The spectrum of epilepsy in children with 15q13.3 microdeletion syndrome.

PURPOSE: To further define the epilepsy phenotype in a cohort of children with 15q13.3 microdeletion syndrome. METHODS: We retrospectively reviewed the phenotypic spectrum of all children aged < 18 years with epilepsy and 15q13.3 microdeletion syndrome. RESULTS: Thirteen children were included, 69% were female. The median age of children in the cohort was 12 years (age range: 3 years-15 years). Median age at seizure onset was 4 years. Eleven children (85%) had intellectual disability. Nine of 13 children (69%) had a history of typical absence seizures with median age of onset at 5 years (2 had absence status epilepticus). Thirty-one percent (4/13) had focal with impaired awareness non-motor onset seizures. ILAE recognized absence epilepsy syndromes were diagnosed in 6/13 (46%). The remainder were classified as having genetic generalized epilepsies with overlap clinical features, combined or focal epilepsies. Electroencephalogram in the cohort showed generalized (85%) and focal epileptiform discharges (62%) and posterior dominant rhythm slowing (33%). One child had electrical status epilepticus of sleep. Neuroimaging was performed in 5 children (38%) and revealed abnormal findings in 3. Seizures were drug resistant in a third of the cohort. Valproate resulted in seizure freedom in 5 (42%). Oxcarbazepine caused clinical worsening in one child with combined seizure types. Two children tried cannabidiol and one tried the ketogenic diet; neither was effective. CONCLUSIONS: The epilepsy phenotype in children with 15q13.3 microdeletion syndrome is defined by childhood onset absence seizures, and may have atypical features such as, early onset absences, persistence into adolescence, status epilepticus, intellectual disability and treatment resistance. Focal seizures and focal EEG findings may be observed and should be treated cautiously, given the possibility of combined seizure types. Valproate appeared effective, although other treatments must be explored further.

Feasibility and Reliability of Muscle Strength Testing in Critically Ill Children.

Diagnosing pediatric intensive care unit-acquired weakness (PICU-AW) is challenging. The Medical Research Council (MRC) score is a widely used screening method for muscle weakness in critically ill adults; however, its utility in critically ill children has not been established. Our objective was to determine the feasibility and interobserver reliability of muscle strength testing using MRC score in critically ill children. A prospective observational substudy of critically ill children aged 1 to 17 years and limited to bed rest during the first 48 hours of PICU admission was evaluated with weekly MRC exams independently performed by two clinical raters. MRC exams were attempted on all 33 participants, but could be completed in only 21 (64%), 9 of who (43%) received at least one exam while in the PICU, and in the remaining 12 (57%), MRC exams could only be completed after PICU discharge. Of the 95 attempted MRC exams, 55 (57%) could not be conducted or completed, most commonly due to patient sedation, and inability to comply due to cognitive ability, pain, or noncooperation. The inter-rater reliability for MRC sum score was excellent (intraclass correlation coefficient: 0.87). However, the inter-rater reliability was only moderate when used to determine PICU-AW (Cohen kappa: 0.48). MRC testing in the PICU was not feasible as an early screening tool for muscle weakness in the majority of critically ill children in this study. Further research is needed to find an appropriate screening tool that is both feasible and predicts clinically relevant outcomes in children, such as function and recovery following critical illness.