Diagnostic Testing for Myasthenia Gravis
Order anti-acetylcholine receptor (AChR) antibodies first, followed by anti-muscle-specific kinase (MuSK) antibodies if AChR is negative, and obtain single-fiber electromyography (SFEMG) as the gold standard electrodiagnostic test. 1, 2, 3
Primary Serologic Testing
Start with anti-AChR antibodies as your first-line test—this confirms the diagnosis in approximately 80% of patients with generalized myasthenia gravis, though sensitivity drops to only 50% in purely ocular disease. 1, 3
Order anti-MuSK antibodies immediately if AChR antibodies are negative, as approximately one-third of seronegative patients will be MuSK-positive. 1, 2, 3
Include anti-striated muscle antibodies in your initial serologic panel. 4, 2
Consider anti-LRP4 (lipoprotein receptor-related protein 4) antibodies in the workup, particularly if both AChR and MuSK are negative, as these are associated with both generalized and ocular myasthenia gravis. 2
Important caveat: About 50% of patients with purely ocular myasthenia gravis remain seronegative for AChR antibodies, so a negative result does not exclude the diagnosis. 2 Recent research using cell-based assays detecting antibodies to clustered AChRs has identified AChR antibodies in approximately 66–70% of previously "seronegative" patients. 5, 6, 7
Electrodiagnostic Studies
Single-fiber electromyography (SFEMG) is the gold standard with >90% sensitivity for ocular myasthenia gravis and should be obtained under neurology consultation. 1, 2, 3
Repetitive nerve stimulation testing is less sensitive (positive in only one-third of ocular myasthenia cases) but more widely available than SFEMG. 1, 3
Include nerve conduction studies (NCS) to exclude neuropathy and needle EMG to evaluate for concomitant myositis. 4
Bedside Clinical Tests
Perform the ice pack test immediately at the bedside—apply an ice pack over closed eyes for 2 minutes when assessing ptosis or 5 minutes for strabismus; a reduction of ptosis by ≥2 mm or improvement in ocular alignment by ≥50% is highly specific for myasthenia gravis. 1, 2, 3
Consider the edrophonium (Tensilon) test if performed by experienced practitioners in a monitored setting with atropine (0.4–0.5 mg IV) readily available; it has 95% sensitivity for generalized myasthenia and 86% for ocular myasthenia. 1, 2, 8
Dosing for adults: Inject 0.2 mL (2 mg) IV over 15–30 seconds; if no reaction after 45 seconds, inject the remaining 0.8 mL (8 mg). 8
Watch for cholinergic side effects: excessive tearing, salivation, sweating, bradycardia, bronchospasm, hypotension, or syncope—if these occur, discontinue and give atropine 0.4–0.5 mg IV. 8
MuSK-positive patients may show hyperreactivity with facial fasciculations and throat stuffiness even at low doses, which can support the clinical diagnosis of MuSK myasthenia. 9
Essential Supplementary Workup
Order CT chest with contrast after confirming the diagnosis to evaluate for thymoma, which occurs in 10–20% of AChR-positive patients and guides decisions about thymectomy. 1, 3
Obtain pulmonary function tests including negative inspiratory force (NIF) and vital capacity (VC) to assess respiratory muscle involvement—this is critical as dysphagia and bulbar weakness precede myasthenic crisis in >50% of cases. 4, 1, 2, 3
Check CPK, aldolase, ESR, and CRP to evaluate for possible concurrent myositis. 4, 1, 3
Obtain troponin and ECG (consider transthoracic echocardiogram or cardiac MRI) to rule out concomitant myocarditis, particularly if respiratory insufficiency or elevated CPK is present. 4, 1, 3
Consider MRI brain and/or spine depending on symptoms to rule out CNS involvement or alternative diagnoses such as brainstem lesions. 4, 1
Check inflammatory markers (ESR and CRP) as part of the comprehensive evaluation. 4
Critical Medication Review
Immediately review and discontinue medications that worsen myasthenia, including β-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolide antibiotics. 4, 1, 2, 3
Common Pitfalls to Avoid
Do not rule out myasthenia gravis based on negative AChR antibodies alone—approximately 20% of generalized and 50% of ocular myasthenia patients are AChR-negative by standard radioimmunoprecipitation assay. 1, 2, 3
Recognize that pupils are characteristically NOT affected in myasthenia gravis—if pupils are abnormal, immediately prioritize evaluation for third nerve palsy, Horner syndrome, or other neurologic causes over myasthenia. 2
Remember that 50–80% of patients presenting with isolated ocular symptoms will progress to generalized myasthenia within a few years, most commonly within the first two years—this makes accurate early diagnosis essential for preventing life-threatening respiratory failure. 2, 3
Do not rely solely on pyridostigmine response for diagnosis—approximately 50% of ocular myasthenia patients show minimal response to pyridostigmine alone, which does not rule out the diagnosis. 2, 3