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)

The "off" painful dystonia (OPD), usually concerning the feet, is a type of abnormal involuntary movement, induced by the chronic use of levodopa. It is mostly observed in the advanced stage of Parkinson's disease (PD), particularly in the early morning, in the evening, and late at night. Indeed, some patients have experienced OPD also during "on" periods when dystonic posture of the foot alternates with dyskinesia. The pain probably is due to sustained muscle contraction, which causes prolonged muscle spasm, as in primary dystonia or torticollis. Dopaminergic drugs like bromocriptine, pergolide, and especially apomorphine (s.c. infusions, or bolus), can dramatically improve the OPD. Anticholinergics baclofen and lithium are alos used in the management of OPD with some benefit. On the other hand, clinical experience shows that in many cases, these therapeutic procedures are not always enough to produce the expected results. Thirty PD patients (22 men and eight women) with OPD of the foot were treated with botulinum toxin (Botox, Btx) using electromyograms to guide injections. Dystonia was evaluated using a quantitative rating scale. The selection of the muscles for Btx treatment was carried out on the basis of foot posture. We injected Btx into tibialis posterior, tibialis anterior, gastrocnemius, flexor digitorum longus, and extensores hallucis longus with a median dose 40 IU for each muscle, distributed in two sites. In all patients, the pain improved within 10 days, whereas in 21 patients, the pain disappeared completely for 4 months (range, 3-7 months); a concomitant improvement in intensity of the dystonic spasm was also observed. No side effects were reported. Seven patients with associated "on" foot dystonia described an improvement of foot posture on walking. In conclusion, in this uncontrolled study, the use of Btx in OPD seemed a promising tool to improve pain linked to foot dystonia; however, because of the well-known underlying dopaminergic defect in OPD, the Btx therapy should be considered only if the dopaminergic treatment established for the management of OPD has failed.
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PMID:"Off" painful dystonia in Parkinson's disease treated with botulinum toxin. 765 52

28 patients suffering from idiopathic Parkinson's disease received subcutaneous apomorphine for the treatment of painful dystonia and of off-phases of long duration. After a mean period of 12.4 months 20 patients still used apomorphine. In this time the mean dose per injection had fallen from 2.5 mg to 2.1 mg and the mean number of daily applications from 2.6 to 2.2. Most patients considered dystonias and off-phases to respond satisfactorily to apomorphine. However, in most cases the treatment effect was impaired by side effects, especially nausea.
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PMID:[Apomorphine as adjuvant treatment in idiopathic Parkinson syndrome]. 770 89

An increasing number of neurodegenerative diseases seem to be associated with or even due to disturbances of cerebral energy metabolism. One generally accepted example is complex I deficiency in substantia nigra from patients with Parkinson's disease. Reports on a complex I defect in platelets from patients with dystonia led us to check for disturbances of the respiratory chain or of the mitochondrial genome in isolated mitochondria from patients with focal or generalized dystonia. We could not confirm the idea of mitochondrial disturbance in platelets from patients with dystonia because we did not find abnormal enzyme activities or any deletions of the mitochondrial genome. Thus, we do not think that blood cells such as platelets can serve as markers for neurodegenerative disorders such as dystonia.
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PMID:Respiratory chain and mitochondrial deoxyribonucleic acid in blood cells from patients with focal and generalized dystonia. 784 98

We describe 16 patients with Parkinson's disease seen during a 6-month period because of aggravation related to the recent introduction of a levodopa/carbidopa controlled-release (CR) preparation, either in combination with or substituting for the standard levodopa preparations. Disease duration was longer than 5 years (mean 8.4 +/- 5.9 years) in most cases at the time the CR preparation was introduced, and the patients were suffering from either severe late levodopa syndrome or progression in disability. For 9 out of 14 patients the CR formula had replaced the older preparation overnight. Though patients often accumulated multiple side-effects, we were able to identify 3 subgroups based on the main problem developing after the CR preparation had been introduced: a) apparent acceleration of the course of disease in patients in advanced stages, even if their response to treatment was otherwise stable (n = 4); b) subacute onset or aggravation of dyskinesias or painful "off"-period dystonia that often prompted reevaluation of the patient (n = 4); c) deterioration of akinetic "off" periods in patients already experiencing response fluctuations (n = 5) or appearance of dose failures in patients who had so far been enjoying stable responses (n = 3). These problems appeared in spite of a significant increase (p = 0.046) in total levodopa daily dose even though there were no differences (p = 0.685) in dose frequency between the CR preparation and standard levodopa.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Aggravation of Parkinson's disease after inadequate use of levodopa in controlled-release preparations]. 789 19

The Steel-Richardson-Olszewski syndrome (progressive supranuclear palsy: PSP) was described over a quarter of a century age. Although the full expressed form is very typical, it is overlooked due to unusual ways without axial dystonia and opthalmic signs, with akinesia and dysequilibrium. The many reports of PSP suggested that the abnormalities of it were vaster than Parkinson's disease. The abnormalities of neurotransmitters or neuromodulators were found not only dopamine system but also serotonin and acetylcholine system. On the basis of them, the various trials of neurotransmitter replacement were done without very successful results so far. Transplantation and nerve growth factor are also tried to treat PSP now.
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PMID:[Steele-Richardson-Olszewski syndrome]. 790 88

We report the first neuropathological and neurochemical study of a patient with dopa-responsive dystonia. She had onset of foot dystonia at age 5 years and by age 8 years it was generalized with prominent right leg and arm involvement. On levodopa 750 mg daily she had complete symptomatic improvement that was sustained for 11 years until death. Pathological studies revealed normal numbers of hypopigmented substantia nigra neurons, normal tyrosine hydroxylase (TH) immunoreactivity and TH protein in the SN, no inclusion bodies or gliosis, and no evidence of a degenerative process in the striatum. Biochemical studies revealed reduced dopamine in the substantia nigra and striatum (8% in the putamen and 18% of control in the caudate) with a similar but not identical subregional distribution as in idiopathic Parkinson's disease. In the striatum, TH protein and TH activity was reduced, with the loss more pronounced in the putamen than the caudate. The GBR 12935 binding to DA transporter was normal in the caudate and at the lower end of the range of control values in the putamen. We conclude that disturbed dopamine synthetic capacity or a reduced arborization of striatal dopamine terminals may be the major disturbance in dopa-responsive dystonia.
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PMID:Dopa-responsive dystonia: pathological and biochemical observations in a case. 815 63

Twenty index patients with hereditary essential tremor and their kindreds were studied to define the phenotype of this condition. Ninety-three first degree and 38 more distant relatives were examined; 53 definite and 18 possible secondary cases were identified. The age of tremor onset was bimodally distributed with a median at approximately 15 years. Segregation analysis indicated autosomal dominant inheritance and penetrance was virtually complete by the age of 65 years. There were no examples of the disease skipping a generation. Men and women were affected in equal proportions. About 50% of cases were alcohol responsive. In the majority of families alcohol responsiveness was either consistently present or did not occur, but in 20% of kindreds definite heterogeneity of responsiveness was encountered within each family. The typical phenotype was a mild symmetrical postural tremor of the upper limbs. Tremor of the legs, head, facial muscles, voice, jaw and tongue occurred but never in isolation and rest, task specific (e.g. primary writing tremor) and primary orthostatic tremors were not found. Head tremor was invariably mild and 75% was of a 'no-no' type. Dystonia (e.g. torticollis and writer's cramp) were not encountered, a finding which strongly suggests that many previous studies of 'essential tremor' were contaminated by cases of idiopathic or hereditary torsion dystonia. No association with Parkinson's disease was found but classical migraine occurred in approximately 26% of cases and co-segregated with tremor. The severity of arm tremor (assessed using a clinical rating scale and by scoring tremor in Archimedes spirals) and disability increased with advancing age and increasing tremor duration, but there was no correlation between age at tremor onset and either tremor severity or disability. Men and women were affected with equal severity. The sex of the affected parent had no influence on the severity of tremor or the degree of disability experienced by an affected child. Disability commenced in the second decade and progressively increased. All the index patients and 59% of the definite secondary cases had tremor induced disabilities. Eighty-five percent of index patients and 38% of secondary cases also reported some degree of social handicap. Twenty-five percent of index patients and 12% of secondary cases had been compelled to change jobs or retire. Biological fitness was normal.
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PMID:A study of hereditary essential tremor. 792 67

Parkinsonian symptoms and levodopa-induced dyskinesias (LIDs) are often considered to occur first, and to predominate, in the upper limbs. We studied the topography, type, sequence, and severity of LIDs in 20 consecutive patients with Parkinson's disease (PD) experiencing LIDs for less than 6 months (Hoehn and Yahr stage II-III; average age at onset of PD, 57 years; average duration of PD, 7.2 years; percent of improvement with levodopa > 50) and compared them with the initial site, form, and evolution of the patient's motor disability. Parkinsonism started in the foot in six of 20 patients. Motor disability in the "off" state was similar in upper and lower extremities, except for akinesia, which was worse in the lower limbs. A careful interview indicated that LIDs had started in the foot in all patients. After administration of a single dose of levodopa ("levodopa test"), LIDs appeared in all patients as dystonia of the foot homolateral to the side most affected by PD (onset-of-dose dyskinesia). LIDs were preceded by "off" dystonia (dystonic foot) in six patients and were followed by mid-dose dyskinesia in eight. This is consistent with an early loss of dopaminergic innervation corresponding somatotopically to the foot area. The similarities among initial LIDs, early morning dystonia, and onset-of-dose dyskinesia suggest a similar pathophysiology.
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PMID:Do parkinsonian symptoms and levodopa-induced dyskinesias start in the foot? 793 84

A major theory regarding the mechanism of neuronal degeneration in several movement disorders is that mitochondrial defects may play a role. Biochemical studies in Parkinson's disease, Huntington's disease, multiple system atrophy, and idiopathic dystonia have shown defects in enzymes of oxidative phosphorylation in postmortem brain tissue, platelets, muscle, or lymphocytes. The basal ganglia and substantia nigra are also particularly susceptible to the accumulation of age-dependent mitochondrial DNA deletions, which may contribute to the delayed onset of movement disorders. The 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine model of Parkinson's disease involves conversion to 1-methyl-4-phenylpyridinium, which then inhibits complex I of the electron transport chain. Our studies show that the complex II inhibitor 3-nitropropionic acid can closely replicate the neurochemical, histologic, and clinical features of Huntington's disease. The mechanism of neuronal death in both these models may be slow excitotoxicity. Both direct biochemical studies and animal models of movement disorders therefore suggest that mitochondrial dysfunction may play a direct role in their pathogenesis.
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PMID:Mitochondrial dysfunction in movement disorders. 795 42

Progressive supranuclear palsy (PSP) is characterized clinically by supranuclear gaze palsy, neck dystonia, parkinsonism, pseudobulbar palsy, gait imbalance with frequent falls and frontal lobe-type dementia. In the advanced typical case, when supranuclear gaze palsy and other main features are present diagnosis is relatively easy. Diagnostic problems, though, are frequent in the early stages due to the variable clinical presentation and in those atypical cases in which gaze palsy does not develop or that present as a severe dementia disorder or as an isolated akinetic-rigid syndrome. In this review we summarize the clinical features of PSP and emphasize those aspects helpful in the differential diagnosis with Parkinson's disease and other motor and cognitive disorders that can pose difficult diagnostic problems. Clinical diagnostic criteria are also discussed and modifications of those currently in used are proposed.
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PMID:Clinical diagnosis and diagnostic criteria of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome). 796 84


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