What is the diagnosis and management of myasthenia crisis?

Diagnosis and Management of Myasthenic Crisis

Myasthenic crisis is a life-threatening manifestation of myasthenia gravis defined by respiratory insufficiency requiring invasive or non-invasive ventilation, and immediate airway management with rapid initiation of immunotherapy is essential for successful treatment. 1

Diagnostic Approach

Clinical Presentation

• Rapidly progressive weakness of respiratory and bulbar muscles leading to respiratory insufficiency and/or aspiration
• May develop within minutes to days
• Can include flaccid tetraparesis, severe dysphagia, dysarthria, facial muscle weakness, and respiratory compromise 2
• May be the first manifestation of undiagnosed myasthenia gravis in up to 20% of cases 2

Diagnostic Tests

1. Laboratory Tests:

   • Acetylcholine receptor (AChR) antibodies (positive in 80-85% of generalized MG) 3
   • If AChR negative, test for MuSK antibodies (positive in 5-8% of cases) 3
   • CPK, aldolase, ESR, CRP to evaluate for concurrent myositis 3
   • Troponin to rule out myocarditis 3

2. Respiratory Assessment:

   • Pulmonary function tests with negative inspiratory force (NIF) and vital capacity (VC) 3
   • Arterial blood gas analysis

3. Neurophysiological Tests:

   • Repetitive nerve stimulation (shows decremental response) 3
   • Single-fiber electromyography (SFEMG) - gold standard with >90% sensitivity 3

4. Additional Studies:

   • Chest imaging to evaluate for thymoma (present in 10-20% of AChR-positive patients) 3
   • MRI brain/spine if CNS involvement is suspected 3
   • ECG and echocardiogram to rule out myocarditis 3

Management Algorithm

Step 1: Immediate Interventions

• Secure airway and ventilation

  • Early intubation if signs of respiratory failure or bulbar dysfunction 2
  • Consider non-invasive ventilation before intubation in appropriate cases 4
  • Monitor respiratory parameters closely

• Discontinue cholinesterase inhibitors (e.g., pyridostigmine) during acute crisis 5

  • Resume prior to extubation 4

Step 2: Acute Immunotherapy (Start within 24 hours)

• First-line treatment: Plasmapheresis/Plasma Exchange

  • Preferred over IVIG for myasthenic crisis 1
  • Typically 5 exchanges over 7-10 days 6
  • Median time to extubation: 8 days 6

• Alternative: Intravenous Immunoglobulin (IVIG)

  • If plasmapheresis is unavailable or contraindicated
  • Standard dose: 2g/kg divided over 2-5 days
  • Median time to extubation: 10 days 6

Step 3: Identify and Treat Precipitating Factors

• Common triggers:

  • Respiratory infections (most common) 1
  • Medication changes or non-compliance
  • Surgery or trauma
  • Pregnancy/postpartum state
  • No specific trigger found in 30-40% of cases 1

• Treat infections aggressively with appropriate antibiotics

Step 4: Initiate or Optimize Immunosuppression

• Corticosteroids

  • Prednisone 0.5-1.5 mg/kg orally daily 3
  • Increase dose once airway is secured 4
  • Note: Initial steroid therapy may worsen symptoms temporarily

• Steroid-sparing agents (start concurrently with steroids)

  • Azathioprine: 2 mg/kg of ideal body weight in divided doses 3
  • Mycophenolate mofetil: Start 500mg twice daily, increase to 1000mg twice daily 3
  • Methotrexate: 15mg weekly 3

Step 5: Supportive Care

• Ventilator management

  • Median duration of ventilation: 12-14 days 2
  • About 20% still require ventilation after 1 month 2

• Prevention of complications

  • Ventilator-associated pneumonia (most common complication, 30%) 6
  • Deep vein thrombosis prophylaxis
  • Stress ulcer prophylaxis
  • Early physical therapy

• Nutritional support

  • Enteral feeding if prolonged intubation

Step 6: Monitoring and Weaning

• Differentiate between myasthenic and cholinergic crisis

  • May require edrophonium test 5
  • Myasthenic crisis: Increased anticholinesterase therapy needed
  • Cholinergic crisis: Prompt withdrawal of anticholinesterase drugs and use of atropine 5

• Criteria for extubation

  • Improved muscle strength
  • Adequate vital capacity and negative inspiratory force
  • Ability to protect airway

• Resume pyridostigmine before extubation

  • Start at 30mg orally three times daily
  • Gradually increase to maximum of 120mg four times daily as tolerated 3

Prognosis and Follow-up

• Mortality rate less than 5% in modern intensive care settings 1
• Median duration of crisis: approximately 2 weeks 2
• Lifetime risk of recurrence: approximately 30% 2
• Most deaths are due to complications rather than the crisis itself 2

Important Cautions

• Avoid medications that can exacerbate MG symptoms:

  • Beta-blockers
  • IV magnesium
  • Fluoroquinolones
  • Aminoglycosides
  • Macrolide antibiotics 3

• Monitor for signs of deterioration:

  • Decreasing vital capacity
  • Worsening bulbar symptoms
  • Increasing secretions
  • Paradoxical breathing

• Recognize high-risk patients:

  • History of previous myasthenic crisis
  • Severe disease
  • Oropharyngeal weakness
  • MuSK antibody positivity
  • Thymoma 1