Download 26-11-13 ipmr Demyelinating Diseases

Demyelinating Diseases
• Demyelination is a common degenerative
change in the nervous system
• secondary to neuronal or axonal injury,
• But in the group of diseases known as the
demyelinating diseases, demyelination is the
primary pathologic process
Multiple Sclerosis
• The most common demyelinating disease.
• Most common in the scandinavian countries,
with a prevalence of 80:100,000 in norway.
The incidence progressively declines as one
moves south (10:100,000 in southern europe).
• Rare in the tropics (1:100,000) and in asia,
• The onset years from 20 to 40.
• Sixty percent of patients are female.
• (Caucasians more commonly affected than
african-americans or native americans).
• Increased familial incidence,
• A 25% concordance in identical twins
compared with 2–3% in fraternal twins,
Etiology
• Immunologically mediated demyelination,
possibly acting via damage to oligodendroglial
cells, which are consistently absent in lesions.
• activation of macrophages and T lymphocytes
• Increased immunoglobulin synthesis
• In both blood and cerebrospinal fluid during the
active phase of the disease.
• Activated T lymphocytes are present in the
lesions of multiple sclerosis
Pathology
• Presence in the white matter of plaques of
demyelination.
• These plaques are perivenular
• Appear as irregular,
• Well-demarcated, gray or translucent lesions
• Diameter varying from 0.1 cm to several
centimeters.
• Multiple plaques, widely disseminated throughout
the central nervous system, are common
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Any area of the brain can be affected.
Optic nerves,
Paraventricular regions,
Brain stem, cerebellum, spinal cord, and deep
cerebral white matter.
Microscopically,
• The plaques show demyelination
• Tangled masses of preserved axons
• Lymphocytic infiltration is present in areas of
active and recent demyelination.
• Macrophages with phagocytosed myelin.
• Reactive astrocytic proliferation at the edges of
the plaque.
• Oligodendroglial cells are typically absent in the
plaque.
Clinical Features
• Chronic disease with an extremely variable
clinical course,
• Episodic relapses and remissions over several
years.
• Mean survival is over 30 years after the onset of
disease.
• A minority rapid course to death within months,
• Some appear to have only one or a few episodes
Common manifestations are
• Abnormalities in vision, cerebellar
dysfunction, paresthesias, weakness, and
spinal cord dysfunction.
• The randomly disseminated nature of the
lesions gives a characteristic clinical picture
when multiple plaques are present.
Degenerative Diseases
Cerebrocortical Degenerations
Alzheimer's Disease
• Extremely common
• Responsible for more than 50% of all cases of
dementia
• Characterized by progressive loss of neurons
in the entire cerebral cortex.
• The frontal lobe is involved preferentially.
• Neuronal loss leads to dementia, which is the
characteristic clinical presentation
• Initially applied dementia under 65 years
(presenile dementia),
• After age 65 was called senile dementia.
• The changes seen in most patients with senile
dementia are identical to those of alzheimer's
disease.
• Alzheimer's disease occurs in 20% of persons
over 80 years old.
Etiology
• Unknown.
• Abnormalities of chromosomes 14, 19, or 21
have been identified in affected families,
• Patients with down syndrome (trisomy 21)
frequently develop lesions of alzheimer's
disease in the third or fourth decade of life.
Pathology
• Grossly, there is atrophy of the cerebral cortex,
• With thinning of the gyri and widening of the
sulci
• Affecting the frontal parietal and medial temporal
lobes.
• The cortical gray matter is greatly thinned and
poorly demarcated.
• The lateral ventricles show compensatory
dilatation.
Microscopically
• Neuronal loss and disorganization of the cerebrocortical
layers.
• Presence of neurofibrillary tangles in the cytoplasm of
affected neurons
• These are complexly interwoven masses of paired helical
filaments 10 nm in diameter consisting of various proteins,
• Neuritic plaques, which are large (150 m) extracellular
collections of degenerated cellular processes disposed
around a central mass of -amyloid protein material
• The degenerated neuritic material contains paired helical
filaments identical to those found in neurofibrillary tangles
in affected neurons.
Neuritic plaques in cerebral cortex in
Alzheimer's disease, showing cellular processes
disposed around a central mass of -amyloid
Clinical Features
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Over 50 years of age.
Loss of higher cortical functions.
The loss of ability to solve problems,
Decreased agility of thought processes
Mild emotional lability
The dementia progresses inexorably over the next
5–10 years to an extent that the patient becomes
unable to carry out daily activities.
• There is no effective treatment
Huntington's Disease(Huntington's
chorea)
• rare disease
• inherited as an AUTOSOMAL DOMINANT
TRAIT with complete penetrance but delayed
appearance.
• The abnormal gene is located on the terminal
segment of 4p.
• DNA probes are now available to detect the
abnormal gene in affected families before
symptoms develop.
• This provides crucial information for genetic
counseling
• Atrophy and loss of neurons of the caudate
nucleus and putamen,
• Associated with variable cerebrocortical atrophy,
particularly in the frontal lobe.
• There is a marked decrease in synthesis of the
neurotransmitter -aminobutyric acid in the basal
ganglia.
• Though inherited, the disease has its onset in adult
life,
• Usually between 20 and 50 years of age.
• It is characterized by dementia, due to cerebral
involvement, and
• Choreiform involuntary movements, due to
involvement of the basal ganglia.
• The disease is slowly but inexorably progressive,
leading to death in 10–20 years.