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Lambert-Eaton myasthenic syndrome (LEMS)

Etiology: 1) 50-70% of patients (especially men) have associated malignancy a) small cell lung carcinoma (most common) b) breast cancer c) prostate cancer d) gastric cancer 2) autoimmune a) autoantibody against voltage-gated calcium channel b) association of LEMS with other autoimmune diseases Epidemiology: - 3% of patients with small cell lung cancer [2,6] Pathology: 1) autoantibody against voltage-gated Ca+2 channel alpha 1D (CACNA1D) - impaired influx of Ca+2 into presynaptic terminals 2) defective release of acetylcholine from presynaptic terminals Clinical manifestations: 1) progressive proximal muscle weakness (especially legs) - improves with repeated effort, then declines with sustained activity 2) autonomic dysfunction a) diplopia b) ptosis (uncommon) c) impotency d) urinary dysfunction e) paresthesias f) dry mouth g) orthostatic hypotension 3) muscle stretch reflexes a) generally decreased or absent b) may sometimes be elicited after exercise or repeated tapping of the tendon 4) generally spares muscles supplied by cranial nerves (in contrast to myasthenia gravis) Laboratory: - serology: a) antibodies against SOX1 in 64% of the patients with LEMS secondary to small-cell carcinoma of the lung, but in 0% of patients with idiopathic LEMS [5] b) antibody to voltage-gated calcium channel CACNA1D [2] Special laboratory: - repetitive nerve stimulation study a) shows low amplitude motor unit potential with distal nerve stimulation that increases in amplitude with repeated stimulation (> 100% increase) [2] b) contrast with myasthenia gravis that shows a decrement in motor unit potential with repeated stimulation Management: 1) glucocorticoids 2) immunosuppressive agents 3) plasma exchange 4) intravenous immunoglobulin 5) 3,4-diaminopyridine - may increase acetylcholine release at the neuromuscular junction 6) treatment of underlying malignancy

Interactions

disease interactions

Related

voltage-dependent L-type Ca+2 channel beta-2; CAB2; Ca+2 channel voltage-dependent subunit beta 2; Lambert-Eaton myasthenic syndrome antigen B; MYSB (CACNB2, CACNLB2, MYSB)

General

neuromuscular junction disorder paraneoplastic neurologic syndrome

Properties

AUTOANTIBODY: voltage-dependent L-type Ca+2 channel beta-2 ASSOCIATED-NEOPLASM[S]: small cell carcinoma

References

  1. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 640
  2. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 18. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015, 2018.
  3. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 624
  4. Geriatrics Review Syllabus, American Geriatrics Society, 5th edition, 2002-2004
  5. Sabater L et al. SOX1 antibodies are markers of paraneoplastic Lambert-Eaton myasthenic syndrome. Neurology 2008 Mar 18; 70:924 PMID: 18032743 - Lang B and Evoli A. SOX1 autoantibodies: Tumor markers in LEMS patients? Neurology 2008 Mar 18; 70:906 PMID: 18347313
  6. Payne M, Bradbury P, Lang B et al Prospective study into the incidence of Lambert Eaton myasthenic syndrome in small cell lung cancer. J Thorac Oncol. 2010 Jan;5(1):34-8. PMID: 19934775
  7. Petty R Lambert Eaton myasthenic syndrome. Pract Neurol. 2007 Aug;7(4):265-7. PMID: 17636143
  8. Sanders DB, Guptill JT. Myasthenia gravis and Lambert-Eaton myasthenic syndrome. Continuum (Minneap Minn). 2014 Oct;20 (5 Peripheral Nervous System Disorders):1413-25. Review. PMID: 2529929