Neuromuscular Diseases Flashcards
Name 3 different causes of sensory neuropathy.
Toxins / drugs (eg Cisplatin, too much Vit B6)
Anti-Hu (ANNA) -associated with small cell carcinoma of lung
Sjogren’s Syndrome
What happens if only some of the motor axons going to a muscle die?
Remaining axons can “sprout” and spread to reinnervate the muscle fibers.
What happens if some muscle fibers lose motor axons and can’t be re-innervated?
Those muscle fibers atrophy, remaining hypertrophy.
What does electromyography tell you about loss of muscle innervation?
It can detect the “sprouting” phenomenon for reinnervation of muscle fibers, as more muscle fibers will be in a single motor group than normally.
What do you think if you see the occasional small spike on an EMG while the patient is not contracting that muscle?
Fibrillation from de-innervated muscle.
What is the genetic basis of spinal muscular atrophy?
Loss of SMA1.
Why can’t SMA2 compensate for the loss of SMA1? How does this affect disease progression?
Only 10% of the protein translated from SMA2 is stable. The more stable protein is made, the milder the disease / slower the progression.
What’s a potential therapy for SMA?
Use an anti-sense oligonucleotide to prevent the splicing event that leads to the SMA2 protein instability.
What are the most common causes of radiculopathy? (2 things)
Herniated intervertebral disc. Bony overgrowth.
What are the most common levels for radiculopathy to occur at? (2 regions)
Cervical: C5, C6, C7, C8
Lumbosacral: L4, L5, S1
What are the very most most common specific vertebral segments affected by radiculopathy?
C7 and L5
Why are neuropathies worse at distal points in the body?
Because the axons have to travel longer to get there (there’s more possibility of getting messed up).
How can EMG be used to measure the progression of neuropathy?
Measure the CAP (compound action potential) amplitude, which is a function of how many intact axons are present at the site.
Why do drugs such as vincristine and taxanes cause neuropathy?
These drugs disrupt microtubules which are needed for axonal transport along loooonnnnng axons.
Defects in what 4 classes of proteins can cause neuropathy? (based on slide 44)
Tubulin, kinesins, dyneins, “cargo” proteins. (if you want to memorize those gene names… go ahead)
Other than being slow, why is else is wrong with a demyelinated axon?
It’s energy inefficient - has to use pumps to restore ion gradients.
What’s the most common hereditary demyelinating neuropathy? What gene is mutated? Mechanism of mutation -> disease?
Charcot-Marie-Tooth syndrome. Caused by duplication in PMP22. Too much PMP22 disrupts myelin structure.
Why shouldn’t you eat too much pufferfish? MoA?
Contains tetrodotoxin… affects V-gated Na+ channels. (just for fun)
What is the Safety Factor concept with regard to the NMJ?
Every motor neuron action potential should have more than sufficient ACh to induce an action potential in the muscle fiber.
What are 3 reasons that a muscle might not contract in response to a pre-NMJ action potential?
Not enough ACh is present in the synapse.
Not enough AChR is present and/or functional.
V-gated Na+ channels are not functional.
Do pre-synaptic NMJ defects tend to get worse or better (where better = more contraction) with use? How about post-synaptic NMJ defects?
Pre-synaptic NMJ defects: Better with use.
Post-synaptic NMJ defects: Worse with use. (think afternoon ptosis with myasthenia gravis)
