Seronegative Myasthenia Gravis: A Retrospective Review of the Clinical Characteristics at a Large Academic Center
Jonathan Morena1, Samantha LoRusso1, Bakri Elsheikh1, Miriam Freimer1, Chad Hoyle1, Benjamin Jiang1, William Arnold1
1The Ohio State University

To describe the clinical characteristics of seronegative myasthenia gravis (SNMG) at a large academic center.


There is variability in the literature regarding the characteristics of SNMG. Most studies have been performed before LRP4 antibodies were discovered, and the frequency of triple seronegative patient characterizations is lacking in the literature.


We retrospectively investigated patients diagnosed with a myasthenic disorder and seen at Ohio State University from 2009 to 2019. SNMG was defined by a history and examination consistent with MG and a positive single-fiber electromyography (SFEMG), repetitive nerve stimulation (RNS) or Tensilon test, but negative serology for AChR, MuSK, and LRP4 antibodies.


A total of 210 AChR+, 9 MuSK+, 6 LRP4+, 9 double SNMG, and 21 triple SNMG patients were reviewed. SNMG patients had a similar age of onset and female:male ratio. A less frequent history of hospitalization (p=0.0291), a trend for less frequent myasthenic crisis (p=0.0913), and a higher frequency of ocular disease (25% versus 13% in AChR+, p=0.0583) was seen in SNMG versus AChR+ patients. There was no significant difference between double and triple SNMG patients. 13 SNMG patients received genetic testing for congenital myasthenia gravis, and they were all negative. One double SNMG (AChR- and MuSK-) and one triple SNMG patient had thymic hyperplasia and they both improved after thymectomy.


Our results further elucidate the clinical characteristics of SNMG and the predominance for ocular disease and a less severe disease course. In our population, we did not tend to find alternative diagnoses in SNMG patients and ancillary testing should be decided in carefully selected patients for cost-effective care. Although likely rare, investigation for thymic pathology should be a consideration even in SNMG, and thymectomy should be considered if there is thymic pathology.