The longitudinal volumetric response of vestibular schwannomas after Gamma Knife radiosurgery

J Neurosurg 138:1273–1280, 2023

Gamma Knife radiosurgery (GKRS) is an effective treatment for vestibular schwannomas (VSs) and has been used in > 100,000 cases worldwide. In the present study the authors sought to define the serial volumetric tumor response of Koos grade I–IV VS after radiosurgery.

METHODS A total of 201 consecutive VS patients underwent GKRS at a single institution between 2015 and 2019. All patients had a minimum follow-up of 18 months and at least 2 interval postprocedure MRI scans. The contrast-enhanced tumor volumes were contoured manually and compared between pre- and post-GKRS imaging. The percentages of tumor volume change at 18 months (short-term follow-up) and up to 5 years after GKRS (long-term follow-up) were compared with the baseline tumor volume. An increase of 20% was considered a significant increase of tumor volume. Trends of tumor volume over time were assessed with linear models using time as a continuous variable. A test for linear trend was evaluated according to the initial Koos tumor classification.

RESULTS Koos grade II VS was the most frequently occurring tumor (n = 74, 36.8%), followed by grade III (n = 57, 28.4%), grade I (n = 41, 20.4%), and grade IV (n = 29, 14.4%). The mean tumor volume at the time of GKRS was 2.12 ±2.82 cm 3 (range 0.12–18.77 cm 3 ) and the median margin dose was 12 Gy. Short-term follow-up revealed that tumor volumes transiently increased in 34.2% and 28.4% of patients at 6 and 18 months, respectively, regardless of Koos grade. Linear regression analysis of Koos grade II, III, and IV tumors showed a significant longitudinal volume decrease on long-term follow-up. At last follow-up (median 30 months, range 18–54 months), 19 patients (9.4%) showed a persistent increase of tumor volume. Five patients received additional management after GKRS.

CONCLUSIONS Although selected VS patients demonstrate an early and measurable transient volumetric increase after GKRS, > 90% have stable or reduced tumor volumes over an observed period of up to 5 years. Volumetric regression is most pronounced in Koos grade II, III, and IV tumors and may not be fully detectable until 3 years after GKRS.

Chronic Encapsulated Expanding Hematomas After Stereotactic Radiosurgery for Intracranial Arteriovenous Malformations

Neurosurgery 92:195–204, 2023

Stereotactic radiosurgery (SRS) offers a minimally invasive treatment modality for appropriately selected intracranial arteriovenous malformations (AVMs). Recent reports have described the development of rare, delayed chronic encapsulated expanding hematomas (CEEHs) at the site of an angiographically confirmed obliterated AVM.

OBJECTIVE: To elucidate the incidence, characteristics, and management of CEEH in patients with AVM after SRS.

METHODS: The records of all patients who underwent SRS for an intracranial AVM at 4 institutions participating in the International Radiosurgery Research Foundation between 1987 and 2021 were retrospectively reviewed. Data regarding characteristics of the AVM, SRS treatment parameters, CEEH presentation, management, and outcomes were collected and analyzed.

RESULTS: Among 5430 patients, 15 developed a CEEH at a crude incidence of 0.28%. Nine patients were female, and the mean age was 43 ± 14.6 years. Nine patients underwent surgical evacuation, while 6 were managed conservatively. The median CEEH development latency was 106 months after SRS. The patients were followed for a median of 32 months, and 9 patients improved clinically, while 6 patients remained stable. No intraoperative complications were reported after CEEH resection, although 1 patient recovered from postoperative meningitis requiring intravenous antibiotics.

CONCLUSION: CEEH is a rare, late complication of AVM SRS with an incidence of 0.28% and a median latency of 106 months. In the presence of a delayed and symptomatic expanding hematoma in the bed of an angiographically obliterated AVM, surgical resection resulted in clinical improvement in most patients. Conservative management is possible in asymptomatic patients with stable, small-sized hematomas in deeply seated locations.

Stereotactic radiosurgery for Koos grade IV vestibular schwannoma in patients ≥ 65 years old

Acta Neurochirurgica (2023) 165:211–220

Surgery is the preferred treatment for large vestibular schwannomas (VS). Good tumor control and cranial nerve outcomes were described in selected Koos IV VS after single-session stereotactic radiosurgery (SRS), but outcomes in elderly patients have never been specifically studied. The aim of this study is to report clinical and radiological outcomes after single-session SRS for Koos IV VS in patients ≥ 65 years old.

Method This multicenter, retrospective study included patients ≥ 65 years old, treated with primary, single-session SRS for a Koos IV VS, and at least 12 months of follow-up. Patients with life-threatening or incapacitating symptoms were excluded. Tumor control rate, hearing, trigeminal, and facial nerve function were studied at last follow-up.

Results One-hundred and fifty patients (median age of 71.0 (IQR 9.0) years old with a median tumor volume of 8.3 cc (IQR 4.4)) were included. The median prescription dose was 12.0 Gy (IQR 1.4). The local tumor control rate was 96.0% and 86.2% at 5 and 10 years, respectively. Early tumor expansion occurred in 6.7% and was symptomatic in 40% of cases. A serviceable hearing was present in 16.1% prior to SRS and in 7.4% at a last follow-up of 46.5 months (IQR 55.8). The actuarial serviceable hearing preservation rate was 69.3% and 50.9% at 5 and 10 years, respectively. Facial nerve function preservation or improvement rates at 5 and 10 years were 98.7% and 91.0%, respectively. At last follow-up, the trigeminal nerve function was improved in 14.0%, stable in 80.7%, and worsened in 5.3% of the patients. ARE were noted in 12.7%. New hydrocephalus was seen in 8.0% of patients.

Conclusion SRS can be a safe alternative to surgery for selected Koos IV VS in patients ≥ 65 years old. Further follow-up is warranted.

Audiovestibular symptoms and facial nerve function comparing microsurgery versus SRS for vestibular schwannomas

Acta Neurochirurgica (2022) 164:3221–3233

Surgery and radiosurgery represent the most common treatment options forcvestibular schwannoma. A systematic review and meta-analysis were conducted to compare the outcomes of surgery versus stereotactic radiosurgery (SRS).

Methods The Cochrane library, PubMed, Embase, and were searched through 01/2021 to find all studies on surgical and stereotactic procedures performed to treat vestibular schwannoma. Using a random-effects model, pooled odds ratios (OR) and their 95% confidence intervals (CI) comparing post- to pre-intervention were derived for pre-post studies, and pooled incidence of adverse events post-intervention were calculated for case series and stratified by intervention type.

Results Twenty-one studies (18 pre-post design; three case series) with 987 patients were included in the final analysis. Comparing post- to pre-intervention, both surgery (OR: 3.52, 95%CI 2.13, 5.81) and SRS (OR: 3.30, 95%CI 1.39, 7.80) resulted in greater odds of hearing loss, lower odds of dizziness (surgery OR: 0.10; 95%CI 0.02, 0.47 vs. SRS OR: 0.22; 95%CI 0.05, 0.99), and tinnitus (surgery OR: 0.23; 95%CI 0.00, 37.9; two studies vs. SRS OR: 0.11; 95%CI 0.01, 1.07; one study). Pooled incidence of facial symmetry loss was larger post-surgery (14.3%, 95%CI 6.8%, 22.7%) than post-SRS (7%, 95%CI 1%, 36%). Tumor control was larger in the surgery (94%, 95%CI 83%, 98%) than the SRS group (80%, 95%CI 31%, 97%) for small-to-medium size tumors.

Conclusion Both surgery and SRS resulted in similar odds of hearing loss and similar improvements in dizziness and tinnitus among patients with vestibular schwannoma; however, facial symmetry loss appeared higher post-surgery.

Stereotactic radiosurgery for intracranial chordomas: an international multiinstitutional study

J Neurosurg 137:977–984, 2022

The object of this study was to evaluate the safety, efficacy, and long-term outcomes of stereotactic radiosurgery (SRS) in the management of intracranial chordomas.

METHODS This retrospective multicenter study involved consecutive patients managed with single-session SRS for an intracranial chordoma at 10 participating centers. Radiological and neurological outcomes were assessed after SRS, and predictive factors were evaluated via statistical methodology.

RESULTS A total of 93 patients (56 males [60.2%], mean age 44.8 years [SD 16.6]) underwent single-session SRS for intracranial chordoma. SRS was utilized as adjuvant treatment in 77 (82.8%) cases, at recurrence in 13 (14.0%) cases, and as primary treatment in 3 (3.2%) cases. The mean tumor volume was 8 cm 3 (SD 7.3), and the mean prescription volume was 9.1 cm 3 (SD 8.7). The mean margin and maximum radiosurgical doses utilized were 17 Gy (SD 3.6) and 34.2 Gy (SD 6.4), respectively. On multivariate analysis, treatment failure due to tumor progression (p = 0.001) was associated with an increased risk for post-SRS neurological deterioration, and a maximum dose > 29 Gy (p = 0.006) was associated with a decreased risk. A maximum dose > 29 Gy was also associated with improved local tumor control (p = 0.02), whereas the presence of neurological deficits prior to SRS (p = 0.04) and an age > 65 years at SRS (p = 0.03) were associated with worse local tumor control. The 5- and 10-year tumor progression-free survival rates were 54.7% and 34.7%, respectively. An age > 65 years at SRS (p = 0.01) was associated with decreased overall survival. The 5and 10-year overall survival rates were 83% and 70%, respectively.

CONCLUSIONS SRS appears to be a safe and relatively effective adjuvant management option for intracranial chordomas. The best outcomes were obtained in younger patients without significant neurological deficits. Further well-designed studies are necessary to define the best timing for the use of SRS in the multidisciplinary management of intracranial chordomas.

Matched Comparison of Hearing Outcomes in Patients With Vestibular Schwannoma Treated With Stereotactic Radiosurgery or Observation

Neurosurgery 91:641–647, 2022

Previous studies comparing hearing outcomes in patients managed with stereotactic radiosurgery (SRS) and a watch-and-wait strategy were limited by small sample sizes that prevented controlling for potential confounders, including initial hearing status, tumor size, and age.

OBJECTIVE: To compare hearing outcomes for patients with vestibular schwannomas (VS) managed with observation and SRS while controlling for confounders with propensity score matching.

METHODS: Propensity score matching was used to compare 198 patients with unilateral VS with initial serviceable hearing (99 treated with SRS and 99 managed with observation alone) and 116 with initial class A hearing (58 managed with SRS and 58 with observation), matched by initial hearing status, tumor volume, age, and sex. Kaplan–Meier survival methods were used to compare risk of losing class A and serviceable hearing.

RESULTS: Between patients with VS managed with SRS or observation alone, there was no significant difference in loss of class A hearing (median time 27.2 months, 95% CI 16.843.4, and 29.2 months, 95% CI 20.4-62.5, P = .88) or serviceable hearing (median time 37.7 months, 95% CI 25.7-58.4, and 48.8 months, 95% CI 38.4-86.3, P = .18). For SRS patients, increasing mean cochlear dose was not related to loss of class A hearing (hazard ratio 1.3, P = .17) but was associated with increasing risk of serviceable hearing loss (hazard ratio of 1.5 per increase in Gy, P = .017).

CONCLUSION: When controlling for potential confounders, there was no significant difference in loss of class A or serviceable hearing between patients managed with SRS or with observation alone.

Long-Term Risks of Hemorrhage and Adverse Radiation Effects of Stereotactic Radiosurgery for Brain Arteriovenous Malformations

Neurosurgery 90:784–792, 2022

The information about long-term risks of hemorrhage and late adverse radiation effects (AREs) after stereotactic radiosurgery for brain arteriovenous malformations (AVMs) is lacking.

OBJECTIVE: To evaluate the long-term risks of hemorrhage and late ARE rates in patients with AVM treated with Gamma Knife surgery (GKS). METHODS: We examined 1249 patients with AVM treated with GKS. The Spetzler–Martin grade was I in 313 patients (25%), II in 394 (32%), III in 458 (37%), and IV/V in 84 (7%). The median treatment volume was 2.5 cm3, and the median marginal dose was 20 Gy.

RESULTS: The median follow-up period was 61 months. The 5- and 10-year nidus obliteration rates were 63% and 82%, respectively. The 5- and 10-year cumulative hemorrhage rates were 7% and 10%, respectively. The annual hemorrhage rate was 1.5% for the first 5 years post-GKS, which decreased to 0.5% thereafter. During the follow-up period, 42 symptomatic cyst formations/ chronic encapsulated hematomas ([CFs/CEHs], 3%) and 3 radiation-induced tumors (0.2%) were observed. The 10- and 15-year cumulative CF/CEH rates were 3.7% and 9.4%, respectively.

CONCLUSION: GKS is associated with reduced hemorrhage risk and high nidus obliteration rates in patients with AVM. The incidence of late AREs tended to increase over time. The most common ARE was CF/CEH, which can be safely removed; however, careful attention should be paid to the long-term development of fatal radiation-induced tumors.

Management of cavernous sinus meningiomas: Consensus statement on behalf of the EANS skull base section

Brain and Spine 2 (2022) 100864

The evolution of cavernous sinus meningiomas (CSMs) might be unpredictable and the efficacy of their treatments is challenging due to their indolent evolution, variations and fluctuations of symptoms, heterogeneity of classifications and lack of randomized controlled trials. Here, a dedicated task force provides a consensus statement on the overall management of CSMs. Research question: To determine the best overall management of CSMs, depending on their clinical presentation, size, and evolution as well as patient characteristics.

Material and methods: Using the PRISMA 2020 guidelines, we included literature from January 2000 to December 2020. A total of 400 abstracts and 77 titles were kept for full-paper screening.

Results: The task force formulated 8 recommendations (Level C evidence). CSMs should be managed by a highly specialized multidisciplinary team. The initial evaluation of patients includes clinical, ophthalmological, endocrinological and radiological assessment. Treatment of CSM should involve experienced skull-base neurosurgeons or neuro-radiosurgeons, radiation oncologists, radiologists, ophthalmologists, and endocrinologists.

Discussion and conclusion: Radiosurgery is preferred as first-line treatment in small, enclosed, pauci-symptomatic lesions/in elderly patients, while large CSMs not amenable to resection or WHO grade II-III are candidates for radiotherapy. Microsurgery is an option in aggressive/rapidly progressing lesions in young patients presenting with oculomotor/visual/endocrinological impairment. Whenever surgery is offered, open cranial approaches are the current standard. There is limited experience reported about endoscopic endonasal approach for CSMs and the main indication is decompression of the cavernous sinus to improve symptoms. Whenever surgery is indicated, the current trend is to offer decompression followed by radiosurgery.

Stereotactic radiosurgery for cerebral cavernous malformation: comparison of hemorrhage rates before and after stereotactic radiosurgery

J Neurosurg 136:655–661, 2022

Cerebral cavernous malformation (CM) is an angiographically occult vascular pathology. Although microsurgery is the gold standard treatment to control the symptoms of CM, resection carries high risk in some situations, especially eloquent areas. The objective was to evaluate annual hemorrhage rates (AHRs) before and after stereotactic radiosurgery (SRS) treatment of cerebral CM in different locations.

METHODS A total of 195 patients (119 women and 76 men) with CM treated at the Gazi University Gamma Knife Center between April 2005 and June 2017 were analyzed. The mean   SD follow-up period was 67.4   31.1 months (range 12 days to 170 months). AHR before SRS, AHR after SRS, morbidity associated with radiation, seizure control rate after SRS, lesion volume, coexistence with developmental venous anomaly, and SRS treatment parameters were analyzed, with evaluation of radiological data and clinical charts performed retrospectively. The seizure control rate was assessed using the Engel outcome scale.

RESULTS The AHR before SRS was 15.3%. Application of SRS to these patients significantly reduced the AHR rates to 2.6% during the first 2 years after treatment and to 1.4% thereafter. Favorable seizure control (Engel class I and II) after radiosurgery was achieved in 23 patients (88.5%) with epilepsy. Radiation-related temporary complications occurred in 15.4% of patients, and permanent morbidity occurred in 4.6%.

CONCLUSIONS SRS is a safe and effective treatment modality for reducing the hemorrhage risk of CM. The authors suggest that SRS should be considered for the treatment of patients with CM, high surgical risks, and hemorrhage history, instead of a using a wait-and-see policy.

Results of three or more Gamma Knife radiosurgery procedures for recurrent trigeminal neuralgia

J Neurosurg 135:1789–1798, 2021

Gamma Knife radiosurgery (GKRS) is an established surgical option for the treatment of trigeminal neuralgia (TN), particularly for high-risk surgical candidates and those with recurrent pain. However, outcomes after three or more GKRS treatments have rarely been reported. Herein, the authors reviewed outcomes among patients who had undergone three or more GKRS procedures for recurrent TN.

METHODS The authors conducted a multicenter retrospective analysis of patients who had undergone at least three GKRS treatments for TN between July 1997 and April 2019 at two different institutions. Clinical characteristics, radiosurgical dosimetry and technique, pain outcomes, and complications were reviewed. Pain outcomes were scored on the Barrow Neurological Institute (BNI) scale, including time to pain relief (BNI score ≤ III) and recurrence (BNI score > III).

RESULTS A total of 30 patients were identified, including 16 women and 14 men. Median pain duration prior to the first GKRS treatment was 10 years. Three patients (10%) had multiple sclerosis. Time to pain relief was longer after the third treatment (p = 0.0003), whereas time to pain recurrence was similar across each of the successive treatments (p = 0.842). Complete or partial pain relief was achieved in 93.1% of patients after the third treatment. The maximum pain relief achieved after the third treatment was significantly better among patients with no prior percutaneous procedures (p = 0.0111) and patients with shorter durations of pain before initiation of GKRS therapy (p = 0.0449). New or progressive facial sensory dysfunction occurred in 29% of patients after the third GKRS treatment and was reported as bothersome in 14%. One patient developed facial twitching, while another experienced persistent lacrimation. No statistically significant predictors of adverse effects following the third treatment were found. Over a median of 39 months of follow-up, 77% of patients maintained complete or partial pain relief. Three patients underwent a fourth GKRS treatment, including one who ultimately received five treatments; all of them reported sustained pain relief at the extended follow-up.

CONCLUSIONS The authors describe the largest series to date of patients undergoing three or more GKRS treatments for refractory TN. A third treatment may produce outcomes similar to those of the first two treatments in terms of longterm pain relief, recurrence, and adverse effects.


Stereotactic Radiosurgery for Olfactory Groove Meningiomas: An International, Multicenter Study

Neurosurgery 89:784–791, 2021

Stereotactic radiosurgery (SRS) is increasingly considered for selected olfactory groove meningiomas (OGMs).

OBJECTIVE: To investigate the safety and efficacy of SRS for OGMs.

METHODS: From 20 institutions participating in the International Radiosurgery Research Foundation, we pooled patients who underwent SRS for histologically confirmed or radiologically suspected WHO grade I OGMs and were followed for 6 mo or more after the SRS.

RESULTS: In total, 278 (median age 57 yr) patients underwent SRS for histologically confirmed (29%) or radiologically suspected (71%) WHO grade I OGMs Median treatment volume was 4.60 cm3 (range: 0.12-27.3 cm3), median prescription dose was 12 Gy, and median dose to the olfactory nerve was 11.20 Gy. During median post-SRS imaging follow- up of 39 mo (range: 6-240 mo), 43% of patients had partial or marginal response, 54% of patients had stable disease, and 3% of patients experienced progression. During median post-SRS clinical follow-up of 51 mo (range: 6-240 mo), 36 (13%) patients experienced clinical and/or radiological adverse radiation events (AREs). Elevated risk of AREs was associated with larger OGM volume (P = .009) and pre-SRS peritumoral T2/fluid-attenuated inversion- recovery signal abnormalities (P < .001). After the SRS, olfaction remained stable, improved, or deteriorated in 90%, 8%, and 2% of patients, respectively. Complete post-SRS anosmia was predicted by partial/complete anosmia before the SRS (odds ratio [OR] = 83.125; 95% CI [24.589-281.01], P < .001) and prior resection of OGM (OR = 3.919; 95% CI [1.713-8.970], P = .001).

CONCLUSION: SRS is associated with durable local control of the majority of OGM patients with acceptable safety profile. SRS allows preservation or improvement of olfactory function in the majority of OGM patients.


Stereotactic radiosurgery for clinoid meningiomas: a multi‐institutional study

Acta Neurochirurgica (2021) 163:2861–2869

Resection of clinoid meningiomas can be associated with significant morbidity. Experience with stereotactic radiosurgery (SRS) for clinoid meningiomas remains limited. We studied the safety and effectiveness of SRS for clinoid meningiomas.

Methods From twelve institutions participating in the International Radiosurgery Research Foundation, we pooled patients treated with SRS for radiologically suspected or histologically confirmed WHO grade I clinoid meningiomas.

Results Two hundred seven patients (median age: 56 years) underwent SRS for clinoid meningiomas. Median treatment volume was 8.02 cm3, and 87% of tumors were immediately adjacent to the optic apparatus. The median tumor prescription dose was 12 Gy, and the median maximal dose to the anterior optic apparatus was 8.5 Gy. During a median post-SRS imaging follow-up of 51.1 months, 7% of patients experienced tumor progression. Greater margin SRS dose (HR = 0.700, p = 0.007) and pre-SRS radiotherapy (HR = 0.004, p < 0.001) were independent predictors of better tumor control. During median visual follow-up of 48 months, visual function declined in 8% of patients. Pre-SRS visual deficit (HR=2.938, p=0.048) and maximal radiation dose to the optic apparatus of ≥ 10 Gy (HR = 11.297, p = 0.02) independently predicted greater risk of post-SRS visual decline. Four patients experienced new post-SRS cranial nerve V neuropathy.

Conclusions SRS allows durable control of clinoid meningiomas and visual preservation in the majority of patients. Greater radiosurgical prescription dose is associated with better tumor control. Radiation dose to the optic apparatus of ≥ 10 Gy and visual impairment before the SRS increase risk of visual deterioration.

Stereotactic radiosurgery as the first-line treatment for intracanalicular vestibular schwannomas

J Neurosurg 135:1051–1057, 2021

This report evaluates the outcomes of stereotactic radiosurgery (SRS) as the first-line treatment of intracanalicular vestibular schwannomas (VSs).

METHODS Between 1987 and 2017, the authors identified 209 patients who underwent SRS as the primary intervention for a unilateral intracanalicular VS. The median patient age was 54 years (range 22–85 years); 94 patients were male and 115 were female. Three patients had facial neuropathy at the time of SRS. One hundred fifty-five patients (74%) had serviceable hearing (Gardner-Robertson [GR] grades I and II) at the time of SRS. The median tumor volume was 0.17 cm3 (range 0.015–0.63 cm3). The median margin dose was 12.5 Gy (range 11.0–25.0 Gy). The median maximum dose was 24.0 Gy (range 15.7–50.0 Gy).

RESULTS The progression-free survival rates of all patients with intracanalicular VS were 97.5% at 3 years, 95.6% at 5 years, and 92.1% at 10 years. The rates of freedom from the need for any additional intervention were 99.4% at 3 years, 98.3% at 5 years, and 98.3% at 10 years. The serviceable hearing preservation rates in GR grade I and II patients at the time of SRS were 76.6% at 3 years, 63.5% at 5 years, and 27.3% at 10 years. In univariate analysis, younger age (< 55 years, p = 0.011), better initial hearing (GR grade I, p < 0.001), and smaller tumor volumes (< 0.14 cm3, p = 0.016) were significantly associated with improved hearing preservation. In multivariate analysis, better hearing (GR grade I, p = 0.001, HR 2.869, 95% CI 1.569–5.248) and smaller tumor volumes (< 0.14 cm3, p = 0.033, HR 2.071, 95% CI 1.059–4.047) at the time of SRS were significantly associated with improved hearing preservation. The hearing preservation rates of patients with GR grade I VS were 88.1% at 3 years, 77.9% at 5 years, and 38.1% at 10 years. The hearing preservation rates of patients with VSs smaller than 0.14 cm3 were 85.5% at 3 years, 77.7% at 5 years, and 42.6% at 10 years. Facial neuropathy developed in 1.4% from 6 to 156 months after SRS.

CONCLUSIONS SRS provided sustained tumor control in more than 90% of patients with intracanalicular VS at 10 years and freedom from the need for additional intervention in more than 98% at 10 years. Patients with initially better hearing and smaller VSs had enhanced serviceable hearing preservation during an observation interval up to 10 years after SRS.

Stereotactic radiosurgery with versus without prior Onyx embolization for brain arteriovenous malformations

J Neurosurg 135:742–750, 2021

Investigations of the combined effects of neoadjuvant Onyx embolization and stereotactic radiosurgery (SRS) on brain arteriovenous malformations (AVMs) have not accounted for initial angioarchitectural features prior to neuroendovascular intervention. The aim of this retrospective, multicenter matched cohort study is to compare the outcomes of SRS with versus without upfront Onyx embolization for AVMs using de novo characteristics of the preembolized nidus.

METHODS The International Radiosurgery Research Foundation AVM databases from 1987 to 2018 were retrospectively reviewed. Patients were categorized based on AVM treatment approach into Onyx embolization (OE) and SRS (OE+SRS) or SRS alone (SRS-only) cohorts and then propensity score matched in a 1:1 ratio. The primary outcome was AVM obliteration. Secondary outcomes were post-SRS hemorrhage, all-cause mortality, radiological and symptomatic radiation-induced changes (RICs), and cyst formation. Comparisons were analyzed using crude rates and cumulative probabilities adjusted for competing risk of death.

RESULTS The matched OE+SRS and SRS-only cohorts each comprised 53 patients. Crude rates (37.7% vs 47.2% for the OE+SRS vs SRS-only cohorts, respectively; OR 0.679, p = 0.327) and cumulative probabilities at 3, 4, 5, and 6 years (33.7%, 44.1%, 57.5%, and 65.7% for the OE+SRS cohort vs 34.8%, 45.5%, 59.0%, and 67.1% for the SRS-only cohort, respectively; subhazard ratio 0.961, p = 0.896) of AVM obliteration were similar between the matched cohorts. The secondary outcomes of the matched cohorts were also similar. Asymptomatic and symptomatic embolization-related complication rates in the matched OE+SRS cohort were 18.9% and 9.4%, respectively.

CONCLUSIONS Pre-SRS AVM embolization with Onyx does not appear to negatively influence outcomes after SRS. These analyses, based on de novo nidal characteristics, thereby refute previous studies that found detrimental effects of Onyx embolization on SRS-induced AVM obliteration. However, given the risks incurred by nidal embolization using Onyx, this neoadjuvant intervention should be used judiciously in multimodal treatment strategies involving SRS for appropriately selected large-volume or angioarchitecturally high-risk AVMs.

Outcomes of stereotactic radiosurgery for hemorrhagic arteriovenous malformations with or without prior resection or embolization

J Neurosurg 135:733–741, 2021

The major concern about ruptured arteriovenous malformations (rAVMs) is recurrent hemorrhage, which tends to preclude stereotactic radiosurgery (SRS) as a therapeutic modality for these brain malformations. In this study, the authors aimed to clarify the role of SRS for rAVM as a stand-alone modality and an adjunct for a remnant nidus after surgery or embolization.

METHODS Data on 410 consecutive patients with rAVMs treated with SRS were analyzed. The patients were classified into groups, according to prior interventions: SRS-alone, surgery and SRS (Surg-SRS), and embolization and SRS (Embol- SRS) groups. The outcomes of the SRS-alone group were analyzed in comparison with those of the other two groups.

RESULTS The obliteration rate was higher in the Surg-SRS group than in the SRS-alone group (5-year cumulative rate 97% vs 79%, p < 0.001), whereas no significant difference was observed between the Embol-SRS and SRS-alone groups. Prior resection (HR 1.78, 95% CI 1.30–2.43, p < 0.001), a maximum AVM diameter ≤ 20 mm (HR 1.81, 95% CI 1.43–2.30, p < 0.001), and a prescription dose ≥ 20 Gy (HR 2.04, 95% CI 1.28–3.27, p = 0.003) were associated with a better obliteration rate, as demonstrated by multivariate Cox proportional hazards analyses. In the SRS-alone group, the annual post-SRS hemorrhage rates were 1.5% within 5 years and 0.2% thereafter and the 10-year significant neurological event–free rate was 95%; no intergroup difference was observed in either outcome. The exclusive performance of SRS (SRS alone) was not a risk for post-SRS hemorrhage or for significant neurological events based on multivariate analyses. These results were also confirmed with propensity score–matched analyses.

CONCLUSIONS The treatment strategy for rAVMs should be tailored with due consideration of multiple factors associated with the patients. Stand-alone SRS is effective for hemorrhagic AVMs, and the risk of post-SRS hemorrhage was low. SRS can also be favorably used for residual AVMs after initial interventions, especially after failed resection.

Surgery versus radiosurgery for facial nerve schwannoma

J Neurosurg 135:542–553, 2021

Intracranial facial nerve schwannomas (FNS) requiring treatment are frequently recommended for surgery or stereotactic radiosurgery (SRS). The objective of this study was to compare facial nerve function outcomes between these two interventions for FNS via a systematic review and meta-analysis.

METHODS A search of the Ovid EMBASE, PubMed, SCOPUS, and Cochrane databases from inception to July 2019 was conducted following PRISMA guidelines. Articles were screened against prespecified criteria. Facial nerve out- comes were classified as improved, stabilized, or worsened by last follow-up. Incidence was pooled by random-effects meta-analysis of proportions.

RESULTS Thirty-three articles with a pooled cohort of 519 patients with FNS satisfied all criteria. Twenty-five articles described operative outcomes in 407 (78%) patients; 10 articles reported SRS outcomes in 112 (22%). In the surgical cohort, facial nerve function improved in 23% (95% CI 15%–32%), stabilized in 41% (95% CI 32%–50%), and worsened in 30% (95% CI 21%–40%). In the SRS cohort, facial nerve function was improved in 20% (95% CI 9%–34%), stable in 66% (95% CI 54%–78%), and worsened in 9% (95% CI 3%–16%). Compared with SRS, microsurgery was associated with a significantly lower incidence of stable facial nerve function (p < 0.01) and a significantly higher incidence of wors- ened facial nerve function (p < 0.01). Tumor progression and complication rates were comparable. Outcome certainty assessments were very low to moderate for all parameters.

CONCLUSIONS Unfavorable facial nerve function outcomes are associated with surgical treatment of intracranial FNS, whereas stable facial nerve function outcomes are associated with SRS. Therefore, SRS should be recommended to patients with FNS who require treatment, and surgery should be reserved for patients with another indication, such as decompression of the brainstem. Further study is required to definitively optimize and validate management strategies for these rare skull base tumors.

Gamma Knife central lateral thalamotomy for the treatment of neuropathic pain

J Neurosurg 135:228–236, 2021

The goal of this study was to assess the safety and efficacy of stereotactic central lateral thalamotomy with Gamma Knife radiosurgery in patients with neuropathic pain.

METHODS Clinical and radiosurgical data were prospectively collected and analyzed in patients with neuropathic pain who underwent Gamma Knife central lateral thalamotomy. The safety and efficacy of the lesioning procedure were evaluated by neurological examination and standardized scales for pain intensity and health-related quality of life. Visual analog scale (VAS) for pain, McGill Pain Questionnaire (MPQ), EuroQol–5 dimensions (EQ-5D), and the 36-Item Short Form Health Survey, version 2 (SF-36v2) were measured during baseline and postoperative follow-up evaluations at 3, 6, 12, 24, and 36 months.

RESULTS Eight patients with neuropathic pain underwent Gamma Knife central lateral thalamotomy. Four patients suffered from trigeminal deafferentation pain, 2 from brachial plexus injury, 1 from central poststroke facial neuropathic pain, and 1 from postherpetic neuralgia. No lesioning-related adverse effect was recorded during the follow-up periods. All patients had pain reduction following thalamotomy. The mean follow-up time was 24 months. At the last follow-up visits, 5 patients reported ≥ 50% VAS pain reduction. The overall mean VAS pain score was 9.4 (range 8–10) before radiosurgery. After 1 year, the mean VAS pain score decreased significantly, from 9.4 (range 8–10) to 5.5 (mean -41.33%, p = 0.01). MPQ scores significantly decreased (mean -22.18%, p = 0.014). Statistically significant improvements of the SF-36v2 quality of life survey (mean +48.16%, p = 0.012) and EQ-5D (+45.16%, p = 0.012) were observed. At 2 years after radiosurgery, the VAS pain score remained significantly reduced to a mean value of 5.5 (p = 0.027). Statistically significant improvements were also observed for the MPQ (mean -16.05%, p = 0.034); the EQ-5D (mean +35.48%, p = 0.028); and the SF-36v2 (mean +35.84%, p = 0.043). At the last follow-up visits, pain had recurred in 2 patients, who were suffering from central poststroke neuropathic pain and brachial plexus injury, respectively.

CONCLUSIONS Safe, nonpharmacological therapies are imperative for the management of refectory chronic pain conditions. The present series demonstrates that Gamma Knife central lateral thalamotomy is safe and potentially effective in the long term for relieving chronic neuropathic pain refractory to pharmacotherapy and for restoring quality of life.


Results of a third Gamma Knife radiosurgery for trigeminal neuralgia

J Neurosurg 134:1237–1243, 2021

Gamma Knife radiosurgery (GKRS) is a commonly used procedure for medically refractory trigeminal neuralgia (TN), with repeat GKRS routinely done in cases of pain relapse. The results of a third GKRS in cases of further pain relapse have not been well described. In this study, the authors report the largest series of patients treated with a third GKRS for TN to date.

METHODS Retrospective review of institutional electronic medical records and a GKRS database was performed to identify patients who had been treated with a third GKRS at the authors’ institution in the period from 2010 to 2018. Telephone interviews were used to collect long-term follow-up data. Pain outcomes were measured using the Barrow Neurological Institute (BNI) pain intensity scale, with a score ≤ IIIb indicating successful treatment.

RESULTS Twenty-two nerves in 21 patients had sufficient follow-up to determine BNI pain score outcomes. Eighteen of 22 cases had a successful third GKRS, with a median durability of pain relief of 3.88 years. There was no significant difference in the durability of pain relief after a third GKRS compared with those of institutional historical controls of prior series of first and second GKRS procedures. Ten cases had new or worsening facial numbness, with 1 case being bothersome. Four cases of toxicity other than facial numbness were reported, including 1 case of corneal abrasions and possible neurotrophic keratopathy. No cases of anesthesia dolorosa were reported. No factors predicting treatment success or the durability of pain relief were identified. Nonnumbness toxicity was more common in those with a proximally placed shot at the third GKRS.

CONCLUSIONS A third GKRS is an effective treatment option for TN patients who have pain relapse after repeat GKRS. Pain outcomes of a third GKRS are similar to those following a first or second GKRS. Toxicity is tolerable in patients with a distally placed shot at the third GKRS.


The Zap-X Radiosurgical System in the Treatment of Intracranial Tumors

Neurosurgery 88:E351–E355, 2021

The Zap-X system (Zap Surgical Systems Inc, San Carlos, California) is a radically new surgical robot designed for brain and head and neck radiosurgery. It represents the first new dedicated brain stereotactic radiosurgery platform in almost half a century optimizing the goals of safety, speed, and accuracy. The Zap-X system was used in a required Chinese National Medical Products Administration clinical study. In early January 2020, 2 patientswere treatedwith the Zap-X robot prior to a national COVID-19 lockdown. Both were closely followed via clinical exam andmagnetic resonance imaging (MRI) imaging. Prospectively collected data were used to generate this report.

CLINICAL PRESENTATION: Two female patients, each harboring either a trigeminal schwannoma or petroclival meningioma, were treated with the Zap-X robot. Respective tumor volumes were 2.60 and 4.02 cm3. A radiation dose of 13 Gy was prescribed to the 50% isodose line. At 8 mo of follow-up, preoperative symptoms were either resolved or stable and MRI imaging demonstrated a 31% and 56% reduction in lesion volume, respectively. In both patients, symptoms improved, and tumor volumes decreased, whereas no major complication was observed.

CONCLUSION: Given only 2 patients and short-term follow-up, any conclusions about the safety and efficacy of the Zap-X radiosurgery robot are preliminary. However, in the absence of any other published outcomes to date, this small case seriesmay be of interest to many radiosurgical specialists.

Embolization of Brain Arteriovenous Malformations With VersusWithout Onyx Before Stereotactic Radiosurgery

Neurosurgery 88:366–374, 2021

Embolization of brain arteriovenous malformations (AVMs) using ethylene-vinyl alcohol copolymer (Onyx) embolization may influence the treatment effects of stereotactic radiosurgery (SRS) differently than other embolysates.

OBJECTIVE: To compare the outcomes of pre-SRS AVM embolization with vs without Onyx through a multicenter, retrospective matched cohort study.

METHODS: We retrospectively reviewed International Radiosurgery Research Foundation AVM databases from 1987 to 2018. Embolized AVMs treated with SRS were selected and categorized based on embolysate usage into Onyx embolization (OE + SRS) or non-Onyx embolization (NOE + SRS) cohorts. The 2 cohorts were matched in a 1:1 ratio using de novo AVM features for comparative analysis of outcomes.

RESULTS: The matched cohorts each comprised 45 patients. Crude AVM obliteration rates were similar between the matched OE + SRS vs NOE + SRS cohorts (47% vs 51%; odds ratio [OR] = 0.837, P = .673). Cumulative probabilities of obliteration were also similar between the OE + SRS vs NOE + SRS cohorts (subhazard ratio = 0.992, P = .980). Rates of post-SRS hemorrhage, all-cause mortality, radiation-induced changes, cyst formation, and embolization-associated complications were similar between the matched cohorts. Sensitivity analysis for AVMs in the OE + SRS cohort embolized with Onyx alone revealed a higher rate of asymptomatic embolization-associated complications in this subgroup compared to the NOE + SRS cohort (36% vs 15%; OR = 3.297, P = .034), but the symptomatic complication rates were similar.

CONCLUSION: Nidal embolization using Onyx does not appear to differentially impact the outcomes of AVM SRS compared with non-Onyx embolysates. The embolic agent selected for pre-SRS AVM embolization should reflect both the experience of the neurointerven- tionalist and target of endovascular intervention.

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