Myasthenia Gravis

Pathophysiology of Myasthenia Gravis

Myasthenia gravis is a progressive autoimmune disease caused by autoantibodies directed agains the nicotinic cholinergic (or acetylcholine) postsynaptic receptors of the neuromuscular junction

Signs and Symptoms

1) muscular weakness and fatigability on exertion, with some recovery with rest
2) often presents with ptosis, vision problems, dysarthria, and difficulties chewing and swallowing
3) facial sneer
4) asymmetrical limb weakness
5) can involve diaphragm with respiratory difficulty in late stages

Characteristic Test Findings

Laboratory

1) positive edrophonium (Tensilon) test
2) positive antiacetylchone receptor antibody assay
3) red cell aplasia

EMG

4) decreased action potentials on repetitive nerve stimulation

Histology and Gross Pathology

1) atrophy of type 2 muscle fibers
2) lymphocytic infiltrates
3) flattening of post synaptic folds

Associated Conditions

1) 60% with thymic hyperplasia
2) 15% with thymomas
3) increased incidence of hyperthyroidism (6%)
4) increased incidence of rheumatoid arthritis and lupus (SLE)

Treatment

1) pyridostigmine (anticholinesterase drug)
2) thymemctomy often causes dramatic improvement
3) plasmapheresis
4) intravenous immunoglobulin
5) immunosuppressive drugs (steroids, cyclosporin, azathioprine, mycophenolate mofetil)

Biochemistry

1) type 2 hypersensitivity reaction
2) marked by increased complement activation

Epidemiology

1) female to male, 3:1
2) affects women at age 10-30 years; men, age 50-60 years
3) affects 1/7500

Tips for USMLE

1) if question describes a 24 year old office worker who experiences facial weakness and slurred speech after talking on the phone that resolves 15 minutes after she stops, think myasthenia gravis
2) can be distinguished from other neuromuscular disorders because there are normal deep tendon reflexes and no sensory deficits
3) key pathologic fact is a decrease in number of acetylcholine receptors at the neuromuscular junction