Elsevier

Clinical Neurophysiology

Volume 118, Issue 2, February 2007, Pages 269-277
Clinical Neurophysiology

Quantitative EMG of facial muscles in myasthenia patients with MuSK antibodies

https://doi.org/10.1016/j.clinph.2006.10.004Get rights and content

Abstract

Objective

Our aim was to study the pathophysiological process leading to facial muscle atrophy in 13 patients with MuSK antibody positive myasthenia gravis (MuSK-MG), and to compare with findings from 12 acetylcholine receptor antibody positive myasthenia patients (AChR-MG), selected because they suffered from the same degree of disease severity and required similar treatment.

Methods

Motor unit action potential (MUAP) and interference pattern analysis from orbicularis oculi (O oculi) and orbicularis oris (O oris) muscles were studied using a concentric needle electrode, and compared with findings in 20 normal subjects, 6 patients receiving botulinum toxin injections (representing a neurogenic model) and 6 patients with a muscle dystrophy (representing a myopathic model). The techniques and control data have been reported previously.

Results

The mean MUAP durations for O oculi and O oris were significantly reduced (p < 0.001) in both MG cohorts when compared with healthy subjects, and were similar to those in the myopathic control group. They were significantly different from those obtained from the neurogenic control group (p < 0.001 for both O oculi and O oris). The MUAP findings in O oculi occurred independently from neuromuscular blocking on single fibre EMG (SFEMG) in the same muscle. On turns amplitude analysis (TAA), 50% of MuSK-MG patients and 42% of AChR-MG patients had a pattern in O oculi which was similar to that in the myopathic control group, and 62% of MuSK-MG patients and 50% of AChR-MG patients had a pattern in O oris that was also similar to that in the myopathic control group. The TAA findings for O oculi and O oris in both MG cohorts were different from those obtained from the neurogenic control group.

Conclusions

Facial muscle atrophy in MuSK-MG patients is not neurogenic and the pathophysiological changes are akin to a myopathic process. The selected AChR-MG patients also show evidence of a similar pathophysiological process in the facial muscles albeit to a lesser degree.

Significance

We propose that muscle atrophy in MuSK-MG is a myopathic process consisting of either muscle fibre shrinkage or loss of muscle fibres from motor units. The duration of disease and long-term steroid treatment may be further contributory factors.

Introduction

Myasthenia gravis (MG) is an acquired immune-mediated condition of the neuromuscular junction (NMJ), which is associated with the presence of antibodies to the muscle nicotinic acetylcholine receptor (AChR) in 85% of patients with generalised disease (AChR-MG). Between 3% and 70% of seronegative MG patients have antibodies to muscle specific tyrosine kinase (MuSK; MuSK-MG) (Hoch et al., 2001, Sanders et al., 2003, Vincent et al., 2004, Zhou et al., 2004, Yeh et al., 2004, Vincent and Leite, 2005). MuSK-MG patients are distinct in that they often have severe and pronounced oculobulbar disease (Scuderi et al., 2002, Sanders et al., 2003, Zhou et al., 2004, Evoli et al., 2003) and some patients may develop wasting of the facial muscles, particularly of the tongue. Wasting of the tongue has been previously described in AChR-MG but this is not a common feature (De Assis et al., 1994). The pathophysiological mechanisms leading to muscle wasting in MuSK-MG are not well understood. Limb muscle biopsies have indicated a myopathic process (Sanders et al., 2003; Evoli et al., 2003) but pathological specimens have not been obtained from clinically-involved facial muscles.

In order to investigate the pathological process leading to and resulting in facial muscle atrophy, we have used quantitative EMG studies in MuSK-MG patients and compared findings with those from AChR-MG patients, who also had severe bulbar disease, and with those from two pathological control groups representing defined diseases that lead to neurogenic or myopathic muscle wasting.

Section snippets

Participants and materials

We recruited 13 MuSK-MG patients attending the myasthenia gravis centre in Oxford, UK (age range 21–58, median age of 40) and 12 AChR-MG patients (age range 26–71, median 50.5). The latter group was selected from over 190 case notes, on the basis that they had prominent and persistent bulbar disease with similar requirements for immunosuppressive treatment as the MuSK-MG patients. They were also chosen so that they demonstrated similar age and gender ranges to the MuSK-MG cohort. The

Results

Table 1 shows the demographic details of the MG patients who were included in this study. The maximal MGFA disease score for each patient is included in this table, as well as the respective MGFA and facial muscle strength score at the time of the study.

Discussion

We investigated the pathophysiological processes that could lead to wasting in the facial muscles of MuSK-MG and AChR-MG patients, using electrophysiological methods since facial muscle biopsy is not ethically feasible. All MuSK-MG patients, who were available for the study in Oxford, UK, were recruited and examined. The AChR-MG patients were selected so that their disease was comparable in severity, with prominent facial and bulbar muscle involvement and that they had similar treatment

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