Myasthenia Gravis Overview

Myasthenia Gravis (MG)

• Pathophysiology: IgG antibodies destroy post-junctional nicotinic acetylcholine receptors at the neuromuscular junction (NMJ), causing skeletal muscle weakness.
• Weakness worsens later in the day or with exercise; rest improves function.
• Thymectomy may relieve symptoms.
• Signs and symptoms: Diplopia, ptosis (earliest), bulbar muscle weakness (dysphagia, dysarthria, drooling), dyspnea, proximal muscle weakness.
• Exacerbating factors: Pregnancy, infection, electrolyte abnormalities, stress, aminoglycoside antibiotics.
• Neonatal considerations: Maternal anti-AchR IgG antibodies cross the placenta, causing neonatal weakness.
• Diagnosis: Edrophonium (Tensilon) test; improved strength suggests MG, worsening suggests cholinergic crisis.
• Treatment: Anticholinesterases (pyridostigmine), immunosuppressants (corticosteroids, cyclosporine, azathioprine, mycophenolate), thymectomy, plasmapheresis.

Eaton-Lambert Syndrome

• Associated with small-cell lung carcinoma. Consider in patients with suspected lung cancer undergoing relevant procedures.
• Patients are sensitive to succinylcholine and non-depolarizing neuromuscular blockers (NDMBs). Volatile anesthetics usually provide sufficient muscle relaxation.
• Reversal with anticholinesterases may be inadequate.

Guillain-Barré Syndrome (GBS)

• Pathophysiology: Immunologic assault on myelin in peripheral nerves, disrupting action potential conduction.
• Often preceded by a flu-like illness (1-3 weeks prior). Common etiologies include Campylobacter jejuni, Epstein-Barr virus, CMV, vaccinations, surgery, and lymphoma.
• Signs and symptoms: Flaccid paralysis (distal to proximal, bilateral), intercostal muscle weakness (impaired ventilation), facial and pharyngeal weakness (dysphagia), sensory deficits (paresthesias, numbness, pain).

Familial Periodic Paralysis (FPP)

• Hypokalemic FPP: Avoid glucose-containing solutions, potassium-wasting diuretics, beta-2 agonists, and succinylcholine. NDMBs and acetazolamide are safe. Possible association with malignant hyperthermia (MH), but muscle rigidity may occur without the metabolic changes seen in MH.
• Hyperkalemic FPP: Avoid succinylcholine and potassium-containing solutions. Glucose-containing solutions, potassium-wasting diuretics, beta-2 agonists, NDMBs, and acetazolamide are safe. Succinylcholine use is risky due to potential for hyperkalemia.
• NDMBs are safe for both types, but patients may be sensitive; short-acting agents are best.

Malignant Hyperthermia (MH)

• Triggers: Halogenated anesthetic agents and succinylcholine.
• Pathophysiology: Defective ryanodine receptor (RYR1) causes excessive calcium release from the sarcoplasmic reticulum, leading to sustained contraction, ATP depletion, increased oxygen consumption and CO2 production, acidosis, rhabdomyolysis, and hyperkalemia.
• Consequences of increased intracellular calcium: Rigidity, accelerated metabolism, increased oxygen consumption and CO2/heat production, acidosis, sarcolemma breakdown, potassium and myoglobin release.
• Associated diseases: King-Denborough syndrome, central core disease, multiminicore disease.
• Duchenne Muscular Dystrophy (DMD) association: An MH-like syndrome can occur due to rhabdomyolysis (not true MH). Avoid halogenated agents and succinylcholine; use total intravenous anesthesia (TIVA).
• Treatment of cardiac arrest in DMD patients: Treat as severe hyperkalemia with calcium chloride.
• Most sensitive indicator: EtCO2 rising disproportionately to minute ventilation. Hyperthermia is a late sign.
• Signs and symptoms: Early: Tachycardia, tachypnea, hyperventilation; Intermediate: Muscle rigidity, increased temperature, metabolic acidosis; Late: Severe hyperthermia, cardiac arrhythmias, rhabdomyolysis, disseminated intravascular coagulation (DIC).
• Treatment: 1. Discontinue triggering agents; 2. Hyperventilate with 100% O2; 3a. Change anesthesia circuit and vaporizers if available; 3b. Apply charcoal filter to inspiratory/expiratory ports; 4. Administer dantrolene (or Ryanodex); 5. Cool the patient (<38° C); 6. Correct acidosis with sodium bicarbonate; 7. Treat hyperkalemia (CaCl2, insulin/D50, hyperventilation); 8. Protect against dysrhythmias (procainamide, lidocaine); 9. Maintain urine output (>2 mL/kg/hr) to prevent renal injury; 10. Monitor coagulation.

Duchenne Muscular Dystrophy (DMD)

• Pathophysiology: Absence of dystrophin destabilizes the sarcolemma, increasing membrane permeability during muscle contraction.

This quiz covers the key aspects of Myasthenia Gravis (MG), including its pathophysiology, symptoms, diagnosis, and treatment options. Test your understanding of how MG affects skeletal muscle function and the factors that exacerbate this condition. Explore the critical concepts essential for recognizing and managing MG.