Lambert-Eaton Myasthenic syndrome: early diagnosis is key

摘要

Lambert-Eaton myasthenic syndrome (LEMS) is an uncommon disorder of neuromuscular transmission with distinctive pathophysiological, clinical, electrophysiological and laboratory features. There are two forms of LEMS. The paraneoplastic (P-LEMS) form is associated with a malignant tumor that is most frequently a small cell lung carcinoma (SCLC), and the autoimmune (A-LEMS) form is often related to other dysimmune diseases. Approximately 90% of LEMS patients present antibodies against presynaptic membrane P/Q-type voltage-gated calcium channels (VGCC). These antibodies are directly implicated in the pathophysiology of the disorder, provoke reduced acetylcholine (ACh) at the nerve terminal and consequently lead to muscle weakness. LEMS is clinically characterized by proximal muscle weakness, autonomic dysfunction and areflexia. In clinically suspected cases, diagnoses are confirmed by serological and electrodiagnostic tests. The detection of P/Q-type VGCC antibodies is supportive when there is clinical suspicion but should be carefully interpreted in the absence of characteristic clinical or electrodiagnostic features. Typical electrodiagnostic findings (ie, reduced compound motor action potentials (CMAPs), significant decrements in the responses to low frequency stimulation and incremental responses after brief exercise or high-frequency stimulation) reflect the existence of a presynaptic transmission defect and are key confirmatory criteria. Diagnosis requires a high level of awareness and necessitates the initiation of a prompt screening and surveillance process to detect and treat malignant tumors. In clinically affected patients without cancer and after cancer treatment, symptomatic treatment with 3,4-diaminopyridine or immunosuppressive agents can significantly improve neurologic symptoms and the quality of life. We present a detailed review of LEMS with special emphasis on the pathophysiological mechanisms, clinical manifestation and diagnostic procedure.