Case ReportProgressive encephalopathy with cerebral oedema and infarctions associated with valproate and diazepam overdose
Introduction
Valproic Acid (VPA) has been used extensively for the treatment of epilepsy and bipolar affective disorder, among other indications. According to Australian hospital data from 2004 to 2005, nearly half (45.8%,10,931) of all patients who self harmed used antiepileptic, sedative-hypnotic, antiparkinsonism and psychotropic drugs together as a group.1 VPA exposures alone were responsible for 214 calls to the Victorian Poisons Information Centre (VPIC) in 2008.2 VPA in overdose is known to cause encephalopathy with or without cerebral oedema, hyperammonaemia,3 hepatotoxicity,4 bone marrow suppression and non-gap acidosis.5 Most of these conditions are reversible but for the patient presented, irreversible brain ischaemia resulted from VPA-related cerebral oedema.
Section snippets
Case report
A 29-year-old male presented 5 hours after an intentional overdose of 4 g VPA that had been recently prescribed for his bipolar affective disorder. He had also taken 75 mg of diazepam for insomnia 10 hours prior. On presentation the patient was agitated, unsteady on his feet and was vomiting. Vital signs were stable and neurological examination was otherwise normal.
While in emergency his consciousness progressively deteriorated and 9 hours post ingestion his Glasgow Coma Scale score was 8/15. He
Discussion
Coma is an uncommon outcome of VPA poisoning,7 but its frequency increases with the dose consumed and higher serum VPA levels.5 The pathogenicity of cerebral oedema is related to hyperammonaemia-induced intracellular glutamate retention in brain cells and osmotic swelling,3 which would have been aggravated by anoxia from respiratory depression secondary to diazepam. However, there is poor correlation between encephalopathy and plasma concentrations of VPA8 and ammonia.9 Brain infarcts have not
Conclusion
This patient suffered the non-reversible effects of cerebral oedema which should be kept in mind when treating severe VPA poisoning. Early detection and treament of cerebral oedema is essential. Activated charcoal, L-carnitine and haemofiltration are available options to antagonise and remove the toxic metabolites of VPA. Further clinical trials are necessary to establish therapeutic guidelines for the management of VPA poisoning.
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