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)

In 1954, when he was five years old, a patient suffered from encephalitis with a prolonged lethargic state. Following this episode, he presented a severe parkinsonian syndrome which was associated, after a few years, with an axial dystonia and stereotyped involuntary movements of the upper limbs. These abnormal movements were particular by their coordinated appearance, their rhythmicity and their relative slowness. Treatment with L-dopa suppressed all akinetic, dystonic and dyskinetic symptoms. At age of 40 years, all the akinetic, dystonic and dyskinetic symptoms reappeared after drug withdrawal. Cerebral computed tomography, magnetic resonance imaging and fluorodeoxyglucose positron emission tomography were normal. Fluorodopa positron emission tomography revealed a significant bilateral reduction of tracer accumulation in the posterior part of both putamen, similar to that observed in patients with idiopathic Parkinson's disease. In this patient, pharmacological tests revealed that effectiveness of L-dopa was abolished by administration of a D2 antagonist, and was fully reproduced by a D2 agonist. Clinical signs, pharmacological data and past-medical history strongly suggested a limited lesion of the zona compacta of substantia nigra induced by viral agression. This complex and progressive extrapyramidal syndrome had strong similarities with the lethargic encephalitis of Von Economo and its late symptoms. Other diseases associating akinesia and dyskinesia or dystonic phenomena, like dopa-sensitive dystonia and juvenile Parkinson's disease, are very unlikely. Thus, the persistance of sporadic forms of Von Economo's encephalitis could be discussed.
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PMID:[Parkinsonian syndrome and post-encephalitic stereotyped involuntary movements responsive to L-dopa]. 876 55

Progressive supranuclear palsy (PSP) is a distinct clinicopathological syndrome described by Steele, Richardson and Olszewski in 1964. Its clinical features include supranuclear ophthalmoplegia, pseudobulbar palsy, dysarthria, nuchal dystonia, and dementia. The neuropathological changes are characteristic and include cell loss, gliosis, and neurofibrillary degeneration in the basal ganglia, brain stem and cerebellum. But, all these clinical features are not present in the early stage and diagnosis of PSP is sometimes difficult. Atypical presentation of PSP includes the case without ophthalmoplegia, with markedly dementia, or pure akinesia. Pure akinesia presents freezing of gait, handwriting and speech without rigidity or tremor, and can be the initial and early symptom-complex of PSP.
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PMID:[Progressive supranuclear palsy]. 901 35

We report the clinicopathological features of 203 cases of pathologically proven multiple system atrophy (MSA) from 108 publications up to February 1995. The majority of patients showed symptoms in their early fifties, and men were more commonly affected than women (ratio of 1.3:1). Most patients suffered from some degree of autonomic failure (74%). Parkinsonism was the most common motor disorder (87%), followed by cerebellar ataxia (54%) and pyramidal signs (49%). The response to levodopa was poor in most patients, but there was a subgroup with a good response, who also often developed axial levodopa-induced dyskinesias. Other characteristic features included severe dysarthria, stridor, and, in a few patients, contractures and dystonia (antecollis). Mild or moderate intellectual impairment occurred in some cases, but severe dementing illness was most unusual. The main pathological change comprised cell loss and gliosis in the putamen, caudate nucleus, external pallidum, substantia nigra, locus ceruleus, inferior olives, pontine nuclei, cerebellar Purkinje cells, and intermediolateral cell columns of the spinal cord. However, other neuronal populations were also involved to varying degrees, such as the thalamus, vestibular nucleus, dorsal vagal nucleus, corticospinal tracts, and anterior horn cells. Characteristic glial and/or neuronal cytoplasmic inclusions were identified in all cases in which they were sought, irrespective of clinical presentation. Akinesia correlated with the degree of nigral and putaminal cell loss, whereas rigidity was related only to the later. Tremor was unrelated to cell loss at any site. Ataxia correlated with the degree of olivopontocerebellar atrophy. Pyramidal signs were associated with pyramidal tract pallor. Our analysis also confirmed an association of postural hypotension with intermediolateral cell column degeneration.
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PMID:Multiple system atrophy: a review of 203 pathologically proven cases. 908 71

Inhibitory control of basal ganglia output to thalamocortical projection plays an important role in normal cortical activity in the current model of the basal ganglia motor circuit. Hypokinetic and hyperkinetic movement disorders of basal ganglia origin can be explained by excess or collapse of the basal ganglia output. An abundance of evidence indicates that parkinsonian akinesia results from hyperactivity of the basal ganglia output. Reversal of akinesia by lesions of the internal division of the globus pallidus (GPi) or its excitatory source, the subthalamic nucleus, agrees with this pathological schema. Ballism associated with subthalamic lesions, and dopa-induced dyskinesia are regarded as hyperkinetic disorders resulting from suppressed subthalamopallidal projection. Decreased firing rate in GPi was reported in both disorders. However, pallidotomy has recently been postulated to abolish both ballism and dopa-induced dyskinesia. A possible mechanism for the effect of GPi destruction in these hyperkinetic disorders may be blockade of the generation or conduction of phasic neuronal activities driving choreic movements. Symptomatologically, dystonia has aspects of both hypokinetic and hyperkinetic disorders. Overactivity of the premotor cortices, which receive projections from the basal ganglia via the ventral thalamus, was found both at rest and on movement in idiopathic dystonia. This abnormal cortical activity may arise from underactivity of basal ganglia output; however, the amelioration of dystonia with pallidotomy suggests a complex pathomechanism of the pallidothalamic system in dystonia.
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PMID:[Pathophysiology of involuntary movements in adults]. 914 23

We studied the clinical features and molecular genetics of a family, afflicted with a form of atypical parkinsonism, originating from the Madeira Islands of Portugal. We examined four affected individuals and reviewed clinical information on one other affected family member. Mean age at onset was 31 years. Parkinsonism (akinesia, rigidity, gait disturbance) was the most prominent feature in advanced disease. Levodopa responsiveness with peak-dose dyskinesia was present in one individual. Initial symptoms and other clinical features were variable and included other extrapyramidal signs (dystonia, action tremor of the limbs and bulbar muscles, synkinesis), ophthalmologic abnormalities (ptosis, slow saccades, progressive external ophthalmoplegia, hypometric saccades, saccadic pursuit movements), speech abnormalities (dysarthria, hypernasality), cortical impairment (dementia, frontal lobe dysfunction, palilalia, perseveration), minor cerebellar signs (dysmetria, gait ataxia), pyramidal abnormalities (spasticity, hyperreflexia), and peripheral nervous system abnormalities (propioceptive loss, areflexia, distal weakness, atrophy). The length of trinucleotide repeats in the MJD1 gene was in the normal range for all affected individuals.
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PMID:Atypical parkinsonism in a family of Portuguese ancestry: absence of CAG repeat expansion in the MJD1 gene. 915 59

Since 1992 there has been renewed interest in pallidotomy now that the limitations and adverse effects of long-term dopaminergic therapy have become more apparent and more difficult to control in patients with advanced Parkinson's disease. The authors describe the effect of pallidotomy in 19 patients, sixteen of whom had advanced Parkinson's disease with painful dystonia and/or response fluctuations with severe akinesia while in "off" and dyskinesias while in "on". One patient had cortico-basal degeneration with rigidity, one patient had secondary dystonia and one had dystonic posturing due to Wilson's disease. Fifteen patients underwent unilateral pallidotomy, four patients had a staged bilateral procedure. Follow-up ranged from 3 to 42 months (mean 18 months). All patients with peak-dose dyskinesias and/or dystonia had marked reduction of symptoms, including the cases of Wilson's disease and secondary dystonia. The akinesia and rigidity scores of Parkinson-patients in "off" were greatly reduced, mainly but not only on the contralateral side. Evaluation by the patients showed remarkable improvement of symptoms in 79%, leading to substantially improved functional abilities in 68%. In this series the decrease in dopamine-response fluctuations, dystonia, hypokinesia and rigidity with functional improvement as judged by examiners and patients reflect a significant regain of independence.
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PMID:Posteroventral pallidotomy in movement disorders. 923 7

This is a multicentric double blind comparison of the effects of standard and slow release levodopa + carbidopa formulations in patients with Parkinson's disease. Sixty four patients with simple fluctuations were included and 43 finished the study. The study had three phases: a) optimal dose findings phase with standard levodopa + carbidopa; b) open label, cross over study with the two formulations, and c) double blind, parallel investigation. The following results were obtained. There was not a difference in the severity of disability according to UPDRS, part 3, scores though the subjective impressions of patients were in favor of standard formulations. The Sustained release levodopa + carbidopa produced significant improvement of dystonia in off period, pain due to akinesia in off and the number of hours in off and the quality and latency of sleep. In addition there was a tendency in favor of slow release compounds for early morning akinesia, global effect and impression of the examining physician. Low protein diet improved the kinetics of levodopa and the clinical response with both formulations. The clinical usefulness of standard and slow release levodopa + carbidopa formulation should be weighted according to individual problems of patients with Parkinson's disease.
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PMID:[The effect of controlled release of DOPA and carbidopa on clinical response and plasma pharmacokinetics of DOPA in parkinsonian patients]. 923 23

The pathophysiology of akinesia and chorea involve disruption of the motor basal ganglia circuit. This circuit begins with cortical output to the striatum, followed by projections from striatum to pallidum, pallidum to thalamus, and finally thalamus to cortex. Abnormal thalamic output to the frontal cortex, particularly the supplementary motor cortex, is responsible for chorea and akinesia. The substantia nigra and subthalamic nucleus are also important parts of this circuit. Chemical or pathological changes in these nuclei that lead to reduced thalamic outflow to the cortex are associated with parkinsonism. Most disorders affect the nigrostriatal dopaminergic projection. The overall consequence of loss of nigrostriatal dopamine is a loss of inhibitory input to the striatum. This feeds through the circuit resulting in reduced thalamic outflow. Local factors that may affect symptoms are the degree of dopamine loss, the involvement of ventral or dorsal parts of substantia nigra, effect on direct and indirect pallidal pathways, topographical representation of the body in the striatum, and the presence of parallel basal ganglia circuits serving cognition and mood. Ageing, dopa-responsive dystonia, juvenile dystonia-Parkinson syndrome and Parkinson's disease have different effects on the nigrostriatal tract. In Parkinson's disease the speed and regional variation in nigrostriatal dopamine loss are associated with a significant pre-symptomatic period, steady rate of progression and a particular topography of L-dopa dyskinesias.
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PMID:Functional neuropathology in Parkinson's disease. 938 99

A 56-year-old woman was admitted because of chronic postural reflex disorder. A cerebral MRI revealed symmetrical high intensity area mainly in the globus pallidus on T1-weighted image. The symptom became manifested as gait disturbance from the age of 2 and gradually progressed. Her condition has, however, remained stable since the age of 26. The only sign of parkinsonism was akinesia. There was clear retropulsion but cerebellar ataxia was minimal, and dystonia was negligible. She had no dementia. Her parents were cousins and similar symptoms and high intensity area were found in one of her sisters. Routine liver function tests were normal, with only ICG elevated. Serum copper and ceruloplasmin were normal. A hereditary factor was suspected. There are no similar cases reported in the literature, thus we thought it worth reporting.
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PMID:[A familial case of postural reflex disorder presenting high intensity area mainly in the globus pallidus on T1-weighted cerebral MRI without clear liver damage]. 939 63

Progressive supranuclear paly (PSP) was firstly reported by Steel in 1964. This condition was separated from Parkinsonism by both clinical symptoms and neuropathological findings. Recently, in an attempt to improve diagnostic accuracy to give appropriate informed concepts and to select correct cases for drug studies or other research purpose, diagnostic criteria for PSP have been developed. PSP begins in the presenile period and duration of illness is 5.9 years (1.2-10.3 years; Maher and Lees, 1986). Cardinal clinical symptoms of PSP are supranuclear gaze palsy, neck dystonia, parkinsonism, pseudobulbar palsy, gait imbalance with frequent falls and subcortical dementia. Supranuclear gaze palsy and bradykinesia are essential for diagnosis. MR-imaging of PSP shows dilatation of the third ventricle. Other laboratory examinations show no specific findings. Neuropathologically, marked dilation of the third ventricle and volume loss of periaqueductal area of the midbrain are noted in macroscopic view. Microscopical examination reveals neuronal loss and gliosis in the tegmentum, the tectum, periaqueductal gray, the dentate-rubro-pallido-luysial area, and the inferior olivary nucleus. Neuropathological hallmarks of PSP are neuronal loss, presence of the globose typed neurofibrillary degeneration, and glial tangles (so called tuft shaped astrocyte and coiled body). Atypical cases of PSP are reported. Such cases are reported as pure akinesia, PSP without ophthalmoplegia, dementia predominant PSP, pathologically diagnosed pallido-nigro-luysial atrophy (PNLA), pathologically diagnosed corticobasal degeneration which showed no laterality, and so on. Reported cases as pure akinesia was diagnosed as PSP or PNLA by neuropathological findings. Improvement of diagnostic accuracy in PSP is expected to ithrapeutic trials, to investigate the etiology, and to separate the other clinical entity from PSP.
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PMID:[Progressive supranuclear palsy]. 957 67


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