Glossary of SFS - Multiple Sclerosis

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Disorder where myelin initially forms normally, only to be affected or damaged later in life.
demyelinating disease
Desorder of white matter where there is a genetic abnormality and the person's myelin never forms properly.
dysmyelinating disease
Is there an axonal component to the demyelinating disease of MS?
What is most accurate? MS is an autoimmune/immune-mediated/immune system disease.
immune-mediated (could be intrinsic or triggered by something else)
PNS myelin diseases without CNS components
peripheral neuropathies
MS affects ___________ (cells) in the __________ nervous system.
oligodendrocytes; central
What is the hallmark of MS?
A dissemination in space and time. Different parts are affected at different times, resulting in different symptoms.
Why is MS difficult for the healthcare provider?
No single test to diagnose
No 2 cases are alike
No proven cause or cure
Unpredictable course that is unique to each patient
Treatments are only partially effective
Typical age of MS diagnosis
20-40 years old
MS proportionally affects more men or women?
Women at a ratio of 2:1 under the age of 40. Above 40, goes to 1:1.
MS especially affects what ethnic groups?
Caucasians (northern european and scandanavian primarily). There are also examples of clusters of MS.
If a person moves from a high-risk area to a low-risk area before age 15, what is their MS risk like? What about if they move after age 15?
They acquire the lower risk.

They retain the higher risk.
Another theory of MS (dealing with climate, etc)
Increases as you go north or south from the equator, so perhaps there is an infectious agent more prevalent in temporate than equatorial climates.
What is the current life-expectancy of someone with MS?
The same as that of an age-matched control. 30% will develop a severe disability, while 70% will become unemployed mostly as a result of the cognitive effects of MS
A combination of what 2 factors leads to an immunological response that leads to MS?
Genetic (not enough by itself) and environmental (viruses, bacteria, and toxins)
Process where naive T-cell is activated against an infectius agent then identifies a similar epitope on an internal protein and attacks that protein.
molecular mimicry
Where is the immune response initiated in MS?
Outside the CNS.
Process of initiation of MS immune response.
Initiated outside the CNS by a molecular mimic of myelin: T-cells activated, releasing cytokines, which activate T and B cells. Cytokines also cause activation of adhesion molecules which T-cells will bind to and walk through the blood-brain barrier.
Once inside the CNS, what happens in the MS mechanism?
T-cells that entered are now releasing pro-inflammatory cytokines. Other inflammatory cells (B and macrophages) are also entering the CNS via the BBB. These cells attack the myelin.
The symptoms of MS are thought to be due to problems of nerve conduction due to what?
axon demyelination and disruption. However, some remyelination occurs. BUT, axons are now vulnerable to inflammatory factors.
What causes plaques in MS?
Gliosis (proliferation of glial cells to fill in the damage areas). Occurs after initial lesions.
Is there a gradient of pathological changes in MS?
What are the 3 main pathological processes seen in MS?
1. Inflammation - problem starts around a blood vessel.
2. Demyelination - axons
3. Axonal loss - confirmed by confocal microscopy. Some will recover/regenerate, and some will not. Accumulation of axonal loss results in disability.
Hopeful MS treatment strategies.
Modulate balance of pro- and anti-inflammatory cytokines.
Enhancing remyelination and regeneration.
Is MS a purely demyelinating disease?
No, it affects gray matter as well as subcortical white matter. This is primarily responsible for cognitive difficulties seen in MS.
What is the most common presenting symptom in MS patients? Hows abouts da 2nd most common problem? And the next?
Numbness that begins in an arm or leg and gradually spreads to waist or neck levels.

2nd most: Visual loss (optic neuritis) with partial or complete loss, scotomas, color vision effects, and extraocular movement pain.

Next most common: polysymptomatic presentation with multiple symptoms
Most common, established (not at onset), symptoms. (What they have experienced)
(listed by prevalence)
Bladder problems
Sexual dysfunction
Pain and cognictive dysfunction
80% of patients will present with _________-_________ MS. What is it?
Relapsing-remitting MS. Acute onset, Symptoms persist for a few weeks and then resolve (remission), which may last a few weeks or months. And so on...
If untreated 50% of RR MS patients will develop what within 10 years?
Secondary Progressive MS. Instead of having steady baseline as with RR MS, they gradually worsen.
10% of patients have what type of MS that is most common in men?
Primary Progressive MS. Patients never have relapses. Makes dissemination in space and time landmark harder to observe.
Affects 5% of patients. Starts out as primary progressive, then develop relapses superimposed on that course.
Progressive Relapsing MS
Example of variable course of MS.
Benign MS (mild MS) -> relapsing MS -> different flavors of progressive MS -> malignant MS (Marburg's variant is a subtype; death in 6-12 months)
Things to look for in MRI scan.
T2 lesions, active lesions, atrophy, T1 black holes, lesions in the spinal cord.

This is useful because you can follow the disease over time.
Is MS a disease that just because it may be in clinical remission and the patient has had no relapses in a year, that the MS is fine?

*BAD GRAMMAR, sorry.
Study using changing checkerboard pattern to cause measurable changes in the visual cortex.
Visual Evoked Potentials. A delay on one side will infer that the person has optic neuritis on that side.
Helpful diagnostic study that looks for MBP, a nonspecific marker, IgG abnormalities, or oligoclonal bands.
Checking the CSF
Definition of a relapse.
New symptom or worsening of a previous symptom that has been stable for 30 days, is associated with objective changes on examination, lasts for more than 24 hours, occurs in the absence of any fever or infection or other symptoms. Tingling in the had or fingers with carpal tunnel is not MS.
Clinical course of typical MS patient:
-Do the relapses become more or less frequent?
-Does the MRI burden increase/decrease over time?
-Does the patient develop atrophy?
-Relapses become less frequent

-MRI burden increases over time

-Patient develops atrophy
A marker of axonal loss increased over the clinical progression of MS.
NAA (N-Acetyl Aspartate)
Generally speaking,
a. Who does better, women or men?
b. What are the characteristics of a patient that tends to have a better prognosis?
a. women do better

b. RR MS, younger patients, pts who have fewer relapses, less disability in early stages, and low burden of disease on MRI
When a patient presents with an acute event (relapse) and cannot walk, what is the standard treatment?
steroids - IV methylprednisone (solumedrol) for 3-5 days, followed by oral prednisone for 2-4 wks. This tends to reduce duration of the relapse and patients seem to recover more completely.
Treatment of the underlying disease of RR MS.
interferons and non-interferon agents
What are 3 interferons used in treatment of MS?
-betaseron - subcutaneous injection taken by pts every other day

-interferon beta-1A (Avonex) intramuscular injection 1x/wk

-Rebif - subcutaneous Interferon Beta-1A 3x/wk
What are 2 non-interferon agents used in treatment of MS?
Copaxone - synthetic complex polymer of amino acids taken subcutaneously 1x/day.

Natalizumab - monoclonal antibody to VLA4 given IV every 4 wks. Not approved right now, but will be.
What is the treatment of secondary progressive MS?
All interferon therapies have proven effective.

Novantrone (mitoxantrone) is a chemotherapy drug given IV
What are 3 proposed mechanisms that interferons help in MS?
1. Tend to interfere with T-cell activation. Cells become TH2 instead of activated TH1.

2. Act on MMPs (matrix metalloproteinases) that help prevent entry of T-cells into CNS.

3. Also stabilize the BBB, preventing T-cell entry into CNS.
Auto-peptide ligand that changes TH1 cells to TH2 cells and produces glatiramer acetate specific cells.
Cells that go into CNS and cause bystander suppression and produce cytokines and chemokines that would reduce inflammatory response.
glatiramer acetate specific cells (produced by copaxone). Work in periphery and in CNS!
Momonclonal antibody that acts by blocking VLA4, which prevents T-cells from getting into CNS.
Used for progressive MS. A "god" immunosupressant."
What are the benefits of treatment of MS? A cure?
Not a cure, but effective therapies that will prevent and reduce relapses, delay progression, reduce MRI burden, and reduce disabilities. Hopefully, just slow down disease process.
Issue of treatment with interferons.
They tend to produce neutralizing Abs which reduce effectiveness of these drugs.
Side-effects of MS drugs.
flu-like, injectino site problems and necrosis, liver abnormalities, blood count abnormalities
Keys to success with MS patients.
Set realistic expectations (will be lifelong therapy), improve compliance by education and encouragement
4 other demyelinating diseases (other than MS)
Acute disseminated encephalomyelitis
Devic's disease (neuromyelitis optica)
Balo's concentric sclerosis
Marburg variant

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