🎯 Pathology

• autoimmune condition affecting the neuromuscular junction (NMJ) of skeletal muscle

• caused by antibodies targeting postsynaptic acetylcholine receptors at the NMJ —> increased competition between acetylcholine with antibodies —> less electrical impulses —> muscle weakness

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💡 Risk factors

• thymomas are the key association (seen in 15%)

• younger women, older men

• other autoimmune conditions such as autoimmune thyroid disorders, SLE, rheumatoid arthritis

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🩺 Clinical features

• muscle fatigability (muscles get steadily weaker on exertion and recover with rest)

• typically affects extraocular muscles of the eye, bulbar muscles, and proximal muscles of the limbs

  • extraocular muscle weakness

    • diplopia and/or ptosis

  • bulbar muscle weakness

    • dysarthria, dysphagia and/or hoarseness

    • expressionless face if facial muscles are involved

  • limb weakness

    • proximal muscles are usually affected causing difficulties with tasks such as combing and climbing stairs

• symptoms classically fluctuate and get worse at the end of the day as muscles fatigue

• myasthenic crisis

  • very rare but life-threatening and is a medical emergency

  • due to Involvement of intercostal muscles and diaphragm —> respiratory compromise and aspiration

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🕵️‍♂️ Investigations

• serological tests

  • acetylcholine receptor antibodies (positive in 80%)

  • very specific and confirms the diagnosis in patients with classic clinical presentation

  • in the rest of the patients, a proportion may demonstrate anti-muscle-specific tyrosine kinase (anti-MuSK) antibodies

• electrophysiological tests to assess for nerve conduction delays at the NMJ

  • single fibre electromyography

  • repetitive nerve stimulation

• imaging

  • CT thorax to exclude a thymoma

• tensilon test

  • IV edrophonium is a short-acting anticholinesterase inhibitor which increases the concentration of acetylcholine in the NMJ

  • can temporarily reverse muscle weakness

  • carries a risk cardiac arrhythmia therefore its use is not commonplace

• ice-pack test

  • apply an ice pack to the eyes between 2-5 minutes

  • cooling reduces the activity of acetylcholinesterase therefore more acetylcholine is available at the NMJ

  • positive test: improved function of levator palpebrae superioris muscle

• bloods

  • normal creatine kinase

  • screen for other autoimmune conditions (e.g. ANA, rheumatoid factor)

  • thyroid function tests

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💆‍♂️ Management

• 1st line

  • long-acting acetylcholinesterase inhibitors (pyridostigmine)

• if still symptomatic despite adherence to pyridostigmine

  • ​immunosuppression

    • 1st line: prednisolone

    • other medications: azathioprine, methotrexate, mycophenolate mofetil, cyclophosphamide

• surgical

  • thymectomy

• management of myasthenic crisis

  • airway management

  • plasmapheresis

  • IV immunoglobulin

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🧲 High-yield tips

• medications that exacerbate myasthenia gravis

  • beta-blockers

  • lithium

  • phenytoin

  • penicillamine

  • certain antibiotics: aminoglycosides, macrolides, quinolones, tetracyclines