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Myasthenia Gravis (MG)

Diagnosis

Weakness and fatigue are common complaints in the general population, but the degree and pattern of these symptoms — particularly diplopiaptosis, and other signs of weakness in the eye muscles — should alert a neurologist to the possibility of myasthenia gravis (MG).

A neurologist will ask many questions and conduct a physical exam to determine the extent of weakness. To look for evidence of increased weakness following exertion, a neurologist might ask the patient to look up without blinking for one or two minutes, hold the arms out for as long as possible, or climb up steps.

Bedside tests

An ice pack test can be used as a part of a neurologic examination for patients with ptosis (weakness of the eyelid muscles). Cooling the eyelid muscles helps patients to overcome ptosis and serves as an indication that the patient might have MG. The sensitivity of an ice pack test is only 80%, as false positive results can be frequently observed. This test should not be considered as a standalone test but rather an extension of the physical examination.1, 2

Serologic testing

Serologic tests check for the presence of antibodies in the serum (a component of blood). Seropositive means that there is presence of the antibody in the blood, and seronegative means that the antibody was not detected.

If a physical exam is consistent with MG, a neurologist usually orders a blood test designed to detect antibodies to the acetylcholine (Ach) receptor. A blood test for muscle-specific tyrosine kinase (MuSK) antibodies is also available. In approximately 90% of patients with MG, a positive test result confirms a diagnosis of MG. However, in 6% to 12% of patients with myasthenia may test negative for both AchR antibodies and MuSK antibodies. These patients have seronegative MG and are more likely to have ocular MG than those who are seropositive.3 Antibodies to proteins in the body other than AChR and MuSK antibodies have been detected in some cases of seronegative MG, however a clear causal association has not been established yet.4, 5, 6

Electrodiagnostic testing

The next step is usually electrodiagnostic testing, in which electrodes are used to measure the electrical signals in muscle. Surface electrodes (similar to those used in electrocardiograms) deliver small shocks to a nerve in the arm, leg, or face, while other surface electrodes record the responses in muscle. In MG, a muscle’s response to repeated nerve stimulation declines rapidly. There are two types of tests that can be done to confirm the diagnosis of MG:

  • Repetitive nerve stimulation (RNS) is commonly used, with 75% to 80% accuracy and is described above.7
  • Single-fiber electromyography (SFEMG) is a more sensitive test (with 95% accuracy) but is less widely available and technically demanding.4, 7

If a diagnosis of MG is confirmed, a CT scan, chest X-rays, or magnetic resonance imaging (MRI) will be used to examine the thymus and look for evidence of a thymic tumor, which occurs in about 15% of people with MG.

References

  1. Benatar, M. A systematic review of diagnostic studies in myasthenia gravis. Neuromuscul. Disord. (2006). doi:10.1016/j.nmd.2006.05.006
  2. Golnik, K. C., Pena, R., Lee, A. G. & Eggenberger, E. R. An ice test for the diagnosis of myasthenia gravis. Ophthalmology (1999). doi:10.1016/S0161-6420(99)00709-5
  3. Deymeer, F. et al. Clinical comparison of anti-MuSK- vs anti-AChR-positive and seronegative myasthenia gravis. Neurology (2007). doi:10.1212/01.wnl.0000254620.45529.97
  4. Nicolle, M. W. Myasthenia Gravis and Lambert-Eaton Myasthenic Syndrome. CONTINUUM Lifelong Learning in Neurology (2016). doi:10.1212/CON.0000000000000415
  5. Vincent, A. et al. Antibodies in myasthenia gravis and related disorders. in Annals of the New York Academy of Sciences (2003). doi:10.1196/annals.1254.036
  6. Decroos, E. C., Hobson-Webb, L. D., Juel, V. C., Massey, J. M. & Sanders, D. B. Do acetylcholine receptor and striated muscle antibodies predict the presence of thymoma in patients with myasthenia gravis? Muscle and Nerve (2014). doi:10.1002/mus.23882
  7. Oh, S. J., Kim, D. E., Kuruoglu, R., Bradley, R. J. & Dwyer, D. Diagnostic sensitivity of the laboratory tests in myasthenia gravis. Muscle Nerve (1992). doi:10.1002/mus.880150616

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