Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied whether assessment of medium latency (ML) and long latency (LL) reflex amplitudes may serve as a marker for early Parkinson's disease. Twenty-three patients with idiopathic Parkinson's disease (Hoehn and Yahr stage 1 to 4) and 24 controls received 20 4 degrees toe-up rotations of a platform upon which they were standing. All antiparkinsonian medication was withheld for at least 12 h before the study. ML reflexes in the stretched gastrocnemius muscle and LL reflexes in the shortened tibialis anterior muscle were recorded from both legs. ML responses were significantly enhanced in patients compared to controls. In contrast to previous studies which studied patients who continued their usual treatment, we observed that LL responses were significantly reduced in patients compared to controls. For the purpose of individual analysis, we subsequently determined the optimal specificity and sensitivity using various criteria for abnormality. The presence of either enhanced ML responses or reduced LL responses (or both) in at least one leg yielded a maximum sensitivity of 65.2% with a specificity of 75.0% (positive likelihood ratio 2.6; negative likelihood ratio 0.5). Abnormal reflexes were almost exclusively present in patients with advanced and long-standing Parkinson's disease. These results show abnormalities of ML and LL responses in advanced Parkinson's disease, but render it unlikely that these abnormalities are a suitable screening tool for early stages of the disease. The fact that LL responses were reduced in patients taken off antiparkinsonian medication raises the possibility that this reflex is under supraspinal dopaminergic control.
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PMID:Are medium and long latency reflexes a screening tool for early Parkinson's disease? 146 53

In subjects standing on a movable platform, sudden dorsiflexion of the ankle joint elicits a set of reflexes in leg muscles. These responses include a short latency (SL) and medium latency (ML) stretch reflex in the gastrocnemius muscle and a distal to proximal innervation sequence of long latency (LL) reflexes in the shortened tibialis anterior and vastus lateralis muscles. Because of their role in maintaining upright stance these responses have been termed postural reflexes. In patients with Parkinson's disease (PD), the following abnormalities have been described: 1) enhanced ML-amplitudes; 2) a reversed LL innervation sequence; and 3) delayed onset latencies. These abnormalities are thought to be due to defective motor programming and disturbed control of spinal and supraspinal reflex centers by basal ganglia circuits. The altered reflexes have been held responsible for some of the clinical features of PD, including balance impairment and rigidity. In this paper, we argue the reverse hypothesis that postural reflexes are essentially normal in PD, and that the observed alterations are at least in part consequence rather than cause of balance impairment, the stooped parkinsonian posture and rigidity of PD patients.
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PMID:Altered postural reflexes in Parkinson's disease: a reverse hypothesis. 147 51

Postural reflexes in response to sudden toe-up tilts of a supporting forceplate platform were studied in free-standing patients with stage III (N = 5) and stage IV (N = 5) Parkinson's disease and compared to 5 age- and sex-matched normals. Latencies of the short (SL), medium (ML) and long latency (LL) responses were normal in the patients. The normalized mean amplitudes of the ML responses were significantly increased only in the stage IV Parkinson patients (P less than 0.0005). The distal-proximal activation sequence of LL responses observed in all 5 controls was reversed in 1 of the stage III and 4 of the stage IV Parkinson patients. Both the enlargement of the ML response (P less than 0.01) and the inverted activation sequence of LL responses (P less than 0.01) were significantly correlated with severity of the disease. The data establish an association between abnormal modulation of postural reflexes in the lower extremity and clinically rated balance impairment in Parkinson's disease.
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PMID:Electrophysiological correlates of postural instability in Parkinson's disease. 171 20

Short and medium latency electromyographic (EMG) responses to stretch of the triceps surae muscle and long latency EMG responses (LL) in the anterior tibial muscle (TA) were evoked by toe-up tilt of a movable platform while standing or sitting, in normal subjects and patients with Parkinson's disease. With the stimulus parameters used (amplitude 4 degrees, velocity 50 degrees/s), LL in TA were absent in normals while sitting, but were present in 11 of the 12 patients with Parkinson's disease. In patients, LL latencies were identical in both positions. The results indicate that patients with Parkinson's disease have difficulty modulating long latency responses according to functional demands. Long latency responses in TA in the sitting position may correspond to the shortening reaction observed by others when much stronger stimuli were used.
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PMID:Increased shortening reaction in Parkinson's disease reflects a difficulty in modulating long loop reflexes. 350 58

Postural reflexes in leg muscles appear to be set at a fixed gain in Parkinson's disease. To further investigate gain adaptation, we instructed 16 patients with idiopathic Parkinson's disease (studied during the 'off' phase) and 21 healthy controls to either 'resist' or 'yield' in response to 20 serial 4 degrees toe-up perturbations of a supporting platform on which they were standing. We bilaterally recorded destabilizing medium latency (ML) reflexes from stretched gastrocnemius muscles and corrective long latency (LL) reflexes from shortened tibialis anterior muscles. We also assessed changes in center of foot pressure (CFP) and center of gravity (COG). During the 'resist' condition, patients had increased destabilizing ML reflexes, decreased corrective LL reflexes, increased backward displacement of the COG and increased forward (destabilizing) displacement of the CFP. In addition, the backward (corrective) displacement of CFP between 150 and 250 ms was delayed. During the 'yield' condition, reflex gains were modified in controls: LL reflexes were markedly attenuated, whereas ML reflexes were markedly increased. Although this reflex pattern resembled the 'resist' condition in patients, it was not associated with an increased forward displacement of the CFP, but only with a strongly delayed backward displacement of CFP which started after 150 ms. In patients, ML reflex amplitudes remained unchanged during the 'yield' condition, suggesting a fixed reflex gain. LL reflex amplitudes were reduced in patients but significantly less compared to controls, which again suggests a fixed reflex gain. This 'inflexibility' of postural reflexes was reflected by the CFP which showed much smaller changes between 0 and 250 ms in patients than controls. These results could not be ascribed to a different ability to yield because posterior displacement of the COG was identical in patients and controls during the 'yield' condition. We conclude that (1) patients with Parkinson's disease have abnormal and 'inflexible' postural reflexes, associated with delayed corrective movements about the ankle joint and increased body sway; and (2) the increased forward displacement of the CFP in patients likely reflects high stiffness in ankle muscles because reflex changes in controls only affected the CFP more than 150 ms after the perturbation. The increased muscle stiffness and inflexibility of postural reflexes in Parkinson's disease may contribute to balance impairment in daily life.
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PMID:Postural reflexes in Parkinson's disease during 'resist' and 'yield' tasks. 760 24

Young normal subjects adapt the size of posturally stabilizing reflexes in the lower extremity to predictable and unpredictable perturbations through shifts in cognitive set. It is unknown whether limitations in this ability to shift cognitive set may contribute to impaired scaling of postural reflexes in patients with Parkinson's disease. In this study, we have addressed this issue in 12 posturally unstable Parkinson patients and 13 age- and sex-matched controls. Postural stability was disturbed by sudden toe-up rotations of a supporting platform upon which subjects were standing. Subjects' cognitive set was altered by varying the perturbation amplitude either predictably (serial 4 degrees versus serial 10 degrees) or unpredictably (random mixture of 4 degrees and 10 degrees). Posturally stabilizing long latency (LL) reflexes were recorded from the shortened tibialis anterior muscle of both legs. We found that Parkinson patients, unlike some control subjects, were unable to scale the size of their LL reflex in response to variations in perturbation amplitude during predictable conditions. In addition, we observed that Parkinson patients could not modify the amplitude of the LL reflex through alterations in cognitive set during random conditions. We conclude that Parkinson patients have a fundamental difficulty in modifying the size of posturally stabilizing LL reflexes, as reflected by both problems with amplitude scaling and difficulties with changes in cognitive set. It is possible that this inability to modify LL reflexes may be a factor contributing to postural instability in Parkinson's disease.
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PMID:Impaired scaling of long latency postural reflexes in patients with Parkinson's disease. 767 26

Scaling of posturally stabilizing long latency (LL) reflexes in tibialis anterior muscles induced by "toe-up" rotational perturbations is abnormal in standing patients with Parkinson's disease. To investigate the contribution of dopaminergic pathways to abnormal scaling, we studied LL reflexes in 22 patients with selective hypodopaminergic syndromes: 10 psychiatric patients taking chronic neuroleptic medication (7 with mild parkinsonism), 8 patients with young-onset Parkinson's disease, and 4 patients with MPTP-induced parkinsonism. Results were compared with those of 10 healthy controls. Stimuli consisted of (a) 10 serial (predictable) perturbations of 4 degrees amplitude, (b) 10 serial (predictable) perturbations of 10 degrees amplitude, and (c) 20 randomly mixed (unpredictable) perturbations of either 4 or 10 degrees amplitude. In normal subjects, LL reflex amplitudes were adapted to match predictable variations in stimulus size, whereas under unpredictable conditions a "default" response emerged that anticipated the 10 degrees perturbation. LL reflex scaling under predictable conditions was intact in patients with neuroleptic-induced parkinsonism and young-onset Parkinson's disease, but the large default LL response under unpredictable conditions was absent. In patients with MPTP-induced parkinsonism, LL reflex scaling was absent during both predictable and unpredictable conditions. We conclude that abnormal scaling of posturally stabilizing LL reflexes is related to decreased supraspinal dopaminergic influence.
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PMID:Long latency postural reflexes are under supraspinal dopaminergic control. 855 9

It is still unclear why balance impairment in Parkinson's disease (PD) often responds insufficiently to dopaminergic medication. We have studied this issue in 23 patients with idiopathic PD and 24 healthy controls. Our specific purposes were (a) to investigate the contribution of abnormal automatic postural responses to balance impairment in PD and (b) to assess the influence of dopaminergic medication on abnormal automatic postural responses and balance impairment. Standing subjects received 4 degrees "toe-up" rotational perturbations of a supporting forceplate. We bilaterally recorded posturally destabilizing medium latency (ML) responses from the stretched gastrocnemius muscles and functionally corrective long latency (LL) responses from the shortened tibialis anterior (TA) muscles. We also assessed changes in the center of foot pressure (CFP) and the center of gravity (COG). All patients were tested in the "off" and "on" phases. All controls were tested and retested after 1 h. During the off phase, we found enlarged ML amplitudes and diminished LL amplitudes in patients, together with a markedly increased posterior displacement of the COG. The abnormal ML and LL responses were partially responsible for the increased body sway in patients because the initial forward (destabilizing) displacement of the CFP was increased, while the subsequent backward displacement of the CFP (a measure of the corrective braking action of LL responses) was delayed. Abnormal late automatic or possibly more voluntary postural corrections also contributed substantially to the increased body sway. During the on phase, ML amplitudes were reduced in patients but remained increased compared with controls. LL amplitudes no longer differed between both groups due to a modest, possibly dopamine-related increase in patients and a simultaneous decrease in controls. The abnormal CFP displacement was only partially improved by dopaminergic medication. The later postural corrections were not improved at all. Consequently, the increased posterior COG displacement was not ameliorated during the on phase. We conclude that (a) a combination of abnormal automatic and perhaps more voluntary postural corrections contributes to increased body sway in PD and (b) dopaminergic medication fails to improve balance impairment in PD because early automatic postural responses are only partially corrected, while later occurring postural corrections are not improved at all. These electrophysiological results support clinical observations and suggest that nondopaminergic lesions play a significant role in the pathophysiology of postural abnormalities in PD.
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PMID:Influence of dopaminergic medication on automatic postural responses and balance impairment in Parkinson's disease. 886 92

Abnormal automatic postural responses are thought to contribute to balance impairment in Parkinson's disease. However, because postural responses are modifiable by stance, we have speculated that some postural abnormalities in patients with Parkinson's disease are secondary to their stooped stance. We have studied this assumption by assessing automatic postural responses in 30 healthy subjects who were instructed either to stand upright or to assume a typical parkinsonian posture. During both conditions, subjects received 20 serial 4 degrees 'toe-up' rotational perturbations from a supporting forceplate. We recorded short-latency (SL) and medium-latency (ML) responses from stretched gastrocnemius muscles and long-latency (LL) responses from shortened tibialis anterior muscles. We also assessed changes in the center of foot pressure (CFP) and the center of gravity (COG). The results were qualitatively compared to a previously described group of patients with Parkinson's disease who, under these circumstances, typically have large ML responses, small LL responses and insufficient voluntary postural corrections, accompanied by a slow rate of backward CFP displacement and an increased posterior COG displacement. The stooped posture resulted in unloading of medial gastrocnemius muscles and loading of tibialis anterior muscles. Onset latencies of stretch responses in gastrocnemius muscles were delayed in stooped subjects, but the onset of LL responses was markedly reduced. Amplitudes of both ML and LL responses were reduced in stooped subjects. Prestimulus COG and, to a lesser extent, CFP were shifted forwards in stooped subjects. Posterior COG displacement and the rate of backward CFP displacement were diminished in stooped subjects. Voluntary postural corrections were unchanged while standing stooped. These results indicate that some postural abnormalities of patients with Parkinson's disease (most notably the reduced LL responses) can be reproduced in healthy subjects mimicking a stooped parkinsonian posture. Other postural abnormalities (most notably the increased ML responses and insufficient voluntary responses) did not appear in stooped controls and may contribute to balance impairment in Parkinson's disease.
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PMID:Are automatic postural responses in patients with Parkinson's disease abnormal due to their stooped posture? 1009 Jun 60

To determine the effects of endogenous and exogenous melatonin on experimental models of Parkinson's disease (PD), Sprague-Dawley rats were exposed to intracerebroventricular implants of slow release melatonin, pinealectomy (PX), or constant light (LL) and then injected with central 6-hydroxydopamine (6-OHDA) or i.p. 1-methyl-4-phenyl,1-1,2,3,6-tetrahydropyridine (MPTP). The resulting impairment of motor function and related behavioural impairment were exacerbated by melatonin implantation, while PX and exposure to LL significantly reduced the severity of experimental PD. These results are consistent with previous work highlighting the importance of aberrant amine production in neurological disease and demonstrate that treatments that reduce endogenous melatonin bioavailability can ameliorate experimental PD. Furthermore, these findings illustrate that melatonin is not the universal remedy that it is currently claimed to be, and may pose considerable problems in neurological diseases characterised by dopamine degeneration.
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PMID:A therapeutic role for melatonin antagonism in experimental models of Parkinson's disease. 1040 6


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