Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper reports findings relative to a simple, rapid and reproducible technique for the induction of physical dependence upon ethanol in the rat. The dependence was induced by intragastric intubation of 20% (w/v) ethanol solutions at 9-15 g/kg in 3-5 fractional doses daily for 4 days, maintaining blood ethanol concentrations above a threshold level sufficient to sustain observable sedation throughout the entire period of intubation. Two phases were distinguished during the withdrawal period: 1. Prodromal detoxication, characterized by a spectrum of signs and responses of diminishing severity, related to the decline in blood ethanol concentrations (mg/dl): death, greater than 640; coma, 780-460; loss of righting reflex, 640-400; ataxia 3-1, 570-250; sedation 340-190; neutrality, 220-130; 2. Ethanol dependence, characterized by a spectrum of withdrawal signs and reactions of progressively increasing severity as blood ehtanol concentration approached 100 mg/dl: hyperactivity, tremors, akinesia, spastic rigidity, and induced and spontaneous convulsions. A rapid sucession of two diverse clusters of signs and reactions represents a reversal of the central nervous system function from the extremes of ethanol intoxication (CNS depression) to the extremes of ethanol dependence (CNS hyperexcitability) during the withdrawal period. Both extremes may terminate in death.
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PMID:Induction of physical dependence upon ethanol and the associated behavioral changes in rats. 123 14

The akinesia induced by reserpine in mice was effectively reversed by the dopamine D1 receptor agonists SKF 38393 (5-30 mg/kg IP) and CY 208-243 (1-5 mg/kg IP), and by the mixed D1/D2 agonist pergolide (5 mg/kg SC), but less well by the D2 agonists lisuride, PHNO, LY 171555 and RU 24213 (each at 5 mg/kg SC) and not at all by the NMDA receptor antagonist MK 801 (0.1-10 mg/kg IP). MK 801 potentiated D1-dependent locomotion, but always suppressed rearing and grooming. D2-dependent locomotion was inhibited by MK 801. The D2 agonist RU 24213 was antagonised by as little as 6.25 micrograms/kg MK 801, while PHNO and LY 171555 were antagonised by 0.1 mg/kg MK 801. Lisuride was not inhibited by up to 1.6 mg/kg MK 801. Importantly, all animals showed signs of incapacitation with MK 801 in certain elements of their behaviour, most notably ataxia and hind limb abduction. Thus whilst NMDA receptor blockade can facilitate the restoration of movement by dopamine D1 (though not D2) agonists in monoamine-depleted mice, the fluency of the motor response is adversely affected.
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PMID:Motor responses to dopamine D1 and D2 agonists in the reserpine-treated mouse are affected differentially by the NMDA receptor antagonist MK 801. 153 57

The best-known example of motor deficits after cortical lesions is contralateral paresis and spasticity after damage to the precentral motor strip. After recovery the residual motor functions can be used in a purposive and skillful manner. In patients with lesions of the supplementary motor area (SMA) and cingulate gyrus transient akinesia and mutism have been described. Lesions restricted to more lateral parts of the premotor field interfere with proximal muscle function and interlimb coordination, whereas distal motor activity and bimanual coordination are unimpaired. In contrast, hand function in patients with parietal lesions is severely disturbed. This dysfunction includes deficits such as ataxia, dysmetria and postural instability that are typically observed in deafferented patients. Severe disturbances of the purposive behaviour of the hand during exploratory finger movements and manipulation of objects are seen in patients with posterior parietal lesions. Observations in human patients are compatible with the hypothesis that lesions of the frontal agranular motor fields interfere with the control of postural and force control whereas parietal lesions are associated with motor programme disorders affecting the use of the hand or the eye as a sense organ or affecting more complex motor behaviour.
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PMID:Differential effects of cortical lesions in humans. 332 19

The clinical observations in five patients, of a family of catalan origin (NE of Spain), affected with Machado-Joseph disease are reported. The pedigree showed the presence of 22 members affected (15 men, 7 women) over six generations. The symptoms and signs were variable among the patients and also variable in a same patient during the course of the disease. However, the main neurological alterations were ataxia, akinesia, distal amyotrophy, progressive external ophthalmoplegia, facial and lingual fasciculations and bulging eyes. The neuropathological examination performed in one patient disclosed degeneration of the posterior and spinocerebellar tracts in the spinal cord, marked nerve cell loss in Clarke's column and anterior horns and axonal degeneration of the peripheral nerves, in addition to nerve cell loss in the nuclei of the III, IV and VII cranial nerves and neuronal depletion in the substantia nigra. No other structures, including the striate complex and dentate nucleus, were significantly affected.
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PMID:[Machado-Joseph disease in a family of Spanish origin]. 347 47

N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a potent dopaminergic neurotoxin, was administered to cats systemically for 5 to 7 days. This treatment produced a behavioral syndrome characterized by akinesia, ataxia, bradykinesia, and feeding difficulties, lasting for several weeks. During this period of severe behavioral impairment, caudate and nucleus accumbens dopamine and norepinephrine concentrations were quite depleted. Behavioral recovery ensued over the next several weeks as did some recovery of striatal catecholamines. MPTP destroyed the majority of substantia nigra pars compacta neurons while affecting a much lesser number of locus ceruleus and ventral tegmental neurons. These results demonstrated for the first time that MPTP can cause long-lasting deficits in nigrostriatal functioning in the cat and may provide a means for studying the apparently selective neurotoxic effects of MPTP as well as for understanding the pathophysiology of Parkinson's disease.
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PMID:Production of a Parkinson-like syndrome in the cat with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): behavior, histology, and biochemistry. 348 7

We have examined 138 cases of a disorder previously described in people of Portuguese origin and which has received many names. By computer analysis of 46 different items of a standardized neurological examination carried out in each patient, we have been able to delineate the main components of the clinical presentation, to conclude that the marked variability in clinical expressions does not negate the homogeneity of the disorder, and to describe the natural history of this entity which should be called, for historical reasons, "Machado-Joseph Disease". This hereditary disease has an autosomal dominant pattern of inheritance, presenting as a progressive ataxia with external ophthalmoplegia, and should be classified within the group of "Ataxic multisystem degenerations". When the disease starts before the age of 20, it may present with marked spasticity, of a non progressive nature but often so severe that it can be accompanied by "Gegenhalten" countermovements and dystonic postures but little frank dystonia. There are few true extrapyramidal symptoms except akinesia. When the disease starts after the age of 50, the clinical spectrum is mostly that of an amyotrophic polyneuropathy with fasciculations accompanying the ataxia. For all the other cases the clinical picture is a continuum between these two extremes, the main determinant of the clinical phenotype being the age of onset and a secondary factor, the place of origin of the given kindred. The ataxic and amyotrophic components are clearly progressive with time in contrast to the spasticity component. Although the majority of known cases are of Portuguese origin, this is not obligatory. The next research endeavour should be a search for the chromosomal site of the gene, using molecular biology technology such as those for recombinant DNA.
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PMID:The natural history of Machado-Joseph disease. An analysis of 138 personally examined cases. 650 98

Recent reports have demonstrated that organolead and -tin compounds can alter behavioral reactivity to noxious stimuli. To further define the dose response and temporal characteristics of these neurobehavioral effects, male Fischer 344 rats were injected sc with either one-fourth, one-half, or three-fourths the acute LD50 of triethyl lead (TEL), triethyl tin (TET), trimethyl lead (TML), trimethyl tin (TMT), or distilled water and tested on a 57.5 degrees C hot plate 1, 7, 14, 21, and 28 days after dosing. All four organometals altered hot plate latencies, but the magnitude and time course of these effects differed among the compounds. TEL produced a dose-related increase in latencies which was maximal 1 and 7 days postdosing and had dissipated by 28 days. In contrast, the group administered TML (3/4 LD50) exhibited a late developing antinocioception which became evident 14 days after dosing and persisted throughout the period of testing. The intermediate dose of TMT (1/2 LD50) also produced a delayed increase in response times which was observed 21 and 28 days post-treatment. The 3/4 LD50 dose of TMT produced increased hot plate latencies on all post-treatment test days except Day 14. TET (1/2 LD50) produced increased hot plate latencies 1, 7, 14, and 21 days postdosing and also induced a reversible ataxia and akinesia. Higher doses of TET proved lethal to 80% of the animals and lower doses failed to alter response times in the hot plate. These data demonstrate that trialkyl lead and tin compounds can produce time- and dose-related increases in hot plate latencies.
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PMID:Organometal-induced antinociception: a time- and dose-response comparison of triethyl and trimethyl lead and tin. 671 May 29

A female patient, who died at the age of 61 and had suffered from several manic-depressive psychoses for more than 30 years, developed three phases of intoxication under lithium therapy. There was a 15-year history of electro- and Pentetrazol-induced convulsive therapy prior to lithium medication; neuroleptics were still administered during lithium therapy. The last lithium intoxication, 3 years prior to death was during a low-dosage therapy with normal lithium levels followed by severe lasting impairment: akinesia, rigidity, dysarthria, ataxia, and an organic alteration in character. For the first time, neuropathological findings could be established in such a case: extensive damage to granule and Purkinje cells in the cerebellum; gliosis in the dentate nucleus, the inferior olives, and the nucleus ruber; cytoplasmic inclusions in various nerve cells of the cranial nerve nuclei; cytoplasmic vacuoles, especially in the cells of the supra-optic nucleus. Surprisingly little damage could be found in the substantia nigra and in the neostriatum. The clinical course as well as the pattern and intensity of the brain damage oppose an interpretation as a consequence of preceding convulsive shock therapy.
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PMID:Clinical and neuropathological aspects of long-term damage to the central nervous system after lithium medication. 679 83

In singly- and group-housed cats, an intraventricular injection of 6-hydroxydopamine (6-OHDA) in doses up to 1.0 mg, after a latent period of 1 to 3 days, evoked motor responses including tremor, ataxia, rigidity, weakness with adynamia and clonic-tonic convulsions. However, the intraventricular administration of 6-OHDA in a dose of 2.0 mg in group-housed cats, also after a latent period of 1 to 3 days, caused aggression, a restlessness, irritability, rage, fear, threat, attack, fighting and flight. These responses were accompanied by autonomic signs of mydriasis and dyspnoea and motor changes including tremor, ataxia, rigidity, weakness with adynamia and clinic-tonic convulsions. In the singly-housed cat only the latter motor phenomena were observed after the higher dose. Intraventricular injection of reserpine (0.5-1.0 mg) in both singly- and group-housed cats produced catalepsy, sedation, miosis, ptosis, defecation and micturition as well as motor responses of tremor, rigidity and akinesia. It is concluded that although 6-OHDA and reserpine evoke different behavioral effects, the motor changes are similar.
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PMID:Comparison of behavioral changes in cats treated with intracerebroventricular 6-hydroxydopamine and reserpine. 719 23

Paroxysmal symptoms are described in 14 patients with undoubted or suspected multiple sclerosis (MS). In seven of the patients the paroxysms were the first symptom of the disease, although only one has developed definite MS so far. The clinical features have been compared with 153 patients previously reported in the literature which has been reviewed, with special reference to 36 in whom paroxysmal symptoms were the initial manifestations of MS. Attention has been focused on paroxysmal symptoms of brain stem and spinal cord origin of the following types: paroxysmal dysarthria and ataxia, diplopia, tonic seizures, paroxysmal akinesia, paroxysmal sensory disturbances and pains. Examples of each type have been reported as the first symptoms of MS with remissions ranging from less than one to 21 years before other manifestations of MS have developed.
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PMID:Paroxysmal symptoms as the first manifestations of multiple sclerosis. 737 30


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