Demyelinating Disorders Flashcards
What cells myelinate the CNS?
Oligodendrocytes
What cells myelinate the PNS?
Schwann cells
What are leukodystrophies?
Inherited mutations in enzymes necessary for production or maintenance of myelin
What enzyme is deficient in metachromatic leukodystrophy?
Arylsulfatase deficiency; autosomal recessive disorder
What happens due to the arylsulfatase deficiency in metachromatic leukodystrophy?
Myelin cannot be degraded and accumulates in the lysosomes of oligodendrocytes
What enzyme is deficient in Krabbe disease?
Galactocerebroside-beta-galactosidase is deficient; autosomal recessive
What accumulates in Krabbe disease?
Galactocerebroside accumulates in marcophages
What causes adrenoleukodystrophy?
Impaired addition of coenzymeA to long chain fatty acids; X-linked defect
What is accumulated in adrenoleukodystrophy?
Accumulation of fatty acids damages adrenal glands and white matter of the brain
What is multiple sclerosis?
Autoimmune destruction of **CNS myelin and oligodendrocytes **
What gene is associated with multiple sclerosis?
HLA-DR2
In what region is multiple sclerosis commonly seenm?
Regions away from the equator
How does multiple sclerosis present?
Relapsing neurologic deficits with periods of remission
What are the clinical features of multiple sclerosis?
Features depend on strcture that is affected
Blurred vision in one eye (optic nerve)
Vertigo and scanning speech mimicking alcohol intoxication (brainstem)
Internuclear ophthalmoplegia (medial longitudinal fasciculus)
Hemiparesis or unilateral loss of sensation (cerebral white matter, usually periventricular)
Lower extremity loss of sensation or weakness (spinal cord)
Bowel, bladder and sexual dysfunction (ANS)
How is the diagnosis for multiple sclerosis made?
MRI - reveals plaques (areas of white matter demyelination)
Lumbar puncture - Increased immunoglobulins with oligoclonal IgG bands, increased lmyphocytes and myelin basic protein
What is seen on gross exam of MS?
Grey-appearing plaques in the white matter
Tx for MS
Treat acute attacks with high dose steroids
Long term treatment with interferon-beta to slow progression
What is subacute sclerosing panencephalitis?
progressive, debilitating encephalitis leading to death
What is the cause of subacute sclerosing panencephalitis?
Slow progressing, persistent infection of the brain by measles virus
What can be found in the neurons and oligodendrocytes in subacute sclerosing panencephalitis?
Viral inclusions
What is progressive multifocal leukoencephalopathy?
JC virus infection of oligodendrocytes (white matter)
What causes reactivation of a latent JC virus infection?
Immunosupression (ie AIDS or leukemia)
What is the clinical presentation of progressive multifocal leukoencephalopathy?
Rapidly progressive neurologic signs (visual loss, weakness, dementia) leading to death
What is central pontine myelinolysis?
Focal demyelination of the pons (anterior brain stem)
