🧠 What is Myasthenia Gravis?
Myasthenia Gravis (MG) is an autoimmune disorder of the neuromuscular junction (NMJ) characterised by fatigable weakness — weakness that worsens with activity and improves with rest.
Pathophysiology
- Autoantibodies (most commonly anti-AChR antibodies — acetylcholine receptor antibodies) block and destroy postsynaptic acetylcholine receptors at the NMJ
- Result: reduced available receptors → fewer action potentials → muscle weakness with repeated stimulation (fatigue)
- 10% of MG: Anti-MuSK antibodies (more severe, bulbar-predominant, thymoma less common)
- Thymus gland: Plays a central role — 65–70% of MG patients have thymic hyperplasia; 10–15% have thymoma
Key Facts
Demographics
- Bimodal incidence: young women (20–40s) and older men (50–70s)
- Prevalence: ~200 per million population
- More common in women overall (3:2 ratio)
Associated Conditions
- Thymoma (10–15%)
- Autoimmune thyroid disease (Hashimoto's, Graves')
- Rheumatoid arthritis
- SLE
- Lambert-Eaton syndrome (opposite pattern — improves with activity)
Diagnosis
- Anti-AChR antibodies: Positive in 85% of generalised MG; highly specific
- Anti-MuSK antibodies: Positive in seronegative MG cases
- Tensilon (Edrophonium) test: IV short-acting acetylcholinesterase inhibitor → brief dramatic improvement in weakness = positive. Now rarely used due to cardiac side effects; replaced by ice pack test for ocular MG
- Ice pack test: Ice applied to closed eye for 2 minutes → if ptosis improves = suggests MG (cold inhibits acetylcholinesterase → more ACh available)
- Repetitive nerve stimulation: Decremental response on EMG — characteristic of MG
- CT chest: ALL MG patients need CT chest to exclude thymoma
👁️ Clinical Features
Hallmark: Fatigable Weakness
Key concept: MG weakness is FATIGABLE — it worsens with repeated activity and improves with rest. This distinguishes it from most other causes of muscle weakness.
Typical Symptoms
| Feature | Detail | Frequency |
|---|
| Ptosis | Drooping eyelid — usually bilateral but asymmetric; worse as day progresses | ~90% present with ocular symptoms |
| Diplopia | Double vision from extraocular muscle weakness; improves with covering one eye | Common early symptom |
| Bulbar weakness | Dysarthria (nasal voice), dysphagia, difficulty chewing | 50–60% |
| Proximal limb weakness | Arms more than legs; difficulty raising arms above head; difficulty climbing stairs | Generalised MG |
| Respiratory muscle weakness | Dyspnoea, orthopnoea, weak cough — can lead to respiratory failure | Myasthenic crisis |
Osserman Classification
- Class I (Ocular MG): Only ocular muscles affected; no respiratory risk
- Class II: Generalised mild (IIa) or moderate (IIb) weakness
- Class III: Acute severe generalised MG
- Class IV: Chronic severe MG
- Class V: Intubated MG (respiratory failure)
Triggers of Worsening
Drugs that WORSEN myasthenia gravis (avoid or use with extreme caution):
- Aminoglycosides (gentamicin, tobramycin) — block NMJ transmission
- Fluoroquinolones (ciprofloxacin, levofloxacin)
- Macrolides (azithromycin)
- Magnesium sulphate (MgSO4) — antagonises calcium at NMJ
- Beta-blockers (propranolol)
- Neuromuscular blocking agents (prolonged effect)
- D-penicillamine
- Chloroquine/hydroxychloroquine
Other Triggers
- Infection (most common trigger for myasthenic crisis)
- Surgery / anaesthesia
- Stress, physical exertion
- Pregnancy (especially post-partum period)
- Heat (worsens NMJ dysfunction)
- Thyroid dysfunction
🚨 Myasthenic Crisis vs Cholinergic Crisis
MYASTHENIC CRISIS = Medical Emergency. Respiratory failure from muscle weakness in an MG patient. ICU admission, respiratory monitoring, and possibly intubation required.
Myasthenic Crisis
- Caused by INADEQUATE acetylcholine at NMJ (too little treatment, or disease worsening)
- Trigger: infection, surgery, medication changes, stress
- Signs: increasing weakness, dyspnoea, worsening ptosis/diplopia, dysphagia, weak cough
- Respiratory assessment: Single Breath Count (SBC), FVC — if FVC <1.0L or <20 mL/kg = consider intubation
Cholinergic Crisis
- Caused by EXCESS acetylcholine at NMJ (overdose of pyridostigmine/neostigmine)
- Signs: muscarinic effects (DUMBELS) + paradoxical WEAKNESS (excess depolarisation)
- DUMBELS: Diarrhoea, Urination, Miosis, Bradycardia, Emesis, Lacrimation, Salivation + Sweating
- Plus: fasciculations, muscle cramps
Differentiating the Two Crises
| Feature | Myasthenic Crisis | Cholinergic Crisis |
|---|
| Cause | Too little acetylcholine | Too much acetylcholine (drug overdose) |
| Pupils | Normal or dilated | MIOSIS (pinpoint) |
| Secretions | Dry | Excessive (SLUDGE) |
| Bowel/bladder | Normal | Diarrhoea, urinary incontinence |
| Fasciculations | Absent | Present |
| Response to edrophonium (Tensilon) | Improves briefly | Worsens |
| Treatment | Increase immunotherapy, plasma exchange/IVIG, intubate if needed | STOP pyridostigmine; IV atropine for muscarinic symptoms |
Respiratory monitoring in MG crisis:
- Bedside spirometry: FVC (Forced Vital Capacity) hourly in acute deterioration
- The "20-30-40 rule": FVC <20 mL/kg → consider intubation; NIF <-30 cmH₂O → concerning; FVC <1.5L → concerning
- SpO₂ is a LATE indicator — desaturation in MG means already in crisis. Use FVC, not SpO₂ to guide intubation decision
Treatment of Myasthenic Crisis
- Intubate if FVC <15–20 mL/kg or rapidly deteriorating
- IVIG (Intravenous Immunoglobulin): 2 g/kg total over 5 days — onset 3–5 days
- Plasma exchange (PLEX): Removes circulating AChR antibodies — faster onset than IVIG (3–5 exchanges); preferred when faster response needed
- Hold pyridostigmine during intubation (increases secretions)
- Treat precipitating infection
- Avoid drugs that worsen MG (see triggers)
💊 Long-Term MG Treatment
Symptomatic Treatment
Pyridostigmine (Mestinon): Acetylcholinesterase inhibitor — prevents breakdown of ACh at NMJ → more ACh available → improved muscle strength. Does NOT treat the underlying autoimmune process.
Dose: 30–60 mg every 4–6 hours (titrated to symptoms)
Side effects (muscarinic): nausea, diarrhoea, abdominal cramps, excessive salivation — take with food
Immunosuppression (Disease-Modifying)
| Drug | Role | Key Notes |
|---|
| Prednisolone | First-line immunosuppression | Can cause initial worsening in first 2–3 weeks — start low and increase; Cushing's side effects; monitor BGL |
| Azathioprine | Steroid-sparing agent | Takes 6–18 months for full effect; check TPMT enzyme before starting; LFTs and FBC monitoring |
| Mycophenolate mofetil | Alternative steroid-sparing | Better tolerated than azathioprine; 6–12 months for effect |
| Ciclosporin/Tacrolimus | Refractory MG | Nephrotoxic; monitor renal function and drug levels |
| Rituximab | Anti-MuSK MG; refractory MG | Anti-CD20; effective for seronegative/anti-MuSK MG |
| Eculizumab / Efgartigimod | Novel biologics for refractory MG | FcRn inhibitor (efgartigimod) reduces AChR antibody levels rapidly |
Thymectomy
- Recommended for ALL MG patients with thymoma (mandatory)
- Recommended for generalised AChR-positive MG in patients <65 years even without thymoma — MGTX trial showed significant benefit (improved outcomes, reduced medication requirements)
- Less benefit for ocular-only MG, elderly patients, anti-MuSK positive MG
- Benefits may not appear for 2–5 years post-thymectomy
Nursing Care Priorities
- Swallowing assessment — bulbar MG at risk of aspiration; involve speech and language therapy
- Medication timing: pyridostigmine 30–60 min BEFORE meals to aid chewing/swallowing
- Respiratory monitoring: FVC measurements, SpO₂, respiratory rate — report deterioration immediately
- Avoid heat exposure (worsens weakness) — cool environment important especially in GCC climate
- Fall risk assessment — proximal weakness affects balance
- Educate patient on drugs to avoid and when to seek emergency care