Robust compression and detection of epileptiform patterns in ECoG using a real-time spiking neural network hardware framework.

Interictal Epileptiform Discharges (IED) and High Frequency Oscillations (HFO) in intraoperative electrocorticography (ECoG) may guide the surgeon by delineating the epileptogenic zone. We designed a modular spiking neural network (SNN) in a mixed-signal neuromorphic device to process the ECoG in real-time. We exploit the variability of the inhomogeneous silicon neurons to achieve efficient sparse and decorrelated temporal signal encoding. We interface the full-custom SNN device to the BCI2000 real-time framework and configure the setup to detect HFO and IED co-occurring with HFO (IED-HFO). We validate the setup on pre-recorded data and obtain HFO rates that are concordant with a previously validated offline algorithm (Spearman's ρ = 0.75, p = 1e-4), achieving the same postsurgical seizure freedom predictions for all patients. In a remote on-line analysis, intraoperative ECoG recorded in Utrecht was compressed and transferred to Zurich for SNN processing and successful IED-HFO detection in real-time. These results further demonstrate how automated remote real-time detection may enable the use of HFO in clinical practice.

Functional hemispheric disconnection procedures for chronic epilepsy: history, indications, techniques, complications and current practice in Europe. A consensus statement on behalf of the EANS functional neurosurgery section.

Introduction: The surgical procedure for severe, drug-resistant, unilateral hemispheric epilepsy is challenging. Over the last decades the surgical landscape for hemispheric disconnection procedures changed from anatomical hemispherectomy to functional hemispherotomy with a reduction of complications and stable good seizure outcome. Here, a task force of European epilepsy surgeons prepared, on behalf of the EANS Section for Functional Neurosurgery, a consensus statement on different aspects of the hemispheric disconnection procedure. Research question: To determine history, indication, timing, techniques, complications and current practice in Europe for hemispheric disconnection procedures in drug-resistant epilepsy. Material and methods: Relevant literature on the topic was collected by a literature search based on the PRISMA 2020 guidelines. Results: A comprehensive overview on the historical development of hemispheric disconnection procedures for epilepsy is presented, while discussing indications, timing, surgical techniques and complications. Current practice for this procedure in European epilepsy surgery centers is provided. At present, our knowledge of long-term seizure outcomes primarily stems from open surgical disconnection procedures. Although minimal invasive surgical techniques in epilepsy are rapidly developing and reported in case reports or small case series, long-term seizure outcome remain uncertain and needs to be reported. Discussion and conclusion: This is the first paper presenting a European consensus statement regarding history, indications, techniques and complications of hemispheric disconnection procedures for different causes of chronic, drug-resistant epilepsy. Furthermore, it serves as the pioneering document to report a comprehensive overview of the current surgical practices regarding this type of surgery employed in renowned epilepsy surgery centers across Europe.

Defining benchmark outcomes for mesial temporal lobe epilepsy surgery: A global multicenter analysis of 1119 cases.

OBJECTIVE: Benchmarking has been proposed to reflect surgical quality and represents the highest standard reference values for desirable results. We sought to determine benchmark outcomes in patients after surgery for drug-resistant mesial temporal lobe epilepsy (MTLE). METHODS: This retrospective multicenter study included patients who underwent MTLE surgery at 19 expert centers on five continents. Benchmarks were defined for 15 endpoints covering surgery and epilepsy outcome at discharge, 1 year after surgery, and the last available follow-up. Patients were risk-stratified by applying outcome-relevant comorbidities, and benchmarks were calculated for low-risk ("benchmark") cases. Respective measures were derived from the median value at each center, and the 75th percentile was considered the benchmark cutoff. RESULTS: A total of 1119 patients with a mean age (range) of 36.7 (1-74) years and a male-to-female ratio of 1:1.1 were included. Most patients (59.2%) underwent anterior temporal lobe resection with amygdalohippocampectomy. The overall rate of complications or neurological deficits was 14.4%, with no in-hospital death. After risk stratification, 377 (33.7%) benchmark cases of 1119 patients were identified, representing 13.6%-72.9% of cases per center and leaving 742 patients in the high-risk cohort. Benchmark cutoffs for any complication, clinically apparent stroke, and reoperation rate at discharge were ≤24.6%, ≤.5%, and ≤3.9%, respectively. A favorable seizure outcome (defined as International League Against Epilepsy class I and II) was reached in 83.6% at 1 year and 79.0% at the last follow-up in benchmark cases, leading to benchmark cutoffs of ≥75.2% (1-year follow-up) and ≥69.5% (mean follow-up of 39.0 months). SIGNIFICANCE: This study presents internationally applicable benchmark outcomes for the efficacy and safety of MTLE surgery. It may allow for comparison between centers, patient registries, and novel surgical and interventional techniques.

Intraoperative ultrasonography in microsurgical resection of vestibular schwannomas via retrosigmoid approach: surgical technique and proof-of-concept illustrative case series.

PURPOSE: Intraoperative ultrasonography (ioUS) is an established tool for the real-time intraoperative orientation and resection control in intra-axial oncological neurosurgery. Conversely, reports about its implementation in the resection of vestibular schwannomas (VS) are scarce. The aim of this study is to describe the role of ioUS in microsurgical resection of VS. METHODS: ioUS (Craniotomy Transducer N13C5, BK5000, B Freq 8 MHz, BK Medical, Burlington, MA, USA) is integrated into the surgical workflow according to a 4-step protocol (transdural preresection, intradural debulking control, intradural resection control, transdural postclosure). Illustrative cases of patients undergoing VS resection through a retrosigmoid approach with the use of ioUS are showed to illustrate advantages and pitfalls of the technique. RESULTS: ioUS allows clear transdural identification of the VS and its relationships with surgically relevant structures of the posterior fossa and of the cerebellopontine cistern prior to dural opening. Intradural ioUS reliably estimates the extent of tumor debulking, thereby helping in the choice of the right moment to start peripheral preparation and in the optimization of the extent of resection in those cases where subtotal resection is the ultimate goal of surgery. Transdural postclosure ioUS accurately depicts surgical situs. CONCLUSION: ioUS is a cost-effective, safe, and easy-to-use intraoperative adjunctive tool that can provide a significant assistance during VS surgery. It can potentially improve patient safety and reduce complication rates. Its efficacy on clinical outcomes, operative time, and complication rate should be validated in further studies.

Determinants of Functional Outcome after Pediatric Hemispherotomy.

OBJECTIVE: We aimed to evaluate determinants of functional outcome after pediatric hemispherotomy in a large and recent multicenter cohort. METHODS: We retrospectively investigated the functional outcomes of 455 children who underwent hemispherotomy at 5 epilepsy centers in 2000-2016. We identified determinants of unaided walking, voluntary grasping with the hemiplegic hand, and speaking through Bayesian multivariable regression modeling using missing data imputation. RESULTS: Seventy-five percent of children were seizure-free, and 44% stopped antiseizure medication at a 5.1-year mean follow-up (range = 1-17.1). Seventy-seven percent of children could walk unaided, 8% could grasp voluntarily, and 68% could speak at the last follow-up. Children were unlikely to walk when they had contralateral magnetic resonance imaging (MRI) abnormalities (40/73, p = 0.04), recurrent seizures following hemispherotomy (62/109, p = 0.04), and moderately (50/61, p = 0.03) or severely impaired (127/199, p = 0.001) postsurgical intellectual functioning, but were likely to walk when they were older at outcome determination (p = 0.01). Children were unlikely to grasp voluntarily with the hand contralateral to surgery when they had Rasmussen encephalitis (0/61, p = 0.001) or Sturge-Weber syndrome (0/32, p = 0.007). Children were unlikely to speak when they had contralateral MRI abnormalities (30/69, p = 0.002) and longer epilepsy duration (p = 0.01), but likely to speak when they had Sturge-Weber syndrome (29/35, p = 0.01), were older at surgery (p = 0.04), and were older at outcome determination (p < 0.001). INTERPRETATION: Etiology and bilaterality of structural brain abnormalities were key determinants of functional outcome after hemispherotomy. Longer epilepsy duration affected language outcomes. Not surprisingly, walking and talking ability increased with older age at outcome evaluation. ANN NEUROL 2024;95:377-387.

Safety of microneurosurgical interventions for superficial and deep-seated brain metastases: single-center cohort study of 637 consecutive cases.

PURPOSE: Microneurosurgical techniques have greatly improved over the past years due to the introduction of new technology and surgical concepts. To reevaluate the role of micro-neurosurgery in brain metastases (BM) resection in the era of new systemic and local treatment options, its safety profile needs to be reassessed. The aim of this study was to analyze the rate of adverse events (AEs) according to a systematic, comprehensive and reliably reproducible grading system after microneurosurgical BM resection in a large and modern microneurosurgical series with special emphasis on anatomical location. METHODS: Prospectively collected cases of BM resection between 2013 and 2022 were retrospectively analyzed. Number of AEs, defined as any deviations from the expected postoperative course according to Clavien-Dindo-Grade (CDG) were evaluated. Patient, surgical, and lesion characteristics, including exact anatomic tumor locations, were analyzed using uni- and multivariate logistic regression and survival analysis to identify predictive factors for AEs. RESULTS: We identified 664 eligible patients with lung cancer being the most common primary tumor (44%), followed by melanoma (25%) and breast cancer (11%). 29 patients (4%) underwent biopsy only whereas BM were resected in 637 (96%) of cases. The overall rate of AEs was 8% at discharge. However, severe AEs (≥ CDG 3a; requiring surgical intervention under local/general anesthesia or ICU treatment) occurred in only 1.9% (n = 12) of cases with a perioperative mortality of 0.6% (n = 4). Infratentorial tumor location (OR 5.46, 95% 2.31-13.8, p = .001), reoperation (OR 2.31, 95% 1.07-4.81, p = .033) and central region tumor location (OR 3.03, 95% 1.03-8.60) showed to be significant predictors in a multivariate analysis for major AEs (CDG ≥ 2 or new neurological deficits). Neither deep supratentorial nor central region tumors were associated with more major AEs compared to convexity lesions. CONCLUSIONS: Modern microneurosurgical resection can be considered an excellent option in the management of BM in terms of safety, as the overall rate of major AEs are very rare even in eloquent and deep-seated lesions.

Laser interstitial thermal therapy in pediatric cerebellar epilepsy.

Cerebellar lesional epilepsy is rare, commonly manifesting in early life and posing diagnostic and treatment challenges. Seizure semiology may be subtle, with repetitive eye blinking, face twitching, and irregular breathing, while EEG commonly remains unremarkable. Pharmacoresistance is the rule, and surgical intervention is the only treatment with the potential for cure. Novel minimally invasive techniques, such as laser interstitial thermal therapy (LITT), are emerging for surgically less accessible, deep-seated epileptogenic lesions. We report the case of a patient who presented with peculiar eye and face movements occurring episodically and stereotypically since the first weeks of life and was later diagnosed with cerebellar epilepsy related to a hamartoma. Refractory daily seizures, unresponsive to antiseizure medication, were followed by increasingly prominent gait ataxia and delayed speech development. Staged LITT was performed in two consecutive sessions at 3 and 4 years, leading to seizure cessation, neurological improvement, and developmental gains over a postsurgical follow-up period of 8 months. Our case highlights cerebellar lesional epilepsy as a rare but important differential diagnosis in children with paroxysmal disorders predominantly involving the face. Furthermore, we illustrate the radiological correlates of neurocognitive deficit related to the cerebellar lesion, manifesting as cerebello-cerebral diaschisis. Most importantly, our observations showcase LITT as a safe and effective therapeutic approach in cerebellar lesional epilepsy and an attractive alternative to open brain surgery, especially for deep-seated lesions in the pediatric population.

A T-cell antigen atlas for meningioma: novel options for immunotherapy.

Meningiomas are the most common primary intracranial tumors. Although most symptomatic cases can be managed by surgery and/or radiotherapy, a relevant number of patients experience an unfavorable clinical course and additional treatment options are needed. As meningiomas are often perfused by dural branches of the external carotid artery, which is located outside the blood-brain barrier, they might be an accessible target for immunotherapy. However, the landscape of naturally presented tumor antigens in meningioma is unknown. We here provide a T-cell antigen atlas for meningioma by in-depth profiling of the naturally presented immunopeptidome using LC-MS/MS. Candidate target antigens were selected based on a comparative approach using an extensive immunopeptidome data set of normal tissues. Meningioma-exclusive antigens for HLA class I and II are described here for the first time. Top-ranking targets were further functionally characterized by showing their immunogenicity through in vitro T-cell priming assays. Thus, we provide an atlas of meningioma T-cell antigens which will be publicly available for further research. In addition, we have identified novel actionable targets that warrant further investigation as an immunotherapy option for meningioma.

The anatomy of neuroepithelial tumours.

Many neurological conditions conceal specific anatomical patterns. Their study contributes to the understanding of disease biology and to tailored diagnostics and therapy. Neuroepithelial tumours exhibit distinct anatomical phenotypes and spatiotemporal dynamics that differ from those of other brain tumours. Brain metastases display a preference for the cortico-subcortical boundaries of watershed areas and have a predominantly spherical growth. Primary CNS lymphomas localize to the white matter and generally invade along fibre tracts. In neuroepithelial tumours, topographic probability mapping and unsupervised topological clustering have identified an inherent radial anatomy and adherence to ventriculopial configurations of specific hierarchical orders. Spatiotemporal probability and multivariate survival analyses have identified a temporal and prognostic sequence underlying the anatomical phenotypes of neuroepithelial tumours. Gradual neuroepithelial de-differentiation and declining prognosis follow (i) an expansion into higher order radial units; (ii) a subventricular spread; and (iii) the presence of mesenchymal patterns (expansion along white matter tracts, leptomeningeal or perivascular invasion, CSF spread). While different pathophysiological hypotheses have been proposed, the cellular and molecular mechanisms dictating this anatomical behaviour remain largely unknown. Here we adopt an ontogenetic approach towards the understanding of neuroepithelial tumour anatomy. Contemporary perception of histo- and morphogenetic processes during neurodevelopment permit us to conceptualize the architecture of the brain into hierarchically organized radial units. The anatomical phenotypes in neuroepithelial tumours and their temporal and prognostic sequences share remarkable similarities with the ontogenetic organization of the brain and the anatomical specifications that occur during neurodevelopment. This macroscopic coherence is reinforced by cellular and molecular observations that the initiation of various neuroepithelial tumours, their intratumoural hierarchy and tumour progression are associated with the aberrant reactivation of surprisingly normal ontogenetic programs. Generalizable topological phenotypes could provide the basis for an anatomical refinement of the current classification of neuroepithelial tumours. In addition, we have proposed a staging system for adult-type diffuse gliomas that is based on the prognostically critical steps along the sequence of anatomical tumour progression. Considering the parallels in anatomical behaviour between different neuroepithelial tumours, analogous staging systems may be implemented for other neuroepithelial tumour types and subtypes. Both the anatomical stage of a neuroepithelial tumour and the spatial configuration of its hosting radial unit harbour the potential to stratify treatment decisions at diagnosis and during follow-up. More data on specific neuroepithelial tumour types and subtypes are needed to increase the anatomical granularity in their classification and to determine the clinical impact of stage-adapted and anatomically tailored therapy and surveillance.

Impact of Long-Term Antithrombotic and Statin Therapy on the Clinical Outcome in Patients with Cavernous Malformations of the Central Nervous System: A Single-Center Case Series of 428 Patients.

INTRODUCTION: Literature regarding the safety and efficacy of antithrombotic (antiplatelet or anticoagulant) therapy and statins in patients with cavernous malformations (CMs) of the central nervous system is sparse, resulting in uncertainty about its use in clinical practice. The aim of this study was to analyze the impact of antithrombotic therapy and statins on the risk of hemorrhage and focal neurological deficit in patients with CMs. METHODS: The authors' institutional database was screened for all patients with CMs of the central nervous system treated at their institution between 2006 and 2018. Patients with radiological and/or histological diagnosis of CMs, clinical baseline characteristics, available patient's medication history, and follow-up data were included in this study. Time-to-event probability (hemorrhage or focal neurological deficit) as well as the number of events (hemorrhage or focal neurological deficit) during follow-up were assessed in patients who were categorized according to their medical treatment (antithrombotic therapy, statins, combined therapy, or no treatment). RESULTS: Four hundred twenty-eight patients with CMs were eligible and included in the final analysis. Sixty-nine (16.1%) patients were on long-term antithrombotic therapy and 46 (10.6%) on long-term statins, of whom 31 patients were on a combination of both. The probability of experiencing first hemorrhage or focal neurological deficit was less likely in patients on antiplatelet therapy (HR 0.09, 95% CI 0.021-0.39, p = 0.001), anticoagulant therapy (HR 0.12, 95% CI 0.016-0.85, p = 0.034), or the combination thereof (HR 0.12, 95% CI 0.016-0.93, p = 0.043) compared to patients with no antithrombotic treatment. The number of hemorrhages and focal neurological deficits were significantly lower in patients on antithrombotic therapy compared to patients on no treatment during follow-up. In patients on statins alone, the time-to-event probability was comparable to that of patients on no treatment (HR 0.91, 95% CI 0.438-1.91, p = 0.812), and the number of events was similar to patients on no treatment. CONCLUSION: The results of our study provide further evidence that antithrombotic therapy alone or in combination with statins in patients with CMs of the central nervous system does not increase the risk of hemorrhage or focal neurological deficit but, on the contrary, may have some benefit.

Incisional CSF leakage after intradural cranial surgery in children: incidence, risk factors, and complications.

OBJECTIVE: The risk of cerebrospinal fluid (CSF) leakage after cranial surgery and its associated complications in children are unclear because of variable definitions and the lack of multicenter studies. In this study, the authors aimed to establish the incidence of CSF leakage after intradural cranial surgery in the pediatric population. In addition, they evaluated potential risk factors and complications related to CSF leakage in the pediatric population. METHODS: The authors performed an international multicenter retrospective cohort study in three tertiary neurosurgical referral centers. Included were all patients aged 18 years or younger who had undergone cranial surgery to reach the subdural space during the period between 2015 and 2021. Patients who died or were lost to follow-up within 6 weeks after surgery were excluded. The primary outcome measure was the incidence of CSF leakage, defined as leakage through the skin, within 6 weeks after surgery. Univariable and multivariable logistic regression analyses were performed to identify risk factors for and complications related to CSF leakage. RESULTS: In total, 759 procedures were identified, performed in 687 individual patients. The incidence of CSF leakage was 7.5% (95% CI 5.7%-9.6%). In the multivariate model, independent risk factors for CSF leakage were hydrocephalus (OR 4.5, 95% CI 2.2-8.9) and craniectomy (OR 7.6, 95% CI 3.0-19.5). Patients with CSF leakage had higher odds of pseudomeningocele (5.7, 95% CI 3.0-10.8), meningitis (21.1, 95% CI 9.5-46.8), and surgical site infection (7.4, 95% CI 2.6-20.8) than patients without leakage. CONCLUSIONS: CSF leakage risk in children after cranial surgery, which is comparable to the risk reported in adults, is an event of major concern and has a serious clinical impact.

Cerebrospinal fluid leakage after intradural spinal surgery in children.

PURPOSE: This study aimed to establish the incidence of CSF leakage in children and associated complications after intradural spinal surgery in three tertiary neurosurgical referral centers and to describe the treatment strategies applied. METHODS: Patients of 18 years or younger who underwent intradural spinal surgery between 2015 and 2021 in three tertiary neurosurgical referral centers were included. Patients who died or were lost to follow-up within six weeks after surgery were excluded. The primary outcome measure was CSF leakage within six weeks after surgery, defined as leakage of CSF through the skin. Secondary outcome measures included the presence of pseudomeningocele (PMC), meningitis, and surgical site infection (SSI). RESULTS: We included a total of 75 procedures, representing 66 individual patients. The median age in this cohort was 5 (IQR = 0-13 years. CSF leakage occurred in 2.7% (2/75) of procedures. It occurred on days 3 and 21 after the index procedure, respectively. One patient was treated with a pressure bandage and an external lumbar drain on day 4 after diagnosis of the leak, and the other was treated with wound revision surgery on day 1 after the leak occurred. In total, 1 patient developed a PMC without a CSF leak which was treated with wound revision surgery. SSI occurred in 10.7%, which included both cases of CSF leak. CONCLUSIONS: CSF leakage after intradural spinal surgery in the pediatric population is relatively rare (2.7%). Nevertheless, the clinical consequences with respect to secondary complications such as infection and the necessity for invasive treatment are serious.

Meta-topologies define distinct anatomical classes of brain tumours linked to histology and survival.

The current World Health Organization classification integrates histological and molecular features of brain tumours. The aim of this study was to identify generalizable topological patterns with the potential to add an anatomical dimension to the classification of brain tumours. We applied non-negative matrix factorization as an unsupervised pattern discovery strategy to the fine-grained topographic tumour profiles of 936 patients with neuroepithelial tumours and brain metastases. From the anatomical features alone, this machine learning algorithm enabled the extraction of latent topological tumour patterns, termed meta-topologies. The optimal part-based representation was automatically determined in 10 000 split-half iterations. We further characterized each meta-topology's unique histopathologic profile and survival probability, thus linking important biological and clinical information to the underlying anatomical patterns. In neuroepithelial tumours, six meta-topologies were extracted, each detailing a transpallial pattern with distinct parenchymal and ventricular compositions. We identified one infratentorial, one allopallial, three neopallial (parieto-occipital, frontal, temporal) and one unisegmental meta-topology. Each meta-topology mapped to distinct histopathologic and molecular profiles. The unisegmental meta-topology showed the strongest anatomical-clinical link demonstrating a survival advantage in histologically identical tumours. Brain metastases separated to an infra- and supratentorial meta-topology with anatomical patterns highlighting their affinity to the cortico-subcortical boundary of arterial watershed areas.Using a novel data-driven approach, we identified generalizable topological patterns in both neuroepithelial tumours and brain metastases. Differences in the histopathologic profiles and prognosis of these anatomical tumour classes provide insights into the heterogeneity of tumour biology and might add to personalized clinical decision-making.

Real-time drug testing of paediatric diffuse midline glioma to support clinical decision making: The Zurich DIPG/DMG centre experience.

BACKGROUND: Children diagnosed with diffuse midline gliomas (DMG) have an extremely poor overall survival: 9-12 months from diagnosis with currently no curative treatment options. Given DMG molecular heterogeneity, surgical biopsies are needed for molecular profiling and as part of enrolment into molecular-based and precision medicine type clinical interventions. In this study, we describe the results of real time profiling and drug testing at the diffuse intrinsic pontine glioma/DMG Research Centre at University Children's Hospital Zurich. METHOD: Biopsies were taken using a frame based stereotactic robot system (NeuroMate®, Renishaw) at University Children's Hospital Zurich. Tissue samples were evaluated to confirm diagnosis by H3K27M and H3K27 trimethylation loss. Genomic analyses were done using a variety of platforms (INFORM, Oncomine, UCSF500 gene panel). Cell lines were developed by mechanical tissue dissociation and verified by either sequencing or immunofluorescence staining confirming H3K27M mutation and used afterwards for drug testing. RESULTS: Twenty-five robot-assisted primary biopsies were successfully performed. Median hospital stay was 2 days (range 1-4 days). Nine low-passage patient-derived cells were developed, whereas 8 cell lines were used to inform response to clinically relevant drugs. Genome and RNA expression were used to further guide treatment strategies with targeted agents such as dual PI3K/mTOR inhibitor paxalisib. CONCLUSION: We established a systematic workflow for safe, robot-assisted brainstem biopsies and in-house tissue processing, followed by real-time drug testing. This provides valuable insights into tumour prognostic and individual treatment strategies targeting relevant vulnerabilities in these tumours in a clinically meaningful time frame.

Multimodal anatomy of the human forniceal commissure.

Ambiguity surrounds the existence and morphology of the human forniceal commissure. We combine advanced in-vivo tractography, multidirectional ex-vivo fiber dissection, and multiplanar histological analysis to characterize this structure's anatomy. Across all 178 subjects, in-vivo fiber dissection based on the Human Connectome Project 7 T MRI data identifies no interhemispheric connections between the crura fornicis. Multidirectional ex-vivo fiber dissection under the operating microscope demonstrates the psalterium as a thin soft-tissue membrane spanning between the right and left crus fornicis, but exposes no commissural fibers. Multiplanar histological analysis with myelin and Bielchowsky silver staining, however, visualizes delicate cruciform fibers extending between the crura fornicis, enclosed by connective tissue, the psalterium. The human forniceal commissure is therefore much more delicate than previously described and presented in anatomical textbooks. This finding is consistent with the observed phylogenetic trend of a reduction of the forniceal commissure in non-human primates compared to non-primate eutherian mammals.

Pediatric brainstem cavernous malformations: 2-center experience in 40 children.

OBJECTIVE: Brainstem cavernous malformations (BSCMs) are relatively uncommon, low-flow vascular lesions in children. Given the paucity of data, guidelines regarding the clinical management of BSCMs in children are lacking and the surgical indication is most commonly based on an individual surgeon's judgment and experience. The goal in this study was to evaluate the clinical behavior of BSCMs in childhood and the long-term outcome in children managed conservatively and surgically. METHODS: This was an observational, retrospective study including all children with BSCMs who were followed at 2 institutions between 2008 and 2020. RESULTS: The study population consisted of 40 children (27 boys, 67.5%) with a mean age of 11.4 years. Twenty-three children (57.5%) were managed conservatively, whereas 17 children (42.5%) underwent resection of BSCMs. An aggressive clinical course was observed in 13 children (32.5%), who experienced multiple hemorrhages with a progressive pattern of neurological decline. Multiple BSCMs were observed in 8 patients, of whom 3 patients presented with a complex of multiple tightly attached BSCMs and posed a significant therapeutic challenge. The overall long-term outcome was favorable (modified Rankin Scale [mRS] scores 0-2) in 36 patients (90%), whereas an unfavorable outcome (mRS scores 3 and 4) was seen in 4 children (10%). An mRS score of 5 or 6 was not observed. The mean (± SD) follow-up was 88.0 (± 92.6) months. CONCLUSIONS: The clinical course of BSCMs in children is highly variable, with benign lesions on the one hand and highly aggressive lesions with repetitive hemorrhages on the other. Given the greater life expectancy and the known higher functional recovery in children, surgical treatment should be considered early in young patients presenting with surgically accessible lesions and an aggressive clinical course, and it should be performed in a high-volume center.

Central nervous system tumors in children under 5 years of age: a report on treatment burden, survival and long-term outcomes.

PURPOSE: The challenges of treating central nervous system (CNS) tumors in young children are many. These include age-specific tumor characteristics, limited treatment options, and susceptibility of the developing CNS to cytotoxic therapy. The aim of this study was to analyze the long-term survival, health-related, and educational/occupational outcomes of this vulnerable patient population. METHODS: Retrospective study of 128 children diagnosed with a CNS tumor under 5 years of age at a single center in Switzerland between 1990 and 2019. RESULTS: Median age at diagnosis was 1.81 years [IQR, 0.98-3.17]. Median follow-up time of surviving patients was 8.39 years [range, 0.74-23.65]. The main tumor subtypes were pediatric low-grade glioma (36%), pediatric high-grade glioma (11%), ependymoma (16%), medulloblastoma (11%), other embryonal tumors (7%), germ cell tumors (3%), choroid plexus tumors (6%), and others (9%). The 5-year overall survival (OS) was 78.8% (95% CI, 71.8-86.4%) for the whole cohort. Eighty-seven percent of survivors > 5 years had any tumor- or treatment-related sequelae with 61% neurological complications, 30% endocrine sequelae, 17% hearing impairment, and 56% visual impairment at last follow-up. Most patients (72%) attended regular school or worked in a skilled job at last follow-up. CONCLUSION: Young children diagnosed with a CNS tumor experience a range of complications after treatment, many of which are long-lasting and potentially debilitating. Our findings highlight the vulnerabilities of this population, the need for long-term support and strategies for rehabilitation, specifically tailored for young children.

Anatomical phenotyping and staging of brain tumours.

Unlike other tumours, the anatomical extent of brain tumours is not objectified and quantified through staging. Staging systems are based on understanding the anatomical sequence of tumour progression and its relationship to histopathological dedifferentiation and survival. The aim of this study was to describe the spatiotemporal phenotype of the most frequent brain tumour entities, to assess the association of anatomical tumour features with survival probability and to develop a staging system for WHO grade 2 and 3 gliomas and glioblastoma. Anatomical phenotyping was performed on a consecutive cohort of 1000 patients with first diagnosis of a primary or secondary brain tumour. Tumour probability in different topographic, phylogenetic and ontogenetic parcellation units was assessed on preoperative MRI through normalization of the relative tumour prevalence to the relative volume of the respective structure. We analysed the spatiotemporal tumour dynamics by cross-referencing preoperative against preceding and subsequent MRIs of the respective patient. The association between anatomical phenotype and outcome defined prognostically critical anatomical tumour features at diagnosis. Based on a hypothesized sequence of anatomical tumour progression, we developed a three-level staging system for WHO grade 2 and 3 gliomas and glioblastoma. This staging system was validated internally in the original cohort and externally in an independent cohort of 300 consecutive patients. While primary CNS lymphoma showed highest probability along white matter tracts, metastases enriched along terminal arterial flow areas. Neuroepithelial tumours mapped along all sectors of the ventriculocortical axis, while adjacent units were spared, consistent with a transpallial behaviour within phylo-ontogenetic radial units. Their topographic pattern correlated with morphogenetic processes of convergence and divergence of radial units during phylo- and ontogenesis. While a ventriculofugal growth dominated in neuroepithelial tumours, a gradual deviation from this neuroepithelial spatiotemporal behaviour was found with progressive histopathological dedifferentiation. The proposed three-level staging system for WHO grade 2 and 3 gliomas and glioblastoma correlated with the degree of histological dedifferentiation and proved accurate in terms of survival upon both internal and external validation. In conclusion, this study identified specific spatiotemporal phenotypes in brain tumours through topographic probability and growth pattern assessment. The association of anatomical tumour features with survival defined critical steps in the anatomical sequence of neuroepithelial tumour progression, based on which a staging system for WHO grade 2 and 3 gliomas and glioblastoma was developed and validated.

Enhancing Safety in Epilepsy Surgery (EASINESS): Study Protocol for a Retrospective, Multicenter, Open Registry.

Introduction: Optimizing patient safety and quality improvement is increasingly important in surgery. Benchmarks and clinical quality registries are being developed to assess the best achievable results for several surgical procedures and reduce unwarranted variation between different centers. However, there is no clinical database from international centers for establishing standardized reference values of patients undergoing surgery for mesial temporal lobe epilepsy. Design: The Enhancing Safety in Epilepsy Surgery (EASINESS) study is a retrospectively conducted, multicenter, open registry. All patients undergoing mesial temporal lobe epilepsy surgery in participating centers between January 2015 and December 2019 are included in this study. The patient characteristics, preoperative diagnostic tools, surgical data, postoperative complications, and long-term seizure outcomes are recorded. Outcomes: The collected data will be used for establishing standardized reference values ("benchmarks") for this type of surgical procedure. The primary endpoints include seizure outcomes according to the International League Against Epilepsy (ILAE) classification and defined postoperative complications. Discussion: The EASINESS will define robust and standardized outcome references after amygdalohippocampectomy for temporal lobe epilepsy. After the successful definition of benchmarks from an international cohort of renowned centers, these data will serve as reference values for the evaluation of novel surgical techniques and comparisons among centers for future clinical trials. Clinical trial registration: This study is indexed at clinicaltrials.gov (NT 04952298).