RESUMO
Seven patients affected by Huntington's chorea were given an acute administration of 2-Br-alpha-ergocryptine (CB 154, Sandoz), a direct agonist at dopamine receptor sites. Seven nonobese hospitalized patients were used as controls. Oral administration of CB 154 (2.5 mg) induced a more prompt and consistent rise in plasma growth hormone (GH) levels in patients than in controls. GH levels rose from baseline values of 0.3+/-0.1 ng/ml to mean peak values of 20.4+/-5.1 ng/ml (120-270 min) in choreic subjects and from baseline values of 1.0+/-0.4 ng/ml to mean peak values of 5.7+/-1.6 ng/ml (180-300 min) in control subjects (P less than 0.02). Baseline plasma prolactin (PRL) values were significantly higher in choreic than in control subjects (22.1+/-6.6 ng/ml vs. 8.1+/-1.4 ng/ml, respectively, P less than 0.02); administration of CB 154 induced a more consistent PRL decrease in control than in choreic subjects. Collectively, these results suggest the existence of an abnormal regulation of GH and PRL secretion in Huntington's chorea, probably due to alterations in central dopaminergic neurotransmission.
Assuntos
Bromocriptina , Ergolinas , Hormônio do Crescimento/sangue , Doença de Huntington/sangue , Prolactina/sangue , Adulto , Idoso , Feminino , Humanos , Cinética , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: A frontostriatal pattern of cognitive decline, consisting of a frontal lobe-like syndrome without genuine cortical defects such as amnesia, apraxia, aphasia, or agnosia, is well established in basal ganglial diseases. Recent pathological investigations, however, have again noted cortical damage in progressive supranuclear palsy (PSP), suggesting that cortical defects could be present. OBJECTIVES: To delineate the pattern of cognitive impairment and to detect higher-order motor impairments (including ideomotor apraxia) in parkinsonian syndromes. PATIENTS AND METHODS: We assessed ideomotor apraxia, and simple and sequential tapping in patients with Parkinson disease, multiple system atrophy, and PSP with similar disease severity, age range, and education. We also administered a comprehensive battery of neuropsychological tests to examine general intelligence, memory, executive functions, attention, and visuospatial orientation. The results were compared between groups and with a matched normal control group. RESULTS: Sequential tapping and the imitation of sequences of gestures were impaired in all patient groups, with patients with PSP performing worse than the other groups. Based on ideomotor apraxia scores and a qualitative analysis of errors, 3 patients with PSP and 2 with multiple system atrophy were considered apraxic. General intelligence and executive functions were compromised in all patient groups. The impairment of patients with PSP was more pervasive than that of the other groups, and included compromise of visuospatial functions, attention, and memory. Discriminant analysis of all cognitive and motor tests showed that the tapping and ideomotor apraxia tests best identified the patients vs control subjects. CONCLUSIONS: The presence of cortical as well as subcortical damage in patients with PSP and those with multiple system atrophy is indicated by the presence of pervasive cognitive and motor disturbances in the former, substantial motor disorganization in the latter, and the finding of ideomotor apraxia in some patients with these diseases. Furthermore, the discovery that tests of motor and gesture best identified all patients vs control subjects is consistent with the existence of a common motor disorganization in these parkinsonian syndromes, in agreement with the known damage to the corticostriatal pathways in these conditions.
Assuntos
Apraxias/etiologia , Transtornos Cognitivos/diagnóstico , Doença de Parkinson/diagnóstico , Idoso , Apraxias/diagnóstico , Transtornos Cognitivos/etiologia , Corpo Estriado/fisiopatologia , Feminino , Dedos/fisiologia , Lobo Frontal/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Movimento , Testes Neuropsicológicos , Doença de Parkinson/complicaçõesRESUMO
OBJECTIVES: To investigate the hypothesis that psychiatric disturbances in Huntington's disease are related to degree of cognitive or motor compromise and to determine correlations between CAG repeat length within the gene for Huntington's disease and disease severity. DESIGN: Consecutive series of patients with Huntington's disease. SETTING: Neurological specialty hospital. PATIENTS: Seventeen men and 12 women from 24 families. MAIN OUTCOME MEASURES: The Hamilton Psychiatric and Anxiety Rating Scales and Brief Psychiatric Rating Scale were used to assess psychiatric disturbances; Folstein's Quantified Neurological Examination to evaluate motor status; and the Mini-Mental State Examination, Raven Progressive Matrices), Phonemic Verbal Fluency Test, Short Tale Test, Visual Search Test, and Benton's Visual Orientation Line Test to evaluate cognitive function. The length of the CAG repeat sequence in the Huntington's gene was determined by quantitative polymerase chain reaction. RESULTS: Cognitive test scores correlated significantly with each other; of these, results of the Visual Search and Short Tale tests correlated significantly with the Folstein's Quantified Neurological Examination score (P = .05 and P = .03, respectively). Results of the Folstein's Quantified Neurological Examination also correlated with the illness duration and the length of the CAG repeat. Although psychiatric scores correlated significantly among themselves (P < .01), neither cognitive compromise, motor deterioration, nor CAG length were related to the extent of psychiatric compromise. Patients who were depressed when they were examined tended to have a history of psychiatric disorders. CONCLUSIONS: The lack of correlation between disease severity and psychiatric disturbances indicates that psychiatric disorders progress nonlinearly, possibly because of differential degeneration of the striatal-cortical circuits; the possibility that psychiatric disorders are prevalent in certain families with a member who has Huntington's disease is being further investigated. The lack of correlation between CAG length and cognitive and psychiatric variables needs further investigation.
Assuntos
Transtornos Cognitivos/genética , Doença de Huntington/genética , Transtornos Neurocognitivos/genética , Transtornos Psicomotores/genética , Repetições de Trinucleotídeos/genética , Adulto , Conscientização , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/psicologia , Negação em Psicologia , Feminino , Humanos , Doença de Huntington/diagnóstico , Doença de Huntington/psicologia , Entrevista Psicológica , Masculino , Pessoa de Meia-Idade , Transtornos Neurocognitivos/diagnóstico , Transtornos Neurocognitivos/psicologia , Exame Neurológico , Testes Neuropsicológicos , Reação em Cadeia da Polimerase , Transtornos Psicomotores/diagnóstico , Transtornos Psicomotores/psicologia , Papel do DoenteRESUMO
OBJECTIVE: To evaluate the regional cerebral metabolic involvement; the relationships among regional brain metabolism, clinical features, and quantitative measures of disease severity; and the patterns of brain involvement that can be related to the different types of onset: striatonigral degeneration vs olivopontocerebellar atrophy. DESIGN: Fludeoxyglucose F 18 positron emission tomography (PET) studies performed in patients with multiple system atrophy (MSA) were evaluated for their clinical features at the onset of the disease and at the time of the PET study. CASES: Seventeen patients diagnosed as having probable MSA and 10 age-matched controls. RESULTS: The hypometabolism in the putamen-pallidum complex and in the cerebellum was the best discriminant for disease classification. The efficacy of levodopa treatment was positively correlated with the metabolic activity of the putamen-pallidum complex. The patients with olivopontocerebellar atrophy type (N = 8) had a prevalent hypometabolism in the cerebellum, while the patients with striatonigral degeneration type (N = 9) had a prevalent impairment in the pallidum-putamen complex. We demonstrated a negative correlation between (1) severity of parkinsonism and metabolic values of putamen and caudate; (2) severity of cerebellar signs and metabolism in the cerebellum; and (3) autonomic dysfunction and metabolic activity in the thalamus, frontal, and temporal regions, bilaterally. CONCLUSIONS: These findings support the selective metabolic reduction in the putamen and cerebellum as a marker of MSA. The clinical/metabolic correlations, demonstrating the expected dependence of extrapyramidal and cerebellar signs by dysfunction of basal ganglia and cerebellum, also support a possible involvement of central nervous system structures in autonomic control.
Assuntos
Encefalopatias/metabolismo , Corpo Estriado/metabolismo , Corpo Estriado/patologia , Glucose/metabolismo , Atrofias Olivopontocerebelares/metabolismo , Substância Negra/metabolismo , Substância Negra/patologia , Atrofia , Encefalopatias/diagnóstico por imagem , Encefalopatias/patologia , Corpo Estriado/diagnóstico por imagem , Desoxiglucose/análogos & derivados , Feminino , Fluordesoxiglucose F18 , Humanos , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Atrofias Olivopontocerebelares/diagnóstico por imagem , Atrofias Olivopontocerebelares/patologia , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Substância Negra/diagnóstico por imagem , Tomografia Computadorizada de EmissãoRESUMO
Huntington's chorea (HC) was studied in 14 untreated patients, in six patients receiving long-term neuroleptic treatment, and in four patients after drug withdrawal. Our results showed that patients with HC may be divided into three groups, otherwise clinically indistinguishable, on the basis of growth hormone responsiveness to dopaminergic stimuli. The existence of subpopulations of patients with HC must be considered in further studies on these subjects.
Assuntos
Doença de Huntington/metabolismo , Adulto , Bromocriptina/uso terapêutico , Feminino , Hormônio do Crescimento/metabolismo , Humanos , Doença de Huntington/tratamento farmacológico , Lisurida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Prolactina/metabolismo , Tireotropina/metabolismo , Hormônio Liberador de Tireotropina/uso terapêuticoRESUMO
We studied 32 patients with confirmed Huntington's disease (HD); six (mean age, 31.7 years) had the akinetic-rigid form and 26 (mean age, 46.1 years) had the classic hyperkinetic form. Clinical examination included a count of abnormal involuntary movements, motor self-sufficiency evaluation by the Physical Disability Rating Scale, cognitive function assessment by the Mini-Mental State examination, and a verbal fluency test. Magnetic resonance imaging permitted measurement of bicaudate diameter, a sensitive indicator of caudate atrophy in HD. Patients with the akinetic-rigid form of HD were younger and had earlier disease onset than those with the classic form of HD. All patients with akinetic-rigid HD (group 1) had striatal hyperintensity on T2-weighted magnetic resonance images; seven patients with classic HD (group 2) had a similar abnormality. Groups 1 and 2 were in fact similar in all other respects, except that the number of abnormal involuntary movements was greater in group 2. Groups 1 and 2 together had significantly younger age at onset, lower Mini-Mental State Examination score, more severe motor disability, worse verbal fluency test result, and greater bicaudate diameter than the 19 patients with classic HD without magnetic resonance signal abnormality (group 3) and appear to be a uniform population, distinct from group 3. The abnormalities on magnetic resonance images indicated greater striatal damage in groups 1 and 2, which could be the neuroanatomic substrate of their greater motor and cognitive compromise.
Assuntos
Doença de Huntington/patologia , Adulto , Idoso , Encéfalo/patologia , Humanos , Doença de Huntington/fisiopatologia , Doença de Huntington/psicologia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Destreza Motora , Escalas de Graduação PsiquiátricaRESUMO
The aim of this study is to evaluate what factors influence the risk of occurrence of motor fluctuations in patients with Parkinson's disease (PD) with particular reference to the role of early or delayed introduction of levodopa therapy during the course of the disease. One hundred twenty-five consecutive newly diagnosed patients with PD started levodopa treatment at the time diagnosis and were followed for 2 to 10 years. During follow-up, 60 patients had wearing-off or early morning akinesia. We estimated the cumulative time-dependent risk of motor fluctuation occurrence through a multivariable analysis. The risk was lower for patients with tremor-predominant PD, for those with shorter disease duration prior to levodopa, and for those who were relatively older at levodopa initiation. Our results suggest that, as far as motor fluctuations are concerned, disease prognosis is not influenced by early levodopa treatment. These observation support the introduction of levodopa as soon as there is a subjective need for the patients to maintain their level of social and work performance.
Assuntos
Levodopa/uso terapêutico , Movimento/efeitos dos fármacos , Doença de Parkinson/tratamento farmacológico , Fatores Etários , Feminino , Previsões , Humanos , Masculino , Análise Multivariada , Doença de Parkinson/classificação , Doença de Parkinson/fisiopatologia , Fatores de RiscoRESUMO
Sixty-seven parkinsonian patients and 44 control subjects were tested for cognitive function and motor performance, using reaction times and movement times. Parkinsonian subjects did significantly worse in tests that required visuoperceptual and perceptual motor abilities, such as Object Assembly, Block Design, and Zazzo's test. Analysis of covariance of test scores showed that Block Design and Object Assembly scores were not significantly different between patients and controls when adjusted for reaction and movement times. Also, reaction and movement times were more delayed in parkinsonian patients than in controls. These results stress the main role of motor dysfunction in visuospatial and perceptual motor impairment.
Assuntos
Cognição , Doença de Parkinson/psicologia , Desempenho Psicomotor , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Movimento , Doença de Parkinson/fisiopatologia , Tempo de ReaçãoRESUMO
There are several reports of a defect of complex I in the substantia nigra (SN) of Parkinson's disease (PD) patients. To evaluate whether this is specific to dopaminergic neurons or the phenotypically relevant consequence of a widespread failure of the mitochondrial oxidative phosphorylation (OXPHOS) system, we measured respiratory enzyme activities in muscle homogenates from 16 PD patients and eight age-matched controls, and in muscle isolated mitochondria of six PD patients and six age-matched controls. We found no difference between the PD and control groups. In addition, we detected, by polymerase chain reaction, the mitochondrial DNA (mtDNA) "common deletion" (CD) in muscle specimens of 14 of 17 PD patients, but we obtained similar results in age-matched controls. In both groups, the amount of CD-specific deleted (delta) mtDNA ranged from 0.0% to 0.1%. Our data suggest that PD cannot be attributed to a multisystem decline of mitochondrial OXPHOS, and that lesions of muscle mtDNA in PD are likely due to normal aging. However, there was a remarkable accumulation of delta mtDNA in the SN of a PD patient and an age-matched control, suggesting that the SN is exquisitely sensitive to age-dependent damage of the mitochondrial genome.
Assuntos
Química Encefálica/genética , DNA Mitocondrial/análise , Transporte de Elétrons/genética , Mitocôndrias Musculares/metabolismo , Doença de Parkinson/metabolismo , Adulto , Idoso , DNA Mitocondrial/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/genética , Reação em Cadeia da PolimeraseRESUMO
We evaluated the possible influence of early levodopa treatment on the mortality of Parkinson's disease (PD). One hundred forty-five consecutive parkinsonian patients initiated treatment with levodopa between 1970 and 1983. Ninety-eight of those started levodopa therapy 2 or more years after symptom onset, while 47 received levodopa within the 1st 2 years of the disease. At the end of follow-up, in December 1985, 49 patients had died. Mortality was 2.5 times higher among patients who delayed initiation of levodopa therapy 2 or more years than among those who initiated the therapy earlier. Age and disease severity were the most significant predictors of survival after initiation of levodopa treatment. The risk of death was 10% higher every year of age increase and was 2 and 4 times higher, respectively, for patients at Hoehn and Yahr stages II and III than for patients at Hoehn and Yahr stage I. When we controlled for the effect of age and disease severity on mortality, the cumulative death probability was no longer significantly higher among patients who delayed levodopa treatment than among patients treated within 2 years from disease onset. As far as mortality is concerned, the results show that the time of levodopa treatment initiation during PD has no influence and the drug can be introduced as soon as indicated by the severity of the disease progression.
Assuntos
Levodopa/uso terapêutico , Doença de Parkinson/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/tratamento farmacológico , Modelos de Riscos Proporcionais , Análise de Sobrevida , Fatores de TempoRESUMO
Six patients with different forms of dystonia were treated with gamma-vinyl GABA, a specific enzyme-activated inhibitor of GABA-transaminase, in a double-blind, placebo-controlled crossover study. gamma-Vinyl GABA therapy, 2 g daily for 2 weeks, was compared with placebo by weekly assessments. There were no consistent changes in three evaluation scores. Agents that augment CNS GABA are unlikely to benefit patients with generalized dystonia.
Assuntos
Aminocaproatos/uso terapêutico , Distonia/tratamento farmacológico , Administração Oral , Adolescente , Adulto , Aminocaproatos/administração & dosagem , Aminocaproatos/efeitos adversos , Método Duplo-Cego , Distonia/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Movimento , Índice de Gravidade de Doença , VigabatrinaRESUMO
One hundred ninety L-dopa-treated parkinsonian patients have been studied according to the age at onset and to age at last examination. The frequency of major mental disturbances was significantly higher in patients older than 60 years, whereas abnormal involuntary movements and on-off phenomenon were more frequent in patients with onset before age 60. The association of normal aging and of Parkinson's disease may be responsible for the prevalence of mental disease in older patients.
Assuntos
Levodopa/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Levodopa/efeitos adversos , Assistência de Longa Duração , Masculino , Pessoa de Meia-IdadeRESUMO
In a double-blind, crossover study gamma-vinyl GABA, 2 g/day, and placebo were administered orally for 2 weeks each to six patients with Huntington's disease. Five patients were treated concomitantly with a neuroleptic maintained at constant dose. No consistent beneficial effects on the hyperkinetic movements, abnormal motor function, or ability to carry out normal activities were evident with gamma-vinyl GABA treatment. Treatment was tolerated without clinically significant alterations in the physiologic or biochemical tests used for monitoring. These results suggest that increasing CNS GABAergic function is unlikely to ameliorate Huntington's disease.
Assuntos
Aminocaproatos/uso terapêutico , Doença de Huntington/tratamento farmacológico , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , VigabatrinaRESUMO
In eight subjects with Parkinson's disease under an optimal daily dose of L-dopa, acute administration of MIF-I (200 mg i.v.) did not ameliorate either the total disability score or the intellectual test PM 38 when evaluated in comparison with the effect induced by acute administration of a placebo. Also concomitant evaluation of the effect of MIF-I on the secretion of anterior pituitary hormones which are under dopaminergic control i.e., growth hormone and prolactin, did not reveal any potentiation of the L-dopa-induced stimulus.
Assuntos
Comportamento/efeitos dos fármacos , Levodopa/uso terapêutico , Hormônio Inibidor da Liberação de MSH/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Idoso , Feminino , Hormônio do Crescimento/sangue , Humanos , Hormônio Inibidor da Liberação de MSH/farmacologia , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/psicologia , Placebos , Prolactina/sangue , Fatores de TempoRESUMO
Thirty-two patients affected by amyotrophic lateral sclerosis (ALS) were included in a controlled, open therapeutic trial with branched chain amino acids (BCAA). Patients with bulbar muscle involvement were evaluated separately. No statistically significant differences were found in the clinical outcome between the patients treated and the control groups. Blood L-glutamate levels measured in eight patients were normal. The failure of BCAA in the treatment of the patients could be due to different disorders with unpredictable outcome included under the diagnosis of ALS.
Assuntos
Aminoácidos de Cadeia Ramificada/uso terapêutico , Esclerose Lateral Amiotrófica/tratamento farmacológico , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The various clinical features of multiple system atrophy (MSA) make the diagnosis of the disease difficult, especially in its early stages, when signs of differentiated neuroanatomical system involvement have not yet appeared. Mortality studies may be affected by the variability of the diagnostic criteria and selection bias. We used strict clinical and MRI criteria to diagnose MSA in 59 patients. Patients with parkinsonian and cerebellar onset were compared. Median survival time from the onset of the first motor symptom was 7.5 years. Our results indicated a trend (P = 0.09) for the Northwestern University Disability Scale score to correlate with mortality, but we failed to find other characteristics identifying subgroups or predictors for survival.
Assuntos
Corpo Estriado/fisiologia , Degeneração Neural/fisiologia , Atrofias Olivopontocerebelares/mortalidade , Síndrome de Shy-Drager/mortalidade , Substância Negra/fisiologia , Adulto , Idoso , Doenças do Sistema Nervoso Autônomo/etiologia , Corpo Estriado/patologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atrofias Olivopontocerebelares/complicações , Atrofias Olivopontocerebelares/patologia , Doença de Parkinson/etiologia , Prognóstico , Estudos Retrospectivos , Síndrome de Shy-Drager/complicações , Síndrome de Shy-Drager/patologia , Substância Negra/patologia , Taxa de SobrevidaRESUMO
A total of 15 patients affected by idiopathic dystonia (7 with generalized and 8 with focal or segmental dystonia) were subjected to therapy with bromocriptine at low doses, pimozide and trihexyphenidyl. The symptoms were evaluated by giving a progressive score in relation to the intensity of the dystonic symptom to each of the body segments involved by the dystonia. Bromocriptine did not significantly modify the dystonia. Pimozide showed a slight nonsignificant improvement of the dystonic symptoms. Trihexyphenidyl was effective in the generalized dystonias, in agreement with previous reports in the literature. The variation in the pharmacological results could be due to the diversity of the dystonic syndromes, which comprise cases that are different in age at onset, site of dystonic symptoms, and evolution.
Assuntos
Bromocriptina/uso terapêutico , Distonia/tratamento farmacológico , Pimozida/uso terapêutico , Triexifenidil/uso terapêutico , Adolescente , Adulto , Idoso , Bromocriptina/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pimozida/efeitos adversos , Síndrome , Torcicolo/tratamento farmacológico , Triexifenidil/efeitos adversosRESUMO
We performed a longitudinal study (mean follow-up 86.7 months) to evaluate motor and mental deterioration in patients with Parkinson's disease. Of the original 91 patients, only 61 could be re-examined 7 years later and 11 of these had become demented (PD-Dems). PD-Dems were older with worse motor and, obviously, cognitive performance than non-demented parkinsonian patients (PDs). A global cognitive decay index (DI) was calculated for each patient. Based on this, non-demented PDs were further split into 38 stable parkinsonian patients (S-PDs) with DI-30% to +30%, and 10 deteriorated but non-demented parkinsonian patients (D-PDs) with a DI worse than -30% (as had PD-Dems). D-PDs were older and had greater motor impairment than S-PDs but did not differ from PD-Dems on these measures. D-PDs and PD-Dems deteriorated especially in attention, visuospatial and executive ability tests. Ageing seems to be the main predictive factor for mental deterioration.
Assuntos
Transtornos Cognitivos/etiologia , Doença de Parkinson/complicações , Desempenho Psicomotor , Adulto , Idoso , Envelhecimento/psicologia , Análise de Variância , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The pharmacological approaches to Parkinson's disease in the different phases of evolution (initial or slight, complete and complicated) are discussed. The modality of confronting the therapeutic approach according to the different evolutive phases makes it possible to personalize the therapy, in an attempt to obtain the optimal clinical effect with minimum side effects. Various drugs available and future perspectives are considered.
Assuntos
Doença de Parkinson/tratamento farmacológico , Antidepressivos Tricíclicos/uso terapêutico , Antiparkinsonianos/uso terapêutico , Carboxiliases/antagonistas & inibidores , Quimioterapia Combinada , Humanos , Levodopa/uso terapêutico , Parassimpatolíticos/uso terapêutico , Doença de Parkinson/fisiopatologia , Receptores Dopaminérgicos/efeitos dos fármacos , Selegilina/uso terapêuticoRESUMO
Some aspects of the problems of long-term L-dopa treatment syndrome are reviewed, with special attention to the changes in response to treatment with dopaminergic agents, specifically end-of-dose deterioration, the on-off phenomenon and hyperkinesia. The various hypotheses for interpreting these are presented, with particular stress on changes in the function of DA-ergic receptors. It is concluded that the on-off phenomenon is probably related to changes in plasma L-dopa levels and to decreased stores of intraneural dopamine.