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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Long-term exposure of the fruit bat Rousettus aegyptiacus to nitrous oxide, which inactivates methylcobalamin, leads to neurological impairment and ataxia. 2. In N2O-exposed animals, liver concentrations of total folates and methyl folates decreased to less than one-fifth that of control animals. Pediococcus cerevisiae-active folates were also reduced. 3. In brain, there were no changes in total or methyl folates, but P. cerevisiae-active folates were lower in N2O-exposed animals. 4. Supplementation with methionine retarded the development of neurological impairment and the fall in liver total and methyl folates, but not that in P. cerevisiae-active folates. 5. Supplementation with serine failed to retard the development of neurological impairment or fall in hepatic folates. 6. The present results suggest that the N2O-induced neurological impairment in the bat is not related to depletion of cerebral folates, but do not exclude changes in the subcellular distribution of folates.
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PMID:Tissue folates in fruit bats (Rousettus aegyptiacus) with nitrous oxide-induced vitamin B12 deficiency and neurological impairment. 312 Jul 68

Pigs were treated with N2O which is known to impair vitamin B12 function in vivo. Such pigs demonstrated an inability to gain weight, progressive ataxia, and spinal neuropathy. The ataxia was totally and the neuropathy partially preventable by dietary methionine supplementation. Methionine synthase activity was inhibited in both the liver and brain. There was a marked elevation of S-adenosylhomocysteine in the neural tissues and a concomitant failure of S-adenosylmethionine to rise and thus maintain the methylation ratio, except when supplementary dietary methionine was added. In contrast, the methylation ratio in the rat was affected to a lesser extent. The neuropathy, it is suggested, is caused by raised S-adenosylhomocysteine levels in neural tissue; as a result, the methylation ratio is inverted and S-adenosylmethionine-dependent methylation reactions are inhibited.
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PMID:Methylation deficiency causes vitamin B12-associated neuropathy in the pig. 318 71

After four months of excessive nitrous oxide (N2O) exposure, a dentist had myeloneuropathy with spastic paraparesis, Lhermitte's sign, sensory shading, loss of position and vibration sense, ataxia, and impotence. Macrocytosis, hypersegmented neutrophils, and a reduced vitamin B12 level were associated with normal findings on gastric analysis and Schilling test. Complete hematologic and neurologic recovery followed N2O avoidance and vitamin therapy for six months.
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PMID:Myeloneuropathy and macrocytosis associated with nitrous oxide abuse. 630 15

The fruit bat Rousettus aegyptiacus, when exposed to nitrous oxide (N2O) for 8-10 weeks develops cobalamin deficiency and neurological impairment leading to ataxia and death. We report the lipid composition of cerebral tissue of control animals and impaired animals following exposure to N2O, with or without dietary folic acid supplements. There were no statistically significant differences in the concentrations of total lipids, phospholipid, glycosphingolipid, plasmalogen and cholesterol between the different groups, although the ratio of choline phosphoglyceride to ethanolamine phosphoglyceride in N2O exposed animals was slightly lower than in controls. Bats exposed to N2O showed slightly higher levels of the fatty acid linoleate (18:2) in their phosphatidylethanolamine relative to arachidonate (20:4) compared with controls. This increase tended to be more pronounced in the bats receiving dietary folic acid supplements (but p greater than 0.05).
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PMID:Lipid composition of the brain in the cobalamin inactivated fruit bat Rousettus aegyptiacus. 650 Aug 45

In order to obtain information on the mechanisms of neurotoxicity of 1,1,1-trichloroethane, rats maintained artificially ventilated on N2O:O2 (70:30) were exposed to a concentration of 1,1,1-trichloroethane of 8000 ppm, 43.7 mg L-1, that induces moderate ataxia in awake, spontaneously breathing animals. After 5 and 60 min of exposure, as well as after a 60-min recovery period following 60 min of exposure, the brain was frozen in situ and cortical tissue was assayed for phosphocreatine (PCr), + ATP, ADP, AMP, glycogen, glucose, pyruvate, lactate, citric acid cycle intermediates, associated amino acids, and cyclic nucleotides; in addition, purine nucleotides, nucleosides, and bases were assayed by HPLC techniques. Exposure of animals to 1,1,1-trichloroethane failed to alter blood glucose, lactate, and pyruvate concentrations. However, the solvent induced highly significant increases in tissue lactate and pyruvate concentrations that were also reflected in cisternal CSF. Associated with these changes were increases in all citric acid cycle intermediates except succinate, an increase in alanine concentration, and a rise in the glutamate/aspartate ratio. After 5 min, a small decrease in glycogen concentration also occurred. All these changes were reversed when the exposure was terminated. No changes were observed in tissue concentrations of purine nucleotides, nucleosides, and bases except for a small reduction of ATP concentration after 60 min of exposure, still noticeable after 60 min of recovery. Apart from a small reduction in cAMP concentration after 5 min of exposure, cyclic nucleotide concentrations did not change.
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PMID:Cerebral metabolic and circulatory effects of 1,1,1-trichloroethane, a neurotoxic industrial solvent. 2. Tissue concentrations of labile phosphates, glycolytic metabolites, citric acid cycle intermediates, amino acids, and cyclic nucleotides. 653 82

The effect of cobalamin inactivation by the anaesthetic gas nitrous oxide on the concentration of S-adenosylmethionine (Ado Met) in brain and liver of fruit bats (Rousettus aegyptiacus) was examined. Test animals exposed to N2O-oxygen (50:50, v/v) developed ataxia and paralysis leading to death after an average of 9.8 weeks (n6). Animals receiving pteroylmonoglutamic acid supplements in the diet became ataxic earlier (mean 8.8 weeks) while those receiving methionine supplements survived for significantly longer periods (12.5 weeks, P less than 0.01). Plasma cobalamin levels indicated severe depletion of cobalamin stores in N2O-exposed animals. The mean concentration of Ado Met in the brain of N2O-treated bats was nearly 50% higher than that of untreated controls. Ado Met levels in treated bats receiving pteroylmonoglutamic acid or methionine supplements were respectively 18 and 25% higher than in controls. In contrast, the concentration of Ado Met in the liver of all the N2O-treated groups was slightly lower than in controls. These results suggest that the N2O-induced neuropathy in the fruit bat is not related to a depletion of Ado Met in the nervous system.
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PMID:Tissue S-adenosylmethionine levels in fruit bats (Rousettus aegyptiacus) with nitrous oxide-induced neuropathy. 661 64

The mechanism whereby vitamin B-12 deficiency leads to neurological changes in humans is still uncertain. Nitrous oxide (N2O), which inactivates vitamin B-12 in vivo, results in neurological impairment leading to ataxia and death in the fruit bat Rousettus . These changes were prevented by the injection of the vitamin. The effect of dietary betaine (a catalytic product of choline) or methionine supplementation was studied in bats exposed to N2O. Supplementation with betaine resulted in less weight loss and delayed onset of neurological impairment when compared with unsupplemented animals. Supplementation with methionine at similar concentrations (600 mg/kg fruit and 2 g/kg fruit) was more effective in preventing weight loss and delaying the onset of neurological impairment than the corresponding levels of betaine. These results suggest that dietary betaine was effective in increasing that part of methionine synthesis that is not dependent on vitamin B-12 in N2O-exposed bats with impairment of the vitamin B-12-dependent methionine synthase reaction.
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PMID:Betaine delays the onset of neurological impairment in nitrous oxide-induced vitamin B-12 deficiency in fruit bats. 672 73

Nitrous oxide, which inactivates cobalamin when administered to fruit bats, results in severe neurological impairment leading to ataxia, paralysis and death. This occurs after about 6 weeks in animals depleted of cobalamin by dietary restriction, and after about 10 weeks in cobalamin replete bats. Supplementation of the diet with pteroylglutamic acid caused acceleration of the neurological impairment - the first unequivocal demonstration of aggravation of the neurological lesion in cobalamin deficiency by pteroylglutamic acid. The administration of formyltetrahydropteroylglutamic acid produced similar aggravation of the neurological lesion. Supplementation of the diet with methionine protected the bats from neurological impairment, but failed to prevent death. Methionine supplementation protected against the exacerbating effect of folate, preventing the development of neurological changes. These findings lend support to the hypothesis that the neurological lesion in cobalamin deficiency may be related to a deficiency in the methyl donor S-adenosylmethionine which follows diminished synthesis of methionine.
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PMID:Cobalamin inactivation by nitrous oxide produces severe neurological impairment in fruit bats : protection by methionine and aggravation by folates. 717 8

Neuropsychiatric syndromes occur in about 40% of Cbl-deficient patients and are characterized by progressive and variable damage to the spinal cord, peripheral nerves and cerebrum. The first abnormality is usually sensory impairment, most often presenting as distal and symmetrical paraesthesiae of the lower limbs and frequently associated with ataxia. Almost all patients demonstrate loss of vibratory sensation, often in association with diminished proprioception and cutaneous sensation and a Romberg sign. Corticospinal tract involvement is common in more advanced cases, with abnormal reflexes, motor impairment and, ultimately, spastic paraparesis. A minority of patients exhibit mental or psychiatric disturbances or autonomic signs, but these rarely if ever occur in the absence of other neurological changes. Because N2O inactivates Cbl, abuse of the gas may lead to typical Cbl neuropathy. Haematological changes are minimal and serum Cbl levels and Schilling tests normal in most patients. The severity of neurological abnormalities prior to treatment correlates with the duration of symptoms and the haemoglobin level. Initial severity, symptom duration and initial haemoglobin also correlate with residual neurological damage after Cbl therapy. The inverse correlation between severity of anaemia and neurological damage is not understood. Diagnosis of Cbl neuropathy can usually be made in the presence of the typical neuropsychiatric abnormalities, a low serum Cbl level and evidence of megaloblastic haemopoiesis. In some patients serum MMA and HCYS determinations or a therapeutic trial may be required. A neurological response usually occurs within the first 3 months, although further improvement may occur with time. Patients with advanced disease may be left with major residual disability. Therefore early diagnosis is critical. Pharmacological doses of folic acid reverse the haematological abnormalities of Cbl deficiency. This may allow neuropathy to develop or progress and make recognition of deficiency more difficult. There is no clear evidence that folic acid therapy precipitates or exacerbates Cbl neuropathy. Haematological improvement may occur in a fraction of patients receiving small doses of folate, but the data are inadequate to predict the danger of low levels of folate supplementation in the general population.
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PMID:Neurological complications of acquired cobalamin deficiency: clinical aspects. 853 66

A 50 year-old man was referred with history of acute ataxia and lower extremity paresthesia 10 days after general anesthesia with nitrous oxide. Cervical MRI showed long hypersignal lesion in posterior segment of the cord. Blood analysis revealed vitamin B12 deficiency. Nitrous oxide-induced myelopathy should be considered in patients who develop acute neurological manifestation after general anesthesia. It is recommended for physicians to think about symptoms and signs of B12 deficiency when evaluating patients in postoperative visits.
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PMID:Clinical and MRI manifestations of nitrous oxide induced vitamin B12 deficiency: A case report. 2425 Sep 16


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