Neuropathology Study Questions

Question 1

What is the function of oligodendrocytes?

Astrocytes?

Microglia?

Gitter cells?

Answer 1

Oligodendrocytes: form the myelin that wraps around axons in CNS.

Astrocytes: star shaped cells that form the blood-brain barrier; interstitial cells of the brain; possibly signal the endothelial cells to make tight junctions for blood-brain barrier

Microglia: phagocytic cells with small nuclei and little cytoplasm. Fixed macrophages of CNS.

Gitter cells: microglia ingesting myelin debris with foamy cytoplasm

Question 2

What is central chromatolysis?

Answer 2

Degenerative change → first step to neuronal necrosis

Swelling of the cell, nucleus gets pushed off to the side, dispersal of Nissl substance

Question 3

What is neuronophagia?

Answer 3

Microglia gather around a necrotic neuron and phagocytose it to remove the debris

Seen with viral infections

Question 4

What are histologic characteristics of axonal degeneration?

Answer 4

Wallerian degeneration: focal damage to a myelinated axon resulting in degeneration of the axon segment distal to the site of damage

Axon degenerates (spheroid) → gitter cells remove axon and myelin debris → empty dilated axon sheath

Question 5

What is a spheroid?

Answer 5

Focal axonal swellings filled with degenerate organelles

Question 6

What kind of necrosis is typically seen in the CNS, and what are the characteristics of this type of necrosis?

Answer 6

Neuronal necrosis

“Red is dead,” shrunken, angular, pink cytoplasm indicates a dead neuron

Liquefactive necrosis

Can also have a pyknotic nucleus

Question 7

What is astrocytosis?

Answer 7

Increase in size and number of astrocytes in response to injury; repair

Swell & divide as cell processes proliferate

Question 8

What are gemistocytic astrocytes?

Answer 8

Plump, reactive astrocytes with eosinophilic cytoplasm; almost look like a dead neuron

Seen w/ significant damage

Question 9

What is the appearance of Alzheimer’s type II astrocytes, and what disease process are these cells typically seen in?

Answer 9

Enlarged, vesicular nuclei that tend to cluster around the neurons

Seen w/ hepatic encephalopathy

Question 10

What is hydrocephalus?

What are the different types of hydrocephalus?

In which breeds of dog is hydrocephalus most common?

Answer 10

Excess fluid in the brain

3 types:

Internal – fluid in ventricles

External – fluid in arachnoid space (rare)

Communicating – fluid in ventricles & arachnoid space (rare)

Most common in brachycephalic dogs and toy breeds

Question 11

Define microencephaly

Answer 11

Abnormally small brain

Usually the cerebrum is the most affected part; can have smaller cranial cavity

Seen w/ BVD in cattle, classical swine fever in pigs

Question 12

Define hydranencephaly

Answer 12

Cerebral hemispheres are almost gone or completely gone, leaving fluid-filled sacs formed by the meninges filled with CSF

Associated w/ viral infections → during development, they cause subventricular necrosis

Question 13

Define proencephaly

Answer 13

Cystic cavitation of the brain, usually involving cerebral white matter

Less severe end of the spectrum as hydranencephaly & is caused by the same things

Question 14

Define lissencephaly

Answer 14

Brain lacks normal gyri and sulci

Lhasa Apso’s = poster child

Can be normal in some species of mammals, but not normal in any of our domestic mammals (everything that is not a mammal is normally lissencephalic)

Question 15

Define anencephaly

Answer 15

Absence of the brain = RARE

Question 16

Define prosencephalic hypoplasia (cerebral aplasia)

Answer 16

Absence of the cerebral hemispheres with preservation of at least some portion of the brainstem

Question 17

Define canium bifidum/spina bifidum

Answer 17

Defect through which the brain/spinal cord & meninges can protrude

Almost always on dorsal midline

Question 18

Define meningocele

Answer 18

Herniation of meninges

Question 19

Define meningoencephalocele

Answer 19

Herniation of meninges & brain/spinal cord

Question 20

What is the most common brain malformation seen with BVD infection?

Answer 20

Microencephaly

Cerebellar hypoplasia during days 100-170 of gestation

Question 21

What is the underlying cause of storage diseases?

What happens to cells which accumulate substrate in lysosomal storage diseases?

How are these conditions inherited, and when do they typically present with neurologic signs?

How are storage diseases named (in general, you do not need to know specific names)?

Answer 21

Underlying cause: defective catabolism from a defect in lysosomal enzymes

Cells that accumulate substances don’t die, they just become distended with vacuoles with excess stored material

Autosomal recessive conditions & present with neuro signs early in life → progressive and fatal

Naming: according to the substrate that has defective degradation

Question 22

Which cells in the CNS are most sensitive to ischemia?

Answer 22

Neurons & oligodendroglia: cerebral cortical neurons, hippocampal neurons, Purkinje cells

Can also affect nuclei if severe/prolonged

Grey matter more sensitive than white matter

Question 23

What are the causes of polioencephalomalacia?

Where are the lesions located?

Answer 23

Causes: often unknown but can be due to a thiamine (B1) deficiency, defect in thiamine metabolism, or high sulfur intake b/c that cleaves thiamine & makes unusable; occ seen w/ water deprivation

Lesions: necrosis of the grey matter of the brain, laminar cortical necrosis.

Question 24

What is the cause of leukoencephalomalacia?

Where are the lesions located?

Answer 24

Cause: moldy corn consumption for >1 month → fumonisin toxin is produced by Fusarium verticillioides & Fusarium proliferatum

Lesions: necrosis of the cerebral white matter +/- hemorrhage

Question 25

What are the lesions of indirect salt poisoning? What is the cause of indirect salt poisoning?

Answer 25

_Cause_: ingestion of a high (\>2%) salt diet in conjunction with restricted water intake for several days _Lesions_: cerebral edema, laminar cortical necrosis, n**on-suppurative & eosinophilic meningoencephalitis** (pathognomonic)

Question 26

What are the ways in which bacterial infections get to the CNS?

Answer 26

**They breach the BBB and BCSFB** Most commonly _secondary to septicemia_ in young animals Can have septic embolism with endocarditis; can have abscesses form from hematogenous spread or direct invasion (cribriform plate from nasal infection or middle ear from otitis interna)

Question 27

In what species do we most often see listeriosis? What is the causative agent of listeriosis? What are the characteristic lesions, and where are the lesions typically located? What is the pathogenesis of the encephalitis?

Answer 27

**Most often seen in ruminants (sheep)** Caused by *Listeria monocytogenes* _Lesions_: most common in the brain stem; no gross lesions; histo can have microabscesses, sometimes within foci of microgliosis _Pathogenesis_: bacteria invade oral mucosa then spread up the branches of the trigeminal nerve to the brain; outbreaks assoc w/ heavy feeding of improperly fermented silage

Question 28

What is the causative agent of thrombotic meningoencephalitis? Which species does it affect? What is the pathogenesis of development of CNS lesions, and what are the lesions?

Answer 28

Caused by *Histophilus somni* **Affects cattle (usually young cattle in feedlots) & sheep** _Pathogenesis_: animals have septicemia which causes cerebral vasculitis with hemorrhages, necrosis, and thrombosis _Gross lesions_: multifocal hemorrhage and necrosis _Histo lesions:_ vasculitis, thrombosis, &, neutrophilic meningoencephalitis, may form abscesses

Question 29

What are the general histologic features of viral infections?

Answer 29

**Nonsuppurative meningoencephalitis +/- myelitis** **Perivascular cuffing** **Gliosis** +/- viral inclusions, neuronal degeneration/necrosis

Question 30

What are the principal reservoirs for rabies in the US? What tissues is the virus tropic for? What is the pathogenesis of viral infection from inoculation to spread to the CNS? What are the lesions?

Answer 30

_US Reservoirs:_ skunks, foxes, raccoons, and bats **Tropism for CNS & salivary glands** _Pathogenesis_: virus inoculated into the wound (usually from a bite) → replicates in the muscle cells near the site → spreads to sensory paravertebral ganglia & travels along the peripheral nerves into the CNS _Lesions_: non-suppurative encephalomyelitis, ganglioneuritis, parotid gland adenitis; inflammation & neuronal degeneration are variable; **Negri bodies** (eosinophilic cytoplasmic inclusions) in the hippocampus of carnivores or Purkinje cells of herbivores.

Question 31

What is the cause of pseudorabies? What species are affected by this disease? What are the clinical signs?

Answer 31

Caused by *Suid Herpesvirus-1* **Can affect _all_ common domestic species** _CS in species other than pigs_: intense pruritus (mad itch), high mortality rate, fever, neuro signs; **always fatal** _CS in most pigs_: mild fever, no pruritus _CS in young pigs_: prostration, convulsions, muscle tremors/twitching, may have high mortality rate _CS in sows_: abortion, stillbirth, mummified fetuses

Question 32

What are the clinical signs of caprine arthritis-encephalitis virus? In what age animals is neurologic disease typically observed with this virus? What are the lesions of this disease?

Answer 32

_CS in kids 2-4m_: hind limb ataxia, paresis, paralysis, death _CS in adults_: **arthritis**, mastitis, pneumonia **Neuro signs seen in kids 2-4 months** _Lesions_: non-suppurative leukoencephalomyelitis, demyelination, perivascular cuffing

Question 33

What are the clinical signs of maedi-visna virus? In what age animals is neurologic disease typically observed with this virus? What are the lesions of this disease?

Answer 33

_CS in adults \>2y_: hind limb ataxia, trembling of lips, progressing to hind limb paralysis; death d/t secondary infection or starvation; pneumonia, mastitis, and arthritis **Neuro signs seen in adults over 2 y/o** _Lesions_: non-suppurative meningoencephalitis most severely affecting the white matter, demyelination

Question 34

What species are typically affected by fungal infections with *Cryptococcus neoformans*? How do infections get into the brain? What are the histologic lesions?

Answer 34

**Affects cats, dogs, and horses** _Starts as a nasal or sinus infection_ (can be very destructive) & enters brain via cribriform plate; can also have a _pulmonary infection_ that travels hematogenously to the brain _Histo_: variable inflammatory response (no inflammation or severe granulomatous lesion); thick, non-staining mucopolysaccharide capsule which creates a soap bubble appearance in tissue sections

Question 35

What is the cause of equine protozoal myelitis? Why are organisms not seen in most cases?

Answer 35

_Cause_: *Sarcosystic neurona* Most animals with EPM are treated prior to euthanasia with Marquis (ponazuril)

Question 36

What is the cause of transmissible spongiform encephalopathies (TSEs)? How do animals typically acquire TSEs? What are the lesions of TSEs?

Answer 36

_Cause_: **prions** which are abnormal isoforms **(PrPsc)** of a normal cellular protein called the prion protein (PrPc) _Transmission_: horizontally by infected feed material; don't use brain or spinal cord from other mammals in the feed! _Lesions_: intracytoplasmic neuronal vacuolation and astrocytosis; no inflammatory component

Question 37

What are the histologic lesions of FIP?

Answer 37

Periventriculitis & perivasculitis = around ventricle & vessles Mixed cell population: neutrophils, macrophages, lymphocytes, & plasma cells May also see reactive astrocytes