Neuro - Ms And Diseases Of Myelin

Front 1

MS prevalance

Back 1

Northern NE

Much more common in women

Front 2

Genetic predisp of MS

Back 2

DR2 predominant.

Front 3

Relapsing-remitting MS

Back 3

Most common.

Attack, disability, return almost to baseline, repeat.

Front 4

Secondary progressive MS

Back 4

Second most common

After disability, basically no return to a baseline. But it stays there for a while.

So it gets worse much quicker the RRMS.

Front 5

Primary progressive MS

Back 5

Later onset, male dominant.

Patient just gradually gets worse and worse.

Front 6

Progressive relapsing MS

Back 6

After disability, It goes back to baseline but then gradually gets worse. Then there is a quick jump up in disability. Repeat.

Front 7

Dx of MS - general

Back 7

Easily missed, must be thinking about it.

Also it is kinda treatable, so early detection is critical.

Front 8

What is an MS attack?

Back 8

This is what causes the disability.

Can be subjective (e.g. change in sensory) or objective (strange gait, vision change, etc.)

24 hour duration minimum

Must be 30 day gap between attacks.

Front 9

Psuedoattack

Back 9

not a true MS attack

It lasts less than 24 hours.

Front 10

Pathophys of MS

Back 10

T cell activated and upregulated Alpha-4-beta-1. This recognizes VCAM on BBB and chemokines are secreted to allow metalloproteinases to break BBB and let T cell in.

The T cell is then reactivated in CNS (most likely by a B cell) and then NO eventually causes demyelination.

Front 11

Common clincial sx of MS

Back 11

Fatigue (due to IL-6 - just like in CA)
Numbness
Optic Neuritis
Weakness (hemiparesis or transverse myelitis)
Diplopia
Poor coordination (gait ataxia, dysmetria)
Short-term memory loss (executive functions)
Depression and sexual dysfunction
Bladder and bowel dysfunction
Slurred speech

IT IS ALSO A DISEASE OF GRAY MATTER!!!

Front 12

Time/space dissemination

Back 12

Two neuro events must be separated by 30 days and two anatomic events must be confirmed (e.g. optic neuritis and leg parasthesia).

Front 13

Dx criteria of MS

Back 13

Often a dx of exclusion

Not due to another disease (lupud, thyroid, B12, Lyme, etc.)

Time/space dissemination

Positive MRI

Front 14

3 categories of MS dx

Back 14

Clinically defined - all criteria met

Probable - All criteria met except only one objective change on exam despite two symptomatic episodes or one symptomatic episode and 2+ objective changes.

At risk for MS - all criteria met except only 1 symptomative and 1 objective finding on exam. Or it is a clinically isolated syndrome (a 1 time neurological episode)

Front 15

MRI - T1

Back 15

ASSESSMENT OF THE DEGEN PROCESS

Assess black holes and atrophies determined by brain paraenchymal fraction. This is ebcasue inflammation over time causes holes in the brain near the ventricles and they fuse together to reduce brain mass.

Front 16

MRI - T2

Back 16

ASSESS INFLAMMATORY PROCESS

AKA FLAIR-assess disease burden.

Front 17

MRI - T1 plus gadolinium

Back 17

Assess recent events disrupting BBB. To tell if it is active within past 2-4 weeks.

Front 18

Upwards extensions on sagittal view of MRI (from corpus callosum)

Back 18

Dawson's fingers

very characteristic of MS.

Front 19

Positive MRI for MS

Back 19

3/4:

1 gadolinium enhancing CNS lesion or 9 T2 (or FLAIR) hyperintensities

1 or more cord/infratentorial lesion

1 or more juxtacortical lesion

3 or more paraventricular lesions.

Front 20

2 other lab studies to confirm MS

Back 20

Positive CSF - oligoclonal IgG bands in CSF, and not in serum. (this is bc there are b cell germinal centers in brains of MS patients. Must also have low cellularity)

Positive VER - (visual evoked response) - Asymm. in time for optic nerve signal to get to back of brain - signals demyelination. Wave form will be delayed but well preserved.

Front 21

2 parts of MS

Back 21

1st part - inflammatory

2nd part - degenerative

Front 22

What happens to axons in MS?

Back 22

Transected (cut) - independent of areas of inflammation.

Front 23

MS is an ____ disease

Back 23

immunological!

(remember, ventricles will expand dramatically)

Front 24

Pro-inflammatory and neurotoxic factors

Back 24

IL-17,2
Th1 cytokines
TNF alpha
NO
ROS
glutamate
Abs and complement
cell-mediated neurotoxicity.

Front 25

Anti-inflammatory and neuroprot. factors

Back 25

Th2
TGF-beta
IL-10
Neurotrophic factors (BDNF, NGF, NT-3, CNTF, GDNF)

Front 26

Tregs in MS

Back 26

Dysfunctional. Missing foxp3.

Front 27

BDNF levels in MS

Back 27

increase during relapses and recovery to repair damaged tissue.

Dramatic increase near MS lesions.

Front 28

IFN-beta

Back 28

All injections

Avonex (lose dose - once per week)

Betaseron (every other day - "qod") or Rebif (3x per week)

This is pro-inflammatory normally, but at high levels it turns itself off.

Used in tx of relapsing MS.

For RRMS

Front 29

Glatiramer acetate (Copaxone)

Back 29

For RRMS or clinically isolated syndrome

It is random AAs that is the core of myelin basic protein. Shifts to a Th2 response and assists TRegs.

Front 30

Natalizumab (Tysabri)

Back 30

RRMS
Antibody to alpha-4-beta-1 so T cells can't cross BBB.

Also used for Crohn's disease.

Can cause bad infections

Front 31

Mitoxantrone

Back 31

For secondary progressive MS. A chemo agent.

Front 32

IFN beta mech of action

Back 32

Downreg matrix metalloproteinases (they break BBB) and make more soluble VCAM receptor (to outcompete the VCAM on BBB). Also downreg IL-12 (key to autoimmune diseases).

This decreases Gd enhancing activity (less BBB instability) and promotes neuroprotection

Front 33

Glatiramer acetat (Copraxone)e mech of action

Back 33

Induces TH2 shift.

Neuroprotection

Front 34

Interferon SE

Back 34

Flulike sx, leukopenia, high LFTs

Front 35

glatiramer acetate (Copaxone) SE

Back 35

Injection site rxn and chest pain.

Front 36

Mitoxantrone SE

Back 36

Want to use it sparingly bc it is a chemo agent. Cardio toxicity and leukopenia. and N/V

Front 37

Natalizumab (Tysabri) SE

Back 37

Opportunistic infections and survival of tumor cells.

Front 38

MS - whole brain phenomena - other sx

Back 38

weakness, spasticity, pain, depression, bladder