NMJ Dysfunction

Question 1

Key feature of Myesthenia gravis

Answer 1

Antibodies to AchR - block AcH binding

Question 2

What happens to the receptors?

Answer 2

Destruction due to complement - and removal

Question 3

In what percent of patients are there antibodies to AchR

Answer 3

80%

Question 4

What is Myesthenia gravis due to

Answer 4

10% - Thymoma

70% Thymic hyperplasia

Question 5

Key clinical feature of MG

Answer 5

Muscle weakness

a) Fatigability
b) Proximal>distal muscles AND SYMMETRIC
c) Droopy eye lids
d) CN 9.10.11.12 weakness - bulbar

Question 6

What is the safety factor?

Answer 6

It ensures that the action potential can still cause firing even though less Ach is available due to repetitive stimulation
In MG - repetitive stimulation results in drop below threshold and no firing

Question 7

How do you assess for MG?

Answer 7

1. Ask patient to look up, count, or hold limb position
2. Give edrophonium - block AchEsterases, and more Ach is in the cleft
3. Ice-pack test - reduce enzyme function

Question 8

What is Lambert-Eaton syndrome?

Answer 8

Antibodies against the calcium channels, so no Ach is released from presynaptic membrane

Question 9

What is the common cause of LES?

Answer 9

1. 50% with malignancy (of those 80% are SCLC)

Question 10

Key clinical features of LES

Answer 10

1. Post-exercise, stronger muscles
2. Gradual leg weakness
3. Autonomic dysfunction (dry mouth, constipation)
4. Minimal ocular and bulbar symptoms

Question 11

How do you get stronger post-exercise in LES?

Answer 11

1. Repetitive stimulation - results in calcium accumulation

2. Give 3,4Diaminopyridine - increase calcium and block sodium channel and prolong AP