Multiple Sclerosis Vignette

Question 1

MS symptoms

Answer 1

Muscle and mental fatigue. Multi-tasking challenging (cognitive dysfx). Pts most likely don't return to baseline after relapses. 
Spasticity. 
Gait issues. 
bladder dysfx. 
Depression anxiety.

Question 2

Optimal treatment window

Answer 2

Treat early! Treat before you get degeneration.

Question 3

BBB

Answer 3

the BBB is compromised, so you see enhancement/ contrast on imaging.
Can visualize tracts, measure myelination.. can see beyond lesions and where brain is affected. FmRI (can see activated area with task). MS pts use more neurons (why more fatigue) because try to compensate.

Question 4

Moleculary mimicry

Answer 4

Immune system responding to an antigen that looks like a virus, but they are actually attacking the host.

Question 5

Genetics

Answer 5

Over 100 genes implicated (they may increase chance of immune system dysfx.). You don’t inherit MS, just pass certain genes on. Chance with relative 3%, without 0.7%

Question 6

Pathology

Answer 6

Immune cells get activated and destroy myelin. T and B cells and macrophages.
Perpendicular from lateral ventricles (Dawson’s fingers) get demyelination.

Question 7

Why symptoms?

Answer 7

Muscles want to contract but brain stops them.

Question 8

Tests

Answer 8

You can measure all the gait issues.
we also have a tool to measure how fast nerve cells respond.
Visual response (signal, record activity in occipital lobe with electrodes).

Question 9

What are results of visual testing?

Answer 9

You have DECREASED amplitude (amount of response, lost axons), and prolonged latency.

Question 10

Demyelination

Answer 10

Proliferation of Na channels along axon. This is compensation so you can get better signals in Naked axons.
Don’t have nodes.

Question 11

Result of increased Na channels?

Answer 11

Increased Na entry, slowed nerve conduction. Get worse with this intended compensation.
Ultimately may get reversal of Na/Ca exchanger, Ca influx (get Ca mediated nerve injury).

Question 12

Na blockers

Answer 12

Drugs. Phenytoin and Flecainide. To preserve axons (sig. side effects).

Question 13

MS drugs?

Answer 13

Naked axon, K channels not protected by myelin and you get K leakage.
Dafampridine. Targets these and blocks, keeps K inside, helps return resting potential to normal.
Helps with ambulation (25-30% increase in walking speed), thinking, less fatigue.
May avoid tissues b/c normal axons have hidden K+.

Question 14

General axon fx. resting

Answer 14

1.) Start AP at axon hillock w/ depolarization (decreased Vm). Often via Na influx.
Essential to maintain resting state’s distribution of ions for AP (via diffusion & active transport). K greater inside, Na greater outside.
2.) Nav closed at rest. Neg charge builds up in cell. Impermeable to anions. Potential diff is -70 (closer to Ek). RESTING POTENTIAL.

Question 15

Rising phase

Answer 15

Nav open (b/c of depol) Na FLOWS INTO cell, down gradient. Electric current created. Go to +40mV (closer to Ena), ICF now positive.
Depol must be large enough to overwhelm outward K, run away.
Nav close/inactivate

Question 16

Falling phase/ repolarization

Answer 16

Kav open, K flows out. Slowly restore to resting potential. Back to Ek.
Refractory period now.

Question 17

Why is transmission unidirectional?

Answer 17

Because refractory period.

Question 18

Where is electrical activity?

Answer 18

Only at nodes of ranvier. AP’s generated here only.

Large diameter, decreased resistance, faster conduction.

Question 19

Propagation

Answer 19

local depol causes passive diffusion of ions in adjacent areas, get to -50mV. Thus get propagation.

Question 20

AP definition

Answer 20

Change in electrical potential across membrane.