RESUMO
BACKGROUND: GTP cyclohydrolase I (GCH1) mutations are the commonest cause of Dopa-responsive dystonia (DRD). Clinical phenotypes can be broad, even within a single family. METHODS: We present clinical, genetic and functional imaging data on a British kindred in which affected subjects display phenotypes ranging from DRD to Parkinson's disease (PD). Twelve family members were studied. Clinical examination, dopamine transporter (DAT) imaging, and molecular genetic analysis of GCH1 and the commonest known familial PD-related genes were performed. RESULTS: We have identified a novel missense variant, c.5A > G, p.(Glu2Gly), within the GCH1 gene in affected family members displaying a range of phenotypes. Two affected subjects carrying this variant had abnormal DAT imaging. These two with abnormal DAT imaging had a PD phenotype, while the remaining three subjects with the novel GCH1 variant had normal DAT imaging and a DRD phenotype. CONCLUSIONS: We propose that this GCH1 variant is pathogenic in this family and these findings suggest that similar mechanisms involving abnormal GTP cyclohydolase I may underlie both PD and DRD. GCH1 genetic testing should be considered in patients with PD and a family history of DRD.
Assuntos
Distúrbios Distônicos/genética , GTP Cicloidrolase/genética , Doença de Parkinson/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Distúrbios Distônicos/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Doença de Parkinson/fisiopatologia , Linhagem , FenótipoRESUMO
Two chronic schizophrenic out-patients with tardive dyskinesia were treated with chlorpromazine in 2 regimens -- once-daily and four times-daily -- using a cross-over design. Two "blind" raters evaluated the severity of symptoms of tardive dyskinesia, pseudoparkinsonism and schizophrenia on rating scales every week during the 14-week-trial period. Results showed that the intensity of dyskinesia was significantly lower, and that of pseudoparkinsonism higher (but not significantly) with Q.I.D. than with O.D. medication. Symptoms of schizophrenia did not vary in severity appreciably with the two frequencies of drug intake. It is suggested that multiple-dose administration of a phenothiazine maintains a steady level of dopamine blockade throughout the day and thus masks the manifestations of tardive dyskinesia.
Assuntos
Clorpromazina/administração & dosagem , Discinesia Induzida por Medicamentos/prevenção & controle , Esquizofrenia/tratamento farmacológico , Adulto , Esquema de Medicação , Feminino , HumanosAssuntos
Ansiolíticos/uso terapêutico , Transtornos de Ansiedade/tratamento farmacológico , Lorazepam/uso terapêutico , Adulto , Transtornos de Ansiedade/diagnóstico , Ensaios Clínicos como Assunto , Avaliação de Medicamentos , Feminino , Humanos , Lorazepam/administração & dosagem , Lorazepam/efeitos adversos , Masculino , Pessoa de Meia-Idade , Relações Médico-Paciente , Placebos , Escalas de Graduação Psiquiátrica , Autoavaliação (Psicologia)RESUMO
Pizotyline at two dosage levels or one dosage level of amitriptyline were administered under double-blind conditions to 100 depressed out-patients in a community mental health clinic; 73 patients completed the four-week study. Their psychological response was assessed with four ECDEU rating scales and a psychiatrist's clinical examination. Their physiological response was measured with standard hematology tests, blood chemistries, and urinalyses. Statistical analyses of the results showed one significant difference among the three treatment groups' responses: sleep disturbance decreased significantly (p < 0.05) more in patients receiving the higher pizotyline dosage. The three treatment groups' responses measured by the other rating scale items did not differ significantly. Ten of the 75 patients taking pizotyline and four of the 25 patients taking amitriptyline developed side effects. To clarify dose-and time-related variables, additional studies would be required.
