Tayeb Sekhara

Oral ketamine in paediatric non-convulsive status epilepticus.

In children, non-convulsive status epilepticus (NCSE) is rare and difficult to treat. Response to steroids and GABAergic medication is variable and often decreases with increasing duration of NCSE. We present our experience with oral ketamine, an NMDA-receptor antagonist, administered to five children with severe epilepsy (Lennox-Gastaut Syndrome, myoclonic-astatic epilepsy, progressive myoclonic epilepsy and Pseudo-Lennox Syndrome) during an episode of NCSE. Resolution of NCSE was documented in all cases clinically and electroencephalographically within 24-48 hours of starting ketamine. No significant side effects were noted.

MRI spectrum of cortical malformations in tuberous sclerosis complex

The diagnostic and prognostic value of magnetic resonance imaging in the tuberous sclerosis complex has increasingly been recognized. In this paper, we review the presumed pathogenesis of the cerebral dysgenesis seen in this condition in the light of magnetic resonance imaging features of selected patients. In addition to typical findings related to tubers, we show and discuss varied cortical malformations (from simple localized cortical dysplasia to transmantle dysplasia and schizencephaly) similar to those seen in sporadic cerebral dysgenesis. These cases support the hypothesis that the tuberous sclerosis complex focally affects the radial glial-neuronal complex as a basic unit for brain development. Abnormal stem cells would create dysplastic glia and neurons that fail to differentiate, proliferate, migrate and form a normally organized cortex.

A de novo SOX10 mutation causing severe type 4 Waardenburg syndrome without Hirschsprung disease

Type 4 Waardenburg syndrome represents a well define entity caused by neural crest derivatives anomalies (melanocytes, intrinsic ganglion cells, central, autonomous and peripheral nervous systems) leading, with variable expressivity, to pigmentary anomalies, deafness, mental retardation, peripheral neuropathy, and Hirschsprung disease. Autosomal dominant mode of inheritance is prevalent when Sox10 gene mutation is identified. We report the natural history of a child who presented with synophrys, vivid blue eye, deafness, bilateral complete semicircular canals agenesis with mental retardation, subtle signs for peripheral neuropathy and lack of Hirschsprung disease. SOX10 gene sequencing identified “de novo” splice site mutation (c.698‐2A > C). The present phenotype and the genotype findings underline the wide spectrum of SOX10 gene implication in unusual type 4 Waardenburg syndrome patient.

Benign intracranial hypertension : atypical presentation of Miller Fisher syndrome?

Acute ocular paresis, nausea, vomiting, and headaches associated with high intracranial pressure without obvious intracranial pathology are typical features of benign intracranial hypertension. We describe two young children whose presentation, initially suggestive of idiopathic or benign intracranial hypertension, evolved to comprise ophthalmoplegia, ataxia, and areflexia. This triad characterizes Miller Fisher syndrome, a clinical variant of Guillain-Barré syndrome that occurs rarely among children. In both patients, this diagnosis was supported by the clinical course and neurophysiologic findings. Plasma serology was positive for Campylobacter jejuni and anti-GQ1b antibodies in one patient and for antimyelin antibodies in the other. This report of two children with Miller Fisher syndrome presenting with intracranial hypertension adds to the findings for a similar patient treated previously, which raises the question concerning the possible role or contribution of benign intracranial hypertension in Miller Fisher syndrome.

Complications of lumbar puncture in a child treated for leukaemia

Lumbar puncture may lead to neurological complications. These include intracranial hypotension, cervical epidural haematomas, and cranial and lumbar subdural haematomas. MRI is the modality of choice to diagnose these complications. This report documents MRI findings of such complications in a child treated for leukaemia.

Novel promoters and coding first exons in DLG2 linked to developmental disorders and intellectual disability

BackgroundTissue-specific integrative omics has the potential to reveal new genic elements important for developmental disorders.MethodsTwo pediatric patients with global developmental delay and intellectual disability phenotype underwent array-CGH genetic testing, both showing a partial deletion of the DLG2 gene. From independent human and murine omics datasets, we combined copy number variations, histone modifications, developmental tissue-specific regulation, and protein data to explore the molecular mechanism at play.ResultsIntegrating genomics, transcriptomics, and epigenomics data, we describe two novel DLG2 promoters and coding first exons expressed in human fetal brain. Their murine conservation and protein-level evidence allowed us to produce new DLG2 gene models for human and mouse. These new genic elements are deleted in 90% of 29 patients (public and in-house) showing partial deletion of the DLG2 gene. The patients’ clinical characteristics expand the neurodevelopmental phenotypic spectrum linked to DLG2 gene disruption to cognitive and behavioral categories.ConclusionsWhile protein-coding genes are regarded as well known, our work shows that integration of multiple omics datasets can unveil novel coding elements. From a clinical perspective, our work demonstrates that two new DLG2 promoters and exons are crucial for the neurodevelopmental phenotypes associated with this gene. In addition, our work brings evidence for the lack of cross-annotation in human versus mouse reference genomes and nucleotide versus protein databases.