Myasthenia Gravis

Diagnostics and Likelihood Ratios, Explained

Positive Findings (Patient Has This)

SymptomsIncreased Disease Probability (Positive Likelihood Ratio)
Food in mouth after swallowing13.0 (0.85-212.0)
Unintelligible speech after prolonged speaking4.5× (1.2-17.0)
Signs on Physical ExamIncreased Disease Probability (Positive Likelihood Ratio)
Sleep Test53.0× (3.4-832.0)
Ice Test24.0× (8.5-67.0)
Rest Test16.0 (0.98-261.0)
Anticholinesterase Test15.0× (7.5-31.0)
Quiver eye movements4.1 (0.22-75.0)

Negative Findings (Patient Doesn't Have This)

SymptomsDecreased Disease Probability (Negative Likelihood Ratio)
Unintelligible speech after prolonged speaking0.61 (0.46-0.8)
Food in mouth after swallowing0.70 (0.58-0.84)
Signs on Physical ExamDecreased Disease Probability (Negative Likelihood Ratio)
Sleep Test0.01× (0.00-0.16)
Anticholinesterase Test0.11× (0.06-0.21)
Ice Test0.16× (0.09-0.27)
Rest Test0.52 (0.29-0.95)
Quiver eye movements0.82 (0.57-1.2)
Peek Sign0.88 (0.76-1.0)


Myasthenia gravis is the most common neuromuscular transmission disease, with prevalence rates as high as 20.4 per 100,000.1 The disorder is associated with severe morbidity and mortality, however is very amenable to treatment.

The review summarized here examines the accuracy and utility of history, physical examination, and bedside testing for diagnosing myasthenia. 15 studies met inclusion criteria for the review, including 12 prospective studies (n=896) evaluating the performance of individual elements of the history, physical exam, and bedside clinical tests.

There are several clinical tests that can be performed at the bedside to help in the evaluation for myasthenia gravis. The ice test involves placing ice over the more ptotic eye, while the rest test involves placing a small amount of cotton over a closed lid to rest the eye. Either is placed for 2 minutes, with a positive result being a 2 mm improvement in ptosis. The sleep test is performed by having the patient close their eyes in a dark room for 30 minutes, and then re-evaluating for improvement in ptosis. The peek test is performed by having the patient try to gently close their eyes for 30 seconds. A positive result is the so-called “peeking” of the sclera due to the patient’s inability to maintain eye closure for 30 seconds.

Unintelligible speech after a prolonged period (LR+ 4.5 ) and a positive sleep test (LR+ 53), appear to be useful findings that increase the likelihood of the diagnosis. The ice test (LR- 0.16) and sleep test (LR- 0.01) both appear to significantly decrease the likelihood of the diagnosis when negative. Acetylcholinesterase testing (typically with edrophonium) appears to be among the most useful bedside clinical tests with a LR+ of 15 and a LR- of 0.1.


The data presented here are based on a small number of studies, each with a small number of subjects. The sleep test, for instance, generated the most extreme (i.e. theoretically useful) LR’s, but comes from a single study of 68 subjects, 42 of whom were found to have MG. The high prevalence suggests verification and referral bias in these studies, as the LR findings were generated from samples in which myasthenia was common—a characteristic that may be quite different in many settings where the tests will be used in common clinical practice. Furthermore, because several of these tests depend on the skill and experience of the examiner, and because the inter-observer reliability of the findings was not assessed in any study, the reliability of these findings remains unknown.

Finally, not every patient with weakness can be evaluated with sophisticated examinations like acetylcholinesterase testing or single fiber electromyography, or by an experienced neurologist. Therefore while this is the best published information available on diagnostic findings for myasthenia gravis, the generalizability of these data is difficult to predict.


Rodrigo Kong, MD, and Maxwell Morrison


February 16, 2013

What are Likelihood Ratios?

LR, pretest probability and posttest (or posterior) probability are daunting terms that describe simple concepts that we all intuitively understand.

Let's start with pretest probability: that's just a fancy term for my initial impression, before we perform whatever test it is that we're going to use.

For example, a patient with prior stents comes in sweating and clutching his chest in agony, I have a pretty high suspicion that he's having an MI – let's say, 60%. That is my pretest probability.

He immediately gets an ECG (known here as the "test") showing an obvious STEMI.

Now, I know there are some STEMI mimics, so I'm not quite 100%, but based on my experience I'm 99.5% sure that he's having an MI right now. This is my posttest probability - the new impression I have that the patient has the disease after we did our test.

And likelihood ration? That's just the name for the statistical tool that converted the pretest probability to the posttest probability - it's just a mathematical description of the strength of that test.

Using an online calculator, that means the LR+ that got me from 60% to 99.5% is 145, which is about as high an LR you can get (and the actual LR for an emergency physician who thinks an ECG shows an obvious STEMI).

(Thank you to Seth Trueger, MD for this explanation!)