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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Administration of ammonium acetate to mice caused seizures and alterations of brain energy metabolites. Pretreatment of animals with L-carnitine suppressed the frequency of the seizures and prolonged the latency to the first fit. When examined using the 'freeze clamp' method, brain energy metabolites were well preserved and the elevation of ammonia was less marked on administration of L-carnitine. Thus, L-carnitine suppresses ammonia-induced seizures and biochemical alterations of the brain in mice.
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PMID:Suppression of neurotoxicity of ammonia by L-carnitine. 181 38

Ten epileptic children with chronic valproic acid (VPA) treatment were given L-carnitine for 14 days. As compared to age and sex matched control subjects the carnitine status of the VPA treated children showed carnitine insufficiency prior to the carnitine administration with lower total and free carnitine in plasma and in urine. In response to the extra intake the plasma free and esterified carnitines increased 1.7-fold. The daily excreted amount of esterified carnitines increased 6.5-fold (1.55 +/- 0.23 vs 10.1 +/- 1.68 mumol/kg/day, means +/- SEM, p less than 0.005) showing that a considerable part of the administered carnitine participated in the elimination of acyl groups from the body. The depressed level of beta-hydroxybutyrate in the plasma (31.8 +/- 7.42 vs controls 118.0 +/- 16.0 mumol/l, means +/- SEM, p less than 0.005) remained unaffected by the carnitine administration (29.7 +/- 7.06 mumol/l) suggesting that the hypoketonemia is not a direct consequence of the carnitine insufficiency. No differences were observed in the plasma level of free fatty acids, triglycerides and in insulin: glucagon ratios between the VPA treated and control subjects, suggesting that lipolysis of fats and the hepatic hormonal control mediated by these hormones are not the sites at which VPA causes reduced fasting ketogenesis. The plasma level of VPA and the seizure control remained unaffected by carnitine treatment.
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PMID:L-carnitine replacement therapy in chronic valproate treatment. 210 56

Miniature piglets underwent total parenteral nutrition (TPN) with and without L-carnitine supplementation during a 7-day period. Thereafter the tissue amino acid concentrations of liver, heart, skeletal muscle and brain were determined and compared to those of orally fed animals. The altered tissue amino acid concentrations during TPN without carnitine returned to normal when L-carnitine was supplemented. The most striking changes of tissue concentrations showed taurine in liver, muscle and brain and ethanolamine in heart and brain. In muscle the branched-chain amino acids were increased when L-carnitine was added to the TPN regime. Ethanolamine changes were discussed with respect to the position of this amino acid in the synthesis of phospholipids. The marked decrease of brain taurine concentrations after carnitine-free TPN was accompanied by reduced values for GABA. Both the substances function as inhibitory transmitters in the brain and should be considered when seizure activity in patients with systemic carnitine deficiency is discussed.
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PMID:The effect of L-carnitine-supplemented total parenteral nutrition on tissue amino acid concentrations in piglets. 642 69

The anticonvulsant potency of valproate (VPA), as measured by the maximal electroshock seizure model in mice, was improved by pretreatment with the microsomal inhibitor SKF525A and by fasting, but was reduced by chronic phenobarbital pretreatment. Carnitine did not significantly alter the anticonvulsant properties of VPA. These findings suggest that the efficacy of VPA can be improved by factors that alter its metabolic pattern.
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PMID:Effects of SKF525A, phenobarbital, fasting, and carnitine on the anticonvulsant activity and neurotoxicity of valproate in mice. 643 97

Carnitine (beta-hydroxy-gamma-trimethylammonium butyrate) is widely distributed in the body including the nervous system. Its physiological function, viz. a carrier of long-chain fatty acids through the inner mitochondrial membrane, has been well established. In this review, mainly based on our experiments, we discuss the possibility that carnitine may have effects other than the "physiological" function and that it may be a potent protector of the brain. When mice were exposed to ammonia (intraperitoneal injection of ammonium acetate), they developed seizures and concentrations of brain energy metabolites were altered; ATP and phosphocreatine decreased while ADP, AMP, pyruvate and lactate increased. The seizures and changes in brain energy metabolites were clearly suppressed when the mice were pre-treated with carnitine. Furthermore, changes in energy metabolites in the brain caused by severe ischemia (decapitation) were also suppressed by carnitine. Since D-carnitine showed similar effects as those of L-carnitine, the effects seem due to function(s) of carnitine yet to be defined. Intrinsic substances including carnitine appear to deserve further studies for possible use in protecting the brain.
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PMID:Protection of the brain by carnitine. 774 96

We describe on a 3-year-old child referred for evaluation and therapy of a cerebral vascular accident with residual hemiplegia and partial epilepsy. Metabolic investigations initially showed normal urinary organic acids as well as normal blood and urinary amino acids. Blood carnitine fractions had been pathological and a secondary carnitine deficiency was diagnosed and treated by oral L-carnitine supplementation. During carnitine treatment, abnormal urinary acylcarnitine profiles were noticed with excessive amounts of several carnitine esters including propionylcarnitine, butyryl- and/or isobutyryl-carnitine, isovaleryl- and/or 2-methylbutyryl-carnitine, hexanoylcarnitine and octanoylcarnitine. Subsequently, an urinary organic acid profile suggestive of glutaric aciduria type II was recorded during a clinical decompensation crisis. Morphological and biochemical studies on skeletal muscle and skin fibroblasts were performed and confirmed the existence of a defect of the mitochondrial beta-oxidation pathways with lipidic myopathy, reduced palmitate and octanoate oxidation rates in cultured fibroblasts. Glutaric aciduria type II increases the list of metabolic disorders characterized by hemiplegia and other sequelae of brain ischaemia such as stroke-like episode, seizures, aphasia, ataxia and myoclonia, similar to those seen in MELAS.
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PMID:Stroke, hemiparesis and deficient mitochondrial beta-oxidation. 795 9

Although L-carnitine has been reported to have protective effects against ammonia toxicity, conflicting results have also been presented and the mechanisms underlying the protection, if any, are not clear. In the present study, we examined the effects of L-carnitine, D-carnitine and acetyl-L-carnitine on the neurotoxicity of ammonia. Administration of ammonium acetate (15 mmol/kg) to mice caused seizures, elevation of blood ammonia and urea concentrations, and marked alterations of brain energy metabolites. Pretreatment with either L-carnitine, D-carnitine or acetyl-L-carnitine reduced the frequency of the seizures, prolonged the time until the first fit, lowered the levels of ammonia in the blood and brain, and suppressed the alterations of brain energy metabolites caused by hyperammonemia. there was no significant difference between L- and D-carnitine in the potency to inhibit the seizures. In addition, there was no difference between the two chemicals in the potency to decrease the ammonia contents in the blood and brain, or to suppress the alterations of energy metabolites in the brain. When compared with L-carnitine, however, acetyl-L-carnitine better preserved ATP in the brain, while it lowered ammonia in the blood and brain less markedly. These results show that L-carnitine and its analogues do have the potential to suppress the neurotoxicity of ammonia. Moreover, the results suggest that the protective effects of carnitine against the toxicity of ammonia are systemic, that the action of acetyl-L-carnitine may differ from that of L- or D-carnitine, and that the "classical" function of carnitine is not the sole mechanism underlying the suppression of the neurotoxicity of ammonia.
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PMID:Comparison of the effects of L-carnitine, D-carnitine and acetyl-L-carnitine on the neurotoxicity of ammonia. 834 26

Previous studies in our laboratory have shown that L-carnitine suppresses seizures and alterations of brain energy metabolism in mice caused by hyperammonemia. The present study was done to exclude the effects of seizures on brain energy metabolism. When sublethal dose of ammonium acetate (12 mmol/kg b.wt.) was injected to mice, all mice survived without developing seizures, while clear increase of brain ammonia and alterations of brain energy metabolites were seen. In L-carnitine-treated animals, the levels of ammonia, AMP and lactate were lower and those of ATP and phosphocreatine were higher than in untreated animals. Treatment with D-carnitine also preserved the phosphocreatine level. This indicates that the improvement of brain energy metabolism by L-carnitine in hyperammonemia is not simply a result of the suppression of seizures, and that the "physiological" function of carnitine may not be the sole mechanism underlying this effect.
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PMID:Effects of L and D-carnitine on brain energy metabolites in mice given sublethal doses of ammonium acetate. 851 63

Numerous studies have shown that plasma carnitine levels are significantly lower in patients taking valproate than in controls. Free carnitine deficiency is not uncommon in these patients and also occurs in newborns with seizures and in patients taking other anticonvulsant drugs. Carnitine deficiency in epilepsy results from a variety of etiologic factors including underlying metabolic diseases, nutritional inadequacy, and specific drug effects. The relationship between carnitine deficiency and valproate-induced hepatotoxicity is unclear. Carnitine treatment does not always prevent the emergence of serious hepatotoxicity, but it does alleviate valproate-induced hyperammonemia. These studies suggest that specific risk factors for carnitine deficiency can be identified. Preliminary data suggest that carnitine treatment may benefit high-risk, symptomatic patients and those with free carnitine deficiency. Carnitine treatment is not likely to benefit low-risk, asymptomatic patients and those with normal carnitine levels.
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PMID:Carnitine deficiency in epilepsy: Risk factors and treatment. 857 67

Five patients presenting with non-ketotic hyperglycinemia in the neonatal period were treated with sodium benzoate to normalize plasma glycine levels. This therapy resulted in seizure reduction and a marked increase in wakefulness. Plasma carnitine deficiency was noted in three of four patients tested, and benzoylcarnitine was identified in plasma, urine, and CSF. Treatment with L-carnitine normalized plasma free carnitine. L-carnitine showed a tendency to increase the glycine conjugation of benzoate. An episode of coma and increased seizures in one patient was associated with a toxic level of benzoate, probably due to insufficient mobilization of glycine for conjugation. High dose benzoate therapy improved the quality of life of surviving patients. Close monitoring of glycine, benzoate and carnitine levels is advised.
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PMID:Benzoate therapy and carnitine deficiency in non-ketotic hyperglycinemia. 858 64


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