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)

To evaluate the pathogenesis of end-of-dose dystonia in levodopa-treated patients with Parkinson's disease, we discontinued a steady-state optimal-dose levodopa infusion either abruptly or slowly. Although dystonic signs appeared sooner after sudden levodopa termination, in both situations dystonia emerged only when circulating drug levels had fallen to the same concentration and parkinsonian scores had declined by the same amount. Dystonia onset thus appears to reflect the degree, rather than the rate, of reduction in dopaminergic stimulation, and may involve the preferential interaction of dopamine with a receptor subpopulation that does not mediate its antiparkinsonian efficacy.
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PMID:End-of-dose dystonia in Parkinson's disease. 841 78

Dyskinesias are frequently observed in parkinsonian patients during levodopa treatment. The occurrence of these movement disorders usually makes the therapeutic management of the patients very difficult. The clinical characteristics of 176 patients with dyskinesias were retrospectively studied. Dyskinesias occurred, on average, after 6.2 years of duration of Parkinson's disease and after 4.2 years on treatment with levodopa. Patients were more likely to have dyskinesias during more advanced stages (measured by Hoehn and Yahr scale). Peak of dose and square wave were the types of dyskinesia more frequently described and were associated with choreic movements in most cases. Dystonia occurred in 40% of the cases and was predominant in end of dose and diphasic dyskinesias. Thirty-five percent of dystonia cases presented as "early morning dystonia". Chorea was the most frequent involuntary movement and mostly generalized. Dystonia was most commonly described in lower limbs. Orofacial dyskinesia, when occurred alone, was more frequently seen in old rather than young patients. When dyskinesia was unilateral it was more likely to occur in the side where Parkinson's disease was more severe.
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PMID:[Levodopa-induced dyskinesia in 176 patients with Parkinson's disease]. 872 65

The pathophysiology of dystonia is unclear, but several clues implicate striatal dopamine dysfunction. In contrast, the causal relationship between striatal dopamine deficiency and parkinsonism is well defined. We now suggest that parkinsonism or dystonia may occur following striatal dopamine deficiency. Baboons treated with intracarotid 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) developed transient hemidystonia prior to hemiparkinsonism. The day after MPTP treatment, most animals had spontaneous ipsilateral turning. Within a few days, all developed contralateral hemidystonia, with the arm and leg extended and externally rotated. This transient dystonia preceded hemiparkinsonism with flexed posture, bradykinesia, and postural tremor that persisted for up to 1.5 years. Dystonia corresponded temporally with a decreased striatal dopamine content and a transient decrease in D2-like receptor number. The time course of dystonia and parkinsonism is analogous to lower limb dystonia as the first, frequently transient, symptom of Parkinson's disease in humans. The association of striatal dopamine deficiency with dystonia and parkinsonism implies that other factors influence clinical manifestations.
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PMID:MPTP induces dystonia and parkinsonism. Clues to the pathophysiology of dystonia. 937 34

This article reviews the cytoskeletal abnormalities, morphologic lesion patterns, and resulting pathophysiology of the most frequent neurodegenerative movement disorders caused by dysfunction of the basal ganglia and related neuronal loops. The following topics are discussed: Among the akinetic-rigid Lewy body disorders is idiopathic Parkinson's disease, which reveals specific lesion patterns of pathophysiologic and therapeutic relevance. Dementia with Lewy bodies characterized by cortical Lewy bodies appears intermediate between Parkinson's and Alzheimer's diseases. Tau pathologic disorders may show some clinical and morphologic overlap. Multiple system atrophy has ubiquitous oligodendroglial inclusions as a cytopathologic hallmark. Secondary parkinsonism includes drug-related, toxic, and other symptomatic disorders. Hyperkinetic disorders include CAG-related inherited diseases, showing specific genetic defects and morphologic lesions. Dystonia syndromes show inconsistent pathologic findings, and myoclonus may be related to a variety of disorders. Consensus data on clinical and neuropathologic criteria already existing for some disorders, together with molecular genetic and biochemical data will provide further insight into the complex pathophysiology and pathogenesis of movement disorders.
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PMID:Neuropathology of movement disorders. 949 89

Any model for the physiology of dystonia must be able to explain how dystonia can be produced in various circumstances. Brain lesions can cause dystonia; responsible sites include the basal ganglia, brainstem, and thalamus, but the most common site is the putamen. Dystonia can be hereditary, and genetic linkage has been found for both generalized and focal dystonia. The only genetic dystonia for which the gene product is known is Segawa disease, a hereditary progressive dystonia with marked diurnal fluctuation. The defect is in guanosine triphosphate cyclohydrolase I, a gene that makes a cofactor for the synthesis of dopamine, which explains why this form of dystonia should be amenable to treatment with levodopa. Another example of dystonia in which a disorder of dopamine pharmacology appears responsible is the dystonia occurring in Parkinson disease, either spontaneously or as a result of treatment. Curiously, the dystonia occurs at both peak and trough dopamine levels.
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PMID:The neurophysiology of dystonia. 960 16

The most common types of levodopa-induced dyskinesias in patients with Parkinson's disease (PD) are chorea and dystonia, and often the two types are intermixed. Myoclonus is a far less common problem. The dyskinesias tend to develop over time, not usually being encountered at the initiation of levodopa therapy. Eventually, they affect more than 50% of patients on long-term levodopa treatment. Once they appear, they are difficult to eliminate. Substituting weaker dopaminergic agents for levodopa often fails to eliminate the dyskinesias. Most of the dyskinesias occur at the time of the highest brain concentration of levodopa and its product, dopamine--so-called peak-dose dyskinesias. Chorea and dystonia, usually in the legs, occur less commonly at the beginning and end of dosing, and these are called diphasic dyskinesias. Dystonia can also occur during the 'off' state, i.e. when the levodopa concentration is low. These 'off' dystonias are often painful and must be distinguished from peak-dose dystonia and from dystonia that may be a feature of PD itself.
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PMID:The spectrum of levodopa-induced dyskinesias. 1076 27

We studied the clinical features, laboratory investigation, management and natural history of a cohort of patients with Juvenile Parkinsonism (JP), seen at a tertiary referral centre. JP was defined as Parkinsonism with onset at age 20 years or less. Six patients (five male, one female) entered the study. The mean age at onset of Parkinsonism was 12.5 years (range 7-19) and the mean follow-up time was 49.3 months (range 40-57). Bradykinesia, rigidity, and postural instability were observed in all patients and five subjects had tremor. Dystonia was present in four subjects. Other clinical features were dementia (five subjects), supranuclear ophthalmoparesis (five subjects), seizures (three subjects), multifocal myoclonus (one subject), decreased deep reflexes (one subject), pyramidal signs (one subject). Family history of Parkinson's disease (PD) was positive in one subject. Work-up for Wilson's disease was negative in all patients. Neuroimaging studies showed cortical atrophy in two subjects and mild brainstem atrophy in two others. Sea-blue histiocytes were found in one subject. L-dopa improved the Parkinsonism in all subjects but four rapidly developed fluctuations and dyskinesias, requiring, in one, stereotaxic surgery. After a mean disease duration of 6.5 years, five subjects require assistance for performance of all daily activities. JP is a heterogeneous clinical entity. In the majority of patients, no underlying cause is identified. The unusual clinical features suggest most subjects have a CNS degenerative disease distinct from PD. There is, however, evidence suggesting that PD may rarely cause JP. Gangliosidosis is another cause of L-dopa-responsive JP. Regardless of the cause, in the present study JP displays an aggressive and rapidly progressive course in most patients.
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PMID:Juvenile parkinsonism: a heterogeneous entity. 1105 29

We assessed the oropharyngeal swallowing ability in 8 patients with Parkinson's disease (PD), 8 patients with progressive supranuclear palsy (PSP), and 10 age-matched healthy controls (CTL) using videofluorography (VF). In VF studies, PD and PSP patients demonstrated food pooling on the tongue, difficulty in bolus formation, and bolus falling into pharynx before swallow. PSP patients had a significantly longer delay in the pharyngeal phase and showed food falling into larynx more often than PD patients (p < 0.05). On measurement of swallowing time periods as proposed by Robbins et al., both patient groups showed significantly longer periods during many swallowing phases (P < 0.05) compared to those in the control group, but there were no significant differences between the PD and PSP groups. However, in PSP patients, the time for "transferring the food bolus from the oral cavity to pharynx" which we defined as a distinct stage was significantly longer (p < 0.05) than that in the PD group. We think that the difference in dysphagia characteristics between the two diseases arises from the variations in pathological changes in PSP, including those in the cerebral cortex, cerebellum, pons and medulla tegmentum in addition to the basal ganglia. Dystonia in the neck muscle also plays a role in dysphagia in PSP patients. Levodopa medication, changing the form of foods and training in rehabilitation techniques such as the chin down posture, supraglottic swallowing and ice-massage of the oral region are probably effective for dysphagia in PD patients. In patients with PSP, there are few research reports about the treatment of dysphagia. However, several dysphagia treatments seem to be useful depending on the abnormal patterns in the VF. Further studies are necessary to establish more effective treatments for dysphagia in PD and PSP.
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PMID:[An assessment of dysphagia using videofluorography in Parkinson's disease and progressive supranuclear palsy]. 1133 86

Parkinsonism and dystonia may coexist in a number of neurodegenerative, genetic, toxic, and metabolic disorders and as a result of structural lesions in the basal ganglia. Parkinson's disease (PD) and the 'Parkinson-plus' syndromes (PPS) account for the majority of patients with the parkinsonism-dystonia combination. Dystonia, particularly when it involves the foot, may be the presenting sign of PD or PPS and these disorders should be suspected when adults present with isolated foot dystonia. Young age, female gender, and long disease duration are risk factors for PD-related dystonia, but dystonia in patients with PD is usually related to levodopa therapy. The mechanism of dystonia in PD is not well understood and the management is often challenging because levodopa and other dopaminergic agents may either improve or worsen dystonia. Other therapeutic strategies include oral medications (baclofen, anticholinergics and benzodiazepines), local injections of botulinum toxin, intrathecal baclofen, and surgical lesions or high frequency stimulation of the thalamus, globus pallidus, or subthalamus.
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PMID:Dystonia and parkinsonism. 1148 76

Fourteen patients with "dystonic clenched fist" (three with Corticobasal Ganglionic Degeneration, seven with Parkinson's disease, and four with Dystonic-Complex Regional Pain Syndrome) were treated with botulinum toxin A (BTXA, Dysport). The muscles involved were identified by the hand posture and EMG activity recorded at rest and during active and passive flexion/extension movements of the finger and wrist. EMG was useful in distinguishing between muscle contraction and underlying contractures and to determine the dosage of BTX. All patients had some degree of flexion at the proximal metacarpophalangeal joints and required injections into the lumbricals. The response in patients depended on the severity of the deformity and the degree of contracture. All patients had significant benefit to pain, with accompanying muscle relaxation, and palmar infection, when present, was eradicated. Four patients with Parkinson's disease and one patient with Dystonia-Complex Regional Pain Syndrome obtained functional benefit.
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PMID:Treatment of dystonic clenched fist with botulinum toxin. 1174 21


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