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Hydrocephalus (HC) is a heterogenous disease characterized by alterations in cerebrospinal fluid (CSF) dynamics that may cause increased intracranial pressure. HC is a component of a wide array of genetic syndromes as well as a secondary consequence of brain injury (intraventricular hemorrhage (IVH), infection, etc.) that can present across the age spectrum, highlighting the phenotypic heterogeneity of the disease. Surgical treatments include ventricular shunting and endoscopic third ventriculostomy with or without choroid plexus cauterization, both of which are prone to failure, and no effective pharmacologic treatments for HC have been developed. Thus, there is an urgent need to understand the genetic architecture and molecular pathogenesis of HC. Without this knowledge, the development of preventive, diagnostic, and therapeutic measures is impeded. However, the genetics of HC is extraordinarily complex, based on studies of varying size, scope, and rigor. This review serves to provide a comprehensive overview of genes, pathways, mechanisms, and global impact of genetics contributing to all etiologies of HC in humans., (© 2024. The Author(s).)

Epilepsy surgery is an established safe and effective treatment for selected candidates with drug-resistant epilepsy. In this opinion piece, we outline the clinical and experimental evidence for selectively considering epilepsy surgery prior to drug resistance. Our rationale for expedited surgery is based on the observations that (i) a high proportion of patients with lesional epilepsies (e.g. focal cortical dysplasia, epilepsy-associated tumours) will progress to drug resistance; (ii) surgical treatment of these lesions, especially in non-eloquent areas of brain, is safe; and (iii) earlier surgery may be associated with better seizure outcomes. Potential benefits beyond seizure reduction or elimination include less exposure to antiseizure medications, which may lead to improved developmental trajectories in children and optimize long-term neurocognitive outcomes and quality of life. Further, there exists emerging experimental evidence that brain network dysfunction exists at the onset of epilepsy, where continuing dysfunctional activity could exacerbate network perturbations. This in turn could lead to expanded seizure foci and contribution to the comorbidities associated with epilepsy. Taken together, we rationalize that epilepsy surgery, in carefully selected cases, may be considered prior to drug resistance. Last, we outline the path forward, including the challenges associated with developing the evidence base and implementing this paradigm into clinical care., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Several instruments and outcomes measures have been reported in pediatric patients undergoing epilepsy surgery. The objective of this systematic review is to summarize, evaluate, and quantify outcome metrics for the surgical treatment of pediatric epilepsy that address seizure frequency, neuropsychological, and health-related quality of life (HRQL). We performed a systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify publications between 2010 and June 2021 from PubMed, Embase, and the Cochrane Database of Systematic Reviews that report clinical outcomes in pediatric epilepsy surgery. Eighty-one articles were included for review. Overall, rates of postoperative seizure frequency were the most common metric reported (n = 78 studies, 96%). Among the seizure frequency metrics, the Engel Epilepsy Surgery Outcome Scale (n = 48 studies, 59%) was most commonly reported. Neuropsychological outcomes, performed in 32 studies (40%) were assessed using 36 different named metrics. HRQL outcomes were performed in 16 studies (20%) using 13 different metrics. Forty-six studies (57%) reported postoperative changes in antiepileptic drug (AED) regimen, and time-to-event analysis was performed in 15 (19%) studies. Only 13 outcomes metrics (1/5 seizure frequency, 6/13 HRQL, 6/36 neuropsychological) have been validated for use in pediatric patients with epilepsy and only 13 have been assessed through reliability studies (4/5 seizure frequency, 6/13 HRQL, and 3/36 neuropsychological). Of the 81 included studies, 17 (21%) used at least one validated metric. Outcome variable metrics in pediatric epilepsy surgery are highly variable. Although nearly all studies report seizure frequency, there is considerable variation in reporting. HRQL and neuropsychological outcomes are less frequently and much more heterogeneously reported. Reliable and validated outcomes metrics should be used to increase standardization and accuracy of reporting outcomes in pediatric patients undergoing epilepsy surgery., (© 2022 International League Against Epilepsy.)

Introduction: Understanding outcomes after Vein of Galen malformation (VOGM) embolization has been limited by small sample size in reported series and predominantly single center studies. To address these limitations, we perform an individual-participant meta-analysis (IPMA) to identify risk factors associated with all-cause mortality and clinical outcome after VOGM endovascular embolization., Methods: We performed a systematic review and IPMA of VOGM endovascular outcomes according to PRISMA guidelines. Individual patient characteristics including demographic, intra/post-operative adverse events, treatment efficacy (partial or complete occlusion), and clinical outcome were collected. Mixed-effects logistic regression with random effects modeling and Bonferroni correction was used ( p  ≤ 0.003 threshold for statistical significance). The primary and secondary outcomes were all-cause mortality and poor clinical outcome (moderate/severe developmental delay or permanent disabling injury), respectively. Data are expressed as (mean ± standard deviation (SD)) or (odds ratio (OR), 95% confidence interval (CI), I 2 , p -value)., Results: Thirty-five studies totaling 307 participants quantifying outcomes after endovascular embolization for VOGM were included. Follow up time was 42 (±57) months. Our analysis contained 42% neonates (<1 month) at first embolization, 45% infants (1 month ≤2 years), and 13% children (>2 years). Complete occlusion was reported in 48% of participants. Overall all-cause mortality was 16%. Overall, good clinical outcome was achieved in 68% of participants. First embolization as a neonate [OR = 6.93; 95% CI (1.99-24.08); I 2  < 0.01; p  < 0.001] and incomplete embolization [OR = 10.87; 95% CI (1.86-63.55); I 2  < 0.01; p  < 0.001] were associated with mortality. First embolization as a neonate [OR = 3.24; 95% CI (1.47-7.15); I 2  < 0.01; p  < 0.001], incomplete embolization [OR = 5.26; 95% CI (2.06-13.43); I 2  < 0.01; p  < 0.001], and heart failure at presentation [OR = 3.10; 95% CI (1.03-9.33); I 2  < 0.01; p  = 0.002] were associated with poor clinical outcomes. Sex, angioarchitecture of lesion, embolization approach (transvenous vs. transarterial), and single or multistage embolization were not associated with mortality or clinical outcome., Conclusions: We identify incomplete VOGM embolization independently associated with mortality and poor clinical outcome. While this study provides the highest level of evidence for VOGM embolization to date, prospective multicenter studies are needed to understand the optimal treatment strategies, outcomes, and natural history after VOGM embolization., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Savage, Hale, Parr, Hedaya, Saccomano, Tsemo, Hafeez, Tanweer, Kan, Solomon, Meila, Dirks, Blount, Johnston, Rocque, Rozzelle, Bhatia, Muthusami, Krings and Jones.)

Background: The COVID-19 pandemic has transformed medical education, including the upcoming residency application cycle. External rotations have been restricted, but virtual opportunities for applicants have not yet been assessed., Objectives: To describe how neurosurgical residency programs are adapting to the 2021 application cycle through augmented social media usage and establishment of virtual sub-I's and open houses., Methods: One hundred fifteen separate programs were identified on ERAS. Twitter, Facebook, Instagram, residency websites, and the Visiting Student Application Service (VSAS) were reviewed for virtual open house and sub-I opportunities. Professional neurosurgery society websites were also reviewed. All data is updated as of February 14 th, 2021., Results: Eighty-eight (77%) programs had some social media presence. Fourty-three (30%) departmental accounts were created in 2020. Twenty-four (57%) of the residency program accounts were created in 2020. Programs offered 35 (18%) open house opportunities on Twitter, 19 (17%) on Facebook, and 23 (20%) on Instagram. Nineteen (17%) virtual sub-I opportunities were on Twitter, 9 (8%) on Facebook, and 10 (9%) on Instagram.Virtual opportunities were updated on 13 (12%) residency websites. The National Neurosurgery MedEd website had the most website listings of virtual opportunities with 34 (30%) programs listing open houses and 18 (16%) programs listing virtual sub-I's. No program specific virtual opportunities were found on the AANS or CNS websites. VSAS identified only 4 (4%) virtual sub-internships., Conclusion: Many neurosurgical residency programs increased their virtual presence amid the COVID-19 pandemic. More programs could utilize these platforms to mitigate applicant restriction in upcoming neurosurgery residency application cycles., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Objective: Efforts directed at mitigating neurological disability in preterm infants with intraventricular hemorrhage (IVH) and post hemorrhagic hydrocephalus (PHH) are limited by a dearth of quantifiable metrics capable of predicting long-term outcome. The objective of this study was to examine the relationships between candidate cerebrospinal fluid (CSF) biomarkers of PHH and neurodevelopmental outcomes in infants undergoing neurosurgical treatment for PHH., Study Design: Preterm infants with PHH were enrolled across the Hydrocephalus Clinical Research Network. CSF samples were collected at the time of temporizing neurosurgical procedure (n = 98). Amyloid precursor protein (APP), L1CAM, NCAM-1, and total protein (TP) were compared in PHH versus control CSF. Fifty-four of these PHH subjects underwent Bayley Scales of Infant Development-III (Bayley-III) testing at 15-30 months corrected age. Controlling for false discovery rate (FDR) and adjusting for post-menstrual age (PMA) and IVH grade, Pearson's partial correlation coefficients were used to examine relationships between CSF proteins and Bayley-III composite cognitive, language, and motor scores., Results: CSF APP, L1CAM, NCAM-1, and TP were elevated in PHH over control at temporizing surgery. CSF NCAM-1 was associated with Bayley-III motor score (R = -0.422, p = 0.007, FDR Q = 0.089), with modest relationships noted with cognition (R = -0.335, p = 0.030, FDR Q = 0.182) and language (R = -0.314, p = 0.048, FDR Q = 0.194) scores. No relationships were observed between CSF APP, L1CAM, or TP and Bayley-III scores. FOHR at the time of temporization did not correlate with Bayley-III scores, though trends were observed with Bayley-III motor (p = 0.0647 and R = -0.2912) and cognitive scores (p = 0.0506 and R = -0.2966)., Conclusion: CSF NCAM-1 was associated with neurodevelopment in this multi-institutional PHH cohort. This is the first report relating a specific CSF protein, NCAM-1, to neurodevelopment in PHH. Future work will further investigate a possible role for NCAM-1 as a biomarker of PHH-associated neurological disability., Competing Interests: The authors have read the journal’s policy and have the following potential competing interests: DDL has received support for unrelated research efforts from Microbot Medical, Inc. and Medtronic, Inc. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare.

Objective: The goal of this study was to evaluate the predictive value and relative contribution of noninvasive presurgical functional imaging modalities based on the authors' institutional experience in pursuing seizure-free surgical outcomes in children with medically refractory epilepsy., Methods: This was a retrospective, single-institution, observational cohort study of pediatric patients who underwent evaluation and surgical treatment for medically refractory partial epilepsy between December 2003 and June 2016. During this interval, 108 children with medically refractory partial epilepsy underwent evaluation for localization and resective epilepsy surgery. Different noninvasive functional imaging modalities, including ictal SPECT, FDG-PET, and magnetoencephalography-magnetic source imaging, were utilized to augment a standardized paradigm (electroencephalography/semiology, MRI, and neuropsychology findings) for localization. Outcomes were evaluated at a minimum of 2 years (mean 7.5 years) utilizing area under the receiver operating characteristic curve analysis. Localizing modalities and other clinical covariates were examined in relation to long-term surgical outcomes., Results: There was variation in the contribution of each test, and no single presurgical workup modality could singularly and reliably predict a seizure-free outcome. However, concordance of presurgical modalities yielded a high predictive value. No difference in long-term outcomes between inconclusive (normal or diffusely abnormal) and abnormal focal MRI results were found. Long-term survival analyses revealed a statistically significant association between seizure freedom and patients with focal ictal EEG, early surgical intervention, and no history of generalized convulsions., Conclusions: Comprehensive preoperative evaluation utilizing multiple noninvasive functional imaging modalities is not redundant and can improve pediatric epilepsy surgical outcomes.

OBJECTIVE It is generally accepted that cerebrospinal fluid shunts fail most frequently in the first years of life. The purpose of this study was to describe the risk of shunt failure for a given patient age in a well-defined cohort with shunted hydrocephalus due to myelomeningocele (MMC). METHODS The authors analyzed data from their institutional spina bifida research database including all patients with MMC and shunted hydrocephalus. For the entire population, the number of shunt revisions in each year of life was determined. Then the number of patients at risk for shunt revision during each year of life was calculated, thus enabling them to calculate the rate of shunt revision per patient in each year of life. In this way, the timing of all shunt revision operations for the entire clinic population and the likelihood of having a shunt revision during each year of life were calculated. RESULTS A total of 655 patients were enrolled in the spina bifida research database, 519 of whom had a diagnosis of MMC and whose mean age was 17.48 ± 11.7 years (median 16 years, range 0-63 years). Four hundred seventeen patients had had a CSF shunt for the treatment of hydrocephalus and thus are included in this analysis. There were 94 shunt revisions in the 1st year of life, which represents a rate of 0.23 revisions per patient in that year. The rate of shunt revision per patient-year initially decreased as age increased, except for an increase in revision frequency in the early teen years. Shunt revisions continued to occur as late as 43 years of age. CONCLUSIONS These data substantiate the idea that shunt revision surgeries in patients with MMC are most common in the 1st year of life and decrease thereafter, except for an increase in the early teen years. A persistent risk of shunt failure was observed well into adult life. These findings underscore the importance of routine follow-up of all MMC patients with shunted hydrocephalus and will aid in counseling patients and families.

Introduction: Entrapment of the suprascapular nerve at the suprascapular notch may be due to an ossified suprascapular ligament. The present study was conducted in order to investigate the incidence of this anomaly and to analyze the resultant bony foramen (foramen scapula) for gross nerve compression., Materials and Methods: We evaluated 104 human scapulae from 52 adult skeletons for the presence of complete ossification of the suprascapular ligament. When an ossified suprascapular ligament was identified, the diameter of the resultant foramen was measured. Also, the suprascapular regions of 50 adult cadavers (100 sides) were dissected. When an ossified suprascapular ligament was identified, the spinati musculature was evaluated for gross atrophy and the diameters of the resultant foramen scapulae and the suprascapular nerve were measured. Immunohistochemical analysis of the nerve was also performed., Results: For dry scapular specimens, 5.7% were found to have an ossified suprascapular ligament. The mean diameter of these resultant foramina was 2.6 mm. For cadavers, an ossified suprascapular ligament was identified in 5% of sides. Sections of the suprascapular nerve at the foramen scapulae ranged from 2 to 2.8 mm in diameter. In all cadaveric samples, the suprascapular nerve was grossly compressed (~10-20%) at this site. All nerves demonstrated histologic signs of neural degeneration distal to the site of compression. The presence of these foramina in male cadavers and on right sides was statistically significant., Conclusions: Based on our study, even in the absence of symptoms, gross compression of the suprascapular nerve exists in cases of an ossified suprascapular ligament. Asymptomatic patients with an ossified suprascapular ligament may warrant additional testing such as electromyography.