Seizure exacerbation with anti-seizure medications in adult patients with epilepsy.

There are numerous reports of seizure exacerbation related to specific anti-seizure medications (ASMs); however, a quantitative analysis with clearly defined parameters for seizure exacerbation in an outpatient setting is lacking. This retrospective study examines adult patients starting a single ASM and follows patient outcomes over the course of treatment, with quantitative evaluation of the incidence of paradoxical seizure exacerbation. In this study, outpatient encounters with five epileptologists at the Baylor College of Medicine Comprehensive Epilepsy Center were evaluated over a 10-month period. Seizure exacerbation was defined as an increase in seizure frequency at least 2 times greater than the baseline seizure frequency after initiation of an ASM, with return to baseline after ASM discontinuation. Patients were stratified into four categories: (1) probable ASM-induced seizure exacerbation; (2) possible ASM-induced seizure exacerbation; (3) non-ASM induced seizure exacerbation; or (4) no seizure exacerbation. Out of a total of 236 encounters where an ASM was initiated, we found that 5.5% of patients experienced some form of seizure exacerbation. However, only 1.3% of patients had probable ASM-induced seizure exacerbation. Consistent with prior studies, our data indicate seizure exacerbation in adults is rare with the initiation of ASMs. However, further studies with a larger sample size are necessary to better understand what factors may predispose patients to potential medication-induced seizure exacerbation.

Early postnatal in vivo gliogenesis from nestin-lineage progenitors requires cdk5.

The early postnatal period is a unique time of brain development, as diminishing amounts of neurogenesis coexist with waves of gliogenesis. Understanding the molecular regulation of early postnatal gliogenesis may provide clues to normal and pathological embryonic brain ontogeny, particularly in regards to the development of astrocytes and oligodendrocytes. Cyclin dependent kinase 5 (Cdk5) contributes to neuronal migration and cell cycle control during embryogenesis, and to the differentiation of neurons and oligodendrocytes during adulthood. However, Cdk5's function in the postnatal period and within discrete progenitor lineages is unknown. Therefore, we selectively removed Cdk5 from nestin-expressing cells and their progeny by giving transgenic mice (nestin-CreERT2/R26R-YFP/CDK5(flox/flox) [iCdk5] and nestin-CreERT2/R26R-YFP/CDK5(wt/wt) [WT]) tamoxifen during postnatal (P) days P2-P 4 or P7-P 9, and quantified and phenotyped recombined (YFP+) cells at P14 and P21. When Cdk5 gene deletion was induced in nestin-expressing cells and their progeny during the wave of cortical and hippocampal gliogenesis (P2-P4), significantly fewer YFP+ cells were evident in the cortex, corpus callosum, and hippocampus. Phenotypic analysis revealed the cortical decrease was due to fewer YFP+ astrocytes and oligodendrocytes, with a slightly earlier influence seen in oligodendrocytes vs. astrocytes. This effect on cortical gliogenesis was accompanied by a decrease in YFP+ proliferative cells, but not increased cell death. The role of Cdk5 in gliogenesis appeared specific to the early postnatal period, as induction of recombination at a later postnatal period (P7-P9) resulted in no change YFP+ cell number in the cortex or hippocampus. Thus, glial cells that originate from nestin-expressing cells and their progeny require Cdk5 for proper development during the early postnatal period.