Impaired post-tetanic potentiation of muscle twitch in myasthenia gravis
Introduction
Although defective neuromuscular transmission is known to be a cause of muscle weakness in myasthenia gravis (MG), previous studies have shown the possible roles of other processes, the failure of which may also cause muscle weakness in MG. Especially, excitation–contraction coupling may be defective in patients with MG (Pagala et al., 1990, Pagala et al., 1993, Slomić et al., 1968). The excitation–contraction coupling in skeletal muscle is the process whereby an action potential triggers a muscle fiber to contract. Some investigators have applied the post-tetanic potentiation and/or the staircase phenomenon to elucidate the impairment of excitation–contraction coupling in MG (Krarup, 1977, Slomić et al., 1968). Post-tetanic potentiation is the enhancement of active twitch force following high-frequency tetanic stimulation (Brown and von Euler, 1938), while the staircase phenomenon is the progressive increase in active twitch force during repetitive low-frequency stimulation (Bowditch, 1870/71). The post-tetanic potentiation and staircase phenomenon have been explained by an increase in sarcoplasmic Ca2+, which may induce facilitation of excitation–contraction coupling after tetanic stimulation and stepwise increase in response during repetitive twitch, respectively. Studies in MG patients have demonstrated a correlation between the magnitude of potentiation and the severity of MG, and proposed the significance of impaired excitation–contraction coupling in MG (Krarup, 1977, Slomić et al., 1968). However, post-tetanic potentiation and staircase phenomenon are rarely used to evaluate the impairment of excitation–contraction coupling in the clinical laboratory, presumably because complicated apparatus using a strain gauge is required.
In this study, we describe a novel procedure to measure post-tetanic potentiation using an accelerometer attached to the hand muscle instead of the complicated apparatus with a strain gauge used in previous studies. Our method is simple and may be a useful clinical test for the detection of impairment of excitation–contraction coupling in MG.
Section snippets
Subjects and protocol
We studied 11 patients with MG (3 males and 8 females; aged 33–67 years, mean 47.2 years) at Sapporo Medical University Hospital. The diagnosis of MG was based on typical clinical features and electrophysiological evidence of a defect in neuromuscular transmission, which is either an abnormal decrement in repetitive nerve stimulation tests (muscles tested: orbicularis oculi, nasalis, trapezius, abductor pollicis brevis and abductor digiti minimi), or increased jitter on concentric needle single
Clinical features
Eleven MG patients comprised 2 patients with a purely ocular form (MGFA class 1) and 9 patients with generalized form (MGFA class 2–4). The mean grip strength was 19.2 kg in MG patients (11 subjects, 22 hands), 32.4 kg in healthy controls (25 subjects, 50 hands), and 16.4 kg in patients with myopathy (9 subjects, 18 hands). Mann–Whitney U-test showed significantly lower grip strength in MG and myopathy groups (p < 0.01) compared to healthy controls (Table 1). Serum antibodies against AChR were
Discussion
In the present method, the amplitude and area of CMAP did not change significantly after tetanic stimulation compared to baseline. In our study, we verified carefully that the muscle lengths did not change after tetanic stimulation. In addition, the unchanged CMAP parameters confirm that muscle lengths were the same during all recordings even after tetanic stimulation. If muscle shortening remains after tetanic stimulation, the movement-induced effect would increase the amplitude and decrease
Acknowledgements
This study was supported in part by Grant-in Aid for Scientific Research (No. 25461321, Tomihiro Imai) from Japan Society for the Promotion of Science. We wish to thank Dr. Masakatsu Motomura (Medical Engineering Course, The Department of Engineering, The Faculty of Engineering, Nagasaki Institute of Applied Science) and Dr. Kiyoe Ohta (Clinical Research Center, National Hospital Organization Utano Hospital) for assaying anti-MuSK antibodies.
Conflict of interest: There are no competing
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