About This Page
This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
The Bottom Line
- Fatigable muscle weakness that worsens with repeated use and improves with rest — the hallmark
- Ocular symptoms (ptosis, diplopia) are the most common initial presentation (~65%)
- Anti-AChR antibodies positive in ~85% of generalised MG. Anti-MuSK antibodies in ~5–10% of seronegative patients
- CT thorax in ALL patients — thymoma in ~10–15%, thymic hyperplasia in ~60%
- Treatment: pyridostigmine (symptomatic), immunosuppression (prednisolone, azathioprine), thymectomy if thymoma or generalised MG
Overview
Myasthenia gravis (MG) is an autoimmune disorder caused by antibodies targeting the postsynaptic neuromuscular junction (NMJ). In ~85% of cases, antibodies are directed against nicotinic acetylcholine receptors (AChR); in ~5–10% against muscle-specific kinase (MuSK); and in a minority against LRP4 or other NMJ components. Antibody binding leads to complement-mediated damage, reduced functional AChR density, and failure of neuromuscular transmission. It causes fatigable weakness that characteristically worsens with activity and improves with rest. The thymus gland is implicated in pathogenesis: thymoma in ~10–15%, thymic hyperplasia in ~60%.
Epidemiology
MG has a UK prevalence of approximately 15 per 100,000. It shows a bimodal age distribution: younger adults (20–40 years, predominantly female) and older adults (60–80 years, predominantly male). Associated with other autoimmune conditions: thyroid disease, rheumatoid arthritis, SLE, pernicious anaemia. Lambert-Eaton myasthenic syndrome (LEMS) is a paraneoplastic differential — associated with small cell lung cancer and anti-VGCC antibodies.
Clinical Features
Symptoms
Fatigable weakness: worsens with repeated use, better in the morning, worse at end of day
Ptosis: drooping eyelid — unilateral or bilateral. May become bilateral on sustained upgaze
Diplopia (double vision) from extraocular muscle weakness
Dysarthria and dysphagia (bulbar weakness) — voice becomes nasal or weak with prolonged speaking
Proximal limb weakness — difficulty with arms above head, climbing stairs
Breathlessness: diaphragmatic weakness (myasthenic crisis)
Difficulty chewing: jaw fatigue — unable to finish a meal
Signs
Fatigable ptosis: sustained upgaze for 60 seconds worsens ptosis
Complex ophthalmoplegia (does not conform to single nerve pattern)
Myasthenic snarl: weakness of facial muscles producing a snarling expression on attempted smile
Nasal or quiet speech on prolonged counting
Normal reflexes and normal sensation (distinguishes from GBS and neuropathy)
Ice pack test: improvement of ptosis after applying ice to eyelid for 2 minutes (cooling improves NMJ transmission)
Investigations
First-line
Anti-AChR antibodiesPositive in ~85% of generalised MG and ~50% of pure ocular MG. Highly specific
CT thoraxMANDATORY in all patients — thymoma in ~10–15%. If thymoma found, surgical excision required
Second-line
Anti-MuSK antibodiesIn ~5–10% of AChR-seronegative patients. MuSK-MG has different clinical profile: more bulbar/respiratory, less ocular
Neurophysiology: repetitive nerve stimulation (RNS)Decrement of >10% on repetitive stimulation at 3 Hz = positive. Single-fibre EMG is the most sensitive test (~95%)
Edrophonium (Tensilon) testRarely used now — IV edrophonium (short-acting AChE inhibitor) causes transient improvement. Risk of bradycardia. Largely replaced by antibody testing and neurophysiology
Specialist
TFTs and autoimmune screenAutoimmune thyroid disease is common in MG. Screen for associated conditions
FVC monitoringIn myasthenic crisis or perioperatively — assess respiratory muscle function
1
Symptomatic treatment
- Pyridostigmine 60 mg QDS (dose titrated to effect, max ~360 mg/day) — acetylcholinesterase inhibitor, improves NMJ transmission
- Side effects: GI cramping, diarrhoea, excessive salivation (muscarinic effects). Excessive dose causes cholinergic crisis
2
Immunosuppression
- Prednisolone: start low, titrate slowly (rapid high-dose initiation can worsen weakness). Target dose typically 0.5–1 mg/kg on alternate days
- Azathioprine: steroid-sparing agent, takes 3–6 months to reach full effect. Check TPMT level before starting
- Other options: mycophenolate, ciclosporin, methotrexate, rituximab (for refractory disease)
3
Thymectomy
- MANDATORY if thymoma present
- Consider in generalised AChR-positive MG aged 18–65 even without thymoma (MGTX trial showed benefit)
- Not beneficial in MuSK-positive MG
4
Myasthenic crisis
- Life-threatening respiratory failure — admit to ITU
- Monitor FVC serially: intubate if FVC <15–20 mL/kg
- IV immunoglobulin (IVIg 0.4 g/kg/day for 5 days) or plasma exchange — rapid onset of action
- Identify and treat trigger: infection, medication (aminoglycosides, beta-blockers, see drug list), missed medication, surgery
Complications
- Myasthenic crisis: Acute respiratory failure requiring ventilation — triggered by infection, surgery, or medications. Mortality ~5%
- Cholinergic crisis: Excessive pyridostigmine causes worsened weakness + muscarinic symptoms (salivation, diarrhoea, miosis, bradycardia) — stop pyridostigmine
- Thymoma: Present in ~10–15% — may be locally invasive. Requires surgical excision
- Associated autoimmune conditions: Thyroid disease, RA, SLE, pernicious anaemia
- Drug-induced worsening: Many drugs can exacerbate MG — aminoglycosides, macrolides, beta-blockers, phenytoin, lithium, D-penicillamine, ciprofloxacin
UKMLA Exam Tips
- 1Fatigable weakness (worse with use, better with rest) = myasthenia gravis. Ptosis + diplopia that worsen through the day = classic
- 2Anti-AChR antibodies: positive in ~85% of generalised MG, highly specific
- 3CT thorax in ALL patients — screen for thymoma
- 4Pyridostigmine = first-line symptomatic. Prednisolone + azathioprine = immunosuppression
- 5Myasthenic crisis: IVIg or plasma exchange. Monitor FVC. Intubate if FVC <15–20 mL/kg
- 6Avoid aminoglycosides, beta-blockers, and many other drugs in MG — they worsen weakness
- 7Lambert-Eaton (LEMS): proximal weakness that IMPROVES with activity (opposite of MG). Anti-VGCC antibodies. Associated with small cell lung cancer
practicetest your knowledge on myasthenia gravisApply what you've learnt with UKMLA-style questions from the iatroX Q-Bank — neurology and beyond.
open q-bank