Flashcards in 32. Diseases of Myelin Deck (58)
define Guillian Barre syndrome
myelin is attacked by the immune system
a few qualities of myelin?
INERT, cell membrane, functions as an insulator, can be antigenic (MS, Guillian-Barre)
what cells make myelin in the CNS?
what cells make myelin in the PNS?
general definition of leukodystrophies?
DYSmyelinating disease. the MYELIN itself is abnormal
myelin loss due to enzymatic deficiency, gene mutations, accum of toxins.
describe myelin as it is wrapped around an axon
very compact layering, cytoplasm has been squeezed out of inner rings. inner leaflets of membrane are touching each other
Olig cell in CNS: a few qualities?
metabolically active. each Oligo supports up to 20 segments of myelin.
with demyelination diseases, is the myelin itself normal or abnl?
pathological definition of MS?
IMMUNE ATTACK on oligos.
chronic inf disease of CNS, causing demyelination, death of Oligs, tissue damage.
a few variants of MS?
Charcot (classical), Marburg, Balo's, Devic's, Schilder's, Massive Demyelinating Lesions
typical epidemiology of relapsing-remitting MS?
women > men
onset in 20s
tissue affected in relapsing-remitting MS?
plaque of periventricular white matter
do plaques in MS follow a particular pattern?
no, random plaques. tend to be sharp-edged, can extend to grey matter. do not follow tracts, vessels, nT pathway. can be anywhere.
(later slides: maybe they do follow blood vessels: beads on a string?)
what happens to axons after demyelination?
what cells are in the MS plaque?
CD4+ T cells, macrophages
the 4 main clinical types of MS?
clinical course of relapsing-remitting MS?
neuro problems, then they resolve within a few weeks. but resolution is indication that inflammation is subsiding, not re-myelination.
clinical course of progressive types of MS?
people have neuro problems, and they don't improve functioning between attacks. more axonal damage is occuring.
relapsing-remitting is also called what?
Charcot (classic MS)
Schilder's type MS: characteistics?
large, bilateral demyelinating lesions. quick onset. white matter is melted away.
Balo's Concentric Sclerosis (MS): characteristics?
path: think HALOs. alternating layers of myelin loss and preserved/normal oligs. unusual pattern! like tree rings.
Acute Disseminated Encephalomyelitis (ADEM): a few points/characteristics?
NOT MS. etiology is post-infection.
fulminant (sudden/severe) perivenous demyelinating disease.
usually seen after a viral infection (vaccine, measles, rabies).
it will reverse after the acute attack
what bacterium is associated with ADEM?
campylobacter jejuni. disease has been known to develop after exposure to this. prevalent in China. CJ may cross-react with CNS myelin -> attack of myelin
why might the BBB fail after ADEM?
breakdown of vessels (ADEM is perivenous)
what does ADEM look like on pathology?
white-enhancement in white matter, wide dissemination. with myelin stain, may see PINK STREAKS on brainstem slices. remember follows vessels.
post-measles encephalitis: typical presentation?
post-infectious demyelinating, usually 2-7 days after initial rash. fever, depressed consciousness.
less common now due to measles vaccine
post-measles encephalitis: appearance of brain imaging?
ring-enhancing, (not sure what type of scan)
on T2-weighted, widespread edema or demyelination in entire subcortical white matter
begins as perivascular.
Acute Hemorrhagic Encephalomyelitis (Weston Hurst Dz): characteristics?
abrupt onset, progressing to seizures, motor signs and death in 1-5 days (due to brainstem herniation)
necrosis of vessels plus demyelination
Acute Hemorrhagic Encephalomyelitis (Weston Hurst Dz): inflammatory infiltrate contains what?
Tcells, macrophages, VASCULAR NECROSIS DUE TO NEUTROPHIL ATTACK OF VESSEL WALL
Acute Hemorrhagic Encephalomyelitis (Weston Hurst Dz): appearance on gross brain?
looks like contusions but more widespread. tiny hemorrhages (necrotic blood vessels) in white matter
Central Pontine Myelinolytis: a few characteristics?
only in CENTRAL PONS. no inflammation. edema from vascular leakage. oligo cells die, axons are transected.
found in individuals who are ill from another cause (may be alcs with liver failure)
rapid onset of motor and sensory sx, freq coma and death
Central Pontine Myelinolitis: etiology?
iatrogenic. from rapid correction of electrolyte imbalance.
Central Pontine Myelinolitis: appearance on imaging?
very distinct: a hole in the central pons. symmetrical. starts in center of pons and moves outward.
Central Pontine Myelinolitis: how to diagnose?
3 types of Leukodistrophy?
-Globoid Cell (Krabbe's Disease)
if leukodyst is an error of metabolism or enzyme deficiency, why does it appear in the CNS mainly?
because the CNS uses specific pathways/materials that are affected by these problems.
another list of features of leukodystrophies?
-all body tissues are affected
-material that accum is heterogenous
-a single enzyme is defective/absent
-material accumulates in membrane-bound intracellular compartments
-tissues that most use the enzyme are most affected
Clinical features of Globoid Cell Leukodystrophy?
dev delay, retardation, blindness.
coma/death in 1-2 y.
usually late infantile
Globoid Cell: enzyme that is defective?
Globoid Cell Leukodystrophy? what happens at the cellular level?
Galactocerebroside accum in cells of CNS.
large macrophages called GLOBOID CELLS develop.
Oligo cells are vulnerable, the die, hence demyelination
Globoid Cell Leukodystrophy: appearance on gross brain?
widespread demyelination, bilateral
looks a lot like Schilder's type of MS.
Globoid Cell Leukodystrophy: appearance on histo?
accumulation of large macrophages
globoid cells with foamy cytoplasm
Metachromatic Leukodystrophy: clinical profile?
loss of abilities, motor/gait problems, behavior probs, blindness and decr abilities
Metachromatic Leukodystrophy: what is accumulating? is there inflammation?
a sulfated liquid accumulates in CNS and kidney. oligo's die, hence myelin is lost.
no inflammation despite macrophages in CNS to remove debris
Metachromatic Leukodystrophy: how did it get its name?
appearance with a specific stain. stain is purple but pathological area (macrophages) -> brown.
Pelizaeus-Merzbacher: clinical profile?
neurodegeneration with blindness and seizures, spacticity, leading to death.
Pelizaeus-Merzbacher: is PNS involved? is there inflammation in the CNS?
PNS not involved becuase it uses a diff gene.
CNS: no inflammation
Pelizaeus-Merzbacher: feature of knockout mouse?
PLP knockout mouse basically normal. meaning: better to not have any PLP at all than to have mutated PLP
but seen in some families.
higher risk for people who are farther away from equator in first 15 yrs of life
what do we call a single episode of demyelination?
clinically isolated syndrome
a single episode of demyelination is a risk for what?
50% risk of going on to have recurrent episodes (ie, MS)
can we dx MS if a patient only has one single location of damage?
no. look for local cause before assuming this is demyelinating.
MS: symptoms focal or diffuse?
scattered throughout nervous system
what is L'Hermitte's sign?
finding in MS. aka Barber Chair phenomenon.
electrical sensation down back or legs when neck is flexed (chin to chest). due to irritation of cervical spinal cord sensory tracts.
does MS damage neuron cell bodies?
NO. does not result in LMN damage, damage to cranial nerve nuclei, damage to peripheral nerves
MS and aphasia, memory, cognition: what is seen?
MS does not produce aphasia or effect memory/cognition until late
MS: what will be seen in CSF?
oligoclonal bands, elevated IgG.