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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 - J Clin Neurol (2014)

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Yonsei University College of Medicine, Seoul, Korea.

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.

No MeSH data available.


Related in: MedlinePlus

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).
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Figure 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).

Mentions: The results of EDx were reviewed by two neurologists (H.J.P. and H.E.L.) who were blinded to clinical information. The two neurologists consensually determined the presence of R-CMAP and a DIP on the ADM muscle at normal gain (5 mV/division). R-CMAP was defined as a CMAP followed by repetitive discharges that did not exist prior to NT (Fig. 1). A DIP was defined as the pattern of RNS that shows the maximum decrement of amplitude in the second CMAP and then progressive recovery of the amplitude from the third CMAP (Fig. 2).


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 - J Clin Neurol (2014)

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).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4017014&req=5

Figure 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).
Mentions: The results of EDx were reviewed by two neurologists (H.J.P. and H.E.L.) who were blinded to clinical information. The two neurologists consensually determined the presence of R-CMAP and a DIP on the ADM muscle at normal gain (5 mV/division). R-CMAP was defined as a CMAP followed by repetitive discharges that did not exist prior to NT (Fig. 1). A DIP was defined as the pattern of RNS that shows the maximum decrement of amplitude in the second CMAP and then progressive recovery of the amplitude from the third CMAP (Fig. 2).

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Yonsei University College of Medicine, Seoul, Korea.

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.

No MeSH data available.


Related in: MedlinePlus