Aneurysms Associated with Arteriovenous Malformations Beatrice Gardenghi, MD, Carlo Bortolotti, MD, and Giuseppe Lanzino, MD

VOLUMEVOLUME 3636 • • NUMBER NUMBER 122 JanuaryNovember 31, 1,2014 2014

A BIWEEKLY PUBLICATION FOR CLINICAL NEUROSURGICAL CONTINUING MEDICAL EDUCATION

Aneurysms Associated With Arteriovenous Malformations Beatrice Gardenghi, MD, Carlo Bortolotti, MD, and Giuseppe Lanzino, MD

Learning Objectives: After participating in this CME activity, the neurosurgeon should be better able to: 1. Assess the various classiﬁ cations of cerebral aneurysms associated with arteriovenous malformations (AVMs). 2. Compare the various hypotheses about the pathogenesis of the cerebral aneurysms associated with AVMs. 3. Evaluate the role of surgery, endovascular therapy, and radiosurgery in the treatment of intracranial aneurysms associated with AVMs.

Intracranial aneurysms can occur in patients with brain Classifi cation arteriovenous malformations (AVMs), and this not uncom- A clear understanding of the various types of aneurysms mon association poses important therapeutic challenges. In and aneurysm-like dilations that occur in patients with AVMs patients presenting with intracranial hemorrhage, the AVM is paramount to clarify their pathophysiology and clinical is responsible for bleeding in 93% of cases, with the remaining signifi cance. These aneurysms can be classifi ed on the basis 7% related to associated intracranial aneurysms. The inci- of location, histopathologic characteristics, and hemodynamic dence of aneurysms in patients with AVMs is higher than features. expected on the basis of the frequency of each lesion indi- vidually. This observation suggests that factors such as Location increased regional fl ow (hence hemodynamic stress) may Aneurysms associated with AVMs can occur on the arterial play a causative role in the formation of aneurysms associated side (arterial aneurysms) or the venous side (venous aneurysms). with AVMs, although other causative factors such as genetic In relation to the nidus of the AVM, aneurysms and aneurysm- predisposition cannot be excluded. In this article, we review like dilations are categorized as either extranidal (arterial or the various types of aneurysms and aneurismal-like dilations venous) or intranidal. Intranidal aneurysms are within the seen in patients with AVMs and discuss their clinical signifi - nidus and fi ll “early” during angiography, before substantial cance and therapeutic implications. venous fi lling has occurred. Intranidal aneurysms are usually venous aneurysms. Arterial aneurysms can be localized on vessels that do not contribute to the vascular supply of the AVM (unrelated Dr. Gardenghi is Research Fellow, Department of Neurologic Sur- aneurysms, Figure 1A) or arise from vessels that participate gery, Mayo Clinic, Rochester, Minnesota; Dr. Bortolotti is Attending Physician, Division of Neurosurgery, IRCCS Institute of Neuro- in the vascular supply of the AVM (Figures 1A–C) and as logical Science, Bologna, Italy; and Dr. Lanzino is Professor, Depart- such are related to fl ow dynamics (fl ow-related aneurysms). ment of Neurologic Surgery, Mayo Clinic, 200 SW First St, Rochester, MN 55905; E-mail: [email protected]. All faculty and staff in a position to control the content of this CME Category: Cerebrovascular activity, and their spouses/life partners (if any), have disclosed that they have no fi nancial relationships with, or fi nancial interests in, Key Words: Intracranial aneurysms, Cerebral arteriovenous malformations, any commercial organizations related to this CME activity. Risk of hemorrhage, Multidisciplinary treatment

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CCNEv36n22.inddNEv36n22.indd 1 112/1/142/1/14 3:473:47 PMPM Figure 1. A 57-year-old woman had undergone fractioned radiotherapy for a left frontal AVM at another institution 20 years previously. She was referred for evaluation of multiple aneurysms. A, Catheter angiography, right internal carotid artery (ICA) injection, anteroposterior view showing multiple proximal ﬂ ow-related aneurysms (white arrows) and an unrelated middle cerebral artery aneurysm (red arrow). B, Anteroposterior view and C, lateral view of left ICA injection showing multiple proximal ﬂ ow-related aneurysms (arrows) and the per- sistent large AVM.

Flow-related arterial aneurysms can occur away from the usually are close to the nidus, with irregular shape. They nidus (proximal flow-related aneurysms, Figures 1A–C) or often originate from small or perforating arteries, very close originate from feeding vessels adjacent to the nidus (distal to the ependymal surfaces. Defi nitive diagnosis can be flow-related aneurysms). Although proximal flow-related made on histologic analysis, but their nature is often aneurysms usually occur at bifurcation points (a result of the implied by progressive growth on serial early angiograms. combined effects of hemodynamic stress and intrinsic The term venous aneurysm is a misnomer, because the weakness of the vessel wall at bifurcation points), distal fl ow- venous aneurysm does not contain the typical wall related aneurysms often occur along the feeding pedicle not components of the aneurysm wall, but this term is established related to branching points. in the terminology of aneurysms associated with AVMs and A different subcategory of arterial aneurysm-like dilation will be maintained in this article. Intranidal aneurysms are a is the arterial pseudoaneurysm, which is thought to be the subtype of venous aneurysms. Venous pseudoaneurysms can result of rupture of thin-walled small perforating arteries be seen at the periphery of the nidus and can be identifi ed if that supply the AVM. A pseudoaneurysm results from the surgery is performed shortly after a parenchymal bleed as unclotted portion of the hematoma still in communication areas of venous dilation at the periphery of the nidus partially with vessel lumen and as such can show rapid interval fi lled with clotted blood. The draining veins of the AVM often growth on subsequent imaging studies. Pseudoaneurysms present dilations and varices (Table 1).

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CCNEv36n22.inddNEv36n22.indd 2 112/1/142/1/14 3:473:47 PMPM Table 1. Classifi cation of Cerebral Aneurysms and • The vast majority of aneurysms seen in association with Aneurism-Like Dilations Associated With Arteriovenous AVMs are located on vessels hemodynamically con- Malformations nected to the AVM or within the nidus; Relation to Nidus Arterial Venous • In many cases, excision of the AVM leads to a complete Prenidal Unrelated — or partial reduction of the associated aneurysms, espe- Flow-related — cially those closer to the nidus (fl ow-related distal arte- Proximal rial aneurysms); and Distal • Arterial aneurysms are more frequent in patients with Pseudoaneurysm Pseudoaneurysm high-grade (and often higher-fl ow) AVMs and in elderly Intranidal — Venous pouches patients rather than in children, suggesting that their Postnidal — Venous “aneurysms” formation is acquired, and that time was required for the Variceal enlargements effects of increased fl ow to form them.

Risk of Bleeding Histopathologic Characteristics The presence of associated arterial aneurysms increases Based on the composition of the wall, aneurysms associated the risk of hemorrhage from an unruptured AVM. In a classic with AVMs can be categorized as arterial aneurysms, venous study of patients with unruptured AVMs seen at the Mayo aneurysms, and pseudoaneurysms. Clinic between 1974 and 1985, the risk of intracranial hemorrhage among patients with a coexisting, originally Epidemiology unruptured AVM and aneurysm was 7% at 1 year compared The reported incidence of aneurysms associated with with 3% among those with an AVM alone. In a recent study AVMs varies among various studies depending on factors of patients with Spetzler-Martin grade 1 and 2 AVMs treated such as type of aneurysm considered and imaging modality with gamma knife radiosurgery, the presence of an associated used (whether superselective angiography was performed). aneurysm was identifi ed as an independent risk factor for In the fi rst cooperative study of intracranial aneurysms, bleeding after radiosurgery. The rate of bleeding after multiple aneurysms were found in 8 of 34 patients (24%) stereotactic radiosurgery in patients with associated who had AVM-associated hemorrhage. Similarly, a recent aneurysms was 28% at 5 years versus 2.6% in patients without report from the Scottish AVM study group reported 34 associated aneurysms. These observations underscore the aneurysms in 114 patients with unruptured brain AVMs, importance of considering treatment of aneurysms associated although the type of aneurysm considered was not specifi ed with AVMs in patients undergoing gamma knife radiosurgery. in this study. Unrelated arterial aneurysms (ie, on vessels that do not Treatment participate in the supply of the AVM) have an incidence Management of aneurysms associated with AVMs depends comparable to the incidence of berry aneurysms in the general on several factors, the most important being rupture status. population, and they follow the same anatomic distribution. In patients with ruptured AVMs that harbor associated an Flow-related arterial aneurysms are much more frequent aneurysm, it is critical to understand whether the source of in patients with AVMs than their incidence in the general the hemorrhage is the associated aneurysm or the AVM. The population would indicate, suggesting a causative role of the initial head CT scan obtained after presentation is of AVM in their development. These aneurysms often arise from paramount importance, as it often provides important clues the wall of feeding arteries without any relationship to major about the source of bleeding. bifurcations. Unlike berry aneurysms not associated with The presence of pure subarachnoid hemorrhage (SAH) AVMs (which have a defi nite female preponderance), there without associated intraparenchymal hemorrhage often is no difference in the distribution of fl ow-related aneurysms implicates the aneurysm as the potential source of hemorrhage. between males and females. As these aneurysms are probably If the aneurysm is the source of the bleeding, there is often related to fl ow dynamics, they are more commonly observed more focal clot in the area of the aneurysm with secondary in association with high-fl ow (often larger) AVMs rather than spread to the surrounding subarachnoid space. In patients slower-fl ow (often smaller) AVMs. The incidence of AVM- with intraparenchymal hemorrhage with or without associated associated aneurysms seems to increase with age. SAH, the epicenter of the hemorrhage may give clues as to the potential source. Of course, the information obtained from Pathogenesis the presentation CT scan must be interpreted in relation to The incidence of arterial aneurysms in patients harboring high-defi nition catheter angiography with 3D reconstructions, an AVM is higher than the incidence of aneurysms in the which remains the gold standard for detailed depiction of the general population, and this observation suggests a causal AVM angioarchitecture and associated aneurysms. From the relationship. The most valid theory to explain this association angiogram, the shape, size, and exact location of associated is the hemodynamic theory (ie, the genesis of aneurysms in aneurysms can help in determining whether the aneurysm patients with AVMs is most likely related to hemodynamic may be the offending source. factors attributable to the AVM). This theory is supported by If the aneurysm is suspected to be the source of hemorrhage, the following observations: it should be treated as early as safely possible in accordance

CCNEv36n22.inddNEv36n22.indd 3 112/1/142/1/14 3:473:47 PMPM with treatment protocols for any ruptured arterial aneurysm. also dictates therapeutic strategy, is rupture status. In If the source of bleeding is a pseudoaneurysm arising from a patients presenting with intracranial hemorrhage, it is small perforating branch, this should also be treated early, as mandatory to understand the source of bleeding. If the pseudoaneurysms lack a true wall and are at risk for early aneurysm is suspected to be the cause of hemorrhage, then expansion and rerupture. In such cases, the AVM can be treatment of this lesion should be prompt. If the source of treated at a later time, once the source of bleeding has been the hemorrhage is suspected to be within the nidus, however, secured and the patient has recovered from the acute effects treatment can be delayed, as the risk of early rebleeding from of the hemorrhage. If the suspected source of bleeding is an a ruptured AVM is relatively low as long as there is no severe intranidal aneurysm, treatment may not need to be urgent, outfl ow obstruction to the AVM drainage. as the risk of early rerupture is relatively low if no signifi cant In most patients with unruptured AVMs, the treatment outfl ow obstruction is identifi ed on the angiogram. In recent strategy for associated aneurysms follows the same criteria years, with evolution of endovascular techniques, some applied to isolated unruptured aneurysms in the general authors have advocated superselective catheterization, with population. Distal fl ow-related aneurysms may decrease in embolization of the portion of the nidus/feeding pedicle size or even disappear after AVM treatment. Thus, supplying that portion of the AVM harboring the intranidal conservative management of a small distal aneurysm can aneurysms. At present, however, it is unknown whether this be considered if the AVM is treated. strategy protects the patient from recurrent hemorrhage. In patients with unruptured AVMs, the treatment strategy Readings of the associated aneurysm(s) follows the criteria applied to Brown RD, Jr, Wiebers DO, Forbes SG. Unruptured intracranial aneurysms the treatment of unruptured incidental aneurysms in general, and arteriovenous malformations: frequency of intracranial hemorrhage with the caveat that some aneurysms hemodynamically and relationship of lesions. J Neurosurg. 1990;73(6):859-863. Cordonnier C, Al-Shahi Salman R, Bhattacharya JJ, et al. Differences between connected to the AVM may decrease in size or even disappear intracranial vascular malformation types in the characteristics of their after treatment of the AVM. In one study, which analyzed the presenting haemorrhages: prospective, population-based study. J Neurol fate of untreated aneurysms associated with AVMs after Neurosurg Psych. 2008;79(1):47-51. treatment of the AVM, 4 of the 5 (80%) distal fl ow-related Cunha e Sa MJ, Stein BM, Solomon RA, et al. The treatment of associated aneurysms disappeared after complete excision of the AVM, intracranial aneurysms and arteriovenous malformations. J Neurosurg. 1992;77(6):853-859. and only 1 (20%) was unchanged. There were no instances of D’Aliberti G, Talamonti G, Cenzato M, et al. Arterial and venous aneurysms SAH from a fl ow-related aneurysm after AVM cure during associated with arteriovenous malformations. World Neurosurg. 2014; the follow-up period (7.4 years). Instead, of the 23 proximal Jun 7 [Epub ahead of print]. aneurysms, 18 (78.3%) were unchanged, 4 (17.4%) were Elhammady MS, Aziz-Sultan MA, Heros RC. The management of cerebral smaller, and only 1 (4.3%) regressed completely after arteriovenous malformations associated with aneurysms. World Neuro- surg. 2013;80(5):e123-e129. treatment of the AVM. Because distal fl ow-related arterial Fleetwood IG, Steinberg GK. Arteriovenous malformations. Lancet. aneurysms more often resolve or decrease in size after 2002;359(9309):863-873. effective AVM treatment compared with other types of Garcia-Monaco R, Rodesch G, Alvarez H, et al. Pseudoaneurysms within aneurysms, conservative management of small distal ruptured intracranial arteriovenous malformations: diagnosis and aneurysms may be indicated if the AVM is treated. early endovascular management. AJNR Am J Neuroradiol. 1993;14(2): 315-321. Kano H, Lunsford LD, Flickinger JC, et al. Stereotactic radiosurgery for arte- Conclusions riovenous malformations. Part 1: management of Spetzler-Martin Grade I Intracranial aneurysms can be associated with cerebral and II arteriovenous malformations. J Neurosurg. 2012;116(1):11-20. AVMs. The incidence of aneurysms in patients harboring an Lasjaunias P, Piske R, Terbrugge K, et al. Cerebral arteriovenous malforma- AVM is higher than the incidence of aneurysms in the tions (C. AVM) and associated arterial aneurysms (AA). Analysis of 101 C. AVM cases with 37 AA in 23 patients. Acta Neurochir. 1998;91:29-36. general population. The presence of an aneurysm associated Redekop G, TerBrugge K, Montanera W, et al. Arterial aneurysms associated with an AVM may increase the risk of hemorrhage and poses with cerebral arteriovenous malformations: classifi cation, incidence, and therapeutic challenges. The most important factor, which risk of hemorrhage. J Neurosurg. 1998;89:539-546.

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1. Distal ﬂ ow-related aneurysms may not be related to arterial 6. The most valid explanation of the association of aneurysms branching points. and AVMs is the hemodynamic theory. True or False? True or False? 2. Pseudoaneurysms have an irregular shape and are thought 7. The presence of associated aneurysms in a patient with an to be related to rupture of thin-walled perforating vessels feed- AVM increases the risk of bleeding. ing the AVM. True or False? True or False? 8. If an aneurysm is suspected to be a source of hemorrhage, 3. Unrelated aneurysms follow the same anatomic distribution treatment of the bleeding source can be delayed and is not as berry aneurysms in the general population. urgent. True or False? True or False? 4. Flow-related aneurysms in patients with AVMs are as frequent 9. In a patient who presents with hemorrhage and is found to as aneurysms in the general population. have an AVM associated with aneurysms, head CT at admis- sion may provide invaluable information regarding the poten- True or False? tial source of the hemorrhage. 5. Flow-related aneurysms are more often associated with high- True or False? ﬂ ow AVMs. 10. In a patient with unruptured AVMs, treatment considerations True or False? with regard to the one or more associated aneurysms follow the same general criteria applied to the treatment of incidental unruptured aneurysms. True or False?

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