Treatment of infantile spasms.

BACKGROUND: Infantile spasms (West's Syndrome) is a syndrome that includes a peculiar type of epileptic seizure-the spasms-and an electroencephalographic (EEG) abnormality often called hypsarrhythmia. Psychomotor retardation is frequently found at follow-up. Approximately two-thirds of affected infants will have a detectable underlying neurological abnormality, but still little is known about the pathophysiological basis for infantile spasms, and treatment remains problematic. OBJECTIVES: To compare the effects of single pharmaceutical therapies used to treat infantile spasms in terms of control of the spasms, resolution of the EEG, relapse rates, psychomotor development, subsequent epilepsy, side effects, and mortality. SEARCH METHODS: To identify published data, we searched the Cochrane Epilepsy Group Specialised Register (October 2012), CENTRAL (The Cochrane Library 2012, Issue 9), MEDLINE (1946 to September Week 4, 2012), EMBASE (1980 to March 2003), and the reference lists of all retrieved articles.To identify unpublished data, we searched the ISRCTN Register (www.controlled-trials.com), corresponded with colleagues and drug companies, and made requests at international conferences. SELECTION CRITERIA: All randomised controlled trials (RCTs) of the administration of drug therapy to patients with infantile spasms. DATA COLLECTION AND ANALYSIS: Data collection from all relevant publications was independently undertaken by three review authors (before 2010) or by two review authors using a standard proforma. Analysis included assessment of study quality and a search for sources of heterogeneity. MAIN RESULTS: We found 16 small RCTs (fewer than 100 patients enrolled) and 2 larger RCTs (more than 100 patients enrolled). These 18 studies looked at a total of 916 patients treated with a total of 12 different pharmaceutical agents. Overall methodology of the studies was poor, in part because of ethical dilemmas such as giving placebo injections to children. Two studies showed that placebo was not as good as active treatment in resolving the spasms. The strongest evidence suggested that hormonal treatment (prednisolone or tetracosactide depot) leads to resolution of spasms faster and in more infants than does vigabatrin. Responses without subsequent relapse may be no different. The same study suggests that hormonal treatments might improve the long-term developmental outcome compared with vigabatrin in infants not found to have an underlying cause for their infantile spasms. AUTHORS' CONCLUSIONS: To date, few well-designed RCTs have considered the treatment of infantile spasms, and the numbers of patients enrolled have been small. In the majority, methodology has been poor, hence it is not clear which treatment is optimal in the treatment of this epilepsy syndrome. Hormonal treatment resolves spasms in more infants than vigabatrin, but this may or may not translate into better long-term outcomes. If prednisolone or vigabatrin is used, high dosage is recommended. Vigabatrin may be the treatment of choice in tuberous sclerosis. Resolution of the EEG features may be important, but this has not been proven. Further research using large studies with robust methodology is required.

Treatment of Lennox-Gastaut syndrome.

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.

Treatment of Lennox-Gastaut syndrome.

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.

Treatment of infantile spasms.

BACKGROUND: Infantile spasms (West's Syndrome) is a syndrome which includes a peculiar type of epileptic seizure, the spasms, and an electroencephalogram (EEG) abnormality often called hypsarrhythmia. Psychomotor retardation is frequently found at follow up. Approximately two thirds of affected infants will have a detectable underlying neurological abnormality, but still little is known about the pathophysiological basis for infantile spasms and treatment remains problematic. OBJECTIVES: To compare the effects of single pharmaceutical therapies used to treat infantile spasms in terms of control of the spasms, resolution of the EEG, relapse rates, psychomotor development, subsequent epilepsy, side effects, and mortality. SEARCH STRATEGY: Published data: Cochrane Epilepsy Group Specialised Register, CENTRAL (The Cochrane Library 2007, Issue 4), MEDLINE, EMBASE, and the reference lists of all retrieved articles.Unpublished data: ISRCTN Register (www.controlled-trials.com), correspondence with colleagues and drug companies, and requests at international conferences. SELECTION CRITERIA: All randomised controlled trials of the administration of drug therapy to patients with infantile spasms. DATA COLLECTION AND ANALYSIS: Data collection from all relevant publications was independently undertaken by three review authors using a standard proforma. Analysis included assessment of study quality and looking for sources of heterogeneity. MAIN RESULTS: We found 12 small RCTs (less than 60 patients enrolled) and two larger RCT (more than 100 patients enrolled). These 14 studies looked at a total of 681 patients treated with a total of nine different pharmaceutical agents. Overall methodology of the studies was poor, partly because of ethical dilemmas such as giving placebo injections to children. Two studies showed that placebo was not as good as active treatment in resolving the spasms. The strongest evidence suggested that hormonal treatment leads to resolution of spasms faster and in more infants than does vigabatrin. Responses without subsequent relapse may be no different. The same study suggests that hormonal treatments (prednisolone or tetracosactide) might improve the long-term developmental outcome compared with vigabatrin in infants not found to have an underlying cause for their infantile spasms. AUTHORS' CONCLUSIONS: To date, there have been few well-designed RCTs that considered the treatment of infantile spasms, and the numbers of patients enrolled have been small. Overall methodology has been poor, hence it is not clear which treatment is optimal in the treatment of this epilepsy syndrome. Hormonal treatment resolves spasms in more infants than vigabatrin but this may or may not translate into a better long-term outcome. If prednisone or vigabatrin are used then high dosage is recommended. Vigabatrin may be the treatment of choice in tuberous sclerosis. Resolution of the EEG features may be important but this has not been proven. Further research using large studies with robust methodology is still required.