Common Demyelinating Disorders

Front 1

Know the three mechanisms for demyelinating disorders and examples of each.

Back 1

1. Destruction of normal myelin
-Example: multiple sclerosis
2. Production of abnormal myelin
-Example: leukodystrophy
3. Destruction of oligodendrocytes
-Examples: multiple sclerosis, slow virus infections

Front 2

Epidemiology of multiple sclerosis

Back 2

1) Most common demyelinating disease
2) Female predominance
-Occurs in women 20-40 years old.
3) Most common demyelinating disease

Front 3

Pathogenesis of multiple sclerosis.

Back 3

(1)CD8 T cell destruction of myelin sheaths and/or oligodendrocytes.
(2) Antibodies directed against myelin basic protein in oligodendrocytes

Front 4

Gross findings (be able to identify)of multiple sclerosis.

Back 4

Demyelinating plaques occur in white matter of brain/spinal cord (Slide 35, 36)

Front 5

Clinical findings of multiple sclerosis.

Back 5

(1) Episodic course punctuated by acute relapses and remissions
(2) Sensory and motor dysfunction
•Paresthesias, muscle weakness
(3) Optic neuritis
(a)Inflammation of the optic nerve
(b)Blurry vision or sudden loss of vision
(4) Cerebellar ataxia
(5) Scanning speech (sound drunk)
(6) Intention tremor, nystagmus
(7) Bilateral internuclear ophthalmoplegia (see schematic next page)
• Demyelination of medial longitudinal fasciculus

Front 6

Regarding multiple sclerosis, laboratory findings.

Back 6

(1) Increased CSF leukocyte count
•Primarily T lymphocytes
(2) Increased CSF protein
•Primarily an increase in γ-globulins
(3) Increased CSF myelin basic protein
•Indicates active disease
(4) Normal CSF glucose
(5) High resolution electrophoresis shows oligoclonal bands
(a) Discrete bands of protein in the γ-globulin region
(b) Sign of demyelination

Front 7

MS:

Back 7

autoimmune destruction of myelin sheath and oligodendrocytes

Front 8

Oligoclonal bands in CSF electrophoresis:

Back 8

sign of demyelination

Front 9

Epidemiology of central pontine myelinolysis.

Back 9

Most often occurs in alcoholics who have hyponatremia

Front 10

pathogenesis of central pontine myelinolysis

Back 10

Rapid intravenous correction causes demyelination in the basis pontis.

Front 11

What is this?

Back 11

Gross findings of central pontine myelinolysis

Front 12

Central pontine myelinolysis:

Back 12

due to rapid intravenous correction of hyponatremia

Front 13

State examples of viral infections that infect oligodendrocytes causing demyelination.

Back 13

-subacute sclerosing panencephalitis
-progressive multifocal leukoencephalopathy

Front 14

Mendelian inheritance of Adrenoleukodystrophy

Back 14

X-linked recessive disorder

Front 15

Enzyme deficiency of
Adrenoleukodystrophy

Back 15

Enzyme deficiency in β-oxidation of fatty acids in peroxisomes.

Front 16

Accumulation products of Adrenoleukodystrophy

Back 16

Results in accumulation of long-chain fatty acids

Front 17

Clinical findings and gross findings of Adrenoleukodystrophy

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Causes generalized loss of myelin in the brain and adrenal insufficiency

Front 18

Mendelian Inheritance of Metachromatic leukodystrophy

Back 18

Autosomal recessive disorder

Front 19

Enzyme deficiency of Metachromatic leukodystrophy

Back 19

Deficiency of arylsulfatase A

Front 20

Accumulation Products of Metachromatic leukodystrophy

Back 20

Results in accumulation of sulfatides

Front 21

Clinical and Gross Findings of Metachromatic leukodystrophy

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Lysosomal storage disease

Front 22

Mendelian inheritance of Krabbe’s disease

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Autosomal recessive disorder

Front 23

Enzyme Deficiency of Krabbe's disease

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Galactocerebroside β-galactocerebrosidase deficiency

Front 24

Accumulation product of Krabbe’s disease

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galactocerebroside

Front 25

Clinical and Gross Findings of Krabbe’s disease

Back 25

Brain shows large, multinucleated, histiocytic cells (globoid cells)