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)

As a possible preventive measure for brain dysfunction in Menkes disease, prenatal treatment by maternal administration of zinc, vitamin E and copper was examined in brindled mutant mice. During pregnancy and lactation, female heterozygous mice received 20 ppm zinc or 0.004% alpha-tocopherol acetate (vitamin E) throughout and 6 ppm copper from gestational day 13 in the drinking fluid, ad libitum. The maternal administration of zinc and vitamin E, as antioxidants, or copper resulted in decreased fetal and neonatal death of offspring, especially those of hemizygous males, as compared with the administration of water only. When offspring did not grow, maternal abnormal movements, which comprised rotatory movements of high speed with tremor and ataxia, were frequently observed. In the heterozygotes with abnormal movements, the level of lipid peroxidation in cerebrum and the concentration of copper in kidney were much higher than those in the heterozygotes with normal movement. Morphologically, in cerebellum of the heterozygotes with abnormal movements, the loss of Purkinje cells, abundance of lipofuscin granules and abnormal mitochondria or degenerative bodies of high electron density were frequently observed, as compared with heterozygotes with normal movement. These findings suggest that the development of hemizygous male mice may be influenced by both copper and oxygen radical metabolism.
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PMID:Abnormal movements in brindled mutant mouse heterozygotes: as related to the development of their offspring--biochemical and morphological studies. 216 11

A 68 year old man with a creatinine clearance rate of only 15 ml/min took twice the recommended dose of tripotassium dicitrato bismuthate (TDB) as DeNol liquid; 10 ml qds; a total of 864 mg bismuth daily for two months. Whole blood bismuth concentrations rose to 880 micrograms/l and he developed global cerebral dysfunction with hallucinations, ataxia, and an abnormal EEG. Renal clearance of bismuth rose from 0.24 to 2.4 ml/min when the heavy metal chelator 2-3 dimercapto-1 propane sulphonic acid (DMPS) was given by mouth. Bismuth was measured by a novel method involving inductively coupled plasma source mass spectrometry. Fifty days after stopping TDB, whole blood bismuth concentrations fell to 46 micrograms/l and the patient's EEG returned to normal. His mental function also recovered completely. The case serves as a timely reminder that TDB should not be administered to patients with renal disorders, as stated in the data sheet.
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PMID:Bismuth induced encephalopathy caused by tri potassium dicitrato bismuthate in a patient with chronic renal failure. 221 Apr 58

Sons of community dwelling alcoholic, depressed, and normal men were administered a comprehensive battery of neuropsychological tests. A generalized cognitive deficit was not found in the sons of alcoholics. The sons of alcoholics demonstrated greater ataxia than offspring in the two control groups and also performed more poorly on tests measuring visual scanning and attention, planning ability, and impulse control. These findings raise the possibility that an anterior cerebral dysfunction underlies the cognitive deficit observed in children of alcoholics.
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PMID:Cognitive status of sons of alcoholic men. 265 62

A family is described with familial myoclonic epilepsy associated with mitochondrial myopathy. The disorder follows a maternal inheritance pattern consistent with a mitochondrial DNA (mtDNA) mutation. The large kindred permitted exclusion of autosomal dominant, recessive, and X-linked patterns of transmission. Several characteristics of the inheritance and variability of expression within the pedigree are consistent with recently acquired knowledge about the genetics of human mtDNA. The clinical spectrum of disease is compatible with a proportionality model of mutant and wild-type mtDNAs. Muscle biopsies of affected patients showed an increased number of abnormal muscle mitochondria. Serum levels of pyruvate or pyruvate and lactate were elevated. The most severely affected patient had constant myoclonic jerking, dementia, ataxia, spasticity, hearing loss, and hypoventilation. Cerebral dysfunction in patients with mild involvement was marked by prominent photic driving seen on electroencephalograms and high-amplitude visual and somatosensory evoked responses but no myoclonus, ataxia, or dementia. The individual clinical features of the disease worsen over time for all patients; however, mildly affected patients have not become moderately affected and moderately affected patients have not become severely affected.
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PMID:Maternally inherited mitochondrial myopathy and myoclonic epilepsy. 392 81

A series of 12 patients with cerebellar infarcts diagnosed by computerized tomography are reviewed. The clinical features of cerebellar infarctions cover a wide spectrum, mimicking symptoms and signs from an acute labyrinthitis to a rapidly expanding posterior fossa mass lesion with brain stem and cerebral dysfunction. Two patients were asymptomatic and three showed signs of cerebellar dysfunction only. Three patients had evidence of brain stem dysfunction with cranial nerve palsies accompanying the cerebellar deficit. Two presented a pseudovestibular form with sudden onset of nausea, vomiting, rotary dizziness and ataxia. A pseudotumoral form with intracranial hypertension was found in two cases, in which softening tissue acts as a rapidly expanding posterior foss mass lesion. It is difficult to identify the exact artery involved in a cerebellar infarct because of the collateral circulation and connections between the three major arteries. Atherosclerosis and general decrease in blood flow can be regarded as the most likely factors precipitating focal cerebellar infarction. Surveillance is necessary during the first days with anti-edematous therapy. Rapid deterioration of consciousness should be considered a sign of increasing intracranial pressure progressing with the development of hydrocephalus. If necessary, surgical decompression by external drainage or by direct access to the posterior fossa can be carried out.
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PMID:[Cerebellar infarct. Clinical presentation and x-ray computed tomography of the brain]. 394 88

A group of 23 professional divers was investigated before and after dives to 300 and 350 metres of sea water. 12 divers were also studied during the actual dive. All divers presented neurological symptoms and signs during compression. Intention tremor, ataxia, motor weakness, sensory symptoms, vertigo, nausea and reduced memory were the most prominent features of the High Pressure Nervous Syndrome (HPNS). There were considerable individual differences. Neuropsychological and neurophysiological investigations performed after one dive showed no significant changes in any of the divers, while there was a clear-cut impairment in a group of 6 divers who had performed 2 dives 3 months apart. These changes indicate that there may be pressure-induced brain dysfunction which persists for a transient post-dive period. Loss of short-term memory is a prominent part of this dysfunction. Transitory neurological signs indicating focal cerebral dysfunction were found immediately post-dive in 4 divers, presumably reflecting the unmasking of pre-existing subclinical minimal CNS lesions.
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PMID:Central nervous dysfunction associated with deep-sea diving. 397 49

Development of novel antiepileptic drugs (AEDs) requires determining the margin between the desired anticonvulsant effect and undesired adverse effects (AE) (therapeutic index). For this purpose, drug-induced "minimal neurological deficits" (e.g., motor dysfunctions) are commonly quantified by simple tests, such as the rotarod test, in normal, i.e., nonepileptic animals. However, increasing evidence shows that chronic brain dysfunction associated with epilepsy may increase susceptibility to the AE of certain AEDs, e.g., N-methyl-D-aspartate (NMDA) receptor antagonists. The increased AE potential of such investigational drugs can be predicted by using kindled rats instead of normal rodents in preclinical drug evaluation studies. In the present experiments, we wished to determine whether kindled rats also exhibit an altered susceptibility to neurological adverse effects of standard AEDs, i.e., carbamazepine (CBZ), phenobarbital (PB), valproate (VPA), and diazepam (DZP). Abecarnil, a novel benzodiazepine (BZD) receptor agonist, was included in the study for comparison. All drugs were administered in diverse doses in kindled and nonkindled rats, and all behavioral alterations were scored in the cage and open field. Furthermore, the rotarod test was used to detect and quantify motor impairment induced by drug treatments. Kindled rats were more susceptible than nonkindled rats to motor impairment (ataxia and/or rotarod failures) induced by high doses of AEDs, although differences were noted between the drugs tested. VPA was the only drug that induced stereotyped behavior; it was much more potent in this respect in kindled than nonkindled rats. Abecarnil did not differ substantially in its AE in either subgroup of animals. Our data indicate that epileptogenesis induced by kindling renders the brain more susceptible to certain AE of AEDs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Kindling increases the sensitivity of rats to adverse effects of certain antiepileptic drugs. 763 95

We measured the activity of the thiamine pyrophosphate-dependent enzyme alpha-ketoglutarate dehydrogenase complex in postmortem brain of 12 patients with the spinocerebellar ataxia type 1 form of olivopontocerebellar atrophy. alpha-Ketoglutarate dehydrogenase complex activity measured in the absence of thiamine pyrophosphate was markedly reduced (-72%) in olivopontocerebellar atrophy cerebellar cortex. Decreased activity of this key rate-limiting Krebs cycle enzyme could compromise cerebellar energy metabolism and excitatory amino acid synthesis and thereby contribute to the brain dysfunction of olivopontocerebellar atrophy.
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PMID:Cerebellar alpha-ketoglutarate dehydrogenase activity is reduced in spinocerebellar ataxia type 1. 791 5

Acute and chronic toxicity complicates all antiepileptic medications (AED) and is idiosyncratic. Acute toxicity can be categorized into 1) acute brain dysfunction or 2) acute organ dysfunction when AED's are started. Despite promising in vitro lymphocyte testing, anticipation of acute reactions cannot be offered. Furthermore, screening for AED toxicity by routine blood and urine tests in asymptomatic patients is of doubtful value and should be abandoned. Patients should be informed of possible reactions and immediately report early symptoms. Treatment for acute reactions is largely unstudied. It is unclear how to reintroduce AED's following acute reactions. Often patients are sensitive to drugs with a similar chemical structure. The "desensitization" protocol of Purvis may be of merit. Three major chronic toxicities of AED's have been noted--soft tissue and gum hypertrophy, progressive ataxia, and peripheral neuropathy. New AED's require careful post-marketing surveillance since long term toxicity data are not yet available.
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PMID:Acute and chronic toxicity of antiepileptic medications: a selective review. 800 Sep 71

Human GM1-gangliosidosis is caused by a genetic deficiency of lysosomal acid beta-galactosidase (beta-gal). The disease manifests itself either as an infantile, juvenile or adult form and is primarily a neurological disorder with progressive brain dysfunction. A mouse model lacking a functional beta-gal gene has been generated by homologous recombination and embryonic stem cell technology. Tissues from affected mice are devoid of beta-gal mRNA and totally deficient in GM1-ganglioside-hydrolyzing capacity. Storage material was already conspicuous in the brain at 3 weeks. By 5 weeks, extensive storage of periodic acid Schiff-positive material was observed in neurons throughout the brain and spinal cord. Consistent with the neuropathology, abnormal accumulation of GM1-ganglioside in the brain progressed from twice to almost five times the normal amount during the period from 3 weeks to 3.5 months. Despite the accumulation of brain GM1-ganglioside at the level equal to or exceeding that seen in gravely ill human patients, these mice show no overt clinical phenotype up to 4-5 months. However, tremor, ataxia and abnormal gait become apparent in older mice. Thus, the beta-gal-deficient mice appear to mimic closely the pathological, biochemical and clinical abnormalities of the human disease.
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PMID:Generalized CNS disease and massive GM1-ganglioside accumulation in mice defective in lysosomal acid beta-galactosidase. 906 40


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