Lambert-Eaton Myasthenic Syndrome (LEMS) is a rare, neuromuscular junction autoimmune disease. The immune system produces immunoglobulin G antibodies against voltage-gated calcium channels (VGCC) residing on the cell membrane of the presynaptic nerve ending.1,3,5,6 The etiology of LEMS is decreased exocytosis of the neurotransmitter acetylcholine from presynaptic neurons into the neuromuscular junction (NMJ) caused by autoantibodies attacking VGCCs.3,7.10 There are two distinct groups of LEMS patients: those with small cell lung carcinoma (SCLC) and those without SCLC. SCLS is the cause of LEMS in about 50% of SCLS-LEMS patients and treatment for these patients with the underlying paraneoplastic malignancy is cancer therapy. The SCLC-LEMS subgroup
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All LEMS patients are clinically diagnosed using a classical triad of symptoms, electrophysiological measurements, and antibody panels.7 The classical triad of symptoms in LEMS patients is muscle weakness of the limbs, commonly found in the legs, that advances distally, reduced tendon reflexes, and autonomic dysfunction.1,7 Clinicians use electrophysiological measurements in the form of repetitive nerve stimulation (RNS) in order to objectively test for signs of proximal weakness in rested muscle, which is observed in approximately 80% of all LEMS patients.1,3,7 American neurologists Lambert-Eaton first described six cases where an electrophysiological pattern was observed with RNS, so this pattern remains a hallmark for diagnosis.5 In RNS, LEMS patients exhibit an abnormal decrease in compound muscle action potential amplitude when low frequency stimulation of 2-5 Hz is used and an increase in compound muscle action potential amplitude after exercise or high frequency stimulation.5,7 This change in muscular strength is primarily due to the autoantibody-mediated attack on VGCCs, thereby mitigating the ability for acetylcholine to exit from presynaptic vesicles, to bind acetylcholine receptors of the post-synaptic muscle fiber, and to initiate an action potential and muscle contraction. These autoantibodies are highly sensitive and are detected in 85% of patients with LEMS, whose specificity for distinct muscle weakness is 100%.1,3 The second classical symptom, reduced tendon reflexes, is largely related to muscle weakness because these reflexes are typically hypoactive or absent in a LEMS patient upon clinical examination.1 In a high frequency stimulation, maximal isometric contraction of muscle fibers for a period of 10-15s can induce a tendon reflex that was previously diminished or absent. Called post-exercise facilitation, this
All LEMS patients are clinically diagnosed using a classical triad of symptoms, electrophysiological measurements, and antibody panels.7 The classical triad of symptoms in LEMS patients is muscle weakness of the limbs, commonly found in the legs, that advances distally, reduced tendon reflexes, and autonomic dysfunction.1,7 Clinicians use electrophysiological measurements in the form of repetitive nerve stimulation (RNS) in order to objectively test for signs of proximal weakness in rested muscle, which is observed in approximately 80% of all LEMS patients.1,3,7 American neurologists Lambert-Eaton first described six cases where an electrophysiological pattern was observed with RNS, so this pattern remains a hallmark for diagnosis.5 In RNS, LEMS patients exhibit an abnormal decrease in compound muscle action potential amplitude when low frequency stimulation of 2-5 Hz is used and an increase in compound muscle action potential amplitude after exercise or high frequency stimulation.5,7 This change in muscular strength is primarily due to the autoantibody-mediated attack on VGCCs, thereby mitigating the ability for acetylcholine to exit from presynaptic vesicles, to bind acetylcholine receptors of the post-synaptic muscle fiber, and to initiate an action potential and muscle contraction. These autoantibodies are highly sensitive and are detected in 85% of patients with LEMS, whose specificity for distinct muscle weakness is 100%.1,3 The second classical symptom, reduced tendon reflexes, is largely related to muscle weakness because these reflexes are typically hypoactive or absent in a LEMS patient upon clinical examination.1 In a high frequency stimulation, maximal isometric contraction of muscle fibers for a period of 10-15s can induce a tendon reflex that was previously diminished or absent. Called post-exercise facilitation, this