Treatment of Lennox-Gastaut syndrome

Child and Familiy Health Services, Goldsworth Park Health Centre, Denton Way, Woking, UK, GU21 3LQ.
Cochrane database of systematic reviews (Online) (Impact Factor: 5.94). 02/2009; DOI: 10.1002/14651858.CD003277.pub2
Source: PubMed

ABSTRACT 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.
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).
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for ongoing trials and in addition, we contacted pharmaceutical companies and colleagues in the field to seek any unpublished or ongoing studies.
All randomised controlled trials (RCTs) of the administration of drug therapy to patients with Lennox-Gastaut syndrome.
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.
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.
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.

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    ABSTRACT: Purpose To evaluate the efficacy, safety, and pharmacokinetics of rufinamide as an adjunctive therapy for patients with Lennox–Gastaut syndrome (LGS) in a randomized, double-blind, placebo-controlled trial. Methods We conducted a multicenter clinical trial with a 4-week baseline, a 2-week titration, a 10-week maintenance, and either a follow-up visit or entry into an open-label extension. Patients with LGS (4 to 30 years old) taking between one and three antiepileptic drugs were recruited. After the baseline period, patients were randomly assigned to rufinamide or placebo. The primary efficacy variable was the percent change in the tonic-atonic seizure frequency per 28 days. Key findings: Of the 59 patients, 29 were randomized to the rufinamide group and 30 to the placebo group. The frequency of epileptic seizures was significantly decreased in the rufinamide group than in the placebo group; the median percent change in frequency of tonic-atonic seizures was -24.2% and -3.3%, respectively, (p = 0.003) and that of total seizures was -32.9% and -3.1%, respectively (p <0.001). Subgroup analyses indicated that the efficacy of rufinamide was consistent independent of clinical background characteristics. The common treatment-related adverse events in the rufinamide group were decreased appetite (17.2%), somnolence (17.2%), and vomiting (13.8%). Transient seizure aggravations were observed in 13 (22.0%) of the 59 patients, though a causal relationship with rufinamide was suspected in only one patient. All adverse events were mild to moderate in severity. The mean plasma concentration of rufinamide within 12 hours after administration was 17.2 μg/mL. Significance: The present results showed a favorable risk-benefit profile for rufinamide as an adjunctive therapy for patients with LGS.
    Epilepsy Research 09/2014; 108(9). DOI:10.1016/j.eplepsyres.2014.08.019 · 2.19 Impact Factor
  • Journal of Pediatric Neurosciences 01/2010; 5(1):86-8. DOI:10.4103/1817-1745.66666
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    ABSTRACT: Primary generalized tonic-clonic seizures are one of a number of generalized seizure types which also includes absence, myoclonic and atonic seizures. Effective control of tonic-clonic seizures is required to reduce the risk of injury and death and to improve quality of life. While most people achieve seizure control with one antiepileptic drug, around 30% do not and usually take a combination of antiepileptic drugs. To assess the effectiveness of adjunctive lamotrigine for refractory primary generalized tonic-clonic seizures. We searched the Cochrane Epilepsy Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE (Ovid) 1950 to June 2010. No language restrictions were imposed. We also contacted GlaxoSmithKline, manufacturers of lamotrigine. Randomised parallel or cross-over add-on trials of add-on lamotrigine for refractory primary generalized tonic-clonic seizures. Outcome measures were: proportion of people (1) with 50% or greater reduction in frequency; (2) with cessation of seizures; (3) who had treatment withdrawn; (4) with adverse effects; and (5) cognitive effects; (6) quality of life outcome measures. Data were independently extracted by review authors. Two small trials were found that met the inclusion criteria. Due to differences in study design we decided not to undertake a meta-analysis. One placebo controlled cross-over trial (26 participants) showed a significant 50% reduction in tonic-clonic seizure frequency with lamotrigine. Rash was the only adverse effect causing discontinuation (N = 7). A placebo controlled parallel trial comparing 117 participants found a significant median percent reduction in tonic-clonic seizure frequency of 66.5% with lamotrigine compared with 34.2% with placebo (P = 0.006). The most common adverse events were dizziness, somnolence and nausea. Two short term trials indicate that lamotrigine has efficacy against primary generalized tonic-clonic seizures; however, this evidence is insufficient to inform clinical practice and longer term active controlled trials are required.
    Cochrane database of systematic reviews (Online) 01/2010; DOI:10.1002/14651858.CD007783.pub2 · 5.94 Impact Factor