Neurology

Myasthenia gravis

An autoimmune neuromuscular-junction disorder causing fluctuating, fatigable weakness with particular risk to ocular, bulbar and respiratory muscles.

In a nutshell

MG is autoimmune failure of neuromuscular transmission, causing fluctuating fatigable weakness that classically affects the eyes and bulbar muscles. Diagnose with a compatible clinical pattern plus AChR/MuSK-directed testing and specialist neurophysiology, image the thymus, use pyridostigmine for symptoms and daily steroid-based immunotherapy for generalised disease, and treat respiratory or bulbar deterioration as myasthenic crisis.

Classic presentation

Variable ptosis and diplopia that worsen with sustained upgaze or later in the day and improve with rest, with normal sensation and usually preserved reflexes; bulbar or proximal weakness may generalise.

Key points

Fatigability and fluctuation are the diagnostic clues: weakness worsens with sustained use and improves with rest.
AChR antibody testing is first-line; if negative, test MuSK and use specialist cell-based testing and neurophysiology before diagnosing seronegative MG.
Image the thymus in every suspected case; chest X-ray alone is insufficient and thymoma changes management.
Pyridostigmine is symptomatic. Daily corticosteroids and steroid-sparing immunosuppression treat the autoimmune disease; the 2025 ABN guideline has moved away from alternate-day steroid default treatment.
Thymectomy is required for thymoma and is recommended or discussed early in selected AChR-antibody-positive disease, but non-thymoma thymectomy is not indicated for MuSK-MG.
Myasthenic crisis is a respiratory and bulbar emergency: trend vital capacity and clinical respiratory function, involve ICU early, and use IV immunoglobulin or plasma exchange.

First-line investigation

AChR antibody testing with specialist neurological assessment; if negative, MuSK and appropriate neurophysiology, plus thymus imaging and thyroid function.

Management

Recognise and escalate myasthenic crisis

Assess swallow, cough, speech, secretion handling and serial vital capacity; involve neurology and critical care early for respiratory or bulbar deterioration.^1,2

Confirm autoimmune MG and its phenotype

Use AChR and MuSK antibodies, specialist neurophysiology, thyroid function and thymus imaging; only label disease seronegative after appropriate specialist testing.¹

Improve transmission symptomatically

Start pyridostigmine at the lowest effective dose with monitoring for cholinergic and cardiac adverse effects; do not rely on escalating symptomatic treatment for persistent generalised weakness.^1,4

Suppress the autoimmune disease and consider thymectomy

Use daily corticosteroid and steroid-sparing immunosuppression when indicated; offer thymectomy for thymoma and discuss early thymectomy in selected AChR-antibody-positive disease.^1,2

Use rescue or targeted treatment through specialists

Treat crisis with IV immunoglobulin or plasma exchange; discuss rituximab and NICE-approved rozanolixizumab pathways with an MG specialist for refractory generalised disease.^1,3

Prevent triggers and coordinate care

Review interacting medicines, provide a deterioration contact, plan vaccination and surgery, and arrange pregnancy, driving, rehabilitation and speech-and-swallow support through the MDT.^1,2,4

Exam traps

MG usually has normal sensation and preserved reflexes; sensory loss or a clear upper motor-neurone pattern points elsewhere.
Antibody levels do not reliably measure severity or response; use clinical assessment and MG-ADL or MG Composite scores.
Severe dysphagia or respiratory weakness is myasthenic crisis until assessed otherwise; do not wait for desaturation.
Check the drug chart after deterioration: medicines, infection, surgery and pregnancy or postpartum changes can precipitate worsening.
AChR-positive and MuSK-positive MG are not identical: treatment response and thymectomy indications differ, so specialist phenotyping matters.

Illustrations

Neuromuscular junction safety marginDiagram of a normal neuromuscular junction with a wide safety margin of acetylcholine receptors, compared with a myasthenic junction where antibody-mediated receptor loss narrows the margin.PassFinals · original

Fatigable ptosis on sustained upgazeSequential illustration of a patient's eyelids drooping progressively further with sustained upward gaze, recovering after rest.PassFinals · original

Decremental response on repetitive nerve stimulationElectromyography trace showing a progressively smaller muscle action potential with repeated nerve stimulation, illustrating the failing safety margin.PassFinals · original

Key sources

This page is exam revision material, not medical advice, and must not be used for patient care. Always check drug doses against the BNF and current guidance. Full disclaimer.