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 report a patient presenting at age 16 years with postural instability and falls who developed severe generalized dystonia by the age of 20 years. He was the product of a consanguineous marriage. Maternal grandfather and paternal grandmother (brother and sister) living in the Azores were both affected by Machado-Joseph disease (MJD) beginning late in life. To date neither of the patient's parents are clinically affected. Linkage studies in this family and others of Azorean descent have confirmed the recent mapping of the MJD gene to chromosome 14q. Genotyping of the members of this pedigree provides strong genetic evidence that our patient is homozygous for the MJD gene. Our results combined with experience in 2 putative homozygotes previously reported in the literature suggest that gene dosage is an important determinant of age of onset and clinical phenotype in MJD. Other possible influencing factors are discussed.
Ann Neurol 1994 Sep
PMID:Homozygous inheritance of the Machado-Joseph disease gene. 808 Feb 54

Germ-line and somatic mtDNA mutations are hypothesized to act together to shape our history and our health. Germ-line mtDNA mutations, both ancient and recent, have been associated with a variety of degenerative diseases. Mildly to moderately deleterious germ-line mutations, like neutral polymorphisms, have become established in the distant past through genetic drift but now may predispose certain individuals to late-onset degenerative diseases. As an example, a homoplasmic, Caucasian, tRNA(Gln) mutation at nucleotide pair (np) 4336 has been observed in 5% of Alzheimer disease and Parkinson disease patients and may contribute to the multifactorial etiology of these diseases. Moderately to severely deleterious germ-line mutations, on the other hand, appear repeatedly but are eliminated by selection. Hence, all extant mutations of this class are recent and associated with more devastating diseases of young adults and children. Representative of these mutations is a heteroplasmic mutation in MTND6 at np 14459 whose clinical presentations range from adult-onset blindness to pediatric dystonia and basal ganglial degeneration. To the inherited mutations are added somatic mtDNA mutations which accumulate in random arrays within stable tissues. These mutations provide a molecular clock that measures our age and may cause a progressive decline in tissue energy output that could precipitate the onset of degenerative diseases in individuals harboring inherited deleterious mutations.
Proc Natl Acad Sci U S A 1994 Sep 13
PMID:Mitochondrial DNA sequence variation in human evolution and disease. 809 Jul 16

A retrospective examination of lethargic encephalitis finds many parallels with neuroleptic effects. The encephalitis, like the neuroleptics, produced an acute continuum of cognitive disorders from emotional indifference through apathy and onto a rousable stupor. It also produced similar acute dyskinesias, including akinesia, akathisia, dystonia, oculogyric crises, and tremors. The encephalitis also caused similar chronic effects, including dementia and psychosis, and somewhat different persistent dyskinesias. The chronic motor and cognitive disorders, like those associated with the neuroleptics, were often delayed in onset. An acute, severe episode of lethargic encephalitis also finds a parallel in the neuroleptic malignant syndrome. These parallels are probably due to a common site of action in the basal ganglia. They provide a model for understanding many neuroleptic effects and alert us to the probability of persistent cognitive deficits, including dementia, from neuroleptic treatment.
Brain Cogn 1993 Sep
PMID:Parallels between neuroleptic effects and lethargic encephalitis: the production of dyskinesias and cognitive disorders. 810 24

Tardive dyskinesia (TD) has been associated with cognitive deficits, especially in older psychiatric patients on neuroleptic medication. This study investigated the relationship between presence of TD, organic brain dysfunction (OBD), and cognitive deficits in young psychiatric outpatients maintained on minimal doses of oral neuroleptics, with anticholinergics prescribed only on as-needed basis. Sixty-four patients, aged 20-39 years, were evaluated for the presence of abnormal movements, localizing and nonlocalizing physical signs, and deficits in memory, ability to shift, and sustained attention. Sixteen patients showed definite signs of TD. Significant associations were found between TD and OBD, and between cognitive deficits and OBD, but not between TD and cognitive deficits. Significant regression predictors of TD were the interaction between OBD and previous dystonia, as well as duration of neuroleptic treatment. These findings suggest that some potential risk factors for TD already identified in the literature also apply to younger patients with relatively shorter exposure to neuroleptics. However, the results indicate that the relationship between movement disorders and cognitive deficits may be more apparent in older patients.
Brain Cogn 1993 Sep
PMID:Organic brain dysfunction and cognitive deficits in young schizophrenic patients with tardive dyskinesia. 810 25

Forty-six patients with hand dystonia, considered disabling despite optimal pharmacologic therapy, were injected in the forearm musculature with botulinum A toxin. Thirty of these patients were followed long enough to provide adequate data for analysis of 86 treatment sessions. There was a 63% female preponderance, with an average age at initial evaluation of 46 years and symptom duration of 7.9 years. Average baseline severity of dystonia was rated as 3.5 on a severity rating scale (0-4 rating; 4 = maximum severity). The average peak effect response for all injections (79 into wrist flexors and 29 into wrist extensors) was 2.2 for dystonia and 3.0 for pain (0-4 rating; 0 = no response, 4 = maximum benefit). The latency from injection to onset of effect averaged 5.6 days. Total response duration averaged 9.3 weeks and maximum improvement was 7.5 weeks. Only local complications occurred and consisted primarily of hand weakness (25 patients, 44 sessions). The results show that botulinum toxin injections effectively control hand dystonia in instances where other forms of therapy have failed.
J Hand Surg Am 1993 Sep
PMID:Use of botulinum toxin in the treatment of hand dystonia. 822 64

A map comprising 16 distinct markers with heterozygosities of 0.61-0.92 for a 10-cM region of human 9q34.1 is presented. The map incorporates four genes and has a maximum intermarker interval of 2.1 cM. Markers were analyzed in the Venezuelan reference pedigrees and all were placed uniquely in the map with a minimum likelihood of 676:1. The map should prove useful in analysis of families segregating dystonia and tuberous sclerosis, as the DYT1 and TSC1 loci map within this region.
Genomics 1993 Sep
PMID:A high-resolution linkage map of human 9q34.1. 824 74

We have studied the developmental time-course of changes in the noradrenaline (NA) content of cerebellum (CE), cytoarchitecture of the cerebellar cortex, and motor abnormalities induced by the exposure of the cephalic end of rats to a single dose (5 Gy) of X-irradiation immediately after birth. At all ages examined, i.e., from postnatal (PN) d 5 to 90, CE from exposed animals show a marked atrophy, with an agranular cortex that has lost its layered structure. Purkinje cells are scattered at all depths in the cortex, and their primary dendrite is randomly oriented. The motor syndrome includes dystonia-like movements, a fine tremor, and an ataxic gait. Being progressive, the abnormal movements are evident from PN d 10, and fully developed by d 30. On the other hand, no differences in cerebellar NA content between X-irradiated rats and age-matched nonirradiated controls were detected from PN d 5 to 60. However, at PN d 90 a significant increase in NA content of CE from exposed animals is found when compared to either age-matched controls (+36%, p < 0.01), or data from irradiated rats obtained at PN d 5 to 60 (p < 0.01). These results indicate a temporal dissociation between the motor and cytoarchitectural abnormalities and the increase in cerebellar NA content produced by a single dose of X-rays at birth. The late increase in cerebellar NA content might represent a compensatory response of noradrenergic terminals to an altered information flow out of the cerebellar cortex induced by the ionizing noxa.
Mol Chem Neuropathol 1993 Sep
PMID:Motor abnormalities and changes in the noradrenaline content and the cytoarchitecture of developing cerebellum following X-irradiation at birth. 825 Oct 32

To explore the relationship between hereditary motor and sensory neuropathy (HMSN) and movement disorders, we examined 7 patients with HMSN referred to our Movement Disorders Clinic and surveyed members of the Charcot-Marie-Tooth association. The following movement disorders were observed in the index patients: postural tremor in 6, rest tremor in 3, and Parkinsonism and dystonia in 2. Tremor, present in 40% of the 201 patients who responded to the survey, was first noted at a mean age of 36 years, and mostly involved the hands. Family history of tremor was more frequent in the tremor group (P < 0.005), which also had a significantly worse writing score than the nontremor group (P < 0.001). The overlap in clinical features between HMSN-associated tremor and essential tremor (ET), the high frequency of family history of tremor, and the lack of a relationship between the severity of tremor and of peripheral neuropathy suggest that the tremor in HMSN is pathogenically related to ET.
Muscle Nerve 1993 Sep
PMID:Hereditary motor-sensory neuropathy and movement disorders. 835 21

We measured serum antibodies to botulinum toxin (ABT) in 96 patients with focal dystonia who had been treated with type A botulinum toxin. The frequency of detectable ABT was 3% (three patients). Patients with ABT had received more than 50 ng of botulinum toxin, and the shortest time between two injections was significantly less than in patients without ABT. The clinical evolution of the three patients was heterogeneous: one had decreased effectiveness with repeated injections, another had persistent improvement, and the third never responded to toxin injections.
Neurology 1993 Sep
PMID:Botulinum antibodies in dystonic patients treated with type A botulinum toxin: frequency and significance. 788 Mar 4

The clinical correlates of "pure" pallidoluysian atrophy are not well described. A 59-year-old man presented with 20 years of progressive generalized dystonia, dysarthria, gait disorder, supranuclear vertical gaze palsy, and bradykinesia. At autopsy there was severe bilateral atrophy of the external pallidum and subthalamic nucleus with neuronal loss and marked gliosis. This syndrome may epitomize the consequences of "pure" pallidoluysian atrophy. In this case, dystonia appears to occur in the setting of decreased excitation (increased inhibition) of medial pallidal neurons, a pathophysiologic condition common to several hyperkinetic states.
Neurology 1993 Sep
PMID:Pallidoluysian atrophy: dystonia and basal ganglia functional anatomy. 841 28


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