Neuropath Lecture 2

Question 1

what are the 4 types of edema in the brain?

Answer 1

1. vasogenic
2. cytotoxic
   -intramyelinic edema
3. interstitial
4. osmotic`

Question 2

describe vasogenic edema

Answer 2

1. disruption of BBB, EXTRAcellular fluid
2. gross appearance: brain is swollen
3. associated with:
   -traumatic lesions
   -inflammatory lesions
   -hemorrhagic lesions

Question 3

describe cytotoxic edema

Answer 3

1. NO BBB disruption, INTRAcellular fluid
2. gross appearance: brain MAY be swollen; cell swelling in gray and/or white matter
3. associated with:
   -hypoxia
   -metabolic disturbances
   -toxins

Question 4

describe intramyelinic edema

Answer 4

special type of cytotoxic edema

1. cytotoxic edema of oligodendrocytes causes vacuolization and splitting of the myelin lamellae
2. due to:
   -bromethalin: in rodenticide
   -hepatic and renal encephalopathy

Question 5

describe interstitial edema

Answer 5

1. also called hydrostatic or transependymal
2. increased interstitial fluid in periventricular white matter
3. due to hydrocephalus!
   -increased ventricular pressure causes disruption of ependyma, allowing CSF to enter periventricular white matter and dissolve myelin leading to white matter atrophy

Question 6

describe osmotic edema

Answer 6

1. occurs when blood becomes hypotonic relative to hypertonic brain
2. due to overhydration or salt poisoning
3. salt poisoning: high salt diet with restricted water causes hypernatremia, causing fluid from brain to move into blood resulting in brain dehydration but when an animal drinks water to correct, blood become hypotonic relative to brain so fluid moves into hypertonic brain
   -in pigs will histologically see laminar cortical necrosis and eosinophilic meningoencephalitis

Question 7

what is the consequence of brain edema?

Answer 7

herniation! 3 common types

1. transtentorial (subtentorial)
2. cerebellar vermal (foramen magnum)
3. subfalcine (falx/cingulate gyrus)

Question 8

describe transtentorial herniation

Answer 8

1. brain stem pushed through tentorial notch, causing stretching and compression of caudal cerebral artery and a portion of the occipital lobe slips under the tentorium cerebelli
2. results in:
   -infarction of occipital lobe
   -occulomotor nerve is stretched/compressed leading to ipsilateral mydriasis

Question 9

describe subfalcine (cingulate gyrus) herniation

Answer 9

1. unilateral enlargement of ONE cerebral hemisphere
2. cingulate gyrus slips under falx

Question 10

describe cerebellar vermis herniation

Answer 10

1. caudal lobe of vermis slips through foramen magnum, leading to coning of cerebellum
2. cerebellum is pushed caudally and downward by edema and exerts pressure on the medulla respiratory centers, leading to respiratory arrest
3. herniated vermis may be necrotic and hemorrhagic

Question 11

describe hemorrhage

Answer 11

can be traumatic or non-traumatic; location is important! extraparenchymal versus parenchymal

Question 12

what are 2 infectious or toxic vascular damage causes of hemorrhage?

Answer 12

1. sepsis
2. histophilus somni: endotoxin that kills endothelium
   -rocky mountain spotted fever
   -ICSV
   -EHD/BTV

Question 13

what are 6 spontaneous causes of hemorrhage?

Answer 13

1. hypertension
2. DIC
3. congenital coagulation defects
4. tumors: hemangiosarc
5. anticoagulants
6. thrombocytopenia

Question 14

which neurons specifically are most sensitive to ischemic necrosis? (3) what happens as a result?

Answer 14

those in the
1. hippocampus
2. cerebral cortex
3. purkinje cells

glial will swell and die, resulting in a vascular reaction and malacia if severe enough

Question 15

what are 3 brain findings associated with hypoxia?

Answer 15

1. grossly: lilac brain
2. prominent vessels indicating vascular reaction
3. dead neurons in the hippocampus: dead reds

Question 16

describe brain infarction

Answer 16

1. due to insufficient anastomoses of vessels: the brain already has so few anastomoses so obstruction of just one vessel in the brain is very bad (no matter speed or severity of the lesion)
2. results in necrosis and softening and eventually malacia
3. malacia triggers gitter cells to clean up debris, resulting in cavitation

Question 17

compare and contrast the results of fast and severe lesions versus slow lesions in the spinal cord

Answer 17

fast and severe: like type I disk herniation
-no chance for anastomoses to open so results in necrosis

slow: like type II disk herniation
-allows time for anastomoses to open and compensate so less severe injury

Question 18

describe the anatomy of intervertebral discs

Answer 18

1. annulus fibrosis: fibrous tissue and fibrocartilage
2. nucleus pulposus:
   -gelatinous: composed of water, collagen fibrils, and proteoglycans
   -notochord derived

Question 19

describe type I IVD herniation

Answer 19

1. in chnodrodyplastic dogs like dachshunds
2. chondrometaplasia (loose cartilaginous bodies)
3. nucleus ruptures through annulus and dorsal longitudinal ligament, resulting in degenerate disk material in the epidural space and wallerian degeneration and malacia in the cord
4. this is a lot of damage so there is no time for collateral circulation to develop

Question 20

describe ascending-descending myelomalacia

Answer 20

extensive hemorrhage or ischemic necrosis of the cord, usually associated with type I disk herniation

Question 21

describe type II IVD herniation

Answer 21

1. in nonchondrodysplastic dogs, like GSD
2. fibrous metaplasia of the nucleus pulposus while the annulus remains intact
3. wallerian degeneration, but there is less damage so there is time for collateral circulation to develop

Question 22

describe equine cervical stenotic myelopathy

Answer 22

1. can be static (continual) or instability (on flexion of neck); flattened and firm at sites of compression
2. microscopically:
   -at site of impact: gray and white matter degeneration
   -cranial and caudal to impact: wallerian degeneration (axons swell and die back with secondary loss of myelin)

Question 23

describe damage associated with disk disease and stenotic myelopathy

Answer 23

1. direct pressure on nervous tissue (physical trauma)
2. local vascular effects: compress vascular supply leading to ischemia and neuronal excitotoxicity
3. fast (no time for anastomoses) versus slow (more time, less severe damage)

Question 24

describe fibrocartilaginous embolic myelopathy

Answer 24

clinical signs:
1. acute lateralized spinal signs without pain
2. CSF: normal or mild protein increase and mild mixed or neutrophilic pleocytosis

necropsy:
1. disk spaces look normal (this is NOT IVDD)
2. cord swollen brown and soft

pathogenesis:
1. history of mild trauma or vigorous exercise causes migration of disk material into arteries
2. persistence or neovascularization of common blood supply into spinal cord and disk
3. mechanical herniation into vertebral body and subsequent entry into vertebral venous sinuses

distribution of infarction and clinical signs determined by which vessel(s) obstructed

Question 25

describe polioencephalomalacia in ruminants

Answer 25

clinical signs:
1. ataxia
2. blindness
3. opisthotonus
4. paddling
5. head pressing

causes:
1. thiamine deficiency; MOST COMMON
2. sulfur toxicosis, hypoxia, salt toxicosis, lead poisoning, certain plant toxicities

lesion:
edema and necrosis predominantly in the cerebral cortex; laminar cerebrocortical necrosis
-chronic: loss of cortex

Question 26

describe equine mycotoxic leukoenceophalomalacia/moldy corn disease

Answer 26

clinical signs:
1. lethargy/somnolence
2. depression
3. ataxia, aimless walking
4. blindness
5. head pressing
6. seizures

lesion: leukoencephalomalacia

pathogenesis:
fusarium verticillioides (moniliforme) infected grain leads to ingestion of fumonisin toxins which inhibit sphingolipid biosynthesis leading to vascular damage which results in necrosis and edema of white matter

Question 27

describe nigropallidal encephalomalacia

Answer 27

in horses, due to chronic ingestion of yellow star thistle or russian knapweed

clinical signs:
1. difficulty with prehension
2. mouth partially open
3. tongue protruded
4. retention of food in mouth

lesion: malacia in globus pallidus and substantia nigra

Question 28

describe hepatic and renal encephalopathy pathogenesis

Answer 28

1. lack of hepatocyte detoxification of ammonium
2. hyperammonemia
3. metabolized by free astrocytes, eventually inducing free radicals
4. cytotoxic brain edema
5. swollen astrocytic nuclei (alzheimer type II cells) +/- white matter status spongiosus (intramyelinic edema)

Question 29

describe lysosomal storage diseases

Answer 29

deficient lysosomal enzymes result in disrupted degradation of a host-derived glycoprotein/polysaccharide/complex lipids of spent organelles

this leads to accumulation of undigested material in cytoplasm which screws up cell function

neurons are often afflicted because they are post-mitotic permanent cell populations!

Question 30

describe mannosidosis in Salers calves

Answer 30

1. newborns that can’t stand, head bob, and have tremors
2. domed calvaria, severe hydrocephalus, scarcity of white matter, renomegaly
3. cytoplasmic vacuolations of neurons and other brain cells