The Lambert-Eaton Myasthenic Syndrome — an Overview

Abstract

The Lambert Eaton myasthenic syndrome (LEMS) has a prevalence of around 5/100 0000 and is around 10–20 times rarer than myasthenia gravis (MG). Although LEMS does have a number of similarities to MG, there are important differences. The syndrome is characterized by a mostly proximally localised exercise induced muscle weakness that can lead to respiratory failure often accompanied by autonomous dysfunction. Disease symptoms are caused by autoantibodies directed against P/Q type voltage gated calcium channels (VGCC) that are expressed in the presynaptic motoric nerve terminals. The diagnosis of LEMS is based on the detection of the pathogenic anti-VGCC antibodies as well as the observation of an increment of at least 60% in the electrophysiological examination of an affected muscle. An increment is defined by an increase of the at rest reduced compound muscle action potential (CMAP) either after voluntary maximal innervation or after high frequent (≥20 Hz) stimulation. In almost one third LEMS is of paraneoplastic origin. Therefore an intensive tumor screening is necessary after diagnosis.There are some differences in the clinical presentation between paraneoplastic (pLEMS) and the exclusively autoimmune (aiLEMS) form of LEMS. With respect to this the DELTA-P-Score and the detection of SOX1-antibody are important. The most frequent tumor associated with LEMS is small cell lung carcinoma (SCLC). Therapy is based on the initial distinction between paraneoplastic and autoimmune ethiology. pLEMS necessitates therapy of underlying neoplasia. Usually, aiLEMS- as well as pLEMS patients respond well to 3,4 diaminopyridine (3,4 DAP) often augmented by pyridostigmine. Similar to treatment of myasthenia gravis long-term immunosuppressive treatment is usually required to control symptoms effectively. Myasthenic crisis in LEMS can be controlled by intensive care and immunoglobulins, plasmaphereses or immunoadsorption. Based on case reports more specific immunomodulatory treatment approaches such as the B-cell depleting therapeutic antibody rituximab should be considered in therapy refractory courses of LEMS. Long-term prognosis of autoimmune LEMS with respect to clinical stabilization with (pharmacological) remission is good, although in around 75% of patients significant reductions in quality of life remain. Prognosis of tumor-associated LEMS is largely determined by the tumor and its effective therapy. Curative treatment of the tumour as well as complete remission of pLEMS are possible.

Key words

Lambert Eaton myasthenic syndrome - 3,4-diaminopyridine - anti-VGCC antibodies - DELTA-P -score

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