Week 7 Multiple Sclerosis and CNS Demyelinating Disease

Question 1

Name and describe the common acquired and genetic CNS demyelinating diseases

Answer 1

• 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

Question 2

Define multiple sclerosis

Answer 2

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

Question 3

Describe the prevalence, gender and geographical differences of multiple sclerosis

Answer 3

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

Question 4

Describe the temporal course of multiple sclerosis

Answer 4

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

Question 5

What is the diagnostic MRI criteria in MS?

Answer 5

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

Question 6

How is MS diagnosed?

Answer 6

• 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

Question 7

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

Answer 7

• 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

Question 8

What are some histological findings in MS?

Answer 8

• demyelination as well as axonal loss

- T1 hypo intensity directly correlates to degree of axonal loss

Question 9

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

Answer 9

• 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

Question 10

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

Answer 10

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

Question 11

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

Answer 11

subQ injection

• more efficacious than AVONEX
  cons: forms neutralizing antibody

Question 12

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

Answer 12

• 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

Question 13

What is the mechanism of the MS drug MITOXANTRONE?

Answer 13

-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

Question 14

Describe the MS drug Tysabri?

Answer 14

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

Question 15

Describe the MS drug Aubagio (teriflunomide)

Answer 15

• 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

Question 16

Describe the MS drug Gilenya (fingolimod).

Answer 16

• 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

Question 17

Describe Tecfidera (BG-12).

Answer 17

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

Question 18

What is the most common form of MS?

Answer 18

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.