Characteristics of Triple Seronegative Myasthenia Gravis: A Single Center Experience

Background: There is variability in the literature regarding the characteristics of triple seronegative myasthenia gravis (SNMG) patients. Most studies were performed before LRP4 antibodies were discovered, and characterizations of triple seronegative patients are lacking in the literature. Methods: We retrospectively investigated patients diagnosed with myasthenia gravis (MG) at Ohio State University from 2009 to 2019. Triple SNMG was defined by a history and examination that was consistent with MG and positive SFEMG, RNS or edrophonium testing, but negative serology for AChR, MUSK, and LRP4 antibodies. Results: A total of 210 AChR+, 9 MuSK+, 6 LRP4+, 9 double SNMG, and 21 triple SNMG patients were reviewed. Triple SNMG patients required significantly fewer immunosuppressive agents compared with AChR+ patients (p=0.0001) and a trend towards a less frequent history of hospitalizations, myasthenic crises and intubations compared to all antibody positive groups. Triple SNMG patients had a significantly higher frequency of ocular disease (33%) compared to AChR+ patients (13%) (p=0.0250). One triple and one double SNMG patient had thymic hyperplasia and improved after thymectomy. 11 triple SNMG patients had negative genetic testing for CMS. Conclusion: Our results further elucidate the clinical characteristics of triple SNMG, which include the predominance for ocular disease and a less severe disease course. Although likely rare, investigation for thymic pathology should be a consideration even in SNMG, and thymectomy should be considered when there is thymic pathology. We did not find alternate diagnoses in SNMG patients and thus ancillary testing should be considered in carefully selected patients for cost-effective care.

Duke Scholars

Author Jonathan Morena Neurology, Neuromuscular Disease