Myelination Disorders Flashcards
Which cell type is responsible for myelinating axons in the CNS?
oligodendrocyte
How many axons does each oligodendrocyte myelinate?
multiple
What are the 2 major components of myelin?
myelin basic protein
proteolipid protein
What is an inherited demyelination disorder?
Neuromyelitis optica (NMO)
How is MS defined?
demyelination is multifocal and lesions are of different ages (disseminated in space and time)
What are the rapidly progressive types of MS called?
acute (marburg) concentric sclerosis (balo's disease)
Where to plaques usually occur in MS patients?
periventricular white matter optic nerves and chiasm brainstem and spinal cord tracts cerebellum gray matter (but fewer axons so less frequent)
What histologic changes are found in an active plaque?
macrophages wtih myelin debris, perivascular lymphocytes, reactive astrocytes, relative preservation of axons
What histologic changes are found in inactive plaques?
few or no macrophages, few lymphocytes, myelin loss with axonal preservation, fibrillary astrocytes
What histologic changes are seen in shadow plaques?
partial myelin loss
What is acute disseminated encephalomyelitis (ADEM)?
monophasic demyelinating disease, acute onset
assoc w/recent viral illness of vaccines (1-2wk prior)
What are signs and sx of ADEM?
headache, lethargy, coma
How many ADEM pts make a complete recovery?
80%
What changes are seen histologically with ADEM?
perivenous demyelination with axonal preservation
PMNs early, lymphocytes later
What cell type likely precipitates ADEM?
T-cell mediated hypersensitivity rxn
What is seen in an ADEM pt gross specimen?
congested blood vessels in white matter surrounded by zones of gray discoloration
What is neuomyelitis optica?
relapsing synchronous bilateral optic neuriti and spinal cord lesions
What histologic changes are seen in NMO?
necrosis in addition to demyelination with inflammatory cells
What protein is affected in NMO?
Aquaporins (esp AQP 4)
autoantibodies induce complement depenent cytotoxicity, leukocyte infiltration, cytokine release and blod brain barrier break down—>oligodendrocyte death, myelin loss
Are AQP-4 specific IgG antibodies detectable in all NMO patients?
no, only in 60-90%
What is central pontine myelinosis also known as?
osmotic demyelination syndrome
What is central pontine myelinosis?
monophasic process leading to loss of myelin with relative preservation of the axons and neurons in basis points
What are signs/sx of central pontine myelinosis?
limb weakness, gaze/speech abnormalities, dysphagia, hTN
What causes central pontine myelinosis?
usually too rapid correction of hyponatremia
assoc w/alcoholic liver disease, post liver transplant, chronic malnurishment/debilitation, excessive skin burns
What event is believed to initiate the pathogenesis of MS?
myelin specific T cells get activated in the periphery and cross the BBB where they are reactivated in the CNS
What cell type is thought to drive MS?
autoreactive CD4 T cells with specificity for antigens expressed by oligodendrocytes, which comprise myelin (MBP, MOG, PLP)
What factors do CD4 T cells secrete?
IL-17
IFN-y
TNF-a
What types of cells can damage myelin?
T-cells, macrophages, PMNs
Which factors can lead to MHC indepdent cell death via apoptosis?
IFN-y
TNF-a
Fas
TRAIL
What do cytotoxic CD8 lymphoctyes release upon activation via MHC class 1?
granzyme and perforin
Define excitotoxicity
process by which nerve cells are damaged and killed by excessive stimulation by neurotransmitters such as glutamte (NMDA and AMPA)
high levels of glutamate can cause excitotoxicity by allowing high levels of Ca2+ to enter the cell, which activates a number of enzymes that damage cell structures such as the cytoskeleton, membrane and DNA
By what methods can oxidative stress kill cells?
via apoptosis or necrosis
What are the 2 types of Ab mediated cell death?
antibody dependent cell mediated cytotoxicity
complement dependent cytotoxicity
What are the 4 types of clinical courses of MS?
relapsing-remitting (RRMS) secondary progressive (SPMS) primary progressive (PPMS) progressive relapsing (PRMS)
What is clinically isolated syndrome (CIS)?
the first clinical demyelinating event that is suggestive of MS
What is the risk of developing MS after CIS if there are any lesions on initial MRI?
88%
What is the risk of developing MS after CIS if there aren’t any lesions on initial MRI?
19%
What is the most common inflammatory optic neuropathy? What is is associated with?
Demyelinating optic neuritis
associated with MS
What affect do IV steroid have on demyelinating optic neuritis (DON)?
increase the rate at which vision recovers
may also impart short term protective effect against MS
What is the long term of getting MS after having DON on a clean MRI?
25% risk in 15 yrs
What is the longer term risk of getting MS after having DON and an MRI with 1+ lesions?
72% risk in 15 yrs
What sx must ADEM have?
emcephalopathy (behavioral change or alteration in consciousness)
What affect do IV steroid have on demyelinating optic neuritis (DON)?
increase the rate at which vision recovers
may also impart short term protective effect against MS
How is ADEM treated?
high dose IV corticosteroid followed by oral steroid taper over 3-6 wks
What is the longer term risk of getting MS after having DON and an MRI with 1+ lesions?
72% risk in 15 yrs
What sx must ADEM have?
emcephalopathy (behavioral change or alteration in consciousness)
How is ADEM diagnosed?
exclusion
How is ADEM treated?
high dose IV corticosteroid
What might NMO look like in the opthalamoscope?
optic disk may appear normal or swollen acutely, pallor chrnoically
How do most patients with transverse myelitis present?
combo of sensory, motor and bladder/bowel-related sx
What is lhermitte sign?
electircal or dysesthetic sensation in the spine of limbs elicited by neck flexion
How can central pontine myelinosis be treated?
reproduce the original ostmotic state (ie/give hypotonic saline)
What might NMO look like in the opthalamoscope?
optic disk may appear normal or swollen acutely, pallor chrnoically
Which is more likely to be painless? NMO or MS assoc neuritis?
NMO
