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Background and ObjectiveNearly one-third of patients with severe traumatic brain injury (TBI) develop posttraumatic epilepsy (PTE). The relationship between PTE and long-term outcomes is unknown. We tested whether, after controlling for injury severity and age, PTE is associated with worse functional outcomes after severe TBI.MethodsWe performed a retrospective analysis of a prospective database of patients with severe TBI treated from 2002 through 2018 at a single level 1 trauma center. Glasgow Outcome Scale (GOS) was collected at 3, 6, 12, and 24 months postinjury. We used repeated-measures logistic regression predicting GOS, dichotomized as favorable (GOS 4–5) and unfavorable (GOS 1–3), and a separate logistic model predicting mortality at 2 years. We used predictors as defined by the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) base model (i.e., age, pupil reactivity, and GCS motor score), PTE status, and time.ResultsOf 392 patients who survived to discharge, 98 (25%) developed PTE. The proportion of patients with favorable outcomes at 3 months did not differ between those with and without PTE (23% [95% Confidence Interval [CI]: 15%–34%] vs 32% [95% CI: 27%–39%];p= 0.11) but was significantly lower at 6 (33% [95% CI: 23%–44%] vs 46%; [95% CI: 39%–52%]p= 0.03), 12 (41% [95% CI: 30%–52%] vs 54% [95% CI: 47%–61%];p= 0.03), and 24 months (40% [95% CI: 47%–61%] vs 55% [95% CI: 47%–63%];p= 0.04). This was driven by higher rates of GOS 2 (vegetative) and 3 (severe disability) outcomes in the PTE group. By 2 years, the incidence of GOS 2 or 3 was double in the PTE group (46% [95% CI: 34%–59%]) compared with that in the non-PTE group (21% [95% CI: 16%–28%];p< 0.001), while mortality was similar (14% [95% CI: 7%–25%] vs 23% [95% CI: 17%–30%];p= 0.28). In multivariate analysis, patients with PTE had lower odds of favorable outcome (odds radio [OR] 0.1; 95% CI: 0.1–0.4;p< 0.001), but not mortality (OR 0.9; 95% CI: 0.1–1.9;p= 0.46).DiscussionPosttraumatic epilepsy is associated with impaired recovery from severe TBI and poor functional outcomes. Early screening and treatment of PTE may improve patient outcomes.

Background Stereotactic radiosurgical rhizolysis of the trigeminal nerve is an established modality increasingly employed to alleviate the symptoms of refractory trigeminal neuralgia. This study analyzes the academic impact of the top 100 cited articles on the radiosurgical management of trigeminal neuralgia. Methods The Scopus database was searched for articles containing “radiosurgery” and one or more of “trigeminal neuralgia,” “trigeminus neuralgia,” and “tic douloureux.” The top 100 articles written in English were arranged in descending order by citation count. Documents were evaluated for authors, publication year, journal and impact factor, total citations, nationality, study type, radiosurgical modality, and the affiliated institution. Quantitative and qualitative analyses were performed on the data. Results The most cited articles were published between 1971 and 2019. The average citation per year was 4.3. The most targeted anatomic area was the “root entry zone” or proximal portion of the cisternal segment of the trigeminal nerve. The most utilized modality was Gamma Knife radiosurgery. The country with the highest number of publications was the United States. Thirty-six percent of the articles were published in the Journal of Neurosurgery. Lunsford, Kondziolka, Flickinger, and Régis, respectively, were the most frequently listed co-authors. The most prolific institute was the University of Pittsburgh Medical Center. Conclusion Stereotactic radiosurgery is an important modality in the management of medically or surgically refractory trigeminal neuralgia. This analysis assesses its contributions over the past five decades to identify trends in treatment practices for neurosurgeons and to highlight areas where further study is needed.

OBJECTIVE Vestibular schwannomas (VSs) are benign tumors of the cerebellopontine angle that are typically managed with stereotactic radiosurgery (SRS). Intratumoral hemorrhage (ITH) of VSs is a rare occurrence that results in worsening vestibular and new cranial nerve deficits. Few reports have described the management and outcomes of this entity after SRS. To further delineate the incidence and impact of this event, the authors performed a retrospective review of their VS SRS patients at a single center. METHODS Between 1987 and 2022, 2058 patients with VSs underwent Gamma Knife radiosurgery (GKRS) at the University of Pittsburgh Medical Center. The authors performed a review of the prospectively maintained VS database at their center to identify patients with ITH. The presentation, management, and clinical and imaging outcomes of the patients are reported. RESULTS A total of 1902 VS patients had sufficient clinical and imaging follow-up data. Five Koos grade III (n = 1) and IV (n = 4) VS patients developed ITH after GKRS, resulting in a cumulative incidence rate of 0.26%. The age at presentation ranged from 62 to 79 years, and 3 patients were male. The time from VS diagnosis to GKRS ranged from 1 to 13 months, and the time from GKRS to ITH ranged from 2 to 130 months. Three patients had bleeding risk factors. One patient required urgent surgical intervention due to the ITH volume, while the other 4 patients were initially observed. Three patients remained stable and required no delayed intervention; 1 patient required delayed resection because of symptom progression and hemorrhagic expansion. Histopathological analysis revealed multiple fragments of S-100–positive cells, hemorrhage, and hemosiderin-laden macrophages. At last follow-up, 4 patients had clinically improved and 1 patient remained stable. CONCLUSIONS ITH after VS radiosurgery is a rare phenomenon with a cumulative incidence rate of 0.26% in this series. Patient-tailored management in the form of observation or resection is based on patient presentation, acuity, and ITH size.

OBJECTIVE Epilepsy impacts 470,000 children in the United States. For patients with drug-resistant epilepsy (DRE) and unresectable seizure foci, vagus nerve stimulation (VNS) is a treatment option. Predicting response to VNS has been historically challenging. The objective of this study was to create a clinical VNS prediction tool for use in an outpatient setting. METHODS The authors performed an 11-year retrospective cohort analysis with 1-year follow-up. Patients < 21 years of age with DRE who underwent VNS (n = 365) were included. Logistic regressions were performed to assess clinical factors associated with VNS response (≥ 50% seizure frequency reduction after 1 year); 70% and 30% of the sample were used to train and validate the multivariable model, respectively. A prediction score was subsequently developed. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated. RESULTS Variables associated with VNS response were < 4-year epilepsy duration before VNS (p = 0.008) and focal motor seizures (p = 0.037). The variables included in the clinical prediction score were epilepsy duration before VNS, age at seizure onset, number of pre-VNS antiseizure medications, if VNS was the patient’s first therapeutic epilepsy surgery, and predominant seizure semiology. The final AUCs were 0.7013 for the "fitted" sample and 0.6159 for the "validation" sample. CONCLUSIONS The authors developed a clinical model to predict VNS response in a large sample of pediatric patients treated with VNS. Despite the large sample size, clinical variables alone were not able to accurately predict VNS response. This score may be useful after further validation, although its predictive ability underscores the need for more robust biomarkers to predict treatment response.

This section reviews the selection criteria and best practices for endoscopic cerebrovascular surgery, focusing on purely endoscopic endonasal approaches. Although these approaches still play a limited role in open vascular neurosurgery, they offer a robust and potentially safer technique for establishing visualization and vascular control of particular, well-selected pathologies, such as aneurysms of the proximal circulation; this requires strong, multidisciplinary experience with endoscopic anatomy and surgical technique, advanced reconstruction techniques, and instruments designed to be maneuvered within this relatively novel corridor and application.

OBJECTIVE In mesial temporal lobe epilepsy (MTLE), the ideal surgical approach to achieve seizure freedom and minimize morbidity is an unsolved question. Selective approaches to mesial temporal structures often result in suboptimal seizure outcomes. The authors report the results of a pilot study intended to evaluate the clinical feasibility of using an endoscopic anterior transmaxillary (eATM) approach for minimally invasive management of MTLEs. METHODS The study is a prospectively collected case series of four consecutive patients who underwent the eATM approach for the treatment of MTLE and were followed for a minimum of 12 months. All participants underwent an epilepsy workup and surgical care at a tertiary referral comprehensive epilepsy center and had medically refractory epilepsy. The noninvasive evaluations and intracranial recordings of these patients confirmed the presence of anatomically restricted epileptogenic zones located in the mesial temporal structures. Data on seizure freedom at 1 year, neuropsychological outcomes, diffusion tractography, and adverse events were collected and analyzed. RESULTS By applying the eATM technique and approaching the far anterior temporal lobe regions, mesial-basal resections of the temporal polar areas and mesial temporal structures were successfully achieved in all patients (2 with left-sided approaches, 2 with right-sided approaches). No neurological complications or neuropsychological declines were observed. All 4 patients achieved Engel class Ia outcome up to the end of the follow-up period (19, 15, 14, and 12 months). One patient developed hypoesthesia in the left V2 distribution but there were no other adverse events. The low degree of white matter injury from the eATM approach was analyzed using high-definition fiber tractography in 1 patient as a putative mechanism for preserving neuropsychological function. CONCLUSIONS The described series demonstrates the feasibility and potential safety profile of a novel approach for medically refractory MTLE. The study affirms the feasibility of performing efficacious mesial temporal lobe resections through an eATM approach.

Isocitrate dehydrogenase (IDH) is a key enzyme in normal metabolism and homeostasis. However, mutant forms of IDH are also defining features of a subset of diffuse gliomas. In this review, we highlight current techniques targeting IDH-mutated gliomas and summarize current and completed clinical trials exploring these strategies. We discuss clinical data from peptide vaccines, mutant IDH (mIDH) inhibitors, and PARP inhibitors. Peptide vaccines have the unique advantage of targeting the specific epitope of a patient’s tumor, inducing a highly tumor-specific CD4+ T-cell response. mIDH-inhibitors, on the other hand, specifically target mutant IDH proteins in cancer cell metabolism and thus help halt gliomagenesis. We also explore PARP inhibitors and their role in treating diffuse gliomas, which exploit IDH mutant diffuse gliomas by allowing the persistence of unrepaired DNA complexes. We summarize various completed and current trials targeting IDH1 and IDH2 mutations in diffuse gliomas. Therapies targeting mutant IDH have significant promise treating progressive or recurrent IDH-mutant gliomas and may significantly change treatment paradigms in the next decade.

Background: Minimally invasive approaches to the anterior cranial fossa have evolved over the past few decades. The management of frontal epidural abscesses (EDAs) secondary to diffuse sinusitis in the pediatric population using minimally invasive techniques is scarcely reported in the literature. Herein, we report the utilization of a minimally invasive eyebrow approach for multidisciplinary concurrent evacuation of frontal EDA secondary to diffuse sinusitis and trephination of the frontal sinus in three pediatric patients. Case Reports: Three pediatric patients presented to the emergency room with severe headaches, visual changes, somnolence, and significant facial and periorbital swelling. Imaging revealed diffuse sinusitis with focal frontal epidural extension. In all cases, progressive clinical deterioration along with the radiographic findings mandated urgent surgical intervention. The eyebrow approach allowed for concomitant evacuation of the frontal EDA and trephination of the frontal sinus followed by functional endoscopic sinus surgery in the same setting. All patients tolerated the procedure well with complete resolution of their symptoms at the completion of antibiotic therapy and complete resolution of the EDA. Conclusion: The eyebrow approach is a minimally invasive technique that should be considered as part of the armamentarium in the management of select EDA in the pediatric population. It allows for multidisciplinary collaboration between neurosurgeons and otolaryngologists for concomitant evacuation of the EDA and trephination of the frontal sinus. This approach is a feasible, safe, and effective minimally invasive technique that can be employed for the management of EDA secondary to diffuse sinusitis in the pediatric population.

Background: Optic pathway/hypothalamic gliomas are rare pediatric brain tumors. The management paradigm for these challenging tumors includes chemotherapy, radiotherapy, or surgical resection, but the optimal management strategy remains elusive. Gamma knife radiosurgery (GKRS) has emerged as a promising treatment for such lesions as documented by a small number of cases in the literature. Case Presentation: We present a rare case of hypothalamic glioma in a 13-year-old girl who was referred to our service due to growth of an incidentally diagnosed hypothalamic lesion following head injury at the age of 8 years. The lesion demonstrated hypointensity on T1- and hyperintensity on T2-weighted imaging without contrast enhancement. Given the growth of the lesion on serial imaging, a stereotactic biopsy was performed demonstrating low-grade glioma. The patient underwent GKRS treatment with a marginal dose of 15 Gy at 50% isodose line for a tumor volume of 2.2 mL. Annual radiological surveillance over the next 17 years demonstrated a gradual shrinkage of the lesion until it completely disappeared. The patient is currently a healthy 31-year-old female without any visual, endocrine, or neurocognitive deficits. Conclusion: The outcome obtained after extended follow-up in our patient highlights the safety and efficacy of GKRS in the management of hypothalamic gliomas in pediatrics, which in turn can avoid potentially serious complications of surgery in this vulnerable patient population, especially in this sensitive location.

Background Robotic surgery has found increasing use in multiple subfields of neurosurgery. While the initial applications of stereotactic robotic surgery were for the placement of electrodes for extra-operative seizure monitoring, this technique has become increasingly relevant in other areas of neurosurgery. To the best of our knowledge, we report the first case of successful robotic surgery utilization to drain a cerebral abscess and place an external ventricular drain. Case report The authors demonstrate a novel use for stereotactic robotic assistance to drain a cerebral abscess and place ventriculostomy in a 74-year-old female patient who presented with a left basal ganglia Streptococcus intermedius abscess and concomitant ventriculitis. Drainage of a deep-seated abscess and placement of ventriculostomy was successfully performed in this patient without intraoperative difficulties or complications. The total operative time, including registration was 64 minutes and the estimated blood loss was 25 mL. The patient recovered well and was discharged to inpatient rehabilitation on postoperative day 19. Conclusions The use of robotic surgery to drain cerebral abscesses and place ventriculostomies is technically feasible and may potentially decrease operative time and increase accuracy and safety.

While United States (US) neurosurgery residency programs have been subject to many studies, none have focused solely on the program directors (PDs). We aim to analyze the demographics, educational, and academic attributes of this cohort to understand current and future trends of PDs.One hundred sixteen neurosurgeons listed as PDs at US accredited neurosurgical residency training programs as of August 2022 were assessed. Descriptive data including age upon acceptance of role, gender, and h-index were collected from publicly available sources.Most PDs matriculated to their positions before the age of 45, were male, and had been hired internally. Approximately 25% of PDs had earned an additional degree. Departments with higher aggregate h-indexes were more likely to hire PDs with higher average publications per year (p0.001) and have a higher h-index (p0.001). PD subspecialty influenced h-index (p0.05) and total average publications per year (p0.05) with neuro-oncology subspecialists having higher averages in both. More recently hired PDs had a higher average number of publications per year (p0.05) and were more likely to hold an additional degree (OR = 1.14, p0.05). Female PDs were hired at a younger age (p0.05).Neurosurgery PDs typically rise to their position after 10 years of practice and more recent PD hires are more likely to have additional degrees and more publications. As academic neurosurgery becomes more competitive, increased academic productivity and acquisition of additional degrees will become increasingly necessary.

The human cerebrum consists of a precise and stereotyped arrangement of lobes, gyri, and connectivity that underlies human cognition. The development of this arrangement is less clear. Current models of radial glial cell migration explain individual gyral formation but fail to explain the global configuration of the cerebral lobes. Moreover, the insula, buried in the depths of the Sylvian fissure, belies conventional models. Here, we show that the insula has unique morphology in adults, that insular morphology and slow volumetric growth emerge during fetal development, and that a novel theory of curved migration is required to explain these findings. We calculated morphologic data in the insula and other lobes in adults (N=107) and in anin uterofetal brain atlas (N=81 healthy fetuses).In utero, the insula grows an order of magnitude slower than the other lobes and demonstrates shallower sulci, less curvature, and less surface complexity both in adults and progressively throughout fetal development. Novel spherical projection analysis demonstrates that the lenticular nuclei obstruct 60-70% of radial pathways from the ventricular zone (VZ) to the insula, forcing a curved migration path to the insula in contrast to a direct radial pathway. Using fetal diffusion tractography, we identify streams of putative progenitor cells that originate from the VZ and migrate tangentiallyaroundthe lenticular nuclei to form the insula. These results challenge existing models of radial migration to the cortex, provide an alternative model for insular and cerebral development, and lay the groundwork to understand cerebral malformations, insular functional connectivity, and insular pathologies.

The lateral supraorbital approach (LSO) provides an optimal access corridor for various skull bases lesions, including olfactory groove meningiomas (OGMs). The aim of this study is to describe the authors' experience with the management of large and giant OGMs utilizing the LSO approach and describe the technical nuances of the procedure.A retrospective review of seven patients with large and giant OGMs managed with the LSO approach between 2013 and 2019 was performed. Radiographic and clinical data were recorded and analyzed.Seven patients with large and giant OGMs underwent surgical resection via the LSO approach. Six patients were female, with a median age of 56 years. Patients commonly presented with altered mentation, anosmia, and headaches. The average tumor volume was 120.6 ± 64.7 cmThe LSO approach is a safe and effective minimally invasive transcranial corridor for the management of OGMs that should be part of the armamentarium of skull base neurosurgeons.

OBJECTIVE The aim of this study was to describe the efficacy, clinical outcomes, and complications of open cerebrovascular surgery, endovascular surgery, and conservative management of dolichoectatic vertebrobasilar aneurysms (DVBAs). METHODS Relevant articles were retrieved from PubMed, Scopus, Web of Science, and Cochrane databases according to PRISMA guidelines. A meta-analysis was conducted for clinical presentation, treatment protocols, and clinical outcomes—good (improved or stable clinical status) or poor (deteriorated clinical status or death)—and mortality rates. RESULTS The 9 identified articles described 41 cases (27.5%) of open cerebrovascular surgery, 61 endovascular procedures (40.9%), and 47 cases (31.5%) of conservative management for DVBAs. The total cohort had a good outcome rate of 51.9% (95% CI 28.3%–74.6%), a poor outcome rate of 45.5% (95% CI 23.0%–70.1%), and a mortality rate of 22.3% (95% CI 11.8%–38.0%). The treatment groups had comparable good clinical outcome rates (open cerebrovascular surgery group: 24.7% [95% CI 2.9%–78.2%]; endovascular surgery group: 69.0% [95% CI 28.7%–92.5%]; conservative management group: 57.7% [95% CI 13.0%–92.5%]; p = 0.19) and poor outcome rates (open vascular surgery group: 75.3% [95% CI 21.8%–97.1%]; endovascular surgery group: 27.2% [95% CI 5.6%–0.70.2%]; conservative management group: 39.9% [95% CI 9.1%–81.6%]; p = 0.15). The treatment groups also had comparable mortality rates (open vascular surgery group: 39.5% [95% CI 11.4%–76.8%]; endovascular surgery group: 15.8% [95% CI 4.4%–43.0%]; conservative management group: 19.2% [95% CI 6.8%–43.5%]; p = 0.23). CONCLUSIONS The current study of DVBAs illustrated poor outcomes and high mortality rates regardless of the treatment modality. The subgroup analysis showed heterogeneity among the subgroups and advice for personalized management.

Stereotactic radiosurgery (SRS) offers a minimally invasive treatment modality for appropriately selected intracranial arteriovenous malformations (AVMs). Recent reports have described the development of rare, delayed chronic encapsulated expanding hematomas (CEEHs) at the site of an angiographically confirmed obliterated AVM.To elucidate the incidence, characteristics, and management of CEEH in patients with AVM after SRS.The records of all patients who underwent SRS for an intracranial AVM at 4 institutions participating in the International Radiosurgery Research Foundation between 1987 and 2021 were retrospectively reviewed. Data regarding characteristics of the AVM, SRS treatment parameters, CEEH presentation, management, and outcomes were collected and analyzed.Among 5430 patients, 15 developed a CEEH at a crude incidence of 0.28%. Nine patients were female, and the mean age was 43 ± 14.6 years. Nine patients underwent surgical evacuation, while 6 were managed conservatively. The median CEEH development latency was 106 months after SRS. The patients were followed for a median of 32 months, and 9 patients improved clinically, while 6 patients remained stable. No intraoperative complications were reported after CEEH resection, although 1 patient recovered from postoperative meningitis requiring intravenous antibiotics.CEEH is a rare, late complication of AVM SRS with an incidence of 0.28% and a median latency of 106 months. In the presence of a delayed and symptomatic expanding hematoma in the bed of an angiographically obliterated AVM, surgical resection resulted in clinical improvement in most patients. Conservative management is possible in asymptomatic patients with stable, small-sized hematomas in deeply seated locations.

BACKGROUND Hydrocephalus is a common condition associated with high morbidity and mortality rates. Despite advancements in shunt systems and valve designs, complications associated with ventriculoperitoneal (VP) shunts are steadily recognized and reported in the literature. Here, we present an unusual case of VP shunt failure due to catheter kinking at the site of the slits in the distal peritoneal catheter. CASE REPORT A 30-year-old woman with type I Chiari malformation, prior suboccipital craniectomy, and shunted hydrocephalus with prior revisions presented with 2 months of progressive, low-pressure headaches. Shunt series X-rays demonstrated kinking of the distal peritoneal catheter. A computed tomography (CT) scan showed interval enlargement of her ventricles concerning for shunt failure, which prompted return to the operating room. During shunt revision, her valve was nonfunctioning with loss of resistance and her distal catheter was kinked at the most proximal peritoneal slit. Postoperative shunt series X-rays demonstrated an intact shunt system without kinking or discontinuity and a CT of her head showed interval decease in the caliber of her ventricles. CONCLUSIONS Distal peritoneal catheter kinking at the site of slits is an unusual complication of VP shunts and should be considered. Surgeons should add this possibility to the differential diagnosis of shunt malfunction when an imaging irregularity is identified in the peritoneal catheter.

Sterotactic radiosurgery is becoming an integral modality in the management of intracranial meningiomas, both as the primary treatment or as adjuvant therapy. This study analyzes the scholarly impact of the top 100 cited articles on the stereotactic radiosurgical management of intracranial meningiomas.A ranked list of the 100 most-cited articles was generated using the Scopus database by searching the keywords 'intracranial meningioma' and 'stereotactic radiosurgery'. All articles were then evaluated on multiple criteria regarding both the publication of the articles (year of publication, journal, country of origin, and authors) as well as their methods and foci (type of study, location of studied meningiomas, and type of radiosurgical modality). Quantitaitve and qualitative analyses were then performed from the collected data.The most frequently cited articles on stereotactic radiosurgical management of intracranial meningiomas were published between 1990 and 2016. The average citation-per-year across all papers in the list was 6.1. The most studied anatomic area of intracranial meningiomas was the skull base, with the cavernous sinus being the most well-studied specific site. The most utilized stereotactic radiosurgical modality was Gamma Knife radiosurgery. The country with the highest number of publications was the United States. Twenty-six percent of the articles were published in the journal Neurosurgery; Lunsford, Kondziolka, Flickinger, Sheehan, and Pollock were respectively the most frequent listed authors among this list. The most active academic institute publishing on this topic was the University of Pittsburgh Medical Center.Stereotactic radiosurgery is an integral modality in the management of intracranial meningiomas. This bibliometric analysis sheds the light on the ways in which intracranial meningiomas have been studied in the past two decades in order to identify trends among neurosurgeons and radiation oncologists and to reveal areas of rising and declining focus.

Thirty-day readmission following glioblastoma (GBM) resection is not only correlated with decreased overall survival but also increasingly tied to quality metrics and reimbursement. This study aimed to determine factors linked with 30-day readmission to develop a simple risk stratification score. From 2005 to 2016, 666 unique resections (467 patients) of primary/recurrent tissue-confirmed glioblastoma were retrospectively identified. We recorded patient demographics and medical history, tumor characteristics, post-operative complications and 30-day readmission. Univariate and multivariate logistic regression, optimized using a genetic learning algorithm, were used to determine factors associated with readmission. The multivariate model was converted to a simple additive score. The 30-day readmission rate was 20.3% in our cohort of 666 unique resections (60.7% first resection). Lower pre/post-operative KPS, recurrent resection, surgical-site infection, post-operative VTE, post-operative VPS, and discharge to a rehabilitation facility were significantly associated with an increased readmission risk (p 0.05). MGMT methylation and chemoradiation were associated with decreased readmission risk (p 0.05). Medical co-morbidities and past medical history, location of tumor in eloquent areas of the brain, and length of ICU/hospital stay did not predict readmission. The Glioblastoma Readmission Risk Score, developed from the multivariate model, accounts for increased BMI, decreased pre-operative KPS, current smoking, post-operative complications, MGMT methylation, and post-operative radiation. This risk score can be routinely used to stratify risk and assist in clinical decision making and outcome analyses.

The mechanisms by which the human cerebral cortex folds into its final form remain poorly understood. With most of the current models and evidence addressing secondary folds, we sought to focus on the global geometry of the mature brain by studying its most distinctive feature, the Sylvian fissure. A digital human fetal brain atlas was developed using previously obtained MRI imaging of 81 healthy fetuses between gestational ages 21 and 38 weeks. To account for the development of the Sylvian fissure, we compared the growth of the frontotemporal opercula over the insular cortex and compared the transcriptome of the developing cortices for both regions. Spatiotemporal mapping of the lateral hemispheric surface showed the highest rate of organized growth in regions bordering the Sylvian fissure of the frontal, parietal and temporal lobes. Volumetric changes were first observed in the posterior aspect of the fissure moving anteriorly to the frontal lobe and laterally in the direction of the temporal pole. The insular region, delineated by the limiting insular gyri, expanded to a much lesser degree. The gene expression profile, before folding begins in the maturing brain, was significantly different in the developing opercular cortex compared to the insula. The Sylvian fissure forms by the relative overgrowth of the frontal and temporal lobes over the insula, corresponding to domains of highly expressed transcription factors involved in neuroepithelial cell differentiation.

The signature folds of the human brain are formed through a complex and developmentally regulated process. In vitro and in silico models of this process demonstrate a random pattern of sulci and gyri, unlike the highly ordered and conserved structure seen in the human cortex. Here, we account for the large-scale pattern of cortical folding by combining advanced fetal MRI with nonlinear diffeomorphic registration and volumetric analysis. Our analysis demonstrates that in utero brain growth follows a logistic curve, in the absence of a lack of external volume constraints. The Sylvian fissure forms from interlobar folding, where separate lobes overgrow and close an existing subarachnoid space. In contrast, other large sulci, which are the ones represented in existing models, fold through an invagination of a flat surface, a mechanistically different process. Analyzing local variations in volumetric expansion rates, we demonstrate that the three phases of the logistic curve correspond to three different phases of folding - interlobar, large sulcal, and secondary folding. Cortical folding is driven by multiple spatially and temporally different mechanisms, therefore regionally distinct biological process may be responsible for the global geometry of the adult brain.

IntroductionEpilepsy impacts 470,000 children in the United States, and children with epilepsy are estimated to expend 6 times more on healthcare than those without epilepsy. For patients with antiseizure medication (ASM)-resistant epilepsy and unresectable seizure foci, vagus nerve stimulation (VNS) is a treatment option. Predicting response to VNS has been historically challenging. We aimed to create a clinical prediction score which could be utilized in a routine outpatient clinical setting.MethodsWe performed an 11-year, single-center retrospective analysis of patients ResultsThis analysis included 365 patients. Multivariate logistic regression revealed that variables associated with VNS response were: ConclusionsWe developed a clinical model to predict VNS response in one of the largest samples of pediatric VNS patients to date. While the presented clinical prediction model demonstrated an acceptable AUC in the training cohort, clinical variables alone likely do not accurately predict VNS response. This score may be useful upon further validation, though its predictive ability underscores the need for more robust biomarkers of treatment response.

OBJECTIVE The objective of this retrospective study was to compare the survival of patients with biopsy-proven skull base chordoma who had undergone stereotactic radiosurgery (SRS) with versus without prior fractionated radiation therapy (RT). METHODS Relevant articles from database inception to September 2021 were retrieved from the PubMed, Scopus, Web of Science, and Cochrane databases for a systematic review of treatment protocols. Studies were included if they 1) involved adult patients (age ≥ 18 years) with histologically and radiologically confirmed chordomas located within the clival skull base region and treated with SRS; 2) reported data on clinical features, SRS protocols, and outcomes; and 3) were written in the English language. Studies were excluded if they 1) were literature reviews, case reports, technical notes, abstracts, or autopsy reports; 2) did not clearly differentiate the data of patients with chordomas from the data of patients with different tumors or the data of patients with chordomas in locations other than the skull base; or 3) lacked histological confirmation or treatment and outcome data. Extracted data included the following: study author and publication year, patient age and sex, symptoms, cranial nerve involvement, invaded structures, lesion size, treatment modality, surgical details, histopathological type, RT modality, SRS parameters, complications, postradiosurgery outcomes, complications, and survival outcomes. RESULTS After the selection process, 15 articles describing 130 patients met the study eligibility criteria, including 94 patients who had undergone postresection SRS (NoRT group) and 36 who had undergone postresection fractionated RT and subsequent SRS (RT group). The NoRT and RT groups were comparable in age (51.3 vs 47.4 years, respectively), sex (57.1% vs 58.3% male), tumor volume (9.5 vs 11.2 cm3), SRS treatment parameters (maximum dose: 35.4 vs 42.2 Gy, marginal dose: 19.6 vs 20.6 Gy, treatment isodose line: 60.2% vs 65.2%), and SRS adverse effects (10.9% vs 17.6%). For the entire cohort, the 3-, 5-, and 10-year progression-free survival (PFS) rates were 23%, 9%, and 3%, respectively, and the overall survival (OS) rates were 94%, 82%, and 76%, respectively. In the NoRT group, SRS was adjuvant treatment after resection in 38 patients (40.4%), salvage treatment for recurrent tumor treated with resection alone in 10 (10.6%), and not specified in 46 (48.9%). In the RT group, SRS was boost treatment in 9 patients (25.0%), salvage treatment after recurrence in 22 (61.1%), and not specified in 5 (13.9%). There was no difference between the two groups in terms of median PFS (24.0 months [Q1 34.0, Q3 15.0] vs 23.8 months [34.0, 18.0], respectively; p = 0.8) or median OS (293.0 months [not reached, 137.4] vs not reached [not reached, 48.0], respectively; p = 0.36). The adverse radiation effect rates were comparable between the groups (10.9% vs 17.6%, respectively; p = 0.4). CONCLUSIONS The role of SRS in the management of skull base chordomas is still evolving. This systematic literature review of biopsy-proven chordoma revealed that tumor control and survival rates for SRS alone after chordoma surgery were not inferior to those encountered after SRS plus fractionated RT.

OBJECTIVE Corpus callosotomy is a safe and effective procedure for reducing the frequency of drop attacks. MR-guided laser interstitial thermal therapy (MRgLITT) offers a minimally invasive alternative to conventional open craniotomy for callosotomy. We hypothesized that MRgLITT callosotomy could be safely performed in pediatric patients with similar seizure control. METHODS We present an institutional case series of 11 procedures in 10 patients for the treatment of drop attacks in drug-refractory primary generalized epilepsy. MRgLITT was used for complete callosotomy, anterior two-thirds, posterior, or ablation of residual callosal fibers following prior callosotomy (open or MRgLITT). We retrospectively reviewed clinical course, operative details, radiographic imaging, clinical outcomes, and complications. RESULTS Operative time ranged from 4-8 hours, and median hospitalization was 2 days. No complications were encountered. Among the 7 patients with at least 3 months of follow-up, 71% experienced freedom from drop attacks at longest follow-up and 57% of cases showed improvement in their other seizure semiologies as well (Engel Class II: 28%, Class III: 28%, Class IV: 43%). SIGNIFICANCE MR-guided LITT callosotomy is safe and effective modality in the management of pediatric patients with medically intractable epilepsy characterized by drop attacks. While this is among the largest pediatric series to date, further studies are required to delineate its safety and efficacy among such patients.

To summarize the clinical features and outcomes of petroclival meningioma patients treated with stereotactic radiosurgery (SRS) as either a primary or an adjuvant modality.Relevant articles were retrieved from PubMed, Scopus, Web of Science, and Cochrane. A systematic review and meta-analysis of treatment outcomes comparing primary and adjuvant SRS was conducted.Seven articles comprising 722 cases were included. The mean tumor marginal dose was 13.5 Gy. After SRS, symptoms improved in 28.7%, remained unchanged in 61.3%, and worsened in 10.0% of the cohort. Tumor control was achieved in 94.8% of patients. The mean tumor volume change was -6.4 cmSRS of petroclival meningiomas was associated with excellent long-term PFS and local tumor control rates. Primary SRS was highly effective for patients with smaller volume lesions without clinically symptomatic mass effect. In patients who warrant initial resection, adjuvant radiosurgery remains an important modality to prevent regrowth while maintaining postresection function.

Background Fluorescein is an agent that accumulates in areas of blood-brain barrier breakdown and is commonly used in neurosurgical oncology to assist with lesion localization and visualizing the extent of resection. It is considered to be cost-effective and has a favorable safety profile. Studies on the utilization of fluorescein demonstrate an improved extent of tumor resection and increased overall survival. Currently, fluorescein detection systems are all microscope based, leading to limitations such as decreased maneuverability, limited visualization of the entire operative field, and significant cost associated with obtaining and maintaining a neurosurgical operating microscope. Methods Three consecutive craniotomy patients for tumor resection were included, and surgery was carried out under loupe fluorescence guidance using the ReVeal 450 System, and also a surgical microscope for comparison. Results Loupe-mounted fluorescence system enabled excellent visualization of fluorescence in all three cases. Conclusions In this manuscript, we describe our experience with a loupe-mounted fluorescein detection system in 3 patients with malignant gliomas. We found that the loupe-mounted system offered excellent ability to visualize fluorescein fluorescence. Although loupe-mounted systems are not an alternative to surgical microscopes, they could be a useful surgical adjunct for superficial lesions and in low-middle income counties.

Introduction Mirror aneurysms of the middle cerebral artery (MCA) constitute 14% of all MCA aneurysms, which commonly arise from the MCA bifurcation. Giant MCA aneurysms (>25 mm in diameter) have a reported 5-year rupture rate of 40%, though can be difficult to treat surgically given their complex nature. Giant aneurysms may present with symptoms of mass effect, including neurological deficit, headaches, and/or cranial neuropathies. To our knowledge, no case of mirror bilateral giant MCA aneurysms exists in the neurosurgical literature. Case description Here we present a case of mirror bilateral giant MCA aneurysms in an 84-year-old man who presented with altered mental status and increased falls in the last year. Imaging revealed mirror MCA aneurysms, 3.5 and 4 cm in diameter respectively, arising from bilateral M1 segments. The patient opted to forego further evaluation or surgical intervention and was discharged home. Conclusion We report the first known case of mirror bilateral giant MCA aneurysms were found in an 84-year-old man presenting with altered mental status and progressive decline across the last year.

BACKGROUND Invasive sagittal sinus meningiomas are difficult tumors to cure by resection alone. Stereotactic radiosurgery (SRS) can be used as an adjuvant management strategy to improve tumor control after incomplete resection. OBSERVATIONS The authors reported the long-term retrospective follow-up of two patients whose recurrent parasagittal meningiomas eventually occluded their superior sagittal sinus. Both patients underwent staged radiosurgery and fractionated radiation therapy to achieve tumor control that extended to 20 years after their initial surgery. After initial subtotal resection of meningiomas that had invaded major cerebral venous sinuses, adjuvant radiosurgery was performed to enhance local tumor control. Over time, adjacent tumor progression required repeat SRS and fractionated radiation therapy to boost long-term tumor response. Staged multimodality intervention led to extended survival in these patients with otherwise unresectable meningiomas. LESSONS Multimodality management with radiosurgery and fractionated radiation therapy was associated with long-term survival of two patients with otherwise surgically incurable and invasive meningiomas of the dural venous sinuses.