RESUMO
PURPOSE: To clarify the role of epilepsy and genetic background in determining the cognitive outcome of patients with Dravet syndrome. METHODS: In this retrospective study, we reviewed the clinical history and cognitive development of 26 patients who had been followed with standardized evaluations since seizure onset. The cognitive outcome was quantified as differential general quotient (dGQ) between ages 12 and 60 months. Statistical analysis correlated the dGQ with genotype and epilepsy course. KEY FINDINGS: Epilepsy started at the mean age of 5.6 months. All patients experienced prolonged convulsive seizures, whereas absences and myoclonus were reported in 17. Cognitive outcome was poor in almost all patients; the mean dGQ was 33 points, varying from 6-77 points. The analysis of individual cognitive profiles identified seven patients in whom the dGQ was <20 points; the main clinical characteristic in this subset of patients was lack of early absences and myoclonus. The statistical analysis of the whole series failed to reveal significant differences in cognitive outcome with regard to the presence of SCN1A mutations and their type. In particular, mutation-carrier patients with the best cognitive outcome harbored either missense or truncating mutations. SIGNIFICANCE: Dravet syndrome encompasses different epileptic and cognitive phenotypes that probably result from both genetic and epigenetic factors. In this series, early appearance of myoclonus and absences was associated with the worst cognitive outcome.
Assuntos
Desenvolvimento Infantil/fisiologia , Cognição/fisiologia , Epilepsia Mioclônica Juvenil/genética , Epilepsia Mioclônica Juvenil/psicologia , Adolescente , Idade de Início , Criança , Pré-Escolar , Eletroencefalografia , Feminino , Genótipo , Heterozigoto , Humanos , Lactente , Itália , Modelos Lineares , Imageamento por Ressonância Magnética , Masculino , Mutação/fisiologia , Canal de Sódio Disparado por Voltagem NAV1.1 , Proteínas do Tecido Nervoso/genética , Estudos Retrospectivos , Convulsões/complicações , Convulsões/genética , Canais de Sódio/genética , Estado Epiléptico/complicações , Estado Epiléptico/genéticaRESUMO
Aims of our study were to describe the early clinical features of Dravet syndrome (SMEI) and the neurological, cognitive and behavioral outcome. The clinical history of 37 patients with clinical diagnosis of SMEI, associated with a point mutation of SCN1A gene in 84% of cases, were reviewed with particular attention to the symptoms of onset. All the patients received at least one formal cognitive and behavior evaluation. Epilepsy started at a mean age of 5.7 months; the onset was marked by isolated seizure in 25 infants, and by status epilepticus in 12; the first seizure had been triggered by fever, mostly of low degree in 22 infants; the first EEG was normal in all cases. During the second year of life difficult-to-treat seizures recurred, mostly triggered by fever, hot bath, and intermittent lights and delay in psychomotor development became evident. At the last evaluation, performed at a mean age of 16+/-6.9 years, mental retardation was present in 33 patients, associated with behavior disorders in 21. Our data indicate that the most striking features of SMEI are: the early onset of seizures in a previously healthy child, the long duration of the first seizure, the presence of focal ictal symptoms, and sensitivity to low-grade fever. Diagnosis of SMEI may be proposed by the end of the first year of life, and a definite diagnosis can be established during the second year based on the peculiar seizure-favoring factors, EEG photosensitivity and psychomotor slowing. The temporal correlation between high seizure frequency and cognitive impairment support the role of epilepsy in the clinical outcome, even if a role of channelopathy cannot be ruled out.