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The Hannover classification of vestibular schwannomas is designed to stratify tumors based on extrameatal extension and compression of the brainstem. We have previously reported the reliability of the Koos system, but to date, no study has assessed the reliability of the similar Hannover classification.We present an assessment of the intrarater and interrater reliability of the Hannover classification system.After institutional review board approval was obtained, a cross-sectional group of the magnetic resonance imaging of 40 patients with vestibular schwannomas varying in size comprised the study sample. Four raters were selected to assign a Hannover grade to 50 total scans. Interrater and intrarater reliability was calculated and reported using Fleiss's kappa, Kendall's W, and intraclass correlation coefficient (ICC).Interrater observer reliability was found to be moderate when measured using Fleiss' kappa (0.49), extremely strong using Kendall's W (0.93), and excellent as calculated by ICC (0.88). The results were all statistically significant (P0.05). Intrarater reliability for Hannover grade ranged from 0.77 to 1.00 (substantial to perfect). By Kendall's W and ICC, all raters had near perfect or excellent agreement. The results were all statistically significant (P0.05).The Hannover classification is a reliable system for grading the size of vestibular schwannomas. This supports its continued use and previously published results of the literature in studies relying on this classification. Further studies are needed to evaluate its validity and determine its role in preoperative counseling and determining microsurgery and radiosurgery outcomes.

Objective Hydrocephalus is a disorder of cerebrospinal fluid dynamics, traditionally treated by placement of a ventricular shunt. Shunts are effective but imperfect as they fail in an unpredictable pattern, and the patient's well-being is dependent on adequate shunt function. The omnipresent threat of shunt failure along with the potential need for invasive investigations can be stressful for patients and caregivers. Our objective was to measure post-traumatic stress symptoms (PTSS) in children with hydrocephalus and their caregivers. Methods A cross-sectional analysis of children with hydrocephalus and their caregivers was conducted. Caregivers completed a measure of their own PTSS (the Post-Traumatic Stress Disorders Checklist for the Diagnostic and Statistical Manual of Mental Disorders−V) and resilience (the Connor Davidson Resilience Scale). Pediatric patients rated their own PTSS and resilience using the Acute Stress Checklist for Kids and Connor Davidson Resilience Scale. Results Ninety-one caregivers completed the Post-Traumatic Stress Disorders Checklist for the Diagnostic and Statistical Manual of Mental Disorders−V. Mean score was 17.0 (standard deviation 15.7; median 13.0). Fourteen percent scored above 33, the threshold suggestive of a preliminary diagnosis of post-traumatic stress disorder. There was a statistically significant association between caregiver post-traumatic stress and marital status, child's race, and caregiver education. More than half (52%) of caregivers reported their child's hydrocephalus as the most significant source of their PTSS. Children did not have markedly elevated levels of PTSS. Forty-one percent of caregivers and 60% of children scored in the lowest resilience quartile compared with the general population. Conclusions Results from this study suggest that post-traumatic stress affects caregivers with hydrocephalus, yet levels of resilience for caregivers and pediatric patients are low.

Background Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high morbidity and mortality. Among the most common sequelae of aSAH is delayed cerebral ischemia. Hyperdynamic therapy (fluid supplementation and hypertension) is used to increase cerebral perfusion. However, the safety of hyperdynamic therapy in patients with separate unruptured, unsecured intracranial aneurysms is not well-established. Herein, a rare case demonstrating the rapid evolution and rupture of an incidental unsecured aneurysm in the setting of hyperdynamic therapy is presented. Case Description A 56-year-old woman without significant medical history presented with aSAH secondary to rupture of a 3-mm left posterior inferior cerebellar artery aneurysm. After endovascular treatment of this aneurysm, she developed symptomatic vasospasm prompting initiation of hyperdynamic therapy. Seven days after initiation of hyperdynamic therapy, she experienced rupture of an incidental pericallosal artery aneurysm that was found to have increased in size during the hyperdynamic therapy. She ultimately survived and was functionally independent approximately 1 year after her initial ictus. Conclusions This case demonstrates that enlargement and rupture of an incidental, previously unruptured aneurysm may occur during hyperdynamic therapy.

Brain tumors represent the most common pediatric solid neoplasms and leading cause of childhood cancer-related morbidity and mortality. Although most adult brain tumors are supratentorial and arise in the cerebrum, the majority of pediatric brain tumors are infratentorial and arise in the posterior fossa, specifically the cerebellum. Outcomes from malignant cerebellar tumors are unacceptable despite aggressive treatments (surgery, radiation, and/or chemotherapy) that are harmful to the developing brain. Novel treatments/approaches such as oncolytic virotherapy are urgently needed. Preclinical and prior clinical studies suggest that genetically engineered oncolytic herpes simplex virus (HSV-1) G207 can safely target cerebellar malignancies and has potential to induce an antitumor immune response at local and distant sites of disease, including spinal metastases and leptomeningeal disease. Herein, we outline the rationale, design, and significance of a first-in-human immunotherapy Phase 1 clinical trial targeting recurrent cerebellar malignancies with HSV G207 combined with a single low-dose of radiation (5 Gy), designed to enhance virus replication and innate and adaptive immune responses. We discuss the unique challenges of inoculating virus through intratumoral catheters into cerebellar tumors. The trial utilizes a single arm open-label traditional 3 + 3 design with four dose cohorts. The primary objective is to assess safety and tolerability of G207 with radiation in recurrent/progressive malignant pediatric cerebellar tumors. After biopsy to prove recurrence/progression, one to four intratumoral catheters will be placed followed by a controlled-rate infusion of G207 for 6 h followed by the removal of catheters at the bedside. Radiation will be given within 24 h of virus inoculation. Patients will be monitored closely for toxicity and virus shedding. Efficacy will be assessed by measuring radiographic response, performance score, progression-free and overall survival, and quality of life. The data obtained will be invaluable in our efforts to produce more effective and less toxic therapies for children with high-grade brain tumors.

OBJECTIVEHydrocephalus is a chronic medical condition that has a significant impact on children and their caregivers. The objective of this study was to measure the quality of life (QOL) of children with hydrocephalus, as assessed by both caregivers and patients.METHODSPediatric patients with hydrocephalus and their caregivers were enrolled during routine neurosurgery clinic visits. The Hydrocephalus Outcomes Questionnaire (HOQ), a report of hydrocephalus-related QOL, was administered to both children with hydrocephalus (self-report) and their caregivers (proxy report about the child). Patients with hydrocephalus also completed measures of anxiety, depression, fatigue, traumatic stress, and headache. Caregivers completed a proxy report of child traumatic stress and a measure of caregiver burden. Demographic information was collected from administration of the Psychosocial Assessment Tool (version 2.0) and from the medical record. Child and caregiver HOQ scores were analyzed and correlated with clinical, demographic, and psychological variables.RESULTSThe mean overall HOQ score (parent assessment of child QOL) was 0.68. HOQ Physical Health, Social-Emotional Health, and Cognitive Health subscore averages were 0.69, 0.73, and 0.54, respectively. The mean overall child self-assessment (cHOQ) score was 0.77, with cHOQ Physical Health, Social-Emotional Health, and Cognitive Health subscore means of 0.84, 0.79, and 0.66, respectively. Thirty-nine dyads were analyzed, in which both a child with hydrocephalus and his or her caregiver completed the cHOQ and HOQ. There was a positive correlation between parent and child scores (p < 0.004 for all subscores). Child scores were consistently higher than parent scores. Variables that showed association with caregiver-assessed QOL in at least one domain included child age, etiology of hydrocephalus, and history of endoscopic third ventriculostomy. There was a significant negative relationship (rho −0.48 to −0.60) between child-reported cHOQ score and child-reported measures of posttraumatic stress, anxiety, depression, and fatigue. There was a similar significant relationship between caregiver report of child’s QOL (HOQ) and caregiver assessment of the child’s posttraumatic stress symptoms as well as their assessment of burden of care (rho = −0.59 and rho = −0.51, respectively). No relationship between parent-reported HOQ and child-reported psychosocial factors was significant. No clinical or demographic variables were associated with child self-assessed cHOQ.CONCLUSIONSPediatric patients with hydrocephalus consistently rate their own QOL higher than their caregivers do. Psychological factors such as anxiety and posttraumatic stress may be associated with lower QOL. These findings warrant further exploration.

Intraventricular melanoma is a very rare and highly malignant disease. Safe resection is the mainstay of treatment, but no standard guidelines exist for adjuvant therapy. Early histologic and molecular diagnosis is key for improved survival.

Glioblastoma (GBM), the most common primary malignant brain tumor in adults, is associated with significant morbidity and mortality despite maximal safe resection followed by chemo- and radiotherapy. GBMs contain self-renewing, tumorigenic glioma stem cells that contribute to tumor initiation, heterogeneity, therapeutic resistance, and recurrence. Intratumoral heterogeneity (ITH) of GBMs is also a major contributing factor to poor clinical outcomes associated with these high-grade glial tumors. Herein, the authors summarize recent discoveries and advances in the molecular and phenotypic characterization of GBMs with particular focus on ITH. In so doing, they attempt to highlight recent advances in molecular signatures/properties and metabolic alterations in an effort to clarify translational implications that may ultimately improve clinical outcomes.

Epidermal Growth Factor Receptor variant III (EGFRvIII) is an active mutant form of EGFR that drives tumor growth in a subset of glioblastoma (GBM). It occurs in over 20% of GBMs, making it a promising receptor for small molecule targeted therapy. We hypothesize that poor penetration of the blood-brain barrier by previously tested EGFR-tyrosine kinase inhibitors (EGFR-TKIs) such as afateninb, erlotinib, gefitinib, and lapatinib played a role in their limited efficacy. The present study examined the effects of osimertinib (previously known as AZD9291) on EGFRvIII+ GBM models, both in vitro and in vivo. Therefore, a panel of six GBM stem cells (GSCs) expressing EGFRvIII+ was evaluated. The EGFRvIII+ GSC differed in the expression of EGFRvIII and other key genes. The GSC line D317, which expresses high levels of EGFRvIII and has robust tyrosine kinase activity, was selected for assessing osimertinib’s efficacy. Herein, we report that osimertinib inhibits the constitutive activity of EGFRvIII tyrosine kinase with high potency (

Retrosigmoid craniotomy for microvascular decompression (MVD) has been traditionally performed via craniectomy. Various closure techniques have been described, yet factors associated with wound-related complications remain undetermined. Accordingly, herein, we sought to identify risk factors associated with wound-related complications after such procedures. An institutional retrospective case-control study was performed; outcomes of interest were cerebrospinal fluid (CSF) leak, wound dehiscence, wound infection, and pseudomeningocele. Univariate analysis was performed using Wilcoxon rank sum test for non-parametric continuous outcomes and chi-square test for categorical outcomes. Multivariate logistic regression was performed on binomial outcome variables. The study population included 197 patients who underwent MVD for trigeminal neuralgia (83.2%), hemifacial spasm (12.2%), vestibular nerve section (3.0%), and glossopharyngeal neuralgia (1.5%). The overall wound-related complication rate was 14.2% (n = 28), including twelve patients (6.1%) with CSF leak, ten patients (5.1%) with wound infection, ten patients (5.1%) with pseudomeningocele, and nine (4.6%) patients with wound dehiscence. Using multivariate logistic regression, preoperative anemia and current tobacco use were associated with significantly higher rates of complications (OR 6.01 and 4.58, respectively; p

Background Arteriovenous malformations (AVMs) can occur in all regions of the brain and spinal cord, with clinical consequences and risks varying by location. Delayed AVM rupture despite digital subtraction angiography–confirmed obliteration post-radiation is exceedingly rare. Case Description To our knowledge, we present the first documented case of delayed hemorrhage associated with a cerebellar AVM 5 years after linear accelerator–based radiation in a man aged 31 years despite apparent angiographic obliteration. Conclusions Intracranial hemorrhage after radiosurgery in digital subtraction angiography–confirmed obliterated AVMs is rare, with limited understanding of risk factors, appropriate preventative management, and mechanisms of occurrence. This case serves to demonstrate the need for greater awareness of this rare complication, as well as the need for appropriate surveillance and management strategies.

Brain ischaemia is a severe form of metabolic stress that activates a cascade of pathological events involving many signalling pathways. Modulation of these pathways is largely mediated by post-translational modifications (PTMs). Indeed, PTMs can rapidly modify pre-existing proteins by attaching chemical or polypeptide moieties to selected amino acid residues, altering their functions, stability, subcellular localizations, or interactions with other proteins. Subsequently, related signalling pathways can be substantially affected. Thus, PTMs are widely deployed by cells as an adaptive strategy at the front line to efficiently cope with internal and external stresses. Many types of PTMs have been identified, including phosphorylation, O-GlcNAcylation, small ubiquitin-like modifier (SUMO) modification (SUMOylation), and ubiquitination. All these PTMs have been studied in brain ischaemia to some extent. In particular, a large body of evidence has demonstrated that both global SUMOylation and ubiquitination are massively activated after brain ischaemia, and this activation may play a critical role in defining the fate and function of cells in the post-ischaemic brain. The goal of this review will be to summarize the current findings on SUMOylation and ubiquitination in brain ischaemia and discuss their clinical implications.

Glioblastoma (GBM) is the most common primary adult intracranial malignancy and carries a dismal prognosis despite an aggressive multimodal treatment regimen that consists of surgical resection, radiation, and adjuvant chemotherapy. Radiographic evaluation, largely informed by magnetic resonance imaging (MRI), is a critical component of initial diagnosis, surgical planning, and post-treatment monitoring. However, conventional MRI does not provide information regarding tumor microvasculature, necrosis, or neoangiogenesis. In addition, traditional MRI imaging can be further confounded by treatment-related effects such as pseudoprogression, radiation necrosis, and/or pseudoresponse(s) that preclude clinicians from making fully informed decisions when structuring a therapeutic approach. A myriad of novel imaging modalities have been developed to address these deficits. Herein, we provide a clinically oriented review of standard techniques for imaging GBM and highlight emerging technologies utilized in disease characterization and therapeutic development.

Patient satisfaction reflects the patients’ perception of the outcome of care and is being considered for use in future reimbursement schemes. No consensus exists regarding the best instrument to measure patient satisfaction in the field of spine surgery. This systematic review aimed to determine how patient satisfaction for spine surgery has been measured previously and whether a disease-specific, comprehensive instrument to measure patient satisfaction has been established; we also aimed to define the dimensions of care that determine patient satisfaction in spine surgery. A systematic search of three online databases, unpublished sources, and citations was undertaken to identify 156 empirical studies that reported on patient satisfaction in the field of spine surgery. Manuscripts were reviewed in terms of the patient satisfaction instrument used, and the instruments were categorized as per content and method axes. Taxonomy of patient satisfaction with spine surgery identified the major characteristics of providers and medical care that influenced patient satisfaction and acted as a structure to categorically define the dimensions of patient satisfaction in spine surgery. The reviewed studies predominantly used global (108/156) rather than multidimensional (46/156), instruments. Most studies (96.2%) reported satisfaction with outcome rather than with care, and only 18.5% of the studies (29/156) utilized a disease-specific instrument. The following seven dimensions of patient status, outcome, and care experience that affected patient satisfaction were identified: pain, function, patient expectations/preference, specific patient health characteristics, caregiver interpersonal manner, efficacy/clinical outcomes, and postoperative care/therapy. Currently, no disease-specific instrument that includes all dimensions of patient satisfaction in spine surgery has been developed. Such a patient satisfaction instrument should be designed, tested for reliability and validity, and widely implemented.

Central neurocytomas are relatively rare well-differentiated neoplasms that arise from neuronal cells with the atypical variant having been noted to be more uncommon/aggressive. Herein, we present a case of an atypical neurocytoma confined to the third ventricle and in so doing review surgical management and outcomes associated with such tumors. We identify a number of cases of central neurocytomas within the third ventricle and clarify both clinical presentation and disease course. Central neurocytomas within the third ventricle are rare while atypical neurocytomas confined to the third ventricle are exceedingly rare. Review of the literature suggests gross total resection should be the preferred treatment modality for these tumors, atypical or not. When only subtotal resection can be achieved, postoperative radiation might be helpful to control tumor recurrence rates.

Leptomeningeal metastasis is extremely rare in patients with ovarian cancer, but should be considered in patients presenting with neurologic deficits such as cauda equine syndrome. Given its poor prognosis and lack of data currently on management, additional studies are needed to optimize treatment regimens and improve outcomes.

Introduction Intracranial atherosclerotic disease (ICAD) is a major cause of stroke worldwide. The optimal management of patients with symptomatic ICAD is controversial. Therefore, the aim of this systematic review is to compare medical management versus surgical bypass for the treatment of symptomatic ICAD. Methods A literature review was performed to identify studies reporting outcomes of patients with ICAD who were managed medically or surgically with either direct or indirect bypass. Baseline, treatment, and outcomes data were analyzed. Complications included ischemic stroke, intracranial hemorrhage, and cerebrovascular death. Secondary analyses of the surgically treated cohort were performed to compare the outcomes of direct versus indirect bypass. Results The pooled analysis was derived from 18 studies, comprising a total of 2160 patients with ICAD, including 1790 managed medically and 370 treated with surgical bypass. The rates of ischemic stroke, intracranial hemorrhage, and cerebrovascular death were 16%, 1%, and 4.5% in the medical cohort, respectively, versus 8%, 0.6%, and 1.9% in the surgical cohort, respectively. Among patients with ICAD who underwent bypass surgery, the rates of ischemic stroke and cerebrovascular death were 7% and 1.9% in the direct bypass group, respectively, versus 19% and 2.1% in the indirect bypass group, respectively. Conclusions Direct or indirect bypass surgery is a reasonable treatment option for appropriately selected patients with ICAD. Careful preoperative evaluation of hemodynamic parameters and the relevant donor and recipient vessels is crucial to maximizing the success of bypass for ICAD. Further studies remain necessary to clarify the roles of medical versus surgical management for ICAD.

Background The development of flow-diverters such as the Pipeline embolization device (PED) have allowed for safe and effective treatment of challenging and/or previously untreatable intracranial aneurysms. A rare but serious complication during PED deployment involves fracture of single or multiple components, which can lead to retained hardware. To date, there are little data regarding the safety of performing magnetic resonance imaging (MRI) when tip or capture coils remain intracranially. Case Description To the best of our knowledge, we present the first case demonstrating the safe completion of MRI after treatment of 2 posterior circulation aneurysms in a woman aged 69 years presenting with subarachnoid hemorrhage whose treatment was complicated by fracture and subsequent retention of the PED tip and capture coils. Conclusions MRI (1.5T) appears safe and effective in patients who have retained PED tips and/or capture coils.

The use of epsilon-aminocaproic acid (EACA) and other anti-fibrinolytic agents has been explored to prevent re-hemorrhage following subarachnoid hemorrhage (SAH) secondary to aneurysmal rupture. One reported complication includes increased rates of hydrocephalus (HCP) due to EACA administration. Herein, we present a single-institution case-control study investigating the relationship between EACA administration and the development of shunt-dependent HCP. All patients were managed by a single neurosurgeon at the University of Alabama at Birmingham (UAB) Medical Center who treated SAH patients with EACA. A power analysis was performed to determine the sample size, and 57 patients who required a ventriculoperitoneal shunt (VPS) for management of obstructive hydrocephalus after failing an external ventricular drain wean protocol were selected. Control patients with initial obstructive hydrocephalus who did not require VPS were matched by demographic factors. The overall rate of VPS placement was 44%; the odds ratio of VPS placement after treatment with EACA was 0.63. The presence of intraventricular hemorrhage or a poor clinical exam on presentation was closely associated with eventual placement of a VPS, with the odds ratio for a Fisher CT grade 4 hemorrhage being 13.89 and a clinical exam corresponding to a Hunt and Hess score of III and IV being 17.18 and 11.00, respectively. The administration of EACA does not appear to increase the incidence of shunt-dependent HCP following SAH and may therefore be employed if clinically needed. Intraventricular hemorrhage or a poor clinical exam on presentation does appear to increase the incidence of shunt-dependent HCP following SAH.

BACKGROUNDMost of the published literature pertaining to blunt traumatic cerebrovascular injury (BCVI) is focused on extracranial arterial injury. Studies of intracranial arterial injury are relatively uncommon.OBSERVATIONSThe clinical course of a patient who sustained an injury to the right posterior communicating artery followed by infarction due to vasospasm after severe traumatic brain injury is presented, along with a focused literature review.LESSONSIntracranial BCVI is uncommon, and this report may serve to raise awareness of BCVI management and the importance of recognizing symptomatic vasospasm due to BCVI.

Background: Intravenous (IV) methamphetamine abuse is associated with a variety of short- and long-term effects on the nervous system, some of which have yet to be fully elucidated. One known systemic complication that has not been described in nervous system tissues is the deposition of substrate crystals contained in injectable drugs. Case Description: An unusual case is presented of a 35-year-old active IV methamphetamine abuser with posterior reversible encephalopathy syndrome (PRES) who subsequently developed multifocal bilateral cerebellar enhancing lesions and leptomeningeal enhancement due to biopsy-proven crystalline deposits. Conclusion: Although large crystalline substances will not normally penetrate the blood–brain barrier (BBB), during a state of BBB compromise such as with PRES, talc deposition may occur in the central nervous system.

Objective The objective of this study was to determine the incidence of seizures following deep brain stimulation (DBS) electrode implantation and to evaluate factors associated with postoperative seizures. Methods The authors performed a single-center retrospective case-control study. The outcome of interest was seizure associated with DBS implantation. Univariate analyses were performed using the Student t-test for parametric continuous outcomes. The authors used the Kruskal-Wallis test or Wilcoxon rank-sum test for nonparametric continuous outcomes, chi-square statistics for categorical outcomes, and multivariate logistic regression for binomial variables. Results A total of 814 DBS electrode implantations were performed in 645 patients (478 [58.7%] in men and 520 [63.9%] in patients with Parkinson's disease). In total, 22 (3.4%) patients who had undergone 23 (2.8%) placements experienced seizure. Of the 23 DBS implantation-related seizures, 21 were new-onset seizures (3.3% of 645 patients) and 2 were recurrence or worsening of a prior seizure disorder. Among the 23 cases with postimplantation-related seizure, epilepsy developed in 4 (17.4%) postoperatively; the risk of DBS-associated epilepsy was 0.50% per DBS electrode placement and 0.63% per patient. Nine (39.1%) implantation-related seizures had associated postoperative radiographic abnormalities. Multivariate analyses suggested that age at surgery conferred a modest increased risk for postoperative seizures (OR 1.06, 95% CI 1.02-1.10). Sex, primary diagnosis, electrode location and sidedness, and the number of trajectories were not significantly associated with seizures after DBS surgery. Conclusions Seizures associated with DBS electrode placement are uncommon, typically occur early within the postoperative period, and seldom lead to epilepsy. This study suggests that patient characteristics, such as age, may play a greater role than perioperative variables in determining seizure risk. Multiinstitutional studies may help better define and mitigate the risk of seizures after DBS surgery.

Background Given recent technological advancements leading to better outcomes in endovascular therapy for acute ischemic stroke (AIS), updated guidelines recommend thrombectomy as the standard of care in acute large vessel occlusions. However, use of general anesthesia versus conscious sedation continues to be discussed. Two previous randomized trials have shown no significant difference between the use of conscious sedation compared with general anesthesia. Methods The authors performed a retrospective analysis of all consecutive patients with acute ischemia who underwent intra-arterial thrombectomy between September 2014 and May 2020 at a Level 1 stroke center. Patient characteristics along with clinical and operative data were extracted. Frequency distributions of selected characteristics were obtained and statistical significance of any differences according to the mode of anesthesia was assessed. Results A total of 480 patients were included in this study, 257 underwent general anesthesia and 223 underwent conscious sedation. Length of stay (LOS) in the ICU nor length of hospital stay was significantly different between groups. Change in National Institutes of Health Stroke Scale (NIHSS) score from admission to discharge, procedure times, and discharge disposition were not found to be significantly associated with either group although there was a trend towards longer door to puncture time with general anesthesia. Discharge disposition was found to be significantly associated with admission NIHSS (p=0.04). There was a trend towards longer hospital stay in patients with worse admission NIHSS (p=0.09). Success of thrombectomy was not significantly different between both anesthesia groups (p=0.37). Conclusions This large, single-center retrospective cohort study echoes the results of two previous randomized controlled trials in demonstrating non-inferiority of general anesthesia versus conscious sedation in cases of intra-arterial thrombectomy for AIS. These results contrast those of previously published retrospective studies.

Sports-related concussion has been examined extensively in collision sports such as football and hockey. However, historically, lower-risk contact sports such as soccer have only more recently garnered increased attention. Here, we review articles examining the epidemiology, injury mechanisms, sex differences, as well as the neurochemical, neurostructural and neurocognitive changes associated with soccer-related concussion. From 436 titles and abstracts, 121 full texts were reviewed with a total of 64 articles identified for inclusion. Concussion rates are higher during competitions and in female athletes with purposeful heading rarely resulting in concussion. Given a lack of high-level studies examining sports-related concussion in soccer, clinicians and scientists must focus research efforts on large-scale data gathering and development of improved technologies to better detect and understand concussion.

Objective The frequency incidence of decompressive hemicraniectomy following intra-arterial thrombectomy (IAT) in acute ischemic stroke (AIS) involving the middle cerebral artery (MCA) territory was assessed as a surrogate for morbidity. Methods A single-institution retrospective chart review was conducted involving 209 consecutive patients between September 2014 and May 2017 with infarctions affecting the MCA territory and who subsequently underwent IAT. The outcomes of interest included the frequency of hemicraniectomy following IAT and the effects of intravenous tissue plasminogen activator (IV tPA) use and primary occlusion site on the Thrombolysis in Cerebral Infarction (TICI) score. Results Thirty-one patients were excluded for infarctions not involving the MCA territory. A total of 178 patients were included in the study. Sixty-eight patients (38.6%) had infarctions of less than one-third of the MCA territory, 50 (28.4%) had infarctions between one-third and two-thirds, and 58 (33%) had infarctions involving greater than two-thirds with 54.3% suffering infarctions of the left side. Only four patients (2.2%) required a hemicraniectomy with no statistically significant association found between TICI score and hemicraniectomy (p=0.41) or between administration of IV tPA and hemicraniectomy (p=0.36). The primary occlusion site was found to influence TICI score (p=0.045). Conclusion A very small number of patients required hemicraniectomy after IAT as compared to previously published rates in the literature. However, several factors may prevent the patient from being an appropriate hemicraniectomy candidate in the first place and the small number of these patients in this study limits statistical analysis. The variables that determine a patient's candidacy for decompressive hemicraniectomy remains multi-factorial.

BACKGROUND AND PURPOSE: Cephaloceles are relatively rare conditions caused by a congenital and/or acquired skull defect. The incidence of associated venous brain anomalies with regard to cephaloceles remains to be fully elucidated. Accordingly, we sought to assess the prevalence of sigmoid sinus dehiscence and diverticula in patients with spontaneous skull base cephaloceles. MATERIALS AND METHODS: Our institutional data base was retrospectively queried from 2005 to 2018. Patients in whom spontaneous skull base cephaloceles were identified were ultimately included in the study cohort. These patients subsequently had their sigmoid sinuses re-evaluated with focused attention on the possible presence of dehiscence and/or diverticula. RESULTS: We identified 56 patients: 12 men and 44 women. After re-evaluation of the sigmoid sinuses, evidence of dehiscence and/or diverticula was noted in 21 patients. The right sigmoid sinus was involved in 11 patients, and the left sigmoid sinus was involved in 7 patients, including 3 cases of diverticulum. In 3 patients, evidence of bilateral sigmoid sinus dehiscence and diverticula was noted. Female sex was associated with sigmoid sinus dehiscence and diverticula by univariate analysis (P = .019). By linear regression, cephalocele volume was negatively associated with sigmoid sinus dehiscence and diverticula (coefficient, −2266, P value < .007, adjusted R(2) = 0.1077). By univariate logistic regression using average cephalocele volume as a cutoff, we demonstrate a statistically significant finding of lower volumes being associated with sigmoid sinus dehiscence and diverticula with an odds ratio of 3.58 (P = .05). CONCLUSIONS: The prevalence of sigmoid sinus dehiscence and diverticula in patients with cephalocele is high. Female sex is associated with sigmoid sinus dehiscence and diverticula. The cephalocele volume appears to be inversely proportional to sigmoid sinus dehiscence and diverticula.

OBJECTIVE The objective of this study was to determine the incidence of seizures following deep brain stimulation (DBS) electrode implantation and to evaluate factors associated with postoperative seizures. METHODS The authors performed a single-center retrospective case-control study. The outcome of interest was seizure associated with DBS implantation. Univariate analyses were performed using the Student t-test for parametric continuous outcomes. The authors used the Kruskal-Wallis test or Wilcoxon rank-sum test for nonparametric continuous outcomes, chi-square statistics for categorical outcomes, and multivariate logistic regression for binomial variables. RESULTS A total of 814 DBS electrode implantations were performed in 645 patients (478 [58.7%] in men and 520 [63.9%] in patients with Parkinson’s disease). In total, 22 (3.4%) patients who had undergone 23 (2.8%) placements experienced seizure. Of the 23 DBS implantation–related seizures, 21 were new-onset seizures (3.3% of 645 patients) and 2 were recurrence or worsening of a prior seizure disorder. Among the 23 cases with postimplantation-related seizure, epilepsy developed in 4 (17.4%) postoperatively; the risk of DBS-associated epilepsy was 0.50% per DBS electrode placement and 0.63% per patient. Nine (39.1%) implantation-related seizures had associated postoperative radiographic abnormalities. Multivariate analyses suggested that age at surgery conferred a modest increased risk for postoperative seizures (OR 1.06, 95% CI 1.02–1.10). Sex, primary diagnosis, electrode location and sidedness, and the number of trajectories were not significantly associated with seizures after DBS surgery. CONCLUSIONS Seizures associated with DBS electrode placement are uncommon, typically occur early within the postoperative period, and seldom lead to epilepsy. This study suggests that patient characteristics, such as age, may play a greater role than perioperative variables in determining seizure risk. Multiinstitutional studies may help better define and mitigate the risk of seizures after DBS surgery.

BackgroundGlioblastoma remains highly lethal due to its inevitable recurrence. This recurrence is found locally in most cases, indicating that post-surgical tumor-initiating cells (TICs) accumulate at tumor edge. These edge TICs then generate recurrent tumors harboring new core lesions. Here, we investigated the clinical significance of the edge-to-core transition (ECT) signature causing glioblastoma recurrence and sought to identify central mediators for ECT.MethodsFirst, we examined the association of the ETC-related expression changes and patient outcome in matched primary and recurrent samples (n=37). Specifically, we tested whether the combined decrease of the edge TIC marker PROM1 (CD133) with the increase of the core TIC marker CD109 representing ECT during the primary-to-recurrence progression indicates poorer patient outcome. We then investigated the specific molecular mediators that trigger tumor recurrence driven by the ECT signature. Subsequently, the functional and translational significance of the identified molecule was validated within our patient-derived tumor edge-TIC modelsin vitroandin vivo.ResultsPatients exhibiting a CD133down/CD109upsignature during recurrence representing ECT displayed a strong association with poorer progression-free survival and overall survival among all tested patients. Differential gene expression identified that PLAGL1 was tightly correlated with the core TIC marker CD109 and was linked to a shorter survival of glioblastoma patients. Experimentally, forced PLAGL1 overexpression enhanced, while its knockdown reduced, the glioblastoma edge-derived tumor growthin vivoand subsequent mouse survival, suggesting its essential role in the ECT-mediated glioblastoma development.ConclusionsECT is likely an ongoing lethal process in primary glioblastoma contributing to its recurrence partly in a PLAGL1/CD109-mediated mechanism.Key PointsECT is a pathobiological process contributing to glioblastoma lethalityThe CD133down/CD109upsignature is a novel prognostic molecular biomarker in ECTPLAGL1 regulates growth of edge-located tumor-initiating cellsImportance of the StudyVery few studies have sought to longitudinally characterize the transition of molecular landscapes from primary to recurrent glioblastoma. Post-surgical edge-located TICs are presumably the predominant source of tumor recurrence, yet this cellular subpopulation in glioblastoma remains largely uncharacterized. This study evaluates the significance of glioblastoma edge-derived core transition (ECT) for tumor recurrence in the primary-recurrent paired sample set. We elucidate a prognostically-significant shift in molecular and cellular phenotypes associated with ECT in the CD133down/CD109upgroup. Moreover, our results provide clinical and experimental evidence that PLAGL1 is a mediator of glioblastoma ECT and its subsequent tumor development by the direct transcriptional regulation of the core TIC marker CD109.

The cover image is based on the Case Report Cauda Equina Syndrome in an Ovarian Malignant‐Mixed Müllerian Tumor with Leptomeningeal Spread by Joshua Bernstock, Gustavo Chagoya, Andrew Janssen et al., https://doi.org/10.1002/ccr3.2472 [Image: see text]

Retrosigmoid craniotomy for microvascular decompression (MVD) has been traditionally performed via craniectomy. Various closure techniques have been described, yet factors associated with wound-related complications remain undetermined. Accordingly, herein, we sought to identify risk factors associated with wound-related complications after such procedures. An institutional retrospective case-control study was performed; outcomes of interest were cerebrospinal fluid (CSF) leak, wound dehiscence, wound infection, and pseudomeningocele. Univariate analysis was performed using Wilcoxon rank sum test for non-parametric continuous outcomes and chi-square test for categorical outcomes. Multivariate logistic regression was performed on binomial outcome variables. The study population included 197 patients who underwent MVD for trigeminal neuralgia (83.2%), hemifacial spasm (12.2%), vestibular nerve section (3.0%), and glossopharyngeal neuralgia (1.5%). The overall wound-related complication rate was 14.2% (n = 28), including twelve patients (6.1%) with CSF leak, ten patients (5.1%) with wound infection, ten patients (5.1%) with pseudomeningocele, and nine (4.6%) patients with wound dehiscence. Using multivariate logistic regression, preoperative anemia and current tobacco use were associated with significantly higher rates of complications (OR 6.01 and 4.58, respectively; p 0.05), including CSF leak (OR 12.83 and 12.40, respectively, p 0.05). Of note, use of synthetic bone substitute for cranioplasty was associated with a significantly lower rate of complications (OR 0.13, p 0.01). Preoperative anemia and current tobacco use significantly increased, while synthetic bone substitute cranioplasty significantly decreased, odds of wound-related complications, the need for treatment, and CSF leaks. Additionally, higher BMI, longer operative duration, and prior radiosurgery may increase risk for wound-related complications.

Background Procalcitonin, a bloodstream inflammatory biomarker, has proven useful in the diagnosis of sepsis in critically ill patients treated in medical and surgical intensive care units. This study aims to further our understanding of the significance of procalcitonin levels in neuroscience intensive care unit (NICU) patients. Methods Neurosurgical patients who underwent a procalcitonin assay in an NICU over a 2-year period were included in our analysis. A procalcitonin level ≥0.2 ng/mL was considered a positive result. Infection was defined by clinical and/or microbiological diagnosis. Sensitivity, specificity, positive predictive value, and negative predictive value in the diagnosis of clinically and/or microbiologically identified infection were calculated for procalcitonin level ≥0.2 ng/mL. Results The study cohort comprised 203 patients, including 63 with a positive procalcitonin assay (31%). Meeting the criteria for SIRS was the most common reason for a procalcitonin draw (35.5%). A procalcitonin level >0.2 ng/mL was not significantly associated with infection (P = 0.25). With a 37.4% false-negative rate and a 10.8% false-positive rate, the sensitivity of a procalcitonin level >0.2 ng/mL was 35.0%, specificity was 74.4%, the positive predictive value was 65.1%, and the negative predictive value was 45.7%. A receiver operating characteristic analysis revealed an area under the curve of 0.61. Conclusions Although the utility of procalcitonin in sepsis and bacterial pneumonia has been amply demonstrated, this biomarker shows limited utility in diagnosing infection in our cohort, emphasizing the importance of cautious and selective use of procalcitonin assays in NICU patients.

BackgroundBlunt cerebrovascular injuries (BCVI) remain a significant source of disability and mortality among trauma patients. The purpose of the present study was to determine whether knowledge silos exist in the overall BCVI literature.MethodsAn object-oriented programmatic script written in Python programming language was used to extract and categorize articles and references on the topic of BCVI. Additionally, each BCVI article was searched for by digital object identifier in the other BCVI references to build a network analysis and visualize topic reference patterns. Analyses were performed using Stata V.14.2 (StataCorp).ResultsA total of 306 articles with 10 282 references were included for analysis. Of these, 24% (74) were published in neurosurgery journals, 45% (137) were published in trauma journals, and 31% (95) were published in a journal of another specialty. Similar proportions were found when categorized by author departmental affiliation. Trauma surgery authors disproportionately referenced articles in the trauma literature, compared with neurosurgeons (73.5% vs. 48.0%, pConclusionsThis study revealed the existence of a one-way knowledge silo in the BCVI literature. However, a robust preference by both trauma and neurosurgery to cite trauma references when publishing in trauma journals may indicate a possible conscious curating of citations by authors to increase the likelihood of publication. These observations highlight the need for an active role by journal editors, peer reviewers, and authors to actively foster diversity of citations and cross-specialty collaboration to improve dissemination of information between these specialties.Level of evidenceLevel IV. Observational study.

Purpose: Artificial intelligence (AI) has accelerated novel discoveries across multiple disciplines including medicine. Clinical medicine suffers from a lack of AI-based applications, potentially due to lack of awareness of AI methodology. Future collaboration between computer scientists and clinicians is critical to maximize the benefits of transformative technology in this field for patients. To illustrate, we describe AI-based advances in the diagnosis and management of gliomas, the most common primary central nervous system (CNS) malignancy. Methods: Presented is a succinct description of foundational concepts of AI approaches and their relevance to clinical medicine, geared toward clinicians without computer science backgrounds. We also review novel AI approaches in the diagnosis and management of glioma. Results: Novel AI approaches in gliomas have been developed to predict the grading and genomics from imaging, automate the diagnosis from histopathology, and provide insight into prognosis. Conclusion: Novel AI approaches offer acceptable performance in gliomas. Further investigation is necessary to improve the methodology and determine the full clinical utility of these novel approaches.

OBJECTIVEDespite an aggressive multimodal therapeutic regimen, glioblastoma (GBM) continues to portend a grave prognosis, which is driven in part by tumor heterogeneity at both the molecular and cellular levels. Accordingly, herein the authors sought to identify metabolic differences between GBM tumor core cells and edge cells and, in so doing, elucidate novel actionable therapeutic targets centered on tumor metabolism.METHODSComprehensive metabolic analyses were performed on 20 high-grade glioma (HGG) tissues and 30 glioma-initiating cell (GIC) sphere culture models. The results of the metabolic analyses were combined with the Ivy GBM data set. Differences in tumor metabolism between GBM tumor tissue derived from within the contrast-enhancing region (i.e., tumor core) and that from the peritumoral brain lesions (i.e., tumor edge) were sought and explored. Such changes were ultimately confirmed at the protein level via immunohistochemistry.RESULTSMetabolic heterogeneity in both HGG tumor tissues and GBM sphere culture models was identified, and analyses suggested that tyrosine metabolism may serve as a possible therapeutic target in GBM, particularly in the tumor core. Furthermore, activation of the enzyme tyrosine aminotransferase (TAT) within the tyrosine metabolic pathway influenced the noted therapeutic resistance of the GBM core.CONCLUSIONSSelective inhibition of the tyrosine metabolism pathway may prove highly beneficial as an adjuvant to multimodal GBM therapies.

Background Effective treatment for pediatric embryonal brain tumors includes dose-intensive multiagent chemotherapy (DIMAC) followed by high-dose chemotherapy with stem cell rescue (HDCSCR). Use of repeated cycles of DIMAC including high-dose methotrexate (HDMTX) without HDCSCR has not been described. Procedure We retrospectively reviewed the responses/toxicities in 13 patients (aged 2-155 months, median 22 months) with central nervous system (CNS) tumors (atypical teratoid rhabdoid tumors, CNS embryonal tumors not otherwise specified, pineoblastoma, embryonal tumor with multilayered rosettes, and CNS sarcoma) treated over a 12-year period with repeated cycles of HDMTX followed by etoposide, cisplatin, cyclophosphamide, and vincristine. Results Six patients (46.2%) had disseminated disease at presentation and five (38.5%) had gross total resection. A total of 64 courses of therapy were administered with a median of five courses per patient. Eight patients (61.5%) received radiation therapy (one at relapse). By completion of therapy, 11 patients (84.6%) achieved a response (six complete, five partial). Six of the 13 patients (46.2%) remain alive with a median follow-up of 48 months (6-146). Acute toxicities included fever/neutropenia (70.3%), bacteremia (15.6%), and grade 3 mucositis (18.8%). Long-term complications included learning disability, seizure disorder, and brain necrosis, without treatment-related deaths. Conclusions DIMAC with HDMTX without HDCSCR may be an effective treatment option for selected patients with embryonal or high-grade CNS tumors.

Background Angiosarcomas are rare malignant tumors of endothelial origin. Nearly half of all angiosarcomas occur in the head and neck. Temporal bone angiosarcomas are extremely uncommon, and in this case report, we present a case of temporal bone angiosarcoma and a review of the relevant literature. Case report We present a 20-year-old male with a painful right postauricular mass following a closed head injury. Radiologic studies demonstrated a large right osteolytic and heterogeneously enhancing mass. The patient underwent right transpetrosal craniectomy for resection. Histologic studies confirmed high-grade sarcoma. Immunohistochemical stains demonstrated uniformly positive ERG endothelial marker, CD31 stain with cytoplasmic and membranous patterns of immunopositivity, positive nuclear staining for FLI-1, positive cytoplasmic and membranous staining for CD99 and STAT6, and negative SMA stains in the neoplastic cells. The Ki-67 staining showed approximately 94% positivity in the neoplastic cell nuclei. Post-surgical follow-up imaging demonstrated evidence of metastatic right cervical lymphadenopathy. Conclusions Angiosarcoma of the temporal bone is extremely uncommon. In this case report, we explore a relationship between trauma and angiosarcoma of the temporal bone. We reviewed the literature regarding the pathogenesis, diagnosis, treatment, radiologic findings, and histologic characteristics of angiosarcoma of the temporal bone.

Infratentorial glioneuronal neoplasms are overall quite rare and are more commonly low-grade with surgical excision usually being curative. Multiple distinct histologic entities have been described including rosette-forming glioneuronal tumor, papillary glioneuronal tumor, neurocytoma, dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease), cerebellar liponeurocytoma, and ganglioglioma. While each of these entities has distinct findings, in some instances a tumor may demonstrate overlapping histologic features with mixed components. Herein, we report 2 unusual adult cases of a fourth ventricular glioneuronal tumor with features of ganglioglioma and neurocytoma, with one coming from a surgical resection and one found incidentally at autopsy. To the best of our knowledge, this specific histologic combination has not previously been described. As such, the clinical significance is unknown although in both cases the neoplasms were circumscribed and appeared to be low grade. The presence of the gangliogliomatous component was of particular interest since these are extremely rare occurrences in the fourth ventricle and we provide a comprehensive review of infratentorial gangliogliomas.

The objective of the study was to establish how patient satisfaction with surgical treatment of Parkinson's disease (PD) has been previously measured, determine whether an ideal patient satisfaction instrument exists, and to define the dimensions of care that determine patient satisfaction with the surgical treatment of PD. A systematic search of four online databases, unpublished sources, and citations was undertaken to identify 15 studies reporting patient satisfaction with the surgical treatment of PD. Manuscripts were reviewed and instruments were categorized by content and method axes. One study was found to utilize two distinct patient satisfaction instruments, which brought the total number of satisfaction instruments assessed to 16. Major factors influencing patient satisfaction were identified and served as a structure to define the dimensions of patient satisfaction in the surgical treatment of PD. Studies used predominantly multidimensional (10/16), rather than global (6/16) satisfaction instruments. Generic (12/16) rather than disease-specific (4/16) instruments were utilized more frequently. Every study reported on satisfaction with outcome and four studies reported on satisfaction with outcome and care. Six dimensions of patient status, outcome and care experience affecting patient satisfaction were identified: motor function, patient-specific health characteristics, programming/long-term care, surgical considerations, device/hardware, and functional independence. At present, no patient satisfaction instrument exists that is disease-specific and covers all dimensions of patient satisfaction in surgery for PD. For quality improvement, such a disease-specific, comprehensive patient satisfaction instrument should be designed, and, if demonstrated to be reliable and valid, widely implemented.

Neurofibromatosis type 1 (NF1) is an autosomal dominant tumor predisposition syndrome that affects children and adults. Individuals with NF1 are at high risk for central nervous system neoplasms including gliomas. The purpose of this review is to discuss the spectrum of intracranial gliomas arising in individuals with NF1 with a focus on recent preclinical and clinical data. In this review, possible mechanisms of gliomagenesis are discussed, including the contribution of different signaling pathways and tumor microenvironment. Furthermore, we discuss the recent notable advances in the developing therapeutic landscape for NF1-associated gliomas including clinical trials and collaborative efforts.