How is myasthenia gravis (MG) managed during acute illnesses?

Management of Myasthenia Gravis During Acute Illnesses

Immediately hospitalize patients with myasthenic crisis (Grade 3-4) in an ICU setting, discontinue all medications that worsen MG, initiate IVIG (2 g/kg over 5 days) or plasmapheresis, and start high-dose corticosteroids while performing frequent respiratory monitoring with NIF and VC measurements. 1, 2

Immediate Assessment and Recognition

When a patient with MG develops acute illness or exacerbation, rapidly assess respiratory status as this determines the entire management pathway:

• Measure negative inspiratory force (NIF) and vital capacity (VC) immediately - these are critical for identifying impending respiratory failure 3, 1, 2
• Apply the "20/30/40 rule": vital capacity <20 ml/kg, maximum inspiratory pressure <30 cmH₂O, or maximum expiratory pressure <40 cmH₂O indicates high risk of respiratory failure 2
• Evaluate for bulbar symptoms (dysphagia, dysarthria, facial weakness) as these indicate impending respiratory compromise and make non-invasive ventilation likely to fail 4, 2
• Perform single breath count test: inability to count to ≥25 at two numbers per second correlates with respiratory muscle dysfunction 2

The presence of bulbar dysfunction with respiratory compromise makes intubation more likely to be needed and should not be delayed if non-invasive ventilation is failing 4.

Critical Medication Management

Immediately discontinue these medications that can precipitate or worsen myasthenic crisis:

• β-blockers 1, 2
• IV magnesium (absolutely contraindicated) - if severe hypomagnesemia requires treatment, mandatory neurology consultation before any administration 2
• Fluoroquinolone antibiotics 1, 2
• Aminoglycoside antibiotics 1, 2
• Macrolide antibiotics 1, 2
• Anticholinergic medications 4

This is a common pitfall - acute illnesses often prompt antibiotic prescriptions, and choosing the wrong class can precipitate crisis 1.

Grading and Treatment Algorithm

Grade 2 (Mild-Moderate Symptoms)

Symptoms interfering with activities of daily living but no respiratory compromise:

• Optimize pyridostigmine: start at 30 mg orally three times daily, titrate up to maximum 120 mg four times daily based on response 3, 1
• Add corticosteroids if pyridostigmine insufficient: prednisone 1-1.5 mg/kg/day orally 1, 2
• Hold immune checkpoint inhibitors if applicable and may resume only if symptoms resolve 3
• Consult neurology 3
• Avoid IVIG at this stage - it is not indicated for Grade 2 symptoms 1

Grade 3-4 (Myasthenic Crisis)

Severe generalized weakness, respiratory compromise, or hospitalization required:

Immediate actions:

• Admit to ICU for close respiratory monitoring 1, 2
• Initiate IVIG 0.4 g/kg/day × 5 days (total 2 g/kg) OR plasmapheresis (5 sessions over 5 days) 3, 1, 2
• Start high-dose corticosteroids: methylprednisolone 1-2 mg/kg/day IV or prednisone 1-1.5 mg/kg/day 4, 2
• Consider pulse corticosteroids for severe symptoms: methylprednisolone 1 g/day for 5 days 4
• Manage pyridostigmine carefully: discontinue or withhold in intubated patients; for non-intubated patients, may continue at 30 mg orally up to 600 mg daily 2

The FDA label warns that increasing pyridostigmine doses during crisis can be dangerous - overdosage causes cholinergic crisis with increasing muscle weakness that mimics myasthenic crisis 5. This is a critical distinction requiring clinical judgment and potentially edrophonium testing 5.

For parenteral administration when oral route unavailable:

• IV pyridostigmine: 1 mg IV = 30 mg oral 4, 2
• IM neostigmine: 0.75 mg IM = 30 mg oral pyridostigmine 4, 2

Respiratory Monitoring Protocol

Perform frequent pulmonary function assessments:

• Monitor NIF and VC at least daily during crisis 1, 2
• Conduct daily neurologic evaluations 1, 2
• Watch for difficulty achieving adequate oxygenation or rapid desaturation - these indicate need for intubation 4
• Do not delay intubation if non-invasive ventilation failing - deterioration in neuromuscular disease can be very sudden 4
• Intubation indicated for: respiratory arrest, peri-arrest, or inability to clear secretions 4

Pulse oximetry and arterial blood gases are not reliable early indicators of emerging respiratory failure in MG 2.

Diagnostic Workup During Acute Illness

Complete these tests to guide management:

• AChR antibodies and anti-striated muscle antibodies 3, 2
• If AChR negative: test for MuSK and LRP4 antibodies 3, 2
• CPK, aldolase, ESR, CRP to evaluate for concurrent myositis 3, 2
• If respiratory insufficiency or elevated CPK/troponin: ECG and transthoracic echocardiogram to rule out myocarditis 3, 2
• Consider MRI brain/spine depending on symptoms to exclude CNS involvement 3
• Electrodiagnostic studies: repetitive stimulation, jitter studies, NCS, and needle EMG 3

Ongoing Management and Monitoring

Continue these interventions throughout acute illness:

• Monitor for minimum 24 hours in ICU/HDU even after apparent stabilization 2
• Maintain corticosteroids concurrently during IVIG or plasmapheresis 1
• Begin steroid taper 3-4 weeks after initiation based on symptom improvement 2
• Permanently discontinue immune checkpoint inhibitors for Grade 3-4 toxicity 3

Special Considerations

ICPi-associated myasthenia gravis may be monophasic and potentially require less prolonged immunosuppression compared to classic MG 2. However, the acute management remains the same with aggressive immunotherapy 3, 2.

IVIG is not appropriate for chronic maintenance therapy - it should be reserved strictly for acute exacerbations and crisis situations 1. Using IVIG for chronic maintenance represents inappropriate use not supported by guidelines 1.

The key pitfall is failing to recognize that acute illnesses can trigger myasthenic crisis through multiple mechanisms: infection-related stress, inappropriate antibiotic selection, or metabolic derangements 1, 2. Aggressive early intervention with immunotherapy prevents progression to respiratory failure 1, 2, 6.