Myasthenic Crisis

Myasthenic crisis is a life-threatening exacerbation of myasthenia gravis (MG) causing respiratory failure from diaphragmatic and intercostal muscle weakness. In MG, autoantibodies (anti-AChR in 85%, anti-MuSK in 5-8%, anti-LRP4 in 2-3%) attack the postsynaptic neuromuscular junction (NMJ). Anti-AChR antibodies cause NMJ damage through three mechanisms: complement-mediated destruction of the postsynaptic membrane, accelerated AChR internalization (antigenic modulation), and direct blockade of the ACh binding site. This reduces the number of functional AChRs, decreasing the safety factor for neuromuscular transmission. During crisis, the safety factor drops below the threshold for muscle fiber activation in respiratory muscles. Precipitants include infection (most common — 40% of crises), medication changes (antibiotics, beta-blockers, magnesium), surgical stress, pregnancy, and tapering immunotherapy too quickly. Cholinergic crisis (excess acetylcholinesterase inhibitor) can mimic myasthenic crisis — distinguished by muscarinic symptoms (SLUDGE: salivation, lacrimation, urination, defecation, GI cramping, emesis) and miosis.