Antiepileptic drugs for the primary and secondary prevention of seizures in viral encephalitis

BACKGROUND: Viral encephalitis is characterised by diverse clinical and epidemiological features. Seizures are an important clinical manifestation and associated with increased mortality and morbidity. Patients may have seizures during the acute illness or they may develop after recovery. There are no recommendations regarding the use of antiepileptic drugs for the primary or secondary prevention of seizures in patients with viral encephalitis. OBJECTIVES: To assess the efficacy and safety of antiepileptic drugs for the primary and secondary prophylaxis of seizures in viral encephalitis. We intended to answer the following questions. 1. Do antiepileptic drugs used as primary prophylaxis routinely for all patients with suspected or proven viral encephalitis reduce the risk of seizures during the acute illness and reduce neurological morbidity and mortality? 2. Do antiepileptic drugs used as secondary prophylaxis routinely for all patients who have had at least one seizure due to suspected or proven viral encephalitis reduce the risk of further seizures during the acute illness and reduce neurological morbidity and mortality? SEARCH METHODS: We searched the Cochrane Epilepsy Group Specialised Register (13 May 2014), the Cochrane Central Register of Controlled Trials (CENTRAL 2014, Issue 4) (April 2014), MEDLINE (Ovid, 1946 to 13 May 2014), the WHO ICTRP search portal (13 May 2014) and ClinicalTrials.gov (13 May 2014). We did not impose any language restrictions. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials in which patients were assigned to a treatment or control group (placebo or no drug). DATA COLLECTION AND ANALYSIS: One author (SP) searched the publications by title, abstract and keywords and decided on their suitability for inclusion in the review. For any studies where it was unclear whether they would be suitable for inclusion, the co-authors (CR, BM) were consulted. The co-authors (CR, BM) evaluated the selected studies independently. Since there were no included studies, we carried out no data analysis. MAIN RESULTS: We did not find any randomised or quasi-randomised controlled trials that compared the effects of antiepileptic drugs with placebo (or no drug) for the primary or secondary prevention of seizures in viral encephalitis. We identified two studies from the literature search where different antiepileptic drugs were used in patients with viral encephalitis, however both failed to meet the inclusion criteria. The first study included children with viral encephalitis where antiepileptic drugs were given. However, it is not clear how the diagnosis was established or the aetiologies. In addition, the randomisation and blinding method is not disclosed; the patients received a diverse and ill-defined range of antiepileptic drugs and adjunctive therapies, and none of the primary or secondary outcome measures was assessed. In the second study, adults with status epilepticus (of whom a proportion had viral encephalitis), who had failed to respond to two initial boluses of diazepam, were randomised to either valproate or diazepam. The study was open-label and the randomisation methodology was not disclosed; none of the primary or secondary outcomes were reported. Data on treatment response between the two arms for those patients with viral encephalitis are not presented for subgroup analysis; the Cochrane Epilepsy Group have contacted the authors for these data but have yet to receive a response. AUTHORS' CONCLUSIONS: There is insufficient evidence to support the routine use of antiepileptic drugs for the primary or secondary prevention of seizures in viral encephalitis. There is a need for adequately powered randomised controlled trials in viral encephalitis patients to assess the efficacy and safety of antiepileptic drugs for the primary and secondary prophylaxis of seizures, which is an important clinical problem.