Neuromuscular Diseases

Question 1

Name 3 different causes of sensory neuropathy.

Answer 1

Toxins / drugs (eg Cisplatin, too much Vit B6)
Anti-Hu (ANNA) -associated with small cell carcinoma of lung
Sjogren’s Syndrome

Question 2

What happens if only some of the motor axons going to a muscle die?

Answer 2

Remaining axons can “sprout” and spread to reinnervate the muscle fibers.

Question 3

What happens if some muscle fibers lose motor axons and can’t be re-innervated?

Answer 3

Those muscle fibers atrophy, remaining hypertrophy.

Question 4

What does electromyography tell you about loss of muscle innervation?

Answer 4

It can detect the “sprouting” phenomenon for reinnervation of muscle fibers, as more muscle fibers will be in a single motor group than normally.

Question 5

What do you think if you see the occasional small spike on an EMG while the patient is not contracting that muscle?

Answer 5

Fibrillation from de-innervated muscle.

Question 6

What is the genetic basis of spinal muscular atrophy?

Answer 6

Loss of SMA1.

Question 6

Why can’t SMA2 compensate for the loss of SMA1? How does this affect disease progression?

Answer 6

Only 10% of the protein translated from SMA2 is stable. The more stable protein is made, the milder the disease / slower the progression.

Question 7

What’s a potential therapy for SMA?

Answer 7

Use an anti-sense oligonucleotide to prevent the splicing event that leads to the SMA2 protein instability.

Question 8

What are the most common causes of radiculopathy? (2 things)

Answer 8

Herniated intervertebral disc. Bony overgrowth.

Question 9

What are the most common levels for radiculopathy to occur at? (2 regions)

Answer 9

Cervical: C5, C6, C7, C8
Lumbosacral: L4, L5, S1

Question 10

What are the very most most common specific vertebral segments affected by radiculopathy?

Answer 10

C7 and L5

Question 11

Why are neuropathies worse at distal points in the body?

Answer 11

Because the axons have to travel longer to get there (there’s more possibility of getting messed up).

Question 12

How can EMG be used to measure the progression of neuropathy?

Answer 12

Measure the CAP (compound action potential) amplitude, which is a function of how many intact axons are present at the site.

Question 13

Why do drugs such as vincristine and taxanes cause neuropathy?

Answer 13

These drugs disrupt microtubules which are needed for axonal transport along loooonnnnng axons.

Question 14

Defects in what 4 classes of proteins can cause neuropathy? (based on slide 44)

Answer 14

Tubulin, kinesins, dyneins, “cargo” proteins. (if you want to memorize those gene names… go ahead)

Question 15

Other than being slow, why is else is wrong with a demyelinated axon?

Answer 15

It’s energy inefficient - has to use pumps to restore ion gradients.

Question 16

What’s the most common hereditary demyelinating neuropathy? What gene is mutated? Mechanism of mutation -> disease?

Answer 16

Charcot-Marie-Tooth syndrome. Caused by duplication in PMP22. Too much PMP22 disrupts myelin structure.

Question 17

Why shouldn’t you eat too much pufferfish? MoA?

Answer 17

Contains tetrodotoxin… affects V-gated Na+ channels. (just for fun)

Question 18

What is the Safety Factor concept with regard to the NMJ?

Answer 18

Every motor neuron action potential should have more than sufficient ACh to induce an action potential in the muscle fiber.

Question 19

What are 3 reasons that a muscle might not contract in response to a pre-NMJ action potential?

Answer 19

Not enough ACh is present in the synapse.
Not enough AChR is present and/or functional.
V-gated Na+ channels are not functional.

Question 20

Do pre-synaptic NMJ defects tend to get worse or better (where better = more contraction) with use? How about post-synaptic NMJ defects?

Answer 20

Pre-synaptic NMJ defects: Better with use.

Post-synaptic NMJ defects: Worse with use. (think afternoon ptosis with myasthenia gravis)