David Bervini

Validation of the supplemented Spetzler-Martin grading system for brain arteriovenous malformations in a multicenter cohort of 1009 surgical patients

BACKGROUND The supplementary grading system for brain arteriovenous malformations (AVMs) was introduced in 2010 as a tool for improving preoperative risk prediction and selecting surgical patients. OBJECTIVE To demonstrate in this multicenter validation study that supplemented Spetzler-Martin (SM-Supp) grades have greater predictive accuracy than Spetzler-Martin (SM) grades alone. METHODS Data collected from 1009 AVM patients who underwent AVM resection were used to compare the predictive powers of SM and SM-Supp grades. Patients included the original 300 University of California, San Francisco patients plus those treated thereafter (n = 117) and an additional 592 patients from 3 other centers. RESULTS In the combined cohort, the SM-Supp system performed better than SM system alone: area under the receiver-operating characteristics curve (AUROC) = 0.75 (95% confidence interval, 0.71-0.78) for SM-Supp and AUROC = 0.69 (95% confidence interval, 0.65-0.73) for SM (P < .001). Stratified analysis fitting models within 3 different follow-up groupings (<6 months, 6 months-2 years, and >2 years) demonstrated that the SM-Supp system performed better than SM system for both medium (AUROC = 0.71 vs 0.62; P = .003) and long (AUROC = 0.69 vs 0.58; P = .001) follow-up. Patients with SM-Supp grades ≤6 had acceptably low surgical risks (0%-24%), with a significant increase in risk for grades >6 (39%-63%). CONCLUSION This study validates the predictive accuracy of the SM-Supp system in a multicenter cohort. An SM-Supp grade of 6 is a cutoff or boundary for AVM operability. Supplemented grading is currently the best method of estimating neurological outcomes after AVM surgery, and we recommend it as a starting point in the evaluation of AVM operability.

Role of Surgery in the Management of Brain Arteriovenous Malformations Prospective Cohort Study

Background and Purpose— Management of brain arteriovenous malformation (bAVM) is controversial. We have analyzed the largest surgical bAVM cohort for outcome. Methods— Both operated and nonoperated cases were included for analysis. A total of 779 patients with bAVMs were consecutively enrolled between 1989 and 2014. Initial management recommendations were recorded before commencement of treatment. Surgical outcome was prospectively recorded and outcomes assigned at the last follow-up visit using modified Rankin Scale. First, a sensitivity analyses was performed to select a subset of the entire cohort for which the results of surgery could be generalized. Second, from this subset, variables were analyzed for risk of deficit or near miss (intraoperative hemorrhage requiring blood transfusion of ≥2.5 L, hemorrhage in resection bed requiring reoperation, and hemorrhage associated with either digital subtraction angiography or embolization). Results— A total of 7.7% of patients with Spetzler–Ponce classes A and B bAVM had an adverse outcome from surgery leading to a modified Rankin Scale >1. Sensitivity analyses that demonstrated outcome results were not subject to selection bias for Spetzler–Ponce classes A and B bAVMs. Risk factors for adverse outcomes from surgery for these bAVMs include size, presence of deep venous drainage, and eloquent location. Preoperative embolization did not affect the risk of perioperative hemorrhage. Conclusions— Most of the ruptured and unruptured low and middle-grade bAVMs (Spetzler–Ponce A and B) can be surgically treated with a low risk of permanent morbidity and a high likelihood of preventing future hemorrhage. Our results do not apply to Spetzler–Ponce C bAVMs.

Diskogenic microspurs as a major cause of intractable spontaneous intracranial hypotension

Objective: To visualize and treat spinal dural CSF leaks in all patients with intractable spontaneous intracranial hypotension (SIH) who underwent spinal microsurgical exploration. Methods: Patients presenting between February 2013 and July 2015 were included in this consecutive case series. The workup included spinal MRI without and with intrathecal contrast, dynamic myelography, postmyelography CT, and microsurgical exploration. Results: Of 69 consecutive patients, 15 had intractable symptoms. Systematic imaging revealed a suspicious single location of the leak in these 15 patients. Fourteen patients underwent microsurgical exploration; 1 patient refused surgery. Intraoperatively, including intradural exploration, we identified the cause of the CSF leaks as a longitudinal dural slit (6.1 ± 1.7 mm) on the ventral (10), lateral (3), or dorsal (1) aspect of the dura. In 10 patients (71%), a ventral, calcified microspur originating from the intervertebral disk perforated the dura like a knife. Three patients (22%) had a lateral dural tear with an associated spinal meningeal diverticulum, and in 1 patient (7%), a dorsal osteophyte was causal. The microspurs were removed and the dural slits sutured with immediate cessation of CSF leakage. Conclusion: The nature of the CSF leak is a circumscribed longitudinal slit at the ventral, lateral, or dorsal dura mater. An extradural pathology, diskogenic microspurs, was the single cause for all ventral CSF leaks. These findings challenge the notion that CSF leaks in SIH are idiopathic or due to a weak dura. Microsurgery is the treatment of choice in cases with intractable SIH.

Endovascular Treatment of Dural Arteriovenous Fistulas of the Transverse and Sigmoid Sinuses Using Transarterial Balloon-Assisted Embolization Combined with Transvenous Balloon Protection of the Venous Sinus

BACKGROUND AND PURPOSE: Combined transarterial balloon-assisted endovascular embolization with double-lumen balloon microcatheters and concomitant transvenous balloon protection was described as a promising treatment technique for dural arteriovenous fistulae of the transverse and sigmoid sinus. The purpose of this study was to evaluate the technical efficacy and safety of this combined treatment technique. MATERIALS AND METHODS: Nine consecutive patients presenting with dural arteriovenous fistulas of the transverse and sigmoid sinuses underwent combined transarterial and transvenous balloon-assisted endovascular embolization. Prospectively collected data were reviewed to assess the technical success rate, complication rate, and clinical outcome. RESULTS: Six patients presented with clinically symptomatic Borden type I, and 3 patients, with Borden type II dural arteriovenous fistulas of the transverse and sigmoid sinuses (3 men, 6 women; mean age, 50.4 years). Transarterial embolization was performed with a double-lumen balloon with Onyx and concomitant transvenous sinus protection with a dedicated venous remodeling balloon. Complete angiographic occlusion at the latest follow-up (mean, 4.8 months) was achieved in 6 patients, and near-complete occlusion, in 2 patients. Clinical cure or remission of symptoms was obtained in 6 and 2 patients, respectively. One patient with a residual fistula underwent further treatment in which the dural arteriovenous fistula was cured by sinus occlusion. Complete occlusion of the dural arteriovenous fistula was visible on the follow-up angiography after final treatment in 8 patients. One patient refused follow-up angiography but was free of symptoms. There were no immediate or delayed postinterventional complications. CONCLUSIONS: Transarterial balloon-assisted embolization of dural arteriovenous fistulas of the transverse and sigmoid sinuses with combined transvenous balloon protection is safe and offers a high rate of complete dural arteriovenous fistula occlusion and remission of clinical symptoms.

Predictors of In-Hospital Death After Aneurysmal Subarachnoid Hemorrhage: Analysis of a Nationwide Database (Swiss SOS [Swiss Study on Aneurysmal Subarachnoid Hemorrhage])

Background and Purpose— To identify predictors of in-hospital mortality in patients with aneurysmal subarachnoid hemorrhage and to estimate their impact. Methods— Retrospective analysis of prospective data from a nationwide multicenter registry on all aneurysmal subarachnoid hemorrhage cases admitted to a tertiary neurosurgical department in Switzerland (Swiss SOS [Swiss Study on Aneurysmal Subarachnoid Hemorrhage]; 2009–2015). Both clinical and radiological independent predictors of in-hospital mortality were identified, and their effect size was determined by calculating adjusted odds ratios (aORs) using multivariate logistic regression. Survival was displayed using Kaplan–Meier curves. Results— Data of n=1866 aneurysmal subarachnoid hemorrhage patients in the Swiss SOS database were available. In-hospital mortality was 20% (n=373). In n=197 patients (10.6%), active treatment was discontinued after hospital admission (no aneurysm occlusion attempted), and this cohort was excluded from analysis of the main statistical model. In the remaining n=1669 patients, the rate of in-hospital mortality was 13.9% (n=232). Strong independent predictors of in-hospital mortality were rebleeding (aOR, 7.69; 95% confidence interval, 3.00–19.71; P<0.001), cerebral infarction attributable to delayed cerebral ischemia (aOR, 3.66; 95% confidence interval, 1.94–6.89; P<0.001), intraventricular hemorrhage (aOR, 2.65; 95% confidence interval, 1.38–5.09; P=0.003), and new infarction post-treatment (aOR, 2.57; 95% confidence interval, 1.43–4.62; P=0.002). Conclusions— Several—and among them modifiable—factors seem to be associated with in-hospital mortality after aneurysmal subarachnoid hemorrhage. Our data suggest that strategies aiming to reduce the risk of rebleeding are most promising in patients where active treatment is initially pursued. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT03245866.

Results of Surgery for Low-Grade Brain Arteriovenous Malformation Resection by Early Career Neurosurgeons: An Observational Study

BACKGROUND For sustainability of arteriovenous malformation (AVM) surgery, results from early career cerebrovascular neurosurgeons (ECCNs) must be acceptably safe. OBJECTIVE To determine whether ECCNs performance of Spetzler-Ponce Class A AVM (SPC A) resection can be acceptably safe. METHODS ECCNs completing a cerebrovascular fellowship (2004-2015) with the last author were included. Inclusion of the ECCN cases occurred if they: had a prospective database of all AVM cases since commencing independent practice; were the primary surgeon on SPC A; and had made the significant management decisions. All SPC A surgical cases from the beginning of the ECCNs independent surgical practice to a maximum of 8 yr were included. An adverse outcome was considered a complication of surgery leading to a new permanent neurological deficit with a last modified Rankin Scale score >1. A cumulative summation (Cusum) plot examined the performance of each surgery. The highest acceptable level of adverse outcomes for the Cusum was 3.3%, derived from the upper 95% confidence interval of the last authors reported series. RESULTS Six ECCNs contributed 110 cases for analysis. The median number of SPC A cases operated by each ECCN was 16.5 (range 4-40). Preoperative embolization was performed in 5 (4.5%). The incidence of adverse outcomes was 1.8% (95% confidence interval: <0.01%-6.8%). At no point during the accumulated series did the combined cohort become unacceptable by the Cusum plot. CONCLUSION ECCNs with appropriate training appointed to large-volume cerebrovascular centers can achieve results for surgery for SPC A that are not appreciably worse than those published from high-volume neurosurgeons.

The Risk of Seizure After Surgery for Unruptured Intracranial Aneurysms: A Prospective Cohort Study.

BACKGROUND We aimed to identify a group of patients with a low risk of seizure after surgery for unruptured intracranial aneurysms (UIA). OBJECTIVE To determine the risk of seizure after discharge from surgery for UIA. METHODS A consecutive prospectively collected cohort database was interrogated for all surgical UIA cases. There were 726 cases of UIA (excluding cases proximal to the superior cerebellar artery on the vertebrobasilar system) identified and analyzed. Cox proportional hazards regression models and Kaplan-Meier life table analyses were generated assessing risk factors. RESULTS Preoperative seizure history and complication of aneurysm repair were the only risk factors found to be significant. The risk of first seizure after discharge from hospital following surgery for patients with neither preoperative seizure, treated middle cerebral artery aneurysm, nor postoperative complications (leading to a modified Rankin Scale score >1) was <0.1% and 1.1% at 12 months and 7 years, respectively. The risk for those with preoperative seizures was 17.3% and 66% at 12 months and 7 years, respectively. The risk for seizures with either complications (leading to a modified Rankin Scale score >1) from surgery or treated middle cerebral artery aneurysm was 1.4% and 6.8% at 12 months and 7 years, respectively. These differences in the 3 Kaplan-Meier curves were significant (log-rank P < .001). CONCLUSION The risk of seizures after discharge from hospital following surgery for UIA is very low when there is no preexisting history of seizures. If this result can be supported by other series, guidelines that restrict returning to driving because of the risk of postoperative seizures should be reconsidered. ABBREVIATIONS MCA, middle cerebral arterymRS, modified Rankin ScaleUIA, unruptured intracranial aneurysms.

Natural history of brain arteriovenous malformations: systematic review.

INTRODUCTION The appropriate interpretation of natural history of brain arteriovenous malformations (bAVMs) and of factors that negatively affect the risk of future hemorrhage are important when recommending management pathways. With the present systematic review, we aim to provide an overview of the available evidence on natural history of brain arteriovenous malformations (bAVMs), focusing on hemorrhage rates and risk factors for future hemorrhage. EVIDENCE ACQUISITION We performed a systematic literature analysis using the Ovid Medline database, encompassing English language studies (published between 1980 and 2018) reporting the natural history of untreated bAVMs. Annual hemorrhage rates in both unruptured and previously ruptured bAVMs, as well as risk factors for future hemorrhage were extracted for analysis. EVIDENCE SYNTHESIS Eighteen studies with a total of 8418 bAVM-cases could be extracted from the literature. Seventeen studies reported annual hemorrhage rates and ten studies reported risk factors for future hemorrhage. The average annualized hemorrhage rate was 2.2% for unruptured bAVMs and 4.3%, for bAVMs that presented with hemorrhage. Prior hemorrhage and deep AVM location could be identified as most consistently reported risk factors for future hemorrhage. CONCLUSIONS Previously ruptured bAVMs have a higher annual hemorrhage rate than unruptured bAVMs. Deep bAVM location and prior hemorrhage may increase the risk for subsequent hemorrhage.

Bleeding risk of cerebral cavernous malformations in patients on β-blocker medication: a cohort study

OBJECTIVECerebral cavernous malformations (CCMs) are frequently diagnosed vascular malformations of the brain. Although most CCMs are asymptomatic, some can be responsible for intracerebral hemorrhage or seizures. In selected cases, microsurgical resection is the preferred treatment option. Treatment with the unselective β-blocker propranolol has been presumed to stabilize and eventually lead to CCM size regression in a limited number of published case series; however, the underlying mechanism and evidence for this effect remain unclear. The aim of this study was to investigate the risk for CCM-related hemorrhage in patients on long-term β-blocker medication.METHODSA single-center database containing data on patients harboring CCMs was retrospectively interrogated for a time period of 35 years. The database included information about hemorrhage and antihypertensive medication. Descriptive and survival analyses were performed, focusing on the risk of hemorrhage at presentation and during follow-up (first or subsequent hemorrhage) in patients on long-term β-blocker medication versus those who were not. Follow-up was censored at the first occurrence of new hemorrhage, surgery, or the last clinical review. For purposes of this analysis, the β-blocker group was divided into the following main subgroups: any β-blocker, β1-selective β-blocker, and any unselective β-blocker.RESULTSOf 542 CCMs among 408 patients, 81 (14.9%) were under treatment with any β-blocker; 65 (12%) received β1-selective β-blocker, and 16 (3%) received any unselective β-blocker. One hundred thirty-six (25.1%) CCMs presented with hemorrhage at diagnosis. None of the β-blocker groups was associated with a lower risk of hemorrhage at the time of diagnosis in a univariate descriptive analysis (any β-blocker: p = 0.64, β1-selective: p = 0.93, any unselective β-blocker: p = 0.25). Four hundred ninety-six CCMs were followed up after diagnosis and included in the survival analysis, for a total of 1800 lesion-years. Follow-up hemorrhage occurred in 36 (7.3%) CCMs. Neither univariate descriptive nor univariate Cox proportional-hazards regression analysis showed a decreased risk for follow-up hemorrhage under treatment with β-blocker medication (any β-blocker: p = 0.70, HR 1.19, 95% CI 0.49-2.90; β1-selective: p = 0.78, HR 1.15, 95% CI 0.44-3.00; any unselective β-blocker: p = 0.76, HR 1.37, 95% CI 0.19-10.08). Multivariate Cox proportional-hazards regression analysis including brainstem location, hemorrhage at diagnosis, age, and any β-blocker treatment showed no reduced risk for follow-up hemorrhage under any β-blocker treatment (p = 0.53, HR 1.36, 95% CI 0.52-3.56).CONCLUSIONSIn this retrospective cohort study, β-blocker medication does not seem to be associated with a decreased risk of CCM-related hemorrhage at presentation or during follow-up.

Antithrombotic medication and bleeding risk in patients with cerebral cavernous malformations: a cohort study

OBJECTIVECerebral cavernous malformations (CCMs) are frequently diagnosed vascular abnormalities. The hemorrhagic risk associated with the use of long-term antithrombotic medication (ATM) in patients with CCMs is a matter of controversy. The aim of this study was to determine the hemorrhagic risk associated with ATM use in patients diagnosed with one or more CCMs.METHODSDemographic, clinical, treatment, and ATM-related information on patients diagnosed with one or more CCMs at a single institution over more than 34 years was retrospectively recorded. Univariate and multivariate descriptive and survival analyses were used to assess potential risk factors associated with CCM-related hemorrhage at presentation and during follow-up (first or subsequent hemorrhage).RESULTSA total of 408 patients were included in the analysis and 492 CCMs were followed up after diagnosis, for a total of 1616 lesion-years. Thirty-seven (7.5%) CCMs bled during follow-up, leading to an overall annual rate of CCM-related symptomatic hemorrhage of 2.3% (95% CI 1.7%-3.2%). Eighty-two patients harboring 91 CCMs (16.8%) were on ATM. When stratified for ATM, the annual rates of hemorrhage were 0.7% (95% CI < 0.01% to 4.2%) for the lesions in patients on ATM versus 2.5% (95% CI 1.8%-3.4%) for those not on ATM. ATM was not found to be associated with either an increased risk of CCM-related hemorrhage at presentation (p = 0.355) or an increased risk of CCM-related hemorrhage (first or subsequent hemorrhage) in multivariate descriptive (p = 0.912) and survival (p = 0.145) analyses.CONCLUSIONSThe use of ATM does not seem to be associated with an increased risk of hemorrhage in patients diagnosed with CCMs.