Neurodevelopmental and psychiatric comorbidities negatively affect outcome in children with unprovoked seizures-A non-systematic review.

Children with epilepsy have at least one comorbidity in 80% of cases. This unstructured review provides insights into the most common comorbidities, their effects on seizure prognosis and treatment. We also review the epilepsy terminology and classifications. Neurodevelopmental and psychiatric comorbidities were common in children with seizures and had a negative effect on quality of life, and seizure freedom. Children with seizures were treated with drugs used for attention deficit hyperactivity disorder (ADHD), depression or psychosis, more often than the general population but less often than prevalence rates would suggested. CONCLUSION: Multidisciplinary teams should assess comorbidities in children with epilepsy to improve their care and outcomes.

An epigenome atlas of neural progenitors within the embryonic mouse forebrain.

A comprehensive characterization of epigenomic organization in the embryonic mouse forebrain will enhance our understanding of neurodevelopment and provide insight into mechanisms of neurological disease. Here we collected single-cell chromatin accessibility profiles from four distinct neurogenic regions of the embryonic mouse forebrain using single nuclei ATAC-Seq (snATAC-Seq). We identified thousands of differentially accessible peaks, many restricted to distinct progenitor cell types or brain regions. We integrated snATAC-Seq and single cell transcriptome data to characterize changes of chromatin accessibility at enhancers and promoters with associated transcript abundance. Multi-modal integration of histone modifications (CUT&Tag and CUT&RUN), promoter-enhancer interactions (Capture-C) and high-order chromatin structure (Hi-C) extended these initial observations. This dataset reveals a diverse chromatin landscape with region-specific regulatory mechanisms and genomic interactions in distinct neurogenic regions of the embryonic mouse brain and represents an extensive public resource of a 'ground truth' epigenomic landscape at this critical stage of neurogenesis.

Neurodevelopmental comorbidities and seizure control 24 months after a first unprovoked seizure in children.

PURPOSE: To follow children with newly diagnosed unprovoked seizures to determine (1) whether the prevalence of neurodevelopmental comorbidities and cerebral palsy (CP) changed after the initial seizure, and (2) the association between studied comorbidities and seizures 13-24 months after seizure onset or initiation of treatment. METHODS: Analyses were based on 750 children (28 days-18 years) with a first unprovoked seizure (index) included in a population-based Incidence Registry in Stockholm between 2001 and 2006. The children were followed for two years and their medical records were examined for a priori defined neurodevelopmental/psychiatric comorbidities and CP and seizure frequency. Baseline information was collected from medical records from before, and up to six months after, the index seizure. Odds ratios (OR) of repeated seizures 13-24 months after the first seizure or after initiation of anti-epileptic drug treatment was calculated by logistic regression and adjusted for age and sex. RESULTS: At baseline, 32% of the children had neurodevelopmental/psychiatric comorbidities or CP compared to 35%, 24 months later. Children with such comorbidities more often experienced seizures 13-24 months after the index seizure (OR 2.87, CI 2.07-3.99) with the highest OR in those with CP or attention deficit hyperactivity disorder (ADHD). Children diagnosed at age <1 year exhibited the highest prevalence of comorbidities as well as OR for repeated seizures. A combination of young age and comorbidity was associated with an OR for repeated seizures of 5.12 (CI 3.03-8.65). Among the children without comorbidities 76% were seizure free 13-24 months after the index seizure or after initiation of AED treatment compared to 53% of children with comorbidities. CONCLUSIONS: This study indicates that neurodevelopmental comorbidities and CP in children with epilepsy tend to be present already at seizure onset and that such comorbidities are strong indicators of poor outcome regarding seizure control with or without treatment.