Prospective Evaluation of Health-Related Quality-of-Life in Children with Craniosynostosis.

OBJECTIVE: To investigate health-related quality of life (HRQL) in children aged 2 to 7 years, who have undergone surgery for craniosynostosis. DESIGN: Cross-sectional survey. SETTING: A tertiary pediatric academic medical center. PARTICIPANTS: Children with craniosynostosis who underwent surgical correction, and who were 2-7 years old at the time of the study. Children from families that did not speak English were excluded. INTERVENTIONS: Caregivers were asked to fill out the Pediatric Quality of Life Inventory (PedsQL) Core Parent Report and the PedsQL Cognitive Functioning Scale. MAIN OUTCOME MEASURES: PedsQL: Psychosocial Health Summary Score, Physical Health Summary Score, Total Core Score, Cognitive Functioning Scale Score. Scores range from 0 to 100, with higher scores reflecting greater QoLSubject factors: comorbidities, syndromic status, type of craniosynostosis, type of surgery. RESULTS: The study included 53 subjects, of whom 13.2% had a syndrome. Core and cognitive scores did not depend on presence of a syndrome or suture involved. Subjects who underwent posterior cranial distraction achieved higher Total Core Scores than subjects who underwent open vault remodeling. Among subjects with sagittal craniosynostosis, there was a tendency for higher scores among children who underwent minimally-invasive surgery compared to those who underwent open vault remodeling. CONCLUSIONS: This study demonstrates similar HRQL among children with and without a syndrome, higher HRQL among children undergoing posterior cranial distraction than those undergoing open vault remodeling, and trends towards higher HRQL in children with sagittal craniosynostosis who underwent minimally-invasive surgery compared to those who underwent open vault remodeling.

Seizure outcome of pediatric magnetic resonance-guided laser interstitial thermal therapy versus open surgery: A matched noninferiority cohort study.

OBJECTIVE: Minimally invasive magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) has been proposed as an alternative to open epilepsy surgery, to address concerns regarding the risk of open surgery. Our primary hypothesis was that seizure freedom at 1 year after MRgLITT is noninferior to open surgery in children with drug-resistant epilepsy (DRE). The secondary hypothesis was that MRgLITT has fewer complications and shorter hospitalization than surgery. The primary objective was to compare seizure outcome of MRgLITT to open surgery in children with DRE. The secondary objective was to compare complications and length of hospitalization of the two treatments. METHODS: This retrospective multicenter cohort study included children with DRE treated with MRgLITT or open surgery with 1-year follow-up. Exclusion criteria were corpus callosotomy, neurostimulation, multilobar or hemispheric surgery, and lesion with maximal dimension > 60 mm. MRgLITT patients were propensity matched to open surgery patients. The primary outcome was seizure freedom at 1 year posttreatment. The difference in seizure freedom was compared using noninferiority test, with noninferiority margin of -10%. The secondary outcomes were complications and length of hospitalization. RESULTS: One hundred eighty-five MRgLITT patients were matched to 185 open surgery patients. Seizure freedom at 1 year follow-up was observed in 89 of 185 (48.1%) MRgLITT and 114 of 185 (61.6%) open surgery patients (difference = -13.5%, one-sided 97.5% confidence interval = -23.8% to ∞, pNoninferiority  = .79). The lower confidence interval boundary of -23.8% was below the prespecified noninferiority margin of -10%. Overall complications were lower in MRgLITT compared to open surgery (10.8% vs. 29.2%, respectively, p < .001). Hospitalization was shorter for MRgLITT than open surgery (3.1 ± 2.9 vs. 7.2 ± 6.1 days, p < .001). SIGNIFICANCE: Seizure outcome of MRgLITT at 1 year posttreatment was inferior to open surgery. However, MRgLITT has the advantage of better safety profile and shorter hospitalization. The findings will help counsel children and parents on the benefits and risks of MRgLITT and contribute to informed decision-making on treatment options.

Treatment of hydrocephalus following posterior fossa tumor resection: a multicenter collaboration from the Hydrocephalus Clinical Research Network.

OBJECTIVE: Persistent hydrocephalus following posterior fossa brain tumor (PFBT) resection is a common cause of morbidity in pediatric brain tumor patients, for which the optimal treatment is debated. The purpose of this study was to compare treatment outcomes between VPS and ETV in patients with persistent hydrocephalus following surgical resection of a PFBT. METHODS: A post-hoc analysis was performed of the Hydrocephalus Clinical Research Network (HCRN) prospective observational study evaluating VPS and ETV for pediatric patients. Children who experienced hydrocephalus secondary to PFBT from 2008 to 2021 were included. Primary outcomes were VPS/ETV treatment failure and time-to-failure (TTF). RESULTS: Among 241 patients, the VPS (183) and ETV (58) groups were similar in age, extent of tumor resection, and preoperative ETV Success Score. There was no difference in overall treatment failure between VPS and ETV (33.9% vs 31.0%, p = 0.751). However, mean TTF was shorter for ETV than VPS (0.45 years vs 1.30 years, p = 0.001). While major complication profiles were similar, compared to VPS, ETV patients had relatively higher incidence of minor CSF leak (10.3% vs. 1.1%, p = 0.003) and pseudomeningocele (12.1% vs 3.3%, p = 0.02). No ETV failures were identified beyond 3 years, while shunt failures occurred beyond 5 years. Shunt infections occurred in 5.5% of the VPS cohort. CONCLUSIONS: ETV and VPS offer similar overall success rates for PFBT-related postoperative hydrocephalus. ETV failure occurs earlier, while susceptibility to VPS failure persists beyond 5 years. Tumor histology and grade may be considered when selecting the optimal means of CSF diversion.

Detection of brain somatic variation in epilepsy-associated developmental lesions.

OBJECTIVE: Epilepsy-associated developmental lesions, including malformations of cortical development and low-grade developmental tumors, represent a major cause of drug-resistant seizures requiring surgical intervention in children. Brain-restricted somatic mosaicism has been implicated in the genetic etiology of these lesions; however, many contributory genes remain unidentified. METHODS: We enrolled 50 children who were undergoing epilepsy surgery into a translational research study. Resected tissue was divided for clinical neuropathologic evaluation and genomic analysis. We performed exome and RNA sequencing to identify somatic variation and we confirmed our findings using high-depth targeted DNA sequencing. RESULTS: We uncovered candidate disease-causing somatic variation affecting 28 patients (56%), as well as candidate germline variants affecting 4 patients (8%). In agreement with previous studies, we identified somatic variation affecting solute carrier family 35 member A2 (SLC35A2) and mechanistic target of rapamycin kinase (MTOR) pathway genes in patients with focal cortical dysplasia. Somatic gains of chromosome 1q were detected in 30% (3 of 10) of patients with Type I focal cortical dysplasia (FCD)s. Somatic variation in mitogen-activated protein kinase (MAPK) pathway genes (i.e., fibroblast growth factor receptor 1 [FGFR1], FGFR2, B-raf proto-oncogene, serine/threonine kinase [BRAF], and KRAS proto-oncogene, GTPase [KRAS]) was associated with low-grade epilepsy-associated developmental tumors. RNA sequencing enabled the detection of somatic structural variation that would have otherwise been missed, and which accounted for more than one-half of epilepsy-associated tumor diagnoses. Sampling across multiple anatomic regions revealed that somatic variant allele fractions vary widely within epileptogenic tissue. Finally, we identified putative disease-causing variants in genes not yet associated with focal cortical dysplasia. SIGNIFICANCE: These results further elucidate the genetic basis of structural brain abnormalities leading to focal epilepsy in children and point to new candidate disease genes.

An observational report of swallowing outcomes following corpus callosotomy.

AIM: Determine swallowing outcomes following corpus callosotomy (CC) surgery. METHODS: Retrospective chart review of patients undergoing CC between July 2016 and November 2018 at a large, urban children's hospital. RESULTS: Of the 18 patients without prior history of dysphagia who underwent CC, 15 received speech pathology consults for bedside swallowing evaluation (BSE). Four patients were referred for a videofluroscopic swallow study (VFSS), and 3 showed no signs of difficulty and were advanced to regular diets with thin liquids. One patient demonstrated swallowing difficulties during the VFSS and was placed on a regular diet with nectar thick liquids. Following a repeat swallow study 17 days post-surgery, the patient was advanced to thin liquids. INTERPRETATION: Postoperative dysphagia following CC is an uncommon and transient complication. Patients undergoing CC should have their swallowing evaluated prior to advancing their postoperative diet but are likely to return to normal diet and thin liquids by discharge.

Mammalian Skull Dimensions and the Golden Ratio (Φ).

The Golden Ratio (Phi, or Φ = 1.618…) is a potentially unifying quantity of structure and function in nature, as best observed in phyllotactic patterns in plants. For centuries, Φ has been identified in human anatomy, and in recent decades, Φ has been identified in human physiology as well. The anatomy and evolution of the human skull have been the focus of intense study. Evolving over millenia, the human skull embodies an elegant harmonization of structure and function. The authors explored the dimensions of the neurocranium by focusing on the midline calvarial perimeter between the nasion and inion (nasioiniac arc) and its partition by bregma into 2 sub-arcs. The authors studied 100 human skulls and 70 skulls of 6 other mammalian species and calculated 2 ratios: 1) the nasioiniac arc divided by the parieto-occipital arc (between bregma and inion), and 2) the parieto-occipital arc divided by the frontal arc (between nasion and bregma). The authors report that in humans these 2 ratios coincide (1.64 ±â€Š0.04 and 1.57 ±â€Š0.10) and approximate Φ. In the other 6 mammalian species, these 2 ratios were not only different, but also unique to each species. The difference between the ratios showed a trend toward convergence on Φ correlating with species complexity. The partition of the nasioiniac arc by bregma into 2 unequal arcs is a situation analogous to that of the geometrical division of a line into Φ. The authors hypothesize that the Golden Ratio (Φ) principle, documented in other biological systems, may be present in the architecture and evolution of the human skull.

Preoperative evaluation and surgical management of infants and toddlers with drug-resistant epilepsy.

OBJECTIVE Despite perioperative risks, epilepsy surgery represents a legitimate curative or palliative treatment approach for children with drug-resistant epilepsy (DRE). Several factors characterizing infants and toddlers with DRE create unique challenges regarding optimal evaluation and management. Epilepsy surgery within children < 3 years of age has received moderate attention in the literature, including mainly case series and retrospective studies. This article presents a systematic literature review and explores multidisciplinary considerations for the preoperative evaluation and surgical management of infants and toddlers with DRE. METHODS The study team conducted a systematic literature review based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, targeting studies that investigated children < 3 years of age undergoing surgical treatment of DRE. Using the PubMed database, investigators selected peer-reviewed articles that reported seizure outcomes with or without developmental outcomes and/or perioperative complications. Studies were eliminated based on the following exclusion criteria: sample size < 5 patients; and inclusion of patients > 3 years of age, when demographic and outcomes data could not be separated from the cohort of patients < 3 years of age. RESULTS The study team identified 20 studies published between January 1990 and May 2017 that satisfied eligibility criteria. All selected studies represented retrospective reviews, observational studies, and uncontrolled case series. The compiled group of studies incorporated 465 patients who underwent resective or disconnective surgery (18 studies, 444 patients) or vagus nerve stimulator insertion (2 studies, 21 patients). Patient age at surgery ranged between 28 days and 36 months, with a mean of 16.8 months (1.4 years). DISCUSSION The study team provided a detailed summary of the literature review, focusing on the etiologies, preoperative evaluation, surgical treatments, seizure and developmental outcomes, and potential for functional recovery of infants and toddlers with DRE. Additionally, the authors discussed special considerations in this vulnerable age group from the perspective of multiple disciplines. CONCLUSIONS While presenting notable challenges, pediatric epilepsy surgery within infants and toddlers (children < 3 years of age) offers significant opportunities for improved seizure frequency, neuro-cognitive development, and quality of life. Successful evaluation and treatment of young children with DRE requires special consideration of multiple aspects related to neurological and physiological immaturity and surgical morbidity.

Trans-falcine and contralateral sub-frontal electrode placement in pediatric epilepsy surgery: technical note.

INTRODUCTION: Phase II monitoring with intracranial electroencephalography (ICEEG) occasionally requires bilateral placement of subdural (SD) strips, grids, and/or depth electrodes. While phase I monitoring often demonstrates a preponderance of unilateral findings, individual studies (video EEG, single photon emission computed tomography [SPECT], and positron emission tomography [PET]) can suggest or fail to exclude a contralateral epileptogenic onset zone. This study describes previously unreported techniques of trans-falcine and sub-frontal insertion of contralateral SD grids and depth electrodes for phase II monitoring in pediatric epilepsy surgery patients when concern about bilateral abnormalities has been elicited during phase I monitoring. METHODS: Pediatric patients with medically refractory epilepsy undergoing stage I surgery for phase II monitoring involving sub-frontal and/or trans-falcine insertion of SD grids and/or depth electrodes at the senior author's institution were retrospectively reviewed. Intra-operative technical details of sub-frontal and trans-falcine approaches were studied, while intra-operative complications or events were noted. Operative techniques included gentle subfrontal retraction and elevation of the olfactory tracts (while preserving the relationship between the olfactory bulb and cribriform plate) to insert SD grids across the midline for coverage of the contralateral orbito-frontal regions. Trans-falcine approaches involved accessing the inter-hemispheric space, bipolar cauterization of the anterior falx cerebri below the superior sagittal sinus, and sharp dissection using a blunt elevator and small blade scalpel. The falcine window allowed contralateral SD strip, grid, and depth electrodes to be inserted for coverage of the contralateral frontal regions. RESULTS: The study cohort included seven patients undergoing sub-frontal and/or trans-falcine insertion of contralateral SD strip, grid, and/or depth electrodes from February 2012 through June 2015. Five patients (71%) experienced no intra-operative events related to contralateral ICEEG electrode insertion. Intra-operative events of frontal territory venous engorgement (1/7, 14%) due to sacrifice of anterior bridging veins draining into the SSS and avulsion of a contralateral bridging vein (1/7, 14%), probably due to prior anterior corpus callosotomy, each occurred in one patient. There were no intra-operative or peri-operative complications in any of the patients studied. Two patients required additional surgery for supplemental SD strip and/or depth electrodes via burr hole craniectomy to enhance phase II monitoring. All patients proceeded to stage II surgery for resection of ipsilateral epileptogenic onset zones without adverse events. CONCLUSIONS: Trans-falcine and sub-frontal insertion of contralateral SD strip, grid, and depth electrodes are previously unreported techniques for achieving bilateral frontal coverage in phase II monitoring in pediatric epilepsy surgery. This technique obviates the need for contralateral craniotomy and parenchymal exposure with limited, remediable risks. Larger case series using the method described herein are now necessary.

A re-evaluation of the Endoscopic Third Ventriculostomy Success Score: a Hydrocephalus Clinical Research Network study.

OBJECTIVE: The Hydrocephalus Clinical Research Network (HCRN) conducted a prospective study 1) to determine if a new, better-performing version of the Endoscopic Third Ventriculostomy Success Score (ETVSS) could be developed, 2) to explore the performance characteristics of the original ETVSS in a modern endoscopic third ventriculostomy (ETV) cohort, and 3) to determine if the addition of radiological variables to the ETVSS improved its predictive abilities. METHODS: From April 2008 to August 2019, children (corrected age ≤ 17.5 years) who underwent a first-time ETV for hydrocephalus were included in a prospective multicenter HCRN study. All children had at least 6 months of clinical follow-up and were followed since the index ETV in the HCRN Core Data Registry. Children who underwent choroid plexus cauterization were excluded. Outcome (ETV success) was defined as the lack of ETV failure within 6 months of the index procedure. Kaplan-Meier curves were constructed to evaluate time-dependent variables. Multivariable binary logistic models were built to evaluate predictors of ETV success. Model performance was evaluated with Hosmer-Lemeshow and Harrell's C statistics. RESULTS: Seven hundred sixty-one children underwent a first-time ETV. The rate of 6-month ETV success was 76%. The Hosmer-Lemeshow and Harrell's C statistics of the logistic model containing more granular age and etiology categorizations did not differ significantly from a model containing the ETVSS categories. In children ≥ 12 months of age with ETVSSs of 50 or 60, the original ETVSS underestimated success, but this analysis was limited by a small sample size. Fronto-occipital horn ratio (p = 0.37), maximum width of the third ventricle (p = 0.39), and downward concavity of the floor of the third ventricle (p = 0.63) did not predict ETV success. A possible association between the degree of prepontine adhesions on preoperative MRI and ETV success was detected, but this did not reach statistical significance. CONCLUSIONS: This modern, multicenter study of ETV success shows that the original ETVSS continues to demonstrate good predictive ability, which was not substantially improved with a new success score. There might be an association between preoperative prepontine adhesions and ETV success, and this needs to be evaluated in a future large prospective study.

Comparing ventriculoatrial and ventriculopleural shunts in pediatric hydrocephalus: a Hydrocephalus Clinical Research Network study.

OBJECTIVE: When the peritoneal cavity cannot serve as the distal shunt terminus, nonperitoneal shunts, typically terminating in the atrium or pleural space, are used. The comparative effectiveness of these two terminus options has not been evaluated. The authors directly compared shunt survival and complication rates for ventriculoatrial (VA) and ventriculopleural (VPl) shunts in a pediatric cohort. METHODS: The Hydrocephalus Clinical Research Network Core Data Project was used to identify children ≤ 18 years of age who underwent either VA or VPl shunt insertion. The primary outcome was time to shunt failure. Secondary outcomes included distal site complications and frequency of shunt failure at 6, 12, and 24 months. RESULTS: The search criteria yielded 416 children from 14 centers with either a VA (n = 318) or VPl (n = 98) shunt, including those converted from ventriculoperitoneal shunts. Children with VA shunts had a lower median age at insertion (6.1 years vs 12.4 years, p < 0.001). Among those children with VA shunts, a hydrocephalus etiology of intraventricular hemorrhage (IVH) secondary to prematurity comprised a higher proportion (47.0% vs 31.2%) and myelomeningocele comprised a lower proportion (17.8% vs 27.3%) (p = 0.024) compared with those with VPl shunts. At 24 months, there was a higher cumulative number of revisions for VA shunts (48.6% vs 38.9%, p = 0.038). When stratified by patient age at shunt insertion, VA shunts in children < 6 years had the lowest shunt survival rate (p < 0.001, log-rank test). After controlling for age and etiology, multivariable analysis did not find that shunt type (VA vs VPl) was predictive of time to shunt failure. No differences were found in the cumulative frequency of complications (VA 6.0% vs VPl 9.2%, p = 0.257), but there was a higher rate of pneumothorax in the VPl cohort (3.1% vs 0%, p = 0.013). CONCLUSIONS: Shunt survival was similar between VA and VPl shunts, although VA shunts are used more often, particularly in younger patients. Children < 6 years with VA shunts appeared to have the shortest shunt survival, which may be a result of the VA group having more cases of IVH secondary to prematurity; however, when age and etiology were included in a multivariable model, shunt location (atrium vs pleural space) was not associated with time to failure. The baseline differences between children treated with a VA versus a VPl shunt likely explain current practice patterns.

Changes in third ventricular size in pediatric patients undergoing endoscopic third ventriculostomy.

PURPOSE: Optimal methods of evaluating radiographic data following endoscopic third ventriculostomy (ETV) are not yet known. This study analyzes imaging parameters, including third ventricular width and cross-sectional area (CSA), in pediatric ETV patients. METHODS: Hydrocephalic pediatric patients treated by ETV at the senior authors' institution from 2004 to 2011 were stratified clinically (successful versus unsuccessful outcome) and retrospectively reviewed. Measured from pre- and post-operative imaging studies, third ventricular parameters included maximal width and mid-sagittal CSA, while lateral ventricular parameters included the ratio of greatest frontal horn width to co-linear skull internal diameter and the frontal-occipital horn ratio. RESULTS: Ten successful ETV patients (mean age 10.6 years; range 11 months to 19.8 years) obtained imaging at least 2.75 months following surgery, while four unsuccessful ETV patients (mean age 9.8 years; range 4 months to 17.3 years) underwent imaging before repeat intervention. Third ventricular width showed an average decline of 0.32 cm and 17.4 % in the successful ETV cohort, but average increases of 0.35 cm and 21.0 % in the ETV failure group. Successful ETV patients exhibited mean decreases of 1.85 cm(2) and 19.7 % in third ventricular mid-sagittal CSA, while unsuccessful ETV patients showed mean increases of 1.17 cm(2) and 17.3 % per patient. These differences were statistically significant. Measures of lateral ventricular size showed similar trends, but with lower magnitude. CONCLUSIONS: Third ventricular imaging parameters (width and mid-sagittal CSA) exhibited more pronounced responses to ETV than lateral ventricular measurements in pediatric hydrocephalic patients.

Imaging in Chiari I Malformation.

Chiari I Malformation represents a hindbrain anomaly best demonstrated radiographically with MRI. Brain and spine MRI provide optimal anatomic detail of cerebellar tonsillar descent below the foramen magnum and may reveal additional imaging features including ventriculomegaly (potentially leading to the diagnosis of hydrocephalus), characteristics of intracranial hypertension or hypotension, spinal cord syrinx, scoliosis, and/or tethered spinal cord. Specialized imaging sequences provide enhanced visualization of ventral and dorsal cervicomedullary cisterns and cerebrospinal fluid flow. Although these studies contribute critical information for evaluation, their impact on surgical decision-making remains uncertain. Additional radiographic measures (pBC2 and clival-axial angle) may impact surgical planning and risk assessment.

Post-ictal Rhythmic Thalamic Activity of the Centromedian Nucleus.

INTRODUCTION: Deep brain stimulation of the centromedian nucleus of the thalamus (CMN) to treat drug-resistant epilepsy has been of interest for decades. However, little is known about the electrophysiological activity of the CMN during seizures. We describe a novel CMN EEG finding associated with seizure: post-ictal rhythmic thalamic activity. METHODS: Five patients with drug-resistant epilepsy of unknown etiology with focal onset seizures underwent stereoelectroencephalography monitoring as part of evaluation for potential resective surgery or neuromodulation. Two patients had previously undergone complete corpus callosotomy and vagus nerve stimulation. A standardized plan for implantation included targets in the bilateral CMN. RESULTS: Each patient had frontal onset seizures, and two patients had additional insular, parietal, or mesial temporal onset seizures. Contacts of CMN were involved synchronously or rapidly after onset in most recorded seizures, particularly those with frontal onset. Focal onset hemiclonic and bilateral tonic-clonic seizures spread to involve cortical contacts with high-amplitude rhythmic spiking followed by abrupt offset with diffuse voltage attenuation. A post-ictal rhythmic 1.5 to 2.5 Hz delta frequency pattern, post-ictal rhythmic thalamic activity, emerged in CMN contacts amid the suppression of background activity in cortical contacts. In the two patients with corpus callosotomy, unilateral seizure spread and ipsilateral post-ictal rhythmic thalamic activity were observed. CONCLUSIONS: We observed post-ictal rhythmic thalamic activity in five patients with stereoelectroencephalography monitoring of the CMN with convulsive seizures. This rhythm appears late in ictal evolution and may signal an important role of the CMN in seizure termination. Furthermore, this rhythm may help identify CMN involvement in the epileptic network.

Epileptic versus neuro-oncological focus of management in pediatric patients with concurrent primary brain lesion and seizures: a systematic review.

OBJECTIVE: Seizures can be a debilitating manifestation of underlying neoplastic intracranial pathology. Existing literature offers a paucity of scientific consensus regarding risk factors, seizure semiology, operative techniques, and tumor characteristics in pediatric patients with a concurrent diagnosis of primary intracranial neoplasm and seizures. To address the limited evidence in current literature, the authors systematically reviewed published literature on current clinical characteristics and management strategies for patients presenting concurrently with seizures and a newly diagnosed brain lesion, while aiming to synthesize a potential management protocol or set of recommendations for these patients. METHODS: An initial search revealed 792 papers, of which 196 studies were excluded, leaving 596 studies available for abstract review. After further stratification, 546 studies were eliminated, leaving 50 studies for eligibility assessment. Of the 50 studies, 12 met the criteria for outcome extraction. RESULTS: The results indicate that patients with a mean age of 9 years with a newly diagnosed brain tumor and presenting symptoms of seizure are likely to present with daily seizures of the complex partial subtype, with the most likely primary epileptogenic and neoplastic foci occurring in the temporal lobe. The most common tumor subtypes were low-grade gliomas, ganglioglioma, dysembryoplastic neuroepithelial tumor, or astrocytoma. With the aim of gross-total resection, 77.54% of patients are likely to achieve seizure freedom. CONCLUSIONS: This study highlights the demographic, clinical, seizure, tumor, and postoperative outcomes for pediatric patients presenting with a primary brain tumor and concurrent seizures. Further prospective multicenter studies are necessary to understand and compare varying treatment approaches and to develop standardized guidelines for these patients, with the goal of optimizing neuro-oncological and seizure-related outcomes.

Impact of Etiology on Seizure and Quantitative Functional Outcomes in Children with Cerebral Palsy and Medically Intractable Epilepsy Undergoing Hemispherotomy/Hemispherectomy.

OBJECTIVE: To compare functional and seizure outcomes in children with vascular and dysplastic etiologies of cerebral palsy and medically intractable epilepsy following functional hemispherotomy or anatomic hemispherectomy. METHODS: Consecutive patients satisfying inclusion criteria from 07/01/2015 to 12/01/2019 were reviewed for demographic data and seizure (Engel classification) and functional (Functional Independence Measure for Children) outcomes. RESULTS: After a mean follow-up of 2 years 8 months (1 year 2 months), 11 of 18 patients achieved post-operative seizure freedom without significant difference between vascular (5/7) and dysplastic (6/11) etiologies (P = 0.64). Functional assessments were completed for 15 of 18 of subjects, split comparably between groups. Mean change in the Functional Independence Measure for Children from pre-operative baseline to inpatient rehabilitation admission (vascular, -35.3 [13.2]; malformation of cortical development{MCD}, -34.5 [25.0]; P = 0.69), inpatient rehabilitation admission to discharge (vascular, 18.7 [9.0]; MCD, 20.8 [11.4]; P = 0.60), and pre-operative evaluation to clinic follow-up (vascular, -7.6 [9.7]; MCD, -3.6 [19.3]; P = 0.61) did not differ between groups. CONCLUSION: Quantitative functional and seizure outcomes following functional hemispherotomy or anatomic hemispherectomy did not differ significantly between vascular and dysplastic etiologies of cerebral palsy and medically intractable epilepsy in this study. Hemispheric surgery resulted in minor functional declines from baseline following comprehensive multidisciplinary therapy.

Comparison of outcomes in the management of abdominal pseudocyst in children with shunted hydrocephalus: a Hydrocephalus Clinical Research Network study.

OBJECTIVE: Abdominal pseudocyst (APC) can cause distal site failure in children with ventriculoperitoneal shunts and is specifically designated as an infection in Hydrocephalus Clinical Research Network (HCRN) protocols. Specific management and outcomes of children with APCs have not been reported in a multicenter study. In this study, the authors investigated the management and outcomes of APC in children with shunted hydrocephalus who were treated at centers in the HCRN. METHODS: The HCRN Registry was queried to identify children < 18 years old with shunts who were diagnosed with an APC (i.e., a loculated abdominal fluid collection containing the peritoneal catheter with abdominal distention and/or displacement of peritoneal contents). The primary outcome was shunt failure after APC treatment. The primary variable was reimplantation of the distal catheter after pseudocyst treatment back into the peritoneum versus implantation in a nonperitoneal site. Other risk factors for shunt failure after APC treatment and variability in APC management were investigated. RESULTS: Among 141 children from 14 centers who underwent first-time management of an APC over a 14-year period, the median time from previous shunt surgery to APC diagnosis was 3.8 months. Overall, 17.7% of children had a positive culture: APC cultures were positive in 14.2% and CSF cultures in 15.6%. Six other children underwent shunt revision without removal; all underwent reoperation within 1 month. There was no difference in shunt survival (log-rank test, p = 0.42) or number of subsequent revisions within 6, 12, or 24 months for shunts reimplanted in the abdomen versus those implanted in a nonperitoneal location. Nonperitoneal implantation was associated with more noninfectious revisions (42.3% vs 22.9%, p = 0.019), whereas infection was more common after reimplantation in the abdomen (25.7% vs 7.0%, p = 0.003). Univariable analysis demonstrated that younger age at APC diagnosis (8.3 vs 12.2 years, p = 0.006) and prior shunt procedure within 12 weeks of APC diagnosis (59.5% vs 40.5%, p = 0.012) were associated with shunt failure after APC treatment. Multivariable modeling confirmed that prior shunt surgery within 12 weeks of APC diagnosis was independently associated with failure (HR 1.79 [95% CI 1.04-3.07], p = 0.035). CONCLUSIONS: In the HCRN, APCs in the setting of CSF shunts are usually managed with externalization. Shunt surgery within 12 weeks of APC diagnosis was associated with risk of failure after APC treatment. Although no differences were found in overall shunt failure rate, noninfectious shunt revisions were more common in the nonperitoneal distal catheter sites, and infection was a more common reason for failure after reimplantation of the shunt in the abdomen.

Machine learning models for predicting seizure outcome after MR-guided laser interstitial thermal therapy in children.

OBJECTIVE: MR-guided laser interstitial thermal therapy (MRgLITT) is associated with lower seizure-free outcome but better safety profile compared to open surgery. However, the predictors of seizure freedom following MRgLITT remain uncertain. This study aimed to use machine learning to predict seizure-free outcome following MRgLITT and to identify important predictors of seizure freedom in children with drug-resistant epilepsy. METHODS: This multicenter study included children treated with MRgLITT for drug-resistant epilepsy at 13 epilepsy centers. The authors used clinical data, diagnostic investigations, and ablation features to predict seizure-free outcome at 1 year post-MRgLITT. Patients from 12 centers formed the training cohort, and patients in the remaining center formed the testing cohort. Five machine learning algorithms were developed on the training data by using 10-fold cross-validation, and model performance was measured on the testing cohort. The models were developed and tested on the complete feature set. Subsequently, 3 feature selection methods were used to identify important predictors. The authors then assessed performance of the parsimonious models based on these important variables. RESULTS: This study included 268 patients who underwent MRgLITT, of whom 44.4% had achieved seizure freedom at 1 year post-MRgLITT. A gradient-boosting machine algorithm using the complete feature set yielded the highest area under the curve (AUC) on the testing set (AUC 0.67 [95% CI 0.50-0.82], sensitivity 0.71 [95% CI 0.47-0.88], and specificity 0.66 [95% CI 0.50-0.81]). Logistic regression, random forest, support vector machine, and neural network yielded lower AUCs (0.58-0.63) compared to the gradient-boosting machine but the findings were not statistically significant (all p > 0.05). The 3 feature selection methods identified video-EEG concordance, lesion size, preoperative seizure frequency, and number of antiseizure medications as good prognostic features for predicting seizure freedom. The parsimonious models based on important features identified by univariate feature selection slightly improved model performance compared to the complete feature set. CONCLUSIONS: Understanding the predictors of seizure freedom after MRgLITT will assist with prognostication.

Post-zygotic rescue of meiotic errors causes brain mosaicism and focal epilepsy.

Somatic mosaicism is a known cause of neurological disorders, including developmental brain malformations and epilepsy. Brain mosaicism is traditionally attributed to post-zygotic genetic alterations arising in fetal development. Here we describe post-zygotic rescue of meiotic errors as an alternate origin of brain mosaicism in patients with focal epilepsy who have mosaic chromosome 1q copy number gains. Genomic analysis showed evidence of an extra parentally derived chromosome 1q allele in the resected brain tissue from five of six patients. This copy number gain is observed only in patient brain tissue, but not in blood or buccal cells, and is strongly enriched in astrocytes. Astrocytes carrying chromosome 1q gains exhibit distinct gene expression signatures and hyaline inclusions, supporting a novel genetic association for astrocytic inclusions in epilepsy. Further, these data demonstrate an alternate mechanism of brain chromosomal mosaicism, with parentally derived copy number gain isolated to brain, reflecting rescue in other tissues during development.

Diagnosis and Surgical Management of Neonatal Hydrocephalus.

Neonatal hydrocephalus represents an important pathological condition with significant impact on medical care and neurocognitive development. This condition requires early recognition, appropriate medical and surgical management, and long-term surveillance by clinicians and pediatric neurosurgeons. Common etiologies of neonatal and infant hydrocephalus include intraventricular hemorrhage related to prematurity with subsequent post-hemorrhagic hydrocephalus, myelomeningocele, and obstructive hydrocephalus due to aqueductal stenosis. Clinical markers of elevated intracranial pressure include rapid increases in head circumference across percentiles, elevation and firmness of the anterior fontanelle, splitting or splaying of cranial sutures, upgaze palsy, lethargy, frequent emesis, or episodic bradycardia (unrelated to other comorbidities). Complementing these clinical markers, imaging modalities used for the diagnosis of neonatal hydrocephalus include head ultrasonography, brain magnetic resonance imaging, and head computed tomography in urgent or emergent situations. Following diagnosis, temporizing measures may be employed prior to definitive treatment and include ventricular access device or ventriculo-subgaleal shunt insertion. Definitive surgical management involves permanent cerebrospinal fluid (CSF) diversion via CSF shunt insertion, or endoscopic third ventriculostomy with or without choroid plexus cauterization. Surgical decision-making and approaches vary based on patient age, hydrocephalus etiology, neuroanatomy, imaging findings, and medical comorbidities. Indications, surgical techniques, and clinical outcomes of these procedures continue to evolve and elicit significant attention in the research environment. In this review we describe the epidemiology, pathophysiology, clinical markers, imaging findings, early management, definitive surgical management, and clinical outcomes of pediatric patients with neonatal hydrocephalus.

Association between synthetic sealants and increased complication rates in posterior fossa decompression with duraplasty for Chiari malformations regardless of graft type.

OBJECTIVE: Dural sealants are commonly used in posterior fossa decompression with duraplasty (PFDD) for Chiari malformation type I (CMI). Prior evidence suggests that combining certain sealants with some graft material is associated with an increased rate of complications. In 2018, the authors noted an increased rate of symptomatic pseudomeningocele and aseptic meningitis after PFDD in CMI patients. The authors utilized retrospective and prospective analyses to test the hypothesis that complication rates increase with the use or combination of certain sealants and grafts. METHODS: The analysis was split into 2 periods. The authors retrospectively reviewed patients who underwent PFDD for CMI at their center between August 12, 2011, and December 31, 2018. The authors then eliminated use of DuraSeal on the basis of the retrospective analysis and prospectively examined complication rates from January 1, 2019, to August 4, 2021. The authors defined a complication as symptomatic pseudomeningocele, bacterial or aseptic meningitis, cerebrospinal fluid leak, subdural hygroma, hydrocephalus, surgical site infection, or wound dehiscence. RESULTS: From 2011 to 2018, complications occurred in 24.5% of 110 patients. Sealant choice was correlated with complication rates: no sealant (0%), Tisseel (6%), and DuraSeal (15.3%) (p < 0.001). No difference in complication rate was noted on the basis of choice of graft material (p = 0.844). After eliminating DuraSeal, the authors followed 40 patients who underwent PFDD after 2018. The complication rate decreased to 12.5%. All complications after 2018 were associated with Tisseel. CONCLUSIONS: At the authors' single center, use of sealants in PFDD surgery for CMI, especially DuraSeal, was correlated with a higher complication rate. Eliminating DuraSeal led to a significant decrease in the rate of symptomatic pseudomeningocele and aseptic meningitis.