Lambert-Eaton myasthenic syndrome (ORPHA:43393)
Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune, presynaptic disorder of neuromuscular transmission characterized by fluctuating muscle weakness and autonomic dysfunction frequently associated with small-cell lung cancer (SCLC).
Epidemiology
The prevalence is estimated to be between 1/250,000- 1/333,300 worldwide.
Clinical description
The age of onset is typically over 40 years old, although it may occur at any age. LEMS is characterized by the clinical triad of proximal muscle weakness, autonomic disturbance, and depressed tendon reflexes. Tumors, mostly SCLC (see this term), are present in fifty to sixty percent of LEMS patients. Cerebellar ataxia can occur, in which case it is almost always accompanied by SCLC.
Etiology
Around 90% of LEMS patients have pathogenic antibodies against the presynaptic P/Q-type voltage-gate calcium channel (VGCC). Dysfunction or decrease in number of these channels inhibits release of acetylcholine from the presynaptic endplate, resulting in impaired neuromuscular transmission and muscle weakness.
Diagnostic methods
In addition to the classical clinical triad (although all three features are not always present), the diagnosis of LEMS is based on the detection of VGCC antibodies by using radioimmunoprecipitation assays and/or typical abnormalities of the repetitive nerve stimulation (RNS) test: a low amplitude compound muscle action potential (CMAP), a decremental response to low rate stimulation, and an incremental response to high rate stimulation or after brief exercise (postexercise facilitation). Abnormal single fiber EMG (SFEMG) can confirm a disorder of the neuromuscular junction, but is non-specific.The diagnosis of LEMS almost invariably precedes the discovery of SCLC.
Differential diagnosis
In 60% of LEMS patients, a different diagnosis was initially made such as myasthenia gravis (MG), inclusion body myositis, Guillain-Barré syndrome (GBS), amyotrophic lateral sclerosis (ALS) (see these terms), lumbar canal stenosis, early-phase Parkinson's disease and lower body parkinsonism.
Management and treatment
There is no cure for LEMS and treatment is mainly symptomatic. This includes 3, 4-diaminopyridine phosphate (DAP) which is usually well tolerated and effective. In some patients, the combination of pyridostigmine with 3,4-DAP has been suggested to have an additional positive effect. If symptomatic treatment is insufficient, immunosuppressive therapy with prednisone, alone or in combination with azathioprine, can achieve long-term control of the disorder. Plasmapheresis and high dose administration of intravenous immunoglobulins (IVIGs) have a short effect. An effective treatment against any tumor present is mandatory, both to control the tumor and to improve the clinical symptoms of LEMS.
Prognosis
In general, LEMS responds well to symptomatic and immunosuppressive treatments. However, LEMS can affect every day activities and quality of life of individual patients. Life expectancy depends on the presence of lung cancer. Without cancer, the life expectancy is considered normal. As SCLC (see this term) is a very aggressive cancer, prognosis of patients with LEMS and SCLC is often rather poor. Median survival is 17-24 months, although the amount of patients with long-standing remission or cured is approximately 20% (compared to <2% of patients with a SCLC without LEMS).

                            Last update: 
                            November 2013


                            - Expert reviewer(s): 
                            Dr M.J. [Maarten] TITULAER