordi et al. 2017; Spena et al. 2019; Zoia et al. 2018; Antonosante et al. 2020; Campanella et al. 2020; Zoia et al. 2020) have clarified the role of active inflammatory responses in the pathogenesis of aneurysms. Chronic inflammation is mediated by macrophage infiltration and activation, with self-amplifying signaling pathways that determine the generation and progression of aneurysms. The first step is activation of NF-κB, mediated by prostaglandin E2 through the prostaglandin E receptor subtype 2, which induces expression of genes encoding COX-2. There is a clear correlation between WWS and inflammatory reaction. The fluid shear stress and eccessive WSS exerted on vessel walls stimulate translocation into the nucleus and trascription of NF-κB (Mohan, Mohan, and Sprague 1997). NF-κB is involved in production of the majority of pro-inflammatory genes. It synthesizes monocyte chemoattractant protein-1 and vascular cell adhesion molecule-1, which recruit macrophages to the aneurysm wall. Extensive infiltration of macrophages into cerebral arterial walls determines the spread of cytokines and proteinases, intensifying the inflammatory process. There are two different macrophage phenotypes with opposite functions: M1-like (pro- inflammatory) and M2-like (anti-inflammatory). Immunohistochemical studies have shown an increase in the ratio of M1/M2 macrophases in the aneurysmal wall, validating the thesis that M1 are involved in the process of tissue damage since degenerative forces exceed repair ability (D. Hasan, Chalouhi, et al. 2012). Tissue-infiltrating M1-like macrophages induce production of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α). TNF-α, in cooperation with prostaglandin E receptor subtype 2, plays a crucial role in the pathogenesis of aneurysm-amplified expression of pro-inflammatory genes. It induces trascription of monocyte chemoattractant protein-1 and vascular cell adhesion molecule-1, which recruit other Intracranial Aneurysms 85 macrophages, matrix metalloproteinases (MMPs), and IL-1β. TNF-α and IL-1β also determine aneurysm progression by promoting subsequent vascular structural alterations, directly activating MMPs, inhibiting collagen biosynthesis, and promoting cellular apoptosis.

4.2.1. Vascular Remodeling and Vascular Smooth Muscle Cell Phenotypic Switching In 2013 at Thomas Jefferson University, a group carried out research on the role of macrophage infiltration followed by TNF-α and IL-1β production in the vascular inflammatory process and vascular remodeling. Their study highlighted induction of phenotypic modulation and proliferation of vascular smooth muscle cells (VSMCs) by these molecules in the tunica media (Ali et al. 2013). VSMCs undergo phenotypic switching from contractile to pro- inflammatory and promatrix remodeling phenotypes, with decreased expression of actin- myosin proteins and an increase of inflammatory factors and MMPs. Morphologically, modulated VSMCs in aneurysm walls are spider-like in shape and disrupted, unable to produce collagen. VSMCs migrate into the intima layer and proliferate causing myointimal hyperplasia. All these modifications contribute to intimal thickening and thinning of the tunica media layers (Chalouhi et al. 2012). M1-like macrophages produce MMPs, essential in the subsequent pathological remodeling of the vascular wall, which determine proteolytic destruction of the vascular extracellular matrix (Nuki et al. 2009). Overexpression of MMP-1, -2, and -9 in aneurysm walls acts to weaken and stretch the arterial wall progressively, resulting in aneurysm formation, dilatation, and ultimately rupture. Many studies have also revealed the presence of mast cells in the aneurysm wall (International Study of Unruptured Intracranial Aneurysms 1998). Macrophage and mast cell degranulation, in addition of MMP induction, activates inducible NOS. Inducible NOS is an enzyme that produces nitric oxide, which is responsible for the maintenance of vascular homeostasis as well as production of ROS. ROS are major inflammatory mediators in vascular diseases, and oxidative stress is involved in processes leading to aneurysm formation, such as endothelial damage, VSMC phenotypic change, MMP activation, and cellular apopotosis. Recent studies have also demonstrated evidence of a humoral immune reaction; activated immunoglobulin M and G and their complement system have been found on the luminal side of the aneurysm wall (Tulamo et al. 2006).

4.2.2. Contribution of Human Gastrointestinal Microbiota Recently scientific studies have demonstrated the role of human gut microbiota in the pathogenesis of various diseases related to inflammatory mechanisms, such as atherosclerosis and diabetes mellitus. In 2019, Shikata et al. hypothesized the potential contribution of gut microbiota to the formation of intracranial aneurysmsby inducing intracranial aneurysms in mice after depletion of gut microbiota with antibiotics. Their results confirmed the reduction in aneurysm formation after depletion of gut microbiota (Shikata et al. 2019). The microbiota affects aneurysm development by modulating vascular inflammation; indeed, fewer macrophages were found in the aneurysm wall of the microbiota-depleted versus vehicle group. However, despite abundant evidence in animal models supporting the contribution of inflammatory responses in aneurysm development and rupture, the precise pathogenic mechanism has yet to be demonstrated in humans.

86 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

5. HISTOPATHOLOGY

Many structural modifications are considered hallmarks for aneurysms. The disruption of elastic fibers in the internal elastic lamina causes a reduction in arterial wall compliance and constitutive weakening. The luminal surface of the intima seems irregular, with narrow invaginations and destruction of endothelial cell junctions. The tunica media, composed of VSMCs and the extracellular matrix of type III collagen, thins. Disruption of the internal elastic lamina and phenotypically modulated VSMCs leading to myointimal hyperplasia are also common findings reported in atherosclerotic lesions (Owens 2007). The close correlation between pathogenic mechanisms underlying atherosclerosis and aneurysm formation supports the strong role of chronic inflammation in the genesis of these vascular diseases (Kosierkiewicz, Factor, and Dickson 1994).

6. CLASSIFICATION CRITERIA

In recent years, classification criteria for aneurysms have been enanched with the aim of stratifying pre-operative risk, while simultaneously improving the management of this complex disease. The parameters currently proposed are etiology, size, shape, and site of involved vessels. Etiological categorization provides four subdivisions in congenital and acquired aneurysms: traumatic, dissecting, infectious, and tumorous. Depending on the size, aneurysms are considered very small (≤5 mm), small (5–9 mm), large (10–17 mm), very large (18–24 mm), or giant [≥25 mm] (Nishioka et al. 1984; Zeeshan et al. 2018). Great importance must be reserved for classification criteria based on structural properties and location.

6.1. Angioarchitecture

The advent of new diagnostic techniques, such as volume rendering of 3-dimensional angiographic studies, has enabled greater knowledge of aneurysm structure and topographic relationship with vessels involved. Based on geometry, aneurysms can be primarily divided into two large groups: saccular or fusiform. Saccular or berry aneurysms have an abnormal focal outpouching of cerebral arteries on one side, with a tighter neck and sack-like wall. Fusiform aneurysms, representing only 5% of the total, bulge on both sides of the blood vessel, increasing the entire diameter. Both categories are further subdivided according to angioarchitecture, rheologic properties, and relationship with surrounding vessels. For saccular-shaped aneurysms, three groups have been proposed according to parent vessel geometry and have been angiographically documented by computational flow dynamics analysis (Hassan et al. 2005):

 Sidewall Aneurysms. The aneurysm site is on a single vessel with inflow and outflow zones located in the same anatomical neck. The parent vessel’s transverse diameter proximal and distal to the aneurysm are similar, and their ratio is greater than 90%.  Sidewall Aneurysm with a Branching Vessel. This type is geometrically analogous to sidewall aneurysms by the addition of smaller side-branch draining vessel(s) deriving Intracranial Aneurysms 87

from the aneurysm itself. A remarkable example is the internal carotid artery (ICA)– posterior communicating artery (PCoA) aneurysm with fetal PCoA.  Endwall Aneurysms. This category includes the old denomination of “bifurcation aneurysms.” The ratio of the parent vessel’s transverse diameter proximal to the aneurysm to the diameter distal to the aneurysm, measured at the aneurysms neck, is less than 90%. The best examples are basilar tip aneurysms.

In contrast, for fusiform-shaped aneurysms, two chategories are described:

 Simple, which do not give rise to any vascular branch.  Complex, which are associated with one or more side branches.

In 1969, Sundt and Murphey described blister-like aneurysms with specific morphology. Blister-like aneurysms are smaller and brittler, with a wide neck, and broad dome, localized arising from nonbranching sites from the dorsomedial wall of arteries (Princiotta et al. 2011). Supraclinoid ICA is the most common site [>90%] (Peschillo et al. 2016).

6.2. Site

Aneurysms are commonly named based on anatomical location. They can involve a major conducting vessel, such as the ICA, a primary or secondary segment of the anterior, middle, or posterior cerebral artery (PCA) or side-branch vessels (Pia 1978, 1979).

6.2.1. Anterior Circulation

6.2.1.1. Extracranial ICA Aneurysms of the extracranial ICA segment are rare, with an incidence of less than 1%. Most common causes are atherosclerosis and traumatic events; less frequent causes are congenital issues, infections, and fibromuscular dysplasia. The clinical onset is a cervical mass with difficulty swallowing, hoarseness, or Horner syndrome due to disfunction of postganglionic sympathetic nerve fibers. These aneurysms predispose to an increased risk of thromboembolic events and rupture (Sharma et al. 2019).

6.2.1.2. Intracranial ICA The intracranial ICA segment is the most common site of saccular aneurysms, especially within the cirle of Willis. Intracranial ICA is classically divided into a paraclinoid and a supraclinoid portion. The paraclinoid portion involves aneurysms of the cavernous ICA and ophthalmic ones, whereas the supraclinoid portion encompasses posterior communicating and anterior choroidal aneurysms. The supraclinoid portion of the ICA is the most affected, accounting for 35% of all aneurysms (Locksley 1966).

 Paraclinoid ICA. In 2003, paraclinoid ICA aneurysms were classified into four main types (Barami et al. 2003): 88 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

 Type Ia arises from the dorsal surface of the ICA, is directed superiorly in close relation with the ophthalmic arterey, and is placed medial or lateral to the optic nerve.  Type Ib comes from the dorsal surface of the ICA, is sessile-shaped, and has no branches. It is usually lateral to the optic nerve.  Type II arises from the ventral surface of the ICA. The dome is projected toward the roof of the cavernous sinus. It has no relation with collaral branches.  Type IIIa is from the medial wall of the ICA near the superior hypophyseal artery. It is projected medially above the dorsum sellae, is supradiaphragmatic, and involves the carotid cave.  Type IIIb, as IIIa, arises from the medial wall of the ICA, adjacent to the superior hypophyseal artery, but it is directed below the dorsum sellae and sited infradiaphragmatic.  Type IV is very frequently giant, originates with a large neck from the ventral surface of the ICA, and wides the distal dural ring.  Supraclinoid ICA.  PCoA. This artery arises from the posteromedial surface of the ICA, makes the lateral part of the circle of Willis, and overlaps the PCA. ICA-PCoA aneurysms are infrapara, supra-PCoA, and classified based on the origin of the neck and direction (Pia 1978). If they are projected down and backward, they involve the oculomotor cranial nerve (third cranial nerve) at its entrance in the dural roof of the cavernous sinus, causing pupil dilatation, and eye deviation.  Anterior choroidal artery. This artery arises from the posterior wall of the ICA or sometimes from the PCoA. These aneurysms usually project caudal and dorsolateral, closely to the third cranial nerve.  ICA bifurcation. These develop most frequently in the cranioventral direction, involving the anterior, and MCA.

6.2.1.3. Anterior Cerebral Artery  A1 segment. Aneurysms from the A1 segment project ventral and caudal, in close relation with the optic nerve and chiasma. They usually involve the medial lenticulostriate arteries, which arise from the dital part of A1. The most medial among the medial lenticulostriate arteries is the recurrent artery of Heubner. It branches from A2, at the A1-anterior communicating artery junction or A1, in order of frequency, and supplies blood to the medial portion of the orbitofrontal cortex and basal ganglia.  Anterior communicating artery. These aneurysms are usually directed ventrocaudally on the opposite side of anterior cerebral artery aneurysms, mainly involving the optic nerve and chiasma.  A2 segment. These aneurysms are usually projected in the opposite direction from those of A1. They are directed cranially and dorsally, in a very uncomfortable position for the surgical approach.  A3-A4-A5 segments and peripheral braches. In spite their rarity, the importance of these depends on involvement of the corpus callosum and gyrus cinguli. Branches usually involved are: fronto-orbital, frontopolar, callosomarginal artery, and Intracranial Aneurysms 89

pericallosal artery. In most cases, these aneurysms involve the callosomarginal and pericallosal artery at the angled point between these two vessels.

6.2.1.4. Middle Cerebral Artery  M1 segment. Proximal MCA aneurysms are often wide-necked and closely related to lateral lenticulostriate arteries at their origin. Lateral lenticulostriate arteries arise from the superior surface of M1. Together with medial lenticulostriate from A1 and the Heubner artery, they have a fundamental role in the irroration of the ventral striatum.  MCA bifurcation. They are usually saccular-shaped and projected laterally in the direction of the long axis of the bifurcation, involving both M2 trunks.  M2 segment. These are localized between the temporal lobe and the insula, often involving the bifurcation.  M3-M4 segments. These aneurysms involve the distal portion of the MCA, over the motor/somatosensory cortex. The identification of perforating arteries is mandatory during pre-operative planning.

6.2.2. Posterior Circulation

6.2.2.1. Vertebral Artery and Proximal Posterior-Inferior Cerebellar Artery  Extracranial segment. These aneurysms frequently have a traumatic etiology and are located at the craniocervical junction, between the first and second cervical vertebrae.  Intracranial segment. Fusiform aneurysms are rare; the only viariant described is the megalo-dolicho-vertebralis, an enlargement of the whole vessel, with probably an arteriosclerotic origin.  Proximal posterior-inferior cerebellar artery (PICA) [anterior and lateral meduallry segment (Lister et al. 1982)]. The PICA arises at the upper third of the ventrolateral side of the vertebral artery. More rarely, it has an extracranial origin from the vertebral artery at the level of the craniocervical junction, below the dentate ligament (Ciappetta, Luzzi, et al. 2009; Ciappetta, Occhiogrosso, et al. 2009; S. Luzzi, Gallieni, et al. 2018). Aneurysms are in the cerebellomedullary cistern, and the surgical route is between X, XI, and XII cranial nerves.  Vertebrobasilar junction. These aneurysms have difficult surgical access due to the presence of perforating arteries directed to the brainstem and low cranial nerves. They are projected caudally, often current with basilar fenestration. This evidence suggests that the trigger for aneurysm formation is not flow direction but a defect in the wall at the bifurcation.

6.2.2.2. Midbasilar Trunk The basilar artery originates from the confluence of the vertebral artery and ends giving origin to the first tract (P1) of the PCA. During the course, the basilar artery releases two superior cerebellar arteries (SCAs) and two antero-inferior cerebellar arteries (AICAs). Midbasilar trunk aneurysms can be projected laterally, touching the clivus, or posteriorly directed to the pons, close to the sixth cranial nerve (fourth cranial nerve).

90 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

6.2.2.3. Proximal AICA Basically, midbasilar trunk aneurysms also involve those of the proximal AICA. These sites are in the cerebellopontine angle, in close relationship with the internal auditory meatus. In a lot of cases, the origin has been identified at the AICA-labyrinthine artery junction.

6.2.2.4. Proximal SCA The proximal SCA includes anterior and lateral pontomesencephalic segments. Aneurysms are on the midline, below the basilar bifurcation, in the carotid-oculomotor triangle. They are in close relation with perforating arteries, the third cranial nerve, and the PCA.

6.2.2.5. Basilar Tip Basilar artery bifurcations are the most frequent in the posterior circulation. They are always directed cranially in the direction of the long axis of the basilar artery. If the dome is ventrally projected, it obscures the view of the SCA and PCA. In contrast, when dorsally projected, it hides the thalamoperforator arteries behind the neck. During pre-operative assessment, it is of paramount importance to consider the relationship between the the basilar tip and the posterior clinoid process. High-riding basilar bifurcation aneurysms are above the posterior clinoid process and lie within the carotid-oculomotor window; low-riding ones are below, and a posterior clinoidectomy should be considered in the planning of the surgical approach.

6.2.2.6. P1 Segment of the PCA This category represents 1% of all aneurysms, affecting especially younger populations (Drake and Amacher 1969). Aneurysms of the PCA have a higher incidence of being giant (23%) versus other anatomical sites, and a predilection for the P1 and P2 segments and PCA- PCoA junction (Drake 1979). The P1 releases perforating posterior thalamic arteries.

6.2.2.7. P2 Segment of the PCA Those that originate from the P2 tract are directed laterally and in close contact with the third cranial nerve, resulting in oculomotor palsy.

6.2.2.8. Distal Branches

 Distal PICA. Those considered distal include tonsillomedullary, telovelotonsillar, and cortical PICA segments. These aneurysms are frequently located in the cisterna magna and do not require traversing of any nerves to be reached.  Distal AICA. These aneurysms are located in the tract where the AICA runs caudally, reaching the lateral surface of the cerebellarhemisphere, where it releases many branches for the lobulus semilunaris and biventer.  Distal SCA. This comprises the cerebellomesencephalic and cortical portions. These aneurysms are usually sited in the posterior fossa and are projected laterally.  Distal PCA. The P3 (quadrigeminal) segment begins at the posterolateral side of the midbrain. The P4 (calcarine) segment begins at the calcarine fissure and ends at the occipital lobe. Major and terminal branches are the calcarine and parieto-occipital arteries. Several studies report 27% hemianopsia and visual disturbance in PCA aneurysms (Pia and Fontana 1977). Intracranial Aneurysms 91

7. NATURAL HISTORY AND RISK OF RUPTURE

It has been reported that about 3% of the population harbors an occult, unruptured, intracranial aneurysm (Etminan and Rinkel 2016). Several factors define the natural history of each aneurysm in three phases: genesis, growth, and rupture. Despite the understanding of the mechanism of initiation, the processes leading to development and ultimate rupture of a cerebral aneurysm are not yet fully known. Scientific evidence has demonstrated that, above all, patient-related risk factors must be considered in the prediction of rupture of an unruptured intracranial aneurysm. An age greater than 60 years-old, hypertension, cigarette smoking, and alcohol consumption are the most relevant. Hemodynamic factors, wall characteristics, angioarchitectural features, and site also play a role.

7.1. Hemodynamic Stress, Wall Inflammation, and Aneurysm Growth

Recent studies and histological observations have highlighted the role of hemodynamic stress in aneurysm growth. WSS induces structural changes and progressive weakening of the wall, ultimately resulting in aneurysm rupture. This process is explained by two different theories: high-flow and low-flow (Sforza et al. 2016). The high-flow theory holds that WSS elevation is related to endothelial injury, wall remodeling, increasing aneurysm diameter, and wall degeneration (Nakatani et al. 1991). Abnormal WSS also causes endothelial malfunction as well as overexpression of endothelial NOS and nitric oxide production, with a decrease in arterial tone. The wall is unable to endure the transmural pressure and breaks (Fukuda et al. 2000). Low-flow theory considers the effects of low WSS and stasis of blood flow at the level of the dome, this last being the most frequent breaking point. Blood stagnation encourages accumulation and adhesion of platelets and leukocytes along the intimal layer (Griffith 1994). Infiltration of inflammatory cells causes intimal damage and focal disintegration of the aneurysm wall until it breaks. Consequently, opposite vascular forces and infiltration of inflammatory cells are associated with aneurysm instability.

7.2. Dimension and Site

In 1998, the International Study of Unruptured Intracranial Aneurysms trial investigated the association between size, site, and risk of rupture. The estimated annual risk of rupture was 0.05% per year for aneurysms less than 10 mm in diameter and 1% per year for larger ones (International Study of Unruptured Intracranial Aneurysms 1998). The prospective part of the same study, published in 2003, better delineated the cutoff size for rupture in those with a diameter of 7 mm (Wiebers et al. 2003). Site also proved to be an independent risk factor. Cumulative 5-year rupture risk was 0% and 2.5% for anterior and posterior circulation, respectively (International Study of Unruptured Intracranial Aneurysms 1998). A Japanese study by Morita et al. indicated the annual risk of rupture to be of 1.90%, 1.72%, 1.31%, 0.67%, and 0.26% for the basilar artery, PCoA, anterior communicating artery, MCA, and paraclinoid ICA, respectively (Investigators et al. 2012). Based on size, the risk was 0.36%, 0.50%, 1.67%, 4.37%, and 33.4% for aneurysms having a major diameter of 4, 5–6, 7–9, 10–24, and greater than 24 mm, respectively (Investigators et al. 2012). 92 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

7.3. Angioarchitectural Features

Several studies have shown that an increased aneurysm diameter is not always related to an increased risk of rupture. This evidence suggests that geometric parameters contribute to the natural history of the aneurysm. Image-based computational flow dynamics techniques have allowed investigation of intra-aneurysmal hemodynamic patterns. These observations demonstrated a direct relationship between the diameter of the neck, volume, and intra- aneurysmal flow velocities (Black and German 1960). The most studied index is the aspect ratio (dome/neck ratio). Ujiie et al., reported that a dome/neck greater than 1.6 mm is correlated with a higher risk of rupture (Ujiie et al. 1999). Aneurysms with narrowed, bottle-like necks seem to have a higher susceptibility for bleeding at the so-called wall impingement zone. Furthermore, the coexistence of wall irregularities, daughter sacs, or blebs means that focalized wall damage occurred, leading to possible rupture. Likewise, factors such as the geometric disposition of the parent vessels, bifurcation sites, and collateral branches arising from the aneurysm neck or dome may all alter the inflow pattern, ultimately making the aneurysm unstable.

Table 1. PHASES Scoring System

PHASES Parameters Score Population North America, European (other than Finnish) 0 Japanese 3 Finnish 5 Hypertension No 0 Yes 1 Age <70 years-old 0 ≥70 years-old 1 Size of Aneurysm <7 mm 0 7–9.9 mm 3 10–19.9 mm 6 ≥20 mm 10 Earlier SAH No 0 Yes 1 Site of Aneurysm ICA 0 MCA 2 ACA/PCOM/PC 4 SAH: subarachnoid hemorrhage; ICA: internal carotid artery; MCA: middle cerebral artery; ACA: anterior cerebral artery; PcoA: posterior communicating artery; PC: posterior circulation.

Intracranial Aneurysms 93

The decision-making process for treating unruptured intracranial aneurysms is still controversial. In 2012, Greving and colleagues proposed a scoring system aimed at predicting the 5-year risk of bleeding for intracranial aneurysms based on conservative versus surgical/endovascular treatment (Greving et al. 2014). The PHASES score comes from carefull evaluation of key variables, such as Population (geographical location), Hypertension, Age, Size, Earlier SAH from another aneurysm, and Site (Table 1). A PHASES score greater than 3 is an indication for treatment.

8. CLINICAL PRESENTATION

Seldom unruptured intracranial aneurysms cause symptoms. In most cases, they are related to the mass effect. Common aneurysm-related syndromes include third cranial nerve palsy, trigeminal neuralgia, brainstem dysfunction, visual defects, hemiparesis, and seizures, according to the site. SAH is the clincal presentation of aneurysm rupture. Although not pathognomonic, thunderclap headache, nausea, and vomiting are typical. Many patients present with sentinel headaches in the previous days caused by small “warning leaks.” The presence of blood products in the subarachnoid space causes meningeal irritation and subsequent occurrence of meningeal signs. Retinal or vitrous hemorrhage are frequent findings (Obuchowska et al. 2014). The Hunt and Hess scale (Table 2) is classically employed for the clinical grading of SAH (Hunt and Hess 1968).

Table 2. Hunt and Hess Grading Scale (Hunt and Hess 1968)

Grade Clinical Findings I Asymptomatic, mild headache, and slight nucal rigidity II Moderate-severe headache, neurological deficit, and nucal rigidity III Drowsiness, confusion, or mild focal neurological deficit IV Stupor, moderate-severe hemiparesis V Coma, decerebrate posturing

8.1. Complications of SAH

SAH has three main complications, namely rebleeding, hydrocephalus, and vasospasm (Suarez, Tarr, and Selman 2006). The estimated risk of rebleeding is 4% on the first day and 1.5% per day for the next 2 weeks (Suarez, Tarr, and Selman 2006). Hydrocephalus is secondary to obstruction of the cerebrospinal fluid circulation by blood clots. ROS produced by blood degradation in the subarachnoid space are irritating to the arterial walls. Risk of cerebral vasospasm, occurring in 20%–40% of patients, is dramatically high between days 4 and 12 after SAH (Suarez, Tarr, and Selman 2006). The incidence is variable, fairly related to the amount of cisternal blood and individual reactivity factors. The Fisher CT-based grading scale is used for radiological grading of SAH (Fisher, Kistler, and Davis 1980) (Table 3). The Fisher grade is the best predictor of vasospasm (Suarez, Tarr, and Selman 2006), and vasospasm has been reported to be the major cause of morbidity and mortality after SAH (Charpentier et al. 1999).

94 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

Table 3. Fisher Grading Scale for SAH (Fisher, Kistler, and Davis 1980)

Grade Radiological findings I No subarachnoid blood detected II Diffuse or vertical thin layer <1mm thick III Diffuse clot or vertical layers >1 mm thick IV Intraparenchymal or intraventricular clot with/without diffuse SAH SAH: subarachnoid hemorrhage.

9. DIAGNOSTIC IMAGING

The first technique commonly used is noncontrast-enhanced CT. CT is very sensitive in demonstrating the presence of SAH within 24 h. Bleeding occurs with pericephalic and cisternal distribution, sometimes associated with intraparenchymal hematoma. The distribution of blood and extent of hemorrhage are important signs for the localization of a ruptured aneurysm. Second-level diagnostic techniques aim to identify the cause of hemorrhage and delineate size and morphologic features of a ruptured aneurysm. MRI angiography is highly sensitive (87%) and specific (95%) for aneurysm recognition, but the sensitivity decreased for acute bleeding and very small aneurysms less than 3 mm [40%] (Keedy 2006). However, MRI angiography is also useful in identifying chronic SAH and wall alterations, such as intraluminal thrombus. Despite the invasiveness of the procedure, digital subtraction angiography is generally the definitive diagnosis and clarifies topographic details of the aneurysm. Digital subtraction angiography has a sensitivity and specificity of 97.8% and 88.7%, respectively (Lu et al. 2012). Recently, CT angiography has been considered the benchmark for aneurysm preoperative surgical planning. It has a sensitivity and specificity of 96.5%–100% and 87.9%– 96.9%, respectively (Lu et al. 2012). CT angiography is a noninvasive technique which provides images of cerebral vessels in 3-dimensional views, visualizing the smallest aneurysms, and relationships with bony structure. The disadvantages of CT angiography, compared with MRI angiography, are the need to use iodine-based contrast, which may cause allergic reactions, renal injury, and radiation exposure.

10. FUTURE PROSPECTIVES

The future perpsectives of aneurysm involves different aspects, ranging from surgery, where the endoscopic techniques are gaining more and more success (Arnaout et al. 2019; S. Luzzi, Del Maestro, Elia, et al. 2019; S. Luzzi, Del Maestro, Trovarelli, et al. 2019; S. Luzzi, Zoia, et al. 2019; Zoia et al. 2019), to imaging and medical targeted therapies.

10.1. Imaging of Inflammation

In recent years, there has been great interest in new diagnostic techniques specific to vessel structures to be applied for aneurysm risk stratification and treatment choice. Hasan et al. Intracranial Aneurysms 95 studied a new technique that may offer important information about intracranial aneurysm instability called ferumoxytol-enhanced MRI (D.M. Hasan, Mahaney, et al. 2012). Ferumoxytol, an iron oxide used to treat iron deficiency, has been recently adopted for off-label clinical use for vascular imaging and studies involving inflammatory cells. Macrophages of the vascular wall uptake ferumoxytol, which enables the evaluation of inflammary cell activity, amount, and location. The dose to be administered is lower than that for the treatment of anemia, clustered around the 4 mg/kg, and MRI after 24 h exhibited more intense inflammation in the aneurysms walls (Vasanawala et al. 2016). This noninvasive technique is an innovative strategy estimating active inflammatory processes in the aneurysm, with aneurysm wall- enhancement as a predictor of rupture.

10.2. Therapies Targeting the Inflammatory Cascade

Recent advances achieved for aneurysm on par with other neurosurgical pathologies (Bongetta et al. 2019; Ciappetta et al. 2008; De Tommasi, Cascardi, et al. 2006; Millimaggi et al. 2018; Elsawaf et al. 2020) target cells involved in the chronic inflammatory process at the base of aneurysm formation. Decoy oligodeoxynucleotides that inhibit transcription of NF-κB should prevent aneurysm development (Aoki et al. 2012). Unfortunately, oligodeoxynucleotides administered orally or intravenously are degraded in a few hours. Statins have a pleiotropic effect, lowering cholesterol level and preventing endothelial dysfunction by inhibition of NF-κB activation and MMP and inducible NOS expression. Pitavastatin, simvastatin, and pravastatin, have proven effective in preventing aneurysm progression and rupture. In 2012, Tada et al. showed the dose-dependent effects of statins; high-dose pravastatin increased cellular apoptosis in the arterial wall and promoted aneurysm rupture, while lower doses reduced endothelial damage (Tada et al. 2011). The International Study of Unruptured Intracranial Aneurysms trial reported the role of aspirin as a protective agent for aneurysm rupture. Patients who take aspirin three times a week have lower risk of hemorrhage compared with others as a consequence of the role of aspirin in the inhibition of COX-2 and, therefore, the inflammatory cascade. This can also be demonstrated with ferumoxytol-enhanced MRI, which after 3 months of treatment with aspirin, shows marked reduction of ferumoxytol-uptake by macrophages in the wall. Other promising drugs are free radical scavengers (edaravone), COX-2 inhibitors (celecoxib), mast cell degranulation inhibitors (tranilast), inhibitors of phosphodiesterase-4 [ibudilast] (Yagi et al. 2010), and angiotensin receptor blockers (Aoki et al. 2009). This new evidence paves the way for new successful therapeutic strategies to prevent onset of cerebrovascular disease.

CONCLUSION

Aneurysms represent a complex clinical challenge and a wide field of scientific research. Identification of patient risk factors is mandatory in order to implement strategies for screening. Hemodynamic stress and chronic inflammation play a central role in the pathogenesis and natural history of aneurysm since they are involved in aneurysm growth and progression. 96 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

Morphology, angioachitecture, and anatomical sites are the most relevant chacteristics in predicting rupture. In recent years, advances regarding pathogenesis, imaging, and stratification risk have significantly improved the overall management of this challenging pathology.

REFERENCES

Alg, V. S., R. Sofat, H. Houlden, and D. J. Werring. 2013. “Genetic risk factors for intracranial aneurysms: a meta-analysis in more than 116,000 individuals.” Neurology 80 (23): 2154-65. https://doi.org/10.1212/WNL.0b013e318295d751. https://www.ncbi.nlm.nih. gov/pubmed/23733552. Ali, M. S., R. M. Starke, P. M. Jabbour, S. I. Tjoumakaris, L. F. Gonzalez, R. H. Rosenwasser, G. K. Owens, W. J. Koch, N. H. Greig, and A. S. Dumont. 2013. “TNF-alpha induces phenotypic modulation in cerebral vascular smooth muscle cells: implications for cerebral aneurysm pathology.” J Cereb Blood Flow Metab 33 (10): 1564- 73. https://doi.org/10.1038/jcbfm.2013.109. https://www.ncbi.nlm.nih.gov/pubmed/ 23860374. Antonosante, A., L. Brandolini, M. d'Angelo, E. Benedetti, V. Castelli, M. D. Maestro, S. Luzzi, A. Giordano, A. Cimini, and M. Allegretti. 2020. “Autocrine CXCL8-dependent invasiveness triggers modulation of actin cytoskeletal network and cell dynamics.” Aging (Albany NY) 12 (2): 1928-1951. https://doi.org/10.18632/aging.102733. https://www. ncbi.nlm.nih.gov/pubmed/31986121. Aoki, T., H. Kataoka, M. Nishimura, R. Ishibashi, R. Morishita, and S. Miyamoto. 2012. “Regression of intracranial aneurysms by simultaneous inhibition of nuclear factor-kappaB and Ets with chimeric decoy oligodeoxynucleotide treatment.” Neurosurgery 70 (6): 1534- 43; discussion 1543. https://doi.org/10.1227/NEU.0b013e318246a390. https://www.ncbi. nlm.nih.gov/pubmed/22186838. Aoki, T., M. Nishimura, H. Kataoka, R. Ishibashi, T. Miyake, Y. Takagi, R. Morishita, and N. Hashimoto. 2009. “Role of angiotensin II type 1 receptor in cerebral aneurysm formation in rats.” Int J Mol Med 24 (3): 353-9. https://doi.org/10.3892/ijmm_00000239. https://www.ncbi.nlm.nih.gov/pubmed/19639227. Arnaout, M. M., S. Luzzi, R. Galzio, and K. Aziz. 2019. “Supraorbital keyhole approach: Pure endoscopic and endoscope-assisted perspective.” Clin Neurol Neurosurg 189: 105623. https://doi.org/10.1016/j.clineuro.2019.105623. https://www.ncbi.nlm.nih.gov/pubmed/ 31805490. Barami, K., V. S. Hernandez, F. G. Diaz, and M. Guthikonda. 2003. “Paraclinoid Carotid Aneurysms: Surgical Management, Complications, and Outcome Based on a New Classification Scheme.” Skull Base 13 (1): 31-41. https://doi.org/10.1055/s-2003-820555. https://www.ncbi.nlm.nih.gov/pubmed/15912157. Bellantoni, G., F. Guerrini, M. Del Maestro, R. Galzio, and S. Luzzi. 2019. “Simple schwannomatosis or an incomplete Coffin-Siris? Report of a particular case.” eNeurological Sci 14: 31-33. https://doi.org/10.1016/j.ensci.2018.11.021. https://www. ncbi.nlm.nih.gov/pubmed/30555950. Black, S. P., and W. J. German. 1960. “Observations on the relationship between the volume and the size of the orifice of experimental aneurysms.” J Neurosurg 17: 984-90. Intracranial Aneurysms 97

https://doi.org/10.3171/jns.1960.17.6.0984. https://www.ncbi.nlm.nih.gov/pubmed/2021 0035. Bongetta, D., C. Zoia, S. Luzzi, M. D. Maestro, A. Peri, G. Bichisao, D. Sportiello, I. Canavero, A. Pietrabissa, and R. J. Galzio. 2019. “Neurosurgical issues of bariatric surgery: A systematic review of the literature and principles of diagnosis and treatment.” Clin Neurol Neurosurg 176: 34-40. https://doi.org/10.1016/j.clineuro.2018.11.009. https://www. ncbi.nlm.nih.gov/pubmed/30500756. Broderick, J. P., L. R. Sauerbeck, T. Foroud, J. Huston, 3rd, N. Pankratz, I. Meissner, and R. D. Brown, Jr. 2005. “The Familial Intracranial Aneurysm (FIA) study protocol.” BMC Med Genet 6: 17. https://doi.org/10.1186/1471-2350-6-17. https://www.ncbi.nlm.nih.gov/ pubmed/15854227. Bromberg, J. E., G. J. Rinkel, A. Algra, C. M. van Duyn, P. Greebe, L. M. Ramos, and J. van Gijn. 1995. “Familial subarachnoid hemorrhage: distinctive features and patterns of inheritance.” Ann Neurol 38 (6): 929-34. https://doi.org/10.1002/ana.410380614. https://www.ncbi.nlm.nih.gov/pubmed/8526466. Campanella, R., L. Guarnaccia, C. Cordiglieri, E. Trombetta, M. Caroli, G. Carrabba, N. La Verde, P. Rampini, C. Gaudino, A. Costa, S. Luzzi, G. Mantovani, M. Locatelli, L. Riboni, S. E. Navone, and G. Marfia. 2020. “Tumor-Educated Platelets and Angiogenesis in Glioblastoma: Another Brick in the Wall for Novel Prognostic and Targetable Biomarkers, Changing the Vision from a Localized Tumor to a Systemic Pathology.” Cells 9 (2). https://doi.org/10.3390/cells9020294. https://www.ncbi.nlm.nih.gov/pubmed/31991805. Caranci, F., F. Briganti, L. Cirillo, M. Leonardi, and M. Muto. 2013. “Epidemiology and genetics of intracranial aneurysms.” Eur J Radiol 82 (10): 1598- 605. https://doi.org/10.1016/j.ejrad.2012.12.026. https://www.ncbi.nlm.nih.gov/pubmed/ 23399038. Chalouhi, N., M. S. Ali, P. M. Jabbour, S. I. Tjoumakaris, L. F. Gonzalez, R. H. Rosenwasser, W. J. Koch, and A. S. Dumont. 2012. “Biology of intracranial aneurysms: role of inflammation.” J Cereb Blood Flow Metab 32 (9): 1659-76. https://doi.org/ 10.1038/jcbfm.2012.84. https://www.ncbi.nlm.nih.gov/pubmed/22781330. Charpentier, C., G. Audibert, F. Guillemin, T. Civit, X. Ducrocq, S. Bracard, H. Hepner, L. Picard, and M. C. Laxenaire. 1999. “Multivariate analysis of predictors of cerebral vasospasm occurrence after aneurysmal subarachnoid hemorrhage.” Stroke 30 (7): 1402- 8. https://doi.org/10.1161/01.str.30.7.1402. https://www.ncbi.nlm.nih.gov/pubmed/10390 314. Cheng, C. Y., R. Shetty, and L. N. Sekhar. 2018. “Microsurgical Resection of a Large Intraventricular Trigonal Tumor: 3-Dimensional Operative Video.” Oper Neurosurg (Hagerstown) 15 (6): E92-E93. https://doi.org/10.1093/ons/opy068. https://www.ncbi. nlm.nih.gov/pubmed/29618124. Ciappetta, P., I. D'Urso P, S. Luzzi, G. Ingravallo, A. Cimmino, and L. Resta. 2008. “Cystic dilation of the ventriculus terminalis in adults.” J Neurosurg Spine 8 (1): 92-9. https://doi.org/10.3171/SPI-08/01/092. https://www.ncbi.nlm.nih.gov/pubmed/18173354. Ciappetta, P., S. Luzzi, R. De Blasi, and P. I. D'Urso. 2009. “Extracranial aneurysms of the posterior inferior cerebellar artery. Literature review and report of a new case.” J Neurosurg Sci 53 (4): 147-51. https://www.ncbi.nlm.nih.gov/pubmed/20220739. Ciappetta, P., G. Occhiogrosso, S. Luzzi, P. I. D'Urso, and A. P. Garribba. 2009. “Jugular tubercle and vertebral artery/posterior inferior cerebellar artery anatomic relationship: a 3- 98 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

dimensional angiography computed tomography anthropometric study.” Neurosurgery 64 (5 Suppl 2): 429-36; discussion 436. https://doi.org/10.1227/01.NEU.0000337573. 17073.9F. https://www.ncbi.nlm.nih.gov/pubmed/19404121. De Tommasi, A., P. Cascardi, C. De Tommasi, S. Luzzi, and P. Ciappetta. 2006. “Emergency surgery in a severe penetrating skull base injury by a screwdriver: case report and literature review.” World J Emerg Surg 1: 36. https://doi.org/10.1186/1749-7922-1-36. https://www. ncbi.nlm.nih.gov/pubmed/17169147. De Tommasi, A., C. De Tommasi, E. Lauta, S. Luzzi, A. Cimmino, and P. Ciappetta. 2006. “Pre-operative subarachnoid haemorrhage in a patient with spinal tumour.” Cephalalgia 26 (7): 887-90. https://doi.org/10.1111/j.1468-2982.2006.01122.x. https://www.ncbi.nlm. nih.gov/pubmed/16776708. De Tommasi, A., S. Luzzi, P. I. D'Urso, C. De Tommasi, N. Resta, and P. Ciappetta. 2008. “Molecular genetic analysis in a case of ganglioglioma: identification of a new mutation.” Neurosurgery 63 (5): 976-80; discussion 980. https://doi.org/10.1227/01.NEU. 0000327699.93146.CD. https://www.ncbi.nlm.nih.gov/pubmed/19005389. De Tommasi, A., G. Occhiogrosso, C. De Tommasi, S. Luzzi, A. Cimmino, and P. Ciappetta. 2007. “A polycystic variant of a primary intracranial leptomeningeal astrocytoma: case report and literature review.” World J Surg Oncol 5: 72. https://doi.org/10.1186/1477- 7819-5-72. https://www.ncbi.nlm.nih.gov/pubmed/17587463. Del Maestro, M., S. Luzzi, M. Gallieni, D. Trovarelli, A. V. Giordano, M. Gallucci, A. Ricci, and R. Galzio. 2018. “Surgical Treatment of Arteriovenous Malformations: Role of Preoperative Staged Embolization.” Acta Neurochir Suppl 129: 109-113. https://doi.org/ 10.1007/978-3-319-73739-3_16. https://www.ncbi.nlm.nih.gov/pubmed/30171322. Drake, C. G. 1979. “Giant intracranial aneurysms: experience with surgical treatment in 174 patients.” Clin Neurosurg 26: 12-95. https://doi.org/10.1093/neurosurgery/26.cn_suppl_ 1.12. https://www.ncbi.nlm.nih.gov/pubmed/544122. Drake, C. G., and A. L. Amacher. 1969. “Aneurysms of the posterior cerebral artery.” J Neurosurg 30 (4): 468-74. https://doi.org/10.3171/jns.1969.30.4.0468. https://www.ncbi. nlm.nih.gov/pubmed/5800470. Elsawaf, Y., S. Anetsberger, S. Luzzi, and S. K. Elbabaa. 2020. “Early Decompressive Craniectomy as Management for Severe TBI in the Pediatric Population: A Comprehensive Literature Review.” World Neurosurg. https://doi.org/10.1016/j.wneu.2020.02.065. https://www.ncbi.nlm.nih.gov/pubmed/32084616. Etminan, N., and G. J. Rinkel. 2016. “Unruptured intracranial aneurysms: development, rupture and preventive management.” Nat Rev Neurol 12 (12): 699-713. https://doi.org/ 10.1038/nrneurol.2016.150. https://www.ncbi.nlm.nih.gov/pubmed/27808265. Finney, L. H., T. S. Roberts, and R. E. Anderson. 1976. “Giant intracranial aneurysm associated with Marfan's syndrome. Case report.” J Neurosurg 45 (3): 342-7. https://doi.org/ 10.3171/jns.1976.45.3.0342. https://www.ncbi.nlm.nih.gov/pubmed/948022. Fisher, C. M., J. P. Kistler, and J. M. Davis. 1980. “Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning.” Neurosurgery 6 (1): 1-9. https://doi.org/10.1227/00006123-198001000-00001. https://www.ncbi.nlm.nih.gov/pubmed/7354892. Fukuda, S., N. Hashimoto, H. Naritomi, I. Nagata, K. Nozaki, S. Kondo, M. Kurino, and H. Kikuchi. 2000. “Prevention of rat cerebral aneurysm formation by inhibition of nitric oxide Intracranial Aneurysms 99

synthase.” Circulation 101 (21): 2532-8. https://doi.org/10.1161/01.cir.101.21.2532. https://www.ncbi.nlm.nih.gov/pubmed/10831529. Gallieni, M., M. Del Maestro, S. Luzzi, D. Trovarelli, A. Ricci, and R. Galzio. 2018. “Endoscope-Assisted Microneurosurgery for Intracranial Aneurysms: Operative Technique, Reliability, and Feasibility Based on 14 Years of Personal Experience.” Acta Neurochir Suppl 129: 19-24. https://doi.org/10.1007/978-3-319-73739-3_3. https://www. ncbi.nlm.nih.gov/pubmed/30171309. Grassl, E., K. H. Fisch, H. Anton, and H. Grassl. 1979. “[The “spiritual” bond in nature: mathematico-musical acoustics as a structure analysis process. Part V: Physics].” Gegenbaurs Morphol Jahrb 125 (4): 443-65. https://www.ncbi.nlm.nih.gov/pubmed/ 232684. Greving, J. P., M. J. Wermer, R. D. Brown, Jr., A. Morita, S. Juvela, M. Yonekura, T. Ishibashi, J. C. Torner, T. Nakayama, G. J. Rinkel, and A. Algra. 2014. “Development of the PHASES score for prediction of risk of rupture of intracranial aneurysms: a pooled analysis of six prospective cohort studies.” Lancet Neurol 13 (1): 59-66. https://doi.org/ 10.1016/S1474-4422(13)70263-1. https://www.ncbi.nlm.nih.gov/pubmed/24290159. Griffith, T. M. 1994. “Modulation of blood flow and tissue perfusion by endothelium-derived relaxing factor.” Exp Physiol 79 (6): 873-913. https://doi.org/10.1113/expphysiol.1994. sp003816. https://www.ncbi.nlm.nih.gov/pubmed/7873159. Guastamacchia, E., V. Triggiani, E. Tafaro, A. De Tommasi, C. De Tommasi, S. Luzzi, C. Sabba, F. Resta, M. R. Terreni, and M. Losa. 2007. “Evolution of a prolactin-secreting pituitary microadenoma into a fatal carcinoma: a case report.” Minerva Endocrinol 32 (3): 231-6. https://www.ncbi.nlm.nih.gov/pubmed/17912159. Hasan, D., N. Chalouhi, P. Jabbour, and T. Hashimoto. 2012. “Macrophage imbalance (M1 vs. M2) and upregulation of mast cells in wall of ruptured human cerebral aneurysms: preliminary results.” J Neuroinflammation 9: 222. https://doi.org/10.1186/1742-2094-9- 222. https://www.ncbi.nlm.nih.gov/pubmed/22999528. Hasan, D. M., K. B. Mahaney, V. A. Magnotta, D. K. Kung, M. T. Lawton, T. Hashimoto, H. R. Winn, D. Saloner, A. Martin, S. Gahramanov, E. Dosa, E. Neuwelt, and W. L. Young. 2012. “Macrophage imaging within human cerebral aneurysms wall using ferumoxytol- enhanced MRI: a pilot study.” Arterioscler Thromb Vasc Biol 32 (4): 1032-8. https://doi.org/10.1161/ATVBAHA.111.239871. https://www.ncbi.nlm.nih.gov/pubmed/ 22328774. Hassan, T., E. V. Timofeev, T. Saito, H. Shimizu, M. Ezura, Y. Matsumoto, K. Takayama, T. Tominaga, and A. Takahashi. 2005. “A proposed parent vessel geometry-based categorization of saccular intracranial aneurysms: computational flow dynamics analysis of the risk factors for lesion rupture.” J Neurosurg 103 (4): 662- 80. https://doi.org/10.3171/jns.2005.103.4.0662. https://www.ncbi.nlm.nih.gov/pubmed/ 16266049. Hunt, W. E., and R. M. Hess. 1968. “Surgical risk as related to time of intervention in the repair of intracranial aneurysms.” J Neurosurg 28 (1): 14-20. https://doi.org/10.3171/ jns.1968.28.1.0014. https://www.ncbi.nlm.nih.gov/pubmed/5635959. International Study of Unruptured Intracranial Aneurysms, Investigators. 1998. “Unruptured intracranial aneurysms--risk of rupture and risks of surgical intervention.” N Engl J Med 339 (24): 1725-33. https://doi.org/10.1056/NEJM199812103392401. https://www.ncbi. nlm.nih.gov/pubmed/9867550. 100 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

Investigators, Ucas Japan, A. Morita, T. Kirino, K. Hashi, N. Aoki, S. Fukuhara, N. Hashimoto, T. Nakayama, M. Sakai, A. Teramoto, S. Tominari, and T. Yoshimoto. 2012. “The natural course of unruptured cerebral aneurysms in a Japanese cohort.” N Engl J Med 366 (26): 2474-82. https://doi.org/10.1056/NEJMoa1113260. https://www.ncbi.nlm.nih.gov/ pubmed/22738097. Johnston, S. C., S. Selvin, and D. R. Gress. 1998. “The burden, trends, and demographics of mortality from subarachnoid hemorrhage.” Neurology 50 (5): 1413-8. https://doi.org/ 10.1212/wnl.50.5.1413. https://www.ncbi.nlm.nih.gov/pubmed/9595997. Juvela, S. 2011. “Prevalence of and risk factors for intracranial aneurysms.” Lancet Neurol 10 (7): 595-7. https://doi.org/10.1016/S1474-4422(11)70125-9. https://www.ncbi.nlm.nih. gov/pubmed/21641283. Kassell, N. F., J. C. Torner, J. A. Jane, E. C. Haley, Jr., and H. P. Adams. 1990. “The International Cooperative Study on the Timing of Aneurysm Surgery. Part 2: Surgical results.” J Neurosurg 73 (1): 37-47. https://doi.org/10.3171/jns.1990.73.1.0037. https://www.ncbi.nlm.nih.gov/pubmed/2191091. Keedy, A. 2006. “An overview of intracranial aneurysms.” Mcgill J Med 9 (2): 141-6. https://www.ncbi.nlm.nih.gov/pubmed/18523626. Korja, M., H. Lehto, and S. Juvela. 2014. “Lifelong rupture risk of intracranial aneurysms depends on risk factors: a prospective Finnish cohort study.” Stroke 45 (7): 1958- 63. https://doi.org/10.1161/STROKEAHA.114.005318. https://www.ncbi.nlm.nih.gov/ pubmed/24851875. Kosierkiewicz, T. A., S. M. Factor, and D. W. Dickson. 1994. “Immunocytochemical studies of atherosclerotic lesions of cerebral berry aneurysms.” J Neuropathol Exp Neurol 53 (4): 399-406. https://doi.org/10.1097/00005072-199407000-00012. https://www.ncbi.nlm.nih. gov/pubmed/8021714. Li, L., X. Sima, P. Bai, L. Zhang, H. Sun, W. Liang, J. Liu, L. Zhang, and L. Gao. 2012. “Interactions of miR-34b/c and TP53 polymorphisms on the risk of intracranial aneurysm.” Clin Dev Immunol 2012: 567586. https://doi.org/10.1155/2012/567586. https://www. ncbi.nlm.nih.gov/pubmed/22844323. Lister, J. R., A. L. Rhoton, Jr., T. Matsushima, and D. A. Peace. 1982. “Microsurgical anatomy of the posterior inferior cerebellar artery.” Neurosurgery 10 (2): 170-99. https://www. ncbi.nlm.nih.gov/pubmed/7070615. Liu, Y., J. Sun, C. Wu, X. Cao, M. He, and C. You. 2012. “The interleukin-6-572G/C gene polymorphism and the risk of intracranial aneurysms in a Chinese population.” Genet Test Mol Biomarkers 16 (7): 822-6. https://doi.org/10.1089/gtmb.2012.0004. https://www. ncbi.nlm.nih.gov/pubmed/22686131. Locksley, H. B. 1966. “Natural history of subarachnoid hemorrhage, intracranial aneurysms and arteriovenous malformations. Based on 6368 cases in the cooperative study.” J Neurosurg 25 (2): 219-39. https://doi.org/10.3171/jns.1966.25.2.0219. https://www.ncbi. nlm.nih.gov/pubmed/5911370. Lu, L., L. J. Zhang, C. S. Poon, S. Y. Wu, C. S. Zhou, S. Luo, M. Wang, and G. M. Lu. 2012. “Digital subtraction CT angiography for detection of intracranial aneurysms: comparison with three-dimensional digital subtraction angiography.” Radiology 262 (2): 605-12. https://doi.org/10.1148/radiol.11110486. https://www.ncbi.nlm.nih.gov/pubmed/22143 927. Intracranial Aneurysms 101

Luzzi, S., A. M. Crovace, L. Lacitignola, V. Valentini, E. Francioso, G. Rossi, G. Invernici, R. J. Galzio, and A. Crovace. 2018. “Engraftment, neuroglial transdifferentiation and behavioral recovery after complete spinal cord transection in rats.” Surg Neurol Int 9: 19. https://doi.org/10.4103/sni.sni_369_17. https://www.ncbi.nlm.nih.gov/pubmed/29497 572. Luzzi, S., M. Del Maestro, D. Bongetta, C. Zoia, A. V. Giordano, D. Trovarelli, S. Raysi Dehcordi, and R. J. Galzio. 2018. “Onyx Embolization Before the Surgical Treatment of Grade III Spetzler-Martin Brain Arteriovenous Malformations: Single-Center Experience and Technical Nuances.” World Neurosurg 116: e340-e353. https://doi.org/10.1016/ j.wneu.2018.04.203. https://www.ncbi.nlm.nih.gov/pubmed/29751183. Luzzi, S., M. Del Maestro, S. K. Elbabaa, and R. Galzio. 2020. “Letter to the Editor Regarding “One and Done: Multimodal Treatment of Pediatric Cerebral Arteriovenous Malformations in a Single Anesthesia Event.” World Neurosurg 134: 660. https://doi.org/10.1016/j.wneu.2019.09.166. https://www.ncbi.nlm.nih.gov/pubmed/3205 9273. Luzzi, S., M. Del Maestro, A. Elia, F. Vincitorio, G. Di Perna, F. Zenga, D. Garbossa, S. Elbabaa, and R. Galzio. 2019. “Morphometric and Radiomorphometric Study of the Correlation between the Foramen Magnum Region and the Anterior and Posterolateral Approaches to Ventral Intradural Lesions.” Turk Neurosurg. https://doi.org/10.5137/1019- 5149.JTN.26052-19.2. https://www.ncbi.nlm.nih.gov/pubmed/31452176. Luzzi, S., M. Del Maestro, and R. Galzio. 2019. “Letter to the Editor. Preoperative embolization of brain arteriovenous malformations.” J Neurosurg: 1-2. https://doi.org/10.3171/ 2019.6.JNS191541. https://www.ncbi.nlm.nih.gov/pubmed/31812150. https://thejns.org/ view/journals/j-neurosurg/aop/article-10.3171-2019.6.JNS191541/article-10.3171-2019. 6.JNS191541.xml. Luzzi, S., M. Del Maestro, D. Trovarelli, D. De Paulis, S. R. Dechordi, H. Di Vitantonio, V. Di Norcia, D. F. Millimaggi, A. Ricci, and R. J. Galzio. 2019. “Endoscope-Assisted Microneurosurgery for Neurovascular Compression Syndromes: Basic Principles, Methodology, and Technical Notes.” Asian J Neurosurg 14 (1): 193-200. https://doi.org/10.4103/ajns.AJNS_279_17. https://www.ncbi.nlm.nih.gov/pubmed/309 37034. Luzzi, S., A. Elia, M. Del Maestro, S. K. Elbabaa, S. Carnevale, F. Guerrini, M. Caulo, P. Morbini, and R. Galzio. 2019. “Dysembryoplastic Neuroepithelial Tumors: What You Need to Know.” World Neurosurg 127: 255-265. https://doi.org/10.1016/j.wneu. 2019.04.056. https://www.ncbi.nlm.nih.gov/pubmed/30981794. Luzzi, S., A. Elia, M. Del Maestro, A. Morotti, S. K. Elbabaa, A. Cavallini, and R. Galzio. 2019. “Indication, Timing, and Surgical Treatment of Spontaneous Intracerebral Hemorrhage: Systematic Review and Proposal of a Management Algorithm.” World Neurosurg. https://doi.org/10.1016/j.wneu.2019.01.016. https://www.ncbi.nlm.nih.gov/ pubmed/30677572. Luzzi, S., M. Gallieni, M. Del Maestro, D. Trovarelli, A. Ricci, and R. Galzio. 2018. “Giant and Very Large Intracranial Aneurysms: Surgical Strategies and Special Issues.” Acta Neurochir Suppl 129: 25-31. https://doi.org/10.1007/978-3-319-73739-3_4. https://www. ncbi.nlm.nih.gov/pubmed/30171310. Luzzi, S., A. Giotta Lucifero, M. Del Maestro, G. Marfia, S. E. Navone, M. Baldoncini, M. Nunez, A. Campero, S. K. Elbabaa, and R. Galzio. 2019. “Anterolateral Approach for 102 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

Retrostyloid Superior Parapharyngeal Space Schwannomas Involving the Jugular Foramen Area: A 20-Year Experience.” World Neurosurg. https://doi.org/10.1016/j.wneu. 2019.09.006. https://www.ncbi.nlm.nih.gov/pubmed/31520759. Luzzi, S., C. Zoia, A. D. Rampini, A. Elia, M. Del Maestro, S. Carnevale, P. Morbini, and R. Galzio. 2019. “Lateral Transorbital Neuroendoscopic Approach for Intraconal Meningioma of the Orbital Apex: Technical Nuances and Literature Review.” World Neurosurg 131: 10-17. https://doi.org/10.1016/j.wneu.2019.07.152. https://www.ncbi. nlm.nih.gov/pubmed/31356977. Luzzi, Sabino, Alberto Maria Crovace, Mattia Del Maestro, Alice Giotta Lucifero, Samer K. Elbabaa, Benedetta Cinque, Paola Palumbo, Francesca Lombardi, Annamaria Cimini, Maria Grazia Cifone, Antonio Crovace, and Renato Galzio. 2019. “The cell-based approach in neurosurgery: ongoing trends and future perspectives.” Heliyon 5 (11). https://doi.org/10.1016/j.heliyon.2019.e02818. Mackey, J., R. D. Brown, Jr., C. J. Moomaw, L. Sauerbeck, R. Hornung, D. Gandhi, D. Woo, D. Kleindorfer, M. L. Flaherty, I. Meissner, C. Anderson, E. S. Connolly, G. Rouleau, D. F. Kallmes, J. Torner, J. Huston, 3rd, J. P. Broderick, Fia, and Isuia Investigators. 2012. “Unruptured intracranial aneurysms in the Familial Intracranial Aneurysm and International Study of Unruptured Intracranial Aneurysms cohorts: differences in multiplicity and location.” J Neurosurg 117 (1): 60-4. https://doi.org/10.3171/2012. 4.JNS111822. https://www.ncbi.nlm.nih.gov/pubmed/22540404. Marchese, E., A. Vignati, A. Albanese, C. G. Nucci, G. Sabatino, B. Tirpakova, G. Lofrese, G. Zelano, and G. Maira. 2010. “Comparative evaluation of genome-wide gene expression profiles in ruptured and unruptured human intracranial aneurysms.” J Biol Regul Homeost Agents 24 (2): 185-95. https://www.ncbi.nlm.nih.gov/pubmed/20487632. Masoumi, A., B. Reed-Gitomer, C. Kelleher, M. R. Bekheirnia, and R. W. Schrier. 2008. “Developments in the management of autosomal dominant polycystic kidney disease.” Ther Clin Risk Manag 4 (2): 393-407. https://doi.org/10.2147/tcrm.s1617. https://www. ncbi.nlm.nih.gov/pubmed/18728845. Menzies, L., F. D'Arco, V. Ganesan, and J. A. Hurst. 2019. “Intracranial vascular pathology in two further patients with Floating-Harbor syndrome: Proposals for cerebrovascular disease risk management.” Eur J Med Genet: 103785. https://doi.org/10.1016/j.ejmg.2019.103785. https://www.ncbi.nlm.nih.gov/pubmed/31605816. Millimaggi, D. F., V. D. Norcia, S. Luzzi, T. Alfiero, R. J. Galzio, and A. Ricci. 2018. “Minimally Invasive Transforaminal Lumbar Interbody Fusion with Percutaneous Bilateral Pedicle Screw Fixation for Lumbosacral Spine Degenerative Diseases. A Retrospective Database of 40 Consecutive Cases and Literature Review.” Turk Neurosurg 28 (3): 454-461. https://doi.org/10.5137/1019-5149.JTN.19479-16.0. https://www.ncbi. nlm.nih.gov/pubmed/28481388. Mohan, S., N. Mohan, and E. A. Sprague. 1997. “Differential activation of NF-kappa B in human aortic endothelial cells conditioned to specific flow environments.” Am J Physiol 273 (2 Pt 1): C572-8. https://doi.org/10.1152/ajpcell.1997.273.2.C572. https://www.ncbi. nlm.nih.gov/pubmed/9277354. Morooka, Y., and S. Waga. 1983. “Familial intracranial aneurysms: report of four families.” Surg Neurol 19 (3): 260-2. https://doi.org/10.1016/s0090-3019(83)80012-3. https://www. ncbi.nlm.nih.gov/pubmed/6836479. Intracranial Aneurysms 103

Munyer, T. P., and A. R. Margulis. 1981. “Pseudoxanthoma elasticum with internal carotid artery aneurysm.” AJR Am J Roentgenol 136 (5): 1023-4. https://doi.org/10.2214/ ajr.136.5.1023. https://www.ncbi.nlm.nih.gov/pubmed/6784505. Nakatani, H., N. Hashimoto, Y. Kang, N. Yamazoe, H. Kikuchi, S. Yamaguchi, and H. Niimi. 1991. “Cerebral blood flow patterns at major vessel bifurcations and aneurysms in rats.” J Neurosurg 74 (2): 258-62. https://doi.org/10.3171/jns.1991.74.2.0258. https://www.ncbi. nlm.nih.gov/pubmed/1988596. Nishioka, H., J. C. Torner, C. J. Graf, N. F. Kassell, A. L. Sahs, and L. C. Goettler. 1984. “Cooperative study of intracranial aneurysms and subarachnoid hemorrhage: a long-term prognostic study. II. Ruptured intracranial aneurysms managed conservatively.” Arch Neurol 41 (11): 1142-6. https://doi.org/10.1001/archneur.1984.04050220036011. https://www.ncbi.nlm.nih.gov/pubmed/6487096. Nuki, Y., M. M. Matsumoto, E. Tsang, W. L. Young, N. van Rooijen, C. Kurihara, and T. Hashimoto. 2009. “Roles of macrophages in flow-induced outward vascular remodeling.” J Cereb Blood Flow Metab 29 (3): 495-503. https://doi.org/10.1038/jcbfm.2008.136. https://www.ncbi.nlm.nih.gov/pubmed/19002198. Obuchowska, I., G. Turek, Z. Mariak, and Z. Mariak. 2014. “Early Intraocular Complications of Subarachnoid Haemorrhage after Aneurysm Rupture.” Neuroophthalmology 38 (4): 199-204. https://doi.org/10.3109/01658107.2014.911918. https://www.ncbi.nlm.nih.gov/ pubmed/27928299. Owens, G. K. 2007. “Molecular control of vascular smooth muscle cell differentiation and phenotypic plasticity.” Novartis Found Symp 283: 174-91; discussion 191-3, 238-41. https://doi.org/10.1002/9780470319413.ch14. https://www.ncbi.nlm.nih.gov/pubmed/183 00422. Oyesiku, N. M., A. R. Colohan, D. L. Barrow, and A. Reisner. 1993. “Cocaine-induced aneurysmal rupture: an emergent negative factor in the natural history of intracranial aneurysms?” Neurosurgery 32 (4): 518-25; discussion 525-6. https://doi.org/10.1227/ 00006123-199304000-00005. https://www.ncbi.nlm.nih.gov/pubmed/8474641. Palumbo, P., F. Lombardi, F. R. Augello, I. Giusti, S. Luzzi, V. Dolo, M. G. Cifone, and B. Cinque. 2019. “NOS2 inhibitor 1400W Induces Autophagic Flux and Influences Extracellular Vesicle Profile in Human Glioblastoma U87MG Cell Line.” Int J Mol Sci 20 (12). https://doi.org/10.3390/ijms20123010. https://www.ncbi.nlm.nih.gov/pubmed/ 31226744. Palumbo, P., F. Lombardi, G. Siragusa, S. R. Dehcordi, S. Luzzi, A. Cimini, M. G. Cifone, and B. Cinque. 2018. “Involvement of NOS2 Activity on Human Glioma Cell Growth, Clonogenic Potential, and Neurosphere Generation.” Int J Mol Sci 19 (9). https://doi.org/10.3390/ijms19092801. https://www.ncbi.nlm.nih.gov/pubmed/30227679. Peschillo, S., D. Cannizzaro, A. Caporlingua, and P. Missori. 2016. “A Systematic Review and Meta-Analysis of Treatment and Outcome of Blister-Like Aneurysms.” AJNR Am J Neuroradiol 37 (5): 856-61. https://doi.org/10.3174/ajnr.A4606. https://www.ncbi.nlm. nih.gov/pubmed/26635287. Pia, H. W. 1978. “Classification of aneurysms of the internal carotid system.” Acta Neurochir (Wien) 40 (1-2): 5-31. https://doi.org/10.1007/bf01773112. https://www.ncbi.nlm.nih.gov/ pubmed/654969. ---. 1979. “Classification of vertebro-basilar aneurysms.” Acta Neurochir (Wien) 47 (1-2): 3- 30. https://doi.org/10.1007/bf01404659. https://www.ncbi.nlm.nih.gov/pubmed/474201. 104 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

Pia, H. W., and H. Fontana. 1977. “Aneurysms of the posterior cerebral artery. Locations and clinical pictures.” Acta Neurochir (Wien) 38 (1-2): 13-35. https://doi.org/10.1007/ bf01401541. https://www.ncbi.nlm.nih.gov/pubmed/331888. Princiotta, C., M. Dall'olio, L. Cirillo, and M. Leonardi. 2011. “Staged treatment of a blood blister-like aneurysm with stent-assisted coiling followed by flow diverter in-stent insertion. A case report.” Interv Neuroradiol 17 (3): 365-70. https://doi.org/10.1177/ 159101991101700314. https://www.ncbi.nlm.nih.gov/pubmed/22005701. Raysi Dehcordi, S., A. Ricci, H. Di Vitantonio, D. De Paulis, S. Luzzi, P. Palumbo, B. Cinque, D. Tempesta, G. Coletti, G. Cipolloni, M. G. Cifone, and R. Galzio. 2017. “Stemness Marker Detection in the Periphery of Glioblastoma and Ability of Glioblastoma to Generate Glioma Stem Cells: Clinical Correlations.” World Neurosurg 105: 895- 905. https://doi.org/10.1016/j.wneu.2017.05.099. https://www.ncbi.nlm.nih.gov/pubmed/ 28559081. Ricci, A., H. Di Vitantonio, D. De Paulis, M. Del Maestro, S. D. Raysi, D. Murrone, S. Luzzi, and R. J. Galzio. 2017. “Cortical aneurysms of the middle cerebral artery: A review of the literature.” Surg Neurol Int 8: 117. https://doi.org/10.4103/sni.sni_50_17. https://www. ncbi.nlm.nih.gov/pubmed/28680736. Rinkel, G. J., M. Djibuti, A. Algra, and J. van Gijn. 1998. “Prevalence and risk of rupture of intracranial aneurysms: a systematic review.” Stroke 29 (1): 251-6. https://doi.org/ 10.1161/01.str.29.1.251. https://www.ncbi.nlm.nih.gov/pubmed/9445359. Roman, G., M. Fisher, D. P. Perl, and C. M. Poser. 1978. “Neurological manifestations of hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease): report of 2 cases and review of the literature.” Ann Neurol 4 (2): 130-44. https://doi.org/10.1002/ana. 410040207. https://www.ncbi.nlm.nih.gov/pubmed/707984. Sakamoto, N., N. Saito, X. Han, T. Ohashi, and M. Sato. 2010. “Effect of spatial gradient in fluid shear stress on morphological changes in endothelial cells in response to flow.” Biochem Biophys Res Commun 395 (2): 264-9. https://doi.org/10.1016/j.bbrc.2010.04.002. https://www.ncbi.nlm.nih.gov/pubmed/20371223. Schievink, W. I., J. A. Katzmann, D. G. Piepgras, and D. J. Schaid. 1996. “Alpha-1-antitrypsin phenotypes among patients with intracranial aneurysms.” J Neurosurg 84 (5): 781- 4. https://doi.org/10.3171/jns.1996.84.5.0781. https://www.ncbi.nlm.nih.gov/pubmed/ 8622151. Sforza, D. M., K. Kono, S. Tateshima, F. Vinuela, C. Putman, and J. R. Cebral. 2016. “Hemodynamics in growing and stable cerebral aneurysms.” J Neurointerv Surg 8 (4): 407-12. https://doi.org/10.1136/neurintsurg-2014-011339. https://www.ncbi.nlm.nih.gov/ pubmed/25653228. Sforza, D. M., C. M. Putman, and J. R. Cebral. 2009. “Hemodynamics of Cerebral Aneurysms.” Annu Rev Fluid Mech 41: 91-107. https://doi.org/10.1146/annurev.fluid.40.111406. 102126. https://www.ncbi.nlm.nih.gov/pubmed/19784385. Sharma, R. K., A. M. Asiri, Y. Yamada, T. Kawase, and Y. Kato. 2019. “Extracranial Internal Carotid Artery Aneurysm - Challenges in the Management: A Case Report and Review Literature.” Asian J Neurosurg 14 (3): 970-974. https://doi.org/10.4103/ajns.AJNS_ 292_18. https://www.ncbi.nlm.nih.gov/pubmed/31497143. Shikata, F., K. Shimada, H. Sato, T. Ikedo, A. Kuwabara, H. Furukawa, M. Korai, M. Kotoda, K. Yokosuka, H. Makino, E. A. Ziegler, D. Kudo, M. T. Lawton, and T. Hashimoto. 2019. “Potential Influences of Gut Microbiota on the Formation of Intracranial Aneurysm.” Intracranial Aneurysms 105

Hypertension 73 (2): 491-496. https://doi.org/10.1161/HYPERTENSIONAHA.118. 11804. https://www.ncbi.nlm.nih.gov/pubmed/30624992. Spena, G., E. Roca, F. Guerrini, P. P. Panciani, L. Stanzani, A. Salmaggi, S. Luzzi, and M. Fontanella. 2019. “Risk factors for intraoperative stimulation-related seizures during awake surgery: an analysis of 109 consecutive patients.” J Neurooncol. https://doi.org/10.1007/s11060-019-03295-9. https://www.ncbi.nlm.nih.gov/pubmed/315 52589. Suarez, J. I., R. W. Tarr, and W. R. Selman. 2006. “Aneurysmal subarachnoid hemorrhage.” N Engl J Med 354 (4): 387-96. https://doi.org/10.1056/NEJMra052732. https://www. ncbi.nlm.nih.gov/pubmed/16436770. Sun, H., D. Zhang, and J. Zhao. 2008. “The interleukin-6 gene -572G>C promoter polymorphism is related to intracranial aneurysms in Chinese Han nationality.” Neurosci Lett 440 (1): 1-3. https://doi.org/10.1016/j.neulet.2008.04.077. https://www.ncbi.nlm.nih. gov/pubmed/18487018. Szymanski, M. P., E. Metaxa, H. Meng, and J. Kolega. 2008. “Endothelial cell layer subjected to impinging flow mimicking the apex of an arterial bifurcation.” Ann Biomed Eng 36 (10): 1681-9. https://doi.org/10.1007/s10439-008-9540-x. https://www.ncbi.nlm.nih.gov/ pubmed/18654851. Tada, Y., K. T. Kitazato, K. Yagi, K. Shimada, N. Matsushita, T. Kinouchi, Y. Kanematsu, J. Satomi, T. Kageji, and S. Nagahiro. 2011. “Statins promote the growth of experimentally induced cerebral aneurysms in estrogen-deficient rats.” Stroke 42 (8): 2286- 93. https://doi.org/10.1161/STROKEAHA.110.608034. https://www.ncbi.nlm.nih.gov/ pubmed/21737796. Tulamo, R., J. Frosen, S. Junnikkala, A. Paetau, J. Pitkaniemi, M. Kangasniemi, M. Niemela, J. Jaaskelainen, E. Jokitalo, A. Karatas, J. Hernesniemi, and S. Meri. 2006. “Complement activation associates with saccular cerebral artery aneurysm wall degeneration and rupture.” Neurosurgery 59 (5): 1069-76; discussion 1076-7. https://doi.org/10.1227/01. NEU.0000245598.84698.26. https://www.ncbi.nlm.nih.gov/pubmed/17016232. Ujiie, H., H. Tachibana, O. Hiramatsu, A. L. Hazel, T. Matsumoto, Y. Ogasawara, H. Nakajima, T. Hori, K. Takakura, and F. Kajiya. 1999. “Effects of size and shape (aspect ratio) on the hemodynamics of saccular aneurysms: a possible index for surgical treatment of intracranial aneurysms.” Neurosurgery 45 (1): 119-29; discussion 129- 30. https://doi.org/10.1097/00006123-199907000-00028. https://www.ncbi.nlm.nih.gov/ pubmed/10414574. Vasanawala, S. S., K. L. Nguyen, M. D. Hope, M. D. Bridges, T. A. Hope, S. B. Reeder, and M. R. Bashir. 2016. “Safety and technique of ferumoxytol administration for MRI.” Magn Reson Med 75 (5): 2107-11. https://doi.org/10.1002/mrm.26151. https://www.ncbi.nlm. nih.gov/pubmed/26890830. Wiebers, D. O., J. P. Whisnant, J. Huston, 3rd, I. Meissner, R. D. Brown, Jr., D. G. Piepgras, G. S. Forbes, K. Thielen, D. Nichols, W. M. O'Fallon, J. Peacock, L. Jaeger, N. F. Kassell, G. L. Kongable-Beckman, J. C. Torner, and Investigators International Study of Unruptured Intracranial Aneurysms. 2003. “Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment.” Lancet 362 (9378): 103-10. https://doi.org/10.1016/s0140-6736(03)13860-3. https://www.ncbi.nlm. nih.gov/pubmed/12867109. 106 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

Yagi, K., Y. Tada, K. T. Kitazato, T. Tamura, J. Satomi, and S. Nagahiro. 2010. “Ibudilast inhibits cerebral aneurysms by down-regulating inflammation-related molecules in the vascular wall of rats.” Neurosurgery 66 (3): 551-9; discussion 559. https://doi.org/10. 1227/01.NEU.0000365771.89576.77. https://www.ncbi.nlm.nih.gov/pubmed/20124930. Zeeshan, Q., B. V. Ghodke, G. Juric-Sekhar, J. K. Barber, L. J. Kim, and L. N. Sekhar. 2018. “Surgery for very large and giant intracranial aneurysms: Results and complications.” Neurol India 66 (6): 1741-1757. https://doi.org/10.4103/0028-3886.246291. https://www. ncbi.nlm.nih.gov/pubmed/30504576. Zoia, C., D. Bongetta, G. Dorelli, S. Luzzi, M. D. Maestro, and R. J. Galzio. 2019. “Transnasal endoscopic removal of a retrochiasmatic cavernoma: A case report and review of literature.” Surg Neurol Int 10: 76. https://doi.org/10.25259/SNI-132-2019. https://www. ncbi.nlm.nih.gov/pubmed/31528414. Zoia, C., D. Bongetta, F. Guerrini, C. Alicino, A. Cattalani, S. Bianchini, R. J. Galzio, and S. Luzzi. 2018. “Outcome of elderly patients undergoing intracranial meningioma resection: a single center experience.” J Neurosurg Sci. https://doi.org/10.23736/S0390-5616. 18.04333-3. https://www.ncbi.nlm.nih.gov/pubmed/29808631. Zoia, C., F. Lombardi, M. R. Fiore, A. Montalbetti, A. Iannalfi, M. Sansone, D. Bongetta, F. Valvo, M. Del Maestro, S. Luzzi, and R. J. Galzio. 2020. “Sacral solitary fibrous tumour: surgery and hadrontherapy, a combined treatment strategy.” Rep Pract Oncol Radiother 25 (2): 241-244. https://doi.org/10.1016/j.rpor.2020.01.008. https://www.ncbi.nlm.nih. gov/pubmed/32025222.

Chapter 6

BRAIN ARTERIOVENOUS MALFORMATIONS

M. Cenzato1,, MD, PhD and D. Boeris1, MD 1Department of Neurosurgery, Grande Ospedale Metropolitano Niguarda, Milan, Italy

ABSTRACT

Brain arteriovenous malformations (AVMs) are composed of a network of abnormal arteries and veins lacking a capillary bed. They result in complex, dynamic lesions characterized by high-flow arteriovenous shunts. Since the first series, published in 1976 by M. G. Yaşargil, AVM surgery is considered a challenge. Treatment options for brain AVMs include microsurgical resection, endovascular embolization, radiosurgery or combination of these. In this chapter, we comprehensively review the epidemiology, clinical presentation, natural history, pathogenesis, neuroimaging, classification, and treatment options for brain AVMs. Complication avoidance are also described.

INTRODUCTION

The surgical removal of arteriovenous malformations (AVM) is considered one of the most challenging procedures in vascular neurosurgery. Very little was done before the microsurgical era when the AVM treatment was improved with the introduction of surgical microscope by Yasargil. He published, in 1976, the first series of 10 AVM patients treated with microsurgical techniques with no mortality and minimal morbidity (Yaşargil et al. 1976). Since, microsurgery became increasingly accepted as a management option for AVMs and identifying those AVMs that could be resected safely became a priority. Nowadays surgical removal remains one option to be considered in a multidisciplinary approach that requires a thorough understanding of the pathology.

 Corresponding Author’s Email: [email protected]. 108 M. Cenzato and D. Boeris

EPIDEMIOLOGY

There is very little information in the literature regarding the prevalence of AVMs, the rarity of the disease and the existence of asymptomatic patients does not allow to calculate the exact prevalence rate (Stapf et al. 2001). The scientific literature available to date report an incidence range between 0,02% and 0,5% and it is probably influenced by geographical and racial factors (Stapf et al. 2006; Mingrino 1978; Hofmeister et al. 2000). Olivecrona et al. reported in 1948 (Olivecrona and Riives 1948) an incidence for detection of cerebral AVMs in a large autopsy series like 1,4%. Owing to variation in the detection rate of asymptomatic AVMs, Berman (Berman et al. 2000) argued that the most reliable estimate for the occurrence of the disease was the detection rate of 0,94 per 100.000 person-years for symptomatic lesions. Even though brain AVMs are considered to be a congenital disorder, non-systematized familial AVMs are extremely rare and very few familial cases have been reported in the literature (NA and HV 1995). The prevalence of brain AVMs in patients presenting with Rendu-Osler-Weber disease is higher and it is estimated to be between 4% and 13% (Porteous, Burn, and Proctor 1992). Rendu-Osler-Weber disease alias Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant disorder with a prevalence estimated to be between 2 and 40 per 100,000 people (Guttmacher, Marchuk, and White 1995). Rendu-OslerWeber disease is characterized by multi systemic vascular dysplasia and recurrent hemorrhage of the nose, skin, lung, brain, and gastrointestinal tract. Willemse et al. showed that 12% had a brain AVM, and 96% of these were low grade (SM grade I or II). They have no specific characteristics, (Porteous, Burn, and Proctor 1992) though multiple AVMs in this syndrome are more frequent than in the general population. The risk of bleeding has been estimated to be lower than in non-Rendu-Osler- Weber disease brain AVMs, ranging from 0.4 to 0.72 per year (Kjeldsen, Vase, and Green 1999).

CLINICAL PRESENTATION

The most frequent clinical presentations of brain AVMs are: hemorrhage, seizure, chronic headache, and focal deficits not related to hemorrhage (Mast et al. 1995). Hemorrhage is one of the two more common clinical symptoms of symptomatic AVM's presentation. The AVM’s risk of bleeding is a crucial element in considering the opportunity to treat or not to treat an unruptured AVM, because any possible treatment has to be compared with the estimated natural history. Several studies (Auger and Wiebers 1992; RD, n.d.; Crawford et al. 1986; Prayer et al. 1993) have been done and the most accredited reported risk of hemorrhage as the cerebral AVM initial symptom is estimated between 2% to 4% per year. It is important to point out that estimating the risk of bleeding in the individual patient is not an easy process: some morphological details of the AVM must be taken considered as there is consensus that intranidal aneurysms, venous ectasia or stenosis and subependymal ventricular location increase the risk of bleeding, while size seems to be less relevant. The hemorrhagic risk of AVM bleeding increases up to three times after the first hemorrhagic event. Rebleeding generally occurs in the first year, falling the subsequent years and returning to normal after 5 years (Hernesniemi et al. 2008; Ondra et al. 1990; Mohr 1999). Cerebral hemorrhage after AVM ruptures appears to have a lower morbidity and mortality compared to other intracranial Brain Arteriovenous Malformations 109 vascular malformations like aneurysms. The mortality rate associated with the first hemorrhagic event has been estimated to be 10 to 15% and the overall morbidity is between 30% and 50% (Cenzato et al. 2018; RD, n.d.; R. D. Brown et al. 1988), parenchymal hemorrhages were most likely to result in a neurological deficit in 52% of patients (Robert D. Brown et al. 1996). Seizures are the first cerebral AVMs symptom in 16% to 67% of patients (Miyasaka et al. 1994; Pribil, C.Boone, and Waley 1983). In the majority of cases, seizures are partial or partial complex (Osipov et al. 1997) and usually associated with frontal and temporal lobe malformations, especially in the hippocampal area (Frishberg 1997). Cortical AVMs are more often associated with seizures (Turjman et al. 1994). In a large series report antiepileptic drugs provided good control of seizures (Osipov et al. 1997). Focal neurologic deficits without hemorrhage as initial symptoms have been reported in 1% to 40% of patients (Osipov et al. 1997). In fact, this clinical presentation is probably infrequent (Mohr 1999). Focal neurologic deficits encountered in patients with AVMs may be characterized by progressive, stable, or reversible symptoms (Osipov et al. 1997). The steal phenomenon first described in AVM by Carter and Gumerlock in 1995 (Carter and Gumerlock 1995) may not represent the only explanation and venous hypertension, and mass effect (Miyasaka et al. 1992) should be considered as well. The relevance of the steal phenomenon is difficult to demonstrate in patients presenting with progressive neurologic deficits (Osipov et al. 1997). Positron emission tomography studies (Kaminaga T, Hayashida K, Iwama T 1999) showed a decrease of cerebral blood flow in brain tissues surrounding AVMs, but without increase in parenchymal blood volume or modifications of glucose and oxygen extraction fractions. A common but very general symptom of cerebral unruptured AVM is headache, the most common presenting symptom in 7%-48% of patients without distinctive features of frequency, duration, or severity (Osipov et al. 1997). The occipital location of the AVMs is frequently associated with headache that sometimes can be invalidating. Although some authors did not support the relationship between cerebral malformations and headache (Kurita et al. 2000; Stabell and Nornes 1994) we had a few patients where the complete surgical removal of the malformations resolved the headache.

AVMS PATHOGENESIS

Cerebral arteriovenous malformations are a complex tangle of abnormal blood vessels with three morphological components:

1) the dysplastic core (nidus), where a direct connection between arteries and veins is present 2) the feeding arteries and, 3) the draining veins.

The nidus is characterized by the absence of normal to high resistance, arteriolar and capillary beds and is often well-circumscribed from the cerebral parenchyma. Nidus vessels usually have markedly attenuated walls, due to a deficient muscularis. Arterial feeders and 110 M. Cenzato and D. Boeris draining veins are not exclusively devoted to the AVM and also supply normal brain parenchyma, vascular shunt can also induce physiologic changes in the normal vasculature adjacent to the malformation. Cerebral AVMs were considered congenital lesions for several years, recently the scientific community have proposed new theories about malformations pathogenesis and development. Clinical research studies of AVM patients and animal models seem to show a novel paradigm to explain malformations pathogenesis, which so called “response-to-injury” (Ronald M. Lazar et al. 1999). Modest injury from an otherwise unremarkable episode of trauma, infection, inflammation, irradiation, or a mechanical stimulus such as compression may be at the base of a “response-to-injury” mechanisms for AVMs formation. When a cerebral “stimulus” occurred on an underlying structural defect, such as a microscopic developmental venous anomaly or some sort of venous outflow restriction in a microcirculatory bed, or an underlying genetic background such as mutations in key angiogenic genes, the normal injury response is shifted towards an abnormal dysplastic response. There are no reports on AVM findings in utero nor in newborns. The described process seems to occur during infancy or adolescence in a growing brain. There are also reports of the appearance of a new AVM in a patient with previous negative MRI examinations. Several scientific studies have been conducted on cerebral AVM tissue, these studies suggest an active angiogenic and inflammatory lesion with over-expression of several growth factors like vascular endothelial growth factor (VEGF-A), myeloperoxidase (MPO) and interleukin 6 (IL-6) and matrix metalloproteinase (MMP) (H. Kim et al. 2011; Hashimoto et al. 2004; Rothbart et al. 1996; Chen, Fan, et al. 2006; Chen, Pawlikowska, et al. 2006). Cerebral “stimulus” can determine the recruitment of progenitor cell population and this may be one source influencing AVM growth. Endothelial progenitor cells (EPCs), CD133, SDF-1 and CD68-positive may mediate pathological vascular remodeling (Hashimoto et al. 2003; P. Gao et al. 2010; Hao et al. 2007).

NATURAL HISTORY

Knowing the natural history of an unruptured AVM is essential in evaluating the opportunity to propose a treatment. Graf et al. in 1983 (Graf, Perret, and Torner 1983) published one of the first large observational papers including 200 cases of unruptured AVM with a follow up period of six years. This study concluded that the malformations of a small size have a higher risk of bleeding. Other authors like Ondra et al. (Ondra et al. 1990), published in 1990 a paper with 1616 patients observed for a period of 24 years. The patients in this report had a 4%-year risk of bleeding and 1%-year mortality. More recently Hernesniemi et al. in 2008 (Hernesniemi et al. 2008) published a report with 238 cases of arteriovenous malformations and confirmed these numbers. However, they (Graf, Perret, and Torner 1983; Hernesniemi et al. 2008) showed some elements that may increase the risk of bleeding above the standard value of 4% like: a previous hemorrhage, a deep location, the presence of deep vein discharges, exclusively deep venous drainage, presence of an ectasia before a stenosis on the venous side, and the presence of aneurysms on arterial feeders. In particular this paper showed that AVMs size does not seem to be a significant element concerning the risk of bleeding and show how infratentorial malformations have a risk of bleeding markedly higher compared to the supratentorial ones. Brain Arteriovenous Malformations 111

According to the international literature the estimated generic bleeding risk of an unruptured AVM is between 2 and 4% - year with a mortality risk of around 1% - year, this risk increases in presence of the cited elements. What’s the natural history of a ruptured AVMs? Concerning ruptured AVM, the Finnish study 2008 (Hernesniemi et al. 2008) on natural history of arteriovenous malformations, clearly showed that the risk of bleeding in the first years after the episode is increasing much higher by an average value of about 2-4% a year to a value that can reach 6% a year, returning, after 5 years, to the same value of a corresponding unruptured AVM It is important to emphasize that the risks of neurological sequelae after an AVM bleeding are lower than those due to an aneurysm bleeding, but almost one third of the patient experience a persistent neurological problems after a bleeding episode.

ADVANCED NEUROIMAGING

CT scan is usually the first imaging modality used, mainly to rule out hemorrhage as it is a low cost modality able to quickly show intracranial bleedings in an emergency setting (Ducreux et al. 2001). Parenchymatous calcifications are also observed in 20% of cases, related to intravascular thrombosis or evolution of an old hematoma. MRI though, given the different sequences available in MR imaging nowadays, is able to give a thorough analysis of the AVM evaluating anatomical elements as well as may provide functional analysis using fMRI. The size and the anatomical location of the nidus are precisely delineated by MRI. Studies demonstrated that the size of the nidus was more precisely shown by MRI than by conventional angiography, as well as the anatomical location is better defined by MRI than by angiography (Smith et al. 1988). Functional MRI activation has been extensively studied in patients with brain AVMs as fMRI activation is potentially very interesting in the effort to delineate functional areas of the brain. Brain AVM located close to an eloquent area, particularly sensorimotor, visual, and language cortex have to be carefully understood. Bold sequences used for the performance of fMRI are primarily based on hemodynamic changes in the cortex during the performance of a task, though given the huge hemodynamic modifications induced by AVMs in the perinidal parenchyma, there is some doubt regarding fMRI activation patterns (R. M. Lazar et al. 2000; Alkadhi et al. 2000). Selective angiography has to be performed always injecting the internal and external carotid arteries and vertebral arteries. Analysis of the arterial feeders, nidus, and venous drainage should be obtained by performing multiple projections (anteroposterior, lateral, and oblique). Despite excellent quality images, standard angiograms are often inadequate. The exact anatomy of large feeding arteries may need to be further investigated by superselective injections. Small feeding arteries are sometimes not visible on standard angiograms. Intranidal aneurysms (INA), feeding artery aneurysms (FAA) and direct intranidal AV fistulas are often misdiagnosed and represent a real diagnostic challenge, while venous drainage of the AVM is generally well studied by selective angiography. The venous pattern must be well assessed if surgery is planned. It can be risky to interrupt a large venous drainage of the AVM if it also drains part of the cerebral circulation. In this case it may be necessary to evaluate radiosurgery or a staged endovascular reduction of the flow.

112 M. Cenzato and D. Boeris

CLASSIFICATION

Spetzler and Martin (S&M) published a worldwide renowned grading scale in 1986 (R. F. Spetzler and Martin 1986), based on three parameters (eloquence, size and venous drainage) that revealed to be statistically predictive of the outcome after surgery. This classification has the advantage to be simple and easly applicable and rapidly became the refence standard. More recently, Spetzler and Ponce (Robert F. Spetzler and Ponce 2011) presented a variation to the previous classification called 3-tier in which AVMs are divided into 3 classes: class A, including grade I and II of the S-M classification AVMs; class B, including grade III AVMs; and class C, including grade IV and V AVMs. Lawton et al. (Lawton et al. 2010) then introduced three additional parameters affecting the outcome of AVM surgery: patient age, hemorrhagic presentation and nidal diffuseness, better defining the probability that the patient can have a neurological damage after surgery. The importance of these classifications is to guide the surgeon in choosing the proper treatment: higher grades have a high risk of surgical morbidity and mortality, therefore a careful balance between risk of natural history and surgical risk in the individual patient must be evaluated.

TREATMENT

Multimodal treatment of cerebral arteriovenous malformations requires precise knowledge of the risks of individual treatments and should be compared with the risk of the natural history. There is a fundamental different approach to arteriovenous malformations that have bled and unruptured arteriovenous malformations. Most of the literature available unfortunately compares the risk of multimodal treatment and the natural history not considering a clear distinction between ruptured AVMs and unruptured ones. While there is a general consensus that ruptured arteriovenous malformations are at higher risk of further bleeding, for unruptured malformations the arguments are certainly more complex. The ARUBA study, a randomized study that compared the risks of treatment of unruptured arteriovenous malformations with the natural history, had to stop the enrollment phase in advance as the treatment group had worse outcome then the observational group. This study raised several criticisms: the main one over the nature of the treatment that have been compared with natural history No distinction between treatments had been considered, which was mostly endovascular, a treatment already known to have several complications when used as a standalone procedure. On a case study of more than 200 patients evaluated, only 18 were treated surgically, and moreover in the outcome evaluation also temporary deficits where taken in account (Cenzato, Boccardi, et al. 2017; Cenzato et al. 2016). It is common experience that after surgery, especially in AVM surgery, temporary neurological deficits can occur, but most of them disappeared at follow-up. We published in 2017 a multicentric study of more than 500 AVM treated surgically and we found that, in unruptured AVM grades I to III, at a follow up of at least 6 months, severe disability is as lower than 2% of cases while moderate disability in 5.5% of the cases, with no mortality (Hamilton and Spetzler 1994). Hamilton and Spetzler made a prospective study of 120 consecutive patients who underwent complete microsurgical excision of their AVM, with or without previous embolization, to evaluate the correlation between the Spetzler-Martin grade and postoperative clinical complications (Cenzato et al. Brain Arteriovenous Malformations 113

2018). Permanent major morbidities were 0% for grades I–III, 21.9% for grade IV, and 16.7% for grade V. Deficit related to surgery and evaluated 6 weeks after operation was 0% in grade I, 4.2% in grade II, 2.8% in grade III, 31% in grade IV, and 50% in grade V. Mortality directly related to surgery was 0%. Risk of surgery is quite well estimated by the Spetzler-Martin grading system, with a favorable outcome in 92%–100% grade I, 95% grade II, 88% grade III, 73% grade IV, and 57% grade V. Treatment of AV malformations is to be evaluated on a case by case basis by a multidisciplinary team where a careful balance between efficacy and risk of a specific or multiple treatments can be assessed (Cenzato, Boccardi, et al. 2017). Cerebral AVMs treatment can be considered a varied combination of three methods: endovascular, surgical and radiosurgical treatment. Each treatment has specific indications and contraindications but has to aim to the complete elimination of the malformation (Cenzato, Boccardi, et al. 2017). A malformation must be considered healed only when the presence of early venous drainage, residues of the nidus, are no longer observable at a post-treatment angiography. The literature suggests that AVMs partially closed do not have a lower risk of bleeding, on the contrary AVM flow modification, both through an endovascular partial occlusion or through a partial surgical removal, can potentially expose the patient to a much greater AVM rupture risk. Miyamoto and colleagues have recently showed that after incomplete treatment of cerebral AVMs the hemorrhage rate increases to 17% and the associated morbidity and mortality related to the treatment increase to 23% and 9,3% respectively (Miyamoto et al. 2000). It is therefore important that whenever a treatment is planned, the strategy is to completely close the AVM. It is extremely dangerous to obtain a partial treatment without a following step to completely exclude the AVM. Treatment of AVM is essentially a matter of proper strategy and correct planning. A multidisciplinary experienced team is required to balance, in each single case, the risk and the advantage of the different treatment modalities.

ENDOVASCULAR TREATMENT

At the end of the 90's and the early years of this century endovascular procedure became a matter of interest, especially following the introduction of the Onyx. Onyx is made of a mixture of ethylene-vinyl alcohol copolymer (EVOH) and dimethyl sulfoxide (DMSO). EVOH is a copolymer of polyethylene and polyvinyl alcohol. Polyethylene was used for artificial joint implantation and polyvinyl alcohol constituted the particles of PVA used for embolization. The EVOH is dissolved in DMSO at three different concentrations: 6% (with 6% copolymer and 94% solvent), 6.5%, and --8%. A low concentration (6%) is less viscous and can allow more distal nidal penetration. The mixture is made opaque with tantalum powder. Onyx has promised to close arteriovenous malformations in a more comprehensive manner than you could do with glue or with spirals based on the great advantage that with slow injection it may allow the nidus of the malformation to close without the risk of an early occlusion of the venous side. The introduction of this material towards the end of the 90's has addressed the treatment of arteriovenous malformations mainly to the endovascular arm. As the experience accumulated has been observed that the great expectations that were posed on this material in the treatment of AVMs were disregarded. Most of the time, the treatment was not complete and therefore the possibility of relapse and the risk of bleeding potentially increased. Another disadvantage of 114 M. Cenzato and D. Boeris the endovascular treatment is that the injecting of Onyx is somehow unpredictable, in fact the slow flow injection sends the embolic material within the nidus with a pattern which is often unpredictable and uncontrollable. Moreover, Onyx leads to a closure of the superficial part of the malformation leaving the deep part, surgically more difficult to close behind a bulky mass of rubbery material. Therefore, in many experienced centers, primary treatment of AVMs with Onyx has been abandoned.

Adjuvant Role of Endovascular Treatments

Endovascular procedure for cerebral AVMs is nowadays rarely considered a treatment option per se, but can be considered above all an emergency treatment for ruptured AVM and a multi-staged option in preparation for surgery or radiosurgery. Patients with ruptured AVMs undergo emergency angiography to exclude the presence of an AVM-associated aneurysms that can be responsible for the bleeding. In the case of subarachnoid hemorrhage or parenchymal hematoma obviously related to a feeding artery aneurysm (FFA) rupture, the aneurysm should be treated in an emergency. Occluding the aneurysm can secure the AVM from further bleeding. Often, especially in deep located AVMs, the ruptured aneurysm can be located in a subependymal chorhoidal feeder o in a small perforating artery, therefore reaching it by endovascular means is extremely challenging. A different scenario is represented by cases without hemorrhage, where indications for treating first the aneurysm or the AVM are highly controversial. FAA may be regarded as a risk factor of bleeding that should be treated first, the rationale for treatment being that the morbidity and mortality associated with aneurysmal hemorrhage are considerably more severe than those associated with AVM rupture. FAA should be differentiated from Intranidal aneurysms (INA) that are located within or in the immediate vicinity of the AVM nidus. This constitutes a different entity and should be differentiated from pseudoaneurysms observed after an AVM rupture. Where a pseudoaneurysm or a false aneurysm is deemed responsible for the haemorrhage, embolization must be performed in the acute phase and should focus on aneurysm occlusion. Endovascular treatment in preparation for surgery should occlude the AVM deep feeders, that are more difficult to reach for the surgeon and that supply the AVM from the opposite side with respect to the surgical approach. As there is no need to close superficial feeders that can be safely and easily closed directly during surgery. Grade 1 and 2 AVMs can be operated without embolization, otherwise endovascular treatment may represent a good adjunct before surgery for large AVM where a multi-stages malformation flow reduction can reduce the brain oedema and haemorrhage after surgery. We should remember though, that the efficacy of partial embolization to reduce the risk of bleeding has not been proved. On the contrary, the computational model from Gao et al. (E. Gao et al. 1997) suggests that there might be increased pressure gradients and subsequent risk of bleeding during the final stages of embolization. Partial embolization with the aim of reducing the risk of bleeding should therefore not be performed.

Brain Arteriovenous Malformations 115

RADIOSURGERY

Radiosurgery represents an important tool in the AVMs treatment scheme. The mechanism of action is to focus a high radiation dose of rays against the AVMs nidus. With focused beams, radiation to brain tissue surrounding the AVM can be minimized. It has proven to be equally safe and effective whatever the device used, gamma knife, cyclotron, or linear accelerator. As demonstrated by surgical specimens the inflammatory processes driven by the radiation causes a progressive obliteration of the vessel lumen and thereby obliteration of arteriovenous malformations. This process can take several months and it is generally considered worn out after 3 years. During this time span the patient cannot be considered protected by the treatment to further bleeding. It is generally considered that the bleeding risk is unchanged until the AVM has completely disappeared. Several studies indicate that radiosurgery provides good results for AVM cure with low rates of complications. There have been many articles published on the response of AVMs to stereotactic radiosurgery. These studies have looked at clinical outcomes, dose response, safety, lesion location, dose staging, and adverse effects. Since the publication of ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations) (Cenzato, Boccardi, et al. 2017), there have been a number of articles that compare radiosurgical outcomes in patients with unruptured AVMs to data from that trial. The data support the use of radiosurgery for unruptured AVMs in patients expected to live at least 12–15 years. In this fashion, the value of AVM obliteration over time with potential morbidity outweighs the outcomes associated with observation alone. Radiosurgery is to be considered the first treatment option in small AVMs, less than 4 cm in diameter, if surgery is not feasible as they insist in eloquent areas. The chance of obliteration ranges from 60 to 70% for margin doses of 15-16 Gy to 90% or more for margin doses of 20-25 Gy (Niranjan, Lunsford, and Kano, n.d.). Neurologic decline after radiosurgery can occur from either hemorrhage or adverse radiation effects. These lasts can occur when the radiation dose is high and there are some observations that several endovascular procedures can produce a summatory effect. The American Stroke Association estimated that there is a 5%–7% risk of treatment-related complications with radiosurgery and, in addition, a 3%–4% risk per year of hemorrhage prior to obliteration. Over a 3-year period the patient has a 14%– 19% risk of complications or hemorrhage. Promising results come from the use of staged Radiosurgery in large AVMs that are not suitable for surgical treatment as an alternative where other techniques fail. After a careful evaluation of the different compartments of a large AVM radiosurgery can be focused on a single compartment at a time. Different sessions are performed at 6 month intervals obtaining a progressive reduction of the AVM (H. Y. Kim et al. 2010; Yamamoto et al. 2012). Although not yet defined as a standard, preliminary results are encouraging.

SURGERY

Spetzler and Martin in 1986 elaborate a well-known scale of surgical malformations risk based on three radiological parameters. It is now considered the most widely used system and has been validated both prospectively and retrospectively as a practical and reliable method for operative risk assessment and outcome prediction after AVM microsurgery. Hamilton and 116 M. Cenzato and D. Boeris

Spetzler made a prospective study of 120 consecutive patients who underwent complete microsurgical excision of their AVM, with or without previous embolization, to evaluate the correlation between the Spetzler-Martin grade and postoperative clinical complications (Cenzato et al. 2018). Permanent major morbidities were 0% for grades I–III, 21.9% for grade IV, and 16.7% for grade V. Deficit related to surgery and evaluated 6 weeks after operation was 0% in grade I, 4.2% in grade II, 2.8% in grade III, 31% in grade IV, and 50% in grade V. Mortality directly related to surgery was 0%. Risk of surgery is quite well estimated by the Spetzler-Martin grading system, with a favorable outcome in 92%–100% grade I, 95% grade II, 88% grade III, 73% grade IV, and 57% grade V. The scale immediately gives an estimate of the AVM complexity and therefore is widely used also for the medical communication of information. Low or high grade AVM have different surgical management and different morbidity and mortality rate. Therefore for grade I and II the surgical outcome is extremely good with no mortality and very low morbidity. While grade IV and V have a high rate of bad outcomes therefore surgery is not recommended in unruptured ones. Grade III remains difficult to define. Grade III- AVMs (S1V1E1) have a surgical risk similar to that of low-grade AVMs and can be safely treated with microsurgical resection. Grade III+ AVMs (S2V0E1) have a surgical risk similar to that of high-grade AVMs and are best managed conservatively. Grade III AVMs (S2V1E0) have intermediate surgical risks and require judicious selection for surgery. Grade III* AVMs (S3V0E0) are either exceedingly rare, with a surgical risk that is unclear, or theoretical lesions with no clinical relevance. In the computation of risk other elements should be considered such as nidus diffuseness, perforating arteries location, age, level of the eloquence of the involved area, deep venous drainage. Nidus diffuseness is an important predictor to define the difficulty of an AVM resection. High diffuseness AVMs have a nidus without clear anatomical dissection margin and represent a real challenge for the surgeon (Du et al. 2007). When a craniotomy is indicated in emergency to remove a large life-threatening hematoma sustained by an AVM. Only superficial AVMs, more easy to control, may be removed in the emergency setting together with the hematoma. When surgical removal of a brain AVM proves difficult, the hematoma may be removed or decompressed, and the treatment strategy then decided without the rush. Surgical treatment of the AVM is better performed later after the patient has recovered neurologically. In a non-emergent situation by the standard microsurgical technique a craniotomy is shaped large enough to show the gyrus before and after the malformation. Great care to the venous drainage is taken during the craniotomy and the dural opening. An operating microscope or a 3D exoscope is used to perform arachnoidal dissection and expose the AVM. Arterial feeders should be exposed and attacked first, followed by dissection of the nidus, and by the end of treatment the draining veins should be excised. The goal of surgery is complete cure, which should be proven by intraoperative and postoperative angiography. In case of residual AVM a repeat surgical approach should be considered immediately to avoid complications related to subtotal occlusion of the nidus. Is AVMs recurrence an issue? After complete AVM occlusion confirmed by postoperative angiography there is very little evidence that recurrence may exist. Kondziolka in 1992 reported two recurrences in 70 patients who had undergone complete AVM resection, and two patients presented 3 years later with recurrent hemorrhage. AVM regrowth can be considered only in children. An immediate postoperative angiogram may be false by postoperative vasospasm, Brain Arteriovenous Malformations 117 thrombosis of arteries and veins. In the postoperative weeks delayed recruitment of collateral arteries are the more likely explanations for the so-called recurrences.

Figure 1. Examples of diffuse AVMs: MRI images clearly highlight how the interface between AVM and brain parenchyma is poorly defined.

Figure 2. Deep white matter feeders. these vessel are inflated by the AVM. They are extremely fragile and difficult to coagulate because of the high disproportion between the vessel diameter and the vessel wall thickness.

COMPLICATIONS AVOIDANCE

AVM surgery requires careful planning and the appropriate OR setting. While neuronavigation and microscope represent a standard of practice for several other procedures we hereby name several other nuances that have implemented in the last decade the safety of AVMs resection.

118 M. Cenzato and D. Boeris

 Indocyanine green video-angiography (ICG): Indocyanine green is a near-infrared fluorescein diagnostic tool which, once injected, bounds within 1-2 seconds to globulins, remaining intravascular. Raabe et al. first described this tool applied in vascular neurosurgery (Raabe et al. 2003). They described how allows intraoperative real-time assessment of the cerebral circulation and information on the patency of arterial and venous vessels. The use of the ICG in vascular neurosurgery is largely adopted and in AVM surgery can now be considered mandatory (Faber et al. 2011). At the end of the surgical procedure, the ICG can be essential to identify the presence of a residual along the margins of the surgical cavity.  Non-stick bipolar forceps and dirty coagulation: AVMs vessels are hypertrophic and fragile and their bleeding, especially in the deep white matter are hardly controlled with conventional bipolar forceps. The introduction of non stick bipolar has objectively improved the handling of the thin wall of these dilated vessels susceptible of burning and attaching to the conventional bipolar forceps. Compared to conventional bipolars they allow dispersion of the heat (Isocool)reducing the possibility of high temperatures at the tip contact point.  Thulium laser: The introduction of this tool in treatment in vascular neurosurgery has been reported in the literature for AVMs resection by Heiu et al. (Sundt and Kees 1986). The most innovative instrument developed in this field is the thulium laser (Hieu et al. 1997). It consists of thin and reusable optic fibers, at 2µm wavelength gives a quick superficial increase of temperature with minimal parenchymal penetration and thanks to strong absorption of its output radiation in water, it works in wet ambient preventing tissue damage due to heat dispersion. It allows large venous vessels shrinkage, making the nidus smaller, more compact, so easier to mobilize it. During the removal of the deep part of nidus, it can be used to control the bleeding from small vessels (1-2 mm) coming from deep white matter based on a temporary interruption of the blood flow using tweezers and laser coagulation (Cenzato, Dones, et al. 2017).  Intraoperative ultrasound (iUS): The intraoperative ultrasound (iUS) was introduced in the neurosurgical field initially for brain tumor surgery (Hammoud et al. 1996; Prada et al. 2014) and then was extended with good success onto AVM surgery. This tool provides real-time intraoperative images, and can be integrated with a navigation system which allows to merge pre-operative MRI with intraoperative acquired images. Following the craniotomy, the probe is used onto the dura plane to visualize the AVM. During the surgery, contrast-enhanced ultrasound (CEUS) can be used. intraoperative Doppler scans can also be performed in order to evaluate the direction of blood in the main vessels.  Intraoperative neurophysiological monitoring: Surgery of AVM located in eloquent areas and those deep-seated involving the basal ganglia, requires intraoperative neurophysiological monitoring (IONM). SSEPs consist in testing the ascending sensory pathways through the posterior column of the spinal cord. A decrease of more than 50% or an increase of more than 10% of the SSEP amplitude is the alarm for potential injury (Nuwer et al. 1995). Furthermore, the somatosensory stimulation doesn’t provoke unwanted movement of the patient and usually present a high reliability (Lepski et al. 2012). They are always complemented by other modalities. MEPs are usually generated through transcranial electrical stimulation and Brain Arteriovenous Malformations 119

Electroencephalography (EEG) and electromyography (EMG) are other important tools which can be used during IONM.

Figure 3. Presurgical embo: Occipital AVM. The large deep feeder is located on the opposite side of the surgeon’s approach. Endovascular presurgical occlusion can facilitate surgical removal.

Figure 4. Grade 5 AVM treated with staged Gamma knife. Left: before treatment. Middle: two different targets of the radiosurgical treatment, in different sessions. Right: MRI, 3 years later.

 Hybrid operating rooms: In AVMs surgery, the angiographic exam is fundamental to understand the angioarchitecture for an adequate surgery planning. Another mandatory use of this tool is the need of a post-operative angiographic control which can exclude the presence of any residual. Many centers have at their disposal the so called hybrid operating room with the possibility to perform the post-operative angiography directly on the surgical table to establish the complete resection of the lesion. With the progress of technology the 2-D angiography available in many operating theatres has been outdated by the tri dimensional rotational angiography (3D-RA) (Nuwer et al. 1995). 120 M. Cenzato and D. Boeris

REFERENCES

Alkadhi, H., S. S. Kollias, G. R. Crelier, X. Golay, M. C. Hepp-Reymond, and A. Valavanis. 2000. “Plasticity of the Human Motor Cortex in Patients with Arteriovenous Malformations: A Functional MR Imaging Study.” American Journal of Neuroradiology 21 (8): 1423–33. Auger, Raymond G., and David O. Wiebers. 1992. “Management of Unruptured Intracranial Arteriovenous Malformations: A Decision Analysis.” Neurosurgery 30 (4): 561–69. https://doi.org/10.1227/00006123-199204000-00015. Berman, Mitchell F., Robert R. Sciacca, John Pile-Spellman, Christian Stapf, E. Sander Connolly, Jay P. Mohr, and William L. Young. 2000. “The Epidemiology of Brain Arteriovenous Malformations.” Neurosurgery. https://doi.org/10.1097/00006123- 200008000-00023. Brown, R. D., D. O. Wiebers, G. Forbes, W. M. O’Fallon, D. G. Piepgras, W. R. Marsh, and R. J. Maciunas. 1988. “The Natural History of Unruptured Intracranial Arteriovenous Malformations.” Journal of Neurosurgery 68 (3): 352–57. https://doi.org/10.3171/ jns.1988.68.3.0352. Brown, Robert D., David O. Wiebers, James C. Torner, and W. Michael O’Fallon. 1996. “Frequency of Intracranial Hemorrhage as a Presenting Symptom and Subtype Analysis: A Population-Based Study of Intracranial Vascular Malformations in Olmsted County, Minnesota.” Journal of Neurosurgery 85 (1): 29–32. https://doi.org/10.3171/jns.1996. 85.1.0029. Carter, L P, and M K Gumerlock. 1995. “Steal and Cerebral Arteriovenous Malformations.” Stroke 26 (12): 2371–72. http://www.ncbi.nlm.nih.gov/pubmed/7491667. Cenzato, Marco, Edoardo Boccardi, Ettore Beghi, Peter Vajkoczy, Istvan Szikora, Enrico Motti, Luca Regli, et al. 2017. “European Consensus Conference on Unruptured Brain AVMs Treatment (Supported by EANS, ESMINT, EGKS, and SINCH).” In Acta Neurochirurgica, 159:1059–64. Springer-Verlag Wien. https://doi.org/10.1007/s00701- 017-3154-8. Cenzato, Marco, Alberto Delitala, Roberto Delfini, Alberto Pasqualin, Giulio Maira, Vincenzo Esposito, Francesco Tomasello, and Edoardo Boccardi. 2016. “Position Statement from the Italian Society of Neurosurgery on the ARUBA Study.” Journal of Neurosurgical Sciences 60 (1): 126–30. Cenzato, Marco, Flavia Dones, Eleonora Marcati, Alberto Debernardi, Alba Scerrati, and Maurizio Piparo. 2017. “Use of Laser in Arteriovenous Malformation Surgery.” World Neurosurgery 106 (October): 746–49. https://doi.org/10.1016/j.wneu.2017.07.101. Cenzato, Marco, Fulvio Tartara, Giuseppe D’Aliberti, Carlo Bortolotti, Francesco Cardinale, Gianfranco Ligarotti, Alberto Debernardi, et al. 2018. “Unruptured Versus Ruptured AVMs: Outcome Analysis from a Multicentric Consecutive Series of 545 Surgically Treated Cases.” World Neurosurgery 110 (February): e374–82. https://doi.org/10.1016/ j.wneu.2017.11.003. Chen, Yongmei, Yongfeng Fan, K. Y.Trudy Poon, Achal S. Achrol, Michael T. Lawton, Yiqian Zhu, Charles E. McCulloch, et al. 2006. “MMP-9 Expression Is Associated with Leukocytic but Not Endothelial Markers in Brain Arteriovenous Malformations.” Frontiers in Bioscience 11 (SUPPL. 3): 3121–28. https://doi.org/10.2741/2037. Brain Arteriovenous Malformations 121

Chen, Yongmei, Ludmila Pawlikowska, Jianhua S. Yao, Fanxia Shen, Wenwu Zhai, Achal S. Achrol, Michael T. Lawton, Pui Yan Kwok, Guo Yuan Yang, and William L. Young. 2006. “Interleukin-6 Involvement in Brain Arteriovenous Malformations.” Annals of Neurology 59 (1): 72–80. https://doi.org/10.1002/ana.20697. Crawford, P. M., C. R. West, D. W. Chadwick, and M. D.M. Shaw. 1986. “Arteriovenous Malformations of the Brain: Natural History in Unoperated Patients.” Journal of Neurology Neurosurgery and Psychiatry 49 (1): 1–10. https://doi.org/10.1136/jnnp.49.1.1. Du, Rose, H. Michael Keyoung, Christopher F. Dowd, William L. Young, and Michael T. Lawton. 2007. “The Effects of Diffuseness and Deep Perforating Artery Supply on Outcomes after Microsurgical Resection of Brain Arteriovenous Malformations.” Neurosurgery 60 (4): 638–48. https://doi.org/10.1227/01.NEU.0000255401.46151.8A. Ducreux, Denis, Denis Trystram, Catherine Oppenheim, Sylvie Godon-Hardy, Odile Missir, Jean-François Meder, D Enis, et al. 2001. “Imagerie Diagnostique Des Malformations Artério-Veineuses Cérébrales Summary : Imaging of Brain Arteriovenous Malfor- Mations.” Neurochirurgie. Vol. 47. Faber, Florian, Niklas Thon, Gunther Fesl, Walter Rachinger, Roland Guckler, Jörg Christian Tonn, and Christian Schichor. 2011. “Enhanced Analysis of Intracerebral Arterioveneous Malformations by the Intraoperative Use of Analytical Indocyanine Green Videoangiography: Technical Note.” Acta Neurochirurgica 153 (11): 2181–87. https://doi. org/10.1007/s00701-011-1141-z. Frishberg, Benjamin M. 1997. “Neuroimaging in Presumed Primary Headache Disorders.” Seminars in Neurology. Thieme Medical Publishers, Inc. https://doi.org/10.1055/s-2008- 1040951. Gao, Erzhen, William L. Young, John Pile-Spellman, Shailendra Joshi, Hoang Duong, Philip E. Stieg, and Qiyuan Ma. 1997. “Cerebral Arteriovenous Malformation Feeding Artery Aneurysms: A Theoretical Model of Intravascular Pressure Changes after Treatment.” Neurosurgery 41 (6): 1345–58. https://doi.org/10.1097/00006123-199712000-00020. Gao, Peng, Yongmei Chen, Michael T. Lawton, Nicholas M. Barbaro, Guo Yuan Yang, Hua Su, Feng Ling, and William L. Young. 2010. “Evidence of Endothelial Progenitor Cells in the Human Brain and Spinal Cord Arteriovenous Malformations.” Neurosurgery 67 (4): 1029–35. https://doi.org/10.1227/NEU.0b013e3181ecc49e. Graf, C. J., G. E. Perret, and J. C. Torner. 1983. “Bleeding from Cerebral Arteriovenous Malformations as Part of Their Natural History.” Journal of Neurosurgery 58 (3): 331–37. https://doi.org/10.3171/jns.1983.58.3.0331. Guttmacher, Alan E., Douglas A. Marchuk, and Robert I. White. 1995. “Hereditary Hemorrhagic Telangiectasia.” New England Journal of Medicine. N Engl J Med. https://doi.org/10.1056/NEJM199510053331407. Hamilton, Mark G., and Robert F. Spetzler. 1994. “The Prospective Application of a Grading System for Arteriovenous Malformations.” Neurosurgery 34 (1): 2–7. https://doi.org/10. 1227/00006123-199401000-00002. Hammoud, Maarouf A., B. Lee Ligon, Rabih Elsouki, Wei Ming Shi, Donald F. Schomer, and Raymond Sawaya. 1996. “Use of Intraoperative Ultrasound for Localizing Tumors and Determining the Extent of Resection: A Comparative Study with Magnetic Resonance Imaging.” Journal of Neurosurgery 84 (5): 737–41. https://doi.org/10.3171/jns.1996. 84.5.0737. 122 M. Cenzato and D. Boeris

Hao, Qi, Yongmei Chen, Yiqian Zhu, Yongfeng Fan, Daniel Palmer, Hua Su, William L. Young, and Guo Yuan Yang. 2007. “Neutrophil Depletion Decreases VEGF-Induced Focal Angiogenesis in the Mature Mouse Brain.” Journal of Cerebral Blood Flow and Metabolism 27 (11): 1853–60. https://doi.org/10.1038/sj.jcbfm.9600485. Hashimoto, Tomoki, Michael T. Lawton, Gen Wen, Guo Yuan Yang, Thomas Chaly, Campbell L. Stewart, Holly K. Dressman, et al. 2004. “Gene Microarray Analysis of Human Brain Arteriovenous Malformations.” Neurosurgery 54 (2): 410–25. https://doi.org/10.1227/ 01.NEU.0000103421.35266.71. Hashimoto, Tomoki, Gen Wen, Michael T. Lawton, Nancy J. Boudreau, Andrew W. Bollen, Guo Yuan Yang, Nicholas M. Barbaro, et al. 2003. “Abnormal Expression of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Brain Arteriovenous Malformations.” Stroke 34 (4): 925–30. https://doi.org/10.1161/01.STR. 0000061888.71524.DF. Hernesniemi, Juha A., Reza Dashti, Seppo Juvela, Kristjan Väärt, Mika Niemelä, and Aki Laakso. 2008. “Natural History of Brain Arteriovenous Malformations: A Long-Term Follow-up Study of Risk of Hemorrhage in 238 Patients.” Neurosurgery 63 (5): 823–29. https://doi.org/10.1227/01.NEU.0000330401.82582.5E. Hieu, P D, G Besson, S Roncin, and M Nonent. 1997. “Successful Surgical Treatment of Intraorbital Arteriovenous Malformations: Case Report.” Neurosurgery 40 (3): 626–31. http://www.ncbi.nlm.nih.gov/pubmed/9055307. Hofmeister, C., C. Stapf, A. Hartmann, R. R. Sciacca, U. Mansmann, K. TerBrugge, P. Lasjaunias, J. P. Mohr, H. Mast, and J. Meisel. 2000. “Demographic, Morphological, and Clinical Characteristics of 1289 Patients with Brain Arteriovenous Malformation.” Stroke 31 (6): 1307–10. https://doi.org/10.1161/01.STR.31.6.1307. Kaminaga T, Hayashida K, Iwama T, et al. 1999. “Hemodynamic Changes around Cerebral Arteriovenous Malformation before and after Embolization Measured with Pet.” J Neuroradiol. 1999. https://www.em-consulte.com/en/article/119572. Kim, Hae Yu, Won Seok Chang, Dong Joon Kim, Jae Whan Lee, Jin Woo Chang, Dong Ik Kim, Seung Kon Huh, Yong Gou Park, and Jong Hee Chang. 2010. “Gamma Knife Surgery for Large Cerebral Arteriovenous Malformations.” Journal of Neurosurgery 113 Suppl: 2– 8. https://doi.org/10.3171/2010.7.gks101043. Kim, Helen, Hua Su, Shantel Weinsheimer, Ludmila Pawlikowska, and William L. Young. 2011. “Brain Arteriovenous Malformation Pathogenesis: A Response-to-Injury Paradigm.” In Acta Neurochirurgica, Supplementum, 111:83–92. Springer-Verlag Wien. https://doi.org/10.1007/978-3-7091-0693-8_14. Kjeldsen, A. D., P. Vase, and A. Green. 1999. “Hereditary Haemorrhagic Telangiectasia: A Population-Based Study of Prevalence and Mortality in Danish Patients.” Journal of Internal Medicine 245 (1): 31–39. https://doi.org/10.1046/j.1365-2796.1999.00398.x. Kurita, Hiroki, Keisuke Ueki, Masahiro Shin, Shunsuke Kawamoto, Tomio Sasaki, Masao Tago, and Takaaki Kirino. 2000. “Headaches in Patients with Radiosurgically Treated Occipital Arteriovenous Malformations.” Journal of Neurosurgery 93 (2): 224–28. https://doi.org/10.3171/jns.2000.93.2.0224. Lawton, Michael T., Helen Kim, Charles E. McCulloch, Bahar Mikhak, and William L. Young. 2010. “A Supplementary Grading Scale for Selecting Patients with Brain Arteriovenous Malformations for Surgery.” Neurosurgery 66 (4): 702–13. https://doi.org/10.1227/ 01.NEU.0000367555.16733.E1. Brain Arteriovenous Malformations 123

Lazar, R. M., R. S. Marshall, J. Pile-Spellman, H. C. Duong, J. P. Mohr, W. L. Young, R. L. Solomon, G. M. Perera, and R. L. Delapaz. 2000. “Interhemispheric Transfer of Language in Patients with Left Frontal Cerebral Arteriovenous Malformation.” Neuropsychologia 38 (10): 1325–32. https://doi.org/10.1016/S0028-3932 (00)00054-3. Lazar, Ronald M., Kathleen Connaire, Randolph S. Marshall, John Pile-Spellman, Lotfi Hacein-Bey, Robert A. Solomon, Michael B. Sisti, William L. Young, and J. P. Mohr. 1999. “Developmental Deficits in Adult Patients with Arteriovenous Malformations.” Archives of Neurology 56 (1): 103–6. https://doi.org/10.1001/archneur.56.1.103. Lepski, Guilherme, Jürgen Honegger, Marina Liebsch, Marília Grando Sória, Porn Narischat, Kristofer Fingerle Ramina, Thomas Nägele, Ulrike Ernemann, and Marcos Tatagiba. 2012. “Safe Resection of Arteriovenous Malformations in Eloquent Motor Areas Aided by Functional Imaging and Intraoperative Monitoring.” Operative Neurosurgery 70 (suppl_2): ons276–89. https://doi.org/10.1227/neu.0b013e318237aac5. Mast, Henning, J. P. Mohr, Andrei Osipov, John Pile-Spellman, Randolph S. Marshall, Ronald M. Lazar, Bennett M. Stein, and William L. Young. 1995. “‘Steal’ Is an Unestablished Mechanism for the Clinical Presentation of Cerebral Arteriovenous Malformations.” Stroke 26 (7): 1215–20. https://doi.org/10.1161/01.STR.26.7.1215. Mingrino, S. 1978. “Supratentorial Arteriovenous Malformations of the Brain.” In, 93–123. Springer, Vienna. https://doi.org/10.1007/978-3-7091-7062-5_3. Miyamoto, Susumu, Nobuo Hashimoto, Izumi Nagata, Kazuhiko Nozaki, Masafumi Morimoto, Waro Taki, and Haruhiko Kikuchi. 2000. “Posttreatment Sequelae of Palliatively Treated Cerebral Arteriovenous Malformations.” Neurosurgery 46 (3): 589– 95. https://doi.org/10.1097/00006123-200003000-00013. Miyasaka, Y., K. Yada, T. Ohwada, T. Kitahara, A. Kurata, and K. Irikura. 1992. “An Analysis of the Venous Drainage System as a Factor in Hemorrhage from Arteriovenous Malformations.” Journal of Neurosurgery 76 (2): 239–43. https://doi.org/10.3171/ jns.1992.76.2.0239. Miyasaka, Y, K Yada, A Kurata, K Tokiwa, R Tanaka, and T Ohwada. 1994. “An Unruptured Arteriovenous Malformation with Edema.” AJNR. American Journal of Neuroradiology 15 (2): 385–88. http://www.ncbi.nlm.nih.gov/pubmed/8192089. Mohr, J. P. 1999. “Arteriovenous Malformations of the Brain in Adults.” New England Journal of Medicine 340 (23): 1812–18. https://doi.org/10.1056/NEJM199906103402307. NA, Martin, and Vinters HV. 1995. “Arteriovenous Malformations.” Niranjan, Ajay, L. Dade Lunsford, and Hideyuki Kano. n.d. Leksell Radiosurgery. Nuwer, Marc R., Edgar G. Dawson, Linda G. Carlson, Linda E. A. Kanim, and John E. Sherman. 1995. “Somatosensory Evoked Potential Spinal Cord Monitoring Reduces Neurologic Deficits after Scoliosis Surgery: Results of a Large Multicenter Survey.” Electroencephalography and Clinical Neurophysiology/ Evoked Potentials 96 (1): 6–11. https://doi.org/10.1016/0013-4694 (94)00235-D. Olivecrona, Herbert, and Johannes Riives. 1948. “Arteriovenous Aneurysms of the Brain: Their Diagnosis and Treatment.” Archives of Neurology And Psychiatry 59 (5): 567–602. https://doi.org/10.1001/archneurpsyc.1948.02300400003001. Ondra, S. L., H. Troupp, E. D. George, and K. Schwab. 1990. “The Natural History of Symptomatic Arteriovenous Malformations of the Brain: A 24-Year Follow-up Assessment.” Journal of Neurosurgery 73 (3): 387–91. https://doi.org/10.3171/jns.1990. 73.3.0387. 124 M. Cenzato and D. Boeris

Osipov, A., H. C. Koennecke, A. Hartmann, W. L. Young, J. Pile-Spellman, L. Hacein-Bey, J. P. Mohr, and H. Mast. 1997. “Seizures in Cerebral Arteriovenous Malformations: Type, Clinical Course, and Medical Management.” Interventional Neuroradiology 3 (1): 37–41. https://doi.org/10.1177/159101999700300104. Porteous, M. E.M., J. Burn, and S. J. Proctor. 1992. “Hereditary Haemorrhagic Telangiectasia: A Clinical Analysis.” Journal of Medical Genetics 29 (8): 527–30. https://doi.org/ 10.1136/jmg.29.8.527. Prada, F., M. Del Bene, L. Mattei, L. Lodigiani, S. Debeni, V. Kolev, I. Vetrano, L. Solbiati, G. Sakas, and F. Dimeco. 2014. “Preoperative Magnetic Resonance and Intraoperative Ultrasound Fusion Imaging for Real-Time Neuronavigation in Brain Tumor Surgery.” Ultraschall in Der Medizin 9 (12). https://doi.org/10.1055/s-0034-1385347. Prayer, L., D. Wimberger, R. Stiglbauer, J. Kramer, B. Richling, G. Bavinzski, T. Czech, and H. Imhof. 1993. “Haemorrhage in Intracerebral Arteriovenous Malformations: Detection with MRI and Comparison with Clinical History.” Neuroradiology 35 (6): 424–27. https://doi.org/10.1007/BF00602821. Pribil, Stefan, Stephen C.Boone, and Robert Waley. 1983. “Obstructive Hydrocephalus at the Anterior Third Ventricle Caused by Dilated Veins from an Arteriovenous Malformation.” Surgical Neurology 20 (6): 487–92. https://doi.org/10.1016/0090-3019 (83)90032-0. Raabe, Andreas, Jürgen Beck, Rüdiger Gerlach, Michael Zimmermann, Volker Seifert, R. Loch Macdonald, Bernhard Meyer, and Warren R. Selman. 2003. “Near-Infrared Indocyanine Green Video Angiography: A New Method for Intraoperative Assessment of Vascular Flow.” Neurosurgery 52 (1): 132–39. https://doi.org/10.1097/00006123-200301000- 00017. RD, Brown Jr. n.d. “Epidemiology and Natural History of Vascular Malformations of the Central Nervous System.” Rothbart, David, Issam A. Awad, Jiyon Lee, Jung Kim, Robert Harbaugh, and Gregory R. Criscuolo. 1996. “Expression of Angiogenic Factors and Structural Proteins in Central Nervous System Vascular Malformations.” Neurosurgery 38 (5): 915–25. https://doi.org/ 10.1097/00006123-199605000-00011. Smith, H. J., C. M. Strother, Y. Kikuchi, T. Duff, L. Ramirez, A. Merless, and S. Toutant. 1988. “MR Imaging in the Management of Supratentorial Intracranial AVMs.” American Journal of Roentgenology 150 (5): 1143–53. https://doi.org/10.2214/ajr.150.5.1143. Spetzler, R. F., and N. A. Martin. 1986. “A Proposed Grading System for Arteriovenous Malformations.” Journal of Neurosurgery 65 (4): 476–83. https://doi.org/10.3171/jns. 1986.65.4.0476. Spetzler, Robert F., and Francisco A. Ponce. 2011. “A 3-Tier Classification of Cerebral Arteriovenous Malformations.” Journal of Neurosurgery 114 (3): 842–49. https://doi.org/ 10.3171/2010.8.JNS10663. Stabell, K. E., and H. Nornes. 1994. “Prospective Neuropsychological Investigation of Patients with Supratentorial Arteriovenous Malformations.” Acta Neurochirurgica 131 (1–2): 32– 44. https://doi.org/10.1007/BF01401452. Stapf, C., H. Mast, R. R. Sciacca, J. H. Choi, A. V. Khaw, E. S. Connolly, J. Pile-Spellman, and J. P. Mohr. 2006. “Predictors of Hemorrhage in Patients with Untreated Brain Arteriovenous Malformation.” Neurology 66 (9): 1350–55. https://doi.org/10.1212/ 01.wnl.0000210524.68507.87. Brain Arteriovenous Malformations 125

Stapf, C., J. P. Mohr, J. Pile-Spellman, R. A. Solomon, R. L. Sacco, and E. S. Connolly. 2001. “Epidemiology and Natural History of Arteriovenous Malformations.” Neurosurgical Focus. Neurosurg Focus. https://doi.org/10.3171/foc.2001.11.5.2. Sundt, T. M., and G. Kees. 1986. “Miniclips and Microclips for Surgical Hemostasis. Technical Note.” Journal of Neurosurgery 64 (5): 824–25. https://doi.org/10.3171/jns.1986.64.5. 0824. Turjman, F, T F Massoud, F Viñuela, J W Sayre, G Guglielmi, and G Duckwiler. 1994. “Aneurysms Related to Cerebral Arteriovenous Malformations: Superselective Angiographic Assessment in 58 Patients.” AJNR. American Journal of Neuroradiology 15 (9): 1601–5. http://www.ncbi.nlm.nih.gov/pubmed/7847201. Yamamoto, Masaaki, Atsuya Akabane, Yuji Matsumaru, Yoshinori Higuchi, Hidetoshi Kasuya, and Yoichi Urakawa. 2012. “Long-Term Follow-up Results of Intentional 2-Stage Gamma Knife Surgery with an Interval of at Least 3 Years for Arteriovenous Malformations Larger than 10 Cm3.” Journal of Neurosurgery 117 Suppl (December): 126–34. https://doi.org/10.3171/2012.6.gks12757. Yaşargil, M G, K K Jain, J Antic, and R Laciga. 1976. “Arteriovenous Malformations of the Splenium of the Corpus Callosum: Microsurgical Treatment.” Surgical Neurology 5 (1): 5–14. http://www.ncbi.nlm.nih.gov/pubmed/1265626.

Chapter 7

SPINAL ARTERIOVENOUS MALFORMATIONS

D. Boeris1, MD and M. Cenzato1, PhD 1Department of Neurosurgery, Grande Ospedale Metropolitano Niguarda, Milan, Italy

ABSTRACT

Vascular malformations of the spinal cord, namely arteriovenous malformations (AVMs) and fistulas (AVFs), account for less than 5% of the intraspinal pathology and cause severe and progressive symptoms. In this chapter we describe the decision-making process of AVMs and AVFs, along with the main principles of their endovascular and microsurgical treatment.

1. INTRODUCTION

Spinal vascular malformations still represent an undefined niche in the field of Neurosurgery. They have not yet been sufficiently studied both due to the complexity of their diagnosis and the rarity of the pathology itself. Great uncertainty remains due to the lack of a classification that could include both anatomical and hemodynamic information of spinal AVM.

2. EPIDEMIOLOGY

Spinal AVM have relatively equal incidence in males and females with onset typically in the second or third decade. These spinal vascular lesions represent a heterogeneous group of non neoplastic vascular lesions accounting for less than 5% of the intraspinal pathology (Bao and Ling 1997).

 Corresponding Author’s Email: [email protected]. 128 D. Boeris and M. Cenzato

3. CLASSIFICATIONS

As we will see later the early classifications of spinal vascular lesions include tumors and tumor-like diseases, such as hemangioblastomas and hemangiomas. The very first diagnosis dates back to 1887, when Dr Gaupp diagnosed on a cadaver the first AVM as haemorrhoids of the pia mater. Years later in 1942 became available the first classification of Spinal AVMs that was histology based Bergstrand, et al., (Bergstrand, Hook, and Lidvall 1964). Though, we have to wait until 1972 when selective angiography became available for the first clinical classification by Baker and Layton at al. (Hawe et al., 1972; Baker, Love, and Layton 1967). In 1987, Rosenblum, et al., proposed an up-to-date classification of spinal vascular malformations based on the data acquired during examination and treatment of 81 patients (Rosenblum et al., 1987). This 1987 paper divided spinal AVMs into malformations and fistulas, and they distinguished intradural and dural vascular malformations. Intradural malformations were subdivided into intramedullary (glomus and juvenile AVMs) and extramedullary AVFs. These authors defined as dural AVFs the malformations that were situated inside the spinal dura mater and had retrograde drainage toward the perimedullary veins. In 1992 Spetzler proposed the first version of his spinal vascular lesion classification. This classification contained both spinal AVM and AVF (Anson J. A. 1992). In 1997 Bao and Ling distinguished intramedullary AVM, intradural AVF, dural AVF, paravertebral AVM, and Cobb syndrome (metameric localization of AVM) among the types of malformations. Intramedullary processes were subdivided into intramedullary and juvenile AVMs (Bao and Ling 1997). Intradural AVFs were subdivided into Types I, II, and III, according to the intensity of the blood flow and the number of tributaries. In 1995 Borden and colleagues subdivided spinal dural AVFs into three types by analogy with cranial dural AVFs: Type I, which had antegrade drainage into the epidural veins; Type II, which had both retrograde (into the perimedullary veins) and antegrade (into the epidural veins) drainage; and Type III, which had retrograde drainage into the perimedullary veins (Borden, Wu, and Shucart 1995).

Table 1. Baker and Layton Classification of Spinal AVM (Baker, Love, and Layton 1967)

Type 1 Single coiled vessel Type 2 Glomus AVM Type 3 Juvenile AVMs

Table 2. Spetzler Classification of Spinal AVM and AVF (Anson J. A. 1992)

Type 1 Dural arteriovenous fistula Dural arteriovenous fistula Type 2 Intramedullary arteriovenous Intramedullary arteriovenous malformation (AVM) malformation (AVM) Type 3 Juvenile AVM Juvenile AVM Type 4 Intradural perimedullary AVF Intradural perimedullary AVF Spinal Arteriovenous Malformations 129

Table 3. Spetzler Classification of Medullary Arteriovenous Malformations (Spetzler et al., 2002)

Type 1 Extradural-intradural arteriovenous malformations Type 2 Intramedullary arteriovenous malformation Type 3 Conus medullaris arteriovenous malformation

In 2002, Spetzler, et al., offered a new classification of spinal vascular processes. Among these entities the authors distinguished the following: spinal tumor vascular processes (hemangioblastomas, cavernous malformations), spinal aneurysms, AVFs, and AVMs (Spetzler et al., 2002). Spetzler, in this 2002 classification, distinguished extradural-intradural, intradural, and intramedullary lesions (compact, diffuse, or spinal cord conus). Intramedullary diffuse AVMs, which had been described earlier but were nowhere classified, as well as the first AVM distinguished in the spinal cord conus, were added to the classification. This is nowadays one of the most used classification for spinal AVMs. For the benefit of the reader we will refer to Spinal AVMs from now on according to this classification.

4. CLINICAL PRESENTATION

Clinical presentation could be characterized by either progressive or acute symptoms. As in Spinal DAVF, venous engorgement is the main responsible for the progressive neurological symptoms: venous engorgement decreases arterial perfusion gradient and patients may present with progressive symptoms similarly to spinal fistulas. Patients may experience a variety of symptoms such as radiculopathy, paresthesias, spastic paraplegia, urinary incontinence, bowel incontinence, and sexual dysfunction depending on the location of the AVM. The presence of varices and mechanical compression may cause cause radicular or cord compression with related symptoms. Steal phenomenon represent also a cause of onset of symptoms in this pathology. Due to the fistolous tracts the arterial and venous region communicate directly without the interposition of a capillary compartment. This increased velocity does not allow a normal perfusion gradient and blood flow is quickly washed out into the vein. This pathophysiology defines the steal phenomenon. Differently acute neurological and non neurological symptoms such as acute onset back or suboccipital pain, meningismus, and motor deficits are related to venous thrombosis or hemorrhage. Subarachnoid or intramedullary haemorrhage occurs with higher frequency in spinal AVMs than in DAVF. This presentation was early on described as “le coup de poignard rachidian” by Michon in 1928, it is the spinal equivalent of the “thunderclap” headache experienced with intracranial subarachnoid haemorrhage. Nearly half of all patients who present with gait impairment are confined to a wheelchair or bed within 3 years, and one-fifth of patients require crutches or are non ambulatory by 6 months after the onset of deficitarian symptoms (Aminoff and Logue 1974b, 1974a). Hemorrhagic onset is a particularly bad prognostic factor.

130 D. Boeris and M. Cenzato

5. NEURORADIOLOGICAL DIAGNOSIS

5.1. Magnetic Resonance Imaging (MRI)

This is key exam to define the location and anatomical relations of the lesion within the spine. Spinal AVM typically occurs within the cord. High flow into the nidus may result in aneurysms within the feeding spinal arteries. The increased flow may similarly result in ischemia of the adjacent cord parenchyma due to the steal phenomenon or to venous hypertension into the cord. On MRI AVMs appear as multiple flow void representing the nidus along with enlarged extramedullary feeding vessels. T1 weighted and T2 weighted images best identify lesions within the cord and CSF, respectively. CSF pulsation may mimic an AVM. The enlarged draining veins of an AVM brightly enhance, and contrast administration may aid to this distinction and also in the detection of small lesions. Thrombotic lesions while brightly enhance in the periphery do not have flow voids. The high signal inside the cord is a common finding and may represent gliosis or oedema resulting from steal phenomenon or venous congestion. Intramedullary hemorrhage may also be present. MRI appearances depend on the stage of the blood products. Juvenile AVMs are significantly larger than glomus AVM and occupy the entire canal at the level.

5.2. Angiography

The reference diagnostic test remains selective spinal angiography performed under general anaesthesia. This exam best defines the type of malformation, the extension of the lesion and provides mapping of the draining vessels. An experienced eye could also evaluate the presence of flow-related and intranidal aneurysms, and normal arterial supply to the spinal cord. This information needs to be well understood before any treatment could be offered. Investigation of a lesion involving the cervical cord should include injection of both vertebral arteries in addition to the ascending and deep.

5.3. Extradural-Intradural Arteriovenous Malformations

This subgroup is represented by very uncommon lesions. They have been referred previously as juvenile, metameric, or Type III AVMs (Nichols et al., 1992) They extend intradurally as well as extradurally and are often associated with bony erosion and developmental abnormalities. Treatment could be challenging due to their diffused anastomosis. The paramount point is that they should be treated with progressive embolizations. The aim of embolization should be to gradually occlude the fistula points and slow down the flow inside the large nidus. Surgical management is often infeasible and put patients at risk of neurological deficits but could become necessary in case of compressive symptoms.

Spinal Arteriovenous Malformations 131

5.4. Intradural Arteriovenous Malformations

These are the most common kind of spinal vascular lesions, accounting for up to 36-45% of spinal vascular lesions. Intramedullary AVMs have a nidus similar to intracranial AVMs. The most frequent clinical presentation of intradural intramedullary AVMs is hemorrhage or compressive symptoms with acute myelopathy. Progressive myelopathy can occur secondary to vascular steal as described before. In the past these lesions have been referred to as classic AVMs, glomus-type lesions, Type II AVMs, angioma arteriovenosum, and angioma racemosum arteriovenous lesions. This subgroup is associated with neurofibromatosis and the Rendu-Osler-Weber, KlippelTrenaunay-Weber (Djindjian et al., 1977) and Parkes-Weber syndromes (Takai 2017). Aneurysms are present in 20-44% of cases and are associated with an increased risk of hemorrhage (Rosenblum et al., 1987). They can be supplied by multiple branches of the anterior and posterior spinal arteries and are characterized by high pressure, relatively low resistance, and high blood flow.

5.5. Conus Medullaris Arteriovenous Malformations

The conus malformation is characterized by multiple feeding arteries, multiple niduses, and complex venous drainage. These lesions fit none of the aforementioned categories. They have multiple direct arteriovenous shunts that derive from the anterior and posterior spinal arteries and have glomus-type niduses that are usually extramedullary and pial based, but they may also have an intramedullary component. They are attributed to an abnormality during neurulation and are associated with a tethered cord (Hurst et al., 1999). They are location specific (that is, they are always located in the conus medullaris and cauda equina) and can extend along the entire terminal filum. Symptomatically, they can manifest with venous hypertension, compression, or hemorrhage. Unlike other spinal arteriovenous lesions, they frequently produce radiculopathy and myelopathy at the same time. The radicular deficits are often prominent but may improve dramatically over time when these lesions are successfully treated. Hemorrhage at presentation may be more common among children with cord AVMs compared with adults and Re-hemorrhage appears to happen at higher rates for spinal cord AVMs compared with brain AVMs, occurring in 10% of patients at 1 month and 40% within the first year after the initial hemorrhage (Hurst et al., 1999).

6. DECISION MAKING

Decision on how to treat such complex lesions should be made by a multidisciplinary team of experts that should include endovascular neuroradiologists, neurovascular surgeons and experts in radiosurgery (Hurst et al., 1999). The natural history of untreated intramedullary AVMs is not completely clear yet. Nearly half of all patients who present with gait impairment are confined to a wheelchair or bed within 3 years, and one-fifth of patients presenting requiring crutches are non ambulatory by 6 months after the onset of deficitarian symptoms (Aminoff and Logue 1974b, 1974a). Hemorrhagic onset is a particularly bad prognostic factor. Progressive evolution of symptoms, by either worsening myelopathy or subsequent 132 D. Boeris and M. Cenzato hemorrhages, is reported in 31-71% of patients observed over several year (Aminoff and Logue 1974b, 1974a). Decision making should take into account symptoms, age, comorbidities and clinical history. Secondly the lesion should be carefully evaluated with MRI and digital subtraction angiography. Selective angiograms could clearly demonstrate the presence of single or multiple feeders as well as the arteriovenous shunt. The presence of fistulas, with high or low flow, the length of the lesion and the flow velocity should be carefully considered. The MRI, particularly in the axial views can show to the surgeon whether the vascular lesion is superficial and could be managed surgically. Due to the spinal cord AVM anatomy variability and the risk of potential complications on any procedure involving the cord is relatively high, decision making about the management of these patients must be individualized. Patients with a cord AVM consisting of a compact, surgically accessible nidus may be good candidates for surgery. Embolization may be a useful adjunct to surgery, or, in some cases, may provide symptoms control when used alone as suggested by some authors (Hurst et al., 1999).

6.1. Endovascular Treatment

Endovascular treatment can be performed with Onyx, cyanoacrylate or particls. The aim of the endovascular treatment is to reduce the flow and consequently the symptoms. The most used approach in large spinal AVM includes several sessions targeting at first the main fistula points inside the AVM. The risks of the treatment by endovascular means are ischemia due to the closure of normal arteries and intraoperative hemorrhage. A growing role has been achieved by preoperative embolization of spinal AVM with the aim of reducing the pathological arteriovenous shunt in preparation for surgery. Complete obliteration rates with embolization alone range from 24 to 53%, carrying a risk of transient complication rates between 10.6 and 14%, permanent complication rates range the same. Some authors have reported that partial embolization of spinal cord AVMs is protective against hemorrhage, unlike brain AVMs (Berenstein A. 1992).

6.2. Microsurgical Treatment

Microsurgical planning differs according to the lesion treated. A conus medullaris arteriovenous malformation (type 3) should be treated by carefully understanding the location of the main fistula point and by closing the discharging vein at the fistula point. Surgical approach is via a standard laminotomy. Exposure should extend at least one level above and one level below the lesion. Any dissection inside the conus should be avoided to prevent neurological deficits. Vessels around the spinal AVM have pial origin and have normal or close to normal architecture differing from medullary vessels of brain AVMs that have abnormal walls. The main difficulty for the surgeon is to decide which vessels are to close and which are not. Arachnoidal dissection and careful dissection when possible should let the surgeon map the en passage vessels and the Spinal AVM vessels. Direct micro surgical closure of the fistula point suffices to control symptoms in most of the cases (Figure 1).

Spinal Arteriovenous Malformations 133

Figure 1. (A) Intraoperative picture showing a conus medullaris arteriovenous malformation (type 3). (B) Indocyanine green videoangiography showing the pattern of vascularization of the AVM. (C) Intraoperative picture showing the complete removal of AVM.

The new generation of high-resolution ultrasound scanners is extremely useful for identifying vessels on the hidden surface of the spinal cord (Figure 2).

Figure 2. High-resolution ultrasonography used for the identification of the deep sited feeders of a spinal cord AVM.

134 D. Boeris and M. Cenzato

Figure 3. Laser coagulation during spinal AVM surgery.

Figure 4. Sagittal (A) and coronal (B) T2-weighted MRI showing the presence of multiple flow-voids associated with conus medullaris AVM. Spinal digital subtraction angiography before (C) and after (D), selective embolization of the AVM.

In case of a well-defined nidus with feeders and discharging veins (type 2) the aim of the surgeon should be directed toward dissecting the arachnoidal plan in order to understand and map the AVM anatomy with his feeding vessels and discharging veins. Spinal AVM normally have a good dissection plan with the cord. This surgery should always be performed under neurophysiological monitoring, and with the aid of doppler ultrasound and ICG. Spinal AVM are normally superficial but require close to the nidus dissection and coagulation. The authors recommend the use of nonstick bipolar at low voltage and laser coagulation to improve selectivity (Figure 3). Spinal Arteriovenous Malformations 135

Embolization of major feeders prior to surgery can be helpful, particularly for lesions with multiple feeding vessels, as conus AVMs often present (Ausman et al., 1977; Latchaw et al., 1980). With appropriate case selection angiographic obliteration of the lesion can be achieved in almost all cases. As expected, surgical results are better with compact AVMs compared with AVMs with a diffuse nidus. Surgical series in the literature report intramedullary arteriovenous malformation excision outcome with neurologic improvement in 40%, unchanged neurology in 53% and worsened neurology in 7% with a good functional outcome in 86% (Connolly et al., 1998). Similar results are reported in our series of 18 cases. Angiographical exclusion has been achieved in all cases. Of the 18 patients 2 had long term worsening of neurological symptoms. Both patients had large spinal AVM (more than 5 metamers) (Figure 4).

7. COMPLICATIONS

Venous thrombosis seems to be the most invalidating complication, possibly leading to postoperative delayed hemorrhage, ischemia or cord swelling. The rapid change in flow velocity obtained by endovascular or surgical means can cause thrombosis into the venous compartment. It is unclear whether the use of heparin early on in the postoperative phase could control this phenomenon.

REFERENCES

Aminoff, M. J., and Logue V. 1974a. “Clinical features of spinal vascular malformations.” Brain 97 (1): 197-210. https://doi.org/10.1093/brain/97.1.197. https://www.ncbi.nlm.nih. gov/pubmed/4373119. ---. 1974b. “The prognosis of patients with spinal vascular malformations.” Brain 97 (1): 211-8. https://doi.org/10.1093/brain/97.1.211. https://www.ncbi.nlm.nih.gov/pubmed/ 4434169. Anson, J. A., Spetzler, R. F. 1992. “Classification of spinal arteriovenous malformation and implication for treatments.” BNI Q 8: 2-8. Ausman, J. I., Gold, L. H. Tadavarthy, S. M. Amplatz, K. and Chou, S. N. 1977. “Intraparenchymal embolization for obliteration of an intramedullary AVM of the spinal cord. Technical note.” J Neurosurg 47 (1): 119-25. https://doi.org/10.3171/jns.1977.47.1. 0119. https://www.ncbi.nlm.nih.gov/pubmed/864500. Baker, H. L., Love, Jr., J. G. and D. D. Layton, Jr. 1967. “Angiographic and surgical aspects of spinal cord vascular anomalies.” Radiology 88 (6): 1078-85. https://doi.org/10.1148/ 88.6.1078. https://www.ncbi.nlm.nih.gov/pubmed/6024367. Bao, Y. H. and F. Ling. 1997. “Classification and therapeutic modalities of spinal vascular malformations in 80 patients.” Neurosurgery 40 (1): 75-81. https://doi.org/10.1097/ 00006123-199701000-00017. https://www.ncbi.nlm.nih.gov/pubmed/8971827. Berenstein, A., Lasjaunias P. 1992. Surgical Neuroangiography. Endovascular Treatment of Spine and Spinal Cord Lesions. Berlin Heidelberg: Springer-Verlag. 136 D. Boeris and M. Cenzato

Bergstrand, A., Hook, O. and H. Lidvall. 1964. “Vascular Malformations of the Spinal Cord.” Acta Neurol Scand 40 (2): 169-83. https://doi.org/10.1111/j.1600-0404.1964.tb01142.x. https://www.ncbi.nlm.nih.gov/pubmed/14131793. Borden, J. A., Wu, J. K. and W. A. Shucart. 1995. “A proposed classification for spinal and cranial dural arteriovenous fistulous malformations and implications for treatment.” J Neurosurg 82 (2): 166-79. https://doi.org/10.3171/jns.1995.82.2.0166. https://www.ncbi. nlm.nih.gov/pubmed/7815143. Connolly, E. S., Jr., G. P. Zubay, P. C. McCormick and B. M. Stein. 1998. “The posterior approach to a series of glomus (Type II) intramedullary spinal cord arteriovenous malformations.” Neurosurgery 42 (4): 774-85; discussion 785-6. https://doi.org/10.1097/ 00006123-199804000-00057. https://www.ncbi.nlm.nih.gov/pubmed/9574642. Djindjian, M., R. Djindjian, M. Hurth, A. Rey and R. Houdart. 1977. “Spinal cord arteriovenous malformations and the Klippel-Trenaunay-Weber syndrome.” Surg Neurol 8 (4): 229-37. https://www.ncbi.nlm.nih.gov/pubmed/197652. Hawe, A., H. J. Svien, F. H. Ellis, Jr., D. D. Layton, Jr. and H. L. Baker, Jr. 1972. “The surgical treatment of vascular anomalies of the spinal cord.” Surg Gynecol Obstet 135 (3): 369-72. https://www.ncbi.nlm.nih.gov/pubmed/5054157. Hurst, R. W., L. J. Bagley, P. Marcotte, L. Schut and E. S. Flamm. 1999. “Spinal cord arteriovenous fistulas involving the conus medullaris: presentation, management, and embryologic considerations.” Surg Neurol 52 (1): 95-9. https://doi.org/10.1016/s0090- 3019(99)00038-5. https://www.ncbi.nlm.nih.gov/pubmed/10390182. Latchaw, R. E., R. D. Harris, S. N. Chou, and L. H. Gold. 1980. “Combined embolization and operation in the treatment of cervical arteriovenous malformations.” Neurosurgery 6 (2): 131-7. https://www.ncbi.nlm.nih.gov/pubmed/7366804. Nichols, D. A., D. A. Rufenacht, C. R. Jack, Jr., and G. S. Forbes. 1992. “Embolization of spinal dural arteriovenous fistula with polyvinyl alcohol particles: experience in 14 patients.” AJNR Am J Neuroradiol 13 (3): 933-40. https://www.ncbi.nlm.nih.gov/pubmed/ 1590193. Rosenblum, B., E. H. Oldfield, J. L. Doppman and G. Di Chiro. 1987. “Spinal arteriovenous malformations: a comparison of dural arteriovenous fistulas and intradural AVM’s in 81 patients.” J Neurosurg 67 (6): 795-802. https://doi.org/10.3171/jns.1987.67.6.0795. https://www.ncbi.nlm.nih.gov/pubmed/3681418. Spetzler, R. F., P. W. Detwiler, H. A. Riina and R. W. Porter. 2002. “Modified classification of spinal cord vascular lesions.” J Neurosurg 96 (2 Suppl): 145-56. https://doi.org/10. 3171/spi.2002.96.2.0145. https://www.ncbi.nlm.nih.gov/pubmed/12450276. Takai, K. 2017. “Spinal Arteriovenous Shunts: Angioarchitecture and Historical Changes in Classification.” Neurol Med Chir (Tokyo) 57 (7): 356-365. https://doi.org/10.2176/nmc. ra.2016-0316. https://www.ncbi.nlm.nih.gov/pubmed/28515372.

Chapter 8

BRAIN AND SPINAL CORD CAVERNOUS MALFORMATIONS

M. Fontanella1,, MD, L. Zanin1, MD, A. Fiorindi1, MD, G. Spena2, MD, F. Nicolosi3, MD, F. Belotti1, MD, P. Panciani1, MD, L. De Maria1, MD, G. Saraceno1, MD, C. Cornali1, MD and F. Doglietto1, MD, PhD 1Neurosurgery, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy 2Neurosurgery, Alessandro Manzoni Hospital, Lecco, Italy 3Neurosurgery, Humanitas Research Hospital, Milan, Italy

ABSTRACT

Cerebral Cavernous Malformations can be found in approximately 0.5% of the population and in most of the cases are asymptomatic. The diagnosis it’s possible with a MR with T2*, Tl C+ sequences including SWI, but the decision of surgery is often very difficult especially in asymptomatic cases. Removal of accessible lesions is the only direct therapeutic approach for cerebral cavernous malformations (CCMs). A grading scale for the indication of surgery did not exist. We propose a new scale, taking in account several factors: clinical, neuroradiological and epilectic features. The surgical approach should be carefully evaluated according to a precise assess-ment in order to both select the patient and avoid complications. A quantitative anatomical study and a preoperative simulation of surgery can help to plan the operation. Neuronavigation, ultrasound and neurophysiologic monitoring are generally required respectively to locate the CCMs and to avoid critical areas. In any case before performing surgery the physicians should always consider the benign nature of the lesions and the absolute necessity to avoid not only neurological deficits, but also a neuropsychological impairment that could affect the quality of life.

 Corresponding Author’s Email: [email protected]. 138 M. Fontanella, L. Zanin, A. Fiorindi et al.

Keywords: cerebral cavernous malformations, preoperative simulation, surgical management, surgical pyramid, surgical grading

1. INTRODUCTION

Cerebral cavernous malformations (CCMs) are the third most common cerebral vascular malformation and are found in approximately 0.5% of the population (Goldstein and Solomon 2017). CCMs may occur at any age; peak presentation is 40-60 years (younger in the familial multiple cavernous malformation syndrome). There is no sex predilection. CCMs can be solitary and sporadic (80% of cases) or multiple and familial (20%) (Goldstein and Solomon 2017). Multiple CCM syndrome is more common in Hispanic-Americans of Mexican descent. CCMs can be inherited or acquired. Acquired are rare and usually associated with prior radiation therapy (Goldstein and Solomon 2017). Familial CCMs are inherited as an autosomal- dominant disease with variable penetrance. The diagnosis of CCM is often occasional, during a MR study performed for other reasons, or can be made for various symptoms such as headache or dizziness. In some cases CCM can be symptomatic or diagnosed after a bleeding (Hauck et al. 2009). The evaluation, decision of surgery and the surgical planning, is therefore very important and the decision for surgical excision should be performed within a “vascular team,” including neurologist expert in epilepsy, neuroradiologists, neuroanesthesiologists, neurophysiologists, experts in gammaknife therapy, neuropsychologists and of course neurosurgeons. The choice of the right approach for the resection of a CCM implies a perfect knowledge of the regional surgical anatomy of the brain and skull base. This has historically been accomplished through surgical training in “cadaver labs.” Although these still represent the gold standard for the pre-clinical surgical training (Doglietto et al. 2017), in recent years much attention has been devoted to the concept of virtually simulating the surgical approach. In these virtual simulators any surgical approach can be performed with the advantage of multiple repetitions and, even more importantly, of patient-specific anatomy (Bernardo 2017). A correct methodology to decide the surgical removal of CCM must take in account many factors. A “surgical decision scale” (Table 1) can help to plan the surgical removal of a CCM.

2. METHODS

2.1. Diagnosis

2.1.1. Genetic CCM lesions can be sporadic or familial. Familial CCMs usually show multiple lesions. CMM syndrome is autosomal dominant with variable penetrance (Akers et al. 2017). There is nonsense, frame-shift, or splice-site mutations consistent with 2-hit model for CMM. Three separate loci were identified and implicated CCMl, CCM2, CCM3 genes. Mutations in these 3 genes account for >95% of familial CMMs. Mutations encode truncated KRITl protein. KRITl Brain and Spinal Cord Cavernous Malformations 139 interacts with endothelial cell microtubules and loss of function leads to inability of endothelial cells to mature form capillaries (Spiegler et al. 2018). In sporadic CMM there is no KRITI mutation. PTEN promoter methylation mutation is common (also in familial CM syndrome). In some cases, abnormalities are associated, such as:

 Developmental venous anomaly (mainly in sporadic lesions)  Superficial siderosis  Cutaneous abnormalities  Cafe au lait spots  Hyperkeratotic capillary-venous malformations

A patient with multiple CCM, with an history of familial lesions should be checked for genetic mutations (Ardeshiri et al. 2008).

2.1.2. Neuroradiology CCM can be located anywhere in the Central Nervous system and also outside, like in the orbit, in the cerebral cisterns and in the venous sinuses. Most common sites are pons, adjacent to median raphe, adjacent to floor of 4th ventricle, cerebellum, medulla, spinal cord. Up to 1/3 are in cerebral hemispheres in cortical and subcortical site (Spiegler et al. 2018).

Table 1. Recently Proposed Grading for CCMs.

Factor to consider Patient’s condition Assigned Points Stable lesion 0 Lesion increasing in volume 1 Neuroradiology Intralesional bleeding or extralesional <1 cm 2 Associated hematoma >1 cm 3 Focal Neurological No 0 Deficits Yes 1 No 0 Seizures Controlled by medications 1 Drug-resistant 2 Deep seated in critical area 0 (basal ganglia, thalamus) Site Subcortical 1 Cortical in critical area 2 Cortical not critical area 3 >50 0 Age <50 1 The Table Shows the recently proposed grading for CCMs. If the final score (resulting rom the addition of the single points) is less than 4 there is no surgical indication, if the score is higher than 4 the patient can be a candidate for surgery.

140 M. Fontanella, L. Zanin, A. Fiorindi et al.

The introduction of MR studies showed that the best diagnostic clue is hypointense lesion on T2* with faint brush-like enhancement. Usually the size is <1 cm. The sporadic (solitary) form is much more frequent than the familial (multiple) form. Usually there is no mass effect and no edema, if there was’t a previous bleeding. CT study is usually normal if the lesion is small.

Magnetic Resonance Sequences Tl WI is usually normal or may have an hyperintense or hypo-/hyperintense “popcorn” appearance. FLAIR sequence is usually normal; if the CCM is large, may show ill-defined hyperintensity, with no mass effect. The T2* GRE shows lesion moderately hypointense, slows blood flow with oxy- to deoxyhemoglobin, occasionally multifocal BCTs seen as black or gray “dots,” especially if mixed with CMs (de Souza et al. 2008). SWI is more sensitive than GRE. SWI is even more sensitive than standard T2* DTI.

Angiographic Findings Angiography is usually normal and it is not indicated for CMM diagnosis. A faint vascular “stain” can be found and associated DVA can be demonstrated.

Imaging Recommendations The best imaging tool if a CCM is suspected, is MR with T2*, Tl C+ sequences including SWI. The CCM should be classified according with the Zabramski classification in (Zabramski et al. 1994):

 Type 1 = subacute hemorrhage (hyperintense on Tl WI; hyper- or hypo intense on T2WI)  Type 2 = mixed signal intensity on Tl, T2WI with degrading hemorrhage of various ages (classic “popcorn ball” lesion)  Type 3 = chronic hemorrhage (hypo- to isointense on Tl, T2WI)  Type 4 = punctate micro hemorrhages (“black dots”), poorly seen except on GRE sequences

2.2. Preoperative Assesment and Indication for Surgery

2.2.1. Clinical Assessment and Grading The surgical approach to a CCM must be preceded by an accurate study of the clinical and functional status of the patient. Nowadays, pre-operative assessment and perioperative standards vary between centers regarding different aspects, including pre-operative functional and epileptological assessment, the choice of the first antiepileptic drug, and the time to surgery (Akers et al. 2017). Also surgical standards vary significantly between different centers and countries regarding the use of intraoperative imaging systems, intraoperative functional mapping, extent of resection of the hemosiderin rim, tests used for post-operative functional assessment (Cornelius et al. 2016), and its timing (Zanello et al. 2019). Brain and Spinal Cord Cavernous Malformations 141

In our opinion all patients, and especially those with no neurological symptoms before surgery, must be functionally assessed before and after the operation. As even indications for surgery vary between centers, guidelines have been proposed and, recently, a scale for the indication to surgery has been suggested (Table 1) (Akers et al. 2017). In any case surgical planning should take in account many factors:

1. The site of the cavernoma, as it can be Cortical, Subcortical, or Deep seated; the eloquence of the area near the lesion (i.e., the significance of the cortex, which should not be removed to avoid the risk of a permanent neurological deficit); 2. The neurological status of the patient; 3. The neuroradiological assessment, in term of volumetric growth of the lesion and possible signs of bleeding; 4. The pre-operative epileptological status; 5. The age of the patient.

Surgical indication should also take in account the presence of a Developmental Venous Anomaly (DVA, which can be associated with and in close proximity of the cavernoma), even if the risk of coagulating a DVA in the single patient remains unclear.

2.2.2. Neuropsychological and QoL assessment A neuropsychological assessment should be performed in all cases of CCM before and 6 months after surgery (Baxendale 2018). Even not operated cases should be followed up for neuropsychological deficit, especially patients treated with antiepileptics. The administered tests are usually in relation with the location of the CCM, especially for frontal CCM. The assessment of quality of life is also very important and is usually performed through EORTC QLQ Head and Neck-35 (H&N-35) tests.

2.2.3. Epilepsy Assessment CCMs are frequently associated with a seizure disorder, and the risk of developing drug- resistant epilepsy (DRE) is substantial, especially for temporal lobe lesions (Rosenow et al. 2013). In any case we should think that even a single seizure should be recorded with EEG and an early prophylactic treatment must be started because the recurrence of other seizures is very high. Microsurgery is a valuable treatment option, which may provide excellent results on seizures, with 76% of patients on average being seizure-free after surgery. Nevertheless, the optimal surgical strategy to achieve seizure control has not been clearly identified, and several attitudes have been reported in the literature. The choice of lesionectomy, associated or not to removal of surrounding hemosiderin, versus resections extended to epileptogenic cortex depends on several factors, which should be investigated through an adequate epileptological presurgical workup (Dammann, Schaller, and Sure 2017). This should include an epilepsy- oriented brain MRI study, integrated by an appropriate neurophysiological and clinical assessment, and if needed by other functional evaluations. Besides representing the optimal option in CCM-related DRE cases, microsurgery should be considered also at seizure presentation to protect the patient from both the possible development of drug resistance and the risk of hemorrhage (Cossu et al. 2015). 142 M. Fontanella, L. Zanin, A. Fiorindi et al.

Figure 1. It shows the physical model that allows the realization of craniotomies and the achievement of specific surgical targets, in a procedure that can potentially be repeated an infinite number of times.

2.3. Surgical Planning

2.3.1. Preoperative Simulation of Surgery Several methods have been proposed for simulating neurosurgical approaches: the basilar difference is the possibility to shift from a completely virtual scenarios (tridimensional, explorable virtual patient and approaches) to tangible models, which reliably reproduce regional anatomy by also coupling augmented reality (i.e., UpSim, https://upsim.upsurgeon.com). Using mobile phones or tablets, these methods give the unique opportunity to enhance mental 3D imagery of a neurosurgical approach, not only through digital representation, but also by performing the approach on a closest-to-realness physical model (Figure 1). In fact, once an intracranial target and craniotomy have been chosen, the operator can visualize them onto the physical model and eventually change his/her. Then the craniotomy can be completed, and intracranial anatomy explored with the advantage of manipulating almost real vascular and neural structures and of potentially repeating endlessly the procedure (Figure 2).

2.3.2. Quantitative Anatomical Study of Different Approaches Recently the IDEAL paradigm has been suggested to enhance surgical research and it has underlined the importance of improving the quality of pre-clinical studies, which can be as important as in drug-development if a proper, controlled research environment is created (McCulloch et al. 2009). In the anatomy laboratory different neurosurgical approaches to the same intracranial area can be performed and compared.

Brain and Spinal Cord Cavernous Malformations 143

Figure 2. Once the craniotomy has been completed it is possible to explore the internal brain structures with the aid of augmented reality.

Recently, our group developed, in collaboration with the University of Toronto, a dedicated software (ApproachViewer, part of GTxEyesII - UHN = Guided-Therapeutics software developed at University Health Network - Toronto, Canada) that allows the real-time visualization and quantification of the surgical pyramid, which defines the working space of a specific approach (Doglietto et al. 2017). This is quantified once a surgical approach is performed in a specimen; it is visualized in 3D, axial, coronal and sagittal images in the computed tomography of the head, in which the approach has been performed (Figure 3). With this method different surgical approaches have been performed and compared in their essential, anatomical features (i.e., volume, distance to target, area of entry point and exposure of the target) (Doglietto et al. 2017). Coupling the analysis of the surgical pyramid position with eloquent cerebral areas and high risk skull base areas, the morbidity of a specific approach can also be inferred (Doglietto et al. 2017).

3. MATERIAL

3.1. Neurosurgical Planning and Choices of Surgical Approaches

The choice of a surgical approach must be discussed in any case before the operation within the group of all physicians involved in the CCM treatment. In this group there are neurosurgeons, epileptologists, neurologists, neuropsychologists, neuroradiologists, neuroanesthesiologists, and many other physicians (Akers et al. 2017). The patient, already checked about his neuropsychological status, is informed about the risk related to surgery. Neuroradiological images are navigated and the possibility to perform awake surgery is discussed in relation with the location of the cavernoma and its proximity of critical areas. In most of the cases an intraoperative monitoring and possible cortical or subcortical stimulation is planned. All the neuroradiological informations, including cortical 144 M. Fontanella, L. Zanin, A. Fiorindi et al. different areas and subcortical tracts are put together to imagine the best surgical strategy and the surgical volumes can be superimposed on CT images and NMR images (Figure 4). Drawing the surgical pyramids, we have the possibility to measure areas of sections and to measure the distances between them and critical cortical areas and tracts. The choice of the surgical approach should also take in account that the manipulation of some structure can be dangerous, such as the fornix or even the left temporal lobe during a subtemporal approach. CCM can be classified on the basis of their location as shown in Table 2. Therefore, we can have CCM in Cortical not critical area, Cortical critical area, Subcortical and Deep seated in critical area (basal ganglia, thalamus) (Akers et al. 2017).

Figure 3. This picture illustrates the visualization of exemplificative surgical pyramids of ap-proaches to the median anterior cranial fossa using the ApproachViewer software.

Figure 4. Diffusion Tensor Imaging (DTI) of a deeply located supratentorial cavernoma for preoperative assessment and surgical planning. Brain and Spinal Cord Cavernous Malformations 145

Table 2. Schematic representation of CCMs locations with corresponding surgical approaches

Location Surgical approach Convexity Transcortical/trans-sulcal Anterior: Transsylvian, subfrontal Medial temporal Posterior: Subtemporal, Supratentorial Supracerebellar transtentorial Inferomedial occipital Supratentorial infraoccipital Medial frontal and parietal Anterior Interhemispheric Medial occipital Posterior interhemispheric Infratentorial Convexity Cerebellar Transcortical, Transvermian Medial thalamus, internal Transcallosal-transventricular Deep seated capsule Anteroinferior basal ganglia Supracarotid-subfrontal Transsylvian Anterior, anterolateral (pterional, OZ, or OZ variant) Midbrain Posterior and posterolateral Supracerebellar infratentorial midbrain 3rd ventricle Transcallosal transchoroidal Cerebellopontine angle Extended retrosigmoid Anterior, anterolateral Medial transpetrous (Kawase) Posterior pons Transvermian Medial middle cerebellar Pons peduncle and posterolateral Suboccipital telovelar Brainstem pons Lateral/High middle cerebellar Retrosigmoid peduncle Inferolateral pons Transpontomedullary sulcus Inferior cerebellar peduncle Supratonsillar Mid to cervicomedullary Far lateral anterolateral medulla Medulla High anterolateral medulla Far lateral extended retrosigmoid Posterior medulla and fourth Suboccipital transventricular ventricle Posterolateral medulla Suboccipital telovelar

3.2. Intra-Operative Ultra-Sound

Widely used in glioma surgery, intra-operative Ultra-Sound (iUS) is extremely useful also in vascular surgery (Prada et al. 2019). There is an indication for the use of ultrasound in almost every brain surgery. Before incision of the dura, ultrasound helps to assess the target lesion in the craniotomy. Thus a simple verification of neuronavigation can be performed, and if needed, based on iUS findings, a safe extension of craniotomy can be performed before dural opening. After dural opening a significant brain shift may occur which can change surgical anatomy and 146 M. Fontanella, L. Zanin, A. Fiorindi et al. can make the neuronavigator less precise (Prada et al. 2019). A ultrasound might help to identify the targeted lesion and important landmarks. The real strength of iUS is providing real- time information. When in doubt iUS provides more reliable information compared to neuronavigation (Prada et al. 2019).

3.3. Intraoperative Monitoring

In the recent decade, the clinical usefulness of somatosensory evoked potentials (SEPs) entered the operating room, allowing the intraoperative monitoring of the CNS and, thus, safeguarding CNS structures during high risk surgeries (Slotty et al. 2017). Continuous SEP monitoring can warn a surgeon and prompt intervention before impairment becomes permanent. Methods of choice for europhysiological intraoperative monitoring (IOM) within the infratentorial compartment mostly include early brainstem auditory evoked potentials, free- running electromyography, and direct cranial nerve (CN) stimulation (Slotty et al. 2017). Long- tract monitoring with somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) is rarely used. IOM represents an exceptional tool that allows the surgeon to know in real time if he is creating neurological deficits in the structures that are affected by his action, greatly reducing the percentage of permanent deficits.

REFERENCES

Akers, Amy, Rustam Al-Shahi Salman, Issam A. Awad, Kristen Dahlem, Kelly Flemming, Blaine Hart, Helen Kim, et al. 2017. “Synopsis of Guidelines for the Clinical Management of Cerebral Cavernous Malformations: Consensus Recommendations Based on Systematic Literature Review by the Angioma Alliance Scientific Advisory Board Clinical Experts Panel.” Neurosurgery 80 (5): 665-80. https://doi.org/10.1093/neuros/nyx 091. Ardeshiri, Ardavan, Ardeshir Ardeshiri, Andres Beiras-Fernandez, Ortrud K. Steinlein, and Peter A. Winkler. 2008. “Multiple Cerebral Cavernous Malformations Associated with Extracranial Mesenchymal Anomalies.” Neurosurgical Review 31 (1): 11-17; discussion 17-8. https://doi.org/10.1007/s10143-007-0111-7. Baxendale, Sallie. 2018. “Neuropsychological Assessment in Epilepsy.” Practical Neurology 18 (1): 43-48. https://doi.org/10.1136/practneurol-2017-001827. Bernardo, Antonio. 2017. “Virtual Reality and Simulation in Neurosurgical Training.” World Neurosurgery 106 (October): 1015-29. https://doi.org/10.1016/j.wneu.2017.06.140. Cornelius, Jan Frederick, Katharina Kürten, Igor Fischer, Daniel Hänggi, and Hans Jakob Steiger. 2016. “Quality of Life After Surgery for Cerebral Cavernoma: Brainstem Versus Nonbrainstem Location.” World Neurosurgery 95 (November): 315-21. https://doi.org/ 10.1016/j.wneu.2016.08.014. Cossu, M., F. Raneri, G. Casaceli, F. Gozzo, V. Pelliccia, and G. Lo Russo. 2015. “Surgical Treatment of Cavernoma-Related Epilepsy.” Journal of Neurosurgical Sciences 59 (3): 237-53. Dammann, P., C. Schaller, and U. Sure. 2017. “Should We Resect Peri-Lesional Hemosiderin Deposits When Performing Lesionectomy in Patients with Cavernoma-Related Epilepsy Brain and Spinal Cord Cavernous Malformations 147

(CRE)?” Neurosurgical Review 40 (1): 39-43. https://doi.org/10.1007/s10143-016-0797- 5. Doglietto, Francesco, Jimmy Qiu, Mayoorendra Ravichandiran, Ivan Radovanovic, Francesco Belotti, Anne Agur, Gelareh Zadeh, Marco Maria Fontanella, Walter Kucharczyk, and Fred Gentili. 2017. “Quantitative Comparison of Cranial Approaches in the Anatomy Laboratory: A Neuronavigation Based Research Method.” World Journal of Methodology 7 (4): 139-47. https://doi.org/10.5662/wjm.v7.i4.139. Goldstein, Hannah E., and Robert A. Solomon. 2017. “Epidemiology of Cavernous Malformations.” In: Handbook of Clinical Neurology, 143:241-47. https://doi.org/10. 1016/B978-0-444-63640-9.00023-0. Hauck, Erik F., Samuel L. Barnett, Jonathan A. White, and Duke Samson. 2009. “Symptomatic Brainstem Cavernomas.” Neurosurgery 64 (1): 61-70. https://doi.org/10.1227/01.NEU. 0000335158.11692.53. McCulloch, Peter, Douglas G. Altman, W. Bruce Campbell, David R. Flum, Paul Glasziou, John C. Marshall, Jon Nicholl, et al. 2009. “No Surgical Innovation without Evaluation: The IDEAL Recommendations.” The Lancet 374 (9695): 1105-12. https://doi.org/ 10.1016/S0140-6736(09)61116-8. Prada, Francesco, M. Yashar S. Kalani, Kaan Yagmurlu, Pedro Norat, Massimiliano Del Bene, Francesco DiMeco, and Neal F. Kassell. 2019. “Applications of Focused Ultrasound in Cerebrovascular Diseases and Brain Tumors.” Neurotherapeutics : The Journal of the American Society for Experimental NeuroTherapeutics 16 (1): 67-87. https://doi.org/10. 1007/s13311-018-00683-3. Rosenow, Felix, Mario A. Alonso-Vanegas, Christoph Baumgartner, Ingmar Blümcke, Maria Carreño, Elke R. Gizewski, Hajo M. Hamer, et al. 2013. “Cavernoma-Related Epilepsy: Review and Recommendations for Management - Report of the Surgical Task Force of the ILAE Commission on Therapeutic Strategies.” Epilepsia 54 (12): 2025-35. https:// doi.org/10.1111/epi.12402. Slotty, Philipp J., Amr Abdulazim, Kunihiko Kodama, Mani Javadi, Daniel Hänggi, Volker Seifert, and Andrea Szelényi. 2017. “Intraoperative Neurophysiological Monitoring during Resection of Infratentorial Lesions: The Surgeon’s View.” Journal of Neurosurgery 126 (1): 281-88. https://doi.org/10.3171/2015.11.JNS15991. Souza, J. M. de, R. C. Domingues, L. C. H. Cruz, F. S. Domingues, T. Iasbeck, and E. L. Gasparetto. 2008. “Susceptibility-Weighted Imaging for the Evaluation of Patients with Familial Cerebral Cavernous Malformations: A Comparison with T2-Weighted Fast Spin- Echo and Gradient-Echo Sequences.” AJNR. American Journal of Neuroradiology 29 (1): 154-58. https://doi.org/10.3174/ajnr.A0748. Spiegler, Stefanie, Matthias Rath, Christin Paperlein, and Ute Felbor. 2018. “Cerebral Cavernous Malformations: An Update on Prevalence, Molecular Genetic Analyses, and Genetic Counselling.” Molecular Syndromology 9 (2): 60-69. https://doi.org/10.1159/ 000486292. Zabramski, J. M., T. M. Wascher, R. F. Spetzler, B. Johnson, J. Golfinos, B. P. Drayer, B. Brown, D. Rigamonti, and G. Brown. 1994. “The Natural History of Familial Cavernous Malformations: Results of an Ongoing Study.” Journal of Neurosurgery 80 (3): 422-32. https://doi.org/10.3171/jns.1994.80.3.0422. Zanello, Marc, Bernhard Meyer, Megan Still, John R. Goodden, Henry Colle, Christian Schichor, Lorenzo Bello, et al. 2019. “Surgical Resection of Cavernous Angioma Located 148 M. Fontanella, L. Zanin, A. Fiorindi et al.

within Eloquent Brain Areas: International Survey of the Practical Management among 19 Specialized Centers.” Seizure 69 (July): 31-40. https://doi.org/10.1016/j.seizure.2019.03. 022.

Chapter 9

CRANIAL AND SPINAL DURAL ARTERIOVENOUS FISTULAS

G. Baltsavias* Endovascular Neurosurgery, International Neuroscience Institute-INI, Hannover, Germany

ABSTRACT

Three interesting cases of cranial dural arteriovenous fistulae and one case of a spinal dural-epidural shunt are presented. All cases had an aggressive angioarchitecture characterised by leptomeningeal venous reflux (LVR) and all were treated endovascularly. The first case of cranial dural shunt is a typical example of a bridging vein fistula (BVF) with a ruptured venous ectasia treated through a transarterial approach. The second case is an example of an unruptured bridging vein fistula (BVF) treated with a transvenous approach through leptomeningeal veins. The third case is an example of a dural sinus fistula (DSF) developed in an isolated sinus segment treated with a transvenous approach through the thrombosed sinus. The spinal case is an epidural venous plexus fistula with symptomatic reflux to the medullary venous system treated with a transarterial approach. All cases were analysed according to our scheme and the other classification systems. The decisions about treatment are discussed generally and specifically for each case.

Keywords: cranial, dural, arteriovenous, spinal, epidural, shunt, fistula

1. INTRODUCTION

Cranial dural arteriovenous fistulas (DAVFs) are typically described as shunts located “within the dura matter” (Awad et al. 1990). This is a widely-accepted statement; however, it

* Corresponding Author’s Email: [email protected]. 150 G. Baltsavias has low specificity. The exact location of a lesion within what is meant as dura matter is important for the correct definition and understanding of the features and development of these AV-shunts. Over the years, our understanding about the nature, causes, angioarchitecture and treatment has significantly increased. However, regarding the localisation of cranial DAVFs, a topographic approach is still predominant (e.g., anterior fossa or tentorial or superior sagittal sinus) (Awad et al. 1990; Hiramatsu et al. 2019). Recently, an approach overemphasising embryological aspects has been proposed (Tanaka 2019). On the other hand, the development and use of various classification systems is a reflection of our understanding. The two mostly used classification systems in the literature are those proposed by Borden et al. (Borden, Wu and Shucart 1995) and Cognard et al. (Cognard et al. 1995). In parallel, attempts have been made to “update” or improve these schemes by supplementing new relevant criteria (Zipfel et al. 2009; Strom et al. 2009) or detaching clinicians from complex or/and insufficient schemes by introducing rough categorisations as “high risk” or “high grade” vs. low risk lesions (Kakarla et al. 2007; Liu et al. 2009). All the above, together with an alternative anatomy-based and therefore simpler method of analysis, are discussed through 4 DAVF cases. These cases provide the opportunity to discuss not only the crucial aspect of understanding the angioarchitecture, but also the aspect of efficient and selective treatment by presenting concepts on treatment, both endovascular and exovascular.

2. METHODS

2.1. Included Types and Treatment Strategies

The included cases of cranial DAVF and spinal epidural fistula, provide the opportunity to highlight some aspects that we consider to be interesting and relevant. The limitation of the small case number did not enable us though to discuss all types according to the affected level of the venous system. The interesting aspects of the first case are primarily its particular and possibly confusing location and classification as well as the challenges of treatment. The second case was chosen mostly on the basis of its architecture with regard to treatment, which makes the endovascular transarterial approach high-risk and/or technically very challenging and the transvenous approach very demanding. The third case allows us to demonstrate our concept regarding the affected level of the venous system and the corresponding classifications. We opted to include a non-classical spinal dural lesion in order to highlight analogies with the cranial lesions as well as a particular architecture, which may not represent an ideal surgical candidate in all cases, as typically applies for the classical spinal dural variety. The presented treatment modalities offer a good example of superselectivity in endovascular treatment based on a precise analysis of the lesion’s angioarchitecture. Two of the fistulas were treated with the transarterial approach, one of the two through the ophthalmic artery. For the other two fistulas, a transvenous approach through the leptomeningeal veins and through the occluded sinus was used.

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2.2. Case 1

This is a 75-year-old male patient with a severe brainstem bleed due to a ruptured aneurysm of the left peduncular vein, part of the venous drainage of an aggressive DAVF located in the intradural segment of an anterior(-medial) temporal bridging vein, which normally drained into the sinus of the lesser sphenoid wing. The arterial supply is through the recurrent meningeal branch of the left ophthalmic artery and the sphenoidal branch of the left middle meningeal artery. The draining vein shows a large bilobuled aneurysm as an expression of severe structural strain. No signs of regional venous congestion are seen. It was treated with a transarterial approach, distal superselective catheterisation of the feeders with a Magic 1.5 F microcatheter over a Hybrid 0.08 microwire (Balt, Montmorency, France) and intranidal-intravenous penetration of the liquid embolic material (NBCA). The lesion was completely occluded. Nevertheless, the patient did not recover from the severe brainstem haemorrhage. (Figure 1)

2.3. Case 2

This is a 77-year-old female patient with headaches due to a dural arteriovenous fistula of the left superior petrosal bridging vein. The headaches were attributed to the venous aneurysm at the free edge of the tentorium. The indication for treatment, given the above features (LVR with ectatic venous strain) and the risk of bleeding was clear; however, the patient was reluctant to accept any treatment, and specifically refused a surgical approach. She finally accepted the endovascular option and was informed about the risk and low chances of a transarterial approach as well as the challenges of the transvenous one. The lesion was accessed through the right jugular vein and straight sinus with a 3-axial system - soft tip Envoy 7F guide catheter, a DAC Catalyst 5F and a microcatheter SL 10 Excelsior over a microwire Synchro 14. The draining vein was occluded at its subarachnoid segment with few Target coils (Stryker Neurovascular, Fremont, CA, USA). Post-interventionally, the patient experienced an improvement of her headaches. (Figure 2)

2.4. Case 3

This is a 70-year-old male patient experiencing headaches and a single epileptic fit. Investigation with a CT scan and a subsequent MRI-A showed prominent veins and signs of oedema in the left temporal region, a dural arteriovenous fistula of the left distal transverse sinus and thrombosis of the sinus proximal and distal to the shunt segment. The catheter angiogram confirmed the diagnosis of an isolated dural sinus segment fistula with extensive venous reflux and congestive phenomena in the temporal region, which was the apparent cause of epilepsy. It was treated through the transvenous approach via the thrombosed sigmoid sinus with an SL 10 Excelsior microcatheter over a Synchro 14 microwire and complete occlusion of the involved sinus segment with Target coils (Stryker Neurovascular, Fremont, CA, USA) and NBCA 60%. (Figure 3).

152 G. Baltsavias

Figure 1. Ruptured dural arteriovenous fistula of the left anterior-medial temporal bridging vein. (A) CT scan showing bleeding into the brainstem. (B) Selective injection of the left ICA showing the contribution of the ophthalmic artery, the direct (no opacification of any sinus) and exclusive venous drainage into the leptomeningeal venous system with clear signs of structural strain (ectatic venous lesions). (C) Selective injection of the left ECA showing the contribution of the middle meningeal artery. (D) Superselective distal catheterisation and injection of the recurrent meningeal branch of the ophthalmic artery. (E) Superselective catheterisation of the sphenoidal branch of the middle meningeal artery. (F) Injection of glue-NBCA. (G, H, I) Post-embolisation left common carotid artery (CCA) injection (lateral and AP projections) showing the complete occlusion of the shunt (early and late phases) as well as the intact choroidal blush of the eye (late phase). (J) MRI immediately after embolisation. (K) CT post- embolisation. (L) Schematic representation of the local anatomy of the anterior medial temporal bridging vein (arrow), site of the fistula (with permission of G. Baltsavias). Cranial and Spinal Dural Arteriovenous Fistulas 153

2.5. Case 4

This is a 76-year-old female patient with lumbar pain, incontinence and slowly progressive paraparesis over a period of approximately one year due to a spinal epidural arteriovenous fistula with medullary venous reflux. The lesion was diagnosed and evaluated with MRI-A; the indication for treatment was clear and the architecture of the lesion was discussed in an interdisciplinary frame considering potential treatment modalities. The ventral extradural location and the invasiveness of the surgical option were compared with the atraumatic approach and the high chances of superselective catheterization of the feeders away from dangerous spinal arteries of the endovascular option, which appeared more attractive. It was treated through the transarterial approach with a 1.2 F Magic microcatheter over a Hybrid microwire (Balt, Montmorency, France). The immediate complete occlusion of the shunt was accompanied by a rapid neurological improvement over the next few months with the appropriate neurorehabilitation. (Figure 4)

3. DISCUSSION

3.1. General Understanding and Analysis of the DAVFs

Although the term “dural” implies a lesion within the dura matter, this is neither specific nor precise. Nowadays and over the years, a wide spectrum of lesions has been included under the term DAVF, ranging from shunts that are typically dural, such as a shunt between branches of the middle meningeal artery and veins of the dura itself (Freckmann, Sartor, and Herrmann 1981), to shunts involving primarily epidural structures, diploic veins (Nerva, Hallam, and Vannson 2014) or even extracranial ones as the anterior condylar confluence (Miyachi et al. 2008). Moreover, a typical dural AV-shunt, as stated above (e.g., between branches of the middle meningeal artery and veins of the dura itself), is exceptional in terms of frequency and very different in terms of mechanism (mostly after direct trauma) compared to the usually encountered acquired cranial DAVFs. If we accept this wide spectrum of pathologies under the term DAVF, then we have to consider a corresponding vascular anatomic scheme accommodating all these vascular lesions. A DAVF is always located on or linked to a venous structure of the cranial venous system and is supplied by dural and/or osteodural arterial feeders (Baltsavias et al. Part 1, 2015). This venous structure, and not the arterial feeders, is the crucial component of the shunt from all points of view: the vein of the shunt is the diseased structure, and the site of the initial causal event (thrombosis, trauma, other). The vein is the key structure for the diagnosis, i.e., primary opacification of the bridging vein in the angiogram makes the lesion a bridging vein shunt. The vein defines the architecture and the features of the lesion (development of leptomeningeal venous reflux or not) and therefore determines the clinical course. The vein also dictates the concept of cure, i.e., the complete occlusion of the primary draining vein is the ultimate target for the definitive treatment of any AV fistula.

154 G. Baltsavias

Figure 2. Dural arteriovenous fistula of the left superior petrosal bridging vein. (A) The TOF MR shows the lesion, which inevitably demonstrates leptomeningeal venous reflux. (B, C) Digital angiography, left common carotid injection showing multiple arterial feeders. These are mostly tentorial branches of the internal carotid artery (secondary supply through the petrosal branch of the middle meningeal artery as well as branches of the distal internal maxillary artery) opacifiying the superior petrosal vein retrograde – with no opacification of the superior petrosal sinus – draining to the lateral mesencephalic vein. This carries an aneurysm and further drains to the galenic vein through two tributaries, one the distal segment of the basal vein of Rosenthal and the other the occipitotemporal cortical vein. (D) Transvenous approach through the straight sinus, galenic and basal vein, venous aneurysm, lateral mesencephalic and superior petrosal vein. (E) Occlusion of the draining vein with coils. (F, G, H) Digital angiography of the left carotid in arterial, capillary and venous phase, showing the complete occlusion of the fistula. (J) Post- embolisation MRA confirming the occlusion of the fistula. (K, L) TOF MR sequences post (left) and pre (right) treatment showing occlusion of the lesion with normalisation of the previously involved veins. Cranial and Spinal Dural Arteriovenous Fistulas 155

Figure 3. (A) DSA - CCA injection, lateral view, showing a DAVF of the left transverse-sigmoid sinus - isolated sinus - due to thrombosis proximal and distal to the shunt area. (B) late phase of the same injection showing the pseudophlebitic pattern of the regional venous system, expression of venous strain – congestion. (C) External carotid artery ipsilateral injection, lateral view, showing the shunt supplied through the middle meningeal artery and small transosseous/dural branches of the occipital artery and draining non-directly but exclusively into the temporal venous system. The extensive leptomeningeal venous reflux is through more than one bridging veins. (D) Venous injection, lateral projection, at the level of the jugular bulb showing the occlusion of the distal sigmoid sinus. (E) Venous approach through the thrombosed sigmoid sinus to the isolated segment and positioning of the first coil near the exit of the bridging refluxing veins. (F) Occlusion of the isolated sinus segment with coils and glue. (G, H, J) Final control injection of the external and common carotid arteries confirming the complete occlusion of the fistula.

156 G. Baltsavias

Figure 4. Patient with an epidural arteriovenous fistula involving the ventral epidural plexus at the level of the L3 vertebral body. (A) T2 MR sequence showing high signal – oedema of the conus and lower spinal cord up to the Th6 level and flow-voids mostly on the dorsal aspect of the spinal cord. (B) The TOF sequence shows the cause of the oedema, an arteriovenous fistula located in the spinal canal, ventral to the dural sac. (C) The selective injection of the right L3 lumbar artery reveals the exact angioarchitecture of the lesion. A small arterial feeder – dorsal somatic artery – opacifies an isolated, apparently due to thrombosis, arterialised segment of the hexagon-shaped ventral epidural venous plexus, which drains directly and exclusively into a spinal vein normally draining antegrade into the ventral epidural venous plexus, but now having a retrograde flow upwards to the perimedullary venous network of the spinal cord causing venous congestion. (D) Superselective microcatheterisation and injection of the arterial feeder, showing the details of the lesion – magnified view. (E) Selective injection of the right L3 lumbar artery after embolisation showing the complete elimination of the fistula. (F, G) Plain x-ray of the lumbar spine showing the cast of glue (NBCA) dorsal to the L3 vertebral body with a good penetration into the draining vein. (H) MRI-T2 sequence at 5 months showing the disappearance of spinal cord high signal and flow-voids. Cranial and Spinal Dural Arteriovenous Fistulas 157

The cranial venous system should be understood as a system that is organised in 5 levels with their corresponding venous structures from inside to outside as follows:

1. The level of the intradural course of the bridging veins 2. The level of the dura matter itself and its veins 3. The level of the dural sinus meant as a venous conduit 4. The level of the emissary veins 5. The level of the diploic veins of the cranium

We omit deliberately the level of the scalp veins (subgaleal shunts) as not related to the subject. Since the shunts of the dura matter itself are mostly traumatic and rare, for methodological reasons and for the sake of simplicity, we can ignore level 2 and also merge levels 4 and 5 into a single “emissary” level, therefore only considering 3 venous structures as possible locations of a cranial dural arteriovenous fistula:

1. The intradural segment or entry zone of a bridging vein (BV) 2. The wall of a dural sinus (DS) 3. The emissary vein (EV) and/or diploic vein

Therefore, based on the above levels, we can distinguish the following anatomical types of cranial dural fistulas: the bridging vein fistula (BVF), the dural sinus fistula (DSF) and the emissary vein fistula (EVF) (Baltsavias et al. Part 2, 2015). The BVF is a typical aggressive type of lesion, regardless of topography. It can be found anywhere in the dura as long as a bridging vein can be connected anywhere with a typical or atypical, small or large sinus. Therefore, it can occur in the convexial dura matter or in the anterior, middle or posterior fossa, at the entry zone of a bridging vein into an atypical or even remote tributary sinus (Baltsavias, Bhatti and Valavanis 2013) of any of the large sinuses, at the intradural segment of a vein draining into a tentorial (lake-like) sinus, or next to a typical sinus. It involves the intradural segment of a bridging vein, which normally has a seemingly stenotic appearance and drains the brain anterograde to the sinus. In almost all described cases of BVFs, however, the exit of the vein to the sinus is occluded/thrombosed and the blood coming from the feeders refluxes directly (without flowing through a sinus) and exclusively (with no alternative exit) into the leptomeningeal venous system (LVR). Therefore, the microanatomic location of the shunt determines the most crucial feature of the architecture from the beginning: the existence of reflux (Baltsavias et al. Part 2, 2015). The DSF is the classical, often benign, type of DAVF. It involves the sinus wall, which lies in the epidural space and drains more often into the lumen of the sinus. The extent of occlusive/thrombotic phenomena determines the ultimate drainage and therefore the type of the shunt. In case of extensive occlusion of the sinus lumen, the blood coming from the feeders may reflux into the leptomeningeal venous system (Geibprasert et al. 2008). If the lumen is completely occluded distal and proximal to the shunting area, we are dealing with a shunt variety involving an isolated sinus segment with exclusive reflux into one or several bridging veins, although it is non-direct (it flows through the sinus to the cerebral veins) by definition. The EVF is basically the most benign type of DAVF. This is because it involves venous structures as the emissary or osseous veins remote from the cerebral veins. Typical representatives of this type are shunts of the hypoglossal vein. As with the previous 158 G. Baltsavias locations/types, the extent of the occlusive/thrombotic phenomena determines whether reflux (exclusive or non-exclusive but certainly non-direct) will occur. (Baltsavias et al. Part 4, 2015). At the level of the spinal cord, several classification schemes have been proposed (Rodesch et al. 2002; Spetzler et al. 2002). However, the corresponding spinal shunts can be similarly understood and distinguished into 3 types according to the venous structure-location involved, as follows:

1. Spinal bridging vein fistula (SBVF); 2. Fistula affecting the epidural venous plexus; 3. Paraspinal fistula with or without osseous involvement.

These 3 types are essentially equivalent to their cranial counterparts (at least in the adults), despite the lack of analogous terminology. For instance, a transverse sinus DAVF is a fistula of the (dorsal) epidural space (Geibprasert et al. 2008) although it is typically called “dural”. Similarly, the paraspinal fistulas are never described as part of the spinal dural lesions (Lenck et al. 2019); however, a fistula of the anterior condylar confluence, essentially with the same topology, is typically included in the cranial dural group (Miyachi et al. 2008). The SBVF is the classic spinal dural fistula. It is typically described as being located on the dorsal aspect of the spinal dura, close to the spinal root. However, as with cranial DAVFs, a spinal DAVF can be theoretically found anywhere along the circumference (anecdotal data) as long as a bridging vein can be connected anywhere with the spinal dura and then follow a shorter or longer intradural course to the collecting vein (typically the epidural venous plexus). Even when the retrograde draining vein is a radicular vein piercing the dura more lateral than other spinal draining veins, it is still a bridging vein following the sleeve and exiting to the same venous collectors (Kiyosue et al. 2017). A fistula located in the so-called epidural venous plexus, corresponds to the cranial dural sinus fistula, since the plexus is morphologically and functionally equivalent to the dural sinuses as the collecting venous system at the level of the spine (Chaynes et al. 1998; Groen et al. 1997). Often, these lesions present with reflux to the perimedullary veins due to thrombosis of the plexus (Brinjikji et al. 2016). In case of extensive occlusion/thrombosis and isolation of the affected spinal epidural plexus segment, we are dealing with a variety that is equivalent to the isolated sinus shunt at the cranial level. The paraspinal fistula with or without osseous component involves the veins adjacent to the spinal canal and therefore is equivalent to the cranial EVF according to the above scheme. The treatment of choice for DAVFs is the endovascular occlusion of the primary draining vein with a permanent embolic material (Agid et al. 2009; Baltsavias and Valavanis 2014; Cognard et al. 2008), with the transvenous approach being the first choice when possible. Surgery is the first alternative method in cases of failure or high-risk. The surgical disconnection of the retrograde draining bridging vein is a highly effective and straightforward strategy to treat DAVFs with reflux and is used since many years (Collice et al. 1996; Grisoli et al. 1984; Thompson, Doppman and Oldfield 1994); however, this mostly applies for BVFs and not for all the so-called high grade shunts (Baltsavias, Valavanis and Regli 2019; Baltsavias 2016).

Cranial and Spinal Dural Arteriovenous Fistulas 159

3.2. Specific Comments on the Presented Cases

3.2.1. Case 1 This is a DAVF, often described as a “medial or lesser sphenoid wing or sphenoid region” lesion (Kandyba et al. 2018; Shi et al. 2013; Rezende et al. 2006). Such a misnomer using a bony instead of a venous structure for the characterisation of the vascular shunt is an expression of underestimation of the venous system and/or a lack of familiarity with the venous anatomy. As an aneurysm of the anterior communicating artery would never be called an aneurysm of the planum sphenoidale, equally a dural shunt of a bridging vein should not be characterised by the adjacent bone (except in cases with osteodural involvement). This particular location has been also a source of confusion in the literature (Osbun et al. 2013). As stated above, the arterial feeders of a DAVF do not specifically characterise it. The feeding vessels coming from the ophthalmic artery neither reveal a “near-ethmoidal” dural shunt nor imply an aggressive clinical behaviour, since the arterial component of an AV-lesion is not the dictating component. No artery can make a dural fistula aggressive (Halbach et al. 1990). The arterial feeders of the shunt are predictable and amenable to the variations of the arterial territories. The opacification of the bridging vein alone, without any adjacent sinus or part of a sinus, makes the diagnosis of a BVF unambiguous. The fistula drains directly and exclusively into that vein, which through short pial venous collaterals empties anterograde into the first segment of the basal vein, left peduncular vein, contralateral peduncular vein and subsequently second and third segment of the basal vein to the galenic vein and straight sinus. The drainage into the bridging vein is retrograde by definition regardless if the next or ultimate segment of draining vein drains necessarily anterograde to a sinus (Baltsavias 2014). The medial location of the anterior(-medial) temporal bridging vein (Tubbs et al. 2017) makes the first segment of the basal vein the most favourable outflow to the next sinus. These features make it a DES lesion according to our scheme of analysis (Baltsavias, Roth and Valavanis 2015), signifying an aggressive type of CDAVF with direct, exclusive and strained (venous aneurysm) reflux to the leptomeningeal venous system. According to Borden it is a type 3 lesion, and according to Cognard classification it is a type IV fistula. This particular angioarchitecture makes the transvenous approach high-risk due to the ruptured large ectatic lesion and the arterial approach is more feasible and preferable, yet more demanding due to the participation of the ophthalmic artery. The surgical treatment, as with all BVFs, is a highly effective alternative consisting in the clip disconnection of the affected BV.

3.3.2. Case 2 This is a dural arteriovenous fistula typically described as “petrosal”. However, this is a vague description since “petrosal” can also be the superior petrosal (SPS) or the inferior petrosal sinus. The lesion is not located anywhere in the petrosal dura. In the angiogram, we do not see any sinus being opacified. We see only the superior petrosal vein, which makes the lesion a BVF affecting the intradural segment of this vein, with its exit to the sinus being now occluded. Often in this kind of shunts, the superior petrosal sinus itself is patent despite its small size, as in the present case and other cases confirmed with superselective transvenous injections of the SPS (anecdotal data). The complete disappearance of the shunt after coiling of the petrosal vein a few millimetres distal to the fistulous site proves the location of the shunt in the intradural segment of the vein and the pre-existing occlusion of its normal exit to the SPS. 160 G. Baltsavias

Similar to case 1, this is also a DES lesion according to our scheme of analysis, signifying an aggressive type of CDAVF with direct, exclusive and strained (venous aneurysm) reflux. According to Borden it is a type 3 lesion, and according to Cognard classification it is a type IV fistula. For this variety of petrosal BVF with dominant supply through tentorial branches of the internal carotid, the transarterial approach through the multiple small feeders of the carotid or the petrosal branch of the middle meningeal or the artery of the foramen rotundum is technically very challenging and hazardous if we accept superselectivity as the cornerstone of endovascular treatment. This is why the surgical disconnection of the superior petrosal vein with a single clip is a highly efficient option. However, when technically feasible, the transvenous approach and coiling is the endovascular equivalent of surgical disconnection in terms of efficacy but technically is much more selective and elegant and therefore more attractive. In this particular case of transvenous approach, the most challenging aspect was the atraumatic and sensible navigation of the microwire-microcatheter through the venous aneurysm.

3.2.3. Case 3 This is a dural arteriovenous fistula typically described as an “isolated sinus” shunt affecting the distal transverse-proximal sigmoid sinus; therefore, it is located at the level of the dural sinus wall. This case is useful because it shows the shortcomings of the commonly used classification systems. The sinus is thrombosed proximal and distal to the fistulous site and the blood coming from the arterial feeders refluxes through the isolated sinus segment and more than one bridging veins to the regional leptomeningeal venous system causing significant stasis. These congestive phenomena are expressed angiographically with the so-called pseudophlebitic appearance of the temporal venous network (Willinsky et al. 1999). This angioarchitecture is clearly different compared to the previous BVFs of cases 1 and 2. The first difference is that the reflux here is non-direct, because it flows through the sinus to the cerebral venous system. The second difference is that the reflux occurs through several bridging veins and not only through one BV, as is the rule with BVFs. This means that the affected venous territory is larger. Otherwise, this is an nDES lesion according to our scheme of analysis, signifying a less aggressive type of CDAVF (compared to the two previous cases) with non- direct, exclusive and strained due to venous congestion, reflux (Baltsavias et al. Part 4, 2015). According to Borden this is a type 3 lesion, identical to the previous two cases, despite the significant differences in angioarchitecture (Baltsavias, Roth and Valavanis 2015). According to Cognard classification, however, the type of this lesion is difficult to define. It could be type IIb if we consider that the blood flow inside the isolated sinus segment is anterograde or type IIa+b if we accept that the flow inside the isolated sinus segment is retrograde (Baltsavias, Roth and Valavanis 2015). However, this offen cannot be clearly seen (as in this case) or it could be that the flow is neither anterograde nor retrograde, coming from different sites simultaneously. Regardless of the above ambiguities, the most important remark is that the flow-direction criterion itself is irrelevant for the characterisation of such a shunt. It can be either anterograde or retrograde flow, it makes no difference; therefore, the distinction between Type IIb and type IIa+b, according to Cognard, appears to be highly problematic in a case like this, as well as in other cases (Baltsavias, Roth and Valavanis 2015). Moreover, the exceeding consideration of flow directions contrasts with the complete disregard (from both classifications) of the venous congestion as a clear expression of dysfunction and recognisable risk sign for morbidity (Baltsavias, Roth and Valavanis 2015; Willinsky et al. 1999). Cranial and Spinal Dural Arteriovenous Fistulas 161

The treatment of this particular type of DSF can be achieved through the transarterial or transvenous route. As a rule, the goal of both approaches is the occlusion of the already non- functional isolated segment, either with liquid embolic materials or with coils. Despite the thrombosis of the sinus, the navigation through the thrombosed segment is feasible in the majority of cases and it is the preferred method due to higher efficacy and safety. Surgical treatment is also an option but possibly not a simple one with a single approach and clip disconnection because the draining veins can be multiple and supra- and infratentorially located.

3.2.4. Case 4 This case is a typical example of a spinal shunt of the ventral epidural venous plexus, equivalent from the angioarchitecture point of view, with the isolated dural sinus fistula in the cranium due to partial thrombosis of the plexus. As with case 3, this is an nDES lesion according to our scheme, signifying a non-direct, exclusive and strained reflux; due to venous congestion of the medullary venous system, which is responsible for the paraparesis of the patient. A useful remark regarding other classification schemes is that the flow direction in the spinal epidural venous plexus itself, with or without reflux, is practically never used for the grading of a spinal shunt. The treatment of such an epidural shunt with exclusive drainage to the medullary venous system can be equally achieved with surgery and embolisation. The latter is more selective, less invasive and more elegant, which is why it is more attractive. However, large venous pouches with mass effect and high-flow lesions may be challenging for both methods. Generally, the issue of convenience of surgery for the treatment of an epidural spinal shunt compared either with the classic spinal dural fistula or compared to embolisation is very similar to the question about cranial counterparts. The key for the understanding of this comparison is the distinction between 1. single and multiple refluxing draining veins and 2. the isolated sinus/plexus type vs. the non-isolated one. In other words, the complexity of surgery increases when there is more than one retrograde draining bridging vein and in cases of non-exclusive reflux. Non-exclusive reflux means that one has to also deal with the ventrally located epidural plexus for the complete elimination of the lesion (Brinjikji et al. 2016; Niizuma et al. 2013).

4. REFERENCES

Agid, R., Terbrugge, K., Rodesch, G., Andersson, T. & Soderman, M. (2009). “Management strategies for anterior cranial fossa (ethmoidal) dural arteriovenous fistulas with an emphasis on endovascular treatment.” J Neurosurg, 110 (1), 79-84. https://doi.org/ 10.3171/2008.6.17601. https://www.ncbi.nlm.nih.gov/pubmed/18847336. Awad, I. A., Little, J. R., Akarawi, W. P. & Ahl, J. (1990). “Intracranial dural arteriovenous malformations: factors predisposing to an aggressive neurological course.” J Neurosurg, 72 (6), 839-50. https://doi.org/10.3171/jns.1990.72.6.0839. https://www.ncbi.nlm.nih.gov/ pubmed/2140125. Baltsavias, G. (2014). “Aberrant venous drainage pattern in a medial sphenoid wing dural arteriovenous fistula: commentary.” World Neurosurg, 82 (3-4), e563-5. https://doi.org/ 10.1016/j.wneu.2014.05.036. https://www.ncbi.nlm.nih.gov/pubmed/24915071. 162 G. Baltsavias

Baltsavias, G. (2016). “Cranial Dural Arteriovenous Shunts with Leptomeningeal Venous Reflux: What Is the Exact Role of Surgery?” World Neurosurg, 88, 673- 674. https://doi.org/10.1016/j.wneu.2015.08.064. https://www.ncbi.nlm.nih.gov/pubmed/ 27080754. Baltsavias, G., Bhatti, A. & Valavanis, A. (2013). “Lateral convexial tributary sinus of superior sagittal sinus. A rare anatomic variation and the importance of its recognition.” Clin Neurol Neurosurg, 115 (10), 2268-9. https://doi.org/10.1016/j.clineuro.2013.07.020. https://www. ncbi.nlm.nih.gov/pubmed/23932469. Baltsavias, G., Kumar, R., Avinash, K. M. & Valavanis, A. (2015). “Cranial dural arteriovenous shunts. Part 2. The shunts of the bridging veins and leptomeningeal venous drainage.” Neurosurg Rev, 38 (2), 265-71, discussion 272. https://doi.org/10.1007/s10143-014-0594- y. https://www.ncbi.nlm.nih.gov/pubmed/25403687. Baltsavias, G., Parthasarathi, V., Aydin, E., Al Schameri, R. A. Roth, P. & Valavanis, A. (2015). “Cranial dural arteriovenous shunts. Part 1. Anatomy and embryology of the bridging and emissary veins.” Neurosurg Rev, 38 (2), 253-63, discussion 263- 4. https://doi.org/10.1007/s10143-014-0590-2. https://www.ncbi.nlm.nih.gov/pubmed/ 25468011. Baltsavias, G., Roth, P. & Valavanis, A. (2015). “Cranial dural arteriovenous shunts. Part 3. Classification based on the leptomeningeal venous drainage.” Neurosurg Rev, 38 (2), 273- 81, discussion 281. https://doi.org/10.1007/s10143-014-0596-9. https://www.ncbi.nlm.nih. gov/pubmed/25516093. Baltsavias, G., Spiessberger, A., Hothorn, T. & Valavanis, A. (2015). “Cranial dural arteriovenous shunts. Part 4. Clinical presentation of the shunts with leptomeningeal venous drainage.” Neurosurg Rev, 38 (2), 283-91, discussion 291. https://doi.org/10.1007/s10143-014-0595-x. https://www.ncbi.nlm.nih.gov/pubmed/ 25421555. Baltsavias, G. & Valavanis, A. (2014). “Endovascular treatment of 170 consecutive cranial dural arteriovenous fistulae: results and complications.” Neurosurg Rev, 37 (1), 63- 71. https://doi.org/10.1007/s10143-013-0498-2. https://www.ncbi.nlm.nih.gov/pubmed/ 24101196. Baltsavias, G., Valavanis, A. & Regli, L. (2019). “Cranial dural arteriovenous shunts: selection of the ideal lesion for surgical occlusion according to the classification system.” Acta Neurochir (Wien), 161 (9), 1775-1781. https://doi.org/10.1007/s00701-019-03984-4. https://www.ncbi.nlm.nih.gov/pubmed/31267189. Borden, J. A., Wu, J. K. & Shucart, W. A. (1995). “A proposed classification for spinal and cranial dural arteriovenous fistulous malformations and implications for treatment.” J Neurosurg, 82 (2), 166-79. https://doi.org/10.3171/jns.1995.82.2.0166. https://www.ncbi. nlm.nih.gov/pubmed/7815143. Brinjikji, W., Yin, R., Nasr, D. M. & Lanzino, G. (2016). “Spinal epidural arteriovenous fistulas.” J Neurointerv Surg, 8 (12), 1305-1310. https://doi.org/10.1136/neurintsurg-2015- 012181. https://www.ncbi.nlm.nih.gov/pubmed/26790829. Chaynes, P., Verdie, J. C., Moscovici, J., Zadeh, J., Vaysse, P. & Becue, J. (1998). “Microsurgical anatomy of the internal vertebral venous plexuses.” Surg Radiol Anat, 20 (1), 47-51. https://doi.org/10.1007/bf01628115. https://www.ncbi.nlm.nih.gov/pubmed/ 9574489. Cranial and Spinal Dural Arteriovenous Fistulas 163

Cognard, C., Gobin, Y. P., Pierot, L., Bailly, A. L., Houdart, E., Casasco, A., Chiras, J. & Merland, J. J. (1995). “Cerebral dural arteriovenous fistulas: clinical and angiographic correlation with a revised classification of venous drainage.” Radiology, 194 (3), 671-80. https://doi.org/10.1148/radiology.194.3.7862961. https://www.ncbi.nlm.nih.gov/pubmed/ 7862961. Cognard, C., Januel, A. C., Silva, N. A. Jr. & Tall, P. (2008). “Endovascular treatment of intracranial dural arteriovenous fistulas with cortical venous drainage: new management using Onyx.” AJNR Am J Neuroradiol, 29 (2), 235-41. https://doi.org/10.3174/ajnr.A0817. https://www.ncbi.nlm.nih.gov/pubmed/17989374. Collice, M., D’Aliberti, G., Talamonti, G., Branca, V., Boccardi, E., Scialfa, G. & Versari, P. P. (1996). “Surgical interruption of leptomeningeal drainage as treatment for intracranial dural arteriovenous fistulas without dural sinus drainage.” J Neurosurg, 84 (5), 810- 7. https://doi.org/10.3171/jns.1996.84.5.0810. https://www.ncbi.nlm.nih.gov/pubmed/ 8622155. Duvernoy, H. M., Delon, S. & Vannson, J. L. (1981). “Cortical blood vessels of the human brain.” Brain Res Bull, 7 (5), 519-79. Freckmann, N., Sartor, K. & Herrmann, H. D. (1981). “Traumatic arteriovenous fistulae of the middle meningeal artery and neighbouring veins or dural sinuses.” Acta Neurochir (Wien), 55 (3-4), 273-81. https://doi.org/10.1007/bf01808443. https://www.ncbi.nlm.nih.gov/ pubmed/7234533. Geibprasert, S., Pereira, V., Krings, T., Jiarakongmun, P., Toulgoat, F., Pongpech, S. & Lasjaunias, P. (2008). “Dural arteriovenous shunts: a new classification of craniospinal epidural venous anatomical bases and clinical correlations.” Stroke, 39 (10), 2783- 94. https://doi.org/10.1161/STROKEAHA.108.516757. https://www.ncbi.nlm.nih.gov/ pubmed/18635840. Grisoli, F., Vincentelli, F., Fuchs, S., Baldini, M., Raybaud, C., Leclercq, T. A. & Vigouroux, R. P. (1984). “Surgical treatment of tentorial arteriovenous malformations draining into the subarachnoid space. Report of four cases.” J Neurosurg, 60 (5), 1059- 66. https://doi.org/10.3171/jns.1984.60.5.1059. https://www.ncbi.nlm.nih.gov/pubmed/ 6716141. Groen, R. J., Groenewegen, H. J., van Alphen, H. A. & Hoogland, P. V. (1997). “Morphology of the human internal vertebral venous plexus: a cadaver study after intravenous Araldite CY 221 injection.” Anat Rec, 249 (2), 285-94. https://doi.org/10.1002/(SICI) 1097-0185(199710)249:2<285::AID-AR16>3.0.CO;2-K. https://www.ncbi.nlm.nih.gov/ pubmed/9335475. Halbach, V. V., Higashida, R. T., Hieshima, G. B., Wilson, C. B., Barnwell, S. L. & Dowd, C. F. (1990). “Dural arteriovenous fistulas supplied by ethmoidal arteries.” Neurosurgery, 26 (5), 816-23. https://doi.org/10.1097/00006123-199005000-00014. https://www.ncbi.nlm. nih.gov/pubmed/2191241. Hiramatsu, M., Sugiu, K., Hishikawa, T., Nishihiro, S., Kidani, N., Takahashi, Y., Murai, S., Date, I., Kuwayama, N., Satow, T., Iihara, K. & Sakai, N. (2019). “Results of 1940 embolizations for dural arteriovenous fistulas: Japanese Registry of Neuroendovascular Therapy (JR-NET3).” J Neurosurg, 1-8. https://doi.org/10.3171/2019.4.JNS183458. https://www.ncbi.nlm.nih.gov/pubmed/31252394. Kakarla, U. K., Deshmukh, V. R., Zabramski, J. M., Albuquerque, F. C., McDougall, C. G. & Spetzler, R. F. (2007). “Surgical treatment of high-risk intracranial dural arteriovenous 164 G. Baltsavias

fistulae: clinical outcomes and avoidance of complications.” Neurosurgery, 61 (3), 447-57; discussion 457-9. https://doi.org/10.1227/01.NEU.0000290889.62201.7F. https://www.ncbi.nlm.nih.gov/pubmed/17881955. Kandyba, D. V., Babichev, K. N., Stanishevskiy, A. V., Abramyan, A. A. & Svistov, D. V. (2018). “Dural arteriovenous fistula in the sphenoid bone lesser wing region: Endovascular adjuvant techniques of treatment and literature review.” Interv Neuroradiol, 24 (5), 559- 566. https://doi.org/10.1177/1591019918777233. https://www.ncbi.nlm.nih.gov/pubmed/ 29848145. Kiyosue, H., Matsumaru, Y, Niimi, Y., Takai, K., Ishiguro, T., Hiramatsu, M., Tatebayashi, K., Takagi, T., Yoshimura, S. & Jsnet Spinal AV Shunts Study Group. (2017). “Angiographic and Clinical Characteristics of Thoracolumbar Spinal Epidural and Dural Arteriovenous Fistulas.” Stroke, 48 (12), 3215-3222. https://doi.org/10.1161/STROKEAHA.117.019131. https://www.ncbi.nlm.nih.gov/pubmed/29114089. Lenck, S., Nicholson, P., Tymianski, R., Hilditch, C., Nouet, A., Patel, K., Krings, T., Tymianski, M., Radovanovic, I. & Mendes Pereira, V. (2019). “Spinal and Paraspinal Arteriovenous Lesions.” Stroke, 50 (8), 2259-2269. https://doi.org/10.1161/ STROKEAHA.118.012783. https://www.ncbi.nlm.nih.gov/pubmed/31177982. Liu, J. K., Dogan, A., Ellegala, D. B., Carlson, J., Nesbit, G. M., Barnwell, S. L. & Delashaw, J. B. (2009). “The role of surgery for high-grade intracranial dural arteriovenous fistulas: importance of obliteration of venous outflow.” J Neurosurg, 110 (5), 913-20. https://doi. org/10.3171/2008.9.JNS08733. https://www.ncbi.nlm.nih.gov/pubmed/19199500. Miyachi, S., Ohshima, T., Izumi, T., Kojima, T. & Yoshida, J. (2008). “Dural arteriovenous fistula at the anterior condylar confluence.” Interv Neuroradiol, 14 (3), 303-11. https://doi.org/10.1177/159101990801400311. https://www.ncbi.nlm.nih.gov/pubmed/ 20557728. Nerva, J. D., Hallam, D. K. & Ghodke, B. V. (2014). “Percutaneous transfacial direct embolization of an intraosseous dural arteriovenous fistula.” Neurosurgery, 10 Suppl 1, E178-82. https://doi.org/10.1227/NEU.0000000000000213. https://www.ncbi.nlm.nih. gov/pubmed/24141481. Niizuma, K., Endo, T., Sato, K., Takada, S., Sugawara, T., Mikawa, S. & Tominaga, T. (2013). “Surgical treatment of spinal extradural arteriovenous fistula with parenchymal drainage: report on 5 cases.” Neurosurgery, 73 (2 Suppl Operative), onsE287-3; discussion onsE293- 4. https://doi.org/10.1227/NEU.0000000000000189. https://www.ncbi.nlm.nih.gov/ pubmed/24077580. Osbun, J. W., Kim, L. J., Spetzler, R. F. & McDougall, C. G. (2013). “Aberrant venous drainage pattern in a medial sphenoid wing dural arteriovenous fistula: a case report and review of the literature.” World Neurosurg, 80 (6), e381-6. https://doi.org/10.1016/j.wneu. 2013.02.022. https://www.ncbi.nlm.nih.gov/pubmed/23403353. Rezende, M. T., Piotin, M., Mounayer, C., Spelle, L., Abud, D. G. & Moret, J. (2006). “Dural arteriovenous fistula of the lesser sphenoid wing region treated with Onyx: technical note.” Neuroradiology, 48 (2), 130-4. https://doi.org/10.1007/s00234-005-0020-9. https://www. ncbi.nlm.nih.gov/pubmed/16429281. Rodesch, G., Hurth, M., Alvarez, H., Tadie, M. & Lasjaunias, P. (2002). “Classification of spinal cord arteriovenous shunts: proposal for a reappraisal--the Bicetre experience with 155 consecutive patients treated between 1981 and 1999.” Neurosurgery, 51 (2), 374-9, discussion 379-80. https://www.ncbi.nlm.nih.gov/pubmed/12182775. Cranial and Spinal Dural Arteriovenous Fistulas 165

Shi, Z. S., Ziegler, J., Feng, L., Gonzalez, N. R., Tateshima, S., Jahan, R., Martin, N. A., Vinuela, F. & Duckwiler, G. R. (2013). “Middle cranial fossa sphenoidal region dural arteriovenous fistulas: anatomic and treatment considerations.” AJNR Am J Neuroradiol, 34 (2), 373-80. https://doi.org/10.3174/ajnr.A3193. https://www.ncbi.nlm.nih.gov/ pubmed/22790245. Spetzler, R. F., Detwiler, P. W., Riina, H. A. & Porter, R. W. (2002). “Modified classification of spinal cord vascular lesions.” J Neurosurg, 96 (2 Suppl), 145-56. https://doi.org/ 10.3171/spi.2002.96.2.0145. https://www.ncbi.nlm.nih.gov/pubmed/12450276. Strom, R. G., Botros, J. A., Refai, D., Moran, C. J., Cross, D. T., 3rd, Chicoine, M. R., Grubb, R. L., Jr., Rich, K. M., Dacey, R. G., Jr., Derdeyn, C. P. & Zipfel, G. J. (2009). “Cranial dural arteriovenous fistulae: asymptomatic cortical venous drainage portends less aggressive clinical course.” Neurosurgery, 64 (2), 241-7, discussion 247-8. https:// doi.org/10.1227/01.NEU.0000338066.30665.B2. https://www.ncbi.nlm.nih.gov/pubmed/ 19190453. Tanaka, M. (2019). “Embryological Consideration of Dural AVFs in Relation to the Neural Crest and the Mesoderm.” Neurointervention, 14 (1), 9-16. https://doi.org/ 10.5469/neuroint.2018.01095. https://www.ncbi.nlm.nih.gov/pubmed/30827062. Thompson, B. G., Doppman, J. L. & Oldfield, E. H. (1994). “Treatment of cranial dural arteriovenous fistulae by interruption of leptomeningeal venous drainage.” J Neurosurg, 80 (4), 617-23. https://doi.org/10.3171/jns.1994.80.4.0617. https://www.ncbi.nlm.nih.gov/ pubmed/8151339. Tubbs, R. S., Salter, E. G., Wellons, J. C., 3rd, Blount, J. P. & Oakes, W. J. (2007). “The sphenoparietal sinus.” Neurosurgery, 60 (2 Suppl 1), ONS9-12; discussion ONS12. https://doi.org/10.1227/01.NEU.0000249241.35731.C6. https://www.ncbi.nlm.nih.gov/ pubmed/17297360. Willinsky, R., Goyal, M., terBrugge, K. & Montanera, W. (1999). “Tortuous, engorged pial veins in intracranial dural arteriovenous fistulas: correlations with presentation, location, and MR findings in 122 patients.” AJNR Am J Neuroradiol, 20 (6), 1031-6. https://www.ncbi.nlm.nih.gov/pubmed/10445439. Zipfel, G. J., Shah, M. N., Refai, D., Dacey, R. G. Jr. & Derdeyn, C. P. (2009). “Cranial dural arteriovenous fistulas: modification of angiographic classification scales based on new natural history data.” Neurosurg Focus, 26 (5), E14. https://doi.org/ 10.3171/2009.2.FOCUS0928. https://www.ncbi.nlm.nih.gov/pubmed/19408992.

Chapter 10

CEREBRAL HEMORRHAGES

S. Luzzi1,2,*, A. Giotta Lucifero1, M. Del Maestro2,3 and R. Galzio1,2 1Neurosurgery Unit, Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy; 2Neurosurgery Unit, Department of Surgical Sciences, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; 3PhD School in Experimental Medicine, Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy;

ABSTRACT

Spontaneous intracerebral hemorrhage (ICH) is characterized by a sharply increasing incidence secondary to the increase in the average life span and widespread use of anticoagulation treatment. Despite data from several clinical trials conducted recently, the overall management of this devastating pathology is still controversial. In this chapter, we provide an overview of the main epidemiological and clinical aspects of spontaneous ICH, mainly focusing on an evidence-based treatment algorithm according to which patients are selected as candidates for surgery. The surgical techniques commonly employed in the treatment of ICH occupy a large part of the chapter.

Keywords: hemorrhagic stroke, intracerebral hematoma, intracerebral hemorrhage, neuroprotection, decompressive craniectomy

1. OVERVIEW

Spontaneous intracerebral hemorrhage (ICH) is a life-threatening cerebrovascular disease with an incidence rate of 24.6 per 100,000 person-years. Spontaneous ICHs account for 10%–

* Corresponding Author’s Email: [email protected]. 168 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

15% of strokes, with a morbidity and mortality index of 30%–50%, have a higher incidence after the sixth decade of life, and more frequently affect women. Although several steps have been performed in the neurosurgical treatment of different pathologies affecting the central nervous system (Bellantoni et al. 2019; Cheng, Shetty, and Sekhar 2018; De Tommasi et al. 2008; De Tommasi et al. 2007; Guastamacchia et al. 2007; Sabino Luzzi, Crovace, et al. 2019; S. Luzzi, Crovace, et al. 2018; S. Luzzi, Elia, Del Maestro, Elbabaa, et al. 2019; S. Luzzi, Giotta Lucifero, et al. 2019; Palumbo et al. 2019; Palumbo et al. 2018; Raysi Dehcordi et al. 2017; Spena et al. 2019; C. Zoia et al. 2018; Antonosante et al. 2020; Campanella et al. 2020; Cesare Zoia et al. 2020), spontaneous ICH is still burdened by high morbidity and mortality rates to date. The etiology of spontaneous ICHs is mainly attributable to small vessel diseases or cerebral amyloid angiopathy and vasculitis. Hypertensive arteriopathy and anticoagulant/antiplatelet therapies are considered significant concomitant factors. Nevertheless, a non-negligible number of cases seem to be not related to organic causes (Wilkinson et al. 2018). Primary acute brain injury consists of progressive hematoma expansion, mass effect, increased intracranial pressure, and mechanical compression of the neighboring areas, ultimately resulting in brain herniation and ischemia. The pathophysiologic response to hematoma expansion, causing secondary brain injury, mainly consists of edema formation, further worsening the mass effect, inflammatory responses, and cytotoxic effect from the extravasated blood components. Despite the existence of guidelines and treatment algorithms, the overall management of spontaneous ICHs remains controversial on a par with other neurosurgical areas (Bongetta et al. 2019; Ciappetta et al. 2008; De Tommasi, Cascardi, et al. 2006; De Tommasi, De Tommasi, et al. 2006; Millimaggi et al. 2018; Elsawaf et al. 2020). Actually, each proposed treatment should face the peculiarities of each single patient.

2. RISK FACTORS

Female sex, age > 60 years, diabetes mellitus, atrial fibrillation, spontaneous and acquired coagulopathies, cigarette smoking, alcohol consumption, hypertension, and amyloid angiopathy are classically considered as the main risk factors for spontaneous ICH. Compromising endothelial integrity, chronic hypertension plays an even greater role when not adequately treated. Additionally, in patients with cerebral amyloidosis, the accumulation of amyloid-β protein in cerebral and leptomeningeal arterioles and capillaries weakens the walls and makes them prone to rupture. Noteworthy, the coexistence of different factors has an exponential effect on the estimation of the overall risk for ICH (van Asch et al. 2010).

3. CLINICAL ONSET

The clinical onset of hemorrhagic stroke is generally acute and progressive in almost all cases. While considering the heterogeneity of different clinical presentation patterns, derived Cerebral Hemorrhages 169 from different topographic regions involved, headache and vomiting, acute deterioration of consciousness, and focal deficits are constant clinical signs, especially in the first hours. Involvement of the ventricular system is common, being responsible for concurrent acute hydrocephalus and worse outcome.

4. DIAGNOSIS

Non-contrast-enhanced CT is the gold standard in the diagnosis of spontaneous ICH. It allows for an immediate assessment of the site and volume of the hemorrhages, often leading to orientation toward a presumptive diagnosis. The fast timing of execution, possibility of performing in the emergency room, high volume of information provided, and its cost- effectiveness are the main strengths of this first-level examination. Non-contrast-enhanced CT is considered adequate for the etiological diagnosis of most hematomas involving the thalamus, basal ganglia, and claustral area. Lobar hemorrhages or hemorrhages smaller but affecting topographic areas different from those aforementioned impose the need for contrast-enhanced CT or CT angiography in the acute setting. In those cases that are not associated with concomitant lesions, CT angiography reveals the presence of small enhancing foci (spot sign) that are considered suggestive of active hemorrhage. Brain magnetic resonance imaging (MRI) is seldom performed in the acute stage but instead reserved for the subacute phase, often to reveal the pathognomonic radiological pattern of amyloid angiopathy. Cavernous hemangiomas can be generally detected by MRI within the first hours after clinical onset. Isolated ventricular hemorrhage is an indication for the execution of a brain angiography in the light of the frequent findings of plexal arteriovenous malformation in these cases. Every step in the imaging workup will depend on the suspected diagnosis.

5. TREATMENT OPTIONS

5.1. Medical Therapy

5.1.1. Blood Pressure Control Acute hypertension secondary to ICH is associated with early clinical deterioration, poor outcome, and higher mortality rate. Recent trials have confirmed that blood pressure control is essential in the management of ICH. Although most guidelines recommend lowering the blood pressure at systolic target values <180 mmHg in 1–2 h, recently, the INTERACT-2 trial has reduced these values to 140 mmHg within 1 h, and this drastic pressure lowering is associated with better outcome with an effective counteraction of hematoma expansion (Anderson et al. 2008; Anderson et al. 2013). Furthermore, the risk of early rebleeding is lower when the systolic blood pressure is maintained <130 mmHg (Hemphill et al. 2015; Sato, Carcel, and Anderson 2015). In the emergency setting, continuous intravenous infusion of calcium channel blockers, such as nicardipine or nimodipine, or beta-blockers is considered the elective treatment to prevent the detrimental effects of blood pressure fluctuations. 170 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

5.12. Hemostatic Agents Systemic administration of hemostatic agents is performed for the urgent need for the activation of the coagulation cascade, ultimately limiting hematoma expansion. Tranexamic acid (TXA) and activated factor VIIa, administered within 4 h from ICH onset, have been the most common drugs used for this purpose. TXA prevents plasminogen from binding to fibrin. The second international Tranexamic acid for hyperacute primary IntraCerebral Hemorrhage (TICH-2) trial confirmed the role of TXA in limiting the progression of hemorrhage if administered within 8 h after the clinical onset (Mendelow et al. 2005; Mendelow et al. 2013). Mortality and severe disability rates also seem to be lowered by TXA. With these evidences, TXA has been proposed as the first-line treatment in the acute phase. However, it should be stressed that the long-term effects of TXA are not yet detectable in the third month of follow-up. Recombinant factor VIIa is activated by the tissue factor present in the brain vessels. Despite its rapid action in blocking acute bleeding, several side effects, with prothrombotic events first, have been reported, heavily limiting its long-term benefits.

5.1.3. Reversal of Acquired Coagulopathies Antiplatelet–anticoagulant therapies are increasingly used for primary and secondary preventions of ischemic complications in patients with cardiovascular risk factors, such as diabetes mellitus and hypertension, or history of myocardial infarction or stroke. Most patients diagnosed with spontaneous ICH are on antiplatelet therapy, such as cyclooxygenase inhibitors (aspirin) or P2Y2G inhibitors (clopidogrel, prasugrel, and ticagrelor). The iatrogenic reduction of platelet aggregation capacity is responsible for the worse prognosis in these patients. As opposed to previous beliefs, platelet transfusions and administration of von-Willebrand factor have been linked to an even increased risk of poor outcome (Thompson et al. 2010; Naidech et al. 2009; Baharoglu et al. 2016). Unsurprisingly, warfarin and vitamin K antagonists (VKAs) are also associated with worse prognosis. The rapid normalization of coagulation is crucial in these patients. Administration of vitamin K, fresh frozen plasma, and prothrombin complex concentrates is highly effective in the antagonization of the coumarin drugs, with warfarin first. Because they are characterized by higher handling and shorter half-life, non-vitamin K oral anticoagulants (NOACs) are presently considered drugs of choice for primary and secondary preventions of stroke in patients with atrial fibrillation and other cardiopathies. NOACs include direct thrombin inhibitors (dabigatran) and factor Xa inhibitors (apixaban, rivaroxaban, and edoxaban). Despite some unquestionable clinical and pharmacokinetic advantages over VKA, these “new” drugs do not have different risk profiles from VKA with respect to spontaneous ICH. Idarucizumab and andexanet alfa are used for the rapid reversal of dabigatran and factor Xa inhibitors, respectively.

5.2. Surgical Treatment

5.2.1. Timing Wang et al. reported that surgery should be performed within 7 h from clinical onset. The delay beyond this time window is associated with an increased incidence of complications (Y.F. Wang et al. 2008). Cerebral Hemorrhages 171

5.2.2. Decompressive Craniectomies The key technical point of these procedures is that the dimension of decompression must be adequately large to allow expansion of the brain parenchyma despite brain swelling, preventing herniation and vein compression. Three types of decompressive craniectomy (DC) are commonly employed, namely, the fronto-temporo-parietal, bifrontal, and suboccipital types. Fronto-temporo-parietal and bifrontal DCs are indicated for supratentorial hematoma, whereas suboccipital DC is reserved for infratentorial hemorrhage.

5.2.2.1. Fronto-Temporo-Parietal Hemicraniectomy Fronto-temporo-parietal DC is the most commonly performed procedure for unilateral hematomas. The skin incision is a reverse question mark starting from the posterior root of the zygoma, approximately 1 cm anterior to the tragus, and directed to the midline behind the hairline. Care should be taken in preserving the superficial temporal artery to prevent ischemic complications of the skin flap. The temporalis muscle is freed subperiosteally with a blunt dissection technique to skeletonize the temporal fossa before performing hemicraniectomy. As an alternative, a myocutaneous flap can be prepared. According to the guidelines, the anteroposterior diameter of the bone flap must be at least 11–12 cm (Wagner et al. 2001; Tagliaferri et al. 2012). Noteworthy, flattening of the residual squamosal part of the temporal bone until the middle fossa floor is necessary to achieve adequate decompression of the temporal lobe, especially the uncinate gyrus. Four burr holes are generally sufficient, but the need for further burr holes depends on the presence of adhesion between the dura and calvarium. The first and second burr holes are placed behind the zygomatic process of the frontal bone and 2 cm in front of the coronal suture, respectively. Two further burr holes are positioned at the temporal squama and parietal bone. Durotomy and duraplasty also should be targeted upon the extension of craniectomy. Autologous or heterologous dural substitutes can be used for duraplasty.

5.2.2.2. Bifrontal Craniectomy Bifrontal DC is more often employed in rare cases of midline or bilateral hematomas. A coronal incision from tragus to tragus is placed behind the hairline. Both superficial temporal arteries should be preserved, and the frontal galea can be useful in duraplasty. Temporalis muscles are detached to include the anterior part of the temporal fossa within the craniectomy. Two burr holes are placed in the midline over the superior sagittal sinus, whereas two additional burr holes are placed at the most anterior and posterior points of the temporal fossa bilaterally. After the removal of the bone flap and dural opening, the disinsertion of the falx from the crista galli can be performed to maximize the exposure.

5.2.2.3. Suboccipital Craniectomy Suboccipital DC is performed with the patient in prone or concorde position. A midline vertical inion-C2 skin incision allows for early skeletonization of the occipital squama. Nuchal muscles are mobilized laterally, and the posterior arc of C1 is exposed. Attachment of the nuchal muscles into C2 should be preserved to reduce the risk of postoperative mechanical instability of the craniovertebral junction. Suboccipital craniectomy should be adequately large to expose the inferior and medial aspects of the transverse and sigmoid sinus. Opening of the foramen magnum by removal of its posterior edge is mandatory. 172 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

Most surgeons prefer performing C1 laminectomy to prevent the risk of tonsillar herniation. A Y-shaped durotomy allows adequate decompression of the cerebellar hemispheres.

5.2.3. External Ventricular Drainage The presence of blood within the ventricular system is a negative prognostic factor because the blood itself has a risk of irritation and causes early obstruction of the cerebrospinal fluid and subsequent hydrocephalus. In these cases, the placement of an external ventricular drainage plays as a life-saving role. Ventriculostomy is realized by means of a single burr hole, positioned at the level of the coronal suture or just anterior to it, extremely small durotomy, and positioning of the draining catheter at the level of the frontal horn of the ventricle in the majority of cases. Frequently, the bleeding involves both the ventricle and third ventricles. Here, a bilateral ventricular drainage is necessary. Ventricular drainage may also be the route for the intraventricular injection of low doses of clot lytic agents, such as rt-PA or alteplase. These drugs should theoretically catalyze the clearance of ventricular rooms from the blood clots.

5.2.4. Hematoma Evacuation The need for hematoma evacuation is still controversial. As a rule, it may have a rationale in case of life-threatening conditions, especially if the hematoma is superficial and brain transgression required to reach the lesion is presumptively limited. Trials have shown that simple DC without evacuation of the intracerebral hematoma is associated with an even better outcome (Rasras et al. 2018; Takeuchi et al. 2013). From a technical standpoint, the main principles of microneurosurgical techniques should be employed when faced with this condition, as a matter of fact intra-axial pathology. A transsulcal approach must be always performed, when possible, to preserve the normal white matter fiber tracts, at least theoretically. Care should also be taken during hemostasis, which can be difficult to control, especially in patients with acquired coagulopathy secondary to the chronic assumption of anticoagulant drugs.

5.2.5. Minimally Invasive Techniques With the aim to minimize brain transgression during the evacuation of ICH, some minimally invasive techniques have been recently proposed (David Fiorella, Arthur, and Mocco 2016; D. Fiorella et al. 2016). The chapter on minimally invasive techniques includes the transtubular, endoscopic, and stereotactic techniques. The transtubular technique, equal to other minimally invasive techniques, has been designed to drain deep-seated supratentorial hematomas, simultaneously limiting the size of both craniotomy and corticotomy. The endoscopic technique is suitable in the treatment of intraventricular hemorrhage without parenchymal involvement. The main strength of this technique lies in the possibility of being associated with intraventricular infusion of thrombolytic drugs. A non-negligible number of trials proved the efficacy of this approach over the best medical therapy (Labib et al. 2017; Kim and Kim 2009; W.Z. Wang et al. 2009). Cerebral Hemorrhages 173

Minimally Invasive Surgery with Thrombolysis in Intracerebral hemorrhage Evacuation (MISTIE) trials (I, II, and III) assessed the effectiveness of the endoscopic administration of thrombolytic drugs in addition to hematoma evacuation (Morgan et al. 2008). Stereotactic and endoscopic techniques have also been advocated for ICH, although long- term results are lacking, unlike that on the use of these techniques for other diseases (Arnaout et al. 2019; S. Luzzi, Del Maestro, Elia, et al. 2019; S. Luzzi, Del Maestro, Trovarelli, et al. 2019; S. Luzzi, Zoia, et al. 2019; C. Zoia et al. 2019).

5.3. Treatment Algorithm

Equal to other surgical neurovascular pathologies, the difficult treatment algorithm of spontaneous ICH comes from a combination of evidence-based guidelines and specific considerations regarding a patient (Ciappetta, Luzzi, et al. 2009; Ciappetta, Occhiogrosso, et al. 2009; Del Maestro et al. 2018; Gallieni et al. 2018; S. Luzzi, Del Maestro, et al. 2018; S. Luzzi, Del Maestro, and Galzio 2019; S. Luzzi, Elia, Del Maestro, Morotti, et al. 2019; S. Luzzi, Gallieni, et al. 2018; Ricci et al. 2017; S. Luzzi et al. 2020). Treatment algorithm should be focused on defined parameters, such as the site and volume of the hematoma, patient neurological status, and evidence for increased intracranial pressure, ultimately leading to life-threatening conditions. Treatment of spontaneous or acquired coagulopathy should be considered the first step of the management of an ICH. For supratentorial hemorrhages, no evidence of improved outcome postoperatively has been reported for patients with GCS score < 5 or > 12. Therefore, medical treatment is recommended. In patients with a GCS score ranging from 5 to 8, a case-by-case selection of those candidates for surgery should involve the size of the hemorrhage in the initial onset. According to the reported evidences, patients with a GCS score of 5–8 and hematoma of 30– 60 mL are better treated with surgery. Here, minimally invasive techniques seem to be preferred in deep-seated hemorrhages. Conversely, patients with hematoma volume < 30 mL are candidates for medical therapy regardless of the GCS score. Nevertheless, surgery should always be considered in case of rapid neurological decline. Patients with a GCS score of 9–12 are candidates for surgery if the hematoma volume is >30 mL. In smaller hematomas, surgery is still the best option if the lesion is localized at <1 cm from the cortex. In these cases, DC seems to be more indicated. Generally, DC is indicated in patients with a GCS score of 9–12 with supratentorial ICH, especially if the hematoma volume is >30 mL, whereas minimally invasive techniques, with endoscopy first, are recommended for deeper and larger (>60 mL) hematomas, especially in patients with poor neurological conditions. For infratentorial hematomas, a size >30 mL always requires surgical evacuation (Figure 1).

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Figure 1. Evidence-Based Treatment Algorithm for Spontaneous ICH Management.

5.4. Illustrative Cases

Case 1 A 58-year-old man with a history of systemic hypertension was diagnosed with a left spontaneous claustral hematoma (Figure 2 A, B). He did not receive anticoagulant therapy. On admission, the GCS score was 13. The patient was initially treated conservatively, with best medical therapy consisting of intravenous administration of nicardipine and diuretics. Because of a rapid deterioration due to the mass effect of the growing hematoma, the patient underwent DC without hematoma evacuation (Figures 2 C–E). After 6 months, the patient underwent autologous cranioplasty. At the 8th month of follow-up, he completely recovered.

Cerebral Hemorrhages 175

Figure 2. Preoperative axial (A), coronal (B), and sagittal (C) CT showing left spontaneous claustral hemorrhage. Postoperative axial (D), coronal (E), and sagittal (F) decompressive hemicraniectomy CT. (G) 3D volume-rendering postoperative CT with removal of fronto-temporal-parietal bone flap.

Case 2 A 67-year-old man with hypertension, diabetes mellitus, and dyslipidemia was brought to the hospital after losing consciousness. He was receiving aspirin therapy. On admission, the patient was drowsy, without focal deficits. A large bifrontal hematoma was found on CT (Figures 3 A, B). CT angiography was negative for aneurysms. A bifrontal DC, comprehensive of the hematoma evacuation, was performed (Figures 3 C–E). The patient was discharged after 1 month without focal deficits.

Figure 3. Preoperative axial (A) and sagittal (B) CT revealing a large bifrontal intraparenchymal hemorrhage. Postoperative axial (C) and sagittal (D) CT images documenting the total removal of hematomas and 3D volume-rendering CT (E) showing bifrontal craniectomy. 176 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

Case 3 A 34-year-old comatose patient was diagnosed with spontaneous intraventricular hemorrhage involving the lateral, third, and fourth ventricles. Initial dilatation of the supratentorial ventricular system was noted (Figures 4 A–C). CT angiography and digital subtraction angiography did not reveal aneurysms or other vascular lesions. A bilateral external ventricular drainage was placed bilaterally in the frontal horn of the lateral ventricle (Figures 4 D–H). The patient was treated with intraventricular injection of alteplase to obtain clearance of the ventricular system from the clot. After 1 month, a ventriculoperitoneal shunt was positioned, and the patient had an initial and progressive recovery of consciousness.

Figure 4. Preoperative axial (A), sagittal (B), and coronal (C) CT showing tetraventricular hemorrhage, mainly involving the left lateral ventricle. Postoperative axial (D), right coronal (E) and sagittal (F), and left right coronal (G) and sagittal (H) CT demonstrating the right placement of bilateral external ventricular drainage.

6. DISCUSSION

6.1. Neuroprotection

The so-called secondary injury is still an acute event responsible for brain damage even greater than the ICH itself. It seems to be mainly linked with the toxic effects from iron and Cerebral Hemorrhages 177 other degradation products of hemoglobin, all of them involving, in turn, a devastating inflammatory process. In light of these assumptions, the concept of neuroprotection is paramount to prevent this cascade of events and their sequelae (Mracsko and Veltkamp 2014). Different pharmacological approaches have been reported for neuroprotection. Among them, the employment of iron-chelating agents has highly polarized the attention previously. However, data of the recent phase 2 i-DEF placebo-controlled randomized trial failed to demonstrate the superiority of deferoxamine over the placebo (Cui et al. 2015). On the basis of the well-known role of the immune system in neuroinflammation, a phase 2 randomized trial evaluated the efficacy of fingolimod, a sphingosine-1-phosphate receptor modulator reducing lymphocyte activation, in counteracting the formation of peri-hematoma edema, at the same manner as it acts in multiple sclerosis (Fu et al. 2014). An additional potential therapeutic agent is haptoglobin, which inhibits hemoglobin degradation, prevents the toxic effect, and improves outcome (Andersen et al. 2012; Bulters et al. 2018; Cooper et al. 2013). Further studies have deepened the role of the immune response characterized by the activation of the microglia and subsequent production of cytokines (IL1 and IL6) and chemokines. Cytokines and chemokines attract the immune cells, further enhancing neuroinflammation. Therefore, they are also possible targets. A recent phase 2 trial, the subcutaneous interleukin-1 receptor antagonist in ischemic stroke (SCIL-STROKE) trial, proves the neuroprotective role of interleukin-1 receptor antagonist (IL- 1Ra) in peripheral inflammation and brain swelling in patients with ICH (Smith et al. 2018).

6.2. Secondary Prevention

Spontaneous ICH has a high risk of recurrence annually. This risk is mainly related to individual risk factors. Apart from cessation of smoking and implementation of healthy dietary habits, some pharmacological therapeutic strategies should be implemented as needed. Any effort should be made to achieve good control of systemic blood pressure. Guidelines recommend values of 130/80 mmHg as a target after an ICH (systolic target < 120–130 mmHg). Strict blood pressure control also reduces the risk of ischemic stroke and other cardiovascular events. In patients receiving anticoagulant/antiplatelet therapies, an important aspect is the timing of reintroduction of these drugs. The majority of clinical trials are in accordance with the results of the RESTART trial. These data are in favor of early reintroduction of anticoagulant/antiplatelet therapies, having proved that the risk of ischemic cerebral events is much higher than the risk of recurrence of ICH(Collaboration 2019). Other studies proved that early reintroduction of anticoagulation in patients with atrial fibrillation or mechanical heart valve should be implemented to reduce the risk of recurrences (Group 2001; Arima et al. 2012). In patients with atherosclerosis and high risk of atherothrombotic events, the reintroduction of lipid-lowering therapy (statins) is still controversial. However, the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial is attributed to the role of statins in recurrences of ICH (Goldstein et al. 2008).

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7. CONCLUSION

The implementation of an evidence-based treatment algorithm is paramount to correctly manage spontaneous ICH. It allows punctual selection on patients who are candidates for surgery, which, independently from the selected surgical technique, must be treated within 7 h from the clinical onset. DCs and minimally invasive techniques have been proven to have better results. Compulsive control of the blood pressure and rapid reversal from anticoagulation are recommended in all patients. Neuroprotection plays a pivotal role in the correct management of this pathology, which is presently considered a more intense research field. Correction of lifestyle habits and risk factors is also of utmost importance in not only primary but also secondary prevention.

8. REFERENCES

Andersen, C. B., Torvund-Jensen, M., Nielsen, M. J., de Oliveira, C. L., Hersleth, H. P., Andersen, N. H., Pedersen, J. S., Andersen, G. R. & Moestrup, S. K. (2012). “Structure of the haptoglobin-haemoglobin complex.” Nature, 489 (7416), 456-9. https://doi.org/ 10.1038/nature11369. https://www.ncbi.nlm.nih.gov/pubmed/22922649. Anderson, C. S., Heeley, E., Huang, Y., Wang, J., Stapf, C., Delcourt, C., Lindley, R., Robinson, T., Lavados, P., Neal, B., Hata, J., Arima, H., Parsons, M., Li, Y., Wang, J. Heritier, S., Li, Q., Woodward, M., Simes, R. J., Davis, S. M., Chalmers, J. & Interact Investigators. (2013). “Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage.” N Engl J Med, 368 (25), 2355-65. https://doi.org/10.1056/NEJMoa1214609. https://www.ncbi.nlm.nih.gov/pubmed/23713578. Anderson, C. S., Huang, Y., Wang, J. G., Arima, H., Neal, B., Peng, B., Heeley, E., Skulina, C., Parsons, M. W., Kim, J. S., Tao, Q. L., Li, Y. C., Jiang, J. D., Tai, L. W., Zhang, J. L., Xu, E., Cheng, Y., Heritier, S., Morgenstern, L. B. Chalmers, J. & Interact Investigators. (2008). “Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial.” Lancet Neurol, 7 (5), 391-9. https://doi.org/ 10.1016/S1474-4422(08)70069-3. https://www.ncbi.nlm.nih.gov/pubmed/18396107. Antonosante, A., Brandolini, L. d’Angelo, M., Benedetti, E., Castelli, V., Del Maestro, M., Luzzi, S., Giordano, A., Cimini, A. & Allegretti, M. (2020). “Autocrine CXCL8-dependent invasiveness triggers modulation of actin cytoskeletal network and cell dynamics.” Aging (Albany NY), 12. https://doi.org/10.18632/aging.102733. https://www.ncbi.nlm.nih.gov/ pubmed/31986121. Arima, H., Anderson, C., Omae, T., Woodward, M., MacMahon, S., Mancia, G., Bousser, M. G., Tzourio, C., Rodgers, A., Neal, B., Chalmers, J. & Group Perindopril Protection Against Recurrent Stroke Study Collaborative. (2012). “Effects of blood pressure lowering on intracranial and extracranial bleeding in patients on antithrombotic therapy: the PROGRESS trial.” Stroke, 43 (6), 1675-7. https://doi.org/10.1161/STROKEAHA.112. 651448. https://www.ncbi.nlm.nih.gov/pubmed/22535269. Cerebral Hemorrhages 179

Arnaout, M. M., Luzzi, S., Galzio, R. & Aziz, K. (2019). “Supraorbital keyhole approach: Pure endoscopic and endoscope-assisted perspective.” Clin Neurol Neurosurg, 189, 105623. https://doi.org/10.1016/j.clineuro.2019.105623. https://www.ncbi.nlm.nih.gov/pubmed/ 31805490. Baharoglu, M. I., Cordonnier, C., Salman, R. A., de Gans, K., Koopman, M. M., Brand, A., Majoie, C. B., Beenen, L. F., Marquering, H. A., Vermeulen, M., Nederkoorn, P. J., de Haan, R. J., Roos, Y. B. & Patch Investigators. (2016). “Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH): a randomised, open-label, phase 3 trial.” Lancet, 387 (10038), 2605-2613. https://doi.org/10.1016/S0140-6736(16)30392-0. https://www.ncbi. nlm.nih.gov/pubmed/27178479. Bellantoni, G., Guerrini, F., Del Maestro, M., Galzio, R. & Luzzi, S. (2019). “Simple schwannomatosis or an incomplete Coffin-Siris? Report of a particular case.” eNeurologicalSci, 14, 31-33. https://doi.org/10.1016/j.ensci.2018.11.021. https://www. ncbi.nlm.nih.gov/pubmed/30555950. Bongetta, D., Zoia, C., Luzzi, S., Maestro, M. D., Peri, A., Bichisao, G., Sportiello, D., Canavero, I., Pietrabissa, A. & Galzio, R. J. (2019). “Neurosurgical issues of bariatric surgery: A systematic review of the literature and principles of diagnosis and treatment.” Clin Neurol Neurosurg, 176, 34-40. https://doi.org/10.1016/j.clineuro.2018.11.009. https://www.ncbi.nlm.nih.gov/pubmed/30500756. Bulters, D., Gaastra, B., Zolnourian, A., Alexander, S., Ren, D., Blackburn, S. L., Borsody, M., Dore, S., Galea, J., Iihara, K., Nyquist, P. & Galea, I. (2018). “Haemoglobin scavenging in intracranial bleeding: biology and clinical implications.” Nat Rev Neurol, 14 (7):, 416- 432. https://doi.org/10.1038/s41582-018-0020-0. https://www.ncbi.nlm.nih.gov/pubmed/ 29925923. Campanella, R., Guarnaccia, L., Cordiglieri, C., Trombetta, E., Caroli, M., Carrabba, G., La Verde, N., Rampini, P., Gaudino, C., Costa, A., Luzzi, S., Mantovani, G., Locatelli, M., Riboni, L., Navone, S. E. & Marfia, G. (2020). “Tumor-Educated Platelets and Angiogenesis in Glioblastoma: Another Brick in the Wall for Novel Prognostic and Targetable Biomarkers, Changing the Vision from a Localized Tumor to a Systemic Pathology.” Cells, 9 (2), https://doi.org/10.3390/cells9020294. https://www.ncbi.nlm.nih. gov/pubmed/31991805. Cheng, C. Y., Shetty, R. & Sekhar, L. N. (2018). “Microsurgical Resection of a Large Intraventricular Trigonal Tumor: 3-Dimensional Operative Video.” Oper Neurosurg (Hagerstown), 15 (6), E92-E93. https://doi.org/10.1093/ons/opy068. https://www.ncbi. nlm.nih.gov/pubmed/29618124. Ciappetta, P., D’Urso, P. I., Luzzi, S., Ingravallo, G., Cimmino, A. & Resta, L. (2008). “Cystic dilation of the ventriculus terminalis in adults.” J Neurosurg Spine, 8 (1), 92-9. https://doi.org/10.3171/SPI-08/01/092. https://www.ncbi.nlm.nih.gov/pubmed/18173354. Ciappetta, P., Luzzi, S., De Blasi, R. & D’Urso, P. I. (2009). “Extracranial aneurysms of the posterior inferior cerebellar artery. Literature review and report of a new case.” J Neurosurg Sci, 53 (4), 147-51. https://www.ncbi.nlm.nih.gov/pubmed/20220739. Ciappetta, P., Occhiogrosso, G., Luzzi, S., D’Urso, P. I. & Garribba, A. P. (2009). “Jugular tubercle and vertebral artery/posterior inferior cerebellar artery anatomic relationship: a 3- dimensional angiography computed tomography anthropometric study.” Neurosurgery, 64 180 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

(5 Suppl 2), 429-36, discussion 436. https://doi.org/10.1227/01.NEU.0000337573. 17073.9F. https://www.ncbi.nlm.nih.gov/pubmed/19404121. Collaboration, Restart. (2019). “Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial.” Lancet, 393 (10191), 2613- 2623. https://doi.org/10.1016/S0140-6736(19)30840-2. https://www.ncbi.nlm.nih.gov/ pubmed/31128924. Cooper, C. E., Schaer, D. J., Buehler, P. W., Wilson, M. T., Reeder, B. J., Silkstone, G., Svistunenko, D. A., Bulow, L. & Alayash, A. I. (2013). “Haptoglobin binding stabilizes hemoglobin ferryl iron and the globin radical on tyrosine beta145.” Antioxid Redox Signal, 18 (17), 2264-73. https://doi.org/10.1089/ars.2012.4547. https://www.ncbi.nlm.nih.gov/ pubmed/22702311. Cui, H. J., He, H. Y., Yang, A. L., Zhou, H. J., Wang, C., Luo, J. K., Lin, Y. & Tang, T. (2015). “Efficacy of deferoxamine in animal models of intracerebral hemorrhage: a systematic review and stratified meta-analysis.” PLoS One, 10 (5), e0127256. https://doi.org/ 10.1371/journal.pone.0127256. https://www.ncbi.nlm.nih.gov/pubmed/26000830. De Tommasi, A., Cascardi, P., De Tommasi, C., Luzzi, S. & Ciappetta, P. (2006). “Emergency surgery in a severe penetrating skull base injury by a screwdriver: case report and literature review.” World J Emerg Surg, 1, 36. https://doi.org/10.1186/1749-7922-1-36. https://www.ncbi.nlm.nih.gov/pubmed/17169147. De Tommasi, A., De Tommasi, C., Lauta, E., Luzzi, S., Cimmino, A. & Ciappetta, P. (2006). “Pre-operative subarachnoid haemorrhage in a patient with spinal tumour.” Cephalalgia, 26 (7), 887-90. https://doi.org/10.1111/j.1468-2982.2006.01122.x. https://www.ncbi.nlm. nih.gov/pubmed/16776708. De Tommasi, A., Luzzi, S., D’Urso, P. I., De Tommasi, C., Resta, N. & Ciappetta, P. (2008). “Molecular genetic analysis in a case of ganglioglioma: identification of a new mutation.” Neurosurgery, 63 (5), 976-80, discussion 980. https://doi.org/10.1227/01.NEU. 0000327699.93146.CD. https://www.ncbi.nlm.nih.gov/pubmed/19005389. De Tommasi, A., Occhiogrosso, G., De Tommasi, C., Luzzi, S., Cimmino, A. & Ciappetta, P. (2007). “A polycystic variant of a primary intracranial leptomeningeal astrocytoma: case report and literature review.” World J Surg Oncol, 5, 72. https://doi.org/10.1186/1477- 7819-5-72. https://www.ncbi.nlm.nih.gov/pubmed/17587463. Del Maestro, M., Luzzi, S., Gallieni, M., Trovarelli, D., Giordano, A. V., Gallucci, M., Ricci, A. & Galzio, R. (2018). “Surgical Treatment of Arteriovenous Malformations: Role of Preoperative Staged Embolization.” Acta Neurochir Suppl, 129, 109-113. https://doi.org/10.1007/978-3-319-73739-3_16. https://www.ncbi.nlm.nih.gov/pubmed/ 30171322. Elsawaf, Y., Anetsberger, S., Luzzi, S. & Elbabaa, S. K. (2020). “Early Decompressive Craniectomy as Management for Severe TBI in the Pediatric Population: A Comprehensive Literature Review.” World Neurosurg., https://doi.org/10.1016/j.wneu.2020.02.065. https://www.ncbi.nlm.nih.gov/pubmed/32084616. Fiorella, D., Arthur, A., Bain, M. & Mocco, J. (2016). “Minimally Invasive Surgery for Intracerebral and Intraventricular Hemorrhage: Rationale, Review of Existing Data and Emerging Technologies.” Stroke, 47 (5), 1399- 406. https://doi.org/10.1161/STROKEAHA.115.011415. https://www.ncbi.nlm.nih.gov/ pubmed/27048700. Cerebral Hemorrhages 181

Fiorella, David, Adam Arthur, & Mocco, J. D. (2016). “305 The INVEST Trial: A Randomized, Controlled Trial to Investigate the Safety and Efficacy of Image-Guided Minimally Invasive Endoscopic Surgery With Apollo vs Best Medical Management for Supratentorial Intracerebral Hemorrhage.” Neurosurgery, 63, 187. https://doi.org/10.1227/01.neu. 0000489793.60158.20. Fu, Y., Hao, J., Zhang, N., Ren, L., Sun, N., Li, Y. J., Yan, Y., Huang, D., Yu, C. & Shi, F. D. (2014). “Fingolimod for the treatment of intracerebral hemorrhage: a 2-arm proof-of- concept study.” JAMA Neurol, 71 (9), 1092-101. https://doi.org/10.1001/jamaneurol. 2014.1065. https://www.ncbi.nlm.nih.gov/pubmed/25003359. Gallieni, M., Del Maestro, M., Luzzi, S., Trovarelli, D., Ricci, A. & Galzio, R. (2018). “Endoscope-Assisted Microneurosurgery for Intracranial Aneurysms: Operative Technique, Reliability, and Feasibility Based on 14 Years of Personal Experience.” Acta Neurochir Suppl, 129, 19-24. https://doi.org/10.1007/978-3-319-73739-3_3. https://www. ncbi.nlm.nih.gov/pubmed/30171309. Goldstein, L. B., Amarenco, P., Lamonte, M., Gilbert, S., Messig, M., Callahan, A., Hennerici, M., Sillesen, H., Welch, K. M. & Sparcl Investigators. (2008). “Relative effects of statin therapy on stroke and cardiovascular events in men and women: secondary analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Study.” Stroke, 39 (9), 2444-8. https://doi.org/10.1161/STROKEAHA.107.513747. https://www. ncbi.nlm.nih.gov/pubmed/18617654. Group, Progress Collaborative. (2001). “Randomised trial of a perindopril-based blood- pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack.” Lancet, 358 (9287), 1033-41. https://doi.org/10.1016/S0140- 6736(01)06178-5. https://www.ncbi.nlm.nih.gov/pubmed/11589932. Guastamacchia, E., Triggiani, V., Tafaro, E., De Tommasi, A., De Tommasi, C., Luzzi, S., Sabba, C., Resta, F., Terreni, M. R. & Losa, M. (2007). “Evolution of a prolactin-secreting pituitary microadenoma into a fatal carcinoma: a case report.” Minerva Endocrinol, 32 (3), 231-6. https://www.ncbi.nlm.nih.gov/pubmed/17912159. Hemphill, J. C., 3rd, Greenberg, S. M., Anderson, C. S., Becker, K., Bendok, B. R., Cushman, M., Fung, G. L., Goldstein, J. N., Macdonald, R. L., Mitchell, P. H., Scott, P. A., Selim, M. H., Woo, D., Council American Heart Association Stroke, Cardiovascular Council on, Nursing Stroke. & Cardiology Council on Clinical. (2015). “Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association.” Stroke, 46 (7), 2032-60. https://doi.org/10.1161/STR.0000000000000069. https://www. ncbi.nlm.nih.gov/pubmed/26022637. Kim, Y. Z. & Kim, K. H. (2009). “Even in patients with a small hemorrhagic volume, stereotactic-guided evacuation of spontaneous intracerebral hemorrhage improves functional outcome.” J Korean Neurosurg Soc, 46 (2), 109-15. https://doi.org/ 10.3340/jkns.2009.46.2.109. https://www.ncbi.nlm.nih.gov/pubmed/19763212. Labib, M. A., Shah, M., Kassam, A. B., Young, R., Zucker, L., Maioriello, A., Britz, G., Agbi, C., Day, J. D., Gallia, G., Kerr, R., Pradilla, G., Rovin, R., Kulwin, C. & Bailes, J. (2017). “The Safety and Feasibility of Image-Guided BrainPath-Mediated Transsulcul Hematoma Evacuation: A Multicenter Study.” Neurosurgery, 80 (4), 515-524. https://doi.org/ 10.1227/NEU.0000000000001316. https://www.ncbi.nlm.nih.gov/pubmed/27322807. 182 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

Luzzi, S., Crovace, A. M., Lacitignola, L., Valentini, V., Francioso, E., Rossi, G., Invernici, G., Galzio, R. J. & Crovace, A. (2018). “Engraftment, neuroglial transdifferentiation and behavioral recovery after complete spinal cord transection in rats.” Surg Neurol Int, 9, 19. https://doi.org/10.4103/sni.sni_369_17. https://www.ncbi.nlm.nih.gov/pubmed/29497572. Luzzi, S., Del Maestro, M., Bongetta, D., Zoia, C., Giordano, A. V., Trovarelli, D., Raysi Dehcordi, S. & Galzio, R. J. (2018). “Onyx Embolization Before the Surgical Treatment of Grade III Spetzler-Martin Brain Arteriovenous Malformations: Single- Center Experience and Technical Nuances.” World Neurosurg, 116, e340- e353. https://doi.org/10.1016/j.wneu.2018.04.203. https://www.ncbi.nlm.nih.gov/pubmed/ 29751183. Luzzi, S., Del Maestro, M., Elbabaa, S. K. & Galzio, R. (2020). “Letter to the Editor Regarding “One and Done: Multimodal Treatment of Pediatric Cerebral Arteriovenous Malformations in a Single Anesthesia Event”.” World Neurosurg, 134, 660. https://doi.org/ 10.1016/j.wneu.2019.09.166. https://www.ncbi.nlm.nih.gov/pubmed/32059273. Luzzi, S., Del Maestro, M., Elia, A., Vincitorio, F., Di Perna, G., Zenga, F., Garbossa, D., Elbabaa, S. & Galzio, R. (2019). “Morphometric and Radiomorphometric Study of the Correlation Between the Foramen Magnum Region and the Anterior and Posterolateral Approaches to Ventral Intradural Lesions.” Turk Neurosurg., https://doi.org/ 10.5137/1019-5149.JTN.26052-19.2. https://www.ncbi.nlm.nih.gov/pubmed/31452176. Luzzi, S., Del Maestro, M. & Galzio, R. (2019). “Letter to the Editor. Preoperative embolization of brain arteriovenous malformations.” J Neurosurg, 1-2. https://doi.org/10.3171/2019.6. JNS191541. https://www.ncbi.nlm.nih.gov/pubmed/31812150 https://thejns.org/view/journals/j-neurosurg/aop/article-10.3171-2019.6.JNS191541/ article-10.3171-2019.6.JNS191541.xml. Luzzi, S., Del Maestro, M., Trovarelli, D., De Paulis, D., Dechordi, S. R., Di Vitantonio, H., Di Norcia, V., Millimaggi, D. F., Ricci, A. & Galzio, R. J. (2019). “Endoscope-Assisted Microneurosurgery for Neurovascular Compression Syndromes: Basic Principles, Methodology, & Technical Notes.” Asian J Neurosurg, 14 (1), 193-200. https://doi.org/ 10.4103/ajns.AJNS_279_17. https://www.ncbi.nlm.nih.gov/pubmed/30937034. Luzzi, S., Elia, A., Del Maestro, M., Elbabaa, S. K., Carnevale, S., Guerrini, F., Caulo, M., Morbini, P. & Galzio, R. (2019). “Dysembryoplastic Neuroepithelial Tumors: What You Need to Know.” World Neurosurg, 127, 255-265. https://doi.org/10.1016/ j.wneu.2019.04.056. https://www.ncbi.nlm.nih.gov/pubmed/30981794. Luzzi, S., Elia, A., Del Maestro, M., Morotti, A., Elbabaa, S. K., Cavallini, A. & Galzio, R. (2019). “Indication, Timing, and Surgical Treatment of Spontaneous Intracerebral Hemorrhage: Systematic Review and Proposal of a Management Algorithm.” World Neurosurg., https://doi.org/10.1016/j.wneu.2019.01.016. https://www.ncbi.nlm.nih.gov/ pubmed/30677572. Luzzi, S., Gallieni, M., Del Maestro, M., Trovarelli, D., Ricci, A. & Galzio, R. (2018). “Giant and Very Large Intracranial Aneurysms: Surgical Strategies and Special Issues.” Acta Neurochir Suppl, 129, 25-31. https://doi.org/10.1007/978-3-319-73739-3_4. https://www.ncbi.nlm.nih.gov/pubmed/30171310. Luzzi, S., Giotta Lucifero, A., Del Maestro, M., Marfia, G., Navone, S. E., Baldoncini, M., Nunez, M., Campero, A., Elbabaa, S. K. & Galzio, R. (2019). “Anterolateral Approach for Retrostyloid Superior Parapharyngeal Space Schwannomas Involving the Jugular Foramen Cerebral Hemorrhages 183

Area: A 20-Year Experience.” World Neurosurg., https://doi.org/10.1016/j.wneu. 2019.09.006. https://www.ncbi.nlm.nih.gov/pubmed/31520759. Luzzi, S., Zoia, C., Rampini, A. D., Elia, A., Del Maestro, M., Carnevale, S., Morbini, P. & Galzio, R. (2019). “Lateral Transorbital Neuroendoscopic Approach for Intraconal Meningioma of the Orbital Apex: Technical Nuances and Literature Review.” World Neurosurg, 131, 10-17. https://doi.org/10.1016/j.wneu.2019.07.152. https://www.ncbi. nlm.nih.gov/pubmed/31356977. Luzzi, Sabino, Alberto Maria Crovace, Mattia Del Maestro, Alice Giotta Lucifero, Samer K. Elbabaa, Benedetta Cinque, Paola Palumbo, Francesca Lombardi, Annamaria Cimini, Maria Grazia Cifone, Antonio Crovace. & Renato Galzio. (2019). “The cell-based approach in neurosurgery: ongoing trends and future perspectives.” Heliyon, 5 (11). https://doi.org/10.1016/j.heliyon.2019.e02818. Mendelow, A. D., Gregson, B. A., Fernandes, H. M., Murray, G. D., Teasdale, G. M., Hope, D. T., Karimi, A., Shaw, M. D., Barer, D. H. & Stich investigators. (2005). “Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial.” Lancet, 365 (9457), 387-97. https://doi.org/10.1016/S0140- 6736(05)17826-X. https://www.ncbi.nlm.nih.gov/pubmed/15680453. Mendelow, A. D., Gregson, B. A., Rowan, E. N., Murray, G. D., Gholkar, A., Mitchell, P. M. & Stich Ii Investigators. (2013). “Early surgery versus initial conservative treatment in patients with spontaneous supratentorial lobar intracerebral haematomas (STICH II): a randomised trial.” Lancet, 382 (9890), 397-408. https://doi.org/10.1016/S0140- 6736(13)60986-1. https://www.ncbi.nlm.nih.gov/pubmed/23726393. Millimaggi, D. F., Norcia, V. D., Luzzi, S., Alfiero, T., Galzio, R. J. & Ricci, A. (2018). “Minimally Invasive Transforaminal Lumbar Interbody Fusion with Percutaneous Bilateral Pedicle Screw Fixation for Lumbosacral Spine Degenerative Diseases. A Retrospective Database of 40 Consecutive Cases and Literature Review.” Turk Neurosurg, 28 (3), 454-461. https://doi.org/10.5137/1019-5149.JTN.19479-16.0. https://www.ncbi. nlm.nih.gov/pubmed/28481388. Morgan, T., Zuccarello, M., Narayan, R., Keyl, P., Lane, K. & Hanley, D. (2008). “Preliminary findings of the minimally-invasive surgery plus rtPA for intracerebral hemorrhage evacuation (MISTIE) clinical trial.” Acta Neurochir Suppl, 105, 147-51. https://doi.org/ 10.1007/978-3-211-09469-3_30. https://www.ncbi.nlm.nih.gov/pubmed/19066101. Mracsko, E. & Veltkamp, R. (2014). “Neuroinflammation after intracerebral hemorrhage.” Front Cell Neurosci, 8, 388. https://doi.org/10.3389/fncel.2014.00388. https://www.ncbi. nlm.nih.gov/pubmed/25477782. Naidech, A. M., Jovanovic, B., Liebling, S., Garg, R. K., Bassin, S. L., Bendok, B. R., Bernstein, R. A., Alberts, M. J. & Batjer, H. H. (2009). “Reduced platelet activity is associated with early clot growth and worse 3-month outcome after intracerebral hemorrhage.” Stroke, 40 (7), 2398-401. https://doi.org/10.1161/STROKEAHA. 109.550939. https://www.ncbi.nlm.nih.gov/pubmed/19443791. Palumbo, P., Lombardi, F., Augello, F. R., Giusti, I., Luzzi, S., Dolo, V., Cifone, M. G. & Cinque, B. (2019). “NOS2 inhibitor 1400W Induces Autophagic Flux and Influences Extracellular Vesicle Profile in Human Glioblastoma U87MG Cell Line.” Int J Mol Sci, 20 (12), https://doi.org/10.3390/ijms20123010. https://www.ncbi.nlm.nih.gov/pubmed/ 31226744. 184 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

Palumbo, P., Lombardi, F., Siragusa, G., Dehcordi, S. R., Luzzi, S., Cimini, A., Cifone, M. G. & Cinque, B. (2018). “Involvement of NOS2 Activity on Human Glioma Cell Growth, Clonogenic Potential, and Neurosphere Generation.” Int J Mol Sci, 19 (9), https://doi.org/10.3390/ijms19092801. https://www.ncbi.nlm.nih.gov/pubmed/30227679. Rasras, S., Safari, H., Zeinali, M. & Jahangiri, M. (2018). “Decompressive hemicraniectomy without clot evacuation in supratentorial deep-seated intracerebral hemorrhage.” Clin Neurol Neurosurg, 174, 1-6. https://doi.org/10.1016/j.clineuro.2018.08.017. https://www. ncbi.nlm.nih.gov/pubmed/30172088. Raysi Dehcordi, S., Ricci, A., Di Vitantonio, H., De Paulis, D., Luzzi, S., Palumbo, P., Cinque, B., Tempesta, D., Coletti, G., Cipolloni, G., Cifone, M. G. & Galzio, R. (2017). “Stemness Marker Detection in the Periphery of Glioblastoma and Ability of Glioblastoma to Generate Glioma Stem Cells: Clinical Correlations.” World Neurosurg, 105, 895- 905. https://doi.org/10.1016/j.wneu.2017.05.099. https://www.ncbi.nlm.nih.gov/pubmed/ 28559081. Ricci, A., Di Vitantonio, H., De Paulis, D., Del Maestro, M., Raysi, S. D., Murrone, D., Luzzi, S. & Galzio, R. J. (2017). “Cortical aneurysms of the middle cerebral artery: A review of the literature.” Surg Neurol Int, 8, 117. https://doi.org/10.4103/sni.sni_50_17. https://www.ncbi.nlm.nih.gov/pubmed/28680736. Sato, S., Carcel, C. & Anderson, C. S. (2015). “Blood Pressure Management After Intracerebral Hemorrhage.” Curr Treat Options Neurol, 17 (12), 49. https://doi.org/10.1007/s11940- 015-0382-1. https://www.ncbi.nlm.nih.gov/pubmed/26478247. Smith, C. J., Hulme, S., Vail, A., Heal, C., Parry-Jones, A. R., Scarth, S., Hopkins, K., Hoadley, M., Allan, S. M., Rothwell, N. J., Hopkins, S. J. & Tyrrell, P. J. (2018). “SCIL-STROKE (Subcutaneous Interleukin-1 Receptor Antagonist in Ischemic Stroke): A Randomized Controlled Phase 2 Trial.” Stroke, 49 (5), 1210-1216. https://doi.org/10.1161/ STROKEAHA.118.020750. https://www.ncbi.nlm.nih.gov/pubmed/29567761. Spena, G., Roca, E., Guerrini, F., Panciani, P. P., Stanzani, L., Salmaggi, A., Luzzi, S. & Fontanella, M. (2019). “Risk factors for intraoperative stimulation-related seizures during awake surgery: an analysis of 109 consecutive patients.” J Neurooncol., https://doi.org/10.1007/s11060-019-03295-9. https://www.ncbi.nlm.nih.gov/pubmed/ 31552589. Tagliaferri, F., Zani, G., Iaccarino, C., Ferro, S., Ridolfi, L., Basaglia, N., Hutchinson, P.& Servadei, F. (2012). “Decompressive craniectomies, facts and fiction: a retrospective analysis of 526 cases.” Acta Neurochir (Wien), 154 (5), 919-26. https://doi.org/ 10.1007/s00701-012-1318-0. https://www.ncbi.nlm.nih.gov/pubmed/22402877. Takeuchi, S., Wada, K., Nagatani, K., Otani, N. & Mori, K. (2013). “Decompressive hemicraniectomy for spontaneous intracerebral hemorrhage.” Neurosurg Focus, 34 (5), E5. https://doi.org/10.3171/2013.2.FOCUS12424. https://www.ncbi.nlm.nih.gov/pubmed/ 23634924. Thompson, B. B., Bejot, Y., Caso, V., Castillo, J., Christensen, H., Flaherty, M. L., Foerch, C., Ghandehari, K., Giroud, M., Greenberg, S. M., Hallevi, H., Hemphill, J. C., 3rd, Heuschmann, P., Juvela, S., Kimura, K., Myint, P. K., Nagakane, Y., Naritomi, H., Passero, S., Rodriguez-Yanez, M. R., Roquer, J., Rosand, J., Rost, N. S., Saloheimo, P., Salomaa, V., Sivenius, J., Sorimachi, T., Togha, M., Toyoda, K., Turaj, W., Vemmos, K. N., Wolfe, C. D., Woo, D. & Smith, E. E. (2010). “Prior antiplatelet therapy and outcome following intracerebral hemorrhage: a systematic review.” Neurology, 75 (15), 1333-42. Cerebral Hemorrhages 185

https://doi.org/10.1212/WNL.0b013e3181f735e5. https://www.ncbi.nlm.nih.gov/pubmed/ 20826714. van Asch, C. J., Luitse, M. J., Rinkel, G. J., van der Tweel, I., Algra, A. & Klijn, C. J. (2010). “Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis.” Lancet Neurol, 9 (2), 167-76. https://doi.org/10.1016/S1474-4422(09)70340-0. https://www.ncbi. nlm.nih.gov/pubmed/20056489. Wagner, S., Schnippering, H., Aschoff, A., Koziol, J. A., Schwab, S. & Steiner, T. (2001). “Suboptimum hemicraniectomy as a cause of additional cerebral lesions in patients with malignant infarction of the middle cerebral artery.” J Neurosurg, 94 (5), 693- 6. https://doi.org/10.3171/jns.2001.94.5.0693. https://www.ncbi.nlm.nih.gov/pubmed/ 11354398. Wang, W. Z., Jiang, B., Liu, H. M., Li, D., Lu, C. Z., Zhao, Y. D. & Sander, J. W. (2009). “Minimally invasive craniopuncture therapy vs. conservative treatment for spontaneous intracerebral hemorrhage: results from a randomized clinical trial in China.” Int J Stroke, 4 (1), 11-6. https://doi.org/10.1111/j.1747-4949.2009.00239.x. https://www.ncbi.nlm.nih. gov/pubmed/19236490. Wang, Y. F., Wu, J. S., Mao, Y., Chen, X. C., Zhou, L. F. & Zhang, Y. (2008). “The optimal time-window for surgical treatment of spontaneous intracerebral hemorrhage: result of prospective randomized controlled trial of 500 cases.” Acta Neurochir Suppl, 105, 141-5. https://doi.org/10.1007/978-3-211-09469-3_29. https://www.ncbi.nlm.nih.gov/pubmed/ 19066100. Wilkinson, D. A., Pandey, A. S., Thompson, B. G., Keep, R. F., Hua, Y. & Xi, G. (2018). “Injury mechanisms in acute intracerebral hemorrhage.” Neuropharmacology, 134 (Pt B), 240-248. https://doi.org/10.1016/j.neuropharm.2017.09.033. https://www.ncbi.nlm.nih. gov/pubmed/28947377. Zoia, C., Bongetta, D., Dorelli, G., Luzzi, S., Maestro, M. D. & Galzio, R. J. (2019). “Transnasal endoscopic removal of a retrochiasmatic cavernoma: A case report and review of literature.” Surg Neurol Int, 10, 76. https://doi.org/10.25259/SNI-132-2019. https://www.ncbi.nlm.nih.gov/pubmed/31528414. Zoia, C., Bongetta, D., Guerrini, F., Alicino, C., Cattalani, A., Bianchini, S., Galzio, R. J. & Luzzi, S. (2018). “Outcome of elderly patients undergoing intracranial meningioma resection: a single center experience.” J Neurosurg Sci., https://doi.org/10.23736/S0390- 5616.18.04333-3. https://www.ncbi.nlm.nih.gov/pubmed/29808631. Zoia, Cesare, Francesco Lombardi, Maria Fiore, Andrea Montalbetti, Alberto Iannalfi, Mattia Sansone, Daniele Bongetta, Francesca Valvo, Mattia Del Maestro, Sabino Luzzi. & Renato Galzio. (2020). “Sacral solitary fibrous tumour: surgery and hadrontherapy, a combined treatment strategy.” Reports of Practical Oncology & Radiotherapy., https://doi.org/10. 1016/j.rpor.2020.01.008.

Chapter 11

PRINCIPLES OF NEUROANESTHESIA

M. Seveso*, MD and D. Caldiroli, MD, PhD Neuroanesthesia and Neurointensive Care, C. Besta Neurological Institute, Milan, Italy

ABSTRACT

Neuroanesthesia has a pivotal role in the preoperative, intraoperative and postoperative management of the patients with “cerebrovascular insufficiency”. Common issues are the maintenance of the systemic homeostasis and brain relaxation. In this chapter we present an overview on the most important principles of neuroanesthesia, focusing on the airways, anesthetics and monitoring management. We also report special considerations on the control of the blood pressure during aneurysms, arteriovenous malformations and bypass surgery.

1. INTRODUCTION

Neuroprotection is the goal of care for any surgical patient in the presence of “cerebrovascular insufficiency”. What anesthesiologists do, mostly with understanding of the basics (the role of paCO2 and positioning-related difference in venous drainage; the danger of uncontrolled hypertension; the ability to recognize risks and communicate with neurosurgeon) matters a great deal to the well-being of the high-risk brain (Todd 2012). The practice of neurovascular anesthesia covers the preoperative period, which may start electively or with resuscitation and urgent stabilization for Subarachnoid Hemorrhage (SAH) or Intracerebral Hemorrhage (ICH); the operative treatment of the lesion (Aneurysm, Arteriovenous Malformation, Cavernous Malformation, Dural Arteriovenous Fistula), either in the operating room or radiological suite (Lee and Young 2012) and the postoperative care with the aim to reduce long term morbidity/mortality (Bendo 2002). At all stages of perioperative care, prevention strategies to avoid cerebral ischemia or hemorrhage must be tailored to the

* Corresponding Author’s Email: [email protected]. 188 M. Seveso and D. Caldiroli type of planned surgery and to each patient’s particular lesion through the definition of the cerebrovascular “reserve”. Aneurysmal disease may be now better conceived as a “process”, characterized by vascular dysfunction and inflammatory reaction, which contributes to pathogenesis of intracranial hemorrhage. Genetic variations and plasma cytokine assays have the potential for development in the future, to affect multiple aspects of management (Logvinova et al. 2010). The estimated prevalence of unruptured aneurysm is 5% in the adult population, with rupture incidence around 0.05% per year (Wiebers and Marsh 1998) (if size is < 10 mm and no history of SAH). Despite significant advances, the leading causes of death and disability are in decreasing order: vasospasm, the direct effect of primary hemorrhage (massive subarachnoid, subdural or intracerebral and permanent ischemic effects of increased intracranial pressure), rebleeding and surgical complications. According to SAH - treatment published guidelines, from the mid-1980s up to date there was: - increase in the use of nimodipine; - earlier treatment of ruptured aneurysms; - an increase in coiling and a decreasing in clipping for aneurysm treatment; - lesser use of prophylactic anticonvulsants; - static use of triple H - therapy, but with a shift in the collective use of this treatment modality in very recent years, towards induced hypertension being used more frequently, without concomitant hypervolemia and hemodiluition (Pasternak 2019). The anesthetic management of patients who have or are at risk for vasospasm requires an understanding of the natural course of vasospasm, concurrent therapy, the importance of the intravascular volume status, the change in electrolytes and hemodynamic variables associated with vasospasm. Preoperative evaluation starts with patient’s neurological status, estimate of intracranial blood mass and associated shift suggesting the presence of intracranial hypertension. Understanding the grading scales (Hunt–Hess, World Federation Neurological Surgeon, Fisher- CT) allows the anesthesiologist to communicate effectively, facilitates assessment of pathophysiologic derangements and the planning of perioperative management. Intracranial pressure (ICP) correlates well with clinical grade. Patients with SAH grade 0, 1, 2 generally have normal ICP and do not experience acute ischemia. In contrast patients with poor clinical grades frequently have increased ICP, low cerebral perfusion pressure (CPP) and ischemia. An elevated ICP, however, decreases transmural pressure gradient (TMPG) and partially protect the aneurism from rupture. Both TMPG and CPP are determined by the same equation (= MAP – ICP). Therefore, decreasing the risk of rupture (through reduced TMPG) and prevention of ischemia by maintaining CPP, could represent opposite objectives. In the presence of SAH/ICH is important to maintain adequate cerebral perfusion because poor grades frequently have impaired autoregulation, decreased responsiveness to changes in arterial carbon dioxide tension, abnormalities of regional cerebral blood flow (rCBF) and increased intracranial pressure. The severity of autoregulatory dysfunction correlates directly with the clinical grade. Impaired autoregulation in the presence of vasospasm may also result in delayed ischemic deficit (DCI). Management relies on hemodynamic and ventilator support to promote adequate organ perfusion and function. To reduce the risk of rupture or ischemia, the change in TMPG or CPP should always be gradual. SAH/ICH could induce not only neurological but also serious systemic complications (myocardial ischemia, arrhythmias, pulmonary edema). For all these Principles of Neuroanesthesia 189 reasons, it has been shown that an early admission to neurocritical care unit can prevent mortality in cases of ICH/SAH (D’Souza 2015; Kundra et al. 2014). Fever is commonly observed and may be central in origin or due to medical complications of cerebral hemorrhage (pneumonia, urinary tract infection, deep vein thrombosis). An abnormal ECG caused by “overstressing” of the sympathetic nervous system is commonly recognized and presents different waves: peaked P waves, short PR interval, prolonged QT interval, large U waves, peaked T waves, and rarely electrical transformations to subendocardial ischemia or infarction. These changes are often accompanied by mild elevation of cardiac enzymes, but do not usually correlate with significant myocardial dysfunction. The majority of patients with cardiac dysfunction secondary to SAH has normal coronary artery anatomy and suffers from a neurogenic stressed myocardium. Predictors of ventricular dysfunction include elevated cardiac troponin I, poor clinical grade and female gender. Leukocytosis, with white blood cell count increase over 20000 mm3 after SAH, presents a poor clinical grading scale value, and the mortality reaches 50%. Other associated changes include electrolyte imbalances, particularly hyponatremia and acid-base abnormalities secondary to the syndrome of inappropriate antidiuretic hormone secretion, diabetes insipidus and cerebral salt wasting syndrome. Clinical vasospasm with ischemic deficit is observed in approximately 30% of patients, most often between days 4-12, with a peak at 6-7 days following SAH. Early vasospasm observed within 48 h after rupture of a cerebral aneurysm is recognized in 10% of patients and suggests a worse prognosis. Acute or chronic hydrocephalus occurs in patients after SAH. Seizures, occurring more frequently in patients with lobar hemorrhage, are deleterious because they may increase CBF and cerebral metabolic rate for oxygen (CMRO2). Endovascular treatment is an alternative to surgical treatment (Molyneux et al. 2005). Multiple factors must be evaluated and a detailed anesthetic assessment is mandatory in determining the best balance between patient’s risks and possible harm linked to a “delayed” surgery. Routine investigations include a full blood count, coagulation studies, urea/electrolytes and ECG. Further investigations may include chest X-ray, echocardiography, transcranial Doppler and others if appropriate. Baseline blood pressure and cardiovascular reserve should be assessed carefully. Blood pressure manipulation is commonly required and treatment - related perturbations should be anticipated (Avitsian and Schubert 2007). Patients presenting with cerebrovascular disease have a greater incidence of cardiovascular disease. Obstructive Sleep Apnea Syndrome (OSAS) is an independent predictor of cardiovascular disorders and associated with an impairment of cerebral autoregulation likely contributing to increased incidence of stroke as well as poor outcome after stroke (Durgan and Bryan 2012). STOP-BANG questionnaire (Snoring – Tiredness - Observed apnea - Blood pressure - Body Mass Index – Age - Neck Circumference - Gender) and major clinical predictors of increased cardiovascular risk (unstable coronary syndrome, acute or recent myocardial infarction, unstable angina, decompensated heart failure, high grade atrioventricular block, symptomatic ventricular arrhythmias, supraventricular arrhythmia with uncontrolled ventricular rate, severe valvular disease) need to be assessed and results should be shared with the neurosurgeons. Also important is the identification of comorbid conditions frequently associated with intracranial aneurysm: polycystic kidney disease, coartation of the aorta, sickle cell disease, 190 M. Seveso and D. Caldiroli drug abuse, hypertension and rarely: fibromuscular dysplasia, Marfan’s syndrome, tuberous sclerosis, Ehlers - Danlos syndrome, hereditary telangiectasia, Moyamoya disease.

2. “CHALLENGING” NEUROANESTHESIOLOGICAL ISSUES

The design of an ideal anesthetic plan is based on the essential knowledge of common and specific pathophysiology of cerebrovascular insufficiency adapted to individual patient needs. Common issues are the maintenance of cerebral and systemic homeostasis, brain relaxation and neuroprotection. To achieve and maintain homeostasis, it is essential to understand not only the regulation of the cerebral blood flow (CBF) in a healthy brain and during a number of pathological states, but also to know the effects of the anesthetic agents on it (Flexman, Wang, and Meng 2019). Possible mechanisms of anatomical injury from neurosurgeon include brain retraction, direct vascular injury (ischemia, thrombosis, venous occlusion) and mechanical disruption of neuronal tissue or white matters tracts. Anesthetic physiologic injury may result from systemic hypotension or hypertension, decreased O2 content, hypoosmolarity, hyperglycemia. It must be stressed that these mechanisms of injury are interactive. The brain is highly active metabolically but is essentially devoid of oxygen and glucose reserves, making it dependent on the continuous delivery of its substrates by the cerebral circulation. In normal adult CBF is approximately 45 to 55 ml/100 g of brain tissue per minute (almost 15% of the cardiac output for an organ that account for only 2% of body weight) and metabolic rate for oxygen (CMRO2) is 3.5 to 4.5 ml/100 g/min. CBF is normally autoregulated in response to cerebral metabolic requirements and it depends on cerebral perfusion pressure (CPP) and cerebral vascular resistance (CVR) according to the equation:

CBF = CPP/CVR

CPP is a useful and practical estimate of the adequacy of the cerebral circulation because CBF is neither easily nor widely measured. CPP is defined as pressure gradient across the brain, the difference between systemic mean arterial pressure (MAP) at the entrance to the brain and the mean exit pressure (CVP). When ICP is increased it replace CVP in the calculation of CPP. The three fundamental physiological mechanisms governing cerebrovascular homeostasis are cerebrovascular autoregulation, vasomotor reactivity (CO2 or O2-reactivity) and neurovascular coupling also described as ‘flow metabolism coupling’. It is important to understand that these mechanisms interact considerably under physiological conditions and are also influenced by anesthetics. Some evidence suggest that neurovascular coupling remains functional in anesthetized patients (Slupe and Kirsch 2018). Autoregulation enables brain perfusion to remain stable despite moderate changes in MAP or ICP. Normally CBF is maintained relatively constant within the range of mean arterial pressure from 50 to 150 mmHg. Beyond this range the limit of vasomotor activity is exceeded and CBF becomes directly dependent on changes in CPP. In patient with chronic hypertension both the upper and lower limits of autoregulation are shifted toward higher pressures. These mechanisms are often disrupted after SAH/ICH (Figure 1).

Principles of Neuroanesthesia 191

Figure 1. Autoregulation which ideally mantain constant CBF at CPP between 50 and 150 mmHg (a) does not fail in all or nothing manner. Typically incremental failure is observed (the plateau of the autoregulatory curve is shortened and shifted to the right (b, c). Only with severe failure a complete loss and a passive increase of CBF with changes in CPP are observed (d).

The CO2 responsiveness of intracranial vessels and regulation of CBF play an important role in normal ICP modulation (Akkermans et al. 2019). Intraoperative management should include provision for a relaxed brain (to reduce retractor – induced ischemia); control of systemic and cerebral hemodynamics, avoidance of hypotonicity, hyperglycemia and hyperthermia and timely emergence from anesthesia without significant hypertension, tachycardia or coughing. The drug-induced reversible coma of general anesthesia requires three clinical outcomes that can be imperfectly assessed in real time: unconsciousness, immobility, and the control of autonomic nervous system (ANS) responses to surgical stimulation. The neuroanatomical targets involved in inducing anesthesia are increasingly well understood. The characteristics of these circuits are extremely complex, but in few words, unconsciousness and amnesia, produced at the lowest concentrations of volatile agents, are achieved by targeting mostly higher brain centers in the cortex, limbic system and thalamus. Immobility, requiring modestly higher concentrations, is achieved primarily by targeting evolutionarily more primitive circuits in the spinal cord. The neurophysiologic mechanisms (receptor systems) involved in producing anesthesia are also increasingly well described. Although many other receptor systems can be leveraged to produce anesthesia, the traditional “balanced anesthesia”, popular and dominant over the past 50yrs, relies mostly upon the GABAA-receptor and the µ-opioid receptor. Both receptors are widely expressed in the CNS of mammals and both respond to their respective endogenous ligands and pharmacologic agonists (and antagonists). A key point relating to the receptor systems involved in producing the traditional balanced anesthetic is that two receptor systems are involved (GABAA and MOR), not just one. In recent years, the concept of “multimodal” general anesthesia has extended the concept of balanced anesthesia to include more drugs that target different neuroanatomical circuits and multiple neurophysiologic mechanisms, emulating the model of multimodal analgesia in the acute pain management domain. The proposed pharmacopeia for multimodal general anesthesia includes a host of anesthetic adjuncts including opioids 192 M. Seveso and D. Caldiroli

(remifentanil), alpha-2 agonists (dexmedetomidine), local anesthetics (lidocaine), and N- methyl-D-aspartate receptor antagonists (magnesium, ketamine). The pharmacologic foundation of the multimodal approach is built on the firmly established observation that when anesthetic drugs of different mechanisms are combined, they typically interact synergistically (Egan 2019; Koerner and Brambrink 2006).

Table 1. Common Used Agents Inducing in a Dose - Dependent Manner Loss of Consciousness, Loss of Motor Response to Nociceptive Stimulation and a Loss of Autonomic Nociception

Propofol Opioid Alpha 2 agonist Benzodiazepine Sedation ++ + + ++ Anxiolysis + + Analgesia Preservation of arousability + Suppression of respiratory + ++ + + drive Reduction of delirium ++ Disruption of sleep ++ ++ ++

3. HOW TO MANAGE AIRWAY?

Conceptually it is useful to consider the initial phase of general anesthesia as consisting of two parts: induction to achieve loss of consciousness and laryngoscopy leading to tracheal intubation to achieve control of airway. The incidence of aneurysm rupture during induction of anesthesia, although rare (estimated < 1%), is usually precipitated by sudden rise in blood pressure during intubation and is associated with high mortality. It is crucial that airway management be effective and smooth to avoid the possible negative effects of hypoxemia, hypercapnia and coughing. Because of these reasons it is also important to reduce laryngeal stimulation and minimize the attempts to intubation. To avoid coughing, tracheal intubation should be performed only when muscular paralysis is complete. Rocuronium may be the non-depolarizing muscle relaxant of choice for two reasons: given at 1,2 mg/kg it has a brief onset time and the antagonist (sugammadex) can be used to rapidly reverse (60 secs) the block (Keating 2016). The role and availability of sugammadex - if neurophysiologic monitoring is used – is fundamental as muscle relaxants may impede an adequate monitoring. A detailed preoperative airway assessment is mandatory to prepare for anticipated difficult intubation. The potential risk of aneurysm rupture should be increased in patients with a difficult airway management.

Principles of Neuroanesthesia 193

Table 2. El Ganzouri Risk Index Assessment. Score Ranges from 0 to 12 (if EGRI > 6: “difficult” airway)

EGRI 0 1 2 Mouth opening >=4 cm < 4 cm Thyromental distance >6.5 cm 6 – 6.5 cm < 6 cm Mallampati 1 2 3-4 Neck movement >90° 80-90° <80° Ability to prognat yes no Body Weight < 90Kg 90-110 Kg >110 Kg Difficult intubation History none questionable definite

The El Ganzouri Risk Index (EGRI) might be considered as a decisional tool (Table 2), as it could decrease the possibility of unpredicted difficult intubation, which can be particularly problematic in this cohort of patients. In 2007 our group proposed a rule for decision, based on the same predictors of difficult intubation identified in the EGRI, and implementing the use of Glidescope video laryngoscope (VLS) (Cortellazzi et al. 2007) as the main intubation tool. Subsequently in 2011 the retrospective results of 6278 routine tracheal intubations using glidescope VLS in neurosurgical patients, following the adoption of an institutional algorithm for difficult airway management, were published. Adherence to the decisional process of the algorithm and to glidescope VLS achieved successful tracheal intubations in a cohort of neurosurgical patients (Caldiroli and Cortellazzi 2011). The routine use of VLS allows to maintain skill mastery, avoid trauma of failed laryngoscopy, decrease patient response to intubation as well as as our stress and avoid loosing valuable seconds trying to retrieve a unit (Figure 2).

Figure 2. Lateral profile of the Glidescope Videolaryngoscope blade and improved laryngeal structures view after introduction of the tube into the trachea 18.

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4. HOW TO CHOOSE ANESTHETICS AND MONITORING?

As a general suggestion, no choices of anesthetics and (neuro)monitoring can replace good communication with the neurosurgeon regarding patient clinical grade, patient position, likehood of temporary clip application, anticipated blood loss and need for hemodynamic manipulations during surgery. The first common principle for improving functional survival and minimizing complications is an individualized patient management through choice of timing and target interventions to balance risks of bleeding/rebleeding and cerebral ischemia. No definitive data exist about the influence of anesthetic drugs on the outcome of neurovascular surgery. Again, there is no clear superiority of one modern anesthetic over another in terms of pharmacologic protection against neuronal injury (Badenes, Gruenbaum, and Bilotta 2015). Anesthetics that decrease ICP and CMRO2 and maintain CPP are the most ‘desirable’ for neurovascular surgery. It is fundamental to avoid associated negative hemodynamic changes. Brain relaxation is probably served by maintenance of normal arterial pressure, as cerebral blood volume is kept to a minimum by autoregulatory vasoconstriction (Li et al. 2016). All potent inhalation agent are cerebral vasodilators, but the effects are clinically significant at doses higher than 1 MAC (minimum alveolar concentration). Deep inhalation should be avoided in patients with increased ICP. Low concentration combined with mild hyperventilation minimally affect CBF and ICP. Other than inhalation agents, intravenous anesthetics can be used to achieve loss of consciousness, while opioids provide the analgesic component of general anesthesia (balanced anesthesia). Propofol has superseded thiopental as hypnotic and remifentanil and fentanyl are the preferred narcotics. With careful titration, they can be used without compromising cerebral perfusion. Intravenous propofol reduce the cerebral metabolic rate and since it has no vasodilatory effects, both cerebral blood flow and ICP are reduced. Remifentanil is used in combination with propofol as a part of total intravenous anesthesia regimen. The context –sensitive half time of remifentanil is very short at 3 min after 3 hours infusion. This ultra - short acting narcotic facilitates the emergence from anesthesia and allows assessment of neurologic function. Target Control Infusion systems (based on distribution volume and clearance pharmacokinetic data model) are able to rapidly achieve, maintain and titrate the intravenous anesthetic concentrations at the site of drug effect (Ce), which is the clinically relevant target (brain). Total intravenous technique or combination of inhalation and intravenous methods may optimize rapid emergence (Engelhard and Werner 2006). Following induction and intubation additional catheters are placed. Monitoring should always include arterial pressure (before or after induction) with transducer placed at the level of the base of the skull (acoustic meatus) to accurately reflect CPP. A clinical strategy is to administer vasoactive drug to improve hemodynamic variables (mean arterial pressure) and thereby maintain or restore adequate perfusion (CPP) and Principles of Neuroanesthesia 195 oxygenation in according with metabolic demand. Without firm outcome data indicating the superiority of one regimen or another, the choice of agent to manipulate blood pressure must be placed in the context of the clinical situation. Limited experimental and clinical evidence suggests that norepinephrine might be the most appropriate catecholamine to augment cerebral perfusion (Thorup et al. 2020; Steiner and Siegemund 2019). Optimization of brain perfusion remains a difficult therapeutic goal. Standard practice continues to aim for increasing or decreasing systemic arterial pressure with vasopressors or vasodilators to a more or less arbitrary threshold. However, because of the interindividual, temporal and spatial heterogeneity of pathophysiology and the effects of drugs, the results of the attempts to manipulate cerebral perfusion are often unpredictable. Recent data suggest that optimizing perfusion pressure using an index of cerebrovascular autoregulation may be beneficial, as it theoretically allows avoiding insufficient and excessive perfusion pressures. Responses to vasoactive drugs are much easier to regulate if a normal blood volume has been established and maintained through the anesthetic period. The aim is to maintain normovolemia during neurosurgery, which can be complex, considering, between other variables, the difficulty of an accurate estimate of blood loss (van der Jagt 2016). Intermittent blood arterial gas sampling permits to look beyond normal vital signs as endpoints of resuscitation to more accurate indicators of tissue perfusion, such as arterial pH, base deficit, lactate level. A central venous catheter should always be placed. Jugular internal vein is preferred and the ecographic guide reduces procedural - related complications (Lamperti et al. 2012). After monitoring the patient is positioned for surgery. Position has profound impact on ICP and brain relaxation (venous drainage). Insertion of the pins for the Mayfield represents a very noxious stimulus and can raise blood pressure if the patient is not pretreated. Infiltration with local anesthetics is effective in combination with additional remifentanil or propofol. An adequate depth of anesthesia should be ensured before any invasive maneuver to prevent precipitous hypertension. Until now the concept of monitoring the depth of anesthesia is mainly based on EEG analysis, using devices (like Bispectral Index) providing automatically calculated indices which vary with the hypnotic concentrations (Rampil 2001). QEEG monitors provide a practical and direct measure of the functional state of the cerebral cortex during all stages of general anesthesia. For the safe clinical use of these monitors, a clear mental picture of the expected raw electroencephalogram (EEG) patterns, as well as a knowledge of the common EEG artifacts, is absolutely necessary (Bennett et al. 2009). The anesthesiologist must be certain that the qEEG number is consistent with the apparent state of the patient, the doses of various anesthetic drugs and the degree of surgical stimulation, and that the qEEG number is consistent with the appearance of the raw EEG signal (Figure 3). Any discrepancy must be a stimulus for an immediate critical examination of the patient’s state using all the available information, rather than reactive therapy to “treat” a number. Artifacts are commonly encountered and may(Badenes, García-Pérez, and Bilotta 2016) be classified as arising from outside the head, from the head but outside the brain (commonly frontal electromyogram), or from within the brain (atypical or pathologic).

196 M. Seveso and D. Caldiroli

Figure 3. EEG and Density Spectral Array monitoring. From Purdon P. Clinical Electroencephalography for Anesthesiologists (Anesthesiology 2015).

Intraoperative EEG and electrophysiological monitoring require coordination among the neurosurgeon, anesthesiologist and neurophysiologist. Somatosensory and motor evoked potential monitoring help to define the limits of temporary vessel occlusion during surgery. Cerebral oximetry (Near Infrared Spectroscopy - NIRS) and brain tissue oxygenation (PtiO2) monitoring have been studied in surgical vascular procedure with inconclusive results (Badenes, García-Pérez, and Bilotta 2016). Hypothermia reduce brain metabolism (-1°C = - 7% CMRO2), so special attention should be focused on temperature monitoring during neurovascular surgery. “Mild” hypothermia improves favorable neurological outcome after cardiac arrest, but during aneurysm clipping failed to show any effect on patient survival. Therefore, it is not indicated as a prophylactic therapy but may be considered in selected cases following vessel occlusion (Randell and Niskanen 2006). Mild hypothermia (33 – 35° C) is not associated with significant complications and benefits are potentially offset if partial rewarming induces systemic physiologic - stress associated with shivering upon emergence (Nguyen et al. 2010). Managing CMRO2 is an integral part of anesthetic management for temporary ischemia even though clinical efficacy remains controversial. About 60% of O2 brain consumption is for maintenance of brain cell function including its electrophysiological activity to generate action potential and synthesis of neurotransmitters. The remaining 40% of the brain’s O2 use is directed toward the maintenance of cellular integrity. Any intervention that decrease cellular activity also decrease CMRO2 and may protect the brain against ischemia. Most anesthetics, except ketamine, decrease cerebral metabolic rate and cerebral blood flow. Propofol and barbiturates, in particular, maintain autoregulation and coupling even at high doses.

5. HOW TO MANAGE BLOOD PRESSURE?

Tight control of blood pressure is mandatory to protect the brain. Some considerations are specific for particular types of neurovascular surgery. Principles of Neuroanesthesia 197 a) Cerebral Aneurysm: Transmural Pressure Gradient, Temporary Clipping, Adenosine

The first target of anesthesia in elective and urgent aneurysm surgery is the maintenance of a stable transmural pressure gradient (TMPG), providing a relaxed brain and at the same time, avoiding cerebral hypoperfusion and finally allowing prompt awakening and neurological assessment of patients with good clinical grades.

TMPG = pressure within blood vessel – pressure outside = MAP – ICP = CPP

It should be remembered that higher TMPG increases the risk of rupture and marked decrease in ICP (particularly in the context of elevated blood pressure) may increase the risk of re - bleeding. An important factor to recognize is that the surgical stimulus varies at different times. The anesthetic plan must take this into consideration to avoid wide fluctuations in CPP or dangerous increase in blood pressure. The use of induced hypotension has declined and has been replaced by temporary clipping. Vascular clips are applied to parent artery in order to improve surgical visualization, before application of permanent clips to the aneurysm. It is important to restore the blood pressure to normal/high values before placement of the temporary clips to maximize collateral blood flow. The safe duration of temporary clipping is not entirely known. However, temporary clipping for an MCA aneurysm should preferably be limited to <10 minutes. A duration >20 minutes of temporary clipping on any intracranial artery puts the patient at risk for ischemia. Patients with poor neurological grades, elderly patients, those with delayed surgery (4 to 10 days after SAH), or patients with episodes of multiple clipping are at increased risk for ischemia and stroke. If a temporary clip is applied for > 2 min, it is “safe” to augment blood pressure (> 20% baseline) to preserve perfusion via collaterals and discuss with surgical team the necessity to induce pharmacologic burst suppression - EEG (consider propofol and/or thiopental), even if the evidence is highly controversial. When temporary arterial occlusion is impractical or difficult for anatomical reason, adenosine administration can produce brief, profound systemic hypotension and flow arrest, as an alternative to logistically complex methods of decreasing parent artery blood flow. Adenosine - induced flow arrest can facilitate the clip ligation of many aneurysms that were previously treated with deep hypothermic circulatory arrest, temporary occlusion of the extracranial carotid artery or endovascular balloon catheter retrograde suction deflation. For giant aneurysms, repeated periods of transient flow arrest may offer an alternative to deep hypothermic circulatory arrest avoiding coagulopathy and cardiopulmonary bypass (Bendok et al. 2011; Bebawy et al. 2010). Adenosine slows electrical conduction through atrioventricular node and has a negative chronotropic effect on sinoatrial node. The rapid decrease in heart rate results in a rapid and profound decrease in cardiac output and mean arterial pressure. When administered as a bolus it can produce transient asystole with concomitant flow arrest. Adenosine is found to be beneficial in 2 retrospective analyses, without increasing the risk for cardiac and neurological morbidity. A mean duration of 45 seconds of circulatory arrest can be achieved with the administration of 0,3 to 0,4 mg/kg of adenosine in patients receiving propofol infusion to induce 198 M. Seveso and D. Caldiroli burst suppression, combined with remifentanil and eventually low dose volatile anesthetic. Consider the placement of external defibrillator pads on all patients who might receive adenosine to provide external pacing if prolonged asystole/bradycardia were to develop or to achieve cardioversion in the case of hemodynamically unstable atrial fibrillation. Additionally, check all patients for biochemical evidence of myocardial injury (troponin I) in the postoperative period. Intraoperative aneurysmal rupture is a potentially catastrophic event. However hemorrhagic shock and death are not the most important consequences. Ischemia may instead result from efforts to slow bleeding, from excessive hypotension (elective or otherwise), more vigorous retraction, or from clips placed on major cerebral vessels (either intentionally or unintentionally) (Chowdhury et al. 2014). The management of rupture depends on the ability to maintain blood volume. Aggressive fluid resuscitation must commence immediately and it is reasonable to keep the duration of hypotension as short as possible with the use of vasopressors. There is no need to subject a hypovolemic patient to the hemodynamic risks of emergent barbiturate loading for “neuroprotection”. A good practice is to ensure adequate vascular volume and then begin barbiturate administration to target EEG burst – suppression.

b) Arteriovenous Malformation: Normal Perfusion Pressure Breakthrough (NPPB)

The anesthetic management of patients with AVM is similar to the management of patients for aneurysm surgery but the hemorrhagic risk is probably higher and clipping is not a surgical option. There may be marginally perfused areas adjacent to AVM that are critically dependent on collateral perfusion pressure and CPP therefore should be maintained. Hyperemic complications defined as perioperative edema or hemorrhage may occur after removal of the AVM. The clinical syndrome of cerebral brain hyperperfusion with normal CPP has been called “normal perfusion pressure breakthrough” (Söderman et al. 2003). Although the mechanism is unclear, one theory proposes that breakthrough cerebral edema and hemorrhage result when blood flow from the surgically obliterated MAV is diverted to the surrounding brain. In vascular territories adjacent to the MAV, the lower limit of autoregulation curve appears to be shifted to the left which is the opposite of chronic arterial hypertension (adaptive autoregulatory displacement). All postoperative complications will be favoured by uncontrolled systemic hypertension. Depending on the presentation the anesthetic approach is modified. For example, a large bleed may present with symptoms relating to mass effects and may require maneuvers to reduce ICP. High flow through a large intact AVM may cause a “steal” with resulting cerebral ischemia. Patients are considered at high risk of normal perfusion pressure breakthrough if the AVM has a nidus > 4 cm in diameter on angiography, there is evidence of rapid fistula flow preventing visualization of normal circulation or the arterial feeders are long and large and focal deficits suggesting hemispheric ischemia are present. These features suggest a significant steal phenomenon and loss of autoregulation in the vascular bed. Occlusive hyperemia is an alternative mechanism potentially explaining cerebral edema and hemorrhage after AVM Principles of Neuroanesthesia 199 resection. Currently the recommendations support maintenance of a normal blood pressure after resection and elimination of residual AVM as a cause of postoperative hemorrhage because intraoperative imaging has a recognized false negative rate. The most vulnerable period for hematoma formation is probably during emergence from anesthesia; the risk of edema remains elevated at least 48 hours after surgery (Miller and Mirski 2012).

c) Cerebral Bypass: Flow

Cerebral revascularization is used to augment or replace blood flow in patients at risk of developing cerebral ischemia (Moyamoya disease, occlusive cerebrovascular disease, skull base tumor and complex aneurysm). Moyamoya disease occurs in both children and adults and is pathophysiologically complex, with fragile vessels and unstable hemodynamics resulting in very high surgical risk. A useful anesthesiological concern is that hyperventilation (and hypocapnia) induced by crying or exercise, has been shown to trigger transient ischemic attacks in children with Moyamoya. Intraoperative ventilation should be aimed at providing normocapnia and normal oxygenation level. Hypercapnia can also have undesiderable effects. The collateral network of vessels is in a state of maximal vasodilatation. During hypercapnia a decrease in CBF may occur by means of an “intracerebral steal” effect when other normal vessels vasodilate. Maintaining adequate blood flow with appropriate blood pressure manipulation is the anesthetic fundamental concern (Chui et al. 2015). Reduction of CBF is poorly tolerated in children, who have higher cerebral metabolic rate, diminished autoregulatory response and higher oxygen extraction ratio than adults. Periods of hypotension most likely will occur during induction of anesthesia and temporary clipping of recipient vessel. During these time, even a short period of arterial hypotension is likely to result in watershed ischemia and subsequent cerebral infarction. During the ischemic time of temporary clipping (while the artery to be bypassed is clamped and graft not yet completed) blood pressure may be augmented to 20% above baseline and burst suppression EEG may be considered. EEG burst suppression and mild hypothermia is important to discuss with the team, especially when there is a plan for temporary occlusion of major cerebral vessels. For the first 2–3 days after graft placement blood pressure targets should be normal. This will prevent graft “leakage” and excessive cerebral perfusion (hyperperfusion syndrome) while preserving graft patency. Many studies have found that several factors such as hypercapnia, hypotension and inadequate hematocrit increase the risk of postoperative ischemia. The level of paCO2 should be actively controlled during the emergence and in the postoperative period because hypercapnia has been associated with an increased incidence of perioperative transient neurological deficits. Appropriate analgesia should be given to prevent agitation and increased “stress” which may affect the bypass.

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6. HOW TO IMPROVE QUALITY OF EMERGENCE?

After surgery, it is necessary to assess neurological findings, therefore “oversedation” must be avoided. Safe transition is important because of the physiologic stress of emergence, resulting in hypertension, tachycardia, shivering, nausea or pain, in these high - risk patients. There is no ideal regimen for maintaining sedation and blood pressure control in the postoperative period. Multimodal analgesia (with opioids, scalp nerve block, acetaminophen) is effective (Ban, Bhoja, and McDonagh 2019). The use of dexmedetomidine (highly selective alfa 2 - adrenergic receptor agonist) may be a solution. It combines sympatholytic and sedative/analgesic effects with the possibility to arouse the patient, thus allowing neurologic examination (Lin et al. 2019; Schwarz et al. 2013). With judicious titration, the occurrence of side effects can be minimized and it is very likely that this pleiotropic drug will ascend to take a much more prominent role in future anesthesia practice. Common current clinical uses include preoperative anxiolysis, heart rate and blood pressure control, treatment of bronchospasm, prevention of laryngospasm and avoiding opioid- induced postoperative respiratory depression and nausea and vomiting. Other problems that could be prevented are tachydysrhythmias, myocardial ischemia, delirium and acute kidney injury (Farag et al. 2011). Patients who received perioperative dexmedetomidine demonstrated a decreased incidence of agitation and reduction of opioid requirements (opioid – sparing effect) (Peng et al. 2014), which can prove fundamental in special population requiring “opioid free – anesthesia” such as: obesity, sleep apnea, chronic obstructive pulmonary disease, complex regional pain syndrome, opioid addiction and cancer surgery (Sultana, Torres, and Schumann 2017). Activation of the sympathetic nervous system, increase of catabolic hormone release and pituitary gland suppression are considered a response to surgical stress. In clinical practice these activities cause changes in heart rate, blood pressure and biochemical fluctuations of noradrenaline, adrenaline, dopamine, and cortisol. Above all, these fluctuations may prolong hospitalization and delay patients discharge. Dexmedetomidine decrease plasma concentration of norepinephrine level by 90% (Jalonen et al. 1997). Low to mid - range infusion doses seem to exert benefits, although there is no standard administration strategy and more highly powered studies are needed (Bekker and Sturaitis 2005). Slow titration of continuous infusion rate is particularly helpful to prevent adverse hemodynamic events (bradycardia, hypotension and hypertension). Its beneficial effects on cerebral hemodynamics and physiology include no increase in intracranial pressure and an unchanged cerebral metabolic rate equivalent/cerebral blood flow ratio (Drummond et al. 2008). For neurosurgery, dexmedetomidine can be used in a “couple” of ways: as a continuous low dose infusion stopped near the end of surgery or alternatively started near the end, as a bridge (transition) to an hypnotic and almost opiod - free awakening. Perioperative hemodynamic instability is associated with increased morbidity after vascular surgery. Dexmedetomidine induces greater stability during emergence and recovery from general anesthesia as documented by low incidence of hypertension and lesser use of vasoactive drugs than placebo (Tsujikawa and Ikeshita 2019; Ge et al. 2019).

Principles of Neuroanesthesia 201

Figure 4. Neurophysiology of dexmedetomidine. From Purdon, Annual Review of Neuroscience 2011. (a) Dexmedetomidine acts pre-synaptically to block the release of norepinephrine (NE) from neurons projecting from the locus coeruleus (LC) to the basal forebrain (BF), the pre-optic area (POA) of the hypothalamus, the intralaminar nucleus (ILN) of the thalamus and the cortex. Blocking the release of NE in the POA leads to activation of its inhibitory GABAergic (GABA) and galanergic (Gal) projections to dorsal raphé (DR) which releases serotonin (5HT), the tuberomamillary nucleus (TMN) which releases histamine (His), the LC, the ventral periacqueductal gray (PAG) which releases dopamine, the lateral dorsal tegmental (LDT) nucleus and the pedunculopontine tegmental (PPT) nucleus which release acetylcholine (Ach). These actions lead to decreased arousal by inhibition of the arousal centers. (b) Ten- second electroencephalogram segment showing spindles, intermittent 9 to 15 Hz oscillations (underlined in red), characteristic of dexmedetomidine sedation. C. The spindles are most likely produced by intermittent oscillations between the cortex and thalamus (light green region).

Dexmedetomidine is a “unique” sedative agent, inducing cooperative sedation which show easy transition from sleep to wakefulness, allowing patient to be cooperative and communicative when stimulated (Figure 4). Emergence agitation, delirium and cognitive dysfunctions are increasingly recognized problems in surgical and critically ill patients (Evered 202 M. Seveso and D. Caldiroli et al. 2018). They may potentially lead to serious consequences such as bleeding, falling, removal of catheters and self - extubation and affect surgical outcome. Data suggest that dexmedetomidine can be used to prevent or treat emergence delirium following surgery and intensive care (Shehabi et al. 2009, 2019) with the advantages of less respiratory depression, minimal impact on neural function, the potential for neuroprotection and maintenance of airway reflexes and patency. The Acute Neurological ICU Sedation Trial demonstrated improvement in cognition function with dexmedetomidine when compared with propofol during sedation in neurologic patients. However, multicenter prospective studies are required to determine the optimal timing and dosage during the perioperative period (Carr et al. 2018; Duan et al. 2018). Recent clinical human studies reported that dexmedetomidine may have a neuroprotective effect (modulation of neurotransmitter release in central and peripheral nervous system) and is safe for neurosurgery. It has also been demonstrated to have protective effects in a variety of animal models of ischemia/reperfusion injury (Cai et al. 2014). Valuable properties on systemic and cerebral hemodynamics makes dexmedetomidine a drug, which could change in a short future, the way we work in vascular neurosurgery.

CONCLUSION

Neuroprotection is a kind of “holy grail” since 1950s. By its wording, it implies maintenance of the integrity or well–being of the neurological system against external insults. Systematic review and metanalysis (Archer et al. 2017) concluded that general anesthetics consistently provide neuroprotection in rodent models of ischemic stroke. However, neuroprotective effects have not been proven in humans, probably because they go beyond CMRO2 suppression and are largely unknown. General anesthetics can cause hypotension which depending on the functional status of autoregulation may lead to hypoperfusion. As neuroanesthesiologists, we have to realize that cerebral hypoperfusion is a real issue in anesthetized patients and the consequences on neurocognitive functions are poorly understood (Wu et al. 2019). Prospective clinical studies are needed to investigate the influence of different factors (medical comorbidities, anesthesia techniques, hemodynamic control, length of time before starting therapy) on patient outcomes and to guide the clinical practice. Finally, recognizing and anticipating potential perioperative crisis and have a clear resuscitation plan coupled with effective and rapid communication with neurosurgeons are central aspects of management of these high – risk patients.

REFERENCES

Akkermans, Annemarie, Judith A. Van Waes, Linda M. Peelen, Gabriel J. Rinkel, and Wilton A. Van Klei. 2019. “Blood Pressure and End-Tidal Carbon Dioxide Ranges during Aneurysm Occlusion and Neurologic Outcome after an Aneurysmal Subarachnoid Hemorrhage.” Anesthesiology 130 (1): 92–105. https://doi.org/10.1097/ALN.000000 0000002482. Principles of Neuroanesthesia 203

Archer, David P., Andrew M. Walker, Sarah K. McCann, Joanna J. Moser, and Ramana M. Appireddy. 2017. “Anesthetic Neuroprotection in Experimental Stroke in Rodents: A Systematic Review and Meta-Analysis.” Anesthesiology. Lippincott Williams and Wilkins. https://doi.org/10.1097/ALN.0000000000001534. Avitsian, Rafi, and Armin Schubert. 2007. “Anesthetic Considerations for Intraoperative Management of Cerebrovascular Disease in Neurovascular Surgical Procedures.” Anesthesiology Clinics. Anesthesiol Clin. https://doi.org/10.1016/j.anclin.2007.06.002. Badenes, Rafael, María L. García-Pérez, and Federico Bilotta. 2016. “Intraoperative Monitoring of Cerebral Oximetry and Depth of Anaesthesia during Neuroanesthesia Procedures.” Current Opinion in Anaesthesiology. Lippincott Williams and Wilkins. https://doi.org/10.1097/ACO.0000000000000371. Badenes, Rafael, Shaun E. Gruenbaum, and Federico Bilotta. 2015. “Cerebral Protection during Neurosurgery and Stroke.” Current Opinion in Anaesthesiology. Lippincott Williams and Wilkins. https://doi.org/10.1097/ACO.0000000000000232. Ban, Vin Shen, Ravi Bhoja, and David L. McDonagh. 2019. “Multimodal Analgesia for Craniotomy.” Current Opinion in Anaesthesiology. Lippincott Williams and Wilkins. https://doi.org/10.1097/ACO.0000000000000766. Bebawy, John F., Dhanesh K. Gupta, Bernard R. Bendok, Laura B. Hemmer, Carine Zeeni, Michael J. Avram, H. Hunt Batjer, and Antoun Koht. 2010. “Adenosine-Induced Flow Arrest to Facilitate Intracranial Aneurysm Clip Ligation: Dose-Response Data and Safety Profile.” Anesthesia and Analgesia 110 (5): 1406–11. https://doi.org/10.1213/ANE. 0b013e3181d65bf5. Bekker, Alex, and Mary K. Sturaitis. 2005. “Dexmedetomidine for Neurological Surgery.” Neurosurgery. Neurosurgery. https://doi.org/10.1227/01.NEU.0000163476.42034.A1. Bendo, Audrée A. 2002. “Intracranial Vascular Surgery.” Anesthesiology Clinics of North America. Anesthesiol Clin North Am. https://doi.org/10.1016/S0889-8537(01)00007-4. Bendok, Bernard R., Dhanesh K. Gupta, Rudy J. Rahme, Christopher S. Eddleman, Joseph G. Adel, Arun K. Sherma, Daniel L. Surdell, John F. Bebawy, Antoun Koht, and H. Hunt Batjer. 2011. “Adenosine for Temporary Flow Arrest during Intracranial Aneurysm Surgery: A Single-Center Retrospective Review.” Neurosurgery. Neurosurgery. https://doi.org/10.1227/NEU.0b013e318226632c. Bennett, Cambell, Logan J. Voss, John P. M. Barnard, and James W. Sleigh. 2009. “Practical Use of the Raw Electroencephalogram Waveform during General Anesthesia: The Art and Science.” Anesthesia and Analgesia 109 (2): 539–50. https://doi.org/10.1213/ane. 0b013e3181a9fc38. Cai, Y. E., Hui Xu, Jia Yan, Lei Zhang, and Y. I. Lu. 2014. “Molecular Targets and Mechanism of Action of Dexmedetomidine in Treatment of Ischemia/Reperfusion Injury (Review).” Molecular Medicine Reports. Spandidos Publications. https://doi.org/10.3892/mmr. 2014.2034. Caldiroli, D., and P. Cortellazzi. 2011. “A New Difficult Airway Management Algorithm Based upon the El Ganzouri Risk Index and Glidescope ® Videolaryngoscope. a New Look for Intubation?” Minerva Anestesiologica 77 (10): 1011–17. Carr, Zyad J., Theodore J. Cios, Kenneth F. Potter, and John T. Swick. 2018. “Does Dexmedetomidine Ameliorate Postoperative Cognitive Dysfunction? A Brief Review of the Recent Literature.” Current Neurology and Neuroscience Reports. Current Medicine Group LLC 1. https://doi.org/10.1007/s11910-018-0873-z. 204 M. Seveso and D. Caldiroli

Chowdhury, Tumul, Andrea Petropolis, Marshall Wilkinson, Bernhard Schaller, Nora Sandu, and Ronald B. Cappellani. 2014. “Controversies in the Anesthetic Management of Intraoperative Rupture of Intracranial Aneurysm.” Anesthesiology Research and Practice. Hindawi Limited. https://doi.org/10.1155/2014/595837. Chui, Jason, Pirjo Manninen, Raphael H. Sacho, and Lashmi Venkatraghavan. 2015. “Anesthetic Management of Patients Undergoing Intracranial Bypass Procedures.” Anesthesia and Analgesia. Lippincott Williams and Wilkins. https://doi.org/10.1213/ ANE.0000000000000470. Cortellazzi, P., L. Minati, C. Falcone, M. Lamperti, and D. Caldiroli. 2007. “Predictive Value of the El-Ganzouri Multivariate Risk Index for Difficult Tracheal Intubation: A Comparison of Glidescope® Videolaryngoscopy and Conventional Macintosh Laryngoscopy.” British Journal of Anaesthesia 99 (6): 906–11. https://doi.org/10.1093/ bja/aem297. D’Souza, Stanlies. 2015. “Aneurysmal Subarachnoid Hemorrhage.” Journal of Neurosurgical Anesthesiology 27 (3): 222–40. https://doi.org/10.1097/ANA.0000000000000130. Drummond, John C., Andrew V. Dao, David M. Roth, Ching Rong Cheng, Benjamin I. Atwater, Anushirvan Minokadeh, Leonardo C. Pasco, and Piyush M. Patel. 2008. “Effect of Dexmedetomidine on Cerebral Blood Flow Velocity, Cerebral Metabolic Rate, and Carbon Dioxide Response in Normal Humans.” Anesthesiology 108 (2): 225–32. https://doi.org/10.1097/01.anes.0000299576.00302.4c. Duan, X., M. Coburn, R. Rossaint, R. D. Sanders, J. V. Waesberghe, and A. Kowark. 2018. “Efficacy of Perioperative Dexmedetomidine on Postoperative Delirium: Systematic Review and Meta-Analysis with Trial Sequential Analysis of Randomised Controlled Trials.” British Journal of Anaesthesia. Elsevier Ltd. https://doi.org/10.1016/j.bja. 2018.04.046. Durgan, David J., and Robert M. Bryan. 2012. “Cerebrovascular Consequences of Obstructive Sleep Apnea.” Journal of the American Heart Association 1 (4). https://doi.org/10.1161/ jaha.111.000091. Egan, Talmage D. 2019. “Are Opioids Indispensable for General Anaesthesia?” British Journal of Anaesthesia. Elsevier Ltd. https://doi.org/10.1016/j.bja.2019.02.018. Engelhard, Kristin, and Christian Werner. 2006. “Inhalational or Intravenous Anesthetics for Craniotomies? Pro Inhalational.” Current Opinion in Anaesthesiology. Curr Opin Anaesthesiol. https://doi.org/10.1097/01.aco.0000245275.76916.87. Evered, L., B. Silbert, D. S. Knopman, D. A. Scott, S. T. DeKosky, L. S. Rasmussen, E. S. Oh, et al. 2018. “Recommendations for the Nomenclature of Cognitive Change Associated with Anaesthesia and Surgery—2018.” British Journal of Anaesthesia. Elsevier Ltd. https://doi.org/10.1016/j.bja.2017.11.087. Farag, Ehab, Maged Argalious, Daniel I. Sessler, Andrea Kurz, Zeyd Y. Ebrahim, and Armin Schubert. 2011. “Use of Α2-Agonists in Neuroanesthesia: An Overview.” Ochsner Journal 11 (1): 57–69. Flexman, Alana M., Tianlong Wang, and Lingzhong Meng. 2019. “Neuroanesthesia and Outcomes: Evidence, Opinions, and Speculations on Clinically Relevant Topics.” Current Opinion in Anaesthesiology. Lippincott Williams and Wilkins. https://doi.org/10.1097/ ACO.0000000000000747. Ge, Yali, Qian Li, Yuyan Nie, Ju Gao, Ke Luo, Xiangzhi Fang, and Cunjing Wang. 2019. “Dexmedetomidine Improves Cognition after Carotid Endarterectomy by Inhibiting Principles of Neuroanesthesia 205

Cerebral Inflammation and Enhancing Brain-Derived Neurotrophic Factor Expression.” Journal of International Medical Research 47 (6): 2471–82. https://doi.org/10.1177/ 0300060519843738. Jagt, Mathieu van der. 2016. “Fluid Management of the Neurological Patient: A Concise Review.” Critical Care 20 (1): 126. https://doi.org/10.1186/s13054-016-1309-2. Jalonen, Jouko, Markku Hynynen, Anne Kuitunen, Hannu Heikkilä, Juha Perttilä, Markku Salmenperä, Mike Valtonen, Riku Aantaa, and Antero Kallio. 1997. “Dexmedetomidine as an Anesthetic Adjunct in Coronary Artery Bypass Grafting.” Anesthesiology 86 (2): 331–45. https://doi.org/10.1097/00000542-199702000-00009. Keating, Gillian M. 2016. “Sugammadex: A Review of Neuromuscular Blockade Reversal.” Drugs 76 (10): 1041–52. https://doi.org/10.1007/s40265-016-0604-1. Koerner, Ines P., and Ansgar M. Brambrink. 2006. “Brain Protection by Anesthetic Agents.” Current Opinion in Anaesthesiology. Curr Opin Anaesthesiol. https://doi.org/10.1097/ 01.aco.0000245271.84539.4c. Kundra, Sandeep, Vidhi Mahendru, Vishnu Gupta, and Ashwani Kumar Choudhary. 2014. “Principles of Neuroanesthesia in Aneurysmal Subarachnoid Hemorrhage.” Journal of Anaesthesiology Clinical Pharmacology. Medknow Publications. https://doi.org/10.4103/ 0970-9185.137261. Lamperti, Massimo, Andrew R. Bodenham, Mauro Pittiruti, Michael Blaivas, John G. Augoustides, Mahmoud Elbarbary, Thierry Pirotte, et al. 2012. “International Evidence- Based Recommendations on Ultrasound-Guided Vascular Access.” In Intensive Care Medicine, 38:1105–17. Intensive Care Med. https://doi.org/10.1007/s00134-012-2597-x. Lee, Chanhung Z., and William L. Young. 2012. “Anesthesia for Endovascular Neurosurgery and Interventional Neuroradiology.” Anesthesiology Clinics. https://doi.org/10.1016/j. anclin.2012.05.009. Li, J., A. W. Gelb, A. M. Flexman, F. Ji, and L. Meng. 2016. “Definition, Evaluation, and Management of Brain Relaxation during Craniotomy.” British Journal of Anaesthesia. Oxford University Press. https://doi.org/10.1093/bja/aew096. Lin, Nan, Laszlo Vutskits, John F. Bebawy, and Adrian W. Gelb. 2019. “Perspectives on Dexmedetomidine Use for Neurosurgical Patients.” Journal of Neurosurgical Anesthesiology. Lippincott Williams and Wilkins. https://doi.org/10.1097/ANA. 0000000000000554. Logvinova, Anna V., Lawrence Litt, William L. Young, and Chanhung Z. Lee. 2010. “Anesthetic Concerns in Patients with Known Cerebrovascular Insufficiency.” Anesthesiology Clinics. Anesthesiol Clin. https://doi.org/10.1016/j.anclin.2010.01.007. Miller, Christina, and Marek Mirski. 2012. “Anesthesia Considerations and Intraoperative Monitoring During Surgery for Arteriovenous Malformations and Dural Arteriovenous Fistulas.” Neurosurgery Clinics of North America. Neurosurg Clin N Am. https://doi.org/ 10.1016/j.nec.2011.09.014. Molyneux, Andrew J., Richard S. Kerr, Ly Mee Yu, Mike Clarke, Mary Sneade, Julia A. Yarnold, and Peter Sandercock. 2005. “International Subarachnoid Aneurysm Trial (ISAT) of Neurosurgical Clipping versus Endovascular Coiling in 2143 Patients with Ruptured Intracranial Aneurysms: A Randomised Comparison of Effects on Survival, Dependency, Seizures, Rebleeding, Subgroups, and Aneurysm Occlusion.” Lancet 366 (9488): 809–17. https://doi.org/10.1016/S0140-6736(05)67214-5. 206 M. Seveso and D. Caldiroli

Nguyen, Hoang P., Jonathan G. Zaroff, Emine O. Bayman, Adrian W. Gelb, Michael M. Todd, Bradley J. Hindman, M. Todd, et al. 2010. “Perioperative Hypothermia (33°C) Does Not Increase the Occurrence of Cardiovascular Events in Patients Undergoing Cerebral Aneurysm Surgery: Findings from the Intraoperative Hypothermia for Aneurysm Surgery Trial.” Anesthesiology 113 (2): 327–42. https://doi.org/10.1097/ALN.0b013e3181dfd4f7. Pasternak, Jeffrey J. 2019. “Neuroanesthesiology Update.” Journal of Neurosurgical Anesthesiology. Lippincott Williams and Wilkins. https://doi.org/10.1097/ANA. 0000000000000581. Peng, Ke, Shaoru Wu, Huayue Liu, and Fuhai Ji. 2014. “Dexmedetomidine as an Anesthetic Adjuvant for Intracranial Procedures: Meta-Analysis of Randomized Controlled Trials.” Journal of Clinical Neuroscience 21 (11): 1951–58. https://doi.org/10.1016/j.jocn.2014. 02.023. Rampil, Ira J. 2001. “Monitoring Depth of Anesthesia.” Current Opinion in Anaesthesiology 14 (6): 649–53. https://doi.org/10.1097/00001503-200112000-00009. Randell, Tarja, and Minna Niskanen. 2006. “Management of Physiological Variables in Neuroanaesthesia: Maintaining Homeostasis during Intracranial Surgery.” Current Opinion in Anaesthesiology. Curr Opin Anaesthesiol. https://doi.org/10.1097/01.aco. 0000245273.92163.8e. Schwarz, Adam, Bobby Nossaman, Dominic Carollo, and Usha Ramadhyani. 2013. “Dexmedetomidine for Neurosurgical Procedures.” Current Anesthesiology Reports 3 (3): 205–9. https://doi.org/10.1007/s40140-013-0021-x. Shehabi, Yahya, Peter Grant, Hugh Wolfenden, Naomi Hammond, Frances Bass, Michelle Campbell, and Jack Chen. 2009. “Prevalence of Delirium with Dexmedetomidine Compared with Morphine Based Therapy after Cardiac Surgery: A Randomized Controlled Trial (DEXmedetomidine Compared to Morphine-DEXCOM Study).” Anesthesiology 111 (5): 1075–84. https://doi.org/10.1097/ALN.0b013e3181b6a783. Shehabi, Yahya, Belinda D. Howe, Rinaldo Bellomo, Yaseen M. Arabi, Michael Bailey, Frances E. Bass, Suhaini Bin Kadiman, et al. 2019. “Early Sedation with Dexmedetomidine in Critically Ill Patients.” New England Journal of Medicine 380 (26): 2506–17. https://doi.org/10.1056/NEJMoa1904710. Slupe, Andrew M., and Jeffrey R. Kirsch. 2018. “Effects of Anesthesia on Cerebral Blood Flow, Metabolism, and Neuroprotection.” Journal of Cerebral Blood Flow and Metabolism. SAGE Publications Ltd. https://doi.org/10.1177/0271678X18789273. Söderman, Michael, Tommy Andersson, Bengt Karlsson, M. Christopher Wallace, and Göran Edner. 2003. “Management of Patients with Brain Arteriovenous Malformations.” European Journal of Radiology. Elsevier Ireland Ltd. https://doi.org/10.1016/S0720- 048X(03)00091-3. Steiner, Luzius A., and Martin Siegemund. 2019. “Vasoactive Agents to Improve Brain Perfusion: Pathophysiology and Clinical Utilization.” Current Opinion in Critical Care 25 (2): 110–16. https://doi.org/10.1097/MCC.0000000000000586. Sultana, Adrian, David Torres, and Roman Schumann. 2017. “Special Indications for Opioid Free Anaesthesia and Analgesia, Patient and Procedure Related: Including Obesity, Sleep Apnoea, Chronic Obstructive Pulmonary Disease, Complex Regional Pain Syndromes, Opioid Addiction and Cancer Surgery.” Best Practice and Research: Clinical Anaesthesiology. Bailliere Tindall Ltd. https://doi.org/10.1016/j.bpa.2017.11.002. Principles of Neuroanesthesia 207

Thorup, Line, Klaus U. Koch, Richard N. Upton, Leif Østergaard, and Mads Rasmussen. 2020. “Effects of Vasopressors on Cerebral Circulation and Oxygenation: A Narrative Review of Pharmacodynamics in Health and Traumatic Brain Injury.” Journal of Neurosurgical Anesthesiology. Lippincott Williams and Wilkins. https://doi.org/10.1097/ANA. 0000000000000596. Todd, Michael M. 2012. “Outcomes After Neuroanesthesia and Neurosurgery. What Makes a Difference.” Anesthesiology Clinics. Elsevier. https://doi.org/10.1016/j.anclin.2012.06. 001. Tsujikawa, Shogo, and Kazutoshi Ikeshita. 2019. “Low-Dose Dexmedetomidine Provides Hemodynamics Stabilization during Emergence and Recovery from General Anesthesia in Patients Undergoing Carotid Endarterectomy: A Randomized Double-Blind, Placebo- Controlled Trial.” Journal of Anesthesia 33 (2): 266–72. https://doi.org/10.1007/s00540- 019-02612-w. Wiebers, David O., and Richard Marsh. 1998. “Unruptured Intracranial Aneurysms - Risk of Rupture and Risks of Surgical Intervention.” New England Journal of Medicine 339 (24): 1725–33. https://doi.org/10.1056/NEJM199812103392401. Wu, Lingzhi, Hailin Zhao, Hao Weng, and Daqing Ma. 2019. “Lasting Effects of General Anesthetics on the Brain in the Young and Elderly: ‘Mixed Picture’ of Neurotoxicity, Neuroprotection and Cognitive Impairment.” Journal of Anesthesia. Springer Tokyo. https://doi.org/10.1007/s00540-019-02623-7.

Chapter 12

INTRAOPERATIVE NEUROPHYSIOLOGICAL MONITORING IN NEUROVASCULAR SURGERY

S. Luzzi1,2,, MD, PhD, G. Mezzini1, MD, M. Del Maestro2,3, MD, A. Giotta Lucifero1, MD and R. Galzio1,2, MD 1Neurosurgery Unit, Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy 2Neurosurgery Unit, Department of Surgical Sciences, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy 3PhD School in Experimental Medicine, Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy

ABSTRACT

Intraoperative neurophysiological monitoring is nowadays an integral part of the armamentarium of neurovascular surgery. The link existing between reduction of blood flow and the nearly real-time change of neurophysiological parameters allows the surgeon to implement some corrective maneuvers to ultimately avoid an ischemic event. For these reasons, intraoperative neurophysiological monitoring is considered a paramount tool by which to improve patient outcome during brain and neurovascular surgery. Nevertheless, due to the non-negligible rate of false-positives and -negatives for any kind of technique, use of neuromonitoring requires knowledge of some technical aspects, along with some criteria for correct interpretation of the data. The main purpose of this chapter is to review in detail the different types of techniques available for neuromonitoring, especially in aneurysm surgery, as well as highlighting the advantages and limitations of each.

Keywords: brainstem auditory evoked potential (BAEP), evoked potentials, intracranial aneurysms, intraoperative neuromonitoring, PEMs, somatosensory evoked potential (SSEP), temporary clipping

 Corresponding Author’s Email: [email protected]. 210 S. Luzzi, G. Mezzini, M. Del Maestro et al.

1. OVERVIEW

Historically employed during epilepsy surgery to test the functional integrity of specific neural pathways (Sakashita et al. 2009), intraoperative neurophysiological monitoring (IONM) is nowadays used during many neurosurgical procedures. In neurovascular surgery, IONM reduces the risk of iatrogenic ischemic damage, which has been reported to be the main cause of morbidity or even mortality in up to 20% of operations (Grundy et al. 1982). The rationale for IONM in aneurysm surgery comes from the proven link existing between the critical decrease in blood flow, subsequent electrophysiological impairments, and risk of function loss (Grundy et al. 1982; Kataoka et al. 1987; Lesnick et al. 1986; Little, Lesser, and Luders 1987; Momma, Wang, and Symon 1987; Mooij, Buchthal, and Belopavlovic 1987; Schramm, Zentner, and Pechstein 1994). In light of the well-known effects of anesthetics and other drugs on IONM, implementation of a specific protocol is the starting point for correct interpretation of intraoperative data. Several techniques are commonly used for IONM in neurovascular surgery, namely, somatosensory evoked potentials (SSEPs), motor evoked potentials (MEPs), brainstem auditory evoked potentials (BAEPs), and electroencephalography (EEG).

2. ANESTHESIOLOGIC MANAGEMENT FOR IONM

Over the years, our group has developed and implemented a dedicated protocol that can be employed in any neurovascular procedure requiring IONM (S. Luzzi, Del Maestro, et al. 2018). Types of monitoring, vascular access, anesthetics, and vasoactive drugs are decided on the basis of recommendations for neuroanesthetic management of the intracranial lesions. Multimodal monitoring of arterial pressure, heart rate, nasopharyngeal temperature, urine output, and end- tidal CO2 concentration is implemented. General anesthesia is induced with propofol (1%) and remifentanil (50 µg/mL) using target-controlled infusion (Base Primeraᵀᴹ, Fresenius, France). A cisatracurium bolus (0.1 mg/kg) is administrated to facilitate endotracheal intubation. During surgery, the effect-site propofol concentration (range: 2–3.5 µg/mL; Schnider model) is administered based on the predominance of delta activity on EEG. The remifentanil concentration (range: 3–9 µg/mL; Minto model) is adjusted based on pain response. Patients are ventilated in volume control mode, with a mixture of 50% oxygen and air in order to achieve a systemic arterial oxygen partial pressure of >100 mmHg and systemic arterial CO2 partial pressure of 35–40 mmHg. Euvolemia, normotension, isotonicity, normoglycemia, and mild hypocapnia are maintained during surgery. Body temperature is maintained constant at 35°C with a warming/cooling blanket. In case of bleeding at the surgical site and/or brain swelling secondary to normal perfusion pressure breakthrough during surgery for brain arteriovenous malformations, α-adrenergic blockades are administered.

Intraoperative Neurophysiological Monitoring in Neurovascular Surgery 211

3. IONM TECHNIQUES

3.1. Somatosensory Evoked Potentials

SSEP monitoring infers the functional integrity of somatosensory pathways by eliciting electric stimuli at some specific peripheral sites and the simultaneous recording of primary somesthesic cortex (post-Rolandic gyrus) activity. Because the primary motor and sensory cortex share the same vascularization, SSEP allows indirect gathering of information about the integrity of the motor pathway. To elicit SSEP, bilateral stimulation of the median and posterior tibial nerves is performed by means of disposable subdermal twisted-pair needle electrodes. Disposable screw needle electrodes are placed on the scalp at C3’, C4’, and Cz, a reference electrode at Fpz, a further one at the CVII vertebra, and the ground electrode above an arm. Regular pulses, ranging between 20 and 30 mA, lasting 500 ms, and with a rate of 4/s, are delivered until a visible muscle twitch is obtained. Regarding nomenclature of SSEP waveforms, the N or P values followed by a number are generally used to indicate the polarity and nominal poststimulus latency (ms) of the recorded wave, respectively. The potentials can be measured in terms of latency (ms), amplitude (lV), and intervals between peaks. For median nerve SSEP, the anode is placed on the wrist crease, whereas the cathode is placed 2 cm proximal to the anode. The recording electrodes, or channels, are placed bilaterally at the shoulder (N9), cervical region (N13), parietal region (P14 and N20), and frontal region (P14, P20, and N30). For tibial nerve SSEP, the cathode is placed midway between the medial border of the Achilles tendon and the posterior border of the medial malleolus, while the anode is placed 3 cm distal to the cathode. Recording electrodes are positioned peripherally (N8) and at the level of lumbar (N22), subcortical (P30), and cortical (P39) region. In neurovascular surgery, SSEP are useful for detection of ischemic events. They are also helpful for localizing lesions, while simultaneously providing a prognostic tool. Monitoring of lower extremity SSEP is of utmost importance for aneurysms involving the distal cerebral arteries (A2 segments) since these vascularize the paracentral lobule last and therefore, the leg area. Conversely, upper extremity SSEPs are more important for aneurysms involving the M2– M4 segments of the middle cerebral arteries (MCA) apart from the internal carotid artery (ICA). The evidence for abnormal SSEP in at least two consecutive registrations is considered a pathological event. Despite their high sensitivity, SSEP results are not reliable for detection of occluded perforating arteries, which is a main weakness of their use in neurovascular surgery (Guo and Gelb 2011; Holland 1998). Indeed, the reported sensitivity and specificity for SSEPs is 100% and 95% for cortical territories, respectively, with the specificity being less than 50% for subcortical areas (Holland 1998; Krieger et al. 1992; Guo and Gelb 2011). On the other hand, MEP is much more specific for detection of subcortical ischemic events. Thus, combination of SSEP and MEP serves to overcome limitations to SSEP alone (Schramm, Zentner, and Pechstein 1994).

212 S. Luzzi, G. Mezzini, M. Del Maestro et al.

3.2. Motor Evoked Potentials

MEP monitoring is used to check the integrity of the corticospinal and corticobulbar tract. The motor cortex can be elicited through the scalp in the form of a transcranial electrical stimulation (TES) or through direct cortical stimulation (DCS). Due to its optimal spatial resolution, DCS MEP is routinely used for intraoperative brain mapping during brain tumor surgery. MEP is largely affected by anesthetics, especially halogenated ones. This is the main reason why total propofol intravenous anesthesia is mandatory (Mooij, Buchthal, and Belopavlovic 1987). For TES MEP, disposable screw needle electrodes are placed on the scalp at C1-C2 according to the 10-20 International System. An electrode placed at Fpz acts as a cathode. In DCS MEP, a subdural strip electrode is located along the precentral gyrus, targeting to the arm and leg motor area. Muscular needle electrodes are placed at the first dorsal interosseous muscles, tibialis anterior muscles, and extensor hallucis longus muscles on both sides. A train of five square wave stimulations, lasting 500 ms, and at the rate of 250 pulses/s are administered to obtain a visible muscle twitch. The resulting muscle responses are referred to as “M-waves.” Some stimulation techniques may optimize MEP monitoring, such as temporal and spatial facilitation. Temporal facilitation is the application of a train stimulus usually composed of four to five pulses; spatial facilitation works applying peripheral tetanic stimulation prior to MEP. There are several differences between TES and DCS MEP. TES MEP is technically easier to record and allows bilateral recording, but needs higher trigger voltages to overcome derma and bone impedance (only 20% of the delivered intensity goes to the brain). Notably, increase of the stimulation threshold also increases the risk of false-negatives coming from stimulation of the corticospinal tract at a subcortical level. Different from SSEP and DCS MEP, TES MEP monitoring is “on-demand” and should be repeated at least every 5 min. DCS MEP requires a lower trigger intensity (8–20 mA on average), it doesn’t involve the movement of the patient during surgery, thus not interfering with surgery, it can be recorded continuously. Furthermore, it is related to a lower risk of false-negatives secondary to subcortical stimulation of the corticospinal tract. Nevertheless, DCS MEP requires positioning of the stimulation strip over the motor cortex, which imposes larger craniotomies and often blind insertion of the strip itself into the subdural space with subsequent bleeding risk. Apart from being dangerous, direct stimulation of the leg area in the mesial motor cortex is technically demanding because of the high number of bridging veins. The recording of eight consecutive stimulations before the skin incision should be performed under general anesthesia, under stable hemodynamic conditions, and with a time interval of at least 30 s and can be assumed as baseline (Guo and Gelb 2011). Disappearance of MEP for more than 10 min is considered an independent factor for the occurrence of postoperative motor deficits (Chung et al. 2018; Thomas and Guo 2017). Having a higher sensitivity and specificity to subcortical ischemia compared with SSEP, MEP monitoring is used specially to detect occlusion of lenticulostriate and thalamoperforating arteries (Horiuchi et al. 2005; Neuloh and Schramm 2004; Quinones-Hinojosa et al. 2004; Szelenyi et al. 2005). Similar to SSEP, lower extremity MEP is used during surgery involving distal cerebral arteries (A2 segments). Upper extremity MEP is most important for aneurysms involving A1 and M1 segments of the anterior and MCA, respectively, and thalamoperforating arteries from P1 segments of posterior cerebral arteries. Intraoperative Neurophysiological Monitoring in Neurovascular Surgery 213

3.3. Brainstem Auditory Evoked Potentials

BAEPs record the path of a sound signal elicited at the level of the cochlea along its ascending course through the cochlear nerve, cochlear nucleus, superior olivary complex, lateral lemniscus, inferior colliculus, medial geniculate body, and cerebral cortex. Because a large part of the auditory pathway lies within the brainstem, evaluation of the BAEPs is clinically useful to detect brainstem damage (Jewett, Romano, and Williston 1970). In neurovascular surgery this damage may come from ischemic events secondary to occlusion of arteries of the posterior circulation or posterior communicating arteries. From the technical standpoint, 2-channel recordings are obtained. Recording electrodes are placed on both mastoids and reference electrodes on the Cz point (vertex). The hearing threshold of each ear is initially determined, and sound clicks 70 dB above the hearing threshold are administered. Generally, the click has a frequency of 11.1 Hz and an intensity of 100 dBnHL, and the opposite ear is masked by a 100 dBnHL white noise (Kang et al. 2007; Youssef and Downes 2009). Under normal conditions, seven waves (I–VII) are usually recorded in the first 10 ms following clicks. Waves I–V are constants and found in all subjects, whereas waves VI and VII are variable. Waves I, II, III, IV, and V correspond to the cochlear nerve, cochlear nucleus, superior olivary complex, lateral lemniscus, and inferior colliculus, respectively. Latencies of waves I, III, and V, interpeak latencies of I–III, III–V, and I–V, and the amplitude ratio of wave V to I are parameters usually employed in clinical practice to assess the integrity of the pathway. Amplitude and latency abnormalities of waves II–III and IV–V suggest lesions located at the level of the pons and midbrain, respectively. Equally, interpeak latencies of I–III and III–V complexes indicate pontine and mesencephalic lesions, respectively (Markand 1994). More than other neuromonitoring techniques, BAEPs are affected by several factors, but mainly hearing deficits, sex, age, temperature, click intensity, stimulus rate, stimulus mode, anesthetics, drugs, and demyelinating disorders (Markand 1994).

3.4. Electroencephalography

EEG allows recording of spontaneous electrical activity generated by the cerebral cortex, which in turn is directly correlated with the cerebral blood flow. Apart from its utility in the assessment of anesthesia planes, EEG is mainly used to monitor induced burst suppression during temporary clipping. EEG has an optimal temporal resolution but poor spatial resolution (Burle et al. 2015). The EEG bispectral index has been shown to be a quantifiable measure of the hypnotic effect of anesthetics on the central nervous system; however, it is not unable to detect ischemia or hypoxia.

4. WARNING CRITERIA

Table 1 reports the main warning criteria, grading of pathologic events, and therapeutic maneuvers to be considered during neuromonitoring of neurovascular surgical procedures (Sahaya et al. 2014; Markand 1994; Grundy et al. 1982; Neuloh and Schramm 2004).

214 S. Luzzi, G. Mezzini, M. Del Maestro et al.

Table 1. Warning Criteria and Grading of Pathologic Events

Abnormalities Suggested Neuromonitoring Corrective Technique Type Grade Maneuvers Anesthetic and  Ampl and  of Lat after N20-P25 Grade 1 hemodynamic complex adjustments SSEPs  Ampl (>50%), or  of Lat (>10%) Grade 2 of the N20-P25 complex Reversal of last Disappearance of P25 +  Ampl of surgical maneuver Grade 3 N20 (>70%), and  Lat (>10%)  Ampl (>50%) +  of Lat (>10%) Major Reversal of last MEPs Need for  motor threshold (>20 abnormality surgical maneuver mA) lasting >10 min  Ampl (>50%) +  of Lat (>10%) of waves I, III (pons), and V (midbrain) Major Reversal of last BAEPs  Interpeak Lat of I–III (pons), III– abnormality surgical maneuver V (midbrain), and I–V complex (pons + midbrain)  of wave V/wave I Ampl ratio Anesthetic and Minor  8-15 Hz activity (>50%) hemodynamic abnormality adjustments EEG   activity (>1Hz) Major Reversal of last Disappearance of - activity +  of abnormality surgical maneuver  activity (>1 Hz) SSEPs: somatosensory evoked potentials; MEPs: motor evoked potentials; BAEPs: brainstem auditory evoked potentials; EEG: electroencephalography; Ampl: amplitude; Lat: latency.

5. ILLUSTRATIVE CASES

Case 1: Giant Posterior Communicating Artery Aneurysm: Sudden SEEPs and MEPs Impairment during a Prolonged Proximal and Distal Temporary Occlusion of the ICA

A 54 year-old man suffered from acute paralysis of the left third cranial nerve caused by a giant calcified posterior communicating artery aneurysm. During surgery, proximal and distal temporary occlusion of the left ICA was necessary to trap the aneurysm before its fragmentation and clip reconstruction. Despite the induced burst suppression, a sudden SEEP/MEP impairment of the left arm occurred after 17 min of occlusion. Proximal and distal clips were immediately released, and the SEEPs/MEPs progressively recovered within 5 min. The aneurysm was successfully clipped, and the patient had no postoperative deficits. No ischemic Intraoperative Neurophysiological Monitoring in Neurovascular Surgery 215 complications were revealed by MRI (Figure 1). This case corroborates the high sensitivity of the combined SSEP/MEP monitoring when detecting cortical hypoperfusion.

Figure 1. (A) Axial noncontrast enhanced CT scan revealing a giant left posterior communicating artery aneurysm; anterior-posterior (B) and lateral (C) projection digital subtraction angiography of the same patient. Patient position (D), intraoperative pictures showing the exposure (E), trapping of the aneurysm (F,G) and its clipping (H), and SSEP monitoring of the upper (upper left: left arm; upper right: right arm) and lower (lower left: left leg; lower right: right leg) extremities (I). The white arrow indicates a severe decrease in amplitude and increase in latency of the right arm. (J) Transcranial electrical stimulation MEP monitoring of the right side (upper track: right arm; lower track: right leg) showing an increase in latency (>10%) at the level of the right arm occurred after 17 min of ICA temporary clipping. Anterior-posterior (K) and lateral (L) projection digital subtraction angiography showing complete exclusion of the aneurysm. Postoperative CT scan (M) and T2-weighted MRI (N) revealing no postoperative ischemia.

Case 2: Giant MCA Bifurcation Aneurysm: MEP Impairment with Unchanged SEEPs after Temporary Clipping of M1 Segment

A 32 year-old female was diagnosed with a left giant calcified complex MCA artery bifurcation aneurysm. During surgery, temporary occlusion of the M1 segment of the MCA 216 S. Luzzi, G. Mezzini, M. Del Maestro et al. was performed in order to clip the aneurysm. After 8 min, an increase in MEP latency occurred in the right arm despite normal SSEPs. Due to profuse bleeding, it was not possible to remove the temporary clip before definitive clipping. SSEPs did not change during the entire surgery. Postoperatively, the patient had incomplete hemiparesis secondary to a documented small infarct at the level of the anterior arm of the internal capsule and head of the caudate nucleus. After 6 months, he completely recovered (Figure 2). This case confirms the higher specificity of MEPs versus SSEPs for subcortical ischemia due to perforating artery occlusion, hypoperfusion, or vasospasm.

Figure 2. Anterior-posterior (A) and lateral (B) projection digital subtraction angiography showing a giant complex MCA bifurcation aneurysm. Intraoperative pictures showing temporary clipping of the M1 segment of the MCA (C) along with clip reconstruction of the aneurysm dome (D). (E) SSEP monitoring of the upper (upper left: left arm; upper right: right arm) and lower (lower left: left leg; lower right: right leg) extremities. TES MEP of the right side (upper track: right arm; lower track: right leg) documenting dramatic decay of the amplitude (>50%) at the level of the right arm after 8 min of temporary occlusion of the M1 segment of the left MCA. Anterior-posterior (G) and lateral (H) projection digital subtraction angiography revealing complete exclusion of the aneurysm. (I, J) Postoperative axial CT scan showing a small infarct at the level of the anterior arm of the internal capsule and head of the caudate nucleus.

DISCUSSION

Nowadays, IONM is considered an imperative tool during surgery for intra-axial lesions of the central nervous system. Its relative simplicity in execution, noninvasiveness, low cost, Intraoperative Neurophysiological Monitoring in Neurovascular Surgery 217 and the myriad of nearly real-time information on function achievable has led to extended routine use of IONM in neurovascular surgery, especially for aneurysms (Chung et al. 2018; Grundy et al. 1982; Guo and Gelb 2011; Holland 1998; Horiuchi et al. 2005; Little, Lesser, and Luders 1987; Mooij, Buchthal, and Belopavlovic 1987; Quinones-Hinojosa et al. 2004; Sahaya et al. 2014; Schramm, Zentner, and Pechstein 1994; Szelenyi et al. 2005; Thomas and Guo 2017). In the last few years, advances and constant refinement of techniques in all fields of neurosurgery (Bellantoni et al. 2019; De Tommasi et al. 2008; De Tommasi et al. 2007; Guastamacchia et al. 2007; Sabino Luzzi, Crovace, et al. 2019; S. Luzzi, Crovace, et al. 2018; S. Luzzi, Elia, Del Maestro, Elbabaa, et al. 2019; S. Luzzi, Giotta Lucifero, et al. 2019; Palumbo et al. 2019; Palumbo et al. 2018; Raysi Dehcordi et al. 2017; Spena et al. 2019; Zoia et al. 2018; Bongetta et al. 2019; Antonosante et al. 2020; Campanella et al. 2020; Zoia et al. 2020; Elsawaf et al. 2020) have led to significative improvements of IONM quality (Chung et al. 2018; Neuloh and Schramm 2004; Thomas and Guo 2017). Most of the advantages of IONM are attributable to multimodal monitoring involving different techniques in order to reduce the risk of false-positives and -negatives. The rationale for IONM is based on the link existing between reduction of blood flow below the critical threshold of ischemia and early appearance of neurophysiological impairments that can be recorded intraoperatively. Furthermore, implementation of corrective maneuvers allows potential reversion of these disturbances; therefore, IONM also gives information about the effectiveness of the corrective maneuver itself. Combination of IONM with all intraoperative flow assessment techniques optimizes the overall surgical management of intracranial aneurysms since, despite the tremendous level of accuracy achieved, none of these techniques alone can punctually predict the neurophysiological sequalae of a reduction in flow. During aneurysm surgery, IONM is paramount during both temporary and definitive clipping. Proximal or proximal/distal temporary clipping of the parent vessel, the latter aimed to trap the aneurysm, are maneuvers routinely performed to achieve satisfactory aneurysm clipping. The same occurs during bypass procedures. While considering the neuroprotective effects of propofol-induced burst suppression, re- establishment of neurophysiological baseline conditions, documented by IONM during and immediately after reversal from electric silence, allows the surgeon the best comfort possible during surgery. These data may be important during implementation of extreme neuroprotective procedures, such as deep hypothermic circulatory arrest. During aneurysm clipping, IONM allows very early assessment of the functional consequences of an inadvertent occlusion of perforating vessels, blood flow reduction coming from accidental stenosis of the parent artery, or vasospasm. By reason of the effects of different drugs on evoked potentials, halogenated first, implementation of a specific anesthesia protocol is a conditio sine qua non for the correct interpretation of data coming from IONM. The reported personal protocol has proved to be effective for this purpose in all neurovascular pathologies for which IONM is indicated (Ciappetta, Luzzi, et al. 2009; Ciappetta, Occhiogrosso, et al. 2009; Del Maestro et al. 2018; Gallieni et al. 2018; S. Luzzi, Del Maestro, et al. 2018; S. Luzzi, Del Maestro, and Galzio 2019; S. Luzzi, Elia, Del Maestro, Morotti, et al. 2019; S. Luzzi, Gallieni, et al. 2018; Ricci et al. 2017; S. Luzzi et al. 2020). Being considered as all-in-one in the form of multimodal assessment involving SSEPs, TES MEPs, BAEPs, and EEG, IONM has a sensitivity, specificity, positive and negative predictive value of postoperative deficit of 90%, 98.04%, 50%, and 99.78%, respectively (Sahaya et al. 2014). Regarding SSEPs, 50% reduction of the amplitude as well as an increase 218 S. Luzzi, G. Mezzini, M. Del Maestro et al. in the latency of more than 25% has been linked to a reduction of cerebral blood flow up to 14 mL/100 g/min, whereas complete loss of SSEP has been reported for a cerebral blood flow less than 12 mL/100 g/min (MacDonald et al. 2019). Conversely, complete N20 recovery within 15–20 min is suggestive of a good clinical outcome (Momma, Wang, and Symon 1987). SSEPs reportedly have a false-negative rate of about 25% mainly due to interference by perforating arteries (Thomas and Guo 2017; Choi et al. 2017; Manninen, Lam, and Nantau 1990). This represents the main weakness of SSEP monitoring and strongly encourages combination of SSEP with MEP to achieve the best predictive value possible for postoperative neurological deficits. In case of unchanged parameters during combined SSEP/MEP monitoring, the length of each single temporary clipping and that of the total may exceed the reported limits of 5 and 20 min, respectively (Nathan et al. 2003; Araki et al. 1999; Kubota et al. 1992; Ogilvy et al. 1996). MEP monitoring is paramount to detect subcortical ischemia due to inadvertent perforating artery occlusion. This aspect was addressed by illustrative case #2. Nevertheless, precise identification of the stimulation threshold is essential to avoid false-negatives. In the context of an excessive threshold, a false-negative may come from bypass of the subcortical level. TES is undoubtedly less invasive compared to DCS, but the rate of false-negatives is higher. The use of a “close-to-motor-threshold” and monophasic (left-right) stimulation are recommended to reduce the risk of false-negatives during TES MEP monitoring (Szelenyi et al. 2005), especially during aneurysm surgery. Conversely, DCS has the highest sensitivity and specificity, but it is burdened by the risk of some serious complications, including epilepsy, brain contusion, and subdural hematoma deriving from the position of the stimulation strip. Furthermore, bigger bone flaps are generally necessary for positioning of the strip (this is contrary to current trends in skull base approaches), which are required to be less invasive both for transcranial and endoscopic surgery (Arnaout et al. 2019; S. Luzzi, Del Maestro, Elia, et al. 2019; S. Luzzi, Del Maestro, Trovarelli, et al. 2019; S. Luzzi, Zoia, et al. 2019; Zoia et al. 2019). Lastly, grading of neurophysiological abnormalities during IONM is possible only for SSEPs and EEG but not for MEPs and BAEPs, which are characterized by an all-or-none modality of assessment. MEP and BAEP abnormalities always impose corrective maneuvers, such as clip repositioning.

CONCLUSION

Multimodal IONM allows execution of real-time corrective maneuvers during surgery making it possible to avoid occurrence of ischemia. Thus, it is essential to reduce the risk of postoperative deficits during neurovascular surgery. Most of its advantages come from combining different techniques, such as SSEP and MEP. SSEPs enable early detection of an abrupt reduction of blood flow at the cortical level, whereas MEPs are more specific for subcortical ischemia stemming from occlusion of perforating arteries. BAEPs play a role in procedures involving the posterior circulation, and EEG is mandatory for burst suppression during temporary clipping of the parent artery. Implementation of a dedicated anesthesiologic protocol is paramount for the execution of IONM and for correct interpretation of its data.

Intraoperative Neurophysiological Monitoring in Neurovascular Surgery 219

REFERENCES

Antonosante, A., L. Brandolini, M. d'Angelo, E. Benedetti, V. Castelli, M. D. Maestro, S. Luzzi, A. Giordano, A. Cimini, and M. Allegretti. 2020. “Autocrine CXCL8-dependent invasiveness triggers modulation of actin cytoskeletal network and cell dynamics.” Aging (Albany NY) 12 (2): 1928-1951. https://doi.org/10.18632/aging.102733. https://www.ncbi. nlm.nih.gov/pubmed/31986121. Araki, Y., H. Andoh, M. Yamada, K. Nakatani, T. Andoh, and N. Sakai. 1999. “Permissible arterial occlusion time in aneurysm surgery: postoperative hyperperfusion caused by temporary clipping.” Neurol Med Chir (Tokyo) 39 (13): 901-6; discussion 906-7. https://doi.org/10.2176/nmc.39.901. https://www.ncbi.nlm.nih.gov/pubmed/10658450. Arnaout, M. M., S. Luzzi, R. Galzio, and K. Aziz. 2019. “Supraorbital keyhole approach: Pure endoscopic and endoscope-assisted perspective.” Clin Neurol Neurosurg 189: 105623. https://doi.org/10.1016/j.clineuro.2019.105623. https://www.ncbi.nlm.nih.gov/pubmed/ 31805490. Bellantoni, G., F. Guerrini, M. Del Maestro, R. Galzio, and S. Luzzi. 2019. “Simple schwannomatosis or an incomplete Coffin-Siris? Report of a particular case.” eNeurological Sci 14: 31-33. https://doi.org/10.1016/j.ensci.2018.11.021. https://www. ncbi.nlm.nih.gov/pubmed/30555950. Bongetta, D., C. Zoia, S. Luzzi, M. D. Maestro, A. Peri, G. Bichisao, D. Sportiello, I. Canavero, A. Pietrabissa, and R. J. Galzio. 2019. “Neurosurgical issues of bariatric surgery: A systematic review of the literature and principles of diagnosis and treatment.” Clin Neurol Neurosurg 176: 34-40. https://doi.org/10.1016/j.clineuro.2018.11.009. https://www.ncbi. nlm.nih.gov/pubmed/30500756. Burle, B., L. Spieser, C. Roger, L. Casini, T. Hasbroucq, and F. Vidal. 2015. “Spatial and temporal resolutions of EEG: Is it really black and white? A scalp current density view.” Int J Psychophysiol 97 (3): 210-20. https://doi.org/10.1016/j.ijpsycho.2015.05.004. https://www.ncbi.nlm.nih.gov/pubmed/25979156. Campanella, R., L. Guarnaccia, C. Cordiglieri, E. Trombetta, M. Caroli, G. Carrabba, N. La Verde, P. Rampini, C. Gaudino, A. Costa, S. Luzzi, G. Mantovani, M. Locatelli, L. Riboni, S. E. Navone, and G. Marfia. 2020. “Tumor-Educated Platelets and Angiogenesis in Glioblastoma: Another Brick in the Wall for Novel Prognostic and Targetable Biomarkers, Changing the Vision from a Localized Tumor to a Systemic Pathology.” Cells 9 (2). https://doi.org/10.3390/cells9020294. https://www.ncbi.nlm.nih.gov/pubmed/31991805. Choi, H. H., E. J. Ha, W. S. Cho, H. S. Kang, and J. E. Kim. 2017. “Effectiveness and Limitations of Intraoperative Monitoring with Combined Motor and Somatosensory Evoked Potentials During Surgical Clipping of Unruptured Intracranial Aneurysms.” World Neurosurg 108: 738-747. https://doi.org/10.1016/j.wneu.2017.09.096. https://www. ncbi.nlm.nih.gov/pubmed/28951267. Chung, J., W. Park, S. H. Hong, J. C. Park, J. S. Ahn, B. D. Kwun, S. A. Lee, S. H. Kim, and J. Y. Jeon. 2018. “Intraoperative use of transcranial motor/sensory evoked potential monitoring in the clipping of intracranial aneurysms: evaluation of false-positive and false- negative cases.” J Neurosurg 130 (3): 936-948. https://doi.org/10.3171/2017. 8.JNS17791. https://www.ncbi.nlm.nih.gov/pubmed/29570008. 220 S. Luzzi, G. Mezzini, M. Del Maestro et al.

Ciappetta, P., S. Luzzi, R. De Blasi, and P. I. D'Urso. 2009. “Extracranial aneurysms of the posterior inferior cerebellar artery. Literature review and report of a new case.” J Neurosurg Sci 53 (4): 147-51. https://www.ncbi.nlm.nih.gov/pubmed/20220739. Ciappetta, P., G. Occhiogrosso, S. Luzzi, P. I. D'Urso, and A. P. Garribba. 2009. “Jugular tubercle and vertebral artery/posterior inferior cerebellar artery anatomic relationship: a 3- dimensional angiography computed tomography anthropometric study.” Neurosurgery 64 (5 Suppl 2): 429-36; discussion 436. https://doi.org/10.1227/01.NEU.0000337573. 17073.9F. https://www.ncbi.nlm.nih.gov/pubmed/19404121. De Tommasi, A., S. Luzzi, P. I. D'Urso, C. De Tommasi, N. Resta, and P. Ciappetta. 2008. “Molecular genetic analysis in a case of ganglioglioma: identification of a new mutation.” Neurosurgery 63 (5): 976-80; discussion 980. https://doi.org/10.1227/01.NEU. 0000327699.93146.CD. https://www.ncbi.nlm.nih.gov/pubmed/19005389. De Tommasi, A., G. Occhiogrosso, C. De Tommasi, S. Luzzi, A. Cimmino, and P. Ciappetta. 2007. “A polycystic variant of a primary intracranial leptomeningeal astrocytoma: case report and literature review.” World J Surg Oncol 5: 72. https://doi.org/10.1186/1477- 7819-5-72. https://www.ncbi.nlm.nih.gov/pubmed/17587463. Del Maestro, M., S. Luzzi, M. Gallieni, D. Trovarelli, A. V. Giordano, M. Gallucci, A. Ricci, and R. Galzio. 2018. “Surgical Treatment of Arteriovenous Malformations: Role of Preoperative Staged Embolization.” Acta Neurochir Suppl 129: 109-113. https://doi.org/10.1007/978-3-319-73739-3_16. https://www.ncbi.nlm.nih.gov/pubmed/ 30171322. Elsawaf, Y., S. Anetsberger, S. Luzzi, and S. K. Elbabaa. 2020. “Early Decompressive Craniectomy as Management for Severe TBI in the Pediatric Population: A Comprehensive Literature Review.” World Neurosurg. https://doi.org/10.1016/j.wneu.2020.02.065. https://www.ncbi.nlm.nih.gov/pubmed/32084616. Gallieni, M., M. Del Maestro, S. Luzzi, D. Trovarelli, A. Ricci, and R. Galzio. 2018. “Endoscope-Assisted Microneurosurgery for Intracranial Aneurysms: Operative Technique, Reliability, and Feasibility Based on 14 Years of Personal Experience.” Acta Neurochir Suppl 129: 19-24. https://doi.org/10.1007/978-3-319-73739-3_3. https://www. ncbi.nlm.nih.gov/pubmed/30171309. Grundy, B. L., P. B. Nelson, A. Lina, and R. C. Heros. 1982. “Monitoring of cortical somatosensory evoked potentials to determine the safety of sacrificing the anterior cerebral artery.” Neurosurgery 11 (1 Pt 1): 64-7. https://doi.org/10.1227/00006123-198207010- 00014. https://www.ncbi.nlm.nih.gov/pubmed/7110571. Guastamacchia, E., V. Triggiani, E. Tafaro, A. De Tommasi, C. De Tommasi, S. Luzzi, C. Sabba, F. Resta, M. R. Terreni, and M. Losa. 2007. “Evolution of a prolactin-secreting pituitary microadenoma into a fatal carcinoma: a case report.” Minerva Endocrinol 32 (3): 231-6. https://www.ncbi.nlm.nih.gov/pubmed/17912159. Guo, L., and A. W. Gelb. 2011. “The use of motor evoked potential monitoring during cerebral aneurysm surgery to predict pure motor deficits due to subcortical ischemia.” Clin Neurophysiol 122 (4): 648-55. https://doi.org/10.1016/j.clinph.2010.09.001. https://www. ncbi.nlm.nih.gov/pubmed/20869304. Holland, N. R. 1998. “Subcortical strokes from intracranial aneurysm surgery: implications for intraoperative neuromonitoring.” J Clin Neurophysiol 15 (5): 439-46. https://doi.org/ 10.1097/00004691-199809000-00008. https://www.ncbi.nlm.nih.gov/pubmed/9821071. Intraoperative Neurophysiological Monitoring in Neurovascular Surgery 221

Horiuchi, K., K. Suzuki, T. Sasaki, M. Matsumoto, J. Sakuma, Y. Konno, M. Oinuma, T. Itakura, and N. Kodama. 2005. “Intraoperative monitoring of blood flow insufficiency during surgery of middle cerebral artery aneurysms.” J Neurosurg 103 (2): 275-83. https://doi.org/10.3171/jns.2005.103.2.0275. https://www.ncbi.nlm.nih.gov/pubmed/161 75857. Jewett, D. L., M. N. Romano, and J. S. Williston. 1970. “Human auditory evoked potentials: possible brain stem components detected on the scalp.” Science 167 (3924): 1517-8. https://doi.org/10.1126/science.167.3924.1517. https://www.ncbi.nlm.nih.gov/pubmed/ 5415287. Kang, D. Z., Z. Y. Wu, Q. Lan, L. H. Yu, Z. Y. Lin, C. Y. Wang, and Y. X. Lin. 2007. “Combined monitoring of evoked potentials during microsurgery for lesions adjacent to the brainstem and intracranial aneurysms.” Chin Med J (Engl) 120 (18): 1567-73. https://www.ncbi.nlm.nih.gov/pubmed/17908471. Kataoka, K., R. Graf, G. Rosner, B. Radermacher, and W. D. Heiss. 1987. “Differentiation between cortical and subcortical lesions following focal ischemia in cats by multimodality evoked potentials.” J Neurol Sci 79 (1-2): 117-27. https://doi.org/10.1016/0022- 510x(87)90266-8. https://www.ncbi.nlm.nih.gov/pubmed/3612168. Krieger, D., H. P. Adams, F. Albert, M. von Haken, and W. Hacke. 1992. “Pure motor hemiparesis with stable somatosensory evoked potential monitoring during aneurysm surgery: case report.” Neurosurgery 31 (1): 145-50. https://doi.org/10.1227/00006123- 199207000-00024. https://www.ncbi.nlm.nih.gov/pubmed/1641096. Kubota, S., N. Tatara, A. Miyoshi, and C. Nagashima. 1992. “[An evaluation of temporary clipping during aneurysmal surgery: a retrospective study].” No Shinkei Geka 20 (12): 1247-54. https://www.ncbi.nlm.nih.gov/pubmed/1484591. Lesnick, J. E., P. E. Coyer, J. J. Michele, F. A. Welsh, and F. A. Simeone. 1986. “Comparison of the somatosensory evoked potential and the direct cortical response following severe incomplete global ischemia: selective vulnerability of the white matter conduction pathways.” Stroke 17 (6): 1247-50. https://doi.org/10.1161/01.str.17.6.1247. https://www. ncbi.nlm.nih.gov/pubmed/3810728. Little, J. R., R. P. Lesser, and H. Luders. 1987. “Electrophysiological monitoring during basilar aneurysm operation.” Neurosurgery 20 (3): 421-7. https://doi.org/10.1227/00006123- 198703000-00011. https://www.ncbi.nlm.nih.gov/pubmed/3574618. Luzzi, S., A. M. Crovace, L. Lacitignola, V. Valentini, E. Francioso, G. Rossi, G. Invernici, R. J. Galzio, and A. Crovace. 2018. “Engraftment, neuroglial transdifferentiation and behavioral recovery after complete spinal cord transection in rats.” Surg Neurol Int 9: 19. https://doi.org/10.4103/sni.sni_369_17. https://www.ncbi.nlm.nih.gov/pubmed/29497572. Luzzi, S., M. Del Maestro, D. Bongetta, C. Zoia, A. V. Giordano, D. Trovarelli, S. Raysi Dehcordi, and R. J. Galzio. 2018. “Onyx Embolization Before the Surgical Treatment of Grade III Spetzler-Martin Brain Arteriovenous Malformations: Single-Center Experience and Technical Nuances.” World Neurosurg 116: e340-e353. https://doi.org/10.1016/ j.wneu.2018.04.203. https://www.ncbi.nlm.nih.gov/pubmed/29751183. Luzzi, S., M. Del Maestro, S. K. Elbabaa, and R. Galzio. 2020. “Letter to the Editor Regarding “One and Done: Multimodal Treatment of Pediatric Cerebral Arteriovenous Malformations in a Single Anesthesia Event.” World Neurosurg 134: 660. https://doi.org/ 10.1016/j.wneu.2019.09.166. https://www.ncbi.nlm.nih.gov/pubmed/32059273. 222 S. Luzzi, G. Mezzini, M. Del Maestro et al.

Luzzi, S., M. Del Maestro, A. Elia, F. Vincitorio, G. Di Perna, F. Zenga, D. Garbossa, S. Elbabaa, and R. Galzio. 2019. “Morphometric and Radiomorphometric Study of the Correlation Between the Foramen Magnum Region and the Anterior and Posterolateral Approaches to Ventral Intradural Lesions.” Turk Neurosurg. https://doi.org/10. 5137/1019-5149.JTN.26052-19.2. https://www.ncbi.nlm.nih.gov/pubmed/31452176. Luzzi, S., M. Del Maestro, and R. Galzio. 2019. “Letter to the Editor. Preoperative embolization of brain arteriovenous malformations.” J Neurosurg: 1-2. https://doi.org/10.3171/2019. 6.JNS191541. https://www.ncbi.nlm.nih.gov/pubmed/31812150. https://thejns.org/view/ journals/j-neurosurg/aop/article-10.3171-2019.6.JNS191541/article-10.3171-2019.6. JNS191541.xml. Luzzi, S., M. Del Maestro, D. Trovarelli, D. De Paulis, S. R. Dechordi, H. Di Vitantonio, V. Di Norcia, D. F. Millimaggi, A. Ricci, and R. J. Galzio. 2019. “Endoscope-Assisted Microneurosurgery for Neurovascular Compression Syndromes: Basic Principles, Methodology, and Technical Notes.” Asian J Neurosurg 14 (1): 193-200. https://doi.org/ 10.4103/ajns.AJNS_279_17. https://www.ncbi.nlm.nih.gov/pubmed/30937034. Luzzi, S., A. Elia, M. Del Maestro, S. K. Elbabaa, S. Carnevale, F. Guerrini, M. Caulo, P. Morbini, and R. Galzio. 2019. “Dysembryoplastic Neuroepithelial Tumors: What You Need to Know.” World Neurosurg 127: 255-265. https://doi.org/10.1016/j.wneu. 2019.04.056. https://www.ncbi.nlm.nih.gov/pubmed/30981794. Luzzi, S., A. Elia, M. Del Maestro, A. Morotti, S. K. Elbabaa, A. Cavallini, and R. Galzio. 2019. “Indication, Timing, and Surgical Treatment of Spontaneous Intracerebral Hemorrhage: Systematic Review and Proposal of a Management Algorithm.” World Neurosurg. https://doi.org/10.1016/j.wneu.2019.01.016. https://www.ncbi.nlm.nih.gov/ pubmed/30677572. Luzzi, S., M. Gallieni, M. Del Maestro, D. Trovarelli, A. Ricci, and R. Galzio. 2018. “Giant and Very Large Intracranial Aneurysms: Surgical Strategies and Special Issues.” Acta Neurochir Suppl 129: 25-31. https://doi.org/10.1007/978-3-319-73739-3_4. https://www. ncbi.nlm.nih.gov/pubmed/30171310. Luzzi, S., A. Giotta Lucifero, M. Del Maestro, G. Marfia, S. E. Navone, M. Baldoncini, M. Nunez, A. Campero, S. K. Elbabaa, and R. Galzio. 2019. “Anterolateral Approach for Retrostyloid Superior Parapharyngeal Space Schwannomas Involving the Jugular Foramen Area: A 20-Year Experience.” World Neurosurg. https://doi.org/10.1016/j.wneu.2019. 09.006. https://www.ncbi.nlm.nih.gov/pubmed/31520759. Luzzi, S., C. Zoia, A. D. Rampini, A. Elia, M. Del Maestro, S. Carnevale, P. Morbini, and R. Galzio. 2019. “Lateral Transorbital Neuroendoscopic Approach for Intraconal Meningioma of the Orbital Apex: Technical Nuances and Literature Review.” World Neurosurg 131: 10-17. https://doi.org/10.1016/j.wneu.2019.07.152. https://www.ncbi. nlm.nih.gov/pubmed/31356977. Luzzi, Sabino, Alberto Maria Crovace, Mattia Del Maestro, Alice Giotta Lucifero, Samer K. Elbabaa, Benedetta Cinque, Paola Palumbo, Francesca Lombardi, Annamaria Cimini, Maria Grazia Cifone, Antonio Crovace, and Renato Galzio. 2019. “The cell-based approach in neurosurgery: ongoing trends and future perspectives.” Heliyon 5 (11). https://doi.org/10.1016/j.heliyon.2019.e02818. MacDonald, D. B., C. Dong, R. Quatrale, F. Sala, S. Skinner, F. Soto, and A. Szelenyi. 2019. “Recommendations of the International Society of Intraoperative Neurophysiology for intraoperative somatosensory evoked potentials.” Clin Neurophysiol 130 (1): 161-179. Intraoperative Neurophysiological Monitoring in Neurovascular Surgery 223

https://doi.org/10.1016/j.clinph.2018.10.008. https://www.ncbi.nlm.nih.gov/pubmed/304 70625. Manninen, P. H., A. M. Lam, and W. E. Nantau. 1990. “Monitoring of somatosensory evoked potentials during temporary arterial occlusion in cerebral aneurysm surgery.” J Neurosurg Anesthesiol 2 (2): 97-104. https://doi.org/10.1097/00008506-199006000-00007. https://www.ncbi.nlm.nih.gov/pubmed/15815328. Markand, O. N. 1994. “Brainstem auditory evoked potentials.” J Clin Neurophysiol 11 (3): 319-42. https://doi.org/10.1097/00004691-199405000-00004. https://www.ncbi.nlm.nih. gov/pubmed/8089204. Momma, F., A. D. Wang, and L. Symon. 1987. “Effects of temporary arterial occlusion on somatosensory evoked responses in aneurysm surgery.” Surg Neurol 27 (4): 343-52. https://doi.org/10.1016/0090-3019(87)90009-7. https://www.ncbi.nlm.nih.gov/pubmed/ 3824140. Mooij, J. J., A. Buchthal, and M. Belopavlovic. 1987. “Somatosensory evoked potential monitoring of temporary middle cerebral artery occlusion during aneurysm operation.” Neurosurgery 21 (4): 492-6. https://doi.org/10.1227/00006123-198710000-00009. https://www.ncbi.nlm.nih.gov/pubmed/3683782. Nathan, N., F. Tabaraud, F. Lacroix, D. Moulies, X. Viviand, A. Lansade, G. Terrier, and P. Feiss. 2003. “Influence of propofol concentrations on multipulse transcranial motor evoked potentials.” Br J Anaesth 91 (4): 493-7. https://doi.org/10.1093/bja/aeg211. https://www. ncbi.nlm.nih.gov/pubmed/14504148. Neuloh, G., and J. Schramm. 2004. “Monitoring of motor evoked potentials compared with somatosensory evoked potentials and microvascular Doppler ultrasonography in cerebral aneurysm surgery.” J Neurosurg 100 (3): 389-99. https://doi.org/10.3171/jns.2004.100. 3.0389. https://www.ncbi.nlm.nih.gov/pubmed/15035273. Ogilvy, C. S., B. S. Carter, S. Kaplan, C. Rich, and R. M. Crowell. 1996. “Temporary vessel occlusion for aneurysm surgery: risk factors for stroke in patients protected by induced hypothermia and hypertension and intravenous mannitol administration.” J Neurosurg 84 (5): 785-91. https://doi.org/10.3171/jns.1996.84.5.0785. https://www.ncbi.nlm.nih.gov/ pubmed/8622152. Palumbo, P., F. Lombardi, F. R. Augello, I. Giusti, S. Luzzi, V. Dolo, M. G. Cifone, and B. Cinque. 2019. “NOS2 inhibitor 1400W Induces Autophagic Flux and Influences Extracellular Vesicle Profile in Human Glioblastoma U87MG Cell Line.” Int J Mol Sci 20 (12). https://doi.org/10.3390/ijms20123010. https://www.ncbi.nlm.nih.gov/pubmed/ 31226744. Palumbo, P., F. Lombardi, G. Siragusa, S. R. Dehcordi, S. Luzzi, A. Cimini, M. G. Cifone, and B. Cinque. 2018. “Involvement of NOS2 Activity on Human Glioma Cell Growth, Clonogenic Potential, and Neurosphere Generation.” Int J Mol Sci 19 (9). https://doi.org/10.3390/ijms19092801. https://www.ncbi.nlm.nih.gov/pubmed/30227679. Quinones-Hinojosa, A., M. Alam, R. Lyon, C. D. Yingling, and M. T. Lawton. 2004. “Transcranial motor evoked potentials during basilar artery aneurysm surgery: technique application for 30 consecutive patients.” Neurosurgery 54 (4): 916-24; discussion 924. https://doi.org/10.1227/01.neu.0000114511.33035.af. https://www.ncbi.nlm.nih.gov/pub med/15046658. Raysi Dehcordi, S., A. Ricci, H. Di Vitantonio, D. De Paulis, S. Luzzi, P. Palumbo, B. Cinque, D. Tempesta, G. Coletti, G. Cipolloni, M. G. Cifone, and R. Galzio. 2017. “Stemness 224 S. Luzzi, G. Mezzini, M. Del Maestro et al.

Marker Detection in the Periphery of Glioblastoma and Ability of Glioblastoma to Generate Glioma Stem Cells: Clinical Correlations.” World Neurosurg 105: 895- 905. https://doi.org/10.1016/j.wneu.2017.05.099. https://www.ncbi.nlm.nih.gov/pubmed/ 28559081. Ricci, A., H. Di Vitantonio, D. De Paulis, M. Del Maestro, S. D. Raysi, D. Murrone, S. Luzzi, and R. J. Galzio. 2017. “Cortical aneurysms of the middle cerebral artery: A review of the literature.” Surg Neurol Int 8: 117. https://doi.org/10.4103/sni.sni_50_17. https://www. ncbi.nlm.nih.gov/pubmed/28680736. Sahaya, K., A. S. Pandey, B. G. Thompson, B. R. Bush, and D. N. Minecan. 2014. “Intraoperative monitoring for intracranial aneurysms: the Michigan experience.” J Clin Neurophysiol 31 (6): 563-7. https://doi.org/10.1097/WNP.0000000000000093. https://www.ncbi.nlm.nih.gov/pubmed/25462143. Sakashita, T., N. Oridate, A. Homma, Y. Nakamaru, F. Suzuki, H. Hatakeyama, S. Taki, Y. Sawamura, Y. Yamamoto, Y. Furuta, and S. Fukuda. 2009. “Complications of skull base surgery: an analysis of 30 cases.” Skull Base 19 (2): 127-32. https://doi.org/10.1055/s- 0028-1096201. https://www.ncbi.nlm.nih.gov/pubmed/19721768. Schramm, J., J. Zentner, and U. Pechstein. 1994. “Intraoperative SEP monitoring in aneurysm surgery.” Neurol Res 16 (1): 20-2. https://doi.org/10.1080/01616412.1994.11740185. https://www.ncbi.nlm.nih.gov/pubmed/7913523. Spena, G., E. Roca, F. Guerrini, P. P. Panciani, L. Stanzani, A. Salmaggi, S. Luzzi, and M. Fontanella. 2019. “Risk factors for intraoperative stimulation-related seizures during awake surgery: an analysis of 109 consecutive patients.” J Neurooncol. https://doi.org/ 10.1007/s11060-019-03295-9. https://www.ncbi.nlm.nih.gov/pubmed/31552589. Szelenyi, A., K. Kothbauer, A. B. de Camargo, D. Langer, E. S. Flamm, and V. Deletis. 2005. “Motor evoked potential monitoring during cerebral aneurysm surgery: technical aspects and comparison of transcranial and direct cortical stimulation.” Neurosurgery 57 (4 Suppl): 331-8; discussion 331-8. https://doi.org/10.1227/01.neu.0000176643.69108.fc. https:// www.ncbi.nlm.nih.gov/pubmed/16234682. Thomas, B., and D. Guo. 2017. “The Diagnostic Accuracy of Evoked Potential Monitoring Techniques During Intracranial Aneurysm Surgery for Predicting Postoperative Ischemic Damage: A Systematic Review and Meta-Analysis.” World Neurosurg 103: 829-840 e3. https://doi.org/10.1016/j.wneu.2017.04.071. https://www.ncbi.nlm.nih.gov/pubmed/ 28433839. Youssef, A. S., and A. E. Downes. 2009. “Intraoperative neurophysiological monitoring in vestibular schwannoma surgery: advances and clinical implications.” Neurosurg Focus 27 (4): E9. https://doi.org/10.3171/2009.8.FOCUS09144. https://www.ncbi.nlm.nih.gov/ pubmed/19795957. Zoia, C., D. Bongetta, G. Dorelli, S. Luzzi, M. D. Maestro, and R. J. Galzio. 2019. “Transnasal endoscopic removal of a retrochiasmatic cavernoma: A case report and review of literature.” Surg Neurol Int 10: 76. https://doi.org/10.25259/SNI-132-2019. https://www.ncbi.nlm.nih.gov/pubmed/31528414. Zoia, C., D. Bongetta, F. Guerrini, C. Alicino, A. Cattalani, S. Bianchini, R. J. Galzio, and S. Luzzi. 2018. “Outcome of elderly patients undergoing intracranial meningioma resection: a single center experience.” J Neurosurg Sci. https://doi.org/10.23736/S0390- 5616.18.04333-3. https://www.ncbi.nlm.nih.gov/pubmed/29808631. Intraoperative Neurophysiological Monitoring in Neurovascular Surgery 225

Zoia, C., F. Lombardi, M. R. Fiore, A. Montalbetti, A. Iannalfi, M. Sansone, D. Bongetta, F. Valvo, M. Del Maestro, S. Luzzi, and R. J. Galzio. 2020. “Sacral solitary fibrous tumour: surgery and hadrontherapy, a combined treatment strategy.” Rep Pract Oncol Radiother 25 (2): 241-244. https://doi.org/10.1016/j.rpor.2020.01.008. https://www.ncbi.nlm.nih. gov/pubmed/32025222.

Chapter 13

INTRAOPERATIVE EVALUATION OF CEREBRAL BLOOD FLOW

A. Pasqualin1,, MD, P. Meneghelli2, MD, F. Cozzi2, MD and A. Musumeci, MD2 1Section of Vascular Neurosurgery, Institute of Neurosurgery, University and City Hospital, Verona, Italy 2Department of Neurosurgery, University Hospital of Verona, Verona, Italy

ABSTRACT

The intraoperative measurement of the cerebral blood flow is based on direct and indirect methods. Both are considered as part of the neurosurgical armamentarium during neurovascular procedures. Qualitative information come from indirect methods as perivascular micro-Doppler, cerebral oximetry and indocyanine green videoangiography, whereas intraoperative flowmetry allows for a quantitative measurement of the cerebral blood flow. Based on a personal long-lasting experience, we herein highlight the advantages and limits of the Charbel Micro-flow probe during aneurysms surgery.

INTRODUCTION

To date, various methods have been proposed for intraoperative measurement of cerebral blood flow, with the aim to help neurosurgeons during vascular procedures (especially in aneurysm surgery); the utility of blood flow measurements has also spread to procedures on brain tumors, flanking the more commonly used intraoperative neurophysiological monitoring. Most of these methods allow only an indirect evaluation of cerebral blood flow, that does not allow a precise measurement of flow (in ml/ min) through the selected vessel. Only

 Corresponding Author’s Email: [email protected]. 228 A. Pasqualin, P. Meneghelli, F. Cozzi et al. intraoperative flowmetry (with a transit- time ultrasonic probe) allows a really quantitative measure of blood flow, and will be presented in detail in this chapter.

INDIRECT METHODS OF EVALUATION OF CEREBRAL BLOOD FLOW

The perivascular micro-Doppler has been – historically – the first tool used for an indirect evaluation of cerebral blood flow along the main cerebral arteries (Bailes et al., 1997; Laborde, Gilsbach, and Harders 1988; Fischer, Stadie, and Oertel 2010; Marchese et al., 2005; Siasios, Kapsalaki, and Fountas 2012; Stendel et al., 2000); although it has been used widely during aneurysm surgery, this methodology allows only to detect blood flow velocity, and cannot give a true quantitative estimate of blood flow through the artery itself. Cerebral oximetry allows an indirect evaluation of cerebral blood flow during surgery and is generally assessed through Near Infrared Spectroscopy (NIRS); although it has been widely used during procedures of carotid endarterectomy – with conflicting results (Manohar, Reddy, and Chakrabarti 2016; Waje, Maddali, and Chatterjee 2017) – there are still insufficient studies to support and validate its use in the neurosurgical setting (Ajayan et al., 2019). A more promising method of blood flow measurement is the application of the FLOW 800 analysis to indocyanine green (ICG) videoangiography; ICG videoangiography has been introduced in 2003 by Raabe (Raabe et al., 2003; Raabe et al. 2005) and is now widely used in the neurosurgical practice (de Oliveira et al., 2007; Dashti and Hernesniemi 2014; Abla and Lawton 2014; Della Puppa et al., 2014; Lai and Morgan 2014; Acerbi et al., 2018). FLOW 800 analysis is an algorithm (integrated in the surgical microscope) that calculates fluorescence intensities in the exposed areas, based on the average arbitrary intensity units (AIs) detected by the camera, and reconstructs maps of maximal fluorescence intensity and of delay times. Specifically, the maps are shown as gray scales of maximal fluorescence intensity, and also as color scales; in addition, the course of fluorescein can be further analyzed in any area of the exposed brain, by using freely definable Regions of Interest (ROIs) (Acerbi et al., 2018). Although this has been considered a useful tool in surgery of cerebral aneurysms (Goertz et al., 2019; Shah and Cohen-Gadol 2019) and brain arterio-venous malformations (Fukuda et al., 2015; Shah and Cohen-Gadol 2019), it must be considered only a semi quantitative measure of cerebral blood flow and cannot replace a truly quantitative method, as stated by the group of Vajkoczy (Prinz et al., 2014); in fact, the arbitrary intensity units (AIs) vary with the method of ICG injection, according to speed of injection, quantity of dye, proximity to vessel of interest, cardiac output and illumination (Morcos and Munich 2018).

INTRAOPERATIVE FLOWMETRY

Since the complete exclusion of an aneurysm – particularly if complex - bears the risk of inadvertent stenosis or even occlusion of the efferent (= distal) branches and subsequent clip- related ischemia, a precise intraoperative measure of blood flow is recommended during this kind of surgery. Visual examination alone cannot identify many instances of vessel compromise; even indocyanine green videoangiography (Abla and Lawton 2014; Raabe et al., Intraoperative Evaluation of Cerebral Blood Flow 229

2005) is of limited value, since it visualizes only superficial vessels in the field of view and does not give a quantitative measure of flow. Intraoperative flowmetry is still the only quantitative method of blood flow measurement; it has been introduced by Charbel in 1998 and consists of a micro probe based on transit-time ultrasonic technology (Charbel et al., 1998). The microprobe is positioned around a given artery, with a hooking maneuver, and gives a real estimate – in ml/min – of blood flow through that artery. In the last 20 years, other authors have described its use in vascular neurosurgery (Nakayama et al., 2001; Amin-Hanjani et al., 2006; Kirk et al., 2009; Della Puppa et al., 2014) confirming the validity of this technique. We have extensively used this ultrasound technique in aneurysm surgery on almost 500 patients (Pasqualin et al., 2018), and we are now applying this method also to AVM surgery. In the Charbel’s flow probe, two ultrasonic transducers are allocated in the tip of the probe with a fixed acoustic reflector in front of them: these structures define the sensing window (Figure 1). The two transducers emit and receive ultrasonic beams; once an ultrasonic beam starts from the first transducer, it will reach the reflector plate and subsequently the second transducer, and then the same will happen from the second transducer to the first. Once the probe is placed around the vessel, the ultrasound beams have to intersect the vessel upstream or downstream to reach the transducers. The ultrasound transit time is affected by the motion of flow through the vessel, and the difference between the upstream and downstream transit time is used to obtain the volume of flow (in ml/min) through the vessel insonated, which is calculated by the electronic flow detection unit (Charbel et al., 1998). This technique does not rely on direct probe contact and the insonation angle is fixed within the probe.

Figure 1. (a) principle of ultrasound transient time measurement based on a sensing probe with two transducers located on the trip of the probe and a reflector in front of them (see explanation in the text); (b) sensing probe mounted on a flexible support (in white); (c) measurement of flow on the right A1 tract (note the flexibility of the system).

Intraoperative flowmetry measurements are performed using a 1.5 and 2.0 mm tip Charbel Micro-flow probe (HQN 1.5MB, HQN 2MB and HQN 3MB respectively) connected to the the electronic flow detection unit (Transonic Flowmeter HT331 series, Transonic, USA). The measurement procedure starts with the accurate circumferential dissection of the vessel at risk in order to allow the correct position of the probe that should encircle the artery; then, the appropriate tip is chosen, according to the vessel’s size. After simple connection and calibration of the probe, recordings are obtained from the vessels at risk, completely immersed in topically irrigated Ringer’s solution, before and after the surgical clipping. Systemic blood pressure and 230 A. Pasqualin, P. Meneghelli, F. Cozzi et al.

PaCO2 levels are recorded at those times. The comparison between the basal and post-clip flow values identifies the possible presence of flow derangement, with consequent need for clip reposition in order to restore a normal perfusion (Amin-Hanjani et al., 2006). The mean basal flow values for the main vessels (internal carotid artery, middle cerebral artery, anterior communicating artery, pericallosal artery) recorded in our experience (Pasqualin et al., 2018) are reported in Table 1.

Table 1. Basal Flow Values (in ml/min) Detected on the Cerebral Arteries of Patients with Cerebral Aneurysms in the Two Surgical Series (Verona-Padua, 2001-2010 and Verona 2011-2016)

Verona and Padua 2001-2010 Verona 2011-2016 Flow values Flow values p value Range Range (± SD) (± SD) A1 tract 32.2 ± 19.3 9 - 68 33,2 ± 12.0 8 - 55 NS A2 tract 23.5 ± 10.6 2 - 65 24.4 ± 12.2 9 - 45 NS M1 tract 39.7 ± 17.3 29 - 80 58.2 ± 16.4 40 - 72 NS M2 tract 21.8 ± 11.2 2 - 89 22.1 ± 11.4 6 - 70 NS M3 tract 18.2 ± 10.4 3.8 - 45 15.8 ± 9.6 5 - 48 NS Supraclinoid ICA 47.8 ± 21.7 13 - 100 - - - Pericallosal A. 15.0 ± 5.3 9 - 27 11.1 ± 2.8 9 - 13 NS PICA 11.1 ± 6.3 6 - 22 - - -

As it appears from the Table, two cohorts of patients were evaluated: a) the first cohort from 2001 to 2010 (Verona and Padua Centers) consisting of 312 patients; b) the second cohort from 2011 to 2016 (Verona Center) consisting of 112 patients. When evaluating flow values in patients with ruptured versus unruptured aneurysms (Table 2) no significant difference was found, even by dividing the aneurysms according to their location.

Table 2. Basal Flow Values Detected on Cerebral Arteries in Patients with Unruptured and Ruptured Aneurysms (Verona and Padua Common Experience, 2001-2010)

Ruptured Aneurysms Unruptured Aneurysms p value Flow values ± SD Flow values ± SD A1 tract 28.6 ± 10.9 30.9 ± 14.5 NS A2 tract 24.7 ± 11.5 22.8 ± 10.3 NS M1 tract 39.7 ± 14.5 39.2 ± 16.0 NS M2 tract 21.7 ± 11.7 21.0 ± 10.6 NS M3 tract 18.8 ± 11.0 13.5 ± 5.6 NS Supraclinoid ICA. 50.2 ± 23.0 42.0 ± 19.9 NS Pericallosal A. 15.1 ± 4.6 14.9 ± 6.3 NS PICA - 12.2 ± 7.1 -

Intraoperative Evaluation of Cerebral Blood Flow 231

Although we are aware that other neurosurgeons – using the same probe – found slightly different values (Amin-Hanjani et al., 2006; Kirk et al., 2009; Nakayama et al., 2001) - possibly due to different modalities of anesthesia and different values of intraoperative CO2 -, our values are based on the largest reported series of patients with intracranial aneurysms submitted to intraoperative monitoring of blood flow (almost 500 cases) and should be considered very useful for reference data, especially when flow is not recorded before clipping the aneurysm (and this can happen for many reasons). A significant reduction of blood flow in the efferent vessel/s was observed after clipping in 16.9% of cases in the first cohort (Verona and Padua, years 2001- 2010) and in 5.3% of cases in the second cohort (Verona, years 2011 -2016); it could be promptly corrected - with clip repositioning – in 75% of cases in the first cohort and in 83% of cases in the second cohort. More specifically, in the first series after SAH 15 clip replacements were done on MCA (62%), 7 on ACoA and 2 on ICA; no reposition was needed for pericallosal artery and posterior circulation artery aneurysms. In the unruptured aneurysms group, 24 clip replacements were done on MCA (82%), 1 on ACoA, 2 on ICA, 2 on pericallosal artery aneurysms; no replacement was needed for posterior circulation artery aneurysms. In the second cohort, clip replacement was needed in 6 patients (2 in ruptured and 4 in unruptured aneurysms). In the unruptured aneurysms, clip repositioning was done in two cases for MCA aneurysm and in two cases for ACoA aneurysms; in the SAH patients, it was need in two cases for MCA aneurysm. The relation between intraoperative flow values and clipping- related ischemia is analyzed in Table 3.

Table 3. Relation Between Intraoperative Flow Values and Clipping Related Ischemia

Flow Baseline Aneurysm Ruptured Aneurysm after Further Clipping-related flow site Unruptured Size clip changes ischemia (ml/min) (ml/min) MCA Ruptured 16 mm 20 (M2) 9 15 (papav.) possible 32 MCA Ruptured 10 mm 45 (M2) 12 certain (clip repos.) ACoA Ruptured 9 mm 35 (A2) 14 - possible ACoA Ruptured 15 mm 18 (A2) 4 - certain MCA Ruptured 20 mm 19 (M2) 2 - certain MCA Ruptured 40 mm 21 (M2) 3.8 - certain MCA+ACoA Ruptured 10 mm 23 (A1) 8 - certain ACoA Ruptured 12 mm 48 (A2) 24 - certain ACoA Ruptured 18 mm 27 (A2) 18 - certain ICA Ruptured 18 mm 40 (M1) 10 - certain MCA Unruptured 25 mm 8 (M2) 2 - certain PCA Unruptured 15 mm 24 (P2) 4 - certain MCA Unruptured 15 mm 0 (M2) 0 - certain MCA Unruptured 18 mm 49 (M2) 12 - certain

As it appears from the table, clipping- related ischemia occurred mostly in ruptured aneurysms and in aneurysms of large size (with a diameter of at least 15 mm in 10 out of 14 232 A. Pasqualin, P. Meneghelli, F. Cozzi et al. cases); in this group of patients, the application of papaverine increased the flow in only 2 cases, but did not avoid ischemia. The validity of a comparison between basal and post-clip values is true in most – but not in all – cases, considering two phenomena that can occur after clipping, namely flow redistribution and post-occlusive hyperemia. Flow redistribution – i.e., decrease in flow in one efferent branch and increase in the other branch after clipping – is a rare phenomenon, observed in 5% of cases in our series; it is probably due to re-direction of flow caused by the position of the clip, or by spastic changes in one efferent vessel. In this situation, we have never observed ischemic postoperative deterioration, and we now consider the sum of the values detected in each efferent branch more important than the single value; in other words, if the sum of the post-clip values in the efferent branches is equal or similar to the sum of the pre-clip values, we do not try to reposition the clip. Post- occlusion hyperemia is observed when post-clip values are significantly increased (or even doubled) in comparison to pre-clip values; this event was observed in 15% - 20% of our cases submitted to temporary clipping. The occurrence of hyperemia immediately following experimental occlusion of a vessel has been already reported in the literature (Hossmann 1998); this phenomenon is probably short-lasting, roughly corresponding to the duration of the preceding ischemia (Hossmann 1998). Since the measurement of flow in our patients is not always performed immediately after the end of temporary occlusion, this could explain the relatively low detection of hyperemia after temporary occlusion in this series. Our impression is that hyperemia occurs immediately after restoration of flow, and can contribute to an overestimation of the real flow remaining in the efferent vessels after a period of temporary clipping; when in doubt, we suggest to record the flow values again, at least 10 – 15 minutes after the end of temporary clipping. A limitation of intraoperative flowmetry is still constituted by the probe size; in fact the minimum size of probes currently used for flowmetry (1.5 mm) is still too large to record flow in small vessels, such as the perforators and also – in most cases – the anterior choroidal artery; moreover, a measurement of flow through the posterior communicating artery is hampered by the small surgical field. Although technological advances should lead to the development of smaller probes in the near future, evaluation of flow in these vessels can be done only with indocyanine green videoangiography (Abla and Lawton 2014; de Oliveira et al., 2007) or indirectly through intraoperative neurophysiological monitoring with motor evoked potentials (Irie et al., 2010; Neuloh et al., 2004; Szelenyi et al., 2006).

CONCLUSION

In conclusion, intraoperative flowmetry allows – nowadays – a very accurate evaluation of blood flow through brain arteries of sufficient caliber, such as the internal carotid artery, the anterior, middle and posterior cerebral arteries and their branches, and the vertebro/ basilar system (comprehending the cerebellar arteries). For smaller vessels and in a narrow surgical field, evaluation of flow is difficult or not possible with the present probe; in these cases ICG videoangiography can give an indirect evaluation of vessel patency.

Intraoperative Evaluation of Cerebral Blood Flow 233

Figure 2. A 49-years-old man presenting with subarachnoid hemorrhage, Glasgow Coma Scale (GCS) 13 on admission, Fisher III on CT scan (A); digital subtraction angiography (DSA) showed a large (antero-inferiorly projecting) anterior communicating artery aneurysm (B), which was then submitted to endovascular occlusion with 7 coils (C); follow-up DSA showed recanalization of the aneurysm at 11 months (D); progressive enlargement of the sac at two years (E). The patient was then submitted to surgery: flow was measured on the A2 segments before clipping (F) then the clip was placed on the neck of the aneurysm (G); the flow measured after clipping did not show any significant difference from the pre-clip values (H). Post-operative DSA showed the correct exclusion of the aneurysm and normal injection of both the A2 segments. The patient did not show neurological deficits after surgery. 234 A. Pasqualin, P. Meneghelli, F. Cozzi et al.

REFERENCES

Abla, A. A., and M. T. Lawton. 2014. "Indocyanine green angiography for cerebral aneurysm surgery: advantages, limitations, and neurosurgeon intuition." World Neurosurg. 82 (5): e585-6. https://doi.org/10.1016/j.wneu.2014.08.019. Acerbi, F., I. G. Vetrano, T. Sattin, C. de Laurentis, L. Bosio, Z. Rossini, M. Broggi, M. Schiariti, and P. Ferroli. 2018. "The role of indocyanine green videoangiography with FLOW 800 analysis for the surgical management of central nervous system tumors: an update." Neurosurg. Focus 44 (6): E6. https://doi.org/10.3171/2018.3.focus1862. Ajayan, N., K. Thakkar, K. R. Lionel, and A. P. Hrishi. 2019. "Limitations of near infrared spectroscopy (NIRS) in neurosurgical setting: our case experience." J. Clin. Monit. Comput. 33 (4): 743-746. https://doi.org/10.1007/s10877-018-0209-1. Amin-Hanjani, S., G. Meglio, R. Gatto, A. Bauer, and F. T. Charbel. 2006. "The utility of intraoperative blood flow measurement during aneurysm surgery using an ultrasonic perivascular flow probe." Neurosurgery 58 (4 Suppl 2): ONS-305-12; discussion ONS- 312. https://doi.org/10.1227/01.neu.0000209339.47929.34. Bailes, J. E., L. S. Tantuwaya, T. Fukushima, G. W. Schurman, and D. Davis. 1997. "Intraoperative microvascular Doppler sonography in aneurysm surgery." Neurosurgery 40 (5): 965-70; discussion 970-2. Charbel, F. T., W. E. Hoffman, M. Misra, and L. Ostergren. 1998. "Ultrasonic perivascular flow probe: technique and application in neurosurgery." Neurol. Res. 20 (5): 439-42. Dashti, R., and J. Hernesniemi. 2014. "Intraoperative assessment of a quality of microneurosurgical clipping: role of indocyanine green videoangiography." World Neurosurg. 82 (5): e589-90. https://doi.org/10.1016/j.wneu.2014.08.060. de Oliveira, J. G., J. Beck, V. Seifert, M. J. Teixeira, and A. Raabe. 2007. "Assessment of flow in perforating arteries during intracranial aneurysm surgery using intraoperative near- infrared indocyanine green videoangiography." Neurosurgery 61 (3 Suppl): 63-72; discussion 72-3. https://doi.org/10.1227/01.neu.0000289715.18297.08. Della Puppa, A., F. Volpin, G. Gioffre, O. Rustemi, I. Troncon, and R. Scienza. 2014. "Microsurgical clipping of intracranial aneurysms assisted by green indocyanine videoangiography (ICGV) and ultrasonic perivascular microflow probe measurement." Clin. Neurol. Neurosurg. 116: 35-40. https://doi.org/10.1016/j.clineuro.2013.11.004. Fischer, G., A. Stadie, and J. M. Oertel. 2010. "Near-infrared indocyanine green videoangiography versus microvascular Doppler sonography in aneurysm surgery." Acta Neurochir. (Wien) 152 (9): 1519-25. https://doi.org/10.1007/s00701-010-0723-5. Fukuda, K., H. Kataoka, N. Nakajima, J. Masuoka, T. Satow, and K. Iihara. 2015. "Efficacy of FLOW 800 with indocyanine green videoangiography for the quantitative assessment of flow dynamics in cerebral arteriovenous malformation surgery." World Neurosurg. 83 (2): 203-10. https://doi.org/10.1016/j.wneu.2014.07.012. Goertz, L., M. Hof, M. Timmer, A. P. Schulte, C. Kabbasch, B. Krischek, P. Stavrinou, M. Reiner, R. Goldbrunner, and G. Brinker. 2019. "Application of Intraoperative FLOW 800 Indocyanine Green Videoangiography Color-Coded Maps for Microsurgical Clipping of Intracranial Aneurysms." World Neurosurg. 131: e192-e200. https://doi.org/10.1016/j. wneu.2019.07.113. Intraoperative Evaluation of Cerebral Blood Flow 235

Hossmann, K. A. 1998. "Experimental models for the investigation of brain ischemia." Cardiovasc. Res. 39 (1): 106-20. Irie, T., K. Yoshitani, Y. Ohnishi, M. Shinzawa, N. Miura, Y. Kusaka, S. Miyazaki, and S. Miyamoto. 2010. "The efficacy of motor-evoked potentials on cerebral aneurysm surgery and new-onset postoperative motor deficits." J. Neurosurg. Anesthesiol. 22 (3): 247-51. https://doi.org/10.1097/ANA.0b013e3181de4eae. Kirk, H. J., P. J. Rao, K. Seow, J. Fuller, N. Chandran, and V. G. Khurana. 2009. "Intra- operative transit time flowmetry reduces the risk of ischemic neurological deficits in neurosurgery." Br. J. Neurosurg. 23 (1): 40-7. https://doi.org/10.1080/02688690 80254 6880. Laborde, G., J. Gilsbach, and A. Harders. 1988. "The microvascular Doppler--an intraoperative tool for the treatment of large and giant aneurysms." Acta Neurochir. Suppl. (Wien) 42: 75-80. Lai, L. T., and M. K. Morgan. 2014. "Use of indocyanine green videoangiography during intracranial aneurysm surgery reduces the incidence of postoperative ischaemic complications." J. Clin. Neurosci. 21 (1): 67-72. https://doi.org/10.1016/j.jocn.2013.04. 002. Manohar, N., K. R. Reddy, and D. Chakrabarti. 2016. "Is NIRS-based Cerebral Oximetry Sufficient Monitoring Modality During ICG Utilization in CEA?" J. Neurosurg. Anesthesiol. 28 (1): 87-8. https://doi.org/10.1097/ana.0000000000000218. Marchese, E., A. Albanese, L. Denaro, A. Vignati, E. Fernandez, and G. Maira. 2005. "Intraoperative microvascular Doppler in intracranial aneurysm surgery." Surg Neurol 63 (4): 336-42; discussion 342. https://doi.org/10.1016/j.surneu.2004.05.031. Morcos, J. J., and S. A. Munich. 2018. "Editorial. The use of ICG videoangiography and FLOW 800 analysis." Neurosurg. Focus 45 (1): E8. https://doi.org/10.3171/2018.4. focus18207. Nakayama, N., S. Kuroda, K. Houkin, S. Takikawa, and H. Abe. 2001. "Intraoperative measurement of arterial blood flow using a transit time flowmeter: monitoring of hemodynamic changes during cerebrovascular surgery." Acta Neurochir. (Wien) 143 (1): 17-24. Neuloh, G., U. Pechstein, C. Cedzich, and J. Schramm. 2004. "Motor evoked potential monitoring with supratentorial surgery." Neurosurgery 54 (5): 1061-70; discussion 1070- 2. Pasqualin, A., P. Meneghelli, A. Musumeci, A. Della Puppa, G. Pavesi, G. Pinna, and R. Scienza. 2018. "Intraoperative Measurement of Arterial Blood Flow in Aneurysm Surgery." Acta Neurochir. Suppl. 129: 43-52. https://doi.org/10.1007/978-3-319-73739- 3_7. Prinz, V., N. Hecht, N. Kato, and P. Vajkoczy. 2014. "FLOW 800 allows visualization of hemodynamic changes after extracranial-to-intracranial bypass surgery but not assessment of quantitative perfusion or flow." Neurosurgery 10 Suppl 2: 231-8; discussion 238-9. https://doi.org/10.1227/neu.0000000000000277. Raabe, A., J. Beck, R. Gerlach, M. Zimmermann, and V. Seifert. 2003. "Near-infrared indocyanine green video angiography: a new method for intraoperative assessment of vascular flow." Neurosurgery 52 (1): 132-9; discussion 139. Raabe, A., P. Nakaji, J. Beck, L. J. Kim, F. P. Hsu, J. D. Kamerman, V. Seifert, and R. F. Spetzler. 2005. "Prospective evaluation of surgical microscope-integrated intraoperative 236 A. Pasqualin, P. Meneghelli, F. Cozzi et al.

near-infrared indocyanine green videoangiography during aneurysm surgery." J. Neurosurg. 103 (6): 982-9. https://doi.org/10.3171/jns.2005.103.6.0982. Shah, K. J., and A. A. Cohen-Gadol. 2019. "The Application of FLOW 800 ICG Videoangiography Color Maps for Neurovascular Surgery and Intraoperative Decision Making." World Neurosurg. 122: e186-e197. https://doi.org/10.1016/j.wneu.2018.09.195. Siasios, I., E. Z. Kapsalaki, and K. N. Fountas. 2012. "The role of intraoperative micro-Doppler ultrasound in verifying proper clip placement in intracranial aneurysm surgery." Neuroradiology 54 (10): 1109-18. https://doi.org/10.1007/s00234-012-1023-y. Stendel, R., T. Pietila, A. A. Al Hassan, A. Schilling, and M. Brock. 2000. "Intraoperative microvascular Doppler ultrasonography in cerebral aneurysm surgery." J. Neurol. Neurosurg. Psychiatry 68 (1): 29-35. Szelenyi, A., D. Langer, K. Kothbauer, A. B. De Camargo, E. S. Flamm, and V. Deletis. 2006. "Monitoring of muscle motor evoked potentials during cerebral aneurysm surgery: intraoperative changes and postoperative outcome." J. Neurosurg. 105 (5): 675-81. https://doi.org/10.3171/jns.2006.105.5.675. Waje, N. D., M. M. Maddali, and N. Chatterjee. 2017. "Cerebral Oximetry During CEA: Is It an Ideal Monitor?" J. Neurosurg. Anesthesiol. 29 (4): 465-466. https://doi. org/10.1097/ ana.0000000000000367.

SECTION III: CASE-BASED SURGICAL APPROACHES

Chapter 14

PTERIONAL APPROACH

S. Luzzi1,2,*, MD, PhD, M. Del Maestro2,3, MD, A. Giotta Lucifero1, MD and R. Galzio1,2, MD 1Neurosurgery Unit, Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy 2Neurosurgery Unit, Department of Surgical Sciences, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy 3PhD School in Experimental Medicine, Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy

ABSTRACT

Pterional approach is a workhorse in neurosurgery, to the point where perfect knowledge of its execution is an imprescindible aspect of the clinical neurosurgical practice. In neurovascular surgery, the pterional approach is used to clip most anterior circulation aneurysms, small basilar tip aneurysms, and arteriovenous malformations and cavernous hemangiomas involving the anterior part of the forebrain. In this chapter, we describe in detail the technical aspects of the pterional approach.

Keywords: aneurysms clipping, intracranial aneurysms, neurovascular surgery, pterional approach, sylvian fissure

1. INTRODUCTION

Introduced by Yasargil in the 1970s(MG 1987; Yaşargil M.G. 1975), the pterional or frontotemporosphenoidal approach is the most used approach in neurosurgery. It basically consists of the removal of a part of the frontal, temporal, and greater wing of the sphenoid bone to access the entire anterior and middle skull base.

* Corresponding Author’s Email: [email protected]. 240 S. Luzzi, M. Del Maestro, Giotta Lucifero et al.

Because of its wide versatility, the pterional approach may have several vascular targets, such as the internal carotid artery (ICA) with its branches, middle cerebral artery (MCA), anterior communicating artery (ACoA), basilar tip, P1 segment of the posterior cerebral artery (PCA), and proximal segment of the superior cerebellar artery (SCA). The possible intra-axial targets are the frontal, temporal, and parietal opercula, uncus, insula, basal ganglia, lateral ventricle, lamina terminalis, and interpeduncular fossa. The pterional approach may also be effectively used to treat orbital lesions. The key steps in the pterional approach are positioning, skin incision, dissection of the temporalis muscle, craniotomy, drilling of the greater sphenoid wing, and dural opening. The correct execution of all of these steps leads to splitting of the sylvian fissure, which is the door to the anterior and middle skull base.

2. INDICATIONS

The pterional approach allows full access to the most supratentorial basal cisterns and uppermost and median infratentorial cisterns. Accordingly, it is the approach of choice for most extra-axial lesions involving the anterior and middle skull base and a large proportion of intra- axial lesions affecting the anterior basal part of the forebrain and ventral midbrain. Regarding the neurovascular pathology, the pterional approach is indicated in most anterior circulation aneurysms and selected median and paramedian aneurysms involving the upper part of the posterior circulation. Arteriovenous malformations and cavernous hemangiomas involving the fronto-basal, anterior temporal, and opercular areas and the sylvian fissure are approached by the pterional route in most cases.

3. TECHNIQUE

3.1. Positioning

The pterional approach is performed with the patient in supine position, with the head fixed to a Mayfield–Kees or Sugita headrest and elevated above the level of the heart to allow optimal venous outflow. In the classic description by Yasargil in 1976, an extension of approximately 20° is recommended, so the malar eminence became the highest point of the patient’s head. Furthermore, a contralateral rotation of the head, ranging from 15° to 45° according to the different intradural neurovascular targets, was described (MG 1987; Yaşargil M.G. 1975) (Figure 1a). Chaddad-Neto et al. reported a study in which they revised the concept of extension and rotation of the head during the pterional approach for anterior circulation aneurysms (Chaddad- Neto et al. 2014). They demonstrated that excessive extension of the head causes a dramatic hindering of the optico-carotid complex by the orbital roof and deepens the anterior clinoid process and plane of the ICA, ultimately making anterior clinoidectomy and exposure of the ophthalmic artery more difficult. Furthermore, a rotation of 15° without extension makes the longest axis of the clinoid process parallel to the floor. Pterional Approach 241

Figure 1. Head positioning (A), skin mark (B) and incision (C) of a left pterional skin flap; (D) hemostatis of the skin flap with Raney clips; (E-J) construction of the galeal-pericranial flap; (J-N) incision of the superficial temporal fascia along with the temporalis muscle, and retrograde subperiosteal dissection of the deep temporalis fascia according to the Oikawa technique (submuscular technique); (O) identification of the main sutures of the pterional region and drawing of the bone flap; (P) first and second burr-hole placed just above the McCarty key and above the posterior root of the zygoma, respectively; (Q) partial drillig of the lateral third of the greater sphenoid wing before to complete the craniotomy; (R) frontotemporal bone flap.

Accordingly, they recommended a neutral extension of the head with 15° of rotation for ophthalmic, posterior communicating artery (PCoA), and anterior choroidal artery (AChA) aneurysms. Conversely, 15° of extension, with no more than 10°, or rotation is suggested for aneurysms involving the bifurcation of the MCA and ICA and anterior and inferior projecting ACoA aneurysms (Chaddad-Neto et al. 2014). Superior and posterior projecting aneurysms are better approached through the subfrontal perspective offered by the cranio-orbital (orbitopterional) approach.

3.2. Skin Incision and Soft Tissue Dissection

Local subcutaneous infiltration, along the skin incision mark, of a solution containing lidocaine hydrochloride 1% or mepivacaine chlorhydrate 2% plus adrenaline diluted in normal saline 0.9% (1:1) is recommended to promote easier detachment of the skin from the subcutaneous tissues and for antalgic purposes. The skin incision starts 1 cm in front of the tragus, anteriorly to the superficial temporal artery and auriculotemporal nerve. The incision curves upward, behind the hairline, to reach the midline. The skin incision should not involve the galea, which should be preserved and eventually used as an autologous patch graft in case of duraplasty. The galea is subperiosteally dissected to prepare a galeal-pericranial vascularized flap which, apart from duraplasty, can also be used to repair the frontal sinus in case of accidental violation. Hemostatic spring scalp clips, universally known as Raney clips, are generally placed along the edge of the incision to reflect the flap. In the classic description by Yasargil, the skin flap is divided by the temporalis muscle and reflected forward. The superficial and deep layers of the superficial temporal fascia, between 242 S. Luzzi, M. Del Maestro, Giotta Lucifero et al. which the frontal branch of the facial nerve runs along with a fat cushion, are separated to preserve the nerve (interfascial technique) (MG 1987; Yaşargil M.G. 1975). Two main variations have been reported in the following years: The first variant involves the incision of the superficial and deep layers of the superficial temporal fascia in a single leaflet, with subsequent exposure of the anterior third of the muscle without its superficial fascia (subfascial technique). The second variant encompasses the incision of the deep temporal fascia, subperiosteal blunt dissection of the temporalis muscle, and forward reflection of the skin and temporalis muscle as a single myocutaneous flap (submuscular technique). Presently, the submuscular technique is employed by most surgeons because it is faster and associated with a negligible risk of iatrogenic damage to the frontal branch of the facial nerve. Independent on the technique used for the preparation of the skin flap, the handling of the temporalis muscle should involve its incision just above the posterior root of the zygoma and subperiosteal detachment from the underlying bone in a retrograde superior to posterior and backward to forward direction (Oikawa technique) (Oikawa et al. 1996). In doing so, electrocauterization must be avoided to preserve the anatomical integrity of the deep fascia together with the blood supply to the muscle from the internal maxillary artery. Preservation of the deep fascia is the key to preventing temporalis muscle atrophy and related functional and cosmetic complications (Zabramski et al. 1998; Yasargil, Reichman, and Kubik 1987; Coscarella et al. 2000; Oikawa et al. 1996). A compulsive subperiosteal dissection of the temporalis muscle is also greatly helpful in the recognition of the sutures, this aspect being important for the following bone work. The fronto-zygomatic suture and superior aspect of the posterior root of the zygomatic process of the temporal bone inferiorly should always be exposed (Figure 1).

3.3. Bony Landmarks

Most advantages of the pterional approach lie in the perfect execution of the bone work. For this purpose, the key aspect is the recognition of all sutures involved in the pterional region, which serve as landmarks to localize some important bony structures, as the lateral third of the greater sphenoid wing or superior orbital fissure (SOF) and lesser sphenoid wing at the intracranial side. The identification of different sutures also allows tailoring of the pterional approach according to the site and extension of the lesion to be treated. The frontal, parietal, temporal, and sphenoid bones join at the level of the pterion. Identification of the coronal, spheno-parietal, spheno-frontal, spheno-squamosal, and spheno- zygomatic sutures is of utmost importance to localize the lateral third of the lesser sphenoid wing. Spheno-squamosal suture basically consists of the anterior third of the squamosal (temporo-parietal) suture. The highest point of the spheno-squamosal suture is located at the same level of the spheno-parietal and spheno-frontal sutures. Therefore, it marks the uppermost point of the greater sphenoid wing and, indirectly, the SOF. The spheno-zygomatic suture marks the midpoint of the lateral wall of the orbit, which is formed by the frontal process of the zygomatic bone anteriorly and greater sphenoid wing posteriorly. The fronto-zygomatic suture, located antero-superiorly to the spheno-zygomatic one, is located at the roof of the orbit. It also marks the limit between the lateral wall and roof. The supraorbital foramen and nerve should also be identified early to mentally mark the medial limit of the craniotomy (Figure 1o and Figures 2a and c). Rarely, the air frontal sinus extends Pterional Approach 243 laterally beyond the vertical line passing through the supraorbital foramen, and medial extension of the pterional approach is necessary. This last point is important to avoid accidental violation of the frontal sinus.

3.4. Craniotomy

Classically, the first burr hole is referred to as the MacCarty keyhole. The MacCarty keyhole is placed 5 mm behind the junction between the fronto-zygomatic, spheno-zygomatic, and fronto-sphenoidal sutures. It exposes the dura of the anterior fossa and periorbita, which are separated by the thin orbital roof (Shimizu et al. 2005; Aziz et al. 2002). However, in most cases, the exposure of the orbit and its contents is not necessary to treat the lesion for which the pterional approach has its indication. As a consequence, the first burr hole is generally placed just above the McCarty keyhole to access the anterior cranial fossa only. The second burr hole is placed at the level of the temporal squama, just above the posterior root of the zygoma, below the superior temporal line. Two burr holes are sufficient in most patients. However, if the dura is firmly adherent to the bone, a third burr hole can be placed at the level of the superior temporal line. This is in the case of older patients, patients with an internal frontal hyperostosis, or those with chronic renal insufficiency. Before performing craniotomy, partial drilling of the lateral third of the greater sphenoid wing will make the passage of the craniotome and detachment of the bone flap easier. In doing so, the cancellous bone of the greater sphenoid wing and middle meningeal artery may be sources of bleeding, which are, however, easily controlled with bone wax or bipolar cautery. The first cut starts at the caudal burr hole and is directed toward the orbital bar, at a point that depends on the need for exposure of the subfrontal area. Nevertheless, craniotomy is always lateral to the supraorbital foramen. In cases of hyperpneumatization of the frontal sinus or where a huge subfrontal exposure is unnecessary, the lateral limit of craniotomy at the level of the frontal bone may correspond to the superior temporal line. The second cut is directed from the first burr hole to the most anterior part of the first cut. The third cut connects the first and second burr holes in a curvilinear fashion at the level of the inferior aspect of the temporal fossa. Then, the bone flap is elevated with the aid of a Penfield Dissector No. 3, carefully completing the detachment of the underlying dura. In case the flap is still attached to the inner cortical surface of the greater sphenoid wing, it can be easily fractured. This first step of the approach does not differ from the fronto-temporal approach. The key aspect of the pterional approach consists of wide drilling of the lateral part of the greater sphenoid wing until the SOF. This allows for a full and unobstructed view of the sphenoidal part of the sylvian fissure, which must be intended as the access door of the entire anterior and middle skull base. Drilling of the lateral part of the greater sphenoid wing prevents brain retraction, at the point where the greater the drilling of this bony component, the lesser the need to use spatulas. The meningo-orbital artery serves as a useful landmark to early identify the lateral third of the SOF between the lesser and greater sphenoid wing. Skeletonization and partial enlargement of the SOF are helpful in allowing the forward reflection of the dural flap. Drilling of the orbital crests at the intracranial side of the orbital roof is strongly recommended to achieve a line of sight and working corridor as flat as possible to the anterior cranial fossa, once again avoiding brain retraction (Figures 2a–c).

244 S. Luzzi, M. Del Maestro, Giotta Lucifero et al.

3.5. Dura Opening

The dura may be opened in a curvilinear fashion around the SOF, but this cut is perpendicular to the sylvian fissure and middle meningeal artery. Sylvian veins may be potentially injured, especially in case of brain inflammation, and the middle meningeal artery can be a source of important bleeding. To prevent these complications, a cut parallel to the posterior ramus of the sylvian fissure can be added to two further curvilinear cuts at the level of the frontal and temporal lobes, making a Z-shaped opening. To avoid subdural blood collection, the placement of both tack-up sutures along the edge of the craniotomy and tenting temporary stiches of the dural leaflet are paramount to maintaining a clean surgical field (Figures 2d–e).

3.6. Intradural Corridors

The pterional approach is related to four well-defined surgical perspectives, namely, the subfrontal, transsylvian, pretemporal, and anterior subtemporal perspectives. The transsylvian corridor to the posterior fossa is posteriorly limited only by the Liliequist’s membrane, the opening of which allows access to the basilar tip and ventral midbrain. Thus, three different deep windows may be passed through. They are the optico-carotid, carotid-oculomotor, and supra-carotid windows. Splitting of the sylvian fissure is the key point for all of these corridors, which can be tailored on a case-by-case basis depending on the lesion to be treated. The combined subfrontal- transsylvian perspective is used for all anterior circulation aneurysms, whereas the aforementioned deep windows related to the transsylvian approach, together with the pretemporal and subtemporal perspectives, are the routes used for clipping of aneurysms involving the basilar tip, P1 segment of the PCA, and proximal segment of the SCA. Anterior clinoidectomy, both extradural and intradural, dramatically increases the working space around the proximal intradural portion of the optico-carotid complex, also allowing lateral mobilization of the carotid artery after opening of the distal dural ring (Figures 2f–k).

3.7. Closure

The dura is closed in a watertight fashion. In case of duraplasty, the galea is widely preferred to any other heterologous or synthetic substitutes. The bone flap is fixed to the skull with low-profile titanium plates, burr-hole covers, and 4-mm or 5-mm self-tapping screws (Figure 2l). In cases where full exposure of the temporal lobe is required, a bony gap may be the result of a wider drilling of the greater sphenoid wing and temporal squama. If a compulsive preservation of the deep fascia of the temporalis muscle has been conducted, this gap does not represent a problem because it is covered by the temporalis muscle itself. However, temporalis muscle atrophy may be the cause of a poor cosmetic outcome. A titanium mesh or, more rarely, an autologous fat graft may be used to cover the defect. Interrupted suture of the muscle is performed with reabsorbable 2/0 Vicryl stiches. A separate suture of the superficial temporalis fascia is recommended to achieve better functional and cosmetic results. In case of neither interfascial nor submuscular technique, the preparation of a muscle cuff along the superior Pterional Approach 245 temporal line is necessary to re-approximate the temporalis muscle in the pterional approach. A subcutaneous drainage, to be left in place for 2 days, may be useful in preventing blood collections or hematomas. To the best of our knowledge, interrupted suture with 3/0 silk stiches is the best technique to achieve a perfect aesthetic result (Figure 3).

Figure 2. (A-C) left fronto-temporal craniotomy and bone flap; exposure of the sphenoidal part of the sylvian fissure before (D) and after (E) drilling of the lateral third of the greater sphenoid wing; splitting of the sylvian fissure (F) and intradural exposure of optico-carotid complex (G), lamina terminalis (H), anterior cerebral artery (I), Liliequist’s membrane (J), and posterior communicating and posterior cerebral artery (K); osteosynthesis of the bone flap with titanium low profile burr-hole covers, minioplates and self-screwing unicortical screws (L).

246 S. Luzzi, M. Del Maestro, Giotta Lucifero et al.

Figure 3. Aesthetic and functional outcome in three different patients underwent to a pterional approach.

4. TAILORING OF THE PTERIONAL APPROACH

The pterional approach is versatile. It can be adapted to different lesions. The main parameters at the basis of its tailoring are the size of the bone flap and frontal versus temporal extension. Focusing on aneurysms, flaps with extremely limited size are generally required to clip, e.g., unruptured paraclinoid aneurysms, in which wide splitting of the sylvian fissure (transcavernous approach) is unnecessary. The same concept can be applied to small unruptured MCA bifurcation aneurysms, for which a limited opening on the posterior ramus of the sylvian fissure allows easy access of the lesion (minipterional approach). By contrast, larger bone flaps are required as a rule for ruptured aneurysms, large or giant aneurysms, and complex aneurysms of the ACoA complex. Regarding frontal versus temporal extension, a wider subfrontal extension is useful is instances where a subfrontal perspective is the prevalent working corridor. This is the case of superior and posterior projecting ACoA aneurysms. Conversely, a greater temporal extension is essential to clip basilar tip or P1 PCA aneurysms. Here, in fact, the pretemporal corridor is the elective route to the target. Indeed, in selected cases, the only temporal extension of the pterional approach may be claimed to achieve a combined transsylvian–pretemporal working perspective to the basilar tip (half-and-half approach) (Zenonos et al. 2019; Lanzino et al. 2018). The transsylvian exposure of the supraclinoid segment of the ICA and anterior and inferior projecting ACoA, anterior and MCA aneurysms, is related to a symmetrical uncovering of the frontal and temporal opercula on both sides of the sylvian fissure.

5. COMPLICATIONS AND PREVENTION

The pterional approach involves potential complications that can be functional or aesthetic in nature or both. Iatrogenic injury of the fronto-temporal branch of the facial nerve, temporalis muscle atrophy, masticatory imbalance, and hypo-anesthesia of the auricle and external acoustic meatus have a more concrete risk. The more frequent use of the submuscular technique has dramatically decreased the incidence of iatrogenic injury to the fronto-temporal branch of the facial nerve, which is associated with a poor aesthetic outcome mainly from the paralysis of the frontalis and corrugator supercilii muscles. Pterional Approach 247

The implementation of a subperiosteal blunt and “cold” (avoiding electrocauterization) dissection of the deep temporal fascia is the key to preventing postoperative atrophy of the temporalis muscle with all related aesthetic and functional complications, with masticatory imbalance first. The preservation of the auriculotemporal nerve during skin incision and soft tissue dissection prevents troublesome dysesthesia of the pinna.

6. ILLUSTRATIVE CASE

Multiple Bilateral Intracranial Aneurysms Treated in A Single-Stage Surgery with Pterional Approach

A 58-year-old woman was diagnosed with a subarachnoid hemorrhage mainly involving the left sylvian and parasellar cisterns. The patient has a Hunt–Hess score of 4. CT angiography and digital subtraction angiography (DSA) revealed six aneurysms, of which three are left and three are right sided. On the left side, MCA bifurcation, PCoA, and AChA aneurysms were found. On the right side, PCoA, M1 MCA, and MCA bifurcation aneurysms were detected. Because of the poor neurological condition, the patient was a candidate for late surgery. After 60 days, after partial neurological recovery, the patient underwent left pterional transsylvian approach, in which five of six aneurysms were clipped in a single-stage surgery. Noteworthy, a suprachiasmatic corridor was used to clip the contralateral, unruptured, supratentorial, and medial projecting PCoA aneurysms. Endoscopic assistance was of utmost importance during the clip ligation. The right unruptured M1 MCA aneurysm was also clipped through the same corridor (Figure 4). The left giant partially thrombosed MCA bifurcation aneurysm was clipped after 2 months using a right pterional approach. The overall outcome was good, and the patient completely recovered after 3 months with no deficits.

Figure 4. (A) 3D volume rendering pre-operative CT-angio of a 58 years-old female diagnosed with a subarachnoid hemorrhage. Six intracranial aneurysms were found; anterior (B) and lateral (C) projection DSA after the injection of the right ICA revealing a PCoA, an M1 MCA, and an MCA bifurcation aneurysm; Anterior (D) and lateral (E) projection DSA of the left ICA showing an MCA bifurcation, a PCoA, and an AChA aneurysm; intraoperative view during left pterional approach for clipping of left MCA bifurcation (F-G), left PCoA (H), left AChA (I), right PCoA (J), and right M1 MCA (K) aneurysm, respectively; (L) 3D volume rendering post-operative CT-angio, anterior (M) and lateral (N) projection DSA of the right ICA and anterior (O) and lateral (P) projection DSA of the left ICA showing the complete exclusion of the 5 aneurysms treated by means of a single-stage pterional approach. 248 S. Luzzi, M. Del Maestro, Giotta Lucifero et al.

7. DISCUSSION

After >40 years from its original description by Yasargil (MG 1987; Yaşargil M.G. 1975), the pterional approach is presently the most used skull base approach in neurosurgery. It is routinely employed in the treatment of neurovascular pathologies and extra- and intra-axial tumors of, or close to, the anterior and middle skull base. Noteworthy, despite the revolution of the treatment techniques in neurovascular surgery (Ciappetta, Luzzi, et al. 2009; Ciappetta, Occhiogrosso, et al. 2009; Del Maestro et al. 2018; Gallieni et al. 2018; S. Luzzi, Del Maestro, et al. 2018; S. Luzzi, Del Maestro, and Galzio 2019; S. Luzzi, Elia, Del Maestro, Morotti, et al. 2019; S. Luzzi, Gallieni, et al. 2018; Ricci et al. 2017; S. Luzzi et al. 2020), the pterional approach has maintained its primary role in the surgical treatment of most vascular lesions. Nevertheless, it also has obtained technical evolution in accordance with the development of skull base surgery techniques (Arnaout et al. 2019; S. Luzzi, Del Maestro, Elia, et al. 2019; S. Luzzi, Del Maestro, Trovarelli, et al. 2019; S. Luzzi, Zoia, et al. 2019; C. Zoia et al. 2019), on a par with other fields of neurosurgery (Bellantoni et al. 2019; Cheng, Shetty, and Sekhar 2018; De Tommasi et al. 2008; De Tommasi et al. 2007; Guastamacchia et al. 2007; Sabino Luzzi, Crovace, et al. 2019; S. Luzzi, Crovace, et al. 2018; S. Luzzi, Elia, Del Maestro, Elbabaa, et al. 2019; S. Luzzi, Giotta Lucifero, et al. 2019; Palumbo et al. 2019; Palumbo et al. 2018; Raysi Dehcordi et al. 2017; Spena et al. 2019; C. Zoia et al. 2018; Bongetta et al. 2019; Ciappetta et al. 2008; De Tommasi, Cascardi, et al. 2006; De Tommasi, De Tommasi, et al. 2006; Millimaggi et al. 2018; Antonosante et al. 2020; Campanella et al. 2020; Cesare Zoia et al. 2020; Elsawaf et al. 2020). Several morphometric and dimensional studies have led to better understanding of the technical aspects at the base of tailoring of the pterional approach, in accordance with the lesion to be treated (Park et al. 2018; Yagmurlu et al. 2017; Mocco et al. 2013; Bir et al. 2017). They also have led to drawing the exact limits between the pterional approach and other skull base approaches, classically considered as extensions of it, for what is regarded as the overall surgical freedom to the target. The reported illustrative case confirms the extreme versatility of the pterional approach. Some technical tips of the workhorse approach by definition in neurosurgery deserve to be stressed, from skin incision to skin closure. The skin incision must be placed behind the hairline to achieve the best aesthetic outcome and must not be excessively anterior in those cases where full exposure of the posterior ramus of the sylvian fissure is planned. This is because the more anterior the skin incision is, the more limited and anterior the size of the bone flap will be. Another reason to avoid an excessively anterior skin incision lies in the fact that the splitting of the sylvian fissure should start at the tip of the pars triangularis of the frontal operculum, which should remain uncovered in case of an excessively anterior bone flap. In performing the blunt subperiosteal dissection of the temporalis muscle according to the Oikawa technique, the best method to preserve the deep fascia is to detach the muscle from the back to the front but especially upward toward the superior temporal line, which is the point where the muscle is more tenaciously attached. In doing so, paradoxically, sharp tips such as those of the Langenbeck elevator or even the tip of the knife plays better than blunt ones because the deep temporal fascia is extremely thin and may be damaged by coarse instruments. A simple trick to ensure adequately low muscle detachment is to expose the midpoint of the spheno-zygomatic suture. The key aspect of the pterional approach is drilling the most lateral Pterional Approach 249 aspect of the greater sphenoid wing and orbital crests. This step allows for a working corridor that is fully parallel to the anterior skull base, simultaneously avoiding the need of brain retraction. Compared with that in the front-temporal approach, drilling of the sphenoid wing also shallows the target and shortens the working distance. During closure, the placement of some hitch stiches onto the temporal squama reduces the risk of epidural hematoma. The bone gap remaining on the temporal side of the bone flap can be filled with hemostatic and fibrin glue sealant. Bone dust can also be used for this purpose and has an intrinsic hemostatic power. To obtain a good aesthetic outcome, the use of silk or Ethilon 3/0 stiches is strongly recommended.

CONCLUSION

The pterional approach is the skull base approach with excellence in neurosurgery. Its tremendous versatility makes it suitable for most lesions involving the anterior and middle skull base. In neurovascular surgery, the pterional approach is a milestone in the treatment of most aneurysms involving the anterior circulation and basilar tip aneurysms. Accurate planning, meticulous execution, and vast knowledge of the skull base anatomy are essential factors to exploit all advantages of this approach, simultaneously decreasing the risks of complications.

REFERENCES

Antonosante, A., L. Brandolini, M. d'Angelo, E. Benedetti, V. Castelli, M. Del Maestro, S. Luzzi, A. Giordano, A. Cimini, and M. Allegretti. 2020. “Autocrine CXCL8-dependent invasiveness triggers modulation of actin cytoskeletal network and cell dynamics.” Aging (Albany NY) 12. https://doi.org/10.18632/aging.102733. https://www.ncbi.nlm.nih.gov/ pubmed/31986121. Arnaout, M. M., S. Luzzi, R. Galzio, and K. Aziz. 2019. “Supraorbital keyhole approach: Pure endoscopic and endoscope-assisted perspective.” Clin Neurol Neurosurg 189: 105623. https://doi.org/10.1016/j.clineuro.2019.105623. https://www.ncbi.nlm.nih.gov/pubmed/ 31805490. Aziz, K. M., S. C. Froelich, P. L. Cohen, A. Sanan, J. T. Keller, and H. R. van Loveren. 2002. “The one-piece orbitozygomatic approach: the MacCarty burr hole and the inferior orbital fissure as keys to technique and application.” Acta Neurochir (Wien) 144 (1): 15-24. https://doi.org/10.1007/s701-002-8270-1. https://www.ncbi.nlm.nih.gov/pubmed/ 11807643. Bellantoni, G., F. Guerrini, M. Del Maestro, R. Galzio, and S. Luzzi. 2019. “Simple schwannomatosis or an incomplete Coffin-Siris? Report of a particular case.” eNeurologicalSci 14: 31-33. https://doi.org/10.1016/j.ensci.2018.11.021. https://www. ncbi.nlm.nih.gov/pubmed/30555950. 250 S. Luzzi, M. Del Maestro, Giotta Lucifero et al.

Bir, S. C., T. Maiti, S. Konar, and A. Nanda. 2017. “Comparison of the Surgical Outcome of Pterional and Frontotemporal-Orbitozygomatic Approaches and Determination of Predictors of Recurrence for Sphenoid Wing Meningiomas.” World Neurosurg 99: 308- 319. https://doi.org/10.1016/j.wneu.2016.10.057. https://www.ncbi.nlm.nih.gov/pubmed/ 27771478. Bongetta, D., C. Zoia, S. Luzzi, M. D. Maestro, A. Peri, G. Bichisao, D. Sportiello, I. Canavero, A. Pietrabissa, and R. J. Galzio. 2019. “Neurosurgical issues of bariatric surgery: A systematic review of the literature and principles of diagnosis and treatment.” Clin Neurol Neurosurg 176: 34-40. https://doi.org/10.1016/j.clineuro.2018.11.009. https://www.ncbi. nlm.nih.gov/pubmed/30500756. Campanella, R., L. Guarnaccia, C. Cordiglieri, E. Trombetta, M. Caroli, G. Carrabba, N. La Verde, P. Rampini, C. Gaudino, A. Costa, S. Luzzi, G. Mantovani, M. Locatelli, L. Riboni, S. E. Navone, and G. Marfia. 2020. “Tumor-Educated Platelets and Angiogenesis in Glioblastoma: Another Brick in the Wall for Novel Prognostic and Targetable Biomarkers, Changing the Vision from a Localized Tumor to a Systemic Pathology.” Cells 9 (2). https://doi.org/10.3390/cells9020294. https://www.ncbi.nlm.nih.gov/pubmed/31991805. Chaddad-Neto, F., H. L. Doria-Netto, J. M. Campos-Filho, E. S. Ribas, G. C. Ribas, and Ed Oliveira. 2014. “Head positioning for anterior circulation aneurysms microsurgery.” Arq Neuropsiquiatr 72 (11): 832-40. https://doi.org/10.1590/0004-282x20140156. https://www.ncbi.nlm.nih.gov/pubmed/25410448. Cheng, C. Y., R. Shetty, and L. N. Sekhar. 2018. “Microsurgical Resection of a Large Intraventricular Trigonal Tumor: 3-Dimensional Operative Video.” Oper Neurosurg (Hagerstown) 15 (6): E92-E93. https://doi.org/10.1093/ons/opy068. https://www.ncbi. nlm.nih.gov/pubmed/29618124. Ciappetta, P., I. D'Urso P, S. Luzzi, G. Ingravallo, A. Cimmino, and L. Resta. 2008. “Cystic dilation of the ventriculus terminalis in adults.” J Neurosurg Spine 8 (1): 92-9. https://doi.org/10.3171/SPI-08/01/092. https://www.ncbi.nlm.nih.gov/pubmed/18173354. Ciappetta, P., S. Luzzi, R. De Blasi, and P. I. D'Urso. 2009. “Extracranial aneurysms of the posterior inferior cerebellar artery. Literature review and report of a new case.” J Neurosurg Sci 53 (4): 147-51. https://www.ncbi.nlm.nih.gov/pubmed/20220739. Ciappetta, P., G. Occhiogrosso, S. Luzzi, P. I. D'Urso, and A. P. Garribba. 2009. “Jugular tubercle and vertebral artery/posterior inferior cerebellar artery anatomic relationship: a 3- dimensional angiography computed tomography anthropometric study.” Neurosurgery 64 (5 Suppl 2): 429-36; discussion 436. https://doi.org/10.1227/01.NEU.0000337573. 17073.9F. https://www.ncbi.nlm.nih.gov/pubmed/19404121. Coscarella, E., A. G. Vishteh, R. F. Spetzler, E. Seoane, and J. M. Zabramski. 2000. “Subfascial and submuscular methods of temporal muscle dissection and their relationship to the frontal branch of the facial nerve. Technical note.” J Neurosurg 92 (5): 877- 80. https://doi.org/10.3171/jns.2000.92.5.0877. https://www.ncbi.nlm.nih.gov/pubmed/ 10794306. De Tommasi, A., P. Cascardi, C. De Tommasi, S. Luzzi, and P. Ciappetta. 2006. “Emergency surgery in a severe penetrating skull base injury by a screwdriver: case report and literature review.” World J Emerg Surg 1: 36. https://doi.org/10.1186/1749-7922-1-36. https://www. ncbi.nlm.nih.gov/pubmed/17169147. De Tommasi, A., C. De Tommasi, E. Lauta, S. Luzzi, A. Cimmino, and P. Ciappetta. 2006. “Pre-operative subarachnoid haemorrhage in a patient with spinal tumour.” Cephalalgia Pterional Approach 251

26 (7): 887-90. https://doi.org/10.1111/j.1468-2982.2006.01122.x. https://www.ncbi.nlm. nih.gov/pubmed/16776708. De Tommasi, A., S. Luzzi, P. I. D'Urso, C. De Tommasi, N. Resta, and P. Ciappetta. 2008. “Molecular genetic analysis in a case of ganglioglioma: identification of a new mutation.” Neurosurgery 63 (5): 976-80; discussion 980. https://doi.org/10.1227/01.NEU. 0000327699.93146.CD. https://www.ncbi.nlm.nih.gov/pubmed/19005389. De Tommasi, A., G. Occhiogrosso, C. De Tommasi, S. Luzzi, A. Cimmino, and P. Ciappetta. 2007. “A polycystic variant of a primary intracranial leptomeningeal astrocytoma: case report and literature review.” World J Surg Oncol 5: 72. https://doi.org/10.1186/1477- 7819-5-72. https://www.ncbi.nlm.nih.gov/pubmed/17587463. Del Maestro, M., S. Luzzi, M. Gallieni, D. Trovarelli, A. V. Giordano, M. Gallucci, A. Ricci, and R. Galzio. 2018. “Surgical Treatment of Arteriovenous Malformations: Role of Preoperative Staged Embolization.” Acta Neurochir Suppl 129: 109-113. https://doi.org/ 10.1007/978-3-319-73739-3_16. https://www.ncbi.nlm.nih.gov/pubmed/30171322. Elsawaf, Y., S. Anetsberger, S. Luzzi, and S. K. Elbabaa. 2020. “Early Decompressive Craniectomy as Management for Severe TBI in the Pediatric Population: A Comprehensive Literature Review.” World Neurosurg. https://doi.org/10.1016/j.wneu.2020.02.065. https://www.ncbi.nlm.nih.gov/pubmed/32084616. Gallieni, M., M. Del Maestro, S. Luzzi, D. Trovarelli, A. Ricci, and R. Galzio. 2018. “Endoscope-Assisted Microneurosurgery for Intracranial Aneurysms: Operative Technique, Reliability, and Feasibility Based on 14 Years of Personal Experience.” Acta Neurochir Suppl 129: 19-24. https://doi.org/10.1007/978-3-319-73739-3_3. https://www. ncbi.nlm.nih.gov/pubmed/30171309. Guastamacchia, E., V. Triggiani, E. Tafaro, A. De Tommasi, C. De Tommasi, S. Luzzi, C. Sabba, F. Resta, M. R. Terreni, and M. Losa. 2007. “Evolution of a prolactin-secreting pituitary microadenoma into a fatal carcinoma: a case report.” Minerva Endocrinol 32 (3): 231-6. https://www.ncbi.nlm.nih.gov/pubmed/17912159. Lanzino, G., D. Cannizzaro, S. L. Villa, and F. B. Meyer. 2018. “Pretemporal (“Half-and-Half”) Approach for Posterior Circulation Aneurysms in a Patient With Internal Carotid Artery Occlusion.” Oper Neurosurg (Hagerstown) 14 (4): 457. https://doi.org/10.1093/ons/ opx153. https://www.ncbi.nlm.nih.gov/pubmed/28961943. Luzzi, S., A. M. Crovace, L. Lacitignola, V. Valentini, E. Francioso, G. Rossi, G. Invernici, R. J. Galzio, and A. Crovace. 2018. “Engraftment, neuroglial transdifferentiation and behavioral recovery after complete spinal cord transection in rats.” Surg Neurol Int 9: 19. https://doi.org/10.4103/sni.sni_369_17. https://www.ncbi.nlm.nih.gov/pubmed/29497572. Luzzi, S., M. Del Maestro, D. Bongetta, C. Zoia, A. V. Giordano, D. Trovarelli, S. Raysi Dehcordi, and R. J. Galzio. 2018. “Onyx Embolization Before the Surgical Treatment of Grade III Spetzler-Martin Brain Arteriovenous Malformations: Single-Center Experience and Technical Nuances.” World Neurosurg 116: e340-e353. https://doi.org/10.1016/j. wneu.2018.04.203. https://www.ncbi.nlm.nih.gov/pubmed/29751183. Luzzi, S., M. Del Maestro, S. K. Elbabaa, and R. Galzio. 2020. “Letter to the Editor Regarding “One and Done: Multimodal Treatment of Pediatric Cerebral Arteriovenous Malformations in a Single Anesthesia Event”.” World Neurosurg 134: 660. https://doi.org/ 10.1016/j.wneu.2019.09.166. https://www.ncbi.nlm.nih.gov/pubmed/32059273. Luzzi, S., M. Del Maestro, A. Elia, F. Vincitorio, G. Di Perna, F. Zenga, D. Garbossa, S. Elbabaa, and R. Galzio. 2019. “Morphometric and Radiomorphometric Study of the 252 S. Luzzi, M. Del Maestro, Giotta Lucifero et al.

Correlation Between the Foramen Magnum Region and the Anterior and Posterolateral Approaches to Ventral Intradural Lesions.” Turk Neurosurg. https://doi.org/10.5137/1019- 5149.JTN.26052-19.2. https://www.ncbi.nlm.nih.gov/pubmed/31452176. Luzzi, S., M. Del Maestro, and R. Galzio. 2019. “Letter to the Editor. Preoperative embolization of brain arteriovenous malformations.” J Neurosurg: 1-2. https://doi.org/10.3171/2019. 6.JNS191541 https://www.ncbi.nlm.nih.gov/pubmed/31812150. https://thejns.org/view/ journals/j-neurosurg/aop/article-10.3171-2019.6.JNS191541/article-10.3171- 2019.6.JNS191541.xml. Luzzi, S., M. Del Maestro, D. Trovarelli, D. De Paulis, S. R. Dechordi, H. Di Vitantonio, V. Di Norcia, D. F. Millimaggi, A. Ricci, and R. J. Galzio. 2019. “Endoscope-Assisted Microneurosurgery for Neurovascular Compression Syndromes: Basic Principles, Methodology, and Technical Notes.” Asian J Neurosurg 14 (1): 193-200. https://doi.org/ 10.4103/ajns.AJNS_279_17. https://www.ncbi.nlm.nih.gov/pubmed/30937034. Luzzi, S., A. Elia, M. Del Maestro, S. K. Elbabaa, S. Carnevale, F. Guerrini, M. Caulo, P. Morbini, and R. Galzio. 2019. “Dysembryoplastic Neuroepithelial Tumors: What You Need to Know.” World Neurosurg 127: 255-265. https://doi.org/10.1016/j.wneu. 2019.04.056. https://www.ncbi.nlm.nih.gov/pubmed/30981794. Luzzi, S., A. Elia, M. Del Maestro, A. Morotti, S. K. Elbabaa, A. Cavallini, and R. Galzio. 2019. “Indication, Timing, and Surgical Treatment of Spontaneous Intracerebral Hemorrhage: Systematic Review and Proposal of a Management Algorithm.” World Neurosurg. https://doi.org/10.1016/j.wneu.2019.01.016. https://www.ncbi.nlm.nih.gov/ pubmed/30677572. Luzzi, S., M. Gallieni, M. Del Maestro, D. Trovarelli, A. Ricci, and R. Galzio. 2018. “Giant and Very Large Intracranial Aneurysms: Surgical Strategies and Special Issues.” Acta Neurochir Suppl 129: 25-31. https://doi.org/10.1007/978-3-319-73739-3_4. https://www. ncbi.nlm.nih.gov/pubmed/30171310. Luzzi, S., A. Giotta Lucifero, M. Del Maestro, G. Marfia, S. E. Navone, M. Baldoncini, M. Nunez, A. Campero, S. K. Elbabaa, and R. Galzio. 2019. “Anterolateral Approach for Retrostyloid Superior Parapharyngeal Space Schwannomas Involving the Jugular Foramen Area: A 20-Year Experience.” World Neurosurg. https://doi.org/10.1016/j.wneu. 2019.09.006. https://www.ncbi.nlm.nih.gov/pubmed/31520759. Luzzi, S., C. Zoia, A. D. Rampini, A. Elia, M. Del Maestro, S. Carnevale, P. Morbini, and R. Galzio. 2019. “Lateral Transorbital Neuroendoscopic Approach for Intraconal Meningioma of the Orbital Apex: Technical Nuances and Literature Review.” World Neurosurg 131: 10-17. https://doi.org/10.1016/j.wneu.2019.07.152. https://www.ncbi. nlm.nih.gov/pubmed/31356977. Luzzi, Sabino, Alberto Maria Crovace, Mattia Del Maestro, Alice Giotta Lucifero, Samer K. Elbabaa, Benedetta Cinque, Paola Palumbo, Francesca Lombardi, Annamaria Cimini, Maria Grazia Cifone, Antonio Crovace, and Renato Galzio. 2019. “The cell-based approach in neurosurgery: ongoing trends and future perspectives.” Heliyon 5 (11). https://doi.org/10.1016/j.heliyon.2019.e02818. Millimaggi, D. F., V. D. Norcia, S. Luzzi, T. Alfiero, R. J. Galzio, and A. Ricci. 2018. “Minimally Invasive Transforaminal Lumbar Interbody Fusion with Percutaneous Bilateral Pedicle Screw Fixation for Lumbosacral Spine Degenerative Diseases. A Retrospective Database of 40 Consecutive Cases and Literature Review.” Turk Neurosurg Pterional Approach 253

28 (3): 454-461. https://doi.org/10.5137/1019-5149.JTN.19479-16.0. https://www.ncbi. nlm.nih.gov/pubmed/28481388. Mocco, J., R. J. Komotar, D. M. Raper, C. P. Kellner, E. S. Connolly, and R. A. Solomon. 2013. “The modified pterional keyhole craniotomy for open cerebrovascular surgery: a new workhorse?” J Neurol Surg A Cent Eur Neurosurg 74 (6): 400-4. https://doi.org/ 10.1055/s-0032-1333130. https://www.ncbi.nlm.nih.gov/pubmed/23427039. Oikawa, S., M. Mizuno, S. Muraoka, and S. Kobayashi. 1996. “Retrograde dissection of the temporalis muscle preventing muscle atrophy for pterional craniotomy. Technical note.” J Neurosurg 84 (2): 297-9. https://doi.org/10.3171/jns.1996.84.2.0297. https://www.ncbi. nlm.nih.gov/pubmed/8592239. Palumbo, P., F. Lombardi, F. R. Augello, I. Giusti, S. Luzzi, V. Dolo, M. G. Cifone, and B. Cinque. 2019. “NOS2 inhibitor 1400W Induces Autophagic Flux and Influences Extracellular Vesicle Profile in Human Glioblastoma U87MG Cell Line.” Int J Mol Sci 20 (12). https://doi.org/10.3390/ijms20123010. https://www.ncbi.nlm.nih.gov/pubmed/ 31226744. Palumbo, P., F. Lombardi, G. Siragusa, S. R. Dehcordi, S. Luzzi, A. Cimini, M. G. Cifone, and B. Cinque. 2018. “Involvement of NOS2 Activity on Human Glioma Cell Growth, Clonogenic Potential, and Neurosphere Generation.” Int J Mol Sci 19 (9). https://doi.org/10.3390/ijms19092801. https://www.ncbi.nlm.nih.gov/pubmed/30227679. Park, J., W. Son, Y. Kwak, and B. Ohk. 2018. “Pterional versus superciliary keyhole approach: direct comparison of approach-related complaints and satisfaction in the same patient.” J Neurosurg 130 (1): 220-226. https://doi.org/10.3171/2017.8.JNS171167. https://www. ncbi.nlm.nih.gov/pubmed/29498570. Raysi Dehcordi, S., A. Ricci, H. Di Vitantonio, D. De Paulis, S. Luzzi, P. Palumbo, B. Cinque, D. Tempesta, G. Coletti, G. Cipolloni, M. G. Cifone, and R. Galzio. 2017. “Stemness Marker Detection in the Periphery of Glioblastoma and Ability of Glioblastoma to Generate Glioma Stem Cells: Clinical Correlations.” World Neurosurg 105: 895- 905. https://doi.org/10.1016/j.wneu.2017.05.099. https://www.ncbi.nlm.nih.gov/pubmed/ 28559081. Ricci, A., H. Di Vitantonio, D. De Paulis, M. Del Maestro, S. D. Raysi, D. Murrone, S. Luzzi, and R. J. Galzio. 2017. “Cortical aneurysms of the middle cerebral artery: A review of the literature.” Surg Neurol Int 8: 117. https://doi.org/10.4103/sni.sni_50_17. https://www. ncbi.nlm.nih.gov/pubmed/28680736. Shimizu, S., N. Tanriover, A. L. Rhoton, Jr., N. Yoshioka, and K. Fujii. 2005. “MacCarty keyhole and inferior orbital fissure in orbitozygomatic craniotomy.” Neurosurgery 57 (1 Suppl): 152-9; discussion 152-9. https://doi.org/10.1227/01.neu.0000163600.31460.d8. https://www.ncbi.nlm.nih.gov/pubmed/15987582. Spena, G., E. Roca, F. Guerrini, P. P. Panciani, L. Stanzani, A. Salmaggi, S. Luzzi, and M. Fontanella. 2019. “Risk factors for intraoperative stimulation-related seizures during awake surgery: an analysis of 109 consecutive patients.” J Neurooncol. https://doi.org/ 10.1007/s11060-019-03295-9. https://www.ncbi.nlm.nih.gov/pubmed/31552589. Yagmurlu, K., S. Safavi-Abbasi, E. Belykh, M. Y. S. Kalani, P. Nakaji, A. L. Rhoton, Jr., R. F. Spetzler, and M. C. Preul. 2017. “Quantitative anatomical analysis and clinical experience with mini-pterional and mini-orbitozygomatic approaches for intracranial aneurysm surgery.” J Neurosurg 127 (3): 646-659. https://doi.org/10.3171/2016.6. JNS16306. https://www.ncbi.nlm.nih.gov/pubmed/27858574. 254 S. Luzzi, M. Del Maestro, Giotta Lucifero et al.

Yasargil, M. G., M. V. Reichman, and S. Kubik. 1987. “Preservation of the frontotemporal branch of the facial nerve using the interfascial temporalis flap for pterional craniotomy. Technical article.” J Neurosurg 67 (3): 463-6. https://doi.org/10.3171/jns.1987.67.3.0463. https://www.ncbi.nlm.nih.gov/pubmed/3612281. Yasargil, M. G. 1987. Microneurosurgery. Stuttgart: Thieme. Yaşargil M. G., Fox J. L., Ray M. W. 1975. “The Operative Approach to Aneurysms of the Anterior Communicating Artery.” In Advances and Technical Standards in Neurosurgery, vol 2., edited by Krayenbühl H. et al. Vienna: Springer. Zabramski, J. M., T. Kiris, S. K. Sankhla, J. Cabiol, and R. F. Spetzler. 1998. “Orbitozygomatic craniotomy. Technical note.” J Neurosurg 89 (2): 336-41. https://doi.org/10.3171/jns. 1998.89.2.0336. https://www.ncbi.nlm.nih.gov/pubmed/9688133. Zenonos, G. A., S. H. Chen, S. Sur, and J. J. Morcos. 2019. “Transcavernous Transclinoidal Half-and-Half Approach for Clipping of Twice-Recurrent Stent-Coiled Giant Basilar Tip Aneurysm: 3-Dimensional Surgical Video.” World Neurosurg 127: 330. https://doi.org/ 10.1016/j.wneu. 2019.04.045. https://www.ncbi.nlm.nih.gov/pubmed/30995560. Zoia, C., D. Bongetta, G. Dorelli, S. Luzzi, M. D. Maestro, and R. J. Galzio. 2019. “Transnasal endoscopic removal of a retrochiasmatic cavernoma: A case report and review of literature.” Surg Neurol Int 10: 76. https://doi.org/10.25259/SNI-132-2019. https://www. ncbi.nlm.nih.gov/pubmed/31528414. Zoia, C., D. Bongetta, F. Guerrini, C. Alicino, A. Cattalani, S. Bianchini, R. J. Galzio, and S. Luzzi. 2018. “Outcome of elderly patients undergoing intracranial meningioma resection: a single center experience.” J Neurosurg Sci. https://doi.org/10.23736/S0390-5616. 18.04333-3. https://www.ncbi.nlm.nih.gov/pubmed/29808631. Zoia, Cesare, Francesco Lombardi, Maria Fiore, Andrea Montalbetti, Alberto Iannalfi, Mattia Sansone, Daniele Bongetta, Francesca Valvo, Mattia Del Maestro, Sabino Luzzi, and Renato Galzio. 2020. “Sacral solitary fibrous tumour: surgery and hadrontherapy, a combined treatment strategy.” Reports of Practical Oncology & Radiotherapy. https://doi.org/10.1016/j.rpor.2020.01.008.

Chapter 15

TRANS-EYEBROW KEYHOLE APPROACH

G. Esposito, MD, PhD and L. Regli, MD Department of Neurosurgery, Clinical Neuroscience Center Zurich, University Hospital Zurich, University of Zurich, Zurich, Switzerland

ABSTRACT

The lateral supraorbital approach has been described as a minimally invasive alternative to the pterional approach for selected types of anterior circulation aneurysms. In this chapter, we report a step-by-step description of the trans-eyebrow keyhole approach, highliting its pros and cons.

INTRODUCTION

The lateral supraorbital (Cha, Hong, and Kim 2012; Hernesniemi et al., 2005) has been reported during the last decade as an alternative to the pterional approach (Yasargil and Fox 1975) for the treatment of anterior circulation aneurysms (Cha, Hong, and Kim 2012; Paladino et al., 2005). Aim of this chapter is to describe and illustrate the lateral supraorbital (LS) approach via trans-eyebrow incision.

POSITIONING

The patient is positioned in supine position. The head of the bed is elevated of 20° degrees. The head is fixed in a Mayfield head-holder, extended 20°, slightly elevated, rotated between about 20-40° (depending on the location of the aneurysm) contralateral to the aneurysm side.

 Corresponding Author’s Email: [email protected]. 256 G. Esposito and L. Regli

The malar eminence is at the superior point of the operating field (Yaşargil 1984; G. Esposito et al., 2018; G. Esposito, 2019).

TRANS-EYEBROW INCISION FOR LATERAL SUPRAORBITAL APPROACH

The eyebrow is not shaved. A trans-eyebrow scalp incision is made and runs parallel for ca. 4 cm to the orbital bar between the supraorbital notch (medial limit) and the frontal process of the zygoma (toward the frontozygomatic suture) (Zador and Gnanalingham 2013). The supraorbital notch marks the entry site for the supraorbital nerve, the frontal process of the zygoma is 1 cm anterior to the course of the frontal branch of the facial nerve: the skin incision is guided by these palpable bony landmarks to spare the two nerves described above during exposure (Zador and Gnanalingham 2013). Alternatively, the skin incision can be performed just above the eyebrow (at its most upper edge). If the eyebrow is not evident, one could perform the incision in a crease (if evident). The scalp edges are retracted medially, laterally and posteriorly to expose a limited portion of the frontal bone and the keyhole (G. Esposito, 2019; G. Esposito et al., 2018). The skin incision extends in the deep through the fascia of the frontalis muscle, exposing the periosteum. Laterally, the superficial temporal fascia is incised and retracted together with the dissected (from the bone) underlying temporal muscle posteriorly and laterally. The burr-hole is placed at the keyhole, under the temporal line, superior to the fronto- zygomatic suture, paying attention not to enter the orbit (Figure 1A) (G. Esposito et al., 2018).

Figure 1. Figures 1 A-B show a left trans-eyebrow lateral supraorbital approach. The same craniotomy can be performed via a fronto-temporal skin incision (Figures 1 C-D). The craniotomy is positioned two-thirds above and one-third below the superior temporal line. After opening of the dura mater, the Sylvian fissure is not directly visualized and lies on the lateral limit of the craniotomy, under the dural edge, below the sphenoid ridge (Figures 1B, D) (G. Esposito et al., 2018, 2019). Trans-Eyebrow Keyhole Approach 257

ALTERNATIVE FRONTO-TEMPORAL SKIN INCISION FOR LATERAL SUPRAORBITAL APPROACH

In circumstances like a not evident eyebrow, or if the patient has a large frontal sinus which requires cranialization, the trans-eyebrow incision should be avoided and a classic frontotemporal skin incision can be made. In this case the scalp incision starts 3 cm above the zygoma, extends superiorly to the superior temporal line (in a direction perpendicular to the zygoma) and curves finally anteriorly ending at the hairline (till the midline). The superficial temporal artery should not be injured as well as the temporal branch of the facial nerve. The musculo- cutaneous flap includes scalp, galea, pericranium, temporal fascia and temporal muscle. This flap is elevated and reflected anteriorly toward the orbit and fixed with hook-retractors. The frontal bone and the keyhole region are now exposed, but not the whole pterion. In this case the burr-hole is made 2.5 cm posteriorly to the key-hole, beneath the superior temporal line (for cosmetic reason, because in this way the temporal muscle provides a better coverage) (Figure 1C) (G. Esposito et al., 2018).

MINICRANIOTOMY

Once the burr-hole has been made, the dura is detached with a small curved periosteal elevator, thereafter the craniotomy is performed. The aim is to make a minicraniotomy (ca. 3 x 2cm) which extends two-third above and one-third below the superior temporal line. The anterior margin of the craniotomy runs parallel to the orbital rim till the sphenoid ridge. Over the sphenoid ridge, the craniotomy is completed with a high-speed 4mm electric drill (or can be extended, if necessary). In patients with a large ipsilateral frontal sinus, the use of navigation may be considered to avoid sinus violation (Figure 1A). Lateral take-up sutures can be placed. The dura is detached from the orbital roof and from the medial side of the sphenoid ridge. The inner edge of the craniotomy above the exposed orbital rim, the orbital crests, the orbital roof and the medial side of the sphenoid ridge are drilled and flattened with a high-speed drill (4 mm). For a classic LS approach, the meningo- orbital band is left intact. The dura is opened under the microscope in a C-fashion with its base toward the orbital rim (Figures 1B-D) (G. Esposito et al., 2018).

SYLVIAN FISSURE AND CISTERNAL ANATOMY

The lateral supraorbital (LS) approach does not expose directly the Sylvian fissure. In fact, the Sylvian fissure lies at the lateral edge or just under the exposed lateral dural edge and the sphenoid ridge. By application of gentle retraction on the frontal lobe (for instance with the suction on a cottonoid), the Sylvian fissure is exposed and can be opened with microsurgical technique (Muhammad et al., 2019) (Figure B). Not drilling the entire sphenoid ridge helps in exposing and dissecting the Sylvian fissure with the LS craniotomy. In fact, the sphenoid ridge left in place works like a natural retractor that holds the temporal lobe in place, this way allowing stretching of the arachnoid and visualization of the Sylvian fissure (Figure 2B) (G. Esposito et al., 2018). 258 G. Esposito and L. Regli

Figure 2. The craniotomy is positioned two-thirds above and one-third below the superior temporal line and does not expose directly the Sylvian fissure (Figure 2A - see also Figure 1). By application of gentle traction on the frontal lobe for instance with a cottonoid, the Sylvian fissure is exposed and can be dissected/opened (Figure B). Not drilling the sphenoid ridge helps in exposing and dissecting the Sylvian fissure with the lateral supraorbital craniotomy. In fact, the sphenoid ridge left in place works like a natural retractor that holds the temporal lobe in place allowing stretching of the arachnoid and visualization of the Sylvian fissure. Figure 2C shows the dissected carotid cistern (G. Esposito et al., 2018, 2019).

We favor a limited and targeted opening of the sylvian fissure to treat the underlying aneurysm (Muhammad et al., 2019). Some lesions or surgeon’s preference may justify a wider splitting of the Sylvian fissure. With the LS approach, regardless of the incision, the microsurgical dissection of the Sylvian fissure can be performed either using a distal-to- proximal dissection technique or a proximal-to-distal technique. The distal-to-proximal technique starts from the Sylvian cistern superficially. The proximal-to-distal technique starts from the carotid cistern (Figure 2C) (G. Esposito et al., 2018). The LS approach allows dissection of the following cisterns: sylvian, olfactory, carotid, interpeduncular, crural, chiasmatic, lamina terminalis, callosal (anterior part) (G. Esposito et al., 2018; Cha, Hong, and Kim 2012). Even though the craniotomy flap area is bigger with the pterional approach, there is no significant difference on the total area of surgical exposure between the pterional and the LS approach. The difference is mainly the angle of work: with the LS approach the angle of work is more subfrontal, with the pterional is along the sphenoid ridge (G. Esposito et al., 2018; Cha, Hong, and Kim 2012). If needed, the sphenoid wing can be further drilled for better exposition of the temporal fossa and of the sylvian fissure. By cutting the meningo-orbital band, and separating the dura of the temporal pole from the dura of the cavernous sinus, one can proceed with opening of the superior orbital fissure, unroofing of the optic canal and perform an anterior clinoidectomy (G. Esposito et al., 2018).

Trans-Eyebrow Keyhole Approach 259

INDICATION FOR THE LATERAL-SUPRAORBITAL APPROACH IN SURGERY OF ANTERIOR CIRCULATION ANEURYSMS

We use the minimally invasive keyhole LS approach for clipping unruptured as well as ruptured “non-complex” aneurysms of the posterior communicating artery (PCom), choroidal artery (ACho), Carotis-T, anterior communicating (ACom) complex, and middle cerebral artery (M1-M2 segment). Basilar tip aneurysms can also be reached (G. Esposito et al., 2018). As alternative minimally invasive approach for non-complex MCA aneurysms, we use the minipterional craniotomy. To choose which non-complex MCA aneurysm is best treated with which mini-craniotomy (lateral supraorbital vs. minipterional), we consider the depth of the aneurysm within the Sylvian fissure. As marker of a superficial vs. deep location of the aneurysm within the sylvian fissure, we consider the distance between the M1-origin and the neck of the MCA aneurysm. We use a threshold of 15 mm. When this distance is <15 mm, we chose lateral supraorbital approach; when this distance is ≥15 mm, we consider the aneurysm lying superficially within the Sylvian fissure and chose a minipterional approach. We have recently reported on our decision making for the selection of the keyhole approach for non- complex MCA aneurysms. We refer to the pertinent literature for further details (G. Esposito et al., 2018). For distal aneurysms of the MCA (M3 or M4 branches), we contemplate neither pterional nor lateral supraorbital nor minipterional. In these cases the craniotomy is centered on the Sylvian fissure but is located more posteriorly: neuronavigation is useful to correctly plan the craniotomy (G. R. Esposito, L. 2019). For complex aneurysms of the anterior circulation we prefer to use the pterional approach or its modifications (G. Esposito et al., 2012; G. Esposito and L. Regli 2014). The criteria which we consider for planning the approach are (G. Esposito, 2019).:

1. aneurysm complexity; 2. aneurysm location; 3. the presence of other aneurysms to be treated during the same surgery; 4. previous craniotomies; 5. size of the frontal sinus

CLOSURE

The closure is performed by re-approximation of the dura with a continuous 4-0 watertight suture. With the trans-eyebrow incision, if the frontal sinus has been violated, it can be filled with muscle or fat and fibrin glue. This incision allows only small periosteal flap preparation (as limitation of the of the trans-eyebrow incision). Therefore in case of large frontal sinus, we suggest the use of a fronto-temporal incision that allows preparation of a periosteal flap to cover the sinus and safe cranialization. One or two central take-up sutures can be placed to take up the dura. The bone flap is secured with mini-plates and mini-screws (G. R. Esposito, L. 2019). 260 G. Esposito and L. Regli

By the use of the trans-eyebrow incision, frontal muscle and subcutaneous tissue are closed in layers. The skin incision is closed with interruptured 5-0 or 6-0 monofilament sutures. No subgaleal drainage is employed (G. Esposito et al., 2018). By the use of the fronto-temporal incision, the temporal fascia and the galea are closed in layers with interrupted sutures. The skin can be closed with staples. Subgaleal drainage at a low suction pressure can be employed for 24 hours (G. Esposito et al., 2018).

REFERENCES

Cha, K. C., S. C. Hong and J. S. Kim. 2012. “Comparison between Lateral Supraorbital Approach and Pterional Approach in the Surgical Treatment of Unruptured Intracranial Aneurysms.” J Korean Neurosurg Soc 51 (6): 334-7. https://doi.org/10.3340/jkns.2012. 51.6.334. http://www.ncbi.nlm.nih.gov/pubmed/22949961. Esposito, G., S. F. Dias, J. K. Burkhardt, J. Fierstra, C. Serra, O. Bozinov and L. Regli. 2018. “Selection strategy for optimal keyhole approaches for MCA aneurysms: lateral supraorbital versus minipterional craniotomy.” World Neurosurg. https://doi.org/10.1016/ j.wneu.2018.09.238. https://www.ncbi.nlm.nih.gov/pubmed/30326308. ---. 2019. “Selection Strategy for Optimal Keyhole Approaches for Middle Cerebral Artery Aneurysms: Lateral Supraorbital Versus Minipterional Craniotomy.” World Neurosurg 122: e349-e357. https://doi.org/10.1016/j.wneu.2018.09.238. https://www.ncbi.nlm.nih. gov/pubmed/30326308. Esposito, G., A. Durand, T. Van Doormaal and L. Regli. 2012. “Selective-targeted extra- intracranial bypass surgery in complex middle cerebral artery aneurysms: correctly identifying the recipient artery using indocyanine green videoangiography.” Neurosurgery 71 (2 Suppl Operative): ons274-84; discussion ons284-5. https://doi.org/10.1227/NEU. 0b013e3182684c45. https://www.ncbi.nlm.nih.gov/pubmed/22902337. Esposito, G. and L. Regli. 2014. “Surgical decision-making for managing complex intracranial aneurysms.” Acta Neurochir Suppl 119: 3-11. https://doi.org/10.1007/978-3-319-02411- 0_1. https://www.ncbi.nlm.nih.gov/pubmed/24728625. Esposito, G., Regli, L. 2019. “Approaches to the aneurysms of the anterior circulation: pterional, lateral supraorbital, minipterional and parasagittal craniotomies.” In Clip Exlusion of anterior circulation aneurysms: a surgical atlas. Poletto Editors. Hernesniemi, J., K. Ishii, M. Niemela, M. Smrcka, L. Kivipelto, M. Fujiki and H. Shen. 2005. “Lateral supraorbital approach as an alternative to the classical pterional approach.” Acta Neurochir Suppl 94: 17-21. http://www.ncbi.nlm.nih.gov/pubmed/16060236. Muhammad, S., R. Tanikawa, M. Lawton, L. Regli, M. Niemela and M. Korja. 2019. “Microsurgical dissection of Sylvian fissure-short technical videos of third generation cerebrovascular neurosurgeons.” Acta Neurochir (Wien) 161 (9): 1743-1746. https://doi. org/10.1007/s00701-019-03999-x. https://www.ncbi.nlm.nih.gov/pubmed/31281944. Paladino, J., G. Mrak, P. Miklic, H. Jednacak and D. Mihaljevic. 2005. “The keyhole concept in aneurysm surgery - a comparative study: keyhole versus standard craniotomy.” Minim Invasive Neurosurg 48 (5): 251-8. https://doi.org/10.1055/s-2005-915599. http://www. ncbi.nlm.nih.gov/pubmed/16320184. Trans-Eyebrow Keyhole Approach 261

Yasargil, M. G. and J. L. Fox. 1975. “The microsurgical approach to intracranial aneurysms.” Surg Neurol 3 (1): 7-14. https://www.ncbi.nlm.nih.gov/pubmed/1111150. Yaşargil, M. G. 1984. Microsurgical Anatomy of the Basal cisterns and Vessels of the Brain, Diagnostics Studies, General Operative Techniques and Pathological Considerations of the Intracranial Aneurysms. Vol. 1. edited by Georg Thieme Verlag. Zador, Z. and K. Gnanalingham. 2013. “Eyebrow craniotomy for anterior skull base lesions: how I do it.” Acta Neurochir (Wien) 155 (1): 99-106. https://doi.org/10.1007/s00701-012- 1552-5. http://www.ncbi.nlm.nih.gov/pubmed/23135067.

Chapter 16

CRANIO-ORBITO-ZYGOMATIC APPROACH

S. Luzzi1,2,, MD, PhD, A. Giotta Lucifero1, MD, M. Del Maestro2,3, MD and R. Galzio1,2, MD 1Neurosurgery Unit, Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy 2Neurosurgery Unit, Department of Surgical Sciences, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy 3PhD School in Experimental Medicine, Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy

ABSTRACT

The cranio-orbito-zygomatic approach is basically derived from the inclusion of the orbito-zygomatic bar in the pterional approach. Actually, this apparently simple extension of the pterional approach has dramatic effects in terms of the increase in the angular exposure to most deep targets to the skull base, ultimately increasing the overall surgical freedom to the lesion. A large number of quantitative and morphometric studies have delineated in detail the differential effects related to the osteotomy of the orbital rim and those of zygomatic osteotomy, thereby tailoring the orbito-zygomatic approach. In neurovascular surgery, the orbito-zygomatic approach finds its main indication in large to giant aneurysms of the anterior communicating artery and basilar bifurcation. In this chapter, we review the main technical aspects regarding the cranio-orbitozygomatic approach, mainly focusing on the differential quantitative analysis of the orbital and zygomatic osteotomy.

Keywords: anterior communicating artery aneurysms, basilar tip aneurysms, oculomotor window, optico-carotid window, orbitopterional approach, orbito-zygomatic approach

 Corresponding Author’s Email: [email protected]. 264 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

1. INTRODUCTION

The cranio-orbito-zygomatic (COZ) approach allows wide exposure of the anterior and middle skull base until the upper clivus. The COZ approach involves the addition of an orbito-zygomatic (OZ) osteotomy to a pterional approach which, in turn, should be inclusive of an extradural or intradural anterior clinoidectomy and intradural posterior clinoidectomy, with the latter performed in case of lesions extending in the retrosellar area. Removal of the OZ bar has three main advantages. The first is the dramatic increase in the subfrontal and subtemporal angles of view to those lesions projecting extensively above the clinoid line. The second is shortening of the working distance to some deep neurovascular targets. The third is obtaining a wide working space with the capability of handling the lesion from different angles of view.

2. INDICATIONS

The COZ approach is indicated for high-riding large to giant aneurysms of the anterior communicating artery (ACoA) and distal basilar artery, especially when projecting posteriorly. Large meningiomas of the anterior clinoid and spheno-orbital region, large craniopharyngiomas, and giant pituitary adenomas are additional indications. The COZ approach also provides direct access to the ipsilateral crural and ambient cisterns, interpeduncular fossa, ipsilateral cerebral peduncle, and hypothalamic region. Therefore, it is also the most widely used corridor for the treatment of cavernous hemangiomas of the ventral midbrain and hypothalamus.

3. TECHNIQUE

3.1. Positioning

The patient is placed in a supine position with the head secured to a Mayfield–Kees headrest. The head is elevated, extended 20°, and rotated 20° to 60° to the contralateral side, depending on the target. The malar eminence is the highest point of the patient’s head. A rotation of 30° leads to a line of sight that is parallel to the longer axis of the anterior clinoid. Conversely, a rotation of 45° optimizes the exposure of the subfrontal area.

3.2. Skin Incision and Soft Tissue Dissection

The curvilinear skin incision is made behind the hairline, from the contralateral midpupillary line to the level of the zygomatic process of the temporal bone, 1 cm in front of the tragus to spare the superficial temporal artery and auriculotemporal nerve. The skin flap is dissected from the galea and reflected forward. Then, the preserved galea is incised along the superior temporal lines and reflected anteriorly. Subperiosteal dissection prepares the galeal- pericranial vascularized flap, which, together with the fat graft, is paramount for repair of the Cranio-Orbito-Zygomatic Approach 265 frontal sinus in case of violation. At the level of the temporalis muscle, the superficial and deep layers of the superficial temporal fascia are incised together 2.5 cm behind the fronto-zygomatic suture. The cut is directed obliquely toward the posterior root of the zygoma, thus making an anterior, containing the frontotemporal branch of the facial nerve with its interfascial fat pad, and posterior two-layer fascial leaflets. The anterior leaflet is reflected forward, whereas the posterior leaflet is reflected backward. This technique is referred to as subfascial dissection. The temporalis muscle is cut at the level of the fronto-zygomatic suture, 2 cm below the superior temporal line, to leave a muscle cuff. The cuff will be useful in anchoring the temporalis muscle during closure. The cut curves posteriorly to reach the posterior third of the zygoma, and the muscle is subperiosteally detached from the underlying bone in a retrograde superior-to-posterior and backward-to-forward direction according to the Oikawa technique (Oikawa et al. 1996). Electrocauterization must be avoided during this phase to preserve the blood supply from the internal maxillary artery and prevent muscle atrophy (Zabramski et al. 1998; Yasargil, Reichman, and Kubik 1987; Coscarella et al. 2000; Oikawa et al. 1996). Then, the periorbita is freed from the superior and lateral orbital wall to a depth of 3 cm until the lateral aspect of the superior orbital fissure (SOF). Care must be taken to not endanger the lacrimal gland and maintain the periorbita intact to prevent postoperative orbital enophthalmos (Figure 1).

Figure 1. Head positioning, skin incision (a), construction of the galeal-pericranial flap (b), and subfascial dissection of the superficial temporal fascia (c–d) during the COZ approach. Retrograde subperiosteal dissection of the temporalis muscle according to the Oikawa technique, with setting up of the muscle cuff and skeletonization of the O-pt region (e–h). 1, midline; 2, left midpupillary line.

3.3. Craniotomy

The COZ approach can be performed in a single- (Pellerin et al. 1984; Hakuba, Liu, and Nishimura 1986; Al-Mefty 1987; Aziz et al. 2002; Delashaw, Tedeschi, and Rhoton 1992; Lemole et al. 2003), two- (Yaşargil M.G. 1975; Jane et al. 1982; Zabramski et al. 1998), or three-piece fashion (Matsuo et al. 2019; Campero et al. 2010; S. Luzzi, Gallieni, et al. 2018) (Figure 2).

266 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

Figure 2. Comparison between pterional (a) approach and one- (b), two- (c-d), and three- (e) piece COZ approaches, with the relative main surgical steps (f–l). Comparison in terms of surgical exposure between the pterional (m) and O-pt (n) approaches and pterional (o) and transzygomatic (p) approaches.

3.2.1. One-Piece Orbito-Zygomatic Craniotomy MacCarty keyhole is placed 5 mm behind the junction between the fronto-zygomatic, spheno-zygomatic, and fronto-sphenoidal sutures. This burr hole exposes the dura of the anterior fossa and periorbita, which are separated by the thin orbital roof (Shimizu et al. 2005; Aziz et al. 2002). An additional burr hole is placed at the level of the temporal squama, just above the posterior root of the zygoma, and at the superior temporal line. The first cut is made with a reciprocating saw at the posterior root of the zygoma. The cut is oblique to ensure mechanical support for reconstruction. Preplating may be useful for subsequent osteosynthesis. The second cut is directed from the keyhole to the inferior orbital fissure (IOF). A simple method to identify the IOF at the level of the infratemporal fossa is passing a Penfield Dissector No. 4 placed parallel to the zygoma. The third cut involves the lateral orbital wall, where the eyeball and periorbita are protected with a spatula, and is conducted across the malar eminence. The fourth cut is made on the intraorbital side, just lateral to the supraorbital notch. It crosses the superior orbital rim and orbital roof, reaching the lateral aspect of the SOF. The supraorbital nerve may be released and mobilized. The keyhole and Cranio-Orbito-Zygomatic Approach 267 temporal and frontal burr holes are then connected. In case of particularly adherent dura, another burr hole can be placed. The drilling of the temporal squama dramatically increases the exposure of the middle fossa, whereas the drilling of the lesser sphenoid wing, with anterior clinoidectomy, maximizes the surgical freedom to the anterior and middle fossa. The temporalis muscle and galeal-pericranial flap are reflected downward, with the latter slightly pushing the eyeball inferiorly to make the line of sight as flat as possible to the anterior cranial fossa. Intradural posterior clinoidectomy is required to increase the exposure of the basilar tip, interpeduncular fossa, and hypothalamic region.

3.2.2. Two-Piece COZ Craniotomy Two-piece COZ craniotomy may be performed using two different techniques, namely, pterional craniotomy, in which the removal of the OZ bar is added (Zabramski technique), and orbitopterional (O-pt) craniotomy consisting of caudal mobilization of the zygoma (Al-Mefty technique).

3.2.2.1. Orbito-zygomatic Craniotomy (Zabramski Technique) The first step basically consists of pterional craniotomy. The removal of the OZ bar involves six cuts. The first cut is made at the posterior root of the zygoma. The second cut is made at the malar eminence from lateral to medial. The third cut is carried out, from medial to lateral, across the lateral orbital wall. As opposed to the one-piece technique, the fourth cut is intracranial, involving the orbital roof and superior orbital rim and starting from the lateral end of the SOF. The fifth and sixth cuts connect the SOF and IOF, thus freeing the lateral orbital wall. The fifth cut starts at the level of the IOF and ends at the level of the anterior part of the middle fossa. Here, a small notch made with a high-speed drill may be useful. The sixth and final cut is made starting at the most lateral aspect of the IOF and encroaching the fifth cut (Zabramski et al. 1998).

3.2.2.2. O-pt Craniotomy (Al-Mefty Technique) The O-pt variant of the two-piece COZ consists of, as the first step, two zygomatic cuts performed at the level of the anterior and posterior roots of the zygoma, aiming to avoid the detachment of the masseter muscle and subsequent risk of masticatory imbalance. Apart from what concerns the zygomatic osteotomy, further steps are those already described for the one- piece COZ variant. However, all cuts are made extracranially (Al-Mefty 1987).

3.2.3. Three-Piece COZ Craniotomy The three-piece variant of the COZ approach basically consists of a combination of both the aforementioned two-piece techniques, leading to a zygomatic osteotomy, followed by inferior mobilization of the zygomatic arch, with pterional and orbital bone flaps (Campero et al. 2010; Matsuo et al. 2019). This variant is easier to perform. Making the cuts in the intracranial side under direct vision, some authors stress a safer profile of the three-piece technique.

268 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

3.3. Intradural Corridors

The COZ approach offers four different intradural corridors, namely, the subfrontal, transsylvian, pretemporal, and subtemporal corridors. The transylvian corridor to the basilar tip and ventral midbrain is also related to three well-defined deep windows: optico-carotid, carotid- oculomotor, and supra-carotid windows. A wide splitting of the sylvian fissure is the starting point of all of these corridors, which are thereafter tailored case-by-case according to the target. The subfrontal and transylvian perspectives are widely used to clip large and giant ACoA aneurysms, whereas the three deep windows related to the transylvian approach, along with the pretemporal and subtemporal corridors, represent the main access routes to basilar tip aneurysms. The removal of the orbital rim, which is the roof of the subfrontal perspective, basically allows a paramount gain of surgical freedom that comes by the opportunity to increase the obliquity of the line of sight backward and upward. Considering the possible anatomical variability, a shorter internal carotid artery (ICA) is related to a narrower optico-carotid and carotid-oculomotor window and wider supra-carotid corridor to the basilar tip. Nevertheless, the anterior clinoidectomy, opening of the distal dural ring, and possibility of a medial or lateral mobilization of the ICA all make the COZ approach extremely versatile for the possible infratentorial targets. Lateral mobilization of the ICA can be required to further increase the optico-carotid corridor for high-riding basilar tip aneurysms or achieve good hemodynamic control of the basilar artery, independently from the size of the aneurysm, when the artery bifurcates at the infra-mammillary level. Conversely, lateral mobilization of the ICA, posterior clinoidectomy, and splitting of the tentorium dramatically increase the length of the proximal exposure of the basilar trunk in low-riding basilar bifurcations, tending to descend out of the carotid-oculomotor window. Although removal of the orbital rim is useful for high-riding basilar tip aneurysms, the increased illumination and shallowing of the surgical field derived from zygomatic osteotomy also provide substantial advantages during pretemporal, subtemporal transtentorial, and subtemporal transpetrosal (Kawase’s) approaches for low- riding basilar tip aneurysms. The accessibility of the supra-carotid window may be reduced by a high number of perforating arteries to the anterior perforated substance, normally originating from the carotid apex or its back wall.

4. TAILORING THE COZ APPROACH

The COZ approach should be considered as an extension of the pterional approach. From a quantitative standpoint, the comparison between the pterional and COZ approaches, in terms of angular exposure of the target and overall surgical freedom, has led to the assessment that the removal of the OZ bar as a single bloc causes increases of 8°, 6°, and 10° on the sagittal, coronal, and axial planes, respectively. This additional exposure is valid for almost all targets for which the COZ approach has an indication (Alaywan and Sindou 1990). Regarding the surgical perspectives, the angular exposure to the ACoA, basilar bifurcation, and posterior clinoid are increased to 75%, 46%, and 86% in the subfrontal, pterional, and subtemporal approaches, respectively (Alaywan and Sindou 1990). Particularly for the basilar tip and posterior clinoid, the removal of the orbital rim and zygomatic arch as separate steps of the Cranio-Orbito-Zygomatic Approach 269

COZ approach leads to increases in exposure of 28% and 22%, respectively (Schwartz et al. 1999). Although only the removal of the orbital rim has proved to significantly enhance the exposure of the target, zygomatic osteotomy allows non-negligible shallowing of the target, which is paramount for deep areas such as the interpeduncular cistern. The potential for increasing exposure caused by additional bone removal along the OZ complex is as much as the distance between the line tangent to the highest point of the target and that tangent to the sphenoid wing (Schwartz et al. 1999). Table 1 presents the average area of exposure of pterional, O-pt, pterional + zygomatic, and COZ osteotomy. Data are based on the study by Schwartz et al. (Schwartz et al. 1999).

Table 1. Average Area of Exposure to Different Targets of Pterional, O-pt, and COZ Osteotomy

Area of Exposure (mm2  SD) Approach Posterior clinoid Tentorial edge Basilar tip Pterional 2915 ± 585 2521 ± 301 1639 ± 244 O-pt 3702 ± 943 3536 ± 539 2020 ± 350 COZ 4170 ± 1053 4249 ± 1186 2400 ± 386 O-pt, orbitopterional; COZ, cranio-orbito-zygomatic.

Table 2 shows the percentage increase in exposure to different targets, provided by O-pt, pterional + zygomatic, and COZ osteotomy compared with that in the pterional approach. Data are based on the study by Schwartz et al. (Schwartz et al. 1999).

Table 2. Percentage Increase in Exposure to Different Targets Provided by O-pt, Pterional + Zygomatic Osteotomy, and COZ Osteotomy Compared with That in the Pterional Approach (Schwartz et al. 1999)

Surgical Target (% increase in exposure) Approach Posterior clinoid Tentorial edge Basilar tip O-pt 26* 39* 28* Pterional + Zygomatic Osteotomy 13 17 22 COZ 43* 64* 51* O-pt, orbitopterional; COZ, cranio-orbito-zygomatic; *p < 0.05.

Some topographic considerations should also be presented. Superolateral orbitotomy mainly enhances the exposure of the subfrontal area, thereby having a rationale especially for lesions of the anterior fossa and ACoA complex aneurysms. Conversely, zygomatic osteotomy provides advantages especially in the pretemporal and subtemporal routes (Chanda and Nanda 2002; al-Mefty and Anand 1990; da Silva et al. 2019; al-Mefty and Smith 1990; Al-Mefty 1987; Figueiredo et al. 2005; Gonzalez et al. 2002; Lee et al. 2016; Pitelli et al. 1986; Tayebi Meybodi, Benet, Rodriguez Rubio, Yousef, and Lawton 2018). Given these assumptions, COZ craniotomy may be elegantly tailored based on the site and main compartmental extension of the lesion to be treated.

270 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

5. COMPLICATIONS AND PREVENTION

The COZ approach is related to a series of potential complications. They may be functional, aesthetic, or both. Injury of the frontotemporal branch of the facial nerve, atrophy of the temporalis muscle, masticatory imbalance, enophthalmos, diplopia, blindness, and cerebrospinal fluid (CSF) leakage are the most frequent complications. The subfascial technique of dissection of the superficial temporal fascia protects the frontotemporal branch of the facial nerve, whereas a compulsive subperiosteal blunt and “cold” (avoiding electrocauterization) dissection of the deep temporal fascia prevents postoperative atrophy of the temporalis muscle. Actually, the subfascial technique is considered safer than the interfascial technique. This is because of an anatomical variability in the frontotemporal branch of the facial nerve in which, in approximately 30% of cases, some nerve twigs may run within the two fascial layers (Ammirati et al. 1993). Special care in preparing the muscle prevents temporalis muscle atrophy. Apart from the need for the subperiosteal retrograde dissection of the deep temporal fascia based on the Oikawa technique (Oikawa et al. 1996), caudal displacement of the zygomatic arch has been reported to reduce the risk of atrophy secondary to an excessive compression of the muscle (Kadri and Al-Mefty 2004). Among the reasons for the mobilization of the zygomatic arch and three-piece, rather than single-piece, COZ is to avoid detachment of the masseter muscle during zygomatic osteotomy. The anatomical aspect of the temporalis and masseter muscles prevents the risk of masticatory imbalance. Diplopia and facial and orbital asymmetry can be prevented by meticulous osteosynthesis, which is generally performed using low-profile miniplates and screws. Preplating may further aid in the approximation of the bone flaps during closure. The preservation of the anatomical integrity of the periorbita is of utmost importance to prevent enophthalmos and postoperative orbital hematomas. The risk of blindness mainly results from anterior clinoidectomy, which practically represents an integral part of the COZ approach. It may be potentially caused by the overheating of the nerve during drilling. Constant irrigation is mandatory to decrease this risk. An additional potential risk for the optic nerve is the excessive downward displacement of the eyeball to increase the surgical freedom of the subfrontal area. Direct injuries to the optic nerve are extremely rare. The need to expand the subfrontal corridor frequently involves the violation of the frontal sinus during the COZ approach. Further potential communication with the ethmoid sinus may be the consequence of anterior clinoidectomy involving a pneumatized anterior clinoid. A thorough obliteration of both sites with autologous fat graft and galeal-pericranial vascularized flap significantly reduces the risk of infections and CSF leakage.

6. ILLUSTRATIVE CASES

6.1. Case 1: COZ Approach for a Complex Basilar Tip Aneurysm in a Low- Riding Basilar Bifurcation

A 54-year-old woman was diagnosed with an incidental large basilar tip aneurysm. On digital subtraction angiography, the aneurysm had a dome-to-neck ratio of 1.5, and the dome Cranio-Orbito-Zygomatic Approach 271 was projecting superiorly. Both P1 segments of the posterior cerebral arteries extended from the aneurysm’s neck, which was also partially calcified. The basilar bifurcation was low-riding, at 0.8 cm below the dorsum sellae. Owing to the complex angioarchitecture, full exposure of both the distal basilar artery and aneurysm was required. The patient underwent COZ approach inclusive of an extradural anterior clinoidectomy, lateral mobilization of the ICA, and posterior clinoidectomy. Posterior clinoidectomy allowed the widening of the carotid-oculomotor window, with subsequent optimal exposure of the distal basilar trunk. Because of the low-riding basilar bifurcation, this additional exposure was paramount for temporary clipping. Furthermore, anterior clinoidectomy and lateral mobilization of the ICA expanded the optico- carotid deep window, which was, in turn, extremely useful in handling of the neck and thalamoperforating arteries from the ipsilateral P1 segment. In this case, both the enhanced transylvian corridor and pretemporal and subtemporal corridors were greatly important to achieve optimal clip ligation of the aneurysm. The patient was discharged neurologically intact on the fifth postoperative day (Figure 3).

Figure 3. Vertebrobasilar system digital subtraction angiography in the anterior–posterior (a) and lateral projections (b) of a 54-year-old woman with a large, superior projecting basilar tip aneurysm. Operative images showing the full exposure of the optico-carotid complex after a right COZ approach (c–d). Optico- carotid (1), carotid-oculomotor (2), and supra-carotid (3) deep windows to the basilar bifurcation. Exposure (e) and clip ligation (f) of the basilar tip aneurysm. (g) 3D volume-rendering postoperative CT showing the COZ approach using superimposed color. Postoperative digital subtraction angiography of the vertebrobasilar system in the lateral projection showing complete exclusion of the aneurysm (h).

6.2. Case 2: O-pt Approach for a Large ACoA Aneurysm

A 48-year-old woman was diagnosed with an incidental large ACoA aneurysm. Left A1 was hypoplasic, and both A2 appeared to originate from the ACoA in close proximity to the aneurysm’s neck. The aneurysm was projecting anterior-superiorly, but the line of sight to its blind spot on the left A2 had the orbital rim as roof. The patient underwent the O-pt approach, which allowed expansion of the subfrontal corridor and shallowing of the ACoA complex. The aneurysm was successfully clipped, and the postoperative course was uneventful. In this case, the wider surgical freedom from the removal of the orbital rim ultimately allowed for an optimal maneuverability of the neck and enhanced angular exposure of the target. The enhanced exposure also permitted early and better visualization of both the left 272 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

Heubner artery and hypothalamic and subcallosal perforating arteries from the back wall of the ACoA (Figure 4). This case is an example of the advantages derived from tailoring of the COZ approach and its versatility.

Figure 4. 3D volume-rendering preoperative CT of a 48-year-old woman diagnosed with a large ACoA aneurysm (a–e). It presents a progressive sequence regarding the orbital rim removal during the planning of the O-pt approach to show the relationships between the line of sight to the aneurysm and encroachment due to the orbital rim itself. Operative images before (f) and after (g) the clipping of the aneurysm. Post-clipping indocyanine green videoangiography revealing complete exclusion of the aneurysm. (i) 3D volume-rendering postoperative CT showing the O-pt approach (superimposed blue color). (l) Postoperative anterior–posterior digital subtraction angiography, obtained after the injection of the right ICA, showing the complete exclusion of the aneurysm. (m) 3D volume-rendering postoperative CT angiography of the aneurysm exclusion.

DISCUSSION

Recently, there has been an increase in the research on skull base surgery, on a par with other areas of neurosurgery (Bellantoni et al. 2019; De Tommasi et al. 2008; De Tommasi et al. 2007; Guastamacchia et al. 2007; S. Luzzi, Crovace, et al. 2018; S. Luzzi, Elia, Del Maestro, Elbabaa, et al. 2019; S. Luzzi, Giotta Lucifero, et al. 2019; Palumbo et al. 2019; Palumbo et al. 2018; Raysi Dehcordi et al. 2017; Cheng, Shetty, and Sekhar 2018; Spena et al. 2019; C. Zoia et al. 2018; Bongetta et al. 2019; Ciappetta et al. 2008; De Tommasi, Cascardi, et al. 2006; De Tommasi, De Tommasi, et al. 2006; Millimaggi et al. 2018; Sabino Luzzi, Crovace, et al. 2019; Cranio-Orbito-Zygomatic Approach 273

Elsawaf et al. 2020). Notably, morphometric quantitative studies have contributed to the in- depth definition of the effects of OZ osteotomy. OZ osteotomy has three main advantages, namely, wide working space, shorter working distance, and increased angular exposure of the target. Generally, these aspects dramatically decrease the need for manipulation and retraction of the neurovascular structures, simultaneously expanding tremendously the limits of the pterional approach. Among the anterolateral approaches on the skull base, the COZ approach allows the highest surgical freedom to the most common deep targets, deriving from the possibility to combine a single access of the subfrontal, transylvian, pretemporal, and subtemporal routes. A large volume of literature claims the performance of OZ osteotomy only for lesions lying upward, as high-riding ACoA and basilar tip aneurysms, or for intra-axial tumors abutting within the interpeduncular fossa. Nevertheless, an equally high number of quantitative anatomical studies on OZ osteotomy have largely proved that the shallowing of several deep targets and increased angular exposure both converge to significantly enhance the working space in those lesions extending downward (Chanda and Nanda 2002; Schwartz et al. 1999; Tayebi Meybodi, Benet, Rodriguez Rubio, Yousef, Mokhtari, et al. 2018; Cavalcanti et al. 2018; da Silva et al. 2019; Alaywan and Sindou 1990; Figueiredo et al. 2010; Gonzalez et al. 2002; Lee et al. 2016; Tayebi Meybodi, Benet, Rodriguez Rubio, Yousef, and Lawton 2018). With the latter, some robust examples are provided for basilar tip aneurysms originating from extremely low-riding basilar bifurcations, as in case 2, or extremely large parasellar lesions, particularly involving the infratemporal fossa. Additional exposure of the target from OZ bar removal should be considered as spherical in shape rather than linear upward or downward. The understanding of the increase in surgical freedom related to the COZ approach compared with the pterional transylvian approach is based on this concept. Regarding the increase in angular exposure, superolateral orbitotomy has quantitative and qualitative effects widely different from those of zygomatic osteotomy (Schwartz et al. 1999; Alaywan and Sindou 1990; Figueiredo et al. 2010; Lee et al. 2016; Tayebi Meybodi, Benet, Rodriguez Rubio, Yousef, and Lawton 2018). In these differences lies the possibility to tailor the COZ approach for different lesions. From a topographic standpoint, the removal of the orbital rim markedly raises the roof of the subfrontal corridor, also enhancing the anterolateral perspective of the subfrontal area through the transylvian route. Conversely, zygomatic osteotomy seems to not significantly affect the increase in exposure of targets, such as the posterior clinoid, tentorial edge, and basilar tip (Schwartz et al. 1999). However, it provides substantial advantages in the expansion of the pretemporal and subtemporal corridors by shallowing of the same targets. Within the same corridors, zygomatic osteotomy provides additional illumination of the blind spots in the depth. The constant refinement of skull base surgical techniques, on a par with other fields of neurosurgery (S. Luzzi, Del Maestro, Elia, et al. 2019; S. Luzzi, Del Maestro, Trovarelli, et al. 2019; S. Luzzi, Zoia, et al. 2019; C. Zoia et al. 2019; Ciappetta, Luzzi, et al. 2009; Ciappetta, Occhiogrosso, et al. 2009; Del Maestro et al. 2018; Gallieni et al. 2018; S. Luzzi, Del Maestro, et al. 2018; S. Luzzi, Elia, Del Maestro, Morotti, et al. 2019; S. Luzzi, Gallieni, et al. 2018; S. Luzzi, Del Maestro, and Galzio 2019; Ricci et al. 2017; Antonosante et al. 2020; Campanella et al. 2020; Cesare Zoia et al. 2020; Arnaout et al. 2019; S. Luzzi et al. 2020), has led to a progressive shift from one- to two- or even three-piece COZ approach, the reasons for this mainly lying in greater facility of execution of the approach and better functional and cosmetic outcomes (Zabramski et al. 1998; Lemole et al. 2003; Tanriover et al. 2006; Andaluz et al. 2003). 274 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

CONCLUSION

The COZ approach should be considered as an extension of the pterional approach, where the removal of the OZ bar dramatically increases the angular exposure of the subfrontal, transylvian, pretemporal, and subtemporal corridors. In neurovascular surgery, the COZ approach finds its main indication in high-riding giant or complex ACoA aneurysms and basilar bifurcation aneurysms. Careful planning and both meticulous execution of the approach and vast knowledge of the skull base anatomy are paramount factors to exploit all advantages of the COZ approach compared with the pterional approach and decrease the risk of complications.

REFERENCES

Al-Mefty, O. 1987. “Supraorbital-pterional approach to skull base lesions.” Neurosurgery 21 (4): 474-7. https://doi.org/10.1227/00006123-198710000-00006. https://www.ncbi.nlm. nih.gov/pubmed/3683780. Al-Mefty, O., and V. K. Anand. 1990. “Zygomatic approach to skull-base lesions.” J Neurosurg 73 (5): 668-73. https://doi.org/10.3171/jns.1990.73.5.0668. https://www.ncbi.nlm.nih. gov/pubmed/2213156. Al-Mefty, O., and R. R. Smith. 1990. “Tailoring the cranio-orbital approach.” Keio J Med 39 (4): 217-24. https://www.ncbi.nlm.nih.gov/pubmed/2287146. Alaywan, M., and M. Sindou. 1990. “Fronto-temporal approach with orbito-zygomatic removal. Surgical anatomy.” Acta Neurochir (Wien) 104 (3-4): 79-83. https://doi.org/ 10.1007/bf01842824. https://www.ncbi.nlm.nih.gov/pubmed/2251947. Ammirati, M., A. Spallone, J. Ma, M. Cheatham, and D. Becker. 1993. “An anatomicosurgical study of the temporal branch of the facial nerve.” Neurosurgery 33 (6): 1038-43; discussion 1044. https://doi.org/10.1227/00006123-199312000-00012. https://www.ncbi.nlm.nih. gov/pubmed/8133989. Andaluz, N., H. R. Van Loveren, J. T. Keller, and M. Zuccarello. 2003. “Anatomic and clinical study of the orbitopterional approach to anterior communicating artery aneurysms.” Neurosurgery 52 (5): 1140-8; discussion 1148-9. https://www.ncbi.nlm.nih.gov/pubmed/ 12699559. Antonosante, A., L. Brandolini, M. d'Angelo, E. Benedetti, V. Castelli, M. Del Maestro, S. Luzzi, A. Giordano, A. Cimini, and M. Allegretti. 2020. “Autocrine CXCL8-dependent invasiveness triggers modulation of actin cytoskeletal network and cell dynamics.” Aging (Albany NY) 12. https://doi.org/10.18632/aging.102733. https://www.ncbi.nlm.nih.gov/ pubmed/31986121. Arnaout, M. M., S. Luzzi, R. Galzio, and K. Aziz. 2019. “Supraorbital keyhole approach: Pure endoscopic and endoscope-assisted perspective.” Clin Neurol Neurosurg 189: 105623. https://doi.org/10.1016/j.clineuro.2019.105623. https://www.ncbi.nlm.nih.gov/pubmed/ 31805490. Aziz, K. M., S. C. Froelich, P. L. Cohen, A. Sanan, J. T. Keller, and H. R. van Loveren. 2002. “The one-piece orbitozygomatic approach: the MacCarty burr hole and the inferior orbital fissure as keys to technique and application.” Acta Neurochir (Wien) 144 (1): 15- Cranio-Orbito-Zygomatic Approach 275

24. https://doi.org/10.1007/s701-002-8270-1. https://www.ncbi.nlm.nih.gov/pubmed/ 11807643. Bellantoni, G., F. Guerrini, M. Del Maestro, R. Galzio, and S. Luzzi. 2019. “Simple schwannomatosis or an incomplete Coffin-Siris? Report of a particular case.” eNeurologicalSci 14: 31-33. https://doi.org/10.1016/j.ensci.2018.11.021. https://www. ncbi.nlm.nih.gov/pubmed/30555950. Bongetta, D., C. Zoia, S. Luzzi, M. D. Maestro, A. Peri, G. Bichisao, D. Sportiello, I. Canavero, A. Pietrabissa, and R. J. Galzio. 2019. “Neurosurgical issues of bariatric surgery: A systematic review of the literature and principles of diagnosis and treatment.” Clin Neurol Neurosurg 176: 34-40. https://doi.org/10.1016/j.clineuro.2018.11.009. https://www.ncbi. nlm.nih.gov/pubmed/30500756. Campanella, R., L. Guarnaccia, C. Cordiglieri, E. Trombetta, M. Caroli, G. Carrabba, N. La Verde, P. Rampini, C. Gaudino, A. Costa, S. Luzzi, G. Mantovani, M. Locatelli, L. Riboni, S. E. Navone, and G. Marfia. 2020. “Tumor-Educated Platelets and Angiogenesis in Glioblastoma: Another Brick in the Wall for Novel Prognostic and Targetable Biomarkers, Changing the Vision from a Localized Tumor to a Systemic Pathology.” Cells 9 (2). https://doi.org/10.3390/cells9020294. https://www.ncbi.nlm.nih.gov/pubmed/31991805. Campero, A., C. Martins, M. Socolovsky, R. Torino, A. Yasuda, L. Domitrovic, and A. Rhoton, Jr. 2010. “Three-piece orbitozygomatic approach.” Neurosurgery 66 (suppl_1): ons-E119- ons-E120. https://doi.org/10.1227/01.NEU.0000348559.82835.21. https://www.ncbi.nlm. nih.gov/pubmed/20173579. Cavalcanti, D. D., B. A. Morais, E. G. Figueiredo, R. F. Spetzler, and M. C. Preul. 2018. “Accessing the Anterior Mesencephalic Zone: Orbitozygomatic Versus Subtemporal Approach.” World Neurosurg 119: e818-e824. https://doi.org/10.1016/j.wneu.2018.07. 272. https://www.ncbi.nlm.nih.gov/pubmed/30096501. Chanda, A., and A. Nanda. 2002. “Anatomical study of the orbitozygomatic transsellar- transcavernous-transclinoidal approach to the basilar artery bifurcation.” J Neurosurg 97 (1): 151-60. https://doi.org/10.3171/jns.2002.97.1.0151. https://www.ncbi.nlm.nih.gov/ pubmed/12134906. Cheng, C. Y., R. Shetty, and L. N. Sekhar. 2018. “Microsurgical Resection of a Large Intraventricular Trigonal Tumor: 3-Dimensional Operative Video.” Oper Neurosurg (Hagerstown) 15 (6): E92-E93. https://doi.org/10.1093/ons/opy068. https://www.ncbi. nlm.nih.gov/pubmed/29618124. Ciappetta, P., I. D'Urso P, S. Luzzi, G. Ingravallo, A. Cimmino, and L. Resta. 2008. “Cystic dilation of the ventriculus terminalis in adults.” J Neurosurg Spine 8 (1): 92-9. https://doi.org/10.3171/SPI-08/01/092. https://www.ncbi.nlm.nih.gov/pubmed/18173354. Ciappetta, P., S. Luzzi, R. De Blasi, and P. I. D'Urso. 2009. “Extracranial aneurysms of the posterior inferior cerebellar artery. Literature review and report of a new case.” J Neurosurg Sci 53 (4): 147-51. https://www.ncbi.nlm.nih.gov/pubmed/20220739. Ciappetta, P., G. Occhiogrosso, S. Luzzi, P. I. D'Urso, and A. P. Garribba. 2009. “Jugular tubercle and vertebral artery/posterior inferior cerebellar artery anatomic relationship: a 3- dimensional angiography computed tomography anthropometric study.” Neurosurgery 64 (5 Suppl 2): 429-36; discussion 436. https://doi.org/10.1227/01.NEU.0000337573. 17073.9F. https://www.ncbi.nlm.nih.gov/pubmed/19404121. Coscarella, E., A. G. Vishteh, R. F. Spetzler, E. Seoane, and J. M. Zabramski. 2000. “Subfascial and submuscular methods of temporal muscle dissection and their relationship to the 276 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

frontal branch of the facial nerve. Technical note.” J Neurosurg 92 (5): 877- 80. https://doi.org/10.3171/jns.2000.92.5.0877. https://www.ncbi.nlm.nih.gov/pubmed/ 10794306. da Silva, S. A., V. N. Yamaki, D. J. F. Solla, A. F. Andrade, M. J. Teixeira, R. F. Spetzler, M. C. Preul, and E. G. Figueiredo. 2019. “Pterional, Pretemporal, and Orbitozygomatic Approaches: Anatomic and Comparative Study.” World Neurosurg 121: e398- e403. https://doi.org/10.1016/j.wneu.2018.09.120. https://www.ncbi.nlm.nih.gov/pubmed/ 30266695. De Tommasi, A., P. Cascardi, C. De Tommasi, S. Luzzi, and P. Ciappetta. 2006. “Emergency surgery in a severe penetrating skull base injury by a screwdriver: case report and literature review.” World J Emerg Surg 1: 36. https://doi.org/10.1186/1749-7922-1-36. https://www.ncbi.nlm.nih.gov/pubmed/17169147. De Tommasi, A., C. De Tommasi, E. Lauta, S. Luzzi, A. Cimmino, and P. Ciappetta. 2006. “Pre-operative subarachnoid haemorrhage in a patient with spinal tumour.” Cephalalgia 26 (7): 887-90. https://doi.org/10.1111/j.1468-2982.2006.01122.x. https://www.ncbi.nlm. nih.gov/pubmed/16776708. De Tommasi, A., S. Luzzi, P. I. D'Urso, C. De Tommasi, N. Resta, and P. Ciappetta. 2008. “Molecular genetic analysis in a case of ganglioglioma: identification of a new mutation.” Neurosurgery 63 (5): 976-80; discussion 980. https://doi.org/10.1227/01.NEU. 0000327699.93146.CD. https://www.ncbi.nlm.nih.gov/pubmed/19005389. De Tommasi, A., G. Occhiogrosso, C. De Tommasi, S. Luzzi, A. Cimmino, and P. Ciappetta. 2007. “A polycystic variant of a primary intracranial leptomeningeal astrocytoma: case report and literature review.” World J Surg Oncol 5: 72. https://doi.org/10.1186/1477- 7819-5-72. https://www.ncbi.nlm.nih.gov/pubmed/17587463. Del Maestro, M., S. Luzzi, M. Gallieni, D. Trovarelli, A. V. Giordano, M. Gallucci, A. Ricci, and R. Galzio. 2018. “Surgical Treatment of Arteriovenous Malformations: Role of Preoperative Staged Embolization.” Acta Neurochir Suppl 129: 109-113. https://doi.org/10.1007/978-3-319-73739-3_16. https://www.ncbi.nlm.nih.gov/pubmed/ 30171322. Delashaw, J. B., Jr., H. Tedeschi, and A. L. Rhoton. 1992. “Modified supraorbital craniotomy: technical note.” Neurosurgery 30 (6): 954-6. https://doi.org/10.1227/00006123- 199206000-00028. https://www.ncbi.nlm.nih.gov/pubmed/1614605. Elsawaf, Y., S. Anetsberger, S. Luzzi, and S. K. Elbabaa. 2020. “Early Decompressive Craniectomy as Management for Severe TBI in the Pediatric Population: A Comprehensive Literature Review.” World Neurosurg. https://doi.org/10.1016/j.wneu.2020.02.065. https://www.ncbi.nlm.nih.gov/pubmed/32084616. Figueiredo, E. G., P. Deshmukh, J. M. Zabramski, M. C. Preul, N. R. Crawford, R. Siwanuwatn, and R. F. Spetzler. 2005. “Quantitative anatomic study of three surgical approaches to the anterior communicating artery complex.” Neurosurgery 56 (2 Suppl): 397-405; discussion 397-405. https://doi.org/10.1227/01.neu.0000156549.96185.6d. https://www.ncbi.nlm. nih.gov/pubmed/15794836. Figueiredo, E. G., W. M. Tavares, A. L. Rhoton, Jr., and E. de Oliveira. 2010. “Nuances and technique of the pretemporal transcavernous approach to treat low-lying basilar artery aneurysms.” Neurosurg Rev 33 (2): 129-35; discussion 135. https://doi.org/ 10.1007/s10143-009-0231-3. https://www.ncbi.nlm.nih.gov/pubmed/19823883. Cranio-Orbito-Zygomatic Approach 277

Gallieni, M., M. Del Maestro, S. Luzzi, D. Trovarelli, A. Ricci, and R. Galzio. 2018. “Endoscope-Assisted Microneurosurgery for Intracranial Aneurysms: Operative Technique, Reliability, and Feasibility Based on 14 Years of Personal Experience.” Acta Neurochir Suppl 129: 19-24. https://doi.org/10.1007/978-3-319-73739-3_3. https://www. ncbi.nlm.nih.gov/pubmed/30171309. Gonzalez, L. F., N. R. Crawford, M. A. Horgan, P. Deshmukh, J. M. Zabramski, and R. F. Spetzler. 2002. “Working area and angle of attack in three cranial base approaches: pterional, orbitozygomatic, and maxillary extension of the orbitozygomatic approach.” Neurosurgery 50 (3): 550-5; discussion 555-7. https://www.ncbi.nlm.nih.gov/pubmed/ 11841723. Guastamacchia, E., V. Triggiani, E. Tafaro, A. De Tommasi, C. De Tommasi, S. Luzzi, C. Sabba, F. Resta, M. R. Terreni, and M. Losa. 2007. “Evolution of a prolactin-secreting pituitary microadenoma into a fatal carcinoma: a case report.” Minerva Endocrinol 32 (3): 231-6. https://www.ncbi.nlm.nih.gov/pubmed/17912159. Hakuba, A., S. Liu, and S. Nishimura. 1986. “The orbitozygomatic infratemporal approach: a new surgical technique.” Surg Neurol 26 (3): 271-6. https://doi.org/10.1016/0090- 3019(86)90161-8. https://www.ncbi.nlm.nih.gov/pubmed/3738722. Jane, J. A., T. S. Park, L. H. Pobereskin, H. R. Winn, and A. B. Butler. 1982. “The supraorbital approach: technical note.” Neurosurgery 11 (4): 537-42. https://www.ncbi.nlm.nih.gov/ pubmed/7145070. Kadri, P. A., and O. Al-Mefty. 2004. “The anatomical basis for surgical preservation of temporal muscle.” J Neurosurg 100 (3): 517-22. https://doi.org/10.3171/jns.2004. 100.3.0517. https://www.ncbi.nlm.nih.gov/pubmed/15035289. Lee, J. S., A. Scerrati, J. Zhang, and M. Ammirati. 2016. “Quantitative analysis of surgical exposure and surgical freedom to the anterosuperior pons: comparison of pterional transtentorial, orbitozygomatic, and anterior petrosal approaches.” Neurosurg Rev 39 (4): 599-605. https://doi.org/10.1007/s10143-016-0710-2. https://www.ncbi.nlm.nih.gov/ pubmed/27075862. Lemole, G. M., Jr., J. S. Henn, J. M. Zabramski, and R. F. Spetzler. 2003. “Modifications to the orbitozygomatic approach. Technical note.” J Neurosurg 99 (5): 924-30. https://doi. org/10.3171/jns.2003.99.5.0924. https://www.ncbi.nlm.nih.gov/pubmed/14609176. Luzzi, S., A. M. Crovace, L. Lacitignola, V. Valentini, E. Francioso, G. Rossi, G. Invernici, R. J. Galzio, and A. Crovace. 2018. “Engraftment, neuroglial transdifferentiation and behavioral recovery after complete spinal cord transection in rats.” Surg Neurol Int 9: 19. https://doi.org/10.4103/sni.sni_369_17. https://www.ncbi.nlm.nih.gov/pubmed/29497572. Luzzi, S., M. Del Maestro, D. Bongetta, C. Zoia, A. V. Giordano, D. Trovarelli, S. Raysi Dehcordi, and R. J. Galzio. 2018. “Onyx Embolization Before the Surgical Treatment of Grade III Spetzler-Martin Brain Arteriovenous Malformations: Single-Center Experience and Technical Nuances.” World Neurosurg 116: e340-e353. https://doi.org/10.1016/ j.wneu.2018.04.203. https://www.ncbi.nlm.nih.gov/pubmed/29751183. Luzzi, S., M. Del Maestro, S. K. Elbabaa, and R. Galzio. 2020. “Letter to the Editor Regarding “One and Done: Multimodal Treatment of Pediatric Cerebral Arteriovenous Malformations in a Single Anesthesia Event”.” World Neurosurg 134: 660. https://doi.org/ 10.1016/j.wneu.2019.09.166. https://www.ncbi.nlm.nih.gov/pubmed/32059273. Luzzi, S., M. Del Maestro, A. Elia, F. Vincitorio, G. Di Perna, F. Zenga, D. Garbossa, S. Elbabaa, and R. Galzio. 2019. “Morphometric and Radiomorphometric Study of the 278 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

Correlation Between the Foramen Magnum Region and the Anterior and Posterolateral Approaches to Ventral Intradural Lesions.” Turk Neurosurg. https://doi.org/10.5137/ 1019-5149.JTN.26052-19.2. https://www.ncbi.nlm.nih.gov/pubmed/31452176. Luzzi, S., M. Del Maestro, and R. Galzio. 2019. “Letter to the Editor. Preoperative embolization of brain arteriovenous malformations.” J Neurosurg: 1-2. https://doi.org/10.3171/ 2019.6.JNS191541. https://www.ncbi.nlm.nih.gov/pubmed/31812150. https://thejns.org/view/journals/j-neurosurg/aop/article-10.3171-2019.6.JNS191541/article- 10.3171-2019.6.JNS191541.xml. Luzzi, S., M. Del Maestro, D. Trovarelli, D. De Paulis, S. R. Dechordi, H. Di Vitantonio, V. Di Norcia, D. F. Millimaggi, A. Ricci, and R. J. Galzio. 2019. “Endoscope-Assisted Microneurosurgery for Neurovascular Compression Syndromes: Basic Principles, Methodology, and Technical Notes.” Asian J Neurosurg 14 (1): 193-200. https://doi.org/ 10.4103/ajns.AJNS_279_17. https://www.ncbi.nlm.nih.gov/pubmed/30937034. Luzzi, S., A. Elia, M. Del Maestro, S. K. Elbabaa, S. Carnevale, F. Guerrini, M. Caulo, P. Morbini, and R. Galzio. 2019. “Dysembryoplastic Neuroepithelial Tumors: What You Need to Know.” World Neurosurg 127: 255-265. https://doi.org/10.1016/j.wneu. 2019.04.056. https://www.ncbi.nlm.nih.gov/pubmed/30981794. Luzzi, S., A. Elia, M. Del Maestro, A. Morotti, S. K. Elbabaa, A. Cavallini, and R. Galzio. 2019. “Indication, Timing, and Surgical Treatment of Spontaneous Intracerebral Hemorrhage: Systematic Review and Proposal of a Management Algorithm.” World Neurosurg. https://doi.org/10.1016/j.wneu.2019.01.016. https://www.ncbi.nlm.nih.gov/pubmed/30677572. Luzzi, S., M. Gallieni, M. Del Maestro, D. Trovarelli, A. Ricci, and R. Galzio. 2018. “Giant and Very Large Intracranial Aneurysms: Surgical Strategies and Special Issues.” Acta Neurochir Suppl 129: 25-31. https://doi.org/10.1007/978-3-319-73739-3_4. https://www. ncbi.nlm.nih.gov/pubmed/30171310. Luzzi, S., A. Giotta Lucifero, M. Del Maestro, G. Marfia, S. E. Navone, M. Baldoncini, M. Nunez, A. Campero, S. K. Elbabaa, and R. Galzio. 2019. “Anterolateral Approach for Retrostyloid Superior Parapharyngeal Space Schwannomas Involving the Jugular Foramen Area: A 20-Year Experience.” World Neurosurg. https://doi.org/10.1016/j.wneu.2019. 09.006. https://www.ncbi.nlm.nih.gov/pubmed/31520759. Luzzi, S., C. Zoia, A. D. Rampini, A. Elia, M. Del Maestro, S. Carnevale, P. Morbini, and R. Galzio. 2019. “Lateral Transorbital Neuroendoscopic Approach for Intraconal Meningioma of the Orbital Apex: Technical Nuances and Literature Review.” World Neurosurg 131: 10-17. https://doi.org/10.1016/j.wneu.2019.07.152. https://www.ncbi.nlm. nih.gov/pubmed/31356977. Luzzi, Sabino, Alberto Maria Crovace, Mattia Del Maestro, Alice Giotta Lucifero, Samer K. Elbabaa, Benedetta Cinque, Paola Palumbo, Francesca Lombardi, Annamaria Cimini, Maria Grazia Cifone, Antonio Crovace, and Renato Galzio. 2019. “The cell-based approach in neurosurgery: ongoing trends and future perspectives.” Heliyon 5 (11). https://doi.org/10.1016/j.heliyon.2019.e02818. Matsuo, S., N. Komune, D. Hayashi, T. Amano, and A. Nakamizo. 2019. “Three-piece orbitozygomatic craniotomy: anatomical and clinical findings.” World Neurosurg. https:// doi.org/10.1016/j.wneu.2019.04.235. https://www.ncbi.nlm.nih.gov/pubmed/31059850. Millimaggi, D. F., V. D. Norcia, S. Luzzi, T. Alfiero, R. J. Galzio, and A. Ricci. 2018. “Minimally Invasive Transforaminal Lumbar Interbody Fusion with Percutaneous Cranio-Orbito-Zygomatic Approach 279

Bilateral Pedicle Screw Fixation for Lumbosacral Spine Degenerative Diseases. A Retrospective Database of 40 Consecutive Cases and Literature Review.” Turk Neurosurg 28 (3): 454-461. https://doi.org/10.5137/1019-5149.JTN.19479-16.0. https://www.ncbi. nlm.nih.gov/pubmed/28481388. Oikawa, S., M. Mizuno, S. Muraoka, and S. Kobayashi. 1996. “Retrograde dissection of the temporalis muscle preventing muscle atrophy for pterional craniotomy. Technical note.” J Neurosurg 84 (2): 297-9. https://doi.org/10.3171/jns.1996.84.2.0297. https://www.ncbi. nlm.nih.gov/pubmed/8592239. Palumbo, P., F. Lombardi, F. R. Augello, I. Giusti, S. Luzzi, V. Dolo, M. G. Cifone, and B. Cinque. 2019. “NOS2 inhibitor 1400W Induces Autophagic Flux and Influences Extracellular Vesicle Profile in Human Glioblastoma U87MG Cell Line.” Int J Mol Sci 20 (12). https://doi.org/10.3390/ijms20123010. https://www.ncbi.nlm.nih.gov/pubmed/ 31226744. Palumbo, P., F. Lombardi, G. Siragusa, S. R. Dehcordi, S. Luzzi, A. Cimini, M. G. Cifone, and B. Cinque. 2018. “Involvement of NOS2 Activity on Human Glioma Cell Growth, Clonogenic Potential, and Neurosphere Generation.” Int J Mol Sci 19 (9). https://doi.org/ 10.3390/ijms19092801. https://www.ncbi.nlm.nih.gov/pubmed/30227679. Pellerin, P., F. Lesoin, P. Dhellemmes, M. Donazzan, and M. Jomin. 1984. “Usefulness of the orbitofrontomalar approach associated with bone reconstruction for frontotemporosphenoid meningiomas.” Neurosurgery 15 (5): 715-8. https://doi.org/10. 1227/00006123-198411000-00016. https://www.ncbi.nlm.nih.gov/pubmed/6504290. Pitelli, S. D., G. G. Almeida, E. J. Nakagawa, A. J. Marchese, and N. D. Cabral. 1986. “Basilar aneurysm surgery: the subtemporal approach with section of the zygomatic arch.” Neurosurgery 18 (2): 125-8. https://doi.org/10.1227/00006123-198602000-00001. https://www.ncbi.nlm.nih.gov/pubmed/3960286. Raysi Dehcordi, S., A. Ricci, H. Di Vitantonio, D. De Paulis, S. Luzzi, P. Palumbo, B. Cinque, D. Tempesta, G. Coletti, G. Cipolloni, M. G. Cifone, and R. Galzio. 2017. “Stemness Marker Detection in the Periphery of Glioblastoma and Ability of Glioblastoma to Generate Glioma Stem Cells: Clinical Correlations.” World Neurosurg 105: 895- 905. https://doi.org/10.1016/j.wneu.2017.05.099. https://www.ncbi.nlm.nih.gov/pubmed/ 28559081. Ricci, A., H. Di Vitantonio, D. De Paulis, M. Del Maestro, S. D. Raysi, D. Murrone, S. Luzzi, and R. J. Galzio. 2017. “Cortical aneurysms of the middle cerebral artery: A review of the literature.” Surg Neurol Int 8: 117. https://doi.org/10.4103/sni.sni_50_17. https://www. ncbi.nlm.nih.gov/pubmed/28680736. Schwartz, M. S., G. J. Anderson, M. A. Horgan, J. X. Kellogg, S. O. McMenomey, and J. B. Delashaw, Jr. 1999. “Quantification of increased exposure resulting from orbital rim and orbitozygomatic osteotomy via the frontotemporal transsylvian approach.” J Neurosurg 91 (6): 1020-6. https://doi.org/10.3171/jns.1999.91.6.1020. https://www.ncbi.nlm.nih.gov/ pubmed/10584849. Shimizu, S., N. Tanriover, A. L. Rhoton, Jr., N. Yoshioka, and K. Fujii. 2005. “MacCarty keyhole and inferior orbital fissure in orbitozygomatic craniotomy.” Neurosurgery 57 (1 Suppl): 152-9; discussion 152-9. https://doi.org/10.1227/01.neu.0000163600.31460.d8. https://www.ncbi.nlm.nih.gov/pubmed/15987582. Spena, G., E. Roca, F. Guerrini, P. P. Panciani, L. Stanzani, A. Salmaggi, S. Luzzi, and M. Fontanella. 2019. “Risk factors for intraoperative stimulation-related seizures during 280 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

awake surgery: an analysis of 109 consecutive patients.” J Neurooncol. https://doi.org/ 10.1007/s11060-019-03295-9. https://www.ncbi.nlm.nih.gov/pubmed/31552589. Tanriover, N., A. J. Ulm, A. L. Rhoton, Jr., M. Kawashima, N. Yoshioka, and S. B. Lewis. 2006. “One-piece versus two-piece orbitozygomatic craniotomy: quantitative and qualitative considerations.” Neurosurgery 58 (4 Suppl 2): ONS-229-37; discussion ONS- 237. https://doi.org/10.1227/01.NEU.0000210010.46680.B4. https://www.ncbi.nlm.nih. gov/pubmed/16582645. Tayebi Meybodi, A., A. Benet, R. Rodriguez Rubio, S. Yousef, and M. T. Lawton. 2018. “Comprehensive Anatomic Assessment of the Pterional, Orbitopterional, and Orbitozygomatic Approaches for Basilar Apex Aneurysm Clipping.” Oper Neurosurg (Hagerstown) 15 (5): 538-550. https://doi.org/10.1093/ons/opx265. https://www.ncbi. nlm.nih.gov/pubmed/29281073. Tayebi Meybodi, A., A. Benet, R. Rodriguez Rubio, S. Yousef, P. Mokhtari, M. C. Preul, and M. T. Lawton. 2018. “Comparative Analysis of Orbitozygomatic and Subtemporal Approaches to the Basilar Apex: A Cadaveric Study.” World Neurosurg 119: e607- e616. https://doi.org/10.1016/j.wneu.2018.07.217. https://www.ncbi.nlm.nih.gov/pubmed/ 30077027. Yasargil, M. G., M. V. Reichman, and S. Kubik. 1987. “Preservation of the frontotemporal branch of the facial nerve using the interfascial temporalis flap for pterional craniotomy. Technical article.” J Neurosurg 67 (3): 463-6. https://doi.org/10.3171/jns.1987.67.3.0463. https://www.ncbi.nlm.nih.gov/pubmed/3612281. Yaşargil M.G., Fox J.L., Ray M.W. 1975. “The Operative Approach to Aneurysms of the Anterior Communicating Artery.” In Advances and Technical Standards in Neurosurgery, vol 2., edited by Krayenbühl H. et al. Vienna: Springer. Zabramski, J. M., T. Kiris, S. K. Sankhla, J. Cabiol, and R. F. Spetzler. 1998. “Orbitozygomatic craniotomy. Technical note.” J Neurosurg 89 (2): 336-41. https://doi. org/10.3171/jns.1998.89.2.0336. https://www.ncbi.nlm.nih.gov/pubmed/9688133. Zoia, C., D. Bongetta, G. Dorelli, S. Luzzi, M. D. Maestro, and R. J. Galzio. 2019. “Transnasal endoscopic removal of a retrochiasmatic cavernoma: A case report and review of literature.” Surg Neurol Int 10: 76. https://doi.org/10.25259/SNI-132-2019. https://www. ncbi.nlm.nih.gov/pubmed/31528414. Zoia, C., D. Bongetta, F. Guerrini, C. Alicino, A. Cattalani, S. Bianchini, R. J. Galzio, and S. Luzzi. 2018. “Outcome of elderly patients undergoing intracranial meningioma resection: a single center experience.” J Neurosurg Sci. https://doi.org/10.23736/S0390-5616. 18.04333-3. https://www.ncbi.nlm.nih.gov/pubmed/29808631. Zoia, Cesare, Francesco Lombardi, Maria Fiore, Andrea Montalbetti, Alberto Iannalfi, Mattia Sansone, Daniele Bongetta, Francesca Valvo, Mattia Del Maestro, Sabino Luzzi, and Renato Galzio. 2020. “Sacral solitary fibrous tumour: surgery and hadrontherapy, a combined treatment strategy.” Reports of Practical Oncology & Radiotherapy. https://doi. org/10.1016/j.rpor.2020.01.008.

Chapter 17

INTERHEMISPHERIC APPROACH

S. Anetsberger1, MD, P. Gonzalez- Lopez 2, MD, PhD, Y. Elsawaf1, BS, S. Luzzi3,4, MD, PhD and S. K. Elbabaa1,, MD, PhD 1Department of Pediatric Neurosurgery, Arnold Palmer Hospital for Children, Orlando, Florida 2Department of Neurosurgery, Hospital General Universitario de Alicante, Miguel Hernandez University, Alicante, Spain 3Neurosurgery Unit, Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy 4Neurosurgery Unit, Department of Surgical Sciences, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy;

ABSTRACT

The interhemispheric approach is the natural route to reach the parafalcine and paraventricular structures through the interhemispheric fissure. In this chapter, we report the main anterior and posterior corridors of the interhemispheric approach.

INTRODUCTION

The anterior and posterior interhemispheric approaches provide access to the deep midline parafalcine and paraventricular structures through the interhemispheric fissure. The first posterior interhemispheric transcallosal approach to the pineal region was originally described by Walter E. Dandy in 1915 with an animal model (Dandy 1915). Since then, the anterior and posterior interhemispheric approaches and their variations have been widely applied. The anterior interhemispheric approach can be applied to access ruptured ACoA aneurysms; Tönnis first described this technique in 1936 (Schmiedek 1996).

282 S. Anetsberger, P. Gonzalez- Lopez, Y. Elsawaf et al.

Additionally, the anterior interhemispheric approach was applied to access the hypothalamic region in 1939 by William van Wagenen (Kimmell et al., 2013). This approach can also aid the resection of medial hemispheric gliomas, metastases, AVMs, or lesions of the lateral or third ventricle from the contralateral side. In 1944, Bush described an anterior interhemispheric transcallosal interforniceal approach for the removal of anterior third ventricular tumors such as colloid cysts, hypothalamic hamartomas and craniopharyngiomas (Bush 1944). A variation of this approach, the anterior inferior interhemispheric subcallosal approach, permits access to the suprasellar region. Here, an anterior midline skull base trajectory provides wide access to resect third ventricular lesions, large craniopharyngiomas or olfactory groove meningiomas, as well as distal aneurysms of the anterior cerebral artery. The location of a pericallosal aneurysm relative to the genu of the corpus callosum determines the approach to the aneurysm. A more ventral interhemispheric approach is preferred for aneurysms located below the callosal genu to secure proximal vascular control. The posterior interhemispheric approach is suitable for the removal of space occupying lesions of the posterior third ventricle, posterior thalamic tumors, and pineal region masses with predominantly superior extension.

ANATOMY

An understanding of the parasagittal venous anatomy is crucial for a safe execution of interhemispheric approaches. (Figure 1) Major topographic elements of the midline corridor are:

 Superior and inferior sagittal sinus  Parasagittal veins  Cingulate gyrus  Pericallosal arteries  Corpus callosum  Fornices  Septum pellucidum  Lateral and third ventricles and the anterior superior aspect of the suprasellar region  Cisterna veli interpositi with the internal cerebral veins

The neurovascular structures should be carefully preserved during each dissection step. Preservation of the sagittal sinus and their venous tributaries, as well as the diencephalic veins, is crucial during the interhemispheric exposure to avoid surgical morbidity. Specific risks involve the combination of brain retraction and venous occlusion, which may result in extended venous infarction and hemiparesis (Table 1).

Interhemispheric Approach 283

Figure 1. Dissection by Pablo Gonzalez-Lopez et al.; 1 Falx cerebri / inferior sagittal sinus, 2 Callosomarginal artery, 3 Pericallosal arteries, 4 Corpus Callosum (Body), 5 lateral Ventricle, 6 III. Ventricle, 7 internal cerebral veins, 8 Fornix.

Table 1. Anatomical Structures Accessible Through the Anterior Interhemispheric Transcallosal Approach (Axel Perneczky 2008)

Ipsilateral Midline

Medial part of the frontal lobe Superior sagittal sinus

Ipsilateral cingulate gyrus Anterior cerebral falx

Frontal horn of the lateral ventricle Distal (A3, A4) segments of anterior cerebral artery

Cella media of the lateral ventricle Anterior corpus callosum

Foramen of Monro Velum interpositum

Septal vein, thalamostriate vein, Third ventricle

Interpeduncular fossa

Tip of the basal artery Choroid plexus Contralateral cingulate gyrus

Lateral aspect of the contralateral ventricle

284 S. Anetsberger, P. Gonzalez- Lopez, Y. Elsawaf et al.

PREOPERATIVE CONSIDERATIONS

Imaging/Preoperative MRI

Accurate surgical planning is crucial; special attention must be payed to the specific underlying pathologies, for example, tributaries of a vascular lesion, or tumor location in regard to the surrounding structures in order to choose the most appropriate and safest surgical corridor. For the interhemispheric approach, localization of the superior sagittal sinus and the corresponding bridging veins, as well as the pericallosal and callosomarginal arteries should be assessed. If necessary, a magnetic resonance venogram or CT-angiogram should be performed. For vascular lesions and aneurysm surgery, a digital subtraction angiography (DSA) is helpful. Neuronavigation aids in accurate orientation in the midline and localization of the lesion. Intraoperative neurophysiological monitoring can be used to avoid postoperative neurological deficits. For vascular procedures, transcranial doppler may be employed.

CSF-DRAINAGE

For large tumors, CSF drainage over an external ventricular drain or a lumbar drain facilitates brain relaxation and mobilization of the tumor. Head elevation and careful CSF drainage from the pericallosal cisterns may avoid the necessity for a perioperative drain.

ANTERIOR INTERHEMISPHERIC APPROACH

Positioning

Careful positioning and head-rotation, gravity assisted self-retraction of the brain, combined with CSF drainage, aids to widen the interhemispheric fissure, allowing for an atraumatic surgical dissection without rigid brain retraction. Patients may be placed in supine or lateral position; the former may allow for improved orientation, while the lateral positioning employs gravity assisted retraction to mobilize the ipsilateral hemisphere for a more ergonomic bimanual maneuverability. Head and operating table should be elevated to approximately 15° to provide sufficient venous drainage. The head should be ante-flexed approximately 15° to 45° and rotated about 10° to 30° as well as latero-flexed to the side of the craniotomy. Latero-flexion and rotation of the head aid in significant relaxation of the frontal lobe falling away from the Falx cerebri, allowing access to the interhemispheric space with or without minimal retraction of the hemispheres. An ipsilateral interhemispheric approach requires 30° latero-flexion and 10º rotation. A contralateral approach requires 10º lateroflexion and 10º rotation. (Figure 2)

Interhemispheric Approach 285

Figure 2. Patient positioning for anterior interhemispheric approach.

INCISION

With the use of neuronavigation, a bone flap is tailored to the capricious venous anatomy to avoid sacrificing the bridging veins. The borders of trephination should be extended over the midline to gain control over the superior sagittal sinus. After defining the craniotomy, a curvilinear incision behind the hairline or a horseshoe incision one-third behind and two thirds

286 S. Anetsberger, P. Gonzalez- Lopez, Y. Elsawaf et al. anterior to the coronal suture and across the midline is made. Then subcutaneous tissue is mobilized, the galea aponeurotica and the periosteal layer are incised in a curvilinear fashion and retracted towards the midline. If necessary, this flap can be utilized for water-tight dural closure.

CRANIOTOMY

For a paramedian craniotomy, two burr holes are placed over the superior sagittal sinus; the first burr hole is made at the frontal-medial corner of the craniotomy, and the second parietally at the posterior-medial corner. Subsequently, an additional 1-2 paramedian burr holes are made. The dura is separated from the inner table of the calvarium over the sinus and deep to the planned craniotomy with a Penfield dissector. The bone cut is made by sawing away from the sagittal sinus. The craniotomy should ideally measure at least 2.0 to 3.0 cm. By undercutting the bone, the angle for visualization can be increased which facilitates the use of micro instruments within the limited craniotomy. After removing the bone flap the sinus should be covered with Gelfoam, Surgicel or Cottonoids. The decision whether to perform the craniotomy ipsilateral or contralateral to the pathology is made preoperatively after a thorough analysis of the preoperative imaging. According to the keyhole concept, deep seated lesions are best exposed through a contralateral interhemispheric approach. This approach offers more flexible working angles for lesions extending laterally.

DURA OPENING

The C-shaped dural-opening is based towards the superior sagittal sinus. The dural-flap is fixed with two sutures. Subsequently, the superior frontal gyrus should be carefully dissected from the midline. Bridging veins running within the dura or the falx cerebri before entering the superior sagittal sinus should be dissected away from the dura and the arachnoid adhesions. If a bridging vein is injured or must be sacrificed, cerebral retraction in this area should be minimized to prevent cerebral infarction and postoperative brain edema from compression of the venous anastomosis.

OPENING OF THE INTERHEMISPHERIC FISSURE AND DISSECTION

After mobilization of the frontal lobe and the falx cerebri, the interhemispheric fissure is carefully opened. Thorough CSF drainage is necessary to gain space in the interhemispheric fissure. After further dissection within the interhemispheric fissure and retraction of the cingulate gyrus, the corpus callosum is approached. The cingulate gyri may be adherent; thus, careful differentiation from the corpus callosum is vital. The ipsilateral callosomarginal arteries may serve as landmarks to define the midline dissection planes and avoid subpial injury until the pericallosal arteries can be defined. The corpus callosum is subsequently exposed in the midline between the paired pericallosal arteries. Neuronavigation guidance aids in planning the precise location of the 1-2cm callosotomy, which is tailored to the needs of surgery with as

Interhemispheric Approach 287 limited exposure as possible. After reaching the goal of surgery, the subdural space and ventricles, if breached throughout the procedure, should be filled with artificial CSF before the dura is closed in a watertight fashion. The coverage on the superior sagittal sinus with Gelfoam or Surgiseal should not be removed. After accessing the ventricular system, a ventricular catheter may be required briefly during the postoperative period (A. 2016).

VARIATIONS OF THE ANTERIOR INTERHEMISPHERIC APPROACH

Anterior Superior Trans-Callosal Interhemispheric Approach for Intraventricular Exposure

Interhemispheric Approach to the Lateral Ventricles Lesions of the lateral ventricles located medially within the ventricular chamber can be exposed through an ipsilateral interhemispheric approach. Optimal positioning of the head enables exposure of the lateral ventricle after gentle mobilization and retraction of the hemisphere through a limited callosotomy. Lesions located laterally in or adjacent to the lateral ventricle, especially within the dominant hemisphere, might better be exposed via a contralateral trans-callosal approach.

Interhemispheric Approach to the Third Ventricle The third ventricle can be entered via an inter-fornical, sub-choroidal, trans-choroidal or trans-foraminal route using an interhemispheric trans-callosal approach. Applying the inter- fornical access, manipulation and contusion of both fornices may result in severe postoperative permanent memory loss. Unilateral impairment may cause minor deficits, especially when accessing through the nondominant hemisphere. Therefore, in order to avoid the risk of memory loss, the sub-choroidal or trans-choroidal approaches are more favorable for third ventricular access.

Anterior Inferior Subcallosal Interhemispheric Exposure for the Skull Base Pathologies

The anterior inferior interhemispheric approach is one of the most frequently employed techniques for lesions of the anterior cranial fossa; via this approach extended lesions of the frontal skull base and anterior plane of the supra-sellar region can be effectively accessed. Preoperative planning of the craniotomy should consider the relationship between the skull base and the corpus callosum, as well as the relationship between the genu and rostrum of the corpus callosum. Through a mid-positioned craniotomy, the anterior plane of the supra-sellar region can be accessed. The rostrum corpus callosum, the lamina terminalis and the third ventricle can be approached via a basal approach (Table 2).

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Table 2. Anatomical Structures Approached Through the Different Variants of the Anterior Inferior Subcallosal Interhemispheric Approach (Axel Perneczky 2008)

Superior variant Mid variant Inferior variant Inferomedial frontal Anterior third of the SSS Anterior superior SSS lobe

Anterior third of the falx Anterior third of the falx Anterior third of the falx cerebri cerebri cerebri

Rostrum of the corpus Frontal skull base Frontal skull base callosum

Tuberculum sellae Tuberculum sellae Lamina terminalis Christa galli Christa galli Anterior third ventricle

Olfactory groove, lamina Sella turcica, diaphragma sellae Optic nerves and chiasm cribrosa

Superior ethmoidal cells Medial part of the frontal lobe

Sphenoid sinus Genu of the corpus callosum

Medial part of the frontal lobe Gyrus rectus

Genu of the corpus callosum Rostrum of the corpus callosum ICA, A1, ACoA, A2, Olfactory bulbs, olfactory Olfactory tracts incl. perforators tracts

Optic nerves and chiasm

Pituitary A3, A4 Segments of the ACA ICA, A1, ACoA, A2, A3 incl. perforators SSS: superior sagittal sinus; ICA: internal carotid artery; ACA: anterior cerebral artery; ACoA: anterior communicating artery

SURGICAL TECHNIQUE OF THE ANTERIOR INFERIOR INTERHEMISPHERIC APPROACH

Patient Positioning

Patients are generally placed in the supine position with the head elevated above the thorax, facilitating cranial venous drainage. The head is flexed according to the level of the approach. The more inferiorly the craniotomy is performed, the more retro flexion is needed. In order to expose the sellar and supra-sellar area, 10-20º retro-flexion is sufficient. To gain access to lesions approached via the superior variant of this route, the head is antero-flexed

Interhemispheric Approach 289 approximately 10°. To approach structures such as the lamina terminalis, the rostrum of the corpus callosum or the anterior third ventricle, a 30-45º flexion is applied. The head is rotated approximately 10° towards the side of the craniotomy to allow the frontal lobe to move away from the falx cerebri.

POSTERIOR INTERHEMISPHERIC APPROACH FOR LESIONS OF THE POSTERIOR SEGMENT OF THE THIRD VENTRICLE AND THE PINEAL REGION

With a posterior interhemispheric approach, the posterior part of the tentorial incisura can be exposed via a supratentorial route. This region is located posterior to the midbrain and corresponds to the area of the quadrigeminal cistern. Through this approach, the splenium, pineal gland, mesencephalic tectum, upper part of the vermis, and complex neurovascular structures can be overlooked. Such complex neurovascular structures include the internal cerebral veins, the vein of Galen, the branches of the posterior cerebral and the superior cerebellar arteries and the trochlear nerve (Table 3).

Table 3. Anatomical Structures Exposed Through the Posterior Interhemispheric Approach (Axel Perneczky 2008)

Supratentorial Infratentorial Posterior part of the superior sagittal sinus Splenium of the corpus callosum Posterior part of the falx Vein of Galen

Straight sinus, tentorium Basal vein of Rosenthal

Medial surface of the occipital lobe Internal cerebral vein Splenium of the corpus callosum Pineal gland

Posterior part of the inferior sagittal sinus Cisterna veli interpositii

Posterior periocallosal artery Quadrigeminal plate Distal segment of the PCA Upper vermis

CN IV Vein of Galen Distal segments of the PCA and SCA PCA: posterior cerebral artery; SCA: superior cerebellar artery

PREOPERATIVE CONSIDERATIONS

Again, a careful study of the venous anatomy in preoperative MRI is crucial, as it provides information regarding the location of the internal cerebral veins, veins of Rosenthal and Galen in relation to the pathology and aids in determination of the pathway of dissection between and around the internal cerebral veins.

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POSTERIOR INTERHEMISPHERIC APPROACH

Positioning

The same basic principles and techniques applied for the anterior interhemispheric approach are employed here. The patient may be positioned supine or lateral; more neck flexion is required as compared to an anterior transcallosal approach. The patient may also be positioned prone or semi-sitting with antero-flexion of the head which allows an optimal venous drainage, but may increase the risk of air embolism. The patient´s head and thorax are elevated ca. 15° for better venous drainage. To bring the tentorium into a horizontal plane the head may be antero-or retro-flexed up to approximately 45° depending on the course of the straight sinus and the location of the planned craniotomy. If the straight sinus is more perpendicular, less retroflexion is required and the craniotomy can be placed next to the occipital protuberance. With a slight head rotation of approximately 10°, the occipital lobe falls away from the falx cerebri allowing access to the deep structures with minimal brain retraction.

Surgery

To access midline regions, a 5-6 cm long bone flap is created on the right side of the skull. Paramedial lesions exposure requires the bone flap to be placed on the ipsilateral side, centered either in the coronal suture or one-third anterior and two-thirds posterior to the coronal suture. An extended posterior approach places the sensorimotor cortex at risk of compromise; further, all parasagittal veins in this area must be preserved. The exact location of the craniotomy is dependent upon the individual shape of the tentorium and the straight sinus, as well as on the individual anatomy. The craniotomy is performed as outlined in the anterior interhemispheric approach section. Intraoperative electrophysiological monitoring and neuronavigation are essential. Compared to the frontal and parietal areas, prominent bridging veins are uncommon in the occipital region. Sufficient CSF drainage is also of paramount importance. Callosotomy may be planned with the aid of neuronavigation, most of the splenium must be spared to prevent the risk of posterior disconnection syndrome. In tumor surgery the endoscope is a helpful tool to inspect the operative blind spots below the splenium and laterally under the corpus callosum for residual tumor (Boop F 2016).

Pitfalls

Incorrect positioning and insufficient surgical planning with inadequate intracranial exposure.

Risk and Complications

Complications may arise via vascular structure compromise; injury of the superior sagittal sinus should be packed immediately. Venous infarction can occur through injuries of the superior sagittal sinus or due to occlusion of large bridging veins coursing into the sinus. The

Interhemispheric Approach 291 bone flap should be fixed without compression of the superior sagittal sinus to avoid sinus thrombosis. Aggressive retraction of both cingulate gyri can cause akinetic mutism; thus, fixed self- retractors must be avoided. The hemisphere should be mobilized via gravity assisted positioning, gentle dynamic retraction, and CSF drainage. There have been suggestions that sectioning of the anterior aspect of the corpus callosum is not associated with severe distinct symptoms, although it can cause a decrease in spontaneity of speech ranging from a mild slowness in initiating speech to mutism. A posterior and complete callosal section has demonstrated a broad array of postoperative behavioral abnormalities. Therefore, commissural section should be restricted to surgical necessity. After intraventricular procedures, the intraventricular and intradural space should be filled with normal saline at body temperature to avoid severe pneumoencephalus. Soleman et al., assessed the risk and morbidity of the interhemispheric approach in 26 patients undergoing 28 procedures. Approach- related morbidity occurred following 7 anterior interhemispheric approaches and one posterior interhemispheric approach including pseudomeningocele (7.1%), persistent subdural effusions (10.7%), epidural bleed (3.6%) and infections (3.6%). In this series there were no CSF leaks, supplementary motor area syndrome, seizures or subdural hematomas. None of the approach related complications led to permanent morbidity or to mortality (Soleman et al., 2019).

CASE ILLUSTRATION

Case 1: Cavernous Malformation in the Gyrus Rectus after Radiation Therapy of a Bifocal Germinoma

Presentation 15-year old girl with a history of a bifocal germinoma treated by biopsy and adjuvant therapy including proton-therapy, presented with an acute headache. Imaging demonstrated a large hemorrhagic brain mass in the left gyrus rectus. The previous imaging depicted remission of the germinoma as well as a small lesion in the same location of the hemorrhage suggestive of a cavernous vascular malformation; Because of suspected recurrent bleeding and rapid growth of the cavernoma within one-year, resection of the cavernoma was recommended. (Figure 3A)

Surgery Under general anesthesia, the patient was placed in supine position, with her head fixed in the Mayfield clamp, elevated at approximately 15°, and slightly extended and rotated 25° to the left side. Baseline SSEPS and MEP neurophysiologic monitoring were obtained. Intraoperative neuronavigation was registered using preoperative MRI, craniotomy and incision were planned accordingly. A left frontal butterfly incision was made behind the hairline with slight extension across the midline to the right side. Three burr holes were made; two were performed over the superior sagittal sinus in the midline, in the anterior and posterior corner of the planed craniotomy, and a third was performed over the left frontal bone. The underlying dura over the superior sagittal sinus and the left frontal lobe was bluntly dissected free from the bone and a craniotomy connecting the three burr-holes was performed. The

292 S. Anetsberger, P. Gonzalez- Lopez, Y. Elsawaf et al. superior sagittal sinus was covered, and the dura was opened in a C-shaped manner. It was then reflected over the midline with two sutures. After sharp dissection of arachnoidal planes, CSF was drained using suction and cottonoid patties until the left cerebral hemisphere was relaxed. An anterior interhemispheric parafalcine approach was performed until the pericallosal arteries were appreciated and continued until edema in the left frontal lobe was noted due to the underlying hemorrhagic mass. Significant adhesions in the interhemispheric fissure were sharply dissected while protecting the branches of the pericallosal arteries. The corticectomy and entry to the cavernous mass were planned using neuronavigation. The edema was managed by repeated CSF drainage, mannitol and hyperventilation. With bipolar electrocautery and microscissors, a horizontal corticectomy was performed. With the assistance of neuronavigation and under careful suction, the cavernoma hemorrhagic mass was entered. An immediate expression of a large amount of fresh and old blood products and hemosiderin resulted in relaxation of the left frontal lobe. The cavernoma mass was circumferentially bluntly dissected first with cottonoid patties, then with a penfield dissector #5; the associated developmental venous anomaly was preserved. Heavy staining of hemosiderin of the cavernoma resection bed was carefully dissected free with the Sonopet aspirator until there was healthy surrounding white matter circumferentially. Thorough inspection of the resection cavity revealed no residual cavernoma. Careful hemostasis was performed using a combination of thrombin-soaked Gelfoam and Floseal. All hemostatic agents were irrigated. Dura was closed using interrupted Nurolon 4-0 sutures, followed by Onlay Duragen Plus and Tisseal sealant agent. Cranioplasty was performed using the native bone flap. There were no SEEP or MEP changes throughout the case. (Figure 3 B, C)

Case 2: Ruptured Flow Aneurysm of Left Pericallosal Artery with Associated AVM Grade 3

Presentation A 12-year-old boy fell unconscious during a soccer match. His admission GCS was 8 and he was intubated. A CT scan revealed a fronto-basal midline hematoma (Figure 4A). An ICP probe was inserted in the left frontal lobe. ICP initially was normal. A digital subtraction angiography was obtained showing a ruptured flow aneurysm descending from the left pericallosal artery pointing towards the left cingulate gyrus as the source of the hemorrhage. This artery, anterior to the caudate nucleus, was feeding a small grade 3 AVM draining into the septal vein. Emergent hematoma evacuation, resection of the AVM as well as clipping of the associated aneurysm, was performed after a challenging attempt at endovascular interventional occlusion.

Surgery General anesthesia was continued. The patient was positioned in a supine position lying on left side with elevation of the right shoulder. The head was fixed in the Mayfield Clamp elevated about 15°, extended and rotated approximately 30° towards the left side. Craniotomy and incision were planned. A left frontal butterfly incision was made behind the hairline with slight extension across the midline to the right side. Three burr holes were made, two were performed over the superior sagittal sinus in the midline, and a third was performed over the

Interhemispheric Approach 293 left frontal bone. The dura was bluntly dissected free from the tabula interna of the bone and a craniotomy was performed. The superior sagittal sinus was covered, and the dura was opened in a C-shaped fashion and reflected over the midline with two sutures. After sharp dissection of arachnoidal planes, CSF of the interhemispheric fissure was drained until the brain was relaxed. The interhemispheric approach was continued until the left callosomarginal artery was identified and followed. The hematoma was entered and the left pericallosal artery was appreciated. The hematoma was carefully evacuated, and the proximal feeding artery of the flow aneurysm dissected and clipped. Afterwards the dissection was continued laterally towards the nidus, which was circumferentially devascularized followed by clipping of the drainage vein into the septal vein. Careful hemostasis was performed, the subdural space was filled with normal saline. Dura was closed in a watertight fashion. Cranioplasty was performed using the native bone flap. (Figure 4 B, C, D)

Figure 3. (A) Preoperative axial T2-weighted and FLAIR MRI showing a left gyrus rectus cavernoma. (B) Intraoperative neuronavigation showing the surgical trajectory to the target. (C) Postoperative axial T2-weighted and FLAIR MRI revealing the complete removal of the cavernoma.

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Figure 4. (A) Pre-operative contrast-enhanced CT scan revealed a fronto-basal midline hematoma. (B) Lateral projection digital subtraction angiography obtained after the injection of the left internal carotid artery showing a small anterior interhemispheric AVM (grade 3) associated with a flow related left pericallosal artery aneurysm. (C) Postoperative axial CT scan showing the complete removal of the hematoma. (D) Lateral projection post-operative digital subtraction angiography confirming the complete exclusion of the AVM.

REFERENCES

Cohen-Gadol, A. 2016. Interhemispheric Craniotomy. Neurosurgical Atlas, Inc. Axel Perneczky, Robert Reisch 2008. Keyhole Approaches in Neurosurgery. Volume 1: Concepts and surgical technique. Edited by Springer. Vienna. Boop F, Klimo P, Cohen-Gadol A. 2016. Posterior Interhemispheric Transcallosal Intervenous/Paravenous Variant. Neurosurgical Atlas, Inc. Bush, E. 1944. “A new approach for the removal of tumors of the third ventricle.” Acta Psychiatr. Scand. https://doi.org/10.1111/j.1600-0447.1944.tb04560.x. Dandy, W. E. 1915. “Extirpation of the Pineal Body.” J. Exp. Med. 22 (2): 237-46. https://doi.org/10.1084/jem.22.2.237. https://www.ncbi.nlm.nih.gov/pubmed/19867913. Kimmell, K. T., A. L. Petraglia, M. A. Ballou, and W. H. Pilcher. 2013. “William P. Van Wagenen (1897-1961): pupil, mentor, and neurosurgical pioneer.” J. Neurosurg. 119 (3): 789-95. https://doi.org/10.3171/2013.4.JNS121520. https://www.ncbi.nlm.nih.gov/ pubmed/23662824.

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Schmiedek, P. 1996. “[Successful treatment of an aneurysm of the anterior communicating artery. A case report by W. Tonnis].” Zentralbl. Neurochir. 57 (1): 2-4. https://www. ncbi.nlm.nih.gov/pubmed/8900892. Soleman, J., R. Ber, S. Constantini, and J. Roth. 2019. “The interhemispheric approach in children: our experience and review of the literature.” Childs Nerv. Syst. 35 (3): 445- 452. https://doi.org/10.1007/s00381-018-04039-2. https://www.ncbi.nlm.nih.gov/pubmed/ 30617576.

Chapter 18

SUBTEMPORAL APPROACH

L. Silveira1, MD, J. Muse1, MD, S. Luzzi3,4, MD, PhD, R. Galzio3,4, MD and C. Gragnaniello2, MD 1Department of Neurosurgery, University of Vermont, Burlington, VT, US 2Department of Neurological Surgery, University of Illinois at Chicago, Chicago, Il, US 3Neurosurgery Unit, Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Polo Didattico “Cesare Brusotti,” Pavia, Italy 4Neurosurgery Unit, Department of Surgical Sciences, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

ABSTRACT

The subtemporal approach involves a temporal craniotomy centered at the temporozygomatic junction made flush with the floor of the middle fossa with subsequent gentle superior elevation of the temporal lobe revealing a surgical corridor directed to the lateral surface of the midbrain and interpeduncular fossa. In neurovascular surgery, the subtemporal approach finds its main indication in treatment of aneurysms of the basilar apex lying below the level of the posterior clinoids or arising at the superior cerebellar artery or basilar trunk. However, the utility of the approach has been expanded to include treatment of proximal posterior cerebral artery (PCA) aneurysms, including fusiform type, via aneurysm bypass trapping, and a variety of other pathologies located in the anterior and middle tentorial incisural spaces and anterior or anterolateral midbrain and pons. In this chapter, we review the main technical aspects regarding the subtemporal approach, focusing on the advantages and disadvantages of the classic approach as well as the employment of surgical adjuncts including division of the tentorium, zygomatic osteotomy, and anterior petrosectomy to widen applicability of this approach. We also explore the complications associated with this approach along with the key precautionary measures to avoid them.

Keywords: subtemporal approach, temporal lobe retraction, zygomatic osteotomy, transtentorial extension, basilar apex, aneurysm

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1. INTRODUCTION

The subtemporal approach was initially pioneered by Hartley and Krause for the treatment of trigeminal neuralgia then refined by Spiller and Frazier at the turn of the nineteenth century (Patel and Liu 2016). However, the subtemporal approach was ultimately popularized by Drake et al. for the treatment of basilar apex aneurysms and utilized to treat 80% of the 1234 patients with basilar tip aneurysms cases within a published series of 1767 patients with vertebrobasilar artery aneurysms from 1959 to 1992 (Drake 1968; C.G.D.J.P.A. Hernesniemi 1996). The subtemporal (ST) approach allows for direct access to the lateral midbrain and interpeduncular fossa, achieved via exercising the minimal superior elevation of the temporal lobe possible to visualize the tentorial incisura (Ulm et al. 2004). The advantages of this approach include its relative simplicity as a mean of accessing the ventral or lateral aspect of the midbrain and pons with minimal reach distance. It also offers a superior view to the posterior aspect of the basilar apex, affording visualization of crucial perforators not possible with the pterional approach when attempting to clip a basilar tip aneurysm (Albert L. Rhoton 2002; Spetzler 2015). Tailoring of the subtemporal approach to include a zygomatic osteotomy enhances superior exposure, while the addition of an anterior petrosectomy enlarges the surgical window to the infratentorial space. Disadvantages of the subtemporal approach primarily include the necessity for temporal lobe retraction and associated risk of temporal lobe injury, inability to visualize the contralateral PCA and SCA when treating basilar apex aneurysms, as well as prohibitive anatomy to the approach in cases of a dominant, anteriorly running vein of Labbe’ (Spetzler 2015; Goehre et al. 2015).

2. INDICATIONS

The standard ST approach, as decribed by Drake, provides a direct lateral window to the interpeduncular fossa as well as the medial temporal lobe. As such, it should be considered as an approach for a multitude of pathologies contained within this space. Within the wide range of skull base approaches routinely employed for the treatmet of neurovascular pathologies (Ricci et al. 2017; Del Maestro et al. 2018; Gallieni et al. 2018; Luzzi, Del Maestro, et al. 2018; Luzzi, Gallieni, et al. 2018; Luzzi, Del Maestro, and Galzio 2019; Luzzi, Elia, Del Maestro, Morotti, et al. 2019; Luzzi et al. 2020), the ST approach has a still valuable role especially in treatment of those basilar apex aneuryms lying below the level of the posterior clinoid process (PCP) or arising at the superior cerebellar artery or basilar trunk (Drake 1968; C.G.D.J.P.A. Hernesniemi 1996). However, the utility of the approach has been expanded to include treatment of proximal PCA aneurysms, including fusiform type, via aneurysm bypass trapping in addition to superior cerebellar artery (SCA) aneurysms and anterior inferior cerebellar artery (AICA) aneurysms (Spetzler 2015; Goehre et al. 2015; Kawashima et al. 2017). The ST approach has additionally been utilized for resection of cavernous malformations and arteriovenous malformations in the upper pons and mesencephalon (Xie et al. 2019; Cannizzaro et al. 2019; Cavalcanti et al. 2019). Outside the realm of neurovascular surgery, lesions of the mesial temporal lobe structures, as in hippocampal sclerosis, can be reached via the ST approach (Hori et al. 2007; Welling et al. 2018). Adjuncts and modifications of the ST approach have additionally been implemented

Subtemporal Approach 299 to treat retrochiasmatic craniopharyngiomas, petroclival meningiomas, chondrosarcomas of the lateral skull base, pontine hematomas, facial nerve neurinomas, superior cerebellar tumors, chordomas of the upper clival region, as well as mesencephalic and perimesencephalic pediatric brainstem tumors (Ammerman, Lonser, and Oldfield 2005; Xu et al. 2016; Goel et al. 2018; Gosal et al. 2018; H.T. Zhang et al. 2018; Zielinski et al. 2018; Chiaramonte, Jacquesson, and Jouanneau 2019; Spennato et al. 2019).

3. TECHNIQUE

3.1. Brain Relaxation Measures

After induction of anesthesia, a lumbar drain is often placed prior to positioning to aid in achievement of brain relaxation with 40-50 cc often drained prior to beginning the craniotomy (Nakov et al. 2017; Spetzler 2015). Mannitol may be additionally administered at the time of craniotomy to further promote brain relaxation and minimize the temporal lobe retraction necessary to achieve an adequate surgical window (Spetzler 2015).

3.2. Positioning

In cases involving a midline lesion, the subtemporal approach should be pursued from the right side to avoid retraction of the dominant temporal lobe. Exceptions to this recommendation include exclusive accessibility of the target from the left, a left oculomotor nerve palsy, a left- sided blindness, or a right hemiparesis (J. Hernesniemi, K Ishii, M Niemelä, L Kivipelto, M Fujiki, and H Shen 2005). The patient is placed in the supine position or in the lateral decubitus position. When in the supine position, the patient’s neck should be rotated as much as possible to the contralateral side while using a large shoulder bump underneath the ipsilateral shoulder to avoid excessive neck torsion (Spetzler 2015; Spiessberger et al. 2018). The vertex of the head is then tilted approximately 15-20 degrees toward the floor to allow for gravity retraction to mobilize the temporal lobe away from the middle fossa. Finally, slight extension of the head by about 10 degrees may aid in avoiding laryngeal or endotracheal tube compression. For the lateral decubitus position, the sagittal suture is maintained near-parallel to the floor with the vertex of the head likewise oriented slightly downward toward the floor to take advantage of gravitational retraction (Spetzler 2015; Kim 2019). In both cases, the head is securred in a 3-pin Mayfield head-holder and kept elevated above the heart to facilitate venous drainage.

3.3. Skin Incision and Soft Tissue Dissection

There are several alternative skin incisions employed for the subtemporal approach. Commonly, either an inverted U-shape incision or question mark incision is made beginning at the root of the zygomatic arch about 1-1.5 cm anteriorly to the tragus curving anteriorly and upward then posteriorly over the pinna and back toward the suboccipital region (Spetzler 2015;

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Kim 2019; Spennato et al. 2019). A one-layer skin-muscle flap can then be everted inferiorly exposing the posterior portion of the zygomatic arch as well as the zygomatic root (Goehre et al. 2015). Subperiosteal detachment of the muscle from the underlying bone in a retrograde superior to inferior and backward to forward direction according to the Oikawa technique can be employed to minimize subsequent temporalis muscle atrophy (Oikawa et al. 1996).

3.4. Craniotomy

A bur hole is made just above the root of the zygomatic arch, and the width of the craniotomy is tailored according to a preoperative plan for the best angle of approach to the target lesion. A blunt instrument should be used to carefully detach the boneflap from the underlying dura. The squamous temporal bone, the inferior edge of the craniotomy, is then drilled flush with the floor of the middle fossa (Choque-Velasquez and Hernesniemi 2018). Removal of the overhanging inferior edge of the craniotomy is important for preparing an unobstructed operative trajectory toward the middle fossa floor. Any exposed mastoid air cells should be waxed to prevent development of a post-operative CSF leak (Spetzler 2015; Kim 2019; Tayebi Meybodi et al. 2018).

3.5. Extradural and Intradural Dissection

The dura is opened in an inverted U-shape and reflected caudally. The dissection is continued below the base of the temporal lobe until the tentorial edge is exposed. Under microscope visualization, the temporal lobe dura is carefully mobilized off the floor of the middle cranial fossa in order to identify the middle meningeal artery at the foramen spinosum, the greatersuperficial petrosal nerve (GSPN), mandibular branch of the trigeminal nerve and foramen ovale, and the arcuate eminence (Figure 1). The meningeal artery (MMA) can be cauterized at the foramen spinosum to avoid subsequent epidural hematoma development. The temporal lobe is gently elevated away from the floor of the temporal fossa until the tentorial edge is visualized. Small anterior infratemporal veins encountered during dissection can be coagulated and sharply divided, but larger posterior bridging veins and the vein of Labbe’ must be preserved. Microdisection is carried out between the basal surface of the temporal lobe and the tentorial edge. Once the tentorial edge is identified, the arachnoid of the interpeduncular and ambient cistern is opened sharply behind the third nerve (Cavalcanti et al. 2016; Lanzino, Cannizzaro, and Villa 2015). The area of exposure provided by this approach, including part of the anterior and the lateral incisural spaces, leads to the entire lateral midbrain surface. The arachnoid of the ambient, crural, and interpeduncular cisterns are opened widely. The oculomotor nerve can be visualized along with the cerebral peduncles, basilar artery, posterior cerebral artery, and superior cerebellar artery (Cavalcanti et al. 2018; Kalani, Yagmurlu, and Spetzler 2018; Tanriover et al. 2009).

Subtemporal Approach 301

Figure 1. Cadaveric dissection showing the surgical view during left subtemporal approach (interdural dissection with peeling of the lateral wall of the cavernous sinus). AE: arcuate eminence; GSPN: greater superficial petrosal nerve; Mand. Div. TN: mandibular division of the trigeminal nerve; MFD: middle fossa dura; MMA: middle meningeal artery; PA: petrous apex; TT: tegmen tympani.

4. TAILORING THE SUBTEMPORAL APPROACH

Modifications to the standard ST approach have been utilized to overcome some of the limitations that have been reported. Major surgical adjuncts to the subtemporal approach incude: division of the tentorium, zygomatic osteotomy, and anterior petrosectomy to widen applicability of this approach.

4.1. Transtentorial Extension

The standard subtemporal approach provides a narrow working area which is often inadaqute in terms of surgical exposure and requires manipulation of the anterior and middle tentorium. Depending on the degree of additional exposure needed, the transtentorial extension to the subtemporal approach is obtained by sectioning and/or retracting the tentorium just before the trochlear nerve pierces it (Archavlis et al. 2019; Nakov et al. 2017). Cutting the tentorium significantly improves visualization of the pontomesencephalic junction (PMJ) and the lateral upper pons, in addition to the SCA running in the direction of the quadrigeminal cistern (Albert L. Rhoton 2002; Spetzler 2015). When treating low-lying basilar aneurysms, sectioning or retracting the tentorium allows the surgeon to reach deeper into the posterior fossa, reach a more proximal segment of the basilar artery, and increase the rostrocaudal and anterolateral exposure.

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4.2. Zygomatic Osteotomy

Superior extension of the operative field can be achieved with the addition of a zygomatic osteotomy. After the ST approach is performed, the zygomatic arch can be cut at 2 points : posteriorly near the temporomandibular joint and anteriorly just behind the zygomatic bone (F. Gagliardi 2019; Saraceno et al. 2019; Ustun et al. 2006). Osteotomy of the zygomatic arch creates a gap, which can be utilized to further reflect the temporalis muscle downward, thereby widening the surgical corridor below the temporal lobe and affording a less oblique view of the subtemporal structures (Harsh and Sekhar 1992). This manuver increases a surgeon’s anterior- superior visualization of the interpeduncular fossa and can be particually useful in visualizing the contralateral P1, very low bifurcating basilar artery aneurysms, SCA origin aneusysms, and AICA aneurysms (Spetzler 2015; Albert L. Rhoton 2002; Ercan et al. 2017; Spiessberger et al. 2019).

4.3. Anterior Petrosectomy

The additon of an anterior petrosectomy extends the subtemporal exposure further into the posterior fossa, exposing the medial pons between the trigeminal nerve and cranial nerves VII/VIII. This modification often involves a zygomatic osteotomy as well as an extradural middle fossa dissection to expose the petrous apex. Drilling of the petrous apex down to the level of the inferior petrosal sinus is then undertaken, which maximixes potential exposure and avoids injury to the abducens nerve. Temporal and posterior fossa dura are then opened and the tentorium is sectioned posterior to the trochlear nerve. Additonal exposure can be gained by further dividing the tentorium to open Meckel’s cave. These manuvers signicantly increase the length of basilar artery exposure and provide visualization of the basilar artery between the trigeminal nerve and CN VII/VIII, enabling treatment of low basilar trunk or vetebrobasilar aneurysms without significantly increased temporal lobe retraction as compared to the standard ST approach (Spetzler 2015; Kim 2019; Albert L. Rhoton 2002; Kawase et al. 1985; Nussbaum 2013). The anterior petrosectomy facilitates visualization of basilar artery trunk aneurysms located as far as 25 mm below the top of the posterior clinoid process as measured on the lateral view of a vertebral angiogram. Exposure can be obtained as deep as the junction of the vertebral arteries (Sugita et al. 1987). This maneuver also allows the surgeon for proximal control, in cases where this cannot be achieved in any other way.

5. COMPLICATIONS AND COMPLICATIONS AVOIDANCE

The ST approach is related to a series of potential complications. The most notable include: temporal lobe edema or retraction injury, venous infarction, perforator infarction, and cranial nerve injury. Additional complicatioins include development of a post-operative epidural hematoma secondary to middle meningeal artery injury and post-operative CSF leak development, with risk of the former minimized by careful cauterization of the MMA at the level of the foramen spinosum and risk of the the latter minimized by diligent waxing of exposed mastoid air cells and meticulous dural closure.

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5.1. Temporal Lobe Retraction Injury

As the ST approach relies on temporal lobe retraction to achieve a visible operative corridor, retraction injury to the temporal lobe logically remains the most well-known complication of this approach. Adequate cerebrospinal fluid drainage is of paramount importance to achieving brain relaxation and limiting pressure placed on the temporal lobe. Ensuring to place the inferior margin of the subtemporal craniotomy flush with the cranial base helps minimize the need for retraction as well (Rhoton 2000). Likewise, optimal patient positioning to harness the aid of gravity can assist in minimizing direct retraction injury. Intermittent temporal lobe retraction with periodic release of tension rather than continous retraction throughout the surgery has been shown to potentially decrease the risk of temporal lobe injury based on experimental retraction studies. Specifically, Yokoh et al. demonstrated that the brain tolerates about 70% more intermittent retraction than continuous retraction from a morphological standpoint, while electrophysiologically the difference is about 40% (Yokoh, Sugita, and Kobayashi 1983). It is assumed that this difference in retraction tolerance derives from the fact that the blood circulation under the retractor recovers during a period of release. While the addition of a zygomatic osteotomy has been shown to marginally decrease the degree of necessary lateral temporal lobe retraction, it does not decrease the degree of deep temporal lobe retraction necessary to access the interpeduncular fossa via the ST approach (Gagliardi et al. 2020).

5.2. Venous Infarction

Brain edema and venous infarction during the ST approach can be caused by venous drainage impairment. The inferior cerebral veins draining to the transverse sinus are at risk of avulsion during temporal lobe retraction. The most significant of these, the vein of Labbe, should be estimated pre-operatively with an MR venogram with subsequent dural opening and extradural temporal lobe elevation adjusted for protection of this vital venous structure (Sindou and Dumot 2019; Ustun et al. 2006). All measures which minimize retraction likewise reduce risk of venous injury and infarction. Venous avulsion injury can also be limited by dissecting and skeletonizing exposed draining veins from adjacent arachnoid for some length to help prevent unnecessary overstretching or injury to these structures (Sugita, Kobayashi, and Yokoo 1982).

5.3. Arterial Injury and Perforator Infarction

Due to the lateral-to-medial line of sight obtained in the ST approach, identification of the contralateral P1 and perforators can be difficult, especially in cases where the aneurysmal dome is oriented posteriorly. In the case of a posteriorly oriented aneurysm, the aneurysm dome can be buried high up in the interpeduncular fossa, and numerous perforators from basilar terminus are often adherent to the back of the aneurysm. It is critical to carefully dissect these perforators off of the region of the aneurysmal neck that the clip will traverse. It is also critical to select an aneurysmal clip of the appropriate length such that the poorly visualized contralateral P1, SCA, and oculomotor nerve are not inadvertently clipped. In some cases, fenestrated clips may prove

304 L. Silveira, J. Muse, S. Luzzi et al. useful in achieving optimal clip placement around the neck of the basilar aneurysm without clipping the ipsilateral PCA, allowing it to pass through the open aperture (Spetzler 2015; Kim 2019).

5.4. Cranial Nerve Injury

The narrow working window of the ST approach can limit maneuverability to a detriment. Reflection of the tentorial edge can be essential to achieving sufficient working space around the cerebral peduncle. However, identification of the trochlear nerve’s dural canal entry point should be achieved prior to making a tentorial incision in order to avoid trochlear nerve injury and associated diploplia. Risk of injury to the trochlear nerve is high during the subtemporal approach, as it hides from surgical visibility just under the tentorial edge, but it can be identified with careful dissection and tentorial incision then ensured to be behind the path of the nerve (Archavlis et al. 2019; Rhoton 2000; Pescatori et al. 2017). The oculomotor nerve often has to be manipulated in performing the ST approach, partilcularly when attempting to expose a BA aneurysm. This often results in a transient postoperative oculomotor nerve palsy, with the nerve recovering in a delayed fashion. Nonetheless, care should be taken to minimize torsion on the nerve during exposure, maintain the nerve’s blood supply, and avoid cautery in the nerve’s vicinity to minimize chances of permanent injury (Spetzler 2015).

6. ILLUSTRATIVE CASE

6.1. Case: Subtemporal Approach for a Large, Left-Projecting Basilar Tip Aneurysm

A 54-year-old male with no pertinent past medical history was diagnosed with an incidental, large basilar tip aneurysm. The patient underwent a formal angiogram for better characterization of the aneurysm (Figure 2), determined to be leftward projecting and with near incorporation of the origins of the posterior cerebral arteries. Based on the aneurysm’s location and said morphology, the descision was made to proceed with a left subtemporal transtentorial approach (Drake approach) for aneurysm clipping as opposed to endovascular intervention.

Figure 2. Preoperative anterior-posterior (A) and lateral (B) projection angiography after left vertebral artery injection showing a large basilar tip aneurysm.

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Figure 3. Preoperative picture showing the patient placed in lateral position with the vertex pointing downward (A-B); intraoperative pictures showing the blunt subperiosteal dissection of the temporalis muscle according to the Oikawa technique (C-D); (E) drilling of the temporal squama until to the middle fossa floor aimed to achieve a line of sight as much tangential as possible to the tentorial incisura and the ambiens cistern; (F) exposure of the tentorium after retraction of the left temporal lobe; subtemporal view before (G) and after (H) clipping of the basilar tip aneurysm.

The patient was placed in the described lateral position with vertex pointing slightly toward the ground to achieve some gravitational fall-away of the temporal lobe from middle cranial fossa floor. An inverted U-shape incision was made beginning at the root of the zygomatic arch, and the skin-muscle flap was everted inferiorly. The craniotomy was performed with the initial bur hole placed just above the root of the zygomatic arch, and the squamous temporal bone was drilled flush with the floor of the middle fossa to achieve the optimal line of sight to the tentorial incisura. Sharp dissection was utilized in order to open the arachnoid planes and expose the oculomotor nerve, basilar aneurysm, and the ipsilateral PCA and SCA. With posterior

306 L. Silveira, J. Muse, S. Luzzi et al. perforators well-visualized, a surgical clip was carefully placed across the neck of the aneurysm (Figure 3). Following water-tight dural closure, the bone flap was resecured and a standard closure followed. The patient underwent a post-operative repeat angiogram demonstrating successful occlusion of the treated aneurym with no evidence of residual filling, representing a technically successful surgery (Figure 4). The patient recovered well with no new neurologic deficits incurred post-operatively. This case represents an example of successful utilization of the subtemporal approach as a means of achieving direct access to the basilar apex for treatment of a very large and complex basilar tip aneurysm with incorporation of the PCAs into the aneurysmal base prohibiting endovascular treatment. Optimal positioning coupled with meticulous dissection and maximal squamosal bone drilling flush to floor of the middle fossa floor afforded an adequate surgical window for aneurysm treatment without venous injury or excessive temporal lobe retraction.

Figure 4. (A) Postoperative 3D CT-scan showing the subtemporal bone flap; (B) Postoperative anterior- posterior angiography showing the complete exclusion of the aneurysm.

DISCUSSION

While the ST approach has been adapted for treatment of a variety of pathologies, treatment of basilar apex (BA) and basilar trunk aneurysms is the most common neurovascular indication for the ST approach. Since Drake’s popularization of this approach in the 1960’s, the ST approach remains one of a limited set of open surgical options for appropriatley treating these complex lesions. While endovascular treatment is largely becoming more commonplace for such BA aneurysms, wide-necked BA aneurysms or aneurysms incorporating the PCAs into their bases preclude endovascular treatment and favor an open approach (Macdonald 2019). Appropriate patient selection for the ST approach to BA aneurysm treatment is an important component to achieving a successful outcome. As the aneurysm is viewed laterally with the ST approach, the surgeon can visualize the many vital perforating arteries that project superiorly and posteriorly from the basilar artery, PCOM, and PCA (J. Hernesniemi and Korja 2014). Additonally, the ST approach provides adequate visualation of the basilar trunk, allowing for achievement of proximal control. Despite these benifits, the ST approach is limited by poor visualization of the contralateral PCA and SCA with the degree of obscurement

Subtemporal Approach 307 amplified when the aneurysmal dome is oriented posteriorly as compared to anteriorly (Kim 2019; Nakov et al. 2017; Albert L. Rhoton 2002). High-positioned basilar aneurysms above the level of the PCP are less amenable to treatment by way of the ST approach and may be better treated by Yasargil’s popularized pterional approach, as such aneurysms fall outside the ST operative corridor and would require additional temporal lobe retraction (Albert L. Rhoton 2002; Kim 2019). Those BA aneurysms best served by the ST approach are anteriorly oriented BA aneurysms located at or slightly below the level of the PCP. Other structural characterisitcs that have been noted as making the ST approach more preferable include a prefixed chiasm as well as low positioned hypothalamic structures (Spetzler 2015; Kim 2019; Albert L. Rhoton 2002; Nussbaum 2013). The significant technical evolutions occurred in any fields of neurosurgery (Raysi Dehcordi et al. 2017; Cheng, Shetty, and Sekhar 2018; Luzzi, Crovace, et al. 2018; Palumbo et al. 2018; Zoia et al. 2018; Bellantoni et al. 2019; Luzzi, Crovace, et al. 2019; Luzzi, Elia, Del Maestro, Elbabaa, et al. 2019; Luzzi, Giotta Lucifero, et al. 2019; Palumbo et al. 2019; Spena et al. 2019; Antonosante et al. 2020; Campanella et al. 2020; Zoia et al. 2020; Millimaggi et al. 2018; Bongetta et al. 2019; Elsawaf et al. 2020) have lead to an equally wide technical evolution and refinement also of the ST. Just to cite few exemples, endoscopic assistance has been repprted to enanche the visualization of the target during ST approach (Ding et al. 2017). The decision as to whether one proceeds with surgical adjuncts to the classic subtemporal approach should be based on location of the lesion to be treated and surgical maneuverability required (Gagliardi et al. 2020; Spiessberger et al. 2019; Ercan et al. 2017). Beyond combining and expanding present surgical approaches, ongoing refinement in optics and instrumentation have yielded efforts to adapt the subtemporal approach, as already reported for other skull base approaches (Luzzi, Del Maestro, et al. 2019; Luzzi, Maestro, et al. 2019; Luzzi, Zoia, et al. 2019; Zoia et al. 2019; Arnaout et al. 2020), into endoscope-assisted microsurgerical approaches via keyhole entry points with the goal of minimizing parenchymal retraction and morbidity (Rehder and Cohen 2017; J. Zhang et al. 2019). While these approaches are generally achieving satisfactrory views of the lesion to be treated, maneuverability and working space remain a limiting factor (Gagliardi et al. 2020).

CONCLUSION

The ST approach remains a valid and effective approach to treating vascular pathology of the interpenduncular fossa, particularly basilar apex aneurysms set below the level of the posterior clinoid processes. The key to successful employment of the subtemporal approach lies in gaining rapid access to the tentorial edge without burdensome retraction of the temporal lobe. This is, in part, accomplished by careful patient selection, respecting prohibitive anatomy to the approach, but also by optimal patient positioning and CSF drainage. Selection of appropriate adjunctive measures to tailor the approach to a specifically located pathology, along with knowledge of the inherent risks and drawbacks of the approach, broadens its applicability and increases the likelihood of a successful outcome in the hands of an experienced neurosurgeon.

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REFERENCES

Albert L. Rhoton, Jr., M.D. 2002. Aneurysms.Neurosurgery, Volume 51. Ammerman, J. M., R. R. Lonser, and E. H. Oldfield. 2005. “Posterior subtemporal transtentorial approach to intraparenchymal lesions of the anteromedial region of the superior cerebellum.” J Neurosurg 103 (5): 783-8. https://doi.org/10.3171/jns.2005. 103.5.0783. https://www.ncbi.nlm.nih.gov/pubmed/16304980. Antonosante, A., L. Brandolini, M. d'Angelo, E. Benedetti, V. Castelli, M. D. Maestro, S. Luzzi, A. Giordano, A. Cimini, and M. Allegretti. 2020. “Autocrine CXCL8-dependent invasiveness triggers modulation of actin cytoskeletal network and cell dynamics.” Aging (Albany NY) 12 (2): 1928-1951. https://doi.org/10.18632/aging.102733. https://www. ncbi.nlm.nih.gov/pubmed/31986121. Archavlis, E., L. Serrano, F. Ringel, and S. R. Kantelhardt. 2019. “Tentorial Incision vs. Retraction of the Tentorial Edge during the Subtemporal Approach: Anatomical Comparison in Cadaveric Dissections and Retrospective Clinical Case Series.” J Neurol Surg B Skull Base 80 (5): 441-448. https://doi.org/10.1055/s-0038-1676077. https://www. ncbi.nlm.nih.gov/pubmed/31534884. Arnaout, M. M., S. Luzzi, R. Galzio, and K. Aziz. 2020. “Supraorbital keyhole approach: Pure endoscopic and endoscope-assisted perspective.” Clin Neurol Neurosurg 189: 105623. https://doi.org/10.1016/j.clineuro.2019.105623. https://www.ncbi.nlm.nih.gov/pubmed/ 31805490. Bellantoni, G., F. Guerrini, M. Del Maestro, R. Galzio, and S. Luzzi. 2019. “Simple schwannomatosis or an incomplete Coffin-Siris? Report of a particular case.” e Neurological Sci 14: 31-33. https://doi.org/10.1016/j.ensci.2018.11.021. https://www.ncbi. nlm.nih.gov/pubmed/30555950. Bongetta, D., C. Zoia, S. Luzzi, M. D. Maestro, A. Peri, G. Bichisao, D. Sportiello, I. Canavero, A. Pietrabissa, and R. J. Galzio. 2019. “Neurosurgical issues of bariatric surgery: A systematic review of the literature and principles of diagnosis and treatment.” Clin Neurol Neurosurg 176: 34-40. https://doi.org/10.1016/j.clineuro.2018.11.009. https://www.ncbi. nlm.nih.gov/pubmed/30500756. Campanella, R., L. Guarnaccia, C. Cordiglieri, E. Trombetta, M. Caroli, G. Carrabba, N. La Verde, P. Rampini, C. Gaudino, A. Costa, S. Luzzi, G. Mantovani, M. Locatelli, L. Riboni, S. E. Navone, and G. Marfia. 2020. “Tumor-Educated Platelets and Angiogenesis in Glioblastoma: Another Brick in the Wall for Novel Prognostic and Targetable Biomarkers, Changing the Vision from a Localized Tumor to a Systemic Pathology.” Cells 9 (2). https://doi.org/10.3390/cells9020294. https://www.ncbi.nlm.nih.gov/pubmed/31991805. Cannizzaro, D., G. Sabatino, C. Mancarella, M. Revay, M. Rossi, G. Pecchioli, A. Cardia, G. Maira, V. D'Angelo, and M. Fornari. 2019. “Management and Surgical Approaches of Brainstem Cavernous Malformations: Our Experience and Literature Review.” Asian J Neurosurg 14 (1): 131-139. https://doi.org/10.4103/ajns.AJNS_290_17. https://www.ncbi. nlm.nih.gov/pubmed/30937024. Cavalcanti, D. D., E. G. Figueiredo, M. C. Preul, and R. F. Spetzler. 2019. “Anatomical and Objective Evaluation of the Main Surgical Approaches to Pontine Intra-Axial Lesions.” World Neurosurg 121: e207-e214. https://doi.org/10.1016/j.wneu.2018.09.077. https://www.ncbi.nlm.nih.gov/pubmed/30261378.

Subtemporal Approach 309

Cavalcanti, D. D., B. A. Morais, E. G. Figueiredo, R. F. Spetzler, and M. C. Preul. 2018. “Accessing the Anterior Mesencephalic Zone: Orbitozygomatic versus Subtemporal Approach.” World Neurosurg 119: e818-e824. https://doi.org/10.1016/j.wneu.2018. 07.272. https://www.ncbi.nlm.nih.gov/pubmed/30096501. Cavalcanti, D. D., M. C. Preul, M. Y. Kalani, and R. F. Spetzler. 2016. “Microsurgical anatomy of safe entry zones to the brainstem.” J Neurosurg 124 (5): 1359-76. https://doi.org/ 10.3171/2015.4.JNS141945. https://www.ncbi.nlm.nih.gov/pubmed/26452114. Cheng, C. Y., R. Shetty, and L. N. Sekhar. 2018. “Microsurgical Resection of a Large Intraventricular Trigonal Tumor: 3-Dimensional Operative Video.” Oper Neurosurg (Hagerstown) 15 (6): E92-E93. https://doi.org/10.1093/ons/opy068. https://www.ncbi. nlm.nih.gov/pubmed/29618124. Chiaramonte, C., T. Jacquesson, and E. Jouanneau. 2019. “Extra-intradural extracavernous subtemporal approach for chondrosarcomas: technical note and case report.” Acta Neurochir (Wien) 161 (11): 2349-2352. https://doi.org/10.1007/s00701-019-03989-z. https://www.ncbi.nlm.nih.gov/pubmed/31273444. Choque-Velasquez, J., and J. Hernesniemi. 2018. “One burr-hole craniotomy: Subtemporal approach in helsinki neurosurgery.” Surg Neurol Int 9: 164. https://doi.org/ 10.4103/sni.sni_187_18. https://www.ncbi.nlm.nih.gov/pubmed/30186665. Del Maestro, M., S. Luzzi, M. Gallieni, D. Trovarelli, A. V. Giordano, M. Gallucci, A. Ricci, and R. Galzio. 2018. “Surgical Treatment of Arteriovenous Malformations: Role of Preoperative Staged Embolization.” Acta Neurochir Suppl 129: 109-113. https://doi.org/ 10.1007/978-3-319-73739-3_16. https://www.ncbi.nlm.nih.gov/pubmed/30171322. Ding, Z., Q. Wang, X. Lu, and X. Qian. 2017. “Endoscopic Intradural Subtemporal Keyhole Approach with Neuronavigational Assistance to the Suprasellar, Petroclival, and Ventrolateral Brainstem Regions: An Anatomic Study.” World Neurosurg 101: 606-614. https://doi.org/10.1016/j.wneu.2017.02.052. https://www.ncbi.nlm.nih.gov/pubmed/2822 3248. Drake, C. G. 1968. “The surgical treatment of aneurysms of the basilar artery.” J Neurosurg 29 (4): 436-46. https://doi.org/10.3171/jns.1968.29.4.0436. https://www.ncbi.nlm.nih.gov/ pubmed/4880820. Elsawaf, Y., S. Anetsberger, S. Luzzi, and S. K. Elbabaa. 2020. “Early Decompressive Craniectomy as Management for Severe TBI in the Pediatric Population: A Comprehensive Literature Review.” World Neurosurg. https://doi.org/10.1016/j.wneu.2020.02.065. https://www.ncbi.nlm.nih.gov/pubmed/32084616. Ercan, S., A. Scerrati, P. Wu, J. Zhang, and M. Ammirati. 2017. “Is less always better? Keyhole and standard subtemporal approaches: evaluation of temporal lobe retraction and surgical volume with and without zygomatic osteotomy in a cadaveric model.” J Neurosurg 127 (1): 157-164. https://doi.org/10.3171/2016.6.JNS16663. https://www.ncbi.nlm.nih.gov/ pubmed/27636184. Gagliardi, F., C. Gragnaniello, P. Mortini, A. Caputy. 2019. Extradural Subtemporal Transzygomatic Approach. Operative Cranial Neurosurgical Anatomy. Stuttgart: Georg Thieme Verlag. Gagliardi, F., M. Piloni, M. Bailo, N. Boari, F. Calvanese, A. Spina, A. J. Caputy, and P. Mortini. 2020. “Comparative anatomical study on the role of zygomatic osteotomy in the extradural subtemporal approach to the clival region, when less is more.” Surg Radiol Anat.

310 L. Silveira, J. Muse, S. Luzzi et al.

https://doi.org/10.1007/s00276-019-02407-4. https://www.ncbi.nlm.nih.gov/pubmed/ 31897653. Gallieni, M., M. Del Maestro, S. Luzzi, D. Trovarelli, A. Ricci, and R. Galzio. 2018. “Endoscope-Assisted Microneurosurgery for Intracranial Aneurysms: Operative Technique, Reliability, and Feasibility Based on 14 Years of Personal Experience.” Acta Neurochir Suppl 129: 19-24. https://doi.org/10.1007/978-3-319-73739-3_3. https://www. ncbi.nlm.nih.gov/pubmed/30171309. Goehre, F., M. Lehecka, B. R. Jahromi, H. Lehto, R. Kivisaari, F. Hijazy, L. Nayeb, T. Sugimoto, M. Morishige, A. Elsharkawy, M. von und zu Fraunberg, J. E. Jaaskelainen, and J. A. Hernesniemi. 2015. “Subtemporal approach to posterior cerebral artery aneurysms.” World Neurosurg 83 (5): 842-51. https://doi.org/10.1016/j.wneu.2015.01.042. https://www.ncbi.nlm.nih.gov/pubmed/25683130. Goel, A., S. Ranjan, A. Shah, S. Rai, S. Gore, and P. Dharurkar. 2018. “Subtemporal “Interdural” Surgical Approach for “Giant” Facial Nerve Neurinomas.” World Neurosurg 110: e835-e841. https://doi.org/10.1016/j.wneu.2017.11.127. https://www.ncbi.nlm.nih. gov/pubmed/29191541. Gosal, J. S., S. Behari, J. Joseph, A. K. Jaiswal, J. C. Sardhara, M. Iqbal, A. Mehrotra, and A. K. Srivastava. 2018. “Surgical excision of large-to-giant petroclival meningiomas focusing on the middle fossa approaches: The lessons learnt.” Neurol India 66 (5): 1434- 1446. https://doi.org/10.4103/0028-3886.241354. https://www.ncbi.nlm.nih.gov/pubmed/ 30233019. Harsh, G. R. th, and L. N. Sekhar. 1992. “The subtemporal, transcavernous, anterior transpetrosal approach to the upper brain stem and clivus.” J Neurosurg 77 (5): 709-17. https://doi.org/10.3171/jns.1992.77.5.0709. https://www.ncbi.nlm.nih.gov/pubmed/140 3112. Hernesniemi, Charles G. Drake Sydney J. PeerlessJuha A. 1996. Surgery of Vertebrobasilar Aneurysms. Vienna: Springer-Verlag. Hernesniemi, J., K. Ishii, M. Niemelä, L. Kivipelto, M. Fujiki, and H. Shen. 2005. Subtemporal Approach to Basilar Bifurcation Aneurysms: Advanced Technique and Clinical Experience. New Trends of Surgery for Stroke and Its Perioperative Management. Edited by Emanuela Keller Yasuhiro Yonekawa, Yoshiharu Sakurai, and Tetsuya Tsukahara. Vienna: Springer-Verlag. Hernesniemi, J., and M. Korja. 2014. “At the apex of cerebrovascular surgery--basilar tip aneurysms.” World Neurosurg 82 (1-2): 37-9. https://doi.org/10.1016/j.wneu.2013. 07.112. https://www.ncbi.nlm.nih.gov/pubmed/23920297. Hori, T., F. Yamane, T. Ochiai, S. Kondo, S. Shimizu, K. Ishii, and H. Miyata. 2007. “Selective subtemporal amygdalohippocampectomy for refractory temporal lobe epilepsy: operative and neuropsychological outcomes.” J Neurosurg 106 (1): 134-41. https://doi.org/ 10.3171/jns.2007.106.1.134. https://www.ncbi.nlm.nih.gov/pubmed/17236499. Kalani, M. Y. S., K. Yagmurlu, and R. F. Spetzler. 2018. “The interpeduncular fossa approach for resection of ventromedial midbrain lesions.” J Neurosurg 128 (3): 834-839. https://doi.org/10.3171/2016.9.JNS161680. https://www.ncbi.nlm.nih.gov/pubmed/2829 8049. Kawase, T., S. Toya, R. Shiobara, and T. Mine. 1985. “Transpetrosal approach for aneurysms of the lower basilar artery.” J Neurosurg 63 (6): 857-61. https://doi.org/10. 3171/jns.1985.63.6.0857. https://www.ncbi.nlm.nih.gov/pubmed/4056899.

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Kawashima, A., H. Andrade-Barazarte, B. R. Jahromi, M. Oinas, A. Elsharkawy, J. Kivelev, Y. Kubota, T. Kawamata, and J. A. Hernesniemi. 2017. “Superficial Temporal Artery: Distal Posterior Cerebral Artery Bypass through the Subtemporal Approach: Technical Note and Pilot Surgical Cases.” Oper Neurosurg (Hagerstown) 13 (3): 309-316. https://doi.org/10.1093/ons/opw033. https://www.ncbi.nlm.nih.gov/pubmed/28521345. Kim, Yong Bae, and Kyu Sung Lee. 2019. Subtemporal Approach. Neurovascular Surgery: Surgical Approaches for Neurovascular Diseases. Singapore: Springer. Lanzino, G., D. Cannizzaro, and S. L. Villa. 2015. “Subtemporal approach for distal basilar occlusion for giant aneurysm. Nuances and advantages of the subtemporal approach.” Neurosurg Focus 38 (Video Suppl 1): Video 5. https://doi.org/10.3171/2015.V1. FOCUS14536. https://www.ncbi.nlm.nih.gov/pubmed/25554846. Luzzi, S., A. M. Crovace, M. Del Maestro, A. Giotta Lucifero, S. K. Elbabaa, B. Cinque, P. Palumbo, F. Lombardi, A. Cimini, M. G. Cifone, A. Crovace, and R. Galzio. 2019. “The cell-based approach in neurosurgery: ongoing trends and future perspectives.” Heliyon 5 (11): e02818. https://doi.org/10.1016/j.heliyon.2019.e02818. https://www.ncbi.nlm.nih. gov/pubmed/31844735. Luzzi, S., A. M. Crovace, L. Lacitignola, V. Valentini, E. Francioso, G. Rossi, G. Invernici, R. J. Galzio, and A. Crovace. 2018. “Engraftment, neuroglial transdifferentiation and behavioral recovery after complete spinal cord transection in rats.” Surg Neurol Int 9: 19. https://doi.org/10.4103/sni.sni_369_17. https://www.ncbi.nlm.nih.gov/pubmed/29497 572. Luzzi, S., M. Del Maestro, D. Bongetta, C. Zoia, A. V. Giordano, D. Trovarelli, S. Raysi Dehcordi, and R. J. Galzio. 2018. “Onyx Embolization before the Surgical Treatment of Grade III Spetzler-Martin Brain Arteriovenous Malformations: Single-Center Experience and Technical Nuances.” World Neurosurg 116: e340-e353. https://doi.org/10.1016/ j.wneu.2018.04.203. https://www.ncbi.nlm.nih.gov/pubmed/29751183. Luzzi, S., M. Del Maestro, S. K. Elbabaa, and R. Galzio. 2020. “Letter to the Editor Regarding “One and Done: Multimodal Treatment of Pediatric Cerebral Arteriovenous Malformations in a Single Anesthesia Event.” World Neurosurg 134: 660. https://doi.org/ 10.1016/j.wneu.2019.09.166. https://www.ncbi.nlm.nih.gov/pubmed/32059273. Luzzi, S., M. Del Maestro, and R. Galzio. 2019. “Letter to the Editor. Preoperative embolization of brain arteriovenous malformations.” J Neurosurg: 1-2. https://doi.org/10.3171/2019. 6.JNS191541. https://www.ncbi.nlm.nih.gov/pubmed/31812150. Luzzi, S., M. Del Maestro, D. Trovarelli, D. De Paulis, S. R. Dechordi, H. Di Vitantonio, V. Di Norcia, D. F. Millimaggi, A. Ricci, and R. J. Galzio. 2019. “Endoscope-Assisted Microneurosurgery for Neurovascular Compression Syndromes: Basic Principles, Methodology, and Technical Notes.” Asian J Neurosurg 14 (1): 193-200. https://doi.org/ 10.4103/ajns.AJNS_279_17. https://www.ncbi.nlm.nih.gov/pubmed/30937034. Luzzi, S., A. Elia, M. Del Maestro, S. K. Elbabaa, S. Carnevale, F. Guerrini, M. Caulo, P. Morbini, and R. Galzio. 2019. “Dysembryoplastic Neuroepithelial Tumors: What You Need to Know.” World Neurosurg 127: 255-265. https://doi.org/10.1016/j.wneu. 2019.04.056. https://www.ncbi.nlm.nih.gov/pubmed/30981794. Luzzi, S., A. Elia, M. Del Maestro, A. Morotti, S. K. Elbabaa, A. Cavallini, and R. Galzio. 2019. “Indication, Timing, and Surgical Treatment of Spontaneous Intracerebral Hemorrhage: Systematic Review and Proposal of a Management Algorithm.” World

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Neurosurg. https://doi.org/10.1016/j.wneu.2019.01.016. https://www.ncbi.nlm.nih.gov/ pubmed/30677572. Luzzi, S., M. Gallieni, M. Del Maestro, D. Trovarelli, A. Ricci, and R. Galzio. 2018. “Giant and Very Large Intracranial Aneurysms: Surgical Strategies and Special Issues.” Acta Neurochir Suppl 129: 25-31. https://doi.org/10.1007/978-3-319-73739-3_4. https://www. ncbi.nlm.nih.gov/pubmed/30171310. Luzzi, S., A. Giotta Lucifero, M. Del Maestro, G. Marfia, S. E. Navone, M. Baldoncini, M. Nunez, A. Campero, S. K. Elbabaa, and R. Galzio. 2019. “Anterolateral Approach for Retrostyloid Superior Parapharyngeal Space Schwannomas Involving the Jugular Foramen Area: A 20-Year Experience.” World Neurosurg 132: e40-e52. https://doi.org/10. 1016/j.wneu.2019.09.006. https://www.ncbi.nlm.nih.gov/pubmed/31520759. Luzzi, S., M. D. Maestro, A. Elia, F. Vincitorio, G. D. Perna, F. Zenga, D. Garbossa, S. K. Elbabaa, and R. Galzio. 2019. “Morphometric and Radiomorphometric Study of the Correlation between the Foramen Magnum Region and the Anterior and Posterolateral Approaches to Ventral Intradural Lesions.” Turk Neurosurg 29 (6): 875-886. https://doi.org/10.5137/1019-5149.JTN.26052-19.2. https://www.ncbi.nlm.nih.gov/pub med/31452176. Luzzi, S., C. Zoia, A. D. Rampini, A. Elia, M. Del Maestro, S. Carnevale, P. Morbini, and R. Galzio. 2019. “Lateral Transorbital Neuroendoscopic Approach for Intraconal Meningioma of the Orbital Apex: Technical Nuances and Literature Review.” World Neurosurg 131: 10-17. https://doi.org/10.1016/j.wneu.2019.07.152. https://www.ncbi. nlm.nih.gov/pubmed/31356977. Macdonald, R. Loch. 2019. Subtemporal and Pretemporal Approaches for Basilar and Posterior Cerebral Artery Aneurysms. Neurosurgical Operative Atlas: Vascular Neurosurgery. Stuttgart. Georg Thieme Verlag. Millimaggi, D. F., V. D. Norcia, S. Luzzi, T. Alfiero, R. J. Galzio, and A. Ricci. 2018. “Minimally Invasive Transforaminal Lumbar Interbody Fusion with Percutaneous Bilateral Pedicle Screw Fixation for Lumbosacral Spine Degenerative Diseases. A Retrospective Database of 40 Consecutive Cases and Literature Review.” Turk Neurosurg 28 (3): 454-461. https://doi.org/10.5137/1019-5149.JTN.19479-16.0. https://www.ncbi. nlm.nih.gov/pubmed/28481388. Nakov, V. S., T. Y. Spiriev, I. T. Todorov, and P. Simeonov. 2017. “Technical nuances of subtemporal approach for the treatment of basilar tip aneurysm.” Surg Neurol Int 8: 15. https://doi.org/10.4103/2152-7806.199555. https://www.ncbi.nlm.nih.gov/pubmed/2821 7394. Nussbaum, Eric S. 2013. Aneurysms of the Basilar Artery. Video Atlas of Intracranial Aneurysm Surgery. . Stuttgart. Georg Thieme Verlag. . Oikawa, S., M. Mizuno, S. Muraoka, and S. Kobayashi. 1996. “Retrograde dissection of the temporalis muscle preventing muscle atrophy for pterional craniotomy. Technical note.” J Neurosurg 84 (2): 297-9. https://doi.org/10.3171/jns.1996.84.2.0297. https://www.ncbi. nlm.nih.gov/pubmed/8592239. Palumbo, P., F. Lombardi, F. R. Augello, I. Giusti, S. Luzzi, V. Dolo, M. G. Cifone, and B. Cinque. 2019. “NOS2 inhibitor 1400W Induces Autophagic Flux and Influences Extracellular Vesicle Profile in Human Glioblastoma U87MG Cell Line.” Int J Mol Sci 20 (12). https://doi.org/10.3390/ijms20123010. https://www.ncbi.nlm.nih.gov/pubmed/ 31226744.

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Palumbo, P., F. Lombardi, G. Siragusa, S. R. Dehcordi, S. Luzzi, A. Cimini, M. G. Cifone, and B. Cinque. 2018. “Involvement of NOS2 Activity on Human Glioma Cell Growth, Clonogenic Potential, and Neurosphere Generation.” Int J Mol Sci 19 (9). https://doi.org/10.3390/ijms19092801. https://www.ncbi.nlm.nih.gov/pubmed/30227679. Patel, S. K., and J. K. Liu. 2016. “Overview and History of Trigeminal Neuralgia.” Neurosurg Clin N Am 27 (3): 265-76. https://doi.org/10.1016/j.nec.2016.02.002. https://www.ncbi. nlm.nih.gov/pubmed/27324994. Pescatori, L., M. Niutta, M. P. Tropeano, G. Santoro, and A. Santoro. 2017. “Fourth cranial nerve: surgical anatomy in the subtemporal transtentorial approach and in the pretemporal combined inter-intradural approach through the fronto-temporo-orbito-zygomatic craniotomy. A cadaveric study.” Neurosurg Rev 40 (1): 143-153. https://doi.org/10.1007/ s10143-016-0777-9. https://www.ncbi.nlm.nih.gov/pubmed/27549625. Raysi Dehcordi, S., A. Ricci, H. Di Vitantonio, D. De Paulis, S. Luzzi, P. Palumbo, B. Cinque, D. Tempesta, G. Coletti, G. Cipolloni, M. G. Cifone, and R. Galzio. 2017. “Stemness Marker Detection in the Periphery of Glioblastoma and Ability of Glioblastoma to Generate Glioma Stem Cells: Clinical Correlations.” World Neurosurg 105: 895- 905. https://doi.org/10.1016/j.wneu.2017.05.099. https://www.ncbi.nlm.nih.gov/pubmed/ 28559081. Rehder, R., and A. R. Cohen. 2017. “Endoscope-Assisted Microsurgical Subtemporal Keyhole Approach to the Posterolateral Suprasellar Region and Basal Cisterns.” World Neurosurg 103: 114-121. https://doi.org/10.1016/j.wneu.2017.02.054. https://www.ncbi.nlm.nih. gov/pubmed/28232212. Rhoton, A. L., Jr. 2000. “Tentorial incisura.” Neurosurgery 47 (3 Suppl): S131-53. https://doi.org/10.1097/00006123-200009001-00015. https://www.ncbi.nlm.nih.gov/pub med/10983307. Ricci, A., H. Di Vitantonio, D. De Paulis, M. Del Maestro, S. D. Raysi, D. Murrone, S. Luzzi, and R. J. Galzio. 2017. “Cortical aneurysms of the middle cerebral artery: A review of the literature.” Surg Neurol Int 8: 117. https://doi.org/10.4103/sni.sni_50_17. https://www.ncbi.nlm.nih.gov/pubmed/28680736. Saraceno, G., E. Agosti, J. Qiu, B. Buffoli, M. Ferrari, E. Raffetti, F. Belotti, M. Ravanelli, D. Mattavelli, A. Schreiber, L. Hirtler, L. F. Rodella, R. Maroldi, P. Nicolai, F. Gentili, W. Kucharczyk, M. M. Fontanella, and F. Doglietto. 2019. “Quantitative Anatomical Comparison of Anterior, Anterolateral and Lateral, Microsurgical and Endoscopic Approaches to the Middle Cranial Fossa.” World Neurosurg. https://doi.org/10.1016/ j.wneu.2019.10.178. https://www.ncbi.nlm.nih.gov/pubmed/31731015. Sindou, M., and C. Dumot. 2019. “Planning of Endocranial Supratentorial Basal Cistern and Skull Base Approaches Depending on Venous Patterns Using a Topogram.” World Neurosurg 134: 365-371. https://doi.org/10.1016/j.wneu.2019.11.009. https://www.ncbi. nlm.nih.gov/pubmed/31715402. Spena, G., E. Roca, F. Guerrini, P. P. Panciani, L. Stanzani, A. Salmaggi, S. Luzzi, and M. Fontanella. 2019. “Risk factors for intraoperative stimulation-related seizures during awake surgery: an analysis of 109 consecutive patients.” J Neurooncol 145 (2): 295- 300. https://doi.org/10.1007/s11060-019-03295-9. https://www.ncbi.nlm.nih.gov/pubmed/ 31552589. Spennato, P., C. Chiaramonte, C. Russo, N. Onorini, G. Mirone, F. Mazio, G. Di Martino, R. S. Parlato, and G. Cinalli. 2019. “Subtemporal Transtentorial Approach in Mesencephalic

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and Perimesencephalic Lesions in Children-A Series of 20 Patients.” Oper Neurosurg (Hagerstown). https://doi.org/10.1093/ons/opz254. https://www.ncbi.nlm.nih.gov/pub med/31504862. Spetzler, Robert F., M. Yashar, S. Kalani, and Peter Nakaji. 2015. Neurovascular Surgery. Surgical Approaches to the Posterior Fossa. Vol. 89. Stuttgart: Georg Thieme Verlag. Spiessberger, A., F. Baumann, A. Stauffer, S. Marbacher, K. F. Kothbauer, J. Fandino, and B. Moriggl. 2019. “The Subtemporal Approach to the Lateral Midbrain with and without Zygomatic Osteotomy: An Anatomical Study.” Clin Anat 32 (5): 710-714. https://doi.org/10.1002/ca.23383. https://www.ncbi.nlm.nih.gov/pubmed/30968458. Spiessberger, A., F. Strange, J. Fandino, and S. Marbacher. 2018. “Microsurgical Clipping of Basilar Apex Aneurysms: A Systematic Historical Review of Approaches and their Results.” World Neurosurg 114: 305-316. https://doi.org/10.1016/j.wneu.2018.03.141. https://www.ncbi.nlm.nih.gov/pubmed/29602006. Sugita, K., S. Kobayashi, T. Takemae, T. Tada, and Y. Tanaka. 1987. “Aneurysms of the basilar artery trunk.” J Neurosurg 66 (4): 500-5. https://doi.org/10.3171/jns.1987.66.4.0500. https://www.ncbi.nlm.nih.gov/pubmed/3559716. Sugita, K., S. Kobayashi, and A. Yokoo. 1982. “Preservation of large bridging veins during brain retraction. Technical note.” J Neurosurg 57 (6): 856-8. https://doi.org/ 10.3171/jns.1982.57.6.0856. https://www.ncbi.nlm.nih.gov/pubmed/7143075. Tanriover, N., G. Z. Sanus, M. O. Ulu, T. Tanriverdi, Z. Akar, P. A. Rubino, and A. L. Rhoton, Jr. 2009. “Middle fossa approach: microsurgical anatomy and surgical technique from the neurosurgical perspective.” Surg Neurol 71 (5): 586-96; discussion 596. https://doi.org/ 10.1016/j.surneu.2008.04.009. https://www.ncbi.nlm.nih.gov/pubmed/18617228. Tayebi Meybodi, A., A. Benet, R. Rodriguez Rubio, S. Yousef, P. Mokhtari, M. C. Preul, and M. T. Lawton. 2018. “Comparative Analysis of Orbitozygomatic and Subtemporal Approaches to the Basilar Apex: A Cadaveric Study.” World Neurosurg 119: e607-e616. https://doi.org/10.1016/j.wneu.2018.07.217. https://www.ncbi.nlm.nih.gov/pubmed/300 77027. Ulm, A. J., N. Tanriover, M. Kawashima, A. Campero, F. J. Bova, and A. Rhoton, Jr. 2004. “Microsurgical approaches to the perimesencephalic cisterns and related segments of the posterior cerebral artery: comparison using a novel application of image guidance.” Neurosurgery 54 (6): 1313-27; discussion 1327-8. https://doi.org/10.1227/01.neu. 0000126129.68707.e7. https://www.ncbi.nlm.nih.gov/pubmed/15157288. Ustun, M. E., M. Buyukmumcu, C. H. Ulku, O. Guney, and A. Salbacak. 2006. “Transzygomatic-Subtemporal Approach for Middle Meningeal-to-P2 Segment of the Posterior Cerebral Artery Bypass: An Anatomical and Technical Study.” Skull Base 16 (1): 39-44. https://doi.org/10.1055/s-2006-931622. https://www.ncbi.nlm.nih.gov/pubmed/ 16880900. Welling, L. C., E. G. Figueiredo, P. Nakaji, M. S. Welling, M. D. Schafranski, M. J. Teixeira, R. F. Spetzler, and M. C. Preul. 2018. “Less is more: Parahippocampal resection or endoscopic assistance in ambient cistern surgery? Qualitative and quantitative assessment of subtemporal approach.” J Clin Neurosci 53: 203-208. https://doi.org/10.1016/ j.jocn.2018.04.018. https://www.ncbi.nlm.nih.gov/pubmed/29685409. Xie, S., X. R. Xiao, H. Li, G. L. Meng, J. T. Zhang, Z. Wu, and L. W. Zhang. 2019. “Surgical treatment of pontine cavernous malformations via subtemporal transtentorial and intradural

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anterior transpetrosal approaches.” Neurosurg Rev. https://doi.org/10.1007/s10143-019- 01156-7. https://www.ncbi.nlm.nih.gov/pubmed/31388841. Xu, Z., X. Zeng, D. Tian, and Q. Chen. 2016. “Microsurgical Resection of Petroclival Tumors via the Subtemporal Transtentorial Approach.” Turk Neurosurg 26 (3): 331- 5. https://doi.org/10.5137/1019-5149.JTN.10897-14.1. https://www.ncbi.nlm.nih.gov/pub med/27161456. Yokoh, A., K. Sugita, and S. Kobayashi. 1983. “Intermittent versus continuous brain retraction. An experimental study.” J Neurosurg 58 (6): 918-23. https://doi.org/10.3171/ jns.1983.58.6.0918. https://www.ncbi.nlm.nih.gov/pubmed/6854385. Zhang, H. T., L. H. Chen, M. C. Bai, and R. X. Xu. 2018. “Anterior subtemporal approach for severe upper pontine hematomas: A report of 28 surgically treated cases.” J Clin Neurosci 54: 20-24. https://doi.org/10.1016/j.jocn.2018.04.063. https://www.ncbi.nlm.nih.gov/ pubmed/29779725. Zhang, J., W. Hua, X. Zhang, K. Quan, J. Song, P. Li, and L. Chen. 2019. “Pure Endoscopic Surgery via Subtemporal Extradural Keyhole Approach for Middle Cranial Fossa Tumors.” World Neurosurg 130: e487-e497. https://doi.org/10.1016/j.wneu.2019.06.131. https://www.ncbi.nlm.nih.gov/pubmed/31254695. Zielinski, G., E. A. Sajjad, L. Robak, and A. Koziarski. 2018. “Subtemporal Approach for Gross Total Resection of Retrochiasmatic Craniopharyngiomas: Our Experience on 30 Cases.” World Neurosurg 109: e265-e273. https://doi.org/10.1016/j.wneu.2017.09.159. https://www.ncbi.nlm.nih.gov/pubmed/28987834. Zoia, C., D. Bongetta, G. Dorelli, S. Luzzi, M. D. Maestro, and R. J. Galzio. 2019. “Transnasal endoscopic removal of a retrochiasmatic cavernoma: A case report and review of literature.” Surg Neurol Int 10: 76. https://doi.org/10.25259/SNI-132-2019. https://www. ncbi.nlm.nih.gov/pubmed/31528414. Zoia, C., D. Bongetta, F. Guerrini, C. Alicino, A. Cattalani, S. Bianchini, R. J. Galzio, and S. Luzzi. 2018. “Outcome of elderly patients undergoing intracranial meningioma resection: a single center experience.” J Neurosurg Sci. https://doi.org/10.23736/S0390- 5616.18.04333-3. https://www.ncbi.nlm.nih.gov/pubmed/29808631. Zoia, C., F. Lombardi, M. R. Fiore, A. Montalbetti, A. Iannalfi, M. Sansone, D. Bongetta, F. Valvo, M. Del Maestro, S. Luzzi, and R. J. Galzio. 2020. “Sacral solitary fibrous tumour: surgery and hadrontherapy, a combined treatment strategy.” Rep Pract Oncol Radiother 25 (2): 241-244. https://doi.org/10.1016/j.rpor.2020.01.008. https://www.ncbi.nlm.nih. gov/pubmed/32025222.

Chapter 19

RETROSIGMOID APPROACH

F. Cofano1, MD, F. Vincitorio1,, MD, F. Zenga1, MD and D. Garbossa1, MD, PhD 1Department of Neurosurgery, University of Turin, Turin, Italy

ABSTRACT

The versatility of the retrosigmoid approach allows for tailored exposure of the cerebello-pontine angle in its full cranio-caudal extension, of the ventrolateral brainstem, and of the region of the transverse and sigmoid sinuses. In this chapter two different cases of vascular diseases that required a retromastoid craniotomy are presented. Infra- and transtentorial vascular lesions can be easily addressed with modifications of the standard approach, when needed, making it a flexible and irreplaceable option for all neurosurgeons.

Keywords: retrosigmoid approach, retromastoid craniotomy, neurovascular disease, Dural Arteriovenous fistula, Cavernous Hemangioma

ABBREVIATIONS

CPA Cerebello-Pontine Angle CT Computed-Tomography MRA Magnetic Resonance Angiography DAVF Dural Arteriovenous fistula PICA Posterior Inferior Cerebellar Artery CSF Cerebro-Spinal Fluid.

 Corresponding Author’s Email: [email protected].

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1. INTRODUCTION

The retrosigmoid approach is a familiar approach to all neurosurgeons. Its technical variations, aimed to tailor more and more this valuable corridor, are part of a wide technical evolutions of the skull base approaches for the treatment of several vascular and neoplastic lesions (Arnaout et al. 2019; Luzzi, Del Maestro, Elia, et al. 2019; Luzzi, Del Maestro, Trovarelli, et al. 2019; Luzzi, Zoia, et al. 2019; Zoia et al. 2019; Ricci et al. 2017; Del Maestro et al. 2018; Gallieni et al. 2018; Luzzi, Del Maestro, et al. 2018; Luzzi, Gallieni, et al. 2018; Luzzi, Del Maestro, and Galzio 2019; Luzzi, Elia, Del Maestro, Morotti, et al. 2019; Kunigelis, Yang, and Youssef 2018; Kurucz et al. 2017; Luzzi et al. 2020; Liu and Dodson 2019; Ishi, Terasaka, and Motegi 2019). Its versatility for a tailored exposure allows to reach the cerebello-pontine angle in its total cranio-caudal extension, the ventrolateral brainstem and the region of the transverse and sigmoid sinuses. Infra- and transtentorial vascular lesions can be easily addressed with modifications of the standard approach, when needed, making it a flexible and irreplaceable option for all neurosurgeons. The implementation of these technical variations has been possible thanks to the remarkable technological improved achieved in the field of skull base surgery, on a par with what occurred in other fields of neurosurgery (Raysi Dehcordi et al. 2017; Cheng, Shetty, and Sekhar 2018; Luzzi, Crovace, et al. 2018; Palumbo et al. 2018; Zoia et al. 2018; Bellantoni et al. 2019; Luzzi, Crovace, et al. 2019; Luzzi, Elia, Del Maestro, Elbabaa, et al. 2019; Luzzi, Giotta Lucifero, et al. 2019; Palumbo et al. 2019; Spena et al. 2019; Antonosante et al. 2020; Campanella et al. 2020; Zoia et al. 2020; Millimaggi et al. 2018; Bongetta et al. 2019; Elsawaf et al. 2020).

2. METHODS

Two different cases of vascular diseases requiring a retromastoid craniotomy are presented. Each case had its particular clinical and radiological features. General principles to perform a safe retrosigmoid approach are then described. Finally, the tailored surgical strategies achieved to manage the aforementioned cases are presented.

2.1. Case 1

A 54-year-old female presented to the attention of the authors after sudden onset of headache and emesis. A CT scan showed tetraventricular hemorrhage without hydrocephalus. Neurological examination revealed a severe loss of central visual acuity of the right eye. Patient was then admitted to the Neurosurgical Department for initial conservative management. A Magnetic Resonance Angiography (MRA) posed the suspicion of the presence of a Dural Arteriovenous fistula (DAVF) and then a selective angiography was performed. The angiography revealed a high-flow DAVF (Figure 1), located at the Right sigmoid- transverse junction. Predominant feeding arteries were recognized to be: a meningeal branch from the right ophthalmic artery; interosseus branches from the right occipital and posterior auricular arteries; branches from the right middle meningeal artery; branches from the right

Retrosigmoid Approach 319 sphenopalatine artery. A retrograde venous drainage was detected from the right transverse sinus to the superior longitudinal sinus. The right jugular gulf was found to be completely thrombosed. The left jugular gulf was patent and received a large portion of the venous drainage of the fistula. A rich venous reflux involved hemispheric bilateral cortical veins. Because of the high-risk features of this fistula, given its radiological pattern and the clinical consequences, a surgical treatment was decided after a collegial briefing with neuroradiologists. Informed consent was obtained from the patient before the procedure.

Figure 1. MRA study showing the DAVF. Meningeal branches from the right ophthalmic artery (A, C); branches from the right middle meningeal artery (B, C). Right jugular gulf was found to be completely thrombosed (D, E).

2.2. Case 2

A 65-year-old female patient presented in the emergency room. Her past history was notable for a conservatively managed pons hemangioma, which one year before caused the

320 F. Cofano, F. Vincitorio, F. Zenga et al. sudden onset of double vision with left abducens palsy, after two episodes of bleeding. Given the deep location and the small size of the lesion, surgery had not been considered a safe option.

Figure 2. Pons Hemangioma. The lesion did not reach the brainstem surface.

At the time of this new admission the patient complained of a severe worsening of double vision, the onset of left hemiparesthesia and headache. A CT scan revealed a new bleeding of the known lesion. MRI showed that the lesion had consistently grown in size in the lower part of the pons (Figure 2). Given the multiple episodes of bleeding and the evidence of fast growth, a surgical strategy was proposed to the patient. Informed consent was obtained from the patient before the procedure.

3. THE RETROSIGMOID APPROACH – GENERAL PRINCIPLES

The retrosigmoid approach is a well-known flexible approach to the cerebello-pontine angle (CPA) (Samii and Gerganov 2008) With different variations, it can be used for vascular lesions, such as arteriovenous malformations of the CPA, posterior circulation aneurysms, DAVFs, for excision of vestibular schwannomas, for microvascular cranial nerve decompressions of the V or VII nerve, or for petroclival pathologies. Correct patient positioning is mandatory to achieve an optimal surgical trajectory, avoiding excessive retraction on the cerebellum but at the same time gaining access to desired targets (Martin Lehecka 2011). A craniotomy/craniectomy, reaching with its upper border the level of the transverse sinus or even above it, is usually the standard for V nerve microvascular decompression (Broggi et al. 2012) A slight caudal extension of the craniotomy is necessary for vestibular schwannomas, while aneurysms at the origin of the Posterior Inferior Cerebellar Artery (PICA) usually require a lower exposure of the CPA (Cohen-Gadol 2011). A wider cranio-caudal exposure is usually needed for brainstem lesions or giant vascular malformations. Other modification of the retrosigmoid approach could represent a useful strategy for reaching lesions of the cerebellar hemisphere, such as intracerebellar hematomas or infarctions, as well as tumors (Martin Lehecka 2011). Regarding tumors, the consistency of the lesion has a key role in dictating the need for a more expanded approach and a wider path to the anterior brainstem. Various patient positions are technically suitable to perform the approach: supine, semi- sitting, lateral park bench or Fukushima lateral position (Black et al. 1988). The risk of postoperative neck stiffness especially in case of long procedures usually advises against the supine position (Martin Lehecka 2011; Black et al. 1988; Rath et al. 2007) The lateral position

Retrosigmoid Approach 321 is generally preferred among surgeons. In our experience we prefer to place the patient in lateral position according to Fukushima’s modifications. The head should be about 20 cm above the level of the heart, elevated together with the trunk. Lateral supports are needed and are usually placed at the level of pelvis and below the level of the upper shoulder (Martin Lehecka 2011; Samii and Gerganov 2008). Chin flexion with the vertex tilted downwards is mandatory, making the mastoid region the highest point of the head. The rotation of the head is, of course, towards the side contralateral to the pathology at hand. Care should be taken to avoid compression of the jugular veins with lateral tilting. The upper shoulder could constitute an important obstruction to the free movements of the surgeon; therefore, care must be taken both in head positioning and in caudal shoulder retraction. Padding should be placed under the breast line and between the lower limbs (Martin Lehecka 2011), as well as around all areas that could be vulnerable to pressure (limb nerves and brachial plexus, joints, hands) (Rath et al. 2007). A lumbar drain can be placed before incision, to achieve posterior fossa decompression (Martin Lehecka 2011; Broggi et al. 2012) A postoperative drain can be useful for the first 48 hours to promote a watertight dural closure. The identification of anatomical landmarks is mandatory for skin incision: the asterion, the junction of the lambdoid, parietomastoid and occipitomastoid sutures; the superior nucal line, overlying the transverse sinus; the squamo‐parietomastoid line to the mastoid tip, landmark for the sigmoid sinus (Sheng et al. 2012; Avci et al. 2003; Ucerler and Govsa 2006). The incision can be made according to surgeon preference: linear, C shaped, or S shaped. It is usually placed about about one inch behind the mastoid process (Martin Lehecka 2011). Depending on the necessary cranio-caudal extension, the skin incision can vary in length. Skin, subcutaneous tissue and galea are reflected together, even if a galea-subcutaneous flap can be harvested for dural closure. A mastoid retractor or hooks can be placed to allow adequate exposure. The junction of the sigmoid and the transverse sinuses is usually located at about the junction of the zygomatic line and a line running through the tip of the mastoid process (Tubbs et al. 2009). The occipital artery needs to be identified and coagulated, since it nearly always runs across the surgical incision. Muscle dissection according to their layers and the direction of their fibers (sternocleidomastoid, splenium capitis) can be made once detached from the bone. A burr hole is usually placed just below the transverse-sigmoid junction (Bozbuga, Boran, and Sahinoglu 2006). Caution is needed in the absence of neuronavigation, since the exact location of dural sinuses is variable. In case of craniectomy, bony rongeurs or a high-speed drill allow for the exposure of the edges of the sigmoid and transverse sinuses. It is mandatory to avoid tears in their walls for the risk of thrombosis. Therefore, an “egg-shell” technique should be used to protect sinuses before identification of proper margins of the exposure. Other authors prefer craniotomy after burr hole and dural detachment from the bone. It could be safer to avoid craniotomy in cases of strong adherence of the dura to the internal surface of the bone, like for example in older patients. In case of a more caudal extension, care must be taken during exposure to recognize the level of the foramen magnum, since caudal to that point a concrete risk of damaging the vertebral artery arises. The vertebral artery runs in a bony sulcus on the superior edge of the lateral part of the posterior arch of the atlas; it then turns anteriorly to enter into the subdural space (Wanibuchi et al. 2009).The identification of the epidural vertebral artery venous plexus bleeding and the surrounding fat tissue constitutes a useful landmark to locate the artery. In case of craniotomy, an “egg-shell” drilling of the bone over the sigmoid sinus is a safe option to protect the sinus wall. If Kerrison’s rongeurs are used, it is important to point their

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“mouth” away from the sinus to avoid tears (Martin Lehecka 2011). An accidental opening of mastoid air cells can be repaired with bone wax and/or fat/muscle grafts in order to avoid postoperative cerebrospinal fluid (CSF) leak (Sanna et al. 2004). The mastoid emissary vein connects the suboccipital venous plexus to the sigmoid sinus and could be found during drilling, with need for waxing (Rhoton 2000). Injury of the sinus with massive bleeding is a complication that needs to be addressed quickly and with the right measures. Coagulation of the tear is not recommended, since it usually further retracts dural edges, increasing the tear and the bleeding. Anti-Trendelenburg position should be promptly exacerbated. Cellulose and hemostatic matrixes should be used to cover the bleeding, with cottonoid patties ensuring pressure. Direct invasion of hemostatic material into the sinus could cause thrombosis. A linear cut could also be repaired with direct suture. Dura mater can be incised in a curvilinear manner just 1.5 to 2 mm medial to the sigmoid and inferior to the transverse sinus. A star-shaped incision is another possibility to allow for primary watertight dural closure. The dural edges are then elevated. The arachnoid over the superolateral or inferolateral cerebellum - depending on the procedure and the target of surgery - should be opened to allow for CSF drainage, achieving proper retraction of the cerebellum medially to expose the CPA avoiding contusions of the cerebellar hemisphere (Martin Lehecka 2011). Arachnoid limiting the cistern can be opened with dissectors and microscissors. The tentorium and the cranial nerves constitute valid landmarks for orientation. Veins should be left intact as much as possible. Proper dural closure is mandatory. If direct dural suture is not possible, a dural substitute can be used; fibrin glue can assist in sealing the dural closure. Mastoid air cells have to be closed as suggested, to avoid postoperative CSF leak (Lawton and Lang 2019). The craniotomy defect can be filled with the patient’s own bone or a cranioplasty can be performed. Accuracy must be taken to properly close the muscle and subcutaneous tissue to further increase the chance to reduce the risk of CSF leak.

3.1. Case 1 - Management

In this case, occlusion of transverse and sigmoid sinuses constituted the best strategy to close the fistula. Therefore an extended retrosigmoid approach was chosen to expose the transverse sinus and the sigmoid sinus, and extending to the presigmoid region and the occipital sovratentorial dura. A hockey-stick incision was carried out and a craniectomy performed with high speed drilling. The exposed sovra- and subtentorial dura mater was coagulated. The transverse sinus was then ligated. The sinus junction was then exposed and hemostasis obtained with hemoclips and cellulose matrix. After ligation, the sinuses in the region of the junction were cut. Dural closure was obtained with dural substitute and fibrin glue. A cranioplasty was made. Post-op study showed the complete closure of the DAVF with a patent left venous sinus drainage (Figure 3). Patient did not show any clinical worsening and at 3 years follow-up her vision has improved.

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Figure 3. After surgery. The left venous drainage was patent (A, B), while the right sigmoid and transverse sinus were completely occluded (A).

3.2. Case 2 - Management

A suboccipital telovelar approach was considered at high risk of facial nucleus damage and thus a lateral pontine entry zone through the middle cerebellar peduncle was chosen (Lawton and Lang 2019). An extended retroauricular C-shaped incision was performed. A retromastoid craniectomy was performed obtaining a wide exposure of the CPA beneath the tentorium, in order to identify all the cranial nerves from trigeminal to the vagus. The dura was incised in a curvilinear manner. The arachnoid in the region of the lower cranial nerves (IX, X) was opened to allow for CSF drainage (Figure 4). The flocculus was then identified together with cranial nerves V, VII and VIII. Then, after neuromonitoring with direct stimulation and neuronavigation, a lateral mielotomy was performed between the root entry zones of nerves VII-VIII and V with micro-dissectors. The hemangioma was then found and gently removed (Figure 4). Direct dural closure with sutures and fibrin glue was performed. A cranioplasty was made. At discharge, patient referred improvement of paresthesia, but double vision persisted. Post-op imaging was satisfactory and showed the complete removal of the hemangioma. No facial deficit was recorded.

Figure 4. Post-operative MRI showing the removal of the hemangioma (A, B). Direct stimulation of the facial nerve (C) and of the surgical entry zone for mielotomy. (D) Hemangioma removal. (E) Black asterisk: VII-VIII complex. Black asterisks: IX-X complex. Black arrow: hemangioma.

324 F. Cofano, F. Vincitorio, F. Zenga et al.

CONCLUSION

The retrosigmoid approach constitutes a safe, familiar and effective way to treat infratentorial lesions. Modifications of the approach can allow to manage vascular diseases involving the posterior fossa in the cerebello-pontin angle, cerebellar hemispheres, and region of the transverse-sigmoid sinuse junction.

REFERENCES

Antonosante, A., L. Brandolini, M. d’Angelo, E. Benedetti, V. Castelli, M. D. Maestro, S. Luzzi, A. Giordano, A. Cimini, and M. Allegretti. 2020. “Autocrine CXCL8-dependent invasiveness triggers modulation of actin cytoskeletal network and cell dynamics.” Aging (Albany NY) 12 (2): 1928-1951. https://doi.org/10.18632/aging.102733. https://www.ncbi. nlm.nih.gov/pubmed/31986121. Arnaout, M. M., S. Luzzi, R. Galzio, and K. Aziz. 2019. “Supraorbital keyhole approach: Pure endoscopic and endoscope-assisted perspective.” Clin Neurol Neurosurg 189: 105623. https://doi.org/10.1016/j.clineuro.2019.105623. https://www.ncbi.nlm.nih.gov/pubmed/ 31805490. Avci, E., Y. Kocaogullar, D. Fossett, and A. Caputy. 2003. “Lateral posterior fossa venous sinus relationships to surface landmarks.” Surg Neurol 59 (5): 392-7; discussion 397. https://doi.org/10.1016/s0090-3019(03)00037-5. https://www.ncbi.nlm.nih.gov/pubmed/ 12765815. Bellantoni, G., F. Guerrini, M. Del Maestro, R. Galzio, and S. Luzzi. 2019. “Simple schwannomatosis or an incomplete Coffin-Siris? Report of a particular case.” eNeurologicalSci 14: 31-33. https://doi.org/10.1016/j.ensci.2018.11.021. https://www. ncbi.nlm.nih.gov/pubmed/30555950. Black, S., D. B. Ockert, W. C. Oliver, Jr., and R. F. Cucchiara. 1988. “Outcome following posterior fossa craniectomy in patients in the sitting or horizontal positions.” Anesthesiology 69 (1): 49-56. https://doi.org/10.1097/00000542-198807000-00008. https://www.ncbi.nlm.nih.gov/pubmed/3389566. Bongetta, D., C. Zoia, S. Luzzi, M. D. Maestro, A. Peri, G. Bichisao, D. Sportiello, I. Canavero, A. Pietrabissa, and R. J. Galzio. 2019. “Neurosurgical issues of bariatric surgery: A systematic review of the literature and principles of diagnosis and treatment.” Clin Neurol Neurosurg 176: 34-40. https://doi.org/10.1016/j.clineuro.2018.11.009. https://www.ncbi. nlm.nih.gov/pubmed/30500756. Bozbuga, M., B. O. Boran, and K. Sahinoglu. 2006. “Surface anatomy of the posterolateral cranium regarding the localization of the initial burr-hole for a retrosigmoid approach.” Neurosurg Rev 29 (1): 61-3. https://doi.org/10.1007/s10143-005-0417-2. https://www. ncbi.nlm.nih.gov/pubmed/16228239. Broggi, G., M. Broggi, P. Ferroli, and A. Franzini. 2012. “Surgical technique for trigeminal microvascular decompression.” Acta Neurochir (Wien) 154 (6): 1089-95. https://doi. org/10.1007/s00701-012-1324-2. https://www.ncbi.nlm.nih.gov/pubmed/22531963. Campanella, R., L. Guarnaccia, C. Cordiglieri, E. Trombetta, M. Caroli, G. Carrabba, N. La Verde, P. Rampini, C. Gaudino, A. Costa, S. Luzzi, G. Mantovani, M. Locatelli, L. Riboni,

Retrosigmoid Approach 325

S. E. Navone, and G. Marfia. 2020. “Tumor-Educated Platelets and Angiogenesis in Glioblastoma: Another Brick in the Wall for Novel Prognostic and Targetable Biomarkers, Changing the Vision from a Localized Tumor to a Systemic Pathology.” Cells 9 (2). https://doi.org/10.3390/cells9020294. https://www.ncbi.nlm.nih.gov/ pubmed/31991805. Cheng, C. Y., R. Shetty, and L. N. Sekhar. 2018. “Microsurgical Resection of a Large Intraventricular Trigonal Tumor: 3-Dimensional Operative Video.” Oper Neurosurg (Hagerstown) 15 (6): E92-E93. https://doi.org/10.1093/ons/opy068. https://www.ncbi. nlm.nih.gov/pubmed/29618124. Cohen-Gadol, A. A. 2011. “Microvascular decompression surgery for trigeminal neuralgia and hemifacial spasm: naunces of the technique based on experiences with 100 patients and review of the literature.” Clin Neurol Neurosurg 113 (10): 844-53. https://doi.org/ 10.1016/j.clineuro.2011.06.003. https://www.ncbi.nlm.nih.gov/pubmed/ 21752534. Del Maestro, M., S. Luzzi, M. Gallieni, D. Trovarelli, A. V. Giordano, M. Gallucci, A. Ricci, and R. Galzio. 2018. “Surgical Treatment of Arteriovenous Malformations: Role of Preoperative Staged Embolization.” Acta Neurochir Suppl 129: 109-113. https://doi.org/ 10.1007/978-3-319-73739-3_16. https://www.ncbi.nlm.nih.gov/pubmed/ 30171322. Elsawaf, Y., S. Anetsberger, S. Luzzi, and S. K. Elbabaa. 2020. “Early Decompressive Craniectomy as Management for Severe TBI in the Pediatric Population: A Comprehensive Literature Review.” World Neurosurg. https://doi.org/10.1016/j.wneu.2020.02.065. https://www.ncbi.nlm.nih.gov/pubmed/32084616. Gallieni, M., M. Del Maestro, S. Luzzi, D. Trovarelli, A. Ricci, and R. Galzio. 2018. “Endoscope-Assisted Microneurosurgery for Intracranial Aneurysms: Operative Technique, Reliability, and Feasibility Based on 14 Years of Personal Experience.” Acta Neurochir Suppl 129: 19-24. https://doi.org/10.1007/978-3-319-73739-3_3. https://www. ncbi.nlm.nih.gov/pubmed/30171309. Ishi, Y., S. Terasaka, and H. Motegi. 2019. “Retrosigmoid Intradural Suprameatal Approach for Petroclival Meningioma.” J Neurol Surg B Skull Base 80 (Suppl 3): S296-S297. https://doi.org/10.1055/s-0038-1675168. https://www.ncbi.nlm.nih.gov/pubmed/31143 599. Kunigelis, K., A. Yang, and A. S. Youssef. 2018. “Endoscopic Assisted Retrosigmoid Approach for Cerebellopontine Angle Epidermoid Tumor.” J Neurol Surg B Skull Base 79 (Suppl 5): S413-S414. https://doi.org/10.1055/s-0038-1669978. https://www.ncbi.nlm. nih.gov/pubmed/30456046. Kurucz, P., G. Baksa, L. Patonay, F. Thaher, M. Buchfelder, and O. Ganslandt. 2017. “Endoscopic approach-routes in the posterior fossa cisterns through the retrosigmoid keyhole craniotomy: an anatomical study.” Neurosurg Rev 40 (3): 427-448. https://doi.org/ 10.1007/s10143-016-0800-1. https://www.ncbi.nlm.nih.gov/pubmed/ 27832380. Lawton, M. T., and M. J. Lang. 2019. “The future of open vascular neurosurgery: perspectives on cavernous malformations, AVMs, and bypasses for complex aneurysms.” J Neurosurg 130 (5): 1409-1425. https://doi.org/10.3171/2019.1.JNS182156. https://www.ncbi.nlm. nih.gov/pubmed/31042667. Liu, J. K., and V. N. Dodson. 2019. “Retrosigmoid Suprameatal Approach for Resection of Petrotentorial Cerebellopontine Angle Meningioma: Operative Video and Technical Nuances.” J Neurol Surg B Skull Base 80 (Suppl 3): S290-S291. https://doi.org/10.1055/s- 0039-1685532. https://www.ncbi.nlm.nih.gov/pubmed/311435 96.

326 F. Cofano, F. Vincitorio, F. Zenga et al.

Luzzi, S., A. M. Crovace, M. Del Maestro, A. Giotta Lucifero, S. K. Elbabaa, B. Cinque, P. Palumbo, F. Lombardi, A. Cimini, M. G. Cifone, A. Crovace, and R. Galzio. 2019. “The cell-based approach in neurosurgery: ongoing trends and future perspectives.” Heliyon 5 (11): e02818. https://doi.org/10.1016/j.heliyon.2019.e02818. https://www.ncbi.nlm.nih. gov/pubmed/31844735. Luzzi, S., A. M. Crovace, L. Lacitignola, V. Valentini, E. Francioso, G. Rossi, G. Invernici, R. J. Galzio, and A. Crovace. 2018. “Engraftment, neuroglial transdifferentiation and behavioral recovery after complete spinal cord transection in rats.” Surg Neurol Int 9: 19. https://doi.org/10.4103/sni.sni_369_17. https://www.ncbi.nlm.nih.gov/pubmed/29497572. Luzzi, S., M. Del Maestro, D. Bongetta, C. Zoia, A. V. Giordano, D. Trovarelli, S. Raysi Dehcordi, and R. J. Galzio. 2018. “Onyx Embolization Before the Surgical Treatment of Grade III Spetzler-Martin Brain Arteriovenous Malformations: Single-Center Experience and Technical Nuances.” World Neurosurg 116: e340-e353. https://doi.org/10.1016/ j.wneu.2018.04.203. https://www.ncbi.nlm.nih.gov/pubmed/29751183. Luzzi, S., M. Del Maestro, S. K. Elbabaa, and R. Galzio. 2020. “Letter to the Editor Regarding “One and Done: Multimodal Treatment of Pediatric Cerebral Arteriovenous Malformations in a Single Anesthesia Event.”” World Neurosurg 134: 660. https://doi.org/ 10.1016/j.wneu.2019.09.166. https://www.ncbi.nlm.nih.gov/pubmed/32059273. Luzzi, S., M. Del Maestro, A. Elia, F. Vincitorio, G. Di Perna, F. Zenga, D. Garbossa, S. Elbabaa, and R. Galzio. 2019. “Morphometric and Radiomorphometric Study of the Correlation Between the Foramen Magnum Region and the Anterior and Posterolateral Approaches to Ventral Intradural Lesions.” Turk Neurosurg. https://doi.org/10. 5137/1019- 5149.JTN.26052-19.2. https://www.ncbi.nlm.nih.gov/pubmed/31452176. Luzzi, S., M. Del Maestro, and R. Galzio. 2019. “Letter to the Editor. Preoperative embolization of brain arteriovenous malformations.” J Neurosurg: 1-2. https://doi.org/10.3171/ 2019.6.JNS191541. https://www.ncbi.nlm.nih.gov/pubmed/31812150. https://thejns.org/ view/journals/j-neurosurg/aop/article-10.3171-2019.6.JNS191541/article-10.3171-2019. 6.JNS191541.xml. Luzzi, S., M. Del Maestro, D. Trovarelli, D. De Paulis, S. R. Dechordi, H. Di Vitantonio, V. Di Norcia, D. F. Millimaggi, A. Ricci, and R. J. Galzio. 2019. “Endoscope-Assisted Microneurosurgery for Neurovascular Compression Syndromes: Basic Principles, Methodology, and Technical Notes.” Asian J Neurosurg 14 (1): 193-200. https://doi. org/10.4103/ajns.AJNS_279_17. https://www.ncbi.nlm.nih.gov/pubmed/30937034. Luzzi, S., A. Elia, M. Del Maestro, S. K. Elbabaa, S. Carnevale, F. Guerrini, M. Caulo, P. Morbini, and R. Galzio. 2019. “Dysembryoplastic Neuroepithelial Tumors: What You Need to Know.” World Neurosurg 127: 255-265. https://doi.org/10.1016/ j.wneu.2019.04.056. https://www.ncbi.nlm.nih.gov/pubmed/30981794. Luzzi, S., A. Elia, M. Del Maestro, A. Morotti, S. K. Elbabaa, A. Cavallini, and R. Galzio. 2019. “Indication, Timing, and Surgical Treatment of Spontaneous Intracerebral Hemorrhage: Systematic Review and Proposal of a Management Algorithm.” World Neurosurg. https://doi.org/10.1016/j.wneu.2019.01.016. https://www.ncbi.nlm.nih.gov/ pubmed/30677572. Luzzi, S., M. Gallieni, M. Del Maestro, D. Trovarelli, A. Ricci, and R. Galzio. 2018. “Giant and Very Large Intracranial Aneurysms: Surgical Strategies and Special Issues.” Acta Neurochir Suppl 129: 25-31. https://doi.org/10.1007/978-3-319-73739-3_4. https://www. ncbi.nlm.nih.gov/pubmed/30171310.

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Luzzi, S., A. Giotta Lucifero, M. Del Maestro, G. Marfia, S. E. Navone, M. Baldoncini, M. Nunez, A. Campero, S. K. Elbabaa, and R. Galzio. 2019. “Anterolateral Approach for Retrostyloid Superior Parapharyngeal Space Schwannomas Involving the Jugular Foramen Area: A 20-Year Experience.” World Neurosurg 132: e40-e52. https://doi.org/10. 1016/j.wneu.2019.09.006. https://www.ncbi.nlm.nih.gov/pubmed/31520759. Luzzi, S., C. Zoia, A. D. Rampini, A. Elia, M. Del Maestro, S. Carnevale, P. Morbini, and R. Galzio. 2019. “Lateral Transorbital Neuroendoscopic Approach for Intraconal Meningioma of the Orbital Apex: Technical Nuances and Literature Review.” World Neurosurg 131: 10-17. https://doi.org/10.1016/j.wneu.2019.07.152. https://www.ncbi. nlm.nih.gov/pubmed/31356977. Martin Lehecka, Aki Laakso and Juha Hernesniemi. 2011. Helsinki Microneurosurgery Basics and Tricks. Helsinki, Finland. Millimaggi, D. F., V. D. Norcia, S. Luzzi, T. Alfiero, R. J. Galzio, and A. Ricci. 2018. “Minimally Invasive Transforaminal Lumbar Interbody Fusion with Percutaneous Bilateral Pedicle Screw Fixation for Lumbosacral Spine Degenerative Diseases. A Retrospective Database of 40 Consecutive Cases and Literature Review.” Turk Neurosurg 28 (3): 454-461. https://doi.org/10.5137/1019-5149.JTN.19479-16.0. https://www.ncbi. nlm.nih.gov/pubmed/28481388. Palumbo, P., F. Lombardi, F. R. Augello, I. Giusti, S. Luzzi, V. Dolo, M. G. Cifone, and B. Cinque. 2019. “NOS2 inhibitor 1400W Induces Autophagic Flux and Influences Extracellular Vesicle Profile in Human Glioblastoma U87MG Cell Line.” Int J Mol Sci 20 (12). https://doi.org/10.3390/ijms20123010. https://www.ncbi.nlm.nih.gov/pubmed/ 31226744. Palumbo, P., F. Lombardi, G. Siragusa, S. R. Dehcordi, S. Luzzi, A. Cimini, M. G. Cifone, and B. Cinque. 2018. “Involvement of NOS2 Activity on Human Glioma Cell Growth, Clonogenic Potential, and Neurosphere Generation.” Int J Mol Sci 19 (9). https://doi.org/10.3390/ijms19092801. https://www.ncbi.nlm.nih.gov/pubmed/30227679. Rath, G. P., P. K. Bithal, A. Chaturvedi, and H. H. Dash. 2007. “Complications related to positioning in posterior fossa craniectomy.” J Clin Neurosci 14 (6): 520-5. https://doi. org/10.1016/j.jocn.2006.02.010. https://www.ncbi.nlm.nih.gov/pubmed/17430775. Raysi Dehcordi, S., A. Ricci, H. Di Vitantonio, D. De Paulis, S. Luzzi, P. Palumbo, B. Cinque, D. Tempesta, G. Coletti, G. Cipolloni, M. G. Cifone, and R. Galzio. 2017. “Stemness Marker Detection in the Periphery of Glioblastoma and Ability of Glioblastoma to Generate Glioma Stem Cells: Clinical Correlations.” World Neurosurg 105: 895- 905. https://doi.org/10.1016/j.wneu.2017.05.099. https://www.ncbi.nlm.nih.gov/pubmed/ 28559081. Rhoton, A. L., Jr. 2000. “The cerebellopontine angle and posterior fossa cranial nerves by the retrosigmoid approach.” Neurosurgery 47 (3 Suppl): S93-129. https://doi.org/10. 1097/00006123-200009001-00013. https://www.ncbi.nlm.nih.gov/pubmed/10983306. Ricci, A., H. Di Vitantonio, D. De Paulis, M. Del Maestro, S. D. Raysi, D. Murrone, S. Luzzi, and R. J. Galzio. 2017. “Cortical aneurysms of the middle cerebral artery: A review of the literature.” Surg Neurol Int 8: 117. https://doi.org/10.4103/sni.sni_50_17. https://www. ncbi.nlm.nih.gov/pubmed/28680736. Samii, M., and V. M. Gerganov. 2008. “Surgery of extra-axial tumors of the cerebral base.” Neurosurgery 62 (6 Suppl 3): 1153-66; discussion 1166-8. https://doi.org/10. 1227/01.neu.0000333782.19682.76. https://www.ncbi.nlm.nih.gov/pubmed/18695537.

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Sanna, M., A. Taibah, A. Russo, M. Falcioni, and M. Agarwal. 2004. “Perioperative complications in acoustic neuroma (vestibular schwannoma) surgery.” Otol Neurotol 25 (3): 379-86. https://doi.org/10.1097/00129492-200405000-00029. https://www.ncbi.nlm. nih.gov/pubmed/15129121. Sheng, B., F. Lv, Z. Xiao, Y. Ouyang, F. Lv, J. Deng, Y. You, and N. Liu. 2012. “Anatomical relationship between cranial surface landmarks and venous sinus in posterior cranial fossa using CT angiography.” Surg Radiol Anat 34 (8): 701-8. https://doi.org/10. 1007/s00276- 011-0916-5. https://www.ncbi.nlm.nih.gov/pubmed/22160178. Spena, G., E. Roca, F. Guerrini, P. P. Panciani, L. Stanzani, A. Salmaggi, S. Luzzi, and M. Fontanella. 2019. “Risk factors for intraoperative stimulation-related seizures during awake surgery: an analysis of 109 consecutive patients.” J Neurooncol 145 (2): 295- 300. https://doi.org/10.1007/s11060-019-03295-9. https://www.ncbi.nlm.nih.gov/pubmed/ 31552589. Tubbs, R. S., M. Loukas, M. M. Shoja, M. P. Bellew, and A. A. Cohen-Gadol. 2009. “Surface landmarks for the junction between the transverse and sigmoid sinuses: application of the “strategic” burr hole for suboccipital craniotomy.” Neurosurgery 65 (6 Suppl): 37-41; discussion 41. https://doi.org/10.1227/01.NEU.0000341517.65174.63. https://www.ncbi. nlm.nih.gov/pubmed/19935000. Ucerler, H., and F. Govsa. 2006. “Asterion as a surgical landmark for lateral cranial base approaches.” J Craniomaxillofac Surg 34 (7): 415-20. https://doi.org/10.1016/j. jcms.2006.05.003. https://www.ncbi.nlm.nih.gov/pubmed/16963269. Wanibuchi, M., T. Fukushima, F. Zenga, and A. H. Friedman. 2009. “Simple identification of the third segment of the extracranial vertebral artery by extreme lateral inferior transcondylar-transtubercular exposure (ELITE).” Acta Neurochir (Wien) 151 (11): 1499- 503. https://doi.org/10.1007/s00701-009-0360-z. https://www.ncbi.nlm.nih.gov/pubmed/ 19657583. Zoia, C., D. Bongetta, G. Dorelli, S. Luzzi, M. D. Maestro, and R. J. Galzio. 2019. “Transnasal endoscopic removal of a retrochiasmatic cavernoma: A case report and review of literature.” Surg Neurol Int 10: 76. https://doi.org/10.25259/SNI-132-2019. https://www.ncbi.nlm.nih.gov/pubmed/31528414. Zoia, C., D. Bongetta, F. Guerrini, C. Alicino, A. Cattalani, S. Bianchini, R. J. Galzio, and S. Luzzi. 2018. “Outcome of elderly patients undergoing intracranial meningioma resection: a single center experience.” J Neurosurg Sci. https://doi.org/10.23736/S0390-5616.18. 04333-3. https://www.ncbi.nlm.nih.gov/pubmed/29808631. Zoia, C., F. Lombardi, M. R. Fiore, A. Montalbetti, A. Iannalfi, M. Sansone, D. Bongetta, F. Valvo, M. Del Maestro, S. Luzzi, and R. J. Galzio. 2020. “Sacral solitary fibrous tumour: surgery and hadrontherapy, a combined treatment strategy.” Rep Pract Oncol Radiother 25 (2): 241-244. https://doi.org/10.1016/j.rpor.2020.01.008. https://www.ncbi.nlm.nih. gov/pubmed/32025222.

Chapter 20

FAR LATERAL APPROACH

S. Luzzi1,2,*, MD, PhD, A. Giotta Lucifero1, MD, M. Del Maestro2,3, MD, C. Gragnaniello4, MD and R. Galzio1,2, MD 1Neurosurgery Unit, Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy 2Neurosurgery Unit, Department of Surgical Sciences, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy 3PhD School in Experimental Medicine, Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy 4Department of Neurological Surgery, University of Illinois at Chicago, Chicago, IL, US

ABSTRACT

The far lateral approach is an inferolateral extension of the lateral suboccipital approach. Introduced for the treatment of the vertebrobasilar junction and proximal posterior-inferior cerebellar artery aneurysms, over the years, it has also become a workhorse approach for ventral foramen magnum meningiomas and, generally, intradural extra-axial lesions located anterior to the dentate ligament. In this chapter, we review the technical steps of the far lateral approach, also focusing on its transcondylar, supracondylar, and paracondylar extensions.

Keywords: far lateral approach, posterior-inferior cerebellar artery aneurysms, posterior circulation aneurysms, transcondylar approach, VA Aneurysms, VBJ Aneurysms

1. INTRODUCTION

The far lateral approach was described by Roberto Heros in 1986 (Heros 1986).

* Corresponding Author’s Email: [email protected].

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It consists of further lateral extension of the lateral suboccipital approach where drilling of the posterolateral aspect of the foramen magnum (FM) and C1 hemilaminectomy dramatically increases the working space in front of the brainstem without the need for retraction. The far lateral approach has unquestionable advantages in exposing the intradural vertebral artery (VA), vertebrobasilar junction (VBJ), proximal segments of the posterior-inferior cerebellar artery (PICA), and anterolateral aspects of the medulla oblongata and the upper cervical cord. It also involves the option of transcondylar, supracondylar, or paracondylar extension, with a further increase in the working space at the anterior edge of the FM, jugular tubercle (JT) area, and posterior edge of the jugular foramen (JF), respectively. Because of all aforementioned reasons, the far lateral approach has become a pillar within the posterolateral approaches to the skull base for the treatment of those lesions involving the anterior and anterolateral FM, lower clivus, premedullary area, and upper spinal cord.

2. INDICATIONS

Basically, the far lateral approach is indicated in those lesions lying in front of the dentate ligament and included between the lower third of the clivus and superior aspect of the body of C2, the last being the anterior limit of the FM region (M. Bruneau and George 2010). Extra- axial lesions of this area involve the premedullary and lateral cerebellomedullary cistern. They are ventral FM meningiomas, aneurysms of the V4 segment of the VA, VBJ, anterior and lateral medullary segment of the PICA, lower cranial nerve schwannomas, and arteriovenous malformations of the lower ventral brainstem. Furthermore, cavernous hemangiomas at the level of the anterolateral aspect of the medulla oblongata or upper cervical cord may be reached with the far lateral approach.

3. TECHNIQUE

3.1. Positioning

Over the years, on the basis of their personal preferences, several authors have introduced some technical modifications to the original description of the far lateral approach by Heros (Heros 1986). Actually, the surgical position and skin incision have been the most revisited aspects of the approach. Apart from personal preferences, in the mental process of the surgical planning of the far lateral approach, the surgeon should select a specific position, always considering some basic principles as follows: achieve the widest possible exposure of the lesion, work through a surgical route having the shortest distance to the target, minimize the need for retraction as much as possible, obtain full hemodynamic control of the VA, preserve an optimal venous outflow, and ensure the best comfort for the patient and surgeon. A variety of surgical positions have been proposed for the far lateral approach as follows:

 Lateral position, with the patient’s head tilted toward the ipsilateral shoulder (Heros 1986; Day, Fukushima, and Giannotta 1997)

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 Sitting position, with the patient’s head rotated toward the lesion (H. Bertalanffy and Seeger 1991; de Oliveira, Rhoton, and Peace 1985; George et al. 1993; George, Dematons, and Cophignon 1988; Michaël Bruneau and George 2008)  Three-quarter prone (modified park-bench) position, with the patient’s head rotated toward the floor and flexed onto the contralateral shoulder to obtain a shallow suboccipital triangle. The arm is secured below the upper end of the operating table, and the axilla is padded (Lanzino, Paolini, and Spetzler 2005; Wen et al. 1997)  Supine position, with the patient’s head rotated 45° opposite to the lesion (al-Mefty et al. 1996; Arnautovic, Al-Mefty, and Husain 2000)  Prone position, with the patient’s head in neutral position (Menezes, Traynelis, and Gantz 1994).

3.2. Skin Incision and Nuchal Muscle Mobilization

A reverse hockey-stick, linear, and C-shaped skin incision has been proposed for the far lateral approach. The classic reverse hockey-stick incision starts below the mastoid tip, runs upward to the superior nuchal line, curves medially to reach the opisthocranion in the midline or inion depending on the lesion, and then proceeds downward until C3 (Lanzino, Paolini, and Spetzler 2005) (Figure 1a). Some authors recommend a technical note of the reverse hockey-stick incision where the cut starts in the midline, 5 cm below the inion, reaches the opisthocranion upward, follows laterally the superior nuchal line, passes above the mastoid, and proceeds downward in front of the posterior border of the sternocleidomastoid muscle to terminate 5 cm below the mastoid tip (Wen et al. 1997; A.L. Rhoton 2000a; de Oliveira, Rhoton, and Peace 1985; Tedeschi and Rhoton 1994; Chaddad-Neto et al. 2014). This hockey-stick incision involves a medial reflection of the muscle block and allows an unobstructed view of the lateral aspect of the C0–C1 complex and V3 segment of the VA. The linear incision is placed between the inion and mastoid tip and aims to obtain an easy, fast, and direct trasmuscular exposure of the suboccipital triangle (H. Bertalanffy and Seeger 1991; Spektor et al. 2000; Hakuba A 1993; Kratimenos and Crockard 1993). The retroauricular C-shaped incision starts 4 cm above the pinna, curves 4 cm behind the mastoid tip, and reaches the anterior border of the sternocleidomastoid muscle. It has a lower risk of postoperative cerebrospinal fluid leakage (Lau et al. 2015). The nuchal muscles are generally reflected in a single block to skeletonize the lateral suboccipital region, lateral (C1) condyle, and C1 hemilamina. In doing this, it is paramount to leave a muscle cuff onto the superior nuchal line that will serve as the approximation of the myocutaneous flap during closure. However, knowledge of the layering of the nuchal muscles is important in both harvesting of the occipital artery and performing the interfascial technique for VA exposure in the suboccipital triangle (Youssef et al. 2010) because some of these muscles serve as a landmark for certain neurovascular structures.

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Figure 1. Layer-by-layer dissection of the nuchal muscles. Skin incision (A) and first muscular layer (B). Trapezius (T), sternocleidomastoid (SCM) muscles, and posterior triangle of the neck (PT) between them. (C) Second layer. Splenius capitis (Spl. C) and semispinalis capitis (Sem. C). (D) occipital artery. (E) Third layer. Longissimus capitis (LC), occipital artery (OA), and semispinalis capitis (Sem. C). (F) Fourth layer. Superior oblique (SO), inferior oblique (IO), rectus capitis posterior major (RC Maj), and suboccipital triangle of the vertebral artery.

The first layer is composed of the trapezius and sternocleidomastoid muscles. They are both ensheathed in the most superficial layer of the deep cervical fascia, the so-called investing or anterior layer. Both the trapezius and sternocleidomastoid muscles continue upward into the galea aponeurotica and occipito-frontalis muscle. Between the lateral border of the trapezius and posterior border of the sternocleidomastoid muscle, it is possible to identify the posterior triangle of the neck. The investing fascia forms the roof of the posterior triangle, whereas the semispinalis capitis, medially, and splenius capitis, laterally, form its floor (Figures 1b–c). Beneath the investing fascia, the deepest layer of the deep vertebral fascia, the so-called prevertebral fascia, envelops the deep muscles of the neck. From the posterior view, the splenius capitis completely covers the longissimus capitis. The anatomical relationship between the occipital artery and longissimus capitis is variable because of the fact that the artery may run under the longissimus capitis. In this case, it can be found as a groove on the occipital squama or above the longissimus capitis. In the latter case, a well-defined arterial groove is absent (Figure 1d). On a deeper plane, just lateral to the midline, lies the semispinalis capitis muscle. Caudally, the semispinalis muscle exposes the superior suboccipital triangle. The superior suboccipital triangle is bounded by the rectus capitis posterior major superomedially, superior oblique muscle superolaterally, and inferior oblique muscle inferiorly.

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In the superior suboccipital triangle runs the VA in its horizontal V3 segment, periarterial autonomic neural plexus, vertebral venous plexus, and C1 nerve root with its branching rami (Figure 1e). Lateral to the suboccipital triangle lies the rectus capitis lateralis, a short flat muscle attaching upward onto the jugular process of the occipital bone, just behind the JF. The rectus capitis lateralis is an important landmark in the identification of the jugular bulb.

3.3. Bone Work and Tailoring in the Far Lateral Approach

Far lateral craniotomy involves a lateral suboccipital flap extended to the posterolateral edge of the FM until the posteromedial tip of the condyle. Bertalanffy et al. have described a technical tip in this step, known as “C0” concept (Helmut Bertalanffy et al. 2010; H. Bertalanffy and Seeger 1991). The “C0” concept considers the posterolateral rim of the FM, thicker than the squama because of the presence of cancellous bone, as a hemilamina similar to that of C1. Suboccipital craniotomy should initially spare the C0 hemilamina. This technique allows easier removal of the posterolateral rim of the FM, better visualization of the caudal third of the sigmoid sinus serving as a landmark for an adequate caudal exposure, and easier detachment of the atlanto-occipital membrane. C0 and C1 hemilaminectomy completes the approach. The main difference between the lateral suboccipital and far lateral craniotomy lies in the fact that the latter allows full exposure of the dural pierce of the VA, ultimately leading to a dura opening, which is located just medial to it (Figures 2a and b). The far lateral approach has three variants, namely, the transcondylar, supracondylar, and paracondylar approaches, which, while sharing the same first steps, largely differ with respect to the bony work.

3.3.1. Far Lateral Transcondylar Approach The posterolateral corridor to the inferior third of the clivus related to the far lateral approach is adequate to treat most meningiomas of the FM. During their slow growth, they displace posterolaterally the medulla oblongata and upper cervical cord, thus widening the route themselves. Nevertheless, smaller lesions, or VBJ aneurysms, need wider exposure by far. Drilling of the posterior part of the condyle allows a progressive and dramatic increase in the working space in front of the brainstem. The amount of the condyle to be drilled may range from only the posterior third, with no sequelae on the biomechanics of the craniovertebral junction (CVJ), to the entire posterior half, generally causing instability and necessity of fixation. However, the biomechanical consequences of condylectomy also depend on other factors such as size, diameter, and shape of the condyle (Bozbuğa et al. 1999; Degno et al. 2018; Guidotti 1984; Hakuba A 1993; Lyrtzis et al. 2017; Muthukumar et al. 2005; S. Naderi, Korman, Citak, Guvencer, et al. 2005; Olivier 1975; Vishteh et al. 1999). The “complete” far lateral transcondylar approach considers the anterior condylar canal (hypoglossal canal) as an anterior limit (Figures 2c–d) (T. Matsushima et al. 1998; Perneczky 1986; A.L. Rhoton, Jr. 2000c; de Oliveira, Rhoton, and Peace 1985; Wen et al. 1997; A.L. Rhoton, Jr. 2000b; Spektor et al. 2000).

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Figure 2. Comparison between the far lateral approach (A, B) and transcondylar (C, D), supracondylar (E, F), and paracondylar extensions (G, H) of the far lateral approach in terms of bone removal and intradural exposure. VAT, vago-accessory triangle; SHT, suprahypoglossal triangle; IHT, infrahypoglossal triangle.

3.3.2. Supracondylar (Transcondylar Fossa Trans-Jugular Tubercle) Approach Some lesions primarily involve the JT area. In these lesions, the supracondylar extension of the far lateral approach is indicated. The supracondylar approach consists of a transcondylar fossa trans-JT corridor considered as a tailored approach to the area of the JT. Contrary to the transcondylar variant, it completely spares the condyle. The condylar fossa is a small depression lying superiorly and posteriorly to the condyle, forming the external surface of the posterior part of the JT. It serves as a landmark in differentiating between the JT and occipital condyle from outside during the approach. The condylar fossa and JT are on the same plane, and both lie 5 mm above the level of the hypoglossal canal. The condylar fossa contains the condylar canal at the bottom, or posterior condylar canal, which transmits the posterior condylar vein. Drilling of the bone through the condylar fossa results in a defect in the posterior part of the JT (T. Matsushima et al. 1998; Perneczky 1986; K. Matsushima et al. 2014; A.L. Rhoton, Jr. 2000c; de Oliveira, Rhoton, and Peace 1985; Wen et al. 1997; A.L. Rhoton, Jr. 2000b; Ginsberg 1994) (Figures 2e–f).

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3.3.3. Paracondylar Approach The paracondylar approach is considered as a route to those lesions primarily or secondarily involving the posterior edge of the JF. The rectus capitis lateralis, having a medial attachment on the superior surface of the transverse process of C1 and lateral upward attachment on the jugular process of the occipital bone, is the key landmark of the jugular bulb. The facial nerve, at its exit from the stylomastoid foramen, is directly lateral to the rectus capitis lateralis. The paracondylar approach is directed through the jugular process of the occipital bone. It involves the skeletonization and opening of the hypoglossal canal, often adding to partial drilling of the lateral occipital condyle and the mastoid tip (T. Matsushima et al. 1998; Perneczky 1986; K. Matsushima et al. 2014; A.L. Rhoton, Jr. 2000c; de Oliveira, Rhoton, and Peace 1985; Wen et al. 1997; A.L. Rhoton, Jr. 2000b; Ginsberg 1994) (Figures 2g–h). Widely exposing the posterior part of the JF, the paracondylar approach is the approach of choice for dumbbell-shaped lower cranial nerve schwannomas and paragangliomas of the JF area.

3.4. Dura Opening

In all types of far lateral approach, the dura is opened in a linear or curvilinear fashion, medial to the dural pierce of the VA (Figures 2b, d, f, and h). This aspect is the key to understanding the main difference between the far lateral transcondylar approach and extreme lateral approach (also known as transcondylar approach), where the dura is opened lateral to the VA (Babu, Sekhar, and Wright 1994; Sen and Sekhar 1990; Hakuba A 1993; Salas et al. 1999; al-Mefty et al. 1996). Care should be taken during dura opening to avoid injury to the PICA. This may originate directly beyond the dural pierce of the VA or even at the level of the dural pierce itself.

3.5. Intradural Corridors

The opening of the arachnoid of the cisterna magna in the upward retraction of the cerebellar tonsil exposes the lateral medullary cistern and all possible intradural corridors to the VBJ, VA-PICA junction, and proximal PICA. Lawton et al. described three well-defined triangles, delimited by the course of the lower cranial nerves, which represent several working corridors. They are the vago-accessory triangle (VAT), along with the two triangles inscribed in it: suprahypoglossal triangle (SHT) and infrahypoglossal triangle (IHT) (Tayebi Meybodi et al. 2019). Owing to the high anatomical variability of the PICA, the surgical corridors of the far lateral approach should be related to specific zones, namely, the anterior, lateral, and tonsillo-medullary zones. The SHT is the corridor to the anterior medullary zone, where the VBJ, VA-PICA junction, and anterior medullary segment of PICA are generally located. The IHT is the route to the lateral medullary zone, where the lateral medullary segment of PICA is found. In case of a more distal PICA origin from the VA, the VA-PICA junction can also be found here. The VA-PICA junction is rarely located more distally, at the level of the tonsillomedullary zone. The tonsillo-medullary zone contains most aneurysms involving the cranial

336 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al. loop (tonsillo-medullary segment) of PICA. While still within the VAT, these aneurysms lie behind the plane of the lower cranial nerves, so working between the nerves is unnecessary.

3.6. Closure

Dura closure may be difficult within this area. Whenever possible, it should be closed in a watertight fashion with a running or interrupted suture. Abdominal or gluteal fat graft has proved to be a valuable alternative in the remaining cases. Although not strictly necessary, the lateral suboccipital bone flap may be fixed to the skull with low profile titanium plates and 4 or 5 mm self-tapping screws. The nuchal muscle block is re-approximated by suturing the investing fascia to the galea at or just above the level of the superior nuchal line. No subcutaneous drainage is generally needed, and a classic interrupted suture with 2-0 silk stitches is used for skin closure.

4. COMPLICATIONS AND PREVENTION

VA lesions and biomechanical instability of the CVJ are the main complications of the distant lateral approach. In the extradural and extracranial compartment, the VA, vertebral venous plexus, and C1 nerve are wrapped in a common periosteal sheath. Compulsive subperiosteal dissection of this sheath on C1 is the key to preventing VA injuries and even bleeding from the vertebral venous plexus. The skeleton should start from the posterior tubercle of the atlas and directly from the medial to lateral to the retrocondylar area. The use of blunt instruments is recommended. On hemilamina C1, the horizontal segment of the VA can flow over the sulcus or complete or incomplete bone canal. Often, the posterior arch of the atlas has a partial cleft, originating from the nonunion of the primitive ossification nuclei in the midline. All of these aspects need to be evaluated on computed tomography (CT) during preoperative planning. Aside from the transcondylar variant, no condyle puncture is involved in the distant lateral approach. However, as needed, partial perforation of the posteromedial aspect of the condyle, typically the posterior third, can dramatically increase angular exposure to the target, which is the reason that this maneuver should not be demonized. However, these cases have a risk of biomechanical instability. A careful preoperative evaluation of the anatomy of the condyles and deep knowledge of the landmarks within this area are fundamental in preventing postoperative instability. Preventing skeletonization of the axis to preserve the muscular pivot of the CVJ is also recommended. Occipitocervical stabilization can also be postponed in these cases and performed after dynamic radiographic studies.

5. ILLUSTRATIVE CASES

Case 1: Small Unruptured Left VA-PICA Aneurysm Anterior to the JT

A 42-year-old woman was diagnosed with an incidental small left VA-PICA aneurysm. The patient had severe drug-resistant systemic hypertension.

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She was candidate for surgery after consultation with interventional neuroradiologists. The aneurysm in the PICA from the VA involved the lateral medullary zone. Furthermore, the aneurysm was located just anterior to the JT. A left far lateral approach with the patient in modified park-bench position was performed. Minimal drilling of the condyle was useful in widening the working space around the aneurysm. The aneurysm was approached through the IHT, and clipping was successful without intraoperative complications. The patient had no deficits, and postoperative CT angiography showed complete exclusion of the aneurysms with complete preservation of the PICA (Figure 3).

Figure 3. Axial contrast-enhanced CT scan (A) and CT angiography (B) of a 42 year-old woman diagnosed with incidental small left VA-PICA aneurysm. (C) Digital subtraction angiography of the left vertebral artery in anterior–posterior projection showing the aneurysm and origin of the left posterior- inferior cerebellar artery. (D) The patient is placed in right modified park-bench position. Dura opening (E) and aneurysm exposure (F). (G, H) Aneurysm clipping with straight Yasargil miniclips. (I) Indocyanine green videoangiography showing complete exclusion of the aneurysm, with patency of the vertebral and proximal posterior-inferior cerebellar arteries. Postoperative axial bone window CT scan (J) showing far lateral craniotomy and 3D CT angiography (K, L) confirming complete exclusion of the aneurysm.

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Case 2: Giant Unruptured Left VBJ Aneurysm

A 41-year-old woman with a long history of dizziness was diagnosed with left giant unthrombosed VBJ aneurysm. The origin of the PICA was extremely close to the aneurysm neck, and the patient failed to pass the balloon occlusion test, which aimed to evaluate the hemodynamic effect of the putative left VA dissection. A left far lateral approach with the patient in modified park-bench position was performed. The suprahypoglossal corridor of the SHT reached the aneurysm. Temporary clipping of both VAs allowed initial placement of a pilot clip. Afterward, the flow was restored, and the use of the staking-seating technique allowed the fragmentation of the aneurysm and its final clipping. The patient was discharged on the fifth postoperative day, and the postoperative DSA showed complete exclusion of the aneurysm (Figure 4).

Figure 4. 3D CT angiography (A) and digital subtraction angiography of the left vertebral artery in the lateral projection (B) showing a left giant vertebrobasilar junction aneurysm in a 41-year-old woman with dizziness. (C) Coronal contrast-enhanced MRI excluding intra-aneurysmal thrombus. (D–F) Patient placed in right modified park-bench position with intraoperative neurophysiological monitoring. Aneurysm exposure (G) through the suprahypoglossal corridor and definitive clip ligation (H) obtained using the staking-seating clipping technique. (I) Indocyanine green videoangiography revealing the complete exclusion of the aneurysm and full visualization of the left vertebral artery. (J) Postoperative bone window 3D CT showing the extent of the craniotomy. Postoperative digital subtraction angiography of the left vertebral artery in lateral projection (K) and anterior–posterior projection with the double catheter approach (L) confirming the complete exclusion of the aneurysm.

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6. DISCUSSION

During the last 40 years, the far lateral approach has become the elective surgical corridor to ventral FM lesions. The reasons for this lie in a wide versatility mainly coming from its variants, namely, the supracondylar, transcondylar, and paracondylar approaches. The technical evolution of the far lateral approach has been an integral part of that related to the techniques in neurovascular surgery (Ciappetta, Luzzi, et al. 2009; Ciappetta, Occhiogrosso, et al. 2009; Del Maestro et al. 2018; Gallieni et al. 2018; S. Luzzi, Del Maestro, et al. 2018; S. Luzzi, Del Maestro, and Galzio 2019; S. Luzzi, Elia, Del Maestro, Morotti, et al. 2019; S. Luzzi, Gallieni, et al. 2018; Ricci et al. 2017; S. Luzzi et al. 2020). Furthermore, the large number of morphometric studies on transcranial and endoscopic skull base approaches has better delineated some technical aspects at the base of the tailoring of the approach (Arnaout et al. 2019; S. Luzzi, Del Maestro, Elia, et al. 2019; S. Luzzi, Del Maestro, Trovarelli, et al. 2019; S. Luzzi, Zoia, et al. 2019; C. Zoia et al. 2019; Muthukumar et al. 2005; Sait Naderi, Korman, Citak, Güvençer, et al. 2005; de Oliveira, Rhoton, and Peace 1985; A.L. Rhoton, Jr. 2000b; “Assessment of the endoscopic endonasal approach to the basilar apex region for aneurysm clipping.” 2018). The improvement in the skull base reconstruction techniques during transnasal endoscopic approaches has led several authors to use these for ventral FM meningiomas and, more generally, intradural pathologies. Conversely, the role of the endoscopic approaches is extremely limited to VBJ, VA, and VA-PICA aneurysms. Our group conducted a morphometric study on the dimensional morphometric variability correlated to the basilar and condylar part of the occipital bone, affecting the choice of the approach to ventral intradural FM lesion (S. Luzzi, Del Maestro, Elia, et al. 2019). We found that the sagittal intercondylar and anterior condylar angles exhibit the highest variability within the bony structures of the CVJ. Furthermore, the average JT-hypoglossal canal interline ratio was 0.8. These data led to the conclusion that a wider sagittal intercondylar and anterior condylar angle with a higher JT-hypoglossal canal interline ratio makes the far lateral approach advantageous. An anterior medial or far-medial endoscopic approach is indicated in opposite conditions. In neurovascular pathology, these data have some additional considerations with respect to the type of lesion. VBJ and proximal PICA aneurysms, different from ventral medullary cavernous hemangiomas, should be approached by a transcranial far lateral route because of the need for proximal hemodynamic control of the intradural VA. In most cases, partial drilling of the condyle or JT is necessary to fully expose the aneurysm. Presently, the size of the condyle and JT to be removed to increase surgical freedom to the target can be anticipated preoperatively, with the risk for mechanical instability (Tai, Herur-Raman, and Jean 2019; Kshettry et al. 2017; Cardoso et al. 2015). This has been possible because of the tremendous ongoing technological evolution of imaging techniques, which has grown on a par with most fields in neurosurgery (Bellantoni et al. 2019; Cheng, Shetty, and Sekhar 2018; De Tommasi et al. 2008; De Tommasi et al. 2007; Guastamacchia et al. 2007; Sabino Luzzi, Crovace, et al. 2019; S. Luzzi, Crovace, et al. 2018; S. Luzzi, Elia, Del Maestro, Elbabaa, et al. 2019; S. Luzzi, Giotta Lucifero, et al. 2019; Palumbo et al. 2019; Palumbo et al. 2018; Raysi Dehcordi et al. 2017; Spena et al. 2019; C. Zoia et al. 2018; Bongetta et al. 2019; Ciappetta et al. 2008; De Tommasi, Cascardi, et al. 2006; De Tommasi, De Tommasi, et al. 2006; Millimaggi et al. 2018; Antonosante et al. 2020; Campanella et al. 2020; Cesare Zoia et al. 2020; Elsawaf et al. 2020).

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CONCLUSION

The far lateral approach consists of an inferolateral extension of the lateral suboccipital approach where widening of the suboccipital craniotomy partially exposes the sigmoid sinus, and C1 hemilaminectomy dramatically increases angular exposure in front of the dentate ligament at the level of the CVJ. The transcondylar, supracondylar, and paracondylar extensions confer great versatility to the far lateral approach that can be tailored according to the different types of lesions. The far lateral approach is the approach of choice for VBJ, VA-PICA, and proximal PICA aneurysms and most ventral FM meningiomas and ventral medullary cavernous hemangiomas.

REFERENCES al-Mefty, O., L. A. Borba, N. Aoki, E. Angtuaco, and T. G. Pait. 1996. “The transcondylar approach to extradural nonneoplastic lesions of the craniovertebral junction.” J Neurosurg 84 (1): 1-6. https://doi.org/10.3171/jns.1996.84.1.0001. https://www.ncbi.nlm.nih.gov/ pubmed/8613814. Antonosante, A., L. Brandolini, M. d’Angelo, E. Benedetti, V. Castelli, M. Del Maestro, S. Luzzi, A. Giordano, A. Cimini, and M. Allegretti. 2020. “Autocrine CXCL8-dependent invasiveness triggers modulation of actin cytoskeletal network and cell dynamics.” Aging (Albany NY) 12. https://doi.org/10.18632/aging.102733. https://www.ncbi.nlm.nih.gov/ pubmed/31986121. Arnaout, M. M., S. Luzzi, R. Galzio, and K. Aziz. 2019. “Supraorbital keyhole approach: Pure endoscopic and endoscope-assisted perspective.” Clin Neurol Neurosurg 189: 105623. https://doi.org/10.1016/j.clineuro.2019.105623. https://www.ncbi.nlm.nih.gov/pubmed/ 31805490. Arnautovic, K. I., O. Al-Mefty, and M. Husain. 2000. “Ventral foramen magnum meninigiomas.” J Neurosurg 92 (1 Suppl): 71-80. https://doi.org/10.3171/spi.2000.92. 1.0071. https://www.ncbi.nlm.nih.gov/pubmed/10616061. “Assessment of the endoscopic endonasal approach to the basilar apex region for aneurysm clipping.” 2018. Journal of neurosurgery: 1-12. https://doi.org/10.3171/2018.1. JNS172813. http://www.ncbi.nlm.nih.gov/pubmed/29932384. Babu, R. P., L. N. Sekhar, and D. C. Wright. 1994. “Extreme lateral transcondylar approach: technical improvements and lessons learned.” J Neurosurg 81 (1): 49-59. https://doi.org/ 10.3171/jns.1994.81.1.0049. https://www.ncbi.nlm.nih.gov/pubmed/8207527. Bellantoni, G., F. Guerrini, M. Del Maestro, R. Galzio, and S. Luzzi. 2019. “Simple schwannomatosis or an incomplete Coffin-Siris? Report of a particular case.” eNeurologicalSci 14: 31-33. https://doi.org/10.1016/j.ensci.2018.11.021. https://www. ncbi.nlm.nih.gov/pubmed/30555950. Bertalanffy, H., and W. Seeger. 1991. “The dorsolateral, suboccipital, transcondylar approach to the lower clivus and anterior portion of the craniocervical junction.” Neurosurgery 29 (6): 815-21. https://doi.org/10.1097/00006123-199112000-00002. https://www.ncbi.nlm. nih.gov/pubmed/1758590.

Far Lateral Approach 341

Bertalanffy, Helmut, Oliver Bozinov, Oguzkan Sürücü, Ulrich Sure, Ludwig Benes, Christoph Kappus, and Niklaus Krayenbühl. 2010. “Dorsolateral Approach to the Craniocervical Junction.” 175-196. Bongetta, D., C. Zoia, S. Luzzi, M. D. Maestro, A. Peri, G. Bichisao, D. Sportiello, I. Canavero, A. Pietrabissa, and R. J. Galzio. 2019. “Neurosurgical issues of bariatric surgery: A systematic review of the literature and principles of diagnosis and treatment.” Clin Neurol Neurosurg 176: 34-40. https://doi.org/10.1016/j.clineuro.2018.11.009. https://www.ncbi. nlm.nih.gov/pubmed/30500756. Bozbuğa, M, A Oztürk, B Bayraktar, Z Ari, K Sahinoğlu, G Polat, and I Gürel. 1999. “Surgical anatomy and morphometric analysis of the occipital condyles and foramen magnum.” Okajimas folia anatomica Japonica 75: 329-34. Bruneau, M., and B. George. 2010. “Classification system of foramen magnum meningiomas.” J Craniovertebr Junction Spine 1 (1): 10-7. https://doi.org/10.4103/0974-8237.65476. https://www.ncbi.nlm.nih.gov/pubmed/20890409. Bruneau, Michaël, and Bernard George. 2008. “Foramen magnum meningiomas: detailed surgical approaches and technical aspects at Lariboisière Hospital and review of the literature.” Neurosurgical review 31: 19-32; discussion 32-3. https://doi.org/10.1007/ s10143-007-0097-1. Campanella, R., L. Guarnaccia, C. Cordiglieri, E. Trombetta, M. Caroli, G. Carrabba, N. La Verde, P. Rampini, C. Gaudino, A. Costa, S. Luzzi, G. Mantovani, M. Locatelli, L. Riboni, S. E. Navone, and G. Marfia. 2020. “Tumor-Educated Platelets and Angiogenesis in Glioblastoma: Another Brick in the Wall for Novel Prognostic and Targetable Biomarkers, Changing the Vision from a Localized Tumor to a Systemic Pathology.” Cells 9 (2). https://doi.org/10.3390/cells9020294. https://www.ncbi.nlm.nih.gov/pubmed/31991805. Cardoso, A. C., R. B. Fontes, L. A. Tan, A. L. Rhoton, Jr., S. W. Roh, and R. G. Fessler. 2015. “Biomechanical effects of the transcondylar approach on the craniovertebral junction.” Clin Anat 28 (5): 683-9. https://doi.org/10.1002/ca.22551. https://www.ncbi.nlm.nih.gov/ pubmed/25914225. Chaddad-Neto, F., H. L. Doria-Netto, J. M. Campos Filho, M. Reghin-Neto, A. L. Rothon, Jr., and Ed Oliveira. 2014. “The far-lateral craniotomy: tips and tricks.” Arq Neuropsiquiatr 72 (9): 699-705. https://doi.org/10.1590/0004-282x20140130. https://www.ncbi.nlm.nih. gov/pubmed/25252234. Cheng, C. Y., R. Shetty, and L. N. Sekhar. 2018. “Microsurgical Resection of a Large Intraventricular Trigonal Tumor: 3-Dimensional Operative Video.” Oper Neurosurg (Hagerstown) 15 (6): E92-E93. https://doi.org/10.1093/ons/opy068. https://www.ncbi. nlm.nih.gov/pubmed/29618124. Ciappetta, P., I. D’Urso P, S. Luzzi, G. Ingravallo, A. Cimmino, and L. Resta. 2008. “Cystic dilation of the ventriculus terminalis in adults.” J Neurosurg Spine 8 (1): 92-9. https://doi.org/10.3171/SPI-08/01/092. https://www.ncbi.nlm.nih.gov/pubmed/18173354. Ciappetta, P., S. Luzzi, R. De Blasi, and P. I. D’Urso. 2009. “Extracranial aneurysms of the posterior inferior cerebellar artery. Literature review and report of a new case.” J Neurosurg Sci 53 (4): 147-51. https://www.ncbi.nlm.nih.gov/pubmed/20220739. Ciappetta, P., G. Occhiogrosso, S. Luzzi, P. I. D’Urso, and A. P. Garribba. 2009. “Jugular tubercle and vertebral artery/posterior inferior cerebellar artery anatomic relationship: a 3- dimensional angiography computed tomography anthropometric study.” Neurosurgery 64

342 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

(5 Suppl 2): 429-36; discussion 436. https://doi.org/10.1227/01.NEU.0000337573. 17073.9F. https://www.ncbi.nlm.nih.gov/pubmed/19404121. Day, J. D., T. Fukushima, and S. L. Giannotta. 1997. “Cranial base approaches to posterior circulation aneurysms.” J Neurosurg 87 (4): 544-54. https://doi.org/10.3171/jns. 1997.87.4.0544. https://www.ncbi.nlm.nih.gov/pubmed/9322845. de Oliveira, E., A. L. Rhoton, Jr., and D. Peace. 1985. “Microsurgical anatomy of the region of the foramen magnum.” Surg Neurol 24 (3): 293-352. https://www.ncbi.nlm.nih.gov/ pubmed/4023912. De Tommasi, A., P. Cascardi, C. De Tommasi, S. Luzzi, and P. Ciappetta. 2006. “Emergency surgery in a severe penetrating skull base injury by a screwdriver: case report and literature review.” World J Emerg Surg 1: 36. https://doi.org/10.1186/1749-7922-1-36. https://www.ncbi.nlm.nih.gov/pubmed/17169147. De Tommasi, A., C. De Tommasi, E. Lauta, S. Luzzi, A. Cimmino, and P. Ciappetta. 2006. “Pre-operative subarachnoid haemorrhage in a patient with spinal tumour.” Cephalalgia 26 (7): 887-90. https://doi.org/10.1111/j.1468-2982.2006.01122.x. https://www.ncbi. nlm.nih.gov/pubmed/16776708. De Tommasi, A., S. Luzzi, P. I. D’Urso, C. De Tommasi, N. Resta, and P. Ciappetta. 2008. “Molecular genetic analysis in a case of ganglioglioma: identification of a new mutation.” Neurosurgery 63 (5): 976-80; discussion 980. https://doi.org/10.1227/01.NEU. 0000327699.93146.CD. https://www.ncbi.nlm.nih.gov/pubmed/19005389. De Tommasi, A., G. Occhiogrosso, C. De Tommasi, S. Luzzi, A. Cimmino, and P. Ciappetta. 2007. “A polycystic variant of a primary intracranial leptomeningeal astrocytoma: case report and literature review.” World J Surg Oncol 5: 72. https://doi.org/10.1186/1477- 7819-5-72. https://www.ncbi.nlm.nih.gov/pubmed/17587463. Degno, Sisay, Mueez Abrha, Yared Asmare, and Abebe Muche. 2018. “Anatomical Variation in Morphometry and Morphology of the Foramen Magnum and Occipital Condyle in Dried Adult Skulls.” The Journal of craniofacial surgery. https://doi.org/10.1097/SCS. 0000000000004925. Del Maestro, M., S. Luzzi, M. Gallieni, D. Trovarelli, A. V. Giordano, M. Gallucci, A. Ricci, and R. Galzio. 2018. “Surgical Treatment of Arteriovenous Malformations: Role of Preoperative Staged Embolization.” Acta Neurochir Suppl 129: 109-113. https://doi. org/10.1007/978-3-319-73739-3_16. https://www.ncbi.nlm.nih.gov/pubmed/30171322. Elsawaf, Y., S. Anetsberger, S. Luzzi, and S. K. Elbabaa. 2020. “Early Decompressive Craniectomy as Management for Severe TBI in the Pediatric Population: A Comprehensive Literature Review.” World Neurosurg. https://doi.org/10.1016/j.wneu.2020.02.065. https://www.ncbi.nlm.nih.gov/pubmed/32084616. Gallieni, M., M. Del Maestro, S. Luzzi, D. Trovarelli, A. Ricci, and R. Galzio. 2018. “Endoscope-Assisted Microneurosurgery for Intracranial Aneurysms: Operative Technique, Reliability, and Feasibility Based on 14 Years of Personal Experience.” Acta Neurochir Suppl 129: 19-24. https://doi.org/10.1007/978-3-319-73739-3_3. https://www. ncbi.nlm.nih.gov/pubmed/30171309. George, B., C. Dematons, and J. Cophignon. 1988. “Lateral approach to the anterior portion of the foramen magnum. Application to surgical removal of 14 benign tumors: technical note.” Surg Neurol 29 (6): 484-90. https://doi.org/10.1016/0090-3019(88)90145-0. https://www.ncbi.nlm.nih.gov/pubmed/3375978.

Far Lateral Approach 343

George, B., G. Lot, S. Velut, F. Gelbert, and K. L. Mourier. 1993. “[French language Society of Neurosurgery. 44th Annual Congress. Brussels, 8-12 June 1993. Tumors of the foramen magnum].” Neurochirurgie 39 Suppl 1: 1-89. https://www.ncbi.nlm.nih.gov/pubmed/ 7902956. Ginsberg, L. E. 1994. “The posterior condylar canal.” AJNR. American journal of neuroradiology 15 (5): 969-72. http://www.ncbi.nlm.nih.gov/pubmed/8059670. Guastamacchia, E., V. Triggiani, E. Tafaro, A. De Tommasi, C. De Tommasi, S. Luzzi, C. Sabba, F. Resta, M. R. Terreni, and M. Losa. 2007. “Evolution of a prolactin-secreting pituitary microadenoma into a fatal carcinoma: a case report.” Minerva Endocrinol 32 (3): 231-6. https://www.ncbi.nlm.nih.gov/pubmed/17912159. Guidotti, A. 1984. “Morphometrical considerations on occipital condyles.” Anthropologischer Anzeiger; Bericht über die biologisch-anthropologische Literatur 42 (2): 117--9. http://www.ncbi.nlm.nih.gov/pubmed/6465869. Hakuba A, Tsujimoto T. 1993. “Transcondyle approach for foramen magnum meningiomas.” In Surgery of Cranial Base Tumors, edited by Janecka IP Sekhar LN, 671–678. New York: Raven Press. Heros, R. C. 1986. “Lateral suboccipital approach for vertebral and vertebrobasilar artery lesions.” J Neurosurg 64 (4): 559-62. https://doi.org/10.3171/jns.1986.64.4.0559. https:// www.ncbi.nlm.nih.gov/pubmed/3950739. Kratimenos, G. P., and H. A. Crockard. 1993. “The far lateral approach for ventrally placed foramen magnum and upper cervical spine tumours.” Br J Neurosurg 7 (2): 129- 40. https://doi.org/10.3109/02688699309103469. https://www.ncbi.nlm.nih.gov/pubmed/ 8494614. Kshettry, V. R., A. T. Healy, R. Colbrunn, D. T. Beckler, E. C. Benzel, and P. F. Recinos. 2017. “Biomechanical evaluation of the craniovertebral junction after unilateral joint-sparing condylectomy: implications for the far lateral approach revisited.” J Neurosurg 127 (4): 829-836. https://doi.org/10.3171/2016.7.JNS16293. https://www.ncbi.nlm.nih.gov/ pubmed/27739941. Lanzino, G., S. Paolini, and R. F. Spetzler. 2005. “Far-lateral approach to the craniocervical junction.” Neurosurgery 57 (4 Suppl): 367-71; discussion 367-71. https://www.ncbi. nlm.nih.gov/pubmed/16234687. Lau, T., S. Reintjes, R. Olivera, H. R. van Loveren, and S. Agazzi. 2015. “C-shaped Incision for Far-Lateral Suboccipital Approach: Anatomical Study and Clinical Correlation.” J Neurol Surg B Skull Base 76 (2): 117-21. https://doi.org/10.1055/s-0034-1390396. https://www.ncbi.nlm.nih.gov/pubmed/25844297. Luzzi, S., A. M. Crovace, L. Lacitignola, V. Valentini, E. Francioso, G. Rossi, G. Invernici, R. J. Galzio, and A. Crovace. 2018. “Engraftment, neuroglial transdifferentiation and behavioral recovery after complete spinal cord transection in rats.” Surg Neurol Int 9: 19. https://doi.org/10.4103/sni.sni_369_17. https://www.ncbi.nlm.nih.gov/pubmed/29497572. Luzzi, S., M. Del Maestro, D. Bongetta, C. Zoia, A. V. Giordano, D. Trovarelli, S. Raysi Dehcordi, and R. J. Galzio. 2018. “Onyx Embolization Before the Surgical Treatment of Grade III Spetzler-Martin Brain Arteriovenous Malformations: Single-Center Experience and Technical Nuances.” World Neurosurg 116: e340-e353. https://doi.org/10.1016/j. wneu.2018.04.203. https://www.ncbi.nlm.nih.gov/pubmed/29751183. Luzzi, S., M. Del Maestro, S. K. Elbabaa, and R. Galzio. 2020. “Letter to the Editor Regarding “One and Done: Multimodal Treatment of Pediatric Cerebral Arteriovenous

344 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

Malformations in a Single Anesthesia Event”.” World Neurosurg 134: 660. https:// doi.org/10.1016/j.wneu.2019.09.166. https://www.ncbi.nlm.nih.gov/pubmed/32059273. Luzzi, S., M. Del Maestro, A. Elia, F. Vincitorio, G. Di Perna, F. Zenga, D. Garbossa, S. Elbabaa, and R. Galzio. 2019. “Morphometric and Radiomorphometric Study of the Correlation Between the Foramen Magnum Region and the Anterior and Posterolateral Approaches to Ventral Intradural Lesions.” Turk Neurosurg. https://doi.org/10.5137/1019- 5149.JTN.26052-19.2. https://www.ncbi.nlm.nih.gov/pubmed/31452176. Luzzi, S., M. Del Maestro, and R. Galzio. 2019. “Letter to the Editor. Preoperative embolization of brain arteriovenous malformations.” J Neurosurg: 1-2. https://doi.org/10.3171/2019. 6.JNS191541. https://www.ncbi.nlm.nih.gov/pubmed/31812150. https://thejns.org/view/ journals/j-neurosurg/aop/article-10.3171-2019.6.JNS191541/article-10.3171-2019.6. JNS191541.xml. Luzzi, S., M. Del Maestro, D. Trovarelli, D. De Paulis, S. R. Dechordi, H. Di Vitantonio, V. Di Norcia, D. F. Millimaggi, A. Ricci, and R. J. Galzio. 2019. “Endoscope-Assisted Microneurosurgery for Neurovascular Compression Syndromes: Basic Principles, Methodology, and Technical Notes.” Asian J Neurosurg 14 (1): 193-200. https://doi. org/10.4103/ajns.AJNS_279_17. https://www.ncbi.nlm.nih.gov/pubmed/30937034. Luzzi, S., A. Elia, M. Del Maestro, S. K. Elbabaa, S. Carnevale, F. Guerrini, M. Caulo, P. Morbini, and R. Galzio. 2019. “Dysembryoplastic Neuroepithelial Tumors: What You Need to Know.” World Neurosurg 127: 255-265. https://doi.org/10.1016/j.wneu. 2019.04.056. https://www.ncbi.nlm.nih.gov/pubmed/30981794. Luzzi, S., A. Elia, M. Del Maestro, A. Morotti, S. K. Elbabaa, A. Cavallini, and R. Galzio. 2019. “Indication, Timing, and Surgical Treatment of Spontaneous Intracerebral Hemorrhage: Systematic Review and Proposal of a Management Algorithm.” World Neurosurg. https://doi.org/10.1016/j.wneu.2019.01.016. https://www.ncbi.nlm.nih.gov/ pubmed/30677572. Luzzi, S., M. Gallieni, M. Del Maestro, D. Trovarelli, A. Ricci, and R. Galzio. 2018. “Giant and Very Large Intracranial Aneurysms: Surgical Strategies and Special Issues.” Acta Neurochir Suppl 129: 25-31. https://doi.org/10.1007/978-3-319-73739-3_4. https://www. ncbi.nlm.nih.gov/pubmed/30171310. Luzzi, S., A. Giotta Lucifero, M. Del Maestro, G. Marfia, S. E. Navone, M. Baldoncini, M. Nunez, A. Campero, S. K. Elbabaa, and R. Galzio. 2019. “Anterolateral Approach for Retrostyloid Superior Parapharyngeal Space Schwannomas Involving the Jugular Foramen Area: A 20-Year Experience.” World Neurosurg. https://doi.org/10.1016/j.wneu.2019. 09.006. https://www.ncbi.nlm.nih.gov/pubmed/31520759. Luzzi, S., C. Zoia, A. D. Rampini, A. Elia, M. Del Maestro, S. Carnevale, P. Morbini, and R. Galzio. 2019. “Lateral Transorbital Neuroendoscopic Approach for Intraconal Meningioma of the Orbital Apex: Technical Nuances and Literature Review.” World Neurosurg 131: 10-17. https://doi.org/10.1016/j.wneu.2019.07.152. https://www.ncbi. nlm.nih.gov/pubmed/31356977. Luzzi, Sabino, Alberto Maria Crovace, Mattia Del Maestro, Alice Giotta Lucifero, Samer K. Elbabaa, Benedetta Cinque, Paola Palumbo, Francesca Lombardi, Annamaria Cimini, Maria Grazia Cifone, Antonio Crovace, and Renato Galzio. 2019. “The cell-based approach in neurosurgery: ongoing trends and future perspectives.” Heliyon 5 (11). https://doi.org/10.1016/j.heliyon.2019.e02818.

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Lyrtzis, C., M. Piagkou, A. Gkioka, N. Anastasopoulos, S. Apostolidis, and K. Natsis. 2017. “Foramen magnum, occipital condyles and hypoglossal canals morphometry: anatomical study with clinical implications.” Folia Morphol (Warsz) 76 (3): 446-457. https://doi.org/ 10.5603/FM.a2017.0002. https://www.ncbi.nlm.nih.gov/pubmed/28150268. Matsushima, Ken, Masatou Kawashima, Toshio Matsushima, Tetsuya Hiraishi, Tomoyuki Noguchi, and Akio Kuraoka. 2014. “Posterior condylar canals and posterior condylar emissary veins-a microsurgical and CT anatomical study.” Neurosurgical review 37: 115- 26. https://doi.org/10.1007/s10143-013-0493-7. Matsushima, T., Y. Natori, T. Katsuta, K. Ikezaki, M. Fukui, and A. L. Rhoton. 1998. “Microsurgical anatomy for lateral approaches to the foramen magnum with special reference to transcondylar fossa (supracondylar transjugular tubercle) approach.” Skull Base Surg 8 (3): 119-25. https://www.ncbi.nlm.nih.gov/pubmed/17171046. Menezes, A. H., V. C. Traynelis, and B. J. Gantz. 1994. “Surgical approaches to the craniovertebral junction.” Clin Neurosurg 41: 187-203. https://www.ncbi.nlm.nih.gov/ pubmed/7842603. Millimaggi, D. F., V. D. Norcia, S. Luzzi, T. Alfiero, R. J. Galzio, and A. Ricci. 2018. “Minimally Invasive Transforaminal Lumbar Interbody Fusion with Percutaneous Bilateral Pedicle Screw Fixation for Lumbosacral Spine Degenerative Diseases. A Retrospective Database of 40 Consecutive Cases and Literature Review.” Turk Neurosurg 28 (3): 454-461. https://doi.org/10.5137/1019-5149.JTN.19479-16.0. https://www.ncbi. nlm.nih.gov/pubmed/28481388. Muthukumar, N., R. Swaminathan, G. Venkatesh, and S. P. Bhanumathy. 2005. “A morphometric analysis of the foramen magnum region as it relates to the transcondylar approach.” Acta Neurochir (Wien) 147 (8): 889-95. https://doi.org/10.1007/s00701-005- 0555-x. https://www.ncbi.nlm.nih.gov/pubmed/15924208. Naderi, S., E. Korman, G. Citak, M. Guvencer, C. Arman, M. Senoglu, S. Tetik, and M. N. Arda. 2005. “Morphometric analysis of human occipital condyle.” Clin Neurol Neurosurg 107 (3): 191-9. https://doi.org/10.1016/j.clineuro.2004.07.014. https://www.ncbi.nlm. nih.gov/pubmed/15823674. Naderi, Sait, Esin Korman, Güven Citak, Mustafa Güvençer, Candan Arman, Mehmet Senoğlu, Süleyman Tetik, and M Nuri Arda. 2005. “Morphometric analysis of human occipital condyle.” Clinical neurology and neurosurgery 107: 191-9. https://doi.org/10.1016/ j.clineuro.2004.07.014. Olivier, G. 1975. “Biometry of the human occipital bone.” J Anat 120 (Pt 3): 507-18. https://www.ncbi.nlm.nih.gov/pubmed/1213952. Palumbo, P., F. Lombardi, F. R. Augello, I. Giusti, S. Luzzi, V. Dolo, M. G. Cifone, and B. Cinque. 2019. “NOS2 inhibitor 1400W Induces Autophagic Flux and Influences Extracellular Vesicle Profile in Human Glioblastoma U87MG Cell Line.” Int J Mol Sci 20 (12). https://doi.org/10.3390/ijms20123010. https://www.ncbi.nlm.nih.gov/pubmed/ 31226744. Palumbo, P., F. Lombardi, G. Siragusa, S. R. Dehcordi, S. Luzzi, A. Cimini, M. G. Cifone, and B. Cinque. 2018. “Involvement of NOS2 Activity on Human Glioma Cell Growth, Clonogenic Potential, and Neurosphere Generation.” Int J Mol Sci 19 (9). https://doi.org/10.3390/ijms19092801. https://www.ncbi.nlm.nih.gov/pubmed/30227679. Perneczky, A. 1986. “The Posterolateral Approach to the Foramen Magnum.” Berlin, Heidelberg.

346 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

Raysi Dehcordi, S., A. Ricci, H. Di Vitantonio, D. De Paulis, S. Luzzi, P. Palumbo, B. Cinque, D. Tempesta, G. Coletti, G. Cipolloni, M. G. Cifone, and R. Galzio. 2017. “Stemness Marker Detection in the Periphery of Glioblastoma and Ability of Glioblastoma to Generate Glioma Stem Cells: Clinical Correlations.” World Neurosurg 105: 895- 905. https://doi.org/10.1016/j.wneu.2017.05.099. https://www.ncbi.nlm.nih.gov/pubmed/ 28559081. Rhoton, A. L. 2000a. “The far-lateral approach and its transcondylar, supracondylar, and paracondylar extensions.” Neurosurgery 47 (3 Suppl): S195--209. http://www.ncbi. nlm.nih.gov/pubmed/10983309. Rhoton, A. L., Jr. 2000b. “The far-lateral approach and its transcondylar, supracondylar, and paracondylar extensions.” Neurosurgery 47 (3 Suppl): S195-209. https://doi.org/10. 1097/00006123-200009001-00020. https://www.ncbi.nlm.nih.gov/pubmed/10983309. ––––– . 2000c. “The foramen magnum.” Neurosurgery 47 (3 Suppl): S155-93. https://www. ncbi.nlm.nih.gov/pubmed/10983308. Ricci, A., H. Di Vitantonio, D. De Paulis, M. Del Maestro, S. D. Raysi, D. Murrone, S. Luzzi, and R. J. Galzio. 2017. “Cortical aneurysms of the middle cerebral artery: A review of the literature.” Surg Neurol Int 8: 117. https://doi.org/10.4103/sni.sni_50_17. https://www. ncbi.nlm.nih.gov/pubmed/28680736. Salas, E., L. N. Sekhar, I. M. Ziyal, A. J. Caputy, and D. C. Wright. 1999. “Variations of the extreme-lateral craniocervical approach: anatomical study and clinical analysis of 69 patients.” J Neurosurg 90 (2 Suppl): 206-19. https://www.ncbi.nlm.nih.gov/pubmed/ 10199250. Sen, C. N., and L. N. Sekhar. 1990. “An extreme lateral approach to intradural lesions of the cervical spine and foramen magnum.” Neurosurgery 27 (2): 197-204. https://www.ncbi. nlm.nih.gov/pubmed/2385336. Spektor, S., G. J. Anderson, S. O. McMenomey, M. A. Horgan, J. X. Kellogg, and J. B. Delashaw, Jr. 2000. “Quantitative description of the far-lateral transcondylar transtubercular approach to the foramen magnum and clivus.” J Neurosurg 92 (5): 824- 31. https://doi.org/10.3171/jns.2000.92.5.0824. https://www.ncbi.nlm.nih.gov/pubmed/ 10794297. Spena, G., E. Roca, F. Guerrini, P. P. Panciani, L. Stanzani, A. Salmaggi, S. Luzzi, and M. Fontanella. 2019. “Risk factors for intraoperative stimulation-related seizures during awake surgery: an analysis of 109 consecutive patients.” J Neurooncol. https://doi.org/ 10.1007/s11060-019-03295-9. https://www.ncbi.nlm.nih.gov/pubmed/31552589. Tai, A. X., A. Herur-Raman, and W. C. Jean. 2019. “The Benefits of Progressive Occipital Condylectomy in Enhancing the Far Lateral Approach to the Foramen Magnum.” World Neurosurg. https://doi.org/10.1016/j.wneu.2019.09.152. https://www.ncbi.nlm.nih.gov/ pubmed/31605848. Tayebi Meybodi, A., L. Borba Moreira, X. Zhao, M. C. Preul, and M. T. Lawton. 2019. “Anatomical Analysis of the Vagoaccessory Triangle and the Triangles Within: The Suprahypoglossal, Infrahypoglossal, and Hypoglossal-Hypoglossal Triangles.” World Neurosurg 126: e463-e472. https://doi.org/10.1016/j.wneu.2019.02.073. https://www. ncbi.nlm.nih.gov/pubmed/30825626. Tedeschi, H., and A. L. Rhoton, Jr. 1994. “Lateral approaches to the petroclival region.” Surg Neurol 41 (3): 180-216. https://doi.org/10.1016/0090-3019(94)90123-6. https://www. ncbi.nlm.nih.gov/pubmed/8146735.

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Vishteh, A G, N R Crawford, M S Melton, R F Spetzler, V K Sonntag, and C A Dickman. 1999. “Stability of the craniovertebral junction after unilateral occipital condyle resection: a biomechanical study.” Journal of neurosurgery 90: 91-8. Wen, H. T., A. L. Rhoton, Jr., T. Katsuta, and E. de Oliveira. 1997. “Microsurgical anatomy of the transcondylar, supracondylar, and paracondylar extensions of the far-lateral approach.” J Neurosurg 87 (4): 555-85. https://doi.org/10.3171/jns.1997.87.4.0555. https://www.ncbi. nlm.nih.gov/pubmed/9322846. Youssef, A. S., J. S. Uribe, E. Ramos, R. Janjua, L. B. Thomas, and H. van Loveren. 2010. “Interfascial technique for vertebral artery exposure in the suboccipital triangle: the road map.” Neurosurgery 67 (2 Suppl Operative): 355-61. https://doi.org/10.1227/NEU. 0b013e3181f741f7. https://www.ncbi.nlm.nih.gov/pubmed/21099558. Zoia, C., D. Bongetta, G. Dorelli, S. Luzzi, M. D. Maestro, and R. J. Galzio. 2019. “Transnasal endoscopic removal of a retrochiasmatic cavernoma: A case report and review of literature.” Surg Neurol Int 10: 76. https://doi.org/10.25259/SNI-132-2019. https://www. ncbi.nlm.nih.gov/pubmed/31528414. Zoia, C., D. Bongetta, F. Guerrini, C. Alicino, A. Cattalani, S. Bianchini, R. J. Galzio, and S. Luzzi. 2018. “Outcome of elderly patients undergoing intracranial meningioma resection: a single center experience.” J Neurosurg Sci. https://doi.org/10.23736/S0390-5616. 18.04333-3. https://www.ncbi.nlm.nih.gov/pubmed/29808631. Zoia, Cesare, Francesco Lombardi, Maria Fiore, Andrea Montalbetti, Alberto Iannalfi, Mattia Sansone, Daniele Bongetta, Francesca Valvo, Mattia Del Maestro, Sabino Luzzi, and Renato Galzio. 2020. “Sacral solitary fibrous tumour: surgery and hadrontherapy, a combined treatment strategy.” Reports of Practical Oncology & Radiotherapy. https://doi.org/10.1016/j.rpor.2020.01.008.

Chapter 21

COMBINED PETROSAL APPROACH

D. T. Di Carlo1, MD, T. Passeri1,2, MD, P. Di Russo1,2, MD, K. Watanabe1,2, MD, A. L. Bernat2, MD and S. Froelich1,2,, MD, PhD 1Skull base and experimental Neurosurgery Laboratory, Hôpital Lariboisière, Université de Paris, Assistance Publique-Hôpitaux de Paris, Paris, France 2Department of Neurosurgery, Hôpital Lariboisière, Université de Paris, Assistance Publique-Hôpitaux de Paris, Paris, France

ABSTRACT

The combined petrosal approach grants a unique surgical trajectory to the petroclival region, allowing multiple direction of work both in the middle and in the posterior fossa. It allows a good control of the cranial nerve from III to XI and the anterior surface of the brainstem, as well as the basilar artery, the antero-inferior cerebellar artery (AICA), the superior cerebellar artery (SCA) and the P2 and P3 segment of the posterior cerebral artery (PCA). Due to the complex anatomy of the petroclival region a detailed knowledge of the 3D surgical anatomy of the petrous bone is paramount when considering a combined petrosal approach. In our practice, it is most often used to resect large or giant petroclival meningiomas, epidermoid cyst, chondrosarcomas, chordomas, and retroinfundibular craniopharyngiomas.

Keywords: petroclival junction, anterior petrosectomy, posterior petrosectomy, combined petrosal approach

 Corresponding Author’s Email: [email protected].

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1. INTRODUCTION

Lesions of the petroclival region remain challenging for all neurosurgeons because of their deep location and complex surrounding anatomy, characterized by critical neurovascular structures. The choice of a lateral corridor to the petroclival region requires a variable removal of the petrous bone, from different angle of work (Erkmen, Pravdenkova and Al-Mefty 2005). First in the 1970 King et al. developed the “extended middle fossa approach” combining a middle fossa craniotomy and a translabyrinthine approach (King 1970). This method was mostly applied for acoustic shwannoma but Hakuba et al. in 1977 reported a variation of this technique for clival tumor removal (Hakuba et al. 1977). Subsequently, in 1985 Kawase described his refined technique of tranpetrosal approach with an anterior petrosectomy to treat aneurysms of the basilar artery (Takeshi Kawase et al. 1985). Nowadays, this approach is one of the most known way to treat petroclival meningiomas, due to the magnificent exposure of the peritrigeminal area from the third cranial nerve to the internal acoustic canal (IAC) (T Kawase, Shiobara and Toya 1994). Furthermore, one of the advantages of this approach is the chance to preserve the audition, which is not possible with a translabyrinthine route. In the last decades, thanks to the progression of the surgical technique, several surgeons proposed different way to perform a hearing-sparing posterior petrosectomy: the retrolabyrinthine approach and the partial labyrintectomy allow the surgeon to reach the posterior fossa from the presigmoid space (Sekhar et al. 1999; Al-Mefty, Fox and Smith 1988). Furthermore, the superior petrosal sinus (SPS) can be ligated and sectioned as well as the tentorium, allowing a generous exposure between the CN V and the upper limit of the jugular tubercle. The combined petrosal approach puts together these two surgical routes, creating multiple surgical corridors to the petroclival area minimizing, in this way, brain retraction. In this chapter we will first review the surgical anatomy relevant to the combined petrosal approach and describe, step-by-step, the surgical technique to expose the petroclival region.

2. THE COMBINED PETROSAL APPROACH

The term combined approach refers to combinations of different approaches that included at least two main surgical routes. The first report was a suboccipital craniectomy combined with a translabyrinthine approach described by Fraenkel and Hunt in 1904 (Fraenkel et al. 1904). Similarly, in 1905 Borchardt associated a suboccipital approach to a lateral extension through the labyrinthine and with sigmoid sinus division (Borchardt 1905). Both approaches were performed to remove cerebellopontine angle tumors. Hakuba et al. managed clival meningioma with a modification of Morrison and King combined approach (Hakuba et al. 1977), preserving the labyrinth, retracting the sigmoid sinus medially, and gaining exposure anteriorly to the sinus through a subtemporal transtentorial route. In 1988 Al-Mefty et al. described their technique combining a complete mastoidectomy with the drilling of the retrolabyrinthine area, with an anterior petrosectomy (Al-Mefty, Fox and Smith 1988). Subsequently, several authors described this technique and the advantages to cut the superior petrosal sinus, remove the tentorium, to maximize the exposition of the petroclival region, minimizing brain retraction (Kusumi, Fukushima, Mehta et al. 2012; Hanakita et al. 2019). However, the intrinsic risk of the approach

Combined Petrosal Approach 351 in association to the long learning curve necessary to master this technique, discourage many surgeons to be familiar with this approach.

2.1. Preoperative Considerations

A detailed study of the preoperative images should be done by an experienced multidisciplinary skull base team. The head CT scan should be examined in detail to identify any anatomic variation that can lead to unintentional complications. Mastoid pneumatisation, superior semicircular canal dehiscence to avoid hearing impairment, fallopian canal trajectory, and amount of space behind the posterior semi-circular canal should be always checked carefully. Similarly, to avoid vascular complications during the mastoidectomy, the height of the jugular bulb in relation to the IAC should be measured. In case a cosmetic mastoidectomy is performed the height of bone covering the transverse and sigmoid sinus junction should be evaluated. During the anterior petrosectomy, no clear landmark exists to locate the cochlea. Accordingly, the pneumatisation of the petrous apex, the thickness of the cortical bone protecting the cochlea, the distance between the cochlea and the ICA, the distance between the cochlea and the petrous bone surface should be measured to give the surgeon additional information before drilling.

Figure 1. Male 54-year-old, negative pre-operative neurological examination. Pre-operative axial (A) and sagittal (B) view of a left petroclival meningioma compressing the brainstem with extension into the Meckel’s cave. No anatomic variation of patient’s petrous bone was revealed by the CT scan except a significant petrous apex pneumatization that could facilitate the drilling and help to locate the cochlea (C).

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The relationship between the Vein of Labbé and the transverse sinus is another critical element to study preoperatively. Variation of vein drainage in the antero-lateral segment of the transverse sinus, in the SPS, or into the tentorium could expose the patient to vascular complications, during SPS cutting and tentorial detachment.

2.2. Neurophysiological Monitoring and Surgical Adjuncts

Electromyographic (EMG) monitoring of the 7th, 9th, 10th, 11th nerves, motor and sensory evoked potentials are done in all cases of combined petrosectomy. Direct stimulation with an EMG probe can be useful in VII cranial nerve identification and preservation. Neurophysiological monitoring with somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) also has a pivotal role in case of brainstem compression. A lumbar drain can be place preoperatively to facilitate brain relaxation. Neuronavigation is used routinely as well as the micro-Doppler probe to identify the petrosal segment of the ICA during the drilling of the petrous apex, and to check the flow into the sinus and veins during the surgery.

2.3. Surgical Anatomy and Technique

2.3.1. Positioning The patient is placed supine, the ipsilateral shoulder is elevated, the head rotated laterally, approximately 60 - 80 degrees, and the vertex slightly tilted toward the floor. Accordingly, the petrous bone is the highest point of the operative filed. The head is then fixed in a three-point Mayfield head clamp.

2.3.2. Skin Incision and Soft Tissue Dissection A postauricular C-shaped incision is performed starting from one cm below the tip of the mastoid to the anterior limit of the superior temporal line behind the hairline. After elevating the scalp by sharp subgaleal dissection, the sternocleidomastoid muscle and the temporalis muscle are exposed. The sternocleidomastoid muscle altogether with the longissimus and the splenius capitis muscle are reflected posteriorly after the detachment from the mastoid process, exposing the asterion and the digastric groove. Interfascial dissection is always preferred, maximizing the retraction of the skin and temporalis muscle anteriorly and avoiding facial nerve injury. The margin of the temporalis muscle is incised, starting along the posterior root of the zygoma and following the superior temporal line. The elevation of the temporalis muscle is performed in a retrograde fashion, preserving the deep periosteal layer and the vascular supply and innervation of the muscle. The root of the zygoma should be exposed and the temporalis muscle elevated and retracted as much as possible anteriorly.

2.3.3. Craniotomy A L-shaped craniotomy to expose both posterior fossa and the middle fossa is performed. For the one-piece craniotomy, 4 burr holes are placed on both side of the transverse-sigmoid sinus junction. Other burr holes are placed on the parietal bone and above the posterior root of

Combined Petrosal Approach 353 the zygoma. Bone cuts over the sinus, should be done with a drill in order to avoid any injury of the sinus. After careful dural and sinus detachment the bone is slowly elevated. Another safe option to avoid sinus injuries is to perform a two or three pieces bone flap, which will be easily reconstructed with plates.

2.3.4. Posterior Petrosectomy (Mastoidectomy) The limit of the mastoidectomy are identified as follows: 1) mastoid tip, 2) posterior root of the zygoma, 3) transverse-sigmoid junction. The spine of Henle is always found as a landmark for the external auditory canal. Care should be taken to avoid excessive retraction of the external auditory canal and rupture of the skin. The cortical bone of the mastoid can be removed in one piece and preserved using the craniotome cutting blade or the chisel, parallel to the mastoid surface, to avoid post-operative cosmetic defects. Afterwards, the mastoidectomy is performed using both cutting and diamond drills. The cortical bone of the superior and posterior aspect of the external auditory canal is identified. First, the antrum is exposed approximately 15mm in the deep of the junction between the spine of Henle and the supramastoid crest, above the external auditory canal. The antrum leads to the middle ear and the short arm of the incus is identified. The short arm is a major landmark as it is pointing towards the facial nerve below the lateral semicircular canal (LSC). Care should be taken to open the middle ear widely. The cortical white bone of the lateral canal is the first structure of the labyrinth to be exposed and shaved. Then, the posterior semicircular canal (PSC) can be identified in relation to the superior semicircular canal (SSC) at the level of the common crus. Behind and below the posterior canal, the endolymphatic sac is identified. This structure is a triangular dura thickening, directed toward the posterior aspect of the posterior semicircular canal.

Figure 2. Intraoperative view of the surgical field after the craniotomy and the combined petrosectomy. A L-shaped craniotomy was performed to expose both posterior fossa and the middle fossa. The retrolabyrinthine corridor was exposed preserving the endolymphatic sac and a small window on the dura of the posterior fossa was opened in the retrosigmoid space to get access to cisterna magna allowing brain relaxation. (MT mastoid tip, PF posterior fossa, psc posterior semicircular canal, SS sigmoid sinus, ssc superior semicircular canal, TD temporal dura).

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The superior semicircular canal’s apex is below the temporal tegmen. Then the drilling continues below the labyrinth from posterior to anterior, in front of the sigmoid sinus. The fallopian canal, which has a vertical downward direction starting from in the inferior mid-point of the lateral semicircular canal, is identified. The mastoidectomy is continued inferiorly, identifying the jugular bulb. Accordingly, the presigmoid dura is completely exposed and the Trautmann’s triangle can be identified delimitated by the sigmoid sinus, the SPS and semicircular canals. The middle ear is sealed with bone wax.

2.3.5. Anterior Petrosectomy The first step of the approach is to identify the landmarks of the middle fossa (Kawase triangle). The location of the arcuate eminence is easily identified as the superior semi-circular canal was previously shaved. Accordingly, the middle meningeal artery is cut 2 - 3mm after its exit from the foramen spinosum. Foramen ovale is identified immediately medial and anterior to foramen spinosum and the dura is then elevated from the mandibular and maxillary nerve. The temporal dura is elevated from the temporal fossa floor from posterior to anterior. The greater superficial petrosal nerve (GSPN) is identified using the EMG probe. The dura-mater is elevated from the petrous apex and the petrous ridge and groove for the SPS are identified. The apicectomy is then performed as follows: 1) drilling of the medial part of the premeatal triangle, 2) identification of the horizontal segment of the ICA, medial and below the GSPN, 3) drilling the anterior aspect of IAC starting at the porus toward the fundus, 4) drilling of the postmeatal volume. Once the posterior and anterior petrosectomy are performed, the labyrinth is further shaved above and behind the SSC and PSC, respectively, in order to gain additional exposure.

Figure 3. The SPS was ligated and sectioned and the tentorium removed. The figure shows the Meckel’s cave opened, and the V CN gently displaced allowing the visualization of the petroclival meningioma (asterisk). Once the posterior cut of the tentorium is made, the temporal dura can be retracted posteriorly over the transverse-sigmoid sinus junction in order to retract the sinus and open the space between temporal lobe and the cerebellum. Furthermore, for petroclival meningioma, tentorial removal allows an early devascularization of the tumor mass. (CN cranial nerve, psc posterior semicircular canal, ssc superior semicircular canal).

Combined Petrosal Approach 355

2.3.6. Dural Incision and Tentorial Cuts If a lumbar drain is not placed pre-operatively, a small dura cut on the retrosigmoid dura allows a direct access to the cisterna magna and the subsequent generous brain relaxation. The dura of the posterior fossa is opened in the presigmoid space toward the jugular bulb in a L-shaped fashion following the SPS toward the lateral aspect of the trigeminal fibrous ring. The trigeminal fibrous ring is incised and Meckel’s cave is opened along the trigiminal nerve. Similarly, the temporal dura is opened above and along the SPS. The temporal incision extends posteriorly 1 cm above the transverse sinus. Care is taken to not injure the vein of labbé. The SPS is ligated and cut as anterior as possible in order to preserve the superior petrosal veins draining into the SPS.

Figure 4. Schematic representation of the final exposure of the combined petrosal approach. Insets indicate anatomic dissection performed in the “Skull base and experimental Neurosurgery Laboratory” of the department of Neurosurgery, Lariboisière hospital, Paris. The light pink inset shows the window looking up in a caudo-cranial and postero-anteior direction, allowing the visualization of the III cranial nerve entering into the cavernous sinus, the PCA, the SCA, and the IV cranial nerve. The red inset shows the corridor provided by the anterior petrosectomy. The V cranial nerve is entirely exposed and the Meckel’s cave opened. The CN VI can be found between the VIII and the V cranial nerves, directed toward the petroclival junction into the Dorello’s canal. Finally, through the green inset the surgeon can visualize VII, VIII, IX, X, XI cranial nerves. (CN cranial nerve, JB jugular bulb, PCA posterior cerebellar artery, psc posterior semicircular canal, SCA superior cerebellar artery, SS sigmoid sinus, ssc superior semicircular canal, SPS superior petrosal sinus, TS transverse sinus).

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The tentorium is then cut and resected in two steps, as follows: 1) the posterior cut begins at the point of the SPS ligation and continues medially, toward the tentorial free edge, behind the entrance of the fourth cranial nerve into the tentorium, 2) the anterior portion of the tentorium is incised starting from the fibrous ring of the fifth nerve to the entrance of the fourth nerve into the posterior cavernous sinus (anterior detachment). The trapezoid-shaped piece of tentorium is then removed. Once the posterior cut of the tentorium is made, the temporal dura can be retracted posteriorly over the transverse-sigmoid sinus junction in order to retract the sinus and open the space between temporal lobe and the cerebellum.

2.3.7. Reconstruction and Closure Although watertight closure is the best way to prevent post-operative CSF leak, it is not always possible in this location. Thin layers of bone wax, followed by pericranium, are used to close the mastoid antrum and middle ear in order to prevent CSF leaks. The dural flaps are re- approximated with 5-0 not resorbable monofilament sutures. Pieces of abnominal fat are then used to fill the defect of the petrous bone and the remaining dural opening. Fibrin glue is used to seal off the closure. The preserved outer cortical bone of the mastoid and the bone flap are fixed with titanium micro plates.

RATIONALE OF THE APPROACH AND ADVANTAGES

The combined petrosal approach, in association to the tentorial removal and the sigmoid sinus retraction, allow the surgeon to have a wide surgical corridor with multiple line of sight avoinding temporal lobe retraction. The main line of sight is characterized by a postero-anterior and caudo-cranial direction toward the retro-infundibular central cisterns, underneath the temporal lobe. Through the presigmoid corridor the surgeon can visualize VII, VIII, IX, X cranial nerves. The VI CN can be found between the VIII and the V cranial nerves, directed toward the petroclival junction into the Dorello’s canal. The anterior subtemporal corridor, provided by the anterior petrosectomy, guarantee the complete visualization of the V nerve, the upper basilar artery and the IV cranial nerve. Finally, from the inferior aspect of the presigmoid window, in a caduo-cranial and postero-anterior direction, the surgeon can look up and visualize the III cranial nerve, the P2 and P3 segment of the PCA, the SCA and the posterior clinoid process. For petroclival meningioma, the combined petrosal approach allows the exposure of the dural base of the tumor and significant devascularization. Tentorial resection completely exposed the postero-lateral hemisphere of the tumor and provides good control of the feeders coming from the ICA through the tentorium. The anterior petrosectomy expose the posterior fossa dura and allows coagulation of a large part of the dural base of the tumor.

REFERENCES

Al-Mefty, O., Fox, J. L. and Smith, R. R. 1988. “Petrosal Approach for Petroclival Meningiomas”. Neurosurgery, 22 (3): 510 - 17. https://doi.org/10.1227/00006123- 198803000-00010.

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Borchardt, M. 1905. “Zur Operation Der Tumoren Des Kleinhirnbruckenwinkels [For Operation Of The Tumors Of The Cerebellar Angle]”. Klin. Wochenschr., 42: 1033 - 35. Erkmen, Kadir, Pravdenkova, Svetlana and Al-Mefty, Ossama. 2005. “Surgical Management of Petroclival Meningiomas: Factors Determining the Choice of Approach”. Neurosurgical Focus, 19 (2): E7. https://doi.org/10.3171/foc.2005.19.2.8. Fraenkel, Joseph, Hunt, J. Ramsay, Woolsey, George and Elsberg, Charles A. 1904. “I. Contribution to the Surgery of Neurofibroma of the Acoustic Nerve: With Remarks on the Surgical Procedure”. Annals of Surgery, 40 (3): 293. Hakuba, Akira, Shuro Nishimura, Kiyoaki Tanaka, Hiroshige Kishi and Tohru Nakamura. 1977. “Clivus Meningioma: Six Cases of Total Removal”. Neurologia Medico-Chirurgica, 17 (1): 63 - 77. Hanakita, Shunya, Kentaro Watanabe, Champagne, Pierre-Olivier and Froelich, Sébastien. 2019. “How I Do It: Combined Petrosectomy”. Acta Neurochirurgica, 1 - 5. Kawase, T., Shiobara, R. and Toya, S. 1994. “Middle Fossa Transpetrosal-Transtentorial Approaches for Petroclival Meningiomas. Selective Pyramid Resection and Radicality”. Acta Neurochirurgica, 129 (3 - 4): 113 - 20. Kawase, Takeshi, Shigeo Toya, Ryuzo Shiobara and Toru Mine. 1985. “Transpetrosal Approach for Aneurysms of the Lower Basilar Artery”. Journal of Neurosurgery, 63 (6): 857 - 61. King, T. T. 1970. “Surgical Treatment of Acoustic Neurinoma: Combined Translabyrinthine- Transtentorial Approach to Acoustic Nerve Tumours”. SAGE Publications. Kusumi, Mari, Takanori Fukushima, Hamidreza Aliabadi, Ankit I. Mehta, Shusaku Noro, Rosen, Charles L. and Kiyotaka Fujii. 2012. “Microplate-Bridge Technique for Watertight Dural Closures in the Combined Petrosal Approach”. Neurosurgery, 70 (2 Suppl. Operative): 264 - 69. https://doi.org/10.1227/NEU.0b013e3182356269. Kusumi, Mari, Takanori Fukushima, Ankit I. Mehta, Hamidreza Aliabadi, Yoichi Nonaka, Friedman, Allan H. and Kiyotaka Fujii. 2012. “Tentorial Detachment Technique in the Combined Petrosal Approach for Petroclival Meningiomas”. Journal of Neurosurgery, 116 (3): 566 - 73. https://doi.org/10.3171/2011.11.JNS11985. Sekhar, L. N., Schessel, D. A., Bucur, S. D., Raso, J. L. and Wright, D. C. 1999. “Partial Labyrinthectomy Petrous Apicectomy Approach to Neoplastic and Vascular Lesions of the Petroclival Area”. Neurosurgery, 44 (3): 532 - 37. https://doi.org/10.1097/00006123- 199903000-00060.

Chapter 22

APPROACHES FOR BRAIN AND SPINAL CORD ARTERIOVENOUS MALFORMATIONS

R. Messina1, MD, G. Cirrottola2, MD, N. Bruno2, MD and F. Signorelli1,2, MD, PhD 1Chair of Neurosurgery, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Italy 2Neurosurgery Complex Unit, Azienda Universitaria-Ospedaliera Policlinico Consorziale, Bari, Italy

ABSTRACT

The approaches to arteriovenous malformations of the central nervous system need high levels of expertise and benefit from a multidisciplinary management as there is no standard solution but, rather, a set of principles which can be applied with the contribution of neurosurgeons, interventional neuroradiologists, neuroradiotherapists and neuroscience specialists. In this chapter, we summarize such principles and illustrate with four clinical cases the way our team apply them in every-day practice.

Keywords: brain arteriovenous malformations, spinal arteriovenous malformations, microsurgery, stereotactic radiosurgery, endovascular treatment

1. INTRODUCTION

Whilst rare, brain and spinal cord arteriovenous malformations attract considerable interest within clinical and research frameworks, as witnessed by the development and attempted clinical validation of numerous classification systems (Krings et al. 2010), recent clinical trials (Mohr et al. 2014; Darsaut et al. 2015) and a great number of scientific articles, monothematic congresses and courses published and advertised regularly. However, their management remains controversial as the strength of recommendations as to whether to treat such malformations are generally weak inasmuch as they are founded on the study of groups of

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AVM patients selected for undergoing treatment or observation and the true natural history of AVMs remains unknown (Derdeyn et al. 2017). Their management is therefore generally determined on a case-by-case basis and largely depends on the grade of expertise of the treating center. Brain (bAVMs) and spinal cord AVMs (scAVMs) are one shining example of a disease requiring a multidisciplinary approach as there is no standard solution but, rather, a set of principles which can be applied with the contribution of neurosurgeons, interventional neuroradiologists, neuroradiotherapists and neuroscience specialists.

2. METHODS

2.1.Treatment of bAVMs

2.1.1. Aims of Treatment Much emphasis is placed on the prevention and treatment of intracranial hemorrhagic complications, for which the only long-term effective treatment is definitive obliteration of the nidus (Signorelli et al. 2014). However, bAVM patients may also develop seizures in around 34% of cases, or, less frequently, progressive neurological deficits (PND) (Derdeyn et al. 2017; Hofmeister et al. 2000; Mast et al. 1995; Spetzler et al. 2002). Chronic headache is also a frequent complaint in between 10% and 19% of patients (Hofmeister et al. 2000). The effect of bAVM treatment on seizures, PND and headache has been inadequately studied. Certain evidence exists regarding the postoperative reduction of seizures after complete obliteration of the nidus (Reinard et al. 2015), with an overall lower seizure risk after surgery compared with embolization and stereotactic radiosurgery (SRS) (Baranoski et al. 2014), with surgery attaining the shortest median time to seizure-free status (Hyun et al. 2012). However, in patients presenting without epileptic symptoms, surgery was reported to be an independent risk factor for de novo seizures (Wang et al. 2013), even though in a meta-analysis studying seizure outcome following intervention, endovascular embolization was more frequently associated with new-onset seizures than surgery or SRS (Baranoski et al. 2014). Instead, the way the effect of treatment on seizures compares with natural history is unclear: in the ARUBA trial (Mohr et al. 2014) and in a prospective, population-based observational study which stratified patients by presentation (Josephson et al. 2012), seizure outcome was similar following intervention or conservative management. Much debate exists over whether PNDs result from a misery perfusion syndrome of the brain surrounding the AVM, a supposed consequence of high blood volume shunted through it, either alone or in combination with venous hypertension (Mohr et al. 2014; Iwama et al. 2002). Nonetheless, data regarding the postoperative reversibility of PND associated with unruptured AVMs are scarce and mostly confined to the pediatric population, where treatment seems to demonstrate a favorable impact on outcomes (Kusske and Kelly 1974). There are few case reports of patients with PND attributed to hemodynamic factors with clinical improvement after targeted embolization (Krings et al. 2010; Kusske and Kelly 1974), yet follow-up is short and treatment likely to be palliative. Further studies are needed in terms of long-term treatment results for chronic headache. There is limited evidence of no benefit from intervention compared to medical management (Mohr et al. 2014), with the possible exception of occipital AVMs (Dehdashti et al. 2010). No specific therapy has proved its efficacy, while

Approaches for Brain and Spinal Cord Arteriovenous Malformations 361 vasoconstriction medications are often contraindicated as they are presumed, without clear evidence, to increase the risk of rupture (Derdeyn et al. 2017).

2.1.2. Patient Selection AVM size, location, angioarchitecture together with clinical presentation, lifetime expectancy and expectations of the patients must be considered in order to prevent bleeding and rebleeding, improve seizure outcome and preserve clinical status and quality of life (QoL). A clear-cut distinction is made between ruptured and unruptured bAVMs as the former presents a higher annual risk of rebleeding, 4.8% to 7% vs 0.9% to 1.3%, especially within the first year, (H. Kim et al. 2014; Choi et al. 2006) and great effort should be made to avoid this complication, associated with high morbidity and mortality rates, up to 50% and 25% respectively (Ding et al. 2013). The tendency of ruptured AVMs to rebleed may represent the consequence of inflammatory mechanisms enhanced by the first hemorrhage (Signorelli F and Turjman F., n.d.). Other factors seemingly associated with bleeding and rebleeding include the presence of feeders or intranidal aneurysms, exclusively deep venous drainage and deep nidus location (Signorelli F and Turjman F., n.d.; Gross and Du 2013), while other factors such as infratentorial location, single draining vein and venous varices have been associated with a risk of increased bleeding, mostly in low-powered series (Maduri, Guyotat, and Signorelli 2016). The ARUBA trial aimed to evaluate whether treatment of unruptured bAVMs in independent patients, mRS 0-1, offered a clinical benefit in terms of mortality and neurological morbidity at 5 years (Mohr et al. 2014). It was ceased early due to interim analysis showing that conservative management was superior to intervention (Mohr et al. 2014). However, flaws in the trial have raised much criticism and undermined its conclusions. Indeed, only a small percentage of screened patients were enrolled, 226 out of 1740, 13%, as 1014 were ineligible, 323 refused participation and 177 were selected for treatment separate to the trial. Moreover, although most patients (76/112, 68%) presented low grade AVMs which are best treated with microsurgery (Davidson and Morgan 2010), only 18 were operated on, whilst the remaining patients were treated with embolization and radiosurgery which have lower occlusion rates than surgery (Katsaridis, Papagiannaki, and Aimar 2008). The worse outcome in ARUBA’s interventional arm may therefore be the effect of treatment but also of rebleeding of partially treated AVMs. For the same reason, the short follow-up of 33 months might favor the conservative arm as the curative effect of radiosurgery could take longer. Patients presenting with seizures may be considered for treatment, especially in the presence of other factors associated with increased seizure risk such as younger age, intracranial hemorrhage (ICH), PND, cortical involvement, temporal and frontal location, superficial venous drainage and possibly nidus > 3 cm (Josephson et al. 2012). Equally, treatment should be evaluated for patients presenting with PND, mostly associated with large AVMs, better managed with staged interventions (Derdeyn et al. 2017). While symptomatic bAVMs portend treatment after due consideration, asymptomatic, incidentally discovered AVMs pose a dilemma in terms of treatment indications. A section of the population included in the ARUBA trial, 93 patients out of 223, 41.7%, where asymptomatic patients, for whom interim analysis showed that conservative management was superior to intervention and halted randomization (Mohr et al. 2014). However, the above criticism of ARUBA methodology may also be applied to this subpopulation of patients.

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In order to guide patient selection, several authors have developed grading systems over time for the prediction of surgical outcomes. The most widely employed system of this kind is that published by Spetzler and Martin (SM) in 1986 which considers AVM size, site, whether eloquent or not and type of venous drainage, whether superficial or deep (Spetzler et al. 2002). One limitation of this nonetheless valuable grading scheme is the overlooking of the heterogeneity of grade III AVMs, whose management is more controversial than low or high grade AVMs. Lawton’s modification to the Spetzler-Martin classification aims at facilitating the decision-making process for this type of AVM, starting from the observation that surgical outcomes of S1V1E1 and S2V1E0 AVMs, designated respectively grade III- and grade III, have a lower surgical risk than S2V0E1 AVMs, whose rate of surgical morbidity approaches 15% (Lawton et al. 2010). Another AVMs feature not considered in the SM classification scheme is the compactness or diffuseness of the nidus, which has nonetheless an impact on the surgical outcome (Lawton et al. 2010). While compact AVMs have regular boundaries and no intervening parenchima, diffuse AVMs exhibit an unraveled tangle of vessels intermingled with nervous tissue which can conduct the dissection plane too close to the nidus and portend bleeding or too far inside the normal parenchima and jeopardize function (Lawton et al. 2010) . Our opinion is that an additional factor of surgical difficulty is the presence of “en passage” veins, not involved in the AVM, straddling the nidus (see Case #1). In this case, the dissection of the nidus from the “en passage” vein should be performed once most of the AVM has been already de-arterialized inasmuch as bleeding from a vital nidus may be brisk and obscure the field, prompting further technical errors such as misinterpreting red veins, which can lead to frank AVM rupture.

2.1.3. Type and Timing of Treatment Once indication to treatment has been decided, both ruptured and unruptured AVMs may be treated with one or a combination of microsurgery, embolization and SRS. While there is little doubt regarding the indication of treating a low-grade ruptured AVM, for which surgical resection is safe and curative (Davidson and Morgan 2010; Rutledge et al. 2014), management remains controversial for high-grade types as it is associated with the greater risk of adverse outcomes, whether ruptured or not (Davidson and Morgan 2010; Ferch and Morgan 2002; Morgan et al. 2004). For unruptured AVMs, SRS may have broader indications compared to ruptured AVMs as the former has an annual bleeding risk in the latency period lower than the latter, 0.9%-1.3% vs 4.8%-7% (Choi et al. 2006; H. Kim et al. 2014). The SRS cumulative obliteration rate is around 60% after 4 years (Ding et al. 2013; Starke et al. 2017), higher for small AVMs, with transient and permanent symptomatic side effects in around 14% and 2% of patients respectively (Ding et al. 2013). Both microsurgery and SRS appear to have higher rates of obliteration than embolization (Starke et al. 2017), microsurgery being the most effective treatment in terms of complete obliteration with a cure rate documented by angiography higher than 90% of cases (Rutledge et al. 2014). Surgery for unruptured low-grade AVMs, SM grade I and II and grade III- and III of the Lawton supplemented grading scale, is considered the gold standard in terms of clinical and radiological outcome (Rutledge et al. 2014; Morgan et al. 2004; Davidson and Morgan 2010). Preoperative embolization could be targeted to inaccessible portions of the AVM or to arterial feeders that are deeply situated or of difficult or late surgical access (Krings et al. 2010). However, small perforating arteries often develop after

Approaches for Brain and Spinal Cord Arteriovenous Malformations 363 embolization, so-called “red devils,” the consequence of AVM revascularization, that increase surgical difficulty (Rutledge et al. 2014). Initial management of ruptured AVMs must weigh the risk of rebleeding against the risk of treatment. Surgical evacuation of a life-threatening ICH from a bAVM is warranted unless the patient’s life expectancy is limited because of severe co-morbidities or already established brain stem damage (Derdeyn et al. 2017). Generally, emergent surgery consists in ICH evacuation, treatment of intracranial hypertension and the control of acute bleeding. While small superficial AVMs may be removed during emergent surgery, the treatment of larger and deep AVMs is generally postponed for 2 to 6 weeks in order to allow brain swelling to recede. This favors a better angiographic and surgical delineation of the AVM’s angioarchitecture, decreases the risk of intraoperative bleeding and avoids dealing with a swollen brain, all features associated with greater likelihood of postoperative morbidity and mortality (Aoun, Bendok, and Batjer 2012). Endovascular treatment may have several indications in the case of ruptured AVMs: selective embolization of the source of bleeding in the acute phase of hemorrhage, whether arterial, nidal or venous (Signorelli et al. 2014) could reduce the immediate risk of rebleeding, carefully avoiding the closure of venous drainage in the rare case of ICH originating from a venous pouch (Signorelli et al. 2014). As in the case of unruptured AVMs, the planned reduction of the vascularization and volume of the AVM nidus, result of a multidisciplinary discussion, may facilitate and lower the risks of microsurgery (Aoun, Bendok, and Batjer 2012). Furthermore, the role of SRS in the treatment of ruptured AVMs should stem from a multidisciplinary approach, weighing up the risk of rebleeding associated with its delayed obliterative effects (Starke et al. 2017). Several authors promote the use of SRS once the source of hemorrhage has been secured (Xu et al. 2014). However, even in these cases, bleeding may ensue from other parts of the ruptured AVM harboring vessel alterations, that may also foster the development of de-novo aneurysms (Signorelli et al. 2014).

2.2. Treatment of scAVMs

2.2.1. Aims of Treatment The goal of treatment of spinal cord AVMs (scAVMs) is obliteration of the arteriovenous (AV) shunt with the preservation of normal arterial supply and venous drainage of the spinal cord. The comprehensive classification proposed by Spetzler et al. may effectively guide their treatment (Spetzler et al. 2002; L. J. Kim and Spetzler 2006). It recognizes two broad categories, arteriovenous fistulas (AVFs), direct AV shunt without a nidus, and AVMs as such, that feature a tangled bundle of vessels where the shunt occurs, which constitutes the nidus. The first category includes three subtypes according to the site of the AV shunt: extradural AVFs; intradural dorsal (type I) AVFs and intradural ventral (type IV) AVFs. The second category is also divided in three subtypes according to the location of the nidus: extradural-intradural AVMs (type III, juvenile, metameric), in which the nidus involves skin, muscle, bone, spinal canal, spinal cord and nerve roots along a somite level; intradural intramedullary AVMs (type II, glomus), whose nidus is located entirely within the spinal cord parenchima; conus medullaris AVMs, that can entail regions of true nidus intermingled with direct AV shunts inside or around the conus.

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While the first category of scAVMs is often amenable to complete obliteration, the second category usually encompasses daunting lesions for which the realistic therapeutic goal is often the reduction of vascular steal and vein dilatation to relieve neurological symptoms(L. J. Kim and Spetzler 2006; Spetzler et al. 2002; Starke et al. 2017).

2.2.2. Patient Selection A team-oriented approach in a highly specialized environment is recommended for judicious patient selection. The treatment is warranted only for symptomatic lesions. It is crucial to differentiate scAVMs from other spinal cord lesions including cavernous malformations, intramedullary tumors, axonal demyelination or infarction. Thus, preoperative work-up should include magnetic resonance (MR) and computed tomographic (CT) imaging together with angiographic sequences as well as selective and superselective spinal angiography, which remains the gold standard. Angiography should be conducted at all spinal levels as well as in the sacral and cranial vasculature as AVFs and AVMs may present with venous congestion many levels away from the symptomatic one as a consequence of the longitudinal orientation and valveless nature of the spinal cord veins (Signorelli F and Turjman F., n.d.). Moreover, the position of the radiculomedullary arteries, especially the artery of Adamkiewicz, should be known before the procedure in order to carefully preserve the spinal cord arterial supply. Preoperative somatosensory and motor evoked potentials are important to assess neurological function and indicate prognosis, both necessary for a correct treatment indication.

2.2.3. Type and Timing of Treatment Once indication to treatment has been decided, this should be undertaken as early as possible as the most reliable prognostic factor is preoperative functional status (Signorelli F and Turjman F., n.d.). Extradural AVFs are almost exclusively treated endovascularly given the absence of the contribution of the feeding artery to the spinal cord supply. Surgery may have a role in relieving cord compression due to dilated draining veins that persist or thrombose after embolization. Intradural dorsal AVFs are often treated microsurgically primarily or following embolization failure as the point of AV shunt, which is the exit of the draining vein from the inner dural surface close to the root sleeve, is easily reached and permanently interrupted with a limited posterior approach. Currently, the stripping of the draining vein from the spinal cord surface is not deemed necessary and may be associated with an adverse outcome (Signorelli et al. 2014). Embolization may be chosen as the first treatment when occlusion with the liquid embolic agent (LEA), chosen according the desired penetration property, can penetrate the point of the AV fistula (Xu et al. 2014; Signorelli F and Turjman F., n.d.). The authors prefer Onyx (ev3, Paris, France) when reflux is not a concern, as is the case when the feeder does not stem from an anterior or posterior radiculomedullary artery (Signorelli F and Turjman F., n.d.). One significant factor in successful treatment is the recognition of cases with multiple sites of AV fistulas, all of which should be addressed (Signorelli F and Turjman F., n.d.). Intradural ventral AVFs are frequently supplied by the anterior spinal artery (ASA). The endovascular treatment of this type of scAVM is well established, however in cases with short feeders stemming directly from the ASA that present a risk of reflux into the main artery, surgery is chosen through transpedicle or costotrasversectomy route that exposes the

Approaches for Brain and Spinal Cord Arteriovenous Malformations 365 anterolateral surface of the spinal cord without excessive traction or rotation maneuvers (Signorelli F and Turjman F., n.d.). Extradural-intradural AVMs are frequently treated partially, mostly endovascularly, in order to reduce the hemodynamic impact on the spinal cord due to their wide metameric extension. Intradural-intramedullary and conus medullaris AVMs frequently undergo combined endovascular and surgical treatment, especially when AV shunt persists after embolization and dilated venous channels indicate surgical decompression. Accurate identification and sparing of the normal spinal cord vasculature not involved in the malformation is crucial for avoiding postoperative neurologic decline.

3. RESULTS

3.1. Illustrative Cases

3.1.1. Case 1: Unruptured SM Grade II Diffuse Right Latero-Basal Temporal AVM A 23-year-old right-handed female presented with a recent onset of focal-onset seizures with secondary generalization. MRI and DSA (digital subtraction angiography) diagnosed a right lateral temporal SM grade II (S2V0E0), Lawton supplementary grade IV (A2U1D1) AVM with temporobasal extension. Right ICA injection (Figure 1 A,B) showed supply from M4 branches of right MCA and rapid flow through the nidus with anterior and posterior irregular margins, extending anteriorly under the vein of Labbé (VoL). The main draining vein, very short, was a tributary of the VoL. The superior anastomotic vein of Trolard (VoT), not involved in the AVM, injected in the early arterial phase for the upstream flow coming from the AVM draining vein through the VoL, sign of high flow through the AVM. Right vertebral artery injection showed also posterior temporobasal and choroidal feeders from right posterior cerebral artery (PCA) together with an unruptured intranidal aneurysm (C). Surgery was chosen considering the young age of the patient, the symptomaticity and the moderate surgical risk of the AVM and the incidental finding of an intranidal aneurysm. Preoperative embolization of the temporobasal supply was decided in order to occlude the feeders more difficult to reach surgically. Glue (Glubran 2, GEM Medical, Viareggio, Italy) was chosen for the high-flow nature of the AVM. At surgery, a nidus with ragged margins that extended beneath the VoL was exposed through a right temporal craniotomy (D). As expected, a short arterialized main draining vein was identified at the antero-inferior corner of the AVM. Due to the high flow of the AVM, even after embolization of the temporobasal supply, the arterialized blood filled, apart the VoL, also the VoT and the superficial sylvian vein. Several microclips were used in order to interrupt the M4 feeders to the diffuse anterior part of the nidus underneath the VoL (H), which was carefully spared. Circumdissection of the AVM included the ependimal tip supplied by PCA. Post-resection ICG-VA (indocyanine-green video-angiography) (G) as well as postoperative DSA (E,F) confirmed complete AVM resection. The patient recovered from surgery without deficit. At one-year follow-up she is seizure-free without medication.

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Figure 1. DSA, lateral (A), anteroposterior (B) projections after R ICA injection: R lateral temporal SM grade II (S2V0E0), Lawton supplementary grade IV (A2U1D1) AVM with temporobasal extension with supply from M4 branches of right MCA and rapid flow through the nidus with anterior and posterior irregular margins, extending anteriorly under the VoL (anterior nidus circled in white dashed line, VoL outlined in blue). The main draining vein, very short (outlined in red), was tributary of the VoL. The superior anastomotic VoT (white arrowheads), not involved in the AVM, injected in the early arterial phase for the upstream flow coming from the AVM draining vein through the VoL, sign of high flow through the AVM. R VA injection, lateral projection (C): posterior temporobasal and choroidal feeders from PCA and an unruptured intranidal aneurysm (blue arrowhead). Intraoperative view before AVM disconnection (D): the nidus with ragged margins extended beneath the VoL (green asterisks) was exposed through a right temporal craniotomy. The short arterialized main draining vein was identified at the antero-inferior corner of the AVM (white asterisk). Due to the high flow of the AVM, the arterialized blood filled the VoL (green asterisks), the VoT (yellow asterisk) and the superficial sylvian vein (black asterisk). Several microclips were used in order to interrupt the M4 feeders to the diffuse anterior part of the nidus underneath the VoL (H), which was carefully spared. Intraoperative view after AVM disconnection (H): veins are no more arterialized, witnessing the complete deafferentation of the AVM (white asterisk: main draining vein). Post-resection ICG-VA (G) and postoperative DSA (E, F) confirmed complete AVM resection.

DSA: digital subtraction angiography; ICA: internal carotid artery; PCA: posterior cerebral artery; R: right; SM: Spetzler-Martin; VA: vertebral artery; VoL: vein of Labbé; VoT: vein of Trolard.

3.1.2. Case 2: Ruptured SM Grade III Diffuse Right Lateral Frontal AVM A 48-year-old female was admitted after a sudden onset of intracranial hypertension due to a right frontal hematoma with intraventricular extension (Figure 2, A). She was graded GCS score 8, with left hemiparesis. Emergent left EVD was placed and the patient underwent angioCT (Figure 2,B), revealing a right diffuse pre-frontal lateral AVM SM grade III (S2V1E0), Lawton supplementary grade IV (A3U0D1), with a venous pouch embedded into the intraventricular hematoma, the likely source of bleeding. DSA further defined the angioarchitecture of the AVM, that was supplied by a hypertrophied M1 branch, several M4 branches and less enlarged ACA branches and was drained by a superficial prefrontal vein tributary of the superior sagittal sinus (SSS) and a deep vein tributary of the right internal cerebral vein, which had the ruptured venous pouch at its origin from the nidus €. Emergent Onyx embolization of the venous pouch with preservation of the deep venous drainage reduced the immediate risk of rebleeding and provided a valuable help to further surgical treatment by

Approaches for Brain and Spinal Cord Arteriovenous Malformations 367 closing M1 perforating branches. At surgery, the main difficulty was the cortico-subcortical diffusenes of the nidus, that conducted the dissection plane too close to the nidus and caused profuse bleeding. Monopolar cortical stimulation confirmed the absence of motor function close to the nidus and allowed the dissection to proceed subpially following the superior frontal and precentral gyruses without compromising function. Postoperative DSA confirmed complete AVM resection (E,F), early MRI excluded ischemic complications (G,H) and the patient regained independence, with a mRS score of 0 at a 6-month follow-up.

Figure 2. CT scan (A): R deep frontal hematoma with intraventricular extension. AngioCT (B): a R diffuse pre-frontal lateral AVM SM grade III (S2V1E0) Lawton supplementary grade IV (A3U0D1), with a venous pouch embedded into the intraventricular hematoma, the likely source of bleeding (black arrow). DSA, R ICA injection, 3D reconstruction (C), lateral projection (D): the AVM was supplied by an hypertrophied branch of M1, several M4 branches and less enlarged ACA branches and was drained by a superficial prefrontal vein tributary of the SSS and a deep vein, tributary of the R internal cerebral vein, which had a venous pouch at its origin from the nidus (white arrow). Postoperative DSA, lateral € and anteroposterior (F) projections: complete AVM resection. Early postoperative MRI (G, H) showed the limits of subpial resection (G), (black arrow: superior frontal sulcus; white arrow: precentral sulcus) without ischemic complications.

EVD (external ventricular drain); mRS: modified Rankin scale; R: right; SSS: superior sagittal sinus.

3.1.3. Case 3: Ruptured SM Grade I Diffuse Left Suboccipital Cerebellar AVM A 15 year-old male presented with a history of persistent headache associated with vomiting after cannabinoids assumption. Urgent CT scan (Figure 3,A) showed a 3x3,7 cm left hemispheric cerebellar hemorrhage with serpiginous images on AngioCT (B), suspicious of venous drainage from AVM. DSA (C) confirmed the presence of a diffuse left suboccipital cerebellar AVM, SM I (S1E0V0), Lawton supplementary grading II (A1U0D1) supplied by two left PICA (posterior-inferior cerebellar artery) branches and several shorter feeders from ipsilateral SCA (superior cerebellar artery), with venous drainage through one larger hemispheric vein tributary of the left transverse sinus and one smaller hemispheric vein tributary of a vermian vein running into the torcular Herophili. After glue (Glubran 2, GEM Medical, Viareggio, Italy) partial embolization of PICA feeders, a diffuse remnant supplied by SCA branches and a small PICA feeder was deemed to be treatable by surgery. A navigated

368 R. Messina, G. Cirrottola, N. Bruno et al. left suboccipital craniotomy (E) exposed the cortical dilated vein draining into the left transverse sinus. An ICG-VA-guided, transcortical approach was performed to microdissect the nidus from gliotic scars from former hemorrhage after having identified and disconnected deep arterial feeders coming from ipsilateral PICA and SCA (F). The AVM was though to be completely disconnected after nidus removal and ICG-VA was repeated, that showed the draining vein still arterialized (G). Thus, further inspection of the surgical cavity revealed residual diffuse nidus underneath the proximal segment of the vein, supplied by tiny SCA branches. After its removal, further ICG injection did not visualize anymore the draining vein (H). Post-operative DSA (I) confirmed complete treatment, without ischemic lesion on MRI (J). The boy resumed his prior activities after 1 month with no neurological sequelae.

Figure 3. CT scan (A) showed a 3x3,7 cm L hemispheric cerebellar hemorrhage with serpiginous images on AngioCT (B), suspicious of venous drainage from AVM. DSA, oblique projection (C) confirmed the presence a diffuse suboccipital cerebellar AVM, SM I (S1V0E0), Lawton supplementary grading II (A1U0D1) supplied from two L PICA branches (larger: white arrow, smaller, black arrow) and several shorter feeders from ipsilateral SCA, with venous drainage through one larger hemispheric vein (white arrowhead) tributary of the L transverse sinus and one smaller hemispheric vein (black arrowhead) tributary of a vermian vein running into the torcular Herophili. After glue (Glubran 2, GEM Medical, Viareggio, Italy) partial embolization of PICA feeders, a diffuse remnant supplied by SCA branches and a small PICA feeder (D) (black arrow) was deemed to be treatable by surgery. A navigated left suboccipital craniotomy (E) exposed the cortical dilated vein draining into left transverse sinus. An ICG- VA-guided, transcortical approach was performed to microdissect the nidus from gliotic scars from former hemorrhage and identify deep arterial feeders coming from ipsilateral PICA and SCA (F). The AVM was though to be completely disconnected after nidus removal and ICG-VA was repeated, that showed the draining vein still arterialized (G). Thus, further inspection of the surgical cavity revealed residual diffuse nidus underneath the proximal segment of the vein, supplied by tiny SCA branches. After its removal, further ICG injection did not visualize anymore the draining vein (H). Post-operative DSA (I) confirmed complete treatment, without ischemic lesion on MRI (J).

ICG-VA: indocyanine-green video-angiography; L: left; PICA: posterior inferior cerebellar artery; SCA: superior cerebellar artery.

3.1.4. Case 4: T9 Intradural Ventral AVF A 19-year-old female presented with a three-month history of progressive lower limb weakness, numbness and burning pain, associated with urinary retention. She was graded Aminoff-Logue scale score 9 (gait 5, micturition 3) and modified Denis scale score 7 (pain 3,

Approaches for Brain and Spinal Cord Arteriovenous Malformations 369 numbness 4). Spinal MRI showed dilated venous channels located mainly on the dorsal surface of the thoracic spinal cord, which displayed a T2 hyperintensity, sign of myelopathy (Figure 4, A). Spinal angiography confirmed the presence of dorsally located dilated venous channels associated with an intradural ventral AVF supplied by the ASA (B). After a right T9 transpedicle approach and slight rotation of the cord by a pulling suture placed on the dentate ligament, the ASA was exposed and the exact point of AV shunt identified (C), coagulated (D) and cut. The comparison of color maps and fluorescence curves before (E,F) and after (G,H) indocyanine green (IGC) injection confirmed the interruption of the AV shunt. Definitive proof of the resolution of the shunt was given by postoperative MRI (I) and angiography (J), that showed the resolution of vein dilatation and mielopathy and the disappearance of the shunt, with a preserved hair-pin shape of the ASA. At a 6-month follow-up the patient was improved and graded Aminoff-Logue scale score 5 (gait 3, micturition 2) and modified Denis scale score 5 (pain 2, numbness 3).

Figure 4. (A) Spinal MRI showed dilated venous channels located mainly on the dorsal surface of the thoracic spinal cord, that displayed a T2 hyperintensity, sign of myelopathy. (B) Spinal angiography confirmed the presence of dorsally located dilated venous channels associated with an intradural ventral AVF supplied by the ASA. (C) Intraoperative view after a right T9 transpedicle approach and slight rotation of the cord by a pulling suture placed on the dentate ligament. The ASA was seen (white arrowheads) and the exact point of AV shunt identified, coagulated (D) and cut. White asterisks indicate bipolar tips. The comparison of color maps and fluorescence curves before (E, F) and after (G, H) IGC injection confirmed the interruption of the AV shunt. In particular, the arterialized vein (blue ROI, E, G) appeared in green in the color map before and in blue after AVF interruption, indicating that the velocity of the dye inside the vein slowed down after treatment, passing from 9.8 sec to 10.2 sec, clue to the fact that the vein was no more arterialized. Confirmation of the effectiveness of the treatment was given by the analysis of the fluorescence curves before (F) and after treatment (H): before treatment the curve of the vein, in blue, reached the fluorescence peak at the same time that the curve of the artery, in red (black arrow and arrowhead, F), while after treatment its fluorescence peak (black arrow, H) was retarded of 6 sec compared to the the fluorescence peak of the artery (black arrowhead,h). Postoperative MRI (I) and angiography (J) showed the resolution of the vein dilatation and mielopathy and the disappearance of the shunt, with a preserved hair-pin shape of the ASA (white arrow). ASA: anterior spinal artery, ROI: region of interest. ICG: indocyanine green.

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DISCUSSION

True progress in the treatment of brain and scAVMs is provided by a team-oriented multidisciplinary approach, where microsurgery plays a leading role. Discussion on a case-by- case basis allows an individualized treatment plan and is likely to shorten intervention times, enhance the rate of complete obliteration and lower the risk of treatment whose main aim remains the preservation of the patients’ quality of life. As a consequence, the expertise of the treating team has the highest impact on the final outcome, as witnessed by the wide variability of results for different series in the literature. One major surgical advance is the introduction of intraoperative ICG video-angiography, that allows a real-time identification of the pathology and verification of the effectiveness of the treatment (Morgan et al. 2004). As for intracranial aneurysms, trials have been designed and conducted in order to define guidelines of treatment. The ARUBA trial proved fundamental in having paved the way for future trials on the management of AVMs. However, wider patient populations, less selection biases, longer follow-up and more equilibrated treatment groups should be included in order to avoid errors that will compromise the value of conclusions. Clinical decision starts with considering patient- related factors such as age and symptoms, particularly bleeding and seizures, and classic AVM- related factors such as size, site and venous drainage, and it is refined with assessment of nidus diffuseness, frequently related to deep perforators supply (Maduri, Guyotat, and Signorelli 2016), direction of the arterial supply, the so-called “arterial fronts,” and position of the veins. Preoperative angiography, CT scans and MRI are studied thoroughly and all phases of surgery carefully planned beforehand, starting from patient positioning and craniotomy. Even though the shape of an AVM is never cubic, it is useful to think of it as a box with six sides, one superficial, often cortical, one deep, generally ependymal, and four, anterior, posterior, medial and lateral, perpendicular to them (Michael T. Lawton 2014). This image may help the organization of microsurgical dissection. Subarachnoidal, pial and parenchymal dissections should proceed orderly and circumdissection spiral around the nidus gradually, avoiding plunging in narrow holes with limited visibility. Once complete deafferentation of the nidus is accomplished and the AVM is only connected to the main draining vein, one may think of vein disconnection as a trivial manoeuver to accomplish. However, overlooking a persistent redness of the vein, that usually suggests a persistent pedicle under it, or transecting the vein before its complete closure, preferably done with a clip in order to avoid back-bleeding from the sinus to whom it is connected, may result in blood filling the resection bed or leaking into the ventricles. However, the operation is finished only when hemostasis is secured after inspection of blind spots, particularly the ependymal surface, the diffuse margins and around skeletonized arteries, that may hide a residual nidus. Final concern is the blood pressure control in the intensive care unit. Patients with large AVMs, which may sometimes be at risk of bleeding from normal perfusion pressure breakthrough, those with difficult hemostasis from “red devils,” for whom large amounts of clips were used, may remain intubated and sedated overnight in order to avoid blood pressure sudden raises triggering postoperative bleeding.

ACKNOWLEDGMENTS

The authors gratefully acknowledge Dr. Jonathan Edward Lang for the revision of the manuscript.

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CONCLUSION

The management of brain and scAVMs remains controversial as the strength of recommendations as to whether or not to treat such malformations are generally weak inasmuch as they are based on the study of groups of AVM patients selected for undergoing treatment or observation. In order to guide treatment, available systems of grading and classification are of great use. However, treatment is mostly decided on a case-by-case basis and the outcome largely depends on the grade of expertise of the treating center. Careful study of preoperative images, mindful organization of the microsurgical dissection manoeuvers beforehand and watchful postoperative care are keys to favorable outcome.

REFERENCES

Aoun, Salah G., Bernard R. Bendok, and H. Hunt Batjer. 2012. “Acute Management of Ruptured Arteriovenous Malformations and Dural Arteriovenous Fistulas.” Neurosurgery Clinics of North America. Neurosurg Clin N Am. https://doi.org/10.1016/j.nec.2011. 09.013. Baranoski, Jacob F., Ryan A. Grant, Lawrence J. Hirsch, Paul Visintainer, Jason L. Gerrard, Murat Günel, Charles C. Matouk, Dennis D. Spencer, and Ketan R. Bulsara. 2014. “Seizure Control for Intracranial Arteriovenous Malformations Is Directly Related to Treatment Modality: A Meta-Analysis.” Journal of NeuroInterventional Surgery 6 (9): 684–90. https://doi.org/10.1136/neurintsurg-2013-010945. Choi, Jae H., Henning Mast, Robert R. Sciacca, Andreas Hartmann, Alexander V. Khaw, Jay P. Mohr, Ralph L. Sacco, and Christian Stapf. 2006. “Clinical Outcome after First and Recurrent Hemorrhage in Patients with Untreated Brain Arteriovenous Malformation.” Stroke 37 (5): 1243–47. https://doi.org/10.1161/01.STR.0000217970.18319.7d. Darsaut, Tim E., Elsa Magro, Jean-Christophe Gentric, André Lima Batista, Chiraz Chaalala, David Roberge, Michel W. Bojanowski, Alain Weill, Daniel Roy, and Jean Raymond. 2015. “Treatment of Brain AVMs (TOBAS): Study Protocol for a Pragmatic Randomized Controlled Trial.” Trials 16 (1): 497. https://doi.org/10.1186/s13063-015-1019-0. Davidson, Andrew S., and Michael K. Morgan. 2010. “How Safe Is Arteriovenous Malformation Surgery? A Prospective, Observational Study of Surgery as First-Line Treatment for Brain Arteriovenous Malformations.” Neurosurgery 66 (3): 498–504. https://doi.org/10.1227/01.NEU.0000365518.47684.98. Dehdashti, Amir R., Laurent Thines, Robert A. Willinsky, Karel G. Terbrugge, Michael L. Schwartz, Michael Tymianski, and M. Christopher Wallace. 2010. “Multidisciplinary Care of Occipital Arteriovenous Malformations: Effect on Nonhemorrhagic Headache, Vision, and Outcome in a Series of 135 Patients: Clinical Article.” Journal of Neurosurgery 113 (4): 742–48. https://doi.org/10.3171/2009.11.JNS09884. Derdeyn, Colin P., Gregory J. Zipfel, Felipe C. Albuquerque, Daniel L. Cooke, Edward Feldmann, Jason P. Sheehan, and James C. Torner. 2017. “Management of Brain Arteriovenous Malformations: A Scientific Statement for Healthcare Professionals from the American Heart Association/American Stroke Association.” Stroke. Lippincott Williams and Wilkins. https://doi.org/10.1161/STR.0000000000000134.

372 R. Messina, G. Cirrottola, N. Bruno et al.

Ding, Dale, Chun Po Yen, Zhiyuan Xu, Robert M. Starke, and Jason P. Sheehan. 2013. “Radiosurgery for Patients with Unruptured Intracranial Arteriovenous Malformations: Clinical Article.” Journal of Neurosurgery 118 (5): 958–66. https://doi.org/10.3171/2013. 2.JNS121239. Ferch, Richard D., and Michael K. Morgan. 2002. “High-Grade Arteriovenous Malformations and Their Management.” Journal of Clinical Neuroscience 9 (1): 37–40. https://doi.org/10. 1054/jocn.2000.0927. Gross, Bradley A., and Rose Du. 2013. “Natural History of Cerebral Arteriovenous Malformations: A Meta-Analysis ; Clinical Article.” Journal of Neurosurgery. J Neurosurg. https://doi.org/10.3171/2012.10.JNS121280. Hofmeister, C., C. Stapf, A. Hartmann, R. R. Sciacca, U. Mansmann, K. TerBrugge, P. Lasjaunias, J. P. Mohr, H. Mast, and J. Meisel. 2000. “Demographic, Morphological, and Clinical Characteristics of 1289 Patients with Brain Arteriovenous Malformation.” Stroke 31 (6): 1307–10. https://doi.org/10.1161/01.STR.31.6.1307. Hyun, Seung Jae, Doo Sik Kong, Jung Il Lee, Jong Soo Kim, and Seung Chyul Hong. 2012. “Cerebral Arteriovenous Malformations and Seizures: Differential Impact on the Time to Seizure-Free State According to the Treatment Modalities.” Acta Neurochirurgica 154 (6): 1003–10. https://doi.org/10.1007/s00701-012-1339-8. Iwama, Toru, Kohei Hayashida, Jun C. Takahashi, Izumi Nagata, and Nobuo Hashimoto. 2002. “Cerebral Hemodynamics and Metabolism in Patients with Cerebral Arteriovenous Malformations: An Evaluation Using Positron Emission Tomography Scanning.” Journal of Neurosurgery 97 (6): 1314–21. https://doi.org/10.3171/jns.2002.97.6.1314. Josephson, Colin B., Jo J. Bhattacharya, Carl E. Counsell, Vakis Papanastassiou, Vaughn Ritchie, Richard Roberts, Robin Sellar, Charles P. Warlow, and Rustam Al-Shahi Salman. 2012. “Seizure Risk with AVM Treatment or Conservative Management: Prospective, Population-Based Study.” Neurology 79 (6): 500–507. https://doi.org/10.1212/WNL. 0b013e3182635696. Katsaridis, Vasilios, Chrysanthi Papagiannaki, and Enrico Aimar. 2008. “Curative Embolization of Cerebral Arteriovenous Malformations (AVMs) with Onyx in 101 Patients.” Neuroradiology 50 (7): 589–97. https://doi.org/10.1007/s00234-008-0382-x. Kim, Helen, Rustam Al-Shahi Salman, Charles E. McCulloch, Christian Stapf, and William L. Young. 2014. “Untreated Brain Arteriovenous Malformation: Patient-Level Meta-Analysis of Hemorrhage Predictors.” Neurology 83 (7): 590–97. https://doi.org/10.1212/WNL. 0000000000000688. Kim, Louis J., and Robert F. Spetzler. 2006. “Classification and Surgical Management of Spinal Arteriovenous Lesions: Arteriovenous Fistulae and Arteriovenous Malformations.” Neurosurgery. Neurosurgery. https://doi.org/10.1227/01.NEU.0000237335.82234.CE. Krings, Timo, Franz Josef Hans, Sasikhan Geibprasert, and Karel Terbrugge. 2010. “Partial ‘Targeted’ Embolisation of Brain Arteriovenous Malformations.” European Radiology. Springer. https://doi.org/10.1007/s00330-010-1834-3. Kusske, J. A., and W. A. Kelly. 1974. “Embolization and Reduction of the ‘steal’ Syndrome in Cerebral Arteriovenous Malformations.” Journal of Neurosurgery 40 (3): 313–21. https://doi.org/10.3171/jns.1974.40.3.0313. Lawton, Michael T., Helen Kim, Charles E. McCulloch, Bahar Mikhak, and William L. Young. 2010. “A Supplementary Grading Scale for Selecting Patients with Brain Arteriovenous

Approaches for Brain and Spinal Cord Arteriovenous Malformations 373

Malformations for Surgery.” Neurosurgery 66 (4): 702–13. https://doi.org/10.1227/01. NEU.0000367555.16733.E1. Maduri, Rodolfo, Jacques Guyotat, and Francesco Signorelli. 2016. “Semi-Quantitative Assessment of Flow Dynamics during Indocyanine Green Video-Angiography in the Treatment of Intracranial Dural Arteriovenous Fistulas: How I Do It.” Acta Neurochirurgica 158 (7): 1387–91. https://doi.org/10.1007/s00701-016-2812-6. Mast, Henning, J. P. Mohr, Andrei Osipov, John Pile-Spellman, Randolph S. Marshall, Ronald M. Lazar, Bennett M. Stein, and William L. Young. 1995. “‘Steal’ Is an Unestablished Mechanism for the Clinical Presentation of Cerebral Arteriovenous Malformations.” Stroke 26 (7): 1215–20. https://doi.org/10.1161/01.STR.26.7.1215. Michael T. Lawton. 2014. “Seven AVMs: Tenets and Techniques for Resection.” Acta Neurochirurgica 156 (9): 1827–28. https://doi.org/10.1007/s00701-014-2153-2. Mohr, J. P., Michael K. Parides, Christian Stapf, Ellen Moquete, Claudia S. Moy, Jessica R. Overbey, Rustam Al Shahi Salman, et al. 2014. “Medical Management with or without Interventional Therapy for Unruptured Brain Arteriovenous Malformations (ARUBA): A Multicentre, Non-Blinded, Randomised Trial.” The Lancet 383 (9917): 614–21. https://doi.org/10.1016/S0140-6736(13)62302-8. Morgan, Michael Kerin, Andrew Michael Rochford, Antonio Tsahtsarlis, Nicholas Little, Kenneth Charles Faulder, Rogerio Turolo Da Silva, Evandro De Oliveira, et al. 2004. “Surgical Risks Associated with the Management of Grade I and II Brain Arteriovenous Malformations.” Neurosurgery 54 (4): 832–39. https://doi.org/10.1227/01.NEU.0000 114264.78966.BE. Reinard, Kevin A., Aqueel H. Pabaney, Azam Basheer, Scott B. Phillips, Max K. Kole, and Ghaus M. Malik. 2015. “Surgical Management of Giant Intracranial Arteriovenous Malformations: A Single Center Experience over 32 Years.” World Neurosurgery 84 (6): 1765–78. https://doi.org/10.1016/j.wneu.2015.07.051. Rutledge, W. Caleb, Adib A. Abla, Jeffrey Nelson, Van V. Halbach, Helen Kim, and Michael T. Lawton. 2014. “Treatment and Outcomes of ARUBA-Eligible Patients with Unruptured Brain Arteriovenous Malformations at a Single Institution.” Neurosurgical Focus 37 (3). https://doi.org/10.3171/2014.7.FOCUS14242. Signorelli F, and Turjman F. n.d. Endovascular Treatment of Spinal Vascular Lesions. In: Nader, Gragnaniello, Berta, Sabbagh, Levy Eds. Neurosurgery Tricks of the Trade. Spine and Peripheral Nerves. Signorelli, Francesco, Benjamin Gory, Isabelle Pelissou-Guyotat, Jacques Guyotat, Roberto Riva, Frédéric Dailler, and Francis Turjman. 2014. “Ruptured Brain Arteriovenous Malformations Associated with Aneurysms: Safety and Efficacy of Selective Embolization in the Acute Phase of Hemorrhage.” Neuroradiology 56 (9): 763–69. https://doi.org/ 10.1007/s00234-014-1395-2. Spetzler, Robert F., Paul W. Detwiler, Howard A. Riina, and Randall W. Porter. 2002. “Modified Classification of Spinal Cord Vascular Lesions.” Journal of Neurosurgery 96 (2 SUPPL.): 145–56. https://doi.org/10.3171/spi.2002.96.2.0145. Starke, Robert M., Hideyuki Kano, Dale Ding, John Y. K. Lee, David Mathieu, Jamie Whitesell, John T. Pierce, et al. 2017. “Stereotactic Radiosurgery for Cerebral Arteriovenous Malformations: Evaluation of Long-Term Outcomes in a Multicenter Cohort.” Journal of Neurosurgery 126 (1): 36–44. https://doi.org/10.3171/2015.9. JNS151311.

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Wang, Joanna Y., Wuyang Yang, Xiaobu Ye, Daniele Rigamonti, Alexander L. Coon, Rafael J. Tamargo, and Judy Huang. 2013. “Impact on Seizure Control of Surgical Resection or Radiosurgery for Cerebral Arteriovenous Malformations.” Neurosurgery 73 (4): 648–55. https://doi.org/10.1227/NEU.0000000000000071. Xu, Feng, Junjie Zhong, Abhishek Ray, Sunil Manjila, and Nicholas C. Bambakidis. 2014. “Stereotactic Radiosurgery with and without Embolization for Intracranial Arteriovenous Malformations: A Systematic Review and Meta-Analysis.” Neurosurgical Focus 37 (3). https://doi.org/10.3171/2014.6.FOCUS14178.

Chapter 23

APPROACHES FOR BRAIN AND SPINAL CORD CAVERNOUS MALFORMATIONS

M. Del Maestro1,2,, MD, S. Luzzi2,3, MD, PhD, G. Mezzini3, MD, A. Giotta Lucifero3, MD and R. Galzio2,3, MD 1PhD School in Experimental Medicine, Department of Clinical-Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, Pavia, Italy 2Neurosurgery Unit, Department of Surgical Sciences, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy 3Neurosurgery Unit, Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy

ABSTRACT

Cavernous malformations (CMs) are relatively rare vascular lesions theoretically inolving any part of the central nervous system. Their natural history, often characterized by hemorrhages and devastating outcomes, imposes a delicate decision-making process. In this chapter, we discuss the management of supratentorial, infratentorial, and spinal cord CMs. A systematization of the main approaches for CMs is proposed.

Keywords: Brainstem, Brainstem approaches, Cavernous malformations, spinal cord, spontaneus hemorrhage

 Corresponding Author’s Email: [email protected].

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BACKGROUND

Cavernous malformations (CMs) are constituted by an abnormally compact bundle of “low flow” vascular channels lacking intervening neural parenchyma, sometimes associated with a developmental venous anomaly (DVA) (Rigamonti et al. 1988; Awad and Polster 2019). CMs range in size from millimeters to several centimeters in diameter and can be found in any site of the central nervous system (CNS). They are classically recognized as one of the four main classes of cerebral vascular malformations, which also include arteriovenous malformations (AVM), developmental venous anomalies (DVA), and capillary telangiectasia (McCormick 1966). In literature, CMs have assumed a variety of names, including cavernomas, cavernous angiomas, and cavernous hemangiomas, although CMs is the preferred nomenclature (Akers et al. 2017). Macroscopically, the lesions are often multilobulated, encapsulated by layers of fibrous adventitia, reddish purple colored, with a characteristic mulberry-like appearance. Histologically, they are composed by a single layer of endothelial cells surrounding sinusoidal spaces without mature vessels structural elements as smooth muscle and elastin (Ellis and Barrow 2017). Astrocytic foot process and pericytes, usually found in the blood-brain barrier, are lacking. The majority of CMs are sporadic, and patients rarely have more than two lesions. Family history is typically absent. Even so, up to 20% of CMs follow a familiar, autosomal dominant inheritance pattern characterized by the presence of multiple CMs in a single patient (Labauge et al. 2007). Several studies have been implemented to identify specific molecular aspects of CMs, with aim to link these mutations to specific clinical features, equally to what occurred for other several lesions involving the CNS (Raysi Dehcordi et al. 2017; Cheng, Shetty, and Sekhar 2018; Luzzi, Crovace, et al. 2018; Palumbo et al. 2018; Zoia et al. 2018; Bellantoni et al. 2019; Luzzi, Crovace, et al. 2019; Luzzi, Elia, Del Maestro, Elbabaa, et al. 2019; Luzzi, Giotta Lucifero, et al. 2019; Palumbo et al. 2019; Spena et al. 2019; Antonosante et al. 2020; Campanella et al. 2020; Zoia et al. 2020). Selective mutations in three homologically distinct genes responsible for CM development were identified: CCM1, CCM2, and CCM3. All of these have a relatively high genetic penetrance. Studies of sporadic CCM support a common pathway involving de novo mutations of CCM genes (Labauge et al. 2007). Cerebral CMs are common, affect approximately 1 in every 200 individuals, and account for 8% to 15% of all vascular malformations of the CNS. No prevalvence of sex has been reported. After aneurysms, CMs are the second most common incidental vascular lesions on brain MRI, with a prevalence of 1 in 625 asymptomatic people (Caton and Shenoy 2020). Up to 90% of cerebral CMs involve the supratentorial compartment. Brainstem is interested in a volume ranging between 9% and 35% of infratentorial cases (Zhang et al. 2013). Patients with CMs associated with DVAs are more likely to have a posterior fossa involvement (Abdulrauf, Kaynar, and Awad 1999). Lastly, medullary spinal CMs account for 5% of cases (Mitha et al. 2011). CMs are dynamic lesions, potentially growing due to the thrombosis and hemorrhagic processes. They can also regress when the products of the bleeding are reabsorbed. In most of the cases CMs are an incidental finding. Seizures are frequent in frontal and temporal lobe lesions. The estimated annual risk of hemorrhage differs dramatically from that reported for other vascular lesions, aneurysms and

Approaches for Brain and Spinal Cord Cavernous Malformations 377 arteriovenous malformations firsts (Ricci et al. 2017; Del Maestro et al. 2018; Gallieni et al. 2018; Luzzi, Del Maestro, et al. 2018; Luzzi, Gallieni, et al. 2018; Luzzi, Del Maestro, and Galzio 2019; Luzzi, Elia, Del Maestro, Morotti, et al. 2019; Luzzi et al. 2020). This risk ranges between 0.25% and 6% (Two A 2012). Large size, deep location, older age and pregnancy have been associated to a higher bleeding risk. Prevoius bleeding also are reported to have a higher risk (Two A 2012). When symptomatic, the occurrence of focal deficits is the most frequent clinical onset of infratentorial CMs. Conversely, acute neurological deficits due to hemorrhage, or progressive myelopathy due to repeated microhemorrhages, are the typical presentations of spinal cord CMs (Sandalcioglu et al. 2003). Magnetic resonance imaging (MRI) is the gold standard for the diagnosis of CMs (Al- Shahi Salman et al. 2008). T2-weighted MRI usually shows a characteristic mixed “popcorn” signal core with a hypointense rim (Ellis and Barrow 2017). The ferromagnetic dephasing of proton spins due to the hemosiderin rim lining the margins of CMs creates a signal void on gradient echo MRI or susceptibility-weighted sequences (SWI), which is easily detected. However, it can overestimate the real size of the lesion. Both digital subtracion angiography (DSA) and computed tomography angiography (CTA) are of limited utility due to the slow transit of blood via the dysplastic channels of CMs. However, they can highlight adjacent DVAs (Petersen et al. 2010). The main role of non-contrast enhanced CT is the identification of hemorrhage in symptomatic patients, although CMs may also present as amorphous calcifications. Nowadays, advanced MR imaging, as diffusion tensor imaging (DTI) and blood oxygen level dependent (BOLD) task-activation mapping of language function, are gaining a paramount role in preoperative workup of CMs (Pouratian et al. 2002). The clinical course of CMs is highly variable and site dependent. Management of CMs require a multidisciplinary approach. When feasible, surgical resection is the preferred treatment option for symptomatic lesions. In select cases, targeted radiotherapy is used to treat lesions which are surgically inaccessible.

SUPRATENTORIAL CMS

For supratentorial CMs, the surgical treatment is indicated for patients who present with neurological deficits and evidence of mass effect coming from an intra- or peri-lesional hemorrhage. In case of drug-resistent epilepsy, early surgery is indicated when there is a high confidence that a solitary CM is the source of epilepsy (Akers et al. 2017; Caton and Shenoy 2020). Also in case of deep located symptomatic cavernomas there is a general agreement for the microsurgical treatment, since the fact that favourable results have been reported in high- volume centers (Lawton, Quinones-Hinojosa, and Jun 2006). Most cases with neurological deficits were treated 2 to 3 weeks after bleeding. Rarely, severe progressive worsenings need an emergency evacuation of the hematoma and lesionectomy.

378 M. Del Maestro, S. Luzzi, G. Mezzini et al.

Supratentorial CMs in eloquent and deep locations can be associated with a significant surgical risk, leading to some neurosurgeons to treat also those lesions characterized by symptomatic hemorrhage with observation. CMs in non-eloquent areas are approached with standard craniotomies and can be often removed with circumferential dissection. On the contrary, lesions in eloquent areas, as thalamus, basal ganglia, corpus callosum, sensorimotor, language, and visual cortex, must be treated equally to those involving the brainstem, namely entering the lesion capsule and dissecting it free from surrounding parenchyma from inside (“inside-out” dissection technique). The integrity of the capsule is preserved to protect the adjacent brain tissue. Electrocautery should be avoided. A careful selection of the patients, along with a comprehensive preoperative planning and analisis of the data, are all integral part of the overall managemnent of these lesions, on a par with other surgical pathologies involving the CNS (Millimaggi et al. 2018; Bongetta et al. 2019; Elsawaf et al. 2020). A comprehensive and systematized description of the supratentorial approaches for deep and eloquent region CMs was reported in 2011 by Chang et. al (Chang et al. 2011). They reported 13 different approaches divided in four groups:

1. Superficial approaches, used with lesions in sensorimotor, language, and visual cortex. All these approaches use a convexity craniotomy centred directly above the lesion.  Transcortical appoaches are employed for eloquent cortex when CM comes to a gyral surface, or when the shortest, most direct route to the lesion is carried out through an overlying gyrus.  Transsulcal approaches are used when the CM came to a sulcal surface, when an overlying sulcus shortens the corridor, or when the sulcus lead to avoid the eloquent cortex. 2. Lateral transsylvian approaches, used when the shortest, direct route to the CM is executed through the insular cortex. They require a wide splitting of the sylvian fissure to exopse the M2 segments of the MCA. For the anterior and posterior transinsular approach a pterional craniotomy is used. For the supracarotid-infrafrontal lesions an orbitozygomatic craniotomy is frequently used.  The anterior transinsular approach require the splitting of the sphenoidal part of the sylvian fissure, in order to separate the anterior temporal lobe from the frontal lobe, thus exposing the limen insula and the short gyri of the insula. That’s the route for CMs involving the head of the caudate nucleus, and the anterior limb of the internal capsule.  The posterior transinsular approach encompasses the opening of the opercular part of the sylvian fissure, thus separating the superior temporal gyrus from the opercular part of the frontal and parietal lobe to expose the ling gyri of the insula. This corridor is generally used to exposed CMs embedded into the claustrum, extreme capsule, putamen, and globus pallidus, or the wedge of basal ganglia lateral to the internal capsule (lateral thalamus).

Approaches for Brain and Spinal Cord Cavernous Malformations 379

 The supracarotid-infrafrontal approach is employed for CMs abitting at the level of the posterior orbital girus. The working corridor is through the supracarotid triangle formed by the A1 and M1 segments of the anterior and middle cerebral artery, respectively. This corridor is just lateral to the lateral lenticulostriate arteries coming form from the M1 segment. This approach leads to expose the putamen, globus pallidus, and anterior limb of internal capsule. 3. Medial interhemispheric approaches are used to reach deep targets in the cingulate gyrus, corpus callosum, septal area, basal ganglia, and thalamus. All these approaches use a parasagittal craniotomy.  Anterior interhemispheric approach exposes the medial aspect of the superior frontal girus, the cingulate gyrus, callosal sulcus. Furthermore, the anterior transcallosal extension of this approach allows to treat those CMs of the rostrum, genu, and body of corpus callosum.  Controlateral transcallosal approach enhances the lateral exposure of a traditional transcallosal approach. It exploits the gravity-assisted retraction and allows to expose the area between the foramen of Monro to the lateral wall of the lateral ventricle.  Transcallosal-transchoroidal approach leads to reach the third ventricle. The choroidal fissure is opened after the splitting of the tenia fornicis and tenia thalami. 4. Posterior approaches are a heterogeneous group. In all cases a torcular craniotomy exposes the superior sagittal sinus, transverse sinuses, and the sinuses confluence, allowing for an unobstructed access to the midline structures. Patient position, head position, and subarachnoid dissection planes varies according to each approach.  Posterior interhemispheric approach is indicated for CMs of the posterior aspect of the cingulate gyrus or callosal sulcus.  Posterior transcallosal approach accesses the splenium of the corpus callosum and the pulvinar.  Supratentorial-infraoccipital approach for pineal region in case of unfavorable callosal angle.  Median supracerebellar-infratentorial approach for tectal lesions or pineal ones in case of favorable callosal angle.  Paramedian supracerebellar-infratentorial approach for CMs abutting at the level of the lateral mesencephalic sulcus.

Illustrative Case A 39 years-old female was referred to us because of a hemorrhagic CMs of the left frontal lobe. A frontal trans-superior frontal sulcus approach was planned. The procedure was performed in augmented reality (AR) mode with volume rendering of the lesion and fibertracking of the left cortico-spinal tract. A left parasagittal fronto-parietal craniotomy was carried out and the trans-sulcal corridor provided the complete exposure of the cavernoma. Post-operative MRI confirmed the gross total removal of the lesion and the patiemts was discharged on the third post-operative day neurologically intact (Figure 1).

380 M. Del Maestro, S. Luzzi, G. Mezzini et al.

Figure 1. (A) Axial gradient echo MRI and T1-weighted MRI with Gadolinium in axial, coronal and sagittal plane (B-D) showing a left frontal CM. (E) Left fronto-parietal tailored craniotomy planning in AR mode. (F) Opening of the dura mater and exposure of the superior and middle frontal gyrus and the superior frontal sulcus. (G) Visualization of the cortico-spinal tract in AR. (H) Study of the frontal cortical veins with indocyanine green videoangiography (ICGVA). (I) Trans-sulcal approach and identification of the superficial part of the CM. (J-K) Circumferential dissection of the CM and its complete removal. (L) ICGVA control showing the integrity of the cortical venous draining pattern at the end of surgery. (M-O) T1-weighted MRI with gadolinium in axial, coronal and sagittal plane and coronal T2-weighted MRI (P) demonstrating the gross total removal of the CM.

INFRATENTORIAL CMS

The correct management of brainstem and cerebellar CMs is complex, not univocal and crucial for the prognosis. It has been reported that the hemorrhagic risk of these lesions is 6.75 times higer than in other locations. In addition, several studies have documented an increased re-bleeding rate, with a severe disabling outcome, among these patients (Two A 2012; Bozinov et al. 2010). Because of the potential for devastating sequelea coming from hemorrhage in this site, surgical treatment of these CMs is indicated.

Brainstem CMs Surgical treatment of brainstem CMs is classically associated with a high morbidity and mortality rate. The aim of surgery for brainstem CMs is to prevent rebleeding and hemosiderin

Approaches for Brain and Spinal Cord Cavernous Malformations 381 deposits. Further advantages lie in the curative intent, as well as recovery from symtpoms (El Ahmadieh et al. 2012) (Abla et al. 2010). Surgery is indicated in all those patients harboring ruptured CMs, especially if associated with deficits, if the lesion itself or the hematoma abuts on the pial or ependymal surface. This is valid also in case of a previous sigle bleeding. Conversely, a wait-and-see approach is recommended for lesions not protruding to an adequate entry point on the surface. Young age and repeated hemorrages are considered risk factors in favour of surgery. A pros and cons balance of possible therapeutic options is always mandatory. Usually, a delayed surgery (2 to 3 weeks after the symptomatic onset) is preferred for patients with stable or improving neurological deficit. Precipitating factors as precocious rebleeding or progressive symptomatology may require an early surgery, whereas life- threatening hematomas require immediate operation (Giliberto et al. 2010). The goal of surgery is the complete evacuation of the hematoma and the radical resection of the lesion, as remnants can grow and bleed. The brainstem incision must be as limited as possible, and a piecemeal removal is advantageous in most instances. Perilesional hemosiderin- laden brain has to be left untouched. Associated developmental venous anomaly (DVA) has to be preserved (associated DVA has to be suspected also if not evident on preoperative imaging). Brainstem retraction has to be avoided, using only the dissection or the suction instruments during the procedure. In this scenario, the endoscopic assistance may be useful during the initial, intermediate and final steps of surgery, with an effectiveness already reported also for other neurosurgical pathologies (Luzzi, Del Maestro, et al. 2019; Gallieni et al. 2018; Luzzi, Maestro, et al. 2019; Luzzi, Zoia, et al. 2019; Zoia et al. 2019; Arnaout et al. 2020). All the intraoperative adjuvant techniques, as intraoperative neurophisiological monitoring, neuronavigation, and augmented reality also have to be performed.

Table 1. Skull Base Approaches for Brainstem CMs

SITE APPROACH PATIENT POSITION Midbrain Anterior surface of the cerebral Pterional, orbitozygomatic, mini- Supine peduncle, pontomesencephalic junction orbitozygomatic Lateral surface of the midbrain Subtemporal Lateral Postero-lateral surface of the midbrain Lateral supracerebellar infratentorial Sitting Tectal plate lesions Supratentorial infraoccipital, Sitting/prone supracerebellar infratentorial Pons Ventral upper pons (midline) Orbitozygomatic Supine Lateral upper pons, Subtemporal transtentorial Lateral lateral pontomesencephalic junction Anterior and lateral pons Retrosigmoid (peritrigeminal, Lateral/sitting supratrigeminal, and lateral pontine safe zones) Dorsal pons Suboccipital telovelar Sitting Medulla Antero-lateral Far lateral Lateral Lateral Retrosigmoid Lateral/sitting Posterior Median suboccipital Prone

382 M. Del Maestro, S. Luzzi, G. Mezzini et al.

The choice of the approach is mainly based on the site of the lesion. The “two point method” (one point placed in the center of the lesion, and the second one where the CM comes to the closest safe entry zone) as described by Brown and Spetzler (Brown AP 1996) has proved to be useful for this pourpose. Each approach is selected on a case-by-case basis. Skull base approaches have been systematized in order to guide the surgeons in the selction of the most appropriate corridor (Cavalcanti et al. 2016; Sandalcioglu et al. 2002; Vinas et al. 2002). Cavalcanti et al. reported a useful scheme (Table 1).

Cerebellar CMs Surgical indication for cerebellar CMs is controversial. However, surgery is mandatory in case of second bleeding, life-threatening hematoma, or progressive neurological impairment. Good outcomes are worldwide reported (Zhang et al. 2013; Wu et al. 2015). Cerebellar peduncles are considered the most dangerous site because related to a higher risk of deficits (Wu et al. 2015). Timing for surgery is still debated. Patients with massive hemorrhage and unstable clinical conditions need an emergency operation. Some authors suggest waiting up to 6 weeks after hemorrhage (Wu et al. 2015). As described for supratentorial and braistem CMs, the choice of the approach is dictated by the size and location. Three different locations are usually distinguished: hemisphere, vermis and cerebellar peduncle. Hemispheric and vermian CMs are considered non-eloquent. Median CMs are well exposed through a standard median suboccipital craniotomy, whereas the lateral ones are exposed with a paramedian approach. The prone position is the most frequently reported, as well as its “concorde” variant. Sitting or modified “park-bench” positions are also reported. CMs on the petrosal surface of the cerebellum can be accessed through a retrosigmoid approach exposing the cerebello-pontine angle. Several surgical approaches have been described for cerebellar peduncles CMs. The transcerebellar, transvermian approach, or the cerebellomedullary fissure approach, can access the inferior and middle cerebellar peduncles (Matsushima et al. 2001). To avoid cerebellar resection minimizing retraction, Lawton et al. have developed a supratonsillar approach to the inferior cerebellar peduncle (Lawton, Quinones-Hinojosa, and Jun 2006). Cavernous malformations on the petrosal surface of the cerebellar peduncle typically required a retrosigmoid or far lateral approach. Cerebellar CMs are frequently associated with DVAs.

Illustrative Cases

Case 1 A 41 years old male, in follow-up for a midline interpeduncular midbrain CMs diagnosed three years earlier, developed a progressive tetraparesis. MRI revealed an increase in size of the lesion, on the basis of which the patient underwent to surgery. The lesion was exposed through a right fronto-temporo-orbito-zygomatic (FTOZ) approach and a supracarotid corridor. Cavernoma was completely removed as confirmed by the post-operative MRI. The patient had a good outcome with an mRS 2 at 6-months (Figure 2).

Approaches for Brain and Spinal Cord Cavernous Malformations 383

Figure 2. (A-C) T1-weighted MRI with Gadolinium in axial, coronal and sagittal plane showing a mesencephalic CM abutting in the interpeduncular cistern. (D-F) Right FTOZ approach and supra-carotid corridor. (G-I) Piece-meal removal of the CM. (J-L) T1-weighted MRI with gadolinium in axial, coronal and sagittal plane demonstrating the gross total removal of the CM.

Case 2 A 50 years-old female with a history of headache, dizziness and gait instability was diagnosed with a hemorrhagic intra-axial lesion of the right antero-lateral aspect of the pons. MRI showed the typical pop-corn appearance of the CM abutting on the pial pontine surface. With the patient in a modified park-bench position, the lesion was exposed through a right retrosigmoid approach. The entry point matched with the peritrigeminal safe zone. After an inspection with a 0-degree endoscope, the lesion was microsurgically removed. Final

384 M. Del Maestro, S. Luzzi, G. Mezzini et al. endoscopic check confirmed the complete removal of the CM. Post-operative MRI confirmed the gross total excision. The patient had an mRS score 1, and the gait instability progressively imporoved (Figure 3).

Figure 3. (A-C) T1-weighted MRI with Gadolinium in axial, coronal and sagittal plane showing a CM abutting on the right anterolateral pial surface of pons. (D) Right retrosigmoid prospective of the peritrigeminal safe entry-zone. (E-F) Microscopic and endoscopic view of the CM. (G) Microsurgical removal of the lesion. (H-I) Final microscopic and endoscopic view of the surgical cavity. (J-K) T1- weighted MRI with gadolinium in axial and coronal plane demonstrating the gross total removal of the CM. (L) Three-dimensional volume rendering of the post-operative CT showing the retrosigmoid craniotomy.

Approaches for Brain and Spinal Cord Cavernous Malformations 385

SPINAL CORD CMS

Spinal cord cavernomas account for 5% of the CNS CMs (Mitha et al. 2011; Stapleton and Barker 2018). Thoracic tract is the most frequently involved. These lesions are seldom symptomatic before the second or third decades, and they occur with an equal frequence in both sexes. Up to 20% of CMs in this site are incidental (Kivelev, Niemela, and Hernesniemi 2012). Usually, their presentation ranges from an acute deficit caused by the hemorrhage to a progressive myelopathy secondary to repeated microhemorrhages (Sandalcioglu et al. 2003). Surgical gross total removal remains the optimal treatment (Vishteh, Zabramski, and Spetzler 1999). Their clinical features depend by the locations. Spinal CMs are more frequently symptomatic than the cerebral ones (Badhiwala et al. 2014). Clinical manifestations of symptomatic intramedullary spinal cord lesions may follows two main pattern: major hemorrhage, with sudden onset of symptoms and deficits, and progressive myelopathic or radicular symptoms, probably related to minor bleedings and gradual growth of the lesion (Jallo et al. 2006; Badhiwala et al. 2014; Ogilvy, Louis, and Ojemann 1992; Sandalcioglu et al. 2003). An episodic symptomatology is also characteristic of intra-medullary microhemorrhages. This episodic course has to be differentiated from multiple sclerosis and transverse myelitis (Balasubramaniam and Mahore 2013). The natural course of spinal CMs is characterized by an estimated annual risk of bleeding of 2.1% (Del Curling et al. 1991). However, once the lesions become symptomatic, there is a progressive neurological deterioration with a significant increase in re-hemorrhage rates (Nikoubashman et al. 2015). Notably, patients with spinal cord cavernomas appear to have an increased risk of associated intracranial lesions (Vishteh, Zabramski, and Spetzler 1999). Symptomatic patients are eligible for surgery. Resection within 3 months from the onset of symptoms is related to a better neurological result (Maslehaty et al. 2011; Kshettry et al. 2015). Intraoperative neuromonitoring with somatosensory and motor evoked potentials is mandatory for all spinal cavernomas in order to inscrease as much as possible the safety of surgery (Jin et al. 2015; Giammattei et al. 2017). In the majority of cases, this kind of lesions are located in the dorsal part of spinal cord. Usually a posterior, postero-lateral, or lateral approach can be used according to the main column involed. Cavernoma located in the lateral columns can be approached through a hemilaminectomy, those crossing the midline requiring instead a laminectomy. Facetectomy or pediculectomy can increases angular exposure of the ventral spinal cord. Spinal CMs usually emerge on the pial surface. Nevertheless, for deeper lesions, ultrasonography may dramatically help their localization (Giammattei et al. 2017). Posterior median septum is the classically reported safe entry zone for the linear longitudinal myelotomy. In the remaining cases, the so-called near the dorsal root postero-lateral entry zone is recommended. Piecemeal removal is generally perfomed by the reason of limited myelotomies. Pial vascularization should be compulsively preserved. The remaining aspects of the surgical technique are similar to those described for brainstem CMs.

Illustrative Case A 21 years-old man suffering from an acute left paresis in the left arm, was diagnosed with a hemorrhagic cervical C6-C7 CMs mainly involving the pial surface of the lateral column of

386 M. Del Maestro, S. Luzzi, G. Mezzini et al. the cord. The lesion was exposed through a left C5-C6 hemilaminectomy, thus achieveing a good exposure of the lesion. A multimodal intraoperative neuromonitoring, also comprehensive of free-running D-wave registration, was done. Cavernoma was completely removed, as revealed by the the post-operative MRI, and the patient completely recovered within two months (Figure 4).

Figure 4. (A) Sagittal gradient-echo MRI and sagittal and coronal T2-weighted MRI (B-C) showing a CM of the spinal cord at C5-C6 level. (D) Left hemilaminectomy, positioning of the registration catheter in the subdural space and exposure of the lesion, abutting on the pial surface. (E-G) Complete piece-meal removal of the CM. (H) Sagittal gradient-echo MRI and sagittal and coronal T2-weighted MRI in sagittal and axial plane demonstrating the gross total removal of the CM.

Approaches for Brain and Spinal Cord Cavernous Malformations 387

REFERENCES

Abdulrauf, S. I., M. Y. Kaynar, and I. A. Awad. 1999. “A comparison of the clinical profile of cavernous malformations with and without associated venous malformations.” Neurosurgery 44 (1): 41-6; discussion 46-7. https://doi.org/10.1097/00006123- 199901000-00020. https://www.ncbi.nlm.nih.gov/pubmed/9894962. Abla, A. A., J. D. Turner, A. P. Mitha, G. Lekovic, and R. F. Spetzler. 2010. “Surgical approaches to brainstem cavernous malformations.” Neurosurg Focus 29 (3): E8. https://doi.org/10.3171/2010.6.FOCUS10128. https://www.ncbi.nlm.nih.gov/pubmed/ 20809766. Akers, A., R. Al-Shahi Salman, A. Awad I, K. Dahlem, K. Flemming, B. Hart, H. Kim, I. Jusue- Torres, D. Kondziolka, C. Lee, L. Morrison, D. Rigamonti, T. Rebeiz, E. Tournier- Lasserve, D. Waggoner, and K. Whitehead. 2017. “Synopsis of Guidelines for the Clinical Management of Cerebral Cavernous Malformations: Consensus Recommendations Based on Systematic Literature Review by the Angioma Alliance Scientific Advisory Board Clinical Experts Panel.” Neurosurgery 80 (5): 665-680. https://doi.org/10.1093/neuros/ nyx091. https://www.ncbi.nlm.nih.gov/pubmed/28387823. Al-Shahi Salman, R., M. J. Berg, L. Morrison, I. A. Awad, and Board Angioma Alliance Scientific Advisory. 2008. “Hemorrhage from cavernous malformations of the brain: definition and reporting standards. Angioma Alliance Scientific Advisory Board.” Stroke 39 (12): 3222-30. https://doi.org/10.1161/STROKEAHA.108.515544. https://www.ncbi. nlm.nih.gov/pubmed/18974380. Antonosante, A., L. Brandolini, M. d'Angelo, E. Benedetti, V. Castelli, M. D. Maestro, S. Luzzi, A. Giordano, A. Cimini, and M. Allegretti. 2020. “Autocrine CXCL8-dependent invasiveness triggers modulation of actin cytoskeletal network and cell dynamics.” Aging (Albany NY) 12 (2): 1928-1951. https://doi.org/10.18632/aging.102733. https://www.ncbi. nlm.nih.gov/pubmed/31986121. Arnaout, M. M., S. Luzzi, R. Galzio, and K. Aziz. 2020. “Supraorbital keyhole approach: Pure endoscopic and endoscope-assisted perspective.” Clin Neurol Neurosurg 189: 105623. https://doi.org/10.1016/j.clineuro.2019.105623. https://www.ncbi.nlm.nih.gov/pubmed/ 31805490. Awad, I. A., and S. P. Polster. 2019. “Cavernous angiomas: deconstructing a neurosurgical disease.” J Neurosurg 131 (1): 1-13. https://doi.org/10.3171/2019.3.JNS181724. https://www.ncbi.nlm.nih.gov/pubmed/31261134. Badhiwala, J. H., F. Farrokhyar, W. Alhazzani, B. Yarascavitch, M. Aref, A. Algird, N. Murty, E. Kachur, A. Cenic, K. Reddy, and S. A. Almenawer. 2014. “Surgical outcomes and natural history of intramedullary spinal cord cavernous malformations: a single-center series and meta-analysis of individual patient data: Clinic article.” J Neurosurg Spine 21 (4): 662-76. https://doi.org/10.3171/2014.6.SPINE13949. https://www.ncbi.nlm.nih.gov/ pubmed/25062285. Balasubramaniam, S., and A. Mahore. 2013. “Cavernoma of the conus medullaris mimicking transverse myelitis.” Singapore Med J 54 (2): e24-7. https://doi.org/10.11622/smedj. 2013034. https://www.ncbi.nlm.nih.gov/pubmed/23462837. Bellantoni, G., F. Guerrini, M. Del Maestro, R. Galzio, and S. Luzzi. 2019. “Simple schwannomatosis or an incomplete Coffin-Siris? Report of a particular case.”

388 M. Del Maestro, S. Luzzi, G. Mezzini et al.

eNeurologicalSci 14: 31-33. https://doi.org/10.1016/j.ensci.2018.11.021. https://www. ncbi.nlm.nih.gov/pubmed/30555950. Bongetta, D., C. Zoia, S. Luzzi, M. D. Maestro, A. Peri, G. Bichisao, D. Sportiello, I. Canavero, A. Pietrabissa, and R. J. Galzio. 2019. “Neurosurgical issues of bariatric surgery: A systematic review of the literature and principles of diagnosis and treatment.” Clin Neurol Neurosurg 176: 34-40. https://doi.org/10.1016/j.clineuro.2018.11.009. https://www.ncbi. nlm.nih.gov/pubmed/30500756. Bozinov, O., T. Hatano, J. Sarnthein, J. K. Burkhardt, and H. Bertalanffy. 2010. “Current clinical management of brainstem cavernomas.” Swiss Med Wkly 140: w13120. https://doi. org/10.4414/smw.2010.13120. https://www.ncbi.nlm.nih.gov/pubmed/21110237. Brown A. P., Thompson BG, Spetzler R. F. 1996. “The two-point method: evaluating brain stem lesions.” BNI Q 12: 20-24. Campanella, R., L. Guarnaccia, C. Cordiglieri, E. Trombetta, M. Caroli, G. Carrabba, N. La Verde, P. Rampini, C. Gaudino, A. Costa, S. Luzzi, G. Mantovani, M. Locatelli, L. Riboni, S. E. Navone, and G. Marfia. 2020. “Tumor-Educated Platelets and Angiogenesis in Glioblastoma: Another Brick in the Wall for Novel Prognostic and Targetable Biomarkers, Changing the Vision from a Localized Tumor to a Systemic Pathology.” Cells 9 (2). https://doi.org/10.3390/cells9020294. https://www.ncbi.nlm.nih.gov/pubmed/31991805. Caton, M. T., and V. S. Shenoy. 2020. “Cerebral Cavernous Malformations.” In StatPearls. Treasure Island (FL). Cavalcanti, D. D., M. C. Preul, M. Y. Kalani, and R. F. Spetzler. 2016. “Microsurgical anatomy of safe entry zones to the brainstem.” J Neurosurg 124 (5): 1359-76. https://doi. org/10.3171/2015.4.JNS141945. https://www.ncbi.nlm.nih.gov/pubmed/26452114. Chang, E. F., R. A. Gabriel, M. B. Potts, M. S. Berger, and M. T. Lawton. 2011. “Supratentorial cavernous malformations in eloquent and deep locations: surgical approaches and outcomes. Clinical article.” J Neurosurg 114 (3): 814-27. https://doi.org/ 10.3171/2010.5.JNS091159. https://www.ncbi.nlm.nih.gov/pubmed/20597603. Cheng, C. Y., R. Shetty, and L. N. Sekhar. 2018. “Microsurgical Resection of a Large Intraventricular Trigonal Tumor: 3-Dimensional Operative Video.” Oper Neurosurg (Hagerstown) 15 (6): E92-E93. https://doi.org/10.1093/ons/opy068. https://www.ncbi. nlm.nih.gov/pubmed/29618124. Del Curling, O., Jr., D. L. Kelly, Jr., A. D. Elster, and T. E. Craven. 1991. “An analysis of the natural history of cavernous angiomas.” J Neurosurg 75 (5): 702-8. https://doi.org/ 10.3171/jns.1991.75.5.0702. https://www.ncbi.nlm.nih.gov/pubmed/1919691. Del Maestro, M., S. Luzzi, M. Gallieni, D. Trovarelli, A. V. Giordano, M. Gallucci, A. Ricci, and R. Galzio. 2018. “Surgical Treatment of Arteriovenous Malformations: Role of Preoperative Staged Embolization.” Acta Neurochir Suppl 129: 109-113. https://doi.org/ 10.1007/978-3-319-73739-3_16. https://www.ncbi.nlm.nih.gov/pubmed/30171322. El Ahmadieh, T. Y., S. G. Aoun, B. R. Bendok, and H. H. Batjer. 2012. “Management of brainstem cavernous malformations.” Curr Treat Options Cardiovasc Med 14 (3): 237- 51. https://doi.org/10.1007/s11936-012-0181-x. https://www.ncbi.nlm.nih.gov/pubmed/ 22555447. Ellis, J. A., and D. L. Barrow. 2017. “Supratentorial cavernous malformations.” Handb Clin Neurol 143: 283-289. https://doi.org/10.1016/B978-0-444-63640-9.00027-8. https://www. ncbi.nlm.nih.gov/pubmed/28552151.

Approaches for Brain and Spinal Cord Cavernous Malformations 389

Elsawaf, Y., S. Anetsberger, S. Luzzi, and S. K. Elbabaa. 2020. “Early Decompressive Craniectomy as Management for Severe TBI in the Pediatric Population: A Comprehensive Literature Review.” World Neurosurg. https://doi.org/10.1016/j.wneu.2020.02.065. https://www.ncbi.nlm.nih.gov/pubmed/32084616. Gallieni, M., M. Del Maestro, S. Luzzi, D. Trovarelli, A. Ricci, and R. Galzio. 2018. “Endoscope-Assisted Microneurosurgery for Intracranial Aneurysms: Operative Technique, Reliability, and Feasibility Based on 14 Years of Personal Experience.” Acta Neurochir Suppl 129: 19-24. https://doi.org/10.1007/978-3-319-73739-3_3. https://www. ncbi.nlm.nih.gov/pubmed/30171309. Giammattei, L., M. Messerer, F. Prada, and F. DiMeco. 2017. “Intramedullary cavernoma: A surgical resection technique.” Neurochirurgie 63 (5): 426-429. https://doi.org/10.1016/ j.neuchi.2016.04.005. https://www.ncbi.nlm.nih.gov/pubmed/27615154. Giliberto, G., D. J. Lanzino, F. E. Diehn, D. Factor, K. D. Flemming, and G. Lanzino. 2010. “Brainstem cavernous malformations: anatomical, clinical, and surgical considerations.” Neurosurg Focus 29 (3): E9. https://doi.org/10.3171/2010.6.FOCUS10133. https://www. ncbi.nlm.nih.gov/pubmed/20809767. Jallo, G. I., D. Freed, M. Zareck, F. Epstein, and K. F. Kothbauer. 2006. “Clinical presentation and optimal management for intramedullary cavernous malformations.” Neurosurg Focus 21 (1): e10. https://doi.org/10.3171/foc.2006.21.1.11. https://www.ncbi.nlm.nih.gov/ pubmed/16859248. Jin, S. H., C. K. Chung, C. H. Kim, Y. D. Choi, G. Kwak, and B. E. Kim. 2015. “Multimodal intraoperative monitoring during intramedullary spinal cord tumor surgery.” Acta Neurochir (Wien) 157 (12): 2149-55. https://doi.org/10.1007/s00701-015-2598-y. https://www.ncbi.nlm.nih.gov/pubmed/26446854. Kivelev, J., M. Niemela, and J. Hernesniemi. 2012. “Characteristics of cavernomas of the brain and spine.” J Clin Neurosci 19 (5): 643-8. https://doi.org/10.1016/j.jocn.2011.08.024. https://www.ncbi.nlm.nih.gov/pubmed/22502911. Kshettry, V. R., A. T. Healy, N. G. Jones, T. E. Mroz, and E. C. Benzel. 2015. “A quantitative analysis of posterolateral approaches to the ventral thoracic spinal canal.” Spine J 15 (10): 2228-38. https://doi.org/10.1016/j.spinee.2015.04.038. https://www.ncbi.nlm.nih.gov/ pubmed/25937117. Labauge, P., C. Denier, F. Bergametti, and E. Tournier-Lasserve. 2007. “Genetics of cavernous angiomas.” Lancet Neurol 6 (3): 237-44. https://doi.org/10.1016/S1474-4422(07)70053-4. https://www.ncbi.nlm.nih.gov/pubmed/17303530. Lawton, M. T., A. Quinones-Hinojosa, and P. Jun. 2006. “The supratonsillar approach to the inferior cerebellar peduncle: anatomy, surgical technique, and clinical application to cavernous malformations.” Neurosurgery 59 (4 Suppl 2): ONS244-51; discussion ONS251-2. https://doi.org/10.1227/01.NEU.0000232767.16809.68. https://www.ncbi. nlm.nih.gov/pubmed/17041494. Luzzi, S., A. M. Crovace, M. Del Maestro, A. Giotta Lucifero, S. K. Elbabaa, B. Cinque, P. Palumbo, F. Lombardi, A. Cimini, M. G. Cifone, A. Crovace, and R. Galzio. 2019. “The cell-based approach in neurosurgery: ongoing trends and future perspectives.” Heliyon 5 (11): e02818. https://doi.org/10.1016/j.heliyon.2019.e02818. https://www.ncbi.nlm.nih. gov/pubmed/31844735. Luzzi, S., A. M. Crovace, L. Lacitignola, V. Valentini, E. Francioso, G. Rossi, G. Invernici, R. J. Galzio, and A. Crovace. 2018. “Engraftment, neuroglial transdifferentiation and

390 M. Del Maestro, S. Luzzi, G. Mezzini et al.

behavioral recovery after complete spinal cord transection in rats.” Surg Neurol Int 9: 19. https://doi.org/10.4103/sni.sni_369_17. https://www.ncbi.nlm.nih.gov/pubmed/29497572. Luzzi, S., M. Del Maestro, D. Bongetta, C. Zoia, A. V. Giordano, D. Trovarelli, S. Raysi Dehcordi, and R. J. Galzio. 2018. “Onyx Embolization before the Surgical Treatment of Grade III Spetzler-Martin Brain Arteriovenous Malformations: Single-Center Experience and Technical Nuances.” World Neurosurg 116: e340-e353. https://doi.org/10.1016/ j.wneu.2018.04.203. https://www.ncbi.nlm.nih.gov/pubmed/29751183. Luzzi, S., M. Del Maestro, S. K. Elbabaa, and R. Galzio. 2020. “Letter to the Editor Regarding “One and Done: Multimodal Treatment of Pediatric Cerebral Arteriovenous Malformations in a Single Anesthesia Event”.” World Neurosurg 134: 660. https://doi.org/ 10.1016/j.wneu.2019.09.166. https://www.ncbi.nlm.nih.gov/pubmed/32059273. Luzzi, S., M. Del Maestro, and R. Galzio. 2019. “Letter to the Editor. Preoperative embolization of brain arteriovenous malformations.” J Neurosurg: 1-2. https://doi.org/10.3171/ 2019.6.JNS191541. https://www.ncbi.nlm.nih.gov/pubmed/31812150. Luzzi, S., M. Del Maestro, D. Trovarelli, D. De Paulis, S. R. Dechordi, H. Di Vitantonio, V. Di Norcia, D. F. Millimaggi, A. Ricci, and R. J. Galzio. 2019. “Endoscope-Assisted Microneurosurgery for Neurovascular Compression Syndromes: Basic Principles, Methodology, and Technical Notes.” Asian J Neurosurg 14 (1): 193-200. https://doi. org/10.4103/ajns.AJNS_279_17. https://www.ncbi.nlm.nih.gov/pubmed/30937034. Luzzi, S., A. Elia, M. Del Maestro, S. K. Elbabaa, S. Carnevale, F. Guerrini, M. Caulo, P. Morbini, and R. Galzio. 2019. “Dysembryoplastic Neuroepithelial Tumors: What You Need to Know.” World Neurosurg 127: 255-265. https://doi.org/10.1016/j.wneu. 2019.04.056. https://www.ncbi.nlm.nih.gov/pubmed/30981794. Luzzi, S., A. Elia, M. Del Maestro, A. Morotti, S. K. Elbabaa, A. Cavallini, and R. Galzio. 2019. “Indication, Timing, and Surgical Treatment of Spontaneous Intracerebral Hemorrhage: Systematic Review and Proposal of a Management Algorithm.” World Neurosurg. https://doi.org/10.1016/j.wneu.2019.01.016. https://www.ncbi.nlm.nih.gov/ pubmed/30677572. Luzzi, S., M. Gallieni, M. Del Maestro, D. Trovarelli, A. Ricci, and R. Galzio. 2018. “Giant and Very Large Intracranial Aneurysms: Surgical Strategies and Special Issues.” Acta Neurochir Suppl 129: 25-31. https://doi.org/10.1007/978-3-319-73739-3_4. https://www. ncbi.nlm.nih.gov/pubmed/30171310. Luzzi, S., A. Giotta Lucifero, M. Del Maestro, G. Marfia, S. E. Navone, M. Baldoncini, M. Nunez, A. Campero, S. K. Elbabaa, and R. Galzio. 2019. “Anterolateral Approach for Retrostyloid Superior Parapharyngeal Space Schwannomas Involving the Jugular Foramen Area: A 20-Year Experience.” World Neurosurg 132: e40-e52. https://doi.org/ 10.1016/j.wneu.2019.09.006. https://www.ncbi.nlm.nih.gov/pubmed/31520759. Luzzi, S., M. D. Maestro, A. Elia, F. Vincitorio, G. D. Perna, F. Zenga, D. Garbossa, S. K. Elbabaa, and R. Galzio. 2019. “Morphometric and Radiomorphometric Study of the Correlation between the Foramen Magnum Region and the Anterior and Posterolateral Approaches to Ventral Intradural Lesions.” Turk Neurosurg 29 (6): 875- 886. https://doi.org/10.5137/1019-5149.JTN.26052-19.2. https://www.ncbi.nlm.nih.gov/ pubmed/31452176. Luzzi, S., C. Zoia, A. D. Rampini, A. Elia, M. Del Maestro, S. Carnevale, P. Morbini, and R. Galzio. 2019. “Lateral Transorbital Neuroendoscopic Approach for Intraconal Meningioma of the Orbital Apex: Technical Nuances and Literature Review.” World

Approaches for Brain and Spinal Cord Cavernous Malformations 391

Neurosurg 131: 10-17. https://doi.org/10.1016/j.wneu.2019.07.152. https://www.ncbi.nlm. nih.gov/pubmed/31356977. Maslehaty, H., H. Barth, A. K. Petridis, A. Doukas, and H. M. Mehdorn. 2011. “Symptomatic spinal cavernous malformations: indication for microsurgical treatment and outcome.” Eur Spine J 20 (10): 1765-70. https://doi.org/10.1007/s00586-011-1898-z. https://www.ncbi. nlm.nih.gov/pubmed/21755413. Matsushima, T., T. Inoue, T. Inamura, Y. Natori, K. Ikezaki, and M. Fukui. 2001. “Transcerebellomedullary fissure approach with special reference to methods of dissecting the fissure.” J Neurosurg 94 (2): 257-64. https://doi.org/10.3171/jns.2001.94.2.0257. https://www.ncbi.nlm.nih.gov/pubmed/11213963. McCormick, W. F. 1966. “The pathology of vascular (“arteriovenous”) malformations.” J Neurosurg 24 (4): 807-16. https://doi.org/10.3171/jns.1966.24.4.0807. https://www.ncbi. nlm.nih.gov/pubmed/5934138. Millimaggi, D. F., V. D. Norcia, S. Luzzi, T. Alfiero, R. J. Galzio, and A. Ricci. 2018. “Minimally Invasive Transforaminal Lumbar Interbody Fusion with Percutaneous Bilateral Pedicle Screw Fixation for Lumbosacral Spine Degenerative Diseases. A Retrospective Database of 40 Consecutive Cases and Literature Review.” Turk Neurosurg 28 (3): 454-461. https://doi.org/10.5137/1019-5149.JTN.19479-16.0. https://www.ncbi. nlm.nih.gov/pubmed/28481388. Mitha, A. P., J. D. Turner, A. A. Abla, A. G. Vishteh, and R. F. Spetzler. 2011. “Outcomes following resection of intramedullary spinal cord cavernous malformations: a 25-year experience.” J Neurosurg Spine 14 (5): 605-11. https://doi.org/10.3171/2011.1. SPINE10454. https://www.ncbi.nlm.nih.gov/pubmed/21388288. Nikoubashman, O., F. Di Rocco, I. Davagnanam, K. Mankad, M. Zerah, and M. Wiesmann. 2015. “Prospective Hemorrhage Rates of Cerebral Cavernous Malformations in Children and Adolescents Based on MRI Appearance.” AJNR Am J Neuroradiol 36 (11): 2177-83. https://doi.org/10.3174/ajnr.A4427. https://www.ncbi.nlm.nih.gov/pubmed/26272978. Ogilvy, C. S., D. N. Louis, and R. G. Ojemann. 1992. “Intramedullary cavernous angiomas of the spinal cord: clinical presentation, pathological features, and surgical management.” Neurosurgery 31 (2): 219-29; discussion 229-30. https://doi.org/10.1227/00006123- 199208000-00007. https://www.ncbi.nlm.nih.gov/pubmed/1513428. Palumbo, P., F. Lombardi, F. R. Augello, I. Giusti, S. Luzzi, V. Dolo, M. G. Cifone, and B. Cinque. 2019. “NOS2 inhibitor 1400W Induces Autophagic Flux and Influences Extracellular Vesicle Profile in Human Glioblastoma U87MG Cell Line.” Int J Mol Sci 20 (12). https://doi.org/10.3390/ijms20123010. https://www.ncbi.nlm.nih.gov/pubmed/ 31226744. Palumbo, P., F. Lombardi, G. Siragusa, S. R. Dehcordi, S. Luzzi, A. Cimini, M. G. Cifone, and B. Cinque. 2018. “Involvement of NOS2 Activity on Human Glioma Cell Growth, Clonogenic Potential, and Neurosphere Generation.” Int J Mol Sci 19 (9). https://doi.org/ 10.3390/ijms19092801. https://www.ncbi.nlm.nih.gov/pubmed/30227679. Petersen, T. A., L. A. Morrison, R. M. Schrader, and B. L. Hart. 2010. “Familial versus sporadic cavernous malformations: differences in developmental venous anomaly association and lesion phenotype.” AJNR Am J Neuroradiol 31 (2): 377-82. https://doi.org/10.3174/ ajnr.A1822. https://www.ncbi.nlm.nih.gov/pubmed/19833796. Pouratian, N., S. Y. Bookheimer, D. E. Rex, N. A. Martin, and A. W. Toga. 2002. “Utility of preoperative functional magnetic resonance imaging for identifying language cortices in

392 M. Del Maestro, S. Luzzi, G. Mezzini et al.

patients with vascular malformations.” Neurosurg Focus 13 (4): e4. https://www.ncbi. nlm.nih.gov/pubmed/15771403. Raysi Dehcordi, S., A. Ricci, H. Di Vitantonio, D. De Paulis, S. Luzzi, P. Palumbo, B. Cinque, D. Tempesta, G. Coletti, G. Cipolloni, M. G. Cifone, and R. Galzio. 2017. “Stemness Marker Detection in the Periphery of Glioblastoma and Ability of Glioblastoma to Generate Glioma Stem Cells: Clinical Correlations.” World Neurosurg 105: 895- 905. https://doi.org/10.1016/j.wneu.2017.05.099. https://www.ncbi.nlm.nih.gov/pubmed/ 28559081. Ricci, A., H. Di Vitantonio, D. De Paulis, M. Del Maestro, S. D. Raysi, D. Murrone, S. Luzzi, and R. J. Galzio. 2017. “Cortical aneurysms of the middle cerebral artery: A review of the literature.” Surg Neurol Int 8: 117. https://doi.org/10.4103/sni.sni_50_17. https://www. ncbi.nlm.nih.gov/pubmed/28680736. Rigamonti, D., M. N. Hadley, B. P. Drayer, P. C. Johnson, K. Hoenig-Rigamonti, J. T. Knight, and R. F. Spetzler. 1988. “Cerebral cavernous malformations. Incidence and familial occurrence.” N Engl J Med 319 (6): 343-7. https://doi.org/10.1056/ NEJM198808113190605. https://www.ncbi.nlm.nih.gov/pubmed/3393196. Sandalcioglu, I. E., H. Wiedemayer, T. Gasser, S. Asgari, T. Engelhorn, and D. Stolke. 2003. “Intramedullary spinal cord cavernous malformations: clinical features and risk of hemorrhage.” Neurosurg Rev 26 (4): 253-6. https://doi.org/10.1007/s10143-003-0260-2. https://www.ncbi.nlm.nih.gov/pubmed/12690529. Sandalcioglu, I. E., H. Wiedemayer, S. Secer, S. Asgari, and D. Stolke. 2002. “Surgical removal of brain stem cavernous malformations: surgical indications, technical considerations, and results.” J Neurol Neurosurg Psychiatry 72 (3): 351-5. https://doi.org/10.1136/ jnnp.72.3.351. https://www.ncbi.nlm.nih.gov/pubmed/11861694. Spena, G., E. Roca, F. Guerrini, P. P. Panciani, L. Stanzani, A. Salmaggi, S. Luzzi, and M. Fontanella. 2019. “Risk factors for intraoperative stimulation-related seizures during awake surgery: an analysis of 109 consecutive patients.” J Neurooncol 145 (2): 295- 300. https://doi.org/10.1007/s11060-019-03295-9. https://www.ncbi.nlm.nih.gov/pubmed/ 31552589. Stapleton, C. J., and F. G. Barker, 2nd. 2018. “Cranial Cavernous Malformations: Natural History and Treatment.” Stroke 49 (4): 1029-1035. https://doi.org/10.1161/ STROKEAHA.117.017074. https://www.ncbi.nlm.nih.gov/pubmed/29535273. Two A., Oztur A. K., Gunel M. 2012. “Cavernous Malformation management Strategies.” In Principles of Neurological Surgery, 249-255. United States of America: Elsevier Saunders. Vinas, F. C., V. Gordon, M. Guthikonda, and F. G. Diaz. 2002. “Surgical management of cavernous malformations of the brainstem.” Neurol Res 24 (1): 61-72. https://doi.org/ 10.1179/016164102101199558. https://www.ncbi.nlm.nih.gov/pubmed/11783755. Vishteh, A. G., J. M. Zabramski, and R. F. Spetzler. 1999. “Patients with spinal cord cavernous malformations are at an increased risk for multiple neuraxis cavernous malformations.” Neurosurgery 45 (1): 30-2; discussion 33. https://doi.org/10.1097/00006123-199907000- 00008. https://www.ncbi.nlm.nih.gov/pubmed/10414563. Wu, H., T. Yu, S. Wang, J. Zhao, and Y. Zhao. 2015. “Surgical Treatment of Cerebellar Cavernous Malformations: A Single-Center Experience with 58 Cases.” World Neurosurg 84 (4): 1103-11. https://doi.org/10.1016/j.wneu.2015.05.062. https://www.ncbi.nlm. nih.gov/pubmed/26070634.

Approaches for Brain and Spinal Cord Cavernous Malformations 393

Zhang, P., L. Liu, Y. Cao, S. Wang, and J. Zhao. 2013. “Cerebellar cavernous malformations with and without associated developmental venous anomalies.” BMC Neurol 13: 134. https://doi.org/10.1186/1471-2377-13-134. https://www.ncbi.nlm.nih.gov/pubmed/ 24088363. Zoia, C., D. Bongetta, G. Dorelli, S. Luzzi, M. D. Maestro, and R. J. Galzio. 2019. “Transnasal endoscopic removal of a retrochiasmatic cavernoma: A case report and review of literature.” Surg Neurol Int 10: 76. https://doi.org/10.25259/SNI-132-2019. https://www. ncbi.nlm.nih.gov/pubmed/31528414. Zoia, C., D. Bongetta, F. Guerrini, C. Alicino, A. Cattalani, S. Bianchini, R. J. Galzio, and S. Luzzi. 2018. “Outcome of elderly patients undergoing intracranial meningioma resection: a single center experience.” J Neurosurg Sci. https://doi.org/10.23736/S0390-5616. 18.04333-3. https://www.ncbi.nlm.nih.gov/pubmed/29808631. Zoia, C., F. Lombardi, M. R. Fiore, A. Montalbetti, A. Iannalfi, M. Sansone, D. Bongetta, F. Valvo, M. Del Maestro, S. Luzzi, and R. J. Galzio. 2020. “Sacral solitary fibrous tumour: surgery and hadrontherapy, a combined treatment strategy.” Rep Pract Oncol Radiother 25 (2): 241-244. https://doi.org/10.1016/j.rpor.2020.01.008. https://www.ncbi.nlm.nih. gov/pubmed/32025222.

Chapter 24

APPROACHES FOR BRAIN AND SPINAL CORD DURAL ARTERIOVENOUS FISTULAS

S. Paolini1,, MD, C. Mancarella2, MD, R. Severino3, MD and V. Esposito4, MD 1Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Italy, Neurosurgery Department, IRCCS Neuromed, Pozzilli, Italy 2Division of Neurosurgery, IRCCS Neuromed, Pozzilli, Italy 3Division of Neurosurgery, IRCCS Neuromed, Pozzilli, Italy 4Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Italy, Neurosurgery Department, IRCCS Neuromed, Pozzilli, Italy

ABSTRACT

Dural arteriovenous fistulas (DAVF) are acquired lesions affecting both the brain and spinal cord. Spontaneous bleeding with potentially severe clinical sequelae characterizes brain DAVFs, while progressive myelopathy is generally the onset of the spinal cord ones. DAVF grading systems classically rely on the pattern of venous drainage, and the goal of the surgical treatment is the interruption of the venous drainage. In this chapter, we report a description of the surgical principles for skull base, tentorial, superior sagittal sinus, and spinal DAVFs.

1. BRAIN DAVFS - SURGICAL APPROACHES

1.1. General Surgical Principles

Dural arteriovenous fistulas are potentially aggressive lesions. The currently adopted grading scales are all based on the pattern of venous drainage (Borden, Wu, and Shucart 1995; Cognard et al., 1995). Spontaneous bleeding may occur whenever the shunt drainage involves

 Corresponding Author’s Email: [email protected].

396 S. Paolini, C. Mancarella, R. Severino et al. a cortical vein as it happens in Borden type II and III malformation, also classified as type IIb, IIa+IIb, III, IV and V in the Cognard grading system. Hemorrhage may be either subarachnoid or intraparenchymal and clinical consequences are potentially severe. Cortical veins are the source of hemorrhage because they are the weakest point of the malformation. Despite its thickened wall, a vein may not withstand the chronic pressure load and break. Dural sinuses participating in the venous drainage have stronger, fibrous walls and will not break under pressure. For this reason, DAVFs draining exclusively within a dural sinus - Borden type I and Cognard type I or IIa - are known to have a more benign course. DAVFs requiring a treatment - i.e., Borden type II and III - are permanently cured with interruption of their venous drainage as soon as it exits the dural surface. This can be achieved both through endovascular and through surgical treatment. Borden II DAVFs are normally addressed to endovascular therapy since surgical management of the diseased sinus is complex. Nonetheless, in selected cases, simple interruption of the leptomeningeal drainage may be used to downgrade the malformation, converting it into the more benign type I. (van Dijk et al., 2004) After clipping, the diseased dura covering or beside the sinus can be coagulated to reduce the flow inside the sinus. Borden type III fistulas, lacking the participation of a sinus, are frequent candidates for surgery because the transvenous route is normally unavailable and the transarterial route is often difficult. Unlike brain AVMs, the nidus of a DAVF is not easily appreciable at surgery, since its tiny network is normally embedded within the dura. Hence, a bleeding or richly vascularized dural surface may be itself part of the malformation. Attempts to close either the nidus or its arterial feeders are not able to cure the disease because the arterial network inside the dura almost invariably recruits other feeders. For this reason, arteries should not be the target of the procedure. The cure for most DAVFs coincides with interruption of their venous drainage as soon as it exits the dural surface. In most cases, a single vein drains the malformation and it can be precisely traced on preoperative neuroimages. Surgery can be risky if not planned adequately. Most issues are related to bleeding during the opening phase. Both the skin flap preparation and the craniotomy may intercept the arterial compartment of the malformation leading to significant blood loss. For this reason, bypassing the arterial compartment and focusing on the venous drainage, even with key-hole approaches, is usually the way to a simpler and effective treatment. Complex cranial base approaches are rarely necessary and contribute increasing the risks of the procedure, making endovascular occlusion a more attractive option. Preoperative neuroimaging, particularly three-dimensional CT angiography, is used to localize the target of the procedure, i.e., the proximal portion of the venous drainage and allows to plan the approach properly. (Paolini et al., 2009). Whenever surgical interference with the arterial side of the shunt cannot be avoided, the surgeon must be prepared to profuse bleeding already from the skin incision. In this scenario, preoperative arterial embolization proves useful. Bleeding from transosseous feeders can be controlled using bone wax or drilling the bone with a diamond bit under minimal or no irrigation. The dura should be opened paying attention not to damage cortical veins recruited by the malformation and attached or embedded within the dura itself. Premature closure of distal veins recruited by the malformation may lead to severe brain swelling and intraoperative hemorrhage.

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Intraoperative navigation, either CT or MRI based, are of great help. The vein is easily recognized for its dural origin and the typical appearance of its wall, thicker than normal veins but thinner than normal arteries; the colour is usually white or pink with superficial vasa vasorum. If in doubt, the surgeon may place a temporary clip on the vessel and check the progressive darkening of the distal venous system under intraoperative neurophysiological monitoring. Multiple clip repositioning should be avoided because the vessel wall is fragile and may be easily torn. For the same reason, the clip should not be applied too close to the dura, to prevent avulsion of the vein. Once clipped, the vein may be coagulated and divided.

2.1. Surgery of Anterior Cranial Fossa DAVFs

Anterior cranial fossa DAVFs are mostly Borden type III and are typically associated with aggressive behaviour. (Deng et al., 2014; Hashiguchi et al., 2007; Xu et al., 2019) Retrograde cortical drainage and venous varices are a frequent source of haemorrhage. The arterial supply comes constantly from ethmoidal branches of the ophthalmic arteries, with occasional contribution from the middle meningeal artery (Xu et al., 2019; Agid et al., 2009; Gross et al., 2016). As a rule, endovascular therapy is not the first choice because the transvenous route is normally unavailable or impractical and embolization through the ophthalmic arteries may be dangerous (Xu et al., 2019; Lawton et al., 1999). Surgery has a definite role, often being simpler and safer than endovascular therapy. The anatomical target of the approach, i.e., the dural origin of the draining vein, is the cribriform plate. As a rule, the drainage is single but bilateral cases have been described (Deshmukh et al., 2005; Yürekli et al., 2013). In most cases, this region is adequately exposed by a fronto-temporal craniotomy extended medially and basally. A perspective tangential to the floor of the anterior fossa allows controlling the venous drainage while minimizing brain retraction. Brain relaxation is obtained by opening the Sylvian fissure and the basal cisterns. In alternative, particularly if a mini-invasive approach is chosen, lumbar CSF drainage can be prepared. If an intraparenchymal hemorrhage has occurred, clots may be partially removed, increasing the operating room with no need for brain retraction. In case of unilateral approach, the crista galli needs to be removed, together with the basal portion of the falx. Significant bleeding may accompany this phase of the procedure and is usually controlled with bipolar coagulation on the dura, drilling with a diamond bit and bone wax on the basal bone. A bifrontal, interhemispheric approach can also be used to gain direct access to both sides of the olfactory groove. In this case, a more invasive craniotomy and transgression of the frontal sinus must be taken into account. Once clipped, the vein can be coagulated and divided.

2.2. Surgery of Tentorial DAVFs

In this subgroup of malformation, retrograde leptomeningeal drainage is frequent and may involve superficial cortical veins as well as the vein of Galen, accounting for a high risk of hemorrhagic presentation (Lawton et al., 2008; Zink et al., 2004; Tomak et al., 2003). Most cases are classified as Borden type III fistulas, where the shunt does not involve a sinus, making transvenous embolization unfeasible. Transarterial embolization is often discarded because the

398 S. Paolini, C. Mancarella, R. Severino et al. main feeders are tentorial branches of the internal carotid artery or the vertebral artery, difficult to navigate. The anatomical features of the fistula and the surgical strategy vary depending on the portion of tentorium involved by the shunt. Those DAVFs whose drainage arises from midline structures such as the straight sinus and the torcular Herophili usually drain infratentorially, toward vermian or superior cerebellar veins. They are best exposed through a supracerebellar infratentorial approach. Prone or semi- sitting position may be used, depending on the surgeon’s preference. The sitting position takes advantage of the spontaneous gravitational retraction of the cerebellum but the uncomfortable position is a major drawback for many surgeons. Arterial feeders involving the bone or the scalp are not infrequent and should be embolized preoperatively or aggressively controlled at the time of surgery. Particularly in the prone position, the working perspective is crucial. In case of hemorrhage or brain edema, the supracerebellar space may be virtual and downward retraction of the cerebellum, if performed blindly, may result in avulsion of the draining vein with significant bleeding. In order to obtain unobstructed exposure of the tentorial undersurface, the head must be adequately flexed and the bone ridge overlying the torcular and the transverse sinuses must be drilled down. The dural flap can be suspended cranially, as to retract the torcular and widen the exposure. Localization of the draining vein through MRI/CT guided navigation allows safer exploration of the supracerebellar space. Once exposed, the vein exiting from the malformation is clipped and eventually coagulated and divided. DAVFs involving the superior petrosal sinus typically drain infratentorially through a petrosal vein. Early collaterals may be recruited by the vein within the cisterna and large varices may also be present, actually obliterating the cerebellopontine angle. A standard retrosigmoid exposure is generally sufficient to expose these fistulas. The park-bench or the supine position may be used depending on the surgeon’s preference. After dural opening the cerebellomedullary cistern is opened to drain CSF and make cerebellar retraction easier. The vein is usually seen arising from the inferior surface of the tentorium or the dural covering of the petrous ridge. Early bifurcation of the vein may occur and the clip should be applied as proximally as possible on the vein origin but taking care not to tear it. Rarely a tentorial fistula may drain supratentorially arising from the superior surface of the tentorium or from the incisura. In these cases, a frontotemporal craniotomy with wide dissection of the Sylvian fissure and exposure of the tentorial apex must be planned.

Illustrative Case

A 67-year-old man presented with severe headache followed by drowsiness. CT scan showed a left paravermian cerebellar hematoma with fourth ventricle compression and supratentorial ventricular enlargement. The patient underwent external ventricular drainage. Conventional angiography showed a tentorial DAVF (Cognard type IV) involving the wall of the sinus rectus and fed mainly by meningeal branches of the left vertebral artery and the occipital arteries. A rich network of transosseous feeders was present. The shunt did not recruit the sinus rectus but drained into a single variceal originating from the inferior wall of the sinus and directed caudally, toward the foramen magnum (Fig. 1A). The anatomy of the fistula was better depicted by a three-dimensional CT rendering (Fig. 1B and 1C). The patient underwent

Approaches for Brain and Spinal Cord Dural Arteriovenous Fistulas 399 surgery through a left paramedian infratentorial supracerebellar approach. Significant bleeding occurred at the time of craniotomy. Transosseous feeders were closed while drilling the bone overlying the torcular and the left transverse sinus. After dural opening, the proximal portion of the draining vein was exposed in the supracerebellar space and occluded with a long straight aneurysm clip. The postoperative course was uneventful. The patient had a full neurological recovery and the external ventricular drainage could be removed without consequences. Postoperative imaging showed exclusion of the fistula.

Figure 1. (A) Digital subtraction angiography showing a tentorial DAVF fed by a meningeal branch (arrow) of the left vertebral artery. The fistula drains through a single variceal vein (double arrow) directed caudally. (B) Three-dimensional CT angiography better depicts the fistula within the wall of the sinus rectus (arrow) and the morphology of the draining vein (double arrow). (C) Transosseous feeders (arrows) from both the occipital arteries are visible.

2.3. Surgery of Transverse-Sigmoid Sinus and Superior Sagittal Sinus DAVFs

The transverse and sigmoid sinuses, along with the cavernous sinus, are the most frequent location of intracranial DAVFs (Kirsch et al., 2009; Xu et al., 2018; Piippo et al., 2013). Transvenous embolization through the affected sinus is feasible and curative in most cases (Houdart et al., 2002; Bruneau et al., 2008). Surgery plays a role only when the sinus is uninvolved or occluded and the drainage occurs via isolated leptomeningeal veins (Borden grade III). In this case, a targeted craniotomy and subsequent clip ligation will be sufficient to treat the malformation. Superior sagittal sinus DAVFs are aggressive malformations often presenting with intracranial hemorrhage or cognitive decline. They are often bilateral, with constant arterial supply from the middle meningeal artery. Scalp arteries or - rarely - pial arteries may participate in the shunt. Occlusion or stenosis along the sinus is frequent. In many cases, though recruited by the fistula, the sinus remains functional and cannot be sacrificed. Surgery is normally reserved form Borden III lesions or Borden II lesions not amenable to endovascular treatment. At surgery, bilateral exposure is often necessary. Attention must be paid while opening the dura, since it may incorporate the draining vein. Disconnection of the draining vein is the target of the procedure and may be sufficient even in case of sinus participation, allowing to convert the fistula into a more benign type I lesion (van Dijk et al., 2004). Coagulation of the

400 S. Paolini, C. Mancarella, R. Severino et al. pathological dura helps to reduce the flow but must be done with caution, so as not to compromise the patency of normal bridging veins coursing within the dura. In selected cases surgical exposure of the sinus can be part of a combined procedure, allowing to perform direct puncture of the sinus and transvenous embolization.

2.4. Surgery of Foramen Magnum DAVFs

DAVFs located in the area of foramen magnum are normally classified as Borden type III or Cognard type V. They are constantly fed by dural branches of the ascending pharyngeal artery; the vertebral artery, rarely the occipital and middle meningeal arteries, may also contribute (Liang et al., 2013). The drainage recruits a leptomeningeal vein that typically moves caudally within the spinal canal. The behaviour of these malformation resembles that of spinal DAVFs, with progressive myelopathy as the main symptom. Spontaneous hemorrhage may occur in case of in intracranial drainage. Transarterial embolization is used with good results but there is a risk of inadvertent occlusion of vasa nervorum stemming from the ascending pharyngeal artery toward the lower cranial nerves (Spiotta et al., 2011). Surgery requires a standard exposure of the foramen magnum with suboccipital craniectomy and C1 posterior arc resection. Clipping of the draining vein is usually uncomplicated.

2. SPINAL DAVFS - SURGICAL PRINCIPLES

DAVFs are by far the most frequent vascular malformations of the spine. The angioarchitecture of these malformations resembles a Borden type III intracranial DAVF, with a dural shunt draining directly into a leptomeningeal vein. Unlike intracranial AVMs, symptoms are chronic. Progressive myelopathy is the rule and hemorrhage due to vein rupture is extremely rare (Koch, Gottschalk, and Giese 2004). Diagnosis is the most difficult step in the whole management of these patients. Once the fistula has been ascertained, surgical disconnection is safe and relatively easy. Endovascular treatment is a feasible alternative but has a lower success rate; it is considered a first-choice option in patients at high-risk for surgery because of advanced age or comorbidities. The shunt is located within the dural sheath of an exiting nerve root. At surgery, it can be seen at high magnification as a tiny arterial network on the radicular dura. The venous drainage is intradural. As a rule, a single dilated vein origins from the inner surface of the dura, runs medially accompanied by the nerve root and reaches the perimedullary venous plexus. Being normally anastomized, the majority of perimedullary veins are involved by the shunt. Very rarely the fistula may have two draining veins (Rizvi et al., 2006). Double, distant DAVFs have been sporadically reported and should always be searched at the time of angiography (Jablawi and Mull 2019; Krings et al., 2004), because the recipient of both shunts is the same perimedullary plexus and treating only one shunt is destined to be ineffective. At surgery the fistula can be exposed via a tailored opening. Mini-invasive approaches with hemilaminectomy centered on the draining vein allow enough room to disconnect the draining vein (Fontes, Tan, and O’Toole 2013; Patel et al., 2013). Intraoperative neurophysiological monitoring is essential.

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Particularly in case of mininvasive approaches, attention must be paid not to misplace the laminectomy. Even with accurate preoperative planning, the bone opening may fail to expose the vein, for a few centimetres. Before widening the bone opening, tilting the microscope or observing the flow direction after indocianine video-angiography may help to discover the shunt level (Paolini et al., 2019). A crucial pitfall may occur in the lower thoracic segment, where an otherwise normal radiculomedullary artery can be misinterpreted as the venous drainage of the malformation. Closure of the Adamkiewicz artery or other radicolomedullary arteries may be the source of profound paraplegia. The arterial nature of the vessel is suggested by the thickness of its wall and the direction of blood flow as seen on indocyanine videoangiography. The vessel will appear as anatomically independent from the venous system and temporary clipping will not affect the color and the degree of congestion of the perimedullary veins. Motor evoked response from the lower limbs will be closely checked after temporary clipping. Once the vessel is identified as the draining vein of the fistula it can be coagulated and divided.

Illustrative Case

A 60-year-old man presented with a six-month history of gait disturbance, burning paresthesias in the lower limbs, urinary and fecal retention. MR imaging showed spinal cord hyperintensity extending from D9 to the medullary cone, with peri-medullary serpiginous vessels (figure 2A). Angiography showed a dural arteriovenous fistula fed by the right T10 radicular artery, and a single draining vein recruiting the perimedullary venous plexus (figure 2B). Surgery was performed under intraoperative neurophysiological monitoring. Right T10 hemilaminectomy and dural opening exposed the arterialized draining vein travelling with the exiting nerve root (figure 2C). After 5-minute temporary clipping the perimedullary venous plexus assumed normal appearance (figure 2D) and motor evoked responses from lower limbs were unchanged. The vein was coagulated and divided. Postoperative angiography confirmed exclusion of the fistula. The patient’s condition, including sphincter function, improved after surgery.

Figure 2. (A) Sagittal T2-weighted spinal MRI showing multiple peri-medullary serpiginous flow- voids. (B) Anterior-posterior projection digital subtraction angiography revealing dural arteriovenous fistula fed by the right T10 radicular artery. (C, D) Intraoperative picture showing the exposure and the temporary clipping of the perimedullary venous plexus.

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REFERENCES

Agid, Ronit, Karel Terbrugge, Georges Rodesch, Tommy Andersson, and Michael Söderman. 2009. ‘Management Strategies for Anterior Cranial Fossa (Ethmoidal) Dural Arteriovenous Fistulas with an Emphasis on Endovascular Treatment’. Journal of Neurosurgery 110 (1): 79–84. https://doi.org/10.3171/2008.6.17601. Borden, J. A., J. K. Wu, and W. A. Shucart. 1995. ‘A Proposed Classification for Spinal and Cranial Dural Arteriovenous Fistulous Malformations and Implications for Treatment’. Journal of Neurosurgery 82 (2): 166–79. https://doi.org/10.3171/jns.1995.82.2.0166. Bruneau, Michaël, Boris Lubicz, Benoit Pirotte, Nordeyn Oulad Ben Taib, David Wikler, Jacques Brotchi, and Marc Levivier. 2008. ‘Selective Image-Guided Venous Sinus Exposure for Direct Embolization of Dural Arteriovenous Fistula: Technical Case Report’. Surgical Neurology 69 (2): 192–96; discussion 196. https://doi.org/10.1016/j.surneu. 2006.11.059. Cognard, C., Y. P. Gobin, L. Pierot, A. L. Bailly, E. Houdart, A. Casasco, J. Chiras, and J. J. Merland. 1995. ‘Cerebral Dural Arteriovenous Fistulas: Clinical and Angiographic Correlation with a Revised Classification of Venous Drainage’. Radiology 194 (3): 671– 80. https://doi.org/10.1148/radiology.194.3.7862961. Deng, Jian-Ping, Jiang Li, Tao Zhang, Jia Yu, Zhen-Wei Zhao, and Guo-Dong Gao. 2014. ‘Embolization of Dural Arteriovenous Fistula of the Anterior Cranial Fossa through the Middle Meningeal Artery with Onyx’. Clinical Neurology and Neurosurgery 117 (February): 1–5. https://doi.org/10.1016/j.clineuro.2013.11.013. Deshmukh, Vivek R., Steve Chang, Felipe C. Albuquerque, Cameron G. McDougall, and Robert F. Spetzler. 2005. ‘Bilateral Ethmoidal Dural Arteriovenous Fistulae: A Previously Unreported Entity: Case Report’. Neurosurgery 57 (4): E809. https://doi.org/10.1093/ neurosurgery/57.4.e809. Dijk, J. Marc C. van, Karel G. TerBrugge, Robert A. Willinsky, and M. Christopher Wallace. 2004. ‘Selective Disconnection of Cortical Venous Reflux as Treatment for Cranial Dural Arteriovenous Fistulas’. Journal of Neurosurgery 101 (1): 31–35. https://doi.org/10. 3171/jns.2004.101.1.0031. Fontes, Ricardo B., Lee A. Tan, and John E. O’Toole. 2013. ‘Minimally Invasive Treatment of Spinal Dural Arteriovenous Fistula with the Use of Intraoperative Indocyanine Green Angiography’. Neurosurgical Focus 35 (2 Suppl): Video 5. https://doi.org/10.3171/2013. V2.FOCUS13191. Gross, Bradley A., Karam Moon, M. Yashar S. Kalani, Felipe C. Albuquerque, Cameron G. McDougall, Peter Nakaji, Joseph M. Zabramski, and Robert F. Spetzler. 2016. ‘Clinical and Anatomic Insights From a Series of Ethmoidal Dural Arteriovenous Fistulas at Barrow Neurological Institute’. World Neurosurgery 93 (September): 94–99. https://doi.org/ 10.1016/j.wneu.2016.05.052. Hashiguchi, Akihito, Chikara Mimata, Homare Ichimura, Motohiro Morioka, and Jun-ichi Kuratsu. 2007. ‘Venous Aneurysm Development Associated With a Dural Arteriovenous Fistula of the Anterior Cranial Fossa With Devastating Hemorrhage’. Neurologia Medico- Chirurgica 47 (2): 70–73. https://doi.org/10.2176/nmc.47.70. Houdart, Emmanuel, Jean-Pierre Saint-Maurice, René Chapot, Adam Ditchfield, Alexandre Blanquet, Guillaume Lot, and Jean-Jacques Merland. 2002. ‘Transcranial Approach for

Approaches for Brain and Spinal Cord Dural Arteriovenous Fistulas 403

Venous Embolization of Dural Arteriovenous Fistulas’. Journal of Neurosurgery 97 (2): 280–86. https://doi.org/10.3171/jns.2002.97.2.0280. Jablawi, F., and M. Mull. 2019. ‘Double Spinal Dural Arteriovenous Fistulas’. Journal of Neuroradiology = Journal De Neuroradiologie 46 (3): 168–72. https://doi.org/ 10.1016/j.neurad.2018.09.004. Kirsch, M., T. Liebig, D. Kühne, and H. Henkes. 2009. ‘Endovascular Management of Dural Arteriovenous Fistulas of the Transverse and Sigmoid Sinus in 150 Patients’. Neuroradiology 51 (7): 477–83. https://doi.org/10.1007/s00234-009-0524-9. Koch, Christoph, Stefan Gottschalk, and Alf Giese. 2004. ‘Dural Arteriovenous Fistula of the Lumbar Spine Presenting with Subarachnoid Hemorrhage’. Journal of Neurosurgery: Spine 100 (4): 385–91. https://doi.org/10.3171/spi.2004.100.4.0385. Krings, T., M. Mull, M. H. T. Reinges, and A. Thron. 2004. ‘Double Spinal Dural Arteriovenous Fistulas: Case Report and Review of the Literature’. Neuroradiology 46 (3): 238–42. Lawton, Michael T., Jay Chun, Charles B. Wilson, and Van V. Halbach. 1999. ‘Ethmoidal Dural Arteriovenous Fistulae: An Assessment of Surgical and Endovascular Management’. Neurosurgery 45 (4): 805–11. https://doi.org/10.1097/00006123-199910000-00014. Lawton, Michael T., Rene O. Sanchez-Mejia, Diep Pham, Jeffrey Tan, and Van V. Halbach. 2008. ‘Tentorial Dural Arteriovenous Fistulae: Operative Strategies and Microsurgical Results for Six Types’. Operative Neurosurgery 62 (suppl_1): ONS110–25. https://doi.org/ 10.1227/01.neu.0000317381.68561.b0. Liang, Guobiao, Xu Gao, Zhiqing Li, Xiaogang Wang, Haifeng Zhang, and Zhongxue Wu. 2013. ‘Endovascular Treatment for Dural Arteriovenous Fistula at the Foramen Magnum: Report of Five Consecutive Patients and Experience with Balloon-Augmented Transarterial Onyx Injection’. Journal of Neuroradiology 40 (2): 134–39. https://doi.org/ 10.1016/j.neurad.2012.09.001. Paolini, Sergio, Giuseppe Lanzino, Claudio Colonnese, Eugenio Venditti, Giampaolo Cantore, and Vincenzo Esposito. 2009. ‘Three-Dimensional Computed Tomography Angiography in Presurgical Planning for Treatment of Infratentorial Dural Arteriovenous Fistulas’. Journal of Neurosurgery 110 (1): 85–89. https://doi.org/10.3171/2008.4.17515. Paolini, Sergio, Rocco Severino, Giovanni Cardarelli, Paolo Missori, Marcello Bartolo, and Vincenzo Esposito. 2019. ‘Indocyanine Green Videoangiography in the Surgical Treatment of Spinal Dural Arterovenous Fistula: A Useful Application’. World Neurosurgery 122 (February): 508–11. https://doi.org/10.1016/j.wneu.2018.11.164. Patel, Naresh P., Barry D. Birch, Mark K. Lyons, Stacie E. DeMent, and Gregg A. Elbert. 2013. ‘Minimally Invasive Intradural Spinal Dural Arteriovenous Fistula Ligation’. World Neurosurgery 80 (6): e267-270. https://doi.org/10.1016/j.wneu.2012.04.003. Piippo, Anna, Aki Laakso, Karri Seppä, Jaakko Rinne, Juha E. Jääskeläinen, Juha Hernesniemi, and Mika Niemelä. 2013. ‘Early and Long-Term Excess Mortality in 227 Patients with Intracranial Dural Arteriovenous Fistulas’. Journal of Neurosurgery 119 (1): 164–71. https://doi.org/10.3171/2013.3.JNS121547. Rizvi, Tanvir, Ajay Garg, Nalini K. Mishra, Shailesh B. Gaikwad, and Vipul Gupta. 2006. ‘Metachronous Double Spinal Dural Arteriovenous Fistulas. Case Report and Review of the Literature’. Journal of Neurosurgery. Spine 4 (6): 503–5. https://doi.org/10.3171/ spi.2006.4.6.503.

404 S. Paolini, C. Mancarella, R. Severino et al.

Spiotta, Alejandro M., Gwyneth Hughes, Thomas J. Masaryk, and Ferdinand K. Hui. 2011. ‘Balloon-Augmented Onyx Embolization of a Dural Arteriovenous Fistula Arising from the Neuromeningeal Trunk of the Ascending Pharyngeal Artery: Technical Report’. Journal of Neurointerventional Surgery 3 (3): 300–303. https://doi.org/10.1136/jnis. 2010.003095. Tomak, Patrick R., Harry J. Cloft, Akihiko Kaga, C. Michael Cawley, Jacques Dion, and Daniel L. Barrow. 2003. ‘Evolution of the Management of Tentorial Dural Arteriovenous Malformations’. Neurosurgery 52 (4): 750–60; discussion 760-762. https://doi.org/10. 1227/01.neu.0000053221.22954.85. Xu, Kan, Tiefeng Ji, Chao Li, and Jinlu Yu. 2019. ‘Current Status of Endovascular Treatment for Dural Arteriovenous Fistulae in the Anterior Cranial Fossa: A Systematic Literature Review’. International Journal of Medical Sciences 16 (2): 203–11. https://doi.org/ 10.7150/ijms.29637. Xu, Kan, Xue Yang, Chao Li, and Jinlu Yu. 2018. ‘Current Status of Endovascular Treatment for Dural Arteriovenous Fistula of the Transverse-Sigmoid Sinus: A Literature Review’. International Journal of Medical Sciences 15 (14): 1600–1610. https://doi.org/10. 7150/ijms.27683. Yürekli, Vedat Ali, Gürdal Orhan, Erdem Gürkas, and Nilgün Senol. 2013. ‘Bilateral Ophthalmic-Ethmoidal Dural Arteriovenous Fistula Presenting with Intracranial Hemorrhage: A Rare Entity’. Neurological Sciences: Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 34 (10): 1851– 53. https://doi.org/10.1007/s10072-013-1331-y. Zink, Walter E., Philip M. Meyers, E. Sander Connolly, and Sean D. Lavine. 2004. ‘Combined Surgical and Endovascular Management of a Complex Posttraumatic Dural Arteriovenous Fistula of the Tentorium and Straight Sinus’. Journal of Neuroimaging: Official Journal of the American Society of Neuroimaging 14 (3): 273–76. https://doi.org/10.1177/ 1051228404265371.

SECTION IV: MISCELLANEOUS

Chapter 25

ENDOSCOPE-ASSISTED MICRONEUROSURGERY FOR INTRACRANIAL ANEURYSMS

M. Del Maestro1,2,, MD, S. Luzzi2,3, MD, PhD, A. Giotta Lucifero1, MD, A. Rampini1, MD and R. Galzio2,3, MD 1PhD School in Experimental Medicine, Department of Clinical-Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, Pavia, Italy 2Neurosurgery Unit, Department of Surgical Sciences, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy 3Neurosurgery Unit, Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy

ABSTRACT

Endoscopic assistance during microneurosurgery is an advanced methodology described for the treatment of selected and deeply located intracranial pathologies. From the first description in 1994, several papers were published on this topic mainly focusing on its advantages during minimally invasive “keyhole” surgical procedures. In this chapter, endoscope-assisted microneurosurgery for treatment of both ruptured and unruptured aneurysms of the anterior and posterior circulation is discussed with different illustrative cases. In particular, the presented data highlight how the endoscope may influence the clipping strategy, improving the visualization of the aneurysm neck, collateral branches, and perforating arteries. In conclusion, endoscope-assisted microneurosurgery can be considered a useful and reliable technique in the surgeon’s armamentarium during treatment of selected intracranial aneurysms, offering some important advantages to obtain the best overall outcome.

Keywords: clipping, endoscope-assisted microsurgery, intracranial aneurysms, microneurosurgery, minimally invasive neurosurgery, subarachnoid hemorrhage

 Corresponding Author’s Email: [email protected].

408 M. Del Maestro, S. Luzzi, A. Giotta Lucifero et al.

INTRODUCTION

Endoscope-assisted microneurosurgery (EAM) is a surgical methodology characterized by the combined and contemporary use of microsurgical and endoscopic techniques useful in the treatment of deep-seated intracranial lesions.

Figure 1. Images showing the set-up of the operating room. The endoscopic monitor is placed in front of the surgeon (A, C). The 7-in high-resolution monitor assembled above the binocular headpiece allows the surgeon to maintain simultaneous control of microscopic and endoscopic views by minimal ergonomic eye movements (B).

Main indications for EAM are the treatment of expansive lesions, aneurysms, and neurovascular conflicts laying in basal cysterns (Luzzi, Del Maestro, et al. 2019; Gallieni et al. 2018). Use of an endoscope to assist microsurgical clipping of an intracranial aneurysm was first reported by Fischer and Mustafa in 1994 (J. Fischer and Mustafa 1994). In 1998, Perneczky systematized and clarified the concept of endoscopic and endoscope-assisted neurosurgery applied to “keyhole” approaches in transcranial neurosurgery, especially for vascular pathology (Perneczky and Fries 1998). During the 2000s, several papers were published, and in 2014, Reisch introduced the acronym “TEAM-work technique” as transcranial endoscope-assisted microneurosurgey-work technique for aneurysms (Reisch et al. 2014). The rationale for EAM comes from the possibility of combining microscopic and endoscopic views. In EAM procedures, the optical properties of surgical microscopes are supplemented by the use of endoscopes that increase light intensity, broaden viewing angles (look around the corner), enlarge the focus range, and clarify details in close-up positions (Reisch et al. 2014). All these advantages allow less traumatic dissection of structures located within a deeper operative field level. To optimize the advantages of both techniques, strategic placement of endoscopic monitors is mandatory, and a specific operative room set-up is required (Figure 1). Employment of a specifically designed endoscope with a 45°-angled eyepiece also allows flexible use under the microscope line-of-sight. In aneurysm surgery, introduction of the endoscope has led to improved visualization of perforating arteries, especially those arising from the posterior wall of the internal carotid artery (ICA), anterior communicating artery, and basilar artery.

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Endoscopic vision is also direct, which has reduced the need for brain retraction and manipulation of the aneurysm before clipping. Endoscope assistance has even allowed for the implementation of some minimally invasive approaches, such as the eyebrow (“supraciliary”) keyhole approach and its variants (Reisch et al. 2014; Kim et al. 2016; Ormond and Hadjipanayis 2013). It has been possible mainly thanks to the refinement of the endoscopic skull base apporoaches for a wide range of diseases(Luzzi, Del Maestro, et al. 2019; Luzzi, Maestro, et al. 2019; Luzzi, Zoia, et al. 2019; Zoia et al. 2019; Arnaout et al. 2020). The main goal of this chapter is to describe the usefulness, advantages, and limitations of EAM in the treatment of intracranial aneurysms based on the senior author’s experience and data reported in the literature.

METHODS

Patient Cohort

The consecutive series of EAM procedures performed from January 2002 to July 2019 by the senior author (R.G.) was retrospectively evaluated. Data collected from January 2002 to October 2017 from the Deptartment of Neurosurgery of the “San Salvatore” City Hospital (L’Aquila, Italy) and data from August 2018 to July 2019 from the Deptartment of Neurosurgery of the Fondazione IRCCS Policlinico “San Matteo” (Pavia, Italy) were analyzed. Clinical assessment was defined by Hunt-Hess (HH) grade. Radiological classification of Bouthillier was used to define the site of ICA aneurysms (Bouthillier, van Loveren, and Keller 1996). The Fisher grade was used for CT classification of subarachnoid hemorrhage. Overall outcome at 6-months was determined with the modified Rankin scale score (mRS).

Inclusion Criteria All patients, males and females, harboring one or multiple aneurysms of the anterior or posterior circulation surgically treated with the assistance of endoscopes. Both hemorragic and nonhemorragic onset was considered.

Exclusion Criteria Patients with an HH grade 4–5 and Fisher grade 3–4 were excluded as well as patients without 6-month follow-up data.

Endoscopic Systems In the Deptartment of Neurosurgery of the “San Salvatore” City Hospital, all EAM procedures were performed with three different rigid endoscopes:

 a straightforward telescope, 0° viewing angle, 2.7 mm in diameter, and 15 cm working length (Karl Storz GmbH and Co. KG, Tuttlingen, Germany, Hopkins Galzio Endoscope);  a forward oblique telescope, 30° viewing angle, 2.7 mm in diameter, 15 cm working length, with a viewing direction at 6 o’clock (Karl Storz GmbH and Co. KG, Hopkins Galzio Endoscope);

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 a forward oblique telescope, 30° viewing angle, 2.7 mm in diameter, 15 cm working length, with a viewing direction at 12 o’clock (Karl Storz GmbH and Co. KG, Hopkins Galzio Endoscope).

A Xenon 300 cold light source connected to the scope by a fiberoptic light cable illuminates the field. The light intensity was usually set at an output up to 20% of the maximum power to avoid thermal injuries. The endoscope can be fixed to the operative field by a mechanical holding system connected to the operative table. Endoscopic images were visualized through a video system comprised of a digital video camera with camera control unit and monitors. A high-definition camera provided superior resolution, color, and clarity for a high-quality video imaging. The video image was displayed on LCD monitors and could also be superimposed using the picture-in-picture mode of a dedicated device, such as a TwinVideo® System (Karl Storz GmbH and Co. KG, Tuttlingen, Germany). Endoscopic and microscopic images were combined and seen together on a 7-in high-resolution LCD screen mounted above the binocular headpiece of the microscope and on a 21-in high-resolution monitor outside the operative field [Karl Storz GmbH and Co. KG] (Galzio and Tschabitsher 2010). In the Deptartment of Neurosurgery of the Fondazione IRCCS Policlinico “San Matteo” from August 2018, the QUEVO® Micro Inspection Tool (Carl Zeiss Meditec, Oberkochen, Germany) was used. It was a forward oblique telescope with a 45° viewing angle, 3.6-mm diameter, 12-cm working length, and viewing direction at 12 o’clock. Illumination was provided by an LED (20–35 lumens). QUEVO® was directly connected in a plug-and-play way to the operative microscope (Kinevo® 900, Carl Zeiss Meditec) and endoscopic high-definition images were observed on the two LCD monitors of the microscope, one in full-screen mode, and one in picture-in-picture mode with the microscopic view.

Operative Microscopes During EAM procedures, the operative microscope provided a straight-ahead view on-axis with the trajectory of penetration and permited visual control of the endoscope. From 2002 to 2017, the OPMI Pentero® 800 (Carl Zeiss Meditec) was used, while the KINEVO® 900 (Carl Zeiss Meditec) was adopted from August 2018.

Operative Technique Standard tailored approaches based on skull base surgery principles were chosen. During surgical procedures, use of the endoscope included three phases: preclipping, clipping, and postclipping.

Preclipping Phase After microsurgical subarachnoid dissection and exposure of the aneurysm, the 0° endoscope was introduced free-hand under microscopic view using the same microsurgical route. If needed, the 30° endoscope was used to obtain the best image. The preclipping phase is basically a pure endoscopic step with initial survey of the aneurysm angioarchitecture and its blind spots as a main goal.

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Clipping Phase This phase consists of endoscope-assisted clipping of the aneurysm, within which endoscopic assistance allows sparing of the collateral branches and perforating arteries. In this phase, the endoscope was fixed on the mechanical holding system. The surgeon had contemporary control of microscopic and endoscopic views.

Postclipping Phase This phase is again an endoscopic inspection aimed at checking complete exclusion of the aneurysm and patency of the branches and perforating arteries.

RESULTS

Over 17 years, the senior author (R.G.) treated 180 patients harboring 191 intracranial aneurysms. Of them, 194 were EAM procedures (7.7% redo surgery because of incomplete exclusion of the aneurysm). Seventy-eight patients were male, 102 were female, and patient age ranged from 14 to 80 years (mean, 53 years); the male/female ratio was 0.8. Forty-seven patients (26.1%) presented with one or more unruptured aneurysms, whereas 133 (73.8%) had subarachnoid hemorrhage. In hemorrhagic patients, the prevalence of HH 1, 2, and 3 were 41%, 42%, and 16%, respectively. Twenty patients (4%) had multiple aneurysms; of multiple surgical procedures. Moreover, 159 procedures were carried out on one or more anterior circulation aneurysms, whereas 49 were carried out on one or more posterior circle aneurysms. Aneurysm sizes [maximal diameter measured by CT angiography (CTA)] ranged between 4 and 42 mm (mean, 9.2 mm). The pre-operative work-up of all cases involved CTA. In 70 elective cases, 6-vessel digital subtraction angiography (DSA) was performed and the balloon test of occlusion was reserved for 12 ICA aneurysms. A neurophysiological baseline assessment was als performed in all elective cases. Complete clipping was achieved in all cases. In this series, the endoscope- assisted clipping technique revealed three main inadvertent events, namely, the neck remnant, collateral branch occlusion, and the perforating artery occlusion. Retrospective analysis of each case allowed assertion that use of the endoscope in 73 aneurysms (38.2%) provided extra important information about perforating arteries hidden by the aneurysm at a specific site at the ICA posterior wall, the backside of the anterior communicating artery complex, and superior or posterior aspects of the basilar top and midbasilar trunk. Specifically, the basilar tip and P1 segment of the posterior cerebral artery had the highest rate of inadvertent perforating artery occlusion due to their high number at these sites. Moreover, EAM revealed the posterior aspect of the aneurysm neck before clipping in the same sites. In 44 cases (44%), the endoscopic view allowed for real-time detection of incorrect clip positioning, leading to repositioning of the definitive clip. Neck remnants and/or inadvertent occlusion of one or more perforators were all considered as “incorrect clip positioning.” The complication rate directly related to use of the endoscope was of 2.4%. In three cases, insertion of the endoscope led to cerebral contusion. In two further cases, transient third nerve palsy was seen. No aneurysm rupture was caused by the endoscope. Table 1 reports the results of the endoscopic check (postclipping phase) performed after temporary or definitive clipping. Clip malpositioning or inadvertent occlusion of the parent

412 M. Del Maestro, S. Luzzi, A. Giotta Lucifero et al. vessels or perforating arteries ultimately led to clip repositioning. The overall outcome on follow-up examination was good in 169 cases (mRS score < 2) and poor in 9 cases (mRS score > 3). Two patients died due to comorbidites within 72 h of surgery.

Illustrative Cases

Case 1

A 32 year-old female who was overweight and a smoker with an acute onset of headhache was referred to the Emergency Department of the Fondazione IRCCS Policlinico “San Matteo.” The World Federation of Neurosurgical Societies grade was 2, and head CT scan revealed subarachnoid hemorrhage (Fisher grade 2). DSA was necessary to reveal a small aneurysm of the posterior wall of the lateral part of the A1 segment of the left anterior cerebral artery. After multidisciplinary discussion, due to patient age, the shape of the aneurysm, and coexistence of risk factors, a surgical indication was made. The aneurysm was exposed through a pterional approach. The endoscopic view (QUEVO® Micro Inspection Tool) revealed two important basal perforating arteries arising from the neck of the aneurysm and hidden by the ICA-anterior cerebral artery junction. Under microscopic vision, the first curved miniclip (FT 722T; Yasargil Aneurysm Clip System, Aesculap) was applied. Endoscopic control showed an anterior remnant and complete preservation of perforators. A second curved clip (FT 722T) was applied. Control with indocyaningreen videoangiography (IR 800 filter, Kinevo® 900, Zeiss) pointed out the patency of the arteries and exclusion of the aneurysm. Definitive clipping was done with two curved miniclips in tandem position. Postoperative DSA confirmed complete exclusion of the aneurysm. The clinical outcome was excellent with an mRS 0 (Figure 2).

Case 2

A healthy 53 year-old male with two warning syndromes underwent a CTA that showed an unruptured aneurysm of the right superior cerebral arerty (SCA)-posterior cerebral artery. Further investigation with DSA revealed the neck of the aneurysm invoved the origin of the pontomesencephalic segment of the SCA so that the aneurysm was judged not amenable to endovascular treatment by neurointerventionalists. The aneurysm was exposed through a right pterional approach plus extradural anterior clinoidectomy and reached using the corridor between the optic nerve and ICA. The 30o forward oblique endoscope (Karl Storz GmbH and Co. KG, Hopkins Galzio Endoscope) revealed a perforating artery closely attached to the aneurysmal dome and allowed perfect visualization of the neck. The endoscope was fixed to a mechanical holder, and one straight miniclip (FT 720T) was applied, sparing the small perforator and the SCA (Yasargil Aneurysm Clip System, Aesculap). The patency of all vessels was confirmed by indocyaningreen videoangiography (IR800 filter, OPMI Pentero®). Postoperative CTA confirmed complete exclusion of the aneurysm. At 6-month follow-up, the patient had an mRS 1 (Figure 3).

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Figure 2. CT scan revealed subarachnoid hemorrhage, Fisher grade 2, with prevalent left lateralization in the perimesencephalic cistern (A). Preopeartive left ICA angiography showed a small aneurysm of the proximal left A1 segment (B). The aneurysm was approached through a left pterional trans-sylvian route (C). Indocyaningreen videoangiography enhanced the aneurysm’s shape (D). During the preclipping phase, the endoscopic view (QUEVO® Micro Inspection Tool, Kinevo® 900) revealed the posteromedial angioarchitecture of the aneurysm with two basal perforating arteries (E). The first temporary curved miniclip (FT 222T; Yasargil Aneurysm Clip System, Aesculap) was applied (F). Endoscopic control showed an anterior remnant and complete preservation of perforators (G). A second temporary curved miniclip (FT 222T) was applied (H). Control with indocyaningreen videoangiography (IR 800 filter, Kinevo® 900) pointed out the patency of the arteries and exclusion of the aneurysm (I). Definitive clipping was done with two permanently curved miniclips (FT722T) in tandem position (J). Postoperative DSA and its 3-dimensional volume rendering confirmed complete exclusion of the aneurysm (K, L).

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Figure 3. Preoperative right vertebral artery DSA revealed a saccular aneurysm with origin at the pontomesencephalic segment of the SCA (A). The 3-dimensional DSA rendering clearly showed the aneurysm’s angioarchitecture (B). The aneurysm was reached through a trans-sylvian approach using the corridor between the oculomotor nerve and ICA (C). The inspection with a 30o forward oblique endoscope (Karl Storz GmbH and Co. KG, Hopkins Galzio Endoscope) revealed a perforating artery hidden by the aneurysmal dome in the microscopic view (picture-in-picture modality, D). The endoscope was fixed to a mechanical holder, and one straight miniclip (FT 720T) was applied, sparing the small perforator and the SCA [Yasargil Aneurysm Clip System, Aesculap] (picture-in-picture modality, E). Indocyaningreen videoangiography (IR800 filter, OPMI Pentero®) showed the patency of all arteries (F). Postoperative 3-dimensional volume rendering of the CTA confirmed complete exclusion of the aneurysm (G). The 3-dimensional volume rendering of the skull confirmed right pterional craniotomy plus anterior clinoidectomy (H).

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Table 1. Results of The Endoscopic Check (Postclipping Phase) Performed After Temporary or Definitive Clipping

Neck Collateral Branch Perforating Arteries Aneurysm Site No. Remnant Occlusion Occlusion Anterior circulation ICA paraclinoid (C5- 18 4 - - C6) AChorA 20 2 2 4 PcomA 24 2 1 2 ICA bifurcation 21 2 - 4 MCA 38 3 1 1 ACA-AcomA 33 3 1 4 ACA A2 2 1 - - Posterior circulation PCA (P1) 7 2 1 3 PCA (P2) 1 1 - - BA tip 8 2 1 4 SCA 4 2 1 - AICA 2 1 - - VBJ + PICA proximal 13 2 - - PICA distal - - - - ICA: internal carotid artery; AChorA: anterior choroidal artery; PcomA: posterior communicating artery;MCA: middle cerebral artery; ACA: anterior cerebral artery; AcomA: anterior communicating artery; PCA: posterior cerebral artery; BA: basilar artery; SCA: superior cerebral artery; AICA: anterior inferior cerebral artery, VBJ: vertebrobasilar junction; PICA: posterior inferior cerebral artery.

DISCUSSION

The progressive, incessant improvement of endovascular techniques and devices dedicated to treatment of intracranial aneurysms completely changed the worldwide scenario about the aforementioned pathology. A dramatic improvement of the surgical neurovascualr technique occurred in parallel, leading to achieve competitive results compared to those of neurointerventionalists (Ricci et al. 2017; Del Maestro et al. 2018; Gallieni et al. 2018; Luzzi, Del Maestro, et al. 2018; Luzzi, Gallieni, et al. 2018; Luzzi, Del Maestro, and Galzio 2019; Luzzi, Elia, Del Maestro, Morotti, et al. 2019; Luzzi et al. 2020). The development of EAM, together with the concept of “keyhole surgery,” could be considered one of the many responses to the growing need to improve the outcome related to intracranial aneurysm surgery. A pioneer in the field of EAM was Perneczky, who refined the role of the endoscope and EAM in transcranial neurosurgery and described the operative technique for aneurysm surgery (G. Fischer, Oertel, and Perneczky 2012; Fries and Perneczky 1998; Perneczky and Fries 1998; Perneczky and Boecher-Schwarz 1998). His theories have also been confirmed by many others who have published several series on the successful use of EAM for aneurysm surgery (Taniguchi et al. 1999; Kato et al. 2000; Kalavakonda et al. 2002; Reisch et al. 2014; Gallieni et al. 2018; Galzio RJ 2010). The rationale behind EAM comes from the possibility of combining microscopic and endoscopic views in order to exploit all of the advantages of both views and to reduce their disadvantages. In particular, in the era of minimally invasive or

416 M. Del Maestro, S. Luzzi, A. Giotta Lucifero et al. keyhole skull base approaches, significant loss of optical control related to the rigid line-of- sight of the operative microscope has emerged (Arnaout et al. 2020). Contemporary use of the endoscope was designed to overcome this limit, minimizing the need for retraction. Indeed, endoscopes allow further illumination and inspection of blind angles of the surgical field, providing a wide panoramic view. Although rigid, endoscopes commonly employed for this purpose are very thin (2.7–3.6 mm) and easily adapt to the working space with little interference with the surgical maneuvers thanks to the 45°-angled eyepiece. Focusing on aneurysms, especially those located in selected sites where perforating arteries are generally hidden within the blind spot of the aneurysm itself or within the back wall of the parent vessel, endoscopic assistance may improve visualization of neurovascular structures involved. With these goals, if the forward oblique telescope is useful during simultaneous microscopic-endoscopic viewing, the 30° line-of-sight of the angled optic is essential to fully and widely inspecting the backside of the aneurysm parent artery, branches, and perforators. In selected cases, clipping of the aneurysm may be performed under a full endoscopic view to obtain real-time sparing of the perforating arteries, thereby avoiding any inadvertent stoppage of flow into these tiny and less tolerant vessels. The same advantage is obtained in the preservation of cranial nerves located behind or very close to the aneurysm, parent vessel, or branch but hidden by the aneurysm itself. However, the role of endoscopic assistance during aneurysm clipping is still debated. The present series highlights that the advantages of this methodology are strictly related to the aneurysm site. As also reported by Ho, the endoscopic view has been very useful to microsurgical treatment for aneurysms located at the posterior wall of the ICA, posterior comunicating artery, ICA posterior comunicating artery, or ICA-anterior choroidal artery junctions because they are located in the depth of the surgical field, hidden by the carotid siphon, and sourrounded by perforators (Rhoton 2002). Furthermore, the paracarotid cysterns offer enough space to introduce and fix the endoscope (Tawk et al. 2014). Another useful application of EAM is for ICA bifurcation aneurysms, where major perforators are often hidden by the aneurysmal sac. About the anterior communicating artery/anterial cerebral artery complex, where pre-existing anatomical space is limited, the endoscope provides a limited benefit in the pre- and postclipping phases. Moreover, endoscopic assistance has also proven useful in the treatment of aneurysms of the basilar tip and first segment of the posterior cerebral artery due to the numerous perforating branches at these sites. In more than 20% of the aforementioned aneurysms, endoscopic inspection allowed changing or repositioning of the clip, sparing one, or more perforating branches. In the present series, and as mentioned by other, EAM is less effective for aneurysms of the middle cerebral artery (G. Fischer, Oertel, and Perneczky 2012; Raysi Dehcordi et al. 2017). However, one useful application has been in the clipping of contralateral M1 mirror aneurysms (Ho and Hwang 2015). Based on the authors’ experience, EAM is not beneficial for vertebrobasilar junction, proximal posterior inferior cerebral artery, distal SCA, and anterior inferior cerebral artery aneurysms, where the need to work through narrowed corridors beyond posterior fossa cranial nerves may lead to severe sequelae by accidental cranial nerve injuries. Regardless of location, the size of the aneurysm affects the usefulness of endoscopic vision because very large and giant aneurysms are usually exposed through larger skull base approaches and because the larger volume of these aneurysms makes insertion and fixation of the endoscope more difficult and potentially dangerous (Zoia et al. 2018). Technically, the best way to obtain a complementary rather than coaxial view between microscope and endoscope, while simultaneously avoiding interference with

Endoscope-Assisted Microneurosurgery for Intracranial Aneurysms 417 instruments and surgical maneuvers, is to choose complementary surgical corridors to the aneurysm. The initial endoscopic inspection of the aneurysm, parent artery, and perforating branches aids in an early understanding of the anatomy and in mentally constructing the final clipping before application of the clip. However, it obviously cannot assist in dissection of the aneurysm, which must be performed by conventional microneurosurgical techniques. Care must be taken that all surgical maneuvers during the true operative time are conducted with the endoscope firmly and mechanically fixed to the operative field. Fixation of the endoscope also allows for 2-handed surgery. During endoscopic postclipping inspection, the usefulness of this technique may be combined with other fundamental and well-established techniques, such as intraoperative neurophysiological monitoring, Doppler flowmetry, and indocyanine green videoangiography to evaluate complete exclusion of the aneurysm and preserved patency of the parent vessel, branches, and perforators. Generous washing of the basal cisterns and continuous irrigation of the endoscope lens during EAM has also made this technique useful and versatile for ruptured aneurysms in the present series. The 2-dimensional view of most endoscopes used for endoscopic assistance represents one of the most important limits as this may pose some problems in terms of spatial orientation during aneurysm surgery. Although recently 3-dimensional endoscopes have been introduced for diagnostic purposes, they are generally larger in diameter than 2-dimensional ones, and this limits their use for EAM (Gallieni et al. 2018). A further aspect regards the tremendous improvements of the endoscopic techniques, included endoscope-assisted ones, which developed in parallel with neurosurgical fields different from that neurovascular (Raysi Dehcordi et al. 2017; Cheng, Shetty, and Sekhar 2018; Luzzi, Crovace, et al. 2018; Palumbo et al. 2018; Zoia et al. 2018; Bellantoni et al. 2019; Luzzi, Crovace, et al. 2019; Luzzi, Elia, Del Maestro, Elbabaa, et al. 2019; Luzzi, Giotta Lucifero, et al. 2019; Palumbo et al. 2019; Spena et al. 2019; Antonosante et al. 2020; Campanella et al. 2020; Zoia et al. 2020; Millimaggi et al. 2018; Bongetta et al. 2019; Elsawaf et al. 2020).

CONCLUSION

EAM is a useful, reliable, and versatile technique that can be used during clip ligation of selected intracranial aneurysms. Posterior comunicating artery, anterior choroidal artery, ICA bifurcation, anterior communicating artery (especially posterior projecting), and basilar artery tip aneurysms have been sites for which endoscope assistance has provided substantial advantages during clipping to decrease the rate of inadvertent collateral branch/perforating artery occlusion. Employment of a dedicated endoscope (45°-angled eyepiece) is needed to simultaneously combine microscopic and endoscopic views during EAM. Last, but not least, appropriate endoscopic training is mandatory to obtain the best results from endoscopic assistance during aneurysm surgery.

REFERENCES

Antonosante, A., L. Brandolini, M. d'Angelo, E. Benedetti, V. Castelli, M. D. Maestro, S. Luzzi, A. Giordano, A. Cimini, and M. Allegretti. 2020. “Autocrine CXCL8-dependent

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invasiveness triggers modulation of actin cytoskeletal network and cell dynamics.” Aging (Albany NY) 12 (2): 1928-1951. https://doi.org/10.18632/aging.102733. https://www. ncbi.nlm.nih.gov/pubmed/31986121. Arnaout, M. M., S. Luzzi, R. Galzio, and K. Aziz. 2020. “Supraorbital keyhole approach: Pure endoscopic and endoscope-assisted perspective.” Clin Neurol Neurosurg 189: 105623. https://doi.org/10.1016/j.clineuro.2019.105623. https://www.ncbi.nlm.nih.gov/pubmed/ 31805490. Bellantoni, G., F. Guerrini, M. Del Maestro, R. Galzio, and S. Luzzi. 2019. “Simple schwannomatosis or an incomplete Coffin-Siris? Report of a particular case.” eNeurologicalSci 14: 31-33. https://doi.org/10.1016/j.ensci.2018.11.021. https://www. ncbi.nlm.nih.gov/pubmed/30555950. Bongetta, D., C. Zoia, S. Luzzi, M. D. Maestro, A. Peri, G. Bichisao, D. Sportiello, I. Canavero, A. Pietrabissa, and R. J. Galzio. 2019. “Neurosurgical issues of bariatric surgery: A systematic review of the literature and principles of diagnosis and treatment.” Clin Neurol Neurosurg 176: 34-40. https://doi.org/10.1016/j.clineuro.2018.11.009. https://www.ncbi. nlm.nih.gov/pubmed/30500756. Bouthillier, A., H. R. van Loveren, and J. T. Keller. 1996. “Segments of the internal carotid artery: a new classification.” Neurosurgery 38 (3): 425-32; discussion 432- 3. https://doi.org/10.1097/00006123-199603000-00001. https://www.ncbi.nlm.nih.gov/ pubmed/8837792. Campanella, R., L. Guarnaccia, C. Cordiglieri, E. Trombetta, M. Caroli, G. Carrabba, N. La Verde, P. Rampini, C. Gaudino, A. Costa, S. Luzzi, G. Mantovani, M. Locatelli, L. Riboni, S. E. Navone, and G. Marfia. 2020. “Tumor-Educated Platelets and Angiogenesis in Glioblastoma: Another Brick in the Wall for Novel Prognostic and Targetable Biomarkers, Changing the Vision from a Localized Tumor to a Systemic Pathology.” Cells 9 (2). https://doi.org/10.3390/cells9020294. https://www.ncbi.nlm.nih.gov/pubmed/31991805. Cheng, C. Y., R. Shetty, and L. N. Sekhar. 2018. “Microsurgical Resection of a Large Intraventricular Trigonal Tumor: 3-Dimensional Operative Video.” Oper Neurosurg (Hagerstown) 15 (6): E92-E93. https://doi.org/10.1093/ons/opy068. https://www.ncbi. nlm.nih.gov/pubmed/29618124. Del Maestro, M., S. Luzzi, M. Gallieni, D. Trovarelli, A. V. Giordano, M. Gallucci, A. Ricci, and R. Galzio. 2018. “Surgical Treatment of Arteriovenous Malformations: Role of Preoperative Staged Embolization.” Acta Neurochir Suppl 129: 109-113. https://doi.org/ 10.1007/978-3-319-73739-3_16. https://www.ncbi.nlm.nih.gov/pubmed/30171322. Elsawaf, Y., S. Anetsberger, S. Luzzi, and S. K. Elbabaa. 2020. “Early Decompressive Craniectomy as Management for Severe TBI in the Pediatric Population: A Comprehensive Literature Review.” World Neurosurg. https://doi.org/10.1016/j.wneu.2020.02.065. https://www.ncbi.nlm.nih.gov/pubmed/32084616. Fischer, G., J. Oertel, and A. Perneczky. 2012. “Endoscopy in aneurysm surgery.” Neurosurgery 70 (2 Suppl Operative): 184-90; discussion 190-1. https://doi.org/ 10.1227/NEU.0b013e3182376a36. https://www.ncbi.nlm.nih.gov/pubmed/21937925. Fischer, J., and H. Mustafa. 1994. “Endoscopic-guided clipping of cerebral aneurysms.” Br J Neurosurg 8 (5): 559-65. https://doi.org/10.3109/02688699409002948. https://www.ncbi. nlm.nih.gov/pubmed/7857536.

Endoscope-Assisted Microneurosurgery for Intracranial Aneurysms 419

Fries, G., and A. Perneczky. 1998. “Endoscope-assisted brain surgery: part 2--analysis of 380 procedures.” Neurosurgery 42 (2): 226-31; discussion 231-2. https://doi.org/ 10.1097/00006123-199802000-00008. https://www.ncbi.nlm.nih.gov/pubmed/9482172. Gallieni, M., M. Del Maestro, S. Luzzi, D. Trovarelli, A. Ricci, and R. Galzio. 2018. “Endoscope-Assisted Microneurosurgery for Intracranial Aneurysms: Operative Technique, Reliability, and Feasibility Based on 14 Years of Personal Experience.” Acta Neurochir Suppl 129: 19-24. https://doi.org/10.1007/978-3-319-73739-3_3. https://www. ncbi.nlm.nih.gov/pubmed/30171309. Galzio R. J., Tschabitsher M. 2010. Endoscope-Assisted Microneurosurgery-Principles, Methodology and Applications. .STORZ DOCTOR-to-DOCTOR MANUAL, edited by Endo-Press. Germany: Endo-Press. Ho, C. L., and P. Y. Hwang. 2015. “Endoscope-assisted Transorbital Keyhole Surgical Approach to Ruptured Supratentorial Aneurysms.” J Neurol Surg A Cent Eur Neurosurg 76 (5): 376-83. https://doi.org/10.1055/s-0035-1547358. https://www.ncbi.nlm.nih.gov/ pubmed/26030374. Kalavakonda, C., L. N. Sekhar, P. Ramachandran, and P. Hechl. 2002. “Endoscope-assisted microsurgery for intracranial aneurysms.” Neurosurgery 51 (5): 1119-26; discussion 1126- 7. https://doi.org/10.1097/00006123-200211000-00004. https://www.ncbi.nlm.nih.gov/ pubmed/12383356. Kato, Y., H. Sano, S. Nagahisa, S. Iwata, K. Yoshida, K. Yamamoto, and T. Kanno. 2000. “Endoscope-assisted microsurgery for cerebral aneurysms.” Minim Invasive Neurosurg 43 (2): 91-7. https://doi.org/10.1055/s-2000-12260. https://www.ncbi.nlm.nih.gov/pubmed/ 10943987. Kim, Y., C. J. Yoo, C. W. Park, M. J. Kim, D. H. Choi, Y. J. Kim, and K. Park. 2016. “Modified Supraorbital Keyhole Approach to Anterior Circulation Aneurysms.” J Cerebrovasc Endovasc Neurosurg 18 (1): 5-11. https://doi.org/10.7461/jcen.2016.18.1.5. https://www. ncbi.nlm.nih.gov/pubmed/27114960. Luzzi, S., A. M. Crovace, M. Del Maestro, A. Giotta Lucifero, S. K. Elbabaa, B. Cinque, P. Palumbo, F. Lombardi, A. Cimini, M. G. Cifone, A. Crovace, and R. Galzio. 2019. “The cell-based approach in neurosurgery: ongoing trends and future perspectives.” Heliyon 5 (11): e02818. https://doi.org/10.1016/j.heliyon.2019.e02818. https://www.ncbi.nlm.nih. gov/pubmed/31844735. Luzzi, S., A. M. Crovace, L. Lacitignola, V. Valentini, E. Francioso, G. Rossi, G. Invernici, R. J. Galzio, and A. Crovace. 2018. “Engraftment, neuroglial transdifferentiation and behavioral recovery after complete spinal cord transection in rats.” Surg Neurol Int 9: 19. https://doi.org/10.4103/sni.sni_369_17. https://www.ncbi.nlm.nih.gov/pubmed/29497572. Luzzi, S., M. Del Maestro, D. Bongetta, C. Zoia, A. V. Giordano, D. Trovarelli, S. Raysi Dehcordi, and R. J. Galzio. 2018. “Onyx Embolization before the Surgical Treatment of Grade III Spetzler-Martin Brain Arteriovenous Malformations: Single-Center Experience and Technical Nuances.” World Neurosurg 116: e340-e353. https://doi.org/10.1016/ j.wneu.2018.04.203. https://www.ncbi.nlm.nih.gov/pubmed/29751183. Luzzi, S., M. Del Maestro, S. K. Elbabaa, and R. Galzio. 2020. “Letter to the Editor Regarding “One and Done: Multimodal Treatment of Pediatric Cerebral Arteriovenous Malformations in a Single Anesthesia Event”.” World Neurosurg 134: 660. https://doi.org/ 10.1016/j.wneu.2019.09.166. https://www.ncbi.nlm.nih.gov/pubmed/32059273.

420 M. Del Maestro, S. Luzzi, A. Giotta Lucifero et al.

Luzzi, S., M. Del Maestro, and R. Galzio. 2019. “Letter to the Editor. Preoperative embolization of brain arteriovenous malformations.” J Neurosurg: 1-2. https://doi.org/ 10.3171/2019.6.JNS191541. https://www.ncbi.nlm.nih.gov/pubmed/31812150. Luzzi, S., M. Del Maestro, D. Trovarelli, D. De Paulis, S. R. Dechordi, H. Di Vitantonio, V. Di Norcia, D. F. Millimaggi, A. Ricci, and R. J. Galzio. 2019. “Endoscope-Assisted Microneurosurgery for Neurovascular Compression Syndromes: Basic Principles, Methodology, and Technical Notes.” Asian J Neurosurg 14 (1): 193-200. https://doi.org/ 10.4103/ajns.AJNS_279_17. https://www.ncbi.nlm.nih.gov/pubmed/30937034. Luzzi, S., A. Elia, M. Del Maestro, S. K. Elbabaa, S. Carnevale, F. Guerrini, M. Caulo, P. Morbini, and R. Galzio. 2019. “Dysembryoplastic Neuroepithelial Tumors: What You Need to Know.” World Neurosurg 127: 255-265. https://doi.org/10.1016/j.wneu. 2019.04.056. https://www.ncbi.nlm.nih.gov/pubmed/30981794. Luzzi, S., A. Elia, M. Del Maestro, A. Morotti, S. K. Elbabaa, A. Cavallini, and R. Galzio. 2019. “Indication, Timing, and Surgical Treatment of Spontaneous Intracerebral Hemorrhage: Systematic Review and Proposal of a Management Algorithm.” World Neurosurg. https://doi.org/10.1016/j.wneu.2019.01.016. https://www.ncbi.nlm.nih.gov/ pubmed/30677572. Luzzi, S., M. Gallieni, M. Del Maestro, D. Trovarelli, A. Ricci, and R. Galzio. 2018. “Giant and Very Large Intracranial Aneurysms: Surgical Strategies and Special Issues.” Acta Neurochir Suppl 129: 25-31. https://doi.org/10.1007/978-3-319-73739-3_4. https://www. ncbi.nlm.nih.gov/pubmed/30171310. Luzzi, S., A. Giotta Lucifero, M. Del Maestro, G. Marfia, S. E. Navone, M. Baldoncini, M. Nunez, A. Campero, S. K. Elbabaa, and R. Galzio. 2019. “Anterolateral Approach for Retrostyloid Superior Parapharyngeal Space Schwannomas Involving the Jugular Foramen Area: A 20-Year Experience.” World Neurosurg 132: e40-e52. https://doi.org/10. 1016/j.wneu.2019.09.006. https://www.ncbi.nlm.nih.gov/pubmed/31520759. Luzzi, S., M. D. Maestro, A. Elia, F. Vincitorio, G. D. Perna, F. Zenga, D. Garbossa, S. K. Elbabaa, and R. Galzio. 2019. “Morphometric and Radiomorphometric Study of the Correlation between the Foramen Magnum Region and the Anterior and Posterolateral Approaches to Ventral Intradural Lesions.” Turk Neurosurg 29 (6): 875- 886. https://doi.org/10.5137/1019-5149.JTN.26052-19.2. https://www.ncbi.nlm.nih.gov/ pubmed/31452176. Luzzi, S., C. Zoia, A. D. Rampini, A. Elia, M. Del Maestro, S. Carnevale, P. Morbini, and R. Galzio. 2019. “Lateral Transorbital Neuroendoscopic Approach for Intraconal Meningioma of the Orbital Apex: Technical Nuances and Literature Review.” World Neurosurg 131: 10-17. https://doi.org/10.1016/j.wneu.2019.07.152. https://www.ncbi. nlm.nih.gov/pubmed/31356977. Millimaggi, D. F., V. D. Norcia, S. Luzzi, T. Alfiero, R. J. Galzio, and A. Ricci. 2018. “Minimally Invasive Transforaminal Lumbar Interbody Fusion with Percutaneous Bilateral Pedicle Screw Fixation for Lumbosacral Spine Degenerative Diseases. A Retrospective Database of 40 Consecutive Cases and Literature Review.” Turk Neurosurg 28 (3): 454-461. https://doi.org/10.5137/1019-5149.JTN.19479-16.0. https://www.ncbi. nlm.nih.gov/pubmed/28481388. Ormond, D. R., and C. G. Hadjipanayis. 2013. “The Supraorbital Keyhole Craniotomy through an Eyebrow Incision: Its Origins and Evolution.” Minim Invasive Surg 2013: 296469. https://doi.org/10.1155/2013/296469. https://www.ncbi.nlm.nih.gov/pubmed/23936644.

Endoscope-Assisted Microneurosurgery for Intracranial Aneurysms 421

Palumbo, P., F. Lombardi, F. R. Augello, I. Giusti, S. Luzzi, V. Dolo, M. G. Cifone, and B. Cinque. 2019. “NOS2 inhibitor 1400W Induces Autophagic Flux and Influences Extracellular Vesicle Profile in Human Glioblastoma U87MG Cell Line.” Int J Mol Sci 20 (12). https://doi.org/10.3390/ijms20123010. https://www.ncbi.nlm.nih.gov/pubmed/ 31226744. Palumbo, P., F. Lombardi, G. Siragusa, S. R. Dehcordi, S. Luzzi, A. Cimini, M. G. Cifone, and B. Cinque. 2018. “Involvement of NOS2 Activity on Human Glioma Cell Growth, Clonogenic Potential, and Neurosphere Generation.” Int J Mol Sci 19 (9). https://doi.org/10.3390/ijms19092801. https://www.ncbi.nlm.nih.gov/pubmed/30227679. Perneczky, A., and H. G. Boecher-Schwarz. 1998. “Endoscope-assisted microsurgery for cerebral aneurysms.” Neurol Med Chir (Tokyo) 38 Suppl: 33-4. https://doi.org/10.2176/ nmc.38.suppl_33. https://www.ncbi.nlm.nih.gov/pubmed/10234974. Perneczky, A., and G. Fries. 1998. “Endoscope-assisted brain surgery: part 1--evolution, basic concept, and current technique.” Neurosurgery 42 (2): 219-24; discussion 224- 5. https://doi.org/10.1097/00006123-199802000-00001. https://www.ncbi.nlm.nih.gov/ pubmed/9482171. Raysi Dehcordi, S., A. Ricci, H. Di Vitantonio, D. De Paulis, S. Luzzi, P. Palumbo, B. Cinque, D. Tempesta, G. Coletti, G. Cipolloni, M. G. Cifone, and R. Galzio. 2017. “Stemness Marker Detection in the Periphery of Glioblastoma and Ability of Glioblastoma to Generate Glioma Stem Cells: Clinical Correlations.” World Neurosurg 105: 895- 905. https://doi.org/10.1016/j.wneu.2017.05.099. https://www.ncbi.nlm.nih.gov/pubmed/ 28559081. Reisch, R., G. Fischer, A. Stadie, R. Kockro, E. Cesnulis, and N. Hopf. 2014. “The supraorbital endoscopic approach for aneurysms.” World Neurosurg 82 (6 Suppl): S130-7. https://doi. org/10.1016/j.wneu.2014.07.038. https://www.ncbi.nlm.nih.gov/pubmed/25496624. Rhoton, A. L., Jr. 2002. “Aneurysms.” Neurosurgery 51 (4 Suppl): S121-58. https://www.ncbi. nlm.nih.gov/pubmed/12234448. Ricci, A., H. Di Vitantonio, D. De Paulis, M. Del Maestro, S. D. Raysi, D. Murrone, S. Luzzi, and R. J. Galzio. 2017. “Cortical aneurysms of the middle cerebral artery: A review of the literature.” Surg Neurol Int 8: 117. https://doi.org/10.4103/sni.sni_50_17. https://www. ncbi.nlm.nih.gov/pubmed/28680736. Spena, G., E. Roca, F. Guerrini, P. P. Panciani, L. Stanzani, A. Salmaggi, S. Luzzi, and M. Fontanella. 2019. “Risk factors for intraoperative stimulation-related seizures during awake surgery: an analysis of 109 consecutive patients.” J Neurooncol 145 (2): 295- 300. https://doi.org/10.1007/s11060-019-03295-9. https://www.ncbi.nlm.nih.gov/pubmed/ 31552589. Taniguchi, M., H. Takimoto, T. Yoshimine, N. Shimada, Y. Miyao, M. Hirata, M. Maruno, A. Kato, E. Kohmura, and T. Hayakawa. 1999. “Application of a rigid endoscope to the microsurgical management of 54 cerebral aneurysms: results in 48 patients.” J Neurosurg 91 (2): 231-7. https://doi.org/10.3171/jns.1999.91.2.0231. https://www.ncbi.nlm.nih.gov/ pubmed/10433311. Tawk, R. G., M. J. Binning, J. M. Thomas, A. H. Siddiqui, and W. Grand. 2014. “Transciliary supraorbital approach (eyebrow approach) for resection of retrochiasmatic craniopharyngiomas: an alternative approach, case series, and literature review.” J Neurol Surg A Cent Eur Neurosurg 75 (5): 354-64. https://doi.org/10.1055/s-0033-1358609. https://www.ncbi.nlm.nih.gov/pubmed/24897027.

422 M. Del Maestro, S. Luzzi, A. Giotta Lucifero et al.

Zoia, C., D. Bongetta, G. Dorelli, S. Luzzi, M. D. Maestro, and R. J. Galzio. 2019. “Transnasal endoscopic removal of a retrochiasmatic cavernoma: A case report and review of literature.” Surg Neurol Int 10: 76. https://doi.org/10.25259/SNI-132-2019. https://www. ncbi.nlm.nih.gov/pubmed/31528414. Zoia, C., D. Bongetta, F. Guerrini, C. Alicino, A. Cattalani, S. Bianchini, R. J. Galzio, and S. Luzzi. 2018. “Outcome of elderly patients undergoing intracranial meningioma resection: a single center experience.” J Neurosurg Sci. https://doi.org/10.23736/S0390-5616. 18.04333-3. https://www.ncbi.nlm.nih.gov/pubmed/29808631. Zoia, C., F. Lombardi, M. R. Fiore, A. Montalbetti, A. Iannalfi, M. Sansone, D. Bongetta, F. Valvo, M. Del Maestro, S. Luzzi, and R. J. Galzio. 2020. “Sacral solitary fibrous tumour: surgery and hadrontherapy, a combined treatment strategy.” Rep Pract Oncol Radiother 25 (2): 241-244. https://doi.org/10.1016/j.rpor.2020.01.008. https://www.ncbi.nlm.nih. gov/pubmed/32025222.

Chapter 26

SURGICAL MANAGEMENT OF GIANT INTRACRANIAL ANEURYSMS

ABSTRACT

Giant intracranial aneurysms have a dismal natural history because of a very high risk of bleeding and ischemic stroke by distal embolization of thrombotic material. They are complex because of the constant finding of atherosclerotic changes of the neck or dome, intrasaccular thrombosis, and origin of collateral branches directly from the neck or even the sac. Surgical management of giant intracranial aneurysms is among the most challenging aspects of neurosurgery, and an exhaustive knowledge of the specific techniques used for their treatment is paramount to achieve the best outcome and reduce risk of complications. This chapter reviews the technical key aspects of surgical management of giant intracranial aneurysms by analysis of the results of a wide personal surgical series.

Keywords: bypass, cerebral revascularization, clipping, complex aneurysms, flow-diverter stents, giant intracranial aneurysms

 Corresponding Author’s Email: [email protected].

424 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

OVERVIEW

Giant intracranial aneurysms (GIAs) have at least one diameter larger than 2.5 cm and are considered “complex” due to their size and neck and dome features that often complicate intracranial aneurysm, such as the presence of a calcified, atherosclerotic, often heavily- thrombosed sac, calcification or absence of the neck, or a neck encompassing >90° of the vessel circumference, and branches originating from the aneurysm neck or sac. GIA formation is very different from simpley enlargement of smaller aneurysms (Barth and de Tribolet 1994); their formation is related to repeated subadventitial hemorrhages by the vasa vasorum, ultimately causing massive degeneration of the elastic lamina with a lack of muscular layer (Krings, Piske, and Lasjaunias 2005). The natural history of GIAs is poor due to the estimated annual risk of bleeding of 8% and 10% for anterior and posterior circulation, respectively. The 5-year cumulative risk is 40% and 50% for the same sites, respectively (Wiebers et al. 2003). Furthermore, a 2-year mortality rate greater than 60% has been reported for untreated GIAs (Barrow and Alleyne 1995; “Unruptured intracranial aneurysms--risk of rupture and risks of surgical intervention. International Study of Unruptured Intracranial Aneurysms Investigators.” 1998). Apart from the risk of heavy bleeding, GIAs are known to cause ischemic strokes due to embolization of thrombotic material (Sakaki et al. 1980; Kobayashi et al. 1989). In light of this information, treatment of GIAs ought to be considered mandatory (Drake 1979; Hosobuchi 1979; M T Lawton and Spetzler 1995; M. T. Lawton and Spetzler 1998; Laligam N Sekhar et al. 2012; Sousa 2015; Spetzler 1980; Sundt 1979; Heros 1984). While recognizing the actual role of neuroendovascular techniques, further emphasized in recent years by the advent of flow-diverter and flow-disruptor stents, microneurosurgery maintains a primary role for most GIAs and is the only possible treatment in cases requiring revascularization. Based on the results of a personal 17-year series, the special features of GIAs along with key technical aspects of their surgical management are reported herein.

SURGICAL TREATMENT OPTIONS FOR GIAS

Clip Reconstruction

Clip reconstruction is indicated when a neck is present, even with minimal atherosclerosis, limited intrasaccular thrombosis, or at least two branches originate close to the neck or directly from it. Conversely, indirect treatment is warranted in case of severe atherosclerotic changes of the neck, massive thrombosis, or a high number of branches arising from the neck or dome. Moreover, a number of conditions not aforementioned actually constitute a “gray zone” where preparation for a bypass should be made. In this last case, the patient should undergo preoperative aspirin. Clip reconstruction for GIAs is more complex than that performed for smaller aneurysms. Clip reconstruction more frequently involves the need for temporary clipping or trapping of the parent vessel in burst suppression, intraoperative neuromonitoring, and induced hypertension. The same neuroprotective maneuvers should be implemented in rare cases where an adenosine- induced cardiac standstill is needed. Apart from temporary clipping or trapping, the key

Surgical Management of Giant Intracranial Aneurysms 425 technical aspects of GIA surgery include dissection of all collateral branches, bipolar coagulation-based aneurysm remodeling, endoaneurysmectomy (intrasaccular thrombectomy) in case of massive thrombosis, and aneurysmorraphy, wherein it is often possible to redefine the neck morphology. In selected cases of paraclinoid internal carotid artery (ICA) aneurysms, retrograde suction-decompression (Dallas technique) may be a valuable option (Batjer and Samson 1990; Flores et al. 2018). The rationale for clipping of GIAs is that “fragmentation” of the aneurysm will make it smaller and easier to clip. Fragmentation techniques, in turn, involve complex constructs within which clips are placed in tandem, encircling the neck, overlapping, under- or over-stacked, and facing. Placement of multiple clips of different shapes and sizes that is commonly used to fragment GIAs is generally referred to as “stacking-seating” clip reconstruction. During clip reconstruction, indocyanine green videoangiography, fluorescence videoangiography, microvascular Doppler ultrasonography, ultrasonic perivascular flow probe-based flow measurement (Charbel Micro-Flow probe, Transonic, NY, USA), and intraoperative digital subtraction angiography [DSA] (in selected cases) are paramount to constantly check the flow through all branches.

Bypass

Cerebral bypass is used to restore or augment blood flow into a brain vessel in order to “revascularize” a specific brain territory. For aneurysms at large and GIAs not amenable to direct treatment, flow replacement bypass surgery is necessary when exclusion of the aneurysm cannot be achieved without sacrifice of the parent artery or its branches. In these cases, bypass prevents immediate postoperative stroke but can potentially inflict long-term complications stemming from a reduced cerebrovascular reserve.

Table 1. Types of Cerebral Bypass

Type of Bypass High-flow (RAG, SVG) Extra-to-Intracranial Bypass Low-flow (STA-MCA, OA-PICA, OA-SCA) Side-to-side anastomosis (A3-A3, M4-M4, PICA-PICA) In Situ Bypass Interposition graft RAG: radial artery graft; SVG: saphenous vein graft; STA: superficial temporal artery; MCA: middle cerebral artery; OA: occipital artery; PICA: posterior-inferior cerebellar artery; SCA: superior cerebellar artery.

During GIA surgery, an arterial occlusion may be planned or unplanned. In case of planned arterial occlusion, the approach relative to the need for revascularization may be “universal” or “selective.” The universal approach involves performing a bypass in any case of vessel occlusion, regardless of quantitative intraoperative flow measurement data. In contrast, the selective approach bases the indication for revascularization on the results of intraoperative flow measurements or neuromonitoring response (L. N. Sekhar and Patel 1993). As opposed to a planned arterial occlusion, bypass is generally considered necessary in cases of unplanned occlusion due to long-term changes in cerebrovascular reserve potentially causing late ischemic

426 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al. complications (L. N. Sekhar and Patel 1993). Table 1 reports the types of bypasses commonly employed for cerebral revascularization. Three factors affect the choice of bypass type: the flow and size of the vessel to be revascularized and the availability of the donor vessel. From the flow standpoint, there is a definite distinction between high-flow and low-flow bypasses. Because of their diameter, radial artery, and saphenous vein grafts have been the classic conduits used for high-flow bypasses, whereas superficial temporal artery (STA) and occipital artery grafts have been used for low- flow. In principle, high-flow bypass is preferred in cases of larger arteries, poor collateral circulation, or temporary bypasses. Low-flow bypass is generally used for revascularization of the distal middle cerebral artery (MCA), superior cerebellar artery, or posterior-inferior cerebellar artery (PICA). Low-flow bypass can be theoretically “augmented” in terms of flow by means of the ‘double-barrel” or “single vessel double anastomosis” technique (Hu et al. 2019; Chung et al. 2017; Cherian et al. 2018; Burkhardt et al. 2019; Arnone, Hage, and Charbel 2019). In cases where the ipsilateral STA is unavailable, a Bonnet or Hemi-Bonnet bypass, depending on the host vessel, are effective alternatives (Seo et al. 2009; Wada et al. 2018). In the last two decades, a more selective flow-based approach has progressively led to the concept of so-called “adequate-flow” bypass, where the choice of bypass type and, consequently, the conduit, is based uniquely upon preoperative (Noninvasive Optimal Vascular Analysis, Vassol, Chicago, IL, USA) and intraoperative flow measurements (Stapleton et al. 2019; Amin-Hanjani et al. 2005; Amin-Hanjani et al. 2006; Amin-Hanjani et al. 2010; Bae et al. 2015). In bypass planning, avoidance of caliper mismatch is of utmost importance to prevent complications. Additional considerations regarding the technical difficulties related to each type of bypass. When possible, low-flow and in situ bypass, frequently employed for the anterior cerebral artery and PICA, is preferred to high-flow. Regarding the vessel graft, six types of conduits have been reported as theoretical interposition grafts for intracranial-intracranial bypass, namely, the STA, radial artery, saphenous vein, descending branch of the lateral circumflex femoral artery, lingual artery, and superior thyroid artery. Arterial grafts are superior to venous ones because of a higher rate of patency and favorable clinical outcome (Wang et al. 2019). Similar data have already been reported for high-flow bypass (L. N. Sekhar et al. 2001; Laligam N Sekhar et al. 2012).

PERSONAL EXPERIENCE

Hereafter, the overall results of a series of 82 consecutively treated GIAs in a timeframe of 17 years are reported.

Demographics

Between January 2000 and October 2019, 82 GIAs in 82 patients were surgically treated. Patient age ranged between 14 and 80 years, with an average age of 53 years. The male sex was prevalent (58%), and onset was hemorrhagic in 54% of cases. Prevalence of multiple aneurysms was 5%. No patients harbored more than one GIA.

Surgical Management of Giant Intracranial Aneurysms 427

Prevalence According to Site

Anterior circulation was involved in 76.8% of cases. The paraclinoid ICA and ICA bifurcation were the most affected sites within the anterior circulation, immediately followed by the MCA (M1+M2 segments). In posterior circulation GIAs, the vertebrobasilar junction and PCA (P1+P2) were mostly involved, followed by the basilar tip and distal PICA.

Preoperative Work-Up

Three-dimensional CT angiography and 6-vessel DSA were performed in all GIAs. Six- vessel DSA was used to study the STA and occipital artery in case of both planned and unplanned revascularization. Furthermore, in all ICA GIAs, balloon test occlusion (BTO) was carried out. Our BTO protocol involves occlusion of the proximal part of the parent vessel with a 5-Fr balloon catheter, evaluation of patient muscle strength, sensation, cognition, and cranial nerve function, and administration of an intravenous bolus of labetalol after 10 min to lower the systolic blood pressure to within 10%–15% of the baseline for 20 min. MRI was performed in elective cases where an intrasaccular thrombus was suspected or detected on CT scan or DSA. In all elective cases, preoperative neurophysiological monitoring baseline assessment was performed, involving somatosensory evoked potentials and motor evoked potentials by default, and brainstem auditory evoked potentials for posterior circulation GIAs.

Choice of Approach

As a rule, minimal invasive or limited approaches are not indicated for GIAs. Full proximal hemodynamic control of the parent artery and the widest angular exposure possible of the neck and dome are both mandatory to successfully clip the aneurysm. This concept becomes even stronger if a bypass is planned or necessary. According to these needs, a broad range of skull base approaches should be mastered by the surgeon who faces a GIA. Apart from the site, size, and angioarchitecture of the lesion, the confidence of the surgeon with a specific corridor is an integral part of approach selection. A classic example is the basilar tip, which some surgeons prefer to approach by means of a cranio-orbito-zygomatic corridor as opposed a subtemporal transtentorial route (Drake’s approach). In the present series, pterional, cranio-orbito-zygomatic, and interhemispheric approaches have been used for anterior circulation GIAs. Pterional and cranio-orbito-zygomatic approaches were also employed for basilar tip aneurysms. A subtemporal approach was the access route for P2-P3 PCA aneurysms, whereas combined petrosal and far lateral approaches were used for the midbasilar trunk and vertebrobasilar junction, respectively. A retrosigmoid approach was utilized for distal segments of the superior and anterior-inferior cerebellar artery. A suboccipital approach was chosen for distal PICA GIAs.

Prevalence of Different Treatments

Direct treatment of the aneurysm was performed in 80% of cases. Clip reconstruction was possible in 74% of GIAs, followed by bypass and aneurysm exclusion (21%). Trapping without

428 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al. the need for revascularization was the solution in 4% of cases. In only 1% of cases, wrapping of the aneurysm was the only possible treatment.

Outcome

Outcome is reported as the modified Rankin Score (mRS). A good overall outcome (mRS 0–2) was achieved in 62 (75.7%) patients, whereas a moderate disability (mRS 3) characterized 7 (8.5%) patients. A severe disability (mRS 4–5) was the final outcome in 4 (4.8%) patients, and 9 (11%) patients fell into the death/vegetative state group.

Illustrative Cases

Case 1: Giant Partially-Thrombosed Left MCA Aneurysm A 64 year-old female was diagnosed with an incidental, giant, and partially-thrombosed aneurysm of the left MCA. The aneurysm involved only the temporal branch of the MCA; therefore, a direct treatment without temporary bypass was planned. A left pterional approach was performed because of the left dominant A1, with direct cortical stimulation motor evoked potential monitoring. The aneurysm was exposed, and temporary clipping of the temporal branch of the MCA was executed with the patient in burst suppression. Deliberate opening of the sac was carried out to perform an intra-aneurysmal thrombectomy from which a dramatic decrease in aneurysm volume was achieved. Definitive counterclipping with multiple angled clips was then possible with reconstruction of the parent vessel silhouette. The patient remained neurologically intact, and postoperative DSA showed complete exclusion of the aneurysm (Figure 1).

Case 2: Giant Calcified Anterior Communicating Artery Aneurysm Secondary to mild head trauma, a 48 year-old male was diagnosed with an incidental giant anterior projecting anterior communicating artery aneurysm. The aneurysm wall was heavily calcified, but no thrombi were detected by DSA. A left orbitopterional approach was performed. Temporary clipping of both A1 with the patient in burst suppression allowed aneurysmectomy with subsequent reconstruction of the aneurysm neck. Clipping was then easily obtained with a single standard straight clip. Postoperative DSA revealed no remnants (Figure 2).

Case 3: Giant Supraclinoid ICA Aneurysm with Optic Nerve Compression Because of a transient ischemic attack, a 54 year-old female underwent an emergency CT scan followed by brain MRI which revealed a giant unruptured right supraclinoid ICA aneurysm. One month later, the patient underwent brain DSA, comprehensive of a BTO of the right ICA. Visual field testing documented a severe defect in the temporal quandrants of the right eye. Based on BTO, direct treatment of the aneurysm without the need for revascularization was planned. A right pterional approach was performed with bipolar coagulation shrinking and remodeling of the aneurysm. The aneurysm was successfully clipped, and effective decompression of the right optic nerve was also acheived. Postoperative DSA confirmed complete exclusion of the aneurysm, and visual field testing appeared improved already at first-month follow-up (Figure 3).

Surgical Management of Giant Intracranial Aneurysms 429

Case 4: Giant Paraclinoid ICA Aneurysm Secondary to two consecutive warning syndromes, an 18 year-old patient underwent a brain MRI which revealed the presence of a giant aneurysm of the right paraclinoid ICA as well as a supraclinoid aneurysm of the left ICA. The treatment plan consisted of a right high-flow extracranial-intracranial bypass with a saphenous vein graft, exclusion of the giant aneurysm, and delayed endovascular embolization of the left aneurysm. The right saphenous vein was harvested before exposure of the right common, external, and internal carotid arteries. After, the aneurysm was exposed by a right pterional approach, comprehensive of an intradural anterior clinoidectomy. At the neck, the external carotid artery was isolated, and the distal anastomosis with saphenous vein graft was carried out with an ethilon 7/0 interrupted suture. The conduit was tunnelized under the preauricular region up to the intracranial side where it was anastomosed with the M4 segment of the distal MCA by an ethilon 7/0 interrupted suture. The aneurysm was then trapped and excluded. The patient had no deficits. Six months after surgery, the left aneurysm was successfully embolized with coils (Figure 4).

Figure 1. (A) Coronal CT angiography showing a giant, partially-thrombosed, left MCA aneurysm. Anterior-posterior (B) and lateral (C) projection DSA of the same patient. (D) Intraoperative pictures showing the aneurysm splitting the left sylvian fissure. (E, F) MCA bifurcation was exposed, and the aneurysm was seen to involve the temporal branch. (G) Indocyanine green videoangiography confirming the presence of a huge intrasaccular thrombus. (H) Temporary clipping of the temporal branch with the patient in burst suppression. (I) Intra-aneurysmal thrombectomy. (J) Counterclipping of the aneurysm with multiple Yasargil standard angled clips. (K) Intraoperative videoangiography showing the distal injection of the temporal branch. (L) Postoperative DSA in anterior-posterior projection confirming complete exclusion of the aneurysm.

430 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

Figure 2. (A) Axial CT angiography revealing a giant calcified anterior communicating artery aneurysm along with a left dominant A1. (B) Anterior-posterior projection DSA documenting full opacification of the aneurysm. (C) Intraoperative photo showing the aneurysm neck, calcification of the sac, both A1, left A2, and left Heubner artery. (D) Temporary clipping of both A1 and placement of a pilot clip just above the neck. (E, F) Definitive clipping obtained after aneurysmectomy. (G) Indocyanine green videoangiography showing the patency of both A2 at the end of surgery. (H) Postoperative DSA.

Figure 3. Axial CT angiography (A) and axial T2-weighted brain MRI (B) both demonstrating the presence of a giant, unthrombosed, right supraclinoid ICA aneurysm. Anterior-posterior (C) and lateral (D) projection DSA. (E) BTO of the right ICA. (F) Preoperative visual field testing of the right eye showing a visual defect in the temporal quadrants because of compression caused by the aneurysm on the right optic nerve. (G-I) Intraoperative photos showing the exposure, bipolar shrinking/remodeling, and clipping of the aneurysm. Postoperative anterior-posterior (J) and lateral (K) projection DSA confirming complete exclusion of the aneurysm. (L) Postoperative visual field testing executed 1 month after surgery showing vision recovery, especially in the upper temporal quadrant.

Surgical Management of Giant Intracranial Aneurysms 431

Figure 4. Axial T2-weighted MRI (A) and Time-of-Flight MRI angiography (B) both revealing the presence of a giant, right, paraclinoid ICA aneurysm along with a smaller contralateral aneurysm of the supraclinoid ICA. Anterior-posterior projection of the right (C) and left (D) ICA showing both aneurysms. Intraoperative pictures showing isolation of the right external carotid artery (E), the M4 segment of the right MCA (F), and the distal anastomosis (G-H). (I-K) Aneurysm trapping and aneurysmectomy. (L) Indocyanine green videoangiography confirming the patency of the bypass. Postoperative axial T2-weighted MRI (M), Time-of-Flight MRI angiography (N), and anterior-posterior projection DSA of the right ICA (O) showing complete exclusion of the aneurysm and patency of the vein graft. (P) Postembolization DSA of the right ICA in anterior-posterior projection documenting complete exclusion of the left supraclinoid ICA aneurysm.

DISCUSSION

Microneurosurgery is still the approach of choice for most GIAs due to two sets of factors. First, apart from specific types of ICA aneurysms, neuroendovascular techniques have not yet achieved for GIAs the same results as smaller ones. Second, GIAs are very frequently associated with the need to perform flow replacement. Noteably still today, the only on-label indication for a pipeline embolization device (Covidien, Irvine, CA, USA), the progenitor of flow-diverter stents, is treatment of a large or giant, wide-necked intracranial aneurysm of the ICA from the petrous to the superior hypophyseal segment (Dmytriw et al. 2019). Furthermore, a dramatically high number (62%) of these patients have been reported to have silent ischemic

432 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al. infarcts, with an equally high number of complications for posterior circulation aneurysms and distal vasculature (Rajah, Narayanan, and Rangel-Castilla 2017; Jahromi et al. 2008). The risk of in-stent thrombosis or stenosis for flow-diverter devices as well as the safety profile of intrasaccular flow-disruptor stents is not yet well-known. Apart from a pipeline embolization device, the literature also reports a series of severe complications secondary to both balloon- assisted coiling for GIAs (or high porosity stents) and coiling (Jahromi et al. 2008). The need for endoaneurysmectomy of these lesions, often in addition to flow replacement, is a further aspect giving microneurosurgery a primary role. In parallel with endoscopic skull base surgery (Arnaout et al. 2019; S. Luzzi, Del Maestro, Elia, et al. 2019; S. Luzzi, Del Maestro, Trovarelli, et al. 2019; S. Luzzi, Zoia, et al. 2019; Zoia et al. 2019), a series of morphometric anatomical studies about common skull base approaches have better delineated concepts as angular exposure and overall surgical freedom, ultimately leading to their tailoring for surgery on GIAs (S. Luzzi, Gallieni, et al. 2018). Important examples are extensions of the pterional approach, such as cranio-orbitary or lateral suboccipital approaches with further variants (Zabramski et al. 1998; Heros 1986; Wen et al. 1997). Neurovascular surgery techniques have evolved tremendously in recent years, involving aneurysms, cavernous hemangiomas, and arteriovenous malformations (Ciappetta, Luzzi, et al. 2009; Ciappetta, Occhiogrosso, et al. 2009; Del Maestro et al. 2018; Gallieni et al. 2018; S. Luzzi, Del Maestro, et al. 2018; S. Luzzi, Del Maestro, and Galzio 2019; S. Luzzi, Elia, Del Maestro, Morotti, et al. 2019; S. Luzzi, Gallieni, et al. 2018; Ricci et al. 2017; S. Luzzi et al. 2020). Regarding GIAs, good knowledge of fragmentation techniques, such as stacking- seating, is required to effectively treat these complex lesions. Furthermore, the frequent need to perform revascularization also requires a level of dexterity in microsuturing techniques that can only be achieved with constant microvascular laboratory training. In the last few years, refinement and technological evolution of techniques has also included the field of neurovascular surgery (Bellantoni et al. 2019; Cheng, Shetty, and Sekhar 2018; De Tommasi et al. 2008; De Tommasi et al. 2007; Guastamacchia et al. 2007; Sabino Luzzi, Crovace, et al. 2019; S. Luzzi, Crovace, et al. 2018; S. Luzzi, Elia, Del Maestro, Elbabaa, et al. 2019; S. Luzzi, Giotta Lucifero, et al. 2019; Palumbo et al. 2019; Palumbo et al. 2018; Raysi Dehcordi et al. 2017; Spena et al. 2019; Zoia et al. 2018; Bongetta et al. 2019; Ciappetta et al. 2008; De Tommasi, Cascardi, et al. 2006; De Tommasi, De Tommasi, et al. 2006; Millimaggi et al. 2018; Antonosante et al. 2020; Campanella et al. 2020; Zoia et al. 2020; Elsawaf et al. 2020). The implementation of tools as neuromonitoring, indocyanine green, and fluorescence videoangiography, micro-Doppler ultrasonography, Doppler flowmetry, and hybrid angiography has dramatically increased the armamentarium of the vascular neurosurgeon, while simultaneously improving patients’ overall outcomes related to these complex lesions. The results of the present series, in terms of both aneurysm exclusion rate and durability of treatment, validate our attitude toward a clip-first policy for most GIAs.

CONCLUSION

GIAsconstitute a specific type of intracranial aneurysm characterized by a very intricate angioarchitecture and equally complex hemodynamics. Microneurosurgery is still the best

Surgical Management of Giant Intracranial Aneurysms 433 treatment option for most, and the only possible therapy in cases needing flow replacement. Clip reconstruction and bypass procedures are key techniques for the surgical management of GIAs. In recent years, the use of a series of tools for the intraoperative check and measurement of flow have dramatically improved the quality of vascular neurosurgery, GIAs included, as well as patients’ overall outcome.

REFERENCES

Amin-Hanjani, S., X. Du, N. Mlinarevich, G. Meglio, M. Zhao, and F. T. Charbel. 2005. “The cut flow index: an intraoperative predictor of the success of extracranial-intracranial bypass for occlusive cerebrovascular disease.” Neurosurgery 56 (1 Suppl): 75-85; discussion 75- 85. https://doi.org/10.1227/01.neu.0000143032.35416.41. https://www.ncbi.nlm.nih.gov/ pubmed/15799795. Amin-Hanjani, S., G. Meglio, R. Gatto, A. Bauer, and F. T. Charbel. 2006. “The utility of intraoperative blood flow measurement during aneurysm surgery using an ultrasonic perivascular flow probe.” Neurosurgery 58 (4 Suppl 2): ONS-305-12; discussion ONS- 312. https://doi.org/10.1227/01.NEU.0000209339.47929.34. https://www.ncbi.nlm.nih. gov/pubmed/16582654. Amin-Hanjani, S., L. Rose-Finnell, D. Richardson, S. Ruland, D. Pandey, K. R. Thulborn, D. S. Liebeskind, G. J. Zipfel, M. S. Elkind, J. Kramer, F. L. Silver, S. E. Kasner, L. R. Caplan, C. P. Derdeyn, P. B. Gorelick, F. T. Charbel, and V. ERiTAS Study Group. 2010. “Vertebrobasilar Flow Evaluation and Risk of Transient Ischaemic Attack and Stroke study (VERiTAS): rationale and design.” Int J Stroke 5 (6): 499-505. https://doi.org/10. 1111/j.1747-4949.2010.00528.x. https://www.ncbi.nlm.nih.gov/pubmed/21050408. Antonosante, A., L. Brandolini, M. d'Angelo, E. Benedetti, V. Castelli, M. D. Maestro, S. Luzzi, A. Giordano, A. Cimini, and M. Allegretti. 2020. “Autocrine CXCL8-dependent invasiveness triggers modulation of actin cytoskeletal network and cell dynamics.” Aging (Albany NY) 12 (2): 1928-1951. https://doi.org/10.18632/aging.102733. https://www.ncbi. nlm.nih.gov/pubmed/31986121. Arnaout, M. M., S. Luzzi, R. Galzio, and K. Aziz. 2019. “Supraorbital keyhole approach: Pure endoscopic and endoscope-assisted perspective.” Clin Neurol Neurosurg 189: 105623. https://doi.org/10.1016/j.clineuro.2019.105623. https://www.ncbi.nlm.nih.gov/pubmed/ 31805490. Arnone, G. D., Z. A. Hage, and F. T. Charbel. 2019. “Single Vessel Double Anastomosis for Flow Augmentation - A Novel Technique for Direct Extracranial to Intracranial Bypass Surgery.” Oper Neurosurg (Hagerstown) 17 (4): 365-375. https://doi.org/10.1093/ ons/opy396. https://www.ncbi.nlm.nih.gov/pubmed/30690506. Bae, Y. J., C. Jung, J. H. Kim, B. S. Choi, and E. Kim. 2015. “Quantitative Magnetic Resonance Angiography in Internal Carotid Artery Occlusion with Primary Collateral Pathway.” J Stroke 17 (3): 320-6. https://doi.org/10.5853/jos.2015.17.3.320. https://www.ncbi.nlm. nih.gov/pubmed/26437997. Barrow, D L, and C Alleyne. 1995. “Natural history of giant intracranial aneurysms and indications for intervention.” Clinical neurosurgery 42: 214-44.

434 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

Barth, A, and N de Tribolet. 1994. “Growth of small saccular aneurysms to giant aneurysms: presentation of three cases.” Surgical neurology 41: 277-80. Batjer, H. H., and D. S. Samson. 1990. “Retrograde suction decompression of giant paraclinoidal aneurysms. Technical note.” J Neurosurg 73 (2): 305-6. https://doi.org/ 10.3171/jns.1990.73.2.0305. https://www.ncbi.nlm.nih.gov/pubmed/2366090. Bellantoni, G., F. Guerrini, M. Del Maestro, R. Galzio, and S. Luzzi. 2019. “Simple schwannomatosis or an incomplete Coffin-Siris? Report of a particular case.” eNeurologicalSci 14: 31-33. https://doi.org/10.1016/j.ensci.2018.11.021. https://www. ncbi.nlm.nih.gov/pubmed/30555950. Bongetta, D., C. Zoia, S. Luzzi, M. D. Maestro, A. Peri, G. Bichisao, D. Sportiello, I. Canavero, A. Pietrabissa, and R. J. Galzio. 2019. “Neurosurgical issues of bariatric surgery: A systematic review of the literature and principles of diagnosis and treatment.” Clin Neurol Neurosurg 176: 34-40. https://doi.org/10.1016/j.clineuro.2018.11.009. https://www.ncbi. nlm.nih.gov/pubmed/30500756. Burkhardt, J. K., E. A. Winkler, S. Gandhi, and M. T. Lawton. 2019. “Single-Barrel Versus Double-Barrel Superficial Temporal Artery to Middle Cerebral Artery Bypass: A Comparative Analysis.” World Neurosurg 125: e408-e415. https://doi.org/10.1016/j. wneu.2019.01.089. https://www.ncbi.nlm.nih.gov/pubmed/30703593. Campanella, R., L. Guarnaccia, C. Cordiglieri, E. Trombetta, M. Caroli, G. Carrabba, N. La Verde, P. Rampini, C. Gaudino, A. Costa, S. Luzzi, G. Mantovani, M. Locatelli, L. Riboni, S. E. Navone, and G. Marfia. 2020. “Tumor-Educated Platelets and Angiogenesis in Glioblastoma: Another Brick in the Wall for Novel Prognostic and Targetable Biomarkers, Changing the Vision from a Localized Tumor to a Systemic Pathology.” Cells 9 (2). https://doi.org/10.3390/cells9020294. https://www.ncbi.nlm.nih.gov/pubmed/31991805. Cheng, C. Y., R. Shetty, and L. N. Sekhar. 2018. “Microsurgical Resection of a Large Intraventricular Trigonal Tumor: 3-Dimensional Operative Video.” Oper Neurosurg (Hagerstown) 15 (6): E92-E93. https://doi.org/10.1093/ons/opy068. https://www.ncbi. nlm.nih.gov/pubmed/29618124. Cherian, J., V. Srinivasan, P. Kan, and E. A. M. Duckworth. 2018. “Double-Barrel Superficial Temporal Artery-Middle Cerebral Artery Bypass: Can It Be Considered “High-Flow?”.” Oper Neurosurg (Hagerstown) 14 (3): 288-294. https://doi.org/10.1093/ons/opx119. https://www.ncbi.nlm.nih.gov/pubmed/28961997. Chung, Y., S. H. Lee, J. Ryu, J. Kim, S. B. Chung, and S. K. Choi. 2017. “Tailored Double- Barrel Bypass Surgery Using an Occipital Artery Graft for Unstable Intracranial Vascular Occlusive Disease.” World Neurosurg 101: 813 e5-813 e9. https://doi.org/10. 1016/j.wneu.2017.03.043. https://www.ncbi.nlm.nih.gov/pubmed/28323188. Ciappetta, P., I. D'Urso P, S. Luzzi, G. Ingravallo, A. Cimmino, and L. Resta. 2008. “Cystic dilation of the ventriculus terminalis in adults.” J Neurosurg Spine 8 (1): 92-9. https://doi.org/10.3171/SPI-08/01/092. https://www.ncbi.nlm.nih.gov/pubmed/18173354. Ciappetta, P., S. Luzzi, R. De Blasi, and P. I. D'Urso. 2009. “Extracranial aneurysms of the posterior inferior cerebellar artery. Literature review and report of a new case.” J Neurosurg Sci 53 (4): 147-51. https://www.ncbi.nlm.nih.gov/pubmed/20220739. Ciappetta, P., G. Occhiogrosso, S. Luzzi, P. I. D'Urso, and A. P. Garribba. 2009. “Jugular tubercle and vertebral artery/posterior inferior cerebellar artery anatomic relationship: a 3- dimensional angiography computed tomography anthropometric study.” Neurosurgery 64

Surgical Management of Giant Intracranial Aneurysms 435

(5 Suppl 2): 429-36; discussion 436. https://doi.org/10.1227/01.NEU.0000337573. 17073.9F. https://www.ncbi.nlm.nih.gov/pubmed/19404121. De Tommasi, A., P. Cascardi, C. De Tommasi, S. Luzzi, and P. Ciappetta. 2006. “Emergency surgery in a severe penetrating skull base injury by a screwdriver: case report and literature review.” World J Emerg Surg 1: 36. https://doi.org/10.1186/1749-7922-1-36. https://www. ncbi.nlm.nih.gov/pubmed/17169147. De Tommasi, A., C. De Tommasi, E. Lauta, S. Luzzi, A. Cimmino, and P. Ciappetta. 2006. “Pre-operative subarachnoid haemorrhage in a patient with spinal tumour.” Cephalalgia 26 (7): 887-90. https://doi.org/10.1111/j.1468-2982.2006.01122.x. https://www.ncbi. nlm.nih.gov/pubmed/16776708. De Tommasi, A., S. Luzzi, P. I. D'Urso, C. De Tommasi, N. Resta, and P. Ciappetta. 2008. “Molecular genetic analysis in a case of ganglioglioma: identification of a new mutation.” Neurosurgery 63 (5): 976-80; discussion 980. https://doi.org/10.1227/01.NEU. 0000327699.93146.CD. https://www.ncbi.nlm.nih.gov/pubmed/19005389. De Tommasi, A., G. Occhiogrosso, C. De Tommasi, S. Luzzi, A. Cimmino, and P. Ciappetta. 2007. “A polycystic variant of a primary intracranial leptomeningeal astrocytoma: case report and literature review.” World J Surg Oncol 5: 72. https://doi.org/10.1186/1477- 7819-5-72. https://www.ncbi.nlm.nih.gov/pubmed/17587463. Del Maestro, M., S. Luzzi, M. Gallieni, D. Trovarelli, A. V. Giordano, M. Gallucci, A. Ricci, and R. Galzio. 2018. “Surgical Treatment of Arteriovenous Malformations: Role of Preoperative Staged Embolization.” Acta Neurochir Suppl 129: 109-113. https://doi.org/ 10.1007/978-3-319-73739-3_16. https://www.ncbi.nlm.nih.gov/pubmed/30171322. Dmytriw, A. A., K. Phan, J. M. Moore, V. M. Pereira, T. Krings, and A. J. Thomas. 2019. “On Flow Diversion: The Changing Landscape of Intracerebral Aneurysm Management.” AJNR Am J Neuroradiol 40 (4): 591-600. https://doi.org/10.3174/ajnr.A6006. https://www. ncbi.nlm.nih.gov/pubmed/30894358. Drake, C. G. 1979. “Giant intracranial aneurysms: experience with surgical treatment in 174 patients.” Clinical neurosurgery 26: 12--95. http://www.ncbi.nlm.nih.gov/pubmed/ 544122. Elsawaf, Y., S. Anetsberger, S. Luzzi, and S. K. Elbabaa. 2020. “Early Decompressive Craniectomy as Management for Severe TBI in the Pediatric Population: A Comprehensive Literature Review.” World Neurosurg. https://doi.org/10.1016/j.wneu.2020.02.065. https://www.ncbi.nlm.nih.gov/pubmed/32084616. Flores, B. C., J. A. White, H. H. Batjer, and D. S. Samson. 2018. “The 25th anniversary of the retrograde suction decompression technique (Dallas technique) for the surgical management of paraclinoid aneurysms: historical background, systematic review, and pooled analysis of the literature.” J Neurosurg 130 (3): 902-916. https://doi.org/ 10.3171/2017.11.JNS17546. https://www.ncbi.nlm.nih.gov/pubmed/29726776. Gallieni, M., M. Del Maestro, S. Luzzi, D. Trovarelli, A. Ricci, and R. Galzio. 2018. “Endoscope-Assisted Microneurosurgery for Intracranial Aneurysms: Operative Technique, Reliability, and Feasibility Based on 14 Years of Personal Experience.” Acta Neurochir Suppl 129: 19-24. https://doi.org/10.1007/978-3-319-73739-3_3. https://www. ncbi.nlm.nih.gov/pubmed/30171309. Guastamacchia, E., V. Triggiani, E. Tafaro, A. De Tommasi, C. De Tommasi, S. Luzzi, C. Sabba, F. Resta, M. R. Terreni, and M. Losa. 2007. “Evolution of a prolactin-secreting

436 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

pituitary microadenoma into a fatal carcinoma: a case report.” Minerva Endocrinol 32 (3): 231-6. https://www.ncbi.nlm.nih.gov/pubmed/17912159. Heros, R. C. 1984. “Thromboembolic complications after combined internal carotid ligation and extra- to-intracranial bypass.” Surgical neurology 21 (1): 75--9. http://www.ncbi. nlm.nih.gov/pubmed/6689814. ---. 1986. “Lateral suboccipital approach for vertebral and vertebrobasilar artery lesions.” J Neurosurg 64 (4): 559-62. https://doi.org/10.3171/jns.1986.64.4.0559. https://www.ncbi. nlm.nih.gov/pubmed/3950739. Hosobuchi, Y. 1979. “Direct surgical treatment of giant intracranial aneurysms.” Journal of neurosurgery 51 (6): 743--56. https://doi.org/10.3171/jns.1979.51.6.0743. http://www. ncbi.nlm.nih.gov/pubmed/501418. Hu, P., H. Q. Zhang, X. Y. Li, and X. Z. Tong. 2019. “Double-Barrel Superficial Temporal Artery to Proximal Middle Cerebral Artery Bypass to Treat Complex Intracranial Aneurysms: A Reliable High Blood Flow Bypass.” World Neurosurg 125: e884- e890. https://doi.org/10.1016/j.wneu.2019.01.203. https://www.ncbi.nlm.nih.gov/pubmed/ 30743025. Jahromi, B. S., J. Mocco, J. A. Bang, Y. Gologorsky, A. H. Siddiqui, M. B. Horowitz, L. N. Hopkins, and E. I. Levy. 2008. “Clinical and angiographic outcome after endovascular management of giant intracranial aneurysms.” Neurosurgery 63 (4): 662-74; discussion 674-5. https://doi.org/10.1227/01.NEU.0000325497.79690.4C. https://www.ncbi.nlm.nih. gov/pubmed/18981877. Kobayashi, H., M. Hayashi, H. Kawano, Y. Handa, M. Kabuto, and Y. Ishii. 1989. “Magnetic resonance imaging of embolism from intracranial aneurysms.” Surg Neurol 32 (3): 225-30. https://doi.org/10.1016/0090-3019(89)90183-3. https://www.ncbi.nlm.nih.gov/ pubmed/2772812. Krings, Timo, Ronie L Piske, and Pierre L Lasjaunias. 2005. “Intracranial arterial aneurysm vasculopathies: targeting the outer vessel wall.” Neuroradiology 47: 931-7. https://doi.org/ 10.1007/s00234-005-1438-9. Lawton, M T, and R F Spetzler. 1995. “Surgical management of giant intracranial aneurysms: experience with 171 patients.” Clinical neurosurgery 42: 245-66. Lawton, M. T., and Robert F. Spetzler. 1998. Surgical Strategies for Giant Intracranial Aneurysms. In Neurosurgery clinics of North America. Vienna: Springer Vienna. Luzzi, S., A. M. Crovace, L. Lacitignola, V. Valentini, E. Francioso, G. Rossi, G. Invernici, R. J. Galzio, and A. Crovace. 2018. “Engraftment, neuroglial transdifferentiation and behavioral recovery after complete spinal cord transection in rats.” Surg Neurol Int 9: 19. https://doi.org/10.4103/sni.sni_369_17. https://www.ncbi.nlm.nih.gov/pubmed/29497572. Luzzi, S., M. Del Maestro, D. Bongetta, C. Zoia, A. V. Giordano, D. Trovarelli, S. Raysi Dehcordi, and R. J. Galzio. 2018. “Onyx Embolization Before the Surgical Treatment of Grade III Spetzler-Martin Brain Arteriovenous Malformations: Single-Center Experience and Technical Nuances.” World Neurosurg 116: e340-e353. https://doi.org/10.1016/ j.wneu.2018.04.203. https://www.ncbi.nlm.nih.gov/pubmed/29751183. Luzzi, S., M. Del Maestro, S. K. Elbabaa, and R. Galzio. 2020. “Letter to the Editor Regarding “One and Done: Multimodal Treatment of Pediatric Cerebral Arteriovenous Malformations in a Single Anesthesia Event”.” World Neurosurg 134: 660. https://doi.org/ 10.1016/j.wneu.2019.09.166. https://www.ncbi.nlm.nih.gov/pubmed/32059273.

Surgical Management of Giant Intracranial Aneurysms 437

Luzzi, S., M. Del Maestro, A. Elia, F. Vincitorio, G. Di Perna, F. Zenga, D. Garbossa, S. Elbabaa, and R. Galzio. 2019. “Morphometric and Radiomorphometric Study of the Correlation between the Foramen Magnum Region and the Anterior and Posterolateral Approaches to Ventral Intradural Lesions.” Turk Neurosurg. https://doi.org/10.5137/ 1019-5149.JTN.26052-19.2. https://www.ncbi.nlm.nih.gov/pubmed/31452176. Luzzi, S., M. Del Maestro, and R. Galzio. 2019. “Letter to the Editor. Preoperative embolization of brain arteriovenous malformations.” J Neurosurg: 1-2. https://doi.org/10.3171/2019. 6.JNS191541. https://www.ncbi.nlm.nih.gov/pubmed/31812150. https://thejns.org/view/journals/j-neurosurg/aop/article-10.3171-2019.6.JNS191541/article- 10.3171-2019.6.JNS191541.xml. Luzzi, S., M. Del Maestro, D. Trovarelli, D. De Paulis, S. R. Dechordi, H. Di Vitantonio, V. Di Norcia, D. F. Millimaggi, A. Ricci, and R. J. Galzio. 2019. “Endoscope-Assisted Microneurosurgery for Neurovascular Compression Syndromes: Basic Principles, Methodology, and Technical Notes.” Asian J Neurosurg 14 (1): 193-200. https://doi.org/ 10.4103/ajns.AJNS_279_17. https://www.ncbi.nlm.nih.gov/pubmed/30937034. Luzzi, S., A. Elia, M. Del Maestro, S. K. Elbabaa, S. Carnevale, F. Guerrini, M. Caulo, P. Morbini, and R. Galzio. 2019. “Dysembryoplastic Neuroepithelial Tumors: What You Need to Know.” World Neurosurg 127: 255-265. https://doi.org/10.1016/j.wneu. 2019.04.056. https://www.ncbi.nlm.nih.gov/pubmed/30981794. Luzzi, S., A. Elia, M. Del Maestro, A. Morotti, S. K. Elbabaa, A. Cavallini, and R. Galzio. 2019. “Indication, Timing, and Surgical Treatment of Spontaneous Intracerebral Hemorrhage: Systematic Review and Proposal of a Management Algorithm.” World Neurosurg. https://doi.org/10.1016/j.wneu.2019.01.016. https://www.ncbi.nlm.nih.gov/ pubmed/30677572. Luzzi, S., M. Gallieni, M. Del Maestro, D. Trovarelli, A. Ricci, and R. Galzio. 2018. “Giant and Very Large Intracranial Aneurysms: Surgical Strategies and Special Issues.” Acta Neurochir Suppl 129: 25-31. https://doi.org/10.1007/978-3-319-73739-3_4. https://www. ncbi.nlm.nih.gov/pubmed/30171310. Luzzi, S., A. Giotta Lucifero, M. Del Maestro, G. Marfia, S. E. Navone, M. Baldoncini, M. Nunez, A. Campero, S. K. Elbabaa, and R. Galzio. 2019. “Anterolateral Approach for Retrostyloid Superior Parapharyngeal Space Schwannomas Involving the Jugular Foramen Area: A 20-Year Experience.” World Neurosurg. https://doi.org/10.1016/j.wneu.2019. 09.006. https://www.ncbi.nlm.nih.gov/pubmed/31520759. Luzzi, S., C. Zoia, A. D. Rampini, A. Elia, M. Del Maestro, S. Carnevale, P. Morbini, and R. Galzio. 2019. “Lateral Transorbital Neuroendoscopic Approach for Intraconal Meningioma of the Orbital Apex: Technical Nuances and Literature Review.” World Neurosurg 131: 10-17. https://doi.org/10.1016/j.wneu.2019.07.152. https://www.ncbi. nlm.nih.gov/pubmed/31356977. Luzzi, Sabino, Alberto Maria Crovace, Mattia Del Maestro, Alice Giotta Lucifero, Samer K. Elbabaa, Benedetta Cinque, Paola Palumbo, Francesca Lombardi, Annamaria Cimini, Maria Grazia Cifone, Antonio Crovace, and Renato Galzio. 2019. “The cell-based approach in neurosurgery: ongoing trends and future perspectives.” Heliyon 5 (11). https://doi.org/10.1016/j.heliyon.2019.e02818. Millimaggi, D. F., V. D. Norcia, S. Luzzi, T. Alfiero, R. J. Galzio, and A. Ricci. 2018. “Minimally Invasive Transforaminal Lumbar Interbody Fusion with Percutaneous Bilateral Pedicle Screw Fixation for Lumbosacral Spine Degenerative Diseases. A

438 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

Retrospective Database of 40 Consecutive Cases and Literature Review.” Turk Neurosurg 28 (3): 454-461. https://doi.org/10.5137/1019-5149.JTN.19479-16.0. https://www.ncbi. nlm.nih.gov/pubmed/28481388. Palumbo, P., F. Lombardi, F. R. Augello, I. Giusti, S. Luzzi, V. Dolo, M. G. Cifone, and B. Cinque. 2019. “NOS2 inhibitor 1400W Induces Autophagic Flux and Influences Extracellular Vesicle Profile in Human Glioblastoma U87MG Cell Line.” Int J Mol Sci 20 (12). https://doi.org/10.3390/ijms20123010. https://www.ncbi.nlm.nih.gov/pubmed/ 31226744. Palumbo, P., F. Lombardi, G. Siragusa, S. R. Dehcordi, S. Luzzi, A. Cimini, M. G. Cifone, and B. Cinque. 2018. “Involvement of NOS2 Activity on Human Glioma Cell Growth, Clonogenic Potential, and Neurosphere Generation.” Int J Mol Sci 19 (9). https://doi.org/10.3390/ijms19092801. https://www.ncbi.nlm.nih.gov/pubmed/30227679. Rajah, G., S. Narayanan, and L. Rangel-Castilla. 2017. “Update on flow diverters for the endovascular management of cerebral aneurysms.” Neurosurg Focus 42 (6): E2. https://doi.org/10.3171/2017.3.FOCUS16427. https://www.ncbi.nlm.nih.gov/pubmed/ 28565980. Raysi Dehcordi, S., A. Ricci, H. Di Vitantonio, D. De Paulis, S. Luzzi, P. Palumbo, B. Cinque, D. Tempesta, G. Coletti, G. Cipolloni, M. G. Cifone, and R. Galzio. 2017. “Stemness Marker Detection in the Periphery of Glioblastoma and Ability of Glioblastoma to Generate Glioma Stem Cells: Clinical Correlations.” World Neurosurg 105: 895- 905. https://doi.org/10.1016/j.wneu.2017.05.099. https://www.ncbi.nlm.nih.gov/pubmed/ 28559081. Ricci, A., H. Di Vitantonio, D. De Paulis, M. Del Maestro, S. D. Raysi, D. Murrone, S. Luzzi, and R. J. Galzio. 2017. “Cortical aneurysms of the middle cerebral artery: A review of the literature.” Surg Neurol Int 8: 117. https://doi.org/10.4103/sni.sni_50_17. https://www. ncbi.nlm.nih.gov/pubmed/28680736. Sakaki, T., K. Kinugawa, T. Tanigake, S. Miyamoto, K. Kyoi, and S. Utsumi. 1980. “Embolism from intracranial aneurysms.” J Neurosurg 53 (3): 300-4. https://doi.org/10.3171/ jns.1980.53.3.0300. https://www.ncbi.nlm.nih.gov/pubmed/7420144. Sekhar, L. N., J. M. Duff, C. Kalavakonda, and M. Olding. 2001. “Cerebral revascularization using radial artery grafts for the treatment of complex intracranial aneurysms: techniques and outcomes for 17 patients.” Neurosurgery 49 (3): 646-58; discussion 658- 9. https://doi.org/10.1097/00006123-200109000-00023. https://www.ncbi.nlm.nih.gov/ pubmed/11523676. Sekhar, L. N., and S. J. Patel. 1993. “Permanent occlusion of the internal carotid artery during skull-base and vascular surgery: is it really safe?” Am J Otol 14 (5): 421- 2. https://doi.org/10.1097/00129492-199309000-00001. https://www.ncbi.nlm.nih.gov/ pubmed/8122701. Sekhar, Laligam N, Farzana Tariq, Jeffrey C Mai, Louis J Kim, Basavaraj Ghodke, Daniel K Hallam, and Ketan R Bulsara. 2012. “Unyielding progress: treatment paradigms for giant aneurysms.” Clinical neurosurgery 59: 6-21. https://doi.org/10.1227/NEU. 0b013e3182698b75. Seo, B. R., T. S. Kim, S. P. Joo, J. M. Lee, J. W. Jang, J. K. Lee, J. H. Kim, and S. H. Kim. 2009. “Surgical strategies using cerebral revascularization in complex middle cerebral artery aneurysms.” Clin Neurol Neurosurg 111 (8): 670-5. https://doi.org/10.1016/ j.clineuro.2009.06.002. https://www.ncbi.nlm.nih.gov/pubmed/19595503.

Surgical Management of Giant Intracranial Aneurysms 439

Sousa, Atos and. 2015. “Treatment of Giant Intracranial Aneurysms: a Review Based on Experience from 286 Cases.” Arquivos Brasileiros de Neurocirurgia: Brazilian Neurosurgery 34 (04): 295--303. https://doi.org/10.1055/s-0035-1566156. http://www. thieme-connect.de/DOI/DOI?10.1055/s-0035-1566156. Spena, G., E. Roca, F. Guerrini, P. P. Panciani, L. Stanzani, A. Salmaggi, S. Luzzi, and M. Fontanella. 2019. “Risk factors for intraoperative stimulation-related seizures during awake surgery: an analysis of 109 consecutive patients.” J Neurooncol. https://doi.org/ 10.1007/s11060-019-03295-9. https://www.ncbi.nlm.nih.gov/pubmed/31552589. Spetzler, R. F. and Schuster H. and Roski R. A. 1980. “Elective extracranial-intracranial arterial bypass in the treatment of inoperable giant aneurysms of the internal carotid artery.” Journal of neurosurgery 53 (1): 22--7. https://doi.org/10.3171/jns.1980.53.1.0022. http://www.ncbi.nlm.nih.gov/pubmed/7411205. Stapleton, C. J., G. S. Atwal, A. E. Hussein, S. Amin-Hanjani, and F. T. Charbel. 2019. “The cut flow index revisited: utility of intraoperative blood flow measurements in extracranial- intracranial bypass surgery for ischemic cerebrovascular disease.” J Neurosurg: 1-5. https://doi.org/10.3171/2019.5.JNS19641. https://www.ncbi.nlm.nih.gov/pubmed/ 31491766. Sundt, T. M. and Piepgras D. G. 1979. “Surgical approach to giant intracranial aneurysms. Operative experience with 80 cases.” Journal of neurosurgery 51 (6): 731-- 42. https://doi.org/10.3171/jns.1979.51.6.0731. http://www.ncbi.nlm.nih.gov/pubmed/ 501417. “Unruptured intracranial aneurysms--risk of rupture and risks of surgical intervention. International Study of Unruptured Intracranial Aneurysms Investigators.”. 1998. The New England journal of medicine 339 (24): 1725--33. https://doi.org/10.1056/NEJM 199812103392401. http://www.ncbi.nlm.nih.gov/pubmed/9867550. Wada, K., N. Otani, T. Toyooka, S. Takeuchi, A. Tomiyama, and K. Mori. 2018. “Superficial Temporal Artery to Anterior Cerebral Artery Hemi-bonnet Bypass Using Radial Artery Graft for Prevention of Complications after Surgical Treatment of Partially Thrombosed Large/Giant Anterior Cerebral Artery Aneurysm.” J Stroke Cerebrovasc Dis 27 (12): 3505- 3510. https://doi.org/10.1016/j.jstrokecerebrovasdis.2018.08.020. https://www.ncbi.nlm. nih.gov/pubmed/30205996. Wang, L., L. Cai, H. Qian, J. Song, R. Tanikawa, M. Lawton, and X. Shi. 2019. “Intracranial- Intracranial Bypass with a Graft Vessel: A Comprehensive Review of Technical Characteristics and Surgical Experience.” World Neurosurg 125: 285-298. https://doi.org/ 10.1016/j.wneu.2019.01.259. https://www.ncbi.nlm.nih.gov/pubmed/30790733. Wen, H. T., A. L. Rhoton, Jr., T. Katsuta, and E. de Oliveira. 1997. “Microsurgical anatomy of the transcondylar, supracondylar, and paracondylar extensions of the far-lateral approach.” J Neurosurg 87 (4): 555-85. https://doi.org/10.3171/jns.1997.87.4.0555. https://www.ncbi. nlm.nih.gov/pubmed/9322846. Wiebers, D. O., J. P. Whisnant, J. Huston, I. Meissner, R. D. Brown, D. G. Piepgras, G. S. Forbes, K. Thielen, D. Nichols, W. M. O'Fallon, J. Peacock, L. Jaeger, N. F. Kassell, G. L. Kongable-Beckman, J. C. Torner, and International Study of Unruptured Intracranial Aneurysms Investigators. 2003. “Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment.” Lancet 362 (9378): 103-10. https://www.ncbi.nlm.nih.gov/pubmed/12867109.

440 S. Luzzi, A. Giotta Lucifero, M. Del Maestro et al.

Zabramski, J. M., T. Kiris, S. K. Sankhla, J. Cabiol, and R. F. Spetzler. 1998. “Orbitozygomatic craniotomy. Technical note.” J Neurosurg 89 (2): 336-41. https://doi.org/10.3171/ jns.1998.89.2.0336. https://www.ncbi.nlm.nih.gov/pubmed/9688133. Zoia, C., D. Bongetta, G. Dorelli, S. Luzzi, M. D. Maestro, and R. J. Galzio. 2019. “Transnasal endoscopic removal of a retrochiasmatic cavernoma: A case report and review of literature.” Surg Neurol Int 10: 76. https://doi.org/10.25259/SNI-132-2019. https://www. ncbi.nlm.nih.gov/pubmed/31528414. Zoia, C., D. Bongetta, F. Guerrini, C. Alicino, A. Cattalani, S. Bianchini, R. J. Galzio, and S. Luzzi. 2018. “Outcome of elderly patients undergoing intracranial meningioma resection: a single center experience.” J Neurosurg Sci. https://doi.org/10.23736/S0390-5616. 18.04333-3. https://www.ncbi.nlm.nih.gov/pubmed/29808631. Zoia, C., F. Lombardi, M. R. Fiore, A. Montalbetti, A. Iannalfi, M. Sansone, D. Bongetta, F. Valvo, M. Del Maestro, S. Luzzi, and R. J. Galzio. 2020. “Sacral solitary fibrous tumour: surgery and hadrontherapy, a combined treatment strategy.” Rep Pract Oncol Radiother 25 (2): 241-244. https://doi.org/10.1016/j.rpor.2020.01.008. https://www.ncbi.nlm.nih. gov/pubmed/32025222.

Chapter 27

REVASCULARIZATION TECHNIQUES FOR COMPLEX INTRACRANIAL ANEURYSMS

L. Berra1, MD and A. Santoro1,, MD, PhD 1Department of Neurosurgery, Policlinico Umberto I - Sapienza Università, Roma, Italy

ABSTRACT

In recent years, the continued progress of endovascular techniques has significantly altered the management of complex pathological conditions such as giant intracranial aneurysms. Despite this, the choice of treating these conditions is not unambiguous and revascularization techniques still represent an indispensable method in the management of intracranial complex vascular diseases, which must be part of the equipment of surgeons dealing with neurovascular disease. Most of the giant aneurysms are characterized by the presence of a lumen whose content is partially thrombosed and of a broad and partially calcified neck from which collateral vessels are often born. In these cases, it is not always possible to perform a direct clipping nor the stent positioning and the revascularization with bypass is the only effective choice

Keywords: Cerebral revcascularization, EC-IC Bypass, Giant aneurysm, Complex intracranial aneurysm

INTRODUCTION

Complex aneurysms are a specific subtype of aneurysm in which the size, location, presence of collateral circles, the peculiarities of the wall, presence of thrombus and previous endovascular or surgical treatment often preclude the possibility of definitive treatment by

 Corresponding Author’s Email: [email protected].

442 L. Berra and A. Santoro direct clipping or standard endovascular techniques (Cantore, Santoro and Da Pian 1999; Cantore et al. 2008). Among the best therapeutic alternatives for complex and giant aneurysms are the most modern endovascular methods, including intracranial stents which, through flow diversion, promote intra-aneurysmal thrombosis (Pescatori, Tropeano and Santoro 2018; MT 2018). Despite the promising results achieved by endovascular treatment for small aneurysms, the resulsts in the treatment of giant and complex aneurysms remain still not verified (Ricci et al. 2017; Del Maestro et al. 2018; Gallieni et al. 2018; Luzzi, Del Maestro et al. 2018; Luzzi, Gallieni et al. 2018; Luzzi, Del Maestro and Galzio 2019; Luzzi et al. 2019; Luzzi S. 2019). The main case series in the literature report high recanalization rates, and low rates of complete exclusion (Sanai, Zador and Lawton 2009; Tayebi Meybodi et al. 2017; Lawton and Lang 2019; Limbucci et al. 2020; Bonney et al. 2020; Zhu et al. 2011; Straus et al. 2017; Pisapia et al. 2011). Large, giant or wide-necked aneurysms, especially those that can be atheromatous, calcified, thrombosed or previously coiled, still remain a formidable challenge for microsurgical or endovascular treatment. In a similar way, fusiform aneurysms that incorporate distal branches and perforators can also be difficult to treat. In these cases, the generation of rapidly evolving stents will, in all probability, play an increasing role as a management tool in the future (Tayebi Meybodi et al. 2017; Lawton and Lang 2019) However, there remains a subset of highly demanding cases that can be excellently addressed with specialized microsurgical techniques. After the advent of new endovascular tools like flow-diverters, cerebral bypass was carried out in a lower proportion of patients with aneurysms. Patients selected for bypass have a greater complexity of the vascular lesions. Cerebral bypass in well-selected patients and revascularization remains an essential technique in vascular neurosurgery and is also beneficial as a rescue technique after failed endovascular treatment of aneurysms (Straus et al. 2017; Gory et al. 2019; Hara et al. 2016). In such cases of complex aneurysms, a therapeutic alternative can be achieved with brain revascularization techniques. The risk of bleeding of these difficult vascular lesions can be controlled by occlusion of the parent artery and by associating cerebral revascularization techniques to maintain adequate blood flow in the distal vascular territory. A partial or complete trapping of the aneurysm is associated as appropriate. Bypasses have different purposes when used during aneurysm surgery. The first is the curative treatment of aneurysm. After revascularization has occurred, some aneurysms can be cured by clipping or complete trapping. For unresectable or unclippable aneurysms, a flow control method (altered flow) involving various bypass techniques it can also be used as a curative treatment. The healing process takes place through the alteration of the flow and the consequent induction of the formation of intra-aneurysmal thrombi, which prevent the growth or rupture of the aneurysm itself. A typical example is the treatment of a giant aneurysm of the cavernous sinus by high flow intra-extracranial bypass and proximal closure of the internal carotid artery, in cases where there is no adequate compensation from the contralateral carotid artery. Another aim is to provide a temporary blood supply during direct clipping (prophylactic bypass), which is sometimes combined with a suction -decompression method. The third purpose is the repair of an accidentally damaged vessel during the surgical procedure (rescue bypass).

Revascularization Techniques for Complex Intracranial Aneurysms 443

PREOPERATIVE ASSESSMENT

Preoperative planning requires careful evaluation of both the morphology and characteristics of the aneurysm and functional and clinical data including perfusion and tolerance of the cerebral parenchyma to the closure of an arterial branch. Typically, a detailed image of the cerebral vascular system is obtained through an angiographic examination in order to reveal detailed anatomy and dynamic characteristics of cerebral blood flow. This technique can be supplemented by transcranial and quantitative Doppler studies and CT or MRI angiography. In somne cases, tha preoperative workup can include perfusion studies like PET scans, SPECT scans, xenon CT perfusion studies, CT perfusion, and perfusion MRIs. These studies permit the extrapolation of CMRO2, OEF, and CBF and provide information on the perfusion of the brain. In several cases it is essential to subject patients to balloon occlusion tests to determine suitability for permanent vessel sacrifice as a means of excluding aneurysm. However, there are many situations where the parent vessel occlusion or dissecting the aneurysm is not possible for inadequate collateral blood flow to the distal circulation. For situations like these, the utility of cerebrovascular revascularization is unquestionable.

SURGICAL TECHNIQUES

STA-MCA is considered the basic and most straightforward technique for cerebral revascularization with the aim to provide flow augmentation to the cerebral tissue. It can be used in the treatment of complex aneurysm of anterior circulation, in particular in the treatment of aneurysms of middle cerebral artery. The patient is positioned in a supine position, with the head turned towards the contralateral side in a slight extension and fixed with a three-pointed head holder. After studying the patient's specific anatomy, STA is found through a microDoppler probe. A frontotemporal incision is made and STA is dissected and carefully released from the surrounding tissues. After reflection of the temporalis muscle, a fronto-temporal craniotomy is performed. The dura is opened and the distal branch of the artery to be revascularized is identified and dissected from the arachnoid. The anastomosis can be performed early in the operation or after the aneurysm have been excluded. The STA is temporarily clipped at the proximal segment and cut at the appropriate distance to reach the donor vessel without traction. The distal stump of the STA is prepared by freeing it from the sorrounding tissue, fishmouthed and marked with blue stain as is marked the recipient vessel. After temporary clipping of the donor and arteriotomy, 9 - 0 or 10 - 0 are used to set the the proximal and distal ends of the fishmouth to the reciopient artery. Subsequently, a running or discontinuous suture is perfromed at the two sides of the arteriotomy. Temporary clipls are remved and the suture is checked for bleeding, usually controlled with hemostatic materials or stitches. Patency of the graft is checked with microdoppler probe and ICG angiography. The revascularization of posterior circulation areteries, when dealing with posterior circulation aneurysms, can be achieved in a similar way with the use of occipital artery or internal maxillary artery.

444 L. Berra and A. Santoro

Interposition graft high-flow EC-IC bypass is used when it is necessary to provide a greater flow of blood in a more proximal vascular territory, as in the case of ICA aneurysms. This technique requires the isolation of the extracranial carotid branches and the harvesting of an interposition graft, which may be the saphenous vein or the radial artery. Aneurysm excision with primary reanastomosis or reimplantation fall into the category of intra-intracranial bypasses and require more skills due to the fact of having to perform micro anastomoses in very confined and deep spaces.

CASE ILLUSTRATION

A 49-year-old woman came to our attention for sudden headache and vomiting. The brain CT scan showed the presence of subarachnoid haemorrhage with prevalent distribution within the left sylvian fissure (Figure 1a). A CT-angiography scan documented the presence of a left ICA aneurysm extending from the supraclinoidal segment to the bifurcation (Figure1b).

Figure 1. (A) Brain CT scan demonstrating subarachnoid hemorrhage mainly localized within the left Sylvian fissure. (B) Angio-CT scan documents the presence of a left ICA aneurysm extended from the supraclinoidal segment to the ICA bifurcation. (C) Cerebral angiography and embolization of the aneurysm.

Figure 2. Follow-up angiography demonstrating the progressive recanalization of the aneurysm.

Revascularization Techniques for Complex Intracranial Aneurysms 445

The aneurysm was treated endovascularly by coils embolization (Figure 1c). After a period of two years, at an angiographic follow-up, an aneurysm regrowth was evident (Figure 2). Given the characteristics of the aneurysm, a revascularization treatment was therefore planned by means of an EC-IC bypass with saphenous interposition graft that connects the extracranial ICA with the temporal branch. Intraoperative ultrasound confirmed the presence of flow inside the graft. The aneurysm was then trapped incompletely through the closure of the ICA proximal to the sac. Post-operative angiography showed the patency of the graft and the exclusion of the aneurysm from the circulation (Figure 3a, 3b). After one year, the angiographic follow-up examination showed a new recanalization of the aneurysm (Figure 3c). This time, in awake surgery, we performed a complete trapping, closing the MCA and the ipsilateral segment A1 as close as possible to aneurysm. Motor and speech functions were monitored for 40 minutes after artery closure. During this period the patient did not have any neurological deficit.

Figure 3. (A, B) Angiography performed after the procedure of EC-IC bypass and closure of the ICA. The graft is patent and ensures an adequate distal flow. After closure of the ICA the aneurysm cannot be visualized. (C) Follow-up angiography shows a further recanalization of the aneurysm.

Figure 4. Angiographic study after closure of the MCA (in awake surgery). The aneurysm has been definitively excluded at early and subsequent follow-up studies.

446 L. Berra and A. Santoro

Postoperative angiography documented the exclusion of the aneurysm and the presence of flow in the distal MCA provided by the graft (Figure 4a). The postoperative course was uneventful. Subsequent follow-up showed persistent aneurysm exclusion and graft patency (Figure 4b).

REFERENCES

Bonney, P. A., Connor, M., Fujii, T., Singh, P., Koch, M. J., Stapleton, C. J., Mack, W. J. and Walcott, B. P. 2020. "Failure of Flow Diverter Therapy: Predictors and Management Strategies". Neurosurgery, 86 (Supplement_1): S64 - S73. https://doi.org/10.1093/ neuros/nyz305. https://www.ncbi.nlm.nih.gov/pubmed/31838530. Cantore, G., Santoro, A. and Da Pian, R. 1999. "Spontaneous occlusion of supraclinoid aneurysms after the creation of extra-intracranial bypasses using long grafts: report of two cases". Neurosurgery, 44 (1): 216 - 9; discussion 219 - 20. https://doi.org/10. 1097/00006123-199901000-00132. https://www.ncbi.nlm.nih.gov/pubmed/9894985. Cantore, G., Santoro, A., Guidetti, G., Delfinis, C. P., Colonnese, C. and Passacantilli, E. 2008. "Surgical treatment of giant intracranial aneurysms: current viewpoint". Neurosurgery, 63 (4 Suppl. 2): 279 - 89; discussion 289 - 90. https://doi.org/10.1227/01.NEU. 0000313122.58694.91. https://www.ncbi.nlm.nih.gov/ pubmed/18981833. Del Maestro, M., Luzzi, S., Gallieni, M., Trovarelli, D., Giordano, A. V., Gallucci, M., Ricci, A. and Galzio, R. 2018. "Surgical Treatment of Arteriovenous Malformations: Role of Preoperative Staged Embolization". Acta Neurochir. Suppl., 129: 109 - 113. https://doi.org/10.1007/978-3-319-73739-3_16. https://www.ncbi.nlm.nih.gov/pubmed/ 30171322. Gallieni, M., Del Maestro, M., Luzzi, S., Trovarelli, D., Ricci, A. and Galzio, R. 2018. "Endoscope-Assisted Microneurosurgery for Intracranial Aneurysms: Operative Technique, Reliability, and Feasibility Based on 14 Years of Personal Experience". Acta Neurochir. Suppl., 129: 19 - 24. https://doi.org/10.1007/978-3-319-73739-3_3. https:// www.ncbi.nlm.nih.gov/pubmed/30171309. Gory, B., Berge, J., Bonafe, A., Pierot, L., Spelle, L., Piotin, M., Biondi, A., Cognard, C., Mounayer, C., Sourour, N., Barbier, C., Desal, H., Herbreteau, D., Chabert, E., Brunel, F. Ricolfi, H., Anxionnat, R., Decullier, E., Huot, L., Turjman, F. and Diversion Investigators. 2019. "Flow Diverters for Intracranial Aneurysms: The DIVERSION National Prospective Cohort Study". Stroke, 50 (12): 3471 - 3480. https://doi.org/10.1161/STROKEAHA. 119.024722. https://www.ncbi.nlm.nih.gov/pubmed/31765296. Hara, T., Arai, S., Goto, Y., Takizawa, T. and Uchida, T. 2016. "Bypass Surgeries in the Treatment of Cerebral Aneurysms". Acta Neurochir. Suppl., 123: 57 - 64. https://doi.org/10.1007/978-3-319-29887-0_8. https://www.ncbi.nlm.nih.gov/pubmed/ 27637629. Lawton, M. T. and Lang, M. J. 2019. "The future of open vascular neurosurgery: perspectives on cavernous malformations, AVMs, and bypasses for complex aneurysms". J. Neurosurg., 130 (5): 1409 - 1425. https://doi.org/10.3171/2019.1.JNS182156. https://www.ncbi. nlm.nih.gov/pubmed/31042667.

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Limbucci, N., Leone, G., Renieri, L., Nappini, S., Cagnazzo, F., Laiso, A., Muto, M. and Mangiafico, S. 2020. "Expanding Indications for Flow Diverters: Distal Aneurysms, Bifurcation Aneurysms, Small Aneurysms, Previously Coiled Aneurysms and Clipped Aneurysms, and Carotid Cavernous Fistulas". Neurosurgery, 86 (Supplement_1): S85 - S94. https://doi.org/10.1093/neuros/nyz334. https://www.ncbi.nlm.nih.gov/pubmed/ 31838532. Luzzi, S., Del Maestro, M., Elbabaa, S. K, Galzio, R. 2019. "Letter to the Editor Regarding The “One and Done” Approach in the Combined Endovascular Surgical Treatment of Pediatric Cerebral Arteriovenous Malformations". World Neurosurg. Luzzi, S., Del Maestro, M., Bongetta, D., Zoia, C., Giordano, A. V., Trovarelli, D., Raysi Dehcordi, S. and Galzio, R. J. 2018. "Onyx Embolization Before the Surgical Treatment of Grade III Spetzler-Martin Brain Arteriovenous Malformations: Single-Center Experience and Technical Nuances". World Neurosurg., 116: e340 - e353. https:// doi.org/10.1016/j.wneu.2018.04.203. https://www.ncbi.nlm.nih.gov/pubmed/29751183. Luzzi, S., Del Maestro, M. and Galzio, R. 2019. "Letter to the Editor. Preoperative embolization of brain arteriovenous malformations". J. Neurosurg., 1 - 2. https://doi.org/10.3171/ 2019.6.JNS191541. https://www.ncbi.nlm.nih.gov/pubmed/31812150. https://thejns.org/ view/journals/j-neurosurg/aop/article-10.3171-2019.6.JNS191541/article-10.3171-2019. 6.JNS191541.xml. Luzzi, S., Elia, A., Del Maestro, M., Morotti, A., Elbabaa, S. K., Cavallini, A. and Galzio, R. 2019. "Indication, Timing, and Surgical Treatment of Spontaneous Intracerebral Hemorrhage: Systematic Review and Proposal of a Management Algorithm". World Neurosurg., https://doi.org/10.1016/j.wneu.2019.01.016. https://www.ncbi.nlm.nih.gov/ pubmed/30677572. Luzzi, S., Gallieni, M., Del Maestro, M., Trovarelli, D., Ricci, A. and Galzio, R. 2018. "Giant and Very Large Intracranial Aneurysms: Surgical Strategies and Special Issues". Acta Neurochir. Suppl., 129: 25 - 31. https://doi.org/10.1007/978-3-319-73739-3_4. https:// www.ncbi.nlm.nih.gov/pubmed/30171310. Lawton, M. T. 2018. Seven Bypasses. edited by Lawton MT. Stuttgart: Georg Thieme Verlag. Pescatori, L., Tropeano, M. P. and Santoro, A. 2018. "Complex Aneurysm: The Unpredictable Pathological Entity". Acta Neurochir. Suppl., 129: 61 - 70. https:// doi.org/10.1007/978-3- 319-73739-3_9. https://www.ncbi.nlm.nih.gov/pubmed/ 30171315. Pisapia, J. M., Walcott, B. P., Nahed, B. V., Kahle, K. T. and Ogilvy, C. S. 2011. "Cerebral revascularization for the treatment of complex intracranial aneurysms of the posterior circulation: microsurgical anatomy, techniques and outcomes". J. Neurointerv. Surg., 3 (3): 249 - 54. https://doi.org/10.1136/jnis.2010.004176. https://www.ncbi.nlm.nih.gov/ pubmed/21990836. Ricci, A., Di Vitantonio, H., De Paulis, D., Del Maestro, M., Raysi, S. D., Murrone, D., Luzzi, S. and Galzio, R. J. 2017. "Cortical aneurysms of the middle cerebral artery: A review of the literature". Surg. Neurol. Int., 8: 117. https://doi.org/10.4103/sni.sni_50_17. https://www.ncbi.nlm.nih.gov/pubmed/28680736. Sanai, N., Zador, Z. and Lawton, M. T. 2009. "Bypass surgery for complex brain aneurysms: an assessment of intracranial-intracranial bypass". Neurosurgery, 65 (4): 670 - 83; discussion 683. https://doi.org/10.1227/01.NEU.0000348557.11968.F1. https://www.ncbi. nlm.nih.gov/pubmed/19834371.

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Straus, D. C., Brito da Silva, H., McGrath, L., Levitt, M. R., Kim, L. J., Ghodke, B. V., Barber, J. K. and Sekhar, L. N. 2017. "Cerebral Revascularization for Aneurysms in the Flow- Diverter Era". Neurosurgery, 80 (5): 759 - 768. https://doi.org/10.1093/neuros/ nyx064. https://www.ncbi.nlm.nih.gov/pubmed/28383672. Tayebi Meybodi, A., Huang, W., Benet, A., Kola, O. and Lawton, M. T. 2017. "Bypass surgery for complex middle cerebral artery aneurysms: an algorithmic approach to revascularization". J. Neurosurg., 127 (3): 463 - 479. https://doi.org/10.3171/2016.7. JNS16772. https://www.ncbi.nlm.nih.gov/pubmed/27813463. Zhu, W., Tian, Y. L., Zhou, L. F., Song, D. L., Xu, B. and Mao, Y. 2011. "Treatment strategies for complex internal carotid artery (ICA) aneurysms: direct ICA sacrifice or combined with extracranial-to-intracranial bypass". World Neurosurg., 75 (3 - 4): 476 - 84. https://doi.org/ 10.1016/j.wneu.2010.07.043. https://www.ncbi.nlm.nih.gov/pubmed/21600500.

Chapter 28

ENDOVASCULAR TREATMENTS FOR INTRACRANIAL ANEURYSMS AND DURAL ARTERIOVENOUS FISTULAS

S. Mangiafico1, MD, PhD, F. Capasso2, MD, S. Vidale3, MD, F. Incandela4, MD and A. Laiso1, MD 1Neurovascular Interventional Unit, Careggi University Hospital, Florence, Italy 2Dipartimento di scienze biomediche avanzate, Università degli studi di Napoli “Federico II,” Naples, Italy 3Neurology Unit, S. Anna Hospital, Como, Italy. 4Department of Otorhinolaryngology, Maxillofacial and Thyroid Surgery, Fondazione IRCCS, National Cancer Institute of Milan, University of Milan, Milan, Italy

INTRACRANIAL ANEURYSMS TREATMENT: INTRODUCTION

Endovascular treatment of intracranial aneurysms has become part of clinical practice since the 1990s, with the introduction of coil embolization procedures, thanks to Professor Guido Guglielmi. The randomised study ISAT (Molyneux et al. 2005) on acutely ruptured aneurysms, multicentric studies (Briganti et al. 2012) and subsequent meta-analysis on non-ruptured aneurysms (Cagnazzo et al. 2018) had demonstrated the safety and efficacy of endovascular approaches which have better clinical outcomes (lower disability and mortality rates) compared to surgery, both at discharge and at long term follow-up. Progressive technological innovation and evolution in the development of coils and endovascular access devices (bearing, intermediate and micro-catheters and micro-guides) and the introduction of new tools (remodelling balloons, stents, flow-diverting stents, intrasaccular devices and coil-supporting devices) had made the treatment of complex cases possible and and safe. The introduction in the clinical practice of Flow Diverter stents and Intrasaccular Flow Disruptor devices has further extended the possibilities of treatment in very complex aneurysms in which the rate of recurrence after coiling was not yet optimal. Nowadays, aneurysms can be approached in multiple different endovascular treatments. The right strategy is chosen basing on patients’ vascular characteristic and clinics, as well as

450 S. Mangiafico, F. Capasso, S. Vidale et al. on aneurysms morphology and operators experience with the techniques. Aim of this work is to give a synthetic description of the different endovascular treatment strategies and their possible indications.

CLINICAL FACTORS INFLUENCING ENDOVASCULAR TREATMENT STRATEGY

Before choosing the adequate endovascular treatment, it is important to discriminate between an acutely ruptured (acute sub-arachnoid haemorrhage) and a non-ruptured aneurysm. Acute sub-arachnoid haemorrhage represents a contraindication for intraluminal devices such as stents and other coil-supporting devices, due to the necessity of double anti-aggregation therapy, that has to be administered at least 10 days before the treatment. Double anti-platelet therapy given in an ‘emergency regimen’ with either a load dose of clopidogrel (4-5 capsules of 75 mg), plus aspirin (500 mg bolus) or GPIIb-IIIa inhibitors (Tirofiban) would lead to a higher treatment-related risk especially in case of intra-operatory sac rupture, or to a higher rate of incomplete embolization (due to a slower luminal thrombosis and consequent possible rebleeding) and would lead to higher risk of haemorrhagic complications (especially in the event of ventricular derivation necessity for acute hydrocephalus). Concomitant cerebral vasospasm does not represent an obstacle for embolization, since it could be treated simultaneously with the aneurysm. The severity of cerebral post-haemorrhagic clinical status, evaluated using the modified Fischer scale (Claassen et al. 2001), does not influence treatment strategy definition. In case of aneurysm’s compressive effect it should be considered that the increasing pressure due to a dense coil-packing of the treated aneurism could lead to negative effects over nerves’ functional restoration (Rizos et al. 2013). In these cases, and specially in acutely ruptured large or giant aneurysms, a partial coiling is followed by a staged intervention of flow diversion at a later time.

ANATOMICAL FACTORS THAT INFLUENCE THE CHOICE OF ENDOVASCULAR TREATMENT

Aneurysms morphology, dimensions, orientation, diameter, the overall geometry, neck width, vessel bifurcation asset, circle of Willis’ anatomical variants and epi-aortic trunks tortuosity should always be studied during the pre-operatory planning. It is crucial to assess if it’s a lateral or a bifurcation aneurysm and its precise dimensions. Lateral ones originate from a lateral wall of their parent artery and include intra-cavernous and sub-arachnoidal (supra and para-clinoid) carotid siphon aneurysms, carotid cavity aneurysms, posterior communicating artery and anterior choroid artery aneurysms; as well as vertebral artery aneurysms located at the origin of PICA (posterior inferior cerebellar artery) and basilar artery ones located at the origin of AICA (anterior-inferior cerebellar artery). Aneurysms at bifurcation of parent artery site include middle cerebral artery ones, those of anterior communicating artery with either agenesis or severe hypoplasia of the contralateral A1 tract, basilar artery and pericallosal bifurcation ones. The endovascular treatment varies according to aneurism sac dimensions, we could distinguished small (Dmax < 5 mm), medium (Dmax 5- 15 mm), large (Dmax 16 -24

Endovascular Treatments for Intracranial Aneurysms … 451 mm) and giant aneurysms (Dmax > 25 mm); we have also to consider neck width (>4 mm defines a ‘wide neck’) and neck to dome ratio (if is it inferior o superior to 1.6). The complexity of these anatomical characteristics not only influences immediate post-procedural occlusion rate but also affects the risk of major re-canalisation and re-intervention necessity. Therefore, the interventional neuro-radiologist must carefully choose the endovascular treatment to be performed not only on the basis of the immediate result (complete exclusion of the aneurysm) and safety of the procedure, but also on the stability of the occlusion rate over time.

ENDOVASCULAR TECHNIQUES

We would examine different endovascular procedures, discussing their indications based on the presence or absence of sub-arachnoid haemorrhage and on the morphological aspect of the aneurysm.

Coiling

Coiling represents the less articulated endovascular intervention to be carried out. It is indicated in all ruptured and non-ruptured small aneurysms, regardless of their position, with a neck smaller than 3 mm and a neck to dome ratio greater than 1.6. In case of a wider neck, adequate coil loops packing might be obtained using geometric shaped coils (3D or frame coils). These latter provide a scaffolding for the subsequent filling coils without shape memory. Polymer-coated coils (Hydrocoils) which increase in volume after their release and ultra-thin ones (mini-coil) might be used during the final embolization phases to stabilise the packing by making it denser, thanks to their ability to fill saccular residual empty spaces. In case of ruptured big aneurysms, coils can be simultaneously deployed using 2 different microcatheters both inside the aneurysm’s sac, so that the first coil allows the endosaccular containment of the second and the following ones (double micro-catheterism technique).

Baloon Assisted Coiling (Remodelling Technique)

This embolization technique is indicated for the treatment of wide neck lateral and bifurcation aneurysms, mainly in acute phase (Consoli et al. 2016) when the coils show the tendency to fall out of the sac and to protrude inside parent artery increasing the risk of embolic complications or late parent artery thrombosis. The balloon inflation at aneurism base allows to retrain coils inside the sac and moreover increases the stability of the micro-catheter for a better aneurysm basal filling and a final denser packing. An additional advantage is represented by the immediate haemostatic role in case of intra- operatory sac rupture. Hyper-compliant balloons are employed in the treatment of bifurcation aneurysms, in which a divisional branch of the parent artery emerges from the sac. In bifurcation aneurysms with particularly wide neck, if one single balloon results insufficient in covering both the

452 S. Mangiafico, F. Capasso, S. Vidale et al. arterial branches, it could possible to position two balloons in the bifurcation by using the “kissing balloons” technique. The effectiveness of the remodelling technique, in terms of packing stability over time, is good for aneurysms with Dmax < 7 mm. In case of bigger sacs, the recanalization rate after balloon assisted coiling goes from 10% to higher than 50% in giant aneurysms, especially if the aneurysms are oriented in the direction of the flow (van Rooij and Sluzewski 2009). Despite these limitations in large and giant acutely ruptured aneurysms balloon assisted coiling represents a valid option to avoid early rebleeding, even if the treatment must be completed later with a flow-diverter stent. It should be pointed out that this technique is associated with a higher haemorrhagic and ischemic rate compared to simple coiling, but this might be, at least partially explained, by the different grade of complexity of the aneurysms treated.

Stent-assisted Coiling

Stent assisted coiling represents the endovascular intervention carried out mainly for the treatment of non-ruptured bifurcation aneurysms smaller than 1 cm. It involves the use of a single stent inside parental artery in order to support coils’ framework. Before the treatment double anti-platelets therapy is mandatory, it must be continued for the next 3 months after the procedure. In bifurcation aneurysms where divisional branches do not originate from the sac (the so called “free neck aneurysms”) it is possible to restore bifurcation anatomy placing 1 or 2 open or closed cell stents deployed between the parental vessel and one or both divisional arterial branches. In case of decentred aneurysms with the base located on one of the divisional branches, one stent can be enough to embolise the sac. If the aneurysm has very wide neck and a single stent might be insufficient to cover the entire neck surface, 2 stents might be deployed with a “Y”, “T” or “X” configuration (Cagnazzo et al. 2019b) according with symmetry of the bifurcation, orientation of the aneurysmal sac, presence or absence of divisional branches originating from the sac. Un-ruptured bifurcation aneurysms of the middle cerebral artery, of the anterior communicating artery (with contralateral A1 agenesis) and of the basilar artery apex might be treated with Y-stent. In anterior communicating artery aneurysms, when both A1 tracts could be catheterized, 2 stents might be positioned in a ‘X’ or in “parallel” configuration. This technique compared with coiling and balloon-assisted coiling, presents a lower recurrence rate but slightly higher peri-operatory ischemic complications’ rate (Figure 1).

Intrasaccular and Intravascular Devices-Assisted Coiling

Bifurcation aneurysms with complex morphologies, in which one of the divisional arterial branches arises forming an angle >90°, or directly from the aneurysm, might be embolised with the support of intrasaccular-intravascular stent-derived devices, such as pCONus e PulseRider (Valente et al. 2018), that allow to avoid a double stent deployment. These systems are supposed to be released inside the parent artery, below the bifurcation, with their distal wings, positioned either on the bifurcation, or completely\partially inside the sac. Pulse Rider was

Endovascular Treatments for Intracranial Aneurysms … 453 demonstrated to be a safer option compare to Y-stenting technique, but it is also associated with a slightly higher recanalization rate (Valente et al. 2018). Purely intra-saccular devices, such as the Woven EndoBridge Device (WEB) might as well be chosen: these nitinol wires nest-shaped systems are supposed to be opened inside the sac where they modify the dynamics of the incoming flow (flow disruption) and determine rapid thrombosis (Limbucci et al. 2018). Moreover, realising them just inside the sac, without any intra-arterial anchoring extremity, no dual anti-platelets therapy is needed. (Figure 2)

Figure 1. Incidental aneurysm of AcoA in 45 y.o.woman, before and after stent assisted coiling (Y-STENT).

Figure 2. AcoA aneurysm in a 49 y.o. man, who underwent Neuroradiological exams for a thunderclap headache. Due to symptoms and to morphological features (irregular wall), a WEB was realised into the sac, without the necessity of anti-platelets therapy.

Flow-diverting Stents Lateral Aneurysms

Flow diverters have structural features quite similar to the braided stents, in which about 48 -64 wires are framed in order to give dense meshes and micro-cells with a high metallic

454 S. Mangiafico, F. Capasso, S. Vidale et al. coating and a low porosity. These devices should be deployed inside the parent vessel covering the site of aneurismal neck, so that they divert flow from the sac into the parent artery, therefore inducing hemodynamic modifications characterized by aneurysm’s hypoperfusion, wall shear stress modifications and progressive intrasaccular thrombosis until the complete exclusion at the angiographic study with an occlusion rate of 95% in 3-12 months after endovascular treatment (D'Urso et al. 2011). Flow diverters are mainly employed for non-ruptured saccular- lateral aneurysms bigger than 1 cm located at the carotid siphon or along the basilar artery (Cagnazzo et al. 2019a). A good selection of eligible patients allows to obtain high long-term efficacy rate (95%) with ischemic and haemorrhagic complications ratios comparable to those of the above-mentioned embolization techniques. Big and giant aneurysms treated with this technique could present a 1% late saccular rupture for wall tearing, due to fresh thrombus formation and related parietal inflammatory phenomena (Kulcsar et al. 2011). In order to reduce this severe complication, in giant aneurysm, it would be better to carry out endovascular treatment in two steps: first with a loss saccular coil packing, then after 6 months, when the clot has already turned into an inert form due to its fibroblastic transformation, completing the treatment with the placement of a flow diverting stent. It should be pointed out that the presence of ophthalmic or posterior communicating artery originating from the sac, should delay sac occlusion. In case of incomplete therapeutic response after 2 years from the flow diversion, the additional coaxial implantation of other flow diverters is recommended: these ulterior stents allow a more intense flow redirection and progressively lead to total saccular occlusion (Hodis et al. 2016). Compared to lateral aneurysms, flow diversion in bifurcation aneurysms has not yet proven to be an adequate treatment option, due to a lower occlusion and higher ischemic complications rate, this last, mainly determined by the covering of a divisional arterial branches, which may lead to territorial hypoperfusion (Briganti et al. 2012; D'Urso et al. 2011)(2,11). However, in case of bifurcation aneurysms that are not eligible for other endovascular treatments or surgical intervention, flow diversion might be considered as a plausible therapeutic approach (Figure 3)

Table 1. Comparison Between Endovascular Embolization Techniques Outcomes and Complication Rate

Results Pubblished by Interventional Neurovascular Team of Careggi Between 2015 and 2019 (Briganti et al. 2012; Cagnazzo et al. 2018; Consoli et al. 2016; Cagnazzo et al. 2019b; Valente et al. 2018; Limbucci et al. 2018; Cagnazzo et al. 2019) Incomplete Embolization Occlusion Thromboembolic Hemorragic Morbidity Mortality Techniques At 6 Mo. Complications Complications F.U. (<80%) Rt 11,1% 0,6% 4,6% 2% 2,6% Fd 15% 6% 3% 3,5% 2,5% Stent-Assisted 5,8% 0,8% 3,4% 0,8% 1,7% Y-Stent 3% 6,5% 2% 2,4% 1,1% Web 12,5% 0% 0% 0% 4%

Endovascular Treatments for Intracranial Aneurysms … 455

DURAL ARTERIOVENOUS FISTULA TREATMENT: INTRODUCTION

Dural Arteriovenous Fistulas are acquired vascular “malformations” with un unknown aetiology, or secondary due to thrombophilic state, phlogistic or traumatic processes, in which multiple dural arteriovenous shunts develop without the interposition of a disembryogenetic nidus. DAVFs are almost exclusively supplied by meningeal arteries, they can also receive afferences from muscle-cutaneous arteries arising from the external carotid artery (osteodural DAVF) and very rarely from intracranial pial branches. Venous drainage can be through Dural sinuses or leptomeningeal bridging veins or by a combined reflux system between sinus and cortical veins. DAVF represent 10-15% of all endocranial vascular malformations, are diagnosed mostly in middle aged patients (50-60 years), with an incidence of 0.16 /100,000 inhabitants. They can be silent or symptomatic, presenting with tinnitus, headache, neurological deficits and intracranial bleedings.

ETIOPATOGENESIS

Intradural AV fistulas develop following inflammatory phenomena of the dura (neo angiogenesis) at the connection between subcutaneous emissary veins - dural sinus and lacunae. The inflammatory process leads to an initial AV shunt, between the dural feeders and dural sinus or cortical veins, thus the resulting hyperflux is followed by thrombosis of the emissary vein, stenosis or by septa organisation with partial or total dural sinus thrombosis. In other cases, bridging vein thrombosis in the intradural tract blocks shunt flow towards the dural sinus and directs it exclusively towards meningeal veins, in which hemodynamic stress causes accentuated varicosities and tortuosity.

CLINICAL PRESENTATION OF DAVF

The clinical presentation of DAVF depends on vascular architecture and anatomical localization. DAVFs draining anterogradely into a dural sinus (i.e., drainage into the transverse sinus with normal efflux into the ipsilateral jugular vein without CVD) usually present with non-aggressive symptoms such as headaches, pulsatile tinnitus, and bruits. Severe clinical manifestations occur in case of direct or indirect involvement of cortical veins (the latter is due to blood reflux from dural sinus to cortical veins) that can be limited to a single vein or extended to more venous territories with signs of focal or regional venous hypertension followed by focal neurological deficits due to intracerebral haemorrhage or venous ischemia. When shunt flow involves the entire cerebral venous circulation, progressive cerebral congestion develops, with consequent cognitive decay and pseudotumor cerebri (Willinsky et al. 1999). While assessing therapeutic indications, it is important to evaluates the natural history of the different types of AVF: when venous flow is exclusively orthodromic to the sinus, there is no haemorrhagic risk and therefore treatment is generally avoided or minimally invasive; on the other hand when there is a cortical venous reflux (risk of haemorrhage is 6%) or exclusive leptomeningeal drainage (risk of haemorrhage is 10%) a correct therapeutic planning must be

456 S. Mangiafico, F. Capasso, S. Vidale et al. defined (Gross, Ropper, and Du 2012). In case of varicose dilation of the draining veins, bleeding risk raises up to 8.1%. Cortical venous drainage is associated with 6.9% risk of non- ischemic neurological deficits (NHND) and venous ectasia has an annual rate of combined events of 15%. According to some authors, after a first bleeding episode, the risk of a new haemorrhage raises to 35% (Elhammady, Ambekar, and Heros 2017). The haemorrhagic events occur mainly in male population (86%) among those sudden onset headaches represents the most common presentation symptom. In these cases, DAVFs had cortical venous drainage, and about one-third were associated with a venous varix. The most common location was the tentorial one (75%) (Daniels et al. 2013). Untreated cortical- drainage dural fistulas have poor prognosis, with bleeding and focal neurological deficits rates respectively of 7.4% and 1.5% at 5 years. Fistula’s location and clinical manifestations are strictly connected (van Dijk et al. 2002): transverse sigmoid sinus and middle cerebral fossa (MFC) DAVF are associated with pulsatile tinnitus, while carotid-cavernous DAVF with exophthalmos, conjunctival chemosis and extrinsic oculomotor function deficit. Those of the anterior cranial fossa (ACF) and of the tentorium are more often asymptomatic or manifest with haemorrhages. Fistulas developing in the posterior cranial fossa (PCF) associated with varicosities, may present with trigeminal neuralgia, oculomotor and VII cranial nerve deficits secondary to neurovascular conflicts, while those of the superior longitudinal sinus can cause focal neurological deficits or seizures. Finally, spinal skull passage and deep venous drainage ones are associated respectively with progressive medullary symptoms, thalamic venous hypertension plus dementia (R. Spetzler 2017).

Table 2. FAVD Classifications Based on Venous Drainage

Djindjian-Merland Cognard Border TYPE (Djindjian et al. 1973) (Cognard et al. 1995) (Borden, Wu, and Shucart 1995) Direct venous drainage into Direct venous drainage Direct venous drainage into dural I dural sinus with anterograde into dural sinus with sinus or into a meningeal vein flow anterograde flow IIa: venous drainage with retrograde flow into dural sinus Venous drainage into dural IIb: venous drainage with Venous drainage inside dural sinus with retrograde flow retrograde flow into one sinus or meningeal vein with II either into the adjacent sinus or more cortical veins retrograde flow into sub- or inside a cortical vein IIa+b: venous drainage arachnoidal veins with retrograde flow into both dural sinus and inside a cortical vein Venous drainage into a Venous drainage with Venous drainage inside subcortical vein with retrograde retrograde flow into one arachnoidal veins without dural III flow or more cortical veins sinus or meningeal vein without venous ectasias involvement Venous drainage into a Venous drainage inside an IV cortical vein with venous ectasic venous pouch ectasias and varicosities Perispinal venous V drainage

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Figure 3. Incidental finding of carotid-ophthalmic aneurysm in 50 y.o. woman before and after flow diverter implantation at the 6 months follow-up.

Figure 4. Superior Sagittal Sinus FAVD (Cognard III type) in 70 y.o. man with tinnitus and vertigo. Onyx embolization of the FAVD is controlled by using venous Remodelling technique by putting a balloon in the SSS, which prevents the dispersion of embolizing material and allow to close fistula points.

458 S. Mangiafico, F. Capasso, S. Vidale et al.

CLASSIFICATIONS

Many authors have been proposed over the years different DAVF classification systems, but the most important and used ones, which focussing on natural history, bleeding risk and treatment indications, are: the Djindjian - Merland (1978), the Cognard et al. (1995) and the Borden et al. classification (1995). These three are based on the morphological and dynamic characteristics of the DAVF venous drainage (see table below). Other classifications are based on Dural embryological origin (Lasjunias - Tanaka), on shunt characteristics such as direct- indirect shunt setting, if it is exclusive or not, and on the presence or not of haemodynamic overload.

ENDOVASCULAR TREATMENTS

The Basis of Treatment

For a better intervention planning, fistulas should be distinguished in 2 groups:

 Sinus DAVF: dural fistulas deriving from dural sinuses with primitive sinus drainage (Borden I and II, Cognard 1, 2 a, 2b, 2 a + b) in which healing is obtained occluding the fistulous dural sinus segment;  Non sinus DAVF: dural fistulas with exclusive leptomeningeal cerebral and / or medullary drainage (Borden 3 and Cognard 3-5) in which endovascular or surgical occlusion of the dural sinus is the target of the intervention.

In addition to these, it should be considered other two subgroups:

a) dural fistulas located at the site of “excluded sinus,” which consists in sinuses occluded both proximal and distal to the fistula. In these cases, despite fistula’s drainage consisting in leptomeningeal venous branches only, healing is provided by the pervious sinus’ endovascular exclusion; b) fistulas located on the dural sinus wall at the junction with a bridging leptomeningeal vein which is still connected with the sinus itself. With these characteristics the endovascular occlusion of the bridging vein origin must be accompanied by the maintenance of sinus patency (venous remodelling technique consisting in transarterial injection of embolizing agents with a balloon temporarily occluding the sinus, see the figure below).

Treatment Planning and Endovascular Intervention

For a correct therapeutic planning it is necessary to:

a) localize the dural fistula and the origin of the emissary vein;

Endovascular Treatments for Intracranial Aneurysms … 459

b) consider whether the dural sinus, that has to be embolised, also receives functional cerebral vein for cerebral venous discharge; in this case the occlusion should not interfere with normal venous drainage.

During embolization, all dural afferences to the fistula must be detected, in order to verify their complete exclusion at the end of the procedure. The feeder to be chosen for the embolization should be the smallest and more distal one both from the anastomosis with functional arteries (i.e., cerebro ocular) and from the origin of cranial nerves arteries. The endovascular fistula’s disconnection from cerebral venous circulation can be obtained with:

1) trans-arterial embolization (passage of Onyx on the venous side of the Fistula); 2) trans-venous embolization, navigating retrogradely either the dural sinus or the drainage vein.

Trans-arterial embolization with non-adhesive liquid agents is indicated in all types of fistulas, especially in those with an exclusive leptomeningeal drainage (Borden 3 and Cognard 3-5) in which venous navigation results generally difficult. It is performed injecting nonadhesive liquid agents from one or more meningeal afferences, with the possibility to use the “pressure cooker” technique in case of feeders located far from dangerous anastomoses. Trans venous embolization is indicated for DAVF with sinus drainages (Borden 1 and 2 and Cognard 2) when the arterial way is risky for the presence of dangerous anastomoses, short dural feeders emerging from the carotid siphon or from the vertebral artery, or for the presence of neuromeningeal arteries. Trans-venous treatment consists in filling the Dural sinus with coil with subsequent injection of acrylic glue to seal the occlusion. In case of DAVF with cortical drainages trans-venous way is adopted only if navigation appears to be easily performed. In extremely large and complex fistulas, when more than one procedure is required to complete the treatments, both embolization techniques can be used. Sinus fistulas with cortical reflux (Borden 2) are all treated endovascularly. Those showing to have only an exclusive leptomeningeal drainage can be treated both surgically and endovascularly without substantial differences in terms of success and complications. Embolization is generally preferred when fistulas are quite large or difficult to reach by surgery, while surgery is generally chosen in the event of concomitant dangerous anastomoses.

REFERENCES

Borden, J. A., J. K. Wu, and W. A. Shucart. 1995. “A proposed classification for spinal and cranial dural arteriovenous fistulous malformations and implications for treatment.” J Neurosurg 82 (2): 166-79. https://doi.org/10.3171/jns.1995.82.2.0166. https://www. ncbi.nlm.nih.gov/pubmed/7815143. Briganti, F., M. Napoli, F. Tortora, D. Solari, M. Bergui, E. Boccardi, E. Cagliari, L. Castellan, F. Causin, E. Ciceri, L. Cirillo, R. De Blasi, L. Delehaye, F. Di Paola, A. Fontana, R. Gasparotti, G. Guidetti, I. Divenuto, G. Iannucci, M. Isalberti, M. Leonardi, F. Lupo, S. Mangiafico, A. Manto, R. Menozzi, M. Muto, N. P. Nuzzi, R. Papa, B. Petralia, M. Piano,

460 S. Mangiafico, F. Capasso, S. Vidale et al.

M. Resta, R. Padolecchia, A. Saletti, G. Sirabella, and L. P. Bolge. 2012. “Italian multicenter experience with flow-diverter devices for intracranial unruptured aneurysm treatment with periprocedural complications--a retrospective data analysis.” Neuroradiology 54 (10): 1145-52. https://doi.org/10.1007/s00234-012-1047-3. https:// www.ncbi.nlm.nih.gov/pubmed/22569955. Cagnazzo, F., D. T. di Carlo, M. Cappucci, P. H. Lefevre, V. Costalat, and P. Perrini. 2018. “Acutely Ruptured Intracranial Aneurysms Treated with Flow-Diverter Stents: A Systematic Review and Meta-Analysis.” AJNR Am J Neuroradiol 39 (9): 1669-1675. https://doi.org/10.3174/ajnr.A5730. https://www.ncbi.nlm.nih.gov/pubmed/30049721. Cagnazzo, F., N. Limbucci, S. Nappini, L. Renieri, A. Rosi, A. Laiso, D. Tiziano di Carlo, P. Perrini, and S. Mangiafico. 2019a. “Flow-Diversion Treatment of Unruptured Saccular Anterior Communicating Artery Aneurysms: A Systematic Review and Meta-Analysis.” AJNR Am J Neuroradiol 40 (3): 497-502. https://doi.org/10.3174/ajnr.A5967. https://www. ncbi.nlm.nih.gov/pubmed/30765379. ---. 2019b. “Y-Stent-Assisted Coiling of Wide-Neck Bifurcation Intracranial Aneurysms: A Meta-Analysis.” AJNR Am J Neuroradiol 40 (1): 122-128. https://doi.org/10.3174/ajnr. A5900. https://www.ncbi.nlm.nih.gov/pubmed/30523146. Claassen, J., G. L. Bernardini, K. Kreiter, J. Bates, Y. E. Du, D. Copeland, E. S. Connolly, and S. A. Mayer. 2001. “Effect of cisternal and ventricular blood on risk of delayed cerebral ischemia after subarachnoid hemorrhage: the Fisher scale revisited.” Stroke 32 (9): 2012-20. https://doi.org/10.1161/hs0901.095677. https://www.ncbi.nlm.nih.gov/pubmed/ 11546890. Cognard, C., Y. P. Gobin, L. Pierot, A. L. Bailly, E. Houdart, A. Casasco, J. Chiras, and J. J. Merland. 1995. “Cerebral dural arteriovenous fistulas: clinical and angiographic correlation with a revised classification of venous drainage.” Radiology 194 (3): 671-80. https://doi.org/10.1148/radiology.194.3.7862961. https://www.ncbi.nlm.nih.gov/pubmed/ 7862961. Consoli, A., C. Vignoli, L. Renieri, A. Rosi, I. Chiarotti, S. Nappini, N. Limbucci, and S. Mangiafico. 2016. “Assisted coiling of saccular wide-necked unruptured intracranial aneurysms: stent versus balloon.” J Neurointerv Surg 8 (1): 52-7. https://doi.org/ 10.1136/neurintsurg-2014-011466. https://www.ncbi.nlm.nih.gov/pubmed/25428449. D'Urso, P. I., G. Lanzino, H. J. Cloft, and D. F. Kallmes. 2011. “Flow diversion for intracranial aneurysms: a review.” Stroke 42 (8): 2363-8. https://doi.org/10.1161/STROKEAHA. 111.620328. https://www.ncbi.nlm.nih.gov/pubmed/21737793. Daniels, D. J., A. K. Vellimana, G. J. Zipfel, and G. Lanzino. 2013. “Intracranial hemorrhage from dural arteriovenous fistulas: clinical features and outcome.” Neurosurg Focus 34 (5): E15. https://doi.org/10.3171/2013.4.FOCUS1335. https://www.ncbi.nlm.nih.gov/pubmed/ 23634919. Djindjian, R., J. J. Merland, A. Rey, J. Thurel, and R. Houdart. 1973. “[Super-selective arteriography of the external carotid artery. Importance of this new technic in neurological diagnosis and in embolization].” Neurochirurgie: 165-71. https://www.ncbi.nlm.nih.gov/ pubmed/4747296. Elhammady, M. S., S. Ambekar, and R. C. Heros. 2017. “Epidemiology, clinical presentation, diagnostic evaluation, and prognosis of cerebral dural arteriovenous fistulas.” Handb Clin Neurol 143: 99-105. https://doi.org/10.1016/B978-0-444-63640-9.00009-6. https://www. ncbi.nlm.nih.gov/pubmed/28552162.

Endovascular Treatments for Intracranial Aneurysms … 461

Gross, B. A., A. E. Ropper, and R. Du. 2012. “Cerebral dural arteriovenous fistulas and aneurysms.” Neurosurg Focus 32 (5): E2. https://doi.org/10.3171/2011.12.FOCUS11336. https://www.ncbi.nlm.nih.gov/pubmed/22537128. Hodis, S., Y. H. Ding, D. Dai, R. Lingineni, F. Mut, J. Cebral, D. Kallmes, and R. Kadirvel. 2016. “Relationship between aneurysm occlusion and flow diverting device oversizing in a rabbit model.” J Neurointerv Surg 8 (1): 94-8. https://doi.org/10.1136/neurintsurg-2014- 011487. https://www.ncbi.nlm.nih.gov/pubmed/25387731. Kulcsar, Z., E. Houdart, A. Bonafe, G. Parker, J. Millar, A. J. Goddard, S. Renowden, G. Gal, B. Turowski, K. Mitchell, F. Gray, M. Rodriguez, R. van den Berg, A. Gruber, H. Desal, I. Wanke, and D. A. Rufenacht. 2011. “Intra-aneurysmal thrombosis as a possible cause of delayed aneurysm rupture after flow-diversion treatment.” AJNR Am J Neuroradiol 32 (1): 20-5. https://doi.org/10.3174/ajnr.A2370. https://www.ncbi.nlm.nih.gov/pubmed/ 21071538. Limbucci, N., G. Leone, A. Rosi, A. Consoli, L. Renieri, A. Laiso, C. Cirelli, A. Wlderk, S. Nappini, and S. Mangiafico. 2018. “Endovascular Treatment of Unruptured Intracranial Aneurysms by the Woven EndoBridge Device (WEB): Are There Any Aspects Influencing Aneurysm Occlusion?” World Neurosurg 109: e183-e193. https://doi.org/10.1016/ j.wneu.2017.09.136. https://www.ncbi.nlm.nih.gov/pubmed/28966153. Molyneux, A. J., R. S. Kerr, L. M. Yu, M. Clarke, M. Sneade, J. A. Yarnold, P. Sandercock, and Group International Subarachnoid Aneurysm Trial Collaborative. 2005. “International subarachnoid aneurysm trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion.” Lancet 366 (9488): 809-17. https://doi.org/10.1016/S0140-6736(05)67214-5. https://www. ncbi.nlm.nih.gov/pubmed/16139655. R. Spetzler, K. Moon, R. O. Almefty. 2017. Handbook of Clinical Neurology. Arteriovenous and Cavernous Malformations, Volume 143. Elsevier. Rizos, T., N. Dorner, E. Jenetzky, M. Sykora, S. Mundiyanapurath, S. Horstmann, R. Veltkamp, S. Rohde, M. Bendszus, and T. Steiner. 2013. “Spot signs in intracerebral hemorrhage: useful for identifying patients at risk for hematoma enlargement?” Cerebrovasc Dis 35 (6): 582-9. https://doi.org/10.1159/000348851. https://www.ncbi.nlm. nih.gov/pubmed/23859836. Valente, I., N. Limbucci, S. Nappini, A. Rosi, A. Laiso, and S. Mangiafico. 2018. “Enterprise Deployment Through PulseRider To Treat Anterior Communicating Artery Aneurysm Recurrence.” World Neurosurg 110: 158-161. https://doi.org/10.1016/j.wneu.2017.11.024. https://www.ncbi.nlm.nih.gov/pubmed/29155064. van Dijk, J. M., K. G. terBrugge, R. A. Willinsky, and M. C. Wallace. 2002. “Clinical course of cranial dural arteriovenous fistulas with long-term persistent cortical venous reflux.” Stroke 33 (5): 1233-6. https://doi.org/10.1161/01.str.0000014772.02908.44. https://www. ncbi.nlm.nih.gov/pubmed/11988596. van Rooij, W. J., and M. Sluzewski. 2009. “Endovascular treatment of large and giant aneurysms.” AJNR Am J Neuroradiol 30 (1): 12-8. https://doi.org/10.3174/ajnr.A1267. https://www.ncbi.nlm.nih.gov/pubmed/18719032. Willinsky, R., M. Goyal, K. terBrugge, and W. Montanera. 1999. “Tortuous, engorged pial veins in intracranial dural arteriovenous fistulas: correlations with presentation, location,

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and MR findings in 122 patients.” AJNR Am J Neuroradiol 20 (6): 1031-6. https://www. ncbi.nlm.nih.gov/pubmed/10445439.

Chapter 29

PREOPERATIVE EMBOLIZATION OF BRAIN ARTERIOVENOUS MALFORMATION

S. Luzzi1,2,, MD, PhD, M. Del Maestro2,3, MD, A. Giotta Lucifero1, MD and R. Galzio1,2, MD 1Neurosurgery Unit, Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy 2Neurosurgery Unit, Department of Surgical Sciences, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy 3PhD School in Experimental Medicine, Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy

ABSTRACT

In this chapter, we discuss the key aspects regarding the preoperative embolization of brain arteriovenous malformation, especially Spetzler–Martin grade III, focusing on the factors affecting the indications and technical aspects. Preoperative embolization is performed to occlude the main arterial feeders but not the shunt. Onyx is largely preferred for this purpose because of its tropism for arteries and manageability. Superselective catheterization of the feeders and understanding of the vascular compartmentalization of the nidus are paramount factors on which to establish the treatment targets. Not involving the shunt, preoperative embolization is associated with a risk of early recruitment of new feeders, justifying the need for a limited time frame between embolization and surgery. Our long-term experience has led to the selection of staged, rather than single-stage, embolization to allow a slower rearrangement of the flow within the nidus and obtain consequent lower risk of bleeding. In our series, preoperative embolization has provided a substantial contribution to surgery, ultimately allowing for an easier and safe removal of the nidus. While unaffecting the volume, Onyx embolization implements an advantageous functional vascular downgrading of the AVM.

Keywords: AVM, Brain Arteriovenous Malformation, Cyanoacrylates, Embolization, Onyx

 Corresponding Author’s Email: [email protected].

464 S. Luzzi, M. Del Maestro, A. Giotta Lucifero et al.

1. INTRODUCTION

Brain arteriovenous malformations (AVMs) have an annual hemorrhage risk rate of 4% and overall mortality rate of 18% (Natarajan et al. 2008; Darsaut et al. 2011). The spectrum of possible treatments for brain AVMs encompasses microneurosurgery, catheter-based embolization, and radiosurgery. Although the indication for microneurosurgery for grade I–II Spetzler–Martin (SM) malformations (Pandey et al. 2012; Robert F Spetzler and Ponce 2011; Schramm et al. 2017; R F Spetzler and Martin 1986; M.T. Lawton et al. 2010; MG 1987, 1988) and conservative treatment for grade IV–V malformations (Darsaut et al. 2011; Nataraj; R.F.a.P.F.A. Spetzler 2011) is unclear, grade III lesions fall into a gray zone, where a combined endovascular-surgical approach is the best option (Natarajan et al. 2008; Schramm et al. 2017; Robert F Spetzler and Ponce 2011; M.T.a. Lawton 2003). Preoperative embolization allows for vascular functional downgrading of the lesion, easier nidus dissection, reduced blood loss, and, ultimately, better outcome in all but medium-eloquent grade III AVMs (Pandey et al. 2012; Gross, Moon, and Mcdougall 2017; F Vinuela, Duckwiler, and Guglielmi). Appropriate planning of the treatment strategy and extensive knowledge of the technical key aspects of preoperative embolization are the foundation of correct management of these difficult lesions.

2. METHODS

2.1. Key Factors Affecting the Indication for Preoperative Embolization

2.1.1. Patient-Related Factors Patients with life-threatening intracerebral hematoma are not candidates for preoperative embolization. In these cases, the indication for surgery should be based on a management algorithm regarding intracerebral hemorrhage (S. Luzzi, Elia, Del Maestro, Morotti, et al. 2019). In adults, no age limitations have been reported, although the frequent finding of atheromatous conditions of the supra-aortic trunks in older patients often precludes the navigability of these vessels. Good results after various combinations of surgery and endovascular and radiosurgery techniques have also been reported in pediatric patients (Darsaut et al. 2011; Soltanolkotabi et al. 2013). As a rule, patients with a moderate to long life expectancy and no prohibitive comorbidities are good candidates for treatment, especially those with supratentorial AVMs.

2.1.2. Angioarchitectural Factors The AVM’s site and size, number of arterial feeders and draining veins, SM grade, presence of intranidal or flow-related aneurysms, and evidence of vascular supply by lenticulostriate or thalamostriate perforating arteries affect the choice of embolization. Preoperative embolization is useful and safe in grade III AVM, making this its major indication (Pandey et al. 2012; Abecassis et al. 2017). A punctual type definition of grade III AVMs, as proposed by Lawton (M.T.a. Lawton 2003), is mandatory before determining which grade III types may benefit from a combined endovascular-surgical treatment.

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Table 1. Identification Criteria for Type Definition of Grade III Arteriovenous Malformations According to the Spetzler–Martin Grading System

Size Involvement of Type of Grade III Type (cm) Eloquent Area Venous Drainage <3 Yes Deep I (S1E1V1) 3–6 No Deep II (S2E0V1) 3–6 Yes Superficial III (S2E1V0) >6 No Superficial IV (S3E0V0) S: size; E: eloquent area; V: venous drainage.

Table 1 shows the identification criteria for type definition of grade III AVMs according to the SM grading system. Preoperative embolization is recommended in all but “medium-eloquent” (type III, Grade III+, S2E1V0) malformations, for which a conservative treatment is suggested because of a surgical risk similar to that of high-grade AVMs (M. T. Lawton and Project 2003). Evidence of bleeding and finding of angiographic features considered at high risk for bleeding are additional treatment indications. Flow-related or intranidal aneurysms and stenosis of the straight sinus or vein of Galen AVMs are independent predictors of bleeding (Viuela 1985; Valavanis 1996). Studies reported that preoperative embolization should be considered in the presence of difficult-to-access deep arterial feeders or direct feeders by perforating arteries that lead to more difficult and less safe surgery (Pandey et al. 2012; Abecassis et al. 2017).

2.1.3. Treatment-Related Factors The indication for a combined treatment of brain AVM must involve a critical evaluation of the intrinsic complexity of the proposed treatment, which ultimately results from the exponential effect of the well-defined morbidity and mortality in each arm. Neither microneurosurgery nor endovascular embolization nor radiosurgery is free from potential complications. Indeed, preoperative embolization may even seriously increase the risk of hemorrhage, normal perfusion pressure breakthrough (NPPB), and further hemodynamic complications. The overall risk of the proposed treatment derives from the sum of the risks of each single treatment arm.

2.2. Rationale and Definition of the Treatment Targets

Preoperative embolization of brain AVM aims to decrease the risk of intraoperative NPPB and occlusion of deeper arterial feeders (Gross, Moon, and Mcdougall 2017; A. Pasqualin et al. 2014; F.a.D.G.a.G.G. Vinuela; F. Vinuela, Duckwiler, and Guglielmi 1997; Hurst et al. 1995). Lariboisière et al. stressed the need for a clear distinction between “proximal” preoperative and distal “therapeutic” embolization, with the latter intended to be a curative treatment (Houdart E. 2017). Basically, preoperative embolization is “proximal” embolization, consisting of occlusion of the main arterial feeders to temporarily reduce the flow to the shunt. As a consequence, draining veins will not be intentionally involved, and the shunt will not be the target (Houdart E. 2017). Not having the shunt as target, “proximal” embolization is

466 S. Luzzi, M. Del Maestro, A. Giotta Lucifero et al. obviously associated with a lower complication rate but a higher risk of early-onset recruitment of new feeders.

2.3. Planning

The paramount starting point in the planning of preoperative embolization is a detailed angiographic study of the AVM. Superselective microcatheterization of the main arterial feeders is paramount to understanding the exact compartmentalization of the lesion (Valavanis 1996). It obtains an insight on nidal features, type of arteriovenous shunts, pattern of venous drainage, associated arterial and venous high-flow angiopathy, perinidal angiogenesis, and presence of high-risk features of bleeding. A precise calculation of the nidal volume before the first embolization session is recommended to estimate the achieved obliteration rate at the completion of embolization (A.a.B.G.a.C.F.a.R.L.a.S.R.a. Pasqualin 1991). The overall treatment strategy and targets of embolization should be the result of a full cooperation between neurosurgeons and interventional neuroradiologists within a consolidated neurovascular team. Ever since, this process involves the selection of the number and type of arterial feeders to embolize, type of liquid embolic agent, number of embolization procedures, time frame between embolization sessions, and time to surgical resection after embolization. Despite being implemented with the aim to reduce the risk of NPPB secondary to single- stage surgery, preoperative embolization is paradoxically burdened by the same complication because of induced prompt alterations of the high-flow arteriovenous shunts inside the nidus (Baharvahdat et al. 2014; Crowley et al. 2015; Jayaraman et al. 2008; Ledezma et al. 2006). The risk of these potentially catastrophic complications must be minimized throughout the pursuit of a slow and progressive but acute vascular occlusion of the AVM by an equal decrease in the blood flow inside the nidus, leading to “staged” embolization. Because of the well-known risk of recruitment of new feeders, the effects of proximal preoperative embolization are classically considered. The existing delicate balance between the risk of NPPB and recruitment of new feeders imposes a scheduled time frame between embolization sessions and between the last embolization and surgical procedure, which consists of 2–3 weeks and 2–7 days, respectively (Del Maestro et al. 2018; S. Luzzi, Del Maestro, et al. 2018; Pandey et al. 2012; Abecassis et al. 2017). The first embolization session should aim to treat the core of the nidus, achieving the maximum but safest nidal volume obliteration possible. Further sessions will have the peripheral parts of the malformation as targets.

2.4. Embolic Agents

2.4.1. Cyanoacrylates Cyanoacrylates are liquid injectable glues that polymerize when in contact with an ionic environment, such as blood, and ultimately occlude the feeders. Polymerization of cyanoacrylates occurs within seconds. It can be delayed by dilution with Lipiodol at various desired concentrations. Lipiodol also acts as an opacifying agent. Given the rapidity of the polymerization process, opacification of cyanoacrylates is necessary for prompt microcatheter

Preoperative Embolization of Brain Arteriovenous Malformation 467 withdrawal. The capacity to perfectly fill small vessels and ability to immediately occlude them make cyanoacrylates the agents of choice for curative embolization (Houdart E. 2017). However, their rapid polymerization kinetics imposes a high level of dexterity, reducing their manageability.

2.4.2. Dimethyl Sulfoxide (DMSO)-Based Liquid Embolic Agents Onyx (Micro Therapeutics, Inc., eV3, Irvine, CA) and Squid (Balt Extrusion, Montmorency, France) are the most commonly employed agents, although some agents such as Menox (Meril Life Sciences, India Pvt. Ltd.) and PHIL (MicroVention, USA) have some advantages over the first-generation DMSO-based liquid embolic agents. Onyx is a nonabsorbable liquid agent consists of an ethylene–vinyl alcohol copolymer–DMSO compound. Tantalum powder is needed for angiographic visualization. Onyx 18, also known as “low-density” Onyx, and Onyx 34 differ in the proportion of polymer and solvent (DMSO). Onyx was first employed for AVMs in 1990 (Terada et al. 1991; Taki) and soon proved to be superior to cyanoacrylates for preoperative “proximal” embolization of brain AVMs because of its versatility (Crowley et al. 2015). Onyx does not involve a real polymerization process but rather settling of the copolymer within the solvent (DMSO), which ultimately causes vessel occlusion. Because of the high power of DMSO, Onyx can be used only with DMSO- compatible microcatheters, including MarathonTM (EV3, Medtronic), ApolloTM (EV3, Medtronic), and Sonic (Balt). Onyx has tropism for the arterial compartment, justifying the typical reflux observed in the arterial lumen after the first cast and the typical trapping of the catheter’s tip. In fact, new-generation catheters have detachable tips, aiding in the retrograde release of the Onyx, thus avoiding catheter adhesion. As a rule, the free microcatheter technique described above is generally used for proximal embolization, instead of the more complex trapped catheter technique (also referred to as “pressure cooker technique”) reserved for curative embolization (Chapot et al. 2014). The aforementioned tropism for arteries makes Onyx dangerous when working extremely close to small-caliber arterial vessels. This is the main reason that cyanoacrylates, Glubran® 2 (GEM), are recommended in case of embolization involving small arteries (Houdart E. 2017). Apart from these rare cases, low-density Onyx is, to date, the preferred embolic agent for preoperative embolization.

2.4.3. Injectable Coils and Particles Platinum flow microcoils (SPIF, Balt), polyvinyl alcohol particles, and spherical particles are solid embolic agents previously employed for AVM embolization. Presently, the role of microcoils is reserved for making a plug to trap the distal end of the detachable tip catheter within the aforementioned free microcatheter embolization technique. Flow microcoils have variable lengths and extremely small diameter, leading to their release through microcatheters. They can be used in both arterial and venous vessels as adjunct to cyanoacrylates or Onyx- based embolization to limit the distal migration of the liquid agent. Particles have been definitely abandoned because they require larger and stiffer microcatheters, potentially damaging the vessel wall. Their long-term effectiveness has also been proved to be poor (Sorimachi et al. 1999). Table 2 presents the characteristics of the main embolic agents used for preoperative embolization of brain AVMs.

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Table 2. Characteristics of Main Embolic Agents Used for Preoperative Embolization of Brain Arteriovenous Malformations

Main Use in Embolic Agents Kinetic AVMs Advantages Shortcomings Embolization Required high level Rapid Liquid state of dexterity due to Cyanoacrylates polymerization capacity to the rapid (few N-butyl-cyanoacrylate when in contact Therapeutic perfectly fill seconds) Histoacryl®, Braun with an ionic embolization feeding arteries. polymerization Glubran® 2 GEM environment, Instant occlusive kinesis such as blood action Low manageability EVOH-DMSO: Need for DMSO- Onyx, Micro compatible Liquid state Therapeutics, microcatheters Slower kinetic Inc., eV3, Settling of the “lava-like” flow (reduced risk of Irvine, CA nonadhesive pattern of catheter Squid, Balt copolymer embolization. It can Liquid adhesion) Extrusion, within the make it difficult to tropism for Montmorency, DMSO evaluate if the vessel DMSO- arteries France is fully occluded by based Preoperative High Menox, Meril the agent or if there Embolic embolization manageability Life Sciences, is an inner area of Agents India Pvt. Ltd. the lumen to be filled Advances into Biocompatible Polymerization the vasculature polymer- of the as a “block” Need for DMSO- DMSO: nonadhesive instead of compatible PHIL, copolymer forming layers microcatheters Microvention, within the (prevents the USA DMSO layering effect) Solid state Capability to Need for larger and Adjuvant role Injectable coils and Mechanical limit the distal stiffer Solid in therapeutic particles vessel occlusion migration of the microcatheters, embolization liquid agents potentially damaging the vessel wall NBCA, N-butyl-cyanoacrylate; EVOH, ethylene–vinyl alcohol copolymer; DMSO, dimethyl sulfoxide; PHIL, precipitating hydrophobic injectable liquid.

2.5. Embolization Specifics

The specifics herein reported are based on a consolidated technical protocol implemented by our neurovascular team with 14 years of experience, which have led to selecting the Onyx as the most useful, safe, and reliable embolic agent for preoperative embolization of brain AVMs (S. Luzzi, Del Maestro, et al. 2018; Del Maestro et al. 2018).

2.5.1. Catheterization The procedure is performed in a biplane angiographic unit with the patient under general anesthesia. Intravenous administration of 5,000 units of heparin is recommended before the

Preoperative Embolization of Brain Arteriovenous Malformation 469 procedure. Systolic blood pressure should range between 110 and 120 mmHg, and a target activated clotting time of 300 s is generally achievable by further intravenous administration of heparin at 1,000 units per 1 l saline. The femoral artery is catheterized using conventional coaxial techniques. After having positioned the guiding catheter into the internal carotid artery (ICA) or the dominant vertebral artery, based on the treatment plan, a flow-directed microcatheter is moved forward in close proximity to the nidus. In the personal series, a 1.3-F microcatheter (Marathon, eV3) was shifted toward the nidus with the aid of a tapered 0.20-mm (0.008-in) hydrophilic microguidewire (Mirage, eV3). The guiding catheter is regularly flushed using a pressure bag with saline solution containing heparin at 5 U/mL. The low-density Onyx is generally preferred.

2.5.2. Perinidal Stage At this stage, the microcatheterization of all main feeders and acquisition of the maximum number of angiographic projections are both needed to study in detail the angioarchitecture of the AVM and its pattern of vascular compartmentalization. In most cases, a feeder feeds a single compartment, which can be well visualized and treated through superselective catheterization. Information on the caliber of the feeders and exact distance between the catheter tip and nidus can also be gathered. The success of each embolization session and, consequently, the entire embolization treatment largely depends on this stage.

2.5.3. Nidal Stage The microcatheter is then advanced inside the nidus as more distal as possible to decrease the risk of reflux of the embolic material inside the normal vessels. The catheter’s dead space should be flushed with saline and filled with pure DMSO to avoid premature precipitation of the embolic agent. Our experience has validated the routine employment of the “plug and push” technique, consisting of an initial plug around the tip of the catheter that aimed to form an initial cast of embolic material. Additional injection of Onyx should be delayed by at least 1 min. The presence of the initial cast will promote an anterograde pressure gradient to the distal part of the nidus during Onyx release, with a subsequent lesser risk of reflux into normal perinidal vessels (Siekmann 2005). Release must be performed under constant angiographic guidance to readily recognize any inadvertent retrograde reflux. The recommended safe flow rate during Onyx release is 0.1 mL/s at maximum.

2.5.3.1. Transvenous Embolization The transvenous route has a role limited to extremely selected cases where endovascular treatment is intended. It was introduced after the implementation of Onyx and theoretically can be combined with transarterial access in case of feeding arteries inaccessible to catheterization or too dangerous to embolize (Houdart E. 2017). Owing to the high risk of bleeding and complexity of the procedure, the transvenous route is seldom employed for therapeutic embolization and contraindicated for preoperative proximal embolization.

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3. RESULTS

3.1. Illustrative Cases

3.1.1. Case 1: Left Trigonal Plexal SM Grade III Type II AVM A 43-year-old man with visual impairment was diagnosed with a left trigonal plexal type II AVM (Figures 1a–d and f). Diffusion weighted imaging (DWI) apparent diffusion coefficient (ADC) revealed a hyperintense signal secondary to a chronic vascular steal (e). Digital subtraction angiography (DSA) showed two feeders by the lateral posterior choroidal and posterior temporal artery (g, h). A large venous drainage to the Galenic system through the straight sinus was also detected (i). A pattern of perinidal angiogenesis was revealed, with flow- related aneurysm. The estimated nidal volume upon admission was 20.3 mL. The planned preoperative embolization program involved three transarterial embolization sessions with Onyx 18, which aimed to occlude the deeper portion of the lesion (l–n). The calculated nidal volume at the end of the overall embolization treatment was 9.8 mL, with an estimated obliteration rate of 51.7%. No complications developed, and after 7 days, the patient underwent the procedure by applying the left posterior interhemispheric transprecuneal approach. The nidus was compact and easy to handle. Blood loss was negligible. Postoperative DSA showed complete removal of the AVM without complications (p, q).

3.1.2. Case 2: Large Frontal SM Grade III Type III AVM Involving the Left Supplementary Motor Area As a consequence of motor seizures, a 19-year-old patient was diagnosed with a large left frontal type III AVM involving the supplementary motor area (Figures 2a and b). AVM had feeders in the distal middle cerebral artery (a, b) and two venous outflows to the superior sagittal sinus and middle cerebral vein. An obliteration rate of nearly 48% was achieved after two-stage transarterial Onyx embolization targeted to the deeper part of the AVM (c, d). On the third day after the last embolization session, the patient underwent surgery, where an easy dissection of that part of the AVM nidus bordering the motor strip was possible. There was no need for cauterization near the motor strip or Broca’s speech area. Postoperative DSA revealed total excision of the AVM (e, f). The patient was discharge on the seventh postoperative day with no deficits.

3.1.3. Case 3: Occipital SM Grade III Type I AVM with Diffuse Nidus Involving the Primary Visual Cortex Because of two photosensitive seizures, a 20-year-old man underwent brain contrast- enhanced magnetic resonance imaging (MRI), which revealed left occipital SM Grade III type I AVM (Figure 3a). DSA after the injection of the left ICA revealed a small AVM in the left primary visual area (c, d) in the presence of a fetal origin of the posterior cerebral artery. Nidus appeared racemose and fed by a feeder from the calcarine artery (c). Flow-related aneurysm was also present. The venous drainage was toward the straight sinus (d). Single-stage Onyx embolization performed by a transarterial access made the nidus more compact, facilitating the excision of the lesion. Postoperative DSA documented a complete excision of the AVM (f). The patient was discharged with no deficits, and seizures completely disappeared within six months.

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Figure 1. Axial (a), coronal (b), and sagittal (c) T1-weighted contrast-enhanced MRI showing a left trigonal SM Grade III type II (S2E0V1) AVM. (d) 2D T2-weighted MRI showing the nidus inside the atrium of the left lateral ventricle. (e) DWI ADC MRI showing a hyperintense signal because of the chronic vascular steal around the AVM (white arrow). (f) 3D volume-rendering T1-weighted contrast- enhanced MRI demonstrating the high-flow shunts inside the nidus and the large vein draining to the straight sinus. (g–i) DSA in the anterior–posterior and lateral projection (h) obtained after the injection of the left dominant VA confirming a left trigonal plexal SM Grade III type II AVM. (j) DSA in the lateral projection during the superselective transarterial trans-LPChA catheterization of the AVM’s nidus at the first embolization session. Anterior–posterior (k) and lateral (l) projection in arterial phase DSA obtained after injection of the right VA at the end of the third Onyx embolization of the AVM. (m) Axial CT scan showing Onyx inside the deeper and most caudal part of the AVM. (n) Anterior–posterior and lateral (o) projection in arterial phase DSA performed 6 months after the surgical excision of the AVM.

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Figure 2. (a) Anterior–posterior and lateral projection of (b) DSA after injection of the left ICA showing a large left frontal SM Grade III type III AVM involving the supplementary motor area. (c) Anterior– posterior and lateral projection (d) of the left ICA after two-stage Onyx embolization of the AVM. (e) Anterior–posterior and lateral projection (f) postoperative DSA confirming the complete excision of the AVM.

Figure 3. (a) Sagittal T1-weighted contrast-enhanced MRI and 3D volume-rendering MRI (b) showing a small SM Grade III type I AVM in the left occipital primary visual cortex. Perinidal flow-related aneurysm was also revealed. (c) Lateral projection of DSA after injection of the left ICA documenting a small AVM with a diffuse nidus in the left primary visual area. AVM had a main arterial feeder in the calcarine artery and venous drainage into the straight sinus. (d) Oblique projection in DSA although the injection of the left ICA showing the early venous drainage into the straight sinus. (e) Axial CT scan showing the hyperdense signal because of the Onyx in the deeper part of the AVM. (f) Postoperative lateral projection in DSA after injection of the left ICA documenting the complete excision of the AVM.

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3.1.4. Case 4: Right Primary Visual Cortex SM Grade III Type III AVM A 48-year-old man was diagnosed with an incidental right occipital SM Grade III AVM (Figures 4a–e). DSA showed two main feeders from the distal right pericallosal artery (a) and P3 segment of the right posterior cerebral artery (b–c). Some tiny feeders also came from the distal left pericallosal artery (d). The large nidus involved the right primary visual cortex, and the venogram showed two draining cortical veins attributed to the posterior third of the superior sagittal sinus (e). The first transarterial Onyx embolization occluded the feeders coming from the right posterior cerebral artery (f–g). After 12 days, the second session eliminated the feeders from the right pericallosal artery (h). Preoperative DSA showed a rearrangement of the venous outflow (i), but MRI revealed no ischemic complications (j). The estimated postembolization nidal volume was 11.3 mL, achieving a volumetric decrease of 49.7%.

Figure 4. DSA of the right ICA (a) and right VA in the lateral (b) and anterior–posterior (c) projection, revealing two main arterial feeders from the distal right pericallosal artery and P3 segment of the right posterior cerebral artery. (d) DSA of the left ICA. (e) Right VA DSA showing the presence of two cortical veins draining into the posterior third of the superior sagittal sinus. (f) DSA of the right VA in the lateral and anterior–posterior (g) projection after the first Onyx embolization session. (h) DSA of the right ICA in the lateral projection after the second Onyx embolization session. (i) Right ICA DSA showing the rearrangement and slowing of the venous outflow at the end of the second embolization session. (j) Sagittal T2-weighted MRI revealing no ischemic complications after the second embolization session despite the evidence of slowing of the venous outflow. (k–l) Intraoperative images obtained during the right posterior interhemispheric approach, showing the compactness of the nidus. (m) Intraoperative imaging confirming the complete exclusion of the nidus at the final stage of surgery. (n) Intraoperative ICG videoangiography in the arterial and venous (o) phases. (p) Postoperative DSA of the right ICA in the lateral and anterior–posterior (q) projection, confirming complete exclusion of the AVM. (r) Postoperative DSA of the left VA in the lateral and anterior–posterior (s) projection. (t) Postoperative DSA of the left ICA in the anterior–posterior projection.

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A posterior interhemispheric approach with the patient in prone position allowed for complete excision of the AVM (k–m). The nidus was compact and easy to dissect. After the AVM removal, indocyanine green videoangiography documented normal filling of neighboring vessels in both the arterial (n) and venous (o) phases. Postoperative DSA confirmed the complete removal of the malformation (p–t), and the patient was discharged on the fifth postoperative day without focal deficits.

3.2. Embolization Caveats

An excessive amount of liquid embolic agent inside the nidus is considered as an overtreatment since it may dramatically limit the shrinking and mobilization of the nidus. Embolization sessions and the overall embolization program should be discontinued when the safest volume of the AVM is reached. The decision to stop should be made on a case-by- case basis according to the angiographic results and targets planned before the treatment. Embolization for perinidal angiogenesis must be avoided in any case because it is reported to be a major source of morbidity (Valavanis and Yasargil 1998). Strict control of the systolic blood pressure for at least 48 h is recommended to reduce the risk of NPPB. A blood pressure of 120 mmHg is considered optimal.

4. DISCUSSION

Although important steps have been conducted for other pathologies affecting the central nervous system (A. De Tommasi et al. 2008; Antonio De Tommasi et al. 2007; S. Luzzi, Elia, Del Maestro, Elbabaa, et al. 2019; Paola Palumbo et al. 2018; Raysi Dehcordi et al. 2017; Sabino et al. 2018; P. Palumbo et al. 2019; Millimaggi et al. 2018; Bongetta et al. 2019; P. Ciappetta et al. 2008; S. Luzzi, Crovace, et al. 2018; Bellantoni et al. 2019; Sabino Luzzi, Crovace, et al. 2019; Spena et al. 2019; Antonosante et al. 2020; Campanella et al. 2020; Cesare Zoia et al. 2020; Elsawaf et al. 2020), information on the molecular mechanisms underlying brain AVMs is still insufficient. Grade III SM AVMs are a specific subset of malformations with a wide variability of size, site, and venous drainage. Vascular functional downgrading of grade III AVM has ultimately facilitated its surgical excision (S. Luzzi, Del Maestro, et al. 2018; Del Maestro et al. 2018; Abecassis et al. 2017). To increase the safety of the preoperative embolization of brain AVMs, implementation of intraoperative neurophysiological monitoring has been advocated, suggesting the same protocol used for AVMs and aneurysm surgery (Berenstein et al. 1984; Gallieni et al. 2018; S. Luzzi, Gallieni, et al. 2018; P. Ciappetta, Luzzi, et al. 2009; Ricci et al. 2017). With the authors’ long-term experience, the combined neuroendovascular-surgical approach is the best treatment option for most grade III SM AVMs. Onyx embolization has helped in the early identification of the lesion in case of small and racemose nidus, resulted in a firmer and more compact nidus, led to finding a clearer dissection plane, facilitated hemostasis that provided negligible blood loss, and, ultimately, allowed easier and safe removal of the nidus.

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In the past few years, our group has proved that image guidance, neurophysiological monitoring, intraoperative videoangiography, Doppler ultrasonography, and endoscopic assistance have dramatically improved the efficacy and safety of the surgical treatment of AVMs and other major neurosurgical pathologies (C. Zoia et al. 2018; Gallieni et al. 2018; Zoia C 2019; Cheng, Shetty, and Sekhar 2018; Pasquale Ciappetta, Occhiogrosso, et al. 2009; Luzzi S 2019; Arnaout et al. 2019; S. Luzzi, Zoia, et al. 2019; C. Zoia et al. 2019; S. Luzzi et al. 2020).

CONCLUSION

Staged preoperative embolization is a safe, feasible, and useful tool in the overall surgical management of both ruptured and unruptured grade III SM AVMs. Low-density DMSO-based liquid embolic agents such as the Onyx, Squid, Manox, and PHIL have some ideal characteristics required to perform planned embolization of the main functional compartments of the AVM. Careful preoperative planning, which is based on a detailed study of the angioarchitecture of the AVM, equally punctual selection of lesions that are candidate for treatment, and full cooperation within the neurosurgical-neuroendovascular team, is an essential factor to achieve the best patient’s outcome.

REFERENCES

Abecassis, Isaac Josh, John D Nerva, Abdullah Feroze, Jason Barber, Basavaraj V Ghodke, Louis J Kim, and Laligam N Sekhar. 2017. “Multimodality Management of Spetzler- Martin Grade 3 Brain Arteriovenous Malformations with Subgroup Analysis.” World neurosurgery 102: 263-274. https://doi.org/10.1016/j.wneu.2017.03.046. Antonosante, A., L. Brandolini, M. d’Angelo, E. Benedetti, V. Castelli, M. Del Maestro, S. Luzzi, A. Giordano, A. Cimini, and M. Allegretti. 2020. “Autocrine CXCL8-dependent invasiveness triggers modulation of actin cytoskeletal network and cell dynamics.” Aging (Albany NY) 12. https://doi.org/10.18632/aging.102733. https://www.ncbi.nlm.nih.gov/ pubmed/31986121. Arnaout, M. M., S. Luzzi, R. Galzio, and K. Aziz. 2019. “Supraorbital keyhole approach: Pure endoscopic and endoscope-assisted perspective.” Clin Neurol Neurosurg 189: 105623. https://doi.org/10.1016/j.clineuro.2019.105623. https://www.ncbi.nlm.nih.gov/pubmed/ 31805490. Baharvahdat, H, R Blanc, R Termechi, S Pistocchi, B Bartolini, H Redjem, and M Piotin. 2014. “Hemorrhagic complications after endovascular treatment of cerebral arteriovenous malformations.” AJNR. American journal of neuroradiology 35: 978-83. https://doi.org/ 10.3174/ajnr.A3906. Bellantoni, G., F. Guerrini, M. Del Maestro, R. Galzio, and S. Luzzi. 2019. “Simple schwannomatosis or an incomplete Coffin-Siris? Report of a particular case.” eNeurologicalSci 14: 31-33. https://doi.org/10.1016/j.ensci.2018.11.021. https://www. ncbi.nlm.nih.gov/pubmed/30555950.

476 S. Luzzi, M. Del Maestro, A. Giotta Lucifero et al.

Berenstein, A., W. Young, J. Ransohoff, V. Benjamin, and H. Merkin. 1984. “Somatosensory evoked potentials during spinal angiography and therapeutic transvascular embolization.” J Neurosurg 60 (4): 777-85. https://doi.org/10.3171/jns.1984.60.4.0777. https://www.ncbi. nlm.nih.gov/pubmed/6707747. Bongetta, D., C. Zoia, S. Luzzi, M. D. Maestro, A. Peri, G. Bichisao, D. Sportiello, I. Canavero, A. Pietrabissa, and R. J. Galzio. 2019. “Neurosurgical issues of bariatric surgery: A systematic review of the literature and principles of diagnosis and treatment.” Clin Neurol Neurosurg 176: 34-40. https://doi.org/10.1016/j.clineuro.2018.11.009. https://www.ncbi. nlm.nih.gov/pubmed/30500756. Campanella, R., L. Guarnaccia, C. Cordiglieri, E. Trombetta, M. Caroli, G. Carrabba, N. La Verde, P. Rampini, C. Gaudino, A. Costa, S. Luzzi, G. Mantovani, M. Locatelli, L. Riboni, S. E. Navone, and G. Marfia. 2020. “Tumor-Educated Platelets and Angiogenesis in Glioblastoma: Another Brick in the Wall for Novel Prognostic and Targetable Biomarkers, Changing the Vision from a Localized Tumor to a Systemic Pathology.” Cells 9 (2). https://doi.org/10.3390/cells9020294. https://www.ncbi.nlm.nih.gov/ pubmed/31991805. Chapot, R., P. Stracke, A. Velasco, H. Nordmeyer, M. Heddier, M. Stauder, P. Schooss, and P. J. Mosimann. 2014. “The pressure cooker technique for the treatment of brain AVMs.” J Neuroradiol 41 (1): 87-91. https://doi.org/10.1016/j.neurad.2013.10.001. https://www. ncbi.nlm.nih.gov/pubmed/24405685. Cheng, C. Y., R. Shetty, and L. N. Sekhar. 2018. “Microsurgical Resection of a Large Intraventricular Trigonal Tumor: 3-Dimensional Operative Video.” Oper Neurosurg (Hagerstown) 15 (6): E92-E93. https://doi.org/10.1093/ons/opy068. https://www.ncbi. nlm.nih.gov/pubmed/29618124. Ciappetta, P., I. D’Urso P, S. Luzzi, G. Ingravallo, A. Cimmino, and L. Resta. 2008. “Cystic dilation of the ventriculus terminalis in adults.” J Neurosurg Spine 8 (1): 92-9. https://doi.org/10.3171/SPI-08/01/092. https://www.ncbi.nlm.nih.gov/pubmed/18173354. Ciappetta, P., S. Luzzi, R. De Blasi, and P. I. D’Urso. 2009. “Extracranial aneurysms of the posterior inferior cerebellar artery. Literature review and report of a new case.” J Neurosurg Sci 53 (4): 147-51. https://www.ncbi.nlm.nih.gov/pubmed/20220739. Ciappetta, Pasquale, Giuseppe Occhiogrosso, Sabino Luzzi, Pietro I. D’Urso, and Angela P. Garribba. 2009. “Jugular tubercle and vertebral artery/posterior inferior cerebellar artery anatomic relationship: A 3-dimensional angiography computed tomography anthropometric study.” Neurosurgery 64. Crowley, R Webster, Andrew F Ducruet, M Yashar S Kalani, Louis J Kim, Felipe C Albuquerque, and Cameron G McDougall. 2015. “Neurological morbidity and mortality associated with the endovascular treatment of cerebral arteriovenous malformations before and during the Onyx era.” Journal of neurosurgery 122: 1492-7. https://doi.org/10.3171/ 2015.2.JNS131368. Darsaut, Tim E, Raphael Guzman, Mary L Marcellus, Michael S Edwards, Lu Tian, Huy M Do, Steven D Chang, Richard P Levy, John R Adler, Michael P Marks, and Gary K Steinberg. 2011. “Management of pediatric intracranial arteriovenous malformations: experience with multimodality therapy.” Neurosurgery 69: 540-56; discussion 556. https://doi.org/10.1227/NEU.0b013e3182181c00. De Tommasi, A., S. Luzzi, P. I. D’Urso, C. De Tommasi, N. Resta, and P. Ciappetta. 2008. “Molecular genetic analysis in a case of ganglioglioma: identification of a new mutation.”

Preoperative Embolization of Brain Arteriovenous Malformation 477

Neurosurgery 63 (5): 976-80; discussion 980. https://doi.org/10.1227/01.NEU. 0000327699.93146.CD. https://www.ncbi.nlm.nih.gov/pubmed/19005389. De Tommasi, Antonio, Giuseppe Occhiogrosso, Claudio De Tommasi, Sabino Luzzi, Antonella Cimmino, and Pasqualino Ciappetta. 2007. “A polycystic variant of a primary intracranial leptomeningeal astrocytoma: case report and literature review.” World J Surg Oncol 5: 72. Del Maestro, M., S. Luzzi, M. Gallieni, D. Trovarelli, A. V. Giordano, M. Gallucci, A. Ricci, and R. Galzio. 2018. “Surgical Treatment of Arteriovenous Malformations: Role of Preoperative Staged Embolization.” Acta Neurochir Suppl 129: 109-113. https://doi.org/10.1007/978-3-319-73739-3_16. https://www.ncbi.nlm.nih.gov/pubmed/ 30171322. Elsawaf, Y., S. Anetsberger, S. Luzzi, and S. K. Elbabaa. 2020. “Early Decompressive Craniectomy as Management for Severe TBI in the Pediatric Population: A Comprehensive Literature Review.” World Neurosurg. https://doi.org/10.1016/j.wneu.2020.02.065. https://www.ncbi.nlm.nih.gov/pubmed/32084616. Gallieni, M., M. Del Maestro, S. Luzzi, D. Trovarelli, A. Ricci, and R. Galzio. 2018. “Endoscope-Assisted Microneurosurgery for Intracranial Aneurysms: Operative Technique, Reliability, and Feasibility Based on 14 Years of Personal Experience.” Acta Neurochir Suppl 129: 19-24. https://doi.org/10.1007/978-3-319-73739-3_3. https://www. ncbi.nlm.nih.gov/pubmed/30171309. Gross, Bradley A, Karam Moon, and Cameron G Mcdougall. 2017. “Endovascular management of arteriovenous malformations.” Handbook of clinical neurology 143: 59- 68. https://doi.org/10.1016/B978-0-444-63640-9.00006-0. Houdart E., Labeyrie M. A., Lenck S., Saint-Maurice J. P. 2017. “Treatment of AVM: Endovascular Methods.” In Brain Arteriovenous Malformations, edited by Bradáč O. Beneš V.: Springer, Cham. Hurst, R. W., A. Berenstein, M. J. Kupersmith, M. Madrid, and E. S. Flamm. 1995. “Deep central arteriovenous malformations of the brain: the role of endovascular treatment.” J Neurosurg 82 (2): 190-5. https://doi.org/10.3171/jns.1995.82.2.0190. https://www.ncbi. nlm.nih.gov/pubmed/7815145. Jayaraman, M V, M L Marcellus, S Hamilton, H M Do, D Campbell, S D Chang, G K Steinberg, and M P Marks. 2008. “Neurologic complications of arteriovenous malformation embolization using liquid embolic agents.” AJNR. American journal of neuroradiology 29: 242-6. https://doi.org/10.3174/ajnr.A0793. Lawton, Michael T, Helen Kim, Charles E McCulloch, Bahar Mikhak, and William L Young. 2010. “A supplementary grading scale for selecting patients with brain arteriovenous malformations for surgery.” Neurosurgery 66: 702-13; discussion 713. https://doi.org/ 10.1227/01.NEU.0000367555.16733.E1. Lawton, Michael T, and UCSF Brain Arteriovenous Malformation Study Project. 2003. “Spetzler-Martin Grade III arteriovenous malformations: surgical results and a modification of the grading scale.” Neurosurgery 52: 740-8; discussion 748-9. Lawton, Michael T. and. 2003. “Spetzler-Martin Grade III arteriovenous malformations: surgical results and a modification of the grading scale.” Neurosurgery 52 (4): 740--8; discussion 748--9. http://www.ncbi.nlm.nih.gov/pubmed/12657169. Ledezma, Carlos J, Brian L Hoh, Bob S Carter, Johnny C Pryor, Christopher M Putman, and Christopher S Ogilvy. 2006. “Complications of cerebral arteriovenous malformation

478 S. Luzzi, M. Del Maestro, A. Giotta Lucifero et al.

embolization: multivariate analysis of predictive factors.” Neurosurgery 58: 602-11; discussion 602-11. https://doi.org/10.1227/01.NEU.0000204103.91793.77. Luzzi S, Del Maestro M, Elia A, Vincitorio F, Di Perna G, Zenga F, Garbossa D, Elbabaa S, Galzio R 2019. “Morphometric and Radiomorphometric Study of the Correlation Between the Foramen Magnum Region and the Anterior and Posterolateral Approaches to Ventral Intradural Lesions.” Turkish Neurosurgery In Press. https://doi.org/10.5137/1019-5149. JTN.26052-19.2. Luzzi, S., A. M. Crovace, L. Lacitignola, V. Valentini, E. Francioso, G. Rossi, G. Invernici, R. J. Galzio, and A. Crovace. 2018. “Engraftment, neuroglial transdifferentiation and behavioral recovery after complete spinal cord transection in rats.” Surg Neurol Int 9: 19. https://doi.org/10.4103/sni.sni_369_17. https://www.ncbi.nlm.nih.gov/pubmed/29497572. Luzzi, S., M. Del Maestro, D. Bongetta, C. Zoia, A. V. Giordano, D. Trovarelli, S. Raysi Dehcordi, and R. J. Galzio. 2018. “Onyx Embolization Before the Surgical Treatment of Grade III Spetzler-Martin Brain Arteriovenous Malformations: Single-Center Experience and Technical Nuances.” World Neurosurg 116: e340-e353. https://doi.org/10.1016/ j.wneu.2018.04.203. https://www.ncbi.nlm.nih.gov/pubmed/29751183. Luzzi, S., M. Del Maestro, S. K. Elbabaa, and R. Galzio. 2020. “Letter to the Editor Regarding “One and Done: Multimodal Treatment of Pediatric Cerebral Arteriovenous Malformations in a Single Anesthesia Event.”” World Neurosurg 134: 660. https://doi. org/10.1016/j.wneu.2019.09.166. https://www.ncbi.nlm.nih.gov/pubmed/32059273. Luzzi, S., A. Elia, M. Del Maestro, S. K. Elbabaa, S. Carnevale, F. Guerrini, M. Caulo, P. Morbini, and R. Galzio. 2019. “Dysembryoplastic Neuroepithelial Tumors: What You Need to Know.” World Neurosurg. https://doi.org/10.1016/j.wneu.2019.04.056. https://www.ncbi.nlm.nih.gov/pubmed/30981794. Luzzi, S., A. Elia, M. Del Maestro, A. Morotti, S. K. Elbabaa, A. Cavallini, and R. Galzio. 2019. “Indication, Timing, and Surgical Treatment of Spontaneous Intracerebral Hemorrhage: Systematic Review and Proposal of a Management Algorithm.” World Neurosurg. https://doi.org/10.1016/j.wneu.2019.01.016. https://www.ncbi.nlm.nih.gov/ pubmed/30677572. Luzzi, S., M. Gallieni, M. Del Maestro, D. Trovarelli, A. Ricci, and R. Galzio. 2018. “Giant and Very Large Intracranial Aneurysms: Surgical Strategies and Special Issues.” Acta Neurochir Suppl 129: 25-31. https://doi.org/10.1007/978-3-319-73739-3_4. https://www.ncbi.nlm.nih.gov/pubmed/30171310. Luzzi, S., C. Zoia, A. D. Rampini, A. Elia, M. Del Maestro, S. Carnevale, P. Morbini, and R. Galzio. 2019. “Lateral Transorbital Neuroendoscopic Approach for Intraconal Meningioma of the Orbital Apex: Technical Nuances and Literature Review.” World Neurosurg 131: 10-17. https://doi.org/10.1016/j.wneu.2019.07.152. https://www.ncbi. nlm.nih.gov/pubmed/31356977. Luzzi, Sabino, Alberto Maria Crovace, Mattia Del Maestro, Alice Giotta Lucifero, Samer K. Elbabaa, Benedetta Cinque, Paola Palumbo, Francesca Lombardi, Annamaria Cimini, Maria Grazia Cifone, Antonio Crovace, and Renato Galzio. 2019. “The cell-based approach in neurosurgery: ongoing trends and future perspectives.” Heliyon 5 (11). https://doi.org/10.1016/j.heliyon.2019.e02818. MG, Yasargil. 1987. Microneurosurgery. Vol. IIIA: AVM of the Brain, History, Embryology, Pathological Considerations, Hemodynamics, Diagnostic Studies, Microsurgical Anatomy., edited by Yasargil MG. New York: Thieme Medical Publishers.

Preoperative Embolization of Brain Arteriovenous Malformation 479

---. 1988. Microneurosurgery. Vol. IIIB: AVM of the Brain, Clinical Considerations, General and Special Operative Techniques, Surgical Results, Nonoperated Cases, Cavernous and Venous Angiomas, Neuro- anesthesia., edited by Yasargil MG. New York: Thieme Medical Publishers. Millimaggi, D. F., V. D. Norcia, S. Luzzi, T. Alfiero, R. J. Galzio, and A. Ricci. 2018. “Minimally Invasive Transforaminal Lumbar Interbody Fusion with Percutaneous Bilateral Pedicle Screw Fixation for Lumbosacral Spine Degenerative Diseases. A Retrospective Database of 40 Consecutive Cases and Literature Review.” Turk Neurosurg 28 (3): 454-461. https://doi.org/10.5137/1019-5149.JTN.19479-16.0. https://www.ncbi. nlm.nih.gov/pubmed/28481388. Nataraj, Andrew and Mohamed M. Bahgaat and Gholkar Anil and Vivar Ramon and Watkins Laurence and Aspoas Robert and Gregson Barbara and Mitchell Patrick and Mendelow A. David. “Multimodality treatment of cerebral arteriovenous malformations.” World neurosurgery 82 (1-2): 149--59. https://doi.org/10.1016/j.wneu.2013.02.064. http://www. ncbi.nlm.nih.gov/pubmed/23454686. Natarajan, Sabareesh K, Basavaraj Ghodke, Gavin W Britz, Donald E Born, and Laligam N Sekhar. 2008. “Multimodality treatment of brain arteriovenous malformations with microsurgery after embolization with onyx: single-center experience and technical nuances.” Neurosurgery 62: 1213-25; discussion 1225-6. https://doi.org/10.1227/01.neu. 0000333293.74986.e5. Palumbo, P., F. Lombardi, F. R. Augello, I. Giusti, S. Luzzi, V. Dolo, M. G. Cifone, and B. Cinque. 2019. “NOS2 inhibitor 1400W Induces Autophagic Flux and Influences Extracellular Vesicle Profile in Human Glioblastoma U87MG Cell Line.” Int J Mol Sci 20 (12). https://doi.org/10.3390/ijms20123010. https://www.ncbi.nlm.nih.gov/pubmed/ 31226744. Palumbo, Paola, Francesca Lombardi, Giuseppe Siragusa, Soheila Raysi Dehcordi, Sabino Luzzi, AnnaMaria Cimini, Maria Grazia Cifone, and Benedetta Cinque. 2018. “Involvement of NOS2 Activity on Human Glioma Cell Growth, Clonogenic Potential, and Neurosphere Generation.” International journal of molecular sciences 19. https://doi.org/10.3390/ijms19092801. Pandey, Paritosh, Michael P Marks, Ciara D Harraher, Erick M Westbroek, Steven D Chang, Huy M Do, Richard P Levy, Robert L Dodd, and Gary K Steinberg. 2012. “Multimodality management of Spetzler-Martin Grade III arteriovenous malformations.” Journal of neurosurgery 116: 1279-88. https://doi.org/10.3171/2012.3.JNS111575. Pasqualin, A, P Zampieri, A Nicolato, P Meneghelli, F Cozzi, and A Beltramello. 2014. “Surgery after embolization of cerebral arterio-venous malformation: experience of 123 cases.” Acta neurochirurgica. Supplement 119: 105-11. https://doi.org/10.1007/978-3- 319-02411-0_18. Pasqualin, A. and Barone G. and Cioffi F. and Rosta L. and Scienza R. and. 1991. “The relevance of anatomic and hemodynamic factors to a classification of cerebral arteriovenous malformations.” Neurosurgery 28 (3): 370--9. http://www.ncbi.nlm.nih. gov/pubmed/2011218. Raysi Dehcordi, Soheila, Alessandro Ricci, Hambra Di Vitantonio, Danilo De Paulis, Sabino Luzzi, Paola Palumbo, Benedetta Cinque, Daniela Tempesta, Gino Coletti, Gianluca Cipolloni, Maria Grazia Cifone, and Renato Galzio. 2017. “Stemness Marker Detection in the Periphery of Glioblastoma and Ability of Glioblastoma to Generate Glioma Stem Cells:

480 S. Luzzi, M. Del Maestro, A. Giotta Lucifero et al.

Clinical Correlations.” World neurosurgery 105: 895-905. https://doi.org/10.1016/j.wneu. 2017.05.099. Ricci, A., H. Di Vitantonio, D. De Paulis, M. Del Maestro, S. D. Raysi, D. Murrone, S. Luzzi, and R. J. Galzio. 2017. “Cortical aneurysms of the middle cerebral artery: A review of the literature.” Surg Neurol Int 8: 117. https://doi.org/10.4103/sni.sni_50_17. https://www. ncbi.nlm.nih.gov/pubmed/28680736. Sabino, Luzzi, Crovace Alberto Maria, Lacitignola Luca, Valentini Valerio, Francioso Edda, Rossi Giacomo, Invernici Gloria, Galzio Renato Juan, and Crovace Antonio. 2018. “Engraftment, neuroglial transdifferentiation and behavioral recovery after complete spinal cord transection in rats.” Surgical neurology international 9: 19. https://doi.org/10.4103/ sni.sni_369_17. Schramm, Johannes, Karl Schaller, Jonas Esche, and Azize Boström. 2017. “Microsurgery for cerebral arteriovenous malformations: subgroup outcomes in a consecutive series of 288 cases.” Journal of neurosurgery 126: 1056-1063. https://doi.org/10.3171/2016.4. JNS153017. Siekmann, R. 2005. “Basics and Principles in the Application of Onyx LD Liquid Embolic System in the Endovascular Treatment of Cerebral Arteriovenous Malformations.” Interventional Neuroradiology 11 (1 \_ suppl): 131--140. https://doi.org/10.1177/ 15910199050110S117. http://journals.sagepub.com/doi/10.1177/15910199050110S117. Soltanolkotabi, Maryam, Samantha E Schoeneman, Tord D Alden, Michael C Hurley, Sameer A Ansari, Arthur J DiPatri, Tadanori Tomita, and Ali Shaibani. 2013. “Onyx embolization of intracranial arteriovenous malformations in pediatric patients.” Journal of neurosurgery. Pediatrics 11: 431-7. https://doi.org/10.3171/2013.1.PEDS12286. Sorimachi, T., T. Koike, S. Takeuchi, T. Minakawa, H. Abe, K. Nishimaki, Y. Ito, and R. Tanaka. 1999. “Embolization of cerebral arteriovenous malformations achieved with polyvinyl alcohol particles: angiographic reappearance and complications.” AJNR Am J Neuroradiol 20 (7): 1323-8. https://www.ncbi.nlm.nih.gov/pubmed/10472993. Spena, G., E. Roca, F. Guerrini, P. P. Panciani, L. Stanzani, A. Salmaggi, S. Luzzi, and M. Fontanella. 2019. “Risk factors for intraoperative stimulation-related seizures during awake surgery: an analysis of 109 consecutive patients.” J Neurooncol. https://doi.org/ 10.1007/s11060-019-03295-9. https://www.ncbi.nlm.nih.gov/pubmed/31552589. Spetzler, R F, and N A Martin. 1986. “A proposed grading system for arteriovenous malformations.” Journal of neurosurgery 65: 476-83. https://doi.org/10.3171/jns.1986. 65.4.0476. Spetzler, Robert F, and Francisco A Ponce. 2011. “A 3-tier classification of cerebral arteriovenous malformations. Clinical article.” Journal of neurosurgery 114: 842-9. https://doi.org/10.3171/2010.8.JNS10663. Spetzler, Robert F. and Ponce Francisco A. 2011. “A 3-tier classification of cerebral arteriovenous malformations. Clinical article.” Journal of neurosurgery 114 (3): 842--9. https://doi.org/10.3171/2010.8.JNS10663. http://www.ncbi.nlm.nih.gov/pubmed/ 20932095. Taki, W. and Yonekawa Y. and Iwata H. and Uno A. and Yamashita K. and Amemiya H. “A new liquid material for embolization of arteriovenous malformations.” AJNR. American journal of neuroradiology 11 (1): 163--8. http://www.ncbi.nlm.nih.gov/pubmed/2105599. Terada, T, Y Nakamura, K Nakai, M Tsuura, T Nishiguchi, S Hayashi, T Kido, W Taki, H Iwata, and N Komai. 1991. “Embolization of arteriovenous malformations with peripheral

Preoperative Embolization of Brain Arteriovenous Malformation 481

aneurysms using ethylene vinyl alcohol copolymer. Report of three cases.” Journal of neurosurgery 75: 655-60. https://doi.org/10.3171/jns.1991.75.4.0655. Valavanis, A. 1996. “The role of angiography in the evaluation of cerebral vascular malformations.” Neuroimaging Clin N Am 6 (3): 679-704. https://www.ncbi.nlm.nih.gov/ pubmed/8873099. Valavanis, A., and M. G. Yasargil. 1998. “The endovascular treatment of brain arteriovenous malformations.” Adv Tech Stand Neurosurg 24: 131-214. https://www.ncbi.nlm.nih.gov/ pubmed/10050213. Vinuela, F, G Duckwiler, and G Guglielmi. “Contribution of interventional neuroradiology in the therapeutic management of brain arteriovenous malformations.” Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 6: 268-71. Vinuela, F. and Duckwiler G. and Guglielmi G. “Contribution of interventional neuroradiology in the therapeutic management of brain arteriovenous malformations.” Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 6 (4): 268--71. http://www.ncbi.nlm.nih.gov/pubmed/17895014. Vinuela, F., G. Duckwiler, and G. Guglielmi. 1997. “Contribution of interventional neuroradiology in the therapeutic management of brain arteriovenous malformations.” J Stroke Cerebrovasc Dis 6 (4): 268-71. https://www.ncbi.nlm.nih.gov/pubmed/17895014. Viuela, F. and Nombela L. and Roach M. R. and Fox A. J. and Pelz D. M. 1985. “Stenotic and occlusive disease of the venous drainage system of deep brain AVM’s.” Journal of neurosurgery 63 (2): 180--4. https://doi.org/10.3171/jns.1985.63.2.0180. http://www. ncbi.nlm.nih.gov/pubmed/4020440. Zoia C, Bongetta D, Dorelli G, Luzzi S, Maestro MD, Galzio RJ. . 2019. “Transnasal endoscopic removal of a retrochiasmatic cavernoma: A case report and review of literature.” Surg Neurol Int 10 (76). https://doi.org/10.25259/SNI-132-2019. Zoia, C., D. Bongetta, G. Dorelli, S. Luzzi, M. D. Maestro, and R. J. Galzio. 2019. “Transnasal endoscopic removal of a retrochiasmatic cavernoma: A case report and review of literature.” Surg Neurol Int 10: 76. https://doi.org/10.25259/SNI-132-2019. https://www. ncbi.nlm.nih.gov/pubmed/31528414. Zoia, C., D. Bongetta, F. Guerrini, C. Alicino, A. Cattalani, S. Bianchini, R. J. Galzio, and S. Luzzi. 2018. “Outcome of elderly patients undergoing intracranial meningioma resection: a single center experience.” J Neurosurg Sci. https://doi.org/10.23736/S0390-5616.18. 04333-3. https://www.ncbi.nlm.nih.gov/pubmed/29808631. Zoia, Cesare, Francesco Lombardi, Maria Fiore, Andrea Montalbetti, Alberto Iannalfi, Mattia Sansone, Daniele Bongetta, Francesca Valvo, Mattia Del Maestro, Sabino Luzzi, and Renato Galzio. 2020. “Sacral solitary fibrous tumour: surgery and hadrontherapy, a combined treatment strategy.” Reports of Practical Oncology & Radiotherapy. https://doi. org/10.1016/j.rpor.2020.01.008.

Chapter 30

RADIOSURGERY FOR BRAIN AND SPINAL CORD ARTERIOVENOUS AND CAVERNOUS MALFORMATIONS

B. C. Bono1, MD, I. Zaed1, MD, L. Attuati1, MD and P. Picozzi1,*, MD 1Department of Neurosurgery, Functional Neurosurgery and Gamma Knife Unit, Humanitas Clinical and Research Center – IRCCS, Rozzano (MI) – Italy

ABSTRACT

Stereotactic radiosurgery is a minimally invasive treatment for AVMs and cavernous malformations (CM), with a favorable risk-to-benefit profile in most patients, with respect to obliteration, hemorrhage, and seizure control. Radiosurgery is ideally suited for small to medium-sized AVMs (diameter <3cm or volume <12cm3) located in deep or eloquent brain regions. Obliteration is ultimately achieved in 70-80% of cases and is directly associated with nidus volume and radiosurgical margin dose. Adverse radiation effects, which appear as T2-weighted hyperintensities on magnetic resonance imaging, develop in 30-40% of patients after AVM radiosurgery, are symptomatic in 10%, and fail to clinically resolve in 2-3%. The risk of AVM hemorrhage may be reduced by radiosurgery, but the hemorrhage risk persists during the latency period between treatment and obliteration. Delayed cyst formation occurs in 2% of cases and may require surgical treatment. Radiosurgery abolishes or ameliorates seizure activity in the majority of patients with AVM-associated epilepsy and induces de novo seizures in 1-2% of those without preoperative seizures. Strategies for radiosurgical treatment of large-volume AVMs include new techniques such as dose- or volume-staged radiosurgery. With regard to CM, a small volume, a single lesion and the presence of symptoms, make them a suitable target for radiosurgical treatment. In contrast to AVMs, obliteration is detectable at follow up imaging only in a minority of cases. Hemorrhagic annual risk after treatment ranges from 4% to 9% for the first two years, then decreasing to 1% after 2 years. Larger volume, previous surgical resection and number of previous hemorrhages are predictive of both higher hemorrhagic rates and symptoms deterioration after SRS.

Keywords: AVM, cavernous malformation, radiosurgery

* Corresponding Author’s Email: [email protected].

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1. INTRODUCTION TO RADIOSURGERY FOR AVM

The term radiosurgery outlines a technique in which a single high dose radiation is stereotactically delivered to a target volume. In 1967 Leksell, together with the neurosurgeon Ladislau Steiner and the radiobiologist Borje Larsson, developed the first Gamma Knife Unit at the Karolinska Institute, that was firstly designed to treat functional neurological diseases such as pain and movement disorders for which conventional treatment was uneffective (Leksell 1983). In 1970 the Ladislau Steiner treated successfully the first AVM, as well as intracranial arteriovenous malformations (AVMs) (Wu et al. 1990). Over the years, treatment indications, clinical applications and technical aspects of stereotactic radio surgery continued to evolve and further improved. In addition to the Leksell Gamma Knife®, other new technologies, such as CyberKnife®, linear accelerators and proton beam therapy are nowadays widespread and available to provide accurate, reliable and precise radiosurgical treatment for a wide range of neurological pathologies, including arteriovenous and cavernous malformations.

1.1. Gamma Knife

A typical modern Gamma Knife device is composed by 192 cobalt-60 sources assembled in a hemispheric array. Gamma radiations coming from each source are focused on a specific target, while sparing the adjacent normal brain tissue. This is possible by means of a stereotactic frame, a particular helmet that is fixed to the patient’s head which provides a cartesian coordinate reference that allows the operator to calculate the position of the lesion along the three axes in space.

1.2. LINAC (Linear Particle Accelerator)

In the early 1980s J. Barcia-Salorio, a Spanish neurosurgeon, began to use LINAC-based radiosurgery for the treatment of AVMs (Barcia-Salorio et al. 1981). In the following years, LINAC radiosurgical treatment of cerebral AVMs further advanced, and it represents nowadays an accurate and reliable tool in selected cases (Betti and Derechinsky 1984; Winston and Lutz 1988; Colombo et al. 1994).

1.3. CyberKnife

CyberKnife was introduced in 1990 by John R. Adler, Russell and Peter Schonberg. The concept behind this technology is similar to linear accelerators, and allows to deliver highly focused x-rays to a precise area of interest thanks to a robotic arm. Patient’s position is constantly monitored by means of fluoroscopy and an infrared computed tracking system. Since its frameless concept, treatment can be employed both for intracranial and spinal AVMs. CyberKnife is mostly effective in small and non-eloquent located AVMs, with positive results in terms of symptoms improvement and obliteration rates.

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1.4. Proton Beam Therapy (PBT)

At the Harvard Cyclotron Laboratory in 1965, Dr Kjellberg was the first who applied proton therapy to the treatment AVMs (Kjellberg et al. 1983). Since then, thousands of cases have been treated with promising results. Proton Beam Therapy (PBT) employs a cyclotron to extract and accelerate protons until they reach sufficient energy to pass through human tissues (usually 200 MeV). Protons are then released and adjusted to the selected target, according to the appropriate degree of penetration. The Bragg peak phenomenon is the basic principle that underlies the efficacy of PBT. This property allows to easily conform doses even to large lesions with highly irregular margins, or to very radiosensitive structures such as optic chiasm or brainstem. Regardless of which technique is used, radiosurgery has some advantages over either microsurgery or endovascular procedures: its noninvasive nature, the relative low risk of acute complications, and the fact that the procedure does not require hospitalization. However, one of the main disadvantages is the latency of the curative effect, during which the risk of hemorrhage is still present, even if reduced. Progressive vessel thrombosis and ultimately nidal obliteration usually occur within three to five years after treatment. Moreover, possible long- term adverse effects of radiation could present, and include cyst formation, parenchymal edema and necrosis of surrounding normal brain tissue.

2. CEREBRAL AVMS

Goals of radiosurgical treatment are to prevent bleeding and resolve neurological signs and symptoms without causing any new deficit. Many classification systems have been introduced in clinical practice to properly select suitable patients and to predict outcome after treatment. The Spetzler Martin grading is the most common surgical-based classification system system (Speizler and Martin 2008; De Oliveira, Tedeschi, and Raso 1998; Spears et al. 2006; Lawton et al. 2010) The RBAS (radiosurgery based AVM score) and VRAS (Virginia Radiosurgery AVM score) are two other radiosurgical-based grading systems that take into account respectively age, AVM volume and location (RBAS) and previous history of hemorrhage, AVM volume and eloquence of AVM location (VRAS). A statistically significant correlation between these scales and radiosurgical outcome have been observed and validated in numerous radiosurgical series (Pollock and Flickinger 2008; Wegner et al. 2011; Pollock and Flickinger 2002a; Starke et al. 2013). As a general rule, grade I, II and IIIa AVMs can be treated either with microsurgery or radiosurgery, while staged radiosurgery, multimodality or conservative treatment are recommended for higher grade AVMs (Ponce and Spetzler 2011). When radiosurgical treatment is employed, outcome is generally assessed through observation of obliteration rates, risk of hemorrhage within the latency period, morbidity/mortality rates, and symptomatic radiation induced changes. Overall outcomes highly depend upon both AVM and technical characteristics, such as lesion volume, location, vascular pattern, and dose delivered (See et al. 2012). Obliteration rates are usually achieved in 70-80% within 5 years post-treatment (Figure 1-2). As mentioned before, the latency period between treatment and AVM obliteration constitutes the main drawback if compared to surgical

486 B. C. Bono, I. Zaed, L. Attuati et al. excision. Indeed, during the latency period, the annual rate of hemorrhage due to residual AVM rupture is progressively decreased if compared to the pre-treatment condition (2-4%). Radiation induced changes (RIC) such as edema, cysts formation and necrosis, represent the most common RS related adverse effects, depending upon nidal volume, prior hemorrhage and marginal dose delivered. RICs can present up to several months following radiosurgery and they are usually identified on follow-up MRIs. Depending on the different series reported in literature, RIC tend to occur in about 30-40% of cases. Usually transient, the most common RIC related symptoms comprise headache, neurological deficit and seizures. In about 1-2% of cases, symptoms are permanent.

Figure 1. Occipital AVM. Treatment planning using MRI and angiographycal images. 21 Gy at 50% isodose were delivered to the nidus.

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Figure 2. (A) pre-radiosurgical angiography of the case illustrated in Figure 1. (B) Angiography obtained 3 years later showing complete obliteration of AVM.

In conclusion, there is an increasing amount of literature supporting SRS as an effective and relatively low-risk procedure for AVM treatment, suitable for patients who cannot undergo surgical removal, due to either medical comorbidities or personal willing. However, accurate patient selection is pivotal to achieve successful results while minimizing SRS-related complications. Hereafter, we report a brief review of the recent literature regarding SRS treatment of brain arteriovenous malformation, with focuses on AVM locations and their relative management options.

2.1. Supratentiorial AVM Spetzler-Martin I-III

Radiosurgical treatment should be considered for small to medium size lesions, located within deep and eloquent areas, in patients who are unsuitable for open surgery or unwilling to undergo surgical resection. It is nowadays assumed that smaller AVM volume, a single venous drainage, lower RBAS and VRAS scores relate to better clinical outcomes, higher rates of nidal obliteration, and lower complication rates following radiosurgery (D. Ding et al. 2014). In 2014 Ding et al., published data from a large cohort of I-II AVMs treated via GK SRS. Authors reported an overall obliteration rate of 76% (60% at 5 yrs. and 80% at 10yrs). Similar results have also been observed by other groups (Kano, Lunsford, et al. 2012; Colombo et al. 2009; Blamek, Tarnawski, and Miszczyk 2011; Bradac, Charvat, and Benes 2013; Sun et al. 2011; Pollock and Flickinger 2008) Annual risk of post radiosurgery hemorrhage was 1.4%. RICs were observed in about 36% of cases at a mean time of 12 months. Symptoms presented in about 8% of patients, and were permanent in 1.4%. No prior hemorrhage, higher VRAS and RBAS scores, and lower prescription doses strongly correlated either with hemorrhage or radiosurgery induced changes.

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Spetzler Martin grade III AVMs comprise a more heterogeneous category which is further divided in to IIIa (medium size, cortical), IIIb (<3 cm, limbic or callosal) and IIIc (<3 cm, central core or insular) AVMs (Mattos et al. 2005; Ding et al. 2014). The same group from the University of Virginia (Ding et al. 2014) reported their results in a large cohort of 398 SM III AVMs. In comparison to their lower grade counterparts, authors observed slightly decreased overall obliteration rates (69%). Hemorrhagic risk during latency period following treatment was about 1.7%. Symptomatic and permanent radiation induced changes rates were also higher if compared to SM I-II subtypes, respectively 12 and 4%. Overall outcome was either way favorable in 63% of cases. (Ding, Starke, Kano, Lee, et al. 2017).

2.2. Cerebellar AVM Grade I–III

Posterior fossa AVMs represent nearly 7-15% of all AVMs (Al-Shahi et al. 2001), with cerebellar AVMs representing the most common location (Neacsu and Ciurea 2010). Radiosurgical treatment and related outcome of cerebellar AVMs have not been widely described in literature. A retrospective single institution study from the University of Pittsburgh has been published in 2014 (Bowden et al. 2014), where they studied the outcomes of 64 patients who underwent radiosurgical treatment. Authors observed obliteration rates of 53% and 69% at 3 and 5 years, and 75% at 10 years. According to other series, the presence of a smaller AVM nidus (< 4 cm3) correlated with higher obliteration rates, as also reported for supratentorial lesions. Conversely, lower obliteration rates have been observed in patients who did not presented with hemorrhage, as well as with patients who underwent prior embolization. The re-bleeding rate for haemorrhagic AVM after SRS within the latency period was about 6% in the 1st year, with a 5% mortality related to hemorrhage. This risk then reduced to an annual rate of 1.5% after 5 yrs. Symptomatic SRS related changes were seen in 3-4% of cases and were mostly temporary. A more recent international multicenter study (Cohen-Inbar et al. 2017) showed similar complications and mortality rates. However, nidal obliteration was achieved in 38%, 74% and 86% at 3, 5 and 10 years respectively. Both VRAS and RBAS were predictive of favorable outcome. These data seem to outline an effective role of radiosurgery in the treatment of cerebellar AVMs, with acceptable results in terms of nidal obliteration, and a relatively low-risk profile if compared to surgical resection (Ding, Starke, et al. 2014a; Kelly et al. 2008; Rodríguez- Hernández et al. 2012). However, clinical decision making regarding optimal treatment options is still challenging.

2.3. Basal Nuclei AVM

Basal ganglia, thalamus, and insular AVMs pose significant treatment challenges. Such deep AVMs are known to have aggressive natural histories, with annual haemorrhage rates ranging from 10% to 34% and mortality rates up to 62.5% (Potts et al. 2014) (Sasaki et al. 1998). Difficulties associated with microsurgical resection of deep AVMs have prompted some to consider them inoperable. However, radiosurgical treatment of deep AVMs is associated

Radiosurgery for Brain and Spinal Cord Arteriovenous and Cavernous Malformations 489 with significant complications and haemorrhage during the latency period as well as lower obliteration rates compared with other locations (Sasaki et al. 1998). Annual rates of posttreatment hemorrhage range between 1.3% and 9.5%, depending on size, location, prior history of hemorrhage, and time since radiosurgical treatment (Potts et al. 2014b; Sasaki et al. 1998). Three-year obliteration rates have been reported ranging from 57% to 68%, with mean overall obliteration rates of 81% (Kano, Kondziolka, et al. 2012a; Pollock and Flickinger 2002b). For patients with incomplete surgical resection, SRS can be taken into consideration as an adjuvant treatment option. Partial or no response to initial SRS is most often treated with a repeated SRS if the same risk factors precluding surgical resection are still present.

2.4. Brain Stem AVMs

Management of brainstem AVMs remains controversial. Safe and successful resections of these lesions have been reported only for selected patients (Solomon and Stein 1986). The compact nature of brainstem parenchyma, and its critical neurological function, undoubtedly increase both radiosurgical and microsurgical complication rates. Mean obliteration rates following radiosurgery range from 52% to 73% at 3 years post-treatment (Massager et al. 2000). These rates are significantly lower than what have been reported for supratentorial AVMs, and likely result from the necessity of dose reduction compared with nonbrainstem locations (Flickinger et al. 1992). Although no convincing data substantiate the theory that radiosurgery protects AVMs prior to complete obliteration, some data raise the intriguing possibility that AVM radiosurgery may provide some degree of protection. (Maruyama et al. 2004). Higher rates of symptomatic adverse radiation effects in brainstem AVMs compared with lesions in other locations has also been reported previously. During radiosurgery, accurate conformal dose planning and appropriate dose selection are key to the reduction of adverse radiation effects (Flickinger et al. 2000). Finally, provided that patients with large brainstem AVMs have no other therapeutic options but observation, staged radiosurgery might be an attractive option

2.5. Large AVMs: Volume Staged vs Dose Staged Fractionated Treatment

Stereotactic radiosurgery, surgical removal, endovascular embolization or observation are possible treatment strategies for large AVMs (volume >10 cm3) (Ilyas et al. 2018; Van Beijnum et al. 2011). Regarding stereotactic radiosurgery, different techniques have been described. As we have detailed before, single session SRS has proven its efficacy in small to medium AVMs. However, obliteration rates of large malformations are significantly lower and still not satisfactory, with a higher risk of complications (Kano et al. 2014; Ding, Starke, Kano, Lee, et al. 2017). Multisession/hypofractionated SRS techniques are designed to improve radiosurgical risk-to-benefit profile. Hypofracionated Proton Beam Therapy are acquiring more and more scientific interest during the last years for the treatment of large AVMs (Silander et al. 2004; Sparks et al. 2019). However, there is still a relative paucity of reports dealing with these types of technology.

490 B. C. Bono, I. Zaed, L. Attuati et al.

On the other hand, GK-based multisession techniques have been more widely utilized in two different modalities: dose-staged (DS) and volume-staged (VS). Both modalities can be used either alone or in combination with embolization or surgical resection. In dose-staged SRS, radiations are repeatedly delivered to the entire AVM volume within a period of few weeks, until a cumulative total dose has been achieved (Ilyas et al. 2018). Volume-staged SRS is based on AVM subdivision into separate volumes of treatment, that are singularly targeted until the entire lesion in finally treated, with an intersession interval of 2-9 month (Moosa et al. 2014; Kano, Kondziolka, et al. 2012b; C. Ding et al. 2013). Several studies have been conducted comparing these two techniques (Hanakita et al. 2016; Lindvall et al. 2015; Nagy et al. 2017; Franzin et al. 2016; Seymour et al. 2016). In a recent systematic review (Ilyas et al. 2018) outcomes of 299 VS SRS and 219 DS SRS procedures for large AVMs (mean volume >10 ml) were compared. Results showed a mean obliteration rate of 40% for the VS, and 32% for DS technique. Radiosurgical related complications were observed in 14% of cases in VS and in 12.5% of cases in DS group. Post-treatment mean re- hemorrhage rates were 18.8% and 11.6%, with mortality rates of 6.4% and 4.6% for VS and DS groups respectively. In conclusion, volume-staged SRS results in higher obliteration rates. However, the mean time to achieve complete obliteration is significantly higher in VS than DS and SS SRS. Also, related complications, hemorrhage and mortality rates seem to be higher in patients treated with VS SRS. Further investigations are still needed regarding effectiveness and safety of multisession techniques in the treatment of large AVMs.

2.6. Pediatric AVM

Many experts consider pediatric and adult AVMs as separate pathologic conditions because of their differences in pathophysiology, clinical and radiological appearance, architectural characteristics, and response to radiation therapy (Pan et al. 2008; Nicolato et al. 2015). As for adults, the annual risk of hemorrhage is about 2-4%. However, if we take in consideration the cumulative lifetime risk, observation does not seem to be an acceptable option. Surgical resection, whenever possible, is still nowadays the first line treatment, and it is particularly effective in treating superficial and non eloquent-located malformations, or in case of an acute hemorrhagic presentation. However, high morbidity and mortality rates related to this kind of surgery, especially if the after mentioned criteria are not present, lead to the choice of safer treatment options. During the last years, numerous studies have been published regarding stereotactic radiosurgery for AVMs in pediatric population with positive results (Tanaka et al. 1995; Dinca et al. 2012; Levy et al. 2000; Kondziolka et al. 2010; Reyns et al. 2007; Yen et al. 2010; Nicolato et al. 2015; Pan et al. 2008). According to the recent literature, obliteration rates vary between 62.5 and 90% while the mean treatment obliteration interval is about 2-3 years, either with Gamma Knife or LINAC. This time is shorter if compared to adult patients, and may suggest a higher radiosensivity of pediatric AVMs (Tanaka et al. 1995; Nicolato et al. 2015). With regard to RS-related permanent complications, average rates range between 1.9 and 11%. Higher complication rates have been observed when LINAC treatment is used (Potts et al. 2014a; Zabel-du Bois et al. 2006; Buis et al. 2008) Also, low marginal doses and large AVM volumes seem to correlate with longer obliteration time and lower overall obliteration rates (Smyth et al. 2002; Potts et al. 2014a; Zabel-du Bois et al. 2006). A series of

Radiosurgery for Brain and Spinal Cord Arteriovenous and Cavernous Malformations 491

100 pediatric patients treated with GK was published by Nicolato et al. in 2015 (Nicolato et al. 2015). Overall obliteration rates were 85% at 8 yrs. A statistically significant correlation between AVM volume, dose delivered and outcome was observed. In particular, smaller volumes (<10mL) and higher doses were strongly associated with higher obliteration rates and lower RS-related complications. Authors therefore proposed a management algorithm. A higher peripheral dose should be administered in non eloquent and <10 mL AVMs. It should also be considered that for eloquent, deep seated and brainstem AVMs, a high dose of radiation is not feasible. In these cases, as well as for nidal volumes >10 mL, a staged radiosurgical treatment should be preferred (Nicolato et al. 2015). Finally, a recent large multicenter study has been published comparing GK-SRS outcomes in pediatric vs adult AVMs (Chen et al. 2018). Results showed no significant differences in terms of favorable outcome, nidal obliteration rates and SRS related complications between pediatric and adult cohorts. (Ding, Starke, Kano, Mathieu, et al. 2017).

3. CONTROVERSIES IN RADIOSURGERY FOR AVM

3.1. Effects of Embolization on AVM Radiosurgery

The utilization of embolization with radiosurgery is an attractive strategy. The main goals of pre-radiosurgery embolization are: (1) volume reduction of large AVMs (diameter >3 cm or volume >12 cm3); (2) occlusion of prenidal or intranidal AVM-associated arterial aneurysms; and (3) occlusion of high-flow intranidal arteriovenous fistulas. However, several studies demonstrated that AVM embolization lowers obliteration rates after radiosurgery, although the etiology of this phenomenon is not well understood (Andrade- Souza et al. 2007; Ding, Starke, et al. 2014b). Several hypotheses have been made to explain such phenomenon: (1) absorption or scattering of radiation beams by embolic agents; (2) increased difficulty in adequately targeting the remaining AVM after embolization due to obscuration of the nidal borders; (3) delayed recanalization of the embolized nidal portion during the latency period after radiosurgery; and (4) embolization-induced neoangiogenesis (Andrade-Souza et al. 2008; Valle et al. 2008; Bing et al. 2012; Buell et al. 2014). A recent study considered a matched cohort of analysis of 484 embolized and nonembolized AVMs (1:1) treated with radiosurgery (Oermann et al. 2015). The actuarial obliteration rate of the embolized AVM cohort was significantly lower than the non-embolized cohort. It is current opinion nowadays in the majority of radiosurgical centers to avoid pre-treatment embolization or limiting its use to the occlusion of a bleeding points.

3.2. Radiosurgery for the Treatment of Unruptured AVMs

In the recent years, the discussion regarding the management of unruptured AVMs focuses on two main issues: (1) the hemorrhage risk of unruptured AVMs is significantly lower than for ruptured AVMs (Pollock et al. 1996; Stapf et al. 2006; Gross and Du 2013; Kim et al. 2014) and (2) the treatment-related morbidity for unruptured AVMs may be higher than for ruptured AVMs (Lawton et al. 2010; Ding et al. 2013). This controversy was brought to the forefront by

492 B. C. Bono, I. Zaed, L. Attuati et al. two well-known studies which found worse short-term outcomes after intervention compared to conservative management. A Randomized Trial of Unruptured Brain AVMs (ARUBA) was a multicenter, randomized controlled trial comparing intervention to conservative management for unruptured AVMs (Mohr et al. 2014). The interim analysis of ARUBA reported significantly higher rates of symptomatic stroke or death in patients assigned to intervention than to conservative management (p < 0.0001). The Scottish Audit of Intracranial Vascular Malformations (SAIVM) prospective AVM cohort study also reported significantly worse outcomes, up to 4 years of follow-up, for unruptured AVMs which underwent intervention compared to conservative management (Al-Shahi Salman 2014). A number of criticisms regarding both of the aforementioned studies have been appropriately raised by various cerebrovascular groups (Cenzato et al. 2016; Starke et al. 2014). At the time of analysis, 64% of patients in ARUBA who were assigned to intervention either had ongoing treatment plans or had not yet begun therapy, which suggests that at least half of patients considered to have treated AVMs had patent nidi at last follow-up (Mohr et al. 2014). When one considers the persistently elevated rate of symptomatic stroke or death over time and the excessive rate of hemorrhage in the interventional arm (22% as randomized, 25% as treated), the findings from ARUBA implicate a potentially increased rupture risk for partially treated, unruptured AVMs (Mohr et al. 2014). However, since treatment-specific radiologic and clinical outcomes from ARUBA have yet to be reported, the degree to which each treatment modality contributed to hemorrhage in the interventional arm is unknown (Starke et al. 2014). Nevertheless, intervention likely yields a long-term benefit for the vast majority of patients harboring unruptured SM grade I and II AVMs, as well as many of those with small (diameter <3 cm) SM grade III AVMs. A critical analysis of ARUBA, that suggests a potentially increased hemorrhage risk from incompletely obliterated AVMs, further emphasizes the importance of achieving complete nidal extirpation or occlusion (Mohr et al. 2014). Microsurgery is thought be the preferred intervention for most SM grade I and II AVMs, due to its high obliteration rate and relatively low risk of morbidity and mortality (Bervini et al. 2014; Potts et al. 2015). However, for AVMs located in eloquent brain regions, for patients who are either medically unfit to tolerate surgical resection, or unwilling to undergo an invasive neurosurgical procedure, radiosurgery should be considered as minimally invasive treatment option which affords an excellent risk-to-benefit (D. Ding et al. 2015). When contemplating the management of an unruptured AVM patient, it has to be considered that natural history of unruptured AVMs can vary considerably based on lesion angioarchitecture, and that most treatment-related morbidity is temporary (Stapf et al. 2006; Kim et al. 2014; Ding et al. 2015; Mouchtouris et al. 2015). Thus, despite the controversial findings of ARUBA and the SAIVM prospective AVM study, intervention is likely warranted, and should remain the preferred management approach for most of these patients.

4. SPINAL AVMS

The development of frameless, image-guided stereotaxy made radiosurgical treatment of spinal cord AVM feasible (Ryu et al. 2001). SRS for spinal AVMs builds on prior studies related to spinal tumors (Ryu et al. 2001; Ryu, Kim, and Chang 2003). Although treatment of

Radiosurgery for Brain and Spinal Cord Arteriovenous and Cavernous Malformations 493 spinal tumors has proven to be successful, radiation toxicity to the spinal cord remains a concern. The ability to deliver multiple sessions of radiosurgery to an intramedullary vascular malformation has played a role in reducing this risk of neurotoxicity related to radiation delivery. Several groups employ the CyberKnife system (Accuray, Sunny-vale, CA, USA) for radiation delivery to patients with radiosurgically treatable lesions (Adler et al. 2012; Sinclair et al. 2006). The use of CyberKnife radiosurgery to treat spinal cord AVM is continually evolving. Over time, improvements in imaging have made treatment of spinal cord AVM safe and accurate. High-resolution 3D images now provide a superior view of many spinal AVM compared to standard two-dimensional angiographic or planar imaging. Algorithms that fuse 3D angiography images to either CT scans or MRI represent another advance in radiosurgical treatment and provide a more accurate lesional targeting. Radiosurgery should be considered for the treatment of these lesions when they are deemed unsafe for microsurgical or embolization obliteration. Ongoing investigations regarding spinal cord radiation tolerance will allow for refinement of safe and efficacious radiosurgical treatment doses for spinal cord AVM. The current state of the art of radiosurgery for spinal AVM provides obliteration rates that are lower than for cerebral AVM of comparable size, probably related to a lack of understanding of spinal cord dose tolerance and efficacy. Various studies have attempted to define spinal cord radiation tolerance but variables such as lesion volume, patient age, single versus multiple fractions, and fraction uniformity make individualizing treatment of utmost importance (Medin and Boike 2011). In conclusion, radiosurgery appears to be a promising tool for treatment of spinal cord AVM. Additional challenges remain with respect to obtaining a better understanding of the tolerance of the spinal cord to radio-surgery, determining the role of radiosurgery in the general management of spinal AVM and the appropriate parameters for radiation delivery. The development of 3D angiography and the possibility of incorporating this imaging into AVM radiosurgery treatment planning may further reduce risks. Bostrom et al. described a 78.5% complete obliteration rate in their series of 20 Type II spinal AVM patients and one (5%) patient suffered permanent neurologic deterioration (Boström et al. 2009). Barrow Neurological Institute also reported a series of 20 patients treated for glomus spinal AVM in 2012. They reported angiographic obliteration in 75% of cases and their reported surgical morbidity rate was 5% (Velat et al. 2012). Radiosurgical obliteration rates are likely to improve as radiosurgical experience expands and radiation tolerance is better understood. Ongoing investigations into the spinal cord radiation tolerance will allow for refinement of safe and efficacious radiosurgical treatment doses for spinal cord AVM. The current state of the art of radiosurgery for spinal AVM provides obliteration rates that are lower than for cerebral AVM of comparable size, possibly related to a lack of understanding of spinal cord dose tolerance and efficacy; thus obliteration rates for spinal AVM will likely remain low due to conservative dosing. Various studies have attempted to define spinal cord radiation tolerance but variables such as lesion volume, patient age, single versus multiple fractions, and fraction uniformity make individualizing treatment of utmost importance (Medin and Boike 2011). As studies better elucidate spinal cord radiation tolerance, higher and more efficacious doses will likely become more common. One could foreseeably escalate the dose

494 B. C. Bono, I. Zaed, L. Attuati et al. of radiation to the spinal AVM when performing multisession radiosurgical treatment in order to achieve greater obliteration rates, while maintaining an acceptable risk. As the role of radiosurgery is better defined in the multimodality management of spinal AVM, indications for its use will also become better delineated. Whether radiosurgery will be used as a standalone modality or in combination with microsurgical and/or endovascular therapies is yet to be determined; it is likely that similar to the management of cerebral AVM, a multi-modality approach will prevail (Adler et al. 2012). Despite favorable outcomes from the Stanford experience, multi-institutional studies should be carried out with more stringent criteria for radiosurgical planning and spinal cord morbidity to determine optimal cases and treatment parameters. Still, long-term follow-up is required to validate the safety of stereotactic radiosurgery for the management of spinal cord AVM.

5. CAVERNOUS MALFORMATIONS

The rationale for observation in asymptomatic patients with a cavernous malformation (CM) is based on the natural history (low bleeding risk), the concern that surgical or radiosurgical intervention risk may exceed benefit, and the knowledge that even after a single bleed the risk of additional hemorrhage remains relatively low. Surgical resection is the treatment of choice for lobar CMs, for patients presenting seizures, or if CM is located within a non-critical brain region. Radiosurgical treatment goal for CMs is 3-fold: to reduce the risk of re-bleeding, to preserve neurological function, and to have a low risk of treatment-related side effects. It was erroneously thought that radiosurgery for CM would lead to lesional obliteration that could be identified by some form of vascular imaging. However, CM are angiographically occult and only in a minority of cases is radiosurgery followed by lesional regression on subsequent MRIs. Only long-term imaging studies and clinical examinations can evaluate outcomes of CM radiosurgery, defined as no new clinical events associated and no new evidence of re- hemorrhage on serial MRIs after radiosurgery. In the absence of prior symptomatic bleeding events, observation is recommended. For patients with symptomatic lobar CMs, hemorrhagic CMs or those with related seizures, surgical lesionectomy via craniotomy is preferred. Radiosurgery should be reserved for patients with at least one bleed and a CM located in a region of critical brain function for which any surgical corridor poses significant clinical risks. SRS must target the CM within the hemosiderin rim and use doses significantly less than needed for true AVM obliteration (13–15 margin doses using small isocenters with a sharp fall- off). SRS provides a definitive and verifiable reduction in the risk of additional bleeds from CM. This has been confirmed by long-term follow-up and is most pronounced after 2 years (Kim et al. 2019).

6. CONCLUSION

Due to the variable natural history and heterogeneous outcomes after intervention, the proper management of an AVM patient is a multifactorial decision. In general, AVMs should

Radiosurgery for Brain and Spinal Cord Arteriovenous and Cavernous Malformations 495 be preferentially referred to high-volume cerebrovascular centers where experienced, multidisciplinary teams comprised of neurosurgeons, neurointerventional radiologists, radiation oncologists, and medical physicists are available to provide the latest microsurgical, radiosurgical, and endovascular techniques and technologies for the management of these challenging lesions. Radiosurgery has a unique and important role in the management of AVMs, and should be preferentially employed in patients with small to medium-sized nidi located in deep or functionally critical brain regions. For appropriately selected unruptured AVMs, radiosurgery affords a reasonable risk-to-benefit profile which likely results in outcomes which are superior to that of conservative management, although a prolonged follow- up duration may be necessary to fully realize this difference. Radiosurgery can decrease the rate of repeat hemorrhage and it is an effective treatment for brainstem CMs. A safe and effective radiation dosage can decrease the rate of radiation- induced complications after radiosurgery. However, the optimal dose for brainstem CMs remains unclear.

REFERENCES

Al-Shahi, R., & Warlow, C. (2001). A systematic review of the frequency and prognosis of arteriovenous malformations of the brain in adults. Brain, 124(10), 1900-1926. Andrade-Souza, Y. M., Ramani, M., Beachey, D. J., Scora, D., Tsao, M. N., & Schwartz, M. L. (2008). Liquid embolisation material reduces the delivered radiation dose: a physical experiment. Acta neurochirurgica, 150(2), 161-164. Andrade-Souza, Y. M., Ramani, M., Scora, D., Tsao, M. N., terBrugge, K., & Schwartz, M. L. (2007). Embolization before radiosurgery reduces the obliteration rate of arteriovenous malformations. Neurosurgery, 60(3), 443-452. Barcia-Salorio, J. L., Hernandez, G., Broseta, J., & Gonzalez-Darder, J. G. (1982). Radiosurgical treatment of carotid-cavernous fistula. Stereotactic and Functional Neurosurgery, 45(4-5), 520-522.. van Beijnum, J., van der Worp, H. B., Buis, D. R., Salman, R. A. S., Kappelle, L. J., Rinkel, G. J., ... & Klijn, C. J. (2011). Treatment of brain arteriovenous malformations: a systematic review and meta-analysis. Jama, 306(18). Bervini, D., Morgan, M. K., Ritson, E. A., & Heller, G. (2014). Surgery for unruptured arteriovenous malformations of the brain is better than conservative management for selected cases: a prospective cohort study. Journal of neurosurgery, 121(4), 878-890. Betti, O. O., & Derechinsky, V. E. (1984). Hyperselective encephalic irradiation with linear accelerator. In Advances in Stereotactic and Functional Neurosurgery 6, 385-390. Springer, Vienna. Bing, F., Doucet, R., Lacroix, F., Bahary, J. P., Darsaut, T., Roy, D., ... & Weill, A. (2012). Liquid embolization material reduces the delivered radiation dose: clinical myth or reality?. American journal of neuroradiology, 33(2), 320-322. Blamek, S., Tarnawski, R., & Miszczyk, L. (2011). Linac-based stereotactic radiosurgery for brain arteriovenous malformations. Clinical Oncology, 23(8), 525-531. Bois, A. Z. D., Milker-Zabel, S., Huber, P., Schlegel, W., & Debus, J. (2006). Stereotactic linac-based radiosurgery in the treatment of cerebral arteriovenous malformations located

496 B. C. Bono, I. Zaed, L. Attuati et al.

deep, involving corpus callosum, motor cortex, or brainstem. International journal of radiation oncology, biology, physics, 64(4), 1044-1048. Boström, A., Krings, T., Hans, F. J., Schramm, J., Thron, A. K., & Gilsbach, J. M. (2009). Spinal glomus-type arteriovenous malformations: microsurgical treatment in 20 cases. Journal of Neurosurgery: Spine, 10(5), 423-429. Bowden, G., Kano, H., Tonetti, D., Niranjan, A., Flickinger, J., & Lunsford, L. D. (2014). Stereotactic radiosurgery for arteriovenous malformations of the cerebellum. Journal of neurosurgery, 120(3), 583-590. Bradac, O., Charvat, F., & Benes, V. (2013). Treatment for brain arteriovenous malformation in the 1998–2011 period and review of the literature. Acta neurochirurgica, 155(2), 199- 209. Buell, T. J., Ding, D., Starke, R. M., Crowley, R. W., & Liu, K. C. (2014). Embolization- induced angiogenesis in cerebral arteriovenous malformations. Journal of Clinical Neuroscience, 21(11), 1866-1871. Buis, D. R., Dirven, C. M. F., Lagerwaard, F. J., Mandl, E. S., á Nijeholt, G. L., Eshghi, D. S., ... & Vandertop, W. P. (2008). Radiosurgery of brain arteriovenous malformations in children. Journal of neurology, 255(4), 551-560. Cenzato, M., Delitala, A., Delfini, R., Pasqualin, A., Maira, G., Esposito, V., ... & Boccardi, E. (2015). Position statement from the Italian Society of Neurosurgery on the ARUBA Study. Journal of Neurosurgical Sciences, 60(1), 126-130. Chen, C. J., Ding, D., Kano, H., Mathieu, D., Kondziolka, D., Feliciano, C., ... & Sheehan, J. P. (2018). Stereotactic radiosurgery for pediatric versus adult brain arteriovenous malformations: a multicenter study. Stroke, 49(8), 1939-1945. Cohen-Inbar, O., Starke, R. M., Kano, H., Bowden, G., Huang, P., Rodriguez-Mercado, R., ... & Abbassy, M. (2016). Stereotactic radiosurgery for cerebellar arteriovenous malformations: an international multicenter study. Journal of neurosurgery, 127(3), 512- 521. Colombo, F., Cavedon, C., Casentini, L., Francescon, P., Causin, F., & Pinna, V. (2009). Early results of CyberKnife radiosurgery for arteriovenous malformations. Journal of neurosurgery, 111(4), 807-819. Colombo, F., Pozza, F., Chierego, G., Casentini, L., De Luca, G., & Francescon, P. (1994). Linear accelerator radiosurgery of cerebral arteriovenous malformations: an update. Neurosurgery, 34(1), 14-21. Del Valle, R., Zenteno, M., Jaramillo, J., Lee, A., & De Anda, S. (2008). Definition of the key target volume in radiosurgical management of arteriovenous malformations: a new dynamic concept based on angiographic circulation time. Journal of neurosurgery, 109(Supplement), 41-50. Dinca, E. B., de Lacy, P., Yianni, J., Rowe, J., Radatz, M. W., Preotiuc-Pietro, D., & Kemeny, A. A. (2012). Gamma knife surgery for pediatric arteriovenous malformations: a 25-year retrospective study. Journal of Neurosurgery: Pediatrics, 10(5), 445-450. Ding, C., Solberg, T. D., Hrycushko, B., Medin, P., Whitworth, L., & Timmerman, R. D. (2013). Multi-staged robotic stereotactic radiosurgery for large cerebral arteriovenous malformations. Radiotherapy and Oncology, 109(3), 452-456. Ding, D., Starke, R. M., Kano, H., Mathieu, D., Huang, P. P., Feliciano, C., ... & Abbassy, M. (2017). International multicenter cohort study of pediatric brain arteriovenous

Radiosurgery for Brain and Spinal Cord Arteriovenous and Cavernous Malformations 497

malformations. Part 1: predictors of hemorrhagic presentation. Journal of Neurosurgery: Pediatrics, 19(2), 127-135. Ding, D., Starke, R. M., Yen, C. P., & Sheehan, J. P. (2014). Radiosurgery for cerebellar arteriovenous malformations: does infratentorial location affect outcome?. World neurosurgery, 82(1-2), e209-e217. Ding, D., Xu, Z., Yen, C. P., Starke, R. M., & Sheehan, J. P. (2015). Radiosurgery for unruptured cerebral arteriovenous malformations in pediatric patients. Acta neurochirurgica, 157(2), 281-291. Ding, D., Yen, C. P., Xu, Z., Starke, R. M., & Sheehan, J. P. (2014). Radiosurgery for low- grade intracranial arteriovenous malformations. Journal of neurosurgery, 121(2), 457-467. Ding, D., Yen, C. P., Starke, R. M., Xu, Z., Sun, X., & Sheehan, J. P. (2014). Radiosurgery for Spetzler-Martin grade III arteriovenous malformations. Journal of neurosurgery, 120(4), 959-969. Flickinger, J. C., Kondziolka, D., Lunsford, L. D., Kassam, A., Phuong, L. K., Liscak, R., ... & Arteriovenous Malformation Radiosurgery Study Group. (2000). Development of a model to predict permanent symptomatic postradiosurgery injury for arteriovenous malformation patients. International Journal of Radiation Oncology Biology Physics, 46(5), 1143-1148. Flickinger, J. C., Lunsford, L. D., Kondziolka, D., Maitz, A. H., Epstein, A. H., Simons, S. R., & Wu, A. (1992). Radiosurgery and brain tolerance: an analysis of neurodiagnostic imaging changes after gamma knife radiosurgery for arteriovenous malformations. International Journal of Radiation Oncology Biology Physics, 23(1), 19-26. Franzin, A., Panni, P., Spatola, G., del Vecchio, A., Gallotti, A. L., Gigliotti, C. R., ... & Mortini, P. (2016). Results of volume-staged fractionated Gamma Knife radiosurgery for large complex arteriovenous malformations: obliteration rates and clinical outcomes of an evolving treatment paradigm. Journal of neurosurgery, 125(Supplement_1), 104-113. Gross, B. A., & Du, R. (2013). Natural history of cerebral arteriovenous malformations: a meta- analysis. Journal of neurosurgery, 118(2), 437-443. Gupta, G., Soltys, S. G., Gibbs, I. C., Steinberg, G. K., & Dodd, R. (2010). CyberKnife ablation for intramedullary spinal cord arteriovenous malformations (AVMs): a promising new therapeutic approach. Cureus, 2(8). Hanakita, S., Shin, M., Koga, T., Igaki, H., & Saito, N. (2016). Outcomes of volume-staged radiosurgery for cerebral arteriovenous malformations larger than 20 cm3 with more than 3 years of follow-up. World neurosurgery, 87, 242-249. Kano, H., Lunsford, L. D., Flickinger, J. C., Yang, H. C., Flannery, T. J., Awan, N. R., ... & Kondziolka, D. (2012). Stereotactic radiosurgery for arteriovenous malformations, Part 1: management of Spetzler-Martin Grade I and II arteriovenous malformations. Journal of neurosurgery, 116(1), 11-20. Ilyas, A., Chen, C. J., Ding, D., Taylor, D. G., Moosa, S., Lee, C. C., ... & Sheehan, J. P. (2017). Volume-staged versus dose-staged stereotactic radiosurgery outcomes for large brain arteriovenous malformations: a systematic review. Journal of neurosurgery, 128(1), 154- 164. JP, M., Ghizoni, E., Oliveira, E., & Tedeschi, H. (2005). Treatment strategy for grade III arteriovenous malformations. Japanese Journal of Neurosurgery, 14(6), 363-367. Kano, H., Flickinger, J. C., Yang, H. C., Flannery, T. J., Tonetti, D., Niranjan, A., & Lunsford, L. D. (2014). Stereotactic radiosurgery for Spetzler-Martin Grade III arteriovenous malformations. Journal of neurosurgery, 120(4), 973-981.

498 B. C. Bono, I. Zaed, L. Attuati et al.

Kano, H., Kondziolka, D., Flickinger, J. C., Park, K. J., Parry, P. V., Yang, H. C., ... & Lunsford, L. D. (2012). Stereotactic radiosurgery for arteriovenous malformations, Part 6: multistaged volumetric management of large arteriovenous malformations. Journal of neurosurgery, 116(1), 54-65. Kano, H., Lunsford, L. D., Flickinger, J. C., Yang, H. C., Flannery, T. J., Awan, N. R., ... & Kondziolka, D. (2012). Stereotactic radiosurgery for arteriovenous malformations, Part 1: management of Spetzler-Martin Grade I and II arteriovenous malformations. Journal of neurosurgery, 116(1), 11-20. Kelly, M. E., Guzman, R., Sinclair, J., Bell-Stephens, T. E., Bower, R., Hamilton, S., ... & Levy, R. P. (2008). Multimodality treatment of posterior fossa arteriovenous malformations. Journal of neurosurgery, 108(6), 1152-1161. Kim, B. S., Kim, K. H., Lee, M. H., & Lee, J. I. (2019). Stereotactic Radiosurgery for Brainstem Cavernous Malformations: An Updated Systematic Review and Meta-Analysis. World neurosurgery, 130, e648-e659. Kim, H., Pourmohamad, T., & Young, W. L. (2012). Cerebellar arteriovenous malformation: Anatomic subtypes, surgical results, and increased predictive accuracy of the supplementary grading system. Neurosurgery, 71, 1111-1124. Kim, H., Salman, R. A. S., McCulloch, C. E., Stapf, C., Young, W. L., & MARS Coinvestigators. (2014). Untreated brain arteriovenous malformation: patient-level meta- analysis of hemorrhage predictors. Neurology, 83(7), 590-597. Kjellberg, R. N., Hanamura, T., Davis, K. R., Lyons, S. L., & Adams, R. D. (1983). Bragg- peak proton-beam therapy for arteriovenous malformations of the brain. New England Journal of Medicine, 309(5), 269-274. Kondziolka, D., Kano, H., Yang, H. C., Flickinger, J. C., & Lunsford, L. (2010). Radiosurgical management of pediatric arteriovenous malformations. Child's Nervous System, 26(10), 1359-1366. Lawton, M. T., Kim, H., McCulloch, C. E., Mikhak, B., & Young, W. L. (2010). A supplementary grading scale for selecting patients with brain arteriovenous malformations for surgery. Neurosurgery, 66(4), 702-713. Leksell, L. (1983). Stereotactic radiosurgery. Journal of Neurology, Neurosurgery & Psychiatry, 46(9), 797-803. Levy, E. I., Niranjan, A., Thompson, T. P., Scarrow, A. M., Kondziolka, D., Flickinger, J. C., & Lunsford, L. D. (2000). Radiosurgery for childhood intracranial arteriovenous malformations. Neurosurgery, 47(4), 834-842. Lindvall, P., Grayson, D., Bergström, P., & Bergenheim, A. T. (2015). Hypofractionated stereotactic radiotherapy in medium-sized to large arteriovenous malformations. Journal of Clinical Neuroscience, 22(6), 955-958. Maruyama, K., Kondziolka, D., Niranjan, A., Flickinger, J. C., & Lunsford, L. D. (2004). Stereotactic radiosurgery for brainstem arteriovenous malformations: factors affecting outcome. Journal of neurosurgery, 100(3), 407-413. Massager, N., Régis, J., Kondziolka, D., Njee, T., & Levivier, M. (2000). Gamma knife radiosurgery for brainstem arteriovenous malformations: preliminary results. Journal of neurosurgery, 93(supplement_3), 102-103. Medin, P. M., & Boike, T. P. (2011). Spinal cord tolerance in the age of spinal radiosurgery: lessons from preclinical studies. International Journal of Radiation Oncology Biology Physics, 79(5), 1302-1309.

Radiosurgery for Brain and Spinal Cord Arteriovenous and Cavernous Malformations 499

Mohr, J. P., Parides, M. K., Stapf, C., Moquete, E., Moy, C. S., Overbey, J. R., ... & Cordonnier, C. (2014). Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial. The Lancet, 383(9917), 614-621. Moosa, S., Chen, C. J., Ding, D., Lee, C. C., Chivukula, S., Starke, R. M., ... & Sheehan, J. P. (2014). Volume-staged versus dose-staged radiosurgery outcomes for large intracranial arteriovenous malformations. Neurosurgical focus, 37(3), E18. Mouchtouris, N., Chalouhi, N., Chitale, A., Starke, R. M., Tjoumakaris, S. I., Rosenwasser, R. H., & Jabbour, P. M. (2015). Management of cerebral cavernous malformations: from diagnosis to treatment. The Scientific World Journal, 2015. Nagy, G., Grainger, A., Hodgson, T. J., Rowe, J. G., Coley, S. C., Kemeny, A. A., & Radatz, M. W. (2017). Staged-volume radiosurgery of large arteriovenous malformations improves outcome by reducing the rate of adverse radiation effects. Neurosurgery, 80(2), 180-192. Nanda, A., Bir, S. C., Maiti, T. K., Konar, S. K., Missios, S., & Guthikonda, B. (2017). Relevance of Simpson grading system and recurrence-free survival after surgery for World Health Organization Grade I meningioma. Journal of neurosurgery, 126(1), 201-211. Neacsu, A., & Ciurea, A. V. (2010). General considerations on posterior fossa arteriovenous malformations (clinics, imaging and therapy). Journal of medicine and life, 3(1), 26. Nicolato, A., Longhi, M., Tommasi, N., Ricciardi, G. K., Spinelli, R., Foroni, R. I., ... & Meglio, M. (2015). Leksell Gamma Knife for pediatric and adolescent cerebral arteriovenous malformations: results of 100 cases followed up for at least 36 months. Journal of Neurosurgery: Pediatrics, 16(6), 736-747. Oermann, E. K., Ding, D., Yen, C. P., Starke, R. M., Bederson, J. B., Kondziolka, D., & Sheehan, J. P. (2015). Effect of prior embolization on cerebral arteriovenous malformation radiosurgery outcomes: a case-control study. Neurosurgery, 77(3), 406-417. de Oliveira, E., Tedeschi, H., & Raso, J. (1998). Comprehensive management of arteriovenous malformations. Neurological research, 20(8), 673-683. Pan, D. H. C., Kuo, Y. H., Guo, W. Y., Chung, W. Y., Wu, H. M., Liu, K. D., ... & Wong, T. T. (2008). Gamma Knife surgery for cerebral arteriovenous malformations in children: a 13-year experience. Journal of Neurosurgery: Pediatrics, 1(4), 296-304. Pollock, B. E., & Flickinger, J. C. (2002). A proposed radiosurgery-based grading system for arteriovenous malformations. Journal of neurosurgery, 96(1), 79-85. Pollock, B. E., & Flickinger, J. C. (2008). Modification of the radiosurgery-based arteriovenous malformation grading system. Neurosurgery, 63(2), 239-243. Pollock, B. E., Kondziolka, D., Flickinger, J. C., Patel, A. K., Bissonette, D. J., & Lunsford, L. D. (1996). Magnetic resonance imaging: an accurate method to evaluate arteriovenous malformations after stereotactic radiosurgery. Journal of neurosurgery, 85(6), 1044-1049. Ponce, F. A., & Spetzler, R. F. (2011). Arteriovenous malformations: classification to cure. Neurosurgery, 58(CN_suppl_1), 10-12. Potts, M. B., Sheth, S. A., Louie, J., Smyth, M. D., Sneed, P. K., McDermott, M. W., ... & Gupta, N. (2014). Stereotactic radiosurgery at a low marginal dose for the treatment of pediatric arteriovenous malformations: obliteration, complications, and functional outcomes. Journal of Neurosurgery: Pediatrics, 14(1), 1-11. Potts, M. B., Sheth, S. A., Louie, J., Smyth, M. D., Sneed, P. K., McDermott, M. W., ... & Gupta, N. (2014). Stereotactic radiosurgery at a low marginal dose for the treatment of

500 B. C. Bono, I. Zaed, L. Attuati et al.

pediatric arteriovenous malformations: obliteration, complications, and functional outcomes. Journal of Neurosurgery: Pediatrics, 14(1), 1-11. Potts, M. B., Lau, D., Abla, A. A., Kim, H., Young, W. L., & Lawton, M. T. (2015). Current surgical results with low-grade brain arteriovenous malformations. Journal of neurosurgery, 122(4), 912-920. Reyns, N., Blond, S., Gauvrit, J. Y., Touzet, G., Coche, B., Pruvo, J. P., & Dhellemmes, P. (2007). Role of radiosurgery in the management of cerebral arteriovenous malformations in the pediatric age group: data from a 100-patient series. Neurosurgery, 60(2), 268-276. Ryu, S. I., Chang, S. D., Kim, D. H., Murphy, M. J., Le, Q. T., Martin, D. P., & Adler Jr, J. R. (2001). Image-guided hypo-fractionated stereotactic radiosurgery to spinal lesions. Neurosurgery, 49(4), 838-846. Ryu, S. I., Kim, D. H., & Chang, S. D. (2003). Stereotactic radiosurgery for hemangiomas and ependymomas of the spinal cord. Neurosurgical focus, 15(5), 1-5. Salman, R. A. S. (2014). Management of brain arteriovenous malformations. The Lancet, 383(9929), 1633-1634. Sasaki, T., Kurita, H., Saito, I., Kawamoto, S., Nemoto, S., Terahara, A., ... & Takakura, K. (1998). Arteriovenous malformations in the basal ganglia and thalamus: management and results in 101 cases. Journal of neurosurgery, 88(2), 285-292. See, A. P., Raza, S., Tamargo, R. J., & Lim, M. (2012). Stereotactic radiosurgery of cranial arteriovenous malformations and dural arteriovenous fistulas. Neurosurgery Clinics, 23(1), 133-146. Seymour, Z. A., Sneed, P. K., Gupta, N., Lawton, M. T., Molinaro, A. M., Young, W., ... & McDermott, M. W. (2016). Volume-staged radiosurgery for large arteriovenous malformations: an evolving paradigm. Journal of neurosurgery, 124(1), 163-174. Silander, H., Pellettieri, L., Enblad, P., Montelius, A., Grusell, E., Vallhagen‐Dahlgren, C., ... & Gál, G. (2004). Fractionated, stereotactic proton beam treatment of cerebral arteriovenous malformations. Acta neurologica scandinavica, 109(2), 85-90. Sinclair, J., Chang, S. D., Gibbs, I. C., & Adler Jr, J. R. (2006). Multisession CyberKnife radiosurgery for intramedullary spinal cord arteriovenous malformations. Neurosurgery, 58(6), 1081-1089. Smyth, M. D., Sneed, P. K., Ciricillo, S. F., Edwards, M. S., Wara, W. M., Larson, D. A., ... & Mcdermott, M. W. (2002). Stereotactic radiosurgery for pediatric intracranial arteriovenous malformations: the University of California at San Francisco experience. Journal of neurosurgery, 97(1), 48-55. Solomon, R. A., & Stein, B. M. (1986). Management of arteriovenous malformations of the brain stem. Journal of neurosurgery, 64(6), 857-864. Sparks, H., Hovsepian, A., Wilson, B., De Salles, A., Selch, M., Kaprealian, T., & Pouratian, N. (2019). Dose Hypofractionated Stereotactic Radiotherapy for Intracranial Arteriovenous Malformations: A Case Series and Review of the Literature. World neurosurgery, 126, e1456-e1467. Spears, J., TerBrugge, K. G., Moosavian, M., Montanera, W., Willinsky, R. A., Wallace, M. C., & Tymianski, M. (2006). A discriminative prediction model of neurological outcome for patients undergoing surgery of brain arteriovenous malformations. Stroke, 37(6), 1457- 1464. Spetzler, R. F., & Martin, N. A. (1986). A proposed grading system for arteriovenous malformations. Journal of neurosurgery, 65(4), 476-483.

Radiosurgery for Brain and Spinal Cord Arteriovenous and Cavernous Malformations 501

Stapf, C., Mast, H., Sciacca, R. R., Choi, J. H., Khaw, A. V., Connolly, E. S., ... & Mohr, J. P. (2006). Predictors of hemorrhage in patients with untreated brain arteriovenous malformation. Neurology, 66(9), 1350-1355. Starke, R. M., Yen, C. P., Chen, C. J., Ding, D., Mohila, C. A., Jensen, M. E., ... & Sheehan, J. P. (2014). An updated assessment of the risk of radiation-induced neoplasia after radiosurgery of arteriovenous malformations. World neurosurgery, 82(3-4), 395-401. Starke, R. M., Yen, C. P., Ding, D., & Sheehan, J. P. (2013). A practical grading scale for predicting outcome after radiosurgery for arteriovenous malformations: analysis of 1012 treated patients. Journal of neurosurgery, 119(4), 981-987. Sun, D. Q., Carson, K. A., Raza, S. M., Batra, S., Kleinberg, L. R., Lim, M., ... & Rigamonti, D. (2011). The radiosurgical treatment of arteriovenous malformations: obliteration, morbidities, and performance status. International Journal of Radiation Oncology Biology Physics, 80(2), 354-361. Tanaka, T., Kobayashi, T., Kida, Y., Oyama, H., & Niwa, M. (1995). The comparison between adult and pediatric AVMs treated by gamma knife radiosurgery. No shinkei geka. Neurological surgery, 23(9), 773-777. Velat, G. J., Chang, S. W., Abla, A. A., Albuquerque, F. C., McDougall, C. G., & Spetzler, R. F. (2012). Microsurgical management of glomus spinal arteriovenous malformations: pial resection technique. Journal of Neurosurgery: Spine, 16(6), 523-531. Wegner, R. E., Oysul, K., Pollock, B. E., Sirin, S., Kondziolka, D., Niranjan, A., ... & Flickinger, J. C. (2011). A modified radiosurgery-based arteriovenous malformation grading scale and its correlation with outcomes. International Journal of Radiation Oncology Biology Physics, 79(4), 1147-1150. Winston, K. R., & Lutz, W. (1988). Linear accelerator as a neurosurgical tool for stereotactic radiosurgery. Neurosurgery, 22(3), 454-464. Wu, A., Lindner, G., Maitz, A. H., Kalend, A. M., Lunsford, L. D., Flickinger, J. C., & Bloomer, W. D. (1990). Physics of gamma knife approach on convergent beams in stereotactic radiosurgery. International Journal of Radiation Oncology Biology Physics, 18(4), 941- 949. Yen, C. P., Monteith, S. J., Nguyen, J. H., Rainey, J., Schlesinger, D. J., & Sheehan, J. P. (2010). Gamma Knife surgery for arteriovenous malformations in children. Journal of Neurosurgery: Pediatrics, 6(5), 426-434.

Chapter 31

INTRAOPERATIVE INDOCYANINE GREEN AND FLUORESCEIN VIDEOANGIOGRAPHY OF BRAIN AND SPINAL CORD VASCULAR LESIONS

F. Acerbi1, MD, PhD, I. G. Vetrano1, MD, G. Faragò2, MD and P. Ferroli1,*, MD 1Neurosurgical Unit II and 2Diagnostic Radiology and Interventional Neuroradiology Unit, Department of Neurosurgery, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy

ABSTRACT

Complete and real-time data on vascular pathophysiology represent a key point in modern neurosurgery. Indocyanine green video-angiography (ICG-VA) is designed to highlight intracranial vessels during neurosurgical procedures; the addition of FLOW 800 analysis software is able to provide a semiquantitative evaluation of cerebral blood flow, further expanding its application. More recently, also sodium fluorescein (SF) has been tested as intraoperative vascular tracer. SF-VA provides a good alternative for real-time assessment of the patency of main intracranial vessels and also perforating arteries, with excellent image quality. In this chapter, the authors present technical indications about ICG and SF videoangiographies in several neurovascular procedures, with different examples. In conclusion, ICG and SF videoangiography appear effective, safe, fast and reliable intraoperative tools in neurovascular procedures. They provide synergistic information about assessment of vessels patency, bypass function, and blood flow and may have dedicated selected indication for specific cases.

Keywords: fluorescein, FLOW 800, indocyanine green, ICG, vascular pathophysiology, videoangiography, YELLOW 560

* Corresponding Author’s Email: [email protected].

504 F. Acerbi, I. G. Vetrano, G. Faragò et al.

ABBREVIATIONS

AI Arbitrary Intensity Unit AVM Arteriovenous malformation AVF Arteriovenous fistula CNS Central nervous system DSA Digital subtraction angiography ICG Indocyanine green ICG-VA Indocyanine green videoangiography MCA Middle cerebral artery ROI Region of Interest SF Sodium fluorescein SF-VA Fluorescein videoangiography STA Superficial temporal artery

1. INTRODUCTION

The accurate, real-time evaluation of blood flow, and the assessment of vascular anatomy, represents a pivotal point in vascular neurosurgery, to confirm aneurysm obliteration, or the patency of adjacent arteries or bypasses. This information is critical to avoid hemorrhagic and ischemic complications. A main cause of post-operative complications after surgical treatment of neurovascular lesions is parent or branching vessel occlusion. It has been reported that rates of unexpected occlusion of major branches during aneurysm surgery, demonstrated with postoperative angiography, ranged up to the 12% (Macdonald, Wallace, and Kestle 1993; Katz et al. 2006). While the digital subtraction angiography (DSA) is the gold standard for perioperative vessels visualization, it is difficult to integrate this tool in intraoperative setting (Katz et al. 2006). In the last years, intraoperative fluorophores have progressively acquired a mandatory role in neurosurgery, not only in neuro-oncological applications but also in vascular procedures. Since the first reports in early 2000 (Raabe et al. 2003, 2005), microscope-integrated indocyanine green video-angiography (ICG-VA) has been employed in vascular neurosurgery to better visualize cerebral vessels during aneurysm clipping, bypass surgery or arteriovenous malformation resection (Acerbi et al. 2019; Ferroli, Nakaji, et al. 2011; Ferroli, Acerbi, Tringali, et al. 2011; Acerbi, Cavallo, and Ferroli 2016; Dashti et al. 2009; De Oliveira et al. 2008; Hettige and Walsh 2010; Kamp et al. 2012; Raabe et al. 2003; D. L. Kim and Cohen- Gadol 2013). In case of unexpected arterial damage, the surgeon would benefit from a fast real- time tool able to identify regions of parenchymal hypoperfusion, to predict the effects of this inadvertent occlusion and, if possible, to perform intraoperatively maneuvers to revert the situation (Acerbi, Cavallo, and Ferroli 2016; Kamp et al. 2012; Ng et al. 2013; Uchino et al. 2014; Woitzik et al. 2005). Moreover, it has been shown that ICG-VA could also have a positive impact on venous management during neuro-oncological and neuro-vascular procedures (Acerbi, Vetrano, et al. 2018; Ferroli, Nakaji, et al. 2011; Vetrano, Ferroli, and Acerbi 2018). More recently, the integration of the new FLOW 800 software (FLOW 800 Software Analysis Tool, Pentero and Kinevo microscopes, Carl Zeiss Co., Oberkochen, Germany) in the operating microscope, allowed to perform a post-processing semi-quantitative analysis of blood flow in

Intraoperative Indocyanine Green and Fluorescein Videoangiography … 505 arteries, brain parenchyma (capillary phase), and venous system (Kamp et al. 2012). This could be associated to a better understanding of the pathophysiology of CNS circulation in neurosurgical procedures (Acerbi, Cavallo, and Ferroli 2016). Another fluorescent dye that had been extensively studied in neurosurgery is the sodium salt of fluorescein (SF). It is a green fluorescent synthetic organic compound that has several medical applications, mainly in ophthalmologic field. Initially its use has been limited to retinal angiography, while historical and sporadic utilizations in neurosurgery were reported for brain tumor surgery (Hubbard and Moore 1949; Moore 1947). Later, in 1967, Feindel described the evaluation of intracranial circulation in humans and in animals trough fluorescein injection (Feindel, Yamamoto, and Hodge 1967); this technique was also applied in 1971 by the same authors to describe AVM surgery (Feindel, Yamamoto, and Hodge 1971). The possibility to use SF in neurosurgical procedures changed dramatically after the introduction of an integrated filter in the surgical microscope (YELLOW 560, Pentero 900 and Kinevo; Carl Zeiss Meditec, Oberkochen, Germany), that allowed to reduce SF dosage, due to the better detection of fluorescence signal, determining also a more natural visualization directly through microscope oculars of the non-fluorescent areas (Acerbi et al. 2013). Since that point, SF applications have exponentially increased, mainly for neuro-oncological applications (Li et al. 2014; Xiao et al. 2018; Cavallo et al. 2018; Schebesch et al. 2015; Acerbi, Broggi, et al. 2018; Acerbi et al. 2017; De Laurentis et al. 2019), due to the concentration of the dye in CNS areas with blood-brain barrier (BBB) disruption, like the process of contrast enhancement on MRI. More recently, the original applications of SF as vascular tracer have been again reported, to perform fluorescein angiography (SF-VA) in neurovascular cases, in particular for superficial temporal artery (STA)-to-middle cerebral artery (MCA) bypass and in aneurysms clipping (Narducci et al. 2018; Matano et al. 2017; Kakucs et al. 2017; Narducci et al. 2019; Hashimoto et al. 2017). SF has been described as a suitable fluorophore for intraoperative angiography primarily for aneurysm clip ligation, in some cases superior to ICG in terms of perforators visualization (Matano et al. 2017). Its usefulness has been also advocated for arteriovenous malformation surgery (Bretonnier et al. 2018; Lane and Cohen-Gadol 2014), and for spinal dural AVF exclusion (Bretonnier, Morandi, and Le Reste 2019). In this chapter, we present our surgical strategies based on fluorescence dyes administration in vascular neurosurgical procedures, both cranial and spinal. Several illustrative cases highlight the feasibility, potentiality and versatility of these intraoperative fluorophores.

2. METHODS

2.1. ICG Videoangiography

Indocyanine green dye is a fluorescent tricarbocyanine with an absorption and emission peaks of 805 and 835 nm, respectively. After its intravenous (i.v.) injection, ICG bounds within 1 to 2 seconds to circulating globulins and remains intravascular. ICG is not metabolized in the body and is excreted by the liver, with a plasma half-life of 3-4 minutes. No reabsorption by the intestine and no enterohepatic recirculation is reported. To perform an ICG-VA, we generally use a standard dose of 12.5 mg of ICG (Verdye 5 mg/ml, Diagnostic Green GmbH, Aschheim, Germany), injected via a central venous line, and a dedicated microscope equipped with IR800 filter (Pentero 900, Carl Zeiss Meditec,

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Oberkochen, Germany). The dose can be repeated if necessary, but never exceeding the maximum daily dose of 5 mg/kg. For optimal image quality, before starting the videoangiography a magnification of 3.5x and a working distance of 300 mm are recommended; however these settings are not compulsory and might be adapted to application needs. Pushing the fluorescence button the first time enters a setup phase guiding the surgeon to set zoom and focus settings within his preset range; by pushing the same button again, the light intensity is set to 50%, the synchronous video recording of the white light view and the near-infrared signal is then started, and the ICG fluorescence is displayed on the screen. During acquisition, if FLOW800 analysis is considered, the microscope has to be maintained in a fixed position, without moving surgical instruments in the exposed area to ensure optimal data recording (duration of at least 60 seconds). The FLOW800 algorithm in the Zeiss Microscopes calculates fluorescence intensities in the exposed areas based on arbitrary intensity units (AIs) detected by the camera; it then reconstructs maps of maximal fluorescence intensities and of delay times (time interval until 50% of maximum fluorescence). The maps are shown as grey- scale of maximal fluorescence intensities, and as color-scale based on the time to half-maximal fluorescence, respectively. In addition, the course of fluorescence could be further analyzed in any area of the exposed brain, including parenchyma, by using freely definable regions of interest (ROIs), manually placed on the microscope monitor. Finally, short and long replay for comparison of images as well as for picture-in-picture comparison are possible. The infrared neuronavigator camera should not be directed on surgical field during ICG-VA, to avoid impairments and interferences due to infrared waves emitted by the camera itself. Due to ICG half-life, ICG videoangiography could be repeated after 10 minutes, as many time as needed, avoiding to exceed the maximal ICG daily dosage of 5 mg/kg. Despite the very high safety profile of ICG and the very low incidence of complications, recently two ICG-related anaphylactic reactions during aneurysms surgery were reported (M. Kim et al. 2019).

2.2. Fluorescein Videoangiography

The SF is a water-soluble dye with a major blue excitation peak in the region of 460–500 nm and a major green emission peak in the region of 540 to 690 nm. A microscope equipped with a dedicated filter (i.e., YELLOW560 module on Zeiss Microscopes) is necessary for intraoperative fluorescein angiography. The excitation of SF under the light at 465–490 nm wave lengths results in yellowish-green fluorescence. We usually administer an i.v. bolus of 75 mg of fluorescein (Sodium fluorescein 20% 1 g/5 ml, Monico SpA, Venice, Italy), which represents the standard dose, through a central venous line, switching the microscope from with light to the YELLOW560 filter for fluorescence visualization. To increase image quality, the operative room lights are usually temporarily switched off. Approximately 15-20 seconds after a bolus venous administration, the fluorescent vessels can be visualized directly through the operating oculars, differently than the ICG-VA. The arterial, capillary, and venous phases are clearly observed in yellow/green color and the related video could be recorded. If necessary, the SF videoangiography can be repeated after 20–25 minutes, due to the time for clearance from brain parenchyma; side effects related to fluorescein administration have been well characterized, due to its extensive use in ophthalmology, and this dye is characterize by a very high safety profile (Kornblau and El-Annan 2019).

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3. RESULTS AND ILLUSTRATIVE CASES

From January 2011 to March 2019, we used ICG-VA in 226 aneurysms, 60 AVMs, 58 bypasses for Moyamoya diseases, and 54 dural AVFs. In a selected percentage of patients, SF was used in an off-label setting, upon written patient consent, to explore its feasibility in vascular cases, on the bases of our extensive experiences in neuro-oncological surgery (Acerbi et al. 2017; Falco et al. 2019). In all cases, both filter for ICG and SF were available on the same operative microscope (Pentero 900). ICG-VA was always performed in aneurysms surgery, just before and after clipping, as well as before and after dural AVFs occlusion. In AVM surgery, ICG-VA was employed before and after AVM resection; however, in selected cases, it was also repeated during AVM resection, for real-time evaluation of flow modification related to arterial feeders progressive occlusion. On the other hand, SF-VA was performed differently: 1) during aneurysms and AVFs surgery, we used SF-VA only either at the beginning or at the end of the procedure to better show the vascular malformation or to confirm complete aneurysm and AVF occlusion and patency of main branches and perforators (for aneurysm only), due to the need of waiting at least 20 minutes before each SF administration; 2) for AVM and bypasses, SF-VA could be repeated more than one time, based on surgeon need, thanks to the more prolonged time of the surgical procedure (i.e AVM removal and microanastomosis). ICG-VA with FLOW-800 analysis always allowed us to optimally visualize arterial, capillary-parenchymal and venous phases of exposed vessels and surrounding parenchyma. Regarding aneurysms, ICG-VA allowed to confirm total sac occlusion and identify main branches patency. In 4 aneurysm cases, ICG-VA suggested a clip repositioning for the evidence of main branches or perforating arteries occlusion. In two other cases, instead, the sac appeared incompletely closed: one MCA trifurcation aneurysm, and one ICA aneurysm. In all these cases, ICG-VA was considered particularly useful because it allowed a real-time modification of the surgical procedure. In all AVMs, ICG-VA determined useful information on nidus site, superficial angioarchitecture, and also on residual arteriovenous shunts. In all AVFs, the fistula occlusion and normalization of venous flow was confirmed through ICG injection at the end of the surgical procedure. Finally, in all Moyamoya diseases the pre-bypass ICG-VA with FLOW800 analysis was performed to better understand the cortical flow and perfusion, and to identify the best cortical recipient artery for the microanastomosis, i.e., the M4 vessel with slower flow in the map of delay time based on FLOW800 analysis. In one cases of STA-MCA bypass, the final videoangiography showed that the bypass appeared thrombosed. However, in all cases with patent bypass, the FLOW800 analysis confirmed the increased cortical perfusion assured by the bypass. Regarding SF-VA, performed in selected cases, it was considered particularly useful in aneurysm surgery, because it allowed a better identification of the patency of small perforating vessels, with higher image quality, compared to ICG-VA. On the contrary, for AVM, AVFs and bypass, SF-VA could give comparable information to ICG-VA about vascular anatomy, taking into consideration the limitation related to the time needed between each injection, and to the impossibility to measure semiquantitatively the blood flow as assured by FLOW800 post- processing analysis. No side effects related to the contemporary use of sodium fluorescein and ICG-VA were registered. We thereby describe four exemplificative cases illustrating the main indication for ICG- VA and SF-VA in vascular neurosurgery.

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3.1. Intracranial Saccular Aneurysms

A 45 years old female, heavy smoker with a history of headache and familiar positive history of intracranial aneurysms, came to our attention for a diagnosis of a 6 mm right irregular MCA aneurysm. After multidisciplinary discussion, due to patient age, shape of the aneurysm and co-existence of risk factors, a surgical indication was made. After exposure of the aneurysm (Figure 1 A), a first ICG injection was performed (Figure 1 B); maps of delay time and maximal fluorescence were then evaluated (Figure 1 C). After clipping (Figure 1 D), ICG videoangiography (Figure 1 E) confirmed the aneurysm’s sac exclusion, with patency and symmetric flow on both M2 branches, demonstrated by FLOW-800 analysis (Figure 1 F, H). SF-VA also showed complete aneurysm occlusion and, with better definition, the small perforating branches, still patent after surgical clipping. The post-operative course was uneventful, without neurological deficits.

3.2. Arteriovenous Malformations

A female patient, 35 years old, with a right cerebellar AVM partially treated in another Institution with embolization and radiosurgery, came to our attention for the surgical treatment of the small residual cerebellar AVM. During the clinical and radiological assessment, a small left occipital AVM was diagnosed (Figure 2 A-C). After removal of the cerebellar AVM, a surgical indication of the second small AVM was made. After dural opening, the small AVM nidus with its draining vein was visualized (Figure 2 D).

Figure 1. (A) Intraoperative white light view of the right irregular MCA aneurysm (white arrow at coronal preoperative angioCT scan in I). The first ICG-VA depicted the flow inside the sac and the distal arterial branch (B). The delay map (C) outlines the blood flow velocity with a color-scale from red to blue, based on time to half-maximal fluorescence. After clip positioning (D) the repeated ICG injection allowed to confirm aneurysm exclusion and patency of both M2 branches (E); FLOW-800 analysis with map of delay time confirmed the blood flow-symmetry between the two M2 branches, as evident in the map of delay time and also in the analysis of flow curves, ruling out any vessels stenosis or spasm related to clip positioning (F, H). SF-VA illustrated aneurysm sac occlusion, patency of main M2 branches, and also highlight with better quality image the patency of small perforating arteries (G).

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The first ICG survey allowed to identify the two superficial arterial feeders, the nidus and the arterialized draining vein (Figure 2 E). These findings were more clearly visible on the map of delay time, based on FLOW800 analysis (Figure 2 F): the superficial feeders, the nidus and the arterialized vein were, in fact, shown in red color, with higher contrast compared to the grey scale map; in addition, a slower cortical flow to the surrounding brain parenchyma was found, indirect sign of perfusion impairment. After complete AVM resection (Figure 2 G-F), the final ICG survey confirmed the absence of residual A-V shunts and the flow speed normalization on the venous site, together with an improvement of brain perfusion compared to the first ICG survey. We also performed a pre-resection SF-VA (Figure 2 J-L), which showed an extremely well-defined 3D vascular cortical network, with identification of superficial arterial feeders, AVM nidus and the draining vein, without additional, relevant information if compared to ICG- VA. After surgery, the patient did not experience any new neurological deficit or seizures.

Figure 2. The axial T1-weightet MRI after contrast (A) and the CT scan with contrast (B) showed a small left occipital AVM (arrow), confirmed also by the DSA, that showed the superficial feeders from left posterior cerebral artery and only one superficial draining vein to the superior sagittal sinus (arrow in C). After dural opening, the small AVM nidus with its draining vein was visualized (arrow in D). The grey scale map based on maximal fluorescence intensity, after the first ICG survey, allowed to identify the two superficial arterial feeders (arrowhead), the nidus and the arterialized draining vein (arrow) (E). The superficial feeders (arrowhead), the nidus and the arterialized vein (arrow) were more clearly visible on the map of delay time, based on the time to half maximal fluorescence derived from FLOW800 analysis, identified in red color, with higher contrast compared to the grey scale map; in addition, a slower cortical flow (green-blue area) to the surrounding brain parenchyma was found, indirect sign of perfusion impairment (F). After removal of the AVM (G), the final ICG survey (H) confirmed the absence of residual nidus or A-V shunt. The FLOW 800 assessment (I) depicted the flow normalization of the vein, that appeared blue, while the flow of surrounding brain parenchyma improved compared to the previous ICG injection. SF-VA clearly showed a better definition of the pail cortical network compared to ICG- VA; however, arterial feeders, AVM nidus and the draining vein could be identified with less details compared to the ICG map of delay time (J-L).

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3.3. STA-MCA Bypass

A 37 years old female with symptomatic Moyamoya disease, characterized by multiple strokes on the left hemispheres, and bilateral hemispheric hypoperfusion, presented to our attention. She firstly underwent a direct and indirect revascularization of the symptomatic and more affected left hemisphere. After four months, a second revascularization procedure surgery was proposed for the right hemisphere. The patient was therefore submitted to STA-MCA bypass and encephaloduromyosynangiosis. After dural opening and brain exposure (Figure 3A), a first ICG-VA was performed to identify possible recipient arteries for the microanastomosis and evaluate the brain cortical perfusion (Figure 3B, C). The map of maximal fluorescence highlighted two frontal M4 branches and one temporal M4 branch (Figure 3B). The map of delay time identified slow flow in the three M4 arteries (green on the color map) with diffused hypoperfusion, that was particularly evident in the frontal lobe (Figure 3C). Therefore, this was the chosen area for revascularization, with the more anterior and slower frontal M4 branch as the recipient artery for STA-MCA bypass. The SF-VA confirmed the worst perfusion in the frontal lobe (Figure 3D). After STA-MCA was completed (Figure 3E), a second ICG-VA was performed (Figure 3F-G). The map of maximal fluorescence confirmed the bypass patency and improvement of brain perfusion (Figure 3F). This information was more evident in the map of delay time that clearly showed the improved perfusion in the frontal lobe, compared with previous ICG injection (Figure 3G). Post-operative CT-angio confirmed bypass patency and absence of complications. Patient was discharged home on post-operative day 5. No further TIA or stroke episodes presented in the follow-up period.

Figure 3. Intraoperative photograph of cortical surface in a patient with Moyamoya disease. After dural opening and brain exposure (A), a first ICG-VA (B) was performed to identify possible recipient arteries for the microanastomosis and evaluate the brain cortical perfusion. The map of maximal fluorescence highlighted two frontal M4 branches (arrows) and one temporal M4 branch (arrowhead). The map of delay time (C) identified slow flow in the three M4 arteries (green on the color map) with diffused hypoperfusion, more pronounced in the anterior part of the frontal lobe. The SF-VA (D) confirmed the worst perfusion in the frontal lobe. After STA-MCA was completed (E), a second ICG-VA (F) confirmed the bypass patency (arrow) and improvement of brain perfusion. This information was more evident in the map of delay time (G) that clearly showed the improved perfusion in the frontal area, compared with previous ICG injection. The post-operative angio-CT scan performed after 24 hours (H) confirmed the bypass patency (dotted arrow).

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3.4. Spinal Dural AVF

A 70 years old male was admitted to our Institution due to progressive hyposthenia of lower limb in the last three years, with more recent onset of urinary incontinence. The dorsal MRI showed myelopathy with characteristic hyperintense signal from D8 to L2, together with hypertrophic perimedullary venous system (Figure 4 A). A subsequent spinal DSA depicted a dural arteriovenous fistula at the level of the left conjugation foramen of D8-D9 (Figure 4 B- C). Therefore, the patient underwent surgery for AVF occlusion (Figure 4 D). Both SF-VA (Figure 4 E) and ICG-VA (Figure 4 F) with FLOW800 analysis (Figure 4 G) confirmed the dural fistula at the level of left D8-D9 radicular cleft, by showing fast and rapid flow inside the arterialized vein. After clipping of the fistula at the level of the dural entrance, confirmation of flow normalization in the perimedullary plexus was shown by the restoration of its natural blue color, which was confirmed by a second ICG survey (Figure 4I). Our policy, in cases when such ICG results were intraoperatively found, is not to perform a standard post-operative spinal DSA, but only post-operative MRI to rule out complications and confirm at long follow-up the improvement of myelopathy and the disappearance of the hypertrophic venous plexus. After surgery, the patient was referred to physical medicine and rehabilitation center.

Figure 4. Spinal dural arteriovenous fistula at left D8 and D9. (A) Pre-operative dorsal MRI showed myelopathy with characteristic hyperintense signal from D8 to L2, together with hypertrophic perimedullary venous system Dyna-CT (B, C) clearly shows the dural AV fistula entering at the level of the left D8-D9 foramen. After dural opening (D) the AV fistula (white arrow) entering the radicular cleft at left D8-D9 was found. SF-VA (E) confirmed the arterialized flow in the vein, symmetric to the small perimedullary arteries. ICG-VA (with map of maximal fluorescence (F) and map of delay time (G) confirmed the origin of the fistula and the fast flow involving perimedullary venous system. After positioning of a temporary clip on the origin of dural fistula (H), a second ICG-VA showed the normalization of the flow (I): the fistula was therefore coagulated and sectioned.

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4. DISCUSSION

Intraoperative videoangiography techniques, mainly ICG-VA and, more recently, SF-VA, have greatly contributed to the safety and accuracy of neurovascular surgical procedures. Indocyanine green video-angiography has been designed to highlight superficial vessels, whereas the FLOW 800 analysis software has greatly expanded the usefulness of ICG-VA, due to the possibility to perform a semiquantitative analysis of blood flow in the exposed area. In particular, the algorithm integrated in the microscope reconstructs maps of gray intensity based on the average AIs of infrared fluorescence detected by the microscope camera, and maps of delay time based on the time needed to reach 50% of the maximal fluorescence intensity. In addition, it is possible to study the curves of fluorescence detected by the camera over the time of ICG-VA registration for multiple ROIs, whereas ROIs hare arbitrarily placed by surgeons. The first authors to explore the use of microscope-integrated semiquantitative analysis of ICG-VA for blood flow assessment were Kamp et al., who analyzed a series of 30 patients harboring neuro-vascular pathologies (Kamp et al. 2012). They hypothesized to use the different parameters derived from FLOW 800 analysis in clinical applications, showing that the maps of delay time could be of great value in giving an immediate representation of blood flow perturbation in cortical areas, either as an effect of the disease itself, or due to iatrogenic damage to arterial manipulation. Since them, ICG-VA with flow analysis have taken on an increasingly predominant role in neurosurgery (Shah and Cohen-Gadol 2019; Roessler et al. 2014), also thanks to the negligible risk of procedural complication. Very recently, Marbecher and coauthor compared ICG-VA with intraoperative DSA, performed in a hybrid operating room for aneurysms clipping: they report an high accuracy of videoangiography with ICG compared with 3D-DSA imaging, whereas DSA was confirmed to be the gold standard (Marbacher et al. 2019). However, a systematic review comparing DSA and ICG-VA in aneurysm surgery, showed a rate of aneurysm misclipping identified with DSA but not with ICG-VA, up to 4.5% (Riva et al. 2018). In our routinely clinical practice, the ICG-VA and the FLOW 800 evaluation are used to confirm arterial and venous patency, and the state of local parenchymal perfusion, predicting therefore the possible complications directly related to vessels management. In case of local hypoperfusion subsequent to vessels manipulation, the flow analysis allows to perform compensatory surgical maneuvers to immediately revert the local hypoperfusion and reduce the risk of complications (Acerbi, Cavallo, and Ferroli 2016; Ng et al. 2013; Kobayashi et al. 2014). Even though this task could be performed also with classic ICG-VA, as already reported in our previous experience and in a similar study by other authors (Ferroli, Acerbi, Albanese, et al. 2011; Kim, Cho, Chang, et al. 2011), the analysis of blood flow by FLOW 800 software allowed to better interpret brain perfusion, particularly with maps of delay times (Kamp et al. 2012). This could be particularly important in cases of STA-MCA bypass performed for ischemic disease such as Moyamoya. In our series, we always analyzed the exposed brain parenchyma immediately after dural opening to evaluate the best M4 recipient for the microanastomosis, i.e, the vessel with slower flow in the area that is less cortically perfused on the map of delay time. In all our cases, apart from one thrombosed bypass, we were able to demonstrate an improved perfusion after the direct revascularization, thanks to the repeated ICG injection and FLOW800 analysis.

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Despite all these advantages, ICG-VA presents some limitations: the major drawback of ICG-VA is that it captures only what is visible within the field of the surgical microscope (Acerbi et al. 2019) and, as a consequence, it requires that the vessels must be cleared of any overlying tissue, such as blood clots or cottonoids (Hänggi, Etminan, and Steiger 2010; Killory et al. 2009); in addition, also calcifications within the vessels could impede a correct evaluation of the flow. Secondly, ICG-VA usefulness is decreased when the surgical field is deep-seated, needing a long, narrow surgical corridor to be reached. In this case, the signal and illumination can be low and the limited depth of field can make interpretation difficult (Killory et al. 2009; Hänggi, Etminan, and Steiger 2010; Ng et al. 2013). Furthermore, the classic ICG method is purely qualitative and its interpretation is based on the judgment of the operating neurosurgeon without any objective measures. Only after the introduction of the software FLOW 800, ICG videoangiography became a reliable method to evaluate vascular and regional cerebral cortical blood flow during surgical procedures (Kamp et al. 2012); however, it requires more time to be performed and interpreted and, more importantly, the microscope must be maintained in a fixed position to perform the flow measurement. This represents an important limitation when it is necessary to look around the corner to visualize patency of multiple perforators, as for instance in anterior communicating artery aneurysms. Furthermore, a learning curve is necessary to acquire the skills to use FLOW800 software and to interpret the results; we suggest starting with superficial analysis on simple cases in order to familiarize with the technique and thereafter proceed to the evaluation of more complex vascular abnormalities. Finally, apart from the recently released Kinevo microscope (Carl Zeiss Meditec), the IR 800 module for ICG does not allow the visualization of videoangiography through the microscope oculars, but the surgeon needs to follow the analysis on the adjacent microscope monitor. A possible alternative to ICG is represented by using SF. Utilization of SF in neurosurgical procedures has expanded recently, in the field of neuro-oncological surgery, due to the availability of dedicated filters in different surgical microscope, by taking advantage of the passage of the dye through a damaged blood-brain barrier (Acerbi et al. 2017; Falco et al. 2019). While the role of SF as fluorescent tracer is therefore well established for brain and spinal tumors surgery, its potential as videoangiographic tracer is less known. Whereas Wrobel in 1994 (Wrobel et al. 1994) and Suzuki in 2007 (Suzuki et al. 2007) presented two preliminary reports about the fluorescein in aneurysm surgery, their results were affected by the lack of a specific filter, requiring a high dose of dye administration. However, Suzuki and coauthors confirmed an excellent image quality in real-time assessment of the patency of the perforating arteries and branches near the aneurysm (comprising anterior choroidal, lenticulostriate, recurrent arteries of Heubner, hypothalamic, and thalamoperforating arteries). In 2017, Misra and coauthors showed the role of SF angiography with a dedicated filter in the surgical microscope, for intra-operative evaluation of a conus medullaris AVM, after administration of a dose of 1.5 mg/kg (Misra, Samantray, and Churi 2017). They also performed ICG-VA to confirm fluorescein findings, but in their experience the tiny perforators were better visualized by SF, compared to ICG videoangiography, thanks to possibility to work with higher magnification. As a matter of fact, while performing an ICG-VA only a fixed magnification is possible. On the other hand, they also noted that the fluorescence due to SF persisted in the vasculature for a longer period than ICG, therefore affecting the possibility to perform a second fluorescence survey.

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The introduction of specific filters integrated in the surgical microscope, led to an increased number of publications on the use of SF-VA in vascular neurosurgery (Narducci et al. 2018, 2019; Bretonnier et al. 2018; Bretonnier, Morandi, and Le Reste 2019; Kakucs et al. 2017; Lane and Cohen-Gadol 2014; Matano et al. 2017). Differently than neuro-oncological procedures, the dose administrated to perform a SF videoangiography is fixed, as a bolus just before the visualization. We suggest, as other authors, to use in every adult case a dose of 75 mg of SF, independently from patient’s weight. During SF-VA, it is possible to visualize the fluorescence flow pattern directly through the oculars, without the need to interrupt the procedure, whereas the angiography is visible through the microscope monitor as well. In 2018, Narducci, Nakaji and coworkers reported on a series of 11 extracranial-to- intracranial bypasses for Moyamoya disease, steno-occlusive cerebrovascular disease, and giant MCA aneurysms (Narducci et al. 2018). In all cases, the bypass patency was excellently intraoperatively demonstrated through SF-VA, and these findings were confirmed by postoperative traditional imaging. They found this technique slightly less sensible than ICG-VA about flow velocity assessment; the lack of a dedicated software to perform hemodynamic analysis as FLOW 800 represented, in their opinion, another pitfall. However, SF-VA depicted a higher number of vessels than ICG, as a consequence of the fluorescein mechanism of act, moreover providing an extremely well defined view of cortical vascular network also in deeper parenchyma areas. We found similar information also in our series, particularly for aneurysm surgery, giving the opportunity to assess small perforators after surgical clipping, with much more details then ICG-VA. Another big advantage of fluorescein videoangiography could be represented by the possibility to real-time manipulate the neurovascular structures during the fluorescent visualization: this is particularly relevant in case of deep surgical field, like in anterior communicating artery aneurysms. Bretonnier and coauthors confirmed the usefulness of SF-VA also in AVMs and spinal AVFs surgery, comparing the resulting findings with the ICG-VA (Bretonnier et al. 2018; Bretonnier, Morandi, and Le Reste 2019). They concluded that SF was useful to understand AVM angioarchitecture and to guide AVM resection and AFV exclusion, confirming its advantages and disadvantages. However, in our experience, we found that the information provided by ICG-VA, particularly using the FLOW800 analysis, is superior to SF-VA for AVM and AVF, because it improved the recognition of feeding arteries from draining vein, that is particularly difficult in complex angioarchitectures. Thus, in these cases, we consider at the moment ICG-VA as the gold standard, with SF-VA representing a valid but still suboptimal alternative. Possible advantages of SF videoangiography over ICG videoangiography are represented by the superior number of cortical of vessels visualized, and the possibility to visualized the fluorescent tracer through the oculars (Matano et al. 2017). Also the parenchymal tissue surrounding the vessels is clearly visualized with the SF filter activated, in almost natural color, while the black and white picture of ICG provides no clear information about the brain parenchyma. Larger depth of focus level provided visualization of deeper areas with more details than ICG. It should be take into consideration, however, that a second analysis with SF- VA after very short time from the previous one can determine false-positive findings, due to the long staining into the vessels and the brain parenchyma: if necessary, it is recommended to wait more than 20 minutes for a second fluorescence visualization. Analyzing all these characteristics, it is reasonable to consider ICG-VA and SF-VA as complementary techniques, particularly for aneurysm surgery, providing different information in the same patient, taking advantages from both dyes. As a matter of fact, ICG-VA with

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FLOW800 could be used to give semiquantitative data about blood flow in the main arteries after clipping, while SF-VA could give complementary data about small perforators’ patency, particularly behind the surgical clips or in deep seated locations. For other vascular malformation, we still consider at the moment that ICG-VA with FLOW800 analysis is superior. However, SF-VA is a very good alternative, particularly if, for economic choice, only a single fluorescent filter could be integrated in the microscope. If this is the case, the versatility of SF as neuro-oncological and neuro-vascular tracer should be taken into consideration. It should be stressed that no adverse events or impairment in visualization have been reported, in our series or in literature, after the simultaneous, use during the same procedure, of both dyes (Matano et al. 2017; Bretonnier et al. 2018; Narducci et al. 2018; Acerbi et al. 2016).

CONCLUSION

Complete and real-time data on vascular pathophysiology represent a key point in modern neurosurgery that should be undoubtedly evaluated, not only in neurovascular cases. Both ICG and SF videoangiography provide information about vascular angioarchitecture and vessels patency, although only ICG-VA provides semiquantitative data on blood flow and brain perfusion. They appear as an effective, safe, fast and reliable intraoperative tool in neurovascular procedures. The use of both techniques during the same procedure can maximize the respective advantages.

REFERENCES

Acerbi, Francesco, Morgan Broggi, Marica Eoli, Elena Anghileri, Lucia Cuppini, Bianca Pollo, Marco Schiariti, et al. 2013. “Fluorescein-Guided Surgery for Grade IV Gliomas with a Dedicated Filter on the Surgical Microscope: Preliminary Results in 12 Cases.” Acta Neurochirurgica 155 (7): 1277–86. https://doi.org/10.1007/s00701-013-1734-9. Acerbi, Francesco, Morgan Broggi, Karl-Michael Schebesch, Julius Höhne, Claudio Cavallo, Camilla De Laurentis, Marica Eoli, et al. 2018. “Fluorescein-Guided Surgery for Resection of High-Grade Gliomas: A Multicentric Prospective Phase II Study (FLUOGLIO).” Clinical Cancer Research 24 (1): 52–61. https://doi.org/10.1158/1078-0432.CCR-17- 1184. Acerbi, Francesco, Claudio Cavallo, and Paolo Ferroli. 2016. “Letter: Intraoperative Assessment of Blood Flow with Quantitative Indocyanine Green Videoangiography: The Role for Diagnosis of Regional Cerebral Hypoperfusion.” Neurosurgery 78 (2): E310-2. https://doi.org/10.1227/NEU.0000000000001053. Acerbi, Francesco, Claudio Cavallo, Karl-Michael Schebesch, Mehmet Osman Akçakaya, Camilla de Laurentis, Mustafa Kemal Hamamcioglu, Morgan Broggi, et al. 2017. “Fluorescein-Guided Resection of Intramedullary Spinal Cord Tumors: Results from a Preliminary, Multicentric, Retrospective Study.” World Neurosurgery 108 (December): 603–9. https://doi.org/10.1016/j.wneu.2017.09.061. Acerbi, Francesco, Francesco Prada, Ignazio G Vetrano, Jacopo Falco, Giuseppe Faragò, Paolo Ferroli, and Francesco DiMeco. 2019. “Indocyanine Green and Contrast-Enhanced

516 F. Acerbi, I. G. Vetrano, G. Faragò et al.

Ultrasound Videoangiography: A Synergistic Approach for Real Time Verification of Distal Revascularization and Aneurysm Occlusion in a Complex Distal Middle Cerebral Artery Aneurysm.” World Neurosurgery 125 (February): 277–84. https://doi.org/10.1016/ j.wneu.2019.01.241. Acerbi, Francesco, Francesco Restelli, Morgan Broggi, Marco Schiariti, and Paolo Ferroli. 2016. “Feasibility of Simultaneous Sodium Fluorescein and Indocyanine Green Injection in Neurosurgical Procedures.” Clinical Neurology and Neurosurgery 146 (July): 123–29. https://doi.org/10.1016/j.clineuro.2016.05.003. Acerbi, Francesco, Ignazio G Vetrano, Tommaso Sattin, Camilla de Laurentis, Lorenzo Bosio, Zefferino Rossini, Morgan Broggi, Marco Schiariti, and Paolo Ferroli. 2018. “The Role of Indocyanine Green Videoangiography with FLOW 800 Analysis for the Surgical Management of Central Nervous System Tumors: An Update.” Neurosurgical Focus 44 (6): E6. https://doi.org/10.3171/2018.3.FOCUS1862. Bretonnier, Maxime, Pierre-Louis Henaux, Xavier Morandi, and Pierre-Jean Le Reste. 2018. “Fluorescein-Guided Resection of Brain Arteriovenous Malformations: A Short Series.” Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia 52 (June): 37–40. https://doi.org/10.1016/j.jocn.2018.02.015. Bretonnier, Maxime, Xavier Morandi, and Pierre-Jean Le Reste. 2019. “Fluorescein-Guided Surgery for Spinal Dural Arteriovenous Fistulas: A Short Series.” Journal of Clinical Neuroscience, August. https://doi.org/10.1016/j.jocn.2019.08.036. Cavallo, Claudio, Camilla De Laurentis, Ignazio G Vetrano, Jacopo Falco, Morgan Broggi, Marco Schiariti, Paolo Ferroli, and Francesco Acerbi. 2018. “The Utilization of Fluorescein in Brain Tumor Surgery: A Systematic Review.” Journal of Neurosurgical Sciences 62 (6): 690–703. https://doi.org/10.23736/S0390-5616.18.04480-6. Dashti, Reza, Aki Laakso, Mika Niemelä, Matti Porras, and Juha Hernesniemi. 2009. “Microscope-Integrated near-Infrared Indocyanine Green Videoangiography during Surgery of Intracranial Aneurysms: The Helsinki Experience.” Surgical Neurology. https://doi.org/10.1016/j.surneu.2009.01.027. Falco, Jacopo, Claudio Cavallo, Ignazio G Vetrano, Camilla de Laurentis, Lampros Siozos, Marco Schiariti, Morgan Broggi, Paolo Ferroli, and Francesco Acerbi. 2019. “Fluorescein Application in Cranial and Spinal Tumors Enhancing at Preoperative MRI and Operated With a Dedicated Filter on the Surgical Microscope: Preliminary Results in 279 Patients Enrolled in the FLUOCERTUM Prospective Study.” Frontiers in Surgery 6 (August): 49. https://doi.org/10.3389/fsurg.2019.00049. Feindel, W, Y L Yamamoto, and C P Hodge. 1967. “Intracarotid Fluorescein Angiography: A New Method for Examination of the Epicerebral Circulation in Man.” Canadian Medical Association Journal 96 (1): 1–7. http://www.ncbi.nlm.nih.gov/pubmed/4959610. ——— . 1971. “Red Cerebral Veins and the Cerebral Steal Syndrome. Evidence from Fluorescein Angiography and Microregional Blood Flow by Radioisotopes during Excision of an Angioma.” Journal of Neurosurgery 35 (2): 167–79. https://doi.org/ 10.3171/jns.1971.35.2.0167. Ferroli, Paolo, Francesco Acerbi, Erminia Albanese, G Tringali, Morgan Broggi, A Franzini, and Giovanni Broggi. 2011. “Application of Intraoperative Indocyanine Green Angiography for CNS Tumors: Results on the First 100 Cases.” In Acta Neurochirurgica. Supplement. https://doi.org/10.1007/978-3-211-99651-5_40.

Intraoperative Indocyanine Green and Fluorescein Videoangiography … 517

Ferroli, Paolo, Francesco Acerbi, Giovanni Tringali, Erminia Albanese, Morgan Broggi, Angelo Franzini, and Giovanni Broggi. 2011. “Venous Sacrifice in Neurosurgery: New Insights from Venous Indocyanine Green Videoangiography.” Journal of Neurosurgery. https://doi.org/10.3171/2011.3.JNS10620. Ferroli, Paolo, Peter Nakaji, Francesco Acerbi, Erminia Albanese, and Giovanni Broggi. 2011. “Indocyanine Green (ICG) Temporary Clipping Test to Assess Collateral Circulation Before Venous Sacrifice.” World Neurosurgery 75 (1): 122–25. https://doi.org/10.1016/ j.wneu.2010.09.011. Hänggi, Daniel, Nima Etminan, and Hans Jakob Steiger. 2010. “The Impact of Microscope- Integrated Intraoperative near-Infrared Indocyanine Green Videoangiography on Surgery of Arteriovenous Malformations and Dural Arteriovenous Fistulae.” Neurosurgery. https://doi.org/10.1227/NEU.0b013e3181eb5049. Hashimoto, Koji, Hiroyuki Kinouchi, Hideyuki Yoshioka, Kazuya Kanemaru, Masakazu Ogiwara, Takashi Yagi, Takuma Wakai, and Yuichiro Fukumoto. 2017. “Efficacy of Endoscopic Fluorescein Video Angiography in Aneurysm Surgery-Novel and Innovative Assessment of Vascular Blood Flow in the Dead Angles of the Microscope.” Operative Neurosurgery 13 (4): 471–80. https://doi.org/10.1093/ons/opw042. Hettige, Samantha, and Daniel Walsh. 2010. “Indocyanine Green Video-Angiography as an Aid to Surgical Treatment of Spinal Dural Arteriovenous Fistulae.” Acta Neurochirurgica 152 (3): 533–36. https://doi.org/10.1007/s00701-009-0445-8. Hubbard, T B, and G E Moore. 1949. “The Use of Fluorescein Dyes in the Diagnosis of Malignancy with Special Reference to Tumors of the Central Nervous System.” Journal of the National Cancer Institute 10 (2): 303–14. http://www.ncbi.nlm.nih.gov/pubmed/ 15393715. Kakucs, Cristian, Ioan-Alexandru Florian, Gheorghe Ungureanu, and Ioan-Stefan Florian. 2017. “Fluorescein Angiography in Intracranial Aneurysm Surgery: A Helpful Method to Evaluate the Security of Clipping and Observe Blood Flow.” World Neurosurgery 105 (September): 406–11. https://doi.org/10.1016/j.wneu.2017.05.172. Kamp, Marcel A, Philipp Slotty, Bernd Turowski, Nima Etminan, Hans-Jakob Steiger, Daniel Hänggi, and Walter Stummer. 2012. “Microscope-Integrated Quantitative Analysis of Intraoperative Indocyanine Green Fluorescence Angiography for Blood Flow Assessment.” Operative Neurosurgery. https://doi.org/10.1227/neu.0b013e31822f7d7c. Katz, Jeffrey M, Yakov Gologorsky, Apostolos J Tsiouris, David Wells-Roth, Justin Mascitelli, Y Pierre Gobin, Philip E Stieg, and Howard A Riina. 2006. “Is Routine Intraoperative Angiography in the Surgical Treatment of Cerebral Aneurysms Justified? A Consecutive Series of 147 Aneurysms.” Neurosurgery 58 (4): 719–27; discussion 719-27. https://doi. org/10.1227/01.NEU.0000204316.49796.A3. Killory, Brendan D, Peter Nakaji, L Fernando Gonzales, Francisco A Ponce, Scott D Wait, and Robert F Spetzler. 2009. “Prospective Evaluation of Surgical Microscope-Integrated Intraoperative near-Infrared Indocyanine Green Angiography during Cerebral Arteriovenous Malformation Surgery.” Neurosurgery. https://doi.org/10.1227/01.NEU. 0000346649.48114.3A. Kim, Daniel L, and Aaron A Cohen-Gadol. 2013. “Indocyanine-Green Videoangiogram to Assess Collateral Circulation before Arterial Sacrifice for Management of Complex Vascular and Neoplastic Lesions: Technical Note.” World Neurosurgery. https://doi.org/ 10.1016/j.wneu.2012.07.028.

518 F. Acerbi, I. G. Vetrano, G. Faragò et al.

Kim, Moinay, Seungjoo Lee, Jung Cheol Park, Dong-Min Jang, Seung il Ha, Joung-Uk Kim, Jae Sung Ahn, and Wonhyoung Park. 2019. “Anaphylactic Shock Followed by Indocyanine Green Videoangiography in Cerebrovascular Surgery.” World Neurosurgery, September. https://doi.org/10.1016/J.WNEU.2019.09.135. Kobayashi, Shinya, Tatsuya Ishikawa, Jun Tanabe, Junta Moroi, and Akifumi Suzuki. 2014. “Quantitative Cerebral Perfusion Assessment Using Microscope-Integrated Analysis of Intraoperative Indocyanine Green Fluorescence Angiography versus Positron Emission Tomography in Superficial Temporal Artery to Middle Cerebral Artery Anastomosis.” Surgical Neurology International. https://doi.org/10.4103/2152-7806.140705. Kornblau, Ilyse S, and Jaafar F El-Annan. 2019. “Adverse Reactions to Fluorescein Angiography: A Comprehensive Review of the Literature.” Survey of Ophthalmology 64 (5): 679–93. https://doi.org/10.1016/j.survophthal.2019.02.004. Lane, Brandon C, and Aaron A Cohen-Gadol. 2014. “A Prospective Study of Microscope- Integrated Intraoperative Fluorescein Videoangiography during Arteriovenous Malformation Surgery: Preliminary Results.” Neurosurgical Focus 36 (2): 1–5. https://doi. org/10.3171/2013.11.FOCUS13483. Laurentis, Camilla De, Julius Höhne, Claudio Cavallo, Francesco Restelli, Jacopo Falco, Morgan Broggi, Lorenzo Bosio, et al. 2019. “The Impact of Fluorescein-Guided Technique in the Surgical Removal of CNS Tumors in a Pediatric Population: Results from a Multicentric Observational Study.” Journal of Neurosurgical Sciences, April. https://doi. org/10.23736/S0390-5616.19.04601-0. Li, Yiping, Roberto Rey-Dios, David W Roberts, Pablo A Valdés, and Aaron A Cohen-Gadol. 2014. “Intraoperative Fluorescence-Guided Resection of High-Grade Gliomas: A Comparison of the Present Techniques and Evolution of Future Strategies.” World Neurosurgery 82 (1–2): 175–85. https://doi.org/10.1016/j.wneu.2013.06.014. Macdonald, R L, M C Wallace, and J R Kestle. 1993. “Role of Angiography Following Aneurysm Surgery.” Journal of Neurosurgery 79 (6): 826–32. https://doi.org/10.3171/jns. 1993.79.6.0826. Marbacher, Serge, Itai Mendelowitsch, Basil Erwin Grüter, Michael Diepers, Luca Remonda, and Javier Fandino. 2019. “Comparison of 3D Intraoperative Digital Subtraction Angiography and Intraoperative Indocyanine Green Video Angiography during Intracranial Aneurysm Surgery.” Journal of Neurosurgery 131 (1): 64–71. https://doi.org/ 10.3171/2018.1.JNS172253. Matano, Fumihiro, Takayuki Mizunari, Yasuo Murai, Asami Kubota, Yu Fujiki, Shiro Kobayashi, and Akio Morita. 2017. “Quantitative Comparison of the Intraoperative Utility of Indocyanine Green and Fluorescein Videoangiographies in Cerebrovascular Surgery.” Operative Neurosurgery (Hagerstown, Md.) 13 (3): 361–66. https://doi.org/10.1093/ons/ opw020. Misra, Basant K, Saurav K Samantray, and Omkar N Churi. 2017. “Application of Fluorescein Sodium Videoangiography in Surgery for Spinal Arteriovenous Malformation.” Journal of Clinical Neuroscience 38: 59–62. https://doi.org/10.1016/j.jocn.2016.12.004. Moore, George E. 1947. “Fluorescein as an Agent in the Differentiation of Normal and Malignant Tissues.” Science (New York, N.Y.) 106 (2745): 130–31. https://doi.org/10. 1126/science.106.2745.130-a. Narducci, Alessandro, Julia Onken, Marcus Czabanka, Nils Hecht, and Peter Vajkoczy. 2018. “Fluorescein Videoangiography during Extracranial-to-Intracranial Bypass Surgery:

Intraoperative Indocyanine Green and Fluorescein Videoangiography … 519

Preliminary Results.” Acta Neurochirurgica 160 (4): 767–74. https://doi.org/10.1007/ s00701-017-3453-0. Narducci, Alessandro, Kaku Yasuyuki, Julia Onken, Kinga Blecharz, and Peter Vajkoczy. 2019. “In Vivo Demonstration of Blood-Brain Barrier Impairment in Moyamoya Disease.” Acta Neurochirurgica 161 (2): 371–78. https://doi.org/10.1007/s00701-019-03811-w. Ng, Yew Poh, Nicolas Kk King, Kai Rui Wan, Ernest Wang, and Ivan Ng. 2013. “Uses and Limitations of Indocyanine Green Videoangiography for Flow Analysis in Arteriovenous Malformation Surgery.” Journal of Clinical Neuroscience. https://doi.org/10.1016/j.jocn. 2011.12.038. Oliveira, Jean G De, Jürgen Beck, Volker Seifert, Manoel J Teixeira, and Andreas Raabe. 2008. “Assessment of Flow in Perforating Arteries during Intracranial Aneurysm Surgery Using Intraoperative Near-Infrared Indocyanine Green Videoangiography.” Neurosurgery. https://doi.org/10.1227/01.NEU.0000279982.48426.A1. Raabe, Andreas, Jürgen Beck, Rüdiger Gerlach, Michael Zimmermann, and Volker Seifert. 2003. “Near-Infrared Indocyanine Green Video Angiography: A New Method for Intraoperative Assessment of Vascular Flow.” Neurosurgery 52 (1): 132–39; discussion 139. http://www.ncbi.nlm.nih.gov/pubmed/12493110. Raabe, Andreas, Andreas Raabe, Peter Nakaji, Peter Nakaji, Jürgen Beck, Jürgen Beck, Louis J Kim, et al. 2005. “Prospective Evaluation of Surgical Microscope-Integrated Intraoperative near-Infrared Indocyanine Green Videoangiography during Aneurysm Surgery.” Journal of Neurosurgery 103: 982–89. http://www.ncbi.nlm.nih.gov/pubmed/ 16381184. Riva, Matteo, Sepideh Amin-Hanjani, Carlo Giussani, Olivier De Witte, and Michael Bruneau. 2018. “Indocyanine Green Videoangiography in Aneurysm Surgery: Systematic Review and Meta-Analysis.” Neurosurgery 83 (2): 166–80. https://doi.org/10.1093/neuros/ nyx387. Roessler, Karl, Maximilian Krawagna, Arnd Dörfler, Michael Buchfelder, and Oliver Ganslandt. 2014. “Essentials in Intraoperative Indocyanine Green Videoangiography Assessment for Intracranial Aneurysm Surgery: Conclusions from 295 Consecutively Clipped Aneurysms and Review of the Literature.” Neurosurgical Focus 36 (2): E7. https://doi.org/10.3171/2013.11.FOCUS13475. Schebesch, Karl-Michael, Julius Hoehne, Christoph Hohenberger, Francesco Acerbi, Morgan Broggi, Martin Proescholdt, Christina Wendl, Markus J Riemenschneider, and Alexander Brawanski. 2015. “Fluorescein Sodium-Guided Surgery in Cerebral Lymphoma.” Clinical Neurology and Neurosurgery 139 (December): 125–28. https://doi.org/10.1016/j.clineuro. 2015.09.015. Shah, Kushal J, and Aaron A Cohen-Gadol. 2019. “The Application of FLOW 800 ICG Videoangiography Color Maps for Neurovascular Surgery and Intraoperative Decision Making.” World Neurosurgery 122: e186–97. https://doi.org/10.1016/j.wneu.2018.09.195. Suzuki, Kyouichi, Namio Kodama, Tatsuya Sasaki, Masato Matsumoto, Tsuyoshi Ichikawa, Ryoji Munakata, Hiroyuki Muramatsu, and Hiromichi Kasuya. 2007. “Confirmation of Blood Flow in Perforating Arteries Using Fluorescein Cerebral Angiography during Aneurysm Surgery.” Journal of Neurosurgery 107 (1): 68–73. https://doi.org/10.3171/ JNS-07/07/0068. Uchino, Haruto, Ken Kazumata, Masaki Ito, Naoki Nakayama, Satoshi Kuroda, and Kiyohiro Houkin. 2014. “Intraoperative Assessment of Cortical Perfusion by Indocyanine Green

520 F. Acerbi, I. G. Vetrano, G. Faragò et al.

Videoangiography in Surgical Revascularization for Moyamoya Disease.” Acta Neurochirurgica. https://doi.org/10.1007/s00701-014-2161-2. Vetrano, Ignazio G, Paolo Ferroli, and Francesco Acerbi. 2018. “Dynamic Intraoperative Assessment of Draining Veins in Parasagittal Meningiomas: Changing the Paradigm?” World Neurosurgery 118 (October): 399. https://doi.org/10.1016/j.wneu.2018.07.094. Woitzik, Johannes, Peter Horn, Peter Vajkoczy, and Peter Schmiedek. 2005. “Intraoperative Control of Extracranial-Intracranial Bypass Patency by near-Infrared Indocyanine Green Videoangiography.” Journal of Neurosurgery 102 (4): 692–98. https://doi.org/10.3171/ jns.2005.102.4.0692. Wrobel, C J, H Meltzer, R Lamond, and J F Alksne. 1994. “Intraoperative Assessment of Aneurysm Clip Placement by Intravenous Fluorescein Angiography.” Neurosurgery 35 (5): 970–73; discussion 973. https://doi.org/10.1227/00006123-199411000-00027. Xiao, Shi-yin, Ji Zhang, Zheng-quan Zhu, You-ping Li, Wei-ying Zhong, Jian-bin Chen, Zhen- yu Pan, and Hai-chen Xia. 2018. “Application of Fluorescein Sodium in Breast Cancer Brain-Metastasis Surgery.” Cancer Management and Research Volume 10 (October): 4325–31. https://doi.org/10.2147/CMAR.S176504.

ABOUT THE EDITORS

Renato Galzio, M.D. Full Professor of Neurosurgery, Chief of Neurosurgery Department at Fondazione IRCCS Policlinico San Matteo, Pavia. University of Pavia, Pavia, Italy.

Renato Galzio is Full Professor of Neurosurgery at University of Pavia, Italy, Chief of Neurosurgery Department at Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, and board-certified Neurosurgeon in USA. He is Director of the prestigious “Italian Course of Applied Microneurosurgery”, officially recognized by the World Federation of Neurosurgical Societies, which accounts 19 editions. He is also lab faculty of several international hands-on courses on microneurosurgical anatomy and skull-base approaches. He is a pioneer of the endoscope-assisted microneurosurgery, for which he has also projected and developed dedicated instruments and endoscopes. He has published more than 150 peer-reviewed articles and several book chapters. He is also in the editorial board of prestigious international journals. Prof. Galzio is in the Anatomy Committee of the World Federation of Neurosurgical Societies and is member of numerous international neurosurgical societies.

522 About the Editors

Prof. Galzio has also performed more than 8.000 neurosurgical procedures mainly in the field of neurovascular and skull base surgery, for which he is today considered a world- renowned expert.

Sabino Luzzi, M.D., Ph.D Assistant Professor of Neurosurgery at the University of Pavia, Italy. University of Pavia, Pavia, Italy.

Sabino Luzzi is Assistant Professor of Neurosurgery at the University of Pavia, Italy, Visiting Professor of University of L’Aquila, Italy, Consultant Neurosurgeon at Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, and GMC Certified Neurosurgeon in UK. He is member of several international neurosurgical societies and lab faculty of world- renowned neurosurgical hands-on courses. Dr. Luzzi has been speaker in many international congresses and is author of numerous scientific articles and book chapters mainly in the field of neurovascular and skull base surgery. He is in the editorial and review board of international neurosurgery top journals. His main surgical and research fields of interests are cerebral aneurysms, cerebral revascularization techniques, vascular malformations, brain and skull base tumors.

INDEX

224, 227, 228, 231, 233, 234, 235, 236, 247, 254, A 255, 258, 259, 260, 268, 270, 271, 272, 279, 280, 282, 284, 292, 293, 294, 295, 297, 298, 303, 304, accelerator, 115, 495, 496, 501 305, 306, 311, 312, 336, 337, 338, 339, 340, 365, access, 11, 89, 210, 239, 240, 243, 244, 246, 264, 366, 399, 402, 407, 408, 410, 411, 412, 413, 414, 268, 273, 281, 282, 284, 287, 288, 290, 298, 303, 415, 416, 417, 418, 424, 425, 427, 428, 429, 430, 306, 307, 320, 353, 355, 362, 379, 382, 397, 427, 431, 432, 433, 435, 436, 439, 441, 442, 443, 444, 449, 465, 469, 470 445, 446, 447, 450, 451, 452, 453, 454, 457, 460, accounting, 87, 127, 131, 397 461, 470, 472, 474, 504, 505, 507, 508, 512, 513, adhesion(s), 84, 91, 171, 286, 292, 467, 468 514, 516, 517, 518, 519, 520 adults, 7, 37, 56, 97, 131, 158, 179, 199, 250, 275, aneurysms clipping, 239, 505, 512 341, 434, 464, 476, 490, 495 angiogenesis, 455, 466, 470, 474, 496 adverse effects, 115, 485, 486 angiogram, 116, 151, 153, 159, 284, 302, 304, 306 aesthetic, 245, 246, 247, 248, 249, 270 angiography, 15, 35, 37, 40, 56, 57, 76, 77, 94, 98, age, 7, 83, 91, 112, 116, 132, 138, 141, 168, 185, 100, 111, 113, 114, 116, 118, 119, 128, 130, 132, 213, 361, 365, 370, 377, 381, 400, 411, 412, 426, 134, 154, 169, 175, 176, 179, 198, 215, 216, 220, 464, 485, 493, 498, 500, 508 233, 234, 235, 247, 250, 270, 271, 272, 275, 284, alcohol consumption, 83, 91, 168 292, 294, 304, 306, 318, 328, 337, 338, 341, 362, algorithm, 167, 173, 178, 193, 228, 464, 491, 506, 364, 365, 366,368, 369, 370, 377, 396, 398, 399, 512 400, 401, 411, 413, 425, 427, 429, 430, 431, 432, American Heart Association, 181, 204, 371 434, 443, 444, 445, 446, 470, 476, 481, 487, 493, amplitude, 118, 211, 213, 214, 215, 216, 217 503, 504, 505, 506, 512, 513, 514 amygdala, 25, 31, 41 annual rate, 456, 486, 488 anastomosis, 35, 66, 69, 70, 71, 72, 73, 130, 286, anterior cerebral artery, 21, 23, 26, 28, 29, 30, 31, 425, 426, 429, 431, 443, 459 40, 48, 88, 92, 220, 245, 282, 283, 288, 412, 415, anatomy, 3, 4, 10, 11, 14, 15, 19, 21, 35, 37, 38, 40, 426 41, 43, 53, 54, 55, 56, 57, 59, 60, 61, 63, 73, 74, anterior communicating artery, 21, 26, 30, 31, 41, 77, 100, 111, 132, 134, 138, 142, 145, 150, 152, 48, 83, 88, 91, 159, 230, 233, 240, 263, 264, 274, 159, 162, 189, 249, 274, 282, 285, 289, 290, 298, 276, 288, 295, 408, 411, 415, 416, 417, 428, 430, 307, 309, 313, 314, 324, 336, 341, 342, 345, 347, 450, 452, 513, 514 349, 350, 388, 389, 398, 417, 439, 443, 447, 452, anterior communicating artery aneurysms, 263, 274, 504, 507, 521 452, 513, 514 anesthesiologist, 188, 195, 196 anterior inferior cerebellar artery, 8, 43, 48, 59, 298 anesthetics, 187, 190, 194, 196, 202, 210, 212, 213 anterior petrosectomy, 297, 298, 301, 302, 349, 350, aneurysm, ix, 81, 82, 83, 84, 85, 86, 87, 89, 91, 92, 351, 354, 355, 356 93, 94, 95, 96, 97, 98, 100, 102, 103, 104, 105, anterior skull base, 3, 4, 10, 11, 249, 261 111, 114, 151, 154, 159, 160, 187, 188, 189, 192, anticoagulant, 168, 170, 172, 174, 177 196, 197, 198, 199, 202, 203, 204, 205, 206, 209, anticoagulation, 167, 177, 178 210, 214, 215, 216, 217, 218, 219, 220, 221, 223, antrum, 33, 353, 356

524 Index apex, 5, 7, 12, 22, 105, 268, 297, 298, 301, 302, 306, 366, 367, 368, 369, 379, 392, 397, 398, 399, 400, 307, 310, 339, 340, 351, 352, 354, 398, 452 401, 408, 411, 412, 414, 415, 416, 417, 418, 421, arteries, 4, 5, 8, 21, 22, 23, 25, 26, 27, 28, 29, 30, 31, 425, 426, 427, 428, 429, 430, 431, 434, 436, 438, 33, 35, 36, 37, 40, 41, 45, 46, 47, 48, 49, 50, 51, 439, 442, 443, 444, 445, 447, 448, 450, 451, 452, 52, 54, 56, 59, 60, 64, 65, 66, 67, 68, 69, 70, 71, 454, 455, 459, 460, 469, 470, 472, 473, 476, 480, 72, 73, 74, 76, 87, 88, 89, 90, 107, 109, 111, 116, 504, 505, 507, 509, 510, 513, 514 117, 130, 131, 132, 153, 163, 171, 211, 212, assessment, 30, 90, 118, 140, 141, 144, 169, 188, 213,218, 232, 234, 268, 271, 272, 282, 283, 284, 189, 192, 194, 197, 213, 217, 218, 234, 235, 268, 286, 289, 292, 302, 306, 318, 337, 362, 364, 370, 314, 370, 409, 411, 427, 447, 501, 503, 504, 508, 379, 396, 397, 398, 399, 400, 401, 407, 408, 411, 509, 512, 513, 514 412, 413, 414, 416, 426, 455, 459, 463, 464, 465, astrocytoma, 15, 37, 56, 98, 180, 220, 251, 276, 342, 467, 468, 469, 503, 504, 505, 507, 508, 510, 511, 435, 477 513, 514, 515 asymptomatic, 108, 137, 165, 361, 376, 456, 494 arteriovenous, v, vi, vii, 10, 11, 13, 15, 17, 30, 31, atherosclerosis, 83, 85, 86, 87, 177, 424 35, 37, 39, 43, 46, 52, 53, 54, 56, 57, 58, 64, 71, atrial fibrillation, 168, 170, 177, 198 74, 75, 98, 100, 101, 107, 109, 110, 111, 112, attachment, 4, 5, 10, 25, 335 113, 115, 120, 121, 122, 123, 124, 125, 127, 128, autosomal dominant, 102, 108, 138, 376 129, 130, 131, 132, 133, 135, 136, 149, 153, 154, AVM, ix, 70, 107, 108, 109, 110, 111, 112, 114, 115, 156, 161, 162, 163, 164, 169, 180, 182, 187, 198, 116, 117, 118, 119, 127, 128, 129, 130, 132, 133, 205, 220, 221, 234, 239, 240, 251, 276, 277, 298, 134, 135, 136, 198, 229, 292, 294, 360, 361, 362, 309, 311, 320, 325, 326, 330, 342, 343, 359, 363, 363, 365, 366, 367, 368, 370, 371, 372, 376, 463, 371, 372, 373, 374, 376, 377, 388, 390, 391, 395, 464, 465, 466, 467, 469, 470, 471, 472, 473, 474, 402, 403, 404, 418, 419, 432, 435, 436, 446, 447, 475, 477, 478, 479, 481, 483, 484, 485, 486, 487, 449, 455, 459, 461, 465, 466, 475, 476, 477, 478, 488, 489, 490, 491, 492, 493, 494, 504, 505, 507, 479, 480, 483, 484, 491, 495, 496, 497, 498, 499, 508, 509, 513, 514 500, 501, 504, 505, 507, 508, 516, 517, 518, 519 avoidance, 107, 164, 191, 426 arteriovenous malformation, v, 10, 11, 13, 17, 30, 31, 35, 39, 43, 46, 52, 53, 57, 58, 71, 74, 100, 101, 107, 109, 110, 111, 112, 113, 115, 120, 121, 122, B 127, 128, 129, 132, 133, 135, 136, 161, 163, 169, basal ganglia, 30, 35, 88, 118, 139, 144, 145, 169, 182, 187, 206, 210, 221, 222, 234, 239, 251, 252, 240, 378, 379, 500 277, 278, 298, 311, 320, 326, 330, 343, 344, 359, base, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 22, 37, 38, 371, 372, 373, 376, 377, 390, 419, 420, 432, 436, 43, 54, 56, 76, 95, 98, 110, 138, 143, 180, 189, 437, 447, 463, 464, 468, 475, 476, 477, 478, 479, 194, 195, 199, 218, 224, 239, 240, 243, 248, 249, 480, 481, 484, 487, 495, 496, 497, 498, 499, 500, 250, 257, 261, 263, 264, 272, 273, 274, 276, 277, 501, 504, 505, 516 282, 287, 288, 298, 299, 300, 303, 306, 307, 318, arteriovenous shunt, 75, 107, 131, 132, 162, 163, 327, 328, 330, 339, 342, 349, 351, 355, 356, 382, 164, 455, 466, 507 395, 396, 409, 410, 416, 427, 432, 435, 438, 451, artery, 5, 6, 7, 8, 10, 11, 12, 13, 15, 16, 19, 21, 23, 452, 464, 467, 499, 501, 521, 522 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 36, 37, 38, basilar apex, 297, 298, 306, 307, 339, 340 40, 41, 42, 43, 44, 45, 47, 48, 49, 50, 51, 52, 54, basilar artery, 11, 15, 16, 30, 43, 46, 48, 60, 83, 89, 55, 56, 57, 59, 60, 61, 64, 65, 66, 67, 68, 69, 70, 90, 91, 223, 264, 268, 271, 275, 276, 300, 301, 71, 72, 73, 75, 77, 83, 87, 88, 89, 90, 91, 92, 97, 302, 306, 309, 310, 314, 349, 350, 356, 408, 415, 98, 100, 103, 104, 105, 111, 114, 150, 151, 152, 417, 450, 452, 454 153, 154, 155, 156, 159, 160, 163, 171, 179, 184, basilar tip aneurysms, 11, 54, 87, 239, 249, 259, 263, 185, 189, 197, 199, 211, 214, 215, 217, 218, 220, 268, 273, 298, 310, 427 221, 223, 224, 228, 229, 230, 231, 232, 233, 240, beams, 115, 229, 491, 501 241, 242, 243, 244, 245, 250, 253, 257, 259, 260, benefits, 170, 196, 200 263, 264, 268, 271, 272, 274, 275, 276, 279, 282, benign, 137, 157, 342, 396, 399 283, 288, 289, 292, 293, 294, 295, 297, 298, 300, bilateral, 70, 171, 172, 176, 211, 212, 319, 397, 399, 301, 302, 304, 306, 309, 310, 313, 314, 318, 319, 510 321, 327, 328, 329, 330, 331, 332, 337, 338, 341, bleeding, 92, 93, 94, 108, 110, 111, 112, 113, 114, 343, 346, 347, 349, 350, 354, 355, 356, 364, 365, 115, 118, 138, 139, 140, 141, 151, 152, 170, 172,

Index 525

178, 179, 194, 197, 198, 202, 210, 212, 216, 243, 210, 221, 222, 251, 252, 277, 278, 311, 326, 343, 244, 291, 320, 321, 322, 336, 361, 362, 363, 366, 344, 359, 371, 372, 373, 390, 419, 420, 436, 437, 367, 370, 376, 377, 380, 381, 382, 385, 395, 396, 447, 463, 464, 468, 475, 477, 478, 479, 481, 487, 397, 398, 399, 423, 424, 442, 443, 456, 458, 463, 495, 496, 497, 498, 499, 500, 501, 516 465, 466, 469, 485, 488, 491, 494 brain arteriovenous malformations, v, 17, 39, 57, 58, blind spot, 271, 273, 290, 370, 410, 416 101, 107, 115, 120, 121, 122, 182, 206, 210, 221, blood, 29, 52, 71, 72, 74, 76, 84, 86, 88, 91, 93, 94, 222, 251, 252, 277, 278, 311, 326, 343, 344, 359, 99, 103, 104, 109, 118, 128, 129, 130, 131, 140, 371, 372, 373, 390, 419, 420, 436, 437, 447, 464, 157, 160, 163, 168, 169, 172, 177, 178, 181, 187, 468, 475, 477, 478, 479, 481, 495, 496, 497, 498, 188, 189, 192, 194, 195, 196, 197, 198, 199, 200, 499, 500, 516 209, 210, 217, 218, 221, 227, 228, 229, 231, 232, brain stem, 221, 310, 363, 388, 392, 500 234, 235, 242, 244, 245, 265, 292, 303, 304, 360, brain tumor, 118, 212, 227, 505 365, 366, 370, 376, 377, 396, 401, 425, 433, 439, brainstem, 49, 51, 52, 53, 54, 59, 89, 93, 145, 146, 442, 443, 444, 455, 460, 464, 466, 468, 469, 474, 147, 151, 152, 209, 210, 213, 214, 221, 223, 299, 503, 504, 505, 507, 508, 512, 513, 515 308, 309, 317, 318, 320, 330, 333, 349, 351, 352, blood clot, 93, 172, 513 375, 376, 378, 380, 381, 385, 387, 388, 389, 392, blood flow, 29, 52, 71, 76, 84, 91, 99, 103, 118, 128, 427, 485, 489, 491, 495, 496, 498 129, 131, 140, 160, 197, 198, 199, 209, 210, 217, brainstem approaches, 375 218, 221, 227, 228, 231, 232, 234, 235, 401, 425, brainstem auditory evoked potential (BAEP), 146, 433, 439, 442, 443, 466, 503, 504, 507, 508, 512, 209, 210, 214, 218, 223, 427 513, 515 bypass, 28, 36, 43, 54, 187, 197, 199, 204, 205, 217, blood pressure, 169, 177, 178, 187, 189, 192, 195, 218, 235, 260, 297, 298, 311, 314, 423, 424, 425, 196, 197, 199, 200, 229, 370, 469, 474 426, 427, 428, 429, 431, 433, 434, 436, 439, 441, blood supply, 71, 72, 242, 265, 304, 442 442, 446, 447, 448, 503, 504, 505, 507, 510, 512, blood vessels, 71, 72, 109, 163 514, 518, 520 blood-brain barrier, 376, 505, 513 bone, 4, 5, 6, 7, 8, 9, 10, 12, 13, 18, 22, 32, 48, 52, 76, 159, 164, 171, 175, 212, 218, 239, 241, 242, C 243, 244, 245, 246, 248, 249, 256, 257, 259, 264, cadaver, 128, 138, 163 267, 269, 270, 279, 285, 286, 290, 291, 293, 300, calcification(s), 111, 377, 424, 430, 513 302, 305, 306, 321, 322, 333, 334, 335, 336, 337, caliber, 68, 69, 71, 73, 232, 467, 469 338, 339, 345, 349, 350, 351, 352, 353, 354, 356, canals, 5, 12, 345 363, 396, 397, 398, 399, 401 candidates, 132, 167, 173, 178, 396, 464 bone form, 4, 7, 8, 10, 12 capillary, 64, 73, 74, 107, 109, 129, 139, 154, 376, bones, 4, 5, 7, 10, 11, 64, 66, 242 505, 506, 507 brain, v, ix, 11, 17, 35, 39, 57, 58, 83, 101, 107, 108, capsule, 25, 26, 27, 28, 30, 31, 50, 51, 52, 145, 216, 109, 110, 111, 114, 115, 116, 117, 118, 120, 121, 378, 379 122, 131, 132, 135, 138, 141, 143, 145, 157, 168, carcinoma, 16, 38, 57, 99, 181, 220, 251, 277, 343, 169, 170, 171, 172, 176, 177, 182, 187, 190, 191, 436 194, 195, 196, 197, 198, 206, 209, 210, 212, 218, cardiac output, 190, 197, 228 221,222, 227, 228, 232, 235, 243, 244, 249, 251, carotid arteries, 35, 111, 155, 429 252, 277, 278, 282, 284, 286, 290, 291, 293, 299, catheter, 76, 151, 172, 195, 197, 287, 338, 386, 427, 303, 310, 311, 314, 315, 326, 343, 344, 350, 352, 451, 464, 467, 468, 469 353, 355, 359, 360, 363, 370, 371, 372, 373, 376, cauda equina, 69, 73, 131 378, 381, 387, 388, 389, 390, 392, 395, 396, 397, cavernous hemangioma, 11, 169, 239, 240, 264, 317, 398, 409, 419, 420, 421, 425, 428, 429, 430, 436, 330, 339, 340, 376, 432 437, 442, 443, 444, 447, 463, 464, 465, 467, 468, cavernous malformation(s), 129, 138, 298, 314, 325, 470, 474, 475, 476, 477, 478, 479, 481, 483, 484, 364, 375, 376, 382, 387, 388, 389, 391, 392, 393, 485, 487, 492, 494, 495, 496, 497, 498, 499, 500, 446, 483, 484, 494 501, 505, 506, 509, 510, 512, 513, 514, 515, 516, central nervous system, 14, 21, 35, 43, 54, 64, 72, 522 168, 213, 216, 234, 359, 375, 376, 474 brain arteriovenous malformation, v, vii, 17, 39, 57, cerebellum, 46, 49, 54, 139, 308, 320, 322, 354, 356, 58, 101, 107, 115, 120, 121, 122, 124, 182, 206, 382, 398, 496

526 Index cerebral aneurysm, 16, 41, 60, 91, 96, 98, 99, 100, communication, 71, 116, 194, 202, 270 104, 105, 106, 189, 220, 223, 224, 228, 234, 235, complex aneurysms, 246, 259, 269, 325, 423, 441, 236, 418, 419, 421, 438, 522 442, 446, 449 cerebral arteries, 22, 47, 81, 86, 211, 212, 228, 232, complex intracranial aneurysm, 260, 438, 441, 447 271, 304 complexity, 116, 127, 161, 259, 442, 451, 452, 465, cerebral blood flow, 109, 188, 190, 194, 196, 200, 469 213, 218, 227, 228, 443, 503 complications, 93, 106, 112, 115, 116, 132, 137, 162, cerebral cavernous malformations, 137, 138, 392, 164, 170, 171, 188, 189, 194, 195, 196, 198, 215, 499 218, 235, 242, 244, 246, 247, 249, 270, 274, 291, cerebral hemisphere, 72, 139, 292 297, 302, 328, 336, 337, 351, 352, 360, 367, 423, cerebral revascularization, 423, 426, 438, 442, 443, 425, 426, 432, 436, 450, 451, 452, 454, 459, 460, 522 465, 466, 470, 473, 475, 477, 480, 485, 487, 488, cerebral revcascularization, 441 489, 490, 495, 499, 500, 504, 506, 510, 511, 512 cerebrospinal fluid, 93, 172, 270, 303, 322, 331 compression, 110, 129, 131, 168, 171, 270, 286, 291, cerebrovascular disease, 81, 82, 95, 102, 167, 189, 299, 321, 352, 364, 398, 430 199, 433, 439, 481, 514 computed tomography, 14, 15, 37, 56, 57, 98, 143, challenges, 150, 151, 488, 493 179, 220, 250, 275, 336, 341, 377, 434, 476 Chicago, 3, 81, 297, 329, 426 configuration, 72, 74, 75, 452 children, 116, 131, 199, 295, 496, 499, 501 consciousness, 169, 175, 176 choroid, 23, 45, 46, 47, 49, 50, 51, 450 consensus, 108, 112, 120, 146, 387 cigarette smoking, 83, 91, 168 consent, 319, 320, 507 circulation, 11, 21, 29, 30, 35, 43, 48, 51, 52, 54, 67, controversial, 93, 114, 167, 168, 172, 177, 196, 197, 76, 90, 91, 92, 93, 111, 118, 190, 198, 213, 218, 359, 362, 371, 382, 489, 492 231, 239, 240, 244, 249, 250, 255, 259, 260, 320, cooperation, 84, 466, 475 329, 342, 407, 409, 411, 415, 424, 426, 427, 432, copolymer, 113, 467, 468, 481 443, 445, 447, 455, 459, 496, 505 corpus callosum, 23, 26, 29, 30, 48, 50, 88, 282, 283, classification, 23, 26, 31, 36, 42, 46, 53, 81, 82, 86, 286, 287, 288, 289, 290, 291, 378, 379, 496 107, 112, 127, 128, 129, 136, 140, 149, 150, 158, correlation(s), 84, 86, 112, 116, 163, 165, 460, 461, 159, 160, 161, 162, 163, 165, 359, 362, 363, 371, 485, 491, 501 409, 418, 458, 459, 460, 479, 480, 485, 499 cortex, 4, 26, 28, 50, 88, 89, 111, 141, 173, 191, 201, clinical application, 389, 484, 512 211, 212, 290, 378, 496 clinical presentation, 107, 108, 109, 131, 168, 361, cortical bone, 351, 353, 356 391, 455, 460 cosmetic, 242, 244, 257, 273, 351, 353 clinical trials, 82, 167, 177, 359 cost, 111, 169, 216 clipping, 16, 30, 38, 57, 188, 196, 197, 198, 205, covering, 45, 351, 396, 398, 451, 454 215, 216, 217, 219, 229, 231, 232, 233, 234, 244, CPP, 188, 190, 191, 194, 197, 198 247, 254, 259, 272, 280, 292, 293, 304, 305, 314, cranial, v, ix, 3, 4, 10, 14, 21, 25, 33, 38, 43, 46, 47, 337, 338, 339, 340, 396, 400, 401, 407, 408, 410, 48, 52, 67, 68, 70, 72, 74, 75, 88, 89, 90, 93, 128, 411, 412, 413, 415, 416, 417, 418, 423, 424, 425, 136, 144, 146, 147, 149, 150, 153, 157, 158, 161, 428, 430, 441, 442, 461, 504, 507, 508, 511, 514, 162, 165, 214, 243, 267, 277, 287, 288, 300, 302, 515, 517 303, 304, 305, 309, 313, 315, 320, 322, 323, 327, closure, 7, 14, 114, 132, 248, 249, 259, 265, 270, 328, 330, 335, 342, 343, 349, 350, 352, 354, 355, 286, 302, 306, 321, 322, 323, 331, 336, 356, 363, 356, 364, 392, 396, 397, 398, 400, 402, 404, 416, 370, 396, 442, 443, 445 427, 456, 459, 461, 500, 505, 516 CNS, 146, 191, 376, 378, 385, 504, 505, 516, 518 cranial nerve, 25, 33, 46, 48, 52, 88, 89, 90, 93, 146, CO2, 190, 191, 210, 231 214, 302, 313, 320, 322, 323, 327, 330, 335, 349, coagulopathy, 172, 173, 197 350, 352, 354, 355, 356, 400, 416, 427, 456, 459 collagen, 83, 85, 86 craniotomy, 116, 118, 142, 143, 145, 172, 240, 241, collateral, 26, 28, 46, 51, 69, 70, 92, 117, 197, 198, 242, 243, 244, 245, 253, 254, 256, 257, 258, 259, 199, 407, 411, 417, 423, 425, 426, 441, 443 260, 261, 267, 269, 276, 278, 279, 280, 284, 285, color, 228, 271, 272, 369, 401, 410, 506, 508, 509, 286, 287, 288, 290, 291, 293, 297, 299, 300, 303, 510, 511, 514 305, 309, 312, 313, 317, 318, 320, 321, 322, 325, combined petrosal approach, 349, 350, 355, 356 328, 333, 337,338, 340, 341, 350, 352, 353, 365,

Index 527

366, 368, 370, 378, 379, 380, 382, 384, 396, 397, 317, 318, 321, 322, 323, 333, 335, 353, 355, 356, 398, 399, 414, 440, 443, 494 357, 364, 371, 373, 395, 396, 397, 398, 399, 400, cranium, 9, 157, 161, 324 401, 402, 403, 404, 449, 455, 456, 458, 459, 460, CSF, 73, 130, 270, 284, 286, 290, 291, 292, 293, 461, 500, 505, 507, 508, 509, 510, 511, 512, 516, 300, 302, 307, 317, 322, 323, 356, 397, 398 517 CT scan, 111, 151, 152, 215, 216, 233, 292, 294, dural arteriovenous fistula, ix, 136, 149, 151, 152, 318, 320, 337, 351, 367, 368, 370, 398, 412, 413, 157, 159, 160, 161, 162, 163, 164, 165, 317, 318, 427, 428, 444, 471, 472, 493, 509, 510 401, 460, 461, 500, 511 CTA, 377, 411, 412, 414 dyes, 505, 514, 515 cure, 115, 116, 153, 362, 396, 499 dysplasia, 87, 108, 190 cyanoacrylates, 463, 466, 467, 468 E D EC-IC bypass, 441, 444, 445 decision-making process, 93, 127, 362, 375 edema, 140, 168, 177, 198, 199, 286, 292, 302, 303, decompressive craniectomy, 167, 171 398, 485, 486 deficit, 93, 109, 141, 188, 189, 195, 217, 323, 365, EEG, 119, 141, 195, 196, 197, 198, 199, 210, 213, 381, 385, 445, 456, 485, 486, 509 214, 217, 218, 219 degradation, 82, 84, 93, 177 electrodes, 211, 212, 213 delirium, 192, 200, 201, 202 emboli, 17, 30, 39, 58, 101, 107, 112, 113, 114, 116, depression, 5, 7, 9, 200, 202, 334 130, 132, 134, 135, 136, 164, 182, 222, 252, 278, depth, 70, 195, 259, 265, 273, 416, 513, 514 311, 326, 344, 360, 361, 362, 363, 364, 365, 366, detachment, 241, 242, 243, 248, 267, 270, 300, 321, 367, 368, 390, 396, 397, 399, 400, 420, 423, 424, 333, 352, 353, 356 429, 431, 437, 444, 445, 447, 449, 450, 451, 454, detection, 100, 108, 130, 211, 218, 229, 232, 411, 457, 459, 460, 463, 464, 465, 466, 467, 468, 469, 505 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, diabetes, 85, 168, 170, 175, 189 480, 488, 489, 490, 491, 493, 495, 499, 508 diaphragm, 7, 10, 52, 55 embolization, vii, 15, 17, 30, 37, 39, 56, 57, 58, 98, dilation, 37, 56, 97, 179, 250, 275, 341, 434, 456, 101, 107, 112, 113, 114, 116, 122, 130, 132, 134, 476 135, 136, 164, 180, 182, 220, 221, 222, 251, 252, disability, 112, 170, 188, 428, 449 276, 277, 278, 309, 311, 325, 326, 342, 343, 344, diseases, ix, 14, 85, 128, 168, 173, 409, 507 360, 361, 362, 363, 364, 365, 366, 367, 368, 372, disorder, 83, 108, 141 373, 374, 388, 390, 396, 397, 399, 400, 402, 403, disposition, 64, 65, 71, 72, 74, 76, 92 404, 418, 419, 420, 423, 424, 429, 431, 435, 436, distribution, 66, 76, 94, 194, 444 437, 444, 445, 446, 447, 449, 450, 451, 454, 457, dizziness, 138, 338, 383 459, 460, 463, 464, 465, 466, 467, 468, 469, 470, doppler, 134, 284, 443 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, dosage, 202, 495, 505, 506 488, 489, 490, 491, 493, 495, 496, 499, 508 drainage, 53, 74, 75, 76, 110, 111, 112, 113, 116, emergency, 111, 114, 116, 169, 319, 377, 382, 428, 128, 131, 151, 152, 157, 159, 161, 162, 163, 164, 450 165, 172, 176, 187, 195, 245, 260, 284, 286, 288, EMG, 119, 352, 354 290, 291, 292, 293, 299, 303, 307, 319, 322, 323, emission, 109, 505, 506 336, 352, 361, 362, 363, 366, 367, 368, 370, 395, employment, 177, 297, 307, 469 396, 397, 398, 399, 400, 401, 455, 456, 458, 459, endoscope, 14, 36, 55, 96, 179, 219, 249, 274, 290, 460, 465, 466, 470, 472, 474, 481, 487 307, 308, 324, 340, 383, 387, 407, 408, 410, 411, drugs, 95, 170, 172, 173, 177, 191, 194, 195, 200, 412, 414, 415, 416, 417, 418, 419, 421, 433, 475, 210, 213, 217 521 dura mater, 66, 76, 128, 256, 322, 380 endoscope-assisted microsurgery, 407, 419, 421 dural, v, vi, vii, ix, 22, 24, 31, 34, 35, 40, 41, 44, 45, endothelial cells, 83, 84, 102, 104, 139, 376 54, 59, 74, 75, 76, 88, 116, 128, 136, 145, 149, endothelial disfunction, 81, 83 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, endovascular occlusion, 158, 233, 396, 458 160, 161, 162, 163, 164, 165, 171, 187, 205, 240, endovascular treatment, 35, 54, 93, 105, 114, 132, 243, 244, 256, 257, 268, 286, 302, 303, 304, 306, 150, 160, 161, 162, 163, 189, 306, 359, 363, 364,

528 Index

399, 400, 412, 439, 442, 449, 450, 454, 461, 469, fibrin, 170, 249, 259, 322, 323 475, 476, 477, 481 fistula, 128, 130, 132, 149, 150, 151, 152, 153, 154, enlargement, 65, 67, 71, 72, 73, 75, 81, 89, 233, 243, 155, 156, 157, 158, 159, 160, 161, 164, 187, 198, 398, 424, 461 319, 322, 364, 398, 399, 400, 401, 402, 403, 404, environment(s), 102, 142, 364, 466, 468 455, 456, 457, 458, 459, 495, 504, 507, 511 ependymal, 73, 370, 381 fistulas, ix, 10, 31, 35, 43, 53, 54, 111, 127, 128, epidural, 76, 128, 149, 150, 153, 156, 157, 158, 161, 129, 132, 136, 149, 150, 157, 158, 161, 162, 163, 162, 163, 164, 249, 291, 300, 302, 321 164, 165, 363, 364, 395, 396, 397, 398, 455, 456, epidural hematoma, 249, 300, 302 458, 459, 460, 461, 491, 500 epilepsy, 138, 141, 151, 210, 218, 377, 483 FLOW 800, 228, 234, 235, 236, 503, 504, 509, 512, ethylene, 113, 467, 468, 481 513, 514, 516, 519 etiology, 86, 89, 168, 491 flow value, 230, 231, 232 evacuation, 172, 173, 174, 175, 181, 183, 184, 292, flow-diverter stents, 423, 431 363, 377, 381 fluctuations, 169, 197, 200 evidence, 81, 85, 89, 91, 92, 95, 116, 167, 173, 178, fluid, 76, 84, 104, 198 190, 195, 197, 198, 211, 306, 320, 360, 377, 464, fluorescein, vii, 118, 228, 503, 504, 505, 506, 507, 473, 494, 507 513, 514, 515, 516, 517, 518, 519, 520 evoked potential(s), 146, 196, 209, 210, 214, 217, fluorescence, 228, 369, 425, 432, 505, 506, 508, 509, 219, 220, 221, 222, 223, 224, 232, 235, 236, 352, 510, 511, 512, 513, 514 364, 385, 427, 428, 476 foramen, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 15, 18, 22, evolution, 83, 111, 131, 248, 307, 339, 421, 432, 449 25, 32, 44, 45, 48, 49, 50, 51, 52, 56, 60, 64, 66, examinations, 66, 75, 110 76, 160, 171, 242, 243, 300, 302, 321, 329, 330, excision, 112, 116, 135, 138, 310, 320, 384, 444, 335, 340, 341, 342, 343, 345, 346, 354, 379, 398, 470, 471, 472, 474, 486 400, 511 exclusion, 135, 215, 216, 228, 233, 247, 271, 272, foramen magnum, 341 294, 306, 337, 338, 399, 401, 411, 412, 413, 414, foramen magnum, 3, 7, 8, 9, 11, 13, 15, 18, 45, 48, 417, 425, 427, 428, 429, 430, 431, 432, 442, 445, 56, 60, 171, 321, 329, 330, 340, 341, 342, 343, 446, 451, 454, 458, 459, 473, 505, 508, 514 345, 346, 398, 400 execution, 4, 14, 43, 169, 216, 218, 239, 240, 242, foramen ovale, 6, 7, 12, 300 249, 273, 274, 282 formation, 5, 50, 51, 52, 74, 81, 82, 83, 84, 85, 86, expertise, 359, 360, 370, 371 89, 95, 96, 98, 110, 168, 177, 199, 424, 442, 454, exposure, 11, 46, 60, 61, 94, 143, 171, 215, 240, 242, 483, 485, 486 243, 244, 245, 246, 248, 256, 258, 263, 264, 266, France, 55, 63, 120, 147, 151, 153, 185, 210, 254, 267, 268, 269, 271, 273, 274, 277, 279, 282, 287, 280, 347, 349, 364, 373, 467, 468, 481, 515, 516, 290, 298, 300, 301, 302, 304, 305, 317, 318, 320, 517, 518, 519, 520 321, 323, 328, 330, 331, 333, 334, 336, 337, 338, freedom, 248, 263, 267, 268, 270, 271, 273, 277, 340, 347,350, 354, 355, 356, 379, 380, 385, 386, 339, 432 398, 399, 400, 401, 410, 427, 429, 430, 432, 508, frontal lobe, 27, 28, 257, 258, 283, 284, 286, 288, 510 289, 291, 292, 378, 379, 510 external carotid artery, 21, 22, 33, 52, 155, 429, 431, fusion, 8, 29, 64, 65, 66, 70 455, 460 extracellular matrix, 84, 85, 86 G

F gadolinium, 380, 383, 384 gait, 129, 131, 368, 383, 401 facial nerve, 10, 52, 242, 246, 250, 254, 256, 257, ganglion, 6, 12, 25, 32 265, 270, 274, 276, 280, 299, 323, 335, 352, 353 general anesthesia, 191, 192, 194, 195, 200, 212, far lateral approach, 11, 329, 330, 331, 333, 334, 291, 468 335, 337, 338, 339, 340, 343, 382, 427 genes, 84, 110, 138, 376 fascia, 7, 33, 46, 241, 242, 244, 247, 248, 256, 257, geometry, 86, 99, 450 260, 265, 270, 332, 336 Germany, 149, 409, 410, 419, 504, 505 fat, 242, 244, 259, 264, 270, 321, 322, 336, 356 giant aneurysm, 197, 235, 246, 263, 264, 311, 416, fibers, 71, 86, 118, 321 429, 434, 438, 439, 441, 442, 450, 452, 454, 461

Index 529 giant intracranial aneurysms, 98, 106, 423, 424, 433, 423, 424, 433, 439, 455, 458, 485, 489, 492, 494, 435, 436, 439, 441, 446 497, 508 gland, 25, 265, 289 homeostasis, 85, 187, 190 Glioblastoma, 15, 18, 36, 40, 55, 59, 97, 103, 104, human, 18, 72, 85, 99, 102, 163, 202, 345, 485 179, 183, 184, 219, 223, 224, 250, 253, 275, 279, hybrid, 119, 432, 512 308, 312, 313, 325, 327, 341, 345, 346, 388, 391, hydrocephalus, 93, 169, 172, 189, 318, 450 392, 418, 421, 434, 438, 476, 479 hypertension, 75, 83, 91, 109, 130, 131, 168, 169, globus, 25, 28, 31, 378, 379 170, 174, 175, 187, 188, 190, 191, 195, 198, 200, glue, 113, 152, 155, 156, 249, 259, 322, 323, 356, 223, 336, 360, 363, 366, 424, 455, 456 367, 368, 459 hyperventilation, 194, 199, 292 grades, 112, 116, 188, 197 hypoglossal nerve, 8, 21, 48 grading, 93, 112, 113, 116, 137, 138, 139, 161, 188, hypotension, 190, 197, 198, 199, 200, 202 189, 213, 218, 362, 367, 368, 371, 395, 465, 477, hypothalamus, 50, 51, 52, 201, 264 480, 485, 498, 499, 500, 501 hypothermia, 196, 199, 223 gravity, 76, 284, 291, 299, 303, 379 hypoxia, 72, 74, 77, 213 growth, 64, 71, 82, 83, 91, 95, 105, 110, 141, 183, 291, 320, 333, 385, 442 guidance, 286, 314, 469, 475 I guidelines, 141, 168, 169, 171, 173, 188, 370 iatrogenic, 71, 74, 170, 210, 242, 246, 512 ICG, 118, 134, 228, 232, 235, 236, 365, 366, 368, H 369, 370, 443, 473, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 517, 519 hair, 171, 241, 248, 257, 264, 285, 291, 292, 352, ideal, 150, 162, 190, 200, 475 369 identification, 15, 37, 56, 60, 89, 98, 133, 180, 189, half-life, 170, 505, 506 218, 220, 241, 242, 251, 276, 303, 304, 321, 328, headache, 93, 108, 109, 129, 138, 169, 291, 318, 333, 342, 352, 354, 365, 370, 377, 380, 435, 465, 320, 360, 367, 383, 398, 444, 453, 455, 486, 508 474, 476, 507, 509 heart rate, 197, 200, 210 illumination, 228, 268, 273, 416, 513 hematoma, 94, 111, 114, 116, 139, 167, 168, 169, image(s), 94, 111, 117, 118, 130, 143, 175, 271, 272, 170, 171, 172, 173, 174, 175, 177, 199, 292, 293, 314, 351, 367, 368, 370, 371, 410, 443, 473, 475, 294, 366, 367, 377, 381, 382, 398, 461, 464 486, 492, 493, 503, 506, 507, 508, 513 hematomas, 169, 171, 172, 173, 175, 245, 270, 299, impairments, 210, 217, 506 315, 320, 381 improvements, 217, 340, 417, 493 hemiparesis, 93, 216, 221, 282, 299, 366 incidence, 82, 87, 90, 93, 108, 127, 167, 170, 188, hemisphere, 28, 45, 47, 284, 287, 291, 320, 322, 356, 189, 192, 199, 200, 235, 246, 455, 506 382, 510 India, 106, 310, 467, 468 hemorrhage, 22, 81, 82, 92, 93, 94, 95, 97, 98, 100, individuals, 96, 181, 376 103, 105, 108, 109, 110, 111, 113, 114, 115, 116, indocyanine green, 118, 133, 227, 228, 232, 234, 129, 130, 131, 132, 135, 140, 141, 167, 169, 170, 235, 236, 260, 272, 337, 338, 369, 380, 417, 425, 171, 172, 173, 175, 176, 178, 180, 181, 183, 184, 429, 430, 431, 432, 474, 503, 504, 505, 512 185, 187, 188, 189, 198, 233, 247, 291, 292, 318, induction, 85, 192, 194, 199, 299, 442 361, 363, 367, 368, 375, 376, 377, 378, 380, 382, infarction, 185, 189, 199, 282, 286, 290, 302, 303, 385, 392, 396, 397, 398, 399, 400, 407, 409, 411, 364 412, 413, 444, 460, 461, 464, 465, 483, 485, 487, inflammation, 81, 84, 85, 86, 91, 94, 95, 97, 106, 488, 489, 490, 491, 492, 494, 495, 498, 501 110, 177, 205, 244 hemorrhagic stroke, 167, 168 inflammatory cells, 83, 91, 95 hemostasis, 172, 292, 293, 322, 370, 474 inflammatory responses, 84, 85, 168 heterogeneity, 168, 195, 362 inhibition, 95, 96, 98, 201 hippocampus, 23, 25, 31 inhibitor, 18, 40, 59, 82, 103, 183, 223, 253, 279, history, 81, 91, 92, 95, 100, 103, 105, 107, 108, 110, 312, 327, 345, 391, 421, 438, 479 111, 112, 131, 139, 165, 170, 174, 188, 291, 319, injuries, 270, 290, 336, 353, 410, 416 338, 360, 367, 368, 375, 376, 383, 387, 388, 401, injury, 37, 56, 91, 94, 98, 110, 118, 168, 176, 180, 190, 194, 198, 200, 202, 246, 250, 276, 286, 290,

530 Index

298, 302, 303, 304, 306, 335, 342, 352, 353, 435, lead, 54, 64, 65, 72, 75, 201, 202, 232, 307, 351, 497 362, 378, 396, 416, 450, 454, 465, 490, 494 insertion, 104, 212, 411, 416 leakage, 199, 270, 331 integrity, 82, 84, 168, 196, 202, 210, 211, 212, 213, leaks, 93, 291, 356 242, 270, 378, 380 learning, ix, 351, 513 interference, 218, 396, 416 lesions, 11, 16, 53, 69, 73, 74, 75, 86, 100, 107, 108, internal carotid artery, 5, 7, 11, 12, 21, 23, 30, 31, 110, 116, 127, 128, 129, 130, 131, 135, 136, 137, 32, 36, 38, 41, 42, 48, 51, 72, 87, 92, 103, 154, 138, 139, 141, 150, 152, 153, 158, 161, 165, 169, 211, 230, 232, 240, 268, 288, 294, 366, 398, 408, 176, 185, 210, 211, 213, 216, 221, 240, 246, 248, 415, 418, 425, 438, 439, 442, 448, 469 249, 258, 261, 264, 269, 273, 274, 282, 284, 286, intervention, 99, 146, 196, 304, 360, 361, 370, 433, 287, 288, 290, 298, 306, 308, 310, 317, 318, 320, 450, 451, 452, 458, 492, 494 324, 329, 330, 333, 334, 335, 336, 339, 340, 343, intracerebral hematoma, 167, 172, 464 346, 364, 375, 376, 377, 378, 379, 380, 381, 385, intracerebral hemorrhage, 167, 173, 178, 180, 181, 388, 395, 399, 408, 432, 436, 442, 464, 475, 485, 183, 184, 185, 461, 464 487, 488, 489, 493, 495, 500, 504 intracranial aneurysm(s), ix, 10, 46, 81, 82, 85, 91, ligament, 5, 12, 22, 24, 46, 89, 329, 330, 340, 369 93, 95, 96, 97, 98, 99, 100, 102, 103, 104, 105, light, 10, 12, 13, 169, 177, 201, 210, 355, 408, 410, 106, 189, 209, 217, 219, 220, 221, 224, 231, 234, 424, 506, 508 235, 236, 239, 247, 253, 260, 261, 370, 407, 408, localization, 35, 54, 94, 128, 284, 324, 385, 455 409, 411, 415, 417, 419, 423, 424, 431, 432, 433, low risk, 150, 485, 492, 494 435, 436, 438, 439, 441, 446, 447, 449, 460, 461, lumen, 115, 157, 441, 467, 468 508 Luo, 100, 180, 204 intracranial pressure, 168, 173, 188, 200 lying, 9, 22, 259, 273, 276, 292, 297, 298, 301, 330, intraoperative neuromonitoring, 209, 220, 385, 386, 334 424 ipsilateral, 64, 65, 155, 257, 264, 271, 284, 286, 287, 290, 299, 304, 305, 330, 352, 367, 368, 426, 445, M 455 macrophages, 84, 85, 95, 103 iron, 95, 176, 177, 180 magnetic resonance (MR), 169, 284, 364, 391, 470, irrigation, 270, 396, 417 483 ischemia, 71, 130, 132, 135, 168, 187, 188, 189, 190, magnetic resonance imaging, 169, 391, 470, 483 191, 194, 196, 197, 198, 199, 202, 212, 213, 215, majority, 84, 109, 161, 172, 177, 189, 376, 385, 400, 216, 217, 218, 220, 221, 228, 231, 232, 235, 455, 483, 491, 492 460 management, ix, 15, 16, 53, 81, 86, 96, 98, 102, 107, isolation, 158, 431, 444 116, 130, 132, 136, 138, 163, 167, 168, 169, 173, issues, 14, 36, 55, 83, 87, 97, 179, 187, 190, 219, 178, 187, 188, 191, 192, 193, 194, 196, 198, 202, 250, 275, 308, 324, 341, 388, 396, 418, 434, 476, 210, 217, 234, 318, 359, 360, 361, 362, 363, 370, 491 371, 375, 380, 388, 389, 391, 392, 396, 400, 421, Italy, 3, 21, 43, 63, 81, 107, 127, 137, 167, 187, 209, 423, 424, 433, 435, 436, 438, 441, 442, 464, 475, 227, 239, 263, 281, 297, 317, 329, 359, 365, 367, 477, 479, 481, 487, 491, 492, 493, 494, 495, 496, 368, 375, 395, 407, 409, 423, 441, 449, 463, 483, 497, 498, 499, 500, 501, 504, 512 503, 506, 521, 522 manipulation, 144, 189, 199, 273, 287, 301, 409, 512 mapping, 130, 140, 212, 377 J mass, 44, 87, 93, 109, 114, 140, 161, 168, 174, 188, 198, 291, 292, 354, 377 jugular foramen, 3, 7, 8, 10, 13, 32, 330 mastoid, 7, 9, 10, 13, 32, 33, 52, 300, 302, 321, 322, 331, 335, 352, 353, 356 matrix, 85, 110, 322 L matter, 71, 74, 113, 149, 153, 157, 172, 513, 514 mean arterial pressure, 190, 194, 197 laminectomy, 172, 385, 401 measurement(s), 227, 228, 229, 232, 234, 235, 425, latency, 211, 213, 214, 215, 216, 218, 362, 483, 485, 426, 433, 439, 513 488, 489, 491 media, 82, 85, 86, 283

Index 531 median, 4, 5, 6, 7, 12, 13, 29, 66, 69, 139, 144, 211, 284, 289, 291, 293, 320, 323, 338, 365, 367, 368, 240, 360, 382, 385 369, 370, 376, 377, 379, 380, 382, 383, 384, 386, medical, 94, 116, 172, 173, 174, 189, 202, 304, 360, 391, 397, 398, 401, 427, 428, 429, 430, 431, 443, 487, 495, 505 470, 471, 472, 473, 486, 493, 505, 509, 511, 516 medicine, ix, 439, 499, 511 muscle atrophy, 242, 244, 246, 253, 265, 270, 279, medulla, 46, 47, 48, 51, 139, 145, 330, 333 300, 312 mellitus, 85, 168, 170, 175 muscles, 10, 25, 32, 33, 46, 52, 171, 212, 246, 270, meningioma, 19, 42, 61, 106, 185, 224, 254, 280, 331, 332 315, 328, 347, 350, 351, 354, 356, 393, 422, 440, mutation, 15, 37, 56, 83, 98, 139, 180, 220, 251, 276, 481, 499 342, 435, 476 meta-analysis, 96, 180, 185, 360, 387, 449, 495, 497, mutations, 110, 138, 376 498 methodology, 138, 228, 361, 407, 408, 416 microneurosurgery, vii, 16, 17, 19, 38, 39, 57, 58, N 61, 99, 101, 181, 182, 220, 222, 251, 252, 254, nerve, 5, 6, 7, 44, 45, 48, 49, 52, 64, 66, 67, 69, 76, 277, 278, 310, 311, 325, 326, 327, 342, 344, 389, 88, 89, 200, 211, 213, 241, 242, 246, 247, 256, 390, 407, 408, 419, 420, 424, 431, 432, 435, 437, 264, 266, 270, 300, 301, 302, 304, 320, 333, 336, 446, 464, 465, 477, 478, 479, 521 354, 355, 356, 363, 400, 401, 411, 416 microscope, 107, 116, 117, 228, 235, 257, 300, 401, neuroimaging, 83, 107, 396 408, 410, 416, 504, 505, 506, 507, 512, 513, 514, neuroprotection, 167, 176, 177, 178, 187, 190, 198, 515 202, 203, 206, 207 microsurgery, 59, 107, 115, 141, 221, 250, 359, 361, neurosurgery, 18, 35, 40, 59, 84, 98, 102, 107, 118, 362, 363, 370, 479, 480, 485, 492 183, 195, 200, 202, 217, 222, 229, 234, 235, 239, midbrain, 50, 51, 90, 145, 213, 214, 240, 244, 264, 248, 249, 252, 272, 273, 278, 307, 309, 311, 318, 268, 289, 297, 298, 300, 310, 381, 382 325, 326, 339, 340, 344, 345, 347, 389, 402, 407, middle cerebral artery, 19, 21, 26, 29, 30, 31, 38, 41, 408, 415, 419, 423, 433, 435, 436, 437, 438, 439, 60, 83, 92, 104, 184, 185, 221, 223, 224, 230, 442, 446, 475, 476, 478, 479, 480, 481, 495, 496, 240, 253, 259, 260, 279, 313, 327, 346, 379, 392, 497, 498, 499, 500, 501, 503, 504, 505, 507, 512, 415, 416, 421, 425, 426, 438, 443, 447, 448, 450, 514, 515, 522 452, 470, 480, 504, 505 neurovascular disease, ix, 14, 35, 54, 317, 441 middle skull base, 3, 4, 5, 6, 9, 10, 11, 12, 239, 240, neurovascular surgery, 82, 194, 196, 209, 210, 211, 243, 248, 249, 264 213, 217, 218, 239, 248, 249, 263, 274, 297, 298, minimally invasive neurosurgery, 407 339, 432 MMA, 300, 301, 302 New England, 121, 123, 206, 207, 439, 498 MMP, 85, 95, 110, 120 nitric oxide, 82, 85, 91, 98 models, 85, 110, 142, 180, 202, 235 norepinephrine, 195, 200, 201 modifications, 66, 84, 85, 109, 111, 259, 298, 317, North America, 92, 203, 205, 371, 436 318, 321, 330, 454 nuclei, 31, 49, 50, 51, 336 Moon, 402, 461, 464, 465, 477 nucleus, 25, 26, 27, 31, 47, 50, 51, 52, 84, 201, 213, morbidity, ix, 54, 82, 93, 107, 108, 112, 113, 114, 216, 292, 323, 378 115, 116, 143, 160, 168, 187, 197, 200, 210, 282, 291, 307, 361, 362, 363, 380, 465, 474, 476, 485, 490, 491, 492, 493, 494 O morphology, 87, 304, 399, 425, 443, 449, 450 morphometric, 15, 18, 248, 263, 273, 339, 341, 345, obstruction, 93, 172, 321 432 occipital lobe, 90, 289, 290 mortality, 82, 93, 100, 107, 108, 110, 111, 112, 114, occlusion, 29, 30, 46, 52, 54, 70, 71, 72, 75, 77, 113, 116, 168, 169, 187, 189, 192, 210, 291, 361, 363, 114, 116, 119, 151, 152, 153, 154, 155, 157, 158, 380, 424, 449, 464, 465, 476, 485, 488, 490, 492 159, 161, 162, 190, 196, 197, 199, 212, 213, 214, mortality rate, 109, 116, 168, 169, 361, 380, 424, 215, 216, 217, 218, 219, 223, 228, 232, 282, 290, 449, 464, 485, 488, 490 292, 306, 311, 322, 338, 361, 364, 400, 411, 417, MRI, 94, 95, 99, 105, 110, 111, 117, 118, 119, 124, 425, 427,438, 442, 443, 446, 451, 454, 458, 459, 130, 132, 134, 141, 151, 152, 153, 156, 169, 215, 461, 465, 467, 468, 491, 492, 504, 507, 508, 511

532 Index oculomotor, 5, 6, 49, 50, 51, 88, 90, 244, 263, 268, phenotype(s), 84, 85, 104, 391 271, 299, 300, 303, 304, 305, 414, 456 pituitary gland, 5, 25, 31, 200 oculomotor nerve, 49, 50, 51, 299, 300, 303, 304, platelets, 91, 452, 453 305, 414 plexus, 5, 6, 22, 25, 34, 41, 44, 45, 46, 47, 49, 50, 51, oculomotor window, 90, 263, 268, 271 76, 149, 156, 158, 161, 163, 283, 321, 322, 333, oedema, 114, 130, 151, 156 336, 400, 401, 511 onyx, 17, 39, 57, 101, 113, 132, 163, 164, 182, 221, polycystic kidney disease, 83, 102, 189 251, 277, 311, 326, 343, 364, 366, 372, 390, 402, polymerization, 466, 467, 468 403, 404, 419, 436, 447, 457, 459, 463, 467, 468, polymorphism, 82, 100, 105 469, 470, 471, 472, 473, 474, 475, 476, 478, 479, polyvinyl alcohol, 113, 136, 467, 480 480 pons, 11, 47, 48, 49, 89, 139, 145, 213, 214, 277, opacification, 152, 153, 154, 159, 430, 466 297, 298, 301, 302, 319, 320, 381, 383, 384 opioids, 191, 194, 200 population, 82, 91, 100, 108, 110, 137, 138, 188, optic chiasm, 22, 25, 485 200, 360, 361, 456, 490 optic nerve, 5, 11, 22, 25, 26, 31, 88, 270, 412, 428, posterior cerebral artery, 22, 26, 27, 30, 43, 48, 50, 430 61, 87, 98, 104, 240, 245, 289, 297, 300, 310, optico-carotid window, 263 314, 349, 365, 366, 411, 412, 415, 416, 470, 473, orbit, 4, 139, 242, 243, 256, 257 509 orbitopterional approach, 263, 274, 428 posterior circulation aneurysms, 11, 52, 320, 329, orbito-zygomatic approach, 263, 427 342, 432, 443 osteotomy, 263, 264, 267, 268, 269, 270, 273, 279, posterior inferior cerebellar artery, 11, 13, 15, 37, 43, 297, 298, 301, 302, 303, 309 46, 48, 56, 57, 97, 100, 179, 220, 250, 275, 341, oxygen, 72, 109, 189, 190, 199, 210, 377 368, 434, 450, 476 posterior petrosectomy, 349, 350 posterior skull base, 3, 6, 7, 9, 11, 12, 13, 43 P posterior-inferior cerebellar artery aneurysms, 329 preoperative simulation, 137, 138 pain, 129, 153, 191, 200, 210, 368, 484 preparation, 114, 132, 242, 244, 259, 396, 424 parallel, 23, 150, 240, 244, 249, 256, 257, 264, 266, preservation, 30, 244, 247, 270, 277, 337, 352, 363, 299, 353, 415, 417, 432, 452 366, 370, 412, 413, 416 paralysis, 192, 214, 246 pressure gradient, 114, 188, 190, 197, 469 parenchyma, 109, 111, 117, 130, 171, 376, 378, 443, prevention, 178, 187, 188, 200, 360 489, 505, 506, 507, 509, 512, 514 principles, 14, 36, 55, 97, 127, 172, 179, 187, 219, parietal lobe, 28, 54, 378 250, 275, 290, 308, 318, 324, 330, 341, 359, 360, pathogenesis, 81, 83, 84, 85, 95, 107, 110, 188 388, 395, 410, 418, 434, 476 pathology, 4, 21, 35, 54, 96, 102, 107, 127, 129, 167, probe, 118, 227, 228, 229, 231, 232, 234, 292, 352, 172, 178, 240, 286, 289, 307, 321, 339, 370, 391, 354, 425, 433, 443 408, 415 prognosis, 135, 170, 189, 364, 380, 456, 460, 495 pathophysiology, 81, 82, 129, 190, 195, 490, 503, pro-inflammatory, 82, 83, 84, 85 505, 515 prolactin, 16, 38, 57, 99, 181, 220, 251, 277, 343, pathway(s), 53, 82, 84, 118, 210, 211, 213, 221, 289, 435 376 prophylactic, 141, 188, 196, 442 PCA, 26, 30, 50, 51, 52, 54, 87, 88, 89, 90, 231, 240, protection, 194, 303, 489 244, 246, 289, 297, 298, 304, 305, 306, 349, 355, pterional approach, 11, 239, 240, 242, 243, 244, 245, 356, 365, 366, 415, 427 246, 247, 248, 249, 255, 258, 259, 260, 263, 264, perforating arteries, 21, 22, 25, 27, 29, 30, 31, 35, 41, 268, 269, 273, 274, 298, 307, 412, 428, 429, 432 45, 49, 51, 52, 54, 69, 70, 71, 89, 90, 116, 211, 218, 234, 268, 271, 272, 306, 362, 407, 408, 411, 412, 413, 416, 464, 465, 503, 507, 508, 513 Q perfusion, 129, 188, 190, 194, 195, 197, 198, 199, 210, 230, 235, 360, 370, 443, 465, 507, 509, 510, quality of life, 137, 141, 361, 370 512, 515 petroclival junction, 349, 355, 356 pharynx, 9, 25, 33

Index 533

risk factors, 81, 83, 91, 95, 96, 99, 100, 168, 177, R 178, 223, 381, 412, 489, 508 risk management, 102 radiation, 94, 115, 118, 138, 483, 484, 485, 488, 489, risk profile, 170, 488 490, 491, 493, 495, 496, 499, 501 root(s), 5, 12, 44, 45, 64, 65, 66, 67, 69, 71, 76, 158, Radiation, 291, 486, 497, 498, 501 171, 241, 242, 243, 265, 266, 267, 299, 300, 305, radio, ix, 100, 484, 493 323, 333, 352, 353, 363, 364, 385, 400, 401 radiosurgery, vii, 107, 111, 114, 115, 123, 131, 361, routes, 11, 244, 268, 269, 273, 325, 350 372, 373, 374, 464, 465, 483, 484, 485, 486, 487, 488, 489, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 508 S reality, 142, 143, 379, 381, 495 receptor, 82, 84, 96, 177, 191, 200 safety, 115, 117, 161, 220, 385, 432, 449, 451, 474, recognition, 94, 162, 242, 364, 514 475, 490, 494, 506, 512 recommendations, 199, 210, 359, 371 seizure, 108, 141, 148, 360, 361, 365, 483 reconstruction, 214, 216, 266, 279, 339, 367, 424, sensitivity, 72, 94, 211, 212, 215, 217, 218 425, 427, 428, 433 septum, 5, 10, 385 recovery, 17, 39, 57, 72, 101, 176, 182, 200, 218, sex, 83, 138, 168, 185, 213, 376, 426 221, 247, 251, 277, 311, 326, 343, 381, 390, 399, shape, 9, 68, 69, 72, 76, 84, 85, 86, 105, 273, 290, 419, 430, 436, 478, 480 299, 300, 305, 333, 369, 370, 412, 413, 451, 508 recurrence, 116, 141, 177, 449, 452, 499 shear, 81, 84, 104, 454 relaxation, 187, 190, 194, 195, 284, 292, 299, 303, showing, 75, 133, 134, 152, 154, 155, 156, 175, 176, 352, 353, 355, 397 201, 215, 216, 247, 271, 272, 292, 293, 294, 301, relevance, 36, 67, 109, 116, 479 304, 305, 306, 319, 323, 337, 338, 361, 380, 383, remodelling, 449, 452, 458 384, 386, 399, 401, 408, 429, 430, 431, 459, 471, repair, 83, 84, 99, 241, 264, 442 472, 473, 487, 511, 512 resection, 19, 41, 42, 61, 106, 107, 116, 117, 118, shunt, 71, 75, 110, 132, 149, 151, 152, 153, 155, 119, 138, 140, 185, 199, 224, 254, 280, 282, 291, 157, 158, 159, 160, 161, 176, 363, 364, 365, 369, 292, 298, 310, 314, 315, 328, 347, 356, 365, 366, 395, 396, 397, 398, 399, 400, 401, 455, 458, 463, 367, 370, 381, 382, 391, 393, 400, 421, 422, 440, 465, 509 481, 488, 489, 490, 494, 501, 504, 507, 509, 514 side effects, 170, 200, 362, 494, 506, 507 resistance, 72, 109, 131, 190 signs, 81, 93, 94, 141, 151, 152, 169, 195, 455, 461, resolution, 133, 212, 213, 369, 408, 410, 493 485 response, 72, 84, 104, 110, 115, 168, 190, 193, 199, silk, 245, 249, 336 200, 210, 221, 401, 425, 454, 489, 490 sinuses, 4, 13, 25, 31, 34, 35, 53, 54, 139, 157, 158, restoration, 232, 450, 511 163, 317, 318, 321, 322, 328, 379, 396, 398, 399, retromastoid craniotomy, 317, 318 455, 458 retrosigmoid approach, 317, 318, 320, 322, 324, 327, siphon, 416, 450, 454, 459 382, 383, 427 skin, 25, 33, 52, 64, 108, 171, 212, 240, 241, 242, rings, 22, 41, 359, 360, 362 247, 248, 256, 257, 260, 264, 265, 299, 305, 321, risk(s), 30, 54, 81, 82, 83, 86, 87, 91, 92, 93, 94, 95, 330, 331, 336, 352, 353, 363, 396 96, 99, 100, 102, 104, 105, 108, 110, 111, 112, skull base, 3, 4, 6, 8, 9, 10, 11, 12, 13, 14, 22, 37, 54, 113, 114, 115, 116, 130, 131, 132, 141, 143, 146, 56, 76, 98, 138, 143, 180, 199, 218, 224, 248, 150, 151, 158, 159, 160, 163, 168, 169, 170, 171, 249, 250, 263, 272, 273, 274, 276, 282, 287, 288, 172, 177, 178, 187, 188, 189, 192, 194, 197, 198, 298, 299, 307, 318, 330, 339, 342, 351, 355, 382, 199, 200, 202, 210, 212, 217, 218, 223, 228, 229, 395, 409, 410, 416, 427, 432, 435, 522 235, 242, 246, 249, 267, 270, 274, 282, 287, 290, smooth muscle, 85, 96, 103, 376 291, 298, 302, 303, 307, 319, 320, 321, 322, 323, sodium, 503, 505, 507 331, 336, 339, 350, 360, 361, 362, 363, 364, 365, software, 143, 144, 503, 504, 512, 513, 514 366, 370, 376, 377, 378, 380, 381, 382, 385, 392, solution, 200, 229, 241, 359, 360, 428, 469 396, 397, 400, 412, 423, 424, 432, 439, 442, 450, somatosensory evoked potential (SSEP), 118, 146, 451, 455, 458, 460, 461, 463, 464, 465, 466, 468, 209, 210, 211, 212, 214, 215, 216, 218, 220, 221, 469, 474, 483, 485, 487, 488, 489, 490, 491, 492, 222, 223, 352, 427, 476 493, 494, 495, 501, 508, 512 speech, 291, 445, 470

534 Index spinal, v, vi, vii, ix, 8, 15, 17, 37, 39, 45, 56, 57, 63, subtraction, 76, 94, 100, 132, 134, 176, 215, 216, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 233, 247, 270, 271, 272, 284, 292, 294, 337, 338, 77, 98, 101, 118, 121, 123, 127, 128, 129, 130, 365, 366, 399, 401, 411, 425, 470, 504 131, 132, 133, 134, 135, 136, 137, 139, 149, 150, Sun, 82, 100, 105, 181, 487, 497, 501 153, 156, 158, 161, 162, 164, 165, 180, 182, 191, superior cerebellar artery, 11, 30, 43, 48, 57, 240, 221, 250, 251, 276, 277, 311, 317, 326, 330, 342, 289, 297, 298, 300, 349, 355, 367, 368, 425, 426 343, 359, 363, 364, 365, 369, 372, 373, 375, 376, suppression, 197, 198, 199, 200, 202, 213, 214, 217, 377, 379, 380, 385, 386, 387, 389, 390, 391, 392, 218, 424, 428, 429 395, 400, 401, 402, 403, 419, 435, 436, 456, 459, surgical grading, 138 476, 478, 480, 483, 484, 492, 493, 494, 496, 497, surgical intervention, 99, 424, 439, 454 498, 500, 501, 503, 505, 511, 513, 514, 515, 516, surgical management, 15, 16, 116, 130, 138, 217, 517, 518 234, 391, 392, 396, 423, 424, 433, 435, 436, 475 spinal arteriovenous malformations, 136, 359, 501 surgical pyramid, 138, 143, 144 spinal cord, ix, 8, 17, 39, 45, 46, 57, 63, 64, 65, 66, surgical removal, 107, 109, 113, 116, 119, 138, 342, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 101, 487, 489 118, 127, 129, 130, 131, 132, 133, 135, 136, 139, surgical resection, 362, 377, 389, 466, 483, 487, 488, 156, 158, 164, 165, 182, 191, 221, 251, 277, 311, 489, 490, 492 326, 330, 343, 359, 363, 364, 365, 369, 375, 377, surgical technique, 167, 178, 273, 277, 294, 314, 385, 386, 387, 389, 390, 391, 392, 395, 401, 419, 350, 385, 389 436, 478, 480, 492, 493, 494, 497, 498, 500 survival, 194, 196, 461, 499 spinal tumor, 129, 492, 513 susceptibility, 82, 92, 377 spine, 5, 9, 57, 64, 76, 130, 158, 343, 346, 353, 389, suture, 8, 12, 171, 172, 242, 244, 248, 256, 259, 265, 400 286, 290, 299, 322, 336, 369, 429, 443 splenius capitis, 52, 332, 352 swelling, 135, 171, 177, 210, 363, 396 SSS, 288, 366, 367, 457 sylvian fissure, 11, 28, 29, 30, 239, 240, 243, 244, stability, 200, 451, 452 245, 246, 248, 256, 257, 258, 259, 260, 268, 378, stasis, 74, 75, 91, 160 397, 398, 429, 444 state(s), 190, 195, 199, 428, 455, 468, 493, 512 symptoms, 73, 93, 109, 127, 129, 130, 131, 132, 135, stenosis, 108, 110, 217, 228, 399, 432, 455, 465, 508 138, 141, 198, 291, 360, 364, 370, 385, 400, 453, stent, 104, 432, 441, 452, 453, 454, 460 455, 456, 483, 484, 485, 486 stereotactic radiosurgery, 115, 359, 360, 483, 489, syndrome, 64, 72, 77, 83, 87, 98, 102, 108, 128, 136, 490, 494, 495, 496, 497, 498, 499, 500, 501 138, 139, 189, 190, 199, 200, 290, 291, 360 sternocleidomastoid, 10, 52, 321, 331, 332, 352 synthesis, 83, 84, 196 stimulation, 19, 41, 60, 105, 118, 143, 146, 184, 191, systolic blood pressure, 169, 427, 474 192, 195, 211, 212, 215, 218, 224, 253, 279, 313, 323, 328, 346, 352, 367, 392, 421, 428, 439, 480 stimulus, 110, 195, 197, 212, 213 T stratification, 81, 82, 94, 96 target, 95, 142, 143, 145, 153, 169, 177, 191, 194, stress, 81, 83, 84, 91, 95, 104, 193, 196, 199, 200, 197, 198, 210, 246, 248, 249, 264, 268, 271, 273, 267, 454, 455 293, 299, 300, 307, 322, 330, 336, 339, 396, 397, striatum, 30, 35, 89 399, 458, 465, 469, 483, 484, 485, 494, 496 stroke, 82, 167, 168, 170, 177, 179, 180, 181, 189, TBI, 16, 37, 56, 98, 180, 220, 251, 276, 309, 325, 197, 202, 223, 423, 425, 481, 492, 510 342, 389, 418, 435, 477 structure, 64, 69, 86, 94, 99, 144, 153, 158, 159, 290, techniques, 54, 81, 82, 86, 92, 94, 107, 115, 164, 303, 353 172, 173, 178, 202, 209, 210, 212, 213, 217, 218, subarachnoid hemorrhage, 81, 82, 92, 94, 97, 98, 248, 267, 287, 290, 339, 381, 408, 415, 417, 423, 100, 103, 105, 114, 233, 247, 407, 409, 411, 412, 424, 425, 431, 432, 433, 438, 441, 442, 447, 449, 413, 444, 460 454, 459, 464, 469, 483, 489, 490, 495, 512, 514, subcutaneous tissue, 241, 260, 286, 321, 322 515, 522 subtemporal approach, 144, 268, 279, 297, 298, 299, technology, ix, 119, 229, 484, 489 301, 304, 306, 307, 309, 310, 311, 312, 314, 315, telangiectasia, 108, 190, 376 427 temperature, 118, 196, 210, 213, 291

Index 535 temporal lobe, 28, 41, 50, 89, 109, 141, 144, 171, 485, 487, 488, 489, 490, 491, 492, 493, 494, 495, 244, 257, 258, 297, 298, 299, 300, 302, 303, 305, 496, 497, 498, 499, 500, 501, 504, 508 306, 307, 309, 310, 354, 356, 376, 378 trial, 83, 91, 95, 115, 169, 170, 177, 178, 179, 180, temporal lobe retraction, 297, 298, 299, 302, 303, 181, 183, 185, 360, 361, 370, 461, 492, 499 306, 307, 309, 356 trigeminal nerve, 49, 300, 301, 302 temporary clipping, 197, 199, 209, 213, 215, 216, trigeminal neuralgia, 93, 298, 325, 456 217, 218, 219, 221, 232, 271, 338, 401, 424, 428, triggers, 14, 36, 55, 84, 96, 178, 219, 249, 274, 308, 429, 430, 443 324, 340, 387, 418, 433, 475 territory, 29, 65, 72, 75, 160, 425, 442, 444 trochlear nerve, 49, 289, 301, 302, 304 testing, 118, 428, 430 tropism, 463, 467, 468 thalamus, 30, 35, 50, 51, 52, 139, 144, 145, 169, 191, tumor, 84, 128, 199, 284, 290, 350, 354, 356, 389 201, 378, 379, 488, 500 tumors, 128, 234, 248, 273, 282, 284, 294, 299, 320, therapy, 138, 170, 172, 173, 174, 175, 177, 178, 179, 327, 364, 493, 522 180, 181, 184, 185, 188, 195, 196, 202, 291, 360, 396, 397, 433, 450, 452, 453, 476, 484, 485, 492, 498, 499 U thrombosis, 75, 111, 117, 129, 135, 151, 153, 155, ultrasonography, 133, 223, 236, 385, 425, 432, 475 156, 158, 161, 189, 190, 291, 321, 322, 376, 423, ultrasound, 118, 133, 134, 137, 145, 229, 236, 445 424, 425, 432, 442, 450, 451, 453, 454, 455, 461, (United States) USA, 151, 229, 392, 425, 426, 431, 485 467, 468, 493, 521 thrombus, 94, 338, 427, 429, 441, 454 thyroid, 21, 32, 34, 36, 426 tinnitus, 455, 456, 457 V tissue, 9, 46, 72, 84, 99, 110, 115, 118, 170, 190, 195, 196, 247, 321, 362, 378, 443, 484, 485, 513, VA Aneurysms, 329 514 vagus, 8, 46, 48, 49, 51, 323 titanium, 244, 245, 336, 356 variables, 93, 188, 194, 195, 493 TNF, 84, 85, 96 variations, 29, 36, 46, 57, 60, 76, 159, 188, 242, 281, training, ix, 138, 417, 432 318, 320 trajectory, 282, 293, 300, 320, 349, 351, 410 vascular diseases, 14, 85, 86, 317, 318, 324, 441 transcondylar approach, 18, 329, 333, 335, 340, 341, vascular pathophysiology, 503, 515 345 vascular surgery, 145, 200, 438 transection, 17, 39, 57, 101, 182, 221, 251, 277, 311, vascular system, 63, 64, 443 326, 343, 390, 419, 436, 478, 480 vascular wall, 83, 84, 85, 95, 106 transtentorial extension, 297, 301 vascularization, 35, 63, 64, 65, 67, 70, 71, 72, 74, trauma, 110, 153, 193 133, 211, 363, 385 treatment, 10, 11, 13, 14, 16, 19, 35, 36, 42, 43, 54, vasculature, 21, 43, 63, 66, 69, 110, 364, 365, 432, 55, 61, 74, 81, 93, 94, 95, 96, 97, 98, 104, 105, 468, 513 106, 107, 108, 110, 112, 113, 114, 115, 116, 118, vasoconstriction, 82, 194, 361 119, 127, 128, 130, 132, 136, 141, 143, 149, 150, vasospasm, 93, 97, 98, 116, 188, 189, 216, 217, 450 151, 153, 154, 158, 159, 160, 161, 162, 163, 164, VBJ aneurysms, 329, 333 165, 167, 168, 169, 170, 172, 173, 178, 179, 181, vein, 4, 6, 9, 10, 21, 34, 35, 52, 53, 54, 75, 76, 110, 183, 185, 187, 188, 189, 200, 219, 225, 235, 248, 129, 132, 149, 151, 152, 153, 154, 156, 157, 158, 249, 250, 254, 255, 264, 275, 280, 295, 297, 298, 159, 160, 161, 171, 189, 195, 283, 286, 289, 292, 302, 306, 308, 309, 312, 314, 315, 318, 319, 324, 293, 298, 300, 303, 322, 334, 352, 355, 361, 362, 328, 329, 330, 341, 347, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 396, 397, 398, 364, 365, 366, 368, 369, 370, 371, 377, 380, 385, 399,400, 401, 425, 426, 429, 431, 444, 455, 456, 388, 391, 393, 395, 396, 399, 400, 407, 408, 409, 458, 459, 465, 470, 471, 508, 509, 511, 514 412, 415, 416, 418, 422, 423, 424, 425, 427, 428, velocity, 129, 132, 135, 228, 369, 508, 514 429, 431, 432, 433, 434, 435, 436, 438, 439, 440, ventricle, 23, 25, 31, 45, 47, 50, 51, 59, 139, 145, 441, 442, 443, 445, 446, 447, 449, 450, 451, 452, 172, 176, 240, 282, 283, 287, 288, 289, 294, 379, 454, 455, 458, 459, 460, 461, 463, 464, 465, 466, 398, 471 469, 470, 474, 475, 476, 477, 479, 481, 483, 484,

536 Index versatility, 240, 248, 249, 272, 317, 318, 339, 340, 467, 505, 515 W vertebrae, 44, 76, 89 wall shear stress, 81, 84, 454 vertebral artery, 11, 13, 15, 37, 43, 44, 45, 47, 48, 52, water, 118, 259, 286, 306, 506 55, 56, 57, 60, 61, 66, 69, 72, 89, 97, 179, 220, white matter, 71, 73, 117, 118, 172, 190, 221, 292 250, 275, 304, 321, 328, 330, 332, 337, 338, 341, windows, 244, 268, 271 347, 365, 366, 398, 399, 400, 414, 434, 450, 459, worldwide, 112, 382, 415 469, 476 vessels, 49, 63, 64, 65, 67, 69, 71, 72, 74, 83, 86, 87, 89, 92, 94, 109, 118, 130, 132, 133, 134, 135, Y 159, 170, 191, 198, 199, 217, 229, 230, 232, 362, 363, 376, 401, 412, 416, 441, 464, 467, 469, 474, YELLOW 560, 503, 505 503, 504, 506, 507, 508, 512, 513, 514, 515 vestibular schwannoma, 224, 320, 328 vestibulocochlear nerve, 8, 48, 49, 59 Z video-angiography, 118, 365, 368, 370, 401, 503, 504, 512, 513 zygoma, 171, 241, 242, 243, 256, 257, 265, 266, vision, 267, 320, 322, 323, 409, 412, 416, 430 267, 352, 353 visualization, 65, 67, 68, 70, 75, 76, 143, 144, 197, zygomatic arch, 267, 268, 270, 279, 299, 300, 302, 198, 235, 257, 258, 271, 286, 298, 300, 301, 302, 305 306, 307, 333, 338, 354, 355, 356, 407, 408, 412, zygomatic osteotomy, 263, 267, 268, 269, 270, 273, 416, 467, 504, 505, 506, 513, 514, 515 297, 298, 301, 302, 303, 309 vomiting, 93, 169, 200, 367, 444