Demyelinating Diseases Flashcards
What are Demyelinating diseases of the CNS ?.
- acquired conditions
- characterized by preferential damage to myelin
- , with relative preservation of axons
The clinical deficits of Demyelinating diseases are due to the effect
of ____________
myelin loss on the transmission of electrical impulses along axons.
-The natural history of
demyelinating diseases is determined, in part, by the________-
limited capacity of the CNS to regenerate
normal myelin and by the degree of secondary damage to axons that occurs as the disease
runs its course.
Several disease processes can cause loss of myelin.
These include destruction of myelin by
_______________
- immunological reactions, as in multiple sclerosis, and by infections.
- In progressive multifocal leukoencephalopathy, JC virus infection of oligodendrocytes results in loss of myelin (described above).
- In addition, inherited disorders may affect synthesis or turnover of myelin components;
these are termed leukodystrophies and are discussed with metabolic disorders
What are you demyelinating diseases?
- MULTIPLE SCLEROSIS
- NEUROMYELITIS OPTICA
- ACUTE DISSEMINATED ENCEPHALOMYELITIS AND ACUTE NECROTIZING HEMORRHAGIC
ENCEPHALOMYELITIS - Central pontine myelinolysis
What is Multiple sclerosis (MS)
- autoimmune demyelinating disorder
- characterized by distinct episodes of neurologic deficits, separated in time, attributable to white matter lesions that are separated in space.
What is the most common demyelinating disorder?
MS
What is the prevalence rate of MS?
having a prevalence
of approximately 1 per 1000 personsin most of the United States and Europe.
What is the age onset of MS?
The disease may
become clinically apparent at any age, although onset in childhood or after age 50 years is
relatively rare.
In terms of gender, which is more affected in MS?
** Women are affected twice as often** as are men.
What is the clinical course of MS?
In most individuals with MS, the
clinical course takes the form of relapsing and remitting episodes of variable duration (weeks to
months to years) marked by neurologic defects, followed by gradual, partial recovery of
neurologic function.
The frequency of relapses tends to decrease during the course of time, but
there is a steady neurologic deterioration in most affected individuals.
The lesions of MS are caused by an _________ that is directed against the components
of the myelin sheath. [27,] [28]
immune response
What is the pathogenesis of MS?
As in other autoimmune disorders, the pathogenesis of this
disease involves both genetic and environmental factors ( Chapter 6 ).
The incidence of MS is
15-fold higher when the disease is present in a first-degree relative and roughly 150-fold higher
with an affected monozygotic twin.
Genetic linkage of MS susceptibility to the_____________extended
haplotype of the major histocompatibility complex is also well established.
DR2
What are the other genetic association in pathogenesis of MS ?
In recent genome-wide
screen supported this association and identified additional associations with single-nucleotide
polymorphisms in IL-2 and IL-7 receptor genes. [29]
The current thinking is that these cytokine
receptor polymorphisms may influence the balance between pathogenic effector T cells and protective regulatory T cells. These genetic associations point to the importance of the immune system in the susceptibility to MS.
What is the pathogenesis of MS?
Given the prominence of chronic inflammatory cells within and around MS plaques as well as
this genetic validation, immune mechanisms that underlie the destruction of myelin are the
focus of much investigation.
The available evidence indicates that the disease is initiated by
CD4+ TH1 and T H17 T cells that react against self myelin antigens and secrete cytokines .
TH1 cells secrete IFNγ, which activates macrophages, and **TH17 cells promote the recruitment
of leukocytes **( Chapter 6 ).
The demyelination is** caused by these activated leukocytes and
their injurious products**.
The infiltrate in plaques and surrounding regions of the brain consistsof T cells (mainly CD4+, some CD8+) and macrophages.
How the autoimmune reaction is
initiated is not understood; a role of viral infection (e.g., EBV) in activating self-reactive T cells
has been proposed but remains controversial.
Based on the growing understanding of the pathogenesis of MS, therapies are being developed
that ________________
modulate or inhibit T cell responses and block the recruitment of T cells into the brain
. A potential contribution of humoral immunity has also been suspected for a long time, based on
the early observation of oligoclonal bands of immunoglobulin in CSF. [31]
The demonstration
that B-cell depletion can decrease the incidence of demyelinating lesions lends support to this
idea.
What is the morphology of MS?
MS is a white matter disease that is best appreciated in sections of the brain
and spinal cord.
Lesions appear as:
- multiple,
- well-circumscribed,
- somewhat depressed,
- glassy,
- graytan,
- irregularly shaped plaques ( Fig. 28-33 ).

What is the appearance of MS In the fresh state?
these are firmer than the surrounding white matter (sclerosis)
Plaques can be found throughout the white matter
and also extend into gray matter, since these have myelinated fibers running through them.
The size of lesions varies considerably, from small foci that are only recognizablemicroscopically to confluent plaques that involve large portions of the centrum semiovale.
The
lesions often have sharply defined borders ( Fig. 28-34 ). Plaques commonly occur adjacent
to the lateral ventricles.
They are also frequent in the optic nerves and chiasm, brainstem,
ascending and descending fiber tracts, cerebellum, and spinal cord.

What is the microscopic finding in MS?
Microscopically, in an active plaque there is evidence of ongoing myelin breakdown with
abundantmacrophages containing lipid-rich, PAS-positive debris.
Inflammatory cells, including
- *both lymphocytes and monocytes**, are present, mostly as perivascular cuffs, especially at the
- *outer edge of the lesion** ( Fig. 28-35A ).
Where Active lesions are often located?
centered on small veins.
Within a plaque there is relative preservation of axons ( Fig. 28-35B ) and depletion of
oligodendrocytes.
In time, astrocytes undergo reactive changes.
As lesions become
quiescent, the inflammatory cells slowly disappear.
Within inactive plaques of MS, which type of cell predominates?
little to no myelin is found, and there is a** reduction in the number of oligodendrocyte nuclei**;
instead,
astrocytic proliferation and gliosis are prominent.
What can you find in the inactive plaques of MS?.
Within inactive plaques,** little to no
myelin is found,and there is areduction in the number of oligodendrocyte nucle**i; instead,
astrocytic proliferation and gliosis are prominent.
Axons in old gliotic plaques show severe
depletion of myelin and are also greatly diminished in number
Active plaques can also be grouped into four basic patterns:
- Pattern 1
- those that are sharply
demarcated and centered on blood vessels, either with (pattern I)
- those that are sharply
- Pattern 2
* or without (pattern II) deposition of immunoglobulin and complement, - (patterns III and IV)
and those that are less well demarcated and are not centered on vessels.

