Treatment for Lambert-Eaton myasthenic syndrome

Lambert-Eaton myasthenic syndrome (LEMS) is a rare disorder of the neuromuscular junction that causes muscle weakness (most commonly in the upper arms and legs). It is an autoimmune disease in which the body's own antibodies prevent the release of the chemical acetylcholine. This interferes with transmission of nerve impulses to the muscles. One of the main treatments is 3,4-diaminopyridine which increases the release of acetylcholine. Four small randomised controlled trials involving 54 participants in total showed that 3,4-diaminopyridine improves muscle strength. This was determined by measuring the compound muscle action potential (CMAP) which is a test that records the amount of electrical activity generated in a muscle when it is stimulated by its nerve. Although the number of trials is relatively small, the quality of evidence from these trials is moderate to high, which supports the findings of this review. The changes are measured over days only. A single trial involving nine participants showed that intravenous immunoglobulin also improved muscle strength up to 8 weeks from treatment. Other possible treatments such as plasma exchange, steroids and immunosuppressive agents have not been tested in randomised controlled trials. Further trials of these treatments are needed.

Authors' conclusions: 

Limited but moderate to high quality evidence from randomised controlled trials showed that over days 3,4-diaminopyridine, or for up to 8 weeks IVIg, improved muscle strength scores and CMAP amplitudes in participants with Lambert-Eaton myasthenic syndrome. There are insufficient data at present to quantify this effect. Other possible treatments have not been tested in randomised controlled trials.

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Background: 

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder of neuromuscular transmission. Treatments attempt to overcome the harmful autoimmune process, or improve residual neuromuscular transmission

Objectives: 

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

Search strategy: 

We searched the Cochrane Neuromuscular Disease Group Specialized Register (12 October 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (12 October 2010, Issue 4 2010 in the Cochrane Library), MEDLINE (January 1966 to September 2010) and EMBASE (January 1980 to September 2010).

Selection criteria: 

All randomised or quasi-randomised trials of adults and children with a diagnosis of Lambert-Eaton myasthenic syndrome, with or without small-cell lung cancer, receiving any form of pharmacological or physical treatment.

Data collection and analysis: 

All authors independently assessed studies for inclusion and extracted data. Study authors were contacted for missing information when possible.

Main results: 

Four controlled trials of 3,4-diaminopyridine compared with placebo in a total of 54 participants with Lambert-Eaton myasthenic syndrome were eligible: three cross-over trials and one parallel group. Two were added at this update. One of these trials also assessed pyridostigmine in conjunction with 3,4-diaminopyridine. A further cross-over trial compared intravenous immunoglobulin (IVIg) to placebo in nine participants.

Four trials of 3,4-diaminopyridine reported significant improvement in the primary outcome, muscle strength score, or myometric limb measurement for between hours and a week following treatment, and significant improvement in resting compound muscle action potential (CMAP) amplitude following 3,4-diaminopyridine, compared with placebo.

A meta-analysis of the primary endpoint showed Quantitative Myasthenia Gravis (QMG) muscle score assessed between three and eight days was likely to improve by a mean of 2.44 points (95% confidence interval 3.6 to 1.22). Meta-analysis of the secondary endpoint CMAP amplitude also showed a mean improvement of 1.36 mV (95% confidence interval 0.99 to 1.72) over the same period. The risk of bias was determined to be low, and quality of evidence moderate to high.

A single cross-over trial reported significant improvement in myometric limb strength and non-significant improvement in mean resting CMAP amplitude with IVIg compared to placebo. Clinical improvement lasted for up to eight weeks.

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