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Serological, pharmacological and electrophysiological tests for the diagnosis of myasthenia gravis

  • Protocol
  • Diagnostic



This is the protocol for a review and there is no abstract. The objectives are as follows:

In view of the likely sequence in which the various diagnostic tests will be used in everyday clinical practice, we have organized this Cochrane review accordingly and our broad goals are to address three related questions. The primary objective of this review is to ascertain the accuracy of anti-AChR antibody testing for the diagnosis of myasthenia gravis (MG).

1) To determine the accuracy of (a) anti-MuSK antibody serological testing; (b) cholinesterase inhibitor testing; (c) RNS; and (d) SFEMG for the diagnosis of MG amongst patients who are seronegative for AChR antibodies.

2) To determine the accuracy of (a) MuSK antibody serological testing; (b) cholinesterase inhibitor testing; (c) RNS; and (d) SFEMG for the diagnosis of MG regardless of the anti-AChR antibody serological status.

The rationale for the first secondary objective is that these diagnostic tests are most relevant clinically in the population of patients who are seronegative for AChR antibodies.

Since we anticipate that many studies will not separately report the diagnostic accuracy of these other tests for seropositive and seronegative myasthenia, our final objective is to examine the accuracy of these other tests amongst all patients combined (irrespective of whether AChR antibodies titers are elevated or not). The hope is that these data will provide an approximation of the accuracy of other tests for the diagnosis of seronegative myasthenia in the event that we are correct and data to answer our first secondary objective are not available.

For the acetylcholine receptor antibody test, we shall investigate whether observed heterogeneity in estimates of sensitivity and specificity between studies is related to assaying for different types of antibodies (binding, blocking and modulating). For RNS, we shall consider the specific nerve-muscle pair examined as well as the number of nerve-muscle fiber pairs that are examined. For SFEMG, we shall consider the type of needle electrode used for the study (for example single fiber versus concentric needle), the specific technique used (that is volitional versus stimulated) as well as the specific muscle studied (for example frontalis versus orbicularis oculi). For all index tests, we shall investigate the effect of study design (that is consecutive series versus case-control) as well as disease severity, focusing primarily on the distinction between ocular and generalized myasthenia gravis (Jaretzki 2000).

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