Path 2 - Neuro 2
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2016-03-07 17:26
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) (**REMEMBER INFLAMMATION IS NOT A FEATURE OF PRION DZs) |
| 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 |
| 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). |
| 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 dz | The 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 |
