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The Rational Clinical Examination |

Does This Patient Have Myasthenia Gravis?

Katalin Scherer, MD; Richard S. Bedlack, MD, PhD; David L. Simel, MD, MHS
JAMA. 2005;293(15):1906-1914. doi:10.1001/jama.293.15.1906.
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Published online

Context Clinicians must be able to diagnose myasthenia gravis, since delays in establishing the diagnosis may put patients at risk for complications from this treatable disease.

Objective To determine if items in the history and examination or results of simple tests change the likelihood of myasthenia gravis as a diagnosis.

Data Sources MEDLINE search of English-language articles (January 1966-January 2005) using the terms myasthenia gravis, diagnosis, and test, and a search of bibliographies of retrieved articles.

Study Selection Studies evaluating a particular symptom or sign in patients both with and without myasthenia gravis. Of 640 articles retrieved, 33 were eligible for review. Of these, 15 met inclusion criteria and form the basis of this review.

Data Extraction Two authors independently reviewed each study to determine eligibility, abstracted data using a standardized instrument, and classified study quality using previously published criteria.

Data Synthesis A history of “speech becoming unintelligible during prolonged speaking” and the presence of the peek sign increase the likelihood of myasthenia gravis (likelihood ratio [LR], 4.5; 95% confidence interval [CI], 1.2-17.0 and LR, 30.0; 95% CI, 3.2-278.0, respectively). Their absence does not significantly reduce the likelihood of myasthenia gravis. The identified studies only assessed 1 other historical feature and sign each (“food remaining in the mouth after swallowing” and quiver eye movements, respectively), and neither of these significantly changes the likelihood of myasthenia. The ice test is useful when the response is abnormal (summary positive LR, 24.0; 95% CI, 8.5-67.0) and diminishes the likelihood of myasthenia gravis when the response is normal (summary negative LR, 0.16; 95% CI, 0.09-0.27). A positive response to an anticholinesterase medication (mainly edrophonium test) increases the probability of a diagnosis of myasthenia gravis (summary positive LR, 15.0; 95% CI, 7.5-31.0), and a negative response reduces the diagnostic probability of myasthenia (summary negative LR, 0.11; 95% CI, 0.06-0.21). An abnormal sleep test result is useful in confirming the diagnosis (LR, 53.0; 95% CI, 3.4-832.0). The rest and sleep tests make the probability of myasthenia unlikely when results are normal (LR, 0.52; 95% CI, 0.29-0.95 and LR, 0.01; 95% CI, 0.00-0.16, respectively).

Conclusions Items in the history and physical examination along with results of certain simple tests performed in the office (ice test, sleep test, and edrophonium test) are useful in predicting the likelihood of myasthenia gravis. These results must be interpreted with caution, however, given the high prevalence of disease in the populations reported in clinical studies. This review is limited by the small number of signs and symptoms scientifically studied and reported in the literature. Future studies evaluating the value of common historical features and easy maneuvers commonly known and practiced by experts in the clinical diagnosis of myasthenia are needed.

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Figure 1. Neuromuscular Junction
Graphic Jump Location

In patients with acetylcholine receptor (AChR) antibody–positive myasthenia gravis, circulating antibodies bind to the AChRs, which may block acetylcholine binding, lead to crosslinking of receptors promoting internalization and degradation, and induce postsynaptic membrane damage via complement activation. The number and availability of receptors are reduced such that end-plate potentials are insufficient to generate action potentials in a number of muscle fibers, causing weakness.

Figure 2. Peek Sign
Graphic Jump Location

Orbicularis oculi weakness may be indicated by a positive peek sign after gentle eyelid closure. After complete initial apposition of the lid margins, they quickly (within 30 seconds) start to separate and the sclera starts to show (ie, a positive peek sign). The presence of a peek sign increases the likelihood of myasthenia gravis (likelihood ratio, 30.0; 95% confidence interval, 3.2-278.0), but absence of the peek sign does not rule it out.




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