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Electrodiagnostic evaluation of the neuromuscular junction

David H Weinberg, MD
Section Editor
Jeremy M Shefner, MD, PhD
Deputy Editor
John F Dashe, MD, PhD


Repetitive nerve stimulation (RNS) and single fiber electromyography (SFEMG) are important confirmatory tests for the diagnosis of disorders of the nicotinic neuromuscular junction, particularly for myasthenia gravis, Lambert-Eaton myasthenic syndrome, and botulism. This topic will review the basic principles of neuromuscular transmission and electrodiagnostic testing with RNS and SFEMG.

Other clinical aspects of neuromuscular junction disorders are reviewed separately. (See "Clinical manifestations of myasthenia gravis" and "Diagnosis of myasthenia gravis" and "Clinical features and diagnosis of Lambert-Eaton myasthenic syndrome" and "Botulism".)


The nicotinic neuromuscular junction is a complex, specialized structure incorporating the distal axon terminal and the muscle membrane that allows for the unidirectional chemical communication between peripheral nerve and muscle. It consists of the presynaptic nerve terminal, the synaptic cleft, and the postsynaptic endplate region on the muscle fiber. Acetylcholine serves as the neurotransmitter for voluntary striated muscle. The sections that follow provide a simplified summary of the morphology and neurophysiology of the neuromuscular junction that permits an adequate understanding of the electrodiagnostic testing principles (figure 1).

Morphology — The presynaptic region of the nicotinic neuromuscular junction consists of a specialized terminal nerve structure surrounded by Schwann cells. The presynaptic region includes voltage-gated calcium channels embedded in the nerve membrane, numerous mitochondria, and acetylcholine-containing synaptic vesicles. Each vesicle contains 5000 to 10,000 molecules of acetylcholine, known as a quantum [1,2]. The populations of vesicles behave as if they are divided roughly into three pools [3]:

The primary pool for immediate release


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Literature review current through: Dec 2016. | This topic last updated: Tue Sep 13 00:00:00 GMT+00:00 2016.
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  1. Fletcher P, Forrester T. The effect of curare on the release of acetylcholine from mammalian motor nerve terminals and an estimate of quantum content. J Physiol 1975; 251:131.
  2. Kuffler SW, Yoshikami D. The number of transmitter molecules in a quantum: an estimate from iontophoretic application of acetylcholine at the neuromuscular synapse. J Physiol 1975; 251:465.
  3. Howard JF Jr. Neuromuscular transmission. In: Neuromuscular function and disease: Basic, clinical and electrodiagnostic aspects, 1st edition, Brown WF, Bolton CF, Aminoff MJ. (Eds), W.B. Saunders Company, Philadelphia 2002. Vol 1, p.401.
  4. Albuquerque EX, Barnard EA, Porter CW, Warnick JE. The density of acetylcholine receptors and their sensitivity in the postsynaptic membrane of muscle endplates. Proc Natl Acad Sci U S A 1974; 71:2818.
  5. Baker PF. Calcium and the control of neuro-secretion. Sci Prog 1977; 64:95.
  6. FATT P, KATZ B. An analysis of the end-plate potential recorded with an intracellular electrode. J Physiol 1951; 115:320.
  7. Hughes BW, Kusner LL, Kaminski HJ. Molecular architecture of the neuromuscular junction. Muscle Nerve 2006; 33:445.
  8. DEL CASTILLO J, KATZ B. Quantal components of the end-plate potential. J Physiol 1954; 124:560.
  9. Wood SJ, Slater CR. Safety factor at the neuromuscular junction. Prog Neurobiol 2001; 64:393.
  10. Preston DC, Shapiro BE. Repetitive nerve stimulation. In: Electromyography and neuromuscular disorders: Clinical-electrophysiologic correlations, 2nd edition, Butterworth-Heinemann, 2005. p.66.
  11. Oh SJ, Kurokawa K, Claussen GC, Ryan HF Jr. Electrophysiological diagnostic criteria of Lambert-Eaton myasthenic syndrome. Muscle Nerve 2005; 32:515.
  12. Preston DC, Shapiro BE. Electromyography and neuromuscular disorders: Clinical-electrophysiologic correlations, 2nd edition, Butterworth-Heinemann, 2005.
  13. Kimura J. Electrodiagnosis in diseases of nerve and muscle: Principles and practice, 3rd edition, Oxford University Press, New York 2001.
  14. Oh SJ, Eslami N, Nishihira T, et al. Electrophysiological and clinical correlation in myasthenia gravis. Ann Neurol 1982; 12:348.
  15. Sanders DB. Clinical neurophysiology of disorders of the neuromuscular junction. J Clin Neurophysiol 1993; 10:167.
  16. Slomić A, Rosenfalck A, Buchthal F. Electrical and mechanical responses of normal and myasthenic muscle. Brain Res 1968; 10:1.
  17. Oh SJ, Head T, Fesenmeier J, Claussen G. Peroneal nerve repetitive nerve stimulation test: its value in diagnosis of myasthenia gravis and Lambert-Eaton myasthenic syndrome. Muscle Nerve 1995; 18:867.
  18. Borenstein S, Desmedt JE. Local cooling in myasthenia. Improvement of neuromuscular failure. Arch Neurol 1975; 32:152.
  19. Petretska A, Jarrar R, Rubin DI. Radial nerve repetitive stimulation in myasthenia gravis. Muscle Nerve 2006; 33:817.
  20. Yiannikas C, Sheean GL, King PJ. The relative sensitivities of the axillary and accessory nerves in the diagnosis of myasthenia gravis. Muscle Nerve 1994; 17:561.
  21. Schumm F, Stöhr M. Accessory nerve stimulation in the assessment of myasthenia gravis. Muscle Nerve 1984; 7:147.
  22. Rubin DI, Harper CM, Auger RG. Trigeminal nerve repetitive stimulation in myasthenia gravis. Muscle Nerve 2004; 29:591.
  23. Ruys-Van Oeyen AE, van Dijk JG. Repetitive nerve stimulation of the nasalis muscle: technique and normal values. Muscle Nerve 2002; 26:279.
  24. Niks EH, Badrising UA, Verschuuren JJ, Van Dijk JG. Decremental response of the nasalis and hypothenar muscles in myasthenia gravis. Muscle Nerve 2003; 28:236.
  25. Mier A, Brophy C, Moxham J, Green M. Repetitive stimulation of phrenic nerves in myasthenia gravis. Thorax 1992; 47:640.
  26. Zifko U, Nicolle MW, Remtulla H, Bolton CF. Repetitive phrenic nerve stimulation study in normal subjects. J Clin Neurophysiol 1997; 14:235.
  27. Zifko UA, Nicolle MW, Grisold W, Bolton CF. Repetitive phrenic nerve stimulation in myasthenia gravis. Neurology 1999; 53:1083.
  28. Maher J, Grand'Maison F, Nicolle MW, et al. Diagnostic difficulties in myasthenia gravis. Muscle Nerve 1998; 21:577.
  29. Bever CT Jr, Aquino AV, Penn AS, et al. Prognosis of ocular myasthenia. Ann Neurol 1983; 14:516.
  30. Horowitz SH, Genkins G, Kornfeld P, Papatestas AE. Electrophysiologic diagnosis of myasthenia gravis and the regional curare test. Neurology 1976; 26:410.
  31. Schady W, MacDermott N. On the choice of muscle in the electrophysiological assessment of myasthenia gravis. Electromyogr Clin Neurophysiol 1992; 32:99.
  32. Oh SJ, Hatanaka Y, Hemmi S, et al. Repetitive nerve stimulation of facial muscles in MuSK antibody-positive myasthenia gravis. Muscle Nerve 2006; 33:500.
  33. Rutkove SB, Shefner JM, Wang AK, et al. High-temperature repetitive nerve stimulation in myasthenia gravis. Muscle Nerve 1998; 21:1414.
  34. Maselli RA, Ellis W, Mandler RN, et al. Cluster of wound botulism in California: clinical, electrophysiologic, and pathologic study. Muscle Nerve 1997; 20:1284.
  35. Padua L, Aprile I, Monaco ML, et al. Neurophysiological assessment in the diagnosis of botulism: usefulness of single-fiber EMG. Muscle Nerve 1999; 22:1388.
  36. Cherington M. Clinical spectrum of botulism. Muscle Nerve 1998; 21:701.
  37. Maselli RA, Bakshi N. AAEM case report 16. Botulism. American Association of Electrodiagnostic Medicine. Muscle Nerve 2000; 23:1137.
  38. Cherington M. Electrophysiologic methods as an aid in diagnosis of botulism: a review. Muscle Nerve 1982; 5:S28.
  39. Cornblath DR, Sladky JT, Sumner AJ. Clinical electrophysiology of infantile botulism. Muscle Nerve 1983; 6:448.
  40. Cherington M. Botulism. Ten-year experience. Arch Neurol 1974; 30:432.
  41. Stålberg E, Trontelj JV. Single fibre electromyography, The Miravalle Press, Woking, Surrey 1979.
  42. Benatar M, Hammad M, Doss-Riney H. Concentric-needle single-fiber electromyography for the diagnosis of myasthenia gravis. Muscle Nerve 2006; 34:163.
  43. Farrugia ME, Weir AI, Cleary M, et al. Concentric and single fiber needle electrodes yield comparable jitter results in myasthenia gravis. Muscle Nerve 2009; 39:579.
  44. Massey JM, Sanders DB, Howard JF Jr. The effect of cholinesterase inhibitors of SFEMG in myasthenia gravis. Muscle Nerve 1989; 12:154.
  45. Single fiber EMG reference values: a collaborative effort. Ad Hoc Committee of the AAEM Special Interest Group on Single Fiber EMG. Muscle Nerve 1992; 15:151.
  46. Bromberg MB, Scott DM. Single fiber EMG reference values: reformatted in tabular form. AD HOC Committee of the AAEM Single Fiber Special Interest Group. Muscle Nerve 1994; 17:820.
  47. Balci K, Turgut N, Nurlu G. Normal values for single fiber EMG parameters of frontalis muscle in healthy subjects older than 70 years. Clin Neurophysiol 2005; 116:1555.
  48. Trontelj JV, Mihelin M, Fernandez JM, Stålberg E. Axonal stimulation for end-plate jitter studies. J Neurol Neurosurg Psychiatry 1986; 49:677.
  49. Trontelj JV, Khuraibet A, Mihelin M. The jitter in stimulated orbicularis oculi muscle: technique and normal values. J Neurol Neurosurg Psychiatry 1988; 51:814.
  50. Sanders DB, Stålberg EV. AAEM minimonograph #25: single-fiber electromyography. Muscle Nerve 1996; 19:1069.
  51. Sanders DB, Howard JF Jr, Johns TR. Single-fiber electromyography in myasthenia gravis. Neurology 1979; 29:68.
  52. Oh SJ, Kim DE, Kuruoglu R, et al. Diagnostic sensitivity of the laboratory tests in myasthenia gravis. Muscle Nerve 1992; 15:720.
  53. Oey PL, Wieneke GH, Hoogenraad TU, van Huffelen AC. Ocular myasthenia gravis: the diagnostic yield of repetitive nerve stimulation and stimulated single fiber EMG of orbicularis oculi muscle and infrared reflection oculography. Muscle Nerve 1993; 16:142.
  54. Valls-Canals J, Povedano M, Montero J, Pradas J. Stimulated single-fiber EMG of the frontalis and orbicularis oculi muscles in ocular myasthenia gravis. Muscle Nerve 2003; 28:501.
  55. Sanders DB, Howard JF Jr. AAEE minimonograph #25: Single-fiber electromyography in myasthenia gravis. Muscle Nerve 1986; 9:809.
  56. Weinberg DH, Rizzo JF 3rd, Hayes MT, et al. Ocular myasthenia gravis: predictive value of single-fiber electromyography. Muscle Nerve 1999; 22:1222.
  57. Stickler DE, Massey JM, Sanders DB. MuSK-antibody positive myasthenia gravis: clinical and electrodiagnostic patterns. Clin Neurophysiol 2005; 116:2065.
  58. Farrugia ME, Kennett RP, Newsom-Davis J, et al. Single-fiber electromyography in limb and facial muscles in muscle-specific kinase antibody and acetylcholine receptor antibody myasthenia gravis. Muscle Nerve 2006; 33:568.
  59. Wolfe GI, Oh SJ. Clinical phenotype of muscle-specific tyrosine kinase-antibody-positive myasthenia gravis. Ann N Y Acad Sci 2008; 1132:71.
  60. Guptill JT, Sanders DB, Evoli A. Anti-MuSK antibody myasthenia gravis: clinical findings and response to treatment in two large cohorts. Muscle Nerve 2011; 44:36.
  61. Murga L, Sánchez F, Menéndez C, Castilla JM. Diagnostic yield of stimulation and voluntary single-fiber electromyography in myasthenia gravis. Muscle Nerve 1998; 21:1081.
  62. Rostedt A, Saders LL, Edards LJ, et al. Predictive value of single-fiber electromyography in the extensor digitorum communis muscle of patients with ocular myasthenia gravis: a retrospective study. J Clin Neuromuscul Dis 2000; 2:6.
  63. Sanders DB. The effect of firing rate on neuromuscular jitter in Lambert-Eaton myasthenic syndrome. Muscle Nerve 1992; 15:256.
  64. Schwartz MS, Stålberg E. Myasthenic syndrome studied with single fiber electromyography. Arch Neurol 1975; 32:815.
  65. Trontelj JV, Stålberg E. Single motor end-plates in myasthenia gravis and LEMS at different firing rates. Muscle Nerve 1991; 14:226.
  66. Chaudhry V, Watson DF, Bird SJ, Cornblath DR. Stimulated single-fiber electromyography in Lambert-Eaton myasthenic syndrome. Muscle Nerve 1991; 14:1227.
  67. Trontelj JV, Stålberg E, Mihelin M, Khuraibet A. Jitter of the stimulated motor axon. Muscle Nerve 1992; 15:449.
  68. Girlanda P, Dattola R, Messina C. Single fibre EMG in 6 cases of botulism. Acta Neurol Scand 1983; 67:118.
  69. Chiou-Tan FY, Gilchrist JM. Repetitive nerve stimulation and single-fiber electromyography in the evaluation of patients with suspected myasthenia gravis or Lambert-Eaton myasthenic syndrome: Review of recent literature. Muscle Nerve 2015; 52:455.
  70. Gable KL, Massey JM. Presynaptic Disorders: Lambert-Eaton Myasthenic Syndrome and Botulism. Semin Neurol 2015; 35:340.
  71. Oh SJ, Ohira M. Single-fiber EMG and clinical correlation in Lambert-Eaton myasthenic syndrome. Muscle Nerve 2013; 47:664.