What are the diagnostic tests and treatment options for a patient suspected of having Myasthenia gravis?

Myasthenia Gravis Examination: Diagnostic Tests and Treatment

For suspected myasthenia gravis, immediately test anti-acetylcholine receptor (AChR) antibodies and perform bedside ice pack testing, followed by electrodiagnostic studies if antibodies are negative, then initiate pyridostigmine 30 mg orally three times daily and escalate to immunosuppressive therapy based on disease severity. 1

Clinical Examination Findings

Key features to identify during examination:

• Fatigable muscle weakness that worsens with repeated use and improves with rest, typically more proximal than distal 1, 2
• Ocular signs: Ptosis worsening with sustained upward gaze, diplopia from asymmetric extraocular muscle weakness 1, 2
• Critical distinguishing feature: Pupils are characteristically NOT affected—pupillary involvement should immediately redirect you toward third nerve palsy or other etiologies 1
• Bulbar involvement: Dysarthria worsening with prolonged speech, dysphagia, facial muscle weakness, hoarseness 1, 2
• Limb weakness: Difficulty climbing stairs, proximal > distal weakness 1, 2
• Respiratory assessment: Shortness of breath with light activity requires urgent evaluation for respiratory muscle involvement 1, 2

Diagnostic Testing Algorithm

First-Line Serologic Testing

Order these tests immediately upon clinical suspicion:

• Anti-AChR antibodies first—present in 80-85% of generalized MG, but only 50% in purely ocular MG 1, 3
• Anti-MuSK antibodies—test when AChR antibodies are negative, as approximately one-third of seronegative patients will be MuSK-positive 1, 3
• Anti-striated muscle antibodies should be included in initial workup 1, 3

Bedside Confirmatory Tests

Perform these immediately in the clinic:

• Ice pack test: Apply ice pack over closed eyes for 2 minutes—highly specific for MG, particularly for ocular symptoms; observe for reduction in ptosis or improvement in extraocular movements 1, 3
• Edrophonium (Tensilon) test: 95% sensitivity for generalized MG, 86% for ocular MG 1
  • Adult IV dose: 2 mg initially over 15-30 seconds, then 8 mg if no reaction after 45 seconds 4
  • Critical safety requirement: Have atropine 0.4-0.5 mg IV immediately available for cholinergic reactions 4

Electrodiagnostic Studies

Order when antibodies are negative or diagnosis remains uncertain:

• Single-fiber EMG (SFEMG): Gold standard with >90% sensitivity for ocular myasthenia 1, 3
• Repetitive nerve stimulation: Less sensitive (positive in only one-third of ocular cases) but more widely available 1, 3

Essential Supplementary Workup

Complete these tests after diagnosis confirmation:

• CT chest with contrast to evaluate for thymoma (occurs in 10-20% of AChR-positive patients) 3
• Pulmonary function testing with negative inspiratory force (NIF) and vital capacity (VC) to assess respiratory muscle involvement 3
• Cardiac evaluation: Troponin, ECG; consider echocardiogram or cardiac MRI to rule out myocarditis 5, 3
• Inflammatory markers: CK, aldolase, ESR, CRP to evaluate for concurrent myositis 5, 3

Treatment Algorithm Based on Disease Severity

Grade 1 (Mild Ocular or Minimal Weakness)

Start symptomatic treatment:

• Pyridostigmine: Begin at 30 mg orally three times daily, gradually increase to maximum 120 mg four times daily based on symptoms 1, 3, 6
• Extended-release formulation: 180 mg once or twice daily (minimum 6-hour interval between doses) for better symptom control 6
• Critical limitation: Approximately 50% of patients, particularly those with ocular symptoms, show minimal response to pyridostigmine alone and require escalation 1, 3

Grade 2 (Moderate Generalized Weakness, MGFA Class I-II)

Escalate to immunosuppressive therapy when symptoms interfere with activities of daily living:

• Continue pyridostigmine at optimized dose 1, 3
• Add prednisone 0.5 mg/kg orally daily 1, 3
• Expected response: 66-85% positive response rate to corticosteroids (superior to pyridostigmine's 50% response rate) 1, 3

Grade 3-4 (Severe Weakness, MGFA Class III-V)

Initiate aggressive immunotherapy:

• IVIG 2 g/kg IV over 5 days (0.4 g/kg/day) OR plasmapheresis for 3-5 days 1, 3
• Prednisone 1 mg/kg/day 1, 3
• ICU-level monitoring may be necessary for rapidly progressive symptoms or respiratory muscle weakness 3
• Daily neurologic review and frequent pulmonary function assessment 3

Third-Line Immunosuppressive Therapy

For moderate to severe disease refractory to corticosteroids:

• Azathioprine as steroid-sparing agent 1, 3
• Efgartigimod alfa-fcab: FDA-approved specifically for AChR-positive patients refractory to conventional therapy 3

Surgical Intervention

Thymectomy evaluation:

• Always perform when thymoma is present 3
• Consider in appropriate AChR-positive patients—may substantially reduce symptoms 3

Critical Medication Avoidance

Immediately review and discontinue these medications that worsen myasthenia:

• β-blockers 1, 3
• IV magnesium 1, 3
• Fluoroquinolones 1, 3
• Aminoglycosides 1, 3
• Macrolide antibiotics 1, 3

Common Pitfalls and Monitoring

Key considerations to prevent complications:

• 50-80% of patients with initial ocular symptoms develop generalized myasthenia within a few years—regular assessment is crucial 1, 3
• Respiratory compromise is life-threatening—maintain low threshold for pulmonary function testing in all patients with generalized disease 1, 3
• Strabismus surgery should only be considered after disease stabilization, typically requiring 2-3 years of medical treatment 3
• Preoperative antibody testing is mandatory for any patient with suspected MG requiring surgery to avoid respiratory failure during anesthesia 1
• Multidisciplinary management requires collaboration between neurology and ophthalmology, with potential involvement of cardiothoracic surgery for thymectomy 3