Abstract Background Neuro-ophthalmological disturbances present frequently in pediatric posterior fossa (PF) tumors, contributing significantly to morbidity. This study evaluates their prevalence, risk factors, and outcomes in affected children. Methods This retrospective study analyzed 119 children with PF tumors treated over a decade at a tertiary care center, including 94 presenting at initial diagnosis and 25 at relapse. Clinical and ophthalmologic evaluations were performed preoperatively and three months, one-year and two-years postoperatively. Prevalence of visual disturbances, central and/or peripheral oculomotor dysfunctions, optic nerve changes, and corrective ophthalmological interventions were evaluated over time. Associations between visual/oculomotor outcomes and tumor location, histology, hydrocephalus, cerebellar mutism syndrome (CMS) and intraventricular chemotherapy were analyzed using χ2-tests. Results At diagnosis n = 21/94 presented due to visual symptoms, while thorough preoperative examination revealed central and peripheral oculomotor disturbances in n = 12/27 and n = 6/27, respectively. Their prevalence increased postoperatively but improved over time in one third of patients, with earlier resolution in peripheral disturbances. Vermis/brainstem location and CMS were associated with higher rates of postoperative oculomotor disorders. Medulloblastomas exhibited an elevated risk of central disturbances. Prism-correction was initially required in n = 16/94 of cases, decreasing to n = 4/64 after two years; strabismus surgery was performed in n = 4/64. Papilledema was common (n = 10/33) at diagnosis, and n = 8/56 developed optic atrophy during follow-up. Among patients presenting at relapse, neuro-ophthalmological disorders were frequent (central: n = 24/25; peripheral: n = 15/25), while visual acuity remained satisfactory. Conclusions Neuro-ophthalmological disturbances are common in pediatric PF tumors and evolve throughout treatment. Regular ophthalmologic examinations including detailed orthoptic assessments are essential for timely intervention.

Resective neurosurgery is a cornerstone treatment for many neurological conditions. Although traditionally viewed as a localized procedure, increasing evidence from advanced MRI shows that non-resected anatomy can degenerate following surgery. The relationship between local tissue removal and these postoperative changes remains speculative. Here, we investigate the hypothesis that degenerative changes to surgically preserved grey and white matter are mediated by transneuronal degeneration, a deterioration of intact neuronal populations due to lost axonal input. Using a robust diffusion-weighted and T1-weighted MRI framework specifically tailored for longitudinal analysis of surgical image data, we evaluated evidence to support this mechanism in a series of patients undergoing resective surgery for epilepsy; namely, anterior temporal lobectomy (ATL, n = 31) or selective amygdalohippocampectomy (SAHE, n = 28). We mapped three key aspects of transneuronal degeneration for anatomical regions: (i) loss of surgically resected white matter; (ii) longitudinal change in cortical thickness; and (iii) longitudinal atrophy of non-resected white matter. Using mixed-effects models, we explored the evidence in support of a sequential progression of degeneration, where the loss of resected white matter leads to downstream atrophy of connected grey matter and the white matter connections thereof. Both ATL and SAHE resulted in extensive resection-related white matter losses predominantly connecting to ipsilateral regions close to the resection. We also found pronounced decreases in cortical thickness in these regions, as well as extensive white matter atrophy across the ipsilateral hemisphere. These postsurgical alterations were closely associated with resection-related white matter losses, with every 10-fold loss of connections leading to a 3.4% decrease in cortical thickness and a 7.2% decrease in density of downstream pathways. Beyond degenerative effects, we also demonstrate how failure to properly tailor longitudinal image processing to such data can yield misleading evidence for extensive structural network reorganization, with our more robust approach indicating limited capacity for macroscale plasticity post-resection.

BACKGROUND AND OBJECTIVES:Dissection of the corpus callosum is a well-established treatment option for patients with pharmaco-resistant epilepsy. Both partial and complete callosotomies are performed to reduce seizure burden. In recent years, multiple minimally invasive variations of corpus callosotomy have been suggested. These techniques, however, can be cost and time demanding, which limits their use to specialized centers in high-resource settings. We present our experience with a mini-open microsurgical technique. METHODS:Our technique employs a parasagittal longitudinal incision followed by a small craniotomy and retractorless interhemispheric dissection. Neuronavigation was used to find an operative corridor between bridging veins to the sagittal sinus. Postoperative computed tomography and magnetic resonance images were analyzed to describe the size of craniotomies and the disconnected area of the corpus callosum. RESULTS:We performed 38 partial callosotomies in 24 patients over a period of 5 years. The median age at the initial surgery was 8.5 years (IQR 5.9-11.9). In 15 patients (62.5%), the first surgery was a posterior callosotomy. The average size of the craniotomy since adoption of this technique was 43.6 mm by 27.8 mm but decreased to an average of 35.8 mm by 24.2 mm in the last 2 years. The mean operating time per procedure was 99.6 minutes (SD ±28.9 minutes). Surgeries were performed by attendings, fellows, and residents in 28, 6, and 4 cases, respectively. We experienced no complications with this approach in the investigated period. CONCLUSION:Mini-open partial callosotomy is a safe and efficient procedure that minimizes the morbidity associated with a larger approach. It can be performed and taught in conventionally equipped microsurgical neurosurgery units, thus contributing to further emphasize the use of epilepsy surgery also in resource constrained environments.

BACKGROUND:For localized germinoma, whole-ventricular radiotherapy (WVRT) is standard-of-care in Europe; 24 Gray (Gy) with 16 Gy boost following chemotherapy. The SIOP-CNS-GCT-II trial aimed to examine the effect of response-adapted radiotherapy on patient outcome. METHODS:Patients with localized germinoma received 4 courses of "carboPEI" chemotherapy, then 24 Gy WVRT if in complete remission (CR), with an additional 16 Gy tumor boost if residual disease was present. Metastatic cases received 24 Gy craniospinal radiotherapy (CSRT) with 16 Gy boost to all sites. RESULTS:Between 2012 and 2018, 227 fully-staged germinoma patients were treated according to protocol. Five-year event-free (EFS) and overall survival (OS) for 166 localized germinoma were 0.94 ± 0.02 and 0.98 ± 0.01, respectively. Sixty-five of 166 (39.2%) were in CR after chemotherapy, of whom 64/65 received 24 Gy WVRT, only 2 of whom (2/64; 3.1%) relapsed. Of 90/166 patients in partial remission (PR) after chemotherapy, 88/90 received 24 Gy WVRT + 16 Gy; 2 relapsed (2/88; 2.3%). Of the 11 remaining patients, 8 had stable disease (SD) after chemotherapy; 7/8 received 24 Gy WVRT + 16 Gy boost and 1 received 24 Gy WVRT + 30 Gy boost because of a teratoma component; none relapsed. Three remaining patients with progressive disease (PD) during chemotherapy had variable treatments, due to differing histologies and disease spread; 1 relapsed. Five-year EFS and OS for 61 metastatic germinoma were 0.98 ± 0.02 and 1.00 ± 0.00, respectively, with 55/61 (90.2%) in CR and 5/61 (11.5%) in PR after 24 Gy CSRT + 16 Gy; 1 relapsed. CONCLUSIONS:Response-adapted radiotherapy for localized germinoma led to excellent survival outcomes. Further treatment de-escalation should be considered in future strategies to reduce treatment burden and late effects.

Background:Bevacizumab (BVZ) is widely used in patients with central nervous system (CNS) tumors. Due to its potential to impair wound healing, a minimum interval of 28 days between BVZ administration and surgery - both before and after the procedure - is generally recommended. However, strict adherence to this interval is often challenging in clinical practice, particularly when urgent oncologic treatment or time-sensitive surgical interventions are required. Methods:Pediatric patients with a CNS tumor receiving intravenous BVZ from January 2005 to December 2022 treated at the Medical University of Vienna were retrospectively analyzed for surgical complications. Results:One hundred and nineteen patients had 344 surgeries with BVZ therapy before and or after surgery. 11 wound complications (3.20%) of any grade (n=1 CTCAE grade I; n=10 CTCAE grade III) occurred in 11 children (9.24%). Group comparison of BVZ exposure intervals (BVZ ≤28/>28 days and ≤14/>14 days) revealed no statistically significant differences in wound complication rates, with odds ratios of 3.91 (≤28/>28 d; P = .55) and 1.15 (≤14/>14 d; P=1.00) before surgery as well as 1.93 (≤28/>28 d; P = .46) and 3.16 (≤14/>14 d; P = .11) after surgery. Conclusion:BVZ can be administered within ≤ 28 days before or after surgery when postponing the procedure is not feasible or when immediate (re)initiation of therapy is required, provided that non-absorbable sutures are used, and close wound-monitoring is ensured.

Hemispherotomy in infants under the age of 3 months is considered a high-risk procedure and is not routinely performed. A 2.5-month-old female infant weighing 5.1 kg successfully underwent a right vertical hemispherotomy after developing status epilepticus due to a right hemispheric Sturge-Weber meningo-angiomatosis. The surgical technique involved skull fixation at the skull base using kid pins to facilitate image-guided surgery with neuronavigation and augmented reality within the eyepiece of the microscope employing the vertical hemispherotomy technique. The surgical course was uneventful, with moderate blood loss (100 mL of red blood cells, 90 mL of fresh frozen plasma, and 150 mg of tranexamic acid transfused). The surgery duration was within 2 h. Postoperatively, seizures ceased immediately, and the infant experienced rapid developmental and neurological progress, remaining seizure-free for 8 months after surgery (Engel 1a) now.

Gliomas are the most common brain tumor type in children and adolescents. To date, diagnosis and therapy monitoring for these tumors rely on magnetic resonance imaging (MRI) and histopathological as well as molecular analyses of tumor tissue. Recently, liquid biopsies (LB) have emerged as promising tool for diagnosis and longitudinal tumor assessment potentially allowing for a more precise therapeutic management. However, the optimal strategy for monitoring gliomas by LB remains to be determined. In this study, we analyzed circulating tumor DNA (ctDNA) from 78 liquid biopsies (plasma n = 44, cerebrospinal fluid n = 34 (CSF)) of 35 glioma patients, determining H3F3A K28M (K27M) and BRAF V600E mutation allele frequency using droplet digital PCR (ddPCR). All results were correlated to clinically relevant parameters including diagnostic imaging and CSF aspiration site (ventricular vs lumbar) with respect to tumor localization. Regarding diagnostic accuracy, the calculated sensitivity score in the H3F3A K27M cohort was 84.61

Resective neurosurgery is a cornerstone treatment for many neurological conditions. Although traditionally viewed as localised procedure, increasing evidence from advanced magnetic resonance imaging (MRI) shows that also non-resected anatomy can degenerate following surgery. The relationship between local tissue removal and these postoperative changes remains thus far speculative. Here, we investigate the hypothesis that degenerative changes to surgically preserved grey and white matter are mediated by transneuronal degeneration, a deterioration of intact neuronal populations due to lost axonal input. Using a robust structural and diffusion MRI framework, we first identify widespread postoperative atrophy: pronounced cortical thickness decreases near the resection, and extensive white matter impairments across the ipsilateral hemisphere. Importantly, we then link these alterations to surgical white matter disruption, revealing a sequential network atrophy following neurosurgery. Beyond degenerative effects, we also demonstrate often reported structural network reorganisations as an artefact of image processing, indicating limited capacity for macroscale plasticity post-resection. ### Competing Interest Statement The authors have declared no competing interest.

OBJECTIVE:Gangliogliomas are commonly found pathologies in patients undergoing epilepsy surgery. While resections can be curative, seizure relapses occur. Expression of CD34 and the BRAF V600E mutation are the most common molecular biomarkers found in gangliogliomas, but their influence on seizure outcomes is unclear. We therefore reviewed our experience over two decades to better describe prognostic factors. METHODS:We performed a retrospective chart review of all patients operated on for ganglioglioma at our institution since the year 2000. We included patients with preoperative epilepsy and a minimum follow-up of 1 year. Available tumor specimens were immunohistochemically stained for CD34 and BRAF V600E. RESULTS:We included 62 patients with epilepsy operated for ganglioglioma. Lesionectomies were performed in 32 (51.6%), extended resections in 21 (33.9%), and partial resections in 9 cases (14.5%). Residual tumor mass on postoperative MRI was diagnosed in 21 patients (33.9%). CD34 reactivity was found in 57 patients (91.9%) and the BRAF V600E mutation was detected in 30 patients (48.4%). Patients with a BRAF V600E mutation were younger at the time of epilepsy onset (9.1 years vs. 15.2 years) and surgery (14.5 years vs. 23.7 years). Residual tumor was the largest risk factor for seizure relapses (hazard ratio 8.45) and the BRAF V600E mutation also increased this risk (hazard ratio 3.94). CONCLUSIONS:BRAF V600E status in patients with ganglioglioma-associated epilepsy is a potential biomarker to stratify the risk for seizure relapse after surgery. BRAF V600E-positive patients might benefit from a more aggressive surgical strategy.

Developmental gene expression data from medulloblastoma (MB) suggest that WNT-MB originate from the region of the embryonic lower rhombic lip (LRL), whereas SHH-MB and non-WNT/non-SHH MB arise from cerebellar precursor matrix regions. This study aims to analyze detailed intraoperative data with regard to the site of origin (STO) and compare these findings with the hypothesized regions of origin associated with the molecular group. A review of the institutional database identified 58 out of 72 pediatric patients who were operated on a MB at our department between 1996 and 2020 that had a detailed operative report, surgical video as well as clinical and genetic classification data available for analysis. The STO was assessed based on intraoperative findings. Using the intraoperatively defined STO, “correct” prediction of molecular groups was feasible in 20% of WNT-MB, 60% of SHH-MB and 71% of non-WNT/non-SHH MB. The positive predictive values of the neurosurgical inspection to detect the molecular group were 0.21 (95% CI 0.08–0.48) for WNT-MB, 0.86 (95% CI 0.49–0.97) for SHH-MB and 0.73 (95% CI 0.57–0.85) for non-WNT/non-SHH MB. In our series of 58 well-documented cases, the intraoperative assessment of the STO could not reliably predict the molecular group. Thus, the current evidence does still not allow for intraoperative group-specific risk stratification that would enable tailoring the neurosurgical strategy to the prognostic and predictive profile of the patient. Prospective multicenter assessments are necessary to systematically evaluate the growth pattern and site of origin of medulloblastoma. Accordingly, a study protocol of an international cohort study will be presented.

Purpose Imaging and resection strategies for pediatric gangliogliomas (GG) and dysembryoplastic neuroepitheliomas (DNET) presenting with epilepsy were retrospectively analyzed in a consecutive institutional series of surgically treated patients. Methods Twenty-two children (median 8 years, 3-18 years) presented with seizures for 30 months median (14-55.2 months) due to a histologically verified GG/DNET. Results There were 20 GG and 2 DNT, 68% located temporal, 32% extra-temporal. Seizure history was significantly longer in temporal cases (38 versus 14 months median, p<0.01). MRI contrast enhancement was present in 50% and methionine (MET) positron emission tomography (PET) uptake in 70% (standard uptake values (SUVs) 2.92 mean, from 1.6 to 6.4). 27% had glucose PET hypometabolism. Primarily, in temporal GG, ECoG (electrocorticography) -guided lesionectomies were performed in 87% and antero-mesial temporal lobe resections (AMTLR) in 13%, whereas in extra-temporal GG/DNETs, lesionectomies were performed in 100%. ILAE Class 1 seizure outcome was primarily achieved in 73% of the temporal cases, and was increased to 93% by performing six repeat surgeries using AMTLR. Extratemporal patients experienced ILAE Class 1 seizure outcomes in 86% without additional surgeries, although harboring significantly more residual tumor (p<0.005, mean follow-up 28 months). Conclusion In children, MET PET imaging for suspected GG is proposed preoperatively showing a high diagnostic sensitivity and an option to delineate the lesions for navigated resection, whereas MRI contrast behavior was of no differential diagnostic use. As a surgical strategy we propose primarily lesionectomies for extratemporal but AMTLR for temporal GG respecting eloquent brain areas.

- OBJECTIVE: To evaluate the neurosurgical and economic effectiveness of a newly launched intraoperative high -field (3T) magnetic resonance imaging (MRI) suite for pediatric tumor and epilepsy neurosurgery. - METHODS: Altogether, 148 procedures for 124 pediatric patients (mean age, 8.7 years; range, 0e18 years) within a 2.5 -year period were undertaken in a 2 -room intraoperative MRI (iopMRI) suite. Surgery was performed mainly for intractable epilepsy (n = 81; 55%) or pediatric brain tumors (n = 65; 44%) in the supine (n = 113; 76%) and prone (n = 35; 24%) positions. The mean time of iopMRI from draping to re -surgery was 50 minutes. - RESULTS: IopMRI was applied not in all but in 64 of 148 procedures (43%); in 45 procedures (31%), iopMRI was estimated unnecessary at the end of surgery based on the leading surgeon's decision. In the remaining 39 procedures (26%), - ltra -early postoperative MRI was carried out after closure with the patient still sterile in the head coil. Of the 64 procedures with iopMRI, second -look surgery was performed in 26% (in epilepsy surgery in 17%, in tumor surgery in 9%). We did not encounter any infections, wound revisions, or position -related or anesthesiology -related complications. - CONCLUSIONS: We used iopMRI in less than half of pediatric tumor and epilepsy surgery for which it was scheduled initially. Therefore, high costs argue against its routine use in pediatric neurosurgery, although it optimized surgical results in one quarter of patients and met high safety standards.

We aimed to present our surgical experience and the impact of a solid or cystic morphology of cerebellar pilocytic astrocytoma (cPA) on surgery and the risk for a re-resection. We retrospectively analyzed all children operated at our institution between 2009 and 2023 for cPA. Tumours were categorized into 4 groups: (i) cystic PA without cyst wall enhancement, (ii) cystic PA with cyst wall enhancement, (iii) solid tumour, (iv) and solid tumour with central necrosis. Forty-two children with a median age at surgery of 7.1 years (range 0.7–14 years; male to female ratio 1.5) were identified. The median follow-up time was 3.1 years (0.6–14 years). Twenty-eight patients (66.6

We aimed to analyze potentially prognostic factors which could have influence on postoperative seizure, neuropsychological and psychiatric outcome in a cohort of patients with mesial temporal lobe epilepsy (MTLE) due to hippocampal sclerosis (HS) after selective amygdalohippocampectomy (SAHE) via transsylvian approach. Clinical variables of 171 patients with drug-resistant MTLE with HS (88 females) who underwent SAHE between 1994 and 2019 were evaluated using univariable and multivariable logistic regression models, to investigate which of the explanatory parameters can best predict the outcome. At the last available follow-up visit 12.3 ± 6.3 years after surgery 114 patients (67.9

Purpose Various surgical nuances of the telovelar approach have been suggested. The necessity of removing the posterior arch of C1 to accomplish optimal tumor exposure is still debated. Therefore, we report on our experience and technical details of the fourth ventricular tumor resection in a modified prone position without systematic removal of the posterior arch of C1.Methods A retrospective analysis of all pediatric patients, who underwent a fourth ventricular tumor resection in the modified prone position between 2012 and 2021, was performed.Results We identified 40 patients with a median age of 6 years and a M:F ratio of 25:15. A telovelar approach was performed in all cases. In 39/40 patients, the posterior arch of C1 was not removed. In the remaining patient, the reason for removing C1 was tumor extension below the level of C2 with ventral extension. Gross or near total resection could be achieved in 34/39 patients, and subtotal resection in 5/39 patients. In none of the patients, a limited exposure, sight of view, or range of motion caused by the posterior arch of C1 was encountered, necessitating an unplanned removal of the posterior arch of C1. Importantly, in none of the cases, the surgeon had the impression of a limited sight of view to the most rostral parts of the fourth ventricle, which necessitated a vermian incision.Conclusion A telovelar approach without the removal of the posterior arch of C1 allows for an optimal exposure of the fourth ventricle provided that critical nuances in patient positioning are considered.

Background Epilepsy surgery can potentially cure pharmacoresistant temporal lobe epilepsy (TLE) in children. However, surgical failures, where patients continue to experience seizures, still exist. We evaluated outcomes in pediatric patients after resective temporal lobe surgery to identify risk factors for failure. Methods Data on pediatric patients with TLE who underwent surgery were prospectively collected at our institution. Minimum follow-up (FU) was three years after surgery. Resections were stratified into extended resections, i.e., anterior temporal lobectomies, and sparing resections, i.e., lesionectomies and selective amygdalohippocampectomies. Ongoing seizures and relapses within the first three years were considered surgical failures. Results We included 96 patients after 43 sparing and 52 extended resections from 1993 to 2019 with a median FU of 10.1 years (range 3.0 to 28.3 years). Pathohistology most frequently revealed epilepsy-associated tumors (44.8%), hippocampal sclerosis (37.5%), and focal cortical dysplasias (12.5%). One year postoperatively, 69.8% were seizure free, increasing to 78.5% after five and 72.9% after 10 years. Sparing resections increased the odds for surgical failure in a multivariate analysis (odds ratio: 4.63, P = 0.006). Preoperative focal onset to bilateral tonic-clonic seizures increased the likelihood of seizure relapses (hazard ratio: 3.89, P = 0.006) and contributed to higher odds of surgical failure (odds ratio: 2.79, P = 0.002). Conclusions Pediatric patients with TLE undergoing surgery have high rates of long-lasting favorable seizure outcomes. Resection strategy is a prognostic factor for early surgical success in favor of larger resections. Relapses were more frequent in children with focal onset to bilateral tonic-clonic seizures beforesurgery.

OBJECTIVES:Although hemispheric surgeries are among the most effective procedures for drug-resistant epilepsy (DRE) in the pediatric population, there is a large variability in seizure outcomes at the group level. A recently developed HOPS score provides individualized estimation of likelihood of seizure freedom to complement clinical judgement. The objective of this study was to develop a freely accessible online calculator that accurately predicts the probability of seizure freedom for any patient at 1-, 2-, and 5-years post-hemispherectomy. METHODS:Retrospective data of all pediatric patients with DRE and seizure outcome data from the original Hemispherectomy Outcome Prediction Scale (HOPS) study were included. The primary outcome of interest was time-to-seizure recurrence. A multivariate Cox proportional-hazards regression model was developed to predict the likelihood of post-hemispheric surgery seizure freedom at three time points (1-, 2- and 5- years) based on a combination of variables identified by clinical judgment and inferential statistics predictive of the primary outcome. The final model from this study was encoded in a publicly accessible online calculator on the International Network for Epilepsy Surgery and Treatment (iNEST) website (https://hops-calculator.com/). RESULTS:The selected variables for inclusion in the final model included the five original HOPS variables (age at seizure onset, etiologic substrate, seizure semiology, prior non-hemispheric resective surgery, and contralateral fluorodeoxyglucose-positron emission tomography [FDG-PET] hypometabolism) and three additional variables (age at surgery, history of infantile spasms, and magnetic resonance imaging [MRI] lesion). Predictors of shorter time-to-seizure recurrence included younger age at seizure onset, prior resective surgery, generalized seizure semiology, FDG-PET hypometabolism contralateral to the side of surgery, contralateral MRI lesion, non-lesional MRI, non-stroke etiologies, and a history of infantile spasms. The area under the curve (AUC) of the final model was 73.0%. SIGNIFICANCE:Online calculators are useful, cost-free tools that can assist physicians in risk estimation and inform joint decision-making processes with patients and families, potentially leading to greater satisfaction. Although the HOPS data was validated in the original analysis, the authors encourage external validation of this new calculator.

Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanometer synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS uses fixation-compatible extracellular labeling and optical imaging, including stimulated emission depletion or expansion microscopy, to comprehensively delineate cellular structures. It enables three-dimensional reconstruction of single synapses and mapping of synaptic connectivity by identification and analysis of putative synaptic cleft regions. Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed and quantified the synaptic input and output structure of identified neurons. We furthermore demonstrate applicability to clinically derived human tissue samples, including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing the cellular architecture of brain tissue in health and disease.