Ms And Demyelinating Disease

Front 1

1. How many axons does an oligodendrocyte myelinate?

Demyelination can be primary or secondary to axonal or neuronal damage so can have loss of myelin and relative preservation of axons

Back 1

1. Many

Front 2

1. What is the most common demyelinating disease?
2. What system, CNS or PNS, does it affect?
3. What is 1 characterized by?
4. What are 3 common Sx?

Back 2

1. MS, 1 in 1000
2. CNS (brain and spinal cord)
3. multiple focal deficits separated in time and space
4. visual deficits related to retrobulbar neuritis, Paresthesias, Isolated sensory or motor Sx

Front 3

1. What color are demyelinated lesions (what color are myelinated areas)?
2. What are the borders like and where are they centered for MS lesions
3. What inflammatory cells are present in active plaques (inactive)?
affects white and gray matter, mb less inflammation in gray matter

Back 3

1. gray-tan-pink, slightly depressed (white)
2. Sharp borders, centered at small blood vessel
3. lymphocytes (mononuclear infiltrates) and macrophages (engulf myelin debris) --- very little

Front 4

1. What is the most common form of MS? - prolonged and variable progression
2. Acute episodes with loss of neurologic fxn are followed by what?
3. What events are associated with relapses

Back 4

1. Relapsing-Remitting MS
2. Recovery w/ little or no neurologic deficits between attacks OR stepwise increase in permannet neurologic deficits
3. Postpartum (just gave birth), infection/immunization

Front 5

1. What are 3 theories as to the cause of MS remission?
2. What might be a reason for permanent deficits?

Back 5

1. Remyelination (thin mb 1 or 2 wraps of myelin), Decreased inflammation and edema, & Redistribution of ion channels (most imp. helps regain fxn)
2. Axonal severing

Front 6

1. What are the 4 types of MS?

Back 6

1. Relapsing remitting MS, Secondary progressive MS (AKA relapsing progressive), Primary progessive MS, & Progressive Relapsing MS

Front 7

Following are clinical features of what:
– Acute episodes with subsequent neurologic
deficits
– Most patients have slowly progressive
disease
– Develops after several (usually 3 or more) years
of relapsing remitting MS

Back 7

Secondary Progressive MS

Front 8

Following are clinical features of what:
Patients have a slow and steady progression of
chronic neurologic deficits without any obvious acute
exacerbations

Back 8

Primary Progressive MS

Front 9

Following are clinical features of what:
Progressive disease from onset
• Clear acute exacerbations with full or partial recovery after exacerbations
• Continuing progression between exacerbations

Back 9

Progressive Relapsing MS

Front 10

1. What is the name for rapidly progressing primary progessive MS?
2. Subcategory of relapsing remitting MS with only 1 or 2 acute episodes w/ little or no permanent neurologic deficits, no clinical evidence of disease

Back 10

1. Rapidly progressive MS (aka Marburg Variant or Malignant MS) - course is months to few yrs, rare, in young adults
2. Benign MS

Front 11

MS is 2/3 more common female than male
Incidence increases with distance from equator

1. What is the main HLA Class I/II component?

Back 11

1. DR2 (also associated with IL-2,7 & 19q13.2)

Front 12

1. Why might viruses cause MS?
2. Main immune cells in inflammatory infiltrate

Back 12

1. break T cell tolerance to myelin antigens, initiates autoimmune attack
2. Majority CD4 (late stages), some CD8 (early stages), also macrophages to eat debris ... mb a B cell role with oligoclonal IgG in CSF

Front 13

1. Dx MS?

Back 13

1. dissemination in time and space demonstrated by a combo of clinical, CSF, and imaging findings

Front 14

MS Dx criteria:
– 2 or more attacks with objective clinical evidence for 2 or more lesions
– 2 or more attacks with clinical evidence of a single lesion, additional evidence of dissemination in space can be obtained by MRI detection of lesions consistent with MS plus positive CSF findings
– A single attack with clinical evidence of two or more lesions, dissemination in time can be obtained by MRI detection of a clinically silent lesion, or by waiting for a second episode

Back 14

– For insidious progression (primary progressive MS) suggestive of MS, additional data needed are 1 year of disease progression and one of the following
• MRI findings in the brain
• MRI findings in the spinal cord
• positive CSF findings

Front 15

1. What is normal CNS WBC count? (MS?)
2. What are the 3 typical CSF findings for MS?
3. CSF studies should include what?

Back 15

1. between 0-5/cm^3 (<50, lymphocytic pleocytosis)
2. Modest pleocytosis, normal pressure, protein moderately increased due to increased IgG with monoclonal bands
3. Isoelectric focusing (IEF- delineate oligoclonal bands) & paired analysis of serum = help rule out multiple myeloma

Front 16

1. What should be done to detect local synthesis of IgG?
2. Presents with giant plaques symmetrically affecting both hemispheres, most commonly affects children, progressive

Back 16

1. determine serum IgG, serum albumen, and CSF albumen levels at the same time
2. Schilder's disease (diffuse schlerosis)

Front 17

1. Presents with:
– Monophasic, rapidly progressive**
– 5-14 days after initiating event**
– Headache, meningeal signs, lethargy, coma, focal deficits
– Marked brain swelling
– 15-20% mortality**
– Resolves, survivors may have mild residua

Back 17

Acute disseminated Encephalomyelitis

Also known as post-infectious encephalomyelitis, postvaccinial encephalomyelitis, perivenous encephalomyelitis, acute hemorrhagic encephalomyelitis

Front 18

1. What is Acute disseminated encephalomyelits commonly associated with?
**Has perivascular cuffing with surrounding demyelination (worse than MS)
-acute necrosis/hemmorhage in severe cases

Back 18

1. Vaccinia and measles (small pox vaccine)

Front 19

Acute disseminated encephalomyelitis:
– Experimental autoimmune encephalitis (EAE)-like
– Acute immunological reaction to myelin components
– DTH response with CD4 (primarily) and CD8 Tcells and macrophages
– Recent data suggests that vaccinia infection in mice
can activate CD8 T-cells with two TcR receptors, -
one for vaccinia virus antigens and a second for MBP, suggesting that incomplete allelic exclusion contributes to pathogenesis
MBP = myelin basic protein

Back 19

...

Front 20

1. What are inherited Leukodystrophies (Krabbe disease) characterized by?
2. What disease are Globoid cells present in? (what is a globoid cell?)
3. What happens in 2?

Back 20

1. loss of myelin from the white matter and are defects of lipid catabolism
2. Krabbes' disease (macrophage engorged w/ myelin)
3. Deficiency of galactocerebroside B-galactosidase ... Galactocerebroside accumulates, and is catabolised to galatosylsphingosine thought to be toxic to oligodendrocytes

Front 21

What presents w/:
• Aryl-sulfatase A deficiency, the enzyme that cleaves sulfate from sulfate containing lipids (sulfatides)
• Accumulation of sulfatides, particularly cereboside sulfate
• Autosomal recessive
• Demyelination and gliosis
• Macrophages with vacuoles
• Metachromasia

Back 21

Metachromatic Leukodystrophy

Metachromasia- Tissue is a different color under the dye than is expected

Front 22

What presents w/:
• Progressive disease with myelin loss in the CNS and peripheral nerves + adrenal insufficiency
• X-linked and one autosomal recessive inheritance
• X-linked mutations are in the ALD gene which encodes a transporter protein called ABCD1, resulting in the inability of peroxisomes to catabolize very long chain fatty acids.
• Loss of myelin, lymphocytic infiltration, and gliosis in the CNS

Back 22

Adrenoleukodystrophy

Front 23

1. What things are secondary to systemic myelin disease?
2. What can malnourishment (ethanol), rapid correction of hyponatremia lead to?
Sx of 2: assymptomatic, quadriparesis to coma usu. rapidly progressive quadriplegia

Back 23

1. Anoxia (affects neurons and axons), Toxins (affects neurons and axons), and Nutrition ** Vit B12 ** - leads to subactue combined degeneration
2. Central pontine myelinolysis