What investigations are required for the diagnosis of myasthenia gravis?

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Diagnostic Investigations for Myasthenia Gravis

The diagnosis of myasthenia gravis requires a combination of serological testing, electrophysiological studies, and specialized clinical tests, with anti-acetylcholine receptor antibody testing and single-fiber electromyography being the most essential diagnostic investigations. 1, 2

Primary Diagnostic Tests

  • Anti-acetylcholine receptor (AChR) antibody testing should be performed as the initial serological test, which is positive in approximately 80% of patients with generalized myasthenia gravis and 50% of patients with purely ocular myasthenia 1

  • If AChR antibodies are negative, test for muscle-specific kinase (MuSK) and lipoprotein-related 4 (LRP4) antibodies, as approximately one-third of seronegative patients will be positive for anti-MuSK antibodies 3, 1

  • Single-fiber electromyography (SFEMG) is the gold standard electrophysiological test with over 90% sensitivity for ocular myasthenia gravis and up to 92% sensitivity overall 1, 4

  • Repetitive nerve stimulation (RNS) should be performed but has lower sensitivity (77%) than SFEMG, particularly in ocular myasthenia where it is positive in only about one-third of patients 1, 4

Pharmacological Testing

  • The Edrophonium (Tensilon) test can be used to confirm the diagnosis when serological and electrophysiological tests are inconclusive 1, 5

  • For adults, administer 2 mg intravenously first, and if no reaction occurs after 45 seconds, inject the remaining 8 mg; have atropine sulfate (0.4-0.5 mg IV) available to counteract potential cholinergic reactions 5

  • The ice pack test (application of ice over closed eyes for 5 minutes) is a simpler alternative with high specificity for myasthenia gravis and can be performed in outpatient settings 1, 6

Respiratory and Systemic Evaluation

  • Pulmonary function assessment with negative inspiratory force and vital capacity measurements is essential to evaluate respiratory muscle involvement and risk of respiratory failure 3, 1

  • Creatine phosphokinase (CPK), aldolase, ESR, and CRP should be tested to evaluate for possible concurrent myositis 3, 1

  • If respiratory insufficiency or elevated CPK/troponin T is present, perform cardiac examination with ECG and transthoracic echocardiogram to rule out concomitant myocarditis 3, 1

Imaging and Additional Testing

  • MRI of brain and/or spine should be considered depending on symptoms to rule out CNS involvement or alternative diagnoses 3, 1

  • Screen for other autoimmune conditions, particularly thyroid disorders, as myasthenia gravis is often associated with other autoimmune diseases 7

Specialist Consultation

  • Neurology consultation is essential for proper diagnosis and management planning 3, 1

  • For patients with ocular symptoms, collaboration between ophthalmologist and neurologist is recommended 6

Important Considerations

  • Avoid medications that can exacerbate myasthenia symptoms during testing, including β-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolides 3, 1

  • The combination of these three tests—AChR antibody assay, RNS, and SFEMG—has been shown to identify virtually all cases of myasthenia gravis, with at least one test being abnormal in all cases 4

  • In patients with suspected myasthenic crisis, rapid diagnostic evaluation is critical, as respiratory compromise can develop quickly 3, 2

References

Guideline

Laboratory Testing for Myasthenia Gravis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Myasthenia gravis.

Orphanet journal of rare diseases, 2007

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Management of Fatigue and Nystagmus in Myasthenia Gravis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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