Myasthenia Gravis

Question 1

What is myasthenia gravis?

Answer 1

autoimmune disorder of neuromuscular transmission

Question 2

What are the hallmarks of myasthenia gravis?

Answer 2

fluctuating degree and variable combination of weakness in ocular, bulbar, limb, and respiratory muscles

Question 3

What is the cause of myasthenia gravis?

Answer 3

antibody-mediated T-cell dependent immunologic attack directed at proteins in the postsynaptic membrane of the neuromuscular junction (acetylcholine receptors)

Question 4

What are common bedside tests for myasthenia gravis?

Answer 4

ice pack test and edrophonium test

Question 5

What is the ice pack test?

Answer 5

used for patients with ptosis - bag of ice is place on closed eyelid for 2 minutes and then removed - improvement in ptosis is a positive response

Question 6

What is the edrophonium test?

Answer 6

Tensilon test - used for patients with ptosis or ophthalmoparesis - 1 mL of edrophonium (10 mg/mL) is drawn up and administered IV - improvement in symptoms after administration of 4-6 mg is a positive response

Question 7

What is edrophonium chloride (Tensilon)?

Answer 7

acetylcholinesterase inhibitor with rapid onset (30-45 seconds) and short duration of action (5-10 minutes) that prolongs presence of acetylcholine in the neuromuscular junction and results in immediate increase in muscle strength (AEs: cardiac decrease and bronchial asthma)

Question 8

What are the serologic indicators for myasthenia gravis?

Answer 8

autoantibodies against the acetylcholine receptor (AChR-Ab) or receptor-associated protein, muscle specific tyrosine kinase (MuSK-Ab)

Question 9

What is the relationship between AChR-Ab and MuSK-Ab in myasthenia gravis?

Answer 9

those positive for AChR-Ab do not have antibodies to MuSK-AB, but nearly half of those who are negative for AChR-Ab are positive for MuSK-Ab (latter less likely to have thymic pathology)

Question 10

What is seronegative myasthenia?

Answer 10

patients who have negative standard assays for both AChR and MuSK antibodies - more likely to have purely occular disease - respond to pyridostigmine, plasma exchange, glucocorticoids, immunosuppressive therapy, thymectomy

Question 11

What types of electrodiagnostic studies are used to confirm diagnosis of myasthenia gravis?

Answer 11

repetitive nerve stimulation and single-fiber electromyography

Question 12

What is repetitive nerve stimulation?

Answer 12

placement of recording electrode over endplate of a muscle and stimulating the motor nerve to that muscle (6-10 times at 2-3 Hz) - progressive decline (> 10%) in compound muscle action potential is consistent with myasthenia gravis

Question 13

What is single fiber electromyography?

Answer 13

most sensitive diagnostic test for myasthenia - allows simultaneous recording of action potentials of two muscle fibers innervated by same motor axon (must be a limb and a facial muscle) - variability of second action potential relative to the first is called “jitter” - increased jitter consistent with myasthenia gravis

Question 14

What are the most common thymic disorders associated with myasthenia gravis?

Answer 14

thymic hyperplasia and thymic tumors (thyoma)

Question 15

What other autoimmune disorders are commonly seen in patients with myasthenia gravis?

Answer 15

rheumatoid arthritis and systemic lupus erythematous

Question 16

What are the clinical forms of myasthenia gravis?

Answer 16

ocular (weakness limited to eyelids and extraocular muscles) and generalized (weakness affects ocular, bulbar [responsible for speech and swallowing], limb, and respiratory muscles)

Question 17

What are the clinical features of myasthenia gravis?

Answer 17

muscle weakness (not fatigue) worse in the evening - ptosis (pupils are always spared), diplopia, dysarthria, dysphagia, fatigable chewing, proximal limb weakness

Question 18

What is the curtain sign?

Answer 18

ptosis that increases with sustained upward gaze or by holding up the opposite eyelid with the examiner’s finger

Question 19

What is the myasthenic sneer?

Answer 19

weakness of facial muscles causes mid-lip to rise but outer corners of mouth fail to move

Question 20

What is the dropped head syndrome?

Answer 20

weight of head overcomes weakness in neck muscles

Question 21

What is myasthenic crisis?

Answer 21

respiratory muscle weakness that leads to respiratory insufficiency and pending respiratory failure

Question 22

What are the phases of myasthenia gravis?

Answer 22

(1) acute - most fluctuations and most severe symptoms - 5-7 years after onset, (2) symptom stability, (3) remission may occur