11-26 NeuroPATH Myelin Diseases Flashcards
What makes CNS myelin?
oligodendrocytes
leukodustrophies, general def
a group of enzymatic dzs result in myelin loss and death of oligodendroglial cells
MS, gen def
chronic inflamm dz of CNS (not PNS!) causing:
—demyelination
—oligodendroglial death
—variable degrees of tissue damage
Who get MS more often, men or women?
women
What pattern do MS plaques show in RRMS?
none, totally random distribution in the CNS WM
What do MS plaques look like pathologically?
Grossly: sharp-bordered areas that look like GM in the WM tracts
Histo: gliosis; late—>axonal death
TEM: no nice donut wrapping around large hole; see astrocytes invading (research: they are likely inhib re-mye, how to stop?)
shadow plaques
initially sharp edges of myelin loss that show RE-myelination; active area of research
Which immune cells come into plaque? What type of hypersensitivity reaction do you get?
CD4+ T-cells and MOs (remove degrading myelin); Type IV hypersensitivity
What gene is most highly correlated across MS pts?
MHC Class II (presents Ags to T-cells)
Natural history of Classical RRMS (Charcot’s)
Relapsing-Remitting predominates first
—Sx due to inflammation which starts as beads of T-cell/MO inflamm along small BVs w/in CNS
—With enough of this infall, demyelination happens, though there will still be slow transmission
—eventually you often get axonal death
Progressive Phase often follows later
—relapses do not full-recover; downward slope of sx/functioning
Schilder’s Disease
bilateral dramatic massive demyelinating lesions; look sort of ring enhancing (r/o cancer, abscess?
**very rare
Balo’s Concentric Sclerosis
big, lots of necrosis; layers of normal and devastated WM —T-cell/MO inflamm —oligos gone in demyelinated zones —myelinated zones normal —more common in asia
ripples on a pond/tree rings —> we don’t know why!
ADEM (Acute Disseminated Encephalomyelitis)
umbrella term
—formerly many: post-vaccinial, p-infectious, p-measles, rabies post-vaccinial, transverse myelitis
—lots of triggers: snake bite, Campylobacter was biggie in China, others
—fulmanant, monophasic, perivenous (losing myeine around small venules) dz usu. s/p viral infx
—T-cell/MO inflamm cause breakdown of BBB seen on MRI
—if pt survives acute fulminant stage, usually full recover
ADEM sub-type: Post-measles encephalitis
—big prob pre-vaccine; common in Peru today
—acute (wks-months after): large ring enchancing lesions w/ edema
—years after: very rare SSPE (subacute sclerosing panencephalitis): progressive, massive demye, years s/p
ADEM sub-type: Acute Hemorrhagic Encephalomyelitis (Weston Hurst Dz)
—inflamm w/ T-cell and MOs but also PMNs
—vascular necrosis in addition to demyelination
—grossly: lots of tiny little hemorrhages in WM
—histo: demyelinated area with MO’s and T-cells + PMNs attacking art wall —>RBCs leaking out
——axons die (“are transected”) in adjacent areas
Central Pontine Myelinolysis
—usually in pts w/ other illness first (usu w/ electrolyte imbalance**Frequently iatrogenic!!)
—locked-in syndrome—>coma—>death
—almost no one survives
—DON’T CORRECT ELECTROLYTES TOO QUICKLY
—no inflamm; oligos die and axons in area are transected
—MRI: someone punched out middle of pons bilaterally
What are Leukodystrophies? Give 3 examples.
DYSmyelinating Dzs —> something wrong with myelin itself; usu inborn error of metabolism causing build-up of some metabolite and its precursors
—present in CNS b/c it uses these prots more
—All kind of present like really bad MS
—very rare; usually peds
1. globoid cell leukodystrophy (Krabbe’s dz)
2. metachromatic leukodystrophy
3. Pelizaeus-Merzbacher’s Dz
globoid cell leukodystrophy (Krabbe’s dz)
—Developmental delay and psychomotor retardation, blindness, myoclonus, coma and death in 1-2 years
—Late infantile form is typical, but adult forms have been described - up to 73 yrs.
—Galactocerebroside-β-galactosidase = lost or mutated —> galactocerebroside builds up
—No inflamm but large MOs (“globoid cells”) appear perivascular
—Oligos die—>myeline bye
—Path: extensive loss of myelin
metachromatic leukodystrophy
—Three types: late-infantile, intermed., juvenile.
—Loss of previous abilities, motor/gait problems. behavior problems, blindness and decr abilities in all modalities leading —> coma and death.
—classic: loss or deficiency of Aryl-sulfatase-A Chr. 22 – multiple mutations reported
—Sulphated lipid – cerebroside sulfate – accumulates in CNS (Also PNS) & kidney—> oligos die —> myelin lost
—Macrophages are abundant in the CNS removing debris, but no inflamm
—Name comes from stain purple stain—>mahogany brown
Pelizaeus-Merzbacher’s Dz
—Neuro degen w/ blindness szs, spacticity —> death
—No inflamm present in CNS
—6 clinical types – vary from congenital type to slow adult form
—Age: neonate to 50s
—Most common mutation is gene duplication of PLP (proteolipid protein) gene on Xq22.33-22 (therefore more males
—Multiple others identified, some not in PLP exons
—PNS myelin not involved
Spastic Parapalegia type 2
—Another PLP mutation
—Animal Models: Rabbit paralytic tremor, “rumpshaker” mouse, “jimpy” mouse
—PLP Knock-out mouse virtually normal
—Minor point mutations range from mild to severe
—Protein misfolding leading to accumulation in the ER and altered oligo apoptosis believed responsible
