Autoimmune myasthenia gravis commonly presents with fatigable ptosis and diplopia. In isolation, these symptoms often herald the restricted form of the disease known as ocular myasthenia gravis. In some cases, ocular myasthenia gravis progresses to involve bulbar musculature as well as limb muscles. Because some individuals with myasthenia have the signs intermittently or may never have ptosis, the diagnosis is sometimes difficult to ascertain on clinical grounds alone.
Benn E. Smith, MD
Clinical and laboratory tests available for confirming the diagnosis have been in use for many years, as well as some recent refinements. These include serologic testing for acetylcholine receptor and MuSK antibodies; the edrophonium (Tensilon) test, in which an acetylcholinesterase inhibitor is delivered IV to temporarily improve ptosis and diplopia; slow repetitive (electrical) nerve stimulation (RNS), particularly of proximal limb and facial nerves; and single-fiber electromyography (SFEMG). Each of these approaches has limitations. Antibody testing has relatively low sensitivity (in the range of 0.50–0.71 for ocular myasthenia gravis and 0.87–0.98 for generalized myasthenia gravis). For RNS, the sensitivity numbers are even less positive (0.11–0.39 for ocular myasthenia gravis and 0.53–0.98 for generalized myasthenia gravis). Even though the edrophonium test is said to have a sensitivity of 0.60–0.90, this procedure has largely fallen into disuse among neuromuscular specialists, partly because of the risks of bradycardia, syncope, and even asystole, as well as high rates of false positivity. Some neurologists use an icepack on the forehead as a diagnostic substitute or so-called “poor man’s edrophonium test,” although false positive rates are considerable. SFEMG is considered the most sensitive diagnostic test for myasthenia gravis (sensitivity of 0.62–1.0 in ocular myasthenia gravis and 0.75–0.98 in generalized myasthenia gravis), but is technically demanding, time consuming, available almost exclusively in academic centers, and until relatively recently meant using expensive SFEMG needle electrodes requiring sterilization and periodic sharpening.
Two recent publications have introduced advances in the diagnosis of myasthenia gravis. The first is a report by Dr. Erik Stålberg and colleagues from Sweden, the United States, United Kingdom, Slovenia, Norway, Brazil, and Spain of normative data for concentric SFEMG using both the stimulated and the volitional techniques in the extensor digitorum, frontalis, and orbicularis oculi muscles from 59 to 92 subjects for each muscle. The value of this set of reference data is that neurologists who perform SFEMG now have a rigorously collected, reliable set of statistically validated normal values using commercially available concentric needle electrodes, as conventional single-fiber needle electrodes are becoming more and more challenging to use in practice.
A second publication by Dr. Yulia Valko and colleagues from Zurich and Sydney describes the novel application of ocular vestibular myogenic potentials (oVEMP) as a new form of RNS in myasthenia gravis. By delivering 4-ms bursts of 500-Hz bone-conducted vibration in trains of 10 stimuli and recording just below the inferior orbital rim with surface electrodes, the investigators found that a frequency of 20 Hz resulted in the cleanest separation of tracings in subjects with documented myasthenia gravis from age- and gender-matched healthy controls. The oVEMP technique has been in use for evaluating vestibular disorders for more than 10 years and is an accepted diagnostic technique for this purpose. While this novel approach also shows promise as a candidate diagnostic technique in evaluating extraocular neuromuscular junction dysfunction, further prospective studies are needed. By comparing the sensitivity and specificity of oVEMP RNS with that of accepted diagnostic tests, including conventional facial RNS and SFEMG, in subjects suspected of having myasthenia gravis, the neurology and neuromuscular communities will be in a better position to judge whether oVEMP will one day be an accepted diagnostic test for myasthenia gravis.
—Benn E. Smith, MD
Department of Neurology
Mayo Clinic
Scottsdale, Arizona