VALPROATE-ASSOCIATED ENCEPHALOPATHY

In contrast to intoxication by valproic acid (VPA), the clinical and electroencephalographical signs of VPA-induced acute encephalopathy are not related to high blood concentration. Symptoms like somnolence, increasing seizure frequency, nausea together with background slowing and generalized high voltage theta-delta-activity usually (in 75 %) appear within the first week after medication has been initiated. In 85 % of the cases the symptoms disappear during 5 days of drug withdrawal; in only 15 % the decrease is prolonged. Apart from few cases of hyperammonaemia (the pathological relevance of which is questionable as it is also seen in clinically asymptomatic patients), laboratory parameters are normal. The cause of the encephalopathy is unclear. The increase of phenobarbitone during polytherapy has been accounted for as well as hyperammonaemia or direct VPA-associated intrinsic effect on the brain. Furthermore, the encephalopathy might even speak in favour of prolonged (focal) epileptic activity provoked by VPA.