What is the recommended workup and treatment for a patient suspected of having Myasthenia Gravis (MG)?

Myasthenia Gravis Workup

Begin with serologic testing for acetylcholine receptor (AChR) antibodies and antistriated muscle antibodies, followed by electrodiagnostic studies if antibodies are negative, and initiate pyridostigmine 30 mg orally three times daily as first-line symptomatic treatment while completing the diagnostic evaluation. 1, 2

Diagnostic Workup Algorithm

Initial Clinical Assessment

Look for these specific features:

• Fatigable or fluctuating muscle weakness that worsens with repeated use and improves with rest 2
• Ptosis and extraocular movement abnormalities (present in 50-80% initially) 2, 3
• Bulbar symptoms: dysphagia, dysarthria, facial muscle weakness 2
• Proximal limb weakness greater than distal 2
• Critically: pupils are characteristically NOT affected - pupillary involvement should immediately redirect you toward third nerve palsy or other diagnoses 2

Perform the ice pack test at bedside: Apply ice pack over closed eyes for 2 minutes - this is highly specific for MG, particularly for ocular symptoms 2

Serologic Testing (First Priority)

Order these antibodies in sequence: 1, 2

• AChR antibodies (positive in 80-85% of generalized MG, but only 40-77% of ocular MG) 2, 3
• Antistriated muscle antibodies 2
• If AChR negative: Test for muscle-specific kinase (MuSK) antibodies (5-8% of patients) and lipoprotein-related protein 4 (LRP4) antibodies (<1%) 2, 3
• Approximately 10% remain seronegative for all known antibodies 3

Electrodiagnostic Studies (If Antibodies Negative or Diagnosis Uncertain)

• Repetitive nerve stimulation: Shows decremental response 2
• Single-fiber EMG: >90% sensitivity for ocular myasthenia, highest yield test when antibodies are negative 2
• Standard EMG and nerve conduction studies may be normal early in disease 2

Pulmonary Function Testing

Measure these parameters in all patients with generalized symptoms: 1, 2

• Negative inspiratory force (NIF)
• Vital capacity (VC)
• Monitor closely for respiratory compromise, especially in patients with bulbar symptoms or shortness of breath

Imaging Studies

Obtain chest CT with contrast to evaluate for thymoma: 10-20% of AChR-positive patients have thymoma, and 30-50% of thymoma patients have MG 2

Cardiac Evaluation

Check troponin to evaluate for myocardial involvement - this is critical as cardiac involvement requires permanent discontinuation of certain immunotherapies 4

Treatment Algorithm Based on Disease Severity

Mild Disease (MGFA Class I-II: Ocular or Mild Generalized)

First-line: 1, 2, 5

• Pyridostigmine 30 mg orally three times daily
• Titrate upward based on response to maximum 120 mg orally four times daily
• Instruct patients to time activities around medication for optimal strength 1

Second-line (if inadequate response to pyridostigmine): 1, 2

• Add prednisone 1-1.5 mg/kg orally daily
• Taper gradually based on symptom improvement
• Note: Approximately 50% of ocular MG patients show minimal response to pyridostigmine alone and require corticosteroids 2

Moderate to Severe Disease (MGFA Class III-IV)

Initiate combination therapy immediately: 1, 2

• Pyridostigmine (as above)
• Prednisone 1-1.5 mg/kg orally daily
• Consider steroid-sparing agents (azathioprine, mycophenolate mofetil) for long-term management 6, 7

Myasthenic Crisis (MGFA Class V: Respiratory Failure)

This is a medical emergency requiring immediate action: 1, 2

1. Admit to ICU with respiratory monitoring capability 1
2. Initiate IVIG 0.4 g/kg/day for 5 consecutive days (total 2 g/kg) OR plasmapheresis 1, 2
3. Continue corticosteroids concurrently 1
4. Monitor pulmonary function frequently using the "20/30/40 rule": patient at risk if vital capacity <20 ml/kg, maximum inspiratory pressure <30 cmH₂O, or maximum expiratory pressure <40 cmH₂O 8
5. Pyridostigmine may be continued but can be withheld if intubation required 1

Critical distinction: IVIG is for acute crisis only - never use IVIG for chronic maintenance therapy 1

Medications That MUST Be Avoided

Educate patients to strictly avoid these medications that worsen neuromuscular transmission: 1, 2

• β-blockers
• Intravenous magnesium
• Fluoroquinolone antibiotics (ciprofloxacin, levofloxacin)
• Aminoglycoside antibiotics (gentamicin, tobramycin)
• Macrolide antibiotics (azithromycin, erythromycin)
• Metoclopramide - can trigger myasthenic crisis 1
• Barbiturate-containing medications (butalbital) 1

Critical Pitfalls to Avoid

Preoperative screening: Any patient with suspected MG requiring surgery MUST have serum AChR antibody levels measured preoperatively to avoid respiratory failure during anesthesia 2

Pupillary involvement: If pupils are abnormal, immediately prioritize evaluation for third nerve palsy, Horner syndrome, or brainstem lesions over MG 2

Progression risk: 50-80% of patients with isolated ocular symptoms will develop generalized MG within a few years - close follow-up is essential 2

Thymectomy consideration: Clear evidence supports thymectomy in AChR-positive generalized MG patients up to age 65 years 7

Sequential therapy: Do NOT use TPE followed by IVIG - sequential therapy is no more effective than either treatment alone 1