Neuroradiology (2019) 61:365–387 https://doi.org/10.1007/s00234-019-02183-3

REVIEW

Neuroradiological and clinical features in ophthalmoplegia

Stefan Weidauer1 & Christian Hofmann2 & Marlies Wagner3 & Elke Hattingen3

Received: 27 November 2018 /Accepted: 4 February 2019 /Published online: 12 February 2019 # Springer-Verlag GmbH Germany, part of Springer Nature 2019

Abstract Purpose Especially in acute onset of ophthalmoplegia, efficient neuroradiological evaluation is necessary to assist differential diagnosis, clinical course, and treatment options. Methods Different manifestations of ophthalmoplegia are explained and illustrated by characteristic neuroradiological and clinical findings. Results To present those ophthalmoplegic disorders in a clear manner, this review refers to different neuroanatomical structures and compartments. From neuroophthalmological point of view, diseases going ahead with ophthalmoplegia can be divided into (1) efferent infranuclear/peripheral disturbances involving oculomotor cranial nerves, (2) conjugate gaze abnormalities due to internuclear or supranuclear lesions, and (3) diseases of the extraocular eye muscles or their impairment due to intraorbital pathologies. Conclusion The knowledge of the relationship between neurological findings in ophthalmoplegia and involved neuroanatomical structures is crucial, and neuroradiology can be focused on circumscribed anatomical regions, using optimized investigation protocols.

Keywords Ophthalmoplegia . MRI . Cranial nerve palsy . Conjugate gaze abnormality . Horner syndrome

Introduction position or motility of both eyes. Almost any case of bin- ocular DV is accompanied by . As a second step, One of the cardinal clinical symptoms in ophthalmology is the neuroophthalmologist should examine the motility of . Since the perception of double vision (DV) is a the eyes in order to differentiate between non-paretic subjective sensation, it is the main task for the (concomitant) and paretic (incomitant) strabismus which neuroophthalmologist to objectify the symptoms [1]. The can roughly be summarized as ophthalmoplegia (OP). OP more precise the clinical description and findings, the bet- can be provoked by harmless and self-limiting causes, but ter the diagnostic clarification can be, which is a conse- it can also be the overture to a severe neurological disease. quent step-by-step procedure. The first step is to differen- Neuroimaging plays a central role in the diagnostic clarifi- tiate between monocular and binocular DV, the former of- cation of OP and planning of treatment options, particularly in ten due to an optical problem or macular diseases. the case of acute onset [1–6]. For optimized imaging, it is Binocular DV, however, is caused by an imbalance of essential to provide the neuroradiologist with precise informa- tion on the neuroophthalmologically involved structures [4, 6]. Consecutive, neuroimaging can be focused on circumscribed anatomical regions, using specialized investi- * Stefan Weidauer gation protocols, e.g., additional thin slice sequences to obtain [email protected] most appropriate neuroanatomical information [1, 2]. At this point, however, it must be mentioned that some causes of OP, 1 Department of Neurology, Sankt Katharinen Hospital, Teaching such as neuromuscular junction disorders, cannot be identified Hospital of the Goethe University, Seckbacher Landstraße 65, 60389 Frankfurt am Main, Germany by imaging [1]. From neuroophthalmological point of view, diseases being 2 Department of Ophthalmology, Neuroophthalmology, Goethe University, Frankfurt am Main, Germany accompanied by OP can be divided into (1) efferent infranuclear/peripheral neuroophthalmic disorders involving 3 Institute of Neuroradiology, Goethe University, Frankfurt am Main, Germany oculomotor cranial nerves (CN), i.e., oculomotor nerve (CN 366 Neuroradiology (2019) 61:365–387

III), (CN IV), and (CN VI) [1–4]; and (3) diseases of the extraocular eye muscles (see Table 1,Fig.1)[1, 7, 8]; (2) conjugate gaze abnormalities (EOM) and orbital diseases affecting the EOM (see Table 3) due to internuclear or supranuclear disorders (see Table 2) [1, 9–13]. In this review, characteristic neurological and

Table 1 Efferent infranuclear/peripheral neuroophthalmic disorders, additional neurological symptoms depending upon lesion site

Syndrome Clinical characteristics Lesion site Etiology

CN III palsy Ophthalmological , hypotropia, reduction of adduction/ Peripheral/subarachnoid space Vasculopathic, inflammation, uncal herniation, upgaze/downgaze, , with tumor, aneurysm (PcomA, BA, SCA), insufficient pupillary constriction intracranial hypotension (ICH), other (parasympathic fibers; ) (e.g., ophthalmoplegic migraine, congenital) Additional Contralateral ptosis Nuclear () Ischemia (microangiopathy), other neurological BCrossed syndromes^ symptoms Contralateral: hemiparesis, hypokinesia, Fascicular (midbrain and cerebral Ischemia, tumor, inflammation, other rigor (Weber syndrome) peduncle) Contralateral: sensation deficits, tremor, Fascicular (midbrain, red nucleus) Ischemia, tumor, inflammation, other hyperkinesia, pyramidal tract signs (Benedikt syndrome) Contralateral: ataxia (Claude-/Nothnagel Fascicular (midbrain, tegmentum/ Ischemia, tumor (pinealis), other syndrome) tectum), superior cerebellar peduncle CN IV palsy Ophthalmological Restricted downgaze in adduction, Peripheral/subarachnoid space Inflammation, tumor (e.g., schwannoma), excyclotropia, head tilt to the intracranial hypotension, other non-affected side (Bielschowsky’ssign) Additional Contralateral: dysmetria, ataxia Nuclear/fascicular (dorsal midbrain, Ischemia, hemorrhage, tumor, inflammation, neurological superior cerebellar peduncle) other symptoms Contralateral: relative afferent pupillary Nuclear/fascicular (dorsal Ischemia, hemorrhage, tumor, defect and/or Horner syndrome pontomesencephal junction, inflammation, other brachium of the superior colliculus) CN VI palsy Ophthalmological , restricted abduction Peripheral/subarachnoid space Inflammation, ICH, ischemia, other Skull base (Dorello’s canal) Trauma, tumor, inflammation Additional Ipsilateral facial pain, facial numbness CN Skull base / Petrous apex neurological V/supraorbital nerve (Gradenigo syndrome) symptoms Horner syndrome (possible) Cavernous sinus ICA aneurysm Contralateral: hemiparesis, sensation deficits Caudal pontine bulb Ischemia, inflammation, other Ipsilateral: nuclear CN VII paresis (caudal pontine bulb syndrome; Millard-Gubler syndrome/Foville syndrome) Contralateral: sensation deficits, ipsilateral: Caudal pontine tegmentum Ischemia, inflammation, other CN VII paresis, ataxia, (caudal pontine tegmentum syndrome) (I–III) Peripheral/nuclear Congenital, other Möbus syndrome Ipsilateral CN VII palsy, ipsiversive Nuclear Ischemia, inflammation, other conjugate gaze palsy (facial colliculus syndrome) Combined CN III, IV, VI palsies Peripheral/subarachnoid Inflammation, e.g., anti-GQ1b-antibody syndrome (Miller Fisher syndrome, Guillain-Barré syndrome) Intracranial hypotension, other Cavernous sinus/skullbase Thrombosis Carotid-cavernous sinus fistula Tolosa Hunt syndrome Inflammation, neoplasm ICA aneurysm, fungal infection Congenital fibrosis syndromes Nuclear/fascicular Inflammation, e.g,. multiple sclerosis Bickerstaff’s brainstem encephalitis (anti-GQ1b-antibody syndrome) Metabolic (e.g., Wernicke encephalopathy, Leigh syndrome), other

BA basilar artery, CN cranial nerve, ICA internal carotid artery, PcomA posterior communicating artery, SCA superior cerebellar artery Neuroradiology (2019) 61:365–387 367

Fig. 1 Schema of the oculomotor cranial nerve (CN) courses and related nucleus (CN VI); g: Dorello’s canal at the clivus; h: cavernous sinus; i: nuclear regions. a: Ncl. Edinger Westphal (nuclei accessorii autonomici); lateral rectus muscle; j: ciliar ganglion; k: optic nerve (CN II); l: superior b: oculomotoric nerve nucleus (CN III; extraocular muscles); c: trochlear oblique muscle; m: superior rectus muscle; n: ophthalmic artery; o: inter- nerve nucleus (CN IV); d: medial longitudinal fascicle (MLF); e: nal carotid artery (ICA); p: posterior communicating artery (PcomA) paramedian pontine reticular formation (PPFR); f: abducens nerve neuroimaging findings and also differential diagnostic aspects (DWI) [21] in axial and coronal acquisition may be necessary. are presented for the individual groups. Taking clinical rele- MR studies focusing on suspected lesions in the orbits and the vance into account, additionally the oculosympathetic paresis cavernous sinus should include axial and coronal spin-echo (Horner syndrome) is discussed (see Table 4)[1, 7, 8]. T1 WI with a slice thickness of 3 mm at most and fat satura- However, description and analysis of the different forms of tion (FS) after intravenous administration of gadolinium (pc pathological forms, impairment of , as T1 WI FS) [12, 22]. well as pathologies of the optic nerve go beyond the scope of this review and will not be discussed. Efferent infranuclear/peripheral neuroophthalmic disorders Neuroimaging protocol Isolated CN paresis Neuroimaging of small structures requires high-resolution MR sequences with thin slices, e.g., slice thickness of 0.75 Isolated paresis of the CN III, IV, and VI are often caused by up to 3 mm [14–17]. For example, the trochlear nerve (CN IV) ischemia, and typical vascular risk factors are diabetes and has a diameter of 0.75 to 1.00 mm [18] and sequences with a hypertension [1, 7]. From neurological point of view, clinical slice thickness of 1.00 mm in maximum without gap are nec- examination cannot reliably differentiate between peripheral essary for clear anatomical detection [14, 15]. Therefore, (infranuclear) and nuclear CN palsy [5, 7, 20]. In contrast, strongly T2-weighted 3D sequences as well as isovolumetric while neuroimaging in peripheral CN palsies is often high-resolution high contrast T1-weighted 3D sequences after negative—apart from inflammatory etiologies, pathologies in- administration of gadolinium contrast agent are recommended volving CN nuclei often have a neuroradiological correlate [14–17]. These sequences allow the reconstruction of the CN [20]. courses in the subarachnoid space, the skull base, the cavern- Painless diabetic-induced CN III palsy often spares the ous sinus, and the orbit. Due to the often small size of mesen- parasympathetic fibers (i.e., external OP) and may be caused cephalic and other brainstem lesions with a diameter between by impaired microcirculation within the CN as well as by 2 and 4 mm, neuroimaging of the posterior fossa structures circumscribed paramedian mesencephalic infarcts (Fig. 2) also requires thin slice sequences [18–20]. Because fluid- [21–24]. However, ischemic involvement of the Edinger- attenuated inversion recovery (FLAIR) sequences are prone Westphal nucleus in the neighborhood causes additional para- to artifacts in this region, one should prefer spin-echo T2- sympathetic neurological features with mydriasis and ptosis weighted images (WI) with thin slices. Depending on the neu- (Fig. 2). rologically suspected etiology of the lesion, e.g., ischemic An important differential diagnosis is the acute painful brainstem disorders, additional diffusion-weighted imaging paresis of CN III due to a so called ophthalmoplegic 368 Neuroradiology (2019) 61:365–387

Table 2 Conjugate gaze abnormalities (internuclear and supranuclear disorders), additional neurological symptoms depending upon lesion site

Conjugategazeabnormality Ophthalmological and clinical characteristics Lesion site Etiology

Horizontal gaze deficits /mesencephalon Internuclear ophthalmoplegia (INO): MLF (upper) pontine tegmentum Inflammation, e.g., multiple ipsilateral limitation of adduction, sclerosis preserved convergence, contralateral abducting Ischemia nystagmus other One-and-a-half syndrome: bilateral limitation of MLF (lower) pontine tegmentum Inflammation adduction and monocular abduction paresis and CN VI nucleus (PPRF) Ischemia Eight-and-a-half syndrome: additional CN VII palsy Additional CN VII fascicle other Foville syndrome: ipsilateral horizontal gaze palsy, Caudal tegmental pons Inflammation CN VII palsy; contralateral hemiparesis Ischemia other Locked-in syndrome: horizontal gaze palsy, Ventral and central pons Ischemia partially sparing of upward gaze and Hemorrhage blinking; quadriplegia, anarthria Bilateral abduction deficit (CN VI palsy), Pontine tegmentum, tectum, Wernicke encephalopathy nystagmus; additional: disturbance of periaqueductal gray, (Vit. B1 deficiency) consciousness (Bglobal state of confusion^), mammillary bodies, ataxia thalamus, other Other, e.g., Leigh syndrome, multiple system atrophy (corticobasal syndrome) Abnormal horizontal Supratentorial conjugate gaze The patient looks at the lesion; Bright way eyes^ Prefrontal cortical eye fields Ischemia deviations sign (contralateral hemiparesis) (Brodman’sarea8) (Focal) epileptic activity the patients looks away from the lesion „wrong (e.g., tumor, way eyes Bsign inflammation) Infratentorial Ipsilateral gaze paresis and contralateral gaze preference CN VI nucleus or PPRF Ischemia, hemorrhage, other Vertical gaze deficits Infra-/supratentorial Parinaud syndrome (pretectal syndrome): upgaze (riMLF), posterior commissure: Pinealis region: tumor, cyst, palsy, convergence-retraction nystagmus, Dorsal midbrain, tectum glioma, , light-near pupillary dissociation, lid lag ischemia, infection, other Top-of-the-basilar-artery syndrome Bilateral paramedian Ischemia, hemorrhage (variable paramedian mesencephalic and rostromesencephalic thalamic symptoms) and infero-medial thalamic lesions (PTPA; Percheron’sar- tery) Progressive supranuclear palsy (PSP), typically Midbrain (hummingbird Neurodegenerative disorder downward > upward; Batypical parkinsonism^ sign),thalamus, brainstem (tau protein) Additional variable neurological symptoms Metabolic diseases M. Whipple Other, e.g., paraneoplastic brainstem encephalitis Ocular tilt reaction: skew deviation (vertical Dorsolateral medulla oblongata Ischemia, other squinting), head tilt, binocular concordant cyclorotation, tilt of subjective vertical Ipsilateral: Horner syndrome, ataxia, facial sensory deficits (CN V); contralateral: hypalgesia; dysphagia, dysarthria (Wallenberg syndrome) Downward deviation of both eyes with/without Thalamus Ischemia, hemorrhage, convergence, infection, tumor, other

CN cranial nerve, MLF medial longitudinal fascicle, PPRF paramedian pontine reticular formation, PSP progressive supranuclear palsy (Steele Richardson Olszewski- or Richardson syndrome), PTPA posterior thalamoperforating arteries, riMLF rostral interstitial nuclei of the medial longitudinal fasciculus aneurysm with consecutive CN compression (Fig. 3)[25]. followed by prompt aneurysm treatment is necessary Aneurysm-related CN III palsy typically leads to mydriasis [26–29]. Most often, aneurysm arises from the terminal with unequal size of pupils (anisocoria; Fig. 3b) due to segment of the internal carotid artery (ICA) at the origin compromised parasympathetic fibers in the external layers of the posterior communicating artery (PcomA; Fig. 3e). of the nerve (internal OP) besides variable palsies of the Rarer aneurysms of the superior cerebellar artery (SCA) or EOM innervated by the CN III (external OP). This repre- the tip of the basilar artery might also cause affection of the sents an emergency situationandacuteneuroimaging third CN [1, 2, 7, 30]. Neuroradiology (2019) 61:365–387 369

Table 3 Disorders of the extraocular eye muscles (EOM) and abducens nerve and/or the CN nucleus [32]. Due to para- intraorbital pathologies doxical coinnervation of the lateral and medial rectus Thyroid-associated orbitopathy (Graves or endocrine ophthalmopathy) muscles, clinical examination exhibits retraction of the Primary ocular myopathies (e.g., Kearns Sayre syndrome, chronic globe and narrowed palpebral fissure in attempted adduc- progressive external ophthalmoplegia) tion [1, 32]. Based on ocular muscle electromyography, Neuromuscular junction/myasthenia gravis three subtypes could be differentiated [33]. Type 1 is the Orbital inflammatory pseudotumor, i.e., IgG 4-related ophthalmic most common pattern characterized by impaired abduc- disease (IgG-4ROD; idiopathic orbital inflammation) tion, normal adduction, and retraction of the adducted Vascular globe [34]. MRI typically shows absence of the CN VI Neoplasia (see Fig. 5)[35–37]. Type 2 is rare going ahead with Inflammation normal abduction and impaired adduction, and in type 3 Trauma/blow-out fractures (Bpseudo-Duane syndrome^) both abduction and adduction are impaired [1, 33]. High- resolution MRI using heavily T2 WI may provide addi- tional information of innervation abnormalities of the In up to 35%, painful precedes extraocular muscles (EOM) [35]. However, also orbital subarachnoid hemorrhage (SAH) as a Bwarning leak^ or sen- blow-out fractures with entrapment of the medial rectus tinel leak [26, 29]. However, most often, clinical presentation muscle may mimic Duane’ssyndrome,i.e.,pseudo- of ruptured distal ICA aneurysms is the apoplectic type with Duane’sretractionsyndrome[1]. SAH. OP due to CN paresis occurs in nearly one-third of pa- Another emergency situation represents CN III paresis tients suffering from intracranial hypotension (ICH), when with initial mydriasis in case of supratentorial space occu- cerebrospinal fluid volume is reduced via spinal meninges pying lesions leading to transtentorial herniation with ipsi- caused by spontaneous leakage or iatrogenic procedures, lateral nerve compression at the level of the plica e.g., lumbar puncture (see Fig. 6)[38–42]. Uni- or bilateral petroclinoidea. If possible, acute neurosurgical interven- abducens nerve paresis (> 80%) is the most common in tion is required [5, 6]. symptomatic spontaneous ICH [39]. Although the precise In contrast to CN IV paresis but similar to CN III affection, etiology of CN palsy is unclear, one reason therefore may lesions of the abducens nerve (CN VI) are also common be traction of the CN due to downward displacement of the (Fig. 4)[1, 7]. Besides disturbance of microcirculation in pa- brainstem [39]. From pathophysiological point of view, the tients suffering from diabetes, possible etiologies include in- abducens nerve is favored to traction-related injury due to flammation (Fig. 4), pathological processes of the scull base the long prepontine subarachnoid course, the subsequent with involvement of the clivus and Dorello’s canal (Fig. 1)[1, travel through Dorello’scanal,andattachmenttothe 2, 7, 17], and in rare cases also infraclinoidal intracavernous Gruber ligament [43, 44]. CN III and CN IV palsies are ICA aneurysms [7, 31]. less common and in advanced cases with progressive her- Differential diagnosis of CN VI palsy include Duane’s niation, CN compression as well as brainstem injury may retraction syndrome caused by hypo- or aplasia of the be likely consequences [38, 39, 42].

Table 4 Different Horner syndromes (HS)

Form Localization Etiology Symptoms

Central (first-order neuron) Uncrossed: hypothalamus–pons–dorsolateral Hemorrhage, infarct, tumor Wallenberg syndrome: ipsilateral: sympathetic tract medulla oblongata–lower cervical spinal CN V, IX, X with Horner syndrome, cord at the level of ciliospinal center of ataxia, hypo-/anhidrosis; contralateral: Budge and Waller (C8–Th2) hypalgesia Preganglionic Spinal nerve roots C8–Th2, aortic arch (le.) Traumatic spinal nerve root Horner syndrome; Ggl. stellatum: (second-order neuron) and subclavian artery (ri.)—superior lesion, pancoast-tumor, hypo-/anhidrosis arm and face; cervical ganglion at the level of the aortic arch dissection superior cervical ggl.: facial ICA origin hypo-/anhidrosis Postganglionic Superior cervical ganglion: as internal carotid ICA dissection, cervical tumor, Painful Horner syndrome, often (third-order neuron) plexus in the arterial wall of the ICA—as lesions of the skull base or without facial anhidrosis external carotid plexus (sudomotoric fibers cavernous sinus towards the facial sweat glands on the surface of the ICA wall)

CN cranial nerve, ICA internal carotid artery, Ggl ganglion 370 Neuroradiology (2019) 61:365–387

Fig. 2 A 73-year-old woman suffering from nuclear right-sided incomplete oculomotor nerve palsy with abduction of the right bulb, ptosis and mydriasis (a). Axial fluid-attenuated inversion recovery (FLAIR) images (b) and diffusion weighted images (DWI; c: ax.; d: cor; b =1000s/mm2) showing a rostromesencephalic paramedian infarct (arrow) with restricted diffusion (c, d) and in- volvement of the Nucleus Edinger-Westphal

Combined CN III, IV, and VI palsies Tolosa-Hunt syndrome

Whereas the CN III, IV, and the first and second branch of the The Tolosa-Hunt syndrome (THS) represents a painful OP trigeminal nerve (CN V; ophthalmic nerve and maxillary characterized by paresis of the CN III, IV, and VI and nerve) run in the lateral wall of the cavernous sinus [22], the severe unilateral retro- or periorbital pain, quickly abducens nerve (CN VI) partially accompanied by additional responding to steroids [47–49]. In addition, the first and sympathetic ocular fibers and the ICA are located in the ve- second branch of the trigeminal nerve may be involved, nous compartment of the cavernous sinus itself [22, 45, 46]. and in rare cases, also the optic nerve (CN II). THS is Therefore, pathological processes in the cavernous sinus may caused by a nonspecific granulomatous lymphocytic in- result in different combinations of CN paresis, often accom- flammation with the soft-tissue mass involving the cavern- panied by retro- or periorbital pain (Figs. 7 and 8;seeTable1) ous sinus with possible extension towards the superior or- [1, 2, 5, 7]. bital fissure and the orbital apex (Fig. 9)[47–49]. Per

Fig. 3 Painful complete left cranial nerve (CN) III palsy (a, b) in a 70-year-old man. Time of flight (ToF) source image (c)and axial T2 WI (d)disclosingdistal left internal carotid artery (ICA) aneurysm (white arrow) and shifted ipsilateral oculomotor nerve (d, black arrow). e 3D ro- tational digital subtraction angi- ography (DSA) demonstrating ophthalmoplegic ICA aneurysm (arrow) at the origin of the poste- rior communicating artery (PcomA; arrowhead) and sche- matized course of the CN III (yellow line) in another patient Neuroradiology (2019) 61:365–387 371

Fig. 4 Abducens nerve palsy right (a) with collocate double vision when looking to the right side. Axial T2 WI (b) and T1 WI pc (c) showing the abducens nerve (arrow) just before entering Dorello’s canal with slight en- hancement (c)dueto oligoradiculitis cranialis

definition, the inflammation may also involve the ICA wall, i.e., periarteritic granuloma [47]. Diagnostic criteria for the THS given by the International Headache Society (IHS) are the following: (1) one or more episodes of uni- lateral orbital pain persisting for weeks if untreated; (2) singular or combined paresis of the CN III, IV, and VI and/or detection of granuloma by MR imaging or biopsy; (3) paresis within a 2-week period after pain onset; (4) remission of pain and paresis within 72 h when treated adequate with steroids; and (5) exclusion of other causes by accurate investigation [49, 50]. MRI features could be classified into primary and sec- ondary criteria [22, 51]. Primary criteria include (1) pres- ence of a lesion within the anterior cavernous sinus (Fig. 9), (2) local increasing size of the cavernous sinus, and (3) bulging of the dural contour of the cavernous sinus. Secondary criteria include (1) involvement of the orbital apex and the optic nerve, (2) extension toward the superior orbital fissure, (3) involvement of the ICA, and (4) blurred dural boarder on T2 WI. If solely intraorbital masses are present, differential diagnosis should include idiopathic in- flammatory orbitopathy (orbital pseudotumor; Fig. 10). However, with regard to histopathological findings, it is supposed that THS [11, 52–54], orbital pseudotumor [10, 55–57], and hypertrophic pachymeningitis [58, 59]are three different manifestations of a common underlying pa- thology, i.e., IgG 4-related diseases [54].

Fig. 5 Duane syndrome type I. a Primary position with mild esotropia in the left eye. b Left gaze with almost complete restriction of abduction in Carotid-cavernous fistula the left eye. c Right gaze with mild restriction of adduction in the left eye and obvious retraction with reduction of the palpebral fissure. d ax. T2 WI (another patient) demonstrating aplasia of the left abducens nerve According to the Barrow classification, carotid-cavernous fistula (arrowhead) and normal right CN VI (arrow) (CCF) can be differentiated into direct (Barrow type A) and 372 Neuroradiology (2019) 61:365–387

Fig. 6 Spontaneous intracranial hypotension (ICH) due to CSF leakage in a 45-year-old man suffering from postural headache and bilateral CN VI palsy. Axial T2 WI (a, b) showing bilateral SDH (a), narrowing of the basal cisterns (b,arrow);c (sag. T1 WI pc): downward displacement of cranial contents

Fig. 7 Combined cranial nerve paresis right sided with external oculomotor nerve (CN III) paresis (a:adductiondeficitright), abducens nerve (CN VI) paresis (b: lateral rectus muscle palsy right), and trochlear nerve (CN IV) paresis (c: superior oblique muscle palsy) due to a space occupying lesion (metastasis) in the anterior lateral cavernous si- nus (d:ax.T2WI;e, f: ax. T1 WI; arrow) and the superior orbital fissure (f, arrowhead) with accen- tuated peripheral enhancement (f, g:arrow;g:cor.pcT1WI) Neuroradiology (2019) 61:365–387 373

Fig. 8 Right-sided acute incomplete cavernous sinus syndrome in an 84- disclosing impressive extension of the intracavernous internal carotid year-old woman with abducens nerve palsy (a) and oculomotor nerve artery (ICA) aneurysm (white arrow) with partial thrombosis (e, white palsy (b) including ptosis and mydriasis. Axial T2 WI (c) and ax. T1 arrowhead) and partial enhancement (e, f: black arrow). Note also ectasia WI pc (d)5yearsbeforeshowingenlargedcavernoussinus(c, d: arrow) of the basilar artery and the left ICA (e, f:blackarrowhead) with inhomogeneous flow void (c, arrowhead). Actual pc CT (e, f)

Fig. 9 Tolosa-Hunt syndrome. Axial (a, b)andcoronal(c, d)T1 WI disclosing slight enlargement of the anterior lateral cavernous sinus left (arrow) with inhomo- geneous enhancement (b–d,ar- row). Complete remission after four weeks of high dosage steroid therapy (not shown) 374 Neuroradiology (2019) 61:365–387

Fig. 10 Orbital pseudotumor. Coronal T2 WI (a) and T1 WI pc (b)showingaspaceoccupying lesion (a, b:arrow)with inhomogeneous contrast enhancement (b,arrow)and involvement of the optic nerve (a, b: arrowhead)

indirect fistula (Barrow type B–D) [60]. Direct CCF are defined Neurological examination discloses (in-)complete com- by a direct vascular connection between the ICA and the cav- bined paresis of the CN III, IV, and VI resulting in (in-)com- ernous sinus and are often caused by traumata involving the plete internal and external OP on the affected side (Fig. 11a, skull base [60, 61]. However, also intracavernous ICA aneurysm b). In addition, patients typically suffer from orbital pain, pro- rupture or iatrogenic lesions caused by surgical or gressive proptosis, conjunctival injection, chemosis, and sec- neurointerventional procedures may lead to direct CCF [31, 62]. ondary [5, 7, 63].

Fig. 11 Painful complete ophthalmoplegia left accompanied by (arrowhead). d, e Digital subtraction angiography (DSA) disclosing direct , chemosis, and conjunctival bleeding (a) due to traumatic CCF (d, arrow) and early retrograde filling of the dilated superior orbital direct carotid cavernous sinus fistula (CCF). b After CCF occlusion vein (d,arrowhead).e Coil embolization (white arrow) and normal filling declined exophthalmos and conjunctival bleeding, but persisting of the ophthalmic artery (black arrow). Note also regular filling of middle complete ophthalmoplegia with mydriasis. c ax. CT pc showing cerebral artery (MCA) and anterior cerebral artery (ACA) branches after enlarged cavernous sinus (arrow) and dilated superior orbital vein endovascular CCF occlusion Neuroradiology (2019) 61:365–387 375

Characteristic MRI features include asymmetric dilation of Erdheim-Chester disease the cavernous sinus with increased flow void, dilatation of the superior orbital vein, and sometimes protrusion of the eyeball In case of unclear intracraniallesionsandadditionalbony (Fig. 11)[63]. Time-resolved CT and MR contrast-enhanced changes of the facial skull, in particular sinus walls and angiography could demonstrate early enhancement of the cav- orbit, the differential diagnosis should include ECD, a rare ernous sinus, and MR time of flight (TOF) angiography may systemic non-Langerhans cell histiocytosis of unknown show arterialized flow signal in the cavernous sinus [60, 61, etiology [76–78]. Erdheim-Chester disease (ECD) is char- 64–66]. In contrast, indirect vascular connection between the acterized by bilateral symmetric long-bone involvement; ICA and cavernous sinus (CCF Barrow types B–D) caused by however, in a recent study, up to 47% of patients had ad- dural arterial branches are often low-flow fistula [60]. In many ditional neurological symptoms [78, 79]. The widespread cases, these CCF are only detectable on digital subtraction spectrum of neurological disorders encompasses cerebellar angiography (DSA), which is the gold standard [62]. CCF and pyramidal signs (41 resp. 45%), sensory disturbances, Barrow type B show arteriovenous fistula by meningeal CN palsies, and ocular symptoms including DV and visual branches of the ICA, Barrow type C meningeal branches of field defects [77–79]. Neuroimaging most often exhibits the external carotid artery (ECA), and type D of both ICA and extraaxial mass lesions by foamy histiocytes with involve- ECA [60, 67]. ment of the meninges, the hypothalamic-pituitary axis, the orbit, and facial and/or skull base bone thickening [76, Anti-GQ1b antibody syndrome 80–82]. Intraaxial lesions are less common (17–23%) and MRI often shows infratentorialhyperintensesignalabnor- OP is also a core clinical feature in (Miller) Fisher syndrome malities on T2 WI especially in the brainstem, the dentate (MFS) [68] and Bickerstaff’s encephalitis (BE) [69], both nucleus, and the middle cerebellar peduncle [76–78, representing different conditions of the anti-GQ1b antibody 81–84]. syndrome [70, 71]. While in MFS the peripheral nervous sys- tem (PNS) involvement is more prominent, in Bickerstaff’s encephalitis as the so-called central nervous system (CNS) Conjugate gaze abnormalities (internuclear variant of the anti-GQ1b antibody syndrome, the alteration and supranuclear disorders) of the reticular formation with impaired consciousness is a typical clinical feature (see Fig. 12)[70–73]. However, neu- Horizontal gaze deficits rological presentation may be incomplete and a continuous spectrum with variable PNS and CNS involvement exists Internuclear opthalmoplegia [70]. Moreover, there is also an overlap between MFS and an axonal subtype of the Guillain-Barré-Syndrome, i.e., acute The medial longitudinal fascicle (MLF) is an internuclear motor axonal neuropathy (AMAN) [74, 75]. pathway between the nuclei of CN III and VI, providing

Fig. 12 Autoimmune (Bickerstaff) encephalitis. A 36-year-old male suf- hyperintense signal changes of the mesencephalon and tegmentum fering from progressive double vision, cranial nerve palsies III, IV, and (arrow) with inhomogeneous enhancement on pc T1 WI (c,arrow) VI, and gait ataxia. Ax. T2 WI (a, b)showingnearlysymmetrical 376 Neuroradiology (2019) 61:365–387 conjugated sideways gaze [1, 3–5]. MLF travels from the Wernicke encephalopathy rostral midbrain along the pontine tegmentum to the cervi- cal spinal cord (Fig. 1). Circumscribed lesion in the course Wernicke encephalopathy (WE) is characterized a global state of the MLF causes internuclear opthalmoplegia (INO) and of confusion, ataxia, OP, and nystagmus [98]. However, clin- neurological examination shows impaired bulb adduction ical presentation is often incomplete and isolated oculomotor ipsilateral and dissociated nystagmus of the abducted bulb disorders or disturbance of consciousness may be present contralateral, resulting in collocate DV during lateral gaze [98–100]. The underlying etiopathology of this serious dis-

(Fig. 13)[1, 3–5]. Both MLF are located close together, ease is thiamine (vitamin B1)deficiencyoftencausedbymal- therefore INO is often bilaterally. In younger patients, eti- nutrition, e.g., chronic alcoholism, and if untreated, WE may ology is most often multiple sclerosis (MS; Fig. 13) be followed by an irreversible amnestic syndrome, i.e., [85–89], whereas in the elderly, vascular lesions according Korsakow psychosis [98]. Oculomotor disturbances most of- to ischemia are more common (Fig. 14)[90–92]. Beside ten consist of an incomplete horizontal gaze palsy with accen- atherosclerosis of the basilar artery leading to occlusion of tuated abduction deficits and horizontal nystagmus (Fig. 16a– the orifices of the median and paramedian pontine perfo- c) [4, 98]. The accountable lesions are located in the rators, microangiopathy may also cause lacunar infarcts in periaqueductal gray matter and the tectal plate (Fig. 16d–f) the dorsal brainstem (Fig. 14)[21, 90–92]. Lesions at the [84, 98–101]. In addition, MRI may show often symmetrical level of the paramedian pontine reticular formation (PPFR) lesions in the periventricular regions of the hypothalamus and (Fig. 1)additionallyinvolvethenucleusoftheabducens thalamus with a high rate of thiamine-related glucose and nerve (CN VI), and the clinical feature is Bone and a half oxidative metabolism, the pulvinar, the mammillary bodies, syndrome^ [1, 3, 5, 93, 94]. In neurological examination, the bottom of the forth ventricle, and midline structures of the ipsilateral bulb adduction and abduction as well as contra- cerebellum [99–101]. Due to the severe irreversible cause of lateral bulb adduction is nullified, and only abduction of the disease without sufficient thiamine (vitamin B1)substitu- the contralateral eyeball with dissociated nystagmus is pre- tion, the knowledge of typical MRI features of WE is of crit- served (see Fig. 15)[1, 93, 94]. Moreover, additional facial ical importance [99, 100]. Moreover, MRI may be the key for nerve involvement during his course around the CN VI correct diagnosis especially in patients showing only psycho- nucleus (inner CN VII knee) will cause the so-called eight pathological abnormalities or incomplete symptoms on neu- and a half syndrome with additive ipsilateral peripheral CN rological examination [100, 102]. Whereas in the acute stage VII palsy [95–97]. of the disease within the first 6 days, contrast enhancement of

Fig. 13 Bilateral internuclear ophthalmoplegia (INO) in a 32-year-old black arrow. b INO right presenting with adduction deficit right. c bilat- man suffering from primary progressive multiple sclerosis (MS). a INO eral hyperintense lesions (white arrows) along the course of the medial left with adduction deficit left; see also divergent eyeballs on ax. T2 WI; c longitudinal fascicles (MLF) in the pontine tegmentum Neuroradiology (2019) 61:365–387 377

Fig. 14 Axial (a) and sag. (d) T2 WI showing a small hyperintense lesion of the MLF in the pontine tegmentum paramedian right (a, arrow) due to acute infarction (b, c: ax. and cor. diffusion-weighted images, DWI; b =1000s/mm2; arrow) in a 66-year-old man suffering from INO right the above-mentioned structures may be detectable, in the sub- may resolve completely. However, residual slight hyperin- acute and chronic phase hyperintense signal changes on T2 tense signal changes on T2 WI and FLAIR may persist WI and FLAIR accompanied with different degrees of over time [99, 103]. circumscribed atrophy are detectable (Fig. 16)[99]. In addi- Also affecting respective mesencephalic and other tion, DWI may exhibit slight lowering of ADC values in brainstem regions, other inflammatory diseases, e.g., the acute phase [103, 104]. When treated sufficiently in Bickerstaff encephalitis [69–73, 105], Beh et’sdisease, due time, clinical syndromes as well as MRI abnormalities and paraneoplastic brainstem encephalitis, metabolic

Fig. 15 One-and-a-half’ syndrome in a 41-year-old woman. Axial (a) paramedian right at the level of the (see also and sag. (d) T2 WI demonstrating lacunar infarct (arrow; b, c:ax.and Fig. 14d). Right (e)andleft(f) gaze exhibiting complete horizontal pare- cor. DWI; b = 1000 s/mm2; arrow) in the lower pontine tegmentum sis of the right eye and adduction deficit of the left eye 378 Neuroradiology (2019) 61:365–387

Fig. 16 A 56-year-old woman suffering from Wernicke’s encephalopathy impairment left. d–f ax. Fluid-attenuated inversion recovery (FLAIR) with impairment of consciousness, gait ataxia, and oculomotor distur- images showing symmetrical hyperintense lesions of the upper pontine bances. a Gaze straight on with slight convergence especially left. b tegmentum (d, arrow), the tectal plate (e, arrow), and the periaqueductal Gaze to the left with abduction deficit left and adduction impairment region (f, arrow) right. c Gaze to the right with abduction deficit right and adduction disorders including mitochondriopathies, e.g., Kearns Abnormal horizontal conjugate gaze deviations Sayre Syndrome [19, 106], Wilson disease, and neoplastic lesions, e.g., brainstem glioma, may cause gaze palsy and/ The frontal eye fields located in the prefrontal cortex, i.e., or combined CN palsies [19]. However, detailed descrip- cortical Brodman’s area 8, initiate and regulate the contralat- tion goes beyond the scope of this review, and it is referred eral gaze movements [1, 5]. Therefore, lesions affecting the to further specific literature. cortical frontal eye fields result in a gaze preference toward the

Fig. 17 Axial T2 WI (a–c) showing nearly symmetrical hyperintense lesions due to bilateral paramedian rostromesencephalic (a, arrow) and inferomedial thalamic (b, c: arrow) infarcts; d:cor.diffusion-weightedimages,DWI;b =1000s/mm2) Neuroradiology (2019) 61:365–387 379 side of lesion due to preponderance of the contralateral corti- gaze palsy, (2) slowing of vertical saccades, and (3) postural cal eye fields [1, 2, 5]. This Bdeviation conjugée^ is also called instability (Fig. 18). However, for clinical diagnosis of pro- Bright way eyes^ sign, and depending on to the extent of the gressive supranuclear palsy (PSP), new criteria have been lesion, additional contralateral neurological symptoms such as established, because two-third of all patients suffering from hemiparesis and sensation deficits may be present. Most often, PSP lack to show characteristic oculomotor disorders large infarcts in the middle cerebral artery (MCA) territory [122–124]. The Richardson syndrome (PSP–RS) is consistent with involvement of the prefrontal branches (anterior M2 seg- with the initial description mentioned above [123]. In addi- ment) cause a Bdeviation conjugée^ toward the side of lesion tion, different clinical phenotypes of PSP were defined includ- [1, 2, 5]. However, exceeding stimulation of the frontal eye ing corticobasal syndrome, PSP with Parkinsonism (PSP–P), fields may provoke preponderance for the contralateral gaze, semantic variant of primary progressive aphasia (PPA), and so-called Bwrong way eyes^ sign [1, 2, 5]. Etiology for the the non-fluent agrammatic variant of PPA [122, 123]. These more rarely contralateral Bdeviation conjugée^ includes sei- new diagnostic PSP criteriadefinedbytheMovement zures especially with focal epileptic activity and atypical lo- Disorder Society differentiate three levels of diagnostic cer- cated intracerebral hemorrhages [1, 2]. Regarding acute tainty, i.e., probable, possible, and suggestive PSP [123]. management, it is of interest if the horizontal conjugate gaze However, definite diagnosis of PSP requires neuropathologi- deviation is conquerable or not and therefore represents an cal conformation of protein tau aggregates. The different clin- important item in the National Institute Health Stroke Scale ical features of PSP may be a likely consequence of different (NIHSS). anatomic seeding and spreading properties of intracellular ag- gregates of protein tau. Vertical gaze deficits Structural MRI in PSP presenting with the classical Richardson syndrome (PSP–RS) disclose midbrain atrophy Paramedian rostromesencephalic and inferomedial thalamic with reduction of the midbrain anterior-posterior (ap.) diame- infarcts ter and concavity of the dorsolateral midbrain margins (Mickey Mouse or Morning Glory sign; Fig. 18)[125–127]. Vertical gaze palsy may be due to bilateral paramedian The reduction of the ap. diameter below 15 mm at the level of rostromesencephalic and inferomedial thalamic infarcts the interpeduncular fossa was described to be specific for PSP (Fig. 17) leading to dysfunction of the rostral interstitial nu- [125–128]. However, reduction of the midsagittal midbrain cleus of the MLF (Bender’stheory)[22–24, 107–112]. The area in manual performed measurement seems to be a sensi- infarcts are located in the territory of the posterior tive tool for PSP identification and differentiation from other thalamoperforating arteries (PTPA) originating from the P1- multisystem atrophies (MSA), e.g., cerebellar type of MSA segment (precommunicating segment) of the posterior cere- (MSA-C; formerly: olivo-ponto-cerebellar atrophy; OPCA) bral artery (PCA) [23, 24, 111–117]. Bilateral inferior [124, 128]. Moreover, the MR Parkinsonism index (MRPI), paramedian infarcts are a likely consequence, when the origin which includes also evaluation of the superior and middles of the PTPA is a common trunk according to type II of cerebellar peduncles, is a very reliable MR biomarker for the Percheron (Percheron’sartery)[113, 114]. Due to the highly diagnosis of PSP–RS [123, 124, 128, 129]. Additionally, T2 variable vascular supply of the rostromesencephalic and WI may show also symmetrical planar hyperintense signal paramedian thalamic nuclei [90, 115, 116], additional neuro- changes in the dorsolateral mesencephalon caused by the neu- logical symptoms such as impairment of consciousness, som- rodegenerative process [126]. nolence up to coma, cognitive deficits, hemisyndromes, and oculomotor nerve palsies may occur (Btop of the basilar artery syndrome^)[110]. Besides Bender’s theory with bilateral in- Parinaud syndrome nervation of vertical eye movement, also unilateral paramedian thalamic infarcts may cause vertical gaze palsy Characteristic neurological presentation in Parinaud syn- [8, 118–120]. One reason therefore might be that drome includes vertical gaze palsy, disturbance of the pu- frontocortical neuronal pathways decussate in the medial thal- pillary motoric going along with mydriasis, light–near–dis- amus and unilateral infarcts may cause interruption of sociation, and convergence–retraction nystagmus [1, 5, supranuclear input [118]. 130, 131]. The syndrome is often caused by compression of the dorsal midbrain and pretectal area, e.g., space- Progressive supranuclear palsy occupying lesions of the pineal gland and the tectal plate. Most often, tectal tumors are gliomas, but also focal dys- In the first clinical description by Steele, Richardson, and plasias as well as ganglioneural tumors may occur [130, Olszewski [121], this neurodegenerative disease was charac- 131]. However, also hydrocephalus and periaqueductal le- terized with the neurological triad of (1) supranuclear vertical sions may generate Parinaud syndrome [5, 9]. 380 Neuroradiology (2019) 61:365–387

Fig. 18 Vertical gaze palsy (a)in a 75-year-old man suffering from progressive supranuclear gaze palsy (PSP). Axial (b) and sag. (c) T2 WI showing mesencephalic atrophy dorsolateral accentuated (b, white arrow; BMickey Mouse sign^; c: black arrow: BHumming bird sign^) with widened ambiens cistern (b, arrowheads)

Disorders of the extraocular eye muscles related orbital diseases (IgG4-ROD) and other systemic auto- and intraorbital pathologies immune associated pathologies, tumors, e.g., lymphoma, me- ningioma, and hemangioma, and also traumatic orbital lesions Widespread different pathological processes in the orbit can (see Table 1)[132, 133]. Besides isolated orbital myositis or cause OP, such as inflammatory diseases including IgG4- systemic myositis (Fig. 19)[134–137], the extraocular

Fig. 19 T1 WI (a:cor;b, c:pccor.andax.)showingimpressive pc fat sat.) disclosing especially enlarged superior rectus muscle (arrow) hypertrophic extraocular muscles (a–c: arrowhead) with compression of in ocular myositis (arrowhead: optic nerve) the optic nerve (a–c: arrow) in endocrine orbitopathy. d, e:cor.T1WI(e: Neuroradiology (2019) 61:365–387 381

Fig. 20 Central Horner syndrome (HS) right with ptosis and miosis (a) and cor. diffusion-weighted images; b =1000s/mm2) causing Wallenberg due to dorsolateral infarction of the medulla oblongata with hyperintense syndrome in a 76-year-old man signal changes on ax. T2 WI (b, arrow) and restricted diffusion (c, d:ax. muscles (EOM) may be affected by myasthenia gravis or met- ipsilateral disturbance of oculosympathetic fibers [5, 45]. abolic disorders [132, 133, 136]. Typical metabolic etiologies Failed sympathetic innervation of the iris dilator muscle on include endocrine orbitopathy (Fig. 19)[138–142] and mito- the affected side caused miosis with consecutive anisocoria, chondrial related disorders, the latter often manifesting as and paresis of the Müller’s muscles of the eyelids results in chronic progressive external OP [143]. In Kearns-Sayre ptosis, also called Bupside down ptosis^ or Breverse ptosis^ Syndrome, MR imaging may show hyperintense brainstem (Fig. 20a) [45]. The combination of the upper eyelid ptosis lesions on T2 WI especially in the pontine tegmentum [19]. and the lower eyelid elevation visually is suggestive of An important differential diagnosis of orbital inflammatory enophthalmus [5, 45]. However, this is not a true processes is the IgG4-ROD (Fig. 9)[9–11, 53–57, 144, 145]. enophthalmus. Due to synaptic interconnections, three topo- Histopathology of this multifocal inflammatory disease ex- graphic locations of the disturbed oculosympathetic pathway hibits dense lymphocytic infiltrates especially containing can be differentiated: (1) central or first-order neuron HS, (2) IgG-4 plasma cells and fibrosis causing tumefactive lesions preganglionic or second-order neuron HS, and (3) postgangli- [53, 144]. Usually, the disease responds promptly to systemic onic or third-order neuron HS (see Table 4)[5, 45, 146–148]. steroid therapy, but relapses may occur and escalation of im- munosuppressive therapy using monoclonal antibodies, e.g., Central or first-order neuron HS Rituximab, is a likely consequence. IgG4-ROD may involve the lacrimal glands, the EOM, and the orbital soft tissue [9–11, In central HS, the lesion of the uncrossed sympathetic fibers is 53–57]. Most often, the so called orbital inflammatory located in their course beginning at the posterolateral hypo- pseudotumor is an IgG4-ROD [53, 132, 144]. In orbital trau- thalamus, passing through the lateral brainstem and the me- ma and OP, differential diagnosis should include fracture of dulla oblongata downwards to the ciliospinal center of Budge the orbital bottom with herniation and entrapment of the infe- and Waller in the intermediolateral gray matter of the spinal rior rectus muscle and also pseudo-Duane syndrome [1, 2]. cord at the level C8–T2 [5, 45, 147]. The heterogeneous eti- ology includes hypothalamic bleedings, tumors, brainstem in- farcts, and inflammatory or infectious myelitis of the lower Oculosympathic paresis (Horner syndrome) cervical and upper thoracic spinal cord. Typical clinical pre- sentation of dorsolateral medulla oblongata infarcts (Fig. 20) The Horner syndrome (HS) is defined by ptosis and miosis but is the Wallenberg Syndrome, defined by ipsilateral HS, ataxia, normally reactive pupil, and facultative anhidrosis due to dysfunction of the CN V, IX, X, and contralateral hypalgesia 382 Neuroradiology (2019) 61:365–387

Fig. 21 Young woman suffering from acute onset of painful Horner syndrome (HS) right (a) due to ipsilateral internal carotid artery (ICA) dissection. b, c:ax. T2 WI (b)andT1WIwithfat saturation (FS, c) showing hyper- intense intramural hematoma (b, c: white arrow) without relevant vascular narrowing (b,black arrow)

[148, 149]. Most often, Wallenberg’ssyndromeiscausedby plexus (Fig. 21)[45, 151–154]. Within the cavernous sinus, the ipsilateral distal vertebral artery occlusion at the level of the oculosympathetic pathway travel a short distance along with intradural V4 segment, but also diseases of the proximal pos- the CN VI and then switch over to the first portion of the terior inferior cerebellar artery (PICA) compromising the cir- trigeminal nerve (CN V), i.e., the ophthalmic nerve. cumferential branches supplying the lateral and especially the Therefore, the combination of CN VI palsy and HS is highly dorsolateral medulla oblongata are possible pathologies [149]. suggestive for a lesion in the dorsolateral portion of the cavern- ous sinus [45, 155]. More peripherally located pathologies of Preganglionic or second-order neuron HS the ophthalmic nerve, e.g., Herpes zoster ophthalmicus, may cause HS. In addition, besides ICA dissection, also neck tu- The lesion of the sympathetic fibers is located between the exit mors, skull base lesions, and diseases of the cavernous sinus from the ciliospinal center and the synapses in the superior may induce postganglionic HS [45, 146, 148]. cervical ganglion at the level of the proximal ICA [5, 45, 148]. In a large case series of 450 patients, Maloney WF et al. Beside traumatic spinal root and/or brachial plexus lesions, [147] reported 65% (270 pat.) to have a demonstrable cause also apical lung diseases, e.g., Pancoast tumor or other for the HS. These 270 patients showed preganglionic HS in space-occupying processes (e.g., metastasis or lymphoma) in 44%, postganglionic HS in 43%, and the remaining 13% suf- the neighborhood of the fiber course toward the superior cer- fered from central HS. In isolated HS, neuroimaging detects vical ganglion as well as inflammatory etiologies may cause underlying pathology in 20%, most often ICA dissection HS (see Table 4). Neuroimaging should encompass complete (Fig. 21)[153]. Therefore, especially painful isolated HS con- course of preganglionic fibers including the aortic arch [45, stitutes a red flag, implicating diagnostic clarification in an 146, 150]. emergency setting [146, 153]. However, when planning the MRI scan, it should be kept in mind that in the acute stage of Postganglionic or third-order neuron HS ICA dissection within day 1–4, especially proton density- weighted images (PD WI) are sensitive for intramural hema- The postganglionic oculosympathetic fibers run in the ICA toma with hyperintense signal changes [151, 153]. In contrast, wall, i.e., the internal carotid plexus, whereas the sudomotoric unenhanced T1 WI with fat suppression (FS) disclose fibers, which innervate the facial sweat glands, travel along the isointense signal of the hematoma due to absent intracellular external carotid plexus on the surface of the arterial wall [45]. methemoglobin within the first days after dissection onset. Therefore, HS caused by ICA dissection is often referred to as Hyperintense signal of the intramural hematoma will appear an incomplete HS, because facial anhidrosis does not occur due after day 4 caused by metabolism of desoxyhemoglobin into to spared sympathetic sudomotoric fibers in the external carotid methemoglobin [151, 153]. Neuroradiology (2019) 61:365–387 383

Key learning points Informed consent Informed consent was obtained from all individual participants included in the study. 1. OP and HS can be the overture to a life-threatening neu- Publisher’s note Springer Nature remains neutral with regard to jurisdic- rological disorder, especially when pain is present at the tional claims in published maps and institutional affiliations. same time. In this respect, imaging plays a central role in the clarification of OP or HS at acute onset. 2. A precise neurological diagnosis with topical assign- References ment of the anatomical structures involved is essential for a targeted neuroimaging using specialized investiga- 1. Liu GT, Volpe NJ, Galetta ST Neuro-Ophthalmology: Diagnosis tion protocols. and Management, 3rd edn. Elsevier, Edinburgh 3. Diseases going ahead with OP can be divided into (a) 2. Danieli L, Montali M, Remonda L et al (2018) Clinically directed neuroimaging of ophthalmoplegia. Clin Neuroradiol 28:3–16 efferent peripheral neuroophthalmic disorders involving 3. Strupp M, Kremmyda O, Adamczyk C et al (2014) Central ocular oculomotor CN, (b) conjugate gaze abnormalities due to motor disorders, including gaze palsy and nystagmus. J Neurol internuclear or supranuclear disorders, and (c) diseases 261(Suppl 2):S542–S558 of the orbit and the EOM. 4. Strupp M, Hüfner K, Sandmann R, Zwergal A, Dieterich M, Jahn K, Brandt T (2011) Central oculomotor disturbances and 4. Isolated or combined oculomotor CN palsies may occur nystagmus—a window into the brainstem and cerebellum. Dtsch particularly in the subarachnoid, cavernous, and orbital Arztebl Int 108:197–204 compartments, and have heterogeneous etiologies. 5. Bähr M, Frotscher M (2012) Duus' topical diagnosis in neurology: 5. Painless induced CN III palsy may be caused by im- anatomy, physiology, signs, symptoms, 5th edn. Georg Thieme Verlag, Stuttgart paired microcirculation within the CN as well as by 6. Meyer A (1920) Herniation of the brain. Arch Neurol Psychiatr 4: circumscribed paramedian mesencephalic infarcts. 387–400 6. Due to its long cisternal course and subsequent entry into 7. Berlit P (1991) Isolated and combined pareses of cranial nerves the Dorello canal with ligamentary fixation, the III, IV and VI. A retrospective study of 412 patients. J Neurol Sci abducens nerve is particularly vulnerable to intracranial 103:10–15 8. Adams ME, Linn J, Yousry I (2008) Pathology of the ocular motor hypotension. nerves III, IV, and VI. Neuroimaging Clin N Am 18:261–282 7. Horizontal gaze deficits are often caused by lesions of 9. Weber A, Romo LV, Sabates NR (1999) Pseudotumor of the orbit. the MLF. Clinical, pathologic, and radiologic evaluation. Radiol Clin N Am 8. Differential diagnosis of acute vertical gaze deficits 37:151–168 10. Sahlmüller M, Schroeter J (2011) Idiopathic inflammatory should include paramedian rostromesencephalic and orbitopathy. Augenheilkunde up2date 1:15–30 inferomedial thalamic infarcts, most often bilaterally. 11. Kashii S (2014) IgG4-related disease: a neuro-ophthalmological 9. Widespread different pathological processes in the orbit perspective. J Neuroophthalmol 34:400–407 can cause OP, such as inflammatory diseases including 12. Purohit BS, Vargas MI, Ailiano A, Merlini L, Poletti PA, Platon A, IgG4-ROD and other systemic autoimmune associated Delattre BM et al (2016) Orbital tumours and tumour-like lesions: exploring the armamentarium of multiparametric imaging. pathologies, tumors, and also traumatic orbital lesions. Insights Imaging 7:43–68 10. The knowledge of pathophysiological aspects of OP is 13. van der Pol CB, Chakraborty S, Gao J, Nguyen T, Torres C, crucial, especially since some entities of OP cannot be Glikstein R (2014) Imaging anatomy and pathology of extraocular identified by imaging, e.g., in neuromuscular junction muscles in adults. Can Assoc Radiol J 65:366–371 14. Blitz AM, Macedo LL, Chonka ZD, Ilica AT, Choudhri AF, Gallia disorders. GL, Aygun N (2014) High-resolution CISS MR imaging with and without contrast for evaluation of the upper cranial nerves: seg- Acknowledgments We thank Dr. Michael Nichtweiß for generously of- mental anatomy and selected pathologic conditions of the cisternal fering his advice and expertise during the process of this review. through extraforaminal segments. Neuroimaging Clin N Am 24: 17–34 Funding No funding was received for this study. 15. Yousry I, Camelio S, Schmid UD, Horsfield MA, Wiesmann M, Brückmann H, Yousry TA (2000) Visualization of cranial nerves I- XII: value of 3D CISS and T2-weighted FSE sequences. Eur Compliance with ethical standards Radiol 10:1061–1067 16. Wen J, Desai NS, Jeffery D, Aygun N, Blitz A (2018) High- Conflict of interest The authors declare that they have no conflict of resolution isotropic three-dimensional MR imaging of the interest. extraforaminal segments of the cranial nerves. Magn Reson Imaging Clin N Am 26:101–119 Ethical approval All procedures performed in the studies involving hu- 17. Yousry I, Camelio S, Wiesmann M, Schmid UD, Moriggl B, man participants were in accordance with the ethical standards of the Brückmann H, Yousry TA (1999) Detailed magnetic resonance institutional and/or national research committee and with the 1964 imaging anatomy of the cisternal segment of the abducent nerve: Helsinki Declaration and its later amendments or comparable ethical Dorello's canal and neurovascular relationships and landmarks. J standards. Neurosurg 91:276–283 384 Neuroradiology (2019) 61:365–387

18. Villain M, Segnarbieux F, Bonnel F, Aubry I, Arnaud B (1993) 38. Schievink WI (2006) Spontaneous spinal cerebrospinal fluid leaks The trochlear nerve: anatomy by microdissection. Surg Radiol and intracranial hypotension. JAMA 295:2286–2296 Anat 15:169–173 39. Zada G, Solomon TC, Giannotta SL (2007) A review of ocular 19. Hattingen E, Blasel S, Nichtweiss M, Zanella FE, Weidauer S manifestations in intracranial hypotension. Neurosurg Focus 23: (2010) MR imaging of midbrain pathologies. Clin Neuroradiol E8 20:81–97 40. Moster SJ, Moster ML (2014) Alternating skew deviation from 20. Thömke F (2004) Brainstem diseases causing isolated ocular mo- traumatic intracranial hypotension. Neuro-Ophthalmology 38: tor nerve palsies. Neuro-Ophthalmology 28:53–67 156–158 21. Kücker W, Weise J, Krapf H, Schmidt F, Friese S, Bähr M (2002) 41. Vahdani K, McVeigh K, Harrison R, Williams M, Garrott H MRI characteristics of acute and subacute brainstem and thalamic (2018) Intracranial hypotension mimicking chronic progressive infarctions: value of T2- and diffusion-weighted sequences. J external ophthalmoplegia. Orbit 37:371–374 Neurol 249:33–42 42. Dandurand C, Haw CS (2016) Oculomotor palsy in spontaneous 22. Linn J, Peters F, Lummel N, Schankin C, Rachinger W, intracranial hypotension: case report and review of the literature. Brueckmann H, Yousry I (2011) Detailed imaging of the normal Can J Neurol Sci 43:747–749 anatomy and pathologic conditions of the cavernous region at 3 43. Ono K, Arai H, Endo T, Tsunoda A, Sato K, Sakai T, Makita J Tesla using a contrast-enhanced MR angiography. (2004) Detailed MR imaging anatomy of the abducens nerve: Neuroradiology 53:947–954 evagination of CSF into Dorello canal. AJNR Am J Neuroradiol 23. Castaigne P, Lhermitte F, Buge A, Escourolle R, Hauw JJ, Lyon- 25:623–626 Caen O (1981) Paramedian thalamic and midbrain infarcts: clini- 44. Icke C, Ozer E, Arda N (2010) Microanatomical characteristics of cal and neuropathological study. Ann Neurol 10:127–148 the petrosphenoidal ligament of Gruber. Turk Neurosurg 20:323– 24. Schlesinger B (1976) The upper brainstem in the human. Its nu- 327 clear configuration and vascular supply. Springer, Berlin, pp 46– 45. Kanagalingam S, Miller N (2015) Horner syndrome: clinical per- 139 spectives. Eye Brain 7:35–46 25. Weidauer S, Moreitz S, Nichtweiss M (2018) Painful oculomotor 46. Striph GG, Burde RM (1988) Abducens nerve palsy and Horner’s nerve palsy. Dtsch Arztebl Int 115:298 syndrome revisited. J Clin Neuroophthalmol 8:13–17 26. Güresir E, Schuss P, Seifert V, Vatter H (2012) Oculomotor nerve 47. Tolosa E (1954) Periarteritic lesions of the carotid siphon with palsy by posterior communicating artery aneurysms: influence of clinical features of a carotid infraclinoid aneurysm. J Neurol Neurosurg Psychiatry 17:300 302 surgical strategy on recovery. J Neurosurg 117:904–910 – 48. Hunt WE, Meagher JN, LeFever HE et al (1961) Painful 27. Gabarel T, Borha A, di Palma C et al (2016) Clipping versus ophthalmoplegia: its relation to indolent inflammation of the cav- coiling in the management of posterior communicating artery an- ernous sinus. Neurology 11:56–62 eurysms with third nerve palsy: a systematic review and meta- 49. Kline LB, Hoyt WF (2001) The Tolosa-Hunt syndrome. J Neurol analysis. World Neurosurg 87:498–5067 Neurosurg Psychiatry 71:577–582 28. Panagiotopoulos V, Ladd SC, Gizewski E, Asgari S, Sandalcioglu 50. Headache Classification Committee of the International Headache EI, Forsting M, Wanke I (2011) Recovery of ophthalmoplegia Society (IHS) (2018) The international classification of headache after endovascular treatment of intracranial aneurysms. AJNR disorders, 3rd edition. Cephalalgia 38:1–211 Am J Neuroradiol 32:276–282 51. Schuknecht B, Sturm V, Huismana TAGM et al (2009) Tolosa- 29. Fu Q, Guan S, Liu C, Wang K, Cheng J (2018) Clinical signifi- Hunt syndrome: MR imaging features in 15 patients with 20 ep- cance of circumferential aneurysmal wall enhancement in symp- isodes of painful ophthalmoplegia. Eur J Radiol 69:445–453 tomatic patients with unruptured intracranial aneurysms: a high- 52. Wasmeier C, Pfadenhauer K, Rößler A (2002) Idiopathic inflam- resolution MRI study. Clin Neuroradiol 28:509–514 matory pseudotumor of the orbit and Tolosa-Hunt syndrome—are 30. Fujiwara S, Fujii K, Nishio S, Matsushima T, Fukui M (1989) they the same disease? J Neurol 249:1237–1241 Oculomotor nerve palsy in patients with cerebral aneurysms. 53. Yamamoto M, Hashimoto M, Takahashi H, Shinomura Y (2014) Neurosurg Rev 12:123–132 IgG4 disease. J Neuroophthalmol 34:393–399 31. Gagliardi D, Faravelli I, Villa L, Pero G, Cinnante C, Brusa R et al 54. Stone HJ, Zen Y, Deshpande V (2012) IgG4-related disease. N (2018) Bilateral cavernous carotid aneurysms: atypical presenta- Engl J Med 366:539–551 tion of a rare cause of mass effect. A case report and a review of 55. Wallace ZS, Deshpande V, Stone JH (2014) Ophthalmic manifes- the literature. Front Neurol 9:619 tations of IgG4-related disease: single-center experience and liter- 32. Duane A (1996) Congenital deficiency of abduction, associated ature review. Semin Arthritis Rheum 43:806–817 with impairment of adduction, retraction movements, contraction 56. Wong AJ, Planck SR, Choi D, Harrington CA, Troxell ML, of the palpebral fissure and oblique movements of the eye. Arch Houghton DC, Stauffer P, Wilson DJ, Grossniklaus HE, Dailey Ophthalmol 1905;34:133–159 RA, Ng JD, Steele EA, Harris GJ, Czyz C, Foster JA, White VA, 33. Huber A (1974) Electrophysiology of the retraction syndromes. Br Dolman PJ, Kazim M, Patel PJ, Edward DP, Katan H, Hussain H, J Ophthalmol 58:293–300 Selva D, Yeatts RP, Korn BS, Kikkawa DO, Rosenbaum JT 34. Kekunnaya R, Negalur M (2017) Duane retraction syndrome: (2014) IgG4 immunostaining and its implications in orbital in- causes, effects and management strategies. Clin Ophthalmol 11: flammatory disease. PLoS One 9:e109847 1917–1930 57. Andrew N, Kearney D, Selva D (2013) IgG4-related orbital dis- 35. Xia S, Li RL, Li YP et al (2014) MRI findings in Duane’s ocular ease: a meta-analysis and review. Acta Ophthalmol 91:694–700 retraction syndrome. Clin Radiol 69e:191–198 58. Bosch J, Ortega-Aznar A, Tintore M et al (2000) Hypertrophic 36. Kim JH, Hwang JM (2017) Imaging of cranial nerves III, IV,VI in pachymeningitis. A review of the histories of two cases and path- congenital cranial dysinnervation disorders. Korean J Ophthalmol ological relationship with the Tolosa-Hunt syndrome and the or- 31:183–193 bital pseudotumor. Rev Neurol 31:946–951 37. Tuzcu EA, Bayarogullari H, Atci N, Basarslan F, Coskun M, 59. Boban J, Ardalı S, Thurnher MM (2018) Leptomeningeal form of Yilmaz C, Ilhan N, Daglioglu M (2014) Magnetic resonance im- immunoglobulin G4-related hypertrophic meningitis with aging findings of the abducens nerves in type 1 Duane's retraction perivascular spread: a case report and review of the literature. syndrome. Semin Ophthalmol 29:142–145 Neuroradiology 60:769–773 Neuroradiology (2019) 61:365–387 385

60. Barrow DL, Spector RH, Braun IF, Landman JA, Tindall SC, neuroradiological presentation of Erdheim-Chester disease: report Tindall GT (1985) cClassification and treatment of spontaneous of 6 cases and systematic review of the literature. J Neurol 253: carotid-cavernous sinus fistulas. J Neurosurg 62:248–256 1267–1277 61. Ringer AJ, Salud L, Tomsick TA (2005) Carotid cavernous fistu- 79. Wright RA, Hermann RC, Parisi JE (1999) Neurological manifes- las: anatomy, classification, and treatment. Neurosurg Clin N Am tations of Erdheim-Chester disease. J Neurol Neurosurg 16:279–295 Psychiatry 66:72–75 62. Henderson AD, Miller NR (2018) Carotid-cavernous fistula: cur- 80. Caparros-Lefebvre D, Pruvo JP, Rémy M, Wallaert B, Petit H rent concepts in aetiology, investigation, and management. Eye (1995) Neuroradiologic aspects of Erdheim-Chester disease. 32:164–172 AJNR Am J Neuroradiol 16:735–740 63. de Keizer R (2003) Carotid-cavernous and orbital arteriovenous 81. Martinez R (1995) Erdheim-Chester disease: MR of intraaxial and fistulas: ocular features, diagnostic and hemodynamic consider- extraaxial brain stem lesions. AJNR Am J Neuroradiol 16:1787– ations in relation to and morbidity. Orbit 22: 1790 121–142 82. Evidente VG, Adler CH, Giannini C, Conley CR, Parisi JE, 64. Coskun O, Hamon M, Catroux G, Gosme L, Courtheoux P, Fletcher GP (1998) Erdheim-Cheser disease with extensive Theron J (2000) Carotid-cavernous fistulas: diagnosis with spiral intraaxial brain stem lesions presenting as a progressive cerebellar CT angiography. AJNR Am J Neuroradiol 21:712–716 syndrome. Mov Disord 13:576–581 65. Hirai T, Korogi Y, Hamatake S, Ikushima I, Sugahara T, 83. Berkman J, Ford C, Johnson E, Malow BA, Aulino JM (2018) Sigematsu Y, Higashida Y, Takahashi M (1998) Three- Misdiagnosis: CNS Erdheim-Chester disease mimicking dimensional FISP imaging in the evaluation of carotid cavernous CLIPPERS. Neuroradiol J 31:399–402 fistula: comparison with contrast-enhanced CT and spin-echo MR. AJNR Am J Neuroradiol 19:253–259 84. Al Bayati A, Plate T, Al Bayati M, Yan Y, Lavi ES, Rosenblatt JD 66. Seeger A, Kramer U, Bischof F, Schuettauf F, Ebner F, Danz S, (2018) Dabrafenib and Trametinib treatment for Erdheim-Chester Ernemann U, Hauser TK (2015) Feasibility of noninvasive diag- disease with brain stem involvement. Mayo Clin Proc Innov Qual nosis and treatment planning in a case series with carotid- Outcomes 4:303–308 cavernous fistula using high-resolution time-resolved MR- 85. Frohman EM, Zhang H, Kramer PD, Fleckenstein J, Hawker K, angiography with stochastic trajectories (TWIST) and extended Racke MK, Frohman TC (2001) MRI characteristics of the MLF parallel acquisition technique (ePAT 6) at 3 T. Clin Neuroradiol in MS patients with chronic internuclear . 25:241–247 Neurology 57:762–768 67. Gemmete J, Chaudhary N, Pandey A et al (2010) Treatment of 86. Wattjes MP, Steenwijk MD, Stangel M (2015) MRI in the diag- carotid cavernous fistulas. Curr Treat Options Neurol 12:43–53 nosis and monitoring of multiple sclerosis: an update. Clin 68. Fisher M (1956) An unusual variant of acute idiopathic polyneu- Neuroradiol 25(Suppl 2):157–165 ritis (syndrome of ophthalmoplegia, ataxia and areflexia). N Engl J 87. Traboulsee A, Simon JH, Stone L, Fisher E, Jones DE, Malhotra Med 255:57–65 A, Newsome SD, Oh J, Reich DS, Richert N, Rammohan K, Khan 69. Bickerstaff ER, Cloake PC (1951) Mesencephalitis and O, Radue EW, Ford C, Halper J, Li D (2016) Revised recommen- Rhomencephalitis. Br Med J 2:77–81 dations of the consortium of MS centers task force for a standard- 70. Shahrizaila N, Yuki N (2013) Bickerstaff brainstem encephalitis ized MRI protocol and clinical guidelines for the diagnosis and and Fisher syndrome: anti-GQ1b antibody syndrome. J Neurol follow-up of multiple sclerosis. AJNR Am J Neuroradiol 37:394– Neurosurg Psychiatry 84:576–583 401 71. Ito M, Kuwabara S, Odaka M, Misawa S, Koga M, Hirata K, Yuki 88. Filippi M, Rocca M, Ciccarelli O, de Stefano N, Evangelou N, N (2008) Bickerstaff’s brainstem encephalitis and Fisher syn- Kappos L, Rovira A, Sastre-Garriga J, Tintorè M, Frederiksen JL, drome form a continuous spectrum. Clinical analysis of 581 cases. Gasperini C, Palace J, Reich DS, Banwell B, Montalban X, J Neurol 255:674–682 Barkhof F, MAGNIMS Study Group (2016) MRI criteria for the 72. Gologorsky RC, Barakos JA, Sahebkar F (2013) Rhomb- and diagnosis of multiple sclerosis: MAGNIMS consensus guidelines. Bickerstaff encephalitis: two clinical phenotypes? Pediatr Neurol Lancet Neurol 15:292–303 48:244–248 89. Wattjes MP, Raab P (2018) Brain and spinal cord MRI in multiple 73. Santoro JD, Lazzareschi DV, Campen CJ, Van Haren KP (2018) sclerosis: an update. Akt Neurol 45:29–43 Pediatric Bickerstaff brainstem encephalitis: a systematic review 90. Duvernoy H (1978) Human brainstem vessels. Springer, Berlin of literature and case series. J Neurol 265:141–150 91. Tatu L, Moulin T, Bogousslavsky J, Duvernoy H (1996) Arterial 74. Odaka M, Yuki N, Yamada M, Koga M, Takemi T, Hirata K, territories of human brain: brainstem and cerebellum. Neurology Kuwabara S (2003) Bickerstaff's brainstem encephalitis: clinical 47:1125–1135 features of 62 cases and a subgroup associated with Guillain-Barré 92. Kim JS (2004) Internuclear ophthalmoplegia as an isolated or syndrome. Brain 126:2279–2290 predominant symptom of brainstem infarction. Neurology 62: 75. Wakerley BR, Uncini A, Yuki N GBS Classification Group (2014) 1491–1496 Guillain-Barré and Miller Fisher syndromes—new diagnostic 93. Pierrot-Deseilligny C, Chain F, Serdaru M et al (1981) The ‘one- classification. Nat Rev Neurol 10:537–544 Erratum in: Nat Rev and-a-half’ syndrome. Electro-oculographic analyses of five cases Neurol 2014;10:612 with deductions about the physiological mechanisms of lateral 76. Drier A, Haroche J, Savatovsky J, Godenèche G, Dormont D, gaze. Brain 104:669–699 Chiras J, Amoura Z, Bonneville F (2010) Cerebral, facial, and 94. Deleu D, Solheid C, Michotte A, Ebinger G (1988) Dissociated orbital involvement in Erdheim-Chester disease: CT and MR im- ipsilateral horizontal gaze palsy in one-and-a-half syndrome. aging findings. Radiology 255:586–594 Neurology 38:1278–1280 77. Weidauer S, von Stuckrad-Barre S, Dettmann E, Zanella FE, Lanfermann H (2003) Cerebral Erdheim-Chester disease: case 95. Eggenberger E (1998) Eight-and-a-half syndrome: one-and-a-half report and review of the literature. Neuroradiology 45:241–245 syndrome plus cranial nerve VII palsy. J Neuroophthalmol 18: 78. Lachenal F, Cotton F, Desmurs-Clavel H, Haroche J, Taillia H, 114–116 Magy N, Hamidou M, Salvatierra J, Piette JC, Vital-Durand D, 96. Skaat A, Huna-Baron R (2012) Eight-and-a-half syndrome: a rare Rousset H (2006) Neurological manifestations and pontine neuroophthalmic syndrome. Arch Neurol 69:934–935 386 Neuroradiology (2019) 61:365–387

97. Uysal S, Demirtas-Tatlidede A, Selcuk OY, Yayla V (2013) 118. Deleu D (1997) Selective vertical saccadic palsy from unilateral Diffusion-weighted imaging in eight-and-a-half syndrome pre- medial thalamic infarction: clinical, neurophysiologic and MRI senting with transient hemiparesis. Clin Neuroradiol 23:235–236 correlates. Acta Neurol Scand 96:332–336 98. Victor M, Adams RD, Collins GH (1971) The Wernicke– 119. Wiest G, Baumgartner C, Schnider P, Trattnig S, Deecke L, Korsakoff syndrome: a clinical and pathological study of 245 Mueller C (1996) Monocular elevation paresis and contralateral patients, 82 with post-mortem examinations. Contemp Neurol downgaze paresis from unilateral mesodiencephalic infarction. J Ser 7:1–206 Neurol Neurosurg Psychiatry 60:579–581 99. Weidauer S, Nichtweiss M, Lanfermann H, Zanella FE (2003) 120. Clark JM, Albers GW (1995) Vertical gaze palsies from medial Wernicke encephalopathy: MR findings and clinical presentation. thalamic infarctions without midbrain involvement. Stroke 26: Eur Radiol 13:1001–1009 1467–1470 100. Antunez E, Estruch R, Cardenal C, Nicolas JM, Fernandez-Sola J, 121. Steele JC, Richardson JC, Olszewski J (1964) Progressive Urbano-Marquez A (1998) Usefulness of CT and MR imaging in supranuclear palsy: a heterogeneous degeneration involving the the diagnosis of acute Wernicke’s encephalopathy. AJR Am J brainstem, basal ganglia and cerebellum with vertical Roentgenol 171:1131–1137 supranuclear gaze and pseudobulbar palsy, nuchal dystonia and 101. Suzuki S, Ichijo M, Fujii H, Matsuoka Y, Ogawa Y (1996) Acute dementia. Arch Neurol 10:333–359 Wernicke’s encephalopathy: comparison of magnetic resonance 122. Respondek G, Levin J, Höglinger GU (2018) Progressive images and autopsy findings. Intern Med 35:831–834 supranuclear palsy and multiple system atrophy: clinicopatholog- 102. Zuccoli G, Santa Cruz D, Bertolini M, Rovira A, Gallucci M, ical concepts and therapeutic challenges. Curr Opin Neurol 31: Carollo C, Pipitone N (2009) MR imaging findings in 56 patients 448–454 with Wernicke encephalopathy: nonalcoholics may differ from 123. Höglinger GU, Respondek G, Stamelou M, Kurz C, Josephs KA, alcoholics. AJNR Am J Neuroradiol 30:171–176 Lang AE, Mollenhauer B, Müller U, Nilsson C, Whitwell JL, 103. Weidauer S, Rösler A, Zanella FE, Lanfermann H (2004) Arzberger T, Englund E, Gelpi E, Giese A, Irwin DJ, Meissner Diffusion-weighted imaging in Wernicke encephalopathy associ- WG, Pantelyat A, Rajput A, van Swieten JC, Troakes C, Antonini ated with stomach cancer: case report and review of the literature. A, Bhatia KP, Bordelon Y, Compta Y, Corvol JC, Colosimo C, Eur Neurol 51:55–57 Dickson DW, Dodel R, Ferguson L, Grossman M, Kassubek J, 104. White ML, Zhang Y, Andrew LG, Hadley WL (2005) MR imag- Krismer F, Levin J, Lorenzl S, Morris HR, Nestor P, Oertel WH, ing with diffusion-weighted imaging in acute and chronic Poewe W, Rabinovici G, Rowe JB, Schellenberg GD, Seppi K, Wernicke encephalopathy. AJNR Am J Neuroradiol 26:2306– van Eimeren T, Wenning GK, Boxer AL, Golbe LI, Litvan I, for 2310 the Movement Disorder Society-endorsed PSP Study Group 105. Weidauer S, Ziemann U, Thomalske C, Gaa J, Lanfermann H, (2017) Clinical diagnosis of progressive supranuclear palsy: the Zanella FE (2003) Vasogenic edema in Bickerstaff’s brainstem movement disorder society criteria. Mov Disord 32:853–864 encephalitis. A serial MRI study. Neurology 61:836–838 124. Whitwell JL, Höglinger GU, Antonini A, Bordelon Y, Boxer AL, 106. Kearns T, Sayre G (1958) pigmentosa, external Colosimo C, van Eimeren T, Golbe LI, Kassubek J, Kurz C, ophthalmoplegia, and complete heart block. Arch Ophthalmol Litvan I, Pantelyat A, Rabinovici G, Respondek G, Rominger A, 60:280–289 Rowe JB, Stamelou M, Josephs KA, for the Movement Disorder 107. Graff-Radford NR, Eslinger PJ, Damasio AR (1984) Society-endorsed PSP Study Group (2017) Radiological bio- Nonhemorrhagic infarction of the thalamus: behavioral, anatom- markers for diagnosis in PSP: where are we and where do we need ic, and physiologic correlates. Neurology 34:14–23 to be? Mov Disord 32:955–971 108. Segarra JM (1970) Cerebral vascular disease and behaviour. The 125. Warmuth-Metz M, Naumann M, Csoti I, Solymosi L (2001) syndrome of the mesencephalic artery. Arch Neurol 22:408–418 Measurement of the midbrain diameter on routine magnetic reso- 109. Bogousslavsky J, Regli F, Uske A (1988) Thalamic infarcts: clin- nance imaging: a simple and accurate method of differentiating ical syndromes, etiology and prognosis. Neurology 38:837–848 between Parkinson disease and progressive supranuclear palsy. Erratum 1988;38:1335 Arch Neurol 58:1076–1079 110. Caplan LR (1980) BTop of the basilar^ syndrome. Neurology 30: 126. Adachi M, Kawanami T, Ohshima H et al (2004) Morning glory 72–79 sign: a particular MR finding in progressive supranuclear palsy. 111. Weidauer S, Nichtweiß M, Zanella FE, Lanfermann H (2004) Magn Reson Med Sci 3:125–132 Assessment of paramedian thalamic infarcts: MR imaging, clinical 127. Möller L, Kassubek J, Südmeyer M, Hilker R, Hattingen E, Egger features and prognosis. Eur Radiol 14:1615–1626 K, Amtage F, Pinkhardt EH, Respondek G, Stamelou M, Möller F, 112. Bender MB (1980) Brain control of conjugate horizontal and ver- Schnitzler A, Oertel WH, Knake S, Huppertz HJ, Höglinger GU tical eye movements. A survey of the structural and functional (2017) Manual MRI morphometry in parkinsonian syndromes. correlates. Brain 103:23–69 Mov Disord 32:778–782 113. Percheron G (1976) Arteries of the human thalamus. I Artery and 128. Doraiswamy PM, Na C, Husain MM, Figiel GS, McDonald W, polar thalamic territory of the posterior communicating artery. Rev Ellinwood EH Jr, Boyko OB, Krishnan KR (1992) Morphometric Neurol (Paris) 132:297–307 changes of the human midbrain with normal aging: MR and 114. Percheron G (1976) Arteries of the human thalamus. II. Arteries stereologic findings. AJNR Am J Neuroradiol 13:383–386 and paramedian thalamic territory of the communicating basilar 129. Huppertz HJ, Moller L, Sudmeyer M et al (2016) Differentiation artery. Rev Neurol (Paris) 132:309–324 of neurodegenerative parkinsonian syndromes by volumetric mag- 115. Lazorthes G, Salamon G (1971) The arteries of the thalamus. J netic resonance imaging analysis and support vector machine clas- Neurosurg 34:23–26 sification. Mov Disord 31:1506–1517 116. Marinkovic SV, Milisavljevic MM, Kovacevic MS (1986) 130. Lapras C, Bognar L, Turjman F, Villanyi E, Mottolese C, Fischer Anastomoses among the thalamoperforating branches of the pos- C et al (1994) Tectal plate gliomas. Part I: Microsurgery of the terior cerebral artery. Arch Neurol 43:811–814 tectal plate gliomas. Acta Neurochir (Wien) 126:76–83 117. Schmahmann JD (2003) Vascular syndromes of the thalamus. 131. Ternier J, Wray A, Puget S, Bodaert N, Zerah M, Sainte-Rose C Stroke 34:2264–2278 (2006) Tectal plate lesions in children. J Neurosurg 104:369–376 Neuroradiology (2019) 61:365–387 387

132. Ferreira TA, Saraiva P, Genders SW, Buchem MV, Luyten GPM, 143. Schoser BG, Pongratz D (2006) Extraocular mitochondrial myop- Beenakker JW (2018) CT and MR imaging of orbital inflamma- athies and their differential diagnoses. Strabismus 14:107–113 tion. Neuroradiology 60:1253–1266 144. Mombaerts I, Bilyk JR, Rose GE, McNab AA, Fay A, Dolman PJ 133. Bhatti MT (2007) Orbital syndromes. Semin Neurol 27:269–287 et al (2017) Consensus on diagnostic criteria of idiopathic orbital 134. Schoser BG (2007) Ocular myositis: diagnostic assessment, dif- inflammation using a modified Delphi approach. JAMA ferential diagnoses, and therapy of a rare muscle disease—five Ophthalmol 135:769–776 new cases and review. Clin Ophthalmol 1:37–42 145. Yeşiltaş YS, Gündüz AK (2018) Idiopathic orbital inflammation: 135. Lacey B, Chang W, Rootman J (1999) Nonthyroid causes of review of literature and new advances. Middle East Afr J extraocular muscle disease. Surv Ophthalmol 44:187–213 Ophthalmol 25:71–80 136. Montagnese F, Wenninger S, Schoser B (2016) "Orbiting around" 146. Beebe JD, Kardon RH, Thurtell MJ (2017) The yield of diagnostic the orbital myositis: clinical features, differential diagnosis and imaging in patients with isolated Horner sSyndrome. Neurol Clin therapy. J Neurol 263:631–640 35:145–151 147. Maloney WF, Younge BR, Moyer NJ (1980) Evaluation of the 137. Fischer M, Kempkes U, Haage P, Isenmann S (2010) Recurrent causes and accuracy of pharmacologic localization in Horner’s orbital myositis mimicking : diagnosis with MR syndrome. Am J Ophthalmol 90:394–402 imaging. AJNR Am J Neuroradiol 31:275–276 148. Davagnanam I, Fraser CI, Miszkiel K, Daniel CS, Plant GT (2013) 138. Garau LM, Guerrieri D, De Cristofaro F, Bruscolini A, Panzironi Adult Horner’s syndrome: a combined clinical, pharmacological, G(2018)ExtraocularmusclesampledvolumeinGraves’ and imaging algorithm. Eye 27:291–298 orbitopathy using 3-T fast spin-echo MRI with iterative decompo- 149. Sacco RL, Fredo L, Bello JA et al (1993) Wallenberg’s lateral sition of water and fat sequences. Acta Radiol Open 7: medullary syndrome. Clinical-magnetic resonance imaging corre- 2058460118780892 lations. Arch Neurol 50:609–614 139. Politi LS, Godi C, Cammarata G, Ambrosi A, Iadanza A, Lanzi R, 150. Sadaka A, Schockman SL, Golnik KC (2017) Evaluation of Falini A, Bianchi Marzoli S (2014) Magnetic resonance imaging Horner syndrome in the MRI era. J Neuroophthalmol 37:268–272 with diffusion-weighted imaging in the evaluation of thyroid- 151. Schievink WI (2001) Spontaneous dissection of the carotid and associated orbitopathy: getting below the tip of the iceberg. Eur vertebral arteries. N Engl J Med 344:898–906 Radiol 24:1118–1126 152. Schievink WI, Mokri B, O'Fallon WM (1994) Recurrent sponta- 140. Lingam RK, Mundada P, Lee V (2018) Novel use of non-echo- neous cervical-artery dissection. N Engl J Med 330:393–397 planar diffusion weighted MRI in monitoring disease activity and 153. Debette S, Leys D (2009) Cervical-artery dissections: predispos- treatment response in active Grave's orbitopathy: an initial obser- ing factors, diagnosis, and outcome. Lancet Neurol 8:668–678 vational cohort study. Orbit 10:1–6 154. Mokri B, Sundt TM Jr, Houser OW, Piepgras DG (1986) 141. Daubner D, Spieth S, Engellandt K, von Kummer R (2012) Spontaneous dissection of the cervical internal carotid artery. Diagnosis and differential diagnosis of Graves' orbitopathy in Ann Neurol 19:126–138 MRI. Radiologe 52:550–559 155. Myles WM, Maxner CE (1994) Localizing value of concurrent 142. Gerlach M, Ferbert A (2008) Pure eye muscle involvement in sixth nerve paresis and postganglionic Horner’ssyndrome.CanJ endocrine orbitopathy. Eur Neurol 60:67–72 Ophthalmol 29:39–42