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OBJECTIVE The aim of this study was to summarize the prognosis of recurrent infratentorial ependymomas based on treatment and molecular characterization. METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the authors searched the PubMed, Scopus, Embase, and Ovid databases for studies on recurrent infratentorial ependymomas in patients younger than 25 years of age. Exclusion criteria included case series of fewer than 5 patients and studies that did not provide time-dependent survival data. RESULTS The authors’ database search yielded 482 unique articles, of which 18 were included in the final analysis. There were 479 recurrent infratentorial pediatric ependymomas reported; 53.4% were WHO grade II and 46.6% were WHO grade III tumors. The overall mortality for recurrent infratentorial pediatric ependymomas was 49.1% (226/460). The pooled mean survival was 30.2 months after recurrence (95% CI 22.4–38.0 months). Gross-total resection (GTR) was achieved in 243 (59.0%) patients at initial presentation. The mean survival postrecurrence for those who received initial GTR was 42.3 months (95% CI 35.7–47.6 months) versus 26.0 months (95% CI 9.6–44.6 months) for those who received subtotal resection (STR) (p = 0.032). There was no difference in the mean survival between patients who received GTR (49.3 months, 95% CI 32.3–66.3 months) versus those who received STR (41.4 months, 95% CI 11.6–71.2 months) for their recurrent tumor (p = 0.610). In the studies that included molecular classification data, there were 169 (83.3%) posterior fossa group A (PFA) tumors and 34 (16.7%) posterior fossa group B (PFB) tumors, with 28 tumors harboring a 1q gain. PFA tumors demonstrated worse mean postprogression patient survival (24.7 months, 95% CI 15.3–34.0 months) compared with PFB tumors (48.0 months, 95% CI 32.8–63.2 months) (p = 0.0073). The average postrecurrence survival for patients with 1q+ tumors was 14.7 months. CONCLUSIONS The overall mortality rate for recurrent infratentorial ependymomas was found to be 49.1%, with a pooled mean survival of 30.2 months in the included sample population. More than 80% of recurrent infratentorial ependymomas were of the PFA molecular subtype, and both PFA tumors and those with 1q gain demonstrated worse prognosis after recurrence.

Seizures are a frequent complication of adult-type diffuse gliomas, and are often difficult to control with medications. Gliomas with mutations in isocitrate dehydrogenase 1 or 2 (IDHmut) are more likely than IDH-wild type (IDHwt) gliomas to cause seizures as part of their initial clinical presentation. However, whether IDHmut is also associated with seizures during the remaining disease course, and whether IDHmut inhibitors can reduce seizure risk, are unclear. Clinical multivariable analyses showed that preoperative seizures, glioma location, extent of resection, and glioma molecular subtype (including IDHmut status) all contributed to postoperative seizure risk in adult-type diffuse glioma patients, and that postoperative seizures were often associated with tumor recurrence. Experimentally, the metabolic product of IDHmut, d-2-hydroxyglutarate, rapidly synchronized neuronal spike firing in a seizure-like manner, but only when non-neoplastic glial cells were present. In vitro and in vivo models recapitulated IDHmut glioma-associated seizures, and IDHmut inhibitors currently being evaluated in glioma clinical trials inhibited seizures in those models, independent of their effects on glioma growth. These data show that postoperative seizure risk in adult-type diffuse gliomas varies in large part by molecular subtype, and that IDHmut inhibitors could play a key role in mitigating such risk in IDHmut glioma patients.

Lennox-Gastaut syndrome (LGS) is a severe form of childhood onset epilepsy in which patients require multiple medications and may be candidates for palliative surgical intervention. In this meta-analysis, we sought to evaluate the impact of palliative vagus nerve stimulation (VNS), corpus callosotomy (CC), and resective surgery (RS) by analyzing their impact on seizure control, antiepileptic drug (AED) usage, quality of life (QOL), behavior, cognition, prognostic factors, and complications. A systematic search of PubMed MEDLINE, Scopus, and Cochrane Database of Systematic Reviews was performed to find articles that met the following criteria: (1) prospective/retrospective study with original data, (2) at least one LGS surgery patient aged less than 18 years, and (3) information on seizure frequency reduction (measured as percentage, Engel class, or qualitative comment). Seizures were analyzed quantitatively in a meta-analysis of proportions and a random-effects model, whereas other outcomes were analyzed qualitatively. Forty studies with 892 LGS patients met the selection criteria, with 19 reporting on CC, 17 on VNS, four on RS, two on RS + CC, one on CC + VNS, and one on deep brain stimulation. CC seizure reduction rate was 74.1% (95% confidence interval [CI] = 64.5%-83.7%), and VNS was 54.6% (95% CI = 42.9%-66.3%), which was significantly different (p < .001). RS seizure reduction was 88.9% (95% CI = 66.1%-99.7%). Many VNS patients reported alertness improvements, and most had no major complications. VNS was most effective for atonic/tonic seizures; higher stimulation settings correlated with better outcomes. CC patients reported moderate cognitive and QOL improvements; disconnection syndrome, transient weakness, and respiratory complications were noted. Greater callosotomy extent correlated with better outcomes. AED usage most often did not change after surgery. RS showed considerable QOL improvements for patients with localized seizure foci. In the reported literature, CC appeared to be more effective than VNS for seizure reduction. VNS may provide a similar or higher level of QOL improvement with lower aggregate risk of complications. Patient selection, anatomy, and seizure type will inform decision-making.

Background Both low and high body mass index (BMI) have been associated with an increased risk of dementia, including that caused by Alzheimer's disease (AD). Specifically, high middle-age BMI or a low late-age BMI has been considered a predictor for the development of AD dementia. Less studied is the relationship between BMI and AD pathology. Objective We explored the association between BMI and cortical amyloid-β (Aβ) burden in cognitively normal participants that were either in mid-life (45-60 years) or late-life (>60). Methods We analyzed cross-sectional baseline data from the Knight Alzheimer Disease Research Center (ADRC) at Washington University. Aβ pathology was measured in 373 individuals with Aβ PET imaging and was quantified using Centiloid units. We split the cohort into mid- and late-life groups for analyses (n = 96 and n = 277, respectively). We ran general linear regression models to predict Aβ levels from BMI while controlling for age, sex, years of education, and APOE4 status. Analyses were also conducted to test the interaction between BMI and APOE4 genotype and between BMI and sex. Results Higher BMI was associated with lower cortical Aβ burden in late-life (β= -0.81, p = 0.0066), but no relationship was found in mid-life (β= 0.04, p > 0.5). The BMI×APOE4+ and BMI×male interaction terms were not significant in the mid-life (β= 0.28, p = 0.41; β= 0.64, p = 0.13) or the late-life (β= 0.17, p > 0.5; β= 0.50, p = 0.43) groups. Conclusion Higher late-life BMI is associated with lower cortical Aβ burden in cognitively normal individuals.

The overall prognosis of infratentorial ependymoma differs based on molecular signature, however the impact of recurrence on prognosis remains poorly defined in the pediatric population. PubMed, Scopus, Embase, and Ovid were searched for publications on recurrent infratentorial ependymomas in patients under 25 years of age. Exclusion criteria were case series of less than 5 patients and studies that did not provide individualized patient data. Our search yielded 472 unique articles, of which 17 were included in the analysis. There was a total of 460 recurrent ependymomas reported, with 52.8% WHO grade II tumors and 47.2% grade III. The overall mortality for recurrent infratentorial ependymoma was 49.1% (226/460). The pooled median survival was 32.39 months after recurrence (95% CI: 23.45-41.33). Gross total resection was achieved in 237 (53.1%) patients at initial presentation. Raw mean survival post-recurrence was 32.9 months (SD: 11.2 months) for those who received GTR for their primary tumor versus 23.7 months (SD: 10.8 months) for those who received subtotal resection (STR) (p < 0.001). There was no difference in survival between those that received GTR (49.3 months, 95% CI: 32.3-66.3) versus STR (41.4 months, 95% CI: 11.6-71.2) of their recurrent tumor (p=0.610). In the studies that provided molecular classification, there were 169 PFA tumors (83.3%) and 34 PFB (16.6%), with 28 that demonstrated 1q gain. PFA-A tumors demonstrated worse post-progression survival (24.7 months, 95% CI: 15.3-34.0) compared to PF-B (48.0 months, 95% CI: 32.8-63.2) (p=0.0073). The average post-recurrence survival for tumors with 1q gain was 5.93 months (SD: 9.15). The overall mortality rate for recurrent infrantentorial ependymomas was found to be 49.8%, with a pooled median survival of 32.39 months. Almost 90% of recurrent infratentorial ependymomas were of the PFA molecular subtype, and those tumors that demonstrated 1q gain had a worse survival than those that did not.

Background Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), and intracranial hemorrhage (ICH) may complicate the post-operative course of patients undergoing craniotomy. While prophylaxis with unfractionated heparin (UFH) has been shown to reduce VTE rates, twice-daily (BID) and three-times-daily (TID) UFH dosing regimens have not been compared in neurosurgical procedures. The objective of this study was to explore the association between UFH dosing regimen and rates of VTE and ICH in craniotomy patients. Methods A retrospective chart review was conducted for 159 patients at Northwestern University receiving 5000 units/0.5 mL UFH injections either BID (n = 132) or TID (n = 27). General linear regression models were run to predict rates of DVT, PE, and reoperation due to bleeding from UFH dosing regimen while controlling for age at surgery, sex, VTE history, craniotomy for tumor resection, surgery duration, length of stay, reoperation, infections, and IDH/MGMT mutations. Results Receiving UFH TID was significantly associated with a lower rate of PE when compared with receiving UFH BID (β = –0.121, P = 0.044; TID rate = 0%, BID rate = 10.6%). UFH TID also showed a trend toward lower rates of DVT (β = –0.0893, P = 0.295; TID rate = 18.5%, BID rate = 21.2%) when compared with UFH BID. UFH TID showed no significant difference in rate of reoperation for bleeding when compared to UFH BID (β = –0.00623, P = 0.725; TID rate = 0%, BID rate = 0.8%). Conclusions UFH TID dosing is associated with lower rates of PE when compared with BID dosing in patients undergoing craniotomy.

BACKGROUNDPatients with spina bifida have repeated interactions with the healthcare system and often require multiple surgeries throughout their lifetime. Latex precautions are often indicated owing to the high risk of anaphylactic reactions. The choice of dressing for these patients represents an opportunity for learning and standardization if appropriate. The authors discuss the various cases of skin reactions to Mastisol in the literature in comparison with their case and explore the possible mechanisms underlying this skin reaction given the high prevalence of latex allergy in patients with spina bifida.OBSERVATIONSThe authors present the case of a 17-year-old girl with a history of spina bifida and shunted hydrocephalus who underwent a shunt externalization operation and subsequently developed an allergic contact dermatitis reaction to Mastisol liquid adhesive. Topical steroid cream was then administered, and signs and symptoms resolved over the next 3 days.LESSONSThe choice of dressing should be considered carefully in patients with spina bifida given their repeated exposures and possible sensitivities. The authors aim to increase the awareness of the possibility of Mastisol-induced skin reactions in patients with spina bifida and set a foundation for future studies to investigate the relationship between latex allergy and sensitization to Mastisol.

Children with neurofibromatosis type I (NF1) have a higher predisposition for low-grade astrocytomas of the optic pathway, commonly referred to as optic pathway gliomas (OPGs). OPGs can result in visual deterioration. Treatment outcomes in OPG-NF1 management are often reported around tumor stabilization. We sought to compare vision outcomes associated with different OPG treatment strategies to inform about this important functional metric. A meta-analysis exploring the different modalities to treat children with OPG-NF1 was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using multiple databases. Of the 113 articles identified in the search, 23 full text articles, representing 564 patients, were included for review. These articles included retrospective, prospective, and randomized controlled studies on observation (n=9), chemotherapy (n=19), radiation therapy (n=6), and surgery (n=7). Of the patients undergoing observation, 87% (60/69) demonstrated stable acuity. In the chemotherapy studies, 27.3% (72/264) demonstrated improved acuity/visual field and/or visual-evoked potential amplitudes, 39.4% (104/264) stable acuity, and 33.3% (88/264) deterioration. Both the radiation and surgical treatments reported worsening acuity at 90.9% (10/11) and 73.3% (11/15), respectively. Causal associations are not known. Indications for and timing of treatment choice warrant larger scale study to provide further understanding.

Introduction Endovascular mechanical thrombectomy is the standard of care treatment for acute ischemic stroke secondary to large vessel occlusions, but racial disparities in stroke interventional management and outcomes are not well studied. Moreover, a robust analysis of multiple relevant variables, with consideration of possible confounders, has not been previously conducted. We aimed to evaluate real-world evidence for racial differences in stroke thrombectomy management, short- and long-term outcomes using the Neurovascular Quality Initiative-Quality Outcomes Database (NVQI-QOD) registry. Methods Data from the NVQI-QOD registry database were analyzed and compared for racial differences with respect to technical and functional outcomes of stroke thrombectomy in 3281 patients from 23 US centers (17 states) between Jan 2015 to March 2020. Race was classified into 4 groups: 1) Caucasian (n=2484), 2) African American (n=563), 3) Hispanic (n=109), and 4) Asian (n=105). Analysis of variances (ANOVAs), Chi-square tests, Mann Whitney U tests, and multivariate regression models were used to assess racial disparities for 10 outcome variables: final thrombolysis in cerebral infarction (TICI) grade (n=3182), 24 hour NIH stroke score (NIHSS) (n=2850), post-procedure length of stay (n=3257), ICU days (n=2787), in-hospital mortality (n=3259), discharge status (n=3281), discharge NIHSS (n=2426), discharge modified Rankin score (mRS) (n=996), 90 day re-admission rate (n=416), and 90 day mRS (n=1184). Regression models controlled for demographics, comorbidities, intravenous tPA thrombolysis, and pre-stroke functional measures. Results ANOVA and Chi-square tests revealed significant differences between racial group means including post-procedure length of stay (p Conclusion Evidence from the NVQI-QOD registry suggests that there are several racial disparities in stroke thrombectomy management and outcomes, with minorities exhibiting increased post-procedural NIHSS, length of stay, and ICU days. Although African Americans were noted to suffer less in-hospital mortality compared to Caucasians, this did not translate into increased odds of a favorable clinical outcome at 90 days. Disclosures V. Thirunavu: None. R. Abdalla: None. D. Cantrell: None. M. Hurley: None. A. Shaibani: None. B. Jahromi: None. M. Potts: None. S. Ansari: None. O. NVQI-QOD Registry: None.

We present the case of an 11 month old boy with history of sagittal synostosis who underwent a cranial vault reconstruction for repair. During the case, surgical irrigation spilled onto the plug in the operating room table, resulting in sparks and a small fire. The fire was contained and extinguished. The patient suffered no injury. We discuss previous cases of fires in neurosurgical operating rooms and identify a new source of ignition for fires. We also explore recommended best practices for fire prevention and safety to identify ways to prevent instances like this from occurring in the future.