Faculty Bibliography

BACKGROUND:Central nervous system tumours affecting the brain and spine are the most common solid tumour site in the paediatric population and the most common causes of cancer death in children and young people. They are associated with high morbidity both from the tumour and the interventions used to treat them. Postoperative morbidity reporting following surgery for paediatric brain tumours is poor. This is due to variability of outcomes measured and reported and the lack of a common language when reporting adverse outcomes. One solution is to develop a core outcome set which will stipulate the minimum postoperative outcomes that should be reported. The COMBAT (Core Postoperative Morbidity Set for Paediatric Brain Tumours) Project will develop a core set of adverse outcomes that can be applied to paediatric brain tumour patients undergoing surgery. METHODS AND ANALYSIS/METHODS:This protocol has been developed using the COS-STAD (Core Outcome Set-Standards for Development) recommendations and the COS-STAP (Core Outcome Set-STAndardised Protocol Items) statement. A systematic review will identify adverse outcomes reported in the literature and how they are measured. Outcomes of importance to patients and their carers will be identified from semi-structured qualitative interviews with patients and their carers from Alder Hey Children's Hospital, Liverpool, UK. Consensus on the most important harms will be sought using a two-round eDelphi survey completed by national and international participants including health professionals, researchers, patients and their carers. Results of the eDelphi survey will be assessed against a pre-defined definition of consensus and discussed at an international consensus meeting attended by participants of the eDelphi survey. DISCUSSION/CONCLUSIONS:There is a clear need for a common language to harmonise measurement and reporting of morbidity following surgery for paediatric brain tumour patients. This project will define postoperative adverse outcomes that are of critical importance to key stakeholders. It will standardise surgical morbidity outcome measurement and reporting in both research studies and routine clinical practice, enabling comparison across different trials, studies and clinical services. It will lay the groundwork for future research in paediatric brain tumour surgical morbidity. STUDY REGISTRATION/BACKGROUND:This study is registered with the COMET database as Study 1968 ( https://www.comet-initiative.org/Studies/Details/1968 ), registration date: 26/10/2021.

BACKGROUND:Small tectal gliomas (TGs) may be unrecognized at initial diagnosis of noncommunicating hydrocephalus, with the etiology typically attributed to idiopathic congenital aqueductal stenosis (CAS). There are 2 published cases of TGs found on follow-up imaging after treatment with endoscopic third ventriculostomy (ETV). The authors investigated for this phenomenon in a large cohort of patients with TG or CAS treated with ETV or CSF shunting. OBSERVATIONS/METHODS:The authors reviewed records at their institution from 1999 to 2024, identifying 10 patients initially diagnosed with presumed idiopathic CAS and later found to have underlying TG. Of these, 7 were younger than 1 year of age at hydrocephalus presentation. The median time from CAS to glioma diagnosis was 13 months. Reasons for repeat imaging that identified glioma included postoperative surveillance and recurrent hydrocephalus. Five (50%) lesions grew over follow-up, and 2 required chemotherapy. LESSONS/CONCLUSIONS:The authors describe the eventual emergence of TG as a probable cause of hydrocephalus in a cohort of patients initially diagnosed with CAS. As most of these cases were identified incidentally on interval imaging to evaluate adequate function of CSF diversion procedures, follow-up imaging to evaluate for tectal expansion should be considered in children, particularly infants, with a new diagnosis of idiopathic CAS. https://thejns.org/doi/10.3171/CASE24695.

OBJECTIVE:Pediatric data regarding treatment via an auditory brainstem implant (ABI) remains sparse. The authors aimed to describe their experience at their institution and to delineate associated demographic data, audiometric outcomes, and surgical parameters. METHODS:An IRB-approved, retrospective chart review was conducted among the authors' pediatric patients who had undergone auditory brainstem implantation between 2012 and 2021. Demographic information including sex, age, race, coexisting syndrome(s), history of cochlear implant placement, average duration of implant use, and follow-up outcomes were collected. Surgical parameters collected included approach, intraoperative findings, number of electrodes activated, and complications. RESULTS:A total of 19 pediatric patients had an ABI placed at the authors' institution, with a mean age at surgery of 4.7 years (range 1.5-17.8 years). A total of 17 patients (89.5%) had bilateral cochlear nerve aplasia/dysplasia, 1 (5.3%) had unilateral cochlear nerve aplasia/dysplasia, and 1 (5.3%) had a hypoplastic cochlea with ossification. A total of 11 patients (57.9%) had a history of cochlear implants that were ineffective and required removal. The mean length of implant use was 5.31 years (0.25-10 years). Two patients (10.5%) experienced CSF-related complications requiring further surgical intervention. The most recent audiometric outcomes demonstrated that 15 patients (78.9%) showed improvement in their hearing ability: 5 with sound/speech awareness, 5 able to discriminate among speech and environmental sounds, and 5 able to understand common phrases/conversation without lip reading. Nine patients (47.4%) are in a school for the deaf and 7 (36.8%) are in a mainstream school with support. CONCLUSIONS:The authors' surgical experience with a multidisciplinary team demonstrates that the retrosigmoid approach for ABI placement in children with inner ear pathologies and severe sensorineural hearing loss is a safe and effective treatment modality. Audiometric outcome data showed that nearly 79% of these patients had an improvement in their environmental and speech awareness. Further multicenter collaborations are necessary to improve these outcomes and potentially standardize/enhance electrode placement.

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.

In aqueduct stenosis, pressure difference below and above level of obstruction leads to bulging of third ventricular floor (TVF) and lamina terminalis (LT). Endoscopic third ventriculocisternostomy (ETV) is the standard treatment in these patients. We tried to assess success of ETV depending on those two radiological changes in aqueduct stenosis. We implemented "Heidelberg ETV score" retrospectively to assess the state of TVF as well as LT in same manner in midsagittal MR image. Every patient had a preoperative, direct, 3-months and one-year postoperative score from -2 to + 2. We correlated the scores to clinical course to decide whether the score is reliable in defining success of ETV. Between 2017-2021, 67 (mean age 25.6 ± 23.9y) patients treated with ETV were included. Success rate of primary and Re-ETVs was 91% over 46.8 ± 19.0 months. A marked shift of score to the left after surgery in success group was noticed through the distribution of score immediate postoperative, 3-months later; 70.2% showed (+ 2) before surgery, 38.9% scored (0) after surgery and 50.9% showed further score drop to (-1) 3 months later, p < 0.001. In cases of failure, there was initial decrease after surgery followed by increase with ETV-failure (mean time to failure: 7.2 ± 5.7 months) in 100%. Significant difference was noticed in Heidelberg score at postoperative 1-year- and failure-MRI follow-up between two groups, p < 0.001. Heidelberg score describes anatomical changes in third ventricle after ETV and can serve in assessment of MR images to define success of the procedure in patients with aqueduct stenosis.

BACKGROUND/UNASSIGNED:Central nervous system (CNS) cancer is the 10th leading cause of cancer-associated deaths for adults, but the leading cause in pediatric patients and young adults. The variety and complexity of histologic subtypes can lead to diagnostic errors. DNA methylation is an epigenetic modification that provides a tumor type-specific signature that can be used for diagnosis. METHODS/UNASSIGNED:We performed a prospective study using DNA methylation analysis as a primary diagnostic method for 1921 brain tumors. All tumors received a pathology diagnosis and profiling by whole genome DNA methylation, followed by next-generation DNA and RNA sequencing. Results were stratified by concordance between DNA methylation and histopathology, establishing diagnostic utility. RESULTS/UNASSIGNED:Of the 1602 cases with a World Health Organization histologic diagnosis, DNA methylation identified a diagnostic mismatch in 225 cases (14%), 78 cases (5%) did not classify with any class, and in an additional 110 (7%) cases DNA methylation confirmed the diagnosis and provided prognostic information. Of 319 cases carrying 195 different descriptive histologic diagnoses, DNA methylation provided a definitive diagnosis in 273 (86%) cases, separated them into 55 methylation classes, and changed the grading in 58 (18%) cases. CONCLUSIONS/UNASSIGNED:DNA methylation analysis is a robust method to diagnose primary CNS tumors, improving diagnostic accuracy, decreasing diagnostic errors and inconclusive diagnoses, and providing prognostic subclassification. This study provides a framework for inclusion of DNA methylation profiling as a primary molecular diagnostic test into professional guidelines for CNS tumors. The benefits include increased diagnostic accuracy, improved patient management, and refinements in clinical trial design.

OBJECTIVE:The aim of this study was to describe the processes and outcomes associated with patients at five sites in the Adult Hydrocephalus Clinical Research Network (AHCRN) who had undergone evaluation and treatment for suspected idiopathic normal pressure hydrocephalus (iNPH) and had 1-year postoperative follow-up. METHODS:Subjects with possible iNPH who had been prospectively enrolled in the AHCRN registry between November 19, 2014, and December 31, 2018, were evaluated by CSF drainage via either lumbar puncture or external lumbar drainage, consistent with recommendations of the international iNPH guidelines. Standardized clinical evaluations of gait, cognition, urinary symptoms, depression, and functional outcomes were conducted at baseline, before and after CSF drainage, and at 4-month intervals after shunt surgery. Complications of CSF drainage and shunt surgery were recorded. RESULTS:Seventy-four percent (424/570) of patients with possible iNPH had CSF drainage, and 46% of them (193/424) underwent shunt surgery. The mean change in gait velocity with CSF drainage was 0.18 m/sec in patients who underwent shunt surgery versus 0.08 m/sec in patients who did not. For shunt surgery patients, gait velocity increased by 54% from 0.67 m/sec before CSF drainage to 0.96 m/sec 8-12 months after surgery, and 80% of patients had an increase of at least 0.1 m/sec by the first postoperative visit. Evaluation of cognition, urinary symptoms, depression, and functional outcomes also revealed improvement after shunt surgery. Of 193 patients who had undergone shunt surgery, 176 (91%) had no complications and 17 (9%) had 28 complications. Eleven patients (6%) had 14 serious complications that resulted in the need for surgery or an extended hospital stay. The 30-day reoperation rate was 3%. CONCLUSIONS:Using criteria recommended by the international iNPH guidelines, the authors found that evaluation and treatment of iNPH are safe and effective. Testing with CSF drainage and treatment with shunt surgery are associated with a high rate of sustained improvement and a low rate of complications for iNPH in the 1st year after shunt surgery. Patients who had undergone shunt surgery for iNPH experienced improvement in gait, cognitive function, bladder symptoms, depression, and functional outcome measures. Gait velocity, which is an easily measured, objective, continuous variable, should be used as a standard outcome measure to test a patient's response to CSF drainage and shunt surgery in iNPH.

OBJECTIVE:The object of this study was to determine the short- and long-term efficacy of primary endoscopic third ventriculostomy (ETV) on cognition and gait in adults with chronic obstructive hydrocephalus. METHODS:Patients were prospectively accrued through the Adult Hydrocephalus Clinical Research Network patient registry. Patients with previously untreated congenital or acquired obstructive hydrocephalus were included in this study. Gait velocity was assessed using a 10-m walk test. Global cognition was assessed with the Montreal Cognitive Assessment (MoCA). Only patients with documented pre- and post-ETV gait analysis and/or pre- and post-ETV MoCA were included. RESULTS:A total of 74 patients had undergone primary ETV, 42 of whom were analyzed. The remaining 32 patients were excluded, as they could not complete both pre- and post-ETV assessments. The mean age of the 42 patients, 19 (45.2%) of whom were female, was 51.9 ± 17.1 years (range 19-79 years). Most patients were White (37 [88.1%]), and the remainder were Asian. Surgical complications were minor. Congenital etiologies occurred in 31 patients (73.8%), with aqueductal stenosis in 23 of those patients (54.8%). The remaining 11 patients (26.2%) had acquired cases. The gait short-term follow-up cohort (mean 4.7 ± 4.1 months, 35 patients) had a baseline median gait velocity of 0.9 m/sec (IQR 0.7-1.3 m/sec) and a post-ETV median velocity of 1.3 m/sec (IQR 1.1-1.4 m/sec). Gait velocity significantly improved post-ETV with a median within-patient change of 0.3 m/sec (IQR 0.0-0.6 m/sec, p < 0.001). Gait velocity improvements were sustained in the long term (mean 14 ± 2.8 months, 12 patients) with a baseline median velocity of 0.7 m/sec (IQR 0.6-1.3 m/sec), post-ETV median of 1.3 m/sec (IQR 1.1-1.7 m/sec), and median within-patient change of 0.4 m/sec (IQR 0.2-0.6 m/sec, p < 0.001). The cognitive short-term follow-up cohort (mean 4.6 ± 4.0 months, 38 patients) had a baseline median MoCA total score (MoCA TS) of 24/30 (IQR 23-27) that improved to 26/30 (IQR 24-28) post-ETV. The median within-patient change was +1 point (IQR 0-2 points, p < 0.001). However, this change is not clinically significant. The cognitive long-term follow-up cohort (mean 14 ± 3.1 months, 15 patients) had a baseline median MoCA TS of 23/30 (IQR 22-27), which improved to 26/30 (IQR 25-28) post-ETV. The median within-patient change was +2 points (IQR 1-3 points, p = 0.007), which is both statistically and clinically significant. CONCLUSIONS:Primary ETV can safely improve symptoms of gait and cognitive dysfunction in adults with chronic obstructive hydrocephalus. Gait velocity and global cognition were significantly improved, and the worsening of either was rare following ETV.