Treatment for Lambert-Eaton myasthenic syndrome

Lambert-Eaton myasthenic syndrome is an autoimmune presynaptic disorder of neuromuscular transmission. Treatments have attempted to overcome the harmful autoimmune process, or to improve residual neuromuscular transmission, in order to reverse the principal neurological symptom of muscle weakness.

The objective was to examine the efficacy of all forms of treatment in Lambert-Eaton myasthenic syndrome.

We searched the Cochrane Neuromuscular Disease Group specialised trials register (September 2002), MEDLINE (January 1966 to November 2002) and EMBASE (January 1980 to November 2002). We checked the bibliographies in reports of the randomised trials and contacted authors to identify additional published or unpublished data.

Types of studies: all randomised or quasi-randomised trials.

all adults and children with a diagnosis of Lambert-Eaton myasthenic syndrome, with or without small-cell lung cancer. Types of interventions: any form of medical (pharmacological or physical) treatment. Types of outcome measures: Primary: change in the muscle strength scale score (Quantitative Myasthenia Gravis score), or limb muscle strength measured by myometry. Secondary: improvement in the mean amplitude of the resting compound muscle action potentials. The mean amplitude used was the mean of all muscles tested.

We identified three randomised controlled trials. Individual patient data were only available for one trial.

The three eligible trials included two controlled trials of the effects of 3,4-diaminopyridine compared with placebo in a total of 38 patients with Lambert-Eaton myasthenic syndrome, one of which was of crossover design. A third crossover trial compared intravenous immunoglobulin treatment to placebo in nine patients with Lambert-Eaton myasthenic syndrome. A meta-analysis of the primary endpoint results of these trials was not possible because of differences in comparisons and endpoints and, in two trials, lack of individual patient data. EFFECTS OF 3,4-DIAMINOPYRIDINE: Two trials of 3,4-diaminopyridine reported a significant improvement in the primary endpoint of muscle strength score, or myometric limb measurement following treatment. Both trials also reported a significant improvement in the secondary endpoint of resting compound muscle action potential amplitude following 3,4-diaminopyridine, compared with placebo. A meta-analysis of the primary endpoint results was not possible because of marked differences in these two trials regarding primary outcome measures. However, a meta-analysis of the secondary endpoint (improvement in the amplitude of the mean resting compound muscle action potential) was possible. It was necessary to assume a known correlation (similarity) of the paired responses for each individual in the two treatment periods in order to properly allow for the crossover design of one of the two trials (the correlation coefficient was assumed to be 0.5 in calculations). Using this approach, meta-analysis revealed a significant overall benefit in compound muscle action potential amplitude after 3,4-diaminopyridine treatment. The overall weighted mean difference was 1.80 mV (95% confidence interval 0.82 to 2.78), favouring treatment. These results were not sensitive to the assumption made because the overall benefit estimated was still significant when the correlation was assumed to be less than 0.1. EFFECTS OF INTRAVENOUS IMMUNOGLOBULIN: A crossover trial reported a significant improvement in the primary outcome measure of myometric limb strength when patients received intravenous immunoglobulin compared to placebo infusions. This trial also demonstrated an improvement in the secondary outcome measure of change in the mean resting compound muscle action potential amplitude following intravenous immunoglobulin, but this improvement did not reach significance. Clinical improvement lasted for up to eight weeks.

Limited evidence from randomised controlled trials showed that either 3,4-diaminopyridine or intravenous immunoglobulin improved muscle strength scores and compound muscle action potential amplitudes in patients with Lambert-Eaton myasthenic syndrome. There are insufficient data at present to quantify this treatment effect. Other possible treatments, such as plasma exchange, steroids and immunosuppressive agents have not been tested in randomised controlled trials.