Myasthenic Crisis
Myasthenia gravis exacerbation with respiratory failure requiring intubation. Triggered by infection, surgery, medication changes, or drug interactions. Same respiratory monitoring as GBS -FVC < 20 → intubate. Know the drugs that worsen MG.
🔍 Overview
Myasthenia Gravis -Key Concepts
- Autoantibodies against AChR (acetylcholine receptor) at the neuromuscular junction → fatigable weakness
- Fatigable: weakness worsens with repeated use and improves with rest. Worse at end of day.
- Ocular symptoms (#1 presenting symptom): ptosis, diplopia -often asymmetric
- Generalized MG: proximal limb weakness, bulbar symptoms (dysphagia, dysarthria, nasal voice), respiratory failure
- Anti-AChR antibodies positive in ~85% of generalized MG. Anti-MuSK antibodies in ~5–8% (more bulbar involvement, worse prognosis).
- CT chest for thymoma -present in ~15% of MG patients. Thymectomy recommended for thymoma and for non-thymomatous generalized AChR+ MG age 18–65.
Drugs That Worsen MG -MUST KNOW
These drugs can precipitate myasthenic crisis. Avoid in all MG patients:
| Drug Class | Specific Agents |
|---|---|
| Antibiotics | Aminoglycosides (gentamicin, tobramycin), fluoroquinolones, macrolides (azithromycin -controversial), tetracyclines |
| Cardiac | Beta-blockers, calcium channel blockers, procainamide, quinidine |
| Neuromuscular blockers | Avoid succinylcholine (unpredictable response). Use non-depolarizing agents with caution (increased sensitivity → prolonged paralysis). |
| Other | Magnesium (blocks NMJ -avoid IV Mg unless life-threatening indication), D-penicillamine, checkpoint inhibitors, botulinum toxin, lithium |
Myasthenic Crisis vs Cholinergic Crisis
| Feature | Myasthenic Crisis | Cholinergic Crisis |
|---|---|---|
| Cause | Disease exacerbation (undertreated) | Pyridostigmine overdose |
| Pupils | Normal or dilated | Miosis (constricted) |
| Secretions | Normal | Excessive (SLUDGE: salivation, lacrimation, urination, diarrhea, GI cramping, emesis) |
| Fasciculations | Absent | Present |
| Response to edrophonium | Improves | Worsens |
| Treatment | IVIG or PLEX + immunosuppression | Hold pyridostigmine, atropine for secretions |
🚨 Management
Myasthenic Crisis Treatment
Respiratory
FVC + NIF q4–6h. Same 20/30/40 rule as GBS. Intubate if FVC < 20 mL/kg or NIF < −30. Avoid succinylcholine and minimize non-depolarizing agents. BiPAP can bridge but do NOT delay intubation if deteriorating.
Rapid immunotherapy
IVIG 0.4 g/kg/day × 5 days OR plasmapheresis × 5 exchanges. Both equally effective. PLEX onset is faster (~24–48h) vs IVIG (3–5 days). Choose based on availability and access.
Steroids
Start high-dose steroids (prednisone 1 mg/kg/day or methylprednisolone 1g IV × 3–5 days). Warning: steroids can cause transient worsening in the first 1–2 weeks → always start WITH IVIG/PLEX, not alone in crisis.
Cholinesterase inhibitor
Hold pyridostigmine during crisis (increased secretions worsen respiratory status, and it may contribute to cholinergic crisis). Resume when improving and extubated.
Trigger
Identify and treat the trigger: infection (#1 -pneumonia, UTI), medication change, surgery, emotional stress. Review medication list for MG-exacerbating drugs.
Chronic MG Management
| Drug | Role | Notes |
|---|---|---|
| Pyridostigmine (Mestinon) SYMPTOMATIC | AChE inhibitor -increases ACh at NMJ | First-line symptomatic treatment. 60 mg PO TID, titrate. Does NOT alter disease course -only improves symptoms. |
| Prednisone (Deltasone) | Immunosuppression | Most patients need immunosuppression beyond pyridostigmine. Start low, escalate slowly (risk of initial worsening). |
| Azathioprine (Imuran) | Steroid-sparing agent | Takes 6–12 months to work. Check TPMT before starting (deficiency → myelosuppression). |
| Mycophenolate (CellCept) | Steroid-sparing agent | Alternative to azathioprine. Common choice. Teratogenic. |
| Rituximab (Rituxan) | Anti-CD20 -refractory MG | Especially effective in anti-MuSK MG. Growing evidence for AChR+ refractory disease. |
| Efgartigimod (Vyvgart) | FcRn inhibitor -reduces pathogenic IgG | ADAPT, 2021: improved MG-ADL by ≥ 2 points in 67.7% vs 29.7% placebo. IV infusion cycles. |
| Thymectomy | Surgical -removes pathogenic antigen source | Indicated if thymoma. Also beneficial in AChR+ non-thymomatous MG < 65 yrs (MGTX, 2016). Response takes months. |
🧪 Workup
Workup
- AChR Ab (~85%)
- MuSK Ab if AChR neg
- CT chest -thymoma
- PFTs (FVC, NIF)
- Ice pack test -ptosis improvement
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Pyridostigmine | 60mg q4-6h | PO | AChE inhibitor |
| Prednisone | Start low, titrate | PO | Can worsen MG initially |
| Azathioprine | 2-3mg/kg/day | PO | Steroid-sparing |
| IVIG | 0.4g/kg×5d | IV | Crisis |
| Rituximab | 375mg/m² | IV | Refractory |
📋 On Rounds
Why should you avoid IV magnesium in myasthenia gravis?
Magnesium acts as a calcium channel blocker at the neuromuscular junction -it inhibits presynaptic calcium-dependent acetylcholine release and reduces postsynaptic sensitivity to ACh. In a patient with MG (where ACh receptor density is already reduced by autoantibodies), adding magnesium further impairs neuromuscular transmission → can precipitate myasthenic crisis and respiratory failure.
What medications are contraindicated in myasthenia gravis and why?
Several common medications can precipitate or worsen myasthenic crisis by impairing neuromuscular transmission: (1) Aminoglycosides (gentamicin, tobramycin) -block presynaptic Ca²⁺ channels → reduced ACh release. (2) Fluoroquinolones -same mechanism, plus direct NMJ blockade. (3) Beta-blockers -impair NMJ safety factor. (4) Magnesium -blocks presynaptic Ca²⁺ channels (don't aggressively replete Mg in MG patients).
What is cholinergic crisis and how do you differentiate it from myasthenic crisis?
Both present with weakness and respiratory failure, but the mechanism is opposite. Myasthenic crisis: under-treated MG → insufficient ACh at NMJ → weakness. Pupils: normal or dilated. Secretions: dry. Responds to: edrophonium/neostigmine (improves). Cholinergic crisis: over-treated with pyridostigmine → excess ACh → depolarization block + muscarinic effects. Pupils: miotic (small).
How do you differentiate MG from Lambert-Eaton syndrome?
MG: autoantibodies against post-synaptic AChR → fatigable weakness that WORSENS with repetitive use, proximal > distal, bulbar symptoms (ptosis, diplopia, dysphagia) prominent, reflexes normal. EMG: decremental response on repetitive nerve stimulation. Lambert-Eaton (LEMS): autoantibodies against pre-synaptic voltage-gated calcium channels (P/Q type)
Clinical Examples
📋 Case 1, Myasthenic Crisis
Patient: 58F with known AChR Ab+ MG on pyridostigmine 60 mg QID. Admitted with worsening dyspnea and dysphagia after UTI (treated with ciprofloxacin). FVC 14 mL/kg (declining). Bilateral ptosis, weak neck flexion, nasal speech.
Key findings: Myasthenic crisis: respiratory failure from MG exacerbation. Triggered by UTI (infection is #1 precipitant) + ciprofloxacin (fluoroquinolones worsen NMJ transmission). FVC < 20 = intubation threshold.
Management:
- ICU admission, check FVC q4h (same monitoring protocol as GBS)
- IVIG 0.4 g/kg/day × 5 days OR PLEX q other day × 5 sessions (both equally effective)
- STOP ciprofloxacin, switch to a non-NMJ-affecting antibiotic (ceftriaxone, TMP-SMX)
- HOLD pyridostigmine during crisis (excess secretions complicate airway management)
- Intubate if FVC < 15 mL/kg, declining rapidly, or unable to handle secretions, use non-depolarizing NMB (avoid succinylcholine, MG patients are resistant)
Teaching point: The most common trigger for myasthenic crisis is infection, not medication non-compliance. Always review the med list, fluoroquinolones, aminoglycosides, beta-blockers, and magnesium can precipitate crisis. The MG medication "hit list" should be at every bedside.
📋 Case 2, New Diagnosis of MG with Thymoma
Patient: 45M with 3 months of fluctuating diplopia, ptosis (worse in evening), difficulty chewing steak. Ice pack test: ptosis improves bilaterally. AChR antibodies positive. CT chest: anterior mediastinal mass 4 cm.
Key findings: New MG with thymoma, ~15% of MG patients have thymoma, and ~30% of thymoma patients develop MG. Thymectomy is indicated for ALL thymomas regardless of MG severity, plus for non-thymomatous MG per MGTX trial.
Management:
- Start pyridostigmine 60 mg PO TID (symptomatic relief, first-line)
- CT-guided biopsy of mediastinal mass → staging
- Thymectomy: robotic or open, both curative for thymoma + improves MG outcomes MGTX, 2016
- Pre-op optimization: may need IVIG or PLEX before surgery (reduce perioperative myasthenic crisis risk)
- Start prednisone LOW (10 mg, titrate up slowly), high-dose steroids can transiently worsen MG in first 2 weeks
Teaching point: Always get CT chest in new MG, thymoma is present in 15%. The MGTX trial showed thymectomy improves outcomes even in NON-thymomatous MG (AChR Ab+, age 18-65). Prednisone must be started low and titrated slowly to avoid initial worsening.
📋 Case 3, MuSK-Positive MG
Patient: 32F with prominent bulbar symptoms: severe dysphagia, dysarthria, facial weakness, tongue atrophy. Minimal limb involvement. AChR antibodies NEGATIVE. MuSK antibodies POSITIVE. Failed pyridostigmine (made worse).
Key findings: MuSK-positive MG, distinct phenotype: bulbar and facial predominance, tongue/facial atrophy, poor response to pyridostigmine (often makes symptoms worse), and no benefit from thymectomy.
Management:
- Stop pyridostigmine (MuSK-MG often worsens with AChE inhibitors)
- Rituximab is emerging as first-line for MuSK-MG (excellent response rate ~70-80%)
- PLEX preferred over IVIG for acute exacerbations (MuSK antibodies are IgG4, not efficiently removed by IVIG)
- Prednisone + mycophenolate as standard immunosuppression
- No thymectomy (thymoma is extremely rare in MuSK-MG, and thymectomy does not improve outcomes)
Teaching point: MuSK-MG breaks all the rules of AChR-MG: pyridostigmine worsens it, thymectomy doesn't help, IVIG is less effective than PLEX, and rituximab works better than traditional immunosuppressants. Always check MuSK antibodies if AChR is negative.
📣 Sample Presentation
One-Liner
"Mrs. Park is a 60-year-old with AChR Ab+ myasthenia gravis on pyridostigmine who presents with worsening dyspnea and dysphagia after a UTI. FVC 16 mL/kg. Diagnosed with myasthenic crisis."
Key Points to Cover on Rounds
Myasthenic crisis triggered by UTI. FVC 16 mL/kg (<20 → intubated for airway protection). NIF −18 cmH₂O. Treatment: IVIG 0.4 g/kg/day × 5 days. Pyridostigmine HELD during crisis (excess secretions worsen airway). Antibiotics for UTI: switched from ciprofloxacin → ceftriaxone (fluoroquinolones contraindicated in MG). Offending meds reviewed -no aminoglycosides, no BB, no Mg supplementation. Methylprednisolone 1g IV × 3 days (cautious -steroids can transiently worsen MG in first 7-10 days). Plan: daily FVC/NIF, restart pyridostigmine when improving and extubated.
Monitoring
- FVC every visit
- Med review -avoid aminoglycosides, FQs, BB, Mg
- Thymoma surveillance
- Infection screening on immunosuppression
⚡ Summary
Summary
Define the Crisis by the Respiratory Numbers
Myasthenic crisis is an exacerbation with respiratory failure requiring ventilatory support. Follow FVC and negative inspiratory force serially, not the oxygen saturation: neuromuscular respiratory failure gives normal saturations until the patient is nearly apneic. FVC below about 20 mL/kg, NIF weaker than -30, or a falling trend means intubate.
Intubate Early, Electively
Do not wait for hypercapnia or exhaustion. A controlled intubation with a full team is far safer than a crash airway in a patient who has just lost their bulbar function. Bulbar weakness with aspiration is an indication in its own right, independent of the vital capacity.
Know the Drugs That Precipitate It
Aminoglycosides, fluoroquinolones, macrolides, beta blockers, magnesium, neuromuscular blockers, and iodinated contrast. Magnesium given for eclampsia or hypomagnesemia can precipitate crisis, and it is one of the commonest inadvertent triggers on a medical ward. Review every new drug against the list.
Find the Trigger
Infection is the commonest, then surgery, pregnancy, tapering immunosuppression, and a new drug. Treat the infection aggressively, choosing antibiotics that do not worsen the disease. A crisis with no identified trigger should prompt a search for thymoma and for a coexisting thyroid disorder.
Plasma Exchange or IVIG, Plus Steroids
Both work and both act within days. Plasma exchange is often faster but needs vascular access and causes hemodynamic shifts; IVIG is easier but carries thrombosis, renal and volume risks. Start high-dose steroids at the same time for the durable effect, warning that steroids cause a transient worsening in the first 1 to 2 weeks, which is why they are started under respiratory monitoring.
Hold the Cholinesterase Inhibitor in Crisis
Pyridostigmine is usually stopped in a ventilated patient in crisis: it increases secretions, which worsens the airway situation, and it contributes to the diagnostic confusion with cholinergic crisis. Restart it as the patient recovers.
Distinguish Cholinergic Crisis
Cholinergic crisis comes from excess cholinesterase inhibitor and adds muscarinic features: SLUDGE (salivation, lacrimation, urination, diarrhea, GI upset, emesis), miosis, bradycardia and fasciculations. Myasthenic crisis has none of those and improves with more treatment; cholinergic crisis worsens. When in doubt, hold the pyridostigmine and support the airway, which is safe in both.
Plan the Long-Term Regimen Before Discharge
Pyridostigmine for symptoms plus a steroid-sparing agent (azathioprine, mycophenolate) for maintenance, with newer targeted options (rituximab, complement and FcRn inhibitors) for refractory disease. CT the chest for thymoma, and consider thymectomy, which improves outcomes in generalized AChR-antibody-positive disease (MGTX). Give the patient a written list of drugs to avoid, since the next crisis is most often triggered by a prescription written elsewhere.
📄 One Pager
Text version
Neurology · One Pager
Myasthenia Gravis
Fatigable weakness (worse with use). AChR antibodies. Pyridostigmine for symptoms. IVIG/PLEX for crisis. Avoid aminoglycosides, FQs, BB, Mg. Thymectomy if thymoma.
Diagnosis
Fluctuating weakness: ptosis, diplopia, bulbar symptoms (dysphagia, dysarthria), proximal limb weakness. AChR Ab positive ~85%. MuSK Ab in some seronegatives. CT chest (thymoma).
Myasthenic Crisis
FVC < 20 mL/kg → intubate. Hold pyridostigmine (excess secretions). IVIG 0.4 g/kg/day × 5d or PLEX. Identify trigger: infection, surgery, medication change.
Dangerous Medications
Aminoglycosides, fluoroquinolones, macrolides, beta-blockers, magnesium IV, D-penicillamine, telithromycin, botulinum toxin. All worsen NMJ transmission.
Key Drugs
Pyridostigmine60 mg q4-6h
PrednisoneStart low, titrate up (can transiently worsen)
Azathioprine2-3 mg/kg/day (steroid-sparing)
IVIG0.4 g/kg × 5d (crisis)
Pitfalls
- Aminoglycosides or FQs in MG patient → crisis
- Not checking FVC (crisis can develop rapidly)
- Missing thymoma (CT chest in all new MG)
- Cholinergic crisis from pyridostigmine excess (SLUDGE symptoms)
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