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70 Cards in this Set
- Front
- Back
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What is involved in the pathological process of demylinating diseases of the nervous system? What is spared?
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-Myelin sheaths involved
-Axons are spared |
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So are all demyelination diseases classified as demyelinating diseases?
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No
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What are 2 pathological conditions that involve myelin breakdown that are NOT classified as demyelinating diseases?
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-Neuron/axon degenerative diseases in which myelin also breaks down
-Death/interruptions of neurons and axons due to infarcts, etc. |
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What are 2 subcategories of Demyelinating Diseases?
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-Myelinoclastic diseases
-Dysmyelinating diseases |
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What is a Myelinoclastic disease?
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When myelin does get formed normally, but then is destroyed by either endogenous or exogenous agents
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What is a Dysmyelinating disease?
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When some enzymatic disorder interferes with the normal formation or maintainence of myelin
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What is the typical onset of
-Myelinoclastic diseases -Dysmyelinating diseases |
Myelinoclastic: Adult
Dysmyelinating: infant/early childhood |
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What is the typical lesion distribution seen in
-Myelinoclastic diseases -Dysmyelinating diseases |
Myelinoclastic: disseminated
Dysmyelinating: bilateral/diffuse |
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What is the typical progression of:
-Myelinoclastic diseases -Dysmyelinating diseases |
Myelinoclastic: Stepwise
Dysmyelinating: Rapidly progressive |
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What does the term Demyelination really mean?
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Breakdown of the normal constituents of myelin and formation of simple lipids or neutral fats.
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What are the 4 histologic steps seen in demyelination?
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1. Loss of normal myelin structures
2. Phagocytosis of myelin sheaths by macrophages 3. Inflammatory cell reaction 4. Reactive gliosis |
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What cell changes either precede or follow the loss of normal myelin structures?
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-Myelin sheath swells/breaks down
-Oligodendroglia degenerate |
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In what type of demyelinating disease is phagocytosis of the breakdwon products by macrophages more widespread?
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Dysmyelinating diseases (childhood)
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Which type of demyelinating disease is more characterized by macrophages moving toward the perivascular spaces?
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Myelinoclastic diseases (adult)
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In which type of demyelinating disease are inflammatory cell reactions more pronounced?
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Myelinoclastic diseases
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What happens last in the process of demylination?
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Macrophages disappear
Reactive gliosis develops |
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Though rare, in which type of demyelinating disease is regeneration and proliferation of oligodendroglia more likely?
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Dysmyelinating disease (child)
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What is the prototypic myelinoclastic disease?
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Multiple sclerosis
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What is the cause of MS?
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Unknown
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What are 3 major theories as to the etiology of MS?
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-Direct viral infection of CNS
-Abnormal viral immune response -Abnormal dairy product response |
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What are 2 other factors that may contribute to the etiology of MS?
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-Environmental factors
-Genetic factors |
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What are the 2 more typical locations of demyelinating lesions in MS?
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In the white matter of
-Periventricular space -Perivenous spaces |
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What are 4 pathological findings other than multiple demyelinating lesions in MS?
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-Norm to slightly increased CSF protein
-Increased gammaglobulins -Oligoclonal IgG and MBP -Elevated Measles titer |
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Why do neurologic symptoms in MS have a tendency to come and go?
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Because the axons themselves are preserved, so reforming myelin by oligodendroglia can occur.
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What causes permanent deficits in MS to develop?
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Destruction of some axons
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How does the reversibility and nonreversibility of axon degeneration in MS affect the disease clinical course?
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It shows a stepwise progression.
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What are the 2 main variants of MS?
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-Neuromyelitis optica
-Acute multiple sclerosis |
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What is another name for Neuromyelitis optica?
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Devic's disease
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Where do the demyelinating lesions occur in Devic's disease?
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1. Optic nerve
2. Spinal cord One follows another |
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How do the pathological changes and prognosis in Devic's disease compare to the usual MS cases?
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Much more severe and poorer
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What is an acute fulminant form of MS called?
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MS of Marburg type
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In what patients is MS of Marburg type typically seen and how long does it last?
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-Young adults
-Lasts a few months |
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What are 2 other Myelinoclastic disease other than MS?
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Post-infectious/Post-vaccinal encephalomyelopathies
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What do the post-infectious or vaccinal encephalomyelopathies likely represent?
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Allergic reactions to the virus or vaccine
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What are the 3 predominant pathological findings in post-infectious or vaccinal encephalomyelopathies?
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-Disseminated demyelination
-Focal hemorrhages -Necroses |
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What is a similar but more fulminant disease that may or may not be associated with infection or vaccination?
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Acute necrotizing hemorrhagic encephalomyelitis
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What is another name for the Dysmyelinating diseases? In what patients are they more often?
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-Leukodystrophies
-Children/young adults |
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In general how does the clinical course and prognosis for the Leukodystrophies compare to that for the myelinoclastic diseases?
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-More progressive
-More fatal |
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How do the lesions in the Leukodystrophies compare to those in myelinoclastic diseases?
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-Bilateral
-Symmetrical -Extensive |
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What are the 3 main clinical manifestations of the dysmyelinating leukodystrophies?
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Motor dysfunction
-Spasticity -Ataxia |
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How are most of the leukodystrophies transmitted?
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By Autosomal recessive genetic inheritence
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How can the enzyme deficiency in the leukodystrophies be determined?
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By biochemical testing
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What are the 3 most frequently encountered leukodystrophies?
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1. Metachromatic leukodystrophy
2. Globoid cell leukodystrophy 3. Adrenoleukodystrophy |
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What is another name for Metachromatic leukodystrophy?
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Sulfatide lipidosis
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What is the enzyme deficiency in Metachromatic leukodystrophy?
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Arylsulfatase-A
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What is Arylsulfatase-A normally needed for?
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Breakdown of sulfatide into cerebroside
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What happens to the Sulfatide that can't be properly broken down in Metachromatic leukodystrophy?
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It accumulates in myelin sheaths, neurons, glial cells, and neuropil
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On what chromosome is the gene for Arylsulfatase-A located?
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Ch' 22q
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Does sulfatide only accumulate in neurons in Metachromatic leukodystrophy?
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No, it accumulates in other organs as well - so it is a systemic disorder.
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Why is Sulfatide lipidosis called Metachromatic leukodystrophy?
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Because the sulfatide turns stains different colors
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What is another name for Globoid cell leukodystrophy?
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Krabbe's disease
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What is the enzyme deficiency in Globoid cell leukodystrophy?
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Galactosylceramidase
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What does galactosylceramidase normally do?
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Breaks down Galactocerebroside into Ceramide and Galactose.
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Where does the Galactocerebroside accumulate then in Globoid cell leukodystrophy?
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Nowhere - it goes thru an alternative catabolic pathway
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What is the product of the alternative catabolic pathway for Galactocerebroside?
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Galactosylsphingosine (psychosin)
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Why is Galactosylsphingosine bad?
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It is toxic to oligodendroglial cells.
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What microscopic feature is hallmark to Globoid cell leukodystrophy?
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Macrophage-transformed multinucleated globoid cells in the perivascular space
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What is the genetic inheritance of Adrenoleukodystrophy?
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Sex-linked
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What was Adrenoleukodystrophy considered to be until recently?
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Schilder's disease - infantile MS
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What is the mutation in ALD?
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-The ALD gene on the X chromosome q28
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What is the enzyme deficiency in ALD?
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Fatty acyl-coA ligase
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What is the Fatty Acyl-CoA ligase enzyme needed for?
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Enzyme transport in lysosomes
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What tissues are affected in Adrenoleukodystrophy?
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-White matter
-Adrenal gland |
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What accumulates as a result of decreased Fatty AcylCoA ligase activity?
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Very long chain fatty acid esters of cholesterol
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What do the FA Cholesterol esters stain positive with?
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Sudan
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What does the adrenal gland involvement in ALD lead to?
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Addison's disease
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What are 2 clinical forms of Adrenoleukodystrophy? Which has better prognosis?
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-Juvenile form
-Adult form - better prognosis |
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When does ALD usually manifest? What is the typical prognosis and progression in the child form?
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Late childhood
-Rapid progression -Death in 5 years |
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What tissues are affected in the adult form of the disease?
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-Spinal cord
-Peripheral nerves |
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What is the adult form of ALD called?
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Adrenomyeloneuropathy
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