Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We compared the chronic (2-year) effect of substitution with Sinemet CR with the effect of continued administration of standard Sinemet on motor fluctuations and drug-induced side effects in Parkinson's disease (PD). Twelve patients in each treatment group were pair-matched for age, PD duration, duration of levodopa therapy, dosage of Sinemet, PD disability, and side-effect prevalence at study entry. After 2 years, both groups were more disabled from their PD than at baseline; the disability scores were equivalent for the 2 treatments. The Sinemet CR group had fewer fluctuations and fewer side effects. Compared with the standard Sinemet group, Sinemet CR patients had more "on" time (mean 83% versus 62%, p less than 0.001), and had a lower prevalence of disabling chorea (p less than 0.007), dystonia (p less than 0.003) and sleep disruption (p less than 0.002). Prevalence of hallucinations was equivalent for the 2 groups. These results suggest that Sinemet CR is beneficial in ameliorating and preventing the high frequency of some side effects of standard Sinemet treatment.
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PMID:Development and progression of motor fluctuations and side effects in Parkinson's disease: comparison of Sinemet CR versus carbidopa/levodopa. 258 64

"Wearing-off" effect, the most common form of levodopa-induced fluctuations, seems to be related to the short plasma half-life of the drug. More sustained plasma levodopa levels may be achieved with a new controlled-release formulation of carbidopa/levodopa, Sinemet CR4. We studied 20 patients, 12 men and 8 women, with Parkinson's disease complicated by "wearing-off" phenomenon. Mean age was 61.1 +/- 8.1 years, duration of symptoms 8.3 +/- 2.4 years, and the Hoehn-Yahr stage 3.0 +/- 0.9. In a 12-week double-blind study, the average number of tablets administered per day decreased from 5.7 +/- 1.2 to 3.8 +/- 0.7 when Sinemet CR4 (50/200) was substituted for the standard Sinemet (25/100) (p less than 0.001). However, this was at the expense of reducing the "on" time (without dyskinesia) from 9.3 +/- 4.6 to 7.5 +/- 4.3 (p less than 0.05), although the total "on" time did not significantly change. In a long-term follow-up of 18 patients, the "on" time with dyskinesia and morning dystonia significantly increased (p less than 0.05). There was no significant change in the total daily dosage of levodopa, but the daily number of doses and tablets significantly decreased (p less than 0.001). Despite increased dyskinesia, most patients preferred taking fewer tablets and have elected to continue taking Sinemet CR4 instead of standard Sinemet. Sinemet CR4 seems to offer a new and effective strategy for the management of levodopa-related fluctuations.
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PMID:Comparison of Sinemet CR4 and standard Sinemet: double blind and long-term open trial in parkinsonian patients with fluctuations. 268 15

Twenty-one patients with Parkinson's disease and motor fluctuations who completed a double-blind study comparing controlled-release carbidopa/levodopa (Sinemet CR4) with standard Sinemet (SS) were evaluated one year following completion of the study. Five patients remained on CR4 alone; 16 continued on CR4 plus SS, and one also required addition of bromocriptine. Patients were significantly worse (p less than 0.05) at one year compared with double-blind CR4 phase (DBCR) for nine parameters of the motor exam, six activities of daily living (ADL), Hoehn & Yahr staging, and physician's global assessment. Compared with baseline SS, patients were worse at one year for four points of the motor exam, two of mentation, behavior, and mood, and 11 parameters of ADL. Improvement at one year was noted for less action and postural tremor and decreased duration of dyskinesias for both comparison periods. There was elimination of early morning dystonia at one year over the DBCR period and more hours "on" without dyskinesias and fewer hours "on" with dyskinesias compared with baseline SS. Total levodopa dosage was not significantly changed over the year. These data suggest that, in long-term use, CR4 remains more efficacious than SS alone for Parkinson's patients experiencing motor fluctuations, although disease progression continues despite optimal medication.
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PMID:Long-term efficacy of controlled-release carbidopa/levodopa in patients with advanced Parkinson's disease. 269 Jul 30

Parkinsonian patients receiving long-term levodopa-carbidopa (Sinemet) therapy often develop fluctuations in motor performance. Although maintenance of stable levels of plasma levodopa by means of its continuous intravenous infusion diminishes these fluctuations, practical limitations attending this therapeutic approach have prompted continuing attempts to develop oral controlled release levodopa-carbidopa formulations. In a double-blind, crossover clinical trial, one such preparation, CR-5 (Merck, Sharp & Dohme), produced significantly less plasma levodopa variations and substantially improved motor performance over Sinemet in 15 patients with mild to moderate fluctuations, all but one of whom chose to continue on CR-5 therapy after the study. Eight patients with severe motor fluctuations could not adjust to this preparation during the open phase and consequently withdrew from the study. Subjectively, most patients noted the convenience of less frequent dosing, improved sleep, and the amelioration of early morning akinesia and dystonia.
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PMID:Controlled release levodopa-carbidopa (CR-5) in the management of parkinsonian motor fluctuations. 363 71

In five patients with parkinsonism, the optimal dosage of a controlled-release levodopa/carbidopa preparation (CR-3) was three times higher than the dosage of Sinemet and produced higher plasma levodopa concentrations, but did not reduce the fluctuations in plasma levodopa or clinical response. Plasma levodopa concentrations were higher and clinical responses better before the first dose of the day with CR-3. CR-3 treatment benefited two patients, reducing the severity of off periods and off dystonia. Two patients were worse on CR-3 despite higher plasma levodopa levels than those adequate for clinical response to Sinemet or levodopa infusions. CR-3 could benefit a few severely affected patients, but it is necessary to understand the factors that affect absorption of levodopa from sustained-release preparations, as well as the consequences of prolonged elevation of plasma levodopa levels.
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PMID:Clinical and biochemical studies with controlled-release levodopa/carbidopa. 374 87

Four different clinical syndromes encompassing the TD spectrum are described: (a) classical TD, which is choreatic in speed of movement and stereotypic in pattern; (b) tardive akathisia; (c) withdrawal emergent syndrome, which presents as true chorea; and (d) tardive dystonia, which presents with dystonic movements and postures. All are made worse or are unmasked by withdrawal of the antipsychotic drugs, and all tend to be reduced in severity by increasing the dosage of the antipsychotic drugs (dopamine-receptor blockers) or utilizing presynaptically acting dopamine-depleting drugs. Treatment depends on discontinuing the causative agent, i.e., the antipsychotic drugs. The withdrawal emergent syndrome is self-limiting. Classical TD and tardive akathisia are persistent. The dopamine-depleting agents can be utilized if the symptoms are severe. Reserpine alone or with AMT is effective in most cases. Tetrabenazine can be substituted for reserpine. With time, the disorder can eventually disappear in many patients as long as the antipsychotic drugs have been eliminated. Carbidopa/levodopa (Sinemet) can be added to counteract parkinsonian symptoms that occur as an adverse effect of these medications. The addition of Sinemet may be useful in hastening a remission of TD. Tardive dystonia is less successfully treated. Some patients will respond to the approach used to treat classical TD, others may respond to anticholinergic agents, and some remain resistant to these methods. They may require reinstitution of the antipsychotic drugs.
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PMID:Treatment of tardive dyskinesia: use of dopamine-depleting agents. 613 19

Determinations of biopterin (BP), homovanilic acid (HVA), glutamic acid (GTA), and glutamine (GT) levels in cerebrospinal fluid (CSF) obtained through a lumbar tap were performed in 20 parkinsonian patients in different stages of evolution and without medication. In patients with motor symptoms not related to Parkinson's disease (dystonia, dyskinesia and essential tremor) (n = 4). In 7 other neurological patients subjected to spinal tap for diagnostic procedures neurotransmitters were also determined and taken as control groups. In 14 of the patients with Parkinson's disease, the symptoms were evaluated using conventional scales (UPDS, NYPDS, NWPDS, Schwab and England, and Hoehn and Yahr scale). The amplitude and the frequency of tremor were quantitatively evaluated through a single plane accelerometer Grass SP-1, akinesia was measured through reaction time to auditory stimuli, and rigidity through the speed of lineal movement. Evaluations were performed with the patient not on any medication for 1 week and repeated 1 h after the intake of 250 mg of 200/50 L-dopa/carbidopa preparation (Sinemet) and on a different day after the intake of biperiden (Akineton) 6 mg/day. Differences in neurotransmitter or metabolites levels between Parkinson's disease and control groups were determined through an independent Student's t test. Correlation between severity of symptoms in the scales and for each individual symptom measured through the quantitative tests and the levels of neurotransmitters in CSF were evaluated through the Pearson correlation analysis test. Modifications in the motor performance after administration of Sinemet and Akineton, and the levels of neurotransmitters were indirectly determined. RESULTS. (1) There were significant differences between the levels of BP and GT in patients with Parkinson's disease and control groups, (2) lower GTA levels correlated with more severe rigidity and akinesia, and with the best response to the administration of L-dopa and may be an important marker for prognosis, and (3) lower levels of GT correlated with least akinesia, but not with tremor, which may indicate that the akinesia depends on other biochemical abnormalities besides dopamine depletion.
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PMID:Neurotransmitter levels in cerebrospinal fluid in relation to severity of symptoms and response to medical therapy in Parkinson's disease. 763 Oct 94

A 15-year-old boy presented with a severe fluctuating foot and ankle dystonia resulting from a basal ganglia insult at the age of 4. This followed an embolic event related to an undiagnosed prolapsed mitral valve. Functionally, the patient was ambulatory with rocker bottom crutches and an ankle-foot orthosis, but there were periods of up to a year when pain and increased dystonic deformity required him to use a wheelchair. A new orthotic was made nearly every month because the orthotist could find no material that would withstand his tone without breaking, yet he could not ambulate without one. Multiple interventions, including biofeedback, contrast baths, stretching and strengthening, oral lioresal (Baclofen), diazepam (Valium), benztropine mesylate (Cogentin), carbidopa-levodopa (Sinemet), carbamazepine (Tegretol), and injections of botulism toxin (BOTOX) were tried, all with minimal effects. Amputation was recommended, based on anatomic and functional considerations. The patient and his family adjusted well to this decision, although not all orthopedists and therapists adjusted easily to the choice. The patient is now functionally independent with a prosthesis and has a normal teenage lifestyle for the first time.
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PMID:An aggressive approach to limb dystonia: a case report. 959 5

Movement disorders following midbrain haemorrhage are infrequently encountered in rehabilitation, and are uncommonly corrected by pharmacologic means. This report describes a 20 year-old male with a prior history of cocaine abuse who presented with a 4 day history of dysarthria and blurred vision following methamphetamine abuse. Physical examination demonstrated hypertension, left facial hemispasm, bilateral upward gaze paresis and ataxic gait. Magnetic resonance imaging/magnetic resonance angiography (MRI/MRA) showed multifocal parenchymal haematomas in the mesencephalic tegmentum, subcortical left front region and right anterior thalamus consistent with cavernous angiomas. The patient was transferred to rehabilitation on hospital day 5. The following day, he developed choreoathetoid movements, dystonia, and aphasia, secondary to an extension of the midbrain haemorrhage. Cogentin was initiated with slight improvement in choreoathetoid movements. The patient began intensive multidisciplinary rehabilitation therapy but after 18 days of therapy, the patient remained totally dependent in activities of daily living (ADLs), transfers, mobility and was unable to communicate in any manner. A trial of Sinemet was initiated, with resultant steady improvement in functional ability over the next month. By discharge, the patient was independent in ADLs and ambulation. By 9 months post discharge follow-up, the patient was fully independent with normal cognition, and had self tapered all medications without ill effect. Dopamine agonist trials of appropriate duration appear indicated in cases of movement disorder (paucity or excess) following midbrain lesions.
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PMID:Pharmacologic management of movement disorder after midbrain haemorrhage. 965 26

This study reports long-term (over 6 years) effect of controlled-release carbidopa/levodopa (CRCL, Sinemet-CR) in levodopa-naive Parkinson's disease patients. Parkinsonian features were evaluated utilizing the Northwestern University Disability Scale (NUDS) and modified New York University Parkinson's Disease Rating Scale (NYUPDRS). The NUDS scores showed significant variation over time by 2-way ANOVA (P < 0.0001). Following treatment, compared to baseline scores, the NYUPDRS scores showed significant improvement in rigidity, tremor, bradykinesia, while the postural stability scores worsened and gait scores, after initial improvement, returned to baseline level. At the end of the study period 5 patients were alive, 1 became disabled due to myocardial infarction and 3 were holding on to full time occupations. Three patients developed medication related dyskinesia, 1 developed myoclonus and 1 developed a combination of dyskinesia, motor fluctuations and early morning dystonia. Due to small number of patients, while a definite conclusion cannot be drawn, it appears that the incidence of motor fluctuation may be much less prevalent than dyskinesia in patients with Parkinson's disease treated with CRCL.
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PMID:Long-term effect of controlled-release carbidopa/levodopa in levodopa-na. 2950 14


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