Myasthenia Gravis in the Older Adult

Definition. An antibody-mediated disorder of the neuromuscular junction in which antibodies against the postsynaptic nicotinic acetylcholine receptor (AChR, ~85%), or against MuSK or LRP4, impair neuromuscular transmission. Late-onset MG (>50 years) is increasing in incidence, shows a male predominance, is usually AChR-antibody positive, and is associated with thymoma in 10–15%.

Clinical features. Fatigable, fluctuating weakness that worsens through the day and with repeated use. Ocular onset in more than half — ptosis and diplopia; bulbar features (dysphagia, nasal regurgitation, nasal speech, jaw fatigue on chewing); proximal limb and neck-extensor weakness (“dropped head”); and respiratory muscle weakness. Reflexes are normal and there is no sensory loss.

Geriatric pitfall — MG is under-diagnosed in the elderly. It is mislabelled as stroke, bulbar palsy, motor neuron disease, myopathy or simply “old age”. Older patients present more often with bulbar and respiratory involvement. Consider MG in any older person with ptosis, diplopia, dysphagia or unexplained fatigable weakness, because it is a highly treatable disease.

Diagnosis. Serum AChR antibody first; test MuSK antibody if negative. Repetitive nerve stimulation shows a decremental response of more than 10%; single-fibre EMG is the most sensitive test. The ice-pack test and the sleep test are safe bedside tests for ptosis and are preferred to edrophonium in older people. CT/MRI thorax is mandatory to exclude thymoma. Screen for associated thyroid and other autoimmune disease.

Treatment. Pyridostigmine for symptomatic relief (cholinergic side effects — colic, diarrhoea, bradycardia, secretions). Prednisolone is the mainstay immunotherapy — start low and increase slowly to avoid the early steroid-induced deterioration. Steroid-sparing agents: azathioprine (check TPMT), mycophenolate, methotrexate. Thymectomy is indicated for thymoma at any age; in non-thymomatous MG it is usually reserved for generalised, AChR-positive patients under 50–60 years, and benefit appears only after 6–12 months.

Crisis, precautions and prognosis. Myasthenic crisis (weakness needing ventilation) is precipitated by infection, surgery or too-rapid reduction of immunotherapy; the rarer cholinergic crisis follows excessive anticholinesterase — if in doubt, ventilate and stop the anticholinesterase. Treat with IVIG or plasma exchange plus aggressive treatment of infection. Avoid aminoglycosides, macrolides, fluoroquinolones, beta-blockers, magnesium, procainamide and iodinated contrast. Prognosis is good — more than 90% achieve remission or substantial improvement.

Targeted biologics have transformed refractory generalised MG. Two classes are now available: complement C5 inhibitors — eculizumab, ravulizumab and zilucoplan (meningococcal vaccination is mandatory) — and FcRn blockers that accelerate IgG catabolism — efgartigimod, rozanolixizumab, and nipocalimab, approved by the FDA in April 2025 and the European Commission in December 2025 for AChR- or MuSK-antibody-positive generalised MG. These give rapid, steroid-sparing IgG reduction (about 70% fall) and are particularly relevant in older adults who tolerate long-term corticosteroids poorly.