Faculty Bibliography

OBJECTIVEThe choice of treatment modality for optic pathway gliomas (OPGs) is controversial. Chemotherapy is widely regarded as first-line therapy; however, subtotal resections have been reported for decompression or salvage therapy as first- and second-line treatment. The goal of this study was to further investigate the role and efficacy of resection for OPGs.METHODSA retrospective chart review was performed on 83 children who underwent surgical treatment for OPGs between 1986 and 2014. Pathology was reviewed by a neuropathologist. Clinical outcomes, including progression-free survival (PFS), overall survival (OS), and complications, were analyzed.RESULTSThe 5- and 10-year PFS rates were 55% and 46%, respectively. The 5- and 10-year OS rates were 87% and 78%, respectively. The median extent of resection was 80% (range 30%-98%). Age less than 2 years at surgery and pilomyxoid features of the tumor were found to be associated with significantly lower 5-year OS. No difference was seen in PFS or OS of children treated with surgery as a first-line treatment compared with children with surgery as a second- or third-line treatment. Severe complications included new disabling visual deficit in 5%, focal neurological deficit in 8%, and infection in 2%. New hormone deficiency occurred in 22% of the children.CONCLUSIONSApproximately half of all children experience a long-term benefit from resection both as primary treatment and as a second-line therapy after failure of primary treatment. Primary surgery does not appear to have a significant benefit for children younger than 2 years or tumors with pilomyxoid features. Given the risks associated with surgery, an interdisciplinary approach is needed to tailor the treatment plan to the individual characteristics of each child.

OBJECTIVE:Incomplete resection of neocortical epileptogenic foci correlates with failed epilepsy surgery in children. We often treat patients with neocortical epilepsy with a staged approach using invasive monitoring to localize the focus, resect the seizure onset zone, and, in select cases, post-resection invasive monitoring (PRM). We report the technique and the outcomes of children treated with staged surgery including PRM. METHODS:We retrospectively reviewed the charts of pediatric patients with neocortical epilepsy who underwent resective surgery with PRM. RESULTS:We identified 71 patients, 5 patients with MRI-negative epilepsy and 66 patients with MRI-identified neocortical lesions; 64/66 (97%) patients had complete lesionectomy. In 61/71 (86%) patients PRM was associated with positive outcomes. Those findings were: 1) clinical seizures with electrographic involvement at resection margins (47%); 2) subclinical seizures and interictal discharges at resection margins (29%); and 3) clinical and subclinical seizures revealing a new epileptogenic focus (20%). In 55/71 (77%) patients, PRM data led to additional resection (re-resection; RR). Six additional patients had no further resection due to overlap with eloquent cortex. Histopathology showed tuberous sclerosis complex (TSC; n = 46), focal cortical dysplasia (FCD; n = 16)), gliosis (n = 4), tumors (n = 4), and Sturge-Weber syndrome (n = 1). There were no major complications. Seizure-free outcome in children with TSC was 63% at 1-year follow-up and 56% at 2-year follow-up. In FCD, seizure freedom after 1 and 2 years was 85%. SIGNIFICANCE/CONCLUSIONS:Post-resection monitoring may provide additional information about the extent of the epileptogenic zone, such as residual epileptogenic activity at the margins of the resection cavity, and may unmask additional seizure foci. This method may be especially useful in achieving long-term stable seizure-free outcome.

PURPOSE/OBJECTIVE:Molecular subgroups of pediatric brain tumors associated with divergent biological, clinical, and prognostic features have been identified. However, data regarding the impact of subgroup affiliation on the outcome of children with malignant brain tumors treated with radiation-sparing protocol is limited. We report long-term clinical outcomes and the molecular subgroups of malignant brain tumors in young children whose first-line treatment was high-dose chemotherapy without irradiation. METHODS:Tumor subclassification was performed using the Illumina HumanMethylation450 BeadChip (450k) genome-wide methylation array profiling platform. Clinical information was obtained from chart review. RESULTS:Methylation array profiling yielded information on molecular subgroups in 22 children. Median age at surgery was 26 months (range 1-119 months). Among medulloblastomas (MB), all 6 children in the infant sonic hedgehog (SHH) subgroup were long-term survivors, whereas all 4 children in subgroup 3 MB died. There was one long-term survivor in subgroup 4 MB. One out of five children with ependymoma was a long-term survivor (RELPOS). Both children with primitive neuroectodermal tumors died. One child with ATRT TYR and one child with choroid plexus carcinoma were long-term survivors. CONCLUSIONS:The efficacy of high-dose chemotherapy radiation-sparing treatment appears to be confined to favorable molecular subgroups of pediatric brain tumors, such as infant SHH MB. Identification of molecular subgroups that benefit from radiation-sparing therapy will aid in the design of prospective, "precision medicine"-driven clinical trials.

In children undergoing craniotomy, the impact of postoperative pain on recovery is receiving growing recognition. While opioids are often the primary treatment, their administration requires a delicate balance between achieving sufficient analgesia and mitigating side effects like sedation, nausea, vomiting, and respiratory depression. We review the emerging adjunct treatment modality regional scalp block (RSB) infiltration for post-craniotomy pain. Postoperative pain after pediatric craniotomy can be challenging to manage and may contribute to unnecessary suffering as well as the development of long-term neurocognitive and psychological sequelae. Pain during the PICU stay is also a major risk factor for post-PICU syndrome, which involves persistent impairments in children's physical, cognitive, or mental health persisting beyond acute hospitalization. Despite increasing awareness and treatment strategies for post-craniotomy pain in adults, significant gaps remain in understanding its assessment and management in children. This review examines the current literature surrounding post-craniotomy pain management in children with a special emphasis on RSB, a treatment option increasingly used in adults and children. RSB has been shown in randomized trials to reduce postoperative pain and opioid use. However, while pediatric perioperative trials support its safety and feasibility, robust clinical evidence supporting RSB's efficacy for post-craniotomy pain in children remains limited, hindering wider translation into clinical standard. RSB infiltration is an emerging and promising technique for pediatric post-craniotomy pain management. Early evidence suggests it is both safe and effective, with potential to enhance postoperative recovery and to be integrated into clinical practice. Further research is critical to validate initial findings and better define the benefits across diverse pediatric populations.

PURPOSE/OBJECTIVE:To identify clinical variables associated with ventricular shunt infection and shunt failure in pediatric hydrocephalus. METHODS:Patients ≤ 18 years treated with ventricular shunts between 2013 and 2024 were identified from one institution's electronic medical record. Children with a confirmed diagnosis of hydrocephalus and ≥ 6 months of postoperative follow-up were included. Primary and revision shunt surgeries were included. Records were manually reviewed for clinical variables. Statistical analyses were performed using R (version 4.2.3). RESULTS:The dataset included 474 surgeries, 146 primary and 328 revisions, undergone by 226 patients. Infection necessitating removal of a previously placed shunt occurred following 3.59% (17/474) of cases. Discharge in ≤ 4 days had a 75% lower relative risk for infection compared to stays > 4 days (1.5% vs. 6% 100-day infection risk; p = 0.011). Patients who underwent revision surgeries for shunt infections were more likely to experience subsequent infections in the first 100 days postoperatively than those revised for other causes (2.42% vs. 21.05%; p < 0.0001). Patient characteristics associated with shunt failure during the 10-year study included younger age (median age: 2.23 years in those with failure vs. 6.62 years in those without; p < 0.0002) and lower weight (median weight: 11.8 kg vs. 20.3 kg; p < 0.0002) at the time of admission. Congenital hydrocephalus (OR = 1.86; p = 0.0045) and aqueductal stenosis (OR = 1.75; p = 0.025) were also associated with shunt failure. CONCLUSIONS:Length of stay > 4 days and previous shunt infection are associated with an increased risk of infection after shunt surgery. These findings are important to consider when counseling pediatric patients and during postoperative monitoring.

BACKGROUND:Sturge-Weber syndrome (SWS) is a congenital neurocutaneous disorder characterized by angiomas of the face, choroid, and leptomeninges. Seizures in these children often present within the first 2 years of life. SWS is typically unilateral, but bilateral SWS occurs in approximately 15% of cases. Bilateral SWS is associated with earlier seizure onset and poorer cognitive, developmental, and functional outcomes. More than half of children with SWS develop drug-resistant epilepsy requiring surgical intervention. Hemispherotomy has been established as a successful treatment for unilateral SWS, but resective surgery has traditionally not been considered a treatment option for patients with bilateral disease. OBSERVATIONS/METHODS:In this report, the authors present the cases of 4 children (7 months-2 years of age) with bilateral SWS and drug-resistant epilepsy with a unilateral electroencephalography predominance. After a multidisciplinary conference in each case, all children were successfully treated with unilateral hemispherotomy. These patients achieved prolonged periods of seizure freedom postoperatively, a better quality of life, and demonstrated improved developmental progress at long-term follow-up. LESSONS/CONCLUSIONS:This case series suggests that functional hemispherotomy may be a safe and effective therapeutic option for improving seizure burden in cases of bilateral drug-resistant SWS with asymmetric seizure burden. https://thejns.org/doi/10.3171/CASE25125.

INTRODUCTION/BACKGROUND:Traumatic brain injury (TBI) is the leading cause of pediatric disability. Most pediatric TBIs are mild but can result in long-term cognitive and functional impairments. Outpatient follow-up is essential to detect post-concussive symptoms and aid recovery. METHODS:All patients 3-18 years of age with positive TBI findings on CT or MRI from 2018-2024 were retrospectively reviewed. Follow-up was defined as an appointment with neurology, neuropsychology, neurosurgery, or physical medicine and rehabilitation within three months of discharge. Analyses were performed with appropriate Chi-squared, Fisher's exact, Mann-Whitney U, or t-tests. RESULTS:Fifty-seven patients (41 male, mean age 11.4 years) were identified, with mild TBIs (GCS 13-15) comprising 41/57 (71.9%). Four patients (7.0%) died from their injury. Of 53 surviving patients, 20 (37.7%) had follow-up appointments scheduled for them at discharge, seven (13.2%) were given a specific date and contact number, 17 (32.1%) received service referrals without a specific date, and eight (15.1%) received nonspecific directions or were directed only to follow-up with non-neuroscience services. Within three months, 32 (60.4%) patients followed up, though only 22/53 (41.5%) patients saw a non-surgical neuroscience discipline. Patients who followed up were more likely to have undergone neurosurgery (p = 0.007) or any surgical procedure at all (p = 0.007). They were also more likely to have a shorter hospital length of stay (p = 0.021). Discharge instruction type was significantly associated with follow-up (p = 0.0013); 62.5% of patients who followed up had an appointment scheduled for them or were given a specific date versus 33.4% of patients who did not follow-up. Conversely, 38.1% of patients without follow-up received nonspecific instructions or were told to follow-up with non-neuroscience specialties. This finding remained significant when excluding patients with severe TBI. Follow-up had no significant associations with demographics, injury severity, or insurance type. CONCLUSION/CONCLUSIONS:Patient-centered discharge instructions with detailed service referrals increase access to critical follow-up care. Children with TBIs should have follow-up care arranged regardless of injury severity. Larger multicenter studies are needed to validate these findings.

OBJECTIVE:Endoscopic third ventriculostomy (ETV) is a treatment option for obstructive hydrocephalus; reported success rates vary. We investigated immediate postoperative magnetic resonance imaging (MRI) to evaluate the role of imaging parameters associated with outcomes. METHODS:Retrospective chart review was performed patients undergoing initial ETV between 2005 -2019. Patients with pre- and postoperative MRI with follow-up >one year were included. The following were noted: changes in subarachnoid CSF, third ventricle diameter (TV), bowing of the TV floor, and postoperative flow void. Kaplan-Meier survival methods were used to assess ETV success, Univariable and multivariable Cox proportional-hazards models were fitted to assess factors contributing to ETV success. RESULTS:Fifty-eight subjects were included. Nineteen (32.8%) experienced failure within one year, individually, no single imaging parameter predicted success. However, all cases with failure had no identifiable flow void. Any postoperative radiological change was not consistently associated with decreased odds of failure. Obstructive hydrocephalus treated with ETV demonstrated significantly better ETV success than patients treated for non-obstructive hydrocephalus Inter-observer reliability was moderate for two of the radiological variables and substantial for one of the radiological variables. CONCLUSIONS:Individually none of the qualitative radiologic parameters measured in our study predicted ETV success. Absence of a flow void predicted ETV failure, but additional studies are needed to determine its true negative predictive value. Inability to clarify which specific parameter predicts success, reflects the limited role of immediate postoperative imaging in influencing clinical management.

UNLABELLED:DNA methylation is an essential molecular assay for central nervous system (CNS) tumor diagnostics. While some fusions define specific brain tumors, others occur across many different diagnoses. We performed a retrospective analysis of 219 primary CNS tumors with whole genome DNA methylation and RNA next-generation sequencing. DNA methylation profiling results were compared with RNAseq detected gene fusions. We detected 105 rare fusions involving 31 driver genes, including 23 fusions previously not implicated in brain tumors. In addition, we identified 6 multi-fusion tumors. Rare fusions and multi-fusion events can impact the diagnostic accuracy of DNA methylation by decreasing confidence in the result, such as BRAF, RAF, or FGFR1 fusions, or result in a complete mismatch, such as NTRK, EWSR1, FGFR, and ALK fusions. IMPLICATIONS/UNASSIGNED:DNA methylation signatures need to be interpreted in the context of pathology and discordant results warrant testing for novel and rare gene fusions.

OBJECTIVES/OBJECTIVE:Although hemispheric surgeries are among the most effective procedures for drug-resistant epilepsy (DRE) in the pediatric population, a large variability in outcomes remains. Identifying ideal hemispherectomy candidates is imperative to maximize the potential for seizure freedom. The objective was to develop an online, freely-accesible tool that accurately predicts the probability of seizure freedom for any patient at 1-, 2-, and 5-years post-hemispherectomy to provide clinicians accessible and reliable prognostic information to complement clinical judgement. 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 duration based on a combination of variables identified by clinical judgement and inferential statistics as predictive of the primary outcome. The final model from this study was encoded in a publicly accessible online calculator on the (iNEST) website. RESULTS:The selected variables for inclusion in the final model included the 5 original HOPS variables (age at seizure onset, etiologic substrate, seizure semiology, prior non-hemispheric resective surgery, and contralateral FDG-PET hypometabolism) and 3 additional variables (age at surgery, history of infantile spasms, and magnetic resonance (MR) imaging lesion). Predictors of shorter time-to-seizure recurrence included younger age at seizure onset, older age at surgery, prior resective surgery, generalized seizure semiology, FDG-PET hypometabolism contralateral to side of surgery, contralateral MR imaging lesion, non-lesional MR imaging, non-stroke etiologies, and history of infantile spasms. The area under the curve (AUC) of the final model was 73.0%. SIGNIFICANCE/CONCLUSIONS:Online calculators are efficient, cost-free tools that can facilitate physicians in risk-estimation and inform joint decision-making with families, potentially leading to greater satisfaction. Although the HOPS data was previously validated in the first analysis, the authors encourage prospective external validation of this new tool.