Demyelinating Diseases. Demyelination is a common degenerative change in the nervous system...
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![Page 1: Demyelinating Diseases. Demyelination is a common degenerative change in the nervous system secondary to neuronal or axonal injury, But in the group of.](https://reader036.fdocuments.in/reader036/viewer/2022062515/56649ccb5503460f949951f1/html5/thumbnails/1.jpg)
Demyelinating Diseases
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• 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
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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,
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• 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,
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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
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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.
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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.
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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
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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.
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Degenerative DiseasesCerebrocortical 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
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• 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.
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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.
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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.
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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.
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Neuritic plaques in cerebral cortex in Alzheimer's disease, showing cellular processes
disposed around a central mass of -amyloid
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Clinical Features
• 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
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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
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• 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.
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• 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.
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