Lambert-Eaton myasthenic syndromes

Abstract

Lambert Eaton Myasthenic Syndrome (LEMS) is a rare disorder of the neuromuscular junction characterized by a presynaptic defect in neuromuscular transmission. It can either be paraneoplastic in about half of the cases, or a primary autoimmune disease. It is caused by autoantibodies directed against the P/Q type voltage gated calcium channels (VGCC), which results in reduced influx of calcium during depolarization, interfering with the calcium dependent release of acetylcholine in the synaptic cleft. LEMS is usually a disease of adults, with the clinical features of weakness, more so in the lower limbs but also affecting upper limbs, hypo or areflexia, and autonomic dysfunction such as dry mouth. Besides the typical clinical features, the diagnosis is dependent on electrodiagnostic findings, characterized by low compound muscle action potentials (CMAP) with prominent post exercise potentiation, a CMAP amplitude decrement on low frequency repetitive stimulation, but with an increment on high frequency repetitive stimulation. Serum anti-P/Q-type VGCC can be detected in about 50% of cases. However, about 90% of paraneoplastic LEMS cases associated with small cell lung cancer (SCLC), test positive for the antibody. Sixty-four percent of LEMS patients with SCLC also test positive for antibodies against SOX1, which may play a role as an early marker for predisposition to LEMS/SCLC. Anti- SOX1 antibodies are 95% specific and about 65% sensitive for LEMS with SCLC. Once LEMS is diagnosed, the patient should be screened for cancer. If cancer is not detected initially, the patient should continue to be screened every 3 to 6 months for at least two years. Treatment of LEMS consists of treating the primary cancer in paraneoplastic cases. The drug of choice for symptomatic treatment of LEMS is 3,4- diaminopyridine. Immunosuppressive therapy with azathioprine and corticosteroids might be helpful in patients who do not respond to symptomatic treatment.