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Valproic acid-induced encephalopathy in very long course treated patients

Rousseau M.C., Montana M, Villano Ph , Catala A, Blaya J, Valkov M, Allouard Y, Bugny E.

Brain inj. 2009 nov;23(12):981-4. DOI: 10.3109/02699050903302344.


Primary objective: In patients receiving valproate (VPA) treatment, valproate induced-encephalopathy (VIE) is among the most serious adverse side-effects and hyperammonaemia is a frequent and well-recognized event. This report evaluates adult patients receiving VPA for several years.

Research design: This study was conducted in adult patients receiving VPA for several years. Many studies have evaluated blood ammonia levels and VPA-related encephalopathy in patients whose treatment was initiated for a few months. Most studies were conducted in children.

Methods and procedures: This study looked at retrospectively occurrences of VIE in 63 patients who were receiving VPA for a minimum duration of at least 2 years. At the beginning of the study basal ammonaemia was measured for all patients.

Main outcomes and results: This study reports a rather frequent onset of VIE. Long duration of VPA treatment was not correlated with encephalopathy onset. In seven cases temporary administration of lactulose alone was effective and VPA was continued.

Conclusions: This study confirms that, under VPA treatment, hyperammonaemia is a current event; 25.4% patients presented isolated elevated ammonaemia when receiving VPA for very long durations. VPA therapy should be monitored closely and clinicians must be warned of VPA encephalopathy signs.