Myasthenia Gravis Diagnostic Panel and Treatment
Diagnostic Panel
For any patient with suspected myasthenia gravis, immediately order anti-acetylcholine receptor (AChR) antibodies as the first-line test, which confirms diagnosis in approximately 80-85% of generalized MG cases. 1, 2
Initial Serologic Testing (in order of priority):
- Anti-AChR antibodies - Test first; positive in 80-85% of generalized MG but only 50% of purely ocular MG 1, 2
- Anti-muscle-specific kinase (MuSK) antibodies - Order when AChR antibodies are negative; approximately one-third of seronegative patients will be MuSK-positive 1, 3
- Anti-striated muscle antibodies - Include in initial workup 4, 1
- Anti-lipoprotein-related protein 4 (LRP4) antibodies - Consider if both AChR and MuSK are negative 4, 3
Electrodiagnostic Studies:
- Single-fiber electromyography (SFEMG) - Gold standard with >90% sensitivity for ocular myasthenia 5, 1
- Repetitive nerve stimulation - Less sensitive (positive in only one-third of ocular cases) but more widely available 1
- Nerve conduction studies - To exclude neuropathy 4
- Needle EMG - To evaluate for concurrent myositis 4
Bedside Clinical Tests:
- Ice pack test - Apply ice pack over closed eyes for 2 minutes; highly specific for MG, particularly for ocular symptoms 5, 1
- Edrophonium (Tensilon) test - 95% sensitivity for generalized MG and 86% for ocular MG, but requires experienced practitioners with atropine available due to muscarinic side effects 1
Essential Supplementary Workup:
- CT chest with contrast - Mandatory after diagnosis to evaluate for thymoma, which occurs in 10-20% of AChR-positive patients 1
- Pulmonary function testing - Negative inspiratory force (NIF) and vital capacity (VC) to assess respiratory muscle involvement 4, 1
- CPK, aldolase, ESR, and CRP - To evaluate for concurrent myositis 4, 1
- Troponin T and ECG - If respiratory insufficiency or elevated CPK present; consider echocardiogram or cardiac MRI to rule out concomitant myocarditis 4, 1
- MRI of brain and/or spine - Consider based on symptoms to rule out CNS involvement or alternate diagnosis 4
Critical Diagnostic Pitfall:
Pupils are characteristically NOT affected in myasthenia gravis - if pupillary abnormalities are present, immediately prioritize evaluation for third nerve palsy, Horner syndrome, or other neurologic causes over MG. 5
Treatment Algorithm
Grade 2 Disease (Mild Generalized Weakness, MGFA Class I-II):
Start pyridostigmine at 30 mg orally three times daily and gradually increase to maximum 120 mg four times daily based on symptoms. 4, 5, 1, 6
- If symptoms interfere with activities of daily living despite pyridostigmine, add prednisone 0.5-1.5 mg/kg orally daily 4, 1
- Approximately 50% of patients with ocular myasthenia show minimal response to pyridostigmine alone and require escalation to corticosteroids 5, 1
- Corticosteroids demonstrate superior efficacy with 66-85% positive response rates compared to pyridostigmine's 50% response rate 5, 1
- May hold checkpoint inhibitors in Grade 2 patients and resume only if symptoms resolve (in immune checkpoint inhibitor-associated MG) 4
Grade 3-4 Disease (Moderate to Severe Weakness, MGFA Class III-V):
Permanently discontinue checkpoint inhibitors if applicable, admit patient with ICU-level monitoring, and immediately initiate IVIG 2 g/kg IV over 5 days (0.4 g/kg/day) or plasmapheresis for 3-5 days in addition to corticosteroids. 4, 1
- Continue daily neurologic evaluation and frequent pulmonary function assessment 4, 1
- Azathioprine can be used as third-line immunosuppressive therapy for moderate to severe disease 5, 1
Surgical Intervention:
Always perform thymectomy when thymoma is present. 1
- Thymectomy should be evaluated in appropriate AChR-positive patients without thymoma, as it may substantially reduce symptoms 1, 3
Novel Therapies for Refractory Disease:
- Efgartigimod alfa-fcab - FDA-approved specifically for AChR-positive patients who are refractory to conventional therapy 1, 3
- Rituximab - Good option especially for MuSK-positive patients 3
- Eculizumab and ravulizumab - FDA-approved for adult patients with generalized MG who are AChR-antibody positive 3
Critical Medication Avoidance
Immediately review and discontinue medications that worsen myasthenia: β-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolide antibiotics. 4, 5, 1
Monitoring Requirements
- Regular pulmonary function assessment is crucial as 50-80% of patients with initial ocular symptoms develop generalized myasthenia within a few years 5, 1
- Daily neurologic review for Grade 3-4 patients 4, 1
- Neurology consultation is mandatory for all grades given potential for progressive disease leading to respiratory compromise 4