RESUMO
Ipsilateral cerebellar and pyramidal signs suddenly developed in three patients. Computed tomography revealed small infarcts of the corona radiata in two patients and a small infarct in the posterior limb of the internal capsule in the third. Ataxic hemiparesis can result from lesions of the corona radiata as well as many other points along the corticopontine pathways.
Assuntos
Ataxia Cerebelar/etiologia , Córtex Cerebral , Infarto Cerebral/complicações , Hemiplegia/etiologia , Idoso , Ataxia Cerebelar/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Infarto Cerebral/diagnóstico por imagem , Feminino , Hemiplegia/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Fibras Nervosas/diagnóstico por imagem , RadiografiaRESUMO
Five well-nourished, alcoholic patients had a progressive myelopathy. Symptoms began with paresthesias of the feet and progressed to a spastic paraparesis with clinical signs of both lateral and dorsal column involvement. Abstinence from alcohol halted progression but did not cause improvement in the myelopathy. The absence of portacaval shunting or notable liver dysfunction in these patients suggests that a direct toxic effect of alcohol must be considered a possible mechanism of spinal cord damage.
Assuntos
Alcoolismo/complicações , Hepatopatias/complicações , Doenças da Medula Espinal/complicações , Idoso , Alcoolismo/diagnóstico , Feminino , Humanos , Hepatopatias/diagnóstico , Masculino , Pessoa de Meia-Idade , Doenças da Medula Espinal/diagnósticoRESUMO
Patients with Parkinson's disease generally have a smooth clinical response from levodopa therapy for the first 3 to 5 years. Motor fluctuations later become noticeable and may ultimately give way to unpredictable responses to treatment. Mechanisms responsible for motor fluctuations are not fully understood, but can be separated into three groups: (1) central pharmacokinetics, or delivery of dopamine from the presynaptic to the postsynaptic receptor; (2) peripheral pharmacokinetics, or delivery of levodopa from an exogenous source to the brain; and (3) pharmacodynamics, or alterations in the interactions between dopamine and the striatal receptor. Changes in central pharmacokinetics caused by diminished presynaptic dopamine storage capacity probably account for early end-of-dose "wearing-off." As patients lose further storage capacity, peripheral levodopa pharmacokinetics may play an important role in the fluctuation response from erratic gastric emptying or variables that change gut-to-blood and blood-brain barrier transport. Finally, erratic motor responses (eg, the "on-off" phenomenon) in advanced Parkinson's disease may be caused in part by alterations at the striatal dopamine receptor.
Assuntos
Levodopa/farmacologia , Doença de Parkinson/fisiopatologia , Desempenho Psicomotor/efeitos dos fármacos , Animais , Humanos , Levodopa/farmacocinética , Doença de Parkinson/metabolismoRESUMO
Continuous dopaminergic stimulation has been shown to stabilize motor fluctuations in patients with advanced Parkinson's disease (PD) who do not respond to more conventional forms of therapy. Levodopa infusions confer immediate benefit as a direct result of maintaining steady plasma levodopa concentrations. Fluctuations of synaptic dopamine inherent in the usual oral treatment of PD might result in deleterious postsynaptic changes. Some of these presumed receptor alterations might revert as a consequence of continuous levodopa infusion.
Assuntos
Dopaminérgicos/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Animais , Ensaios Clínicos como Assunto , Corpo Estriado/metabolismo , Relação Dose-Resposta a Droga , Discinesia Induzida por Medicamentos , Humanos , Bombas de Infusão , Infusões Intravenosas , Levodopa/administração & dosagem , Levodopa/farmacocinética , Levodopa/uso terapêutico , Doença de Parkinson/patologia , Substância Negra/patologiaRESUMO
We studied the nature and frequency of nonmotor "off" phenomena in 130 consecutive patients with Parkinson's disease (PD) with motor fluctuations. Twenty-two patients (17%) experienced nonmotor fluctuations as an end-of-dose phenomenon. Previously unreported, or little appreciated, nonmotor "off" states include sensory dyspnea, nausea, facial flushing, cough, hunger, unilateral limb edema, proximal limb pain, and trigeminal neuralgia-like pain. We attempted treatment modification in 12 of 22 patients; nonmotor "off" symptoms improved in nine of these 12 patients (75%). Recognizing these phenomena will prevent unnecessary tests and treatments.
Assuntos
Atividade Motora/fisiologia , Doença de Parkinson/fisiopatologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
In a prospective study of 34 comatose patients who had an episode of systemic hypotension, 11 had the "man-in-the-barrel" syndrome (MIB). They moved both legs spontaneously or in response to pain, but did not move either arm. One of 11 patients (9%) with MIB survived to leave the hospital; 8 of the 23 patients (35%) without MIB recovered. Of patients who moved at least one limb to pain and had intact pupillary, corneal, and oculocephalic reflexes 24 hours after insult, one of nine (11%) patients with MIB survived, compared with six of nine patients (67%) without MIB. MIB is common after cerebral hypoperfusion and carries a poor prognosis.
Assuntos
Hipotensão/complicações , Paralisia/etiologia , Idoso , Braço/fisiopatologia , Humanos , Hipotensão/fisiopatologia , Pessoa de Meia-Idade , Paralisia/fisiopatologia , SíndromeRESUMO
Two patients had clinical findings of encephalopathy that progressed in 4 to 5 months. One patient had headache, fatigue, lethargy, hemiparesis, and a seizure. The second patient had only forgetfulness, confusion, and lethargy without focal signs. Herpes simplex virus was grown from brain biopsy in the first patient and from CSF in the second patient. These cases suggest that herpes simplex virus caused the encephalitis and that it should be considered in the differential diagnosis of chronic encephalopathy.
Assuntos
Encefalite/etiologia , Herpes Simples/complicações , Adolescente , Idoso , Encéfalo/patologia , Doença Crônica , Encefalite/patologia , Feminino , Herpes Simples/patologia , HumanosRESUMO
Nine patients with advanced Parkinson's disease were started on continuous enteral levodopa infusions during the past 3 years. Six have remained on the infusion system for 1 to 28 months. All patients experienced immediate amelioration of motor fluctuations, and 5 patients continue to obtain relief. One patient found that his ability to achieve the "on" state without unacceptable dyskinesia waned. Experience thus far indicates that continuous long-term levodopa infusions are a practical but complex form of therapy for patients failing more conventional treatment.
Assuntos
Levodopa/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Idoso , Feminino , Humanos , Bombas de Infusão , Intubação Gastrointestinal , Masculino , Pessoa de Meia-IdadeRESUMO
We report two patients with a primarily akinetic form of parkinsonism who were nonresponsive to treatment with levodopa. At autopsy, both patients had many Lewy bodies in brainstem and diencephalic nuclei, with sparse Lewy bodies in association cortices and more numerous Lewy bodies in the limbic cortices, consistent with the transitional form of Lewy body disease. These cases emphasize that (1) Lewy body Parkinson's disease cannot be excluded on the basis of atypical presentation or levodopa nonresponsiveness, and (2) the clinicopathologic spectrum of Lewy body disease is varied.
Assuntos
Levodopa/uso terapêutico , Corpos de Lewy/patologia , Doença de Parkinson/patologia , Idoso , Feminino , Humanos , Imuno-Histoquímica , Corpos de Lewy/química , Locus Cerúleo/química , Locus Cerúleo/patologia , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Substância Negra/química , Substância Negra/patologiaRESUMO
We report the clinical spectrum of 3 patients with Parkinson's disease who experienced complex patterns of levodopa-related dystonia. Dystonia was unrelieved by multiple medication regimens but responded well to continuous, duodenal levodopa infusions. Patients were able to remain mobile without severe dystonia despite a very narrow window of benefit between the levodopa concentration necessary to achieve the "on" state and that which caused the onset of dystonic spasms.
Assuntos
Distonia/tratamento farmacológico , Levodopa/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Idoso , Duodeno , Distonia/complicações , Distonia/fisiopatologia , Feminino , Humanos , Infusões Parenterais , Levodopa/sangue , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Concentração Osmolar , Cuidados Paliativos , Doença de Parkinson/complicações , Doença de Parkinson/fisiopatologiaRESUMO
We report a patient with Meige syndrome (segmental cranial dystonia) who had neuropathologic changes of Parkinson's disease on postmortem examination. Neuropathologic examination showed typical and atypical Lewy bodies in the pigmented nuclei of the brainstem (substantia nigra, locus ceruleus), the nucleus basalis of Meynert, and the nucleus ambiguus. Neurochemical analysis of postmortem brain tissue showed evidence for decreased dopamine turnover in the substantia nigra, striatum, and nucleus accumbens. We propose that some cases of Meige syndrome may be included in the spectrum of Lewy body disease.
Assuntos
Síndrome de Meige/patologia , Doença de Parkinson/patologia , Aminas Biogênicas/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Dopamina/metabolismo , Ácido Homovanílico/metabolismo , Humanos , Masculino , Síndrome de Meige/etiologia , Síndrome de Meige/metabolismo , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Doença de Parkinson/metabolismoRESUMO
We used a family history questionnaire, semi-structured interview, and personal examination of secondary cases to collect data on the prevalence of Parkinson's disease (PD) in relatives of patients seen consecutively for 1 year and assessed the proportion of secondary cases of PD as a function of pedigree completeness. Survival analysis methods were applied to estimate the lifetime risk and age-at-onset distribution of PD among first-degree relatives of probands. When we considered siblings of probands with affected parents, the cumulative risk increased significantly over siblings of probands without affected parents, suggesting significant familial aggregation in a subset of randomly ascertained families. We further analyzed 80 multicase families with two or more affected individuals. Age-adjusted segregation ratios approaching 0.5 and similar proportions of affected parents and siblings, as well as the distribution of ancestral secondary cases, were compatible with an autosomal dominant mode of inheritance with reduced penetrance in a subset of PD.
Assuntos
Doença de Parkinson/genética , Adolescente , Adulto , Distribuição por Idade , Idoso , Feminino , Genes Dominantes , Humanos , Masculino , Pessoa de Meia-Idade , LinhagemRESUMO
The cause of progressive supranuclear palsy (PSP) is not known and has been little studied. The one previous controlled epidemiologic survey, performed at our center in 1986, found small-town experience and greater educational attainment as PSP risks, but, in retrospect, these results may have been produced by ascertainment bias. Since that time, several anecdotal reports have implicated heredity and various environmental exposures in the cause of some cases of PSP. To clarify the results of the previous study and to evaluate the more recently implicated candidate factors in a controlled fashion, we mailed a validated 69-item questionnaire to 91 personally examined patients with PSP and 104 unmatched controls with other neurologic conditions for which they had been referred to our tertiary neurologic center. We were able to match 75 subjects from each group by year of birth, sex, and race and subjected them to a separate matched-pair analysis. We allowed surrogates to supply any or all of the responses. Questions concerned hydrocarbon, pesticide, and herbicide exposure; urban/rural living; auto repair and other occupations; head trauma; educational attainment; maternal age; and family history of PSP, parkinsonism, dementia, and other neurologic conditions. A statistically significant finding was that patients with PSP were less likely to have completed at least 12 years of school (matched odds ratio = 0.35, 95% CI = 0.12-0.95, p = 0.022; unmatched odds ratio = 0.44, 95% CI = 0.21-0.89, p = 0.020). We hypothesize that this result may be a proxy for poor early-life nutrition or for occupational or residential exposure to an as-yet unsuspected toxin. Future studies should examine these potential risk factors in PSP.
Assuntos
Paralisia Supranuclear Progressiva/etiologia , Idoso , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
A polymorphic 44-nucleotide insertion/deletion in the promoter region of the serotonin transporter gene (5-HTTLPR) has been shown to affect the level of expression of the serotonin transporter protein. An association between anxiety-related behavioural traits and the short form of the 5-HTTLPR has been reported. We determined the 5-HTTLPR genotype in genomic DNA samples from 84 subjects (47 Parkinson's disease patients and 37 controls) with a mean age of 67.4 years. The TPQ of Cloninger was used to obtain values for harm avoidance (HA), reward dependence and novelty seeking for all subjects. Analysis of variance showed a significant influence of the s-allele of the 5-HTTLPR on HA in both subject groups, with no significant interaction between diagnosis and genotype. Subjects with the l/l-genotype had significantly lower mean HA scores than the l/s subjects (P < 0.04) and s/s subjects (P < 0.003). A linear change in HA with genotype was observed, indicating a gene dose effect of the 5-HTTLPR s-allele on this personality dimension. Based on these findings it is suggested that there may be increased influence of the 5-HTTLPR short allele on anxiety-related traits during aging.
Assuntos
Comportamento , Proteínas de Transporte/genética , Glicoproteínas de Membrana/genética , Proteínas de Membrana Transportadoras , Proteínas do Tecido Nervoso , Polimorfismo Genético/genética , Regiões Promotoras Genéticas/genética , Serotonina/genética , Idoso , Idoso de 80 Anos ou mais , Ansiedade/genética , Ansiedade/fisiopatologia , Depressão/genética , Depressão/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas da Membrana Plasmática de Transporte de SerotoninaRESUMO
Cerebral blood flow (CBF) techniques based on the principle of indicator fractionation rely upon free diffusibility of the blood flow indicator into brain (i.e. complete cerebral extraction). Extraction of two commonly-used indicators, iodoantipyrine and n-butanol, was evaluated in rats by measuring torcular venous efflux after systemic injection of the indicator under conditions of normal and high CBF. The extraction of n-butanol was found to be virtually complete at all blood flows examined; iodoantipyrine, on the other hand, was completely extracted only at flows under 180 ml/100 g/min, despite the fact that the oil: water partition coefficient for iodoantipyrine exceeds that for n-butanol. Brain uptake indices for the two indicators were also measured: brain uptake of n-butanol was greater than that of iodoantipyrine, and the difference was more marked if the indicator entered brain mixed with blood than if it entered as a bloodless bolus. Blood components may thus interact with iodoantipyrine to retard its movement across the blood-brain barrier and thereby limit extraction of this lipid-soluble substance. Inasmuch as iodoantipyrine is diffusion-limited at blood flows above 180 ml/100 g/min, butanol is a more accurate CBF indicator above the normal flow range in the rat.
Assuntos
Antipirina/análogos & derivados , Encéfalo/irrigação sanguínea , Butanóis/metabolismo , 1-Butanol , Animais , Antipirina/isolamento & purificação , Antipirina/metabolismo , Transporte Biológico , Butanóis/isolamento & purificação , Radioisótopos de Carbono , Cinética , Masculino , Ratos , Ratos Endogâmicos , Fluxo Sanguíneo Regional , TrítioRESUMO
Recently, a functional polymorphism in the promoter region of the serotonin transporter gene has been linked to anxiety. In cell culture, the short allele of this polymorphism synthesizes less serotonin transporter, resulting in a reduction of the removal of serotonin from the synaptic cleft. This pilot study examines depression and anxiety in Parkinson's disease patients as a function of the variation in this polymorphism. Thirty-two patients were genotyped and then blindly administered the Hamilton Depression and Anxiety Scales. Clinical data on the neurologic features of the disease were also gathered. Patients with the short allele of the serotonin transporter promotor scored significantly higher on both the depression and anxiety measures. There were no differences between groups for any neurologic variable. Patients with the short allele were more likely to have scores for anxiety and depression that indicated "caseness." This study suggests that the short allele of the serotonin transporter gene may represent a significant risk factor for the development of anxiety and depression in Parkinson's disease patients.
Assuntos
Ansiedade/etiologia , Proteínas de Transporte/genética , Depressão/etiologia , Doença de Parkinson/genética , Doença de Parkinson/psicologia , Serotonina/farmacologia , Idoso , Alelos , Ansiedade/genética , Proteínas de Transporte/fisiologia , Depressão/genética , Feminino , Genes Reguladores/fisiologia , Predisposição Genética para Doença , Variação Genética , Humanos , Masculino , Doença de Parkinson/complicações , Fatores de Risco , Serotonina/fisiologiaRESUMO
A double-blind, placebo-controlled study was conducted of pergolide as an adjunctive treatment to levodopa in 17 patients with advanced Parkinson's disease. There was a significant improvement (p less than 0.05) in total disability score, in gait, and in "wearing off" and "on-off" phenomena. Pergolide is a useful drug in patients with advanced Parkinson's disease.
Assuntos
Ergolinas/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Adulto , Idoso , Ensaios Clínicos como Assunto , Método Duplo-Cego , Marcha/efeitos dos fármacos , Humanos , Levodopa/uso terapêutico , Pessoa de Meia-Idade , Atividade Motora/efeitos dos fármacos , Transtornos dos Movimentos/tratamento farmacológico , Pergolida , Distribuição AleatóriaRESUMO
We report the clinical course of 35 patients with Parkinson's disease who experienced an initially favorable response to pergolide and who were taking the drug for at least 6 months. The duration of pergolide treatment was 6-50 (25 +/- 16 SD) months. Of the 14 patients who remained on pergolide for over 2 years, 12 remained less disabled for 26 +/- 17 SD months, seven enjoyed increased "on" time for 39 +/- 8 SD months, and nine had a lower Hoehn-Yahr stage for 25 +/- 17 SD months. Pergolide was discontinued after 5-39 months in eight patients; six patients then deteriorated. Pergolide can remain efficacious in the treatment of Parkinson's disease for up to 50 months.
Assuntos
Antiparkinsonianos/uso terapêutico , Ergolinas/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Idoso , Antiparkinsonianos/efeitos adversos , Ergolinas/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/fisiopatologia , Pergolida , Fatores de TempoRESUMO
We retrospectively compared the clinical state of 14 patients with Parkinson's disease who took pergolide continuously for 63 +/- 17 months (Group I) to that of 12 similar patients who started pergolide and then stopped it after 60 +/- 5 days (Group II). Disability measured during the "on" state did not worsen during the observations period in Group I patients, whereas disability in Group II showed significant deterioration. There were no significant differences in the progression of motor fluctuations between the two groups. Combination treatment with pergolide and levodopa is effective long-term symptomatic therapy for advanced Parkinson's disease and deserves more rigorous study to determine whether or not it also retards progression of Parkinson's disease.
Assuntos
Levodopa/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Pergolida/administração & dosagem , Idoso , Quimioterapia Combinada , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Estatística como AssuntoRESUMO
This article reviews the pharmacokinetics of Sinemet CR, a controlled-release (CR) levodopa preparation. The main influences on the kinetic profile are as follows: absorption, which depends on the dissolution characteristics of the tablet, the pattern of gastric emptying, and the rate of uptake in the small intestine; distribution, which is determined by rates of levodopa transport from gut to blood and from blood to brain; and biotransformation, which is affected peripherally by L-aromatic amino acid decarboxylase (LAAAD) and catechol-O-methyl transferase (COMT), and centrally by LAAAD, COMT, and monoamine oxidase. The kinetics of Sinemet CR are limited by rates of absorption (which depend on the dose administered), the conformation of the tablet, and daily variations in the patterns of gastric emptying (influenced by the presence or absence of food). Levodopa must also compete with food-derived amino acids for transport across the gut-blood and blood-brain barriers; this competition effectively limits the drug's rate of distribution. Finally, biotransformation is limited by the activity of LAAAD and COMT in the periphery. Plasma profiles of levodopa after administration of Sinemet CR can vary, depending on the age of the patient and the time of day when the drug is administered. Nevertheless, the pharmacokinetic profile of the preparation has a number of advantages over that of Sinemet, in that it offers a steadier climb to peak plasma concentrations that are less extreme and of greater duration.