Path 2 - Neuro 2

pbhati17's version from 2017-03-04 19:07

Neurodegenerative Dzs

Question Answer
*What is Abiotrophy? What is it NOT?This is PRIMARY premature neuronal degeneration. IT ISNT 2° (which would mean it happened bc of a toxin or infectious agent)
*Abiotrophy → 1° neuronal degeneration may have 2 different patterns of involvement. What are they?(1) Restricted to the cerebellar cortex
(2) Involve connected neural systems
If I say that the neuronal abiotrophy involves connected neural systems, who are you thinking of & in this case what is going on?Think multisystem neuronal degeneration in striatonigral & cerebello-olivary degeneration of the Kerry blue terrier. In this case there is cerebellar cortical abiotrophy → degeneration & loss of Purkinje cells → caudate nuclei, putamen & olivary nuclei → substantia nigra (basically, degeneration all over the brain)
Cerebellar abiotrophy → who gets this? How is this different from cerebellar hypoplasia?Dog (many breeds);
Horse (Arabian). It is distinct from cerebellar hypoplasia bc it develops after the cerebellum has attained its full complement & arrangement of neurons. Also, affected animals appear normal at birth → ataxia & dysmetria before maturity
What are the gross & histologic lesions of cerebellar abiotrophy?GROSS: Cerebellum can be normal or shrunken
HISTOLOGIC: neuronal degeneration & loss, + reactive gliosis
*Prion Dzs → Transmissible spongiform encephalopathies (TSE's): are these Dzs inflammatory? Are they transmissible?NOT inflammatory, but ARE transmissible!
What is PrPc? What is PrPSc/ PrPres? What is PrPd?C=Normal cellular glycoprotein of the CNS & lymphoid tissue ("cellular")
Sc/Res are both the same thing
Sc means scrapie (named after sheep dz) & res means protease resistance (which prions are)
d is "Dz associated isoform”, which is a misfolded form of PrPc. It does have the same amino acid sequence, but a different 3D structure. (Fewer α helices; more β sheets)
How does PrPsc perpetuate/infect the neuro. System?Self-replicates by templating the conformational rearrangement of PrPC (if it touches other proteins, they get the same bad conformation as the PrPsc)
What role does PrPc in prion dzs?C=Normal cellular glycoprotein of the CNS & lymphoid tissue. However, the fxn is not known...what they do know is that its existence allows for the propagation of the PrPsc & the development of the lesions of SE (spongiform encephalopathy). They also discovered that depletion of neuronal PrPC in transgenic mice infected w/ prions prevents the development of clinical Dz & reverses the lesions of spongiosis
*What are 3 major lesions of prion DZs (TSEs)(1) Spongiform change of the neuropil (broad term defined as any area in the nervous system composed of mostly unmyelinated axons, dendrites & glial cell processes that forms a synaptically dense region containing a relatively low number of cell bodies.).
(2) Neuronal degeneration, apoptosis & loss >> prominent cytoplasmic vacuoles
(3) Astrocytosis (mild to severe)
Scrapie in sheep → What is the scrapie prion? Which sheep is it common in? Is age a factor? Is there xmission? What is the prognosis?Scrapie prion: OvPrPSc. Common in Suffolk herds, esp. in 2-5 year olds. Ewe to lamb xmission is common. Scrapie is a progressive, fatal Dz


Question Answer
What are the CS of scrapie in sheep?Common CS are b/h changes, ataxia/incoordination (stiff trotting gait) & intense pruritus >> scrape their hides >> loss of fleece. You will also see restlessness, dilated pupils & debility
Scrapie of sheep → What is the etiological agent? Is it transmissible? What is the incubation period like?The etiologic agent is not completely elucidated (known) → (prion protein; protease-resistant protein, normal gene product (PrP gene), membrane glycoprotein (? fxn)). It IS transmissible. There is a PROLONGED/EXTENDED INCUBATION PERIOD.
Scrapie of sheep → What are the gross lesions of the brain? Microscopic lesions of the brain? What are some characteristics of the lesions? (Location, symmetry?)No significant gross lesions. Microscopically there are large vacuoles in the cytoplasm of neurons & gliosis (NO INFLAMMATORY LESIONS). Lesions are BILATERALLY SYMMETRICAL & limited to the medulla, pons, midbrain & spinal cord
Bovine spongiform encephalopathy → What is the prion for this Dz? What is the incubation period?BSE prion: BoPrPSc. The incubation period is 2-8 years
What are the CS of BSE? (How long till final prognosis?)Nervousness or aggression, abnormal posture, ataxia, ↓ milk production, weight loss despite continued appetite, death w/in 2 weeks to 6 months. Another slide said: progressive apprehension, ataxia, hypermetria, aggression, nervousness, slipping, recumbency
What are the microscopic lesions of BSE?Vacuolation of neuronal cell bodies, astrogliosis
What must you differentiate BSE from & how would you dx it?DDX: hypomagnesemia, acetonemia, Rabies, other CNS
Dzs. DX: histology (brain stem), PrP immunostaining, electron microscopy (SAFs)
Chronic wasting Dz → who does this affect? What is the causative prion?(The only TSE found in free-ranging species). Endemic in free-ranging elk, mule deer & white-tailed deer. CWD prion: MdePrPSc
Chronic wasting dz → what age animal does this usually affect? What are the CS?Affects mainly 3 to 5-year-old animals (elk/mule deer/ white tailed deer) & you will see behavioral changes, weight loss, emaciation & death
Transmissible mink encephalopathy → what is the prion for this dz? How did this happen in minks? What are the lesions?Prion: MkPrPSc. associated w/ feeding of meat & bone meal derived from a downer cow. Lesions: neuronal vacuolation (cerebellar peduncles), neuronal degeneration, gliosis
Feline spongiform encephalopathy → what is the prion for this dz? How do cats get it?Prion: FePrPSc. Infected via consumption of infected bovine tissue
Exotic ungulate encephalopathy → what is the prion for this? Which animals does this occur in?Prion: UngPrPSc. Occurs in in Nyala, greater kudu, Oryx
**Where do you look to diagnose prion dzs w/ Histopathy???Lesions in the brain stem >> obex. Variant forms might be seen in the olfactory bulb, cerebral cortex, hippocampus (associated w/ amyloid plaques)
**Explain Dx of prion dzs via Immunohistochemistry. Where do you take samples from? (Not post mortem)Dx via detection of prion protein. Lymphoid tissue of the 3rd eyelid in live sheep w/ scrapie. Tonsils or retropharyngeal lymph nodes of deer w/ CWD (test is insensitive).


Question Answer
What are the immunohistochemistry tests you can use to screen for prion dzs?ELISA & Dot-Blot tests (screening)
*Lysosomal storage Dzs (LSDs) → in essence, what is happening to cz this storage dz?(Normally, lysosomes perform catabolic activities by degrading stuff not needed anymore) Hydrolytic enzyme is absent or inoperational → catabolic degradation of the substrate interrupted → accumulates w/in the lysosomes= "storage dz"
Animals & humans can both get lysosomal storage dzs. How do they get them? What is the prognosis of these dzs? How common is CNS involvement?Most of these dzs are inherited. They are progressive, lethal, multisystemic disorders & CNS involvement is common
Describe what cells look like when they are under the effect of a lysosomal storage dzThe cells fill up w/ substrate so they are swollen, conspicuous. Cytoplasm: granular or vacuolar. Cytotoxicity → necrosis of neurons, glial cells.
What might be a gross lesion of the brain you'd see in a lysosomal storage dz?No clear distinction btwn gray & white matter
Sphingolipidoses (lipid lysosomal storage dzs) → Globoid cell leukodystrophy: WHO does this happen in? At what age do the CS show up?Reported in dogs & cats, CSs develop btwn 2nd to 7th month of life
LSDs → Globoid cell leukodystrophy → how does an animal get this? What is the problem? What’s up w/ the "globoid" part?This is an INHERITED disorder where there is a deficiency of the catabolic enzyme "galactocerebroside-ß-galactosidase". BC of the lack of this enzyme, microglial cells are transformed into "globoid" cells → PAS-positive inclusion tubules of galactocerebroside accumulate w/in them
LSDs → Globoid cell leukodystrophy → what are the gross lesions in the brain? What are the microscopic lesions in the white & grey matter?Grossly, the involved regions of fixed white matter are gray & soft. The grey matter has only minimal changes, but in the white matter you will see degenerative changes which are bilaterally symmetrical. You will find presence of PAS-positive globoid macrophages in the white matter.
***ABIOTROPHY is WHAT KIND of defect? (& happens bc of?)1° metabolic defect/degeneration due to premature programmed cell loss (APOPTOSIS). Which czs a Loss of Purkinje cells

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