Clinical findings in MuSK‐antibody positive myasthenia gravis: A U.S. experience

Abstract

We performed a retrospective chart review on 53 muscle-specific kinase antibody (MuSK-Ab)-positive myasthenia gravis (MG) patients at nine university-based centers in the U.S. Of these, 66% were Caucasian, 85% were women, and age of onset was 9-79 years. Twenty-seven patients were nonresponsive to anticholinesterase therapy. Myasthenia Gravis Foundation of America improvement status was achieved in 53% patients on corticosteroids, 51% with plasma exchange, and in 20% on intravenous immunoglobulin (IVIG). Thymectomy was beneficial in 7/18 patients at 3 years. Long-term (> or =3 years) outcome was very favorable in 58% of patients who achieved remission and/or minimal manifestation status. Overall, 73% improved. There was one MG-related death. This survey reinforces several cardinal features of MuSK-Ab-positive MG, including prominent bulbar involvement and anticholinesterase nonresponsiveness. Facial or tongue atrophy was rare. Most patients respond favorably to immunotherapy. The best clinical response was to corticosteroids and plasma exchange, and the poorest response was to IVIG. Long-term outcome is favorable in about 60% of cases.

Myasthenia gravis

“…Many case series have begun to elucidate key clinical features, and important distinctions in response to therapy in patients with MuSK vs patients with other generalized MG. One of the more striking differences is the female predominance of patients with MuSK, ranging between series from 78% to 100% women. [10][11][12] Three relatively distinct clinical patterns have emerged: oculopharyngeal weakness, with occasional profound tongue and facial atrophy; neck, shoulder, and respiratory weakness without ocular weakness; and a phenotype indistinguishable from AChR-positive MG. One large series of 53 MuSK-positive patients form 9 US neuromuscular centers found facial and bulbar weakness in 96%, neck weakness in 92%, limb weakness in 81%, ocular weakness in 72%, and breathing difficulties in 60% of patients. 10 The high prevalence of respiratory involvement is important when considering diagnosis and therapeutic options.…”

“…[10][11][12] Three relatively distinct clinical patterns have emerged: oculopharyngeal weakness, with occasional profound tongue and facial atrophy; neck, shoulder, and respiratory weakness without ocular weakness; and a phenotype indistinguishable from AChR-positive MG. One large series of 53 MuSK-positive patients form 9 US neuromuscular centers found facial and bulbar weakness in 96%, neck weakness in 92%, limb weakness in 81%, ocular weakness in 72%, and breathing difficulties in 60% of patients. 10 The high prevalence of respiratory involvement is important when considering diagnosis and therapeutic options. Unlike generalized AChR-positive MG, the majority of case series report poor response to cholinesterase inhibitor medications in MuSK-positive patients, and the response to thymectomy in these patients has ranged from no response to 50%.…”

Anti-MuSK autoantibodies block binding of collagen Q to MuSK

“…10,11 MuSK-MG patients respond favorably to immunotherapy, but usually do not respond to, or are even worsened by, cholinesterase inhibitors. [12][13][14][15] Anti-AChR antibodies comprise IgG1 and IgG3 moieties that bind complement whereas anti-MuSK antibodies are largely IgG4 that do not activate complement, and complement deposits at the NMJ are sparse. 16 -18 However, the exact target of MuSK-IgG remains elusive.…”

Misdiagnosis of Myasthenia Gravis and Subsequent Clinical Implication : A Case Report and Review of Literature

“…2 However, pharmacological testing with edrophonium or neostigmine for unequivocal objective benefits is warranted in all patients with oculo-bulbar symptoms with limb weakness. More importantly, the target weak muscle for such outcome should be pre-specified.…”