EARLY PREDICTORS OF SEIZURE OUTCOME IN NEWLY DIAGNOSED EPILEPSY: A SYSTEMATIC REVIEW OF PROGNOSIS STUDIES

Abstract

The physical and psychosocial consequences of seizures in epilepsy are more prevalent in people with uncontrolled seizures, and are lessened with seizure control. Early management strategies and patient counselling may be informed by the predictors of control in newly diagnosed patients. The main objective of this systematic review was to identify variables that consistently and independently predict seizure outcome in people with newly diagnosed epilepsy. English-language publications identified from electronic databases (MEDLINE and EMBASE) and reference lists of included studies, published until March 2010 were reviewed. The publications were of nested case control and cohort studies of unselected population of at least 100 people with epilepsy with multivariate analysis of the effect on seizure outcome of predictor variables collected within the first year of diagnosis in patients followed up for at least 1 year. The quality of included studies was appraised for their likelihood for bias in five areas: study participation, study attrition, prognostic factor measurement, outcome measurement and statistical analysis. Data from each study were independently extracted three times; at each succeeding stage, the extracted data were compared with the previous extraction and where there were discrepancies, clarification made by consulting the publication. Consistent predictors were identified in more than 1 study from different cohorts. There were 52 studies from a total of 33 publications. Five studies predicted immediate remission of seizures; 9 studies predicted remission off antiepileptic medication; 20 studies predicted remission on or off antiepileptic medication; 12 studies predicted intractability to antiepileptic medication and 1 study developed a model to predict not achieving remission after 1 or more relapses following an initial period of remission. 5 studies externally validated models predicting seizure outcome. Two factors reduce the chance of achieving immediate remission: More than 1 seizure before recruitment [RR 0.63 (95%CI 0.36-1.11)] and remote symptomatic aetiology [childhood-onset epilepsy: RR 0.59 (95%CI 0.41-0.86), adult-onset epilepsy: RR 0.44 (95% CI 0.26-0.77)]. Having more than 1 seizure in the period between 6 and 12 months on medication [RR 0.24 (95%CI 0.10-0.60)] and intellectual disability [RR 0.77 (95%CI 0.61-0.94)] reduce the chance of achieving remission off medication in childhood-onset epilepsy. None of the studies predicting remission off medication were of adult-onset epilepsy. Five factors reduce the chance of achieving remission on or off medication are: More than 1 seizure before diagnosis [childhood-onset epilepsy: RR 0.66 (95%CI 0.46-0.95), adult-onset-epilepsy: 0.81 (95%CI 0.66-0.99)] for the natural logarithm of every additional seizure; seizures in the first 6 months after the index seizure [childhood-onset epilepsy: RR 0.50 (95%CI 0.35- 10 0.72), adult-onset-epilepsy: RR 0.59 (95%CI 0.50-0.70) for the natural logarithm of every additional seizure; mixed seizure types at onset [RR 0.70 (95%CI 0.37-1.04), adult-onset epilepsy: OR 0.23 (95% CI 0.10-0.48)]; intellectual disability [childhood-onset epilepsy: OR 0.40 (95%CI 0.18-0.90), adult-onset epilepsy: OR 0.10 (95%CI 0.05-0.25)]; and remote symptomatic aetiology [childhood-onset epilepsy: RR 0.63 (95% CI 0.47-0.84), adult-onset epilepsy: RR 0.44 (95% CI not reported)]. Onset of seizures in infancy [RR 5.48 (95%CI 2.10-9.64)], intellectual disability [OR 18.2 (95%CI 5.2-63.6)], and remote symptomatic aetiology [RR 5.48 (95%CI 2.10-9.64)] increase the risk of medical intractability, while idiopathic aetiology [RR 0.20 (95%CI 0.0-0.80)] reduces the risk of intractability in childhood-onset epilepsy. None of the studies predicting medical intractability were of adult-onset epilepsy. The externally validated models have little predictive gain over information provided by simple prevalence rates of seizure outcome, and the models predict wrongly in about 1 out of 3 children in the development and external validation cohorts. None of the models developed in adult-onset epilepsy were externally validated. The study suggests that onset of seizures in infancy, number of seizures (before diagnosis, in the first 6 months after diagnosis, and between 6 and 12 months on medication), intellectual disability and the aetiology of seizures are the important predictors of seizure outcome in newly diagnosed epilepsy. The study demonstrates the feasibility of systematic review with thorough quality appraisal as a means of identifying the consistent predictors of an outcome in exploratory prognostic factor studies. The review also shows the need for further studies of the prognosis of adult-onset epilepsy.