Demyelinating disease week 6

Question 1

State whether or not the following nerves are myelinated:

post-ganglionic autonomic nerves

A-delta pain fibers

olfactory nerves

C pain fibers

Answer 1

Unmyelinated: post-ganglionic autonomic, olfactor nerves, C pain fibers. Are all about 1 micron in thickness

myelinated: A-delta pain fibers

Question 2

What are 4 ways in which nerve function may be restored in the case of demyelination?

Answer 2

1. Remyelination
2. Axonal sprouting
3. Renetworking in the brain and spinal cord
4. Redistribute sodium channels throughout the demyelinated region-restores conduction (see attached)

Question 3

Explain the effects cooling has on voltage gated Na and K channels and how this affects APs.

Answer 3

Cooling the body decreases voltage gated Na channel activation and inactivation and also decreases K activation.

These combined prolong the AP. Note that this is a desired effect in demyelinating disease. Increasing the length of an AP increases the chances of the AP reaching the next segment of the axon.

Question 4

Explain the effects scorpion venom has on voltage gated Na and K channels and how this affects APs.

Answer 4

Scorpion venom prolongs the time for Na+ inactivation. This prolongs the AP and allows Na+ to bring the membrane potential closer to its equilibrium potential. A more depolarized membrane means that it takes longer for K+ channels to repolarize the membrane.

Question 5

Explain the effects 4-aminopyridine has on voltage gated Na and K channels and how this affects APs.

Answer 5

4-aminopyridine blocks voltage gated K+ channels. This prolongs the AP because there are less available K+ channels to repolarize the membrane.

Question 6

Explain the effects decreased Ca+ in serum has on voltage gated Na and K channels and how this affects APs.

Answer 6

If there is less Ca2+ in serum, there is more calcium in the neuron making the resting membrane potential less negative. The membrane is closer to its threshold and is therefore more excitable.

Note that there is no direct effect on Na and K voltage gated channels (that was discussed in this lecture).

Question 7

Explain the effects heating has on voltage gated Na and K channels and how this affects APs.

Answer 7

Heating increases Na+ channel activation and inactivation and also increases K+ channel activation. This shortens the AP.

Note that in individuals with demyelinating disease, they may become symptomatic while taking hot showers, for example due to this phenomenon.

Question 8

Explain the effects carbamazepine has on voltage gated Na and K channels and how this affects APs.

Answer 8

Carbamazepine blocks voltage gated Na+ channels. This decreases the amplitude and length of the action potential. K+ can repolarize the membrane faster because the depolarization is not as large (due to blockage of Na+ channels).

Question 9

What is Lhermitte’s sign? In what type of disease may it be present in?

Answer 9

Lhermitte’s sign is an electric sensation shooting down the spine and/or arms/legs upon flexion of the neck.

Lhermitte’s sign is seen in demyelination disease, e.g. MS, but also others such as cervical spondylosis, herniation of a cervical disc, a cervical spinal cord tumor)

Question 10

What are phosphenes?

Answer 10

phosphenes: A visual phenomenon of seeing tiny sparkling lights in dark environment upon moving the eyes (usually monocular)

Question 11

What is Uthoff’s phenomenon? Explain when it is observed?

Answer 11

Uthoff’s phenomenon: dimming or obscuring of vision with increases in body temperature.

Occurs in a person with marginally impaired conduction in the optic nerve whose vision is normal (latency delay on visual evoked response present).

Test: elevating person’s body temperature (exertion, hot bath, circadian) causes vision to become blurry.

Similar worsenings can occur with strength, numbness-tingling.

Question 12

Name examples of congenital causes of demyelination.

Answer 12

• Congenital
• Phenylketonuria and other aminoacidurias
• Tay-Sachs, Niemann-Pick, and Gaucher diseases (lipid storage diseases)
• Hurler syndrome (MPS type 1)
• Leukodystrophies (Krabbe disease)
• Mitochondrial disorders (Leber hereditary optic atrophy)

Question 13

Give examples of infectious causes of demyelination.

Answer 13

• Infectious
• JC virus (progressive multifocal leukoencephalopathy)
• HTLV-1 virus (tropical spastic paraparesis)
• Measles virus (subacute sclerosis panecephalitis)
• Leprosy
• HIV

Question 14

Give examples of mechanical, toxic, and nutritional causes of demelination.

Answer 14

• Mechanical (compression)
• Toxic: EtOH, chloroquine, tacrolimus, CO
• Nutritional:
• Vitamin B12
• Osmotic demyelination syndrome (sodium)
• Marchiafava-Bignami (rare condition of demyelination of the corpus callosum, related to alcoholism)

Question 15

Name examples of inflammatory causes of demyelination.

Answer 15

• Inflammatory
• Multiple sclerosis
• Chronic inflammatory demyelinating polyradiculopathy
• Guillain Barre (Acute Inflammatory Demyelinationg Polyradiculopathy). autoimmune condition that destroys Schwann cells-PNS disease
• Devic’s disease (neuromyelitis optica)
• Multifocal motor neuropathy
• Ig related neuropathies

Question 16

Explain the pathology of MS (how demyelination begins).

Answer 16

• Breakdown of the blood-brain barrier
• Migration of autoreactive T-cells and B-cells
• Production of demyelinating antibodies
• Stimulation of macrophages to destroy myelin and axons