Myasthenia Gravis
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Direct answer
Fatigable, never fixed — ptosis and diplopia that worsen through the day, swallowing that tires with meals, limb power that falls on repeated use, with sensation and reflexes always intact — that is the signature of myasthenia gravis, an autoimmune disorder of the neuromuscular junction in which antibodies attack the postsynaptic acetylcholine receptor (about 80–85 per cent of generalised cases) or MuSK. Diagnosis rests on antibody testing, decremental response on repetitive nerve stimulation (or increased jitter on single-fibre EMG) and the edrophonium or ice-pack test; treatment ranges from pyridostigmine through immunosuppression and thymectomy to plasma exchange and IVIG for crisis.
What you must remember
- The signature is fatigability: weakness increases with sustained use and improves with rest, and the pattern is ocular (about half present this way), bulbar, limb or generalised — reflexes and sensation are always intact.
- AChR antibodies are positive in about 80–85 per cent of generalised and roughly half of ocular myasthenia; MuSK antibodies (5–10 per cent) mark a bulbar- and neck-predominant, more crisis-prone phenotype that responds less to pyridostigmine and anticholinesterases can even worsen it.
- Bedside tests: the ice-pack test (ptosis improves after ice on the lid — useful in ocular disease) and the edrophonium (Tensilon) test with atropine drawn up; electrophysiology: decrement over 10 per cent on 3 Hz repetitive nerve stimulation, and increased jitter on single-fibre EMG, the most sensitive test.
- Chest CT for every patient: thymoma in about 10–15 per cent (resection mandatory; watch for thymoma-associated myasthenia refractoriness) and thymic hyperplasia in many early-onset cases.
- Symptomatic treatment: pyridostigmine 30–60 mg every 4–6 hours — muscarinic effects (diarrhoea, cramps, salivation, bronchial secretions) dose-limiting; immunosuppression with prednisolone titrated up plus azathioprine or mycophenolate for steroid sparing.
- Thymectomy benefits non-thymomatous early-onset AChR-positive generalised myasthenia (randomised evidence) and is mandatory in thymoma.
- Crisis therapy: plasma exchange or IVIG plus ventilatory and bulbar support; hunt the trigger — infection, surgery, and the drug list below.
- Drugs that worsen myasthenia: aminoglycosides, fluoroquinolones, macrolides, beta-blockers, calcium-channel blockers, magnesium, iodinated contrast, D-penicillamine and corticosteroid initiation itself (transient worsening).
One diagnosis from drooping lid to treatment plan
A 32-year-old woman reports six months of double vision toward the evening and drooping eyelids that her ophthalmologist first called "allergic"; yesterday she choked on water. Examination shows ptosis that deepens on sustained upgaze, a "peek sign" of fatiguing lid closure, normal pupils, normal reflexes, power that falls from 5/5 to 3/5 on repeated shoulder abduction, and a positive ice-pack test — fatigable weakness with everything else normal is already the syndrome. Confirmation runs in parallel: AChR antibodies (positive here), repetitive nerve stimulation showing over 10 per cent decrement in a facial or limb muscle, and single-fibre EMG with increased jitter if the others are discordant; chest CT excludes thymoma — a study every patient deserves once. Treatment is layered: pyridostigmine for same-week symptomatic relief, with the warning that MuSK-positive disease (if AChR were negative, MuSK would be sent next) often fails anticholinesterases; prednisolone introduced carefully (transient initial worsening, hence bulbar monitoring or even cover with IVIG when starting in weak patients) plus azathioprine for the long term; and, because she is under 60 with early-onset AChR-positive generalised disease, thymectomy enters the discussion as a steroid-sparing, evidence-backed option. Her crisis card — written, wallet-sized — lists the contraindicated antibiotics and the instruction to present early with any fever or swallowing difficulty, because myasthenic crises are precipitated, rarely spontaneous.
Where students slip
The commonest confusion is fatigable versus fixed: myasthenia fluctuates hour to hour and worsens with use, while the great mimics — thyroid ophthalmopathy, chronic progressive external ophthalmoplegia, or a compressive oculomotor lesion — produce constant deficits, duction restriction or pupillary change. Candidates also forget the MuSK nuance — the neck and bulbar predominance and the poor pyridostigmine response — and miss that corticosteroids can transiently worsen myasthenia at initiation. Finally, the crisis differentials get muddled: worsening weakness plus increased salivation, diarrhoea and fasciculations suggests a cholinergic excess (overtreated) rather than myasthenic (undertreated) crisis — the practical modern answer is to hold anticholinesterases, support ventilation, and let the picture declare itself.
Frequently asked questions
Which antibodies define myasthenia gravis?
Acetylcholine receptor antibodies in about 80–85 per cent of generalised disease; MuSK antibodies in 5–10 per cent with a bulbar-predominant phenotype; LRP4 antibodies occasionally.
What is the electrophysiological hallmark on repetitive nerve stimulation?
A decremental compound muscle action potential response of more than 10 per cent at low-frequency (about 3 Hz) stimulation, with post-exercise facilitation; single-fibre EMG jitter is the most sensitive test.
When is thymectomy indicated?
For all thymoma cases (oncological resection) and for non-thymomatous early-onset AChR-positive generalised myasthenia, where randomised evidence supports benefit.
How is a myasthenic crisis treated?
Plasma exchange or intravenous immunoglobulin with ventilatory and bulbar support in a critical care setting, treatment of the precipitating infection, and withdrawal of worsening drugs.
Which drug classes can precipitate worsening of myasthenia?
Aminoglycosides, fluoroquinolones, macrolides, beta-blockers, calcium-channel blockers, magnesium-containing preparations, iodinated contrast and D-penicillamine.