Week 7 Multiple Sclerosis and CNS Demyelinating Disease Flashcards
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
Define multiple sclerosis
A chronic often disabling disease that attacks the CNS: brain, spinal cord, optic nerves
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
Describe the temporal course of multiple sclerosis
- Inflammation and regeneration initially
- inflammatory CD4 T cells infiltrate white matter, perivascular - Then demyelination and axonal loss (Wallerian degeneration)
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
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
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
What are some histological findings in MS?
- demyelination as well as axonal loss
- T1 hypo intensity directly correlates to degree of axonal loss
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
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
What is the mechanism of the MS drug REBIF, IFNb-1a?
subQ injection
- more efficacious than AVONEX
cons: forms neutralizing antibody
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
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
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
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
