Snapshot A 46-year-old woman with a history of lupus presents with progressive overall weakness. She reports weakness brushing her hair every day and difficulty rising from a seated position. She has no history of smoking, but has a strong history of autoimmune disease in herself (with lupus as well as alopecia areata) and her family. She denies any new dermatological rashes. Her routine labs are all normal. On physical exam, repeated muscle movement resulted in increased strength. Introduction Progressive weakness caused by autoantibody to presynaptic calcium channel on motor neurons type II hypersensitivity reaction Lambert-Eaton syndrome (LES) is also known as Lambert-Eaton myasthenic syndrome Epidemiology less common than myasthenia gravis Pathogenesist antibodies against presynaptic, voltage-gated Ca2+ channels at neuromuscular junction (see illustration) ↓ acetylcholine (ACh) release presynaptic stores of ACh and postsynaptic response to ACh is intact repetitive stimulation will raise endplate potential above threshold generation of muscle action potential disease improves with muscle use May be diagnosed with prolonged paralysis following use of neuromuscular blocking agents after surgery Associated conditions small cell (oat cell) carcinoma of lung recall other paraneoplastic secretions may be ACTH or ADH in 40% of patients with LES, cancer is found non-small cell lung cancer lymphosarcoma malignant thymoma other autoimmune disease Presentation Symptoms/physical exam proximal muscle weakness difficulty rising from a chair difficulty climbing stairs ↓ tendon reflexes autonomic symptoms dry mouth impotence postural hypotension improves temporarily with muscle use (vs myasthenia gravis, where symptoms worsen with muscle use) high temperatures may worsen disease spares extraocular muscles Evaluation Negative edrophonium test cholinesterase inhibitor allows more ACh to present at the neuromuscular junction test is positive if patients regain strength test is negative in LES and positive in myasthenia gravis Voltage-gated Ca2+ channel antibody assay 75-100% of patients ACh receptor antibody assay more commonly positive in myasthenia gravis found occasionally in low titers in LES CT to assess for malignancy Differential Diagnosis Botulism Myasthenia gravis Amyotrophic lateral sclerosis Polymyositis Treatment Treat underlying malignancy Initial treatment pyridostigmine inhibits acetylcholinesterase 3,4-diaminopyridine (DAP) increases the release of ACh Second-line treatment plasma exchange IVIG oral immunosuppressants azathioprine Prognosis, Prevention, and Complications Prognosis if with simultaneous malignancy, prognosis is poorer LES does not affect respiratory system as significantly as myasthenia gravis does Complications impaired quality of life