RESUMEN
Epilepsy is a major feature of Menkes disease, an X-linked recessive infantile neurodegenerative disorder caused by mutations in ATP7A, which produces a copper-transporting ATPase. Three prior surveys indicated clinical seizures and electroencephalographic (EEG) abnormalities in a combined 27 of 29 (93%) symptomatic Menkes disease patients diagnosed at 2 months of age or older. To assess the influence of earlier, presymptomatic diagnosis and treatment on seizure semiology and brain electrical activity, we evaluated 71 EEGs in 24 Menkes disease patients who were diagnosed and treated with copper injections in early infancy (≤6 weeks of age), and whose ATP7A mutations we determined. Clinical seizures were observed in only 12.5% (3/24) of these patients, although 46% (11/24) had at least one abnormal EEG tracing, including 50% of patients with large deletions in ATP7A, 50% of those with small deletions, 60% of those with nonsense mutations, and 57% of those with canonical splice junction mutations. In contrast, five patients with mutations shown to retain partial function, either via some correct RNA splicing or residual copper transport capacity, had neither clinical seizures nor EEG abnormalities. Our findings suggest that early diagnosis and treatment improve brain electrical activity and decrease seizure occurrence in classical Menkes disease irrespective of the precise molecular defect. Subjects with ATP7A mutations that retain some function seem particularly well protected by early intervention against the possibility of epilepsy.
Asunto(s)
Adenosina Trifosfatasas/genética , Proteínas de Transporte de Catión/genética , Epilepsia/genética , Síndrome del Pelo Ensortijado/genética , Mutación , Distribución de Chi-Cuadrado , Cobre/administración & dosificación , ATPasas Transportadoras de Cobre , Análisis Mutacional de ADN , Suplementos Dietéticos , Diagnóstico Precoz , Electroencefalografía , Epilepsia/enzimología , Epilepsia/mortalidad , Epilepsia/fisiopatología , Epilepsia/prevención & control , Predisposición Genética a la Enfermedad , Humanos , Lactante , Recién Nacido , Inyecciones Subcutáneas , Maryland , Síndrome del Pelo Ensortijado/complicaciones , Síndrome del Pelo Ensortijado/diagnóstico , Síndrome del Pelo Ensortijado/enzimología , Síndrome del Pelo Ensortijado/mortalidad , Síndrome del Pelo Ensortijado/fisiopatología , Síndrome del Pelo Ensortijado/terapia , Fenotipo , Valor Predictivo de las Pruebas , Resultado del TratamientoRESUMEN
West Nile virus (WNV) has re-emerged with a much wider geographic distribution and a higher incidence than ever. In spite of some recent reports on the neurological manifestations and EEG changes caused by WNV encephalitis, there are few data on the incidence of seizures, status epilepticus or post-encephalitic epilepsy. There is also no systematic review of EEG changes caused by WNV encephalitis that is based on a large series of patients. Here, we review the pertinent literature, and report the electroclinical evolution and therapeutic complexity of a patient with WNV encephalitis who developed refractory, non-convulsive status epilepticus.