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

The concentrations of 11 amino acids, including the neurotransmitters gamma-aminobutyric acid, glutamate, aspartate, glycine, and taurine, were determined by HPLC in 12 brain regions of genetically dystonic (dtSZ) hamsters and age-matched nondystonic controls. Since dystonia in mutant dtSZ hamsters is transient and disappears after about 70 days of age, amino acids were determined at the age of maximum severity of dystonia (30-40 days) and after disappearance of the disease, to examine which neurochemical changes were related to dystonia. In dtSZ hamsters with the maximum severity of dystonia, significant changes in concentrations of the neurotransmitters gamma-aminobutyric acid, glutamate, aspartate, and taurine were found in several regions involved in motor functions, e.g., cerebellum, thalamus, and corpus striatum. Most of these changes were not permanent but disappeared in parallel with dystonia, implicating a causal relationship between altered aminoacidergic neurotransmission and dystonia in mutant dtSZ hamsters.
 ...
PMID:Abnormalities in amino acid neurotransmitters in discrete brain regions of genetically dystonic hamsters. 135 2

A 13-year-old boy was the victim of attempted strangulation. His condition had returned to normal by the sixth day after the assault; however, from the seventh day, choreoathetosis, dystonia, and marked pseudobulbar paralysis developed in the boy. The computed tomographic scans and T2-weighted magnetic resonance images that were obtained at this time revealed low-density and high-signal intensities in the region of the bilateral putamen and caudate nucleus. These symptoms and the changes in his computed tomographic scans and magnetic resonance images subsided gradually during a 2-month period. Sequential analysis of the cerebrospinal fluid for gamma-aminobutyric acid and dopamine concentrations during his illness revealed reciprocal changes with normal recovery. Because of the delayed onset of neurological changes and the cerebrospinal fluid showing reversible symptoms, the delayed encephalopathy after strangulation had been related to the biochemical alterations that followed anoxia in the vulnerable basal ganglia.
 ...
PMID:Delayed postanoxic encephalopathy after strangulation. Serial neuroradiological and neurochemical studies. 189 66

We performed a neurochemical study of the brain of two unrelated patients, living in different continents, with neuroacanthocytosis. The levels of monoamines and their metabolites, gamma-aminobutyric acid and substance P, were measured in several brain areas and the monoamine metabolites in cerebrospinal fluid. The binding of 3H-spiperone to striatal membranes and to lymphocytes was also measured. Both patients had a progressive neurological disorder with onset in the third decade of life and characterized by a complex movement disorder, epilepsy, muscular wasting, and changes in behavior. The movement disorder initially manifested with oromandibular dystonia and limb chorea, but at the time of death was characterized by a severe dystonic syndrome. The chemical changes were similar in the two patients. The most important neurochemical findings were a depletion of dopamine and its metabolites in most brain areas, most notably in the striatum, and elevation of norepinephrine levels in the putamen and globus pallidus. Substance P was markedly reduced in the striatum and substantia nigra. Our findings may provide clues to the neurochemical mechanisms underlying dystonia.
 ...
PMID:Neurochemical findings in neuroacanthocytosis. 290 27

The use of baclofen, a structural analog of gamma-aminobutyric acid (GABA), is described in the treatment of a patient with tardive dystonia. The patient, a woman with a clinical diagnosis of Alzheimer's disease, developed tardive dystonia after 8 weeks of haloperidol therapy and experienced complete remission of her dystonia while taking baclofen 60 mg/day. This case suggests that baclofen may facilitate remission of tardive dystonia in some cases and provides a basis for further investigation.
 ...
PMID:Baclofen treatment in a patient with tardive dystonia. 374 31

Free amino acid concentrations were measured by conventional amino acid analysis, and gamma-aminobutyric acid (GABA) concentrations were determined, by an ion-exchange fluorometric technique, in CSF specimens from 16 patients with torsion dystonias and in CSF from a large number of control subjects. The mean CSF GABA concentration of the dystonia patients (97 +/- 11 nmol/L) did not differ significantly from the means for CSF GABA in two groups of adult control subjects. Mean concentrations of all commonly determined amino compounds were normal in the CSF of torsion dystonia patients, except for ornithine, which was modestly but significantly reduced.
 ...
PMID:Concentrations of GABA and other amino acids in CSF from torsion dystonia patients. 711 89

Recent findings of antidystonic effects of NMDA and non-NMDA receptor antagonists in an inbred line of Syrian hamsters with primary generalized dystonia prompted us to investigate the effects of lamotrigine, an inhibitor of veratrine-induced glutamate release, on the severity of dystonia in mutant hamsters. In mutant dystonic hamsters the dystonic attacks which can be induced by mild environmental stimuli or handling are age-dependent with maximum severity between days 30 and 40 of life (maximum period). Thereafter the severity of dystonia slowly declines (post-maximum period) until the susceptibility to induction of dystonia disappears completely at an age of about 70 days. Lamotrigine (5.0, 10.0 or 30.0 mg/kg i.p.) dose dependently decreased the latency to onset of dystonic attacks. Furthermore, at a dose of 30 mg/kg the dystonic attacks were aggravated when lamotrigine was administered during the max and post-max period. Even in mutant hamsters older than 70 days, i.e. after spontaneous remission of dystonia, and in an inbred line of non-dystonic Syrian hamsters with genetic origin similar to the mutant hamsters, lamotrigine (10.0 or 30.0 mg/kg i.p. and 30.0 mg/kg p.o.) provoked dystonic disturbances. In a genetically different outbred line of Syrian hamsters, lamotrigine did not cause dystonic movements. The unexpected finding that lamotrigine exerts prodystonic effects in genetically susceptible hamsters may be due to the lack of selectivity of lamotrigine to block glutamate release. Tentatively, simultaneous inhibition of GABA (gamma-aminobutyric acid) release might be critically involved in the prodystonic activity of lamotrigine.
 ...
PMID:The novel antiepileptic drug, lamotrigine, exerts prodystonic effects in a mutant hamster model of generalized dystonia. 769 75

Attacks of sustained dystonia of the limbs and trunk can be initiated by handling or mild environmental stimuli (e.g. new cage) in mutant (gene symbol dtsz) Syrian golden hamsters. The severity of the dystonic syndrome in these mutant hamsters is age-dependent, with a peak at weaning (21 days of age) and a second peak at about 30-40 days of age. Spontaneous remission occurs at an age of about 70 days. The syndrome in hamsters is thus similar to transient paroxysmal dystonia in children. In the present experiments, it was examined whether dystonic hamsters exhibit age-dependent differences in susceptibility to drugs which affect GABA (gamma-aminobutyrate)ergic, glutamatergic or dopaminergic functions. After acute administration, the GABA-elevating drug aminooxyacetic acid was significantly less potent in attenuating the severity of dystonic attacks at 21 days than at 31 days of age. Similar but less marked age-dependent differences in antidystonic activity were found for phenobarbital and diazepam. In contrast to these GABAmimetic drugs, the NMDA receptor antagonist CGP 37849 (DL-[E]-2-amino-4-methyl-5-phosphono-3-pentenoic acid) or the dopamine receptor antagonist haloperidol had about the same antidystonic potency at both 21 and 31 days of age. Chronic treatment of dystonic hamsters with aminooxyacetic acid, starting at 21 days of age, did not alter the time course or the severity of dystonia.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Alterations in pharmacological sensitivity of GABAergic but not dopaminergic and glutamatergic systems during ontogenesis in dystonic mutant hamsters. 838 61

A large German family with "myoclonic dystonia with lightning jerks responsive to alcohol" was identified. Eleven affected pedigree members and six obligate gene carriers from five generations were identified. A description of one branch of this pedigree was published in 1964. Our examination 30 years after the initial report confirms the clinical syndrome of a nonprogressive movement disorder characterized by myoclonic jerks affecting the proximal muscles and the muscles of the trunk, accompanied by mild dystonic features in some affected family members. Segregation analysis favors autosomal dominant inheritance with high, but incomplete, penetrance in males and much lower penetrance in females. Linkage analysis was performed using simple sequence repeat polymorphisms (CA repeats) closely associated with or spanning the chromosomal regions containing 15 candidate genes: the gene for early-onset generalized torsion dystonia, DYT1 (chromosome 9q34); the genes for subunits alpha 2, beta 1, and gamma 1 (chromosome 4p12-4q13); for alpha 1, alpha 6, beta 2, and gamma 2 (chromosome 5q31.1-5q31.3); for alpha 4, alpha 5, beta 3, and gamma 3 (chromosome 15q11-15q13); for rho 1 and rho 2 (chromosome 6q14-6q21) of the gamma-aminobutyric acid A receptor; and for the alpha subunit of the glycine receptor (chromosome 5q31). By a combination of pairwise and multipoint linkage analysis, it could be excluded that any of these candidate gene-bearing chromosomal regions contain the disease gene in this family. We also excluded major portions of three chromosomal regions syntenic with mouse chromosome 3, which carries the murine beta subunit of the glycine receptor.
 ...
PMID:Linkage studies in alcohol-responsive myoclonic dystonia. 881 14

The successful use of intrathecal baclofen, a structural analogue of gamma-aminobutyric acid, is described in the treatment of a 9-year-old boy with intractable torsion dystonia, not responding to conservative treatment. To our knowledge, this is the first reported case of continuous intrathecal baclofen for hereditary torsion dystonia. This case suggests that a continuous intrathecal infusion of baclofen may facilitate remission of intractable torsion dystonia, and provides a basis for further investigation of the treatment of intractable childhood dystonia.
 ...
PMID:Intrathecal baclofen for severe torsion dystonia in a child. 882 16

Baclofen, a gamma-aminobutyric acid agonist, acts at the spinal cord level to impede the release of excitatory neurotransmitters that cause spasticity. Oral baclofen improves cerebral spasticity mildly, but its activity is limited because of its poor lipid solubility. Cerebrospinal fluid baclofen levels after intrathecal administration are many times higher than those achieved after oral administration. Continuous intrathecal baclofen infusion has been used to treat cerebral spasticity in two patient groups: in older ambulatory children with inadequate underlying leg strength, and in patients with severe spasticity in both the upper and lower extremities. Responsiveness to intrathecal baclofen is confirmed by test injections before insertion of a programmable subcutaneous pump. Continuous intrathecal baclofen infusion dosages vary from 27 to 800 micrograms/day. Continuous intrathecal baclofen infusion reduces spasticity in the upper and lower extremities, and improves upper extremity function and activities of daily living but has no effect on athetosis in the dosages used to treat spasticity. Complications related to the intrathecal catheter occur in approximately 20% of patients, and infection requiring pump removal occurs in approximately 5%. Preliminary studies indicate that continuous intrathecal baclofen infusion alleviates some forms of generalized dystonia associated with cerebral palsy.
 ...
PMID:Baclofen in the treatment of cerebral palsy. 888 81


1 2 3 4 Next >>