What is the management approach for an acute exacerbation of myasthenia gravis (MG)?

Management of Acute Myasthenia Gravis Exacerbation

For acute myasthenic crisis (Grade 3-4 exacerbation), immediately admit to the ICU for respiratory monitoring and initiate either IVIG at 2 g/kg total dose over 5 days (0.4 g/kg/day) or plasmapheresis, while continuing corticosteroids and pyridostigmine. 1, 2

Immediate Assessment and Stabilization

Respiratory Evaluation

• Perform urgent pulmonary function testing with negative inspiratory force (NIF) and vital capacity (VC) measurements to assess respiratory compromise 1, 2
• Admit all patients with myasthenic crisis to the ICU for close respiratory monitoring 1, 2
• Consider noninvasive positive-pressure ventilation initially, as this has been successful even in patients with bulbar weakness 3
• If intubation becomes necessary, avoid depolarizing paralytics or use reduced doses of nondepolarizing agents 3
• Intubation is required in approximately 63% of patients with severe exacerbations 4

Diagnostic Confirmation

• Obtain immediate neurologic consultation 2
• Check acetylcholine receptor (AChR) antibodies and antistriated muscle antibodies; if AChR antibodies are negative, test for muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4) antibodies 1, 2
• Perform electrodiagnostic studies with repetitive stimulation and/or jitter studies 2

Acute Treatment Protocol

First-Line Immunotherapy (Choose One)

• IVIG: Administer 0.4 g/kg/day for 5 consecutive days (total dose 2 g/kg) 1, 2
• Plasmapheresis: Perform daily for 5 days 1, 2

Both modalities have similar efficacy; choice depends on availability, contraindications, and institutional expertise 1, 2

Concurrent Medication Management

• Continue corticosteroids if already prescribed (methylprednisolone 1-2 mg/kg daily or prednisone 1-1.5 mg/kg daily) 1, 2
• Maintain pyridostigmine therapy, adjusting dose based on improvement 1, 2
• Continue immunosuppressive agents (azathioprine, mycophenolate) if already prescribed 2

Critical Medication Avoidance

Strictly avoid the following medications that can precipitate or worsen myasthenic crisis: 1, 2, 3

• β-blockers 1, 2
• Intravenous magnesium 1, 2
• Fluoroquinolone antibiotics 1, 2
• Aminoglycoside antibiotics 1, 2
• Macrolide antibiotics 1, 2
• Depolarizing paralytics 3

Important caveat: Avoid acetylcholinesterase inhibitors including edrophonium testing during acute crisis 3. Also avoid initiating corticosteroids during the acute crisis phase if not already prescribed, as they can initially worsen weakness 3

Monitoring During Crisis

Daily Assessments

• Perform frequent pulmonary function testing (NIF/VC) 1, 2
• Conduct daily neurologic examinations 1, 2
• Monitor for concurrent myositis or myocarditis with CPK, aldolase, ESR, CRP, ECG, and transthoracic echocardiography if respiratory insufficiency or elevated cardiac markers are present 2

Identify and Treat Precipitating Factors

• Infection is the most common trigger for myasthenic crisis 3, 5
• Other stressors include surgery, medication changes, pregnancy, and emotional stress 5
• Address the underlying trigger while providing immunotherapy 2

Post-Crisis Management

Stabilization Phase

• After crisis resolution, continue immunosuppressive therapy 2
• Gradually taper corticosteroids based on symptom improvement 1, 2
• Optimize pyridostigmine dosing (30 mg three times daily, titrating to maximum 120 mg four times daily as needed) 1

Long-Term Considerations

• Consider thymectomy evaluation for patients with thymoma after stabilization 2
• Approximately 30-50% of patients with thymomas have myasthenia gravis, and thymoma is associated with poorer outcomes 6, 2
• With specialized neurointensive care, the majority of patients achieve good long-term prognosis with either asymptomatic status or mild symptoms 4
• Current mortality rate for myasthenic crisis is approximately 4-8% 5

Treatment-Refractory Disease

For the small subset of patients with treatment-refractory disease despite standard therapy, consider rituximab, high-dose cyclophosphamide, or eculizumab 7

Prognosis

The outcome of myasthenic crisis has improved significantly with modern ICU management, and patients followed for a mean of 4 years post-crisis demonstrate favorable long-term outcomes in both early- and late-onset MG 4