mTOR Pathway Somatic Pathogenic Variants in Focal Malformations of Cortical Development: Novel Variants, Topographic Mapping, and Clinical Outcomes.

Background And Objectives: Somatic and germline pathogenic variants in genes of the mammalian target of rapamycin (mTOR) signaling pathway are a common mechanism underlying a subset of focal malformations of cortical development (FMCDs) referred to as mTORopathies, which include focal cortical dysplasia (FCD) type II, subtypes of polymicrogyria, and hemimegalencephaly. Our objective is to screen resected FMCD specimens with mTORopathy features on histology for causal somatic variants in mTOR pathway genes, describe novel pathogenic variants, and examine the variant distribution in relation to neuroimaging, histopathologic classification, and clinical outcomes.

Methods: We performed ultra-deep sequencing using a custom HaloPlex Target Enrichment kit in DNA from 21 resected fresh-frozen histologically confirmed FCD type II, tuberous sclerosis complex, or hemimegalencephaly specimens.

Clinical utility of intraoperative electrocorticography for epilepsy surgery: A systematic review and meta-analysis.

Despite the widespread use of intraoperative electrocorticography (iECoG) during resective epilepsy surgery, there are conflicting data on its overall efficacy and inability to predict benefit per pathology. Given the heterogeneity of iECoG use in resective epilepsy surgery, it is important to assess the utility of interictal-based iECoG. This individual patient data (IPD) meta-analysis seeks to identify the benefit of iECoG during resective epilepsy surgery in achieving seizure freedom for various pathologies.

Inhibition of nuclear export restores nuclear localization and residual tumor suppressor function of truncated SMARCB1/INI1 protein in a molecular subset of atypical teratoid/rhabdoid tumors.

Loss of nuclear SMARCB1 (INI1/hSNF5/BAF47) protein expression due to biallelic mutations of the SMARCB1 tumor suppressor gene is a hallmark of atypical teratoid/rhabdoid tumors (ATRT), but the presence of cytoplasmic SMARCB1 protein in these tumors has not yet been described. In a series of 102 primary ATRT, distinct cytoplasmic SMARCB1 staining on immunohistochemistry was encountered in 19 cases (19%) and was highly over-represented in cases showing pathogenic sequence variants leading to truncation or mutation of the C-terminal part of SMARCB1 (15/19 vs. 4/83; Chi-square: 56.

Case Report: Aperiodic Fluctuations of Neural Activity in the Ictal MEG of a Child With Drug-Resistant Fronto-Temporal Epilepsy.

Successful surgical treatment of patients with focal drug-resistant epilepsy remains challenging, especially in cases for which it is difficult to define the area of cortex from which seizures originate, the seizure onset zone (SOZ). Various diagnostic methods are needed to select surgical candidates and determine the extent of resection. Interictal magnetoencephalography (MEG) with source imaging has proven to be useful for presurgical evaluation, but the use of ictal MEG data remains limited.

Prosopagnosia seizure semiology in a 10-year-old boy: a functional neuroimaging study.

We illustrate a case of post-traumatic recurrent transient prosopagnosia in a paediatric patient with a right posterior inferior temporal gyrus haemorrhage seen on imaging and interictal electroencephalogram abnormalities in the right posterior quadrant. Face recognition area mapping with magnetoencephalography (MEG) and functional MRI (fMRI) was performed to clarify the relationship between the lesion and his prosopagnosia, which showed activation of the right fusiform gyrus that colocalised with the lesion. Lesions adjacent to the right fusiform gyrus can result in seizures presenting as transient prosopagnosia.

Correction to: Efficacy of Dabrafenib for three children with brainstem BRAF positive ganglioglioma.

In the original article, the author names were published incorrectly. The names are correct in this publication.

Efficacy of Dabrafenib for three children with brainstem BRAF positive ganglioglioma.

Purpose: Children with unresectable brainstem-infiltrated ganglioglioma have poor progression-free survival when treated with conventional chemotherapy and radiation regimens. The BRAF mutation occurs in a large number of gangliogliomas, making them amenable for targeted therapy using mutation-specific kinase inhibitors. However, limited data exists on the effectiveness and best treatment duration of these inhibitors in this tumor setting.

Hemiconvulsion-Hemiplegia-Epilepsy in a girl with cobalamin C deficiency.

Hemiconvulsion-Hemiplegia-Epilepsy initially involves an infantile presentation of febrile focal motor status epilepticus, with subsequent hemiplegia of the initially affected side. Months to years later, affected children go on to develop a chronic epilepsy with recurrent focal seizures which are often refractory to treatment. This uncommon paediatric epilepsy syndrome is poorly understood, with only a very small minority of cases associated with an underlying genetic or metabolic abnormality.

3-T intraoperative MRI (iMRI) for pediatric epilepsy surgery.

Purpose: Three-tesla intraoperative MRI (iMRI) is a promising tool that could help confirm complete resections and disconnections in pediatric epilepsy surgery, leading to improved outcomes. However, a large proportion of epileptogenic pathologies in children are poorly defined on imaging, which brings into question the utility of iMRI for these cases. Our aim was to compare postoperative seizure outcomes between iMRI- and non-iMRI-based epilepsy surgeries.

Traumatic brain injury in a rural indigenous population in Canada: a community-based approach to surveillance.

Background: Indigenous populations are disproportionately affected by traumatic brain injury. These populations rely on large jurisdiction surveillance efforts to inform their prevention strategies, which may not address their needs. We examined the incidence and determinants of traumatic brain injury in an indigenous population in the Terres-Cries-de-la-Baie-James health region of the province of Quebec and compared them with the incidence and determinants in 2 neighbouring health regions and in the province overall.

Immune Checkpoint Inhibition for Hypermutant Glioblastoma Multiforme Resulting From Germline Biallelic Mismatch Repair Deficiency.

Purpose: Recurrent glioblastoma multiforme (GBM) is incurable with current therapies. Biallelic mismatch repair deficiency (bMMRD) is a highly penetrant childhood cancer syndrome often resulting in GBM characterized by a high mutational burden. Evidence suggests that high mutation and neoantigen loads are associated with response to immune checkpoint inhibition.

The Emergence of Zoonotic Onchocerca lupi Infection in the United States--A Case-Series.

This case-series describes the 6 human infections with Onchocerca lupi, a parasite known to infect cats and dogs, that have been identified in the United States since 2013. Unlike cases reported outside the country, the American patients have not had subconjunctival nodules but have manifested more invasive disease (eg, spinal, orbital, and subdermal nodules). Diagnosis remains challenging in the absence of a serologic test.

Short-term mortality following surgical procedures for the diagnosis of pediatric brain tumors: outcome analysis in 5533 children from SEER, 2004-2011.

OBJECT Thirty-day mortality is increasingly a reference metric regarding surgical outcomes. Recent data estimate a 30-day mortality rate of 1.4-2.

Pediatric low-grade ganglioglioma: epidemiology, treatments, and outcome analysis on 348 children from the surveillance, epidemiology, and end results database.

Background: Low-grade gangliogliomas/gangliocytomas (GGs) are rare tumors of the central nervous system that occur mostly in young people. Because of their rarity, large-scale, population-based studies focusing on epidemiology and outcomes are lacking.

Objective: To use the Surveillance, Epidemiology, and End Results (SEER) data sets of the National Cancer Institute to study demographics, tumor location, initial treatment, and outcome data on low-grade GGs in children.

Pediatric choroid plexus tumors: epidemiology, treatments, and outcome analysis on 202 children from the SEER database.

Choroid plexus papillomas (CPPs) and carcinomas (CPCs) are rare neoplasms that affect mostly children. Due to their rarity, their epidemiology and outcomes are incompletely understood. The National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Program is a well-established population-based group of registries that collects and publishes cancer incidence and survival data representing approximately 28 % of the US population.

Long-term functional benefits of selective dorsal rhizotomy for spastic cerebral palsy.

Object: Large-scale natural history studies of gross motor development have shown that children with spastic cerebral palsy (CP) plateau during childhood and actually decline through adolescence. Selective dorsal rhizotomy (SDR) is a well-recognized treatment for spastic CP, but little is known about long-term outcomes of this treatment. The purpose of this study was to assess the durability of functional outcomes in a large number of patients through adolescence and into early adulthood using standardized assessment tools.

Memory outcome after temporal lobe epilepsy surgery: corticoamygdalohippocampectomy versus selective amygdalohippocampectomy.

Object: The aim of this study was to compare IQ and memory outcomes at the 1-year follow-up in patients with medically refractory mesial temporal lobe epilepsy (MTLE) due to hippocampal sclerosis. All patients were treated using a corticoamygdalohippocampectomy (CAH) or a selective amygdalohippocampectomy (SelAH).

Methods: The data of 256 patients who underwent surgery for MTLE were retrospectively evaluated.

Efficient and fast functional screening of microdystrophin constructs in vivo and in vitro for therapy of duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is an X-linked, lethal genetic disorder affecting the skeletal muscle compartment, and is caused by mutation(s) in the dystrophin gene. Gene delivery of microdystrophin constructs using adeno-associated virus (AAV) and antisense-mediated exon skipping restoring the genetic reading frame are two of the most promising therapeutic strategies for DMD. Both approaches use microdystrophin proteins either directly as a desired construct for gene delivery, using the capacity-limited AAV vectors, or as the therapeutic outcome of gene splicing.

First-drug treatment failures in children newly diagnosed with epilepsy.

In adults newly diagnosed with epilepsy, treatment with the first prescribed antiepileptic drug fails for approximately one half. In two studies that addressed this question in children, the failure rates were 20% and 40%. The present study used a detailed chart review of children newly diagnosed with epilepsy over a 4-year span in a major childhood epilepsy referral clinic to assess (1) the percentage of children for whom first-line antiepileptic drug treatment failed and (2) the reasons for the treatment failure.

Simultaneous dystrophin and dysferlin deficiencies associated with high-level expression of the coxsackie and adenovirus receptor in transgenic mice.

The Coxsackie and adenovirus receptor (CAR), a cell adhesion molecule of the immunoglobulin superfamily, is usually confined to the sarcolemma at the neuromuscular junction in mature skeletal muscle fibers. Previously, we reported that adenovirus-mediated gene transfer is greatly facilitated in hemizygous transgenic mice with extrasynaptic CAR expression driven by a muscle-specific promoter. However, in the present study, when these mice were bred to homozygosity, they developed a severe myopathic phenotype and died prematurely.

Dynamic responses of the glutathione system to acute oxidative stress in dystrophic mouse (mdx) muscles.

The precise mechanisms underlying skeletal muscle damage in Duchenne muscular dystrophy (DMD) remain ill-defined. Functional ischemia during muscle activation, with subsequent reperfusion during rest, has been documented. Therefore, one possibility is the presence of increased oxidative stress.

Sarcolemmal damage in dystrophin deficiency is modulated by synergistic interactions between mechanical and oxidative/nitrosative stresses.

Dystrophin deficiency is the cause of Duchenne muscular dystrophy, but the precise physiological basis for muscle necrosis remains unclear. To determine whether dystrophin-deficient muscles are abnormally susceptible to oxidative and nitric oxide (NO)-driven tissue stress, a hindlimb ischemia/reperfusion (I/R) model was used. Dystrophic mdx mice exhibited abnormally high levels of lipid peroxidation and protein nitration, which were preceded by exaggerated NO production during ischemia.