MS

Question 1

What are potential triggers for MS?

Answer 1

Must involve genetics and environmental factors. Infection and viruses may also play a role

Question 2

Of the hundreds of MS susceptibility genes identified; name 2 important ones

Answer 2

Strongest association with HLA-DRB1*1501 allele which is present in 30% high risk regions (3x risk for heterozygotes; 6x risk for homozygotes) and rare variants of CYP27B1

Question 3

What likely drives the contribution of genes in MS? What effect does HLA have?

Answer 3

HLA Likely driven by gene-gene interactions and likely has an effect on immune-responses

Question 4

Which race has the highest risk of MS?

Answer 4

White caucasians and northern Europeans

Question 5

What is the hygiene hypothesis?

Answer 5

States that lack of exposure to infectious agents as a young child may lead to more diseases later in life. May fail to properly develop autoimmunity and contribute to MS

Question 6

What effect does migration play in MS?

Answer 6

Migrating from higher to lower latitudes before the age of 15 can reduce your risk of MS

Question 7

What is EBV infection?

Answer 7

Leads to infectious mononucleosis (IM)

Question 8

How does EBV/IM infection affect MS?

Answer 8

Early EBV infection early in life seems to reduce MS risk; later in life seems to increase it. Thought is that the EBV nuclear antigen (EBNA) is similar in form/structure to myelin and the immune system might start to recognize myelin as an infection

Question 9

Describe the the relapsing-remitting phase of MS

Answer 9

Characterized by frequent inflammation; demyelination; axonal transection; and remyelination. Relapses are more frequent and complete recovery from disability generally occurs

Question 10

Describe the the secondary-progressive phase of MS

Answer 10

Inflammation and relapses occur infrequently; axonal loss is increased and disability progresses

Question 11

What is thought to result in the loss of compensatory mechanisms that triggers the conversion from RRMS (relapsing-remitting) to SPMS (secondary progressive)?

Answer 11

The loss of axons beyond a critical threshold

Question 12

What do immune cells inside the brain cause in MS? (2 things)

Answer 12

Demylination and axonal loss

Question 13

Why do patients progress in MS?

Answer 13

Toxins (nitrous oxide; glutamate); Mitochondrial exhaustion; Neural-glial uncoupling; Ion channel dysfunction; Accelerated aging; Loss of compensation/Brain Reserve

Question 14

What does CIS stand for?

Answer 14

Clinically isolated syndrome - the Pts 1st neurological episode

Question 15

What does contrast enhancement at the site of a lesion on an MRI mean?

Answer 15

An active demylinating lesion. Site of active BBB disruption

Question 16

Does MS affect white matter or gray matter?

Answer 16

BOTH

Question 17

What forms the myelin sheath in the CNS? In the PNS?

Answer 17

Oligodendrocytes in CNS. Schwann cells in PNS

Question 18

In a myelinated axon; where does electrical activity occur?

Answer 18

nodes of Ranvier (gaps in the myelin)

Question 19

Why does demyelination lead to slowing of conduction velocity?

Answer 19

loss of saltatory conduction

Question 20

Name 8 common MS Symptoms

Answer 20

Fatigue. Walking impairment. Spasticity. Cognitive impairment. Bladder dysfunction. Pain. Mood instability. Sexual dysfunction

Question 21

Gait description in MS

Answer 21

Ataxic. Spastic. Paretic. Foot drop

Question 22

What factors are involved in MS walking impairment?

Answer 22

Muscle weakness (Results in toe drag; foot drop; vaulting). Spasticity. Loss of balance/Sensory deficit (Affects ability to feel the floor/know where the foot is). Fatigue.

Question 23

What affect does demyelination have on sodium channels?

Answer 23

Produces proliferation of sodium channels along the axon

Question 24

How does proliferation of sodium channels affect nerve conduction?

Answer 24

With increased sodium entry into the cell there is slowing of nerve conduction. Ultimately there may be reversal of sodium-calcium exchanger > Calcium Influx (produces calcium-mediated nerve injury)

Question 25

How can axons be preserved in EAE?

Answer 25

Sodium channel blockers (phenytoin and flecainide)

Question 26

What medicine is used to improve walking speed in MS patients?

Answer 26

Dalfampridine

Question 27

What is the mechanism of action of dalfampridine? How does this work?

Answer 27

K+ channel blocker. It enhances conduction of action potentials in demyelinated axons through inhibition of K+ channels. (doesn’t stop the immune response; but helps people walk better; think faster; decrease fatigue)

Question 28

Other ways to treat MS?

Answer 28

Block action of B cells in the brain; block the blood-brain barrier; etc.