[Role of hyperammonemia in stuporous states induced by sodium valproate].
Stuporous states induced by sodium valproate (VPA) are accompanied by an isolated marked hyperammonemia. In reality, hyperammonemia occurs after administration of VPA even in the absence of neurological complications. The hyperammonemia is of purely renal origin and results from modifications in glutamine metabolism, this compound being the main precursor of amino acid neurotransmitters. Combined administration of VPA and phenobarbitone increases the level of hyperammonemia due to lack of detoxification by the liver of the excess of ammonia produced by the kidneys. The anatomical site of origin of the ammoniogenesis, and its intensity, were studied in two patients with a history of stuporous states during combined VPA-phenobarbitone treatment. A single injection of VPA at a later date when they were being treated by combined phenobarbitone-carbamazepine therapy, induced disturbances in ammonia metabolism which did not differ qualitatively from those observed when intolerance to VPA is lacking. It is therefore not possible to rely on simple biological tests to detect patients at risk. Correlation is also lacking between the degree of hyperammonemia and disorders of vigilance. Ammonia does not therefore appear to be the only factor responsible for neurological complications and the role of other factors must be investigated. These include: disturbances of metabolism of inhibitory and excitatory aminoacid neurotransmitters, the condition of the cerebral parenchyma, and the excitatory effect of sodium valproate which could act to varying degrees in synergy with the hyperammonemia to provoke a stuporous state.
D000328:Adult; D000641:Ammonia / Q000097:blood*; D004828:Epilepsies, Partial / Q000188:drug therapy; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy; D005260:Female; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D014474:Unconsciousness / Q000097:blood / Q000139:chemically induced*; D014635:Valproic Acid / Q000009:adverse effects* / Q000097:blood
D005973:Glutamine; D014635:Valproic Acid; D000641:Ammonia
Rôle de l'hyperammoniémie dans les états stuporeux induits par le valproate de sodium.