Further Refining the Myasthenia Gravis Continuum

New myasthenia gravis (MG) research continues to evaluate the subtleties of clinical and serological differences between ocular MG and generalized MG, with conclusions of a recent retrospective chart review in Neuromuscular Disorders pointing toward similar frequencies of positive acetylcholine receptor(AChR) antibodies in both disease forms.¹

This seems to be a novel outcome, the authors reported.

Their aim was to add clarity to—or debunk—a belief that ocular MG and generalized MG are separate disease entities by systematically comparing the characteristics of each. Previous research seems to show that although only half of patients with ocular MG had been reported to carry pathogenic MG-specific antibodies, more than 90% of those with generalized MG did.²

The team summarized their findings by concluding that ocular MG is a presumably more moderate form of generalized MG. Ocular MG is marked by lower AChR antibody titers and a milder phenotype, and responds more quickly to less aggressive treatment (ie, first- and second-line drugs like azathioprine and prednisolone)—meaning it has less need—compared with patients with generalized MG, who require more intense interventions like intravenous immunoglobulin therapy or plasma exchange. Otherwise, the 2 forms are quite similar, the investigators stated.

A Danish research team posits that ocular disease is most likely a more moderate form of generalized myasthenia gravis—not a fully separate condition. | Image Credit: ©syahrir-stock.adobe.com

Study Details

Included were the charts, demographic data, and MG medical history of 350 patients, each of whom fulfilled 2 of 3 diagnostic MG criteria:positive AChR, MuSK, or LRP4 antibodies, evidence of neuromuscular transmission defect on neurophysiological examination, and positive effect of pyridostigmine treatment. The 350 represented one-third of all patients with MG in Denmark, where the study researchers are based. Most had generalized MG, but 15.7% of the included patients had ocular MG.

The significant differences between the generalized MG ocular MG subgroups were that the patients with ocular MG were generally older (by an average 6 years) at onset and had lower AChR antibody titers, longer doctor-to-diagnosis delay, and less intensive MG treatment. They also had their disease under good control more quickly than those with generalized MG.

However, the similarities between the groups included thymus pathology, percentage who were antibody positive (generalized MG, 95.9%; ocular MG, 94.5%), gender breakdown, and number of other autoimmune diseases. That there were no differences in thymus pathology between the 2 subgroups is in contrast with findings of previous reports, which suggested that thymoma is less frequent in oMG.

In the research team’s opinion, their study’s most important findings are that AChR antibodies occurred about equally in generalized MG and ocular MG, and that AChR titers were significantly lower in patients with ocular MG. Additionally, “the findings suggest that an AChR titer above 100 nmol/L at diagnosis predicts generalization of the myasthenia, which is consistent with previous findings of a positive correlation between AChR antibody titers and clinical severity in a general MG population.”^3,4

Disease Facts

An autoimmune disease, MG leads to activity-induced weakness in skeletal muscles. Worldwide, the prevalence of MG is 40 to 180 patients per million people.

Patients with ocular MG experience ptosis and/or diplopia exclusively, while those who develop generalized MG—either from the beginning of their MG journey or after contending first with ocular MG—have additional weakness in the muscles of their extremities, neck, face, and pharynx.

In this study, 44% (n = 154) of those initially diagnosed with ocular MG progressed to having a diagnosis of generalized MG. This finding agrees with those of earlier reports, said the investigators. Another finding of the current work suggests that an AChR titer rising above 100 nmol/L at diagnosis predicts generalized MG, a result consistent with previous ones that noted a positive correlation between AChR antibody titers and clinical severity in a general MG population. Therefore, “the first antibody titer—before intervention—could aid the diagnostic process and prediction of subtype at MG onset,” wrote the team.

They found that more than 90% of both subgroups were antibody positive for AChR, MuSK, or LRP4, which, for oculsr MG, is considerably higher than in previous reports. The discrepancy might be explained, in part, by the current use of better testing methods or higher testing rates, they posited.

References

1. Axelsen KH, Andersen RK, Andersen LK, Vissing J, Witting N. Ocular versus generalized myasthenia gravis: a continuum associated with acetylcholine receptor antibody titers. Neuromuscul Disord. 2024;43:39-43. doi:10.1016/j.nmd.2024.07.002

2. Berrih-Aknin S, Frenkian-Cuvelier M, Eymard B. Diagnostic and clinical classification of autoimmune myasthenia gravis. J Autoimmun. 2014;48-49:143-148. doi:10.1016/j.jaut.2014.01.003

3. Ullah U, Iftikhar S, Javed MA. Relationship between low and high anti-acetylcholine receptor antibody titers and clinical severity in myasthenia gravis. J Coll Physicians Surg Pak. 2021;31(8):965-968. doi:10.29271/jcpsp.2021.08.965

4. Somnier FE. Clinical implementation of anti-acetylcholine receptor antibodies. J Neurol Neurosurg Psychiatry. 1993;56(5):496-504. doi:10.1136/jnnp.56.5.496