GMG

gMG stands for generalized myasthenia gravis, an autoimmune neuromuscular disorder characterized by fatigable weakness due to impaired transmission at the postsynaptic neuromuscular junction. In gMG, weakness involves ocular muscles and at least one other muscle group, commonly the limbs, bulbar muscles, or respiratory muscles, whereas ocular MG is limited to the eye muscles.

Etiology and pathophysiology: Autoantibodies to the acetylcholine receptor (AChR) are the most common cause; antibodies to MuSK or LRP4 also occur. These antibodies disrupt receptor function and reduce receptor numbers. Thymic abnormalities, including hyperplasia and thymoma, are common and thymectomy can improve symptoms in a subset of patients.

Clinical features: Symptoms are fluctuating and worsened by activity, with relief after rest. Ptosis, diplopia, dysphagia, dysarthria, proximal limb weakness, and possible respiratory involvement can occur. A myasthenic crisis, a severe weakening requiring respiratory support, is a potential complication.

Diagnosis: Evaluation combines clinical suspicion with tests such as serology for AChR, MuSK, and LRP4 antibodies; electrophysiology showing a decremental response on repetitive nerve stimulation or abnormal single-fiber EMG; the ice pack test; and imaging to assess for thymoma.

Management: Treatments include acetylcholinesterase inhibitors (e.g., pyridostigmine) for symptomatic relief and immunosuppression (corticosteroids and steroid-sparing agents like azathioprine or mycophenolate) for long-term control. Thymectomy is considered in selected patients. Acute crises may require plasmapheresis or IVIG. Refractory generalized MG may be treated with targeted biologics such as rituximab or FcRn inhibitors (e.g., efgartigimod).

Prognosis and epidemiology: The disease course is variable; many achieve good control with treatment, but crises can occur. Mortality has declined with modern management. MG affects about 20 per 100,000 people; generalized MG accounts for the majority of cases, with a bimodal age distribution (earlier onset in women, later onset in men).