Mechanism of action: immune-mediated disruption of the pre-synaptic structure of the neuromuscular junction . Autoantibodies are usually directed against the voltage-gated calcium channel (VGCC) of the nerve terminal.
While most patients have an underlying neoplasm, some patients have it as a pure autoimmune disorder. The onset of symptoms may antedate the diagnosis of a cancer by months or years, which may make diagnosis as not being paraneoplastic difficult.
Tumors associated with LEMS:
(1) lung, especially small cell carcinoma of the lung
(2) breast cancer
(3) thymoma
(4) carcinoma of the GI tract: gastric, colon, rectum
(5) carcinoma of the GU tract: urinary bladder, kidney, prostate
(6) malignant lymphoma
(7) gallbladder carcinoma
Clinical features:
(1) muscle weakness and fatigability, most prominent in the proximal muscles of the lower extremities
(2) abnormal gait
(3) hyporeflexia
(4) enhancement of deep tendon reflexes after contraction or stimulation (facilitation)
(5) autonomic dysfunction: dry mouth, constipation, male impotence, gastroparesis
(6) cranial nerves may be involved but signs tend to be subtle
(7) ventilatory failure or prolonged apnea after general anesthesia
(8) paresthesias
(9) blurred vision
(10) sphincter dysfunction
(11) difficulty swallowing
Laboratory findings:
(1) antibodies to VGCC (especially the P/Q type)
(2) antibodies to synaptotagmin
(3) anti-CV2
Electrophysiology:
(1) low amplitude of M waves
(2) decrement with slow repetitive nerve stimulation
(3) waxing phenomenon (facilitation) with high-frequency nerve stimulation
Clinical symptoms may improve with:
(1) immunosuppression (prednisone, azathioprine, others)
(2) intravenous immunoglobulin infusion
(3) apheresis
