Asunto(s)
Epilepsias Parciales/diagnóstico , Epilepsias Parciales/etiología , Homocistinuria/complicaciones , Homocistinuria/diagnóstico , Metilenotetrahidrofolato Reductasa (NADPH2)/deficiencia , Espasticidad Muscular/complicaciones , Espasticidad Muscular/diagnóstico , Adolescente , Electroencefalografía , Trastornos Neurológicos de la Marcha/etiología , Humanos , Masculino , Examen Neurológico , Trastornos Psicóticos/complicaciones , Trastornos Psicóticos/diagnóstico , Vitaminas/uso terapéuticoRESUMEN
OBJECTIVE: To examine in detail the relations between seizures and K-complexes in autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). METHODS: Prolonged continuous video-EEG recording and analysis of 30 seizures in an 18-year-old woman suffering from ADNFLE with a CHRNA4 gene mutation. RESULTS: Twenty-seven of 30 recorded seizures started just after a K-complex. In nine cases a sound induced a K-complex that was immediately followed by the seizure. Most seizures preceded repetitive and brief ictal restarts. CONCLUSIONS: Three new characteristics have been observed in this ADNFLE patient: a K-complex is almost invariably present at seizure onset; sounds trigger some seizures; ictal restarts occur often. SIGNIFICANCE: These new observations--the presence of K-complexes at seizure onset and occurrence of sound-triggered seizures--support the view that ADNFLE seizures may be initiated by K-complexes.
Asunto(s)
Ritmo Circadiano , Electroencefalografía , Epilepsia del Lóbulo Frontal/genética , Epilepsia del Lóbulo Frontal/fisiopatología , Genes Dominantes , Adolescente , Femenino , Humanos , Mutación/genética , Receptores Nicotínicos/genética , Convulsiones/genética , Convulsiones/fisiopatología , Grabación en VideoRESUMEN
BACKGROUND: Familial adult myoclonic epilepsy (FAME) is defined by autosomal dominant inheritance, adult onset of myoclonus of the extremities, infrequent epileptic seizures, nonprogressive course, abnormality of polyspikes and waves on examination by EEG and photosensitivity, giant somatosensory evoked potentials, enhancement of C reflex, and premyoclonus spike detected by means of the jerk-locked averaging EEG method. These findings were also observed in patients with benign adult familial myoclonic epilepsy (BAFME) and patients with familial cortical tremor. FAME and BAFME have been described only in Japan. The genes responsible for FAME and BAFME were mapped in the same genetic interval in 8q22.3-q24.1 OBJECTIVE: To study clinical and genetic characteristics of a European family with FAME. METHODS: A four-generation European kindred presenting with FAME, including 18 members, is described. Clinical analysis was performed on 15 living subjects and electrophysiologic study on 5 patients. Linkage analysis was performed with fluorescent microsatellites encompassing the FAME/BAFME locus (8q23.3-q24.1). RESULTS: Ten living and three deceased relatives had the clinical characteristics of FAME. Mean age at onset of the 10 living patients was 41 years (range, 30-60 years). Eight of the 13 affected subjects had generalized tonic-clonic seizures. Electrophysiologic studies confirmed the diagnosis of FAME in the five patients studied. The pattern of inheritance was consistent with an autosomal dominant inheritance. The locus responsible for FAME/BAFME was excluded. CONCLUSION: Observation of a European family extends the occurrence of familial adult myoclonic epilepsy to non-Japanese patients. Exclusion of linkage of this family to the locus for familial adult myoclonic epilepsy/benign adult familial myoclonic epilepsy established the genetic heterogeneity of this disorder.
Asunto(s)
Cromosomas Humanos Par 8/genética , Epilepsias Mioclónicas/genética , Ligamiento Genético/genética , Adulto , Anciano , Mapeo Cromosómico/estadística & datos numéricos , Electroencefalografía , Electromiografía , Electrofisiología , Epilepsias Mioclónicas/fisiopatología , Europa (Continente) , Femenino , Humanos , Masculino , Persona de Mediana Edad , LinajeAsunto(s)
Epilepsia Generalizada/genética , Proteínas del Tejido Nervioso/genética , Neuronas/metabolismo , Convulsiones Febriles/genética , Canales de Sodio/genética , Secuencia de Aminoácidos , Cromosomas Humanos Par 2/genética , Secuencia Conservada , Análisis Mutacional de ADN , Femenino , Ligamiento Genético , Heterocigoto , Humanos , Masculino , Datos de Secuencia Molecular , Canal de Sodio Activado por Voltaje NAV1.1 , Linaje , Fenotipo , Mutación Puntual , Canales de Sodio/metabolismoRESUMEN
Spinocerebellar ataxia type 3 or Machado-Joseph disease (SCA3/MJD) is an autosomal dominant neurodegenerative disorder caused by an unstable and expanded CAG trinucleotide repeat that leads to the expansion of a polyglutamine tract in a protein of unknown function, ataxin-3. We have generated and characterized a panel of monoclonal and polyclonal antibodies raised against ataxin-3 and used them to analyze its expression and localization. In Hela cells, multiple isoforms are expressed besides the major 55-kDa form. While the majority of ataxin-3 is cytosolic, both immunocytofluorescence and subcellular fractionation studies indicate the presence of ataxin-3, in particular, of some of the minor isoforms, in the nuclear and mitochodrial compartments. We also show that ataxin-3 can be phosphorylated. In the brain, only one ataxin-3 isoform containing the polyglutamine stretch was detected, and normal and mutated proteins were found equally expressed in all patient brain regions analyzed. In most neurons, ataxin-3 had a cytoplasmic, dendritic, and axonal localization. Some neurons presented an additional nuclear localization. Ataxin-3 is widely expressed throughout the brain, with a variable intensity specific for subpopulations of neurons. Its expression is, however, not restricted to regions that show intranuclear inclusions and neurodegeneration in SCA3/MJD.