What are the symptoms and treatment of myasthenia crisis?

Myasthenic Crisis: Symptoms and Treatment

Definition and Clinical Presentation

Myasthenic crisis is a life-threatening emergency characterized by rapidly progressive respiratory failure requiring mechanical ventilation, resulting from severe weakness of respiratory and bulbar muscles. 1, 2

Cardinal Symptoms

Respiratory Manifestations:

• Respiratory insufficiency or failure is the defining feature, necessitating invasive or non-invasive ventilation 2, 3
• Weakness of respiratory muscles leading to reduced tidal volumes and inadequate spontaneous respiratory effort 3, 4
• Severe dyspnea that progresses rapidly, often within minutes to days 1
• Inability to maintain adequate ventilation despite maximal effort 4

Bulbar Manifestations:

• Upper airway collapse from severe bulbar muscle weakness 2
• Dysphagia (difficulty swallowing) leading to aspiration risk 1, 3
• Dysarthria (slurred speech) 5
• Globus events with life-threatening, rapidly exhausting coughing and swallowing difficulties 1
• Facial muscle weakness 5, 6

Generalized Weakness:

• Flaccid tetraparesis with complete immobility 1
• Severe proximal muscle weakness affecting limbs and trunk 5, 6
• Neck weakness preventing head support 6

Key Clinical Characteristics

• Rapid progression: Weakness develops within minutes to days, distinguishing crisis from stable disease 1
• Fatigability: Symptoms worsen with continued activity 6
• Bilateral but potentially asymmetric presentation 6

Epidemiology and Risk Factors

• Occurs in 15-20% of patients with myasthenia gravis during their lifetime 1, 2
• Most commonly occurs within the first 2-3 years of disease diagnosis 1, 2
• Up to 20% of patients present with crisis as the first manifestation of previously undiagnosed myasthenia gravis 1, 4
• Lifetime recurrence risk is approximately 30% 1

Common Precipitating Factors:

• Respiratory infections (most common trigger) 2, 3
• Aspiration and sepsis 3
• Surgical procedures 3
• Rapid tapering of immunosuppression 3
• Initiation of corticosteroid therapy 3
• Medications that worsen myasthenia: β-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolides 7, 8, 6
• 30-40% of crises have no identifiable trigger 2

Diagnostic Workup

Immediate Assessment:

• Check and secure vital functions immediately 1
• Pulmonary function testing with negative inspiratory force (NIF) and vital capacity (VC) to quantify respiratory compromise 7, 5
• Neurology consultation 7

Confirmatory Testing:

• Acetylcholine receptor (AChR) antibodies in blood (positive in nearly all generalized MG) 7, 5, 6
• If AChR negative, test for muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4) antibodies 7, 5
• Anti-striated muscle antibodies 7

Electrodiagnostic Studies:

• Repetitive nerve stimulation showing decremental response of compound muscle action potential 4
• Single-fiber EMG with jitter studies (>90% sensitivity in generalized MG) 5
• Nerve conduction studies to exclude neuropathy 7
• Needle EMG to evaluate for concurrent myositis 7

Evaluate for Complications:

• Creatine phosphokinase (CPK), aldolase, ESR, CRP to assess for concurrent myositis 7
• If respiratory insufficiency or elevated CPK/troponin T: Perform ECG and transthoracic echocardiogram to rule out myocarditis 7
• MRI of brain/spine if indicated to exclude CNS involvement 7

Treatment Algorithm

Immediate Management (All Grades 3-4)

Airway and Respiratory Support:

• Early intubation is essential to secure the airway due to bulbar symptoms with aspiration and/or respiratory insufficiency 1
• Admit to intensive care unit with capability for mechanical ventilation 7, 1
• Frequent pulmonary function monitoring (NIF/VC assessments) 7
• Do not delay intubation—early intervention may prevent prolonged ventilation 1

Immunotherapy (Primary Treatment):

• Plasmapheresis is preferred over IVIG as first-line treatment for myasthenic crisis 2, 9
• Plasmapheresis: 5 daily sessions 7, 9
• Alternative: IVIG 2 g/kg IV over 5 days (0.4 g/kg/day) if plasmapheresis unavailable 7
• Median duration of mechanical ventilation is 12-14 days under adequate treatment 1

Corticosteroid Therapy:

• Continue or initiate corticosteroids (methylprednisolone 1-2 mg/kg daily or prednisone 1-1.5 mg/kg daily) 7
• Wean based on symptom improvement 7
• May use pulse dosing: methylprednisolone 1 g/day for 5 days for severe cases 7

Anticholinesterase Therapy:

• Pyridostigmine starting at 30 mg orally three times daily, gradually increasing to maximum 120 mg four times daily as tolerated 7, 5
• Alternative: Neostigmine for acute symptomatic treatment 1
• Note: Approximately 50% of patients may show minimal response to anticholinesterase therapy alone 5, 8

Monitoring Requirements

• Daily neurologic evaluation 7
• Frequent pulmonary function assessment throughout crisis 7
• Monitor for autonomic dysfunction 7
• Assess for complications: infections, delirium, aspiration pneumonia 1

Discontinuation of Immune Checkpoint Inhibitors (if applicable)

• Permanently discontinue immune checkpoint inhibitors for Grade 3-4 myasthenia gravis 7

Long-term Immunosuppression

• Initiate or optimize immunosuppression with corticosteroids and azathioprine during crisis management 1
• For refractory cases: Consider rituximab for escalation 1
• Evaluate for thymectomy if appropriate (indicated in all thymoma cases) 5

Critical Medications to Avoid

The following medications can precipitate or worsen myasthenic crisis and must be avoided: 7, 8, 6

• β-blockers
• IV magnesium
• Fluoroquinolones
• Aminoglycosides
• Macrolide antibiotics

Prognosis

• Current mortality rate is less than 5% in the United States, dramatically improved from historical 75% 2, 3
• Approximately 80% of patients are weaned from ventilation within 1 month 1
• Deaths are almost never from the crisis itself but from comorbidities and complications 1, 2
• Myasthenic crisis does not appear to affect long-term prognosis—many patients achieve good disease control afterward 2
• 20% remain mechanically ventilated after 1 month, often due to complications 1

Common Pitfalls

• Delaying intubation: Early airway protection is critical—do not wait for complete respiratory failure 1
• Missing the diagnosis: Consider myasthenic crisis in any patient with acute respiratory failure without underlying pulmonary disease 4
• Administering contraindicated medications: Always review medication lists for drugs that worsen myasthenia 7
• Inadequate monitoring: Failure to perform frequent pulmonary function assessments can miss deterioration 7
• Not identifying triggers: Aggressively treat infections and remove precipitating factors 1, 2