Treatment for Lambert‐Eaton myasthenic syndrome
Abstract
Background
Lambert‐Eaton myasthenic syndrome is an autoimmune presynaptic disorder of neuromuscular transmission. Treatments attempt to overcome the harmful autoimmune process, or to improve residual neuromuscular transmission, in order to reverse muscle weakness.
Objectives
The objective was to examine the efficacy of treatment in Lambert‐Eaton myasthenic syndrome.
Search methods
We searched the Cochrane Neuromuscular Disease Group Trials Register (April 2007), MEDLINE (January 1966 to February 2007) and EMBASE (January 1980 to February 2007), and checked bibliographies and contacted authors to identify additional published or unpublished data.
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. The primary outcome measure was change in muscle strength scale score (Quantitative Myasthenia Gravis score), or limb muscle strength measured by myometry. The secondary outcome measure was improvement in the mean amplitude of the resting compound muscle action potentials. The mean amplitude used was the mean of all muscles tested.
Data collection and analysis
We identified three randomised controlled trials.
Main results
Two controlled trials of the effects of 3,4‐diaminopyridine compared with placebo in a total of 38 participants with Lambert‐Eaton myasthenic syndrome were eligible, one of which was of crossover design. A third crossover trial compared intravenous immunoglobulin treatment to placebo in nine participants.
Two trials of 3,4‐diaminopyridine reported a significant improvement in muscle strength score, or myometric limb measurement following treatment, and a significant improvement in 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 primary outcome measures. However, a meta‐analysis of the secondary endpoint was possible. The overall weighted mean difference was 1.80 mV (95% confidence interval 0.82 to 2.78), favouring treatment.
A crossover trial reported a significant improvement in myometric limb strength and a non‐significant improvement in change in the mean resting compound muscle action potential amplitude when participants received intravenous immunoglobulin compared to placebo infusions. Clinical improvement lasted for up to eight weeks.
Authors' conclusions
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 participants with Lambert‐Eaton myasthenic syndrome. There are insufficient data at present to quantify this treatment effect. Other possible treatments have not been tested in randomised controlled trials.
Plain language summary
Limited evidence from randomised controlled trials shows that either 3,4 diaminopyridine or intravenous immunoglobulin improves muscle strength in people with Lambert‐Eaton myasthenic syndrome
Lambert‐Eaton myasthenic syndrome (LEMS) is a rare disorder of the neuromuscular junction causing 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. Two small randomised controlled trials involving 38 participants in total showed that 3,4 DAP improves muscle strength. A single trial involving nine participants showed that intravenous immunoglobulin also improved muscle strength. 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.
