Electrographic and pharmacological characterization of a progressive epilepsy phenotype in female MeCP2-deficient...

Rett Syndrome is a neurodevelopmental disorder caused primarily by mutations in the gene encoding Methyl-CpG-binding protein 2 (MECP2). Spontaneous epileptiform activity is a common co-morbidity present in Rett syndrome, and hyper-excitable neural networks are present in MeCP2-deficient mouse models of Rett syndrome. In this study we conducted a longitudinal assessment of spontaneous cortical electrographic discharges in female MeCP2-deficient mice and defined the pharmacological responsiveness of these discharges to anti-convulsant drugs. Our data show that cortical discharge activity in female MeCP2-deficient mice progressively increases in severity as the mice age, with discharges being more frequent and of longer durations at 19-24 months of age compared to 3 months of age. Semiologically and pharmacologically, this basal discharge activity in female MeCP2-deficient mice displayed electroclinical properties consistent with absence epilepsy. Only rarely were convulsive seizures observed in these mice at any age. Since absence epilepsy is infrequently observed in Rett syndrome patients, these results indicate that the predominant spontaneous electroclinical phenotype of MeCP2-deficient mice we examined does not faithfully recapitulate the most prevalent seizure types observed in affected patients.