Comparison of antiepileptic drugs, no treatment, or placebo for children with benign epilepsy with centro temporal spikes.

BACKGROUND: Benign Epilepsy with Centro Temporal Spikes (BECTS) is a common epilepsy syndrome with onset in childhood which almost always remits by adolescence. It is characterised by focal seizures associated with motor signs and somatosensory symptoms, at times progressing to become generalised. The characteristic interictal EEG shows normal background activity with centrotemporal spikes which are more prominent in sleep. The prognosis is good though subtle cognitive impairment has been implicated. Antiepileptic drug (AED) treatment is used if seizures are frequent or occurring in the daytime.

OBJECTIVES: To evaluate whether or not treatment with AEDs changes the short- or long-term outcome of children with BECTS or both.

SEARCH METHODS: We searched the following databases: the Cochrane Epilepsy Group Specialized Register (30 April 2013), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2013, Issue 4: (April 2013)), MEDLINE (Ovid, 1946 to 30 April 2013), SCOPUS (30 April 2013), ClinicalTrials.gov (30 April 2013) and the WHO International Clinical Trials Registry Platform ICTRP (30 April 2013). We also handsearched the reference lists of articles that were considered for inclusion in the review.

SELECTION CRITERIA: All randomised controlled trials (RCTs) that compared the use of different AEDs, or compared the use of AEDs with no treatment, or placebo in children with BECTS.

DATA COLLECTION AND ANALYSIS: Data were independently extracted by all four of the review authors and discrepancies were resolved by discussion. Analysis included assessment of risk of bias, quality of evidence of individual studies, heterogeneity, and statistical analysis of the effects on seizure remission and cognition.

MAIN RESULTS: There were six eligible studies but only four had sufficient data at the time of this review. The four RCTs included in this review reported on a total of 262 participants. One study, a placebo-controlled trial with a low risk of bias, found that individuals on sulthiame were significantly more likely to remain in seizure remission during the three and six months from commencement of treatment than those on placebo (3 months: RR 2.26, 95% CI 1.48 to 3.44; 6 months: RR 2.63, 95% CI 1.43 to 4.86, 66 participants, moderate quality evidence). The other three trials, all open-labelled studies, had a high risk of bias and did not show any significant differences in terms of seizure remission between AEDs. One compared levetiracetam with oxcarbazepine (3 months: RR 1.13, 95% CI of 0.93 - 1.36; 12 months: RR of 1.29 with 95% CI of 0.89 - 1.86, 39 participants, low to very low quality evidence), one clobazam with carbamazepine (4-40 weeks: RR of 1.04, 95% CI of 0.67 - 1.62; last 9 months: RR of 1.06 with 95% CI of 0.84, 1.34, 45 participants, low quality evidence), and one carbamazepine with topiramate (28 weeks: RR 1.02 with 95% CI of 0.8 - 1.3, 112 participants, low quality evidence).Other outcome measures assessed included time to first seizure after randomisation which was only obtained in the sulthiame versus placebo study as a hazard ratio of 7.8 (95% CI 2.66 - 22.87). There were no significant differences between the proportion of participants who had adverse events, apart from a higher incidence of rash in the carbamazepine group (14.8%) when compared with topiramate (1.7%), or the proportion who withdrew from treatment due to adverse events, when this was reported. Two trials (carbamazepine versus topiramate, and clobazam versus carbamazepine) evaluated the effects on cognition. The studies were of low to very low quality evidence showing no clear difference in cognition at the end of the study periods between the AEDs compared. A meta-analysis was not performed as the RCTs evaluated different therapies.

AUTHORS' CONCLUSIONS: There is evidence from one trial reviewed that sulthiame is effective for seizure remission in the short term in children with BECTS although the precision of the effect estimate is uncertain due to its small sample size. There were no significant differences in the proportion of adverse events between treatment groups studied, including those resulting in withdrawal of treatment. There is insufficient evidence about the medium to longer term effects on seizure control, the optimum antiepileptic drug treatment and the effects of AED treatment on cognition. There is a need for more good quality randomised controlled trials to address these questions to aid the management of children with BECTS.