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...

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

1. Inflammation and regeneration initially
-inflammatory CD4 T cells infiltrate white matter, perivascular
2. 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
• 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


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


Describe Tecfidera (BG-12).

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


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):