Neuro Pathology Flashcards
(97 cards)
1
Q
What is Nissl substance?
A
cytoplasmic basophilic granular material found in rough ER and polysomes
2
Q
What substance do you use to stain myelin?
A
Luxol fast blue stain
3
Q
What do ependymal cells do?
A
they line ventricles
4
Q
What is the function of astrocytes?
A
star-shaped cells w/ elaborate cell processes that form the blood-brain barrier
5
Q
What are microglia?
A
phagocytic cells of the CNS w/ small nuclei and relatively little cytoplasm
6
Q
Oligodendrocytes form myelin which wraps around axons in the ____, which Schwann cells form myelin for the ___
A
CNS; PNS
7
Q
Name the various cells and enzymes that make up the blood-brain barrier
A
Active barrier
- efflux transporters
- influx transporters
- metabolizing enzymes
Passive barrier
- astrocytes
- tight junctions
- endothelial cells
8
Q
Rod-shaped microglia are what?
A
activated
9
Q
What are gitter cells?
A
microglia ingesting myelin debris with foamy cytoplasm
10
Q
Define chromatolysis
A
degenerative change, dispersal of Nissl substance
11
Q
Define neuronophagia
A
microglia surround a necrotic neuron and phagocytose it to remove the debris
12
Q
What are spheroids?
A
focal axonal swellings filled w/ degenerate organelles
13
Q
What is Wallerian degeneration?
A
focal damage to a myelinated axon resulting in degeneration of the axon segment distal to the site of damage
14
Q
Describe the process of Wallerian degeneration
A
- Axon degenerates (spheroid)
- Gitter cells remove axon and myelin debris
- Empty dilated axon sheath
15
Q
True or False: Following Wallerian degeneration, regeneration can occur in both the PNS and the CNS
A
False; regeneration can only occur in the PNS, not the CNS
16
Q
What are some features of the CNS that inhibit regeneration following Wallerian degeneration?
A
- 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
17
Q
What are some features of the PNS that allow regeneration following Wallerian degeneration?
A
- Schwann cells have a basement membrane
- after injury, Schwann cells proliferate–> form a scaffold to direct sprouting axons
- Schwann cells then remyelinate new axon
18
Q
Describe the process of astrocytosis (astrogliosis)
A
- 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
19
Q
Define a gemistocytic astrocyte
A
a plump, reactive astrocyte with eosinophilic cytoplasm
20
Q
What are the characteristics of Alzheimer’s type II astrocytes?
A
- enlarged, vesicular nuclei
- these are typical of hepatic encephalopathy
21
Q
What might you see microglial nodules in conjunction with?
A
viral infections
22
Q
What are some types of CNS malformations?
A
- Failure or abnormality of structural development
- Slowing of normal development
- Premature degradation of normally formed tissue (abiotrophy)
- Primary functional disturbances
23
Q
What are some causes of CNS malformations?
A
- 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
24
Q
What are the 3 types of hydrocephalus?
A
- Internal: fluid in ventricles
- External: fluid in arachnoid space
- Communicating: fluid in ventricles and arachnoid space
25
In what breeds is hydrocephalus most common?
brachycephalic and some toy breeds
26
What is another name for an abnormally small brain?
microencephaly
27
What is lissencephaly?
brain lacks normal gyri and sulci
28
In what species is lissencephaly normal?
* certain mammals
* indian flying fox
* mouse
* rabbit
* Florida manatee
* common marmoset
* any non-mammals
29
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
30
What is the difference between a meningocele and a meningoencephalocele?
* Meningocele: herniation of **meninges**
* Meningocephalocele/meningomyelocele: herniation of **meninges and brain/spinal cord**
31
What is hydraencephaly?
* near complete or complete **absence of the cerebral hemispheres**, leaving **CSF-filled sacs** formed by the meninges
32
What is porencephaly?
* **cystic cavitation** of the brain, usually involving _cerebral white matter_
33
What happens in cerebellar hypoplasia, and what disease processes do you see this with?
1. _destroy the external granular layer_
* Border dz
* feline panleukopenia
* BVD d. 100-170 of gestation
2. inhibits cells _division/maturation_
* classical swine fever
34
What might you see cyclopia with?
*Veratum californicum* ingestion (particularly in sheep)
35
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
36
What are the various types of storage diseases?
* Sphingolipidoses
* Glycoproteinosis
* Mucopolysaccharidoses
* Glycogenoses
* Ceroid lipofuscinoses
\*named according to the substrate that has defective degradation
37
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
38
What is lipofuscin?
* "wear and tear" pigment, accumulates w/ advanced age
39
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
40
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
41
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
42
What cell types are most susceptible to ischemic lesions? What about brain matter?
* neurons
* cerebral cortical neurons
* hippocampal neurons
* Purkinje cells
* oligodendroglia
* grey matter
43
When might you see a global ischemic lesions?
* cardiac arrest
* prolonged severe hypotension/hypoxia
44
Histologic lesions of neuronal necrosis typically take a minimum of how long to develop?
3-6 months
45
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_
46
Describe neonatal maladjustment syndrome of foals
* "dummy foals"
* presumed to be **d/t ischemia and reperfusion**
* lesions: laminar neuronal necrosis, multifocal small hemorrhages
47
Describe malacic diseases
i.e. softening - usually means **necrosis in the CNS**
48
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
49
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
50
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
51
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
52
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
53
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**
54
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**
55
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**
56
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
57
What determines the neurotropism of an infectious agent?
their ability to breach the BBB and BCSFB
58
Bacterial infections are most commonly secondary to what in young animals?
septicemia
59
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_
60
What are the most common agents involved in forming abscesses from septic embolism?
* Pigs: Erysipelothrix rhusiopathiae
* Cattle: Trueperella pyogenes
* All species: Streptococccus spp.
61
What are the most common locations of septic emboli formation?
hypothalamus and junction of cerebral gray and white matter
62
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
63
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
64
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
65
What are the lesions of ITME?
* Gross lesions: multifocal hemorrhage, necrosis
* Histo lesions: vasculitis, **thrombosis**, infarction, **neutrophilic meningoencephalitis**, may form abscesses
66
What are the general features of viral infections of the nervous system?s
1. non-suppurative meningoencephalitis (+/- myelitis)
2. perivascular cuffing
3. gliosis
4. +/- viral inclusions
5. +/- neuronal degeneration/necrosis
67
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
68
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
69
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
70
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
71
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.
72
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**
73
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
74
What are three arboviruses?
* Eastern, Western and Venezuelan equine encephalomyelitis viruses
75
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
76
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
77
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_
78
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_
79
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
80
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**
81
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**
82
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
83
What fungus is the only one with a predilection for the CNS?
Cryptococcus neoformans
84
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
85
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_
86
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
87
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
88
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
89
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
90
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
91
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_
92
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**
93
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
94
What are some examples of spongiform diseases?
* Bovine spongiform encephalopathy
* Scrapie
* Chronic wasting disease
* Feline spongiform encephalopathy
* Transmissable mink encepalopathy
95
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
96
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**
97
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
