J Neurosurg 121:637–644, 2014 ©AANS, 2014
Stereotactic radiosurgery for sylvian fissure arteriovenous malformations with emphasis on hemorrhage risks and seizure outcomes Clinical article Greg Bowden, M.D., M.Sc.,1,3,5 Hideyuki Kano, M.D., Ph.D.,1,3 Daniel Tonetti, M.S., 4 Ajay Niranjan, M.C.H., M.B.A.,1,3 John Flickinger, M.D., 2,3 Yoshio Arai, M.D., 2,3 and L. Dade Lunsford, M.D.1,3 Departments of 1Neurological Surgery and 2Radiation Oncology, and 3Center for Image-Guided Neurosurgery, 4University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; and 5Department of Neurological Surgery, University of Western Ontario, London, Ontario, Canada Object. Sylvian fissure arteriovenous malformations (AVMs) present substantial management challenges because of the critical adjacent blood vessels and functional brain. The authors investigated the outcomes, especially hemorrhage and seizure activity, after stereotactic radiosurgery (SRS) of AVMs within or adjacent to the sylvian fissure. Methods. This retrospective single-institution analysis examined the authors’ experiences with Gamma Knife surgery for AVMs of the sylvian fissure in cases treated from 1987 through 2009. During this time, 87 patients underwent SRS for AVMs in the region of the sylvian fissure. Before undergoing SRS, 40 (46%) of these patients had experienced hemorrhage and 36 (41%) had had seizures. The median target volume of the AVM was 3.85 cm3 (range 0.1–17.7 cm3), and the median marginal dose of radiation was 20 Gy (range 13–25 Gy). Results. Over a median follow-up period of 64 months (range 3–275 months), AVM obliteration was confirmed by MRI or angiography for 43 patients. The actuarial rates of confirmation of total obliteration were 35% at 3 years, 60% at 4 and 5 years, and 76% at 10 years. Of the 36 patients who had experienced seizures before SRS, 19 (53%) achieved outcomes of Engel class I after treatment. The rate of seizure improvement was 29% at 3 years, 36% at 5 years, 50% at 10 years, and 60% at 15 years. No seizures developed after SRS in patients who had been seizure free before treatment. The actuarial rate of AVM hemorrhage after SRS was 5% at 1, 5, and 10 years. This rate equated to an annual hemorrhage rate during the latency interval of 1%; no hemorrhages occurred after confirmed obliteration. No permanent neurological deficits developed as an adverse effect of radiation; however, delayed cyst formation occurred in 3 patients. Conclusions. Stereotactic radiosurgery was an effective treatment for AVMs within the region of the sylvian fissure, particularly for smaller-volume AVMs. After SRS, a low rate of hemorrhage and improved seizure control were also evident. (http://thejns.org/doi/abs/10.3171/2014.5.JNS132244)
Key Words • arteriovenous malformation • sylvian fissure • seizure • stereotactic radiosurgery • Gamma Knife • epilepsy • vascular disorders
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prevalence of an intracranial arteriovenous malformation (AVM) is approximately 18 cases per 100,000 persons.41 The frontal and temporal regions that surround the sylvian fissure account for 9%– 11% of such AVMs and present substantial management challenges because of the critical adjacent blood vessels and functional brain.25,26 Hemorrhage from a sylvian fissure AVM can result in major neurological morbidity and warrants therapeutic intervention once recognized.15,43 he
Abbreviations used in this article: AVM = arteriovenous malformation; SRS = stereotactic radiosurgery.
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Cortical regions near the sylvian fissure are often associated with seizure activity. Seizures account for the initial presentation for 24%–40% of patients with intracranial AVMs.2,16,39 For patients with AVMs and seizures, reduced life expectancy and quality of life have been documented.4,5,44 Over the past 25 years, management options for AVMs have evolved. However, the goals of intervention remain complete obliteration of the AVM (to prevent hemorrhage) and preservation of neurological function.45 Over 5 years of observation, rates of AVM occlusion after stereotactic radiosurgery (SRS) range from 70% to 80%.8,20,27,29 Gamma 637
G. Bowden et al. Knife SRS is associated with relatively low risk for adverse radiation effects.30 Our overall experience with more than 1200 patients with intracranial AVMs suggests that patients with AVMs in the region of the sylvian fissure are at higher risk for hemorrhage before and after SRS. Such patients are also at higher risk for seizure development than are patients with deep-seated AVMs. The study reported here was designed to evaluate hemorrhage risks and seizure outcomes in this subgroup of patients with AVMs in the region of the sylvian fissure.
Method Patient Population
This single-institution retrospective analysis was approved by the University of Pittsburgh institutional review board. The study evaluated the outcomes of patients with sylvian fissure AVMs who underwent Gamma Knife SRS at the University of Pittsburgh from 1987 through 2009. All 87 patients underwent initial single-stage SRS for an AVM nidus that was located within or immediately adjacent to the sylvian fissure. The outcome data were collected through an independent medical records review and were analyzed by neurosurgeons who did not initially participate in management of these patients. The median patient age at the time of SRS was 38 years (range 9–77 years); 40 patients were male and 47 were female. At the initial visit, the signs and symptoms that led to a diagnosis for these patients included intracranial hemorrhage for 40 patients (46%), seizures for 30 (34%), headache for 15 (17%), and an incidental finding for 2 (2%). Neurological deficits before SRS were present in 24 patients (28%): intracranial hemorrhage was the cause of the deficit for 21 patients, and a stroke caused by therapeutic embolization was the cause for 3 patients. The primary deficit was hemiparesis for 16 patients, followed by speech abnormalities (4 patients), paresthesias (2 patients), dysphagia (1 patient), and hemianopsia (1 patient). A total of 36 patients (22 male and 14 female) had a history of seizures before SRS; 23 had had partial seizures and 13 had had generalized seizures, and all were receiving treatment with anticonvulsants. Additional AVM characteristics included a coexisting aneurysm in 7 patients (8%) and a venous outflow varix in 12 (14%). Endovascular embolization was performed before referral for SRS for 19 patients (22%). Also before SRS, 15 patients (17%) underwent a craniotomy; 6 patients underwent partial AVM resection, 5 patients underwent hematoma evacuation, and 4 underwent hematoma evacuation and AVM resection. Before patients underwent SRS, the Spetzler-Martin grade was determined by 2 experienced neurosurgeons.37 A Grade II AVM was diagnosed for 26 patients (30%), Grade III for 43 (49%), Grade IV for 16 (18%), and Grade VI for 2. The PollockFlickinger score was calculated as Grade I (< 1) for 22 patients (25%), Grade II (1.0–1.50) for 37 (43%), Grade III (1.51–2.0) for 15 (17%), and Grade IV (> 2) for 13 (15%).33 Radiosurgery Technique
On the day of the procedure, patients were adminis-
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tered intravenous sedation or, for children, general anesthesia after endotracheal intubation. The Leksell stereotactic frame was attached to the head after injection of a local anesthetic at the pin sites. High-resolution axial imaging (MRI after 1991) was then conducted, followed by biplanar stereotactic angiography. Radiosurgery planning was calculated with a marginal dose that enveloped the entire nidus volume. This study spans the use of several Leksell Gamma Knife units (Elekta AB): models U, B, C, 4C, and Perfexion. After treatment, all patients received 20–40 mg of methylprednisolone intravenously. Patients were discharged from the hospital 2–24 hours after the procedure. Expanded technical elements of this technique have been detailed in previous publications.27,28 The median AVM target volume was 3.85 cm3 (range 0.1–17.7 cm3), and the median maximum AVM nidus diameter was 2.3 cm (range 0.6–4.8 cm). The median marginal dose of radiation was 20 Gy (range 13–25 Gy), and the median maximum dose was 36 Gy (range 25–50 Gy). Patient Follow-Up
Clinical and imaging follow-up evaluations (MRI when possible) were requested at 6, 12, 24, 36, 60, and 84 months after SRS. If any changes in neurological symptoms occurred after SRS, imaging was promptly conducted to identify any adverse radiation effects. If 3 years after SRS, MRI demonstrated total obliteration (no flow voids identified on T2-weighted MR images), then angiography was requested. Complete AVM obliteration determined by via angiography was defined as elimination of the AVM nidus and absence of early draining veins.20 However, if a residual nidus was evident on images, then repeat SRS to achieve complete obliteration was recommended. For all 15 patients who underwent a second SRS procedure, a similar protocol was again followed. During each follow-up evaluation, a neurosurgeon assessed seizure activity history, which was supported, when available, by documentation from other physicians involved in the patient’s care. Patients who had had a seizure before SRS were evaluated for potential contributing variables. Seizure response after SRS was determined by using the Engel classification system.7 For statistical analysis, this classification was simplified to 2 categories: improvement (decreased frequency or duration) or no change from previous seizures. The 4 patients who experienced only 1 seizure event were automatically assigned an Engel classification of no change. Statistical Analysis
To evaluate potential factors that affect results, we used Kaplan-Meier survival analysis. Obliteration was determined to have been achieved when MR images or angiograms demonstrated complete occlusion of the AVM. Pollock et al. have determined that the accuracy of MRI confirmation of obliteration is 96%.34 We previously showed that both MRI and angiography provide satisfactory evidence of AVM obliteration.20,41 To calculate significant interactions between obliteration rates and related factors, we used Cox regression for univariate analysis. We defined p < 0.05 as statistically significant. J Neurosurg / Volume 121 / September 2014
Radiosurgery for sylvian fissure AVMs Calculations of hemorrhage were based on the time of a post-SRS bleeding event or loss of patient to followup. The hemorrhage statistics were obtained through Kaplan-Meier survival analysis. Calculation of the annual rate of hemorrhage during the latency period was based on the years of at-risk follow-up evaluations and the number of hemorrhages that occurred. Where appropriate, we compared various groups by using the Fisher exact and Mann-Whitney U-tests.
Results Patient Follow-Up
The median time of follow-up imaging after SRS was 64 months (range 3–275 months). At the time of this review, 6 patients had died; 1 death was directly attributable to AVM hemorrhage, 2 deaths were from cancer (lung and pancreatic), and 3 were from undetermined (nonhemorrhagic) causes. A total of 24 patients had neurological deficits before SRS. Of these, deficits improved for 10 patients and remained unchanged for 14 patients.
AVM Obliteration
Obliteration of the AVM was confirmed by MRI or angiography for 43 patients. The actuarial rates of confirmed obliteration were 45% at 3 years, 60% at 4 years, 60% at 5 years, and 76% at 10 years (Fig. 1). The median time to obliteration was 40 months (95% CI 38–42 months). Obliteration was confirmed by angiography for 31 patients and indicated only by MRI for 12 patients. When only patients with follow-up angiography were in-
cluded in the analysis, the obliteration rates dropped artifactually to 25% at 3 years and 45% at 4, 5, and 10 years. As documented by previous studies, angiography results are falsely lowered when patients decline repeat angiography after obliteration is determined by MRI.20,25,26 According to univariate analysis, several variables that affect AVM obliteration were significant. The obliteration rate for smaller AVMs (< 4 cm3) was increased (p = 0.041) (Fig. 2). As the maximum AVM diameter increased, the rate of obliteration decreased (p = 0.027). The rate of total AVM obliteration was higher among patients who received a marginal dose greater than 20 Gy (p = 0.002) (Fig. 3). Obliteration rates were also higher among patients whose Pollock-Flickinger score was less than 1.20 (p = 0.035). Seizure Activity
A total of 36 patients experienced seizures before SRS. The risk for seizures tended to be lower for younger patients (< 18 years) (p = 0.013), and male patients were more likely than female patients to have experienced seizures (p = 0.018). Seizures were less likely among patients with a history of previous intracranial hemorrhage (p = 0.0004) (Table 1). Seizure activity follow-up examinations by a neurosurgeon and imaging were conducted concomitantly. At the last follow-up visit, the Engel seizure outcome scores for the 36 patients were as follows: Class I (free of disabling seizures) for 19 patients (53%), Class II (rare disabling seizures) for 4 (11%), Class III (significant improvement) for 2 (6%), and Class IV (no improvement) for 11 (31%). After SRS, clinically significant seizure reduc-
Fig. 1. Kaplan-Meier curve for probability of total AVM obliteration after SRS, based on MRI and angiography combined. The numbers of patients remaining in the study at 3, 5, and 10 years were 68, 46, and 24, respectively.
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Fig. 2. Kaplan-Meier curve for probability of total AVM obliteration after SRS (determined by MRI or angiography) based on AVM volume (< 4 cm3 or > 4 cm3).
Fig. 3. Kaplan-Meier curve for probability of total AVM obliteration after SRS (determined by MRI or angiography) based on marginal dose ≤ 20 Gy.
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Radiosurgery for sylvian fissure AVMs TABLE 1: Univariate analysis of variables associated with seizure activity before SRS and seizure improvement after SRS for sylvian fissure AVMs p Value Variable
Seizures Before SRS (36 patients)
Improvement After SRS (17 patients)
age sex AVM diameter volume marginal dose prior hemorrhage neurological deficit varix aneurysm diffuse nidus deep venous drainage
0.019 0.018 0.321 0.135 not applicable 0.0004 0.409 0.983 0.934 0.816 0.752
0.531 0.793 0.035 0.129 0.876 0.045 0.117 0.543 0.620 0.487 0.132
tion of at least 1 Engel class was documented for 17 (47%) of the 36 patients. For the remainder of the patients, seizure frequency did not change, and continued anticonvulsant medication was needed. The median time to seizure reduction was 20 months (range 1–129 months). The rates of seizure improvement were 29% at 3 years, 36% at 5 years, 50% at 10 years, and 60% at 15 years (Fig. 4). In this study, the rate of improved seizure control was higher for patients with incomplete obliteration (p = 0.042).
Within the improved seizure group, the median nidus volume was 7.15 cm3 among those for whom obliteration was not achieved and 3.75 cm3 among those for whom obliteration was achieved. Among patients for whom complete obliteration was achieved, seizures improved at a median of 19 months after SRS; among patients for whom obliteration was not achieved, seizures improved at a median of 29 months after SRS. Seizure reduction was less among patients with a history of prior hemorrhage (p = 0.028). A smaller nidus diameter was associated with seizure improvement (p = 0.031) and was most notable among patients for whom average AVM diameter was less than 20 mm (p = 0.028). No seizure activity developed after SRS among patients who had been seizure free before SRS. Hemorrhage During Latency Interval and Risk for Complications
A single hemorrhage occurred during the latency period at a median of 6 months (range 4–13 months) for 4 (5%) patients. One patient died as a result of a hemorrhage that occurred 8 months after SRS. The cumulative rate of AVM hemorrhage after SRS was 5% at 1, 5, and 10 years. This rate correlated with 387 patient-years of estimated hemorrhage risk for an overall annual rate of 1.0% during the latency interval (the time from SRS treatment until obliteration or last follow-up of a patent with a known residual AVM). The likelihood of hemorrhage occurring during the latency period was significantly greater for patients who had a coexisting proximal aneurysm (p = 0.018). No patient sustained a hemorrhage after AVM obliteration had been confirmed by MRI or angiography.
Fig. 4. Kaplan-Meier curve for probability of improved seizure control after SRS. The numbers of patients with seizures remaining in the study at 3, 5, 10, and 15 years after SRS were 30, 24, 12, and 7, respectively.
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G. Bowden et al. Temporary symptomatic adverse radiation effects developed in 2 patients (2%). These effects are defined as new T2 signal change surrounding the AVM target on MRI and were associated with the development of new neurological signs in the absence of hemorrhage. One patient experienced transient deterioration of neurocognitive status 3 months after SRS, and another patient experienced increased seizure activity 9 months after SRS. For both of these patients, baseline status was achieved after the administration of a short course of oral corticosteroids. The associated MRI signal changes in these patients resolved at 5 and 27 months, respectively. No permanent new neurological deficit associated with adverse radiation effects developed in any patient. Delayed cyst formation in the target region was detected in 3 patients; the median time until detection of the cyst was 31 months (range 6–67 months). The cysts were asymptomatic for 2 patients but required surgical cyst fenestration for the other patient. Repeat SRS
A total of 15 patients with residual AVMs underwent a second SRS procedure at a median of 40 months (range 36–73 months) after the initial procedure. Among these patients, obliteration was confirmed by MRI at a median interval of 37 months (range 33–50 months) for 5 patients. No complications were noted for patients who underwent repeat SRS.
Discussion Factors Associated With Obliteration
Paradigms for management of AVMs have evolved over the past 25 years, and an individualized patient outcome–centered approach has been widely adopted. As we reviewed the SRS literature about AVM management, we found surprisingly little information specifically about AVMs of the sylvian fissure, an anatomical location we suspected of being of high risk. In fact, almost half of the diagnoses for patients reported in this series were made after an initial ictal bleeding event. In the study reported here, obliteration was confirmed by MRI or angiography for 60% of patients at 5 years and 76% at 10 years. This obliteration rate is consistent with rates reported by other authors after SRS for AVMs in other critical brain locations.1,2,14,16,39 As conveyed in these reports, AVM obliteration rates were higher among patients with smaller AVM volumes; this effect was most prominent for AVM volumes less than 4 cm3.4,5,19,44 We noted an increased rate of total obliteration when higher AVM marginal doses of radiation were delivered. Although higher doses are more often prescribed for patients with smaller AVMs, the optimal dose still represents an empirical balance between the goal of obliteration and the associated risk for adverse radiation effects.8,36,45
Factors Associated With Seizures
The incidence of seizures among patients in this series is similar to that among other patients with AVMs located in the motor or sensory cortex.6 Previous studies have indicated a higher risk for seizures in male patients,
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in patients with AVMs larger than 3 cm, in younger (< 18 years) patients, and in patients with superficial venous outflow drainage from a temporal lobe location.10,12,17,18,31,39 Our study also found that males had a higher likelihood of seizure activity and that seizures were less common in younger patients, especially those younger than 18 years. Of interest, we also found that seizures were less common in patients who had sustained an intracranial hemorrhage. Patients with AVM-associated seizures have a worsened quality of life and a reduced ability to maintain regular employment.5,9,44 In our study, 53% of patients who had had a seizure before SRS were free of disabling seizures at their last follow-up visit. This outcome is similar to the rates of seizure elimination reported by Hadjipanayis et al. and Andrade-Souza et al., which were 63% and 52%, respectively, among patients with AVMs in the motor cortex region.1,14 Rates of seizure elimination after SRS for cortical AVMs, regardless of location, range from 50% to 85%.1,11,23,24 Seizure-free outcomes according to treatment modalities are 78% after microsurgery, 63% after radiosurgery, and 50% after embolization.3,18,27,28 We noted that seizure control improved for 17 (47%) of 36 patients, which compares favorably with previously reported rates of 41%–51%.1,20,27 Seizure control tends to improve over time; we noted that seizure control was improved for 60% of patients at 15 years. Among patients in our study for whom complete obliteration was not confirmed, seizure reduction occurred more often. This finding might be a reflection of the relatively small sample size and larger AVM volumes. Although others have noted that AVM obliteration is not required to improve seizure outcomes,7,11 prior reports have indicated that seizure reduction is more frequent among those for whom AVM obliteration is acheived.3,12,34,42,44 Our data also indicate that a history of prior hemorrhage is a negative prognostic factor for seizure improvement. Kida et al. noted a similar correlation of reduced seizure control in patients who had previously experienced hemorrhage.23 A smaller AVM diameter was associated with seizure improvement, which is similar to the finding reported by Schäuble et al.35 In our study, the median time to seizure reduction was 20 months. This finding is similar to the 20.5-month time until seizure reduction that was noted by Hyun et al. after radiosurgery and embolization.18 Previous studies have reported a risk for new-onset seizures of 5%–10% after SRS and up to 36% after microsurgery.3,42 However, in our study, among patients who were seizure free before SRS, no seizures developed after SRS. For 1 patient, transient exacerbation of seizure frequency was correlated with interval T2 MRI recognition of edema surrounding the AVM target volume. Decision Making
Sylvian fissure AVMs present special management challenges.25,40,46 These challenges include the complex neurovascular relationship of the middle cerebral artery as well as the critical functional cortex and connecting pathways located outside the AVM nidus. Although the published results of microsurgical removal of AVMs in the sylvian fissure are relatively sparse, some authors have reported transient morbidity for as few as 0 to as many as 44% of patients. Permanent new neurological morbidity J Neurosurg / Volume 121 / September 2014
Radiosurgery for sylvian fissure AVMs or death occurred for up to 3% of patients.25,40,46 The data generated from our study indicate a transient morbidity in 3% of patients; no disabilities were permanent. However, 1 patient died of hemorrhage that occurred during the latency interval. Complete surgical removal provides the benefit of early hemorrhage protection but can be associated with immediate postoperative morbidity. Forty-six percent of patients presented with an intracranial hemorrhage, which was consistent with the rate of 52% provided by meta-analysis data.13,22,38 In the study reported here, the annual overall rate of hemorrhage during the latency interval was 1%. This is a reflection of the finding that all 4 (5%) hemorrhages occurred during the first year after treatment, which is comparable to results for motor cortex AVMs.1,14 The risk for hemorrhage during the latency interval was increased among patients with a prenidal aneurysm, which has been demonstrated as a risk factor.15,21 Despite our initial concern that the risk for hemorrhage during the latency interval was higher for AVMs in the sylvian region, we found no evidence of such risk. Cysts formed in 3 patients at a median of 31 months after SRS. Two patients were asymptomatic, and treatment was observation only. However, 1 patient required surgical fenestration of the cyst to relieve mass effect. Pollock and Brown also described late cyst development in 6 patients whose target volume cyst was identified at an average of 4 years after SRS. This finding further indicates the need for long-term follow-up evaluations to verify the reduction of the risk for hemorrhage, confirm AVM obliteration, and monitor the risk for long-term complications.32 Repeat SRS was undertaken when incomplete AVM obliteration was noted on MR images at 3 or more years after initial SRS.20 We confirmed that for 5 of 15 additional patients, obliteration was achieved within a further interval of 3–5 years. No patient who underwent repeat SRS experienced additional morbidity or rebleeding. Study Limitations
The limitations of this study include the need for even longer follow-up periods and the retrospective nature of this review. The population of patients with seizures was relatively small, which affected the statistical power regarding seizure outcomes. Data on long-term anticonvulsant medication management were not incorporated into this analysis because of the limited availability and reliability of the required information. Because medication had not been providing adequate seizure control at the time of SRS, we believe that AVM volume reduction or obliteration is important for seizure control. We were also unable to gather information about patient compliance with regard to taking anticonvulsant medication.
Conclusions
Rates of total AVM obliteration were highest among patients with sylvian fissure AVMs of less than 4 cm3 in volume and who received more than 20 Gy of radiation to the nidus. Seizure control improved after SRS for 60% of patients with seizures, and 53% of patients were free of disabling seizure on or off anticonvulsants. Seizure J Neurosurg / Volume 121 / September 2014
disorders did not develop after SRS in patients who had not had seizures before SRS. The annual hemorrhage rate during the latency interval after SRS was 1%, regardless of whether hemorrhage had occurred previously. After confirmation of AVM obliteration, no patients experienced a hemorrhage. Despite the unfavorable location of sylvian fissure AVMs, no permanent neurological deficits occurred. This study indicates that SRS is a relatively safe and effective way to manage sylvian fissure AVMs. Disclosure Dr. Lunsford is a consultant for and stockholder in Elekta AB. Author contributions to the study and manuscript preparation include the following. Conception and design: Kano. Acquisition of data: Kano, Bowden, Tonetti. Analysis and interpretation of data: Kano, Bowden. Drafting the article: Kano, Bowden, Lunsford. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Kano. Statistical analysis: Kano, Bowden. Study supervision: Kano. References 1. Andrade-Souza YM, Ramani M, Scora D, Tsao MN, TerBrugge K, Schwartz ML: Radiosurgical treatment for rolandic arteriovenous malformations. J Neurosurg 105:689–697, 2006 2. ApSimon HT, Reef H, Phadke RV, Popovic EA: A populationbased study of brain arteriovenous malformation: long-term treatment outcomes. Stroke 33:2794–2800, 2002 3. Baranoski JF, Grant RA, Hirsch LJ, Visintainer P, Gerrard JL, Günel M, et al: Seizure control for intracranial arteriovenous malformations is directly related to treatment modality: a meta-analysis. J Neurointerv Surg [epub ahead of print], 2013 4. Cockerell OC, Johnson AL, Sander JW, Hart YM, Goodridge DM, Shorvon SD: Mortality from epilepsy: results from a prospective population-based study. Lancet 344:918–921, 1994 5. DiIorio C, Osborne Shafer P, Letz R, Henry T, Schomer DL, Yeager K: The association of stigma with self-management and perceptions of health care among adults with epilepsy. Epilepsy Behav 4:259–267, 2003 6. Ding D, Yen CP, Xu Z, Starke RM, Sheehan JP: Radiosurgery for primary motor and sensory cortex arteriovenous malformations: outcomes and the effect of eloquent location. Neurosurgery 73:816–824, 2013 7. Engel J Jr (ed): Outcome with respect to epileptic seizures, in Surgical Treatment of the Epilepsies, ed 2. New York: Raven Press, 1993, pp 609–621 8. Flickinger JC, Kondziolka D, Maitz AH, Lunsford LD: An analysis of the dose-response for arteriovenous malformation radiosurgery and other factors affecting obliteration. Radiother Oncol 63:347–354, 2002 9. Gaitatzis A, Trimble MR, Sander JW: The psychiatric comorbidity of epilepsy. Acta Neurol Scand 110:207–220, 2004 10. Garcin B, Houdart E, Porcher R, Manchon E, Saint-Maurice JP, Bresson D, et al: Epileptic seizures at initial presentation in patients with brain arteriovenous malformation. Neurology 78:626–631, 2012 11. Gerszten PC, Adelson PD, Kondziolka D, Flickinger JC, Luns ford LD: Seizure outcome in children treated for arteriovenous malformations using gamma knife radiosurgery. Pediatr Neurosurg 24:139–144, 1996 12. Ghossoub M, Nataf F, Merienne L, Devaux B, Turak B, Page P, et al: [Evolution of epileptic seizures associated with cerebral arteriovenous malformations after radiosurgery.] Neurochirurgie 47:344–349, 2001 (Fr) 13. Gross BA, Du R: Hemorrhage from arteriovenous malformations during pregnancy. Neurosurgery 71:349–356, 2012
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dziolka D, Lunsford LD: Management of adverse radiation effects after radiosurgery for arteriovenous malformations. Prog Neurol Surg 27:107–118, 2013 31. Piepgras DG, Sundt TM Jr, Ragoowansi AT, Stevens L: Seizure outcome in patients with surgically treated cerebral arteriovenous malformations. J Neurosurg 78:5–11, 1993 32. Pollock BE, Brown RD Jr: Management of cysts arising after radiosurgery to treat intracranial arteriovenous malformations. Neurosurgery 49:259–265, 2001 33. Pollock BE, Flickinger JC: A proposed radiosurgery-based grading system for arteriovenous malformations. J Neurosurg 96:79–85, 2002 34. Pollock BE, Kondziolka D, Flickinger JC, Patel AK, Bissonette DJ, Lunsford LD: Magnetic resonance imaging: an accurate method to evaluate arteriovenous malformations after stereotactic radiosurgery. J Neurosurg 85:1044–1049, 1996 35. Schäuble B, Cascino GD, Pollock BE, Gorman DA, Weigand S, Cohen-Gadol AA, et al: Seizure outcomes after stereotactic radiosurgery for cerebral arteriovenous malformations. Neurology 63:683–687, 2004 36. Shin M, Kawahara N, Maruyama K, Tago M, Ueki K, Kirino T: Risk of hemorrhage from an arteriovenous malformation confirmed to have been obliterated on angiography after stereotactic radiosurgery. J Neurosurg 102:842–846, 2005 37. Spetzler RF, Martin NA: A proposed grading system for arteriovenous malformations. J Neurosurg 65:476–483, 1986 38. Stefani MA, Porter PJ, terBrugge KG, Montanera W, Willinsky RA, Wallace MC: Angioarchitectural factors present in brain arteriovenous malformations associated with hemorrhagic presentation. Stroke 33:920–924, 2002 39. Sturiale CL, Rigante L, Puca A, Di Lella G, Albanese A, Marchese E, et al: Angioarchitectural features of brain arteriovenous malformations associated with seizures: a single center retrospective series. Eur J Neurol 20:849–855, 2013 40. Sugita K, Takemae T, Kobayashi S: Sylvian fissure arteriovenous malformations. Neurosurgery 21:7–14, 1987 41. van Beijnum J, van der Worp HB, Buis DR, Al-Shahi Salman R, Kappelle LJ, Rinkel GJ, et al: Treatment of brain arteriovenous malformations: a systematic review and meta-analysis. JAMA 306:2011–2019, 2011 42. Wang JY, Yang W, Ye X, Rigamonti D, Coon AL, Tamargo RJ, et al: Impact on seizure control of surgical resection or radiosurgery for cerebral arteriovenous malformations. Neurosurgery 73:648–656, 2013 43. Yamada S, Takagi Y, Nozaki K, Kikuta K, Hashimoto N: Risk factors for subsequent hemorrhage in patients with cerebral arteriovenous malformations. J Neurosurg 107:965–972, 2007 44. Yang SY, Paek SH, Kim DG, Chung HT: Quality of life after radiosurgery for cerebral arteriovenous malformation patients who present with seizure. Eur J Neurol 19:984–991, 2012 45. Yen CP, Schlesinger D, Sheehan JP: Natural history of cerebral arteriovenous malformations and the risk of hemorrhage after radiosurgery. Prog Neurol Surg 27:5–21, 2013 46. Zimmerman G, Lewis AI, Tew JM Jr: Pure sylvian fissure arteriovenous malformations. J Neurosurg 92:39–44, 2000
Manuscript submitted October 11, 2013. Accepted May 8, 2014. Please include this information when citing this paper: published online June 13, 2014; DOI: 10.3171/2014.5.JNS132244. Address correspondence to: Hideyuki Kano, M.D., Ph.D., Department of Neurological Surgery, University of Pittsburgh, Ste. B-400, UPMC Presbyterian, 200 Lothrop St., Pittsburgh, PA 15213. email: [email protected].
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Stereotactic radiosurgery for sylvian fissure arteriovenous malformations with emphasis on hemorrhage risks and seizure outcomes Clinical article Greg Bowden, M.D., M.Sc.,1,3,5 Hideyuki Kano, M.D., Ph.D.,1,3 Daniel Tonetti, M.S., 4 Ajay Niranjan, M.C.H., M.B.A.,1,3 John Flickinger, M.D., 2,3 Yoshio Arai, M.D., 2,3 and L. Dade Lunsford, M.D.1,3 Departments of 1Neurological Surgery and 2Radiation Oncology, and 3Center for Image-Guided Neurosurgery, 4University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; and 5Department of Neurological Surgery, University of Western Ontario, London, Ontario, Canada Object. Sylvian fissure arteriovenous malformations (AVMs) present substantial management challenges because of the critical adjacent blood vessels and functional brain. The authors investigated the outcomes, especially hemorrhage and seizure activity, after stereotactic radiosurgery (SRS) of AVMs within or adjacent to the sylvian fissure. Methods. This retrospective single-institution analysis examined the authors’ experiences with Gamma Knife surgery for AVMs of the sylvian fissure in cases treated from 1987 through 2009. During this time, 87 patients underwent SRS for AVMs in the region of the sylvian fissure. Before undergoing SRS, 40 (46%) of these patients had experienced hemorrhage and 36 (41%) had had seizures. The median target volume of the AVM was 3.85 cm3 (range 0.1–17.7 cm3), and the median marginal dose of radiation was 20 Gy (range 13–25 Gy). Results. Over a median follow-up period of 64 months (range 3–275 months), AVM obliteration was confirmed by MRI or angiography for 43 patients. The actuarial rates of confirmation of total obliteration were 35% at 3 years, 60% at 4 and 5 years, and 76% at 10 years. Of the 36 patients who had experienced seizures before SRS, 19 (53%) achieved outcomes of Engel class I after treatment. The rate of seizure improvement was 29% at 3 years, 36% at 5 years, 50% at 10 years, and 60% at 15 years. No seizures developed after SRS in patients who had been seizure free before treatment. The actuarial rate of AVM hemorrhage after SRS was 5% at 1, 5, and 10 years. This rate equated to an annual hemorrhage rate during the latency interval of 1%; no hemorrhages occurred after confirmed obliteration. No permanent neurological deficits developed as an adverse effect of radiation; however, delayed cyst formation occurred in 3 patients. Conclusions. Stereotactic radiosurgery was an effective treatment for AVMs within the region of the sylvian fissure, particularly for smaller-volume AVMs. After SRS, a low rate of hemorrhage and improved seizure control were also evident. (http://thejns.org/doi/abs/10.3171/2014.5.JNS132244)
Key Words • arteriovenous malformation • sylvian fissure • seizure • stereotactic radiosurgery • Gamma Knife • epilepsy • vascular disorders
T
prevalence of an intracranial arteriovenous malformation (AVM) is approximately 18 cases per 100,000 persons.41 The frontal and temporal regions that surround the sylvian fissure account for 9%– 11% of such AVMs and present substantial management challenges because of the critical adjacent blood vessels and functional brain.25,26 Hemorrhage from a sylvian fissure AVM can result in major neurological morbidity and warrants therapeutic intervention once recognized.15,43 he
Abbreviations used in this article: AVM = arteriovenous malformation; SRS = stereotactic radiosurgery.
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Cortical regions near the sylvian fissure are often associated with seizure activity. Seizures account for the initial presentation for 24%–40% of patients with intracranial AVMs.2,16,39 For patients with AVMs and seizures, reduced life expectancy and quality of life have been documented.4,5,44 Over the past 25 years, management options for AVMs have evolved. However, the goals of intervention remain complete obliteration of the AVM (to prevent hemorrhage) and preservation of neurological function.45 Over 5 years of observation, rates of AVM occlusion after stereotactic radiosurgery (SRS) range from 70% to 80%.8,20,27,29 Gamma 637
G. Bowden et al. Knife SRS is associated with relatively low risk for adverse radiation effects.30 Our overall experience with more than 1200 patients with intracranial AVMs suggests that patients with AVMs in the region of the sylvian fissure are at higher risk for hemorrhage before and after SRS. Such patients are also at higher risk for seizure development than are patients with deep-seated AVMs. The study reported here was designed to evaluate hemorrhage risks and seizure outcomes in this subgroup of patients with AVMs in the region of the sylvian fissure.
Method Patient Population
This single-institution retrospective analysis was approved by the University of Pittsburgh institutional review board. The study evaluated the outcomes of patients with sylvian fissure AVMs who underwent Gamma Knife SRS at the University of Pittsburgh from 1987 through 2009. All 87 patients underwent initial single-stage SRS for an AVM nidus that was located within or immediately adjacent to the sylvian fissure. The outcome data were collected through an independent medical records review and were analyzed by neurosurgeons who did not initially participate in management of these patients. The median patient age at the time of SRS was 38 years (range 9–77 years); 40 patients were male and 47 were female. At the initial visit, the signs and symptoms that led to a diagnosis for these patients included intracranial hemorrhage for 40 patients (46%), seizures for 30 (34%), headache for 15 (17%), and an incidental finding for 2 (2%). Neurological deficits before SRS were present in 24 patients (28%): intracranial hemorrhage was the cause of the deficit for 21 patients, and a stroke caused by therapeutic embolization was the cause for 3 patients. The primary deficit was hemiparesis for 16 patients, followed by speech abnormalities (4 patients), paresthesias (2 patients), dysphagia (1 patient), and hemianopsia (1 patient). A total of 36 patients (22 male and 14 female) had a history of seizures before SRS; 23 had had partial seizures and 13 had had generalized seizures, and all were receiving treatment with anticonvulsants. Additional AVM characteristics included a coexisting aneurysm in 7 patients (8%) and a venous outflow varix in 12 (14%). Endovascular embolization was performed before referral for SRS for 19 patients (22%). Also before SRS, 15 patients (17%) underwent a craniotomy; 6 patients underwent partial AVM resection, 5 patients underwent hematoma evacuation, and 4 underwent hematoma evacuation and AVM resection. Before patients underwent SRS, the Spetzler-Martin grade was determined by 2 experienced neurosurgeons.37 A Grade II AVM was diagnosed for 26 patients (30%), Grade III for 43 (49%), Grade IV for 16 (18%), and Grade VI for 2. The PollockFlickinger score was calculated as Grade I (< 1) for 22 patients (25%), Grade II (1.0–1.50) for 37 (43%), Grade III (1.51–2.0) for 15 (17%), and Grade IV (> 2) for 13 (15%).33 Radiosurgery Technique
On the day of the procedure, patients were adminis-
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tered intravenous sedation or, for children, general anesthesia after endotracheal intubation. The Leksell stereotactic frame was attached to the head after injection of a local anesthetic at the pin sites. High-resolution axial imaging (MRI after 1991) was then conducted, followed by biplanar stereotactic angiography. Radiosurgery planning was calculated with a marginal dose that enveloped the entire nidus volume. This study spans the use of several Leksell Gamma Knife units (Elekta AB): models U, B, C, 4C, and Perfexion. After treatment, all patients received 20–40 mg of methylprednisolone intravenously. Patients were discharged from the hospital 2–24 hours after the procedure. Expanded technical elements of this technique have been detailed in previous publications.27,28 The median AVM target volume was 3.85 cm3 (range 0.1–17.7 cm3), and the median maximum AVM nidus diameter was 2.3 cm (range 0.6–4.8 cm). The median marginal dose of radiation was 20 Gy (range 13–25 Gy), and the median maximum dose was 36 Gy (range 25–50 Gy). Patient Follow-Up
Clinical and imaging follow-up evaluations (MRI when possible) were requested at 6, 12, 24, 36, 60, and 84 months after SRS. If any changes in neurological symptoms occurred after SRS, imaging was promptly conducted to identify any adverse radiation effects. If 3 years after SRS, MRI demonstrated total obliteration (no flow voids identified on T2-weighted MR images), then angiography was requested. Complete AVM obliteration determined by via angiography was defined as elimination of the AVM nidus and absence of early draining veins.20 However, if a residual nidus was evident on images, then repeat SRS to achieve complete obliteration was recommended. For all 15 patients who underwent a second SRS procedure, a similar protocol was again followed. During each follow-up evaluation, a neurosurgeon assessed seizure activity history, which was supported, when available, by documentation from other physicians involved in the patient’s care. Patients who had had a seizure before SRS were evaluated for potential contributing variables. Seizure response after SRS was determined by using the Engel classification system.7 For statistical analysis, this classification was simplified to 2 categories: improvement (decreased frequency or duration) or no change from previous seizures. The 4 patients who experienced only 1 seizure event were automatically assigned an Engel classification of no change. Statistical Analysis
To evaluate potential factors that affect results, we used Kaplan-Meier survival analysis. Obliteration was determined to have been achieved when MR images or angiograms demonstrated complete occlusion of the AVM. Pollock et al. have determined that the accuracy of MRI confirmation of obliteration is 96%.34 We previously showed that both MRI and angiography provide satisfactory evidence of AVM obliteration.20,41 To calculate significant interactions between obliteration rates and related factors, we used Cox regression for univariate analysis. We defined p < 0.05 as statistically significant. J Neurosurg / Volume 121 / September 2014
Radiosurgery for sylvian fissure AVMs Calculations of hemorrhage were based on the time of a post-SRS bleeding event or loss of patient to followup. The hemorrhage statistics were obtained through Kaplan-Meier survival analysis. Calculation of the annual rate of hemorrhage during the latency period was based on the years of at-risk follow-up evaluations and the number of hemorrhages that occurred. Where appropriate, we compared various groups by using the Fisher exact and Mann-Whitney U-tests.
Results Patient Follow-Up
The median time of follow-up imaging after SRS was 64 months (range 3–275 months). At the time of this review, 6 patients had died; 1 death was directly attributable to AVM hemorrhage, 2 deaths were from cancer (lung and pancreatic), and 3 were from undetermined (nonhemorrhagic) causes. A total of 24 patients had neurological deficits before SRS. Of these, deficits improved for 10 patients and remained unchanged for 14 patients.
AVM Obliteration
Obliteration of the AVM was confirmed by MRI or angiography for 43 patients. The actuarial rates of confirmed obliteration were 45% at 3 years, 60% at 4 years, 60% at 5 years, and 76% at 10 years (Fig. 1). The median time to obliteration was 40 months (95% CI 38–42 months). Obliteration was confirmed by angiography for 31 patients and indicated only by MRI for 12 patients. When only patients with follow-up angiography were in-
cluded in the analysis, the obliteration rates dropped artifactually to 25% at 3 years and 45% at 4, 5, and 10 years. As documented by previous studies, angiography results are falsely lowered when patients decline repeat angiography after obliteration is determined by MRI.20,25,26 According to univariate analysis, several variables that affect AVM obliteration were significant. The obliteration rate for smaller AVMs (< 4 cm3) was increased (p = 0.041) (Fig. 2). As the maximum AVM diameter increased, the rate of obliteration decreased (p = 0.027). The rate of total AVM obliteration was higher among patients who received a marginal dose greater than 20 Gy (p = 0.002) (Fig. 3). Obliteration rates were also higher among patients whose Pollock-Flickinger score was less than 1.20 (p = 0.035). Seizure Activity
A total of 36 patients experienced seizures before SRS. The risk for seizures tended to be lower for younger patients (< 18 years) (p = 0.013), and male patients were more likely than female patients to have experienced seizures (p = 0.018). Seizures were less likely among patients with a history of previous intracranial hemorrhage (p = 0.0004) (Table 1). Seizure activity follow-up examinations by a neurosurgeon and imaging were conducted concomitantly. At the last follow-up visit, the Engel seizure outcome scores for the 36 patients were as follows: Class I (free of disabling seizures) for 19 patients (53%), Class II (rare disabling seizures) for 4 (11%), Class III (significant improvement) for 2 (6%), and Class IV (no improvement) for 11 (31%). After SRS, clinically significant seizure reduc-
Fig. 1. Kaplan-Meier curve for probability of total AVM obliteration after SRS, based on MRI and angiography combined. The numbers of patients remaining in the study at 3, 5, and 10 years were 68, 46, and 24, respectively.
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Fig. 2. Kaplan-Meier curve for probability of total AVM obliteration after SRS (determined by MRI or angiography) based on AVM volume (< 4 cm3 or > 4 cm3).
Fig. 3. Kaplan-Meier curve for probability of total AVM obliteration after SRS (determined by MRI or angiography) based on marginal dose ≤ 20 Gy.
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Radiosurgery for sylvian fissure AVMs TABLE 1: Univariate analysis of variables associated with seizure activity before SRS and seizure improvement after SRS for sylvian fissure AVMs p Value Variable
Seizures Before SRS (36 patients)
Improvement After SRS (17 patients)
age sex AVM diameter volume marginal dose prior hemorrhage neurological deficit varix aneurysm diffuse nidus deep venous drainage
0.019 0.018 0.321 0.135 not applicable 0.0004 0.409 0.983 0.934 0.816 0.752
0.531 0.793 0.035 0.129 0.876 0.045 0.117 0.543 0.620 0.487 0.132
tion of at least 1 Engel class was documented for 17 (47%) of the 36 patients. For the remainder of the patients, seizure frequency did not change, and continued anticonvulsant medication was needed. The median time to seizure reduction was 20 months (range 1–129 months). The rates of seizure improvement were 29% at 3 years, 36% at 5 years, 50% at 10 years, and 60% at 15 years (Fig. 4). In this study, the rate of improved seizure control was higher for patients with incomplete obliteration (p = 0.042).
Within the improved seizure group, the median nidus volume was 7.15 cm3 among those for whom obliteration was not achieved and 3.75 cm3 among those for whom obliteration was achieved. Among patients for whom complete obliteration was achieved, seizures improved at a median of 19 months after SRS; among patients for whom obliteration was not achieved, seizures improved at a median of 29 months after SRS. Seizure reduction was less among patients with a history of prior hemorrhage (p = 0.028). A smaller nidus diameter was associated with seizure improvement (p = 0.031) and was most notable among patients for whom average AVM diameter was less than 20 mm (p = 0.028). No seizure activity developed after SRS among patients who had been seizure free before SRS. Hemorrhage During Latency Interval and Risk for Complications
A single hemorrhage occurred during the latency period at a median of 6 months (range 4–13 months) for 4 (5%) patients. One patient died as a result of a hemorrhage that occurred 8 months after SRS. The cumulative rate of AVM hemorrhage after SRS was 5% at 1, 5, and 10 years. This rate correlated with 387 patient-years of estimated hemorrhage risk for an overall annual rate of 1.0% during the latency interval (the time from SRS treatment until obliteration or last follow-up of a patent with a known residual AVM). The likelihood of hemorrhage occurring during the latency period was significantly greater for patients who had a coexisting proximal aneurysm (p = 0.018). No patient sustained a hemorrhage after AVM obliteration had been confirmed by MRI or angiography.
Fig. 4. Kaplan-Meier curve for probability of improved seizure control after SRS. The numbers of patients with seizures remaining in the study at 3, 5, 10, and 15 years after SRS were 30, 24, 12, and 7, respectively.
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G. Bowden et al. Temporary symptomatic adverse radiation effects developed in 2 patients (2%). These effects are defined as new T2 signal change surrounding the AVM target on MRI and were associated with the development of new neurological signs in the absence of hemorrhage. One patient experienced transient deterioration of neurocognitive status 3 months after SRS, and another patient experienced increased seizure activity 9 months after SRS. For both of these patients, baseline status was achieved after the administration of a short course of oral corticosteroids. The associated MRI signal changes in these patients resolved at 5 and 27 months, respectively. No permanent new neurological deficit associated with adverse radiation effects developed in any patient. Delayed cyst formation in the target region was detected in 3 patients; the median time until detection of the cyst was 31 months (range 6–67 months). The cysts were asymptomatic for 2 patients but required surgical cyst fenestration for the other patient. Repeat SRS
A total of 15 patients with residual AVMs underwent a second SRS procedure at a median of 40 months (range 36–73 months) after the initial procedure. Among these patients, obliteration was confirmed by MRI at a median interval of 37 months (range 33–50 months) for 5 patients. No complications were noted for patients who underwent repeat SRS.
Discussion Factors Associated With Obliteration
Paradigms for management of AVMs have evolved over the past 25 years, and an individualized patient outcome–centered approach has been widely adopted. As we reviewed the SRS literature about AVM management, we found surprisingly little information specifically about AVMs of the sylvian fissure, an anatomical location we suspected of being of high risk. In fact, almost half of the diagnoses for patients reported in this series were made after an initial ictal bleeding event. In the study reported here, obliteration was confirmed by MRI or angiography for 60% of patients at 5 years and 76% at 10 years. This obliteration rate is consistent with rates reported by other authors after SRS for AVMs in other critical brain locations.1,2,14,16,39 As conveyed in these reports, AVM obliteration rates were higher among patients with smaller AVM volumes; this effect was most prominent for AVM volumes less than 4 cm3.4,5,19,44 We noted an increased rate of total obliteration when higher AVM marginal doses of radiation were delivered. Although higher doses are more often prescribed for patients with smaller AVMs, the optimal dose still represents an empirical balance between the goal of obliteration and the associated risk for adverse radiation effects.8,36,45
Factors Associated With Seizures
The incidence of seizures among patients in this series is similar to that among other patients with AVMs located in the motor or sensory cortex.6 Previous studies have indicated a higher risk for seizures in male patients,
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in patients with AVMs larger than 3 cm, in younger (< 18 years) patients, and in patients with superficial venous outflow drainage from a temporal lobe location.10,12,17,18,31,39 Our study also found that males had a higher likelihood of seizure activity and that seizures were less common in younger patients, especially those younger than 18 years. Of interest, we also found that seizures were less common in patients who had sustained an intracranial hemorrhage. Patients with AVM-associated seizures have a worsened quality of life and a reduced ability to maintain regular employment.5,9,44 In our study, 53% of patients who had had a seizure before SRS were free of disabling seizures at their last follow-up visit. This outcome is similar to the rates of seizure elimination reported by Hadjipanayis et al. and Andrade-Souza et al., which were 63% and 52%, respectively, among patients with AVMs in the motor cortex region.1,14 Rates of seizure elimination after SRS for cortical AVMs, regardless of location, range from 50% to 85%.1,11,23,24 Seizure-free outcomes according to treatment modalities are 78% after microsurgery, 63% after radiosurgery, and 50% after embolization.3,18,27,28 We noted that seizure control improved for 17 (47%) of 36 patients, which compares favorably with previously reported rates of 41%–51%.1,20,27 Seizure control tends to improve over time; we noted that seizure control was improved for 60% of patients at 15 years. Among patients in our study for whom complete obliteration was not confirmed, seizure reduction occurred more often. This finding might be a reflection of the relatively small sample size and larger AVM volumes. Although others have noted that AVM obliteration is not required to improve seizure outcomes,7,11 prior reports have indicated that seizure reduction is more frequent among those for whom AVM obliteration is acheived.3,12,34,42,44 Our data also indicate that a history of prior hemorrhage is a negative prognostic factor for seizure improvement. Kida et al. noted a similar correlation of reduced seizure control in patients who had previously experienced hemorrhage.23 A smaller AVM diameter was associated with seizure improvement, which is similar to the finding reported by Schäuble et al.35 In our study, the median time to seizure reduction was 20 months. This finding is similar to the 20.5-month time until seizure reduction that was noted by Hyun et al. after radiosurgery and embolization.18 Previous studies have reported a risk for new-onset seizures of 5%–10% after SRS and up to 36% after microsurgery.3,42 However, in our study, among patients who were seizure free before SRS, no seizures developed after SRS. For 1 patient, transient exacerbation of seizure frequency was correlated with interval T2 MRI recognition of edema surrounding the AVM target volume. Decision Making
Sylvian fissure AVMs present special management challenges.25,40,46 These challenges include the complex neurovascular relationship of the middle cerebral artery as well as the critical functional cortex and connecting pathways located outside the AVM nidus. Although the published results of microsurgical removal of AVMs in the sylvian fissure are relatively sparse, some authors have reported transient morbidity for as few as 0 to as many as 44% of patients. Permanent new neurological morbidity J Neurosurg / Volume 121 / September 2014
Radiosurgery for sylvian fissure AVMs or death occurred for up to 3% of patients.25,40,46 The data generated from our study indicate a transient morbidity in 3% of patients; no disabilities were permanent. However, 1 patient died of hemorrhage that occurred during the latency interval. Complete surgical removal provides the benefit of early hemorrhage protection but can be associated with immediate postoperative morbidity. Forty-six percent of patients presented with an intracranial hemorrhage, which was consistent with the rate of 52% provided by meta-analysis data.13,22,38 In the study reported here, the annual overall rate of hemorrhage during the latency interval was 1%. This is a reflection of the finding that all 4 (5%) hemorrhages occurred during the first year after treatment, which is comparable to results for motor cortex AVMs.1,14 The risk for hemorrhage during the latency interval was increased among patients with a prenidal aneurysm, which has been demonstrated as a risk factor.15,21 Despite our initial concern that the risk for hemorrhage during the latency interval was higher for AVMs in the sylvian region, we found no evidence of such risk. Cysts formed in 3 patients at a median of 31 months after SRS. Two patients were asymptomatic, and treatment was observation only. However, 1 patient required surgical fenestration of the cyst to relieve mass effect. Pollock and Brown also described late cyst development in 6 patients whose target volume cyst was identified at an average of 4 years after SRS. This finding further indicates the need for long-term follow-up evaluations to verify the reduction of the risk for hemorrhage, confirm AVM obliteration, and monitor the risk for long-term complications.32 Repeat SRS was undertaken when incomplete AVM obliteration was noted on MR images at 3 or more years after initial SRS.20 We confirmed that for 5 of 15 additional patients, obliteration was achieved within a further interval of 3–5 years. No patient who underwent repeat SRS experienced additional morbidity or rebleeding. Study Limitations
The limitations of this study include the need for even longer follow-up periods and the retrospective nature of this review. The population of patients with seizures was relatively small, which affected the statistical power regarding seizure outcomes. Data on long-term anticonvulsant medication management were not incorporated into this analysis because of the limited availability and reliability of the required information. Because medication had not been providing adequate seizure control at the time of SRS, we believe that AVM volume reduction or obliteration is important for seizure control. We were also unable to gather information about patient compliance with regard to taking anticonvulsant medication.
Conclusions
Rates of total AVM obliteration were highest among patients with sylvian fissure AVMs of less than 4 cm3 in volume and who received more than 20 Gy of radiation to the nidus. Seizure control improved after SRS for 60% of patients with seizures, and 53% of patients were free of disabling seizure on or off anticonvulsants. Seizure J Neurosurg / Volume 121 / September 2014
disorders did not develop after SRS in patients who had not had seizures before SRS. The annual hemorrhage rate during the latency interval after SRS was 1%, regardless of whether hemorrhage had occurred previously. After confirmation of AVM obliteration, no patients experienced a hemorrhage. Despite the unfavorable location of sylvian fissure AVMs, no permanent neurological deficits occurred. This study indicates that SRS is a relatively safe and effective way to manage sylvian fissure AVMs. Disclosure Dr. Lunsford is a consultant for and stockholder in Elekta AB. Author contributions to the study and manuscript preparation include the following. Conception and design: Kano. Acquisition of data: Kano, Bowden, Tonetti. Analysis and interpretation of data: Kano, Bowden. Drafting the article: Kano, Bowden, Lunsford. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Kano. Statistical analysis: Kano, Bowden. Study supervision: Kano. References 1. Andrade-Souza YM, Ramani M, Scora D, Tsao MN, TerBrugge K, Schwartz ML: Radiosurgical treatment for rolandic arteriovenous malformations. J Neurosurg 105:689–697, 2006 2. ApSimon HT, Reef H, Phadke RV, Popovic EA: A populationbased study of brain arteriovenous malformation: long-term treatment outcomes. Stroke 33:2794–2800, 2002 3. Baranoski JF, Grant RA, Hirsch LJ, Visintainer P, Gerrard JL, Günel M, et al: Seizure control for intracranial arteriovenous malformations is directly related to treatment modality: a meta-analysis. J Neurointerv Surg [epub ahead of print], 2013 4. Cockerell OC, Johnson AL, Sander JW, Hart YM, Goodridge DM, Shorvon SD: Mortality from epilepsy: results from a prospective population-based study. Lancet 344:918–921, 1994 5. DiIorio C, Osborne Shafer P, Letz R, Henry T, Schomer DL, Yeager K: The association of stigma with self-management and perceptions of health care among adults with epilepsy. Epilepsy Behav 4:259–267, 2003 6. Ding D, Yen CP, Xu Z, Starke RM, Sheehan JP: Radiosurgery for primary motor and sensory cortex arteriovenous malformations: outcomes and the effect of eloquent location. Neurosurgery 73:816–824, 2013 7. Engel J Jr (ed): Outcome with respect to epileptic seizures, in Surgical Treatment of the Epilepsies, ed 2. New York: Raven Press, 1993, pp 609–621 8. Flickinger JC, Kondziolka D, Maitz AH, Lunsford LD: An analysis of the dose-response for arteriovenous malformation radiosurgery and other factors affecting obliteration. Radiother Oncol 63:347–354, 2002 9. Gaitatzis A, Trimble MR, Sander JW: The psychiatric comorbidity of epilepsy. Acta Neurol Scand 110:207–220, 2004 10. Garcin B, Houdart E, Porcher R, Manchon E, Saint-Maurice JP, Bresson D, et al: Epileptic seizures at initial presentation in patients with brain arteriovenous malformation. Neurology 78:626–631, 2012 11. Gerszten PC, Adelson PD, Kondziolka D, Flickinger JC, Luns ford LD: Seizure outcome in children treated for arteriovenous malformations using gamma knife radiosurgery. Pediatr Neurosurg 24:139–144, 1996 12. Ghossoub M, Nataf F, Merienne L, Devaux B, Turak B, Page P, et al: [Evolution of epileptic seizures associated with cerebral arteriovenous malformations after radiosurgery.] Neurochirurgie 47:344–349, 2001 (Fr) 13. Gross BA, Du R: Hemorrhage from arteriovenous malformations during pregnancy. Neurosurgery 71:349–356, 2012
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Manuscript submitted October 11, 2013. Accepted May 8, 2014. Please include this information when citing this paper: published online June 13, 2014; DOI: 10.3171/2014.5.JNS132244. Address correspondence to: Hideyuki Kano, M.D., Ph.D., Department of Neurological Surgery, University of Pittsburgh, Ste. B-400, UPMC Presbyterian, 200 Lothrop St., Pittsburgh, PA 15213. email: [email protected].
J Neurosurg / Volume 121 / September 2014
