Quick Recap
Neurology System, Protocol 9/12. Contrasts directly with Guillain-Barré Syndrome (prior protocol) — fluctuating/fatigable weakness pattern, and NIV trial is more often appropriate here.
1. Definition
Myasthenia gravis (MG) = autoimmune disease with antibodies against neuromuscular junction components, impairing neuromuscular transmission. ~85% have anti-acetylcholine receptor ("binding") antibodies; the remaining ~15% target muscle-specific kinase (MuSK) or are seronegative. Fatigable weakness is the clinical hallmark — worsens with sustained/repetitive effort, improves with rest, and fluctuates through the day (classically worse in the evening).
Distribution: can be purely ocular (ptosis, ophthalmoparesis, diplopia) or generalized, involving bulbar muscles (facial weakness, dysarthria, dysphagia), neck, and limb muscles — classically, upper limb weakness is worse than lower limb, with preferential weakness of forearm/finger extensors.
Myasthenic crisis = neuromuscular respiratory failure (NMRF) from diaphragm/respiratory muscle weakness in an MG patient — a neurologic emergency, occurring in ~20% of MG patients over the disease course.
2. Precipitants of Myasthenic Crisis
Medication noncompliance or inappropriate weaning of MG therapy, infection, surgery, and certain medications with theoretical risk of worsening MG control (review before use in known/suspected MG patients — includes some antibiotic classes and other agents; the diagnosis of MG does NOT preclude use of a strongly indicated antibiotic, but awareness of the theoretical risk should inform monitoring). Transient MG worsening can occur when patients are acutely started on high-dose steroids (typically >20mg/day) — an important, counterintuitive pitfall: the very treatment intended to help MG can transiently worsen it before benefit appears, so initiating high-dose steroids in a borderline-stable MG patient requires close respiratory monitoring in anticipation of this dip.
3. Diagnosis
MG is primarily a CLINICAL diagnosis, supported by: EMG showing decrement on repetitive nerve stimulation (standard EMG is usually normal, an important contrast with GBS/myopathy patterns), acetylcholine receptor and MuSK antibody testing, and clinical response to acetylcholinesterase inhibitor trial (edrophonium/Tensilon test, less commonly used now) or ice-pack test for ptosis.
4. Immediate Stabilization (ABCDE) — The NIV Decision Point (Contrast with GBS)
Airway/Breathing:
- A trial of NIV (BiPAP) is a reasonable initial approach in myasthenic crisis specifically — CAN often be employed successfully, PROVIDED mental status, physical ability to remove the mask, and airway/bulbar reflexes are preserved
- This differs meaningfully from GBS, where a patient still progressing toward nadir is unlikely to be rescued by NIV and early/prophylactic intubation is favored instead — myasthenic crisis's fluctuating, potentially rapidly-reversible-with-treatment nature makes an NIV trial more often appropriate
- If the patient has significant bulbar weakness (poor secretion handling, aspiration risk) or altered mental status, NIV is less appropriate and intubation should proceed
AVOID neuromuscular blocking agents where possible:
- Nondepolarizing NMBAs can cause PROLONGED paralysis in MG patients — these patients are at high risk of "myosin loss myopathy" (a form of critical illness myopathy), which can result in prolonged weakness and NMRF extending well beyond the expected drug half-life
- Paralytic agents should be avoided in sick MG patients generally given this heightened vulnerability, not just at the moment of intubation
Checklist:
5. Evidence-Based Treatment
Acute crisis treatment (analogous to GBS in modality, distinct in some specifics):
- IVIG or plasma exchange (PLEX) — mainstay of acute crisis management, similar dosing principles to GBS (IVIG ~2g/kg divided over several days; PLEX as a multi-exchange course)
- Corticosteroids: unlike GBS (where steroids have NO role), corticosteroids DO have a role in MG overall disease management — but as noted in Section 2, acute high-dose initiation can transiently WORSEN weakness before benefit appears, so timing/monitoring matters
- Newer targeted therapy — Efgartigimod: works by reducing IgG levels (including pathogenic antibodies), given in cycles of 4 weekly infusions of 10mg/kg — represents an evolving treatment option beyond traditional IVIG/PLEX/steroids for refractory or recurrent cases
- Address any infectious or metabolic trigger contributing to the exacerbation as part of treatment, not just immunomodulation — crisis is often precipitated by a treatable secondary process
6. Differential Diagnosis (see also GBS protocol Section 3 comparison table)
Distinguish from GBS (absent reflexes, ASCENDING weakness pattern, elevated CSF protein), ALS (chronic course, eye-sparing until late, hyperreflexia), immune myopathies (proximal > distal, oculobulbar relatively spared), and botulism (DESCENDING weakness, autonomic symptoms, more common in children) using the pattern-recognition table established in the GBS protocol. The key distinguishing feature of MG is fluctuating/fatigable weakness with a positive repetitive nerve stimulation decrement, as opposed to the fixed or progressive weakness patterns of these mimics.
7. Organ Support
Mechanical ventilation (NIV trial where appropriate, per Section 4) or invasive ventilation for bulbar-compromised/altered-mental-status patients; nutrition with careful swallow assessment given bulbar involvement; avoid neuromuscular blockade; standard ICU supportive care.
8. Consultation Matrix
Consultation | Trigger | Timing |
Neurology | All myasthenic crisis presentations | Immediate |
Neurocritical Care / ICU | Respiratory failure requiring ventilatory support | Immediate |
Infectious Disease | Infectious precipitant requiring targeted treatment | As needed |
Palliative Care | Symptom management, goals-of-care support | As needed |
9. Monitoring Framework
Serial bulbar/respiratory strength assessment (vital capacity, NIF trending), continuous monitoring during NIV trial for signs of failure (rising work of breathing, declining mental status, poor secretion clearance) with a LOW threshold to convert to invasive ventilation rather than persisting with a failing NIV trial, watch for medication-related theoretical MG-worsening triggers if new drugs are introduced during the admission.
10. Complications
Respiratory failure, aspiration (bulbar weakness), prolonged paralysis/myosin loss myopathy if NMBAs used, NIV failure requiring escalation to invasive ventilation, medication-precipitated worsening (steroid-initiation dip, offending antibiotic exposure). Prevention: avoid NMBAs where feasible, careful medication review, close monitoring during high-dose steroid initiation. Rescue: escalate promptly from NIV to invasive ventilation if failing rather than persisting; standard ICU respiratory support.
11. Escalation & De-escalation
Escalate: NIV trial failing (rising work of breathing, bulbar compromise, declining mental status) -> invasive ventilation without delay.
De-escalate: crisis resolving with IVIG/PLEX response and precipitant treated -> wean ventilatory support, resume/optimize home MG regimen (pyridostigmine, chronic immunosuppression), transition to standard ward-level monitoring.
12. ICU Discharge Criteria
Respiratory status stable off acute ventilatory support (or on a defined weaning trajectory), precipitant identified and treated, home MG regimen optimized, follow-up with neurology arranged, patient/family educated on crisis warning signs and trigger avoidance (including the theoretical medication risk list).
13. Documentation & Medicolegal Checklist
14. Key Guidelines
Hehir MK 2nd, Li Y. Diagnosis and management of myasthenia gravis. Continuum (Minneap Minn). 2022;28(6):1615-1642 — primary contemporary reference.
15. Landmark Evidence
Seneviratne J, Mandrekar J, Wijdicks EF, Rabinstein AA. Noninvasive ventilation in myasthenic crisis. Arch Neurol. 2008;65(1):54-58 — evidence base supporting the NIV-trial-appropriate approach specific to myasthenic crisis, contrasting with GBS.
16. Controversies
The precise threshold for attempting NIV vs proceeding directly to intubation in myasthenic crisis is judgment-based (mental status, bulbar function, airway reflex preservation) rather than a single validated score, unlike the more codified EGRIS approach in GBS. The role and optimal timing of newer agents like efgartigimod relative to traditional IVIG/PLEX in acute crisis (versus their established role in chronic disease management) is still being defined as real-world experience accumulates.
17. References
- Neuromuscular Respiratory Failure / Myasthenia Gravis chapter. Washington Manual of Critical Care, 4th ed, 2025 (Ch. 62).
- Hehir MK 2nd, Li Y. Diagnosis and management of myasthenia gravis. Continuum (Minneap Minn). 2022;28(6):1615-1642.
- Seneviratne J, Mandrekar J, Wijdicks EF, Rabinstein AA. Noninvasive ventilation in myasthenic crisis. Arch Neurol. 2008;65(1):54-58.
- Silvestri NJ. A symptoms and signs approach to the patient with neuromuscular weakness. Continuum (Minneap Minn). 2022;28(6):1580-1595.
- Bucelli R, Harms MB. Neuromuscular emergencies. Semin Neurol. 2015;35(6):683-689.
See also: Guillain-Barré Syndrome (Neurology System) for the contrasting ascending, non-fluctuating neuromuscular respiratory failure pattern and the differential diagnosis table shared between both protocols.