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Katalin Scherer, MD; Richard S. Bedlack, MD, PhD; David L. Simel, MD, MHS

JAMA. 2005;293:1906-1914.

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.

Author Affiliations: Department of Medicine, Duke University Medical Center, Durham, NC (Dr Scherer); Department of Medicine, Durham Veterans Affairs Medical Center and Duke University, Durham (Drs Bedlack and Simel).

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