Atrophy and Fibrosis of Extra-Ocular Muscles in Anti-Acetylcholine Receptor Antibody Myasthenia Gravis

Abstract

Myasthenia gravis (MG) is an autoimmune disorder involving the neuromuscular junction that frequently affects the extra-ocular muscles (EOMs). It has been described as a very rare cause of bilateral EOM atrophy, but histological analysis of such cases is lacking. A 66-year-old man presented with two months of right eyelid drooping and vertical diplopia. Examination showed bilateral ophthalmoparesis and complete right ptosis. The remainder of his exam was normal, and an MRI showed small EOMs. Acetylcholine receptor antibodies were elevated, establishing the diagnosis of MG. Oral corticosteroids and pyridostigmine followed by azathioprine improved his ptosis, but not his ophthalmoparesis. One year later he had surgical correction of his diplopia, and the resected superior rectus muscle showed complete replacement of EOM by connective tissue. MG can rarely cause bilateral EOM atrophy, which is characterized histologically by fibrosis in the muscle itself. Atrophy in the EOMs of a myasthenic patient may indicate a poor response to medical management alone.

Radiological Characteristics of Extraocular Muscles in Myasthenia Gravis Patients with Ocular Manifestations: A Case–Control Study

“…7 Farrugia et al showed MRI evidence of bulbar-and facialmuscle wasting in chronic anti-MuSK-Ab MG. 8 A study of an anti-AChR-Ab-positive patient showed fibrosis in the SR, which corresponded with EOM atrophy in the orbital MRIs. 2 Although fibrosis is a pathological feature of chronic inflammation, we observed atrophic muscles in some acute cases. MG seems to manifest differently among patients as EOM atrophy can occur early or many years later in the course of the disease.…”

“…The study showed that MG, a primary neuromuscular junction disorder, can eventually affect the muscle fibers. 2 Besides, a few pathological studies demonstrated lymphocyte infiltrations in the muscles of MG patients. The inflammatory responses damage the motor endplates, leading to denervation of the muscles and subsequent muscle atrophy.…”

“…The findings were more or less the same as those in previous case reports. [2][3][4][5] Using CT/MRI scans, two case reports demonstrated bilateral EOM atrophy in anti-AChR-Ab and anti-MuSK-Ab MG with long disease duration. 3,5 Keene et al recently demonstrated an increase in fat fraction of EOMs in acute and chronic anti-AChR-Ab MG, using 7-T MRI with Dixon and multi-echo spin-echo sequences.…”

“…The inflammatory responses damage the motor endplates, leading to denervation of the muscles and subsequent muscle atrophy. 2,[9][10][11] Mitochondrial damage and fibro-fatty replacement were commonly found in myasthenic EOMs, particularly in anti-MuSK-Ab MG. 11 Additionally, Martignago et al compared myopathological features between anti-AchR-Ab and anti-MuSK-Ab in skeletal muscles. They demonstrated muscle atrophy in both conditions with more mitochondrial involvement in muscle biopsies of anti-MuSK-Ab MG. 12 These findings contribute to the treatment-resistance of myasthenic ophthalmoplegia.…”

“…However, MRI is not frequently performed in MG cases and radiological characteristics of MG are limited. [1][2][3] The goal of this study was to analyze the radiological patterns of the EOMs in MG cases with ocular manifestations.…”