Week 7 Multiple Sclerosis and CNS Demyelinating Disease Flashcards Preview

Neurosciences > Week 7 Multiple Sclerosis and CNS Demyelinating Disease > Flashcards

Flashcards in Week 7 Multiple Sclerosis and CNS Demyelinating Disease Deck (18)
Loading flashcards...
1

Name and describe the common acquired and genetic CNS demyelinating diseases

-multiple sclerosis
-MS variants, Devics
-Acute disseminated encephalomyelitis: autoimmune demyelinating disease, usually after viral infection
-transverse myelitis: caused by inflammation across both sides of one level, or segment, of the spinal cord
-optic neuritis
-PML due to JC virus
-non inflammatory metabolic diseases

2

Define multiple sclerosis

A chronic often disabling disease that attacks the CNS: brain, spinal cord, optic nerves

3

Describe the prevalence, gender and geographical differences of multiple sclerosis

Most common chronic disease affecting CNS in young adults
-1:1000, currently ~400,000 cases in US
-higher incidence in women (3:1)
-highest incidence in caucasians of northern european ancestry
-affects individuals ages 20-50

4

Describe the temporal course of multiple sclerosis

1. Inflammation and regeneration initially
-inflammatory CD4 T cells infiltrate white matter, perivascular
2. Then demyelination and axonal loss (Wallerian degeneration)

5

What is the diagnostic MRI criteria in MS?

Presence of asymptomatic enhancing and nonenhancing lesions at any time
1 or more new T2 or enhancing lesion

6

How is MS diagnosed?

-Abnormal neuro exam
-MRI (though 10% are normal on presentation)
-evoked potentials particularly visual, but also SS
-CSF with evidence of inflammation such as increased IgG synthesis and oligoclonal bands in the CSF
-fluctuating symptoms and signs after an acute event

7

What are some radiographic appearances of the white matter "plaques" and their distribution in the CNS?

-dawson's fingers: spikes of demyelination seen in sagittal view
-multi-focal plaques seen in horizontal view throughout white matter
-focal lesions in spinal cord

8

What are some histological findings in MS?

-demyelination as well as axonal loss
-T1 hypo intensity directly correlates to degree of axonal loss

9

What is the mechanism of the MS drug Copaxone (glatiramer acetate)?

-shifts Th1 to Th2
-downregulates Th1 associated chemokine receptors after 12 months
-induction of CD4+CD25 regulatory T cells
-higher reduction in relapse compared to IFNs

10

What is the mechanism of the MS drug Avonex, IFNb-1a?

1/week injection
-reduces clinical relapse rate
-reduces development of new MRI lesion
-delays increase of MRI lesion volume
-prevents brain atrophy
-may delay disability progression
-licensed for clinical isolated syndromes
Side effects: 1st 6 weeks of flu like evidence

11

What is the mechanism of the MS drug REBIF, IFNb-1a?

subQ injection
-more efficacious than AVONEX
cons: forms neutralizing antibody

12

What is the mechanism of the MS drug BETASERON, IFNb-1b?

• Reduces clinical relapse rate
• May delay disability progression
• Reduces development of new MRI lesions
• Delays development of new lesion volume
• Question of duration and clinical significance of benefit
Con: Neutralizing antibody

13

What is the mechanism of the MS drug MITOXANTRONE?

-was an anti cancer drug
Reduces attack rate in RRMS
• Appears to have effect on disease progression and is used in SPMS
• Potential side effects considerable
• NOVANTRONE
• Not Prescribed
Side effects: reduction of injection fraction, leukemia

14

Describe the MS drug Tysabri?

MOST Effective therapy
-prevents lymphocytes from entering brain
65% reduction in acute attacks
• 80 % reduction in new MRI lesions saves axons and neurons
• No long term data
-risk of developing PML

15

Describe the MS drug Aubagio (teriflunomide)

• Terflutamide related to anti cancer drug • Efficacious but more like glatiramer
• X rated for pregnancy
• Oral once a day
• Side effects, liver and hair loss
• Have to do TB test prior to treatment

16

Describe the MS drug Gilenya (fingolimod).

• This is a sphingosine 1-phosphate receptor modulator
• First oral therapy
•Prevents lymphocyte egress from secondary lymphoid tissues producing lymphopenia
• Many side effects but effective in RRMS
• No long term data

17

Describe Tecfidera (BG-12).

• Dimethyl Fumarate
• Oral twice a day
• Few side effects
• Efficacy like gilenya
• Just licensed long term effects not known

18

What is the most common form of MS?

relapsing remitting MS
-RRMS is defined by attacks of inflammation (relapses) in the CNS
-People with RRMS tend to have more brain lesions — also called plaques or scars — on magnetic resonance imaging (MRI) scans, and these lesions contain more inflammatory cells
-People with primary-progressive MS (PPMS) tend to have more spinal cord lesions, which contain fewer inflammatory cells.

Decks in Neurosciences Class (59):