Neuro Pathology Flashcards
What is Nissl substance?
cytoplasmic basophilic granular material found in rough ER and polysomes
What substance do you use to stain myelin?
Luxol fast blue stain
What do ependymal cells do?
they line ventricles
What is the function of astrocytes?
star-shaped cells w/ elaborate cell processes that form the blood-brain barrier
What are microglia?
phagocytic cells of the CNS w/ small nuclei and relatively little cytoplasm
Oligodendrocytes form myelin which wraps around axons in the ____, which Schwann cells form myelin for the ___
CNS; PNS
Name the various cells and enzymes that make up the blood-brain barrier
Active barrier
- efflux transporters
- influx transporters
- metabolizing enzymes
Passive barrier
- astrocytes
- tight junctions
- endothelial cells
Rod-shaped microglia are what?
activated
What are gitter cells?
microglia ingesting myelin debris with foamy cytoplasm
Define chromatolysis
degenerative change, dispersal of Nissl substance
Define neuronophagia
microglia surround a necrotic neuron and phagocytose it to remove the debris
What are spheroids?
focal axonal swellings filled w/ degenerate organelles
What is Wallerian degeneration?
focal damage to a myelinated axon resulting in degeneration of the axon segment distal to the site of damage
Describe the process of Wallerian degeneration
- Axon degenerates (spheroid)
- Gitter cells remove axon and myelin debris
- Empty dilated axon sheath
True or False: Following Wallerian degeneration, regeneration can occur in both the PNS and the CNS
False; regeneration can only occur in the PNS, not the CNS
What are some features of the CNS that inhibit regeneration following Wallerian degeneration?
- no basement membrane
- oligodendrocytes poorly regenerative
- CNS astrocytes secrete substances inhibitory to axon growth
- astrocyte proliferation can create a “glial scar” - physical barrier
- myelin breakdown products are inhibitory to axon growth
What are some features of the PNS that allow regeneration following Wallerian degeneration?
- Schwann cells have a basement membrane
- after injury, Schwann cells proliferate–> form a scaffold to direct sprouting axons
- Schwann cells then remyelinate new axon
Describe the process of astrocytosis (astrogliosis)
- incr in size and number of astrocytes in response to injury
- repair after CNS injury is largely the job of astrocytes
- swell and divide and cell processes proliferate
Define a gemistocytic astrocyte
a plump, reactive astrocyte with eosinophilic cytoplasm
What are the characteristics of Alzheimer’s type II astrocytes?
- enlarged, vesicular nuclei
- these are typical of hepatic encephalopathy
What might you see microglial nodules in conjunction with?
viral infections
What are some types of CNS malformations?
- Failure or abnormality of structural development
- Slowing of normal development
- Premature degradation of normally formed tissue (abiotrophy)
- Primary functional disturbances
What are some causes of CNS malformations?
- inheritied genetic mutations
- in utero infections
- in utero exposure to teratogens
- in utero exposure to physical agens (e.g. hyperthermia)
cause in a single individual animal = rarely determined
What are the 3 types of hydrocephalus?
- Internal: fluid in ventricles
- External: fluid in arachnoid space
- Communicating: fluid in ventricles and arachnoid space
In what breeds is hydrocephalus most common?
brachycephalic and some toy breeds
What is another name for an abnormally small brain?
microencephaly
What is lissencephaly?
brain lacks normal gyri and sulci
In what species is lissencephaly normal?
- certain mammals
- indian flying fox
- mouse
- rabbit
- Florida manatee
- common marmoset
- any non-mammals
What is dysraphia and what are two examples of this?
neural tube closure defects
- Anencephaly - absence of the brain
- Prosencephalic hypoplasia (aka cerebral aplasia) - absence of cerebral hemispheres w/ preservation of at least some portion of the brainstem
-
Cranium bifidum/spina bifida - defect through which the brain/spinal cord and meninges protrude; almost always on dorsal midline
- meningocele
- meningoencephalocele
What is the difference between a meningocele and a meningoencephalocele?
- Meningocele: herniation of meninges
- Meningocephalocele/meningomyelocele: herniation of meninges and brain/spinal cord
What is hydraencephaly?
- near complete or complete absence of the cerebral hemispheres, leaving CSF-filled sacs formed by the meninges
What is porencephaly?
- cystic cavitation of the brain, usually involving cerebral white matter
What happens in cerebellar hypoplasia, and what disease processes do you see this with?
-
destroy the external granular layer
- Border dz
- feline panleukopenia
- BVD d. 100-170 of gestation
- inhibits cells division/maturation
- classical swine fever
What might you see cyclopia with?
Veratum californicum ingestion (particularly in sheep)
Describe storage diseases
- accumulation of substances in cells
- usually d/t defective catabolism, particularly lysosomal enzymes
- the most active tissues in turning over substrate are most affected
- typically autosomal recessive conditions, present w/ neuro signs early on in life
- progressive and fatal
What are the various types of storage diseases?
- Sphingolipidoses
- Glycoproteinosis
- Mucopolysaccharidoses
- Glycogenoses
- Ceroid lipofuscinoses
*named according to the substrate that has defective degradation
Describe what the neuronal cells of an animal with a storage disease might look like
- distended cells containing vacuoles w/ excess stored material
- neurons which accumulate substance often don’t die
What is lipofuscin?
- “wear and tear” pigment, accumulates w/ advanced age
What is the pathogenesis of ceroid lipofuscinosis?
- likely a heterogenous dz
- maybe a mitochondiral defect
- presumptively inherited
- accumulation of pale brown to colorless, autoflorescent granular material; neuronal necrosis/loss common
Describe the various types of cerebral edema
- localized edema = trauma, neoplasia, inflammation
- generalized edema = systemic & localized conditions
- cytotoxic edema = d/t direct injury to cells, cell swelling
- vasogenic edema = extracellular fluid accumulation, d/t injury to endothelial cells
What are the gross and histologic lesions seen with cerebral edema?
- Gross: maybe nothing or can see flattening of gyri/sulci, cerebellar herniation
- Histo: vacuolation, incr clear space around vessels; white matter typically more affected than grey matter
What cell types are most susceptible to ischemic lesions? What about brain matter?
- neurons
- cerebral cortical neurons
- hippocampal neurons
- Purkinje cells
- oligodendroglia
- grey matter
When might you see a global ischemic lesions?
- cardiac arrest
- prolonged severe hypotension/hypoxia
Histologic lesions of neuronal necrosis typically take a minimum of how long to develop?
3-6 months
Describe fibrocartilaginous embolisms
- typically asymmetric SC signs, non-progressive after 1st 24-48 hrs
- material thought to arise from nucleus pulposus of IVD
- usually have mult. occluded vessels
Describe neonatal maladjustment syndrome of foals
- “dummy foals”
- presumed to be d/t ischemia and reperfusion
- lesions: laminar neuronal necrosis, multifocal small hemorrhages
Describe malacic diseases
i.e. softening - usually means necrosis in the CNS
What is polioencephalomalacia?
- necrosis of the grey matter of the brain
- affects sheep, goats and cattle
- laminar cortical necrosis
- C/S: blindness, dullness, head pressing, anorexia, mm tremors, opisthotonos, recumbency, bruxism, ptyalism, nystagmus, coma, death
Describe the pathogenesis of polioencephalomalacia
- cause often unknown
- a deficiency in thiamine or disturbance in thiamine metabolism implicated
- maybe d/t a high sulfur intake
- water deprivation
What are the clinical signs of thiamine deficiency, and what species does it affect?
- C/S: ataxia, neck ventroflexion, incoordination, mydriasis, convulsions
- Lesions: hemorrhage, necrosis and neutrophil vacuolation predominantly in periventricular grey matter
- seen in foxes, cats and mink consuming fish/horses consuming plants containing thiaminase
Describe the pathogenesis of direct salt poisoning
- ingestion of excessive salt, usually d/t high salinity in drinking water
- mainly affects cattle
- C/S: V/D, paresis, blindness, abd pain
- Lesions: congestion of abomasal mucosa, dark watery intestinal contents, no CNS lesions
Describe the pathogenesis of indirect salt poisoning
- ingestion of a high salt diet in conjunction with restricted water intake for several days
- C/S: blindness, deafness, head pressing, convulsions
- Lesions: cerebral edema, laminar cortical necrosis, nonsuppurative and eosinophilic meningoencephalitis
What is Nigropallidal encephalomalacia?
- happens in horses d/t ingestion of yellow star thistle and Russian knapweed
- putative neurotoxin is repin - seems to cause glutathione depletion
- C/S: somnolence, incoordination of lips and tongue that leads to difficulty prehending food, persistent chewing motions, death often from starvation/dehydration
- Malacia in the globus pallidus and substantia nigra
Describe leukoencephalomalacia in horses
- caused by moldy corn consumption for > 1 month
- toxin is fumonisin produced by Fusarium
- C/S: circling, somnolence, visual impairment, weakness, pharyngeal paralysis; usually die 2-3d after the onset of C/S
- Lesion: necrosis of the cerebral white matter
What lesions do you see with lead poisoning in cattle?
- C/S -staggering, mm tremors, convulsions, head pressing, blindness, hypersalivation, ruminal atony, recumbency, hyperesthesia, death
- lesions - only seen if dz course is at least several days –> laminar cerebral cortical necrosis
What lesions do you see with lead poisoning in dogs?
- white matter edema in brain/SC, demyelination, vascular damage, hemorrhage, neuronal necrosis/loss in caudate nucleus, subthalamus, deep cortical layers
What determines the neurotropism of an infectious agent?
their ability to breach the BBB and BCSFB
Bacterial infections are most commonly secondary to what in young animals?
septicemia
What are the other causes of neuronal bacterial infections?
- septic emboli with endocarditis
- abscesses
- hematogenous spread
- direct invasion
- usually thru cribriform plate or from middle ear
What are the most common agents involved in forming abscesses from septic embolism?
- Pigs: Erysipelothrix rhusiopathiae
- Cattle: Trueperella pyogenes
- All species: Streptococccus spp.
What are the most common locations of septic emboli formation?
hypothalamus and junction of cerebral gray and white matter
Describe listeriosis
- “circling disease” - caused by Listeria monocytogenes that most commonly affects ruminants
- outbreaks usually assoc. w/ silage feeding
- C/S: head tilt, circling, confusion, depression, head pressing, unilateral facial n. paralysis, masticatory mm paralysis, purulent endophthalmitis
Describe the lesions and pathogenesis of listeriosis
- Lesions most common in brainstem
- usually no gross lesions
- Histologic lesions: microabscesses, sometimes within foci of microgliosis
- Pathogenesis: bacteria invade oral mucosa, spread up the branches of CN V
Describe infectious thrombotic meningoencephalitis (ITME)
- cause by Histophilus somni
- affects cattle (young in feedlots) and sheep
- organism normally in genital tract & nasal cavity
- Causes septicemia –> cerebral vasculitis w/ hemorrhage, necrosis and thrombosis
What are the lesions of ITME?
- Gross lesions: multifocal hemorrhage, necrosis
- Histo lesions: vasculitis, thrombosis, infarction, neutrophilic meningoencephalitis, may form abscesses
What are the general features of viral infections of the nervous system?s
- non-suppurative meningoencephalitis (+/- myelitis)
- perivascular cuffing
- gliosis
- +/- viral inclusions
- +/- neuronal degeneration/necrosis
What are the principal reservoirs of rabies and what structures does it exhibit a tropism for?
- Reservoirs: skunks, foxes, raccoons, bats
- Tropism for CNS and salivary gland
What is the pathogenesis of the rabies virus?
virus inoculated into wound, usually thru a bite –> virus r_eplicates in muscle cells_ near inoculation site –> spreads to sensory paravertebral ganglia –> virus travels along peripheral nerves to the CNS
What are the lesions seen with rabies?
- nonsuppurative encephalomyelitis, ganglioneuritis, and parotid adenitis
- Negri bodies (cytoplasmic inclusions) in hippocampus in carnivores and Purkinje cells in herbivores
Describe pseudorabies
- caused by suid herpesvirus-1
- can affect all of the common domestic species
- spread b/t pigs d/t contact of virus-infected secretions with abraded skin or nasal mucosa
- highly contagious
- carnivores - infected via consuption of infected pig meat
What is the pathogenesis of pseudorabies?
- local reaction at site of inoculation –> spreads up related nerve to SC –> spread within CNS and out into other periph nn.
What are the clinical signs of pseudorabies in pigs? What about all the other species?
- Pigs
- Most: mild fever, no pruritus
- Young: prostration, convulsions, mm tremors/twitching, high mortality rate
- Sows: abortion, stillbirth and mummified fetuses
- Other spp:
- intense pruritus, high mortality rate, fever, neuro signs, always fatal
What are the lesions you see with pseudorabies?
- Gross lesions: no specific lesions, no CNS lesions, may have dermatitis at site of inoculation and lesions of self-trauma
- Histo: nonsuppurative encephalitis, gliosis, neuronal degeneration, intranuclear inclusion bodies in neurons and astrocytes
What are three arboviruses?
- Eastern, Western and Venezuelan equine encephalomyelitis viruses
How are EEE and WEE transmitted and what are the lesions of these viruses?
- Transmission: mosquito-borne
- Lesions:
- lymphohistiocytic and neutrophilic polioencephalomyelitis
- neutrophils may also infiltrate the grey matter
- gliosis, neuronal degeneration/necrosis, vasculitis, meningitis, and thrombosis
How is West Nile transmitted (Flavivirus) transmitted and what are the lesions of these?
- Transmitted: Mosquito-borne
- Lesions: nonsuppurative encephalomyelitis, gliosis, occasional neuronal generation/necrosis
Describe caprine arthritis encephalitis virus
- a lentivirus
- nervous system signs seen in kids 2-4 mo. old
- C/S: hind limb ataxia, paresis, paralysis, often death
- Lesions: non-suppurative leukoencephalomyelitis, demyelination
- Adults can get arthritis, mastitis, pneumonia
Describe visna-maedi virus
- lentivirus
- neuro dz usually occurs in sheep > 2 y.o.
- C/S: hindlimb ataxia, trembling of lips, progressing to hindlimb paralysis; death is d/t secondary infection or starvation
- lesions: nonsuppurative meningoencephalitis most severely affecting the white matter demyelination
- virus also causes pneumonia, mastitis and arthritis
Describe canine distemper virus
- Morbillivirus
- C/S: usually start w/ fever and conjunctivitis, progresses to resp and GI signs; can get neuro signs 1-4 wks later, or neurologic dz may be the primary manifestation
- can get secondary infections d/t immune suppression
What are the lesions of CDV?
- Gross: none in CNS
- Histo: nonsuppurative encephalitis, gliosis, neuronal necrosis, intranuclear and intracytoplasmic inclusions primarily in astrocytes, white matter demyelination
Describe equine herpesviral myelencephalopathy
- caused mainly by EHV1 and 4
- spread: inhalation of nasal aerosols, contact w/ infected fetus/placenta, direct contact
- virus replicates in endothelial cells, causes necrotizing vasculitis w/ thrombosis
- C/S: ataxia, paresis, paralysis
- vaccination does not necessarily protect against neuro dz
- virus infects endothelial cells in CNS
What are the lesions seen with EHV myeloencephalopathy?
- gross lesions: none or random foci of hemorrhage in brain, very severe cases may have small foci of hemorrhage/malacia
- histo: non-suppurative necrotizing vasculitis and thrombosis
What fungus is the only one with a predilection for the CNS?
Cryptococcus neoformans
What is the pathogenesis of Cryptococcus neoformans?
- usually starts as a nasal or sinus infection and enters brain via direct extension thru cribriform plate; may also spread to brain hematogenously from pulm infection
- affects cats, dogs and horses
What are the lesions seen with a Cryptococcus neoformans infection?
- Gross lesions: grey, gelatinous foci in brain and meninges
- Histo lesions: from no inflammation to granulomatous inflammation; thick non-staining mucopolysaccharide capsule which imparts a ‘soap-bubble’ appearance in tissue sections
Describe equine protozoal encephalomyelitis
- primarily Sarcocystic neurona
- C/S: ataxia, lameness, weakness of limb(s), mm atrophy
- Pathogenesis? - think sporocysts are ingested, multiply in viscera and are transported to the CNS
What are the lesions seen with equine protozoal encephalomyelitis?
- Gross lesions: typically none, may see random foci of hemorrhage and necrosis
- Histo lesions: hemorrhage, necrosis, perivascular cuffs of lymphocytes, macrophages, neutrophils and eosinophils; astrocytosis
Why are the organisms that cause equine protozoal encephalomyelitis not seen in most cases?
- b/c it is easily diagnosed, and frequently treated, but typically the horse does not survive
- so by the time the horse is necropsied, the organisms will all be gone
Describe toxoplasmosis
- Toxoplasma gondii
- primates especially susceptible
- Gross lesions: hemorrhage and necrosis
- Histo lesions: necrosis, hemorrhage, perivascular histiocytic and lymphoplasmacytic cuffs, tachyzoites and cysts containing bradyzoites
Describe Neosporosis
- Neospora caninum
- Cattle: abortion – hepatitis, myocarditis, placentitis and myositis in fetus; small foci of necrosis in brain +/- SC
- Dogs: generalized or localized infections, mixed inflamm (granulomatous and lymphoplasmacytic, occasionally w/ eosinophils) meningoencephalomyelitis, gliosis
Describe necrotizing meningoencephalitis (NME) and necrotizing leukoencephalitis (NLE)
- NME = “pug dog encephalitis,” in pugs, Shih tzus, Chi chis, Maltese
- NLE = Bostons, Chi chis, Yorkies
- Causes bilateral, asymmetrical lesions, mostly in cerebral cortex
- lymphoplasmacytic and histiocytic meningitis with cells extending into and destroying underlying cerebral cortex
Describe granulomatous meningoencephalitis (GME)
- affects mostly small breeds, young to middle aged
- unknown cause – infectious or autoimmune?
- Histo lesions: perivascular lymphoplasmacytic and histiocytic infiltrates w/ nodular aggregates of macrophages; predominantly affects white matter
Describe spongiform diseases
- Transmissable spongiform encephalopathies are caused by prions - abnormal isoforms (PrPSc) of a normal cellular protein - the prion protein (PrPc)
- PrPSc acts as a template for re-folding PrPc
- primarily transmitted horizontally via consumption of infected feed material
- lesions: intracytoplasmic neuronal vacuolation, astrocytosis
What are some examples of spongiform diseases?
- Bovine spongiform encephalopathy
- Scrapie
- Chronic wasting disease
- Feline spongiform encephalopathy
- Transmissable mink encepalopathy
Describe meningiomas
- seen in cats, dogs, horses, cattle and sheep
- tumors located on the meningeal surface of the CNS
- well-demarcated, encapsulated, expansile masses that are grey-white to red-brown
Describe astocytomas
- __reported in dogs (esp. brachycephalic breeds), cats and cattle
- poorly demarcated, firm, grey-white masses in white matter and grey matter, well-differentiated neoplasms may be difficult to differentiate from surrounding brain matter
- most commonly affected sites: pyriform and temporal lobes
Describe oligodendroglioma
- reported in dogs (esp. brachcephalic breed), cats and cattle
- grey to pink-red, soft to gelatinous mass in white matter or grey matter of cerebrum and brainstem
