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Myasthenia Gravis


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What is the primary symptom of MG?
Intermittant exertional fatigue
Name 3 pieces of evidence that point to MG being autoimmune in nature.
1. Increased frequency of MHC markers
2. Thymic hyperplasia and improvement of symptoms following thymectomy
3. Transient neonatal MG caused by transfer of maternal antibodies
4. IgG and C3 found bound to nACh receptor
5. MG can be induced in animals by passive transfer of IgG
6. Often associated with other auto-immune disorders
In normal patients does repetitive stimulation of the NMJ cause increase or decrement of the AP strength?
No - in normal patients AP strength remains constant.
How does repetitive stimulation of nerve fibers affect ACh release from the presynaptic neuron?
Even in normal patients, repetitive stimulation leads to less ACh being released from the presynaptic neuron.
In MG patients, what happens to post-synaptic AP strength with repetitive stimulation?
AP strength decrements - this is the basis for the exertional fatigue.
Name 3 means of diagnosing MG.
1. Improvement of muscle fatigue upon administration of Tensilon.
2. Signal decrement upon repetitive stimulation of muscle fibers
3. Presence of ACh receptor antibodies
How does the lack of functional ACh receptors affect threshold in MG patients?
It effectively raises threshold.
What is the mechanism of synaptic failure in MG patients?
*lack of functional ACh receptors effectively raises the AP threshold at the NMJ
*EPP's that are generated are unable to reach AP threshold
*when AP's are generated they are delayed due to the higher threshold
Typically a single autoantibody type is the cause for development of MG.
MG is most often due to polyclonal autoimmune effects.
What are two problems with the use of ACh-esterase inhibitors in the treatment of MG?
1. Short half-life requires frequent dosing
2. Overdosage results in a paralyzing depolarizing blockade.
Which immunosupressive drug used in the treatment of MG is selective for T-cells?
Why has vaccination against autoantibodies been generally unsuccessful in the treatment of MG?
Due to the polyclonal nature of the autoimmune response it has been difficult to generate an effective vaccine.
Why does plasma exchange help in the treatment of MG?
It decreases the level of circulating auto-antibodies.

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