Myasthenia Gravis

Myasthenia gravis (MG) is autoimmune disorder of neuromuscular junction, caused by antibodies against acetylcholine receptors (AChR) or receptor-associated proteins, leading to fatigable weakness. For Zambian students, essential for neurology, critical care, and thymus pathology. Pathophysiology: AChR antibodies (80%) → AChR blockade, cross-linking/internalization, complement-mediated destruction → reduced functional AChRs at postsynaptic membrane. MuSK antibodies (5-10%, female predominant, oculo-bulbar, neck, respiratory). LRP4 antibodies, seronegative. Thymic abnormalities: thymoma (10-15%), thymic hyperplasia (50-70%). Clinical: FATIGABLE WEAKNESS—worse with repetitive use, improves with rest, diurnal variation (worse evening). OCULAR: ptosis (unilateral/bilateral, asymmetric), diplopia—presentation in 50%, isolated ocular MG (15%). BULBAR: dysarthria (nasal speech), dysphagia, fatigable chewing, facial weakness (snarling smile). LIMB: proximal > distal, upper > lower. RESPIRATORY: dyspnoea, orthopnoea—MYASTHENIC CRISIS (respiratory failure requiring ventilation), triggered by infection, surgery, medication, pregnancy, tapering immunotherapy. Diagnosis: CLINICAL—fatigable weakness. ICE PACK TEST: improves ptosis. ACETYLCHOLINESTERASE INHIBITOR TEST: edrophonium (Tensilon) IV—brief improvement (30-60s)—now rarely used, neostigmine IM alternative. SEROLOGY: AChR antibodies (80% generalized, 50% ocular), MuSK antibodies. ELECTROPHYSIOLOGY: repetitive nerve stimulation—decremental response (>10% decline). Single-fibre EMG—increased jitter (most sensitive). THORACIC IMAGING: CT chest—thymoma, thymic hyperplasia. Management: SYMPTOMATIC: pyridostigmine (acetylcholinesterase inhibitor)—first-line, 30-60mg q4-6h. CHRONIC IMMUNOSURPRESSION: corticosteroids (prednisone)—slow titration to avoid exacerbation. Steroid-sparing: azathioprine, mycophenolate, methotrexate, cyclosporine. RAPID IMMUNOMODULATION: plasma exchange, IV immunoglobulin—myasthenic crisis, pre-thymectomy, severe exacerbation. THYMECTOMY: indicated for thymoma, consideration in non-thymomatous AChR+ generalized MG (<60y). MONOCLONAL ANTIBODIES: rituximab (MuSK+, refractory), eculizumab (complement inhibitor, refractory AChR+). MYASTHENIC CRISIS: ICU admission, airway protection, non-invasive/mechanical ventilation, IVIG/PLEX, treat trigger, hold pyridostigmine (secretions). Avoid: aminoglycosides, fluoroquinolones, macrolides, beta-blockers, magnesium, quinine—may worsen weakness. Prognosis: excellent with modern therapy—normal lifespan, good function. Crisis mortality <5%. Zambian context: limited serology, electrophysiology, ICU capacity. Clinical diagnosis—fatigable ptosis, diplopia, bulbar weakness. Pyridostigmine accessible. Prednisone accessible. Azathioprine accessible. Thymectomy available tertiary centres. Crisis management challenging.