RESUMEN
Because molecular mechanisms underlying refractory focal epilepsy are poorly defined, we performed transcriptome analysis on human epileptogenic tissue. Compared with controls, expression of Circadian Locomotor Output Cycles Kaput (CLOCK) is decreased in epileptogenic tissue. To define the function of CLOCK, we generated and tested the Emx-Cre; Clockflox/flox and PV-Cre; Clockflox/flox mouse lines with targeted deletions of the Clock gene in excitatory and parvalbumin (PV)-expressing inhibitory neurons, respectively. The Emx-Cre; Clockflox/flox mouse line alone has decreased seizure thresholds, but no laminar or dendritic defects in the cortex. However, excitatory neurons from the Emx-Cre; Clockflox/flox mouse have spontaneous epileptiform discharges. Both neurons from Emx-Cre; Clockflox/flox mouse and human epileptogenic tissue exhibit decreased spontaneous inhibitory postsynaptic currents. Finally, video-EEG of Emx-Cre; Clockflox/flox mice reveals epileptiform discharges during sleep and also seizures arising from sleep. Altogether, these data show that disruption of CLOCK alters cortical circuits and may lead to generation of focal epilepsy.
Asunto(s)
Encéfalo/metabolismo , Proteínas CLOCK/deficiencia , Proteínas CLOCK/genética , Epilepsias Parciales/genética , Epilepsias Parciales/metabolismo , Red Nerviosa/metabolismo , Animales , Encéfalo/patología , Células Cultivadas , Epilepsias Parciales/patología , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Red Nerviosa/patología , Estudios ProspectivosRESUMEN
We review our experience with high-dose intravenous levetiracetam (IV-LEV) for acute seizure exacerbations in nine children with medically intractable epilepsy. All children had acute repetitive seizures-while on chronic antiepileptic drugs-that either led to hospitalization (eight) or occurred during hospitalization (one), and received doses of IV-LEV of 150 mg/kg/day or greater, with a mean dose of 228 +/- 48 mg/kg/day. Eight of nine children had resolution of the acute repetitive seizures. Seizure frequency was reduced to less than baseline in seven children (seizure-free in two, >/=80% reduction in four, and 50% reduction in one). Except for one child with increased seizures, IV-LEV was well tolerated in all children without complications.
Asunto(s)
Epilepsia/tratamiento farmacológico , Piracetam/análogos & derivados , Convulsiones/tratamiento farmacológico , Niño , Preescolar , Epilepsia/fisiopatología , Femenino , Humanos , Lactante , Inyecciones Intravenosas , Levetiracetam , Masculino , Piracetam/administración & dosificación , Convulsiones/fisiopatología , Factores de Tiempo , Resultado del TratamientoRESUMEN
We present a discussion of recent relevant publications in pediatric epilepsy surgery. In 1998, the Commission on Neurosurgery of the International League Against Epilepsy formed the Subcommission for Pediatric Epilepsy Surgery. Their proposed recommendations are included here. We also discuss updates on identification and selection of children with severe refractory epilepsy. Functional imaging has advanced in recent years as an important adjunct in identifying the epileptogenic zone during the preoperative evaluation. The newer imaging modalities are summarized. Routine positron emission tomography, positron emission tomography with special tracers, and single photon emission computed tomography have proven to be beneficial. Other newer investigative techniques await validation. A number of studies on postoperative outcomes over the past few years have demonstrated the benefits of early surgical treatment for selected children.
