J Clin Neurol.  2014 Apr;10(2):119-124. 10.3988/jcn.2014.10.2.119.

Clinical and Electrophysiologic Responses to Acetylcholinesterase Inhibitors in MuSK-Antibody-Positive Myasthenia Gravis: Evidence for Cholinergic Neuromuscular Hyperactivity

• Shin HY
• Park HJ
• Lee HE
• Choi YC
• Kim SM

• KMID: 2287529
• DOI: http://doi.org/10.3988/jcn.2014.10.2.119

Abstract

BACKGROUND AND PURPOSE
Patients with muscle-specific tyrosine kinase (MuSK) antibody (MuSK-Ab)-positive myasthenia gravis (MG) show distinct responses to acetylcholinesterase inhibitors (AChEIs). Although clinical responses to AChEIs in MuSK-Ab MG are reasonably well known, little is known about the electrophysiologic responses to AChEIs. We therefore investigated the clinical and electrophysiologic responses to AChEIs in MuSK-Ab-positive MG patients.
METHODS
We retrospectively reviewed the medical records and electrodiagnostic findings of 17 MG patients (10 MuSK-Ab-positive and 7 MuSK-Ab-negative patients) who underwent electrodiagnostic testing before and after a neostigmine test (NT).
RESULTS
The frequency of intolerance to pyridostigmine bromide (PB) was higher in MuSK-Ab-positive patients than in MuSK-Ab-negative patients (50% vs. 0%, respectively; p=0.044), while the maximum tolerable dose of PB was lower in the former (90 mg/day vs. 480 mg/day, p=0.023). The frequency of positive NT results was significantly lower in MuSK-Ab-positive patients than in MuSK-Ab-negative patients (40% vs. 100%, p=0.035), while the nicotinic side effects of neostigmine were more frequent in the former (80% vs. 14.3%, p=0.015). Repetitive compound muscle action potentials (R-CMAPs) developed more frequently after NT in MuSK-Ab-positive patients than in MuSK-Ab-negative patients (90% vs. 14.3%, p=0.004). The frequency of a high-frequency-stimulation-induced decrement-increment pattern (DIP) was higher in MuSK-Ab-positive patients than in MuSK-Ab-negative patients (100% vs. 17.7%, p=0.003).
CONCLUSIONS
These results suggest that MuSK-Ab-positive MG patients exhibit unique and hyperactive responses to AChEIs. Furthermore, R-CMAP and DIP development on a standard AChEI dose may be a distinct neurophysiologic feature indicative of MuSK-Ab-positive MG.

Keyword

myasthenia gravis; acetylcholinesterase inhibitor; muscle-specific tyrosine kinase; repetitive compound muscle action potential

MeSH Terms

Action Potentials
Cholinesterase Inhibitors*
Humans
Medical Records
Myasthenia Gravis*
Neostigmine
Protein-Tyrosine Kinases
Pyridostigmine Bromide
Retrospective Studies
Cholinesterase Inhibitors
Neostigmine
Protein-Tyrosine Kinases
Pyridostigmine Bromide

Figure

• 

  Fig. 1 Recording from the abductor digiti minimi muscle. Data are from a single muscle-specific tyrosine kinase antibody-positive myasthenia gravis patient. Repetitive discharges were not seen in the baseline electrodiagnostic testing (A and B) after the first compound muscle action potential (CMAP). Repetitive CMAPs were demonstrated after the intramuscular injection of neostigmine methylsulfate (0.02 mg/kg) (C-F). On repetitive nerve stimulation (RNS) at 3 Hz, the repetitive discharges after the first CMAP were diminished by the second stimulation (D). This reduction was more definite for 10-Hz RNS (E and F).

• 

  Fig. 2 Recording from the abductor digiti minimi muscle for high-frequency repetitive nerve stimulation at 50 Hz for 1 second before (A) and after (B) neostigmine injection. Data are from a single muscle-specific tyrosine kinase-antibody-positive myasthenia gravis patient. After the intramuscular injection of neostigmine methylsulfate (0.02 mg/kg), 50-Hz RNS showed a decrement-increment pattern that was not demonstrated before neostigmine injection. After neostigmine injection, 50-Hz RNS resulted in the amplitude of the second compound mascle action potential (CMAP) (arrow) being reduced maximally compared to the first CMAP (arrowhead), while the amplitude progressively recovered from the third CMAP (B).

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