MG

**Myasthenia Gravis (MG)**

**Pathophysiology:** Type II hypersensitivity. IgG autoantibodies (anti-AChR in ~85%; anti-MuSK in ~5-8% of AChR-negative cases; anti-LRP4 rarely) cause complement-mediated destruction of the postsynaptic membrane, receptor internalization/degradation, and receptor blockade. This reduces the number of functional AChRs, so end-plate potentials fail to reach threshold, especially with repetitive firing.

**Epidemiology:** Bimodal: young women (20s-30s) and older men (60s+). Strong association with thymic abnormalities: thymic hyperplasia (~65%) and thymoma (~10-15%). Also associated with other autoimmune diseases (e.g., thyroid disease, SLE, RA).

**Clinical features:** - Fluctuating, fatigable weakness: worse with repetitive use and at the end of the day; better with rest - Ocular: ptosis and diplopia (often the first sign; extraocular muscles affected first) - Bulbar: dysphagia, dysarthria, nasal speech, chewing fatigue - Proximal limb weakness; neck extensor weakness - Respiratory muscle weakness leads to **myasthenic crisis** (respiratory failure; triggered by infection, surgery, or drugs) - Pupils are spared, and there is no sensory loss. Reflexes are normal.

**Diagnosis:** - Serum anti-AChR antibodies (first-line); if negative, test for anti-MuSK - Edrophonium (Tensilon) test: transient improvement (short-acting AChE inhibitor); rarely used now - Ice pack test for ptosis - Electrodiagnostics: decremental response on repetitive nerve stimulation (low frequency, 2-5 Hz); increased jitter on single-fiber EMG (most sensitive) - CT/MRI chest to look for thymoma

**Treatment:** - Symptomatic: acetylcholinesterase inhibitors (pyridostigmine, which has muscarinic side effects: diarrhea, cramping, salivation, bradycardia) - Immunosuppression: glucocorticoids, azathioprine, mycophenolate - Thymectomy: indicated for thymoma and for generalized AChR+ MG in patients under 65 - Myasthenic crisis/acute exacerbation: IVIG or plasmapheresis, plus ventilatory support - Newer agents: complement inhibitors (eculizumab, ravulizumab) and FcRn inhibitors (efgartigimod, rozanolixizumab) for refractory AChR+ disease

**Drugs that exacerbate MG:** Aminoglycosides, fluoroquinolones, macrolides, magnesium, beta-blockers, and CCBs, among others. Also be careful with neuromuscular blockers (sensitive to nondepolarizing agents, resistant to succinylcholine).

**Key comparisons (high-yield):** - **Lambert-Eaton myasthenic syndrome (LEMS):** Antibodies against presynaptic voltage-gated Ca²⁺ channels. Associated with small cell lung cancer. Proximal weakness that *improves* with repeated use; autonomic symptoms (dry mouth); hyporeflexia. Incremental response on high-frequency stimulation. - **Botulism:** Blocks ACh release; descending paralysis with pupillary involvement and autonomic dysfunction. - **Myasthenic crisis vs. cholinergic crisis:** Over-treatment with AChE inhibitors causes cholinergic crisis (SLUDGE signs, miosis, fasciculations), whereas an edrophonium test worsens cholinergic crisis and improves myasthenic crisis.

**Other meanings of "MG":** mg = milligram; MG can also stand for "Mean Gradient" (e.g., in aortic stenosis) or "Menetrier"/"membranous glomerulopathy" in some contexts. The context determines meaning, but on boards MG almost always means myasthenia gravis.