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CNS Patho > Sheet 3 > Flashcards

Sheet 3 Flashcards

1
Q

What is the myelin sheath?

A

A substance that surrounds the nerve axon

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2
Q

What is the myelin sheath composed of?

A

Fats and proteins (specialized

plasma membrane)

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3
Q

What is the function of the myelin sheath?

A

Insulation of the electricity inside the nerve axon to maintain the rapid
propagation of the neural impulses and protect the axon

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4
Q

What forms the myelin sheath in the CNS?

A

Oligodendrocytes

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5
Q

Any disease that affects the myelin will affect:

A

The white matter of the CNS.

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6
Q

CNS diseases that involve the myelin are categorized into two main groups:

A

1) Demyelinating diseases

2) Dysmyelinating diseases (Leukodystrophy)

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7
Q

Demyelination diseases are all characterized by two main things:

A

1) Are acquired diseases (Not inherited)

2) Involve damage to previously normal myelin.

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8
Q

What could damage normal myelin?

A

A) Immune mediated injury (Multiple sclerosis MS)
B) Viral infection of Oligodendrocytes.
C) Injury caused by drugs.
D) Other toxic agents.

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9
Q

Dysmyelinating diseases share in common:

A

1) Abnormal formation of myelin
2) Caused by mutations that disrupt the function of proteins required for the formation of normal myelin sheaths (Inherited disorders)

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10
Q

What are the main types of demyelinating diseases of the CNS?

A

1) Multiple sclerosis (MS) (Most common)
2) Neuromyelitis Optica
3) Post infectious demyelination
4) Central pontine myelinolysis

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11
Q

What is Multiple sclerosis (MS)?

A

Autoimmune destruction of myelin

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12
Q

What is Multiple sclerosis (MS) characterized by?

A

Episodes of disease activity, separated in time that produce white
matter lesions that are separated in spaces.

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13
Q

What is the prevalence of Multiple sclerosis (MS) in USA and Europe?

A

1/1000 individuals

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14
Q

Is the incidence of Multiple sclerosis (MS) increasing or decreasing?

A

Increasing

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15
Q

At what age does Multiple sclerosis (MS) present?

A

Any age, but usually around 20-40. (Early childhood or after 50 is rare)

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16
Q

Which gender is more affected by Multiple sclerosis (MS)?

A

Women (x2 than men)

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17
Q

What is the development of Multiple sclerosis (MS) related to?

A

1) Undefined environmental triggers

2) Genetic susceptibility

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18
Q

Incidence of MS is _-fold higher when disease is present in a first-degree relative, and _-fold higher with an affected monozygotic twin.

A

15; 150

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19
Q

Which genetic loci are associated with MS?

A

1) HLA (major histocompatibility complex), specifically HLA-DRB1*1501
2) IL-2 & IL-7 receptor genes
3) Other genes encoding proteins involved in immune responses.

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20
Q

Each copy of the HLA allele an individual inherits brings with it _-fold increase in the
risk for MS.

A

3

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21
Q

How is Multiple sclerosis (MS) initiated?

A

1) T-lymphocytes that react against myelin antigen and secrete cytokines:
a) TH1 T-cell: secrete IFN-γ which activate macrophages.
b) TH17 T-cell: promote the recruitment of leukocytes.
2) B-lymphocyte and anti-bodies (humoral part): poorly defined role in MS

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22
Q

What do MS patients benefit from?

A

B-cell depleting therapy (Immune suppressing therapy against B-cells)

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23
Q

What is the main pathogenesis of MS?

A

Inflammation

24
Q

What is the morphology of MS?

A

Multifocal white matter disease (not a single spot).

25
Q

Grossly, the MS lesion is called a __. What is it described as?

A

Plaque; discrete, slightly depressed, glassy appearing, and gray tan in
color.

26
Q

What causes neurological manifestations in MS?

A

Inflammation that affects the white matter = inefficient nerve impulse

27
Q

Where can MS lesions happen?

A

Anywhere in the white matter but most commonly near ventricles, optic
nerve (or chiasm), ascending and descending fiber tract, cerebellum, and spinal cord.

28
Q

Which tool is important in diagnosing CNS disorders (including MS)?

A

MRI

29
Q

How will the MS plaques appear on an MRI?

A

As white areas

30
Q

When is histology used for MS?

A

For researches and autopsies (NO diagnosing)

31
Q

Which stain is used for MS?

A

Luxol-fast-blue: Stains the white matter blue (dark blue is the myelin and inside it we can find pale areas = no myelination (damaged myelin),

Pale areas = MS plaques

32
Q

What are the types of MS plaques?

A

1) Active plaques: with inflammation

2) Inactive plaques (Quiescent): without inflammation

33
Q

What do active plaques contain?

A

1) Abundant macrophages stuffed with myelin debris (to engulf the damaged myelin),
= evidence of ongoing myelin breakdown.
2) Lymphocytes, mostly as
perivascular cuffs) around blood vessels).
3) Small active lesions often are centered on small veins.
4) Axons are relatively preserved.

34
Q

What do inactive (Quiescent) plaques contain?

A

1) The inflammation mostly disappears.
2) Little to no myelin (so the dark blue color seen previously will disappear)
3) Evidence of repair and tissue healing, by astrocyte proliferation and gliosis.

35
Q

What do the clinical features of MS depend on?

A

1) The location of the injury
2) Severity
3) Episodic type

36
Q

What commonly happens in MS?

A

Multiple relapses followed by episodes of incomplete remission = gradual/stepwise accumulation of neurological deficits.

37
Q

How can we determine the site of injury of MS?

A

Depending on the location of symptoms

38
Q

Are the symptoms of MS reversible?

A

Yes, but they tend to recur

39
Q

What is a more mild symptom found in MS?

A

Changes in cognitive function

40
Q

Can we predict when the next relapse will occur?

A

No

41
Q

How else can we diagnose MS?

A

By the cerebrospinal fluid (CSF)

42
Q

What does the cerebrospinal fluid (CSF) consist of?

A

It is an ultrafiltrate of plasma with low protein content and few cells

43
Q

What produces the CSF?

A

1) Choroid plexus

2) Ependymal cells of brain ventricular system

44
Q

What are the functions of the CSF?

A

1) It cushions brain and spinal cord from injury

2) Serves as a nutrient delivery and waste removal system

45
Q

What is the procedure of obtaining CSF?

A

A lumbar puncture; Inserting a needle in the lumbar area between L3 and L4 and taking a small amount
of CSF.

46
Q

How do we examine a CSF sample?

A

By protein electrophoresis:
A biochemical test that detects the presence of proteins in fluids and it separates proteins according to their size and charges.
• It shows proteins as bands.
• Used to compare proteins in serum and CSF.

47
Q

CSF has the same (or less) proteins as:

A

The plasma

48
Q

The presence of extra bands in the CSF means:

A

That these are proteins which are secreted intrathecally (within the CSF) = abnormal = inflammation of CNS.

49
Q

The protein electrophoresis test is also called:

A

Oligoclonal bands

50
Q

Where is the oligoclonal

band found?

A

The plasma ONLY

51
Q

If the CSF has the oligoclonal band, it means that:

A

The extra band in the abnormal CSF contains immunoglobulins which are produced inside the CNS (because of the inflammation).

52
Q

Which protein will the CSF show abnormally high amounts of?

A

Immunoglobulins

53
Q

Patients of MS will show:

A

1) High amount of proteins (especially the Ig)

2) Moderate pleocytosis in 1/3 of cases (the presence of abnormally large number of lymphocytes in the CSF)

54
Q

What is the treatment for MS?

A

1) Immunosuppression (to decrease the rate and severity of relapses which is also called Disease modifying therapies) to treat the original cause (the inflammation)
2) Supportive therapy for the symptoms (physiotherapy to regain the lost function)

55
Q

What makes MS worsen over time?

A

Limited capacity of CNS to regenerate normal myelin

56
Q

What is preserved at the beginning of MS?

A

Axons

57
Q

What characterizes late MS?

A

Secondary damage to axons that might occur after repeated relapses

CNS Patho (8 decks)

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