Anticholinesterase-responsive neuromuscular junction transmission defects in post-poliomyelitis fatigue.
Disabling generalized fatigue and muscle fatiguability are common features of post-poliomyelitis syndrome (PPS). In 17 fatigued PPS patients, we measured jitter on stimulation single-fiber electromyography (S-SFEMG) for at least 3.5 min before and after i.v. injection of 10 mg edrophonium. We observed reduction in jitter (defined as a significant difference in jitter means before and after edrophonium, unpaired t-test P < 0.05) in 7 patients, no change in 8, and a significant increase in 2 patients. Blinded to their edrophonium results, the 17 patients were treated with pyridostigmine 180 mg/day for 1 month, with a subjective improvement of fatigue in 9 patients, and with a significant reduction in mean Hare fatigue scores in the entire group of 17 patients (pre = 2.71, and post = 1.71; Wilcoxan signed rank sum test, P < 0.05). Edrophonium-induced reduction of jitter on S-SFEMG was significantly associated with pyridostigmine-induced subjective improvement of fatigue (Fisher's exact test, P < 0.04). A significant reduction in fatigue with pyridostigmine was observed only in the 7 patients who experienced a significant reduction in jitter with edrophonium (Wilcoxan signed rank sum test, P = 0.03). In addition, the 9 pyridostigmine responders experienced a significant reduction in jitter means pre- and post-edrophonium (100% vs. 88%, Bonferroni corrected, P < 0.01). We conclude that neuromuscular transmission as measured by jitter on S-SFEMG can improve with edrophonium in a proportion of PPS patients, and that generalized fatigue and muscle fatiguability in some patients with PPS may be due to anticholinesterase-responsive NMJ transmission defects.
Department of Neurology and Neurosurgery, McGill University, Montreal Neurological Institute and Hospital, Quebec, Canada.
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Trojan
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Gendron
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Cashman
D000328:Adult; D000368:Aged; D004491:Edrophonium / Q000494:pharmacology*; D004558:Electric Stimulation; D004576:Electromyography; D005221:Fatigue; D006801:Humans; D008875:Middle Aged; D009132:Muscles / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology*; D016262:Postpoliomyelitis Syndrome / Q000188:drug therapy / Q000503:physiopathology*; D011729:Pyridostigmine Bromide / Q000627:therapeutic use*; D012016:Reference Values; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D004491:Edrophonium; D011729:Pyridostigmine Bromide