Myasthenic crisis (MC) is defined as respiratory failure caused by exacerbation of myasthenia gravis (MG) severe enough to necessitate intubation or noninvasive ventilation. [1-2] It occurs in 10–15% of MG patients at least once in their lifetime, with in-hospital mortality now approximately 5–12% with modern intensive care. [3-5]
The following NEJM treatment algorithm outlines the management approach for severe MG exacerbations:
1. History
- Onset and progression: Acute vs. subacute worsening of weakness; timeline from baseline to respiratory distress; prior episodes of crisis [7]
- Precipitating trigger: Recent infection (most common precipitant), surgery, medication changes, emotional stress, heat exposure, pregnancy/postpartum [1][8]
- Medication history: New medications started (antibiotics, cardiac drugs, immune checkpoint inhibitors); recent changes in pyridostigmine or immunosuppressant dosing; corticosteroid initiation or taper [8]
- Bulbar symptoms: Progressive dysphagia, dysarthria, nasal speech, choking on liquids — these often precede respiratory failure [8]
- Respiratory symptoms: Dyspnea on exertion → at rest, orthopnea, inability to count to 20 in a single breath, weak cough
- Known MG subtype: AChR-Ab positive, MuSK-Ab positive, seronegative; thymoma status; MGFA class at baseline [3]
2. Alarm Features
- Dyspnea with tachypnea, orthopnea, or paradoxical breathing [8]
- Use of accessory muscles for breathing
- Inability to clear secretions / choking on secretions [8]
- Rapidly progressive generalized weakness over hours to days
- Forced vital capacity (FVC) < 20 mL/kg or negative inspiratory force (NIF) weaker than −30 cmH₂O ("20/30 rule")
- Single-breath count < 20
- Declining tidal volumes with increasing tachypnea [2]
- Hypoxemia or hypercapnia (though ABG can be falsely reassuring early due to compensatory tachypnea) [6]
- New-onset bulbar weakness in a previously stable patient
3. Medications
Medications to AVOID in crisis: [1-2]
- Acetylcholinesterase inhibitors (pyridostigmine) — discontinue after intubation; they increase secretions and complicate airway management [2]
- Depolarizing paralytics (succinylcholine) — unpredictable response; MG patients are resistant to succinylcholine but sensitive to nondepolarizing agents [1]
- High-dose corticosteroids initially — can transiently worsen weakness in the first 1–2 weeks; if needed, start low and escalate [1][6]
Medications that exacerbate MG: [2][8-9]
- Antibiotics: fluoroquinolones, aminoglycosides, macrolides, telithromycin, tetracyclines
- Cardiovascular: beta-blockers, calcium channel blockers, procainamide, quinidine
- Other: IV magnesium, quinine, botulinum toxin, D-penicillamine, lithium, immune checkpoint inhibitors
- Use caution with: statins, iodinated contrast agents, sedatives
Crisis treatments: [6][9-10]
- IVIg: 2 g/kg total divided over 2–5 days
- Plasma exchange (PLEX): 5 sessions on alternate days, 1–1.5 plasma volumes per exchange
- These are equally effective overall; PLEX may have a slightly faster onset of action [2][11]
4. Diet
- NPO if significant bulbar weakness — aspiration risk is high with dysphagia
- Soft/pureed diet or thickened liquids if mild bulbar symptoms and patient is not in frank crisis
- Adequate hydration; avoid oral magnesium supplements
- Long-term: weight management is important, as obesity worsens respiratory mechanics in patients with diaphragmatic weakness [9]
5. Review of Systems
- Neurologic: Ptosis, diplopia, facial weakness, head drop, limb weakness (proximal > distal), fatigability with repetitive use [7]
- Respiratory: Dyspnea, orthopnea, weak cough, inability to clear secretions
- Bulbar: Dysarthria, dysphagia, nasal regurgitation, drooling
- Autonomic: Typically normal in MG (autonomic dysfunction suggests Lambert-Eaton or botulism) [1]
- Infectious: Fever, cough, URI/UTI symptoms — infection is the #1 trigger for crisis [1][12]
- Cardiac: Chest pain, palpitations — especially if ICI-related MG (overlap with myocarditis) [13]
6. Collateral History and Family History
- Confirm baseline functional status and MGFA class from neurology records
- Medication compliance and recent changes to immunosuppression
- Prior crisis episodes and what treatments were effective [3]
- Family history of autoimmune disease (thyroid disease, rheumatoid arthritis, SLE)
- Social context: access to medications, caregiver support, ability to recognize worsening symptoms
7. Risk Factors
- MuSK antibody-positive disease [3][8]
- Thymoma-associated MG [3]
- AChR-Ab positive late-onset MG [8]
- Infection — most common precipitant, especially respiratory infections [1][12]
- Recent surgery (including thymectomy) [8]
- Initiation or rapid taper of corticosteroids [8]
- Contraindicated medication exposure [8]
- Older age, multiple comorbidities (>3 comorbidities associated with prolonged ventilation and higher mortality) [5]
- Previous myasthenic crisis (strongest predictor of future crisis) [3]
- Pregnancy/postpartum [8]
- Summer months (possibly heat-related) [3]
8. Differential Diagnosis
- Cholinergic crisis: Excess acetylcholinesterase inhibitor causing depolarization block — distinguished by cholinergic symptoms: hypersalivation, lacrimation, miosis, sweating, diarrhea, bradycardia [7]
- Lambert-Eaton myasthenic syndrome (LEMS): Proximal leg weakness predominates, areflexia, autonomic dysfunction (dry mouth, erectile dysfunction); weakness improves with repeated use (opposite of MG); associated with SCLC [8][14]
- Botulism: Descending paralysis, dilated pupils, autonomic dysfunction, no sensory loss
- Guillain-Barré syndrome (GBS): Ascending weakness, areflexia, albuminocytologic dissociation in CSF; Miller Fisher variant can mimic MG with ophthalmoplegia [13]
- Acute stroke (brainstem): Bulbar symptoms but typically with other cranial nerve or long tract signs
- ALS: Progressive weakness but with upper and lower motor neuron signs, fasciculations
- Organophosphate poisoning: Cholinergic toxidrome
Key distinguishing features of MG crisis: Normal reflexes, normal sensation, no autonomic dysfunction, no fasciculations, weakness worsens with repetitive motion [1]
9. Past Medical History
- Duration and subtype of MG; antibody status (AChR, MuSK, LRP4)
- Thymoma or prior thymectomy [3]
- Previous crises — number, triggers, treatments used, response
- Current immunosuppressive regimen and compliance
- Comorbidities: COPD, OSA, cardiac disease (increase risk of prolonged ventilation) [5]
- Surgical history (anesthesia complications)
- Other autoimmune conditions (thyroid disease common)
10. Physical Exam
Vital signs
- Tachypnea, tachycardia, oxygen desaturation (late finding)
- Paradoxical abdominal breathing (diaphragmatic weakness)
Focused exam
- Eyes: Ptosis (worsens with sustained upgaze >60 sec), diplopia, Cogan lid twitch sign [7]
- Face: Flattened nasolabial folds, snarling smile, weak eye closure
- Bulbar: Nasal speech, pooling of secretions, weak palate elevation, weak tongue
- Neck: Head drop (neck flexor weakness)
- Limbs: Proximal > distal weakness; fatigable — test with repetitive shoulder abduction or sustained arm elevation [7]
- Respiratory: Accessory muscle use, weak cough, inability to count to 20 in one breath
- Reflexes: Normal (distinguishes from GBS and LEMS) [1]
- Sensation: Normal [1]
11. Lab Studies
- ABG/VBG: Assess for hypercapnia and hypoxemia (may be normal early) [6]
- CBC, CMP: Baseline; evaluate for infection, electrolyte abnormalities
- Magnesium level: Hypermagnesemia worsens NMJ transmission
- AChR antibodies, MuSK antibodies: If not previously tested (not needed acutely for diagnosis) [13]
- Anti-striational antibodies: If thymoma suspected
- CK, troponin, aldolase: Rule out concurrent myositis/myocarditis (especially if ICI-related) [13]
- Thyroid function: Autoimmune thyroid disease is a common comorbidity
- Blood cultures, UA, CXR: Evaluate for infectious trigger [1]
- Procalcitonin/CRP: If infection suspected
12. Imaging
- Chest X-ray: Evaluate for pneumonia (common trigger), atelectasis (predictor of reintubation), thymoma [2]
- CT chest with contrast: If thymoma not previously evaluated or recurrence suspected
- CT/MRI brain: Only if atypical features suggest stroke or CNS pathology [13]
- Imaging is not required for the diagnosis of myasthenic crisis itself — it is a clinical diagnosis [1]
13. Special Tests
- Bedside pulmonary function:
- Forced vital capacity (FVC): Serial measurements; FVC < 20 mL/kg or < 1 L suggests impending respiratory failure
- Negative inspiratory force (NIF): Weaker than −30 cmH₂O is concerning
- Single-breath count: < 20 suggests significant respiratory compromise
- Ice pack test: Place ice on closed eyelid for 2 min; improvement in ptosis supports MG (useful bedside test)
- EMG/NCS with repetitive nerve stimulation: Decremental response at 3 Hz (>10% decrement); not typically performed in acute crisis but useful for diagnosis [13]
- Single-fiber EMG: Most sensitive test for NMJ dysfunction; increased jitter and blocking [13]
- Edrophonium (Tensilon) test: Avoid in crisis — risk of cholinergic crisis and cardiac arrhythmia [1]
14. ECG
- Obtain ECG in all patients presenting with myasthenic crisis [13]
- Rule out myocarditis (especially ICI-related MG — the "3 M's": myasthenia, myositis, myocarditis) [13]
- Look for: conduction abnormalities, heart block, ST changes, arrhythmias
- Prolonged QT can occur with electrolyte abnormalities or medications
- Baseline ECG important before initiating PLEX (hemodynamic shifts) or IVIg
15. Assessment
Myasthenic crisis is a clinical diagnosis defined by MG-related weakness causing respiratory failure requiring ventilatory support. [1-2] Key clinical pearls:
- Infection is the most common trigger — always search for and treat aggressively [1]
- Deterioration can be rapid and unpredictable due to myasthenic fatigability; vital capacity and ABG may be falsely reassuring [6]
- Crisis can be the first presentation of MG in previously undiagnosed patients [8]
- Distinguish from cholinergic crisis (excess pyridostigmine): look for SLUDGE symptoms [7]
- Severity stratification: MGFA Class V = myasthenic crisis; Classes IVa/IVb = impending crisis
- Complications: aspiration pneumonia, prolonged ventilation (median 12 days), atelectasis, sepsis, DVT/PE [5]
16. Treatment Plan
Initial stabilization (ED)
- Airway: Assess respiratory function immediately with bedside FVC and NIF
- BiPAP/NIPPV: Can be trialed first, even in patients with bulbar weakness; successful in ~38% of cases and reduces ICU stay [2][5]
- Intubation: If FVC < 20 mL/kg, NIF weaker than −30 cmH₂O, hypercapnia (pCO₂ > 50 mmHg), or inability to protect airway [2]
- Avoid succinylcholinereduced dose of nondepolarizing agent[1]
- Discontinue pyridostigmine after intubation [2]
Definitive immunotherapy: [6][9-10]
- Plasma exchange: 5 sessions on alternate days — may have slightly faster onset; preferred by some experts for crisis [2][11]
- IVIg: 2 g/kg divided over 2–5 days — equally effective overall; more convenient, fewer access complications [6][10]
- These can be given sequentially if one fails [9]
Adjunctive therapy
- Treat the precipitating trigger (antibiotics for infection — avoid contraindicated classes)
- Corticosteroids: Use cautiously; start low dose and escalate slowly to avoid transient worsening; or use IV methylprednisolone 1–2 mg/kg/day in severe cases already on ventilatory support [9][13]
- Optimize long-term immunosuppression (azathioprine, mycophenolate) once stabilized
- DVT prophylaxis, stress ulcer prophylaxis, early mobilization
17. Disposition
ICU admission criteria: [5-6]
- Any patient requiring intubation or NIPPV
- FVC < 20 mL/kg or rapidly declining
- Significant bulbar weakness with aspiration risk
- The threshold for ICU admission should be low — deterioration can be rapid and unexpected [6]
Observation/step-down
Discharge criteria
- Stable respiratory function off ventilatory support
- Tolerating oral medications and diet
- Precipitating trigger treated
- Immunosuppressive regimen optimized
- Neurology follow-up arranged
Specialist consultation triggers
- Neurology: All patients with suspected or confirmed myasthenic crisis
- Pulmonology/Critical Care: For ventilator management
- Cardiology: If concern for concurrent myocarditis (especially ICI-related)
18. Follow Up / Return Precautions
- Neurology follow-up within 1–2 weeks of discharge
- Serial FVC monitoring as outpatient if borderline respiratory function
- Medication reconciliation — ensure no contraindicated drugs prescribed
- Return immediately for: worsening shortness of breath, difficulty swallowing, choking, new or worsening weakness, inability to hold head up, weak voice
- Patient and family education on:
- Recognizing early signs of exacerbation (increasing ptosis, dysphagia, dyspnea)
- Medication adherence and avoiding triggers
- Carrying a medical alert card listing contraindicated medications
- Vaccination — influenza and pneumococcal vaccines reduce infection-triggered exacerbations (vaccine-preventable infections are a major cause of crisis) [15]
- Expected recovery: crisis is a reversible condition; with proper treatment, most patients return to pre-crisis baseline, though recovery may take weeks [3][9]
References
1. Myasthenia Gravis and Crisis: Evaluation and Management in the Emergency Department. — Roper J, Fleming ME, Long B, Koyfman A. The Journal of Emergency Medicine. 2017.
2. Autoimmune Myasthenia Gravis: Emerging Clinical and Biological Heterogeneity. — Meriggioli MN, Sanders DB. The Lancet. Neurology. 2009.
3. Occurrence and Severity of Myasthenic Crisis in an Unselected Turkish Cohort of Patients With Myasthenia Gravis. — Ozyurt Kose S, Nazli E, Tutkavul K, Gilhus NE. Frontiers in Neurology. 2023.
4. Outcomes of Myasthenia Gravis Patients Admitted to the Intensive Care Unit: Experience From a Tertiary Care Center in Saudi Arabia. — Attar A, Alshaikh H, Alharbi G, et al. PloS One. 2024.
5. Myasthenic Crisis Demanding Mechanical Ventilation: A Multicenter Analysis of 250 Cases. — Neumann B, Angstwurm K, Mergenthaler P, et al. Neurology. 2020.
6. Myasthenia Gravis. — Gilhus NE. The New England Journal of Medicine. 2016.
7. Myasthenia Gravis. — Vincent A, Palace J, Hilton-Jones D. Lancet. 2001.
8. Epidemiology, Diagnostics, and Biomarkers of Autoimmune Neuromuscular Junction Disorders. — Punga AR, Maddison P, Heckmann JM, Guptill JT, Evoli A. The Lancet. Neurology. 2022.
9. Myasthenia Gravis: Subgroup Classification and Therapeutic Strategies. — Gilhus NE, Verschuuren JJ. The Lancet. Neurology. 2015.
10. Advances and Ongoing Research in the Treatment of Autoimmune Neuromuscular Junction Disorders. — Verschuuren JJ, Palace J, Murai H, et al. The Lancet. Neurology. 2022.
11. Plasma Exchange Versus Intravenous Immunoglobulin in AChR Subtype Myasthenic Crisis: A Prospective Cohort Study. — Wang Y, Huan X, Jiao K, et al. Clinical Immunology. 2022.
12. Patients With Myasthenia Gravis With Acute Onset of Dyspnea: Predictors of Progression to Myasthenic Crisis and Prognosis. — Huang Y, Tan Y, Shi J, et al. Frontiers in Neurology. 2021.
13. Management of Immune Checkpoint Inhibitor-Related Toxicities. — Updated 2025-10-23. National Comprehensive Cancer Network.
14. Lambert-Eaton Myasthenic Syndrome: From Clinical Characteristics to Therapeutic Strategies. — Titulaer MJ, Lang B, Verschuuren JJ. The Lancet. Neurology. 2011.
15. Factors associated with acute exacerbations of myasthenia gravis. — Gummi RR, Kukulka NA, Deroche CB, Govindarajan R. Muscle & Nerve. 2019.