Multiple Sclerosis

Question 1

Is MS just a demyelinating disease?

Answer 1

No. It also causes axonal loss.

Question 2

Two viruses associated with MS?

Answer 2

EBV (which is responsible for most of the bad things in the world)
HHV-6

Question 3

Two bacterial pathogens with a less robustly proven association with MS?

Answer 3

Chlamydia pneumoniae

Mycoplasma

Question 4

What is the age range for peak incidence of MS?

Answer 4

The slides give two different ranges:
Most cases begin in 15 - 45 year olds.
Peak incidence is at 25 - 35 years old.

Question 5

What is the female to male ratio of people with MS?

Answer 5

2:1 (mostly women, but definitely lots of men get it)

Question 6

What’s interesting about the geographic distribution of MS?

Answer 6

It’s most prevalent in temperate latitudes. (why that is, we don’t know)

Question 7

What is the strongest genetic risk factor for MS? Why is this important?

Answer 7

HLA-DRB1501 (an MHC II molecule)

That’s consistent with this being an autoimmune disease.

Question 8

Are environmental triggers important in people who are genetically predisposed to MS?

Answer 8

Yep. (Concordance rate between identical twins is only 30%)

Question 9

Most common form of MS?

Answer 9

RRMS - relapsing remitting MS

Question 10

9 typical signs/symptoms of MS?

Answer 10

Focal UMN weakness
Focal numbness / parethesias (tingling, often in band-like pattern)
Optic neuritis
Dysarthria (speech difficulties)
Lhermite's
Uhthoff's
Dyscoordination / poor balance
Spastic bladder
Spasticity, esp in legs.

Question 11

What is Lhermitte’s phenomenon? What does it indicate?

Answer 11

Flexion of neck causes parathesias. Indicates that nerves are demyelinated.

Question 12

What is Uhthoff’s phenomenon?

Answer 12

Symptoms of MS get worse when patient is overheated. Demyelinated nerves’ conduction speeds steeply drop when temperature increases.

Question 13

4 clinical patterns of MS? Briefly describe each.

Answer 13

RRMS - relapsing remitting MS - symptoms intermittent, with return to baseline.
SPMS - secondary progressive MS - deficits that happen in intermittent attacks tend to persist.
PPMS - primary progressive MS - gradual decline in function.
PRMS - progressive relapsing MS - gradual decline in function accompanied by intermittent attacks that remit.

Question 14

Without treatment, how many years does it take for 50% of MS patients to need help walking? Has this improved with treatment?

Answer 14

About 15 years. We’re not sure how effect disease-modifying therapy is at delaying progression - it has only existed since 1993.

Question 15

Why are MS lesions gadolinium enhancing on T1 MRI?

Answer 15

Immune infiltration / inflammatory cytokines disrupt the BBB.

Question 16

Is MS thought to begin in the CNS?

Answer 16

No, it’s thought to be triggered by some immunogenic something in the periphery.

Question 17

3 pathological results of the immune inflammation in MS?

Answer 17

Demyelination
Axonal loss
Brain atrophy

Question 18

2 histological features of MS?

Answer 18

Lipid(myelin)-laden macrophages.

Perivascular lymphocytosis.

Question 19

To MS lesions respect vascular territory?

Answer 19

Nope.

Question 20

What does FLAIR-weighted MRI show you about MS?

Answer 20

Area of demyelination.

Question 21

What are “black holes” on a T1 MRI in MS?

Answer 21

Areas of axon loss.

Question 22

What are 4 potential self antigens involved in MS? (probably only 1 is important to know, though)

Answer 22

Myelin basic protein (most important)
Proteolipid protein
Myelin oligodendrocyte glycoprotein
Myelin associated glycoprotein

Question 23

What’s key to diagnosing MS?

Answer 23

There must be distinct lesions separated in space and time. (can be clinically, or as old / new lesions seen on an MRI)

Question 24

What are “Dawson’s fingers”? What do they indicate?

Answer 24

On a FLAIR weighted MRI, ovoid hyperintense regions oriented perpendicular to the ventricles. They indicate demyelination (in perivenular areas).

Question 25

Other than clinical examination and MRI, what are 2 tests used to diagnose MS?

Answer 25

Evoked potentials (eg. light in eye -> occipital cortex)
LP for lymphocytes and increased IgG

Question 26

What 4 demyelinating diseases must you exclude when diagnosing MS?

Answer 26

Lyme
Sarcoid
B12 deficiency
HIV

Question 27

What two tracts in the CNS does MS have a particular affinity for? Signs associated with lesion there?

Answer 27

Optic nerve -> optic neuritis.

MLF (medial longitudinal fasciculus) -> INO (internuclear opthalmoplegia - can’t adduct in horizontal gaze)

Question 28

Where does an MS lesion causing bilateral symptoms of both weakness and parathesias probably localize?

Answer 28

Spinal cord (would be hard to do all that with one lesion in the brain).

Question 29

Do all gadolinium-enhancing lesions cause symptoms?

Answer 29

Nope. Only about 1 in 5-10 do.

Question 30

What characteristic must the elevated CSF IgG levels have in order to be consistent with MS?

Answer 30

Must be oligoclonal. Monoclonality would suggest lymphoma.

Question 31

Treatment of moderate/severe acute MS flare-ups? 3 things.

Answer 31

IV steroids
Physical therapy
Symptomatic treatment

Question 32

Name a few different mechanisms of disease modifying therapies for MS?

Answer 32

Type 1 interferon (most common?)
Myelin basic protein analog (soak up auto-Abs)
Anti-alpha 4 integrin antibody (block migration)
Trap T cells in lymph nodes
Block lymphocyte proliferation
Block cell proliferation in general