AKT · Neurology/Demyelinating & NMJ

Myasthenia gravis

Anti-acetylcholine-receptor antibodies at the NMJ (post-synaptic)

Overview

An autoimmune disorder of the neuromuscular junction (antibodies against the post-synaptic acetylcholine receptor) causing FATIGABLE muscle weakness — worse with use and at the end of the day. Ocular and bulbar muscles are typically affected; the emergency is a myasthenic (respiratory) crisis. Associated with thymoma.

Recognise

FATIGABLE weakness: ptosis, diplopia, dysphagia, dysarthria, proximal limb weakness — worse with use/evening
Improves with rest; normal reflexes and sensation
Associated thymoma/thymic hyperplasia; younger women, older men

Red flags

Myasthenic CRISIS — respiratory muscle weakness (monitor FVC), bulbar weakness with aspiration; certain drugs trigger it

Differentials & how to tell them apart

Lambert-Eaton myasthenic syndromeantibodies to pre-synaptic voltage-gated Ca channels; weakness IMPROVES with repeated use; small-cell lung cancer association; reduced reflexes

Guillain-Barré syndromeascending, areflexic, post-infective

Motor neurone diseaseUMN+LMN signs, no fatigability, no ocular sparing

Thyroid eye diseaseproptosis, no fatigable limb weakness

Investigations

Anti-AChR antibodies (90%; anti-MuSK if negative); single-fibre EMG / repetitive nerve stimulation (decrement); CT thorax for THYMOMA; serial FVC in crisis.

Management

Pyridostigmine (+ immunosuppression); crisis: IVIG/plasma exchange + ventilatory support

1Pyridostigmine for symptoms; add corticosteroids + steroid-sparing immunosuppression (azathioprine) for disease control; CT thorax for thymoma (→ thymectomy).Gate: Myasthenic CRISIS (respiratory weakness) → monitor FVC, treat with IVIG or plasma exchange + ventilatory support; AVOID drugs that worsen MG (aminoglycosides, macrolides, quinolones, beta-blockers)
2Thymectomy if thymoma or selected AChR-positive disease; pregnancy and drug-precaution counselling.

Pyridostigmine — acetylcholinesterase inhibitor — symptomatic first-line

Prednisolone + steroid-sparing immunosuppression (azathioprine) — immunomodulation

IVIG / plasma exchange — myasthenic crisis

Thymectomy — if thymoma, or in selected AChR-positive patients

Key points

Fatigable weakness worse with use = myasthenia (anti-AChR); weakness that IMPROVES with use + reduced reflexes + lung cancer = Lambert-Eaton. Always check a CT thorax for thymoma. FVC, not sats, tracks crisis.

Monitor & prognosis

FVC in crisis, symptom fatigability, antibody/EMG, thymus imaging, drug interactions.

Good with treatment; crises are the acute danger.

Source: NICE CKS; Association of British Neurologists