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74 Cards in this Set
- Front
- Back
What is MS?
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a prototypical demyelinating disease
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What are the features of MS?
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1.immune-mediated
2.demylinating disease with axonal component 3.affects the CNS 4.affects primarily white matter 5.hallmark is dissemination in space and time |
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How do you diagnose MS?
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its difficult; there is no single test to rule out or confirm MS; MRIs and CSF tests are supportive but not definitive
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Is MS the same in all patients?
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No, no two cases are alike because it affects different areas of the CNS at different times
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Is there a cause or a cure for MS?
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none proven
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What is the course of MS like?
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unpredictable and individual to each patient in both symptoms and progression
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Are MS treatments effective?
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only partially
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Who does MS commonly affect?
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women between the ages of 20-40 (primarily Caucasians of northern european or scandinavian descent)
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What causes MS?
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don't really know, a combination of genetics and environment
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What is the life expectancy of someone with MS?
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normal (the same as an age-matched control)
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What are some consequences of untreated MS?
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becoming wheelchair bound, vision loss, bowel or bladder dysfunction
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What is the genetic component of MS?
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a complex of genes that predisposes a person to MS
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What are some environmental agents proposed to cause MS?
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viruses (CMG, Epstein-Barr), bacteria, toxins (lead, copper)
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What is the difference between dysmyelinating and demyelinating diseases?
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dys:abnormal or defective myelin formation
de: damage to myelin previously normally formed |
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What is the trimolecular complex that is formed?
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the infectious agent, taken up by APC, presented to naive T-cells
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What is molecular mimicry?
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a naive T cell that is activated agaisnt an infectious agent then identifies a similar epitope on an internal protein and attacks that internal protein
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What is attacked in MS?
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boty the myelin and the myelin producing oligodendrocytes
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The attacking of myelin and oligodendrocytes is thought to be due to...
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a complex interaction of immune system components such as macrophages, T-cells, and various cytokines
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The immune response in MS is initiated __________ the CNS.
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outside
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Explain what happens after a molecular mimic to myelin is detected.
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T cells activated
release cytokines into blood activate B cells and other T cells cytokines cause endothelial cells lining bv to express adhesion molecules activated T cells bind to these adhesion molecules and walk through the BBB into the CNS in the CNS T cells continue to release pro-inflamm cytokines other immune cells including B cells and macrophages enter CNS through BBB these cells attack myelin |
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What is thought to cause the symptoms of MS?
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problems of nerve conduction due to axonal demyelination and disruption
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What can happen afer inflammation?
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some ion channels repopulate the axons and some remyelination occurs
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What leads to plaques?
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gliosis, proliferation of glial cells to fill in the damaged areas
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What does the standard MS plaque look like?
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it shows a gradient of pathological changes- the center of the plaque represents older damage where axons are demyelinated and damaged, near the border the # of macrophages increases and there is ongoing demyelination/remyelination
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How could you create an environment that is favorable to remyelination?
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inhibit gliosis (don't know how to do this yet)
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What was the most promising substance in inhibiting gliosis?
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IVIG, intravenous immunolgobulin (not good in clincal trials)
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What can plasmaphaeresis be used for? What is it not good for?
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to help in acute demyelinating relapses and when someone has a severe relapse that doesn't respond to steroids;
not effective in preventing disability long-term |
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What is the pathological hallmark of MS?
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plaques (MS means multiple scars)
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What are the 3 main pathological processes seen in MS?
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1st: inflammation
2nd: demyelination 3rd: axonal loss |
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Is MS purely a demyelinating disease?
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No, it can affect gray matter too
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Recent studies have suggested that MS lesions tend to:
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1.extend from the subcortical white matter to the cortical grey matter
2.exist purely in the grey matter 3.large areas of demyelination that extend into the grey matter |
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What is the damage to grey matter responsible for?
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cognitive difficulties
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What is the most common symptom of MS?
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numbness that begins in the arm or leg and gradually spreads to waist or neck levels
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What are some symptoms of MS?
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itching,
pain, numbness, visual loss, bladder problems, fatigue, spasticity, sexual dysfunction, cognitive dysfunction |
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What is the second most common symptom of MS?
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visual loss
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What causes visual loss?
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optic neuritis
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Specifically, how does vision loss present?
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partial or complete visual loss
development of scotomas changes in color vision pain with extraocular movements |
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What is the most common pattern of MS? What percentage does this pattern occur in?
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Relapsing Remitting MS
80% |
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What are the four patterns of MS?
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1.relapsing remitting MS
2.secondary progressive MS 3.primary progressive MS 4.progressive relapsing MS |
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What is the second most common type of MS?
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secondary progressive MS
50% |
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Approximately __% of patients with untreated RR MS will develop ____________ within __ years.
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50%
secondary progressive MS 10 |
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What % of patients have primary progressive MS?
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10%
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Which type of MS is more common in men?
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primary progressive MS
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Patients who have progressive relapsing MS start out with ________ MS
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primary progressive
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What are the 4 variations in the course of MS
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mild MS
relapsing MS progressive MS malignant MS |
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What is Marburg's variant of MS? How long do these patients live?
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a malignant subtype of MS in which patients develop diffuse areas of demyelination
die within 6-12 months despite therapy |
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What are the 3 diagnostic tests for MS?
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MRI
Visual evoked potentials CSF |
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What do you look for to diagnose MS on an MRI?
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T2 lesions (scars that appear white)
active lesions atrophy T1 black holes (axonal loss) lesions in th spinal cord |
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Why is the MRI helpful?
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you can follow it over time
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What is visual evoked potentials? What is the average response time in normal person?
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you stimulate the eyes with a checkerboard pattern and the impulses are measured over the occipital area where the visual center is;
100ms |
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What proteins are you looking for in CSF?
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MBP (myelin basic protein)
quantitative indicators of IgG abnormalities oligoclonal bands |
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A patient presents with optic neuritis and transverse myelitis, what diagnostic tests should you order to confirm MS?
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none...you can diagnose because the symptoms disseminate in space
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What is the caveat to diagnosing MS?
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rule out other potential etiologies
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What occurs in the typical course of MS?
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relapses become less frequent
disability increases MRI burden of disease increases patient develops atrophy increase in NAA |
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What is NAA?
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N-Acetyl Aspartate;
a marker of axonal loss |
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Which patients typically have a better prognosis?
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women
younger patients patients with RR MS patients with fewer relapses patietns with less disability early on patients with a low burden of disease (volume of brain affected) on MRI |
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What is the standard treatment for relapse?
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IV methylprednisolone (solmedrol) for 3-5 days followed by oral predinsone for 2-4 weeks
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What is the main goal of treatment?
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treat the underlying disease
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What was the first approved treatment for MS? when?
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Betaseron;
1993 |
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What type of MS are most drugs indicated for?
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RR MS (because it is most common)
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How do you treat MS?
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with interferons or non-interferon agents
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What are the interferons used and what is the method of delivery?
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Betaseron (subcutaneous injection)
Interferon Beta-1A (intramuscular injection) Rebif (subcutaneous interferon beta-1A) |
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What are some non-interferon agents and what is their method of delivery?
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copaxone (subcutaneous)
Natalizumab (intravenously) |
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T/F: All interferon therapies have been proven effective in patients with secondary progressive MS with superimposed relapses.
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True
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What is a chemotherapy drug given intravenously?
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Novantrone
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What are the 3 proposed mechanisms of interferon?
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1.interfere with actions of T-cells (instead of becoming TH1 they become TH2)
2.act on metalloproteinases (MMPs) helping to prevent the entry of T-cells into the CNS 3.stabilize the BBB preventing T cell entry |
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What is copaxone? How does it act?
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a syntehetic complex polymer of amino acids that is taken by subcutaneous injection once a day, an auto-peptide ligand;
by changing TH1 to TH2 and by producing glatiramer acetate specific cells |
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What do glatiramer acetate specific cells do?
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go into the CNS and cause bystander supression adn produce cytokines and chemokines that would reduce the inflammatory response
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Where does Copaxone work?
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in periphery and CNS
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What is the drug that has been taken off the market? How does it work?
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Natalizumab; a monoclonal antibody that acts by blocking VLA4 and thus preventing T-cells from getting into the CNS
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What is novantrone used for? Why?
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progressive MS because it acts on bascially all steps of the immune response
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What are some issues of treatment?
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-interferons produce neutralizing antibodies
-drugs have side effects -setting realistic expectations -managing breakthrough diseas |
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What are some side effects of MS treatment drugs?
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flu-like symptoms, injection site problems and necrosis, liver abnormalities, blood count abnormalities
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What are some other demyelinating diseases?
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Acute disseminated encephalomyelitis
Devic's disease (neuromyelitis optica) Balo's concentric sclerosis Marburg variant |