RESUMO
The frequency of parkin mutations was evaluated in 30 families of highly diverse geographic origin with early-onset autosomal recessive parkinsonism. Twelve different mutations, six of which were new, were found in 10 families from Europe and Brazil. Patients with parkin mutations had significantly longer disease duration than patients without the mutation but with similar severity of disease, suggesting a slower disease course. Two patients with parkin mutations had atypical clinical presentation at onset, with predominant tremor when standing.
Assuntos
Ubiquitina-Proteína Ligases/genética , Adulto , Códon sem Sentido , Análise Mutacional de DNA , Éxons/genética , Feminino , Genes Recessivos , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Mutação Puntual , Reação em Cadeia da Polimerase , Sítios de Splice de RNA/genéticaAssuntos
Corpo Estriado/diagnóstico por imagem , Di-Hidroxifenilalanina , Doença de Parkinson/diagnóstico por imagem , Racloprida , Receptores de Dopamina D2/fisiologia , Tomografia Computadorizada de Emissão , Adulto , Idoso , Antiparkinsonianos/administração & dosagem , Antiparkinsonianos/efeitos adversos , Mapeamento Encefálico , Carbidopa/administração & dosagem , Carbidopa/efeitos adversos , Radioisótopos de Carbono , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/fisiopatologia , Combinação de Medicamentos , Feminino , Radioisótopos de Flúor , Humanos , Levodopa/administração & dosagem , Levodopa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/fisiopatologia , Receptores de Dopamina D2/efeitos dos fármacosRESUMO
Signs of attentional dysfunction mimicking spatial neglect have been described both in humans with lateralised Parkinson's Disease (PD) and in animals with MPTP-related hemiparkinsonism. Such deficits have been attributed to dopamine loss in basal ganglia and cortical targets. However, in previous studies the existence of neglect was assumed from behavioural tests which needed a motor output, thus entailing interpretation ambiguities due to effects of directional hypokinesia. We recorded brain event-related potentials (ERPs) evoked by the presentation of target somatic stimuli to the affected and non-affected sides in 44 patients with unilateral or asymmetrical PD. The N2 and P3 ERP components were specifically analysed, since (a) they are triggered selectively by task-relevant, attended sensory stimuli; (b) their latency reflects stimulus evaluation time, independently from the execution of a motor response, and (c) they have proved to be abnormal in hemineglect syndromes due to focal brain lesions. Irrespective of the side (left or right) of motor symptom predominance there were no significant ERP differences to stimulation of the affected and non-affected limbs, nor was there any correlation between ERP latencies and the degree of dopamine-related motor impairment. The P3 latency was abnormally delayed in 23% of the patients, but there was no trend for abnormalities to concentrate on the affected side. This study does not confirm the existence of a significant attentional impairment toward the affected limb in lateralised PD, and suggests that previous clinical evidence of "neglect' behaviour in PD might be linked to directional hypokinesia, thus reflecting intentional, rather than attentional lateralised deficits.
