Multiple sclerosis

Question 1

What is the autoimmune theory?

Answer 1

Autoimmune attack on the CNS
Inflammatory process leads to disruption of the BBB
Migration of antigen-specific T cells into CNS
Cascade of immunologic events
Demyelination

Question 2

What are the RFs for MS?

Answer 2

Age
US citizen
Environment (virus/bacteria, smoking, vit D deficiency)
Genetics (HLA, MHC< IL2/7alpha)

Question 3

What are primary sx of MS?

Answer 3

Direct consequence of demyelination

Question 4

What are secondary sx of MS?

Answer 4

Complications secondary to primary sx

Question 5

What are tertiary sx of MS?

Answer 5

Sx that relate to the effect of the disease on the patients everyday life

Question 6

What are the ways to measure MS progression?

Answer 6

EDSS
MSFC
MRI

Question 7

What are the 4 classifications of MS?

Answer 7

RRMS
SPMS
PPMS
PRMS

Question 8

What does RRMS stand for?

Answer 8

Relapsing remitting MS

Question 9

What is RRMS?

Answer 9

Clearly defined exacerbations

Acute worsening of neurologic function

Question 10

What is the most common MS form at diagnosis?

Answer 10

RRMS

Question 11

What is the most common form of MS?

Answer 11

RRMS

Question 12

What does SPMS stand for?

Answer 12

Secondary progressive MS

Question 13

What can SPMS develop from?

Answer 13

RRMS

Question 14

What is SPMS?

Answer 14

Steadily worsening w/ or w/o occasional flare ups

Question 15

What does PPMS stand for?

Answer 15

Primary progressive MS

Question 16

What is PPMS?

Answer 16

Slow but continuous worsening of disease from onset
Worse prognosis
No distinct relapse or remission
Variations in rates of progression

Question 17

What does PRMS stand for?

Answer 17

Progressive relapsing MS

Question 18

What is PRMS?

Answer 18

Steadily worsening disease from onset
Clear, acute relapses w/ or w/o recovery
Periods between relapses continue disease progression

Question 19

What are factors that may lead to an exacerbation?

Answer 19

Infection
Heat
Sleep deprivation
Stress
Malnutrition
Anemia
Concurrent organ dysfunction
Exertion
Childbirth

Question 20

What is the first exacerbation known as?

Answer 20

Clinically isolated syndrome (CIS)

Question 21

How does MS affect mortality?

Answer 21

Does not directly decrease mortality

Increased mortality with secondary complications (pneumo, sepsis, decubitus ulcer, UTI)

Question 22

What rate is 7x the normal population for MS?

Answer 22

Suicide

Question 23

How is MS diagnosed?

Answer 23

2 episodes of neurologic disturbance
McDonald criteria
MRI
CSF (IgG)

Question 24

What are the treatment categories for MS?

Answer 24

Tx of acute attacks
Disease-modifying therapies
Symptomatic therapy

Question 25

What type of therapy are attack and disease-modifying therapies?

Answer 25

Immunotherapies

Question 26

What are the goals of immunotherapy in MS?

Answer 26

Decrease frequency and severity of exacerbations Diminish the progression of lesions Slow progression of disability

Question 27

What is the treatment of acute MS exacerbation?

Answer 27

HD IV methylprednisolone (500-1000) x 3-10d

Question 28

What are the disease-modifying therapies?

Answer 28

``` Interferon beta Glatiramer (Copaxone) Natalizumab (Tysabri) Mitoxantrone (Novantrone) Fingolimod (Gilenya Teriflunomide (Aubagio) Dimethyl fumarate (Tecfidera) Alemtuzumab (Lemtrada) Ocrezlizumab (Ocrevus) ```

Question 29

What are the 2 interferon B1b?

Answer 29

Betaseron | Extavia

Question 30

What are the Interferon B1a?

Answer 30

Avonex Rebif Plegridy

Question 31

How does interferon work?

Answer 31

Suppresses T-helper cell response, reducing T cell migration across the BBB into the CNS

Question 32

What is the MOA of glatiramer?

Answer 32

Alteration of T cell activation and differentiation

Question 33

What is the MOA of mitoxantrone?

Answer 33

Decrease the migration of T cells into the CNS by arresting cell cycle

Question 34

What is the MOA of natalizumab?

Answer 34

Monoclonal antibodies of alpha4-integrin of the adhesion molecule VLA-4 on leukocytes. Inhibition of VLA-4 is responsible for blockade of T cells across the BBB

Question 35

What is the MOA of fingolimod?

Answer 35

Reduces the infiltration of T lymphocytes into the CNS

Question 36

What is the MOS of teriflunomide?

Answer 36

Inhibits pyrimidine synthesis thereby decreasing proliferation and inflammation

Question 37

What is the MOA of dimethyl fumarate?

Answer 37

Thought to be protextive against damage to the brain and spinal cord secondary to antioxidant properties brought about by activation of the Nrf2 pathway

Question 38

What is the MOA of alemtuzumab?

Answer 38

Monoclonal antibody directed at CD52, an antigen present on the surface of various types of immune cells Results in depletion of circulating B and T lymphocytes

Question 39

What is first line in PPMS?

Answer 39

Ocrelizumab

Question 40

Which drugs are FDA approved for those with inadequate response or intolerance to other MS therapies?

Answer 40

Natalizumab Alemtuzumab Daclizumab

Question 41

What can be considered in worsening RRMS, SPMS, and PRMS whether or not relapses are occurring?

Answer 41

Mitoxantrone

Question 42

What are comorbidities with MS?

Answer 42

``` Cognitive dysfunction Depression Fatigue Paroxysmal sx Spasticity Sphincter dysfunction Gait impairment ```

Question 43

How do we treat spasticity?

Answer 43

Baclofen | Tizanidine

Question 44

How do we treat bladder sx?

Answer 44

Tolterodine | Oxybutinin

Question 45

How do we treat sensory sx?

Answer 45

Gabapentin

Question 46

How do we treat fatigue?

Answer 46

Amantadine Modafanil Methylphenidate

Question 47

How do we treat gait impairment?

Answer 47

Dalfampridine