key: cord-0818062-7643n6nu
authors: Muhammed, Louwai; Baheerathan, Aravindhan; Cao, Michelangelo; Leite, Maria Isabel; Viegas, Stuart
title: MuSK Antibody–Associated Myasthenia Gravis With SARS-CoV-2 Infection: A Case Report
date: 2021-01-12
journal: Ann Intern Med
DOI: 10.7326/l20-1298
sha: 5e2495ac843df9518fbe680d8d8edb1ba8ee2b74
doc_id: 818062
cord_uid: 7643n6nu

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antineutrophil cytoplasmic, and antiganglioside antibodies yielded negative results, but SARS-CoV-2 antibodies were detected. Magnetic resonance imaging of the brain and spine and routine cerebrospinal fluid analysis were unremarkable. Results of single-fiber electromyography of the left orbicularis oculi were abnormal, and repetitive nerve stimulation of the left abductor digiti minimi muscle showed abnormal decrementing responses, consistent with myasthenia gravis. Computed tomography of the chest revealed no thymoma.

Diagnostic radioimmunoprecipitation assay results were negative for AChR antibodies but positive for MuSK antibodies, confirming the diagnosis of generalized MuSK-MG. Two serum samples, collected 4 weeks apart, were tested for MuSK antibodies with a cell-based assay. Both samples had a higher level of IgG4 than IgG1-3 antibodies, with a proportional reduction in the second sample across all IgG subclasses. No IgM MuSK antibodies were detected in either sample (Figure) .

We administered intravenous immunoglobulin, pyridostigmine, and prednisolone to the patient, and her symptoms improved. However, the effect of intravenous immunoglobulin was relatively short-lived. The patient developed side effects with higher doses of pyridostigmine, so we reduced the dose and added salbutamol. She currently is 20 weeks from symptom onset, is receiving 50 mg of prednisolone every other day, and has mild to moderate dysarthria and mild limb weakness (MRC grade 4+). If her condition relapses as the steroid dosage is reduced, we will consider treatment with rituximab.

Discussion: Other authors have reported that MuSK-MG may develop after viral infection (5), and we note that our patient's clinical syndrome combined with subsequent positive results on SARS-CoV-2 antibody testing means that she probably was infected with SARS-CoV-2 at least 4 weeks before she developed MuSK-MG. Although our findings demonstrate a temporal association between COVID-19 infection and MuSK-MG, we recognize that we cannot definitively conclude causality. Nevertheless, we believe that this report of MuSK-MG associated with COVID-19, along with reports of AChR-MG associated with COVID-19 (1), provide clues to possible mechanisms for the association. For example, cross-reactivation of SARS-CoV-2 antibodies with both AChR and MuSK proteins is highly unlikely given their molecular differences; therefore, the development of myasthenia gravis after COVID-19 more likely represents a breakdown in self-tolerance mechanisms than One pair of symbols shows the MuSK ab of IgG4, and the other shows the MuSK ab of IgG1-3. ab = antibody; CBA = cell-based assay; IVIG = intravenous immunoglobulin; MG = myasthenia gravis, MuSK = muscle-specific kinase; RIPA = radioimmunoprecipitation assay; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.

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