T3 Multiple Sclerosis - Thrower, Bonnie, And Komiskey

Front 1

what is multiple sclerosis?

Back 1

autoimmune disease (CD4 and Th1 dysregulation) characterized by demyelination of the CNS and axonal loss

Front 2

list some common facts/statements about the etiology and epidemiology.

Back 2

genetics (HLA-DR2 and TCR) and environment plays a role (Demographics: further from the equator = more likely to get MS; microbial, Toxins); 200 new cases a week in the US; most common cause of non-traumatic disability in young adults; affects women more often; usual age onset 20-30s;

Front 3

explain molecular mimicry.

Back 3

it is where antigens evoking an immune response have similarities to the body's own proteins and cause an immune rxn; body's inability to distinguish self from non-self; some common non-self antigens (viruses and bacteria/toxins) and potential self antigens (myelin basic protein - looks like a virus - may be the problem)

Front 4

name the four types of MS.

Back 4

1) Benign MS; 2) Relapsing Remitting MS; 3) Secondary Progressive; 4) Primary Progressive

Front 5

name the man responsible for giving us the first signs and symptoms of multiple sclerosis.

Back 5

Jean-Martin Charcot

Front 6

which type of MS doesn't cause cognitive problems but is mainly gait issues; it doesn't follow the typical MS spectrum.

Back 6

Primary Progressive MS - typically males and mainly gait difficulties

Front 7

at diagnosis most people are this type?? and develop into ___________ in 11-15 years.

Back 7

at diagnosis most(85%) are relapsing remitting and develop into 58%-secondary-progressive or 42% stay relapsing remitting

Front 8

what two factors will cause an MS patient to stop working?

Back 8

fatigue and cognition problems

Front 9

MS has been thought to be a dual phase disease. what are the stages.

Back 9

inflammatory --> progressing --> to Degenerative

Front 10

as an MS patient progresses from preclinical --> relapsing --> secondary progressive, how does the brain grossly change?

Back 10

as the disease progresses, the ventricles enlarge and the brain atrophies

Front 11

name the disability scale used to grade the MS disability.

Back 11

EDSS (expanded disability status scale); 0-10; 10 is death; defined by functional, walking, and dependence; scores of 0-6 are subtle changes, once a pt is beyond a 6 the changes are very noticable

Front 12

what are the 3 major groups of cells that are possibly involved in MS?

Back 12

1) Tcell/Macrophage; 2) Antibody/Complement; 3) oligodendrocytes

Front 13

53% of MS patients follow the pattern of having problems with which groups of cells?

Back 13

tcell/macrophage and Antibody/complement are involved, but the oligodendrocytes are normal

Front 14

how will MS axonal loss lesions show up on T1 MRI?

Back 14

hypointense

Front 15

CD4 Tcells differentiate into Th1 and Th2 cells. what do Th1 and Th2 cells produce?

Back 15

Th1: pro-inflammatory cytokines (IL-2, IFN, TNF) macrophage mediated; Th2: anti-inflammatory cytokines (IL-4, IL-5, IL-10, IL-13) Bcell mediated

Front 16

name the newer way to measure MS functionality. it uses a 25 foot walk, a nine-hole peg test, and a PASAT (paced auditory serial addition test).

Back 16

MSFC, Multiple Sclerosis Functional Composite

Front 17

what are the diagnostic tools used to diagnose MS?

Back 17

H&P, MRI of brain and spinal cord, CSF exam, Evoked Potentials (SSEP, VEP, BAER), and other labs

Front 18

on MRI, where are the lesions?

Back 18

most are typically paraventricular

Front 19

is it possible to have MS and be asymptomatic but not have lesions?

Back 19

not normally, axonal damage/inflammatory lesions are common to see on MRI even without symptoms; for every one relapse there are 5-10 inflammatory lesions on MRI

Front 20

when ordering an MRI, what technique do you want?

Back 20

3mm thick sections, no more than a 1mm skip, axial and sagittal FLAIR, wait at least 5 min between contrast and filming

Front 21

name some diseases that mimic MS.

Back 21

Devic's Disease (just neuromyelitis optica); sarcoidosis, Sjogren's, Behcet S, Leukodystrophies of adulthood, PML, ADEM, Lyme dz, primary CNS vasculitis, tertiary syphilis, CADASIL, antiphospholipid syndrome

Front 22

define the diagnostic criteria of Devic's Dz (mimic of MS).

Back 22

1) optic and transverse myelitis; 2) Two of the following: a) MRI evidence of contiguous spinal cord lesion 3 or more segments long; b) brain MR is not consistant with MS; c) NMO-IgG seropositivity (NeuroMyelitis Optica - NMO)

Front 23

If a young adult patient presents with confusion, gait disturbances, seizures, headaches, with bowel/bladder problems after an acute infection, what do you think of?

Back 23

ADEM Acute Disseminated Encephalomyelitis: will reveal an abnormal brain/cord MRI with multiple enhancing lesions; CSF: increase protein, pleocytosis, and no Oligoclonal bands; usually monophasic

Front 24

this MS mimicing dz is a reactivation of JC virus commonly presented in immunocompromised patients. also, what MS drug may cause this to occur?

Back 24

PML - progressive multifocal leukoencephalopathy; the MS drug of last resort is Natalizumab

Front 25

even if a patient is labeled CIS (clinically isolated syndrome) it may be important to start therapy (controversial) since axonal loss may occur early. if a patient has CIS with optic neuritis, what puts that patient at increased and/or decreased risk?

Back 25

INCREASED RISK of developing MS: young adult, female, unilateral, pain, normal disc, brain lesions, abnormal CSF (OCBs, increased leukocytes, protein, myelin basic protein, normal glucose); DECREASED RISK: children, male, bilateral, painless, severe disc edema, normal brain MRI, Normal CSF

Front 26

what are the increased and decreased risk factors of developing MS after an episode of Transverse myelitis?

Back 26

INCREASED: incomplete TM, asymmetric sx, abnormal brain MRI, OCB in CSF, no CSF pleocytosis, smaller cord lesion, no edema; DECREASED RISK: complete TM, symmetric sx, normal brain MRI, no OCB in CSF, CSF pleocytosis, multi-segments, and edema

Front 27

name the two criteria methods used to diagnose MS after CIS.

Back 27

1) Poser Criteria: need evidence of 2 separate attacks (1st is the CIS, 2nd is confirming); 2) McDonald Criteria: since MRI can be abnormal and pt asymptomatic, this criteria uses MRI as the defining 2nd event

Front 28

What is found in the CSF of an MS patient that is sensitive and specific?

Back 28

OCB (oligoclonal bands)

Front 29

there are 3 ways to medically manage MS, name them.

Back 29

1) treat the relapses, 2) manage the symptoms, 3) alter the course of MS

Front 30

common causes for an MS exacerbation or flare up are:

Back 30

new illness, fever

Front 31

name the common steroid treatments for MS relapses.

Back 31

Solumedrol (methylprednisolone); oral prednison; ACTH

Front 32

management of MS patients should include treating the symptoms, name common ones.

Back 32

pain (present in 70%), spasticity (tizanidine), bladder/bowel problems, mood, cognitive dysfxn, fatigue (improve quality of life!)

Front 33

what is the most common symptom in MS?

Back 33

Fatigue is seen in 90% of pts; listed as disabling in 50% (lassitude is the term used to define tiredness not related to activity); fatigue is heat sensitive and occurs in specific muscle groups after use

Front 34

name the phenomenon where symptoms show up after an increase in body temperature.

Back 34

Uthoff's Phenomenon

Front 35

what do activated t-cells express to cross the BBB? what happens if the naive t-cell finds an antigen that it is specific for?

Back 35

activated t-cells express VLA-4 and are able to cross the BBB because the endothelial cells express VCAM-1 and ICAM; if these activated tcells encounter the antigen to which they are specific, they will form effector cells and either secrete pro-inflammatory cytokines (CD4) or kill myelin (cytotoxic CD8)

Front 36

what types of cells vary in early vs late lesions?

Back 36

early lesions have predominately tcells especially CD4 cells (inflammation); chronic lesions: macrophages and microglial predominate with loss of oligodendrocytes and axons (CD8 predominate in chronic)

Front 37

the gene with the strongest link to MS is what?

Back 37

the MHC, particularly the HLA-DR2 (class II HLA are expressed on antigen presenting cells, dendritic cells, activated macrophages, Bcells) - class II allow CD4 cells to attach

Front 38

what do CD4 cells predominately secrete?

Back 38

cytokines: gamma IFN, TNF, and IL-2 (promote mononuclear infiltrate, recruite cytotoxic Tcells, macrophages, adn NK cells into the area)

Front 39

what do the anti-myelin CD8 cells do?

Back 39

attach to class I antigens of oligodendrocytes and cause damage

Front 40

what is the role of glial cells?

Back 40

normally glial cells are the macrophages of the nervous system; microglial cells present antigens to t-cells; activated glial cells proliferate and express MHC I and II, co-stimulatory molecules for CD8 and CD4 activation.

Front 41

explain the role of astrocytes in MS.

Back 41

normally astrocytes maintain the BBB. In MS they are induced to proliferate because of the damage, this causes an astrocyte scar to form, this is a typical lesion in an MS patient. both astrocytes and oligodendrocytes can be induced by cytokines to express MHC II antigens and participate in antigen presention to CD4 cells

Front 42

CD4 secrete IFN, TNK, IL-2. what do they do to myelin?

Back 42

TNF and gamma IFN damage myelin

Front 43

what tolerance mechanism may be dysfunctional in MS?

Back 43

central tolerance may be dysfxnal. normally, central tolerance prevents t-cells from having specificity to self

Front 44

name some commonly suggested microorganism/viruses that may play a role in MS.

Back 44

EBV, HHV-6, retroviruses, chlamydia pneuoniae

Front 45

how infectious agents cause MS is uncertain, but ____________ is the most commonly offered explanation.

Back 45

molecular mimicry (it is where antigens evoking an immune response have similarities to the body's own proteins and cause an immune rxn)

Front 46

normally, there are __________________ protecting the integrity of the BBB.

Back 46

tight junctions

Front 47

overall, if you had a choice of what type of t-cell (Th1 or Th2) you could put into the CNS of a MS pt, which would it be and why?

Back 47

since MS has inflammatory component, you would want to add or stimulate the activation of Th2 cells since they release anti-inflammatory cytokines like IL-10

Front 48

what is the microglia's role in lesion formation and lesion repair?

Back 48

formation: secretes inflammatory mediators and presents antigens to CD4 cells; REPAIR: secretes growth factors that promote remyelination

Front 49

what is the endothelial's role in lesion formation and lesion repair?

Back 49

formation of lesion: recruit mononuclear cells, antigen presentation; REPAIR: maintain BBB

Front 50

what is the macrophage's role in lesion formation and lesion repair?

Back 50

formation: secretion of cytokines and mediators which degrade myelin; antigen presentation to CD4 cells; REPAIR: secrete anti-inflammatory cytokines IL10, TGFb

Front 51

once in the brain, t cells secrete _________ that assist in their migration and degrade type 4 collagen, thereby causing damage to the BBB; it also induces proteolysis of myelin sheath.

Back 51

MMP-9: matrix metalloproteases

Front 52

name the three main categories of treatment meds for MS patients.

Back 52

1) IMMUNOMODULATORS: BETA-IFNs: avonex, betaseron, rebif; glatiramer acetate; natalizumab; 2) CORTICOSTEROIDS: methylpredisolone; 3) IMMUNOSUPPRESSORS: mitoxantrone, cyclophasphamide, azathioprine, methotrexate

Front 53

What is glatiramer acetate and its MOA?

Back 53

immunomodulator; copolymer of 4 amino acids; similar in structure to myelin basic protein; suggested to secrete anti-inflammatory cytokines (IL-4, IL-10, TGF-b) by TH2 t-cells

Front 54

corticosteroids are manily used to treat what in MS?

Back 54

significant relapses; symptomatic management; inhibit pro-inflammatory cytokines

Front 55

the immunomodulators (beta-IFN) are usually indicated to do what in MS?

Back 55

to lower the number of relapses and stop progression; the reduce the activation of Tcells

Front 56

what is the proposed role in the immunomodulator, natalizumab and what may it cause that would most likely be lethal?

Back 56

natalizumab is the drug of last resort for MS patients; most likely it works as an antibody to the alpha 4 subunit of the VLA-4 on activated T-cells (that bind to VCAM on endothelial cells)

Front 57

define primary progressive MS.

Back 57

progressive deterioration without relapses and remissions, there are occasional plateus and temporary minor improvements; mainly have gait problems

Front 58

define progressive-relapsing (PRMS).

Back 58

rare, progressive from onset with acute relapses that may or may not result in complete recovery

Front 59

Name the immunomodulators used to treat MS.

Back 59

Betaseron, Avonex, Rebif, glatiramer acetate

Front 60

name the immunosuppressors used to treat MS.

Back 60

mitoxantrone

Front 61

explain the MOA of interferon beta.

Back 61

reduce production of TNFa, T-cells; reduce inflammation by switching to more TH2 cells and increasing levels of IL-10; decrease antigen presentation, reduce ability of cells to cross the BBB

Front 62

what are the indications of using Avonex, Rebif ( both interferon B-1a) and Betaseron (interferon beta-1b) on MS pts?

Back 62

use in relapsing forms, one IM shot weekly for Avonex and 3 subc shots for Rebif and subc every other day in Betaseron; reduces relapse rate and development of new lesions

Front 63

List some common side-effects of interferons.

Back 63

flu-like symptoms, chills, fever, muscle aches, asthenia, possible injection site rxn

Front 64

name the immunomodulator that is not an interferon.

Back 64

glatiramer acetate (less s/e than interferons but may cause chest pains)

Front 65

name the anitneoplastics/immunosuppresants indications and Side-effects?

Back 65

mitoxantrone: reduction of relapse rate and clinical disability; mainly used for progressive MS; IV infusion every 3months; S/E: bone marrow suppression, cardiac tox, teratogenic effects,

Front 66

what is the astrocyte's role in lesion formation and lesion repair?

Back 66

formation: secretes inflammatory mediators and presents antigens to CD4 cells; REPAIR: secretes growth factors that promote remyelination