Switching abilities in Parkinson's disease.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to R Inzelberg.
Explore the source record for details and available documents.
Using the technique of transcranial magnetic stimulation over the motor areas of cortex and recording electromyographic (EMG) responses from the first dorsal interosseous muscle, we measured the excitability of corticocortical inhibitory circuits at rest using a double pulse paradigm, in 11 patients with Parkinson's disease (PD) studied both on (ON) and off (OFF) (after overnight withdrawal) their normal medication and in 10 age-matched control subjects. There was a significant decrease in the amount of corticocortical inhibition at short (1-5 msec) interstimulus intervals in patients relative to their controls, which improved after L-dopa intake. For comparison with previous reports using transcranial magnetic stimulation we also measured the duration of the EMG silent period when stimuli were given to voluntarily active muscle, and the threshold for evoking an EMG response in both the active and relaxed states. There was no change in the threshold for evoking EMG responses whether muscles were active or relaxed. However, the silent period was significantly prolonged when ON compared with OFF, although in neither state was the duration significantly different from that seen in normals. We suggest that there may be abnormalities of motor cortical inhibitory mechanisms in patients with Parkinson's disease that are not readily detected using threshold or silent period measurements alone.
Motor fluctuations constitute a severe complication of chronic levodopa therapy. The addition of dopamine agonists may partially alleviate these responses; however, due to the short half-life of these drugs, several daily doses are required. Cabergoline is a new dopamine agonist with a long half-life and can be given in a single daily dose. Seventeen patients with severe fluctuations were treated with cabergoline, seven of them for > 1 year (up to 39 months). The motor status ameliorated and the percentage of "off" hours significantly decreased in the first year and did not increase significantly later during long-term follow-up. Cabergoline is a promising treatment for parkinsonian patients with motor fluctuations.
The kinematic properties of upper limb trajectories of simple reaching movements have been analysed in patients with idiopathic torsion dystonia (ITD). The velocity profiles differed from those of neurologically healthy subjects by being less symmetric. In several patients movement execution was slow due to a longer deceleration time. This phenomenon was even more conspicuous in the absence of visual feedback from the limb and was accompanied by a significant decrease in the final accuracy. These findings show that patients with ITD have deficits in central motor mechanisms beyond abnormal muscle activation patterns. Similarities between kinematic properties of patients with ITD and patients with Parkinson's disease including the deterioration of motor performance in ITD in the absence of visual feedback from the limb, suggest the existence of abnormalities in sensorimotor integration in both diseases.
Transcranial magnetic stimulation has been used in a double pulse paradigm to investigate the excitability of intrinsic motor cortical circuits in 15 patients with focal task specific dystonia of the right hand and a group of eight age matched controls. The left hemisphere was examined in five patients; in the remainder, both hemispheres were tested. There was no significant difference in stimulation threshold between patients and controls nor between the left and right hemispheres in the patients. There was a significant decrease in early corticocortical suppression when comparing stimulation of the left hemisphere in the patients and controls at interstimulus intervals of 1-15 ms (P < 0.01). There was no difference in the amount of suppression in the right and left hemispheres of the patients. It is concluded that in focal task specific dystonia there is shift in the balance between excitation and inhibition in local circuits of the motor cortex which leads to a net decrease in the amount of short latency suppression. These changes reflect disturbed basal ganglia input to the motor cortex. Reduced excitability of cortical inhibitory circuits may be one factor which contributes to the excessive and inappropriate muscle contraction which occurs during fine motor tasks in patients with focal dystonia.
Explore the source record for details and available documents.
Cabergoline, a new ergoline derivative with potent and long-lasting dopaminergic activity, is a promising drug for overcoming the akinetic episodes in L-Dopa-treated Parkinson's disease patients with motor fluctuations. Its long plasma half-life (65 h) allows a single daily dose administration. Seventeen patients with Parkinson's disease (mean age 66 years; mean disease duration 8.8 years; median Hoehn and Yahr stage, III) were included in an open-label study. All had persistent motor fluctuations while treated with L-Dopa plus carbidopa (mean dose, 660 mg + 66 mg). Cabergoline was added until a maximal dose was achieved (5 mg daily), while L-Dopa was slightly diminished. Eight patients completed 1 year of treatment. They showed significant improvement in their motor performance (Unified Parkinson's Disease Rating Scale) (bradykinesia score decreased from 8.2 to 4.2, p < 0.005), and in the proportion of "off" time spent during waking hours (32-23%, p < 0.05). Three patients abandoned the trial because of increasing severity of dyskinesias, hallucinations, and depression (one each), six were withdrawn because of poor compliance and refusal to continue the treatment. This study suggests that cabergoline may play an important role in the treatment of Parkinson's disease with motor fluctuations.
Explore the source record for details and available documents.
'Arteriosclerotic' parkinsonism is still a subject of debate. The aim of this study was to investigate whether parkinsonism associated with basal ganglia lacunes possesses peculiar clinical features and a clinical course which enables its distinction from idiopathic Parkinson's disease (IPD). 106 consecutive ambulatory patients with the clinical diagnosis of parkinsonism were referred for CT examination. Patients in whom isolated basal ganglia lacunes were found were interviewed and examined, and their clinical characteristics were compared to those of patients suffering from IPD without lacunes (controls). In 20 patients, isolated basal ganglia lacunes were detected; all had risk factors for stroke (significantly more than controls) and 7 of them had had clinically diagnosed strokes. The extrapyramidal disability evolved slowly in all. The clinical picture was indistinguishable from IPD in individual patients. However, tremor was significantly less frequent in this group. Lower body parkinsonism was not observed. Extra-pyramidal signs were frequently asymmetrical (55%), with no consistent relationship to the side of the lacune. Asymmetrical pyramidal signs were present in 30% of those with unilateral lacunes, always on the appropriate side. Only 1 patient was an L-dopa nonresponder. Patients with parkinsonism associated with basal ganglia lacunes showed tremor less frequently than other IPD patients; otherwise, clinical features and course of the disease were indistinguishable from IPD. In these cases, parkinsonism and basal ganglia lacunes might have occurred independently of each other and tremor might have been prevented by ischemic events.
The natural history of 51 idiopathic torsion dystonia cases identified in a nationwide survey in Israel was studied. In order to take advantage of all data regarding the evolution of the disease, independently of the length of follow-up, we have used a life table method of analysis. An estimate of the mean degree of generalization of the disease at different times from onset was calculated and a curve of the estimated temporal evolution was drawn. This analysis confirmed the heterogeneity of the disease course. The most rapid deterioration occurred in patients with juvenile onset in the lower limbs, particularly in the first 2 years following the onset. The rate of evolution was not influenced by gender or familiarity. The course of the disease seemed more deleterious in non-Ashkenazic Jews. The present statistical method of estimating the evolution in different patient groups should be useful especially for the evaluation of therapeutic interventions.
Idiopathic torsion dystonia (ITD) is a dominantly inherited disorder with incomplete penetrance. It is important to identify factors that may cause dystonia or prevent its occurrence in a genetically predisposed individual. Because dystonia may be precipitated by peripheral triggers, we have investigated whether the preferential use of a limb affects the development of dystonia. Analysis of the correlation between the side of motor dominance and the limbs in which dystonic symptoms first appeared was performed in 49 patients with ITD ascertained in a country-wide survey in Israel. The dominant motor side was determined in 45 cases (92%). Among 29 patients with lateralized limb onset, 24 showed right-side motor dominance, of whom 21 had dystonia onset in a right limb. The first sign was in a left limb for all five cases with left-side motor dominance (90% coincidence). The pattern of limb involvement was studied. Detection bias could be ruled out. The highly significant relationship between the motor dominance and the laterality of limb onset in ITD patients suggests that the preferred use of a limb may trigger the onset of dystonia.
Idiopathic torsion dystonia (ITD) is a dominantly inherited disorder with variable penetrance and expressivity. Factors affecting the penetrance of the ITD gene have not yet been identified. The present study used four published series of cases to test specific hypotheses regarding factors that could affect the expression of ITD. Among the combined 253 families, transmission of ITD did not depend on either the sex of the affected offspring or that of the transmitting parent. Furthermore, neither the specific type of dystonia manifested, the site at which clinical signs of dystonia first appeared, nor age of onset differed significantly as a function of the gender of the transmitting parent. However, in familial cases of later onset (age > or = 20 years), nearly all involved a transmitting mother. There is evidence for consistency of age of onset within the subset of Jewish families. Although anticipation effects are apparent, sampling bias cannot be ruled out.
Dystonia has moved from the status of a rare disease or an uncommon clinical manifestation to the center stage of research in movement disorders. Recent developments have expanded our knowledge of the genetics and understanding of its pathophysiology, and have resulted in significant improvements in the clinical management of this group of disorders. These, as well as the varied and multifaceted phenomenology are reviewed.
The purpose of this study was to analyze the kinematic properties of upper limb trajectories in Parkinson's disease (PD) patients and to investigate the role of visual feedback from the moving limb. Beyond the characteristic bradykinesia, PD patients differed from controls by generating hand trajectories with asymmetrical velocity profiles that lacked smoothness and were composed of a short initial accelerative phase, followed by a prolonged interval composed of alternating decelerative and accelerative phases. In both groups, the reaction times for movements directed away from the body were longer than for movements directed toward the body; this effect was accentuated in PD. In both groups, initial peak accelerations were significantly larger for distally as compared to proximally directed movements. In the absence of visual feedback from the limb a deterioration in the accuracy of reaching the target was observed in both control and PD patients only for distally directed movements. However, this deterioration and the effect of target location on final accuracy was substantially larger in PD. Taken together, our study suggests that in PD visual information is continuously relied upon for ongoing movement correction, therefore accentuating the bradykinesia. The deficit in final accuracy in the absence of visual feedback reflects the important role played by the basal ganglia in sensorimotor integration.
Explore the source record for details and available documents.
The effect of intravenous atropine (1 mg) or saline on mnemonic function was tested in patients with various forms of dementia and age-matched controls. Examinees consisted of 12 subjects having Alzheimer's disease (AD), multi-infarct dementia (MID), Parkinson's disease without dementia or with dementia, and normal aged controls. Wechsler's adult memory scale was used. Orientation, visual reproduction, and associative learning were not affected by this small dose of atropine in any of the subgroups. On the other hand, digit span and logical memory were selectively impaired by atropine in AD. The more sensitive parameters were the improvement on retesting (reflecting learning abilities). This study suggests that cholinergic dysfunction is responsible for abnormalities in logical memory and digit span in AD or the dementia of Parkinson's disease but not in MID.
Explore the source record for details and available documents.