Lambert Eaton Myasthenic Syndrome

Lambert Eaton Myasthenic Syndrome (LEMS) is a pre-synaptic neuromuscular junction disorder characterised clinically by leg-predominant proximal weakness with spread of weakness distally and cranially with increasing severity as well as reduced reflexes and autonomic symptoms such as a dry mouth. Typical electrophysiological findings include small compound muscle action potentials at rest that augment following short exercise, decrement at low frequency (2-5 Hz) repetitive nerve stimulation, and increment at high frequency (20-50 Hz) repetitive nerve stimulation. Immunologically, antibodies to voltage gated calcium channels are present in the majority of patients. LEMS is associated with small cell lung cancer (SCLC), or rarely other tumours, in approximately 50 % of cases, for which patients should be carefully screened. The synaptic physiology of LEMS demonstrates a reduction in the probability of pre-synaptic acetylcholine vesicle release. This results in a reduced number (reduced quantal content) of miniature endplate potentials such that the post-synaptic summative endplate potential is insufficient to trigger myofiber contraction, manifesting as weakness. The clinical electrophysiological findings reflect normal rate-dependent changes at a neuromuscular junction, in the context of a reduction in quantal release. Treatment of LEMS comprises symptomatic treatments such as 3,4 diaminopyridine (amifampridine), which increases quantal release; immunotherapy; and treatment of underlying malignancy if present. The life expectancy of non-tumour LEMS is normal, although complete remission is uncommon. Progression of SCLC determines prognosis in tumour-associated LEMS, which is nonetheless better than in SCLC without LEMS.