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Dale Ding and Kenneth C. Liu

Intracranial atherosclerosis presents a therapeutic challenge to medical and surgical physicians alike. Despite maximal medical therapy, the stroke rate from this disease is still high, especially when arterial stenosis is severe and patients are symptomatic. Open surgical therapy has yet to be shown to be a more efficacious treatment than medical therapy alone, largely due to the relatively high rates of perioperative complications. Angioplasty has a similar fate, with the risk of periprocedural complications outweighing the overall benefit of treatment. With the advent of stents for use in intracranial vasculature, new hope has arisen for the treatment of intracranial atherosclerosis. The NEUROLINK system, the drug-eluting stents Taxus and Cypher, the flexible Wingspan stent, the Apollo stent, and the Pharos stent have all been used in various prospective and retrospective clinical studies with varying technical and clinical results. The authors' objective is to review and loosely compare the data presented for each of these stenting systems. While the Wingspan stent appears to have somewhat of an advantage with regard to technical success in comparison with the other stenting systems, the clinical follow-up time of its studies is too short to properly compare its complication rates with those of other stents. Before we continue to move forward with stenting for intracranial stenosis, a randomized prospective trial is ultimately needed to directly compare intracranial stenting to medical therapy.

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Dale Ding, Chun-Po Yen, Zhiyuan Xu, Robert M. Starke and Jason P. Sheehan

Object

Low-grade, or Spetzler-Martin (SM) Grades I and II, arteriovenous malformations (AVMs) are associated with lower surgical morbidity rates than higher-grade lesions. While radiosurgery is now widely accepted as an effective treatment approach for AVMs, the risks and benefits of the procedure for low-grade AVMs, as compared with microsurgery, remain poorly understood. The authors of this study present the outcomes for a large cohort of low-grade AVMs treated with radiosurgery.

Methods

From an institutional radiosurgery database comprising approximately 1450 AVM cases, all patients with SM Grade I and II lesions were identified. Patients with less than 2 years of radiological follow-up, except those with complete AVM obliteration, were excluded from analysis. Univariate and multivariate Cox proportional-hazards and logistic regression analyses were used to determine factors associated with obliteration, radiation-induced changes (RICs), and hemorrhage following radiosurgery.

Results

Five hundred two patients harboring low-grade AVMs were eligible for analysis. The median age was 35 years, 50% of patients were male, and the most common presentation was hemorrhage (47%). The median AVM volume and prescription dose were 2.4 cm3 and 23 Gy, respectively. The median radiological and clinical follow-up intervals were 48 and 62 months, respectively. The cumulative obliteration rate was 76%. The median time to obliteration was 40 months, and the actuarial obliteration rates were 66% and 80% at 5 and 10 years, respectively. Independent predictors of obliteration were no preradiosurgery embolization (p < 0.001), decreased AVM volume (p = 0.005), single draining vein (p = 0.013), lower radiosurgery-based AVM scale score (p = 0.016), and lower Virginia Radiosurgery AVM Scale (Virginia RAS) score (p = 0.001). The annual postradiosurgery hemorrhage rate was 1.4% with increased AVM volume (p = 0.034) and lower prescription dose (p = 0.006) as independent predictors. Symptomatic and permanent RICs were observed in 8.2% and 1.4% of patients, respectively. No preradiosurgery hemorrhage (p = 0.011), a decreased prescription dose (p = 0.038), and a higher Virginia RAS score (p = 0.001) were independently associated with postradiosurgery RICs.

Conclusions

Spetzler-Martin Grade I and II AVMs are very amenable to successful treatment with stereotactic radiosurgery. While patient, physician, and institutional preferences frequently dictate the final course of treatment, radiosurgery offers a favorable risk-to-benefit profile for the management of low-grade AVMs.

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Robert M. Starke, Chun-Po Yen, Dale Ding and Jason P. Sheehan

Object

The authors performed a study to review outcomes following Gamma Knife radiosurgery for cerebral arteriovenous malformations (AVMs) and to create a practical scale to predict long-term outcome.

Methods

Outcomes were reviewed in 1012 patients who were followed up for more than 2 years. Favorable outcome was defined as AVM obliteration and no posttreatment hemorrhage or permanent, symptomatic, radiation-induced complication. Preradiosurgery patient and AVM characteristics predictive of outcome in multivariate analysis were weighted according to their odds ratios to create the Virginia Radiosurgery AVM Scale.

Results

The mean follow-up time was 8 years (range 2–20 years). Arteriovenous malformation obliteration occurred in 69% of patients. Postradiosurgery hemorrhage occurred in 88 patients, for a yearly incidence of 1.14%. Radiation-induced changes occurred in 387 patients (38.2%), symptoms in 100 (9.9%), and permanent deficits in 21 (2.1%). Favorable outcome was achieved in 649 patients (64.1%). The Virginia Radiosurgery AVM Scale was created such that patients were assigned 1 point each for having an AVM volume of 2–4 cm3, eloquent AVM location, or a history of hemorrhage, and 2 points for having an AVM volume greater than 4 cm3. Eighty percent of patients who had a score of 0–1 points had a favorable outcome, as did 70% who had a score of 2 points and 45% who had a score of 3–4 points. The Virginia Radiosurgery AVM Scale was still predictive of outcome after controlling for predictive Gamma Knife radiosurgery treatment parameters, including peripheral dose and number of isocenters, in a multivariate analysis. The Spetzler-Martin grading scale and the Radiosurgery-Based Grading Scale predicted favorable outcome, but the Virginia Radiosurgery AVM Scale provided the best assessment.

Conclusions

Gamma Knife radiosurgery can be used to achieve long-term AVM obliteration and neurological preservation in a predictable fashion based on patient and AVM characteristics.

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Dale Ding, Zhiyuan Xu, Ian T. McNeill, Chun-Po Yen and Jason P. Sheehan

Object

Parasagittal and parafalcine (PSPF) meningiomas represent the second most common location for intracranial meningiomas. Involvement of the superior sagittal sinus or deep draining veins may prevent gross-total resection of these tumors without significant morbidity. The authors review their results for treatment of PSPF meningiomas with radiosurgery.

Methods

The authors retrospectively reviewed the institutional review board–approved University of Virginia Gamma Knife database and identified 65 patients with 90 WHO Grade I parasagittal (59%) and parafalcine (41%) meningiomas who had a mean MRI follow-up of 56.6 months. The patients' mean age was 57 years, the median preradiosurgery Karnofsky Performance Status score was 80, and the median initial tumor and treatment volumes were 3 and 3.7 cm3, respectively. The median prescription dose was 15 Gy, isodose line was 40%, and the number of isocenters was 5. Kaplan-Meier analysis was used to determine progression-free survival (PFS). Univariate and multivariate Cox regression analyses were used to identify factors associated with PFS.

Results

The median overall PFS was 75.6 months. The actuarial tumor control rate was 85% at 3 years and 70% at 5 years. Parasagittal location, no prior resection, and younger age were found to be independent predictors of tumor PFS. For the 49 patients with clinical follow-up (mean 70.8 months), the median postradiosurgery Karnofsky Performance Status score was 90. Symptomatic postradiosurgery peritumoral edema was observed in 4 patients (8.2%); this group comprised 3 patients (6.1%) with temporary and 1 patient (2%) with permanent clinical sequelae. Two patients (4.1%) died of tumor progression.

Conclusions

Radiosurgery offers a minimally invasive treatment option for PSPF meningiomas, with a good tumor control rate and an acceptable complication rate comparable to most surgical series.

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Gautam U. Mehta, Michael J. Feldman, Herui Wang, Dale Ding and Prashant Chittiboina

The presence of vestibular schwannomas has long been considered an exclusion criterion for the diagnosis of schwannomatosis. Recently, 2 cases of vestibular schwannoma were reported in patients with schwannomatosis, leading to a revision of the diagnostic criteria for this genetic disorder. Overall, the relative infrequency of vestibular schwannomas in schwannomatosis is unexplained, and the genetics of this uncommon phenomenon have not been described. The authors report on a family with clinical manifestations consistent with schwannomatosis, including 4 affected members, that was identified as having an affected member harboring a unilateral cerebellopontine angle mass with extension into the internal auditory canal. Radiologically, this mass was consistent with a vestibular schwannoma and resulted in a symptomatic change in ipsilateral hearing (word recognition 86% at 52 dB) and increased latency of the wave I–V interval on auditory brainstem response testing. The patient was found to be negative for a germline mutation of NF2 and LZTR1, and her affected mother was found to harbor neither NF2 nor SMARCB1 mutations on genetic testing. Although vestibular schwannomas have been classically considered to not occur in the setting of schwannomatosis, this patient with schwannomatosis and a vestibular schwannoma further confirms that schwannomas can occur on the vestibular nerve in this syndrome. Further, this is the first such case found to be negative for a mutation on the LZTR1 gene.

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Douglas Kondziolka

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Dale Ding, Chun-Po Yen, Robert M. Starke, Zhiyuan Xu and Jason P. Sheehan

Object

Ruptured intracranial arteriovenous malformations (AVMs) are at a significantly greater risk for future hemorrhage than unruptured lesions, thereby necessitating treatment in the majority of cases. In a retrospective, single-center study, the authors describe the outcomes after radiosurgery in a large cohort of patients with ruptured AVMs.

Methods

From an institutional review board–approved, prospectively collected AVM radiosurgery database, the authors identified all patients with a history of AVM rupture. They analyzed obliteration rates in all patients in whom radiological follow-up data were available (n = 639). However, to account for the latency period associated with radiosurgery, only those patients with more than 2 years of radiological follow-up and those with earlier AMV obliteration were included in the analysis of prognostic factors related to obliteration and complications. This resulted in a cohort of 565 patients with ruptured AVMs for whom data were analyzed; these patients had a median radiological follow-up of 57 months and a median age of 29 years. Twenty-one percent of the patients underwent preradiosurgery embolization. The median volume and prescription dose were 2.1 cm3 and 22 Gy, respectively. The Spetzler-Martin grade was III or higher in 56% of patients, the median radiosurgery-based AVM score was 1.08, and the Virginia Radiosurgery AVM Scale (RAS) score was 3 to 4 points in 44%. Survival and regression analyses were performed to determine obliteration rates over time and predictors of obliteration and complications.

Results

In the overall population of 639 patients with ruptured AVMs, the obliteration rate was 11.1% based on MRI only (71 of 639 patients), 56.0% based on angiography (358 of 639), and 67.1% based on combined modalities (429 of 639 patients). In the cohort of patients with 2 years of follow-up or an earlier AVM obliteration, the cumulative obliteration rate was 76% and the actuarial obliteration rates were 41% and 64% at 3 and 5 years, respectively. Multivariate analysis identified the absence of preradiosurgery embolization (p < 0.001), increased prescription dose (p = 0.001), the presence of a single draining vein (p = 0.046), no postradiosurgery-related hemorrhage (p = 0.007), and lower Virginia RAS score (p = 0.020) as independent predictors of obliteration. The annual risk of a hemorrhage occurring during the latency period was 2.0% and the rate of hemorrhage-related morbidity and mortality was 1.6%. Multivariate analysis showed that decreased prescription dose (p < 0.001) and multiple draining veins (p = 0.003) were independent predictors of postradiosurgery hemorrhage. The rates of symptomatic and permanent radiation-induced changes were 8% and 2.7%, respectively. In the multivariate analysis, a single draining vein (p < 0.001) and higher Virginia RAS score (p = 0.005) were independent predictors of radiation-induced changes following radiosurgery.

Conclusions

Radiosurgery effectively treats ruptured AVMs with an acceptably low risk-to-benefit ratio. For patients with ruptured AVMs, favorable outcomes are more likely when preradiosurgical embolization is avoided and a higher prescription dose can be delivered.

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Jason Sheehan, Dale Ding and Robert M. Starke

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Dale Ding, Chun-Po Yen, Zhiyuan Xu, Robert M. Starke and Jason P. Sheehan

Object

The appropriate management of unruptured intracranial arteriovenous malformations (AVMs) remains controversial. In the present study, the authors evaluate the radiographic and clinical outcomes of radiosurgery for a large cohort of patients with unruptured AVMs.

Methods

From a prospective database of 1204 cases of AVMs involving patients treated with radiosurgery at their institution, the authors identified 444 patients without evidence of rupture prior to radiosurgery. The patients' mean age was 36.9 years, and 50% were male. The mean AVM nidus volume was 4.2 cm3, 13.5% of the AVMs were in a deep location, and 44.4% were at least Spetzler-Martin Grade III. The median radiosurgical prescription dose was 20 Gy. Univariate and multivariate Cox regression analyses were used to determine risk factors associated with obliteration, postradiosurgery hemorrhage, radiation-induced changes, and postradiosurgery cyst formation. The mean duration of radiological and clinical follow-up was 76 months and 86 months, respectively.

Results

The cumulative AVM obliteration rate was 62%, and the postradiosurgery annual hemorrhage rate was 1.6%. Radiation-induced changes were symptomatic in 13.7% and permanent in 2.0% of patients. The statistically significant independent positive predictors of obliteration were no preradiosurgery embolization (p < 0.001), increased prescription dose (p < 0.001), single draining vein (p < 0.001), radiological presence of radiation-induced changes (p = 0.004), and lower Spetzler-Martin grade (p = 0.016). Increased volume and higher Pittsburgh radiosurgery-based AVM score were predictors of postradiosurgery hemorrhage in the univariate analysis only. Clinical deterioration occurred in 30 patients (6.8%), more commonly in patients with postradiosurgery hemorrhage (p = 0.018).

Conclusions

Radiosurgery afforded a reasonable chance of obliteration of unruptured AVMs with relatively low rates of clinical and radiological complications.