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.

Microsurgery versus Microsurgery With Preoperative Embolization for Brain Arteriovenous Malformation Treatment: A Systematic Review and Meta-analysis

Neurosurgery 92:27–41, 2023

Preoperative embolization has traditionally been regarded as a safe and effective adjunct to microsurgical treatment of brain arteriovenous malformations (bAVM). However, there is currently no high-level evidence to ascertain this presumption.

OBJECTIVE: To compare the outcomes of microsurgery (MS) vs microsurgery with preoperative embolization (E + MS) in patients with bAVM through systematic review.

METHODS: We searched MEDLINE, PubMed, and Embase. The primary outcome was bAVM obliteration. Secondary outcomes were intraoperative bleeding (mL), complications, worsened modified Rankin Scale (mRS), and mortality. The pooled proportions of outcomes were calculated through the logit transformation method. The odds ratio (OR) of categorical data and mean difference of continuous data were estimated through the Mantel-Haenszel and the inverse variance methods, respectively.

RESULTS: Thirty-two studies met the eligibility criteria. One thousand eight hundred twenty-eight patients were treated by microsurgery alone, and 1088 were treated by microsurgery with preoperative embolization, respectively. The meta-analysis revealed no significant difference in AVM obliteration (94.1% vs 95.6%, OR = 1.15 [0.63-2.11], P = .65), mortality (1.7% vs 2%, OR = 0.88 [0.30-2.58], P = .82), procedural complications (18.2% vs 27.2%, OR = 0.47 [0.19-1.17], P = .10), worsened mRS (21.2% vs 18.5%, OR = 1.08 [0.33-3.54], P = .9), and intraoperative blood loss (mean difference = 182.89 [À87.76, 453.55], P = .19).

CONCLUSION: The meta-analysis showed no significant difference in AVM obliteration, mortality, complications, worse mRS, and intraoperative blood loss between MS and E + MS groups. For AVMs where MS alone has acceptable results, it is reasonable to bypass unnecessary preoperative embolization given higher postoperative complication risk.

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.

Intermediate-grade brain arteriovenous malformations and the boundary of operability using the supplemented Spetzler-Martin grading system

J Neurosurg 136:125–133, 2022

Supplemented Spetzler-Martin grading (Supp-SM), which is the combination of Spetzler-Martin and Lawton-Young grades, was validated as being more accurate than stand-alone Spetzler-Martin grading, but an operability cutoff was not established. In this study, the authors surgically treated intermediate-grade AVMs to provide prognostic factors for neurological outcomes and to define AVMs at the boundary of operability.

METHODS Surgically treated Supp-SM intermediate-grade (5, 6, and 7) AVMs were analyzed from 2011 to 2018 at two medical centers. Worsened neurological outcomes were defined as increased modified Rankin Scale (mRS) scores on postoperative examinations. A second analysis of 2000–2011 data for Supp-SM grade 6 and 7 AVMs was performed to determine the subtypes with improved or unchanged outcomes. Patients were separated into three groups based on nidus size (S1: < 3 cm, S2: 3–6 cm, S3: > 6 cm) and age (A1: < 20 years, A2: 20–40 years, A3: > 40 years), followed by any combination of the combined supplemented grade: low risk (S1A1, S1A2, S2A1), intermediate risk (S2A2, S1A3, S3A1, or high risk (S3A3, S3A2, S2A3).

RESULTS Two hundred forty-six patients had intermediate Supp-SM grade AVMs. Of these patients, 102 had Supp-SM grade 5 (41.5%), 99 had Supp-SM grade 6 (40.2%), and 45 had Supp-SM grade 7 (18.3%). Significant differences in the proportions of patients with worse mRS scores at follow-up were found between the groups, with 24.5% (25/102) of patients in Supp-SM grade 5, 29.3% (29/99) in Supp-SM grade 6, and 57.8% (26/45) in Supp-SM grade 7 (p < 0.001). Patients with Supp-SM grade 7 AVMs had significantly increased odds of worse postoperative mRS scores (p < 0.001; OR 3.7, 95% CI 1.9–7.3). In the expanded cohort of 349 Supp-SM grade 6 AVM patients, a significantly higher proportion of older patients with larger Supp-SM grade 6 AVMs (grade 6+, 38.6%) had neurological deterioration than the others with Supp-SM grade 6 AVMs (22.9%, p = 0.02). Conversely, in an expanded cohort of 197 Supp-SM grade 7 AVM patients, a significantly lower proportion of younger patients with smaller Supp-SM grade 7 AVMs (grade 7–, 19%) had neurological deterioration than the others with Supp-SM grade 7 AVMs (44.9%, p = 0.01).

CONCLUSIONS Patients with Supp-SM grade 7 AVMs are at increased risk of worse postoperative neurological outcomes, making Supp-SM grade 6 an appropriate operability cutoff. However, young patients with small niduses in the low-risk Supp-SM grade 7 group (grade 7−) have favorable postoperative outcomes. Outcomes in Supp-SM grade 7 patients did not improve with surgeon experience, indicating that the operability boundary is a hard limit reflecting the complexity of high-grade AVMs.

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.

Spetzler-Martin Grade III Arteriovenous Malformations: A Multicenter Propensity-Adjusted Analysis of the Effects of Preoperative Embolization

Neurosurgery 88:996–1002, 2021

Spetzler-Martin (SM) grade III arteriovenous malformations (AVMs) are at the boundary of safe operability, and preoperative embolizationmay reduce surgical risks.

OBJECTIVE: To evaluate the benefits of preoperative AVM embolization by comparing neurological outcomes in patients with grade III AVMs treated with or without preoperative embolization.

METHODS: All microsurgically treated grade III AVMs were identified from 2011 to 2018 at 2medical centers. Neurological outcomes,measured as final modified Rankin Scale scores (mRS) and changes in mRS from preoperative baseline to last follow-up evaluation, were compared in patients with and without preoperative embolization.

RESULTS: Of the 102 patients with grade III AVMs who were treated microsurgically, 57 (56%) underwent preoperative embolization. Significant differences were found between the patients with and without embolization in AVM eloquence (74% vs 93%, P = .02), size ≥ 3 cm (47% vs 73%, P = .01), diffuseness (7% vs 22%, P = .04), and mean final mRS (1.1 vs 2.0, P = .005). Poor outcomes were more frequent in patients without embolization (38%) than with embolization (7%) (final mRS > 2; P < .001). Propensityadjusted analysis revealed AVM resection without embolization was a risk factor for poor outcome (mRS score > 2; odds ratio, 4.2; 95% CI, 1.1-16; P = .03).

CONCLUSION: Nonembolization of SM grade III AVMs is associated with an increased risk of poor neurological outcomes after microsurgical resection. Preoperative embolization of intermediate-grade AVMs selected because of large AVM size, surgical inaccessibility of feeding arteries, and high flow should be employed more often than anticipated, even in the context of increasing microsurgical experience with AVMs.

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.

Stereotactic Radiosurgery With Versus Without Embolization for Brain ArteriovenousMalformations

Neurosurgery 88(2) 2021: 313–321

Prior comparisons of brain arteriovenous malformations (AVMs) treated using stereotactic radiosurgery (SRS) with or without embolization were inherently flawed, due to differences in the pretreatment nidus volumes.

OBJECTIVE: To compare the outcomes of embolization and SRS, vs SRS alone for AVMs using pre-embolization malformation features.

METHODS: We retrospectively reviewed International Radiosurgery Research Foundation AVM databases from 1987 to 2018. Patients were categorized into the embolization and SRS (E + SRS) or SRS alone (SRS-only) cohorts. The 2 cohorts were matched in a 1:1 ratio using propensity scores. Primary outcome was defined as AVM obliteration. Secondary outcomes were post-SRS hemorrhage, all-cause mortality, radiologic and symptomatic radiation-induced changes (RIC), and cyst formation.

RESULTS: The matched cohorts each comprised 101 patients. Crude AVM obliteration rates were similar between the matched E + SRS vs SRS-only cohorts (48.5% vs 54.5%; odds ratio = 0.788, P = .399). Cumulative probabilities of obliteration at 3, 4, 5, and 6 yr were also similar between the E + SRS (33.0%, 46.4%, 56.2%, and 60.8%, respectively) and SRSonly (32.9%, 46.2%, 56.0%, and 60.6%, respectively) cohorts (subhazard ratio (SHR)=1.005, P = .981). Cumulative probabilities of radiologic RIC at 3, 4, 5, and 6 yr were lower in the E + SRS (25.0%, 25.7%, 26.7%, and 26.7%, respectively) vs SRS-only (45.3%, 46.2%, 47.8%, and 47.8%, respectively) cohort (SHR = 0.478, P = .004). Symptomatic and asymptomatic embolization-related complication rates were 8.3% and 18.6%, respectively. Rates of post- SRS hemorrhage, all-cause mortality, symptomatic RIC, and cyst formation were similar between the matched cohorts.

CONCLUSION: This study refutes the prevalent notion that AVM embolization negatively affects the likelihood of obliteration after SRS.

Design and Physical Properties of 3-Dimensional Printed Models Used for Neurointervention

Neurosurgery DOI:10.1093/neuros/nyaa134

Three-dimensional (3D) printing has revolutionized training, education, and device testing. Understanding the design and physical properties of 3D-printed models is important.

OBJECTIVE: To systematically review the design, physical properties, accuracy, and experimental outcomes of 3D-printed vascular models used in neurointervention.

METHODS: We conducted a systematic review of the literature between January 1, 2000 and September 30, 2018. Public/Publisher MEDLINE (PubMed), Web of Science, Compendex, Cochrane, and Inspec databases were searched using Medical Subject Heading terms for design and physical attributes of 3D-printed models for neurointervention. Information on design and physical properties like compliance, lubricity, flow system, accuracy, and outcome measures were collected.

RESULTS: A total of 23 articles were included. Nine studies described 3D-printed models for stroke intervention. Tango Plus (Stratasys) was the most common material used to develop these models. Four studies described a population-representative geometry model. All other studies reported patient-specific vascular geometry. Eight studies reported complete reconstruction of the circle of Willis, anterior, and posterior circulation. Four studies reported a model with extracranial vasculature. One prototype study reported compliance and lubricity. Reported circulation systems included manual flushing, programmable pistons, peristaltic, and pulsatile pumps. Outcomes included thrombolysis in cerebral infarction, post-thrombectomy flow restoration, surgical performance, and qualitative feedback.

CONCLUSION: Variations exist in the material, design, and extent of reconstruction of vasculature of 3D-printed models. There is a need for objective characterization of 3D-printed vascular models. We propose the development of population representative 3D-printed models for skill improvement or device testing.

Stereotactic Radiosurgery for Spetzler-Martin Grade I and II Arteriovenous Malformations: International Society of Stereotactic Radiosurgery (ISRS) Practice Guideline

Neurosurgery 87:442–452, 2020

No guidelines have been published regarding stereotactic radiosurgery (SRS) in the management of Spetzler-Martin grade I and II arteriovenous malformations (AVMs).

OBJECTIVE: To establish SRS practice guidelines for grade I-II AVMs on the basis of a systematic literature review.

METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant search of Medline, Embase, and Scopus, 1986-2018, for publications reporting post-SRS outcomes in ≥ 10 grade I-II AVMs with a follow-up of ≥ 24 mo. Primary endpoints were obliteration and hemorrhage; secondary outcomes included SpetzlerMartin parameters, dosimetric variables, and “excellent” outcomes (defined as total obliteration without new post-SRS deficit).

RESULTS: Of 447 abstracts screened, 8 were included (n = 1, level 2 evidence; n = 7, level 4 evidence), representing 1102 AVMs, of which 836 (76%) were grade II. Obliteration was achieved in 884 (80%) at a median of 37 mo; 66 hemorrhages (6%) occurred during a median follow-up of 68 mo. Total obliteration without hemorrhage was achieved in 78%. Of 836 grade II AVMs, Spetzler-Martin parameters were reported in 680: 377 were eloquent brain and 178 had deep venous drainage, totaling 555/680 (82%) high-risk SRS-treated grade II AVMs.

CONCLUSION: The literature regarding SRS for grade I-II AVM is low quality, limiting interpretation. Cautiously, we observed that SRS appears to be a safe, effective treatment for grade I-II AVM and may be considered a front-line treatment, particularly for lesions in deep or eloquent locations. Preceding publications may be influenced by selection bias, with favorable AVMs undergoing resection, whereas those at increased risk of complications and nonobliteration are disproportionately referred for SRS.

Incidence of Spontaneous Obliteration in Untreated Brain Arteriovenous Malformations

Neurosurgery 86:139–149, 2020

Spontaneous obliteration (SpO) of untreated arteriovenous malformations (AVMs) is rare with fewer than 100 cases reported. The incidence and predisposing factors of SpO remain unclear, impeding our understanding of lesion progression in untreated patients.

OBJECTIVE: To determine the incidence rate and predisposing factors of SpO in a North American cohort.

METHODS: AVMswere retrospectively evaluated at our institution for over 25 yr.Untreated AVMs were divided into 2 groups: SpO-AVMs and non-SpO-AVMs. All statistical results were based on univariate analyses. Incidence was generated from counts of SpO over the untreated interval in patient years frombirth until obliteration, treatment, or last follow-up.

RESULTS: One hundred fifty-four patients had untreated AVMs; SpO was observed in 4. Average ages were 49.0 ± 23.6 and 48.7 ± 20.4 yr in the SpO-AVM and non-SpO-AVM group, respectively (P=.98). Average AVMsizeswere 2.0±1.8 cm(SpO-AVMs) and 3.7±2.6 cm (non-SpO-AVMs, P= .25). All SpO-AVMs and 40 (27.0%) non-SpO-AVMs had a ruptured presentation (P=.006). A single draining veinwas observed in all SpO-AVMs and 39 (32.8%) non-SpO-AVMs (P=.01). Deep venous drainage was not observed in any SpO-AVMs, but in 81 (57.9%) non-SpO-AVMs (P = .04). Mean follow-up time was 37.0 ± 42.6 and 75.6 ± 161.7 mo in SpO-AVMand non-SpO-AVMs patients, respectively. Of the 2 SpO-AVMpatientswith postobliteration follow-up, 1 experienced recanalization. From a 672-patient cohort, the incidence of SpO over 28 961 patient years was 0.014%.

CONCLUSION: SpO-AVMs have an annual incidence rate of approximately 0.014% and tend to present with rupture, a single draining vein, and superficial venous drainage. Expectation of SpO for untreated AVMs is not justified, and patients should anticipate life-long hemorrhagic risk for untreated AVMs.

Risk of First Hemorrhage of Brain Arteriovenous Malformations During Pregnancy

Neurosurgery 85:E806–E814, 2019

Recommendations on the management of brain arteriovenous malformations (bAVM) with respect to pregnancy are based upon conflicting literature.

OBJECTIVE: To systematically review the reported risk and annualized rate of first intracranial hemorrhage (ICH) from bAVM during pregnancy and puerperium.

METHODS: MEDLINE, EMBASE, and Scopus databases were searched for relevant articles in English published before April 2018. Studies providing a quantitative risk of ICH in bAVM during pregnancy were eligible.

RESULTS: From 7 initially eligible studies, 3 studies met the criteria for providing quanti- tative risk of first ICH bAVM during pregnancy. Data from 47 bAVM ICH during pregnancy across 4 cohorts were extracted for analysis. Due to differences in methodology and defini- tions of exposure period, it was not appropriate to combine the cases. The annualized risk of first ICH during pregnancy for these 4 cohorts was 3.0% (95% confidence interval [CI]: 1.7- 5.2%); 3.5% (95% CI: 2.4-4.5%); 8.6% (95% CI: 1.8-25%); and 30% (95% CI: 18-49%). Only the last result from the last cohort could be considered significantly increased in comparison with the nonpregnant period (relative rate 6.8, 95% CI: 3.6-13). The limited number of eligible studies and variability in results highlighted the need for enhanced rigor of future research.

CONCLUSION: There is no conclusive evidence of an increased risk of first hemorrhage during pregnancy from bAVM. Because advice to women with bAVM may influence the management of pregnancy or bAVM with significant consequences, we believe that a retrospective multicenter, case crossover study is urgently required.

Prospective validation of a molecular prognostication panel for clival chordoma

J Neurosurg 130:1528–1537, 2019

There are currently no reliable means to predict the wide variability in behavior of clival chordoma so as to guide clinical decision-making and patient education. Furthermore, there is no method of predicting a tumor’s response to radiation therapy.

METHODS A molecular prognostication panel, consisting of fluorescence in situ hybridization (FISH) of the chromosomal loci 1p36 and 9p21, as well as immunohistochemistry for Ki-67, was prospectively evaluated in 105 clival chordoma samples from November 2007 to April 2016. The results were correlated with overall progression-free survival after surgery (PFSS), as well as progression-free survival after radiotherapy (PFSR).

RESULTS Although Ki-67 and the percentages of tumor cells with 1q25 hyperploidy, 1p36 deletions, and homozygous 9p21 deletions were all found to be predictive of PFSS and PFSR in univariate analyses, only 1p36 deletions and homozygous 9p21 deletions were shown to be independently predictive in a multivariate analysis. Using a prognostication calculator formulated by a separate multivariate Cox model, two 1p36 deletion strata (0%–15% and > 15% deleted tumor cells) and three 9p21 homozygous deletion strata (0%–3%, 4%–24%, and ≥ 25% deleted tumor cells) accounted for a range of cumulative hazard ratios of 1 to 56.1 for PFSS and 1 to 75.6 for PFSR.

CONCLUSIONS Homozygous 9p21 deletions and 1p36 deletions are independent prognostic factors in clival chordoma and can account for a wide spectrum of overall PFSS and PFSR. This panel can be used to guide management after resection of clival chordomas.


Contralateral posterior interhemispheric approach to deep medial parietooccipital vascular malformations

J Neurosurg 129:198–204, 2018

Deep medial parietooccipital arteriovenous malformations (AVMs) and cerebral cavernous malformations (CCMs) are traditionally resected through an ipsilateral posterior interhemispheric approach (IPIA), which creates a deep, perpendicular perspective with limited access to the lateral margins of the lesion. The contralateral posterior interhemispheric approach (CPIA) flips the positioning, with the midline positioned horizontally for retraction due to gravity, but with the AVM on the upper side and the approach from the contralateral, lower side. The aim of this paper was to analyze whether the perpendicular angle of attack that is used in IPIA would convert to a parallel angle of attack with the CPIA, with less retraction, improved working angles, and no significant increase in risk.

METHODS A retrospective review of pre- and postoperative clinical and radiographic data was performed in 8 patients who underwent a CPIA.

RESULTS Three AVMs and 5 CCMs were resected using the CPIA, with an average nidus size of 2.3 cm and CCM diameter of 1.7 cm. All lesions were resected completely, as confirmed on postoperative catheter angiography or MRI. All patients had good neurological outcomes, with either stable or improved modified Rankin Scale scores at last follow-up.

CONCLUSIONS The CPIA is a safe alternative approach to the IPIA for deep medial parietooccipital vascular malformations that extend 2 cm or more off the midline. Contralaterality and retraction due to gravity optimize the interhemispheric corridor, the surgical trajectory to the lesion, and the visualization of the lateral margin, without resection or retraction of adjacent normal cortex. Although the falx is a physical barrier to accessing the lesion, it stabilizes the ipsilateral hemisphere while gravity delivers the dissected lesion through the transfalcine window. Patient positioning, CSF drainage, venous preservation, and meticulous dissection of the deep margins are critical to the safety of this approach.

Stereotactic radiosurgery alone or combined with embolization for brain arteriovenous malformations

J Neurosurg 128:1338–1348, 2018

Embolization of brain arteriovenous malformations (AVMs) prior to stereotactic radiosurgery (SRS) has been reported to negatively affect obliteration rates. The goal of this systematic review and meta-analysis was to compare the outcomes of AVMs treated with embolization plus SRS (E+SRS group) and those of AVMs treated with SRS alone (SRS group).

METHODS A literature review was performed using PubMed to identify studies with 10 or more AVM patients and obliteration data for both E+SRS and SRS groups. A meta-analysis was performed to compare obliteration rates between the E+SRS and SRS groups.

RESULTS Twelve articles comprising 1716 patients were eligible for analysis. Among the patients with radiological follow-up data, complete obliteration was achieved in 48.4% of patients (330/681) in the E+SRS group compared with 62.7% of patients (613/978) in the SRS group. A meta-analysis of the pooled data revealed that the obliteration rate was significantly lower in the E+SRS group (OR 0.51, 95% CI 0.41–0.64, p < 0.00001). Symptomatic adverse radiation effects were observed in 6.6% (27/412 patients) and 11.1% (48/433 patients) of the E+SRS and SRS groups, respectively. The annual post-SRS hemorrhage rate was 2.0%–6.5% and 0%–2.0% for the E+SRS and SRS groups, respectively. The rates of permanent morbidity were 0%–6.7% and 0%–13.5% for the E+SRS and SRS groups, respectively.

CONCLUSIONS Arteriovenous malformation treatment with combined embolization and SRS is associated with lower obliteration rates than those with SRS treatment alone. However, this comparison does not fully account for differences in the initial AVM characteristics in the E+SRS group as compared with those in the SRS group. Further studies are warranted to address these limitations.

Delayed treatment of ruptured brain AVMs: is it ok to wait?

J Neurosurg 128:999–1005, 2018

Despite a hemorrhagic presentation, many patients with arteriovenous malformations (AVMs) do not require emergency resection. The timing of definitive management is not standardized in the cerebrovascular community. This study was designed to evaluate the safety of delaying AVM treatment in clinically stable patients with a new hemorrhagic presentation. The authors examined the rate of rehemorrhage or neurological decline in a cohort of patients with ruptured brain AVMs during a period of time posthemorrhage.

METHODS Patients presenting to the authors’ institution from January 2000 to December 2015 with ruptured brain AVMs treated at least 4 weeks posthemorrhage were included in this analysis. Exclusion criteria were ruptured AVMs that required emergency surgery involving resection of the AVM, prior treatment of AVM at another institution, or treatment of lesions within 4 weeks for other reasons (subacute surgery). The primary outcome measure was time from initial hemorrhage to treatment failure (defined as rehemorrhage or neurological decline as a direct result of the AVM). Patientdays were calculated from the day of initial rupture until the day AVM treatment was initiated or treatment failed.

RESULTS Of 102 ruptured AVMs in 102 patients meeting inclusion criteria, 7 (6.9%) failed the treatment paradigm. Six patients (5.8%) had a new hemorrhage within a median of 248 days (interquartile range 33–1364 days). The total “at risk” period was 18,740 patient-days, yielding a rehemorrhage rate of 11.5% per patient-year, or 0.96% per patient-month. Twelve (11.8%) of 102 patients were found to have an associated aneurysm. In this group there was a single (8.3%) new hemorrhage during a total at-risk period of 263 patient-days until the aneurysm was secured, yielding a rehemorrhage risk of 11.4% per patient-month.

CONCLUSIONS It is the authors’ practice to rehabilitate patients after brain AVM rupture with a plan for elective treatment of the AVM. The present data are useful in that the findings quantify the risk of the authors’ treatment strategy. These findings indicate that delaying intervention for at least 4 weeks after the initial hemorrhage subjects the patient to a low (< 1%) risk of rehemorrhage. The authors modified the treatment paradigm when a high-risk feature, such as an associated intracranial aneurysm, was identified.

ABC/2 Method Does not Accurately Predict Cerebral Arteriovenous Malformation Volume

Neurosurgery 82:220–225, 2018

Stereotactic radiosurgery (SRS) is a treatment option for cerebral arteriovenous malformations (AVMs) to prevent intracranial hemorrhage. The decision to proceed with SRS is usually based on calculated nidal volume. Physicians commonly use the ABC/2 formula, based on digital subtraction angiography (DSA), when counseling patients for SRS.

OBJECTIVE: To determine whether AVM volume calculated using the ABC/2 method on DSA is accuratewhen compared to the exact volume calculated from thin-cut axial sections used for SRS planning.

METHODS: Retrospective search of neurovascular database to identify AVMs treated with SRS from 1995 to 2015. Maximum nidal diameters in orthogonal planes on DSA images were recorded to determine volume using ABC/2 formula. Nidal target volume was extracted from operative reports of SRS. Volumes were then compared using descriptive statistics and paired t-tests.

RESULTS: Ninety intracranial AVMs were identified. Median volume was 4.96 cm3 [interquartile range (IQR) 1.79-8.85] with SRS planning methods and 6.07 cm3 (IQR 1.3-13.6) with ABC/2 methodology. Moderate correlation was seen between SRS and ABC/2 (r = 0.662; P<.001). Paired sample t-tests revealed significant differences between SRS volume and ABC/2 (t = –3.2; P = .002). When AVMs were dichotomized based on ABC/2 volume, significant differences remained (t = 3.1, P = .003 for ABC/2 volume < 7 cm3; t = –4.4, P < .001 for ABC/2 volume > 7 cm3).

CONCLUSION: The ABC/2 method overestimates cerebral AVM volume when compared to volumetric analysis from SRS planning software. For AVMs > 7 cm3, the overestimation is even greater. SRS planning techniques were also significantly different than values derived from equations for cones and cylinders.

Brainstem arteriovenous malformations: lesion characteristics and treatment outcomes

J Neurosurg 128:126–136, 2018

Brainstem arteriovenous malformations (AVMs) are rare lesions that are difficult to diagnose and treat. They are often more aggressive in their behavior when compared with their supratentorial counterparts. The consequence of a brainstem hemorrhage is often devastating, and many patients are in poor neurological status at presentation. The authors examine the factors associated with angiographically confirmed cure and those affecting management outcomes for these complex lesions.

METHODS This was a retrospective analysis of data gathered from the prospectively maintained Stanford AVM database. Lesions were grouped based on their location in the brainstem (medulla, pons, or midbrain) and the quadrant they occupied. Angiographic cure was dichotomized as completely obliterated or not, and functional outcome was dichotomized as either independent or not independent at last follow-up.

RESULTS Over a 23-year period, 39 lesions were treated. Of these, 3 were located in the medulla, 14 in the pons, and 22 in the midbrain. At presentation, 92% of the patients had hemorrhage, and only 43.6% were functionally independent. Surgery resulted in the best radiographic cure rates, with a morbidity rate of 12.5%. In all, 53% of patients either improved or remained stable after surgery. Absence of residual nidus and female sex correlated with better outcomes.

CONCLUSIONS Brainstem AVMs usually present with hemorrhage. Surgery offers the best chance of cure, either in isolation or in combination with other modalities as appropriate.

Stereotactic Radiosurgery for Brainstem Arteriovenous Malformations

Neurosurgery 81:910–920, 2017

The management of brainstem arteriovenous malformations (bAVMs) is a formidable challenge. bAVMs harbor higher morbidity and mortality compared to other locations.

OBJECTIVE: To review the outcomes following stereotactic radiosurgery (SRS) of bAVMs in a multicenter study.

METHODS: Six medical centers contributed data from 205 patients through the International Gamma Knife Research Foundation. Median age was 32 yr (6-81). Median nidus volume was 1.4 mL (0.1-69 mL). Favorable outcome (FO) was defined as AVM obliteration and no post-treatment hemorrhage or permanent symptomatic radiation-induced complications.

RESULTS: Overall obliteration was reported in 65.4% (n = 134) at a mean follow-up of 69 mo. Obliteration was angiographically proven in 53.2% (n = 109) and on MRA in 12.2% (n=25). Actuarial rate of obliteration at 2, 3, 5, 7, and 10 yr after SRS was 24.5%, 43.3%, 62.3%, 73%, and 81.8% respectively. Patients treated with a margin dose >20 Gy were more likely to achieve obliteration (P = .001). Obliteration occurred earlier in patients who received a higher prescribed margin dose (P = .05) and maximum dose (P = .041). Post-SRS hemorrhage occurred in 8.8% (n = 18). Annual post gamma knife latency period hemorrhage was 1.5%. Radiation-induced complications were radiologically evident in 35.6% (n = 73), symptomatic in 14.6% (n=30), and permanent in 14.6% (n=30, which included long-tract signs and new cranial nerve deficits). FO was achieved in 64.4% (n = 132). Predictors of an FO were a higher Virginia radiosurgery AVM scale score (P = .003), prior hemorrhage (P = .045), and a lower prescribed maximum dose (P = .006).

CONCLUSION: SRS for bAVMs results in obliteration and avoids permanent complications in the majority of patients.

Microsurgery for Spetzler-Ponce Class A and B arteriovenous malformations utilizing an outcome score adopted from Gamma Knife radiosurgery

J Neurosurg 127:1105–1116, 2017

The purpose of this study was to adapt and apply the extended definition of favorable outcome established for Gamma Knife radiosurgery (GKRS) to surgery for brain arteriovenous malformations (bAVMs). The aim was to derive both an error around the point estimate and a model incorporating angioarchitectural features in order to facilitate comparison among different treatments.

METHODS A prospective microsurgical cohort was analyzed. This cohort included patients undergoing embolization who did not proceed to microsurgery and patients denied surgery because of perceived risk of treatment. Data on bAVM residual and recurrence during long-term follow-up as well as complications of surgery and preoperative embolization were analyzed. Patients with Spetzler-Ponce Class C bAVMs were excluded because of extreme selection bias. First, patients with a favorable outcome were identified for both Class A and Class B lesions. Patients were considered to have a favorable outcome if they were free of bAVM recurrence or residual at last follow-up, with no complication of surgery or preoperative embolization, and a modified Rankin Scale score of more than 1 at 12 months after treatment. Patients who were denied surgery because of perceived risk, but would otherwise have been candidates for surgery, were included as not having a favorable outcome. Second, the authors analyzed favorable outcome from microsurgery by means of regression analysis, using as predictors characteristics previously identified to be associated with complications. Third, they created a prediction model of favorable outcome for microsurgery dependent upon angioarchitectural variables derived from the regression analysis.

RESULTS From a cohort of 675 patients who were either treated or denied surgery because of perceived risk of surgery, 562 had Spetzler-Ponce Class A or B bAVMs and were included in the analysis. Logistic regression for favorable outcome found decreasing maximum diameter (continuous, OR 0.62, 95% CI 0.51–0.76), the absence of eloquent location (OR 0.23, 95% CI 0.12–0.43), and the absence of deep venous drainage (OR 0.19, 95% CI 0.10–0.36) to be significant predictors of favorable outcome. These variables are in agreement with previous analyses of microsurgery leading to complications, and the findings support the use of favorable outcome for microsurgery. The model developed for angioarchitectural features predicts a range of favorable outcome at 8 years following microsurgery for Class A bAVMs to be 88%–99%. The same model for Class B bAVMs predicts a range of favorable outcome of 62%–90%.

CONCLUSIONS Favorable outcome, derived from GKRS, can be successfully used for microsurgical cohort series to assist in treatment recommendations. A favorable outcome can be achieved by microsurgery in at least 90% of cases at 8 years following microsurgery for patients with bAVMs smaller than 2.5 cm in maximum diameter and, in the absence of either deep venous drainage or eloquent location, patients with Spetzler-Ponce Class A bAVMs of all diameters. For patients with Class B bAVMs, this rate of favorable outcome can only be approached for lesions with a maximum diameter just above 6 cm or smaller and without deep venous drainage or eloquent location.


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