Treatment of Lennox-Gastaut syndrome

Abstract

Background: The Lennox-Gastaut syndrome (LGS) is an age-specific disorder, characterised by epileptic seizures, a characteristic electroencephalogram (EEG), psychomotor delay and behavioural disorder. It occurs more frequently in males and onset is usually before the age of eight years, with a peak between three and five years of age. Late cases occurring in adolescence and early adulthood have rarely been reported. Language is frequently affected, with both slowness in ideation and expression in addition to difficulties of motor dysfunction. Severe behavioural disorders (e.g. hyperactivity, aggressiveness and autistic tendencies) and personality disorders are nearly always present. There is also a tendency for psychosis to develop with time. The long-term prognosis is poor; although the epilepsy often improves, complete seizure freedom is rare and conversely the mental and psychiatric disorders tend to worsen with time. Objectives: To compare the effects of pharmaceutical therapies used to treat LGS in terms of control of seizures and adverse effects. Many people who suffer from this syndrome will already be receiving other antiepileptic medications at the time of their entry into a trial. However, for the purpose of this review we will only consider the effect of the single therapeutic agent being trialled (often as add-on therapy). Search methods: We searched the Cochrane Epilepsy Group's Specialized Register (18 October 2012), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library Issue 10 of 12, 2012) and MEDLINE (1946 to October week 2, 2012). We also searched EMBASE (1980 to March 2003). We imposed no language restrictions. We searched the International Standard Randomised Controlled Trial Number (ISRCTN) register (18 October 2012) for ongoing trials and in addition, we contacted pharmaceutical companies and colleagues in the field to seek any unpublished or ongoing studies. Selection criteria: All randomised controlled trials (RCTs) of the administration of drug therapy to patients with LGS. Data collection and analysis: Two review authors independently extracted data. Analysis included assessing study quality, as well as statistical analysis of the effects on overall seizure rates and effects on specific seizure types (e.g. drop attacks), adverse effects and mortality. Main results: We found nine RCTs, but were unable to perform any meta-analysis, because each trial looked at different populations, different therapies and considered different outcomes. Authors' conclusions: The optimum treatment for LGS remains uncertain and no study to date has shown any one drug to be highly efficacious; rufinamide, lamotrigine, topiramate and felbamate may be helpful as add-on therapy, clobazam may be helpful for drop seizures. Until further research has been undertaken, clinicians will need to continue to consider each patient individually, taking into account the potential benefit of each therapy weighed against the risk of adverse effects.