Intracranial Hemorrhage Rate and Lesion Burden in Patients With Familial Cerebral Cavernous Malformation.

Background Familial cerebral cavernous alformation (CCM) is an autosomal dominant disease caused by mutations in KRIT1, CCM2, or PDCD10. Cases typically present with multiple lesions, strong family history, and neurological symptoms, including seizures, headaches, or other deficits. Intracranial hemorrhage (ICH) is a severe manifestation of CCM, which can lead to death or long-term neurological deficits. Few studies have reported ICH rates and risk factors in familial CCM. We report ICH rates and assess whether CCM lesion burden, a disease severity marker, is associated with risk of symptomatic ICH during follow-up in a well-characterized cohort of familial CCM cases. Methods and Results We studied 386 patients with familial CCM with follow-up data enrolled in the Brain Vascular Malformation Consortium CCM Project. We estimated symptomatic ICH rates overall and stratified by history of ICH before enrollment. CCM lesion burden (total lesion count and large lesion size) assessed at baseline enrollment was tested for association with increased risk of subsequent ICH during follow-up using Cox regression models adjusted for history of ICH before enrollment, age, sex, and family structure and stratified on recruitment site. The symptomatic ICH rate for familial CCM cases was 2.8 per 100 patient-years (95% CI, 1.9-4.1). Those with ICH before enrollment had a follow-up ICH rate of 4.5 per 100 patient-years (95% CI, 2.6-8.1) compared with 2.0 per 100 patient-years (95% CI, 1.3-3.5) in those without (P=0.042). Total lesion count was associated with increased risk of ICH during follow-up (hazard ratio [HR], 1.37 per doubling of total lesion count [95% CI, 1.10-1.71], P=0.006). The symptomatic ICH rate for familial CCM cases was 2.8 per 100 patient-years (95% CI, 1.9-4.1). Those with ICH before enrollment had a follow-up ICH rate of 4.5 per 100 patient-years (95% CI, 2.6-8.1) compared with 2.0 per 100 patient-years (95% CI, 1.3-3.5) in those without (P=0.042). Total lesion count was associated with increased risk of ICH during follow-up (hazard ratio [HR], 1.37 per doubling of total lesion count [95% CI, 1.10-1.71], P=0.006). Conclusions Patients with familial CCM with prior history of an ICH event are at higher risk for rehemorrhage during follow-up. In addition, total CCM lesion burden is significantly associated with increased risk of subsequent symptomatic ICH; hence lesion burden may be an important predictor of patient outcome and aid patient risk stratification.

Safety and patterns of survivorship in recurrent GBM following resection and surgically targeted radiation therapy: Results from a prospective trial.

BACKGROUND: Treatment of recurrent glioblastoma (GBM) remains problematic with survival after additional therapy typically less than 12 months. We prospectively evaluated whether outcomes might be improved with resection plus permanent implantation of a novel radiation device utilizing the gamma-emitting isotope Cs-131 embedded within bioresorbable collagen tiles. METHODS: Recurrent histologic GBM were treated in a single-arm trial. Following radiation, the surgical bed was lined with the tiles. Subsequent treatments were at the treating physician's discretion. RESULTS: 28 patients were treated (20 at first recurrence, range 1-3). Median age was 58 years, KPS was 80, female:male ratio was 10:18. Methylguanine methyltransferase (MGMT) was methylated in 11%, unmethylated in 18%, and unknown in 71%. Post implant, 17 patients (61%) received ≥1 course of systemic therapy. For all patients, Kaplan-Meier estimates of median time to local failure were 12.1 months, post-implant survival was 10.7 months for all patients and 15.1 months for patients who received systemic therapy; for all patients, median overall survival from diagnosis was 25.0 months (range 9.1-143.1). Sex, age, and number of prior progressions were not statistically significant. Local control was continuously maintained in 46% of patients. Two deaths within 30 days occurred, one from intracranial hemorrhage and one after persistent coma. Three symptomatic adverse events occurred: one wound infection requiring surgery and two late radiation brain injury, resolved non-surgically. CONCLUSION: This pre-commercial trial demonstrated acceptable safety and favorable post-treatment local control and survival. The device has received FDA clearance for use in newly diagnosed malignant and all recurrent intracranial neoplasms.

Cost Comparison of Microsurgery vs Endovascular Treatment for Ruptured Intracranial Aneurysms: A Propensity-Adjusted Analysis.

BACKGROUND: In specialized neurosurgical centers, open microsurgery is routinely performed for aneurysmal subarachnoid hemorrhage (aSAH). OBJECTIVE: To compare the cost of endovascular vs microsurgical treatment for aSAH at a single quaternary center. METHODS: All patients undergoing aSAH treatment from July 1, 2014, to July 31, 2019, were retrospectively reviewed. Patients were grouped based on primary treatment (microsurgery vs endovascular treatment). The primary outcome was the difference in total cost (including hospital, discharge facility, and all follow-up) using a propensity-adjusted analysis. RESULTS: Of 384 patients treated for an aSAH, 234 (61%) were microsurgically treated and 150 (39%) were endovascularly treated. The mean cost of index hospitalization for these patients was marginally higher ($9504) for endovascularly treated patients ($103 980) than for microsurgically treated patients ($94 476) ( P = .047). For the subset of patients with follow-up data available, the mean total cost was $45 040 higher for endovascularly treated patients ($159 406, n = 59) than that for microsurgically treated patients ($114 366, n = 105) ( P < .001). After propensity scoring (adjusted for age, sex, comorbidities, Glasgow Coma Scale score, Hunt and Hess grade, Fisher grade, aneurysms, and type/size/location), linear regression analysis of patients with follow-up data available revealed that microsurgery was independently associated with healthcare costs that were $37 244 less than endovascular treatment costs ( P < .001). An itemized cost analysis suggested that this discrepancy was due to differences in the rates of aneurysm retreatment and long-term surveillance. CONCLUSION: Microsurgical treatment for aSAH is associated with lower total healthcare costs than endovascular therapy. Aneurysm surveillance after endovascular treatments, retreatment, and device costs warrants attention in future studies.

The Times They Are a-Changin': Increasing Complexity of Aneurysmal Subarachnoid Hemorrhages in Patients Treated from 2004 to 2018.

BACKGROUND: Nationwide study results have suggested varying trends in the incidence of aneurysmal subarachnoid hemorrhage (aSAH) over time. Herein, trends over time for aSAH treated at a quaternary care center are compared with low-volume hospitals. METHODS: Cases were retrospectively reviewed for patients with aSAH treated at our institution. Trend analyses were performed on the number of aSAH hospitalizations, treatment type, Charlson Comorbidity Index (CCI), Hunt and Hess grade, aneurysm location, aneurysm type, and in-hospital mortality. The National Inpatient Sample (NIS) was queried to compare the CCI scores of our patients with those of patients in low-volume hospitals (<20 aSAH/year) in our census division. RESULTS: Some 1248 patients (321 during 2004-2006; 927 during 2008-2018) hospitalized with aSAH were treated with endovascular therapy (489, 39%) or microsurgery (759, 61%). A significant downtrend in the annual aSAH caseload occurred (123 patients in 2004, 75 in 2018, P < 0.001). A linear uptrend was observed for the mean CCI score of patients (R 2 = 0.539, P < 0.001), with no change to in-hospital mortality (R 2 = 0.220, P = 0.24). Mean (standard deviation) CCI for small-volume hospitals treating aSAH within our division was significantly lower than that of our patient population (1.8 [1.6] vs 2.1 [2.0]) for 2012-2015. CONCLUSIONS: A decreasing number of patients were hospitalized with aSAH throughout the study. Compared with patients with aSAH admitted in 2004, those admitted more recently were sicker in terms of preexisting comorbidity and neurologic complexity. These trends could be attributable to the increasing availability of neurointerventional services at smaller-volume hospitals capable of treating healthier patients.

Saccular aneurysms in the post-Barrow Ruptured Aneurysm Trial era.

OBJECTIVE: The Barrow Ruptured Aneurysm Trial (BRAT) was a single-center trial that compared endovascular coiling to microsurgical clipping in patients treated for aneurysmal subarachnoid hemorrhage (aSAH). However, because patients in the BRAT were treated more than 15 years ago, and because there have been advances since then-particularly in endovascular techniques-the relevance of the BRAT today remains controversial. Some hypothesize that these technical advances may reduce retreatment rates for endovascular intervention. In this study, the authors analyzed data for the post-BRAT (PBRAT) era to compare microsurgical clipping with endovascular embolization (coiling and flow diverters) in the two time periods and to examine how the results of the original BRAT have influenced the practice of neurosurgeons at the study institution. METHODS: In this retrospective cohort study, the authors evaluated patients with saccular aSAHs who were treated at a single quaternary center from August 1, 2007, to July 31, 2019. The saccular aSAH diagnoses were confirmed by cerebrovascular experts. Patients were separated into two cohorts for comparison on the basis of having undergone microsurgery or endovascular intervention. The primary outcome analyzed for comparison was poor neurological outcome, defined as a modified Rankin Scale (mRS) score > 2. The secondary outcomes that were compared included retreatment rates for both therapies. RESULTS: Of the 1014 patients with aSAH during the study period, 798 (79%) were confirmed to have saccular aneurysms. Neurological outcomes at ≥ 1-year follow-up did not differ between patients treated with microsurgery (n = 451) and those who received endovascular (n = 347) treatment (p = 0.51). The number of retreatments was significantly higher among patients treated endovascularly (32/347, 9%) than among patients treated microsurgically (6/451, 1%) (p < 0.001). The retreatment rate after endovascular treatment was lower in the PBRAT era (9%) than in the BRAT (18%). CONCLUSIONS: Similar to results from the BRAT, results from the PBRAT era showed equivalent neurological outcomes and increased rates of retreatment among patients undergoing endovascular embolization compared with those undergoing microsurgery. However, the rate of retreatment after endovascular intervention was much lower in the PBRAT era than in the BRAT.

Treatment of octogenarians and nonagenarians with aneurysmal subarachnoid hemorrhage: a 17-year institutional analysis.

BACKGROUND: Outcomes for octogenarians and nonagenarians after an aneurysmal subarachnoid hemorrhage (aSAH) are particularly ominous, with mortality rates well above 50%. The present analysis examines the neurologic outcomes of patients ≥ 80 years of age treated for aSAH. METHOD: A retrospective review was performed of all aSAH patients treated at Barrow Neurological Institute from January 1, 2003, to July 31, 2019. Patients were placed in 2 groups by age, < 80 vs ≥ 80 years. The ≥ 80-year-old group of octogenarians and nonagenarians was subsequently analyzed to compare treatment modalities. Poor neurologic outcome was defined as a modified Rankin Scale (mRS) score of > 2. RESULTS: During the study period, 1418 patients were treated for aSAH. The mean (standard deviation) age was 55.1 (13.6) years, the mean follow-up was 24.6 (40.0) months, and the rate of functional independence (mRS 0-2) at follow-up was 54% (751/1395). Logistic regression analysis found increasing age strongly associated with declining functional independence (R2 = 0.929, p < 0.001). Forty-three patients ≥ 80 years old were significantly more likely to be managed endovascularly than with open microsurgery (67% [n = 29] vs 33% [n = 14], p < 0.001). Compared with younger patients, those ≥ 80 years old had an increased risk of mortality and poor neurologic outcomes at follow-up. In the ≥ 80-year-old group, only 4 patients had good outcomes; none of the 4 had preexisting comorbidities, and all 4 were treated endovascularly. CONCLUSIONS: Age is a significant prognostic indicator of functional outcomes and mortality after aSAH. Most octogenarians and nonagenarians with aSAH will become severely disabled or die.

Assessing the association of common genetic variants in EPHB4 and RASA1 with phenotype severity in familial cerebral cavernous malformation.

BACKGROUND: To investigate whether common variants in EPHB4 and RASA1 are associated with cerebral cavernous malformation (CCM) disease severity phenotypes, including intracranial hemorrhage (ICH), total and large lesion counts. METHODS: Familial CCM cases enrolled in the Brain Vascular Malformation Consortium were included (n = 338). Total lesions and large lesions (≥5 mm) were counted on MRI; clinical history of ICH at enrollment was assessed by medical records. Samples were genotyped on the Affymetrix Axiom Genome-Wide LAT1 Human Array. We tested the association of seven common variants (three in EPHB4 and four in RASA1) using multivariable logistic regression for ICH (odds ratio, OR) and multivariable linear regression for total and large lesion counts (proportional increase, PI), adjusting for age, sex, and three principal components. Significance was based on Bonferroni adjustment for multiple comparisons (0.05/7 variants = 0.007). RESULTS: EPHB4 variants were not significantly associated with CCM severity phenotypes. One RASA1 intronic variant (rs72783711 A>C) was significantly associated with ICH (OR = 1.82, 95% CI = 1.21-2.37, p = 0.004) and nominally associated with large lesion count (PI = 1.17, 95% CI = 1.03-1.32, p = 0.02). CONCLUSION: A common RASA1 variant may be associated with ICH and large lesion count in familial CCM. EPHB4 variants were not associated with any of the three CCM severity phenotypes.

Baseline Characteristics of Patients With Cavernous Angiomas With Symptomatic Hemorrhage in Multisite Trial Readiness Project.

BACKGROUND AND PURPOSE: Brain cavernous angiomas with symptomatic hemorrhage (CASH) have a high risk of neurological disability from recurrent bleeding. Systematic assessment of baseline features and multisite validation of novel magnetic resonance imaging biomarkers are needed to optimize clinical trial design aimed at novel pharmacotherapies in CASH. METHODS: This prospective, multicenter, observational cohort study included adults with unresected, adjudicated brain CASH within the prior year. Six US sites screened and enrolled patients starting August 2018. Baseline demographics, clinical and imaging features, functional status (modified Rankin Scale and National Institutes of Health Stroke Scale), and patient quality of life outcomes (Patient-Reported Outcomes Measurement Information System-29 and EuroQol-5D) were summarized using descriptive statistics. Patient-Reported Outcomes Measurement Information System-29 scores were standardized against a reference population (mean 50, SD 10), and one-sample t test was performed for each domain. A subgroup underwent harmonized magnetic resonance imaging assessment of lesional iron content with quantitative susceptibility mapping and vascular permeability with dynamic contrast-enhanced quantitative perfusion. RESULTS: As of May 2020, 849 patients were screened and 110 CASH cases enrolled (13% prevalence of trial eligible cases). The average age at consent was 46±16 years, 53% were female, 41% were familial, and 43% were brainstem lesions. At enrollment, ≥90% of the cohort had independent functional outcome (modified Rankin Scale score ≤2 and National Institutes of Health Stroke Scale score <5). However, perceived health problems affecting quality of life were reported in >30% of patients (EuroQol-5D). Patients had significantly worse Patient-Reported Outcomes Measurement Information System-29 scores for anxiety (P=0.007), but better depression (P=0.002) and social satisfaction scores (P=0.012) compared with the general reference population. Mean baseline quantitative susceptibility mapping and permeability of CASH lesion were 0.45±0.17 ppm and 0.39±0.31 mL/100 g per minute, respectively, which were similar to historical CASH cases and consistent across sites. CONCLUSIONS: These baseline features will aid investigators in patient stratification and determining the most appropriate outcome measures for clinical trials of emerging pharmacotherapies in CASH.

Seizure Incidence Rates in Children and Adults With Familial Cerebral Cavernous Malformations.

BACKGROUND AND OBJECTIVES: Seizure incidence rates related to Familial Cerebral Cavernous Malformation (FCCM) are not well described, especially for children. To measure the seizure incidence rate, examine seizure predictors and characterize epilepsy severity, we studied a cohort of children and adults with FCCM enrolled in the Brain Vascular Malformation Consortium (BVMC). METHODS: Seizure data were collected from participants with FCCM in the BVMC at enrollment and during follow-up. We estimated seizure probability by age, and tested whether cerebral cavernous malformation (CCM) counts or genotype were associated with earlier seizure onset. RESULTS: The study cohort included 479 FCCM cases. Median age at enrollment was 42.5 years (Interquartile Range [IQR] 22.5-55.0) and 19% were children (<18 years old). Median large CCM count was 3 (IQR: 1-5). Among 393 with genotyping, mutations were: CCM1-Common Hispanic Mutations (88%), another CCM1 mutation (5%), CCM2 mutations (5%), and CCM3 mutations (2%). Prior to or during the study, 202 (42%) had a seizure. The cumulative incidence of a childhood seizure was 20.3% (95% CI 17.0 - 23.4) and by age 80 years was 60.4% (95% CI 54.2-65.7). More total CCMs (Hazard Ratio [HR] 1.24 per SD unit increase, 95% CI 1.1 - 1.4) or more large CCMs (HR=1.5 per SD unit increase, 95% CI 1.2-1.9) than expected for age and sex increased seizure risk. A CCM3 mutation also increased risk compared to other mutations (HR 3.11, 95% CI 1.15-8.45). Individuals with a seizure prior to enrollment had increased hospitalization rates during follow-up (Incidence Rate Ratio 10.9, 95% CI 2.41 - 49.32) compared to patients without a seizure history. DISCUSSION: Individuals with FCCM have a high seizure incidence, and those with more CCMs or CCM3 genotype are at greater risk. Seizures increase health care utilization in FCCM.

Intraventricular Tissue Plasminogen Activator and Shunt Dependency in Aneurysmal Subarachnoid Hemorrhage Patients With Cast Ventricles.

BACKGROUND: Patients with intraventricular hemorrhage (IVH) are at higher risk of hydrocephalus requiring an external ventricular drain and long-term ventriculoperitoneal shunt placement. OBJECTIVE: To investigate whether intraventricular tissue plasminogen activator (tPA) administration in patients with ventricular casting due to IVH reduces shunt dependence. METHODS: Patients from the Post-Barrow Ruptured Aneurysm Trial (PBRAT) database treated for aneurysmal subarachnoid hemorrhage (aSAH) from August 1, 2010, to July 31, 2019, were retrospectively reviewed. Patients with and without IVH were compared. A second analysis compared IVH patients with and without ventricular casting. A third analysis compared patients with ventricular casting with and without intraventricular tPA treatment. The primary outcome was chronic hydrocephalus requiring permanent shunt placement. RESULTS: Of 806 patients hospitalized with aSAH, 561 (69.6%) had IVH. IVH was associated with a higher incidence of shunt placement (25.7% vs 4.1%, P < .001). In multivariable logistic regression analysis, IVH was independently associated with increased likelihood of shunt placement (odds ratio [OR]: 7.8, 95% CI: 3.8-16.2, P < .001). Generalized ventricular casting was present in 80 (14.3%) patients with IVH. In a propensity-score adjusted analysis, generalized ventricular casting was an independent predictor of shunt placement (OR: 3.0, 95% CI: 1.8-4.9, P < .001) in patients with IVH. Twenty-one patients with ventricular casting received intraventricular tPA. These patients were significantly less likely to require a shunt (OR: 0.30, 95% CI: 0.010-0.93, P = .04). CONCLUSION: Ventricular casting in aSAH patients was associated with an increased risk of chronic hydrocephalus and shunt dependency. However, this risk decreased with the administration of intraventricular tPA.

Nancy Davis Reagan, First Lady with a Neurosurgical Legacy.

Various well-known people associated with the history of the presidency of the United States have experienced neurologic disease or injury, especially trauma to the head or spine. Nancy Reagan, however, as the wife of President Ronald Reagan and First Lady, would leave a significant and lasting mark on the progress of neurosurgical science and education. Recognized for endeavors against drug abuse, Alzheimer disease, and polio, her interest in neurosurgical research is less well known. Nancy's father Loyal Davis was a remarkable neurosurgeon and educator of extraordinary influence. When Barrow Neurological Institute (BNI) founder John Green experienced complications after an illness, Davis served as BNI director during 1966 - 1967. After Davis's death in 1982, Robert Spetzler, who had been a student of Davis at Northwestern University Medical School and was then BNI director, convinced Green, despite his misgivings, to support a neurosurgical laboratory recognizing Davis. In 1988, Nancy Reagan, then First Lady, dedicated the Loyal and Edith Davis Neurosurgical Research Laboratory. At the dedication, she remarked on her years growing up in the home of a pioneering neurosurgeon and remarked that "my father believed deeply in the importance of research to develop new methods for treating patients." Green and Spetzler's unified efforts honored the extraordinary career of Davis in a manner he would have appreciated, were supported by a First Lady with deep involvement in politics and philanthropy dedicated to promoting advances in medicine, and are part of neurosurgery's unique heritage.

Decompressive Craniectomy and Risk of Wound Infection After Microsurgical Treatment of Ruptured Aneurysms.

BACKGROUND: Owing to prolonged hospitalization and the complexity of care required for patients with aneurysmal subarachnoid hemorrhage (aSAH), these patients have a high risk of complications. The risk for wound infection after microsurgical treatment for aSAH was analyzed. METHODS: All patients who underwent microsurgical treatment for aSAH between August 1, 2007, and July 31, 2019, and were recorded in the Post-Barrow Ruptured Aneurysm Trial database were retrospectively reviewed. The patients were analyzed for risk factors for wound infection after treatment. RESULTS: Of 594 patients who underwent microsurgical treatment for aSAH, 23 (3.9%) had wound infections. There was no significant difference in age between patients with wound infection and patients without infection (mean, 52.6 ± 12.2 years vs. 54.2 ± 4.0 years; P = 0.45). The presence of multiple comorbidities (including diabetes, tobacco use, and obesity), external ventricular drain, ventriculoperitoneal shunt, pneumonia, or urinary tract infection was not associated with an increased risk for wound infection. Furthermore, there was no significant difference in mean operative time between patients with wound infection and those without infection (280 ± 112 minutes vs. 260 ± 92 minutes; P = 0.38). Patients who required decompressive craniectomy (DC) were at increased risk of wound infection (odds ratio, 5.0; 95% confidence interval, 1.8-14.1; P = 0.002). Among the 23 total infections, 9 were diagnosed following cranioplasty after DC. CONCLUSIONS: Microsurgical treatment for aSAH is associated with a relatively low risk of wound infection. However, patients undergoing DC may be at an increased risk for infection. Additional attention and comprehensive wound care are warranted for these patients.

Propranolol inhibits cavernous vascular malformations by ß1 adrenergic receptor antagonism in animal models.

Propranolol, a pleiotropic ß-adrenergic blocker, has been anecdotally reported to reduce cerebral cavernous malformations (CCMs) in humans. However, propranolol has not been rigorously evaluated in animal models, nor has its mechanism of action in CCM been defined. We report that propranolol or its S(-) enantiomer dramatically reduced embryonic venous cavernomas in ccm2 mosaic zebrafish, whereas R-(+)-propranolol, lacking ß antagonism, had no effect. Silencing of the ß1, but not ß2, adrenergic receptor mimicked the beneficial effects of propranolol in a zebrafish CCM model, as did the ß1-selective antagonist metoprolol. Thus, propranolol ameliorated cavernous malformations by ß1 adrenergic antagonism in zebrafish. Oral propranolol significantly reduced lesion burden in 2 chronic murine models of the exceptionally aggressive Pdcd10/Ccm3 form of CCM. Propranolol or other ß1-selective antagonists may be beneficial in CCM disease.

Re-Irradiation Using Brachytherapy for Recurrent Intracranial Tumors: A Systematic Review and Meta-Analysis of the Literature.

Introduction We aim to compare the efficacy and toxicity of re-irradiation using brachytherapy for patients with locally recurrent brain tumors after previous radiation therapy.  Methods We performed a systematic review of the major biomedical databases from 2005 to 2020 for eligible studies where patients were treated with re-irradiation for recurrent same site tumors using brachytherapy. Tumor types included high-grade gliomas (HGG) (World Health Organization (WHO) Grades 3 and 4), meningiomas, and metastases. The outcomes of interest were median overall survival (OS) and progression-free survival (PFS) after re-irradiation, the incidence of radiation necrosis (RN), and other relevant radiation-related adverse events (AE). We used a fixed-effect meta-analysis regression moderation model to compared results of interstitial versus intracavitary therapy, treatment with low-dose-rate (LDR) versus high-dose-rate (HDR) techniques, and outcomes by tumor type. Results The search resulted in a total of 194 articles. A total of 16 articles with 695 patients fulfilled the inclusion criteria and were selected for analysis. For high-grade glioma, meningioma, and brain metastasis the pooled meta-analysis showed mean symptomatic RN rates of 3.3% (standard error (SE) = 0.8%), 17.3% (SE = 5.0%), and 22.4% (SE = 7.0%), respectively, and mean rates of RN requiring surgical intervention of 3.0% (SE = 1.0%), 11.9% (SE = 5.3%), and 10.0% (SE = 7.3%), respectively. The mean symptomatic RN rates in the meta-analysis comparing interstitial versus intracavitary therapy were 3.4% and 4.9%, respectively (p = 0.36), and for the comparison of LDR versus HDR, the rates were 2.6% and 5.7%, respectively (p = 0.046). In comparing the symptomatic RN rates in comparison to HGG versus meningioma, the means were 3.3% and 17.3%, respectively (p = 0.006), and in HGG versus metastatic tumors, the means were 3.3% and 22.4%, respectively (p = 0.007). There was no significant difference in rates of RN requiring surgery in any of these groups. Due to the small number of studies and inconsistent recording of OS and PFS, statistical analysis of these parameters could not be performed. Conclusion Published literature on the same site re-irradiation using brachytherapy for recurrent brain tumors is highly limited, with inconsistent reporting of safety and efficacy outcomes. To overcome these shortcomings, we utilized a structured meta-analysis approach to show that re-irradiation with modern brachytherapy is generally safe in terms of the risks of symptomatic RN. We also found that symptomatic RN rates for brachytherapy are significantly lower in recurrent HGG compared to recurrent meningiomas (p = 0.006) and metastatic tumors (p = 0.007). Re-irradiation with brachytherapy is a feasible option for appropriately selected patients. The availability of Cesium-131 (Cs-131) shows promise in reducing toxicity while achieving excellent local control due to its physical properties, and the recent introduction of a novel surgically targeted radiation therapy device, that makes brachytherapy less technically demanding, may allow for more widespread adoption. Prospective trials with consistent reporting of endpoints are needed to explore whether these advances improve safety and efficacy in patients with recurrent, previously irradiated tumors.

Management of Extracranial Blunt Cerebrovascular Injuries: Experience with an Aspirin-Based Approach.

BACKGROUND: Optimal management of patients with extracranial blunt cerebrovascular injury (BCVI) remains controversial, with both anticoagulation and antiplatelet therapy being recommended. The purpose of this study was to evaluate the efficacy and safety of using acetylsalicylic acid (ASA) in the management of BCVI. METHODS: Patients with BCVI were identified from the registry of a Level 1 trauma center between 2010 and 2017. Digital imaging and electronic medical records were reviewed for patient information including demographic characteristics, injury type, therapy, outcomes, and follow-up. RESULTS: Over the study period, 13,578 patients were admitted following blunt trauma, with 94 (0.7%) having confirmed BCVI (mean age, 42 years; 72% male). Mean Injury Severity Score and Glasgow Coma Score were 27 and 10, respectively. BCVI was identified in 130 vessels with Biffl grade I (38%) and grade II injury (29%) being most common. Twelve (13%) patients experienced an ischemic event, but only 3 events occurred after diagnosis. ASA was primary treatment for 56 (60%) patients. Thirty patients (32%) received no treatment; 21 patients died within 24 hours of primary injury. Only 4 patients had ASA contraindications. Four patients (7%) had ASA-related complications; there were 2 cases of intracranial hemorrhage progression and 2 cases of gastrointestinal bleeding. Follow-up vascular imaging at a mean of 36 days demonstrated stable or improved levels of BCVI in 94% of patients. CONCLUSIONS: An ASA-based management strategy for BCVI was efficacious and relatively safe in this study. This approach may be the preferred treatment for BCVI, but confirmation is needed.