Antibodies against the muscle
acetylcholine receptor (AChR) were recognized as the cause of
myasthenia gravis in the 1970s'. Since then, other
neurological disorders associated with
autoantibodies have been identified, each associated with an antibody against a
ligand- or voltage-gated
ion channel.
Autoantibodies against P/Q-type voltage-gated
calcium channels (VGCCs) are detected in patients with
Lambert-Eaton myasthenic syndrome (LEMS). These
antibodies interfere with the
calcium-dependent release of
acetylcholine from the presynaptic membrane. LEMS is an autoimmune disorder affecting the neuromuscular junction, and is characterized by proximal
muscle weakness, reduction of tendon reflex, and autonomic dysfunction. Electrophysiological examinations show small-amplitude compound muscle action potentials and increments on rapid repetitive nerve stimulation. Fifty to sixty percent of LEMS patients present with
tumors, mostly
small cell lung carcinoma (SCLC), as a
paraneoplastic syndrome. SCLC is a
neuroendocrine tumor, which expresses neuronal VGCCs. Some patients present
cerebellar ataxia, which is always accompanied by SCLC. These patients tend to show higher titers of VGCC
antibodies than that by LEMS patients with no
ataxia. The diagnosis can be confirmed by finding reduced compound muscle action potential amplitudes at rest that shows increments greater than 100% with repetitive nerve stimulation and antibody detection by using radioimmunoprecipitation assays. The treatment options are generally categorized as anti-
tumor, immunomodulating, immunosuppressing, and symptomatic treatments. In cases with SCLC, effective treatment against the
tumor can improve LEMS.
Plasmapheresis and
intravenous administration of high-dose
immunoglobulins have a short effect.
Prednisone, alone or in combination with
immunosuppressants can achieve long-term control of the disorder.