The initial severity of double-seronegative myasthenia gravis (dSNMG), based on clinical scores, is similar to that of antibody-positive myasthenia gravis, according to a new study published in the European Journal of Neurology.

Immunosuppressive therapy leads to significant clinical improvements in these patients, the study also found, supporting an immune pathophysiology in double-seronegative patients. The clinical features and treatment outcomes of dSNMG are not well known. 

In the present study, a team of researchers led by Vera Bril, MD, from Ellen & Martin Prosserman Centre for Neuromuscular Diseases at Toronto General Hospital and University Health Network at the University of Toronto in Canada, conducted a retrospective study in 80 patients with dSNMG and 73 patients who were positive for anti-acetylcholine receptor (AChR) antibody.

The researchers reported there were no significant differences between patients with dSNMG and patients who were anti-AChR antibody positive in terms of baseline Myasthenia Gravis Impairment Index (MGII), a measure of MG severity, and Simple Single Question (SSQ) scores. The SSQ is a validated questionnaire asking what percentage of normal a patient feels with respect to their MG.

Importantly, the MGII and SSQ scores of dSNMG improved significantly following immunosuppressive treatment. As expected, the improvement in the MGII score of anti-AChR antibody-positive patients was even better.

Read more about the etiology of MG

These findings encourage efforts to improve response to treatment in MG patients, the authors of the study concluded.

MG is a rare autoimmune disease affecting the neuromuscular junction characterized by muscle weakness and fatigue mainly affecting the eyes, face, jaw, throat, neck, and limbs. 

Most patients have autoantibodies against the AChR found on the muscle cell membranes while others have autoantibodies against muscle-specific tyrosine kinase (MuSK). In patients with dSNMG, there are no detectable anti-AChR or anti-MuSK antibodies.


Martinez-Harms R, Barnett C, Alcantara M, Bril V. Clinical characteristics and treatment outcomes in patients with double-seronegative myasthenia gravis. Eur J Neurol. Published online August 2, 2023. doi:10.1111/ene.16022