RESUMO
INTRODUCTION: Changes in regional cerebral blood flow (rCBF) have been reported in idiopathic Parkinson's disease (PD). Nonetheless, their typical pattern still remains controversial regarding some features, such as basal ganglia involvement and the main cortical regions affected. Functional neuroimaging makes it possible to identify the brain dysfunctions of the neural circuits underlying the disease. Voxel-based analysis methods make it possible to increase the reliability of the results. OBJECTIVE: To assess the rCBF changes in patients with PD and their relation with disease duration. MATERIALS AND METHODS: Thirty PD adult patients without dementia underwent evaluation with (99m)Tc-ECD SPECT. SPM5 was used for statistical comparison with 25 normal controls of similar ages. The disease course duration in years was added as a covariate. Additionally, patients with a 6-year evolution or less and those with more than 6 years were compared separately with normal controls. RESULTS: Significant hypoperfusion was detected in bilateral premotor and posterior parietal cortex and increase of perfusion was present in the cerebellum. These changes correlated with the years of evolution of the illness. Patients with longer evolution also presented thalamic, subthalamic and basal ganglia hypoperfusion. CONCLUSIONS: We describe rCBF changes in PD in neural circuits related with control of movements. These changes are more manifest in patients with a longer duration of the disease.
Assuntos
Circulação Cerebrovascular , Doença de Parkinson/fisiopatologia , Adulto , Idoso , Cerebelo/irrigação sanguínea , Cerebelo/diagnóstico por imagem , Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/diagnóstico por imagem , Fatores de Confusão Epidemiológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico por imagem , Estudos Prospectivos , Fatores de Tempo , Tomografia Computadorizada de Emissão de Fóton ÚnicoAssuntos
Antiparkinsonianos/uso terapêutico , Levodopa/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Antiparkinsonianos/efeitos adversos , Agonistas de Dopamina/uso terapêutico , Discinesia Induzida por Medicamentos , História do Século XX , Humanos , Levodopa/efeitos adversos , Doença de Parkinson/história , Doença de Parkinson/fisiopatologiaRESUMO
1. Of 22 parkinsonians with fluctuations under long-dating dopatherapy in whom standard Madopar was substituted by the HBS form, 16 who performed the trial longer than 1 year were particularly studied to evaluate some parameters of this long-term follow-up (30-36 months). 2. The outstanding beneficial effects were an enhancement of the antiparkinsonian response, improvement or disappearance of motor oscillations, longer "on" periods, less severe "off" periods, and a more sustained nocturnal antiparkinsonian effect with a reduction of dystonias and pain at night and decreased or absent early morning parkinsonism. 3. The decrease or disappearance of dystonia was observed since the early stages of the trial and can be explained by the more sustained dopaminergic effect. 4. Surprisingly, dyskinesias also decreased in spite of the higher dopaminergic effect. The avoidance of sharp and repeated plasmatic peaks and the lower levels of L-dopa under HBS could explain this phenomenon. 5. The negative aspects of Madopar HBS are a lower bioavailability that means a dosage increase and a longer latency for the therapeutic response in the morning. 6. The dosage increase went up by 80% to 100% in relation to standard Madopar during the long-term treatment. 7. As Madopar HBS is a sustained release preparation, we had to increase the initially reduced the number of intakes, again in order to obtain better results. In the most severe cases with poor or absent response, benefits were achieved only when administering the HBS intake every hour.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Benserazida/administração & dosagem , Carboxiliases/antagonistas & inibidores , Levodopa/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Idoso , Preparações de Ação Retardada , Combinação de Medicamentos , Seguimentos , Humanos , Assistência de Longa Duração , Pessoa de Meia-Idade , Destreza Motora/efeitos dos fármacos , Exame NeurológicoRESUMO
Thirteen parkinsonians with a long duration of the disease and long-term dopa therapy, seven of them showing severe on-off oscillations and 6 an "end-of-dose impairment", were treated with a controlled release (HBS) preparation of L-DOPA/benserazide for more than 3 years. Thereafter, selegiline was added in a progressively increasing dosage up to a maximum of 10 mg/day during 4 months, with the aim of a) further improving the long-term results and b) reducing the doses of the new formula of L-DOPA. A significant decrease of early morning parkinsonism and reduction of motor disability throughout the day were observed; "wearing-off" cases showed better results compared with those presenting "on-off" oscillations. A mean reduction of 20% in the doses of levodopa was achieved. Likewise, a mild reduction of dyskinesias and a mild-moderate enhancement of dystonias were recorded. Only one patient did not tolerate selegiline and two others received lower doses due to side-effects. Selegiline was capable of enhancing the antiparkinsonian effect of the new formula of L-DOPA, while allowing a reduction of the doses administered. It must also be emphasized that such improvement was achieved in complicated patients, most of whom showed some deterioration of response in the late stages of long-term sustained-release levodopa treatment.
Assuntos
Levodopa/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Fenetilaminas/uso terapêutico , Selegilina/uso terapêutico , Adulto , Idoso , Benserazida/administração & dosagem , Benserazida/uso terapêutico , Preparações de Ação Retardada , Quimioterapia Combinada , Feminino , Humanos , Levodopa/administração & dosagem , Masculino , Pessoa de Meia-Idade , Selegilina/administração & dosagemRESUMO
At the first stage of a pilot study involving 14 parkinsonians with motor fluctuations, treatment with standard Madopar was substituted by a sustained-release form, Madopar HBS, which attenuated fluctuations in patients with end-of-dose impairment, but achieved only moderate improvement in patients with on-off phenomena. In a second phase of the trial, 4 parkinsonians exhibiting the most severe fluctuations of mobility and the poorest response to Madopar HBS (Hydrodynamically Balanced System) were selected for treatment with a combined regimen utilizing subcutaneous lisuride infusions as the additional component. The sequence of the trial was as follows: 1. standard Madopar, 2. Madopar HBS, 3. standard Madopar combined with lisuride infusions and 4. Madopar HBS combined with lisuride infusions. Steady improvement was observed along the lines of this schedule, but the best results were obtained when Madopar HBS was combined with lisuride infusions. Subsequently motor fluctuations were less marked or disappeared, early-morning Parkinson symptoms decreased and dystonia was not recorded any longer. Even better results could be accomplished in an extended trial attempting to establish the best dosage ratio of the combination, possibly admitting increased dosage. The tolerance of the combined regimen was excellent, except in one patient who transiently exhibited delusions and postural hypotension. The combination of sustained-release Madopar and continuous infusions of the dopaminergic agonist lisuride seems to prove a more physiological and effective regimen for the treatment of severe motor fluctuations.
Assuntos
Benserazida/administração & dosagem , Ergolinas/administração & dosagem , Hidrazinas/administração & dosagem , Levodopa/uso terapêutico , Lisurida/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Administração Oral , Benserazida/uso terapêutico , Ensaios Clínicos como Assunto , Esquema de Medicação , Combinação de Medicamentos/uso terapêutico , Quimioterapia Combinada , Tolerância a Medicamentos , Humanos , Bombas de Infusão , Lisurida/uso terapêutico , Índice de Gravidade de DoençaRESUMO
Fourteen parkinsonian patients, 10 of them showing severe and long-standing 'on-off' effects and 4 'end-of-dose impairment', received Madopar HBS instead of standard Madopar. At the end of the dosage adaptation phase (9 weeks) most patients improved; in patients with 'on-off' phenomenon, parkinsonism became less severe, on periods were longer, and fluctuations decrease; end-of-dose impairment resolved in 4 patients. However, a longer delay in the onset of the therapeutic effect was observed after the first daily drug intake in those patients still showing severe early-morning parkinsonism. With Madopar HBS, L-dopa dosage was increased by 116%. In spite of a greater dopaminergic effect, dyskinesias were reduced, and dystonias became less marked or even disappeared.