Diagnostic challenges in myasthenia gravis: a clinical approach

The development of antibody tests and neurophysiological techniques have aided in confirming the diagnosis of myasthenia gravis (MG) over the years. However, there still remains an unmet diagnostic need in the subgroup of MG patients with weakness restricted to ocular muscles (OMG) as routine diagnostic tests are less sensitive in this group: around 50% of these patients have no positive antibody test and around 71% have no significant decrement with repetitive stimulation EMG. Moreover, virtually all disorders that can cause a pupil-sparing ptosis or diplopia have been reported to be confused with OMG. Among the most mentioned mimicks for OMG are (concomitant) Graves ophtalmopathy, cranial nerve palsies, ocular tendinomuscular deficits (such as levator dehiscence), myopathy, demyelinating disease and stroke. Diagnostic delay and confusion of OMG with mimicking disorders might lead to a worse prognosis due to a possible increased risk of generalization of disease and the need of emergency treatments. A careful clinical follow-up of patients with suspected OMG by systematically assessing changes in ocular weakness patterns between visits can aid in confirming the diagnosis. In addition, the ice pack test can be a diagnostic aid in cases of both evident ptosis as ophtalmoparesis. In the foreseeable future, cell-based assays (CBA) might aid in the diagnostic confirmation of OMG. There is a need of studies that investigates the yield of new and not-routinely used diagnostic tests in suspected OMG with negative antibody and inconclusive EMG and SF-EMG, such as the repetitive ocular vestibular evoked myogenic potentials (RoVEMP) test and CBA. Lastly, the effect of early immunosuppressive treatment should be further investigated in OMG.