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.

The Experience of Parents of Children With Genetically Determined Leukoencephalopathies With the Health Care System: A Qualitative Study.

Parents of children with genetically determined leukoencephalopathies play a major role in their children's health care. We sought to gain a better understanding of their experience with the public health care system in Quebec, Canada, to obtain suggestions for improving their services, and to identify modifiable factors to improve their quality of life. We conducted interviews with 13 parents.

Surgically Remediable Secondary Network Epileptic Encephalopathies With Continuous Spike Wave in Sleep: Lesions May Not Be Visible on Brain Magnetic Resonance Imaging (MRI).

Background: Continuous spike wave in sleep (CSWS) is an electroencephalogram (EEG) pattern associated with developmental and epileptic encephalopathy with spike-and-wave activation in sleep (DEE-SWAS). This etiologically heterogeneous syndrome may occur because of genetic factors and congenital or acquired brain lesions. We studied the pattern of clinical presentation and underlying etiologies in patients with DEE-SWAS that respond to resective surgery.

Experience of Parents of Children with Genetically Determined Leukoencephalopathies Regarding the Adapted Health Care Services During the COVID-19 Pandemic.

Parents of children with genetically determined leukoencephalopathies play a major role in their children's health care. Because of the COVID-19 pandemic, many health care services were suspended, delayed or delivered remotely with telemedicine. We sought to explore the experience of parents of children with genetically determined leukoencephalopathies during the pandemic given the adapted health care services.

DCC Is Required for the Development of Nociceptive Topognosis in Mice and Humans.

Avoidance of environmental dangers depends on nociceptive topognosis, or the ability to localize painful stimuli. This is proposed to rely on somatotopic maps arising from topographically organized point-to-point connections between the body surface and the CNS. To determine the role of topographic organization of spinal ascending projections in nociceptive topognosis, we generated a conditional knockout mouse lacking expression of the netrin1 receptor DCC in the spinal cord.

Intravenous Immunoglobulin as a Treatment for Intractable Epilepsy Secondary to Focal Cortical Dysplasia: A Meta-analysis.

Background: The observation of a dramatic response to intravenous immunoglobulin (IVIG) by a child from our center with intractable epilepsy due to focal cortical dysplasia prompted us to perform a meta-analysis on the efficiency of IVIG in this condition. Focal cortical dysplasia is a common cause of intractable epilepsy. Microglial activation and upregulation of neuroinflammatory pathways have been documented in brain specimen from surgically treated patients with intractable epilepsy and focal cortical dysplasia.

Clinical and Radiologic Spectrum of Septo-optic Dysplasia: Review of 17 Cases.

We retrospectively reviewed the clinical and radiologic characteristics of 17 individuals with septo-optic dysplasia (SOD) and attempted to identify correlations between imaging findings, clinical features, and neurodevelopmental outcome. Surprisingly, only 1 (6%) individual was classified as classic SOD (with septum pellucidum/corpus callosum dysgenesis), 3 (18%) as SOD-like (with normal septum pellucidum/corpus callosum) and the majority, 13 (76%), as SOD-plus (with cortical brain malformation). Cortical abnormalities included schizencephaly, polymicrogyria, and gray matter heterotopias.

Breaking the cycle: A comparison between intravenous immunoglobulins and high dosage prednisone in the treatment of medically intractable epilepsy in children.

Purpose: Because immune mediated mechanisms are suspected in epileptogenesis, IVIg and corticosteroids have been used as alternatives to treat refractory seizures. We present our experience treating intractable epileptic children with IVIg and prednisone.

Methods: Children with intractable epilepsy treated with prednisone or IVIg between 2005-2016 were reviewed retrospectively.

Somatosensory evoked potentials in neonates with hypoxic-ischemic encephalopathy treated with hypothermia.

Objective: Somatosensory evoked potentials (SEPs) are reported to have high positive predictive value (PPV) for neurodevelopmental impairment (NDI) in neonates with moderate or severe hypoxic-ischemic encephalopathy (HIE). Our objective was to assess if this predictive value remains high with the use of therapeutic hypothermia.

Methods: A cohort of HIE neonates treated with hypothermia was recruited between September 2008 and September 2010.

De novo deletion of FMN2 in a girl with mild non-syndromic intellectual disability.

We present the case of a child with mild non-syndromic intellectual disability in whom array genomic hybridization revealed a de novo heterozygous deletion involving only one gene, FMN2. FMN2 encodes FORMIN-2, a member of the formin homology family, which is primarily expressed in the developing and mature brain, and has an important role in cytoskeletal organization and actin nucleation. A heterozygous deletion of FMN2 along with 2 other genes has been recently reported in a boy with non-syndromic intellectual disability.

Homozygous deletion of Tenascin-R in a patient with intellectual disability.

Background: TNR encodes Tenascin-R, an extracellular matrix glycoprotein that is primarily expressed in the central nervous system. Loss of TNR impairs cognition, synaptic plasticity and motor abilities in mice, however its role in human neurodevelopment and cognition is less clear.

Methods And Results: The authors present the case of a child with intellectual disability and transient choreoathetosis.

Gender differences in the developmental outcomes of children with congenital cardiac defects.

Objective: This study compares the developmental and functional outcomes at school entry between boys and girls born with a congenital cardiac defect who required early surgical correction.

Study Design: A prospective cohort of 94 children, including 49 percent boys, were followed up to 5 years of age and assessed for developmental progress. Developmental measures included Wechsler Preschool and Primary Scale of Intelligence - cognitive; Peabody Picture Vocabulary Test - receptive language; Peabody Developmental Motor Scale - motor; and Child Behaviour Checklist - behaviour.

A de novo 2.1-Mb deletion of 13q12.11 in a child with developmental delay and minor dysmorphic features.

We report on a patient with an interstitial deletion at 13q12.11. He had mild developmental delay, craniofacial dysmorphism, a pectus excavatum, narrow shoulders, malformed toes, and café-au-lait spots.

A new look at outcomes of infants with congenital heart disease.

This article provides an overview of a longitudinal study on a cohort of 131 newborns and young infants with congenital heart defects who required open heart surgery. The rationale for the study design is provided as well as a summary of the procedures used to evaluate these children prior to surgery, at discharge after surgery, 12-18 months later, and at 5 years of age. Results demonstrate that a substantial proportion of these infants had neurologic and developmental abnormalities prior to surgical repair.

Sudden cardiac death in association with the ketogenic diet.

The ketogenic diet is a high-fat, low-carbohydrate, adequate-protein diet that is used to decrease the frequency of seizures in patients who have refractory epilepsy. Despite its positive effects in some patients, there are potential adverse effects. Two complications related to the ketogenic diet are selenium deficiency, which has been associated with impaired myocardial function, and QT prolongation as documented on electrocardiography.

Developmental and functional outcomes at school entry in children with congenital heart defects.

Objective: To describe developmental and functional outcomes of children with congenital heart defects (CHDs) at school entry after open heart surgery.

Study Design: Infants with CHDs who underwent surgical repair in infancy were recruited and assessed prospectively for developmental progress. At 5 years of age (64.

Simultaneous Guillain-Barré syndrome and acute disseminated encephalomyelitis in the pediatric population.

Few cases of simultaneous acute demyelination of the peripheral and central nervous systems are reported. Four patients diagnosed as having Guillain-Barré syndrome and acute disseminated encephalomyelitis during the same hospitalization are described herein. Two patients manifest an atypical form of Guillain-Barré syndrome, with magnetic resonance imaging of the head showing acute disseminated encephalomyelitis.

Patterns of use of educational and rehabilitation services at school age for children with congenitally malformed hearts.

Background: Infants with congenitally malformed hearts who require early open-heart surgery are at high risk for developmental, psychosocial, and academic difficulties. Our objective was to describe the pattern of use of educational supports and rehabilitation services in these children at early school age.

Methods: Parents of children who participated in a prospective study of developmental progress following open-surgery were contacted to participate in a telephone survey.

Health and well-being of children with congenital cardiac malformations, and their families, following open-heart surgery.

Infants who survive open-heart surgery are at risk for developmental disability, which may impact on the well-being not only of the child, but also the family. The objective of our prospective study, therefore, was to determine the long-term health-related quality of life of children with congenital cardiac malformations following open-heart surgery, and to describe the persisting level of stress in their families. To this end, 49 parents completed the Child Health Questionnaire, the Parenting Stress Index, and the Child Behaviour Checklist as part of a developmental follow-up protocol when their child was 5 years of age.

Long-term neuromotor outcome at school entry of infants with congenital heart defects requiring open-heart surgery.

Objectives: Increased survival in infants with complex congenital heart defects (CHDs) has resulted in greater focus on morbidity. This prospective study was conducted to investigate whether or not neuromotor impairments evident acutely persist long-term.

Study Design: A total of 94 infants with CHD were reassessed at school entry (age 64.

Long-term outcome after surgical treatment of temporal lobe epilepsy in children.

Object: Surgery is an accepted treatment for carefully selected patients with focal epilepsy. In the present study, the authors assessed clinical and surgery-related data obtained in a large series of children suffering from intractable temporal lobe epilepsy (TLE).

Methods: Etiological, pathological, and clinical features of possible prognostic significance were studied in 109 children who underwent surgery for TLE at the Montreal Neurological Institute and Hospital and the Montreal Children's Hospital between 1985 and 2000.

Predictors of developmental disabilities after open heart surgery in young children with congenital heart defects.

Objectives: To determine the prevalence of persistent developmental impairments in children with congenital heart defects and to identify factors that enhance risk for an adverse outcome.

Study Design: Eligible infants (n = 131) <2 years of age requiring open heart surgery were recruited prospectively. Subjects were assessed during surgery and again 12 to 18 months later with standardized developmental assessments and formal neurologic examinations.