Severe Myoclonic Epilepsy of Infants (Dravet Syndrome): Natural History and Neuropsychological Findings

Severe Myoclonic Epilepsy in infancy (SMEI, or Dravet syndrome) is a drug-resistant epilepsy that occurs in the first year of life of previously healthy children. The main clinical features are prolonged and repeated febrile and afebrile generalized or unilateral convulsive seizures. In the course of the epilepsy, cognitive deterioration becomes evident, and interictal myoclonus, clumsiness and ataxia appear. One third of the children with SMEI show de novo mutations of the SCN1A gene, and additional familial genes probably contribute to the phenotype. While the clinical picture of SMEI has been well studied, neuropsychological data remain scarce. Global mental retardation, attention deficit and psychotic behavior have been reported but the long-term outcome has not been evaluated. We conducted a longitudinal neuropsychological study of children with SMEI. Twenty children, aged 11 months to 16 years, were prospectively examined using standardized neuropsychological tests. Correlation analysis with other clinical features was performed in 12 cases. Marked slowing or stagnation of psychomotor development, accompanied by psychotic or autistic traits and hyperactivity, was observed between the ages of one and four years. In the later stages (at ages 5 to 16 years), cognitive function stabilized but remained below normal. In children with a more favorable course, language capacities were better preserved than visuospatial functions, and behavior improved. The cognitive and behavioral impairment tended to correlate with the frequency of convulsive seizures (>5 per month). The data suggest that SMEI can be considered as a prototype of an epileptic encephalopathy.