What is a myasthenic crisis, its precipitating factors, and the recommended acute management?

Myasthenic Crisis: Definition, Precipitants, and Acute Management

Definition and Clinical Significance

Myasthenic crisis is a life-threatening maximal manifestation of myasthenia gravis characterized by respiratory failure requiring mechanical ventilation (invasive or non-invasive), resulting from weakness of respiratory muscles, upper airway muscles leading to obstruction and aspiration, or both. 1, 2

• Approximately 15-20% of patients with myasthenia gravis experience at least one crisis during their lifetime, most commonly within the first 2-3 years of disease onset 1, 2
• In up to 20% of cases, myasthenic crisis represents the first manifestation of previously undiagnosed myasthenia gravis 1
• The median duration of mechanical ventilation is 12-14 days under appropriate treatment, though approximately 20% of patients remain ventilated after 1 month due to complications 1
• Current mortality rates are less than 5% in the United States, a dramatic improvement from the historical 75% mortality rate four decades ago 3, 2
• Deaths are almost never caused by the crisis itself but rather by comorbidities and complications 1

Precipitating Factors and Risk Factors

Common Triggers

• Respiratory infections are the most common identifiable precipitant of myasthenic crisis 3, 2
• Aspiration events and sepsis frequently trigger decompensation 3
• Surgical procedures and the perioperative period carry significant risk 3
• Rapid tapering or discontinuation of immunomodulatory therapy can precipitate crisis 3
• Initiation of corticosteroid therapy (particularly at high doses) may paradoxically worsen weakness initially 3
• Exposure to medications that exacerbate myasthenic weakness, including beta-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolide antibiotics 4, 5
• Pregnancy represents a high-risk period 3
• No specific trigger is identified in 30-40% of myasthenic crisis cases 2

High-Risk Patient Populations

• Patients with prior history of myasthenic crisis (lifetime recurrence risk approximately 30%) 1
• Severe generalized disease (MGFA Class III-IV) 4
• Oropharyngeal and bulbar weakness, particularly dysphagia (present in more than 50% of cases preceding crisis) 6, 2
• Muscle-specific kinase (MuSK) antibody-positive patients 2
• Presence of thymoma 2
• Concurrent myocarditis or myositis, especially in immune checkpoint inhibitor-related myasthenia gravis 4, 7

Clinical Recognition: Red Flags

Most episodes of myasthenic crisis do not occur suddenly, providing a critical window for prevention and early intervention. 2

Respiratory Warning Signs

• Rapidly progressive weakness of respiratory muscles with severe dyspnea 1
• Shortness of breath with minimal exertion or at rest 4
• Declining pulmonary function parameters: negative inspiratory force (NIF) and vital capacity (VC) 4, 5
• Respiratory fatigue manifesting as inability to complete sentences or count to 20 in one breath 5

Bulbar Warning Signs

• Severe dysphagia with high aspiration risk 7
• Globus sensation with rapidly exhausting coughing and swallowing 1
• Progressive dysarthria and facial weakness 5
• Inability to manage secretions 1

Systemic Manifestations

• Flaccid tetraparesis with immobility developing within minutes to days 1
• Severe neck weakness preventing head elevation 5
• Inability to maintain upright posture 5

Acute Management Algorithm

Immediate Actions (First Minutes to Hours)

1. Secure vital functions and airway immediately 1

• Early intubation is essential to secure the airway in patients with bulbar symptoms and aspiration risk or respiratory insufficiency 1
• Do not delay intubation waiting for clinical deterioration—proactive airway management prevents complications 1, 3
• Admit to intensive care unit with neurological expertise for all patients with red flags or dynamic symptom deterioration 1

2. Identify and remove precipitating factors 2

• Aggressively treat respiratory infections with appropriate antibiotics (avoiding contraindicated agents) 1, 3
• Discontinue any medications that may worsen myasthenic weakness 4, 3
• Evaluate for sepsis, aspiration pneumonia, and other complications 1, 3

3. Obtain urgent neurology consultation 4

Acute Immunotherapy (First 24-48 Hours)

Plasmapheresis is the preferred first-line acute treatment for myasthenic crisis over intravenous immunoglobulin. 8, 2

• Plasma exchange should be initiated as the primary modality in the acute care setting based on superior efficacy and faster onset 8
• Clinical improvement can be achieved within a few days when plasmapheresis is used early 1
• Alternative option: Intravenous immunoglobulin (IVIG) at 2 g/kg administered over 5 days if plasmapheresis is contraindicated or unavailable 4
• Early use of immunotherapy may prevent intubation if initiated before complete respiratory decompensation 1

Immunosuppressive Therapy

• Initiate or optimize corticosteroids (prednisone 1-1.5 mg/kg orally daily) to support acute immunotherapy 4, 1, 8
• Begin or continue azathioprine as steroid-sparing immunosuppression 4, 1
• Caution: High-dose corticosteroid initiation may transiently worsen weakness; use with concurrent plasmapheresis or IVIG 3
• For refractory cases, consider rituximab as escalation therapy 1

Symptomatic Management

• Continue or initiate pyridostigmine (30-120 mg orally 3-4 times daily) or neostigmine for symptomatic benefit 1
• Note: Cholinesterase inhibitors provide only symptomatic relief and do not substitute for immunotherapy 1
• Some clinicians temporarily discontinue anticholinesterase medications during crisis to simplify management and avoid cholinergic side effects 3

Novel Therapies for Refractory Crisis

Efgartigimod (neonatal Fc receptor antagonist) shows promise as salvage therapy for refractory myasthenic crisis unresponsive to standard treatments. 9

• Case reports demonstrate remarkable improvement within days, allowing successful ventilator weaning in patients who failed plasmapheresis, IVIG, and high-dose corticosteroids 9
• Serial anti-acetylcholine receptor antibody titers decline in parallel with clinical improvement 9
• Consider for patients with persistent crisis despite aggressive conventional therapy 9

Supportive and Preventive Care

Respiratory Management

• Mechanical ventilation (invasive or non-invasive) as clinically indicated 2
• Serial monitoring of pulmonary function with NIF and vital capacity 4, 5
• Aggressive pulmonary toilet and secretion management 1
• Majority of patients can be weaned from mechanical ventilation within 1 month 2

Nutritional Support

• Supportive feeding via nasogastric or gastrostomy tube due to dysphagia and aspiration risk 1
• Maintain adequate nutrition and hydration throughout crisis 1

Complication Prevention and Management

• Early diagnosis and aggressive treatment of infections significantly influences outcomes 1
• Monitor for and manage delirium, which complicates ICU course 1
• Screen for concurrent myocarditis with troponin, ECG, and echocardiography if indicated 4, 7
• Evaluate for myositis with CPK and aldolase if respiratory insufficiency or elevated CPK present 4

Critical Pitfalls to Avoid

• Delayed intubation: Waiting for complete respiratory failure before securing airway increases morbidity 1, 3
• Failure to recognize bulbar dysfunction: Upper airway collapse and aspiration can be as life-threatening as respiratory muscle weakness 3, 2
• Inadequate immunotherapy: Symptomatic treatment with cholinesterase inhibitors alone is insufficient—aggressive immunotherapy is mandatory 1, 8
• Medication errors: Administering contraindicated drugs (beta-blockers, fluoroquinolones, aminoglycosides, macrolides, IV magnesium) can worsen crisis 4, 5
• Underestimating infection: Respiratory infections are the most common trigger and require prompt, appropriate treatment 3, 2

Prognosis and Long-Term Outcomes

• Outcomes of myasthenic crisis are generally favorable with appropriate management 2
• Mortality is driven primarily by age and medical comorbidities rather than the crisis itself 1, 2
• Myasthenic crisis does not appear to affect long-term prognosis—many patients eventually achieve good disease control 2
• Lifetime recurrence risk is approximately 30%, necessitating ongoing vigilance and optimized maintenance therapy 1