Eleanor C Hancock1, Helen H J Cross. 1. Child and Familiy Health Services, Goldsworth Park Health Centre, Denton Way, Woking, UK, GU21 3LQ.
Abstract
BACKGROUND: The Lennox-Gastaut syndrome is an age-specific disorder, characterised by epileptic seizures, a characteristic electroencephalogram (EEG), psychomotor delay and behaviour disorders. It occurs more frequently in males and onset is usually before the age of eight, with a peak between three and five years. 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 (for example 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 Lennox-Gastaut syndrome 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 trialed (often as add-on therapy). SEARCH STRATEGY: We searched the Cochrane Epilepsy Group's Specialized Register (February 2009), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2009), and MEDLINE (1950 to January 2009). We also searched EMBASE (1980 to March 2003). We imposed no language restrictions. We searched the ISRCTN register for ongoing trials and in addition, we contacted pharmaceutical companies and colleagues in the field to seek any unpublished or ongoing studies.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 Lennox-Gastaut syndrome. 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 seven 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 Lennox-Gastaut syndrome 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. 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.
BACKGROUND: The Lennox-Gastaut syndrome is an age-specific disorder, characterised by epileptic seizures, a characteristic electroencephalogram (EEG), psychomotor delay and behaviour disorders. It occurs more frequently in males and onset is usually before the age of eight, with a peak between three and five years. 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 (for example 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 Lennox-Gastaut syndrome 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 trialed (often as add-on therapy). SEARCH STRATEGY: We searched the Cochrane Epilepsy Group's Specialized Register (February 2009), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2009), and MEDLINE (1950 to January 2009). We also searched EMBASE (1980 to March 2003). We imposed no language restrictions. We searched the ISRCTN register 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 Lennox-Gastaut syndrome. 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 seven 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 Lennox-Gastaut syndrome 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. 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.