B7.013 Prework 1: Autoimmune Myasthenia Gravis: Diagnosis and Treatment Flashcards
characterize MG
fluctuating weakness with abnormal fatigability that improves with rest
propensity for external ocular muscles
cause of MG
post synaptic defect of neuromuscular transmission
Ab mediated attack upon nicotinic ACh receptors
-competes with ACh and causes weakness
normally, how much ACh is released into the NMJ to stimulate a contraction?
WAY more than is necessary
this allows for a 1:1 ratio of nerve firing to muscle contraction even after multiple consecutive firings
what structural changes occur in the NMJ with MG?
Ab not only binds to receptors, but also causes a low grade inflammatory response resulting in damage to the connections
clinical manifestations of MG
ocular: diplopia, ptosis
bulbar: dysarthria, dysphagia, dyspnea
extremity: prox > distal weakness, neck weakness
symptoms may be worse later in the day
why can symptoms be worse later in the day?
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
pattern of involvement in MG
bilateral
symmetric weakness
no numbness
ocular / bulbar muscle weakness
initial symptoms of MG
ocular - 53%
leg / arm / neck - 20%
bulbar - 16%
generalized fatigue - 9%
course of MG
50% present with diplopia or ptosis
only 15% remain ocular at 3 yrs
<5% mortality due to invention of mechanical ventilation and steroids
relationship between MG and thymoma
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
diagnosis of MG
- clinical manifestations
- edroponium test (90% sens, poor spec)
- AChR Abs (95% sens, good spec)
- repetitive stimulation (80% sens, poor spec)
- single fiber EMG (>95% sens, poor spec)
function of the edrophonium test
block AChE to allow ACh to remain in the synaptic cleft longer to compete better with the Ab
key features of the edrophonium test
must have something to measure (usually ptosis, CANNOT be extremity symptoms)
not required in all patients
can be positive in other diseases
what % of MG patients have AChR-Abs
85% gen MG
50% ocular MG
describe the repetitive stimulation test in MG
decrement indicates neuromuscular blockage
more likely to be present in weak muscles (usually proximal)
function of single fiber EMG
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
usefulness of single fiber EMG in MG
most sensitive test for MG
but: difficult, time consuming, tedious, requires specialized equipment
treatments for MG
cholinesterase inhibitors (pyridostigmine)
immunosuppressive therapies
surgery (thymectomy)
pyridostigmine
60 mg TID-QID
can have GI side effects
don’t expect too much or use too much
corticosteroids for MG
1st line
improvement in 2-4 weeks
max benefit in 6 months
remission is often steroid dependent
collateral steroid program
1800 cal avoid junk food vit D supplements Ca supplements K+ and H2 blockers if needed yearly bone density scan
plasmapheresis in MG
4-6 exchanges of 3-5 liters of plasma can be daily or QOD indications: -myasthenic crisis -severe exacerbation -pre-thymectomy
IVIg in MG
given IV
expensive
estimated 70% response
how is the thymus related to MG?
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
most specific MG test
serum Ab titers
most sensitive MG test
single fiber EMG
