Child Neurology: cognitive delay in a 7-year-old girl.

Organic acidurias are an important group of inherited metabolic disorders that affect the intermediary metabolic pathways of carbohydrate, amino acid, and fatty acid oxidation, leading to the accumulation of organic acids.(1) The 2-hydroxyglutaric acidurias are rare neurometabolic disorders characterized by developmental delay with or without other neurologic dysfunction. Three different subtypes have been described: d-2-hydroxyglutaric aciduria, l-2-hydroxyglutaric aciduria, and combined d-l-2-hydroxyglutaric aciduria. We describe the case of a child presenting with developmental delay who was found to have the classical biochemical, imaging, and genetic features of l-2-hydroxyglutaric aciduria.

Medication errors in the homes of children with chronic conditions.

BACKGROUND: Children with chronic conditions often have complex medication regimens, usually administered at home by their parents. OBJECTIVE: To describe the types of medication errors in the homes of children with chronic conditions. METHODS Our home visit methods include direct observation of administration, medication review and prescription dose checking. Parents of children with sickle cell disease and seizure disorders taking daily medications were recruited from paediatric subspecialty clinics from November 2007 to April 2009. Potential errors were reviewed by two physicians who made judgments about whether an error had occurred or not, and its severity. RESULTS: On 52 home visits, the authors reviewed 280 medications and found 61 medication errors (95% CI 46 to 123), including 31 with a potential to injure the child and 9 which did injure the child. Injuries often occurred when parents failed to fill prescriptions or to change doses due to communication problems, leading to further testing or continued pain, inflammation, seizures, vitamin deficiencies or other injuries. Errors not previously reported in the literature included communication failures between two parents at home leading to administration errors and difficulty preparing the medication for administration. 95% of parents not using support tools (eg, alarms, reminders) for medication use at home had an error compared to 44% of those using supports (χ(2)=13.9, p=0.0002). CONCLUSIONS: Home visits detected previously undescribed types of outpatient errors which were common among children with sickle cell disease and seizure disorders. These should be targeted in future intervention development.

Glial activation links early-life seizures and long-term neurologic dysfunction: evidence using a small molecule inhibitor of proinflammatory cytokine upregulation.

PURPOSE: Early-life seizures increase vulnerability to subsequent neurologic insult. We tested the hypothesis that early-life seizures increase susceptibility to later neurologic injury by causing chronic glial activation. To determine the mechanisms by which glial activation may modulate neurologic injury, we examined both acute changes in proinflammatory cytokines and long-term changes in astrocyte and microglial activation and astrocyte glutamate transporters in a "two-hit" model of kainic acid (KA)-induced seizures. METHODS: Postnatal day (P) 15 male rats were administered KA or phosphate buffered saline (PBS). On P45 animals either received a second treatment of KA or PBS. On P55, control (PBS-PBS), early-life seizure (KA-PBS), adult seizure (PBS-KA), and "two-hit" (KA-KA) groups were examined for astrocyte and microglial activation, alteration in glutamate transporters, and expression of the glial protein, clusterin. RESULTS: P15 seizures resulted in an acute increase in hippocampal levels of IL-1beta and S100B, followed by behavioral impairment and long-term increases in GFAP and S100B. Animals in the "two-hit" group showed greater microglial activation, neurologic injury, and susceptibility to seizures compared to the adult seizure group. Glutamate transporters increased following seizures but did not differ between these two groups. Treatment with Minozac, a small molecule inhibitor of proinflammatory cytokine upregulation, following early-life seizures prevented both the long-term increase in activated glia and the associated behavioral impairment. CONCLUSIONS: These data suggest that glial activation following early-life seizures results in increased susceptibility to seizures in adulthood, in part through priming microglia and enhanced microglial activation. Glial activation may be a novel therapeutic target in pediatric epilepsy.

Depressive behavior and selective down-regulation of serotonin receptor expression after early-life seizures: reversal by environmental enrichment.

Depression is the most common psychiatric comorbidity in epilepsy. To better understand the contribution of seizures versus environment to depression in epilepsy, we investigated differential gene expression using microarray and quantitative RT-PCR, and depressive behavior, in the Porsolt forced swim test in juvenile rats reared in different environments after kainic acid (KA)-induced seizures. We selected for genes significantly down-regulated by KA seizures and upregulated by environmental enrichment. This common gene selection process yielded one known gene involved in mood and affect: serotonin receptor 5B. The changes in serotonin receptor gene expression were paralleled by decreased mobility in the forced swim tests; depressive behavior exhibited after seizures was no longer evident in rats reared in environmental enrichment. Our results suggest that seizures lead to increased susceptibility to depression through transcriptional regulation while environment, in turn, can interact with gene expression to influence the behavioral outcome of epilepsy.