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Meta-Analysis
. 2011 Feb 16;2011(2):CD003279.
doi: 10.1002/14651858.CD003279.pub3.

Treatment for Lambert-Eaton myasthenic syndrome

Michael Keogh  1 , Saam Sedehizadeh, Paul Maddison
Affiliations
Meta-Analysis

Treatment for Lambert-Eaton myasthenic syndrome

Michael Keogh et al. Cochrane Database Syst Rev. .

Abstract

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.

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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Conflict of interest statement

Michael Keogh ‐ none known.

Saam Sedehizadeh ‐ none known.

Paul Maddison has received an honorarium from BioMarin, manufacturers of Firdapse, for an advisory meeting..

Figures

1
1
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
2
2
Forest plot of comparison: 1 3,4‐diaminopyridine treatment versus placebo, outcome: 1.1 Change in QMG score with generalised inverse variance model.
3
3
Forest plot of comparison: 1 3,4‐diaminopyridine treatment versus placebo, outcome: 1.3 Improvement in mean CMAP amplitude with generalised inverse variance method using the assumption of r = 0.5 correlation in individual patients before and after treatment in the McEvoy trial.
1.1
1.1. Analysis
Comparison 1 3,4‐diaminopyridine treatment versus placebo, Outcome 1 Change in QMG score with generalised inverse variance model.
1.2
1.2. Analysis
Comparison 1 3,4‐diaminopyridine treatment versus placebo, Outcome 2 Improvement in mean CMAP amplitude with generalised inverse variance method (assumed r = 0.5 for within‐patient treatment effects in cross‐over trials).
1.3
1.3. Analysis
Comparison 1 3,4‐diaminopyridine treatment versus placebo, Outcome 3 Improvement in mean CMAP amplitude (assumed r = 0.5 for within‐patient treatment effects in cross‐over trials).
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References

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