Electrophysiological Tests in the Neuromuscular Junction Disorders Seung Hyun Kim, M.D., Hak Jae Roh, M.D.* Department of Neurology, School of Medicine, Hanyang University Department of Neurology, School of Medicine, Soonchunhyang University* Electrodiagnostic studies are valuable in confirming the diagnosis of a disorder of neuromuscular transmission. They are used to distinguish presynaptic and postsynaptic abnormalities. These studies provide an objective measure of the severity of the illness and may be useful in assessing the response to therapy. This article reviews the electrodiagnostic techniques that are commonly used today and highlights their specificity, sensitivity, and pitfalls. Repetitive nerve stimulation test (RNST) and single-fiber electromyography (SFEMG) are the most available electrophysiologic test in the diagnosis of neuromuscular junction disorders. RNS showing 10% decrement in amplitude from the first to fourth or fifth intravolley waveform while stimulating at 2~5 Hz is valid for the diagnosis of MG. The degree of increment needed for the diagnosis of LEMS is at least 25% but most accurate when greater than 100%. Abnormal jitter or impulse blocking are the appropriate criteria for diagnosis of NMJ disorders when using SFEMG. SFEMG is more sensitive than RNS for the diagnosis of disorders of neuromuscular transmission, especially in MG but may be less specific or may not be available. Key Words : Neuromuscular transmission, Myasthenia gravis, Lambert-Eaton myasthenic syndrome, Repetitive nerve stimulation, Single-fiber electromyography Address for correspondence Seung Hyun Kim Department of Neurology, Hanyang University Hospital Hengdang-dong 17, Seongdong-gu, Seoul 133-792, Korea Tel : +82-2-2290-8371 Fax : +82-2-2299-2391 E-mail : kimsh1@hanynag.ac.kr Copyright 2002 by the Korean Society for Clinical Neurophysilology 171
Figure 1. Neuromuscular transmission. At normal neuromuscular synapses (right half of A & B), VGCC in the nerve terminal s specialized active zones open in response to a depolarizing impulse. Ca 2+ entry facilitates fusion of synaptic vesicles with the active zone membrane where Ach is released. The binding of Ach to its post-synaptic receptor opens the receptor s ionic channel, depolarizing the muscle fiber. This triggers an action potential and fiber contraction.(a) In MG, antibodies cause a loss of functional AchRs. If this loss exceed a crucial level, there is insufficient post-synaptic depolarization to trigger an action potential, and the muscle fiber fails to contract.(b) In LEMS, antibodies reduce the number of pre-synaptic Ca 2+ channels. With a critical reduction of Ach release, there is failure to activate a sufficient number of post-synpatic receptors to trigger an action potential, and contraction does not occur. 172 J Korean Society for Clinical Neurophysilology / Volume 4 / November, 2002
α β γ δ α α α Figure 2. Generation of EPP and action potential J Korean Society for Clinical Neurophysilology / Volume 4 / November, 2002 173
Figure 3. Generation of single-fiber action potential (SFAP) and compound muscle action potential (CMAP) Figure 4. Low rate stimulation(<5hz) in normal state Table 1. MEPP amplitude and quantal content in normal, MG and LEMS MEPP Amplitude resting quantal (quantal response, q) frequency content(m) Normal 1mV 0.2/sec 60~100 MG Low Normal Normal LEMS Normal Normal Low 174 J Korean Society for Clinical Neurophysilology / Volume 4 / November, 2002
Figure 5. Low rate stimulation in normal, MG and LEMS J Korean Society for Clinical Neurophysilology / Volume 4 / November, 2002 175
Figure 6. High rate stimulation (>10Hz) in normal state Figure 7. High rate stimulation in normal, MG and LEMS. 176 J Korean Society for Clinical Neurophysilology / Volume 4 / November, 2002
Figure 8. post-tetanic or post-exercise response Figure 9. The relationship between EPPs, CMAPs, single-fiber EMG action potential (SFAPs) & CMAPs recorded in normal & myasthenic muscle. Normally, all EPPs reach the threshold for action potential generation, producing CMAPs of constant size. In MG, EPPs fail to reach threshold in some end-plate, which then do not produce APs or SFAPs. The CMAP, which represent the average number of APs, then falls. J Korean Society for Clinical Neurophysilology / Volume 4 / November, 2002 177
A Figure 10. Post-activation facilitation in a patient with LEMS.(A) shows CMAP responses obtained with repetitive stimulation of the median nerve recording from abductor pollicis brevis muscle.(b) shows results of repetitive stimulation after 10 seconds of maximum voluntary contraction B Figure 11. CMAPs evoked by RNS in patients with MG & LEMS. Top figure shows decremental response to low rate stimulations, early dip phenomenon & partial repair immediately after brief exercise. Increased decrements appears 2~4 minutes after 10 seconds of volitional exercise (post-activation exhaustion). Bottom figure shows low amplitude of CMAPs & decremental responses to low rate stimulation. Abnormal facilitation appears immediately after brief voluntary exercise (post-activation facilitation). 178 J Korean Society for Clinical Neurophysilology / Volume 4 / November, 2002
Figure 12. Decremental response in a patient with myasthenia gravis. Responses were obtained with repetitive stimulation of ulnar nerve at 3Hz, recording from abductor digiti minimi muscle. J Korean Society for Clinical Neurophysilology / Volume 4 / November, 2002 179
µ Figure 13. Effect of temperature on the decrement at low rate stimulation in MG Figure 14. The effect of muscle temperature on the response of RNS in abductor digiti minimi muscle in a patients with MG.. The intramuscular temperature & the change in amplitude of 5 th response of each train are shown. 180 J Korean Society for Clinical Neurophysilology / Volume 4 / November, 2002
Figure 15. RNS studies at 3 Hz stimulation in the abductor pollicis brevis muscle of a patient with diabetic neuropathy & carpal tunnel syndrome. There is a 15% decrement in the 4 th response, and thereafter the CMAPs return toward the initial size. J Korean Society for Clinical Neurophysilology / Volume 4 / November, 2002 181
Figure 16. An activation cycle characteristic for MG., demonstrating changes in the decrement induced by RNS before and at indicated intervals after activation by maximum voluntary contraction or tetanic nerve stimulation. The percentage change in CMAP amplitude of 4 th response of each train is noted. 182 J Korean Society for Clinical Neurophysilology / Volume 4 / November, 2002
Figure 17. Early dip phenomenon. The initial large decrement (stimuli 1 to 3) represent the depletion effect of a previous stimulus. The stabilization of the evoked response amplitude (stimuli 4 to 8) represent mobilization-related facilitation. J Korean Society for Clinical Neurophysilology / Volume 4 / November, 2002 183
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µ µ µ Figure 18. SFEMG recordings. A. Recording position of SFEMG electrode. B. Consecutive paired discharges at a slow sweep speed. C. Same pair of potentials at a faster sweep speed. D. Ten superimposed consecutive discharges demonstrating the neuromuscular jitter µ µ µ J Korean Society for Clinical Neurophysilology / Volume 4 / November, 2002 185
Figure 19. SFEMG recordings. During voluntary activation of extensor digitorum communis muscle, normal jitters are shown in normal subject (left) and markedly abnormal jitter in patient with MG (right). 186 J Korean Society for Clinical Neurophysilology / Volume 4 / November, 2002
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