NMJ and Muscle Disorders

Question 1

mechanism of myasthenia gravis

Answer 1

AB against muscle type nAChR

so less receptors for ACh binding –> decr depol and decr muscle contraction

Question 2

2 clinical forms of myasthenia gravis

Answer 2

1) ocular = weakness limited to eyelids and extraocular muscles
2) generalized = weakness (also affects ocular) but also bulbar, limb, and resp muscles

Question 3

hallmark of myasthenia gravis

Answer 3

acute onset of fluctuating weakness

fatigability
progressively weaker during activity and improve after rest

Question 4

physical exam of myasthenia gravis

Answer 4

can be normal

weakness often asymmetric

Question 5

progression of disease and signs and symptoms

Answer 5

2/3 start with diplopia (double vision or ptosis (droop eyelid)

also

1) facial weakness, dysphagia
2) slurred speech
3) shortness of breath –> resp arrest
4) neck muscle weakness
5) prox arm/leg weak –> quadriplegia
6) ophthalmoparesis (paralysis of EOM)

Question 6

immunopath of myasthenia gravis

effects of diff antibodies

Answer 6

autoantibodies against

1) muscle type nAChR
2) impair ability of ACh to bind R
3) destruction of receptor from complement fixation or induce muscle cell to elim recepotrs via endocytosis

Question 7

mechanism of antibody production

Answer 7

1) B cells make plasma cells via T helper stim

2) T helpers first activated via binding of TCR to AChR epitope

Question 8

what do myasthenia gravis patients often have assoc (another organ problem)

Answer 8

thymoma due to involvement of T cell production and TCR

thymectomy in MG effective

Question 9

drugs used in MG

1) edrophonium

Answer 9

super fast onset and short acting
used to dx MG

should be marked improvement in muscle tone (Tensilon test)

Question 10

drugs used in MG

2) prednisone

Answer 10

immunosuppression but often make patients worse via NMJ block before better

Question 11

drugs used in MG

3) azathioprine

Answer 11

GOLD STANDARD
antimetabolite that blocks cell prolif to inhib T lymphocytes

decr AChR antiboides

Question 12

side effects of azathioprine

Answer 12

1) fever, anorexia, nausea, vomit, abd pain (like flu)

2) takes 3 mo to 1 yr for response

Question 13

drugs used for MG crisis

Answer 13

plasmapharesis

IVIG

Question 14

define Duchenne/Becker

Answer 14

disorder of proximal muscle weakness

Question 15

Duchenne’s

1) age of onset
2) early signs
3) late signs

Answer 15

1) 2-4 y/o
2) lordosis, pseudohypertrophy, Gower’s, awk gait

3) toe walk, tripping, slow run, waddle, mental retard (70%), big tongue
progressive scoliosis & contractures

Question 16

Becker’s

1) age of onset
2) sx

Answer 16

1) 8 y/o

2) same as Duchenne but less severe

Question 17

specific genetic defect in DMD

Answer 17

mutation in dystrophin gene (longest gene in body; found on X chromosome)

either point mutation –> premature stop –> non functional, truncated

but becke’rs = low MW dystrophin so decr fxn (not as severe)

Question 18

function of Dystrophin

Answer 18

connect cytoskeleton of muscle fiber to surrounding ECM via cell membrane

Question 19

pathologic changes of muscle in DMD and Becker’s

Answer 19

DMD = fibrosis, degeneration, opaque fibers

on EM = delta lesion (disruption in plasma membrane) –> hole for calcium to leak in –> activ Ca2+ activ neutral protease –> necrosis of myofiber