RESUMO
Four patients with neurological Wilson's disease were investigated using magnetic resonance imaging (MRI) and positron emission tomography (PET). All patients had dystonia as their major clinical manifestation but also had dysarthria and at the presentation of the disease had choreoathetoid movements in at least one limb. A multitracer approach with PET was used to visualize various aspects of dopaminergic function; [11C]-(+)-nomifensine (NMF), [11C]raclopride (RAC) and [11C]-L-DOPA (one patient). Correlation analysis of RAC and NMF binding as well as putamen/caudate uptake ratios showed corresponding reductions. The patient investigated with [11C]-L-DOPA had a normal striatal uptake. Generally, structural changes as shown by MRI corresponded to reductions both in NMF and RAC binding. There was no evident correspondence between PET findings and the severity of clinical symptoms seen in the individual patient. In two patients with discrete neurological impairment at the time of investigation, PET showed serious presynaptic dopaminergic lesions in the putamen. Our data suggest that the striatal degeneration seen in Wilson's disease comprises a complex pathology involving both afferent and efferent projections. The discrete neurological impairment seen in some patients with gross striatal pathology might be due to concomitant lesions in functionally counteracting basal ganglia circuits.
Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Degeneração Hepatolenticular/diagnóstico , Degeneração Hepatolenticular/fisiopatologia , Imageamento por Ressonância Magnética , Tomografia Computadorizada de Emissão , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Sítios de Ligação , Núcleo Caudado/metabolismo , Núcleo Caudado/fisiopatologia , Ceruloplasmina/análise , Cobre/urina , Corpo Estriado/metabolismo , Corpo Estriado/fisiopatologia , Antagonistas de Dopamina/uso terapêutico , Disartria , Distonia , Feminino , Degeneração Hepatolenticular/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Nomifensina , Penicilamina/administração & dosagem , Penicilamina/uso terapêutico , Putamen/metabolismo , Putamen/fisiopatologia , Racloprida , SalicilamidasRESUMO
The precursor of serotonin, L-5-hydroxytryptophan (L-5-HTP), was radiolabelled with 11C in the beta-position, yielding [beta-11C]serotonin after decarboxylation, allowing positron emission tomography studies of L-5-HTP uptake across the blood-brain barrier. We studied 8 healthy volunteers and 6 patients with histories of DSM-III major depression, 2 with repeated examinations after clinically successful treatment. We report a significantly lower uptake of [11C]5-HTP across the blood-brain barrier in depressed patients, irrespective of phase of illness. The findings emphasize that serotonin is involved in depressive pathophysiology and support earlier suggestions that the transport of 5-HTP across the blood-brain barrier is compromised in major depression.
