B7.013 Prework 1: Autoimmune Myasthenia Gravis: Diagnosis and Treatment

Question 1

characterize MG

Answer 1

fluctuating weakness with abnormal fatigability that improves with rest
propensity for external ocular muscles

Question 2

cause of MG

Answer 2

post synaptic defect of neuromuscular transmission
Ab mediated attack upon nicotinic ACh receptors
-competes with ACh and causes weakness

Question 3

normally, how much ACh is released into the NMJ to stimulate a contraction?

Answer 3

WAY more than is necessary

this allows for a 1:1 ratio of nerve firing to muscle contraction even after multiple consecutive firings

Question 4

what structural changes occur in the NMJ with MG?

Answer 4

Ab not only binds to receptors, but also causes a low grade inflammatory response resulting in damage to the connections

Question 5

clinical manifestations of MG

Answer 5

ocular: diplopia, ptosis
bulbar: dysarthria, dysphagia, dyspnea
extremity: prox > distal weakness, neck weakness
symptoms may be worse later in the day

Question 6

why can symptoms be worse later in the day?

Answer 6

stores of ACh deplete after each contraction

in a normal person, there is still enough, but in MG, there is not enough to overcome the Ab

Question 7

pattern of involvement in MG

Answer 7

bilateral
symmetric weakness
no numbness
ocular / bulbar muscle weakness

Question 8

initial symptoms of MG

Answer 8

ocular - 53%
leg / arm / neck - 20%
bulbar - 16%
generalized fatigue - 9%

Question 9

course of MG

Answer 9

50% present with diplopia or ptosis
only 15% remain ocular at 3 yrs
<5% mortality due to invention of mechanical ventilation and steroids

Question 10

relationship between MG and thymoma

Answer 10

15% of MG patients have a thymoma
mostly in pts > 30
all new MG patients get a chest CT to look for a thymoma bc removal can aid in remission

Question 11

diagnosis of MG

Answer 11

1. clinical manifestations
2. edroponium test (90% sens, poor spec)
3. AChR Abs (95% sens, good spec)
4. repetitive stimulation (80% sens, poor spec)
5. single fiber EMG (>95% sens, poor spec)

Question 12

function of the edrophonium test

Answer 12

block AChE to allow ACh to remain in the synaptic cleft longer to compete better with the Ab

Question 13

key features of the edrophonium test

Answer 13

must have something to measure (usually ptosis, CANNOT be extremity symptoms)
not required in all patients
can be positive in other diseases

Question 14

what % of MG patients have AChR-Abs

Answer 14

85% gen MG

50% ocular MG

Question 15

describe the repetitive stimulation test in MG

Answer 15

decrement indicates neuromuscular blockage

more likely to be present in weak muscles (usually proximal)

Question 16

function of single fiber EMG

Answer 16

measure single muscle fiber action potentials
measure degree of variability of firing time in 2 fibers in same motor unit (normally AP should fire at same time)
in MG this varies due to delays in NMJ transmission

Question 17

usefulness of single fiber EMG in MG

Answer 17

most sensitive test for MG

but: difficult, time consuming, tedious, requires specialized equipment

Question 18

treatments for MG

Answer 18

cholinesterase inhibitors (pyridostigmine)
immunosuppressive therapies
surgery (thymectomy)

Question 19

pyridostigmine

Answer 19

60 mg TID-QID
can have GI side effects
don’t expect too much or use too much

Question 20

corticosteroids for MG

Answer 20

1st line
improvement in 2-4 weeks
max benefit in 6 months
remission is often steroid dependent

Question 21

collateral steroid program

Answer 21

1800 cal
avoid junk food
vit D supplements
Ca supplements
K+ and H2 blockers if needed
yearly bone density scan

Question 22

plasmapheresis in MG

Answer 22

4-6 exchanges of 3-5 liters of plasma
can be daily or QOD
indications:
-myasthenic crisis
-severe exacerbation
-pre-thymectomy

Question 23

IVIg in MG

Answer 23

given IV
expensive
estimated 70% response

Question 24

how is the thymus related to MG?

Answer 24

up to 80% have thymus abnormalities
lymphocytes in the thymus from MG patients produce AChR-Abs
thymectomy results in a slow and gradual fall in the Ab

Question 25

most specific MG test

Answer 25

serum Ab titers

Question 26

most sensitive MG test

Answer 26

single fiber EMG