Neuropathology Flashcards
The outermost layer of the meninges
Dura
“pachymeninges”
send, stores, and receive electical and chemical signals
lots of different types
cell body, dendrytes, axons
neurons
local immune cells of the CNS
Microglia
Types of glial cells (supportive cells)
1) Microglia
2) Astrocytes
3) Oligodendrocytes
cells of the CNS that function for regulation, repair and support
astrocytes
cells of the CNS that produce myeline for insulation
oligodendrocytes
What does polio- root word mean
disease affecting the gray matter (neurons or stroma-neurpil)
What does the leuko- rootword mean
disease affecting the white matter
anterograde transport
moved towards the synapse
retrograde transport
moved away from the synapse (upwards)
in the spinal cord, the white matter is on the _______ while the grey matter is on the _______
inside; outside
layers of the meninges
1) Dura mater
2) Arachnoid
3) Pia mater
Which of the following cell types is local immune cell of CNS
Microglial cell
Encephalo-
brain
myelo-
spinal cord
polio-
greymatter
leuko-
white matter
gross softening of the brain (necrosis)
malacia
malacia
gross softening of the brain (necrosis)
What are the neuronal reactions to injury
1) Chromatolysis
2) Ischemic cell change (acute neuronal necrosis
degenerative change seen in cell body associated with axonal injury
swelling of nerve cell body (perikaryon) with dispersion (loss) of Nissl substance and peripheral displacement of the nucleus
Chromatolysis
Chromatolysis
-degenerative change seen in cell body associated with axonal injury
-swelling of nerve cell body (perikaryon) with dispersion (loss) of Nissl substance and peripheral displacement of the nucleus
Is Chromatolysis reversible ir irreversible
reversible degenerative change seen in cell body associated with axonal injury
-swelling of nerve cell body (perikaryon) with despiersion (loss of Nissl substance and peripheral displacement of the nucleus)
is acute neuronal necrosis reversible or irreversible
irreversible
What might lead to acute neuronal necrosis
1) Ischemia
2) Hypoxia
3) Hypoglycemia
4) Nutritional deficiency
5) Chemical intoxication
6) Excitatory toxicity - excessive sustained release or reduced clearance of excitotoxic neurotransmitters (e.g glutamate, aspartate)
excessive sustained release or reduced clearance of excitotoxic neurotransmitters (e.g glutamate, aspartate)
Excitatory toxicity
What do you see on histo after acute neuronal necrosis
shrunken and angular cell bodies with hypereosinophili cytoplasm and pyknotic nuclei
________________ cause swelling of the neuronal cell body with finely vacuolated cytoplasm
Lysosomal storage diseases- eg Locoweed
What is an example of a toxin that causes swelling of the neuronal cell body with finely vacuolated cytoplasm *lysosomal storage disease
Locoweed (swainsonine) toxicity
transmissible spongiform encephalopathy characterized by large discrete cytoplasmic vacuoles
neuronal vacuolization in prion diseases
prion diseases cause
transmissible spongiform encephalopathy characterized by large discrete cytoplasmic vacuoles
What is the aging pigment seen in aging neurons
Lipofuscin- no harmful effects
-orange-brown granular pigment
What causes Negri bodies (intracytoplasmic neuronal inclusion bodies)
Rabies virus
Are Negri bodies, seen in Rabies, intracytoplasmic or intranuclear?
Intracytoplasmic inclusion bodies
______________ bodies are _______________ inclusions seen in Rabies virus
Negri ; intracytoplasmic
Are herpes viral inclusion bodies intracytoplasmic or intranuclear?
intranuclear
Are Canine distemper viral inclusion bodies intracytoplasmic or intranuclear?
Both - intracytoplasmic and intranuclear
_________ virus only causes intranuclear inclusion bodies
Herpes virus
Why might injury to the cell body result in axonal changes
the axon is dependent on the neuronal cell body for delivery of nutrients and essential materials (neurofilaments) and removal of debris by active transport
the axon is dependent on the ____________ for delivery of nutrients and essential materials (neurofilaments) and removal of debris by active transport
neuronal cell body
Why might there be primary axonal injury
1) Trauma
2) Nutrient deficiencies (Vitamin E deficiency in horses)
3) Toxicoses
4) Inherited defects (ie axonopathies)
What are the progressive changes of axonal degeneration after injury
Swelling (spheroid) -> fragmentation -> removal by microglial cells (Gitter cells)
Cells that eat both the axon and myelin after axon injury/fragmentation. sit in digestion chambers
Gitter cells (microglial cells)
What is Wallerian degeneration*
degeneration of the axon and its myelin sheath distal to the site of focal injury (away from cell body). In the spinal cord, it occurs
1) Ascending tracts (tracts heading cranially towards the brain) cranial to the site of focal axon injury- dorsal funiculi and dorsolateral portion of lateral funiculi
2) Descending tracts (tracts heading further caudally towards the axon synapse) caudal to the site of axon injury- ventral funiculi and deep tracts of lateral funiculi
degeneration of the axon and its myelin sheath occurs _________ to the site of focal injury (away from cell body).
distal
What happens in the neuronal cell body survives following axonal injury
Regeneration from proximal stump can occur
Budding axon sprouts “neurites” can grow 2-4mm/day in pNS but much slower in the CNS
*Requires intact endoneurium and guiding influences of Schwann cells (PNS) or oligodendrocytes (CNS)
Schwann cells are in the
PNS
Oligodendrocytes are in the
CNS
What does the neuronal cell body need to grow new axons after injury
Requires intact endoneurium and guiding influences of Schwann cells (PNS) or oligodendrocytes (CNS)
What is the difference between Astrocytosis vs Astrogliosis
Astrocytosis is hyperplasia after injury
Astrogliosis is hypertrophy (increased number, size, and complexity of processes)
Gemistocyte
a reactive astrocyte with prominent eosinophilic cytoplasm (really large)
Alzheimer type II astrocytes
swollen ,degenerating astrocyte cells with clear cytoplasm and pale staining nuclei
-most often with renal or hepatic encephalopathy
When are Alzheimer type II astrocytes most commonly seen
with renal or hepatic encephalopathy
What are the two types of oligodendrocytes (CNS)
1) Interfascicular (white matter)- formation of maintenance of myelin in CNS
2) Perineuronal “satellite” cells (gray matter)- neuronal metabolism
myelinating cell of PNS
Schwann Cell
Satellitosis
hyperplasia of satellite cells in response to neurons in distress
T/F: if satellite cells die, the injury is irreversible and it leads to primary demyelination
true
T/F: Schwann cells have a limited capacity, compared to oligodendrocytes to remyelinate
False- oligodendrocytes are the cells whos damage is irreversible and leads to primary demyelination
*limited capacity compared to Schwann cells in PNS
degeneration/degradation of myelin sheath, with sparing of axon
-direct damage to myelin sheath or damage to myelin-producing cells (Schwann and oligodendrocytes)
primary demyelination
due to:
toxic (bromethalin), metabolic (hepatic encephalopathy), inherited enzymes defect in myelin metabolism, inflammatory/ immune mediated (canine distemper, caprine artheritis- encephalomyelitis)
what toxin might lead to primary demyelination
bromethalin
demyelination that is secondary to primary axonal injury (wallerian degeneration)
myelin depends on integrity of axon
Secondary demyelination
insufficient or absent myelin production
-in-utero pestivirus infections
Hypomyelination
formation of abnormal or unstable myelin leading to premature demyelination
-inherited leukodystrophies
Dysmyelination
Hypomyelinogenesis
insufficient or absent myelin production
-in-utero pestivirus infections
Dysmyelination
formation of abnormal or unstable myelin leading to premature demyelination
-inherited leukodystrophies
resident mononuclear phagocytes *resident macrophages of the CNS)
Microglial cells
Responses of microglial cells due to injury
1) Hypertrophy- activated macrophages with prominent cytoplasm- Rod cells
2) Hyperplasia: clusters of microglia in glial nodules- common with viral infections
3) Phagocytosis of: Lipid/myelin debris = Gitter cells and dead neurons (neuronophagia)
Rod cells
activated microglial cells (macrophages) with a prominent cytoplasm
Status spongiosis
spongy appearance of parenchyma (non-specific change) that can result from
-Postmortem artifact
-Intra-myelinic edema
-Loss of axons and/or myelin
-Vacuolation of neurons, glial cells, or their processes
How are small vs large CNS lesions healed
Small: proliferation of astrocytes/ processes
Large: astrocyte proliferation cannot occur leading to cavitation or cystic spaces
What are the types teratogens that can lead to congenital malformation of the nervous system
1) Physical agents: trauma, radiation
2) Nutritional factors (hypovitaminosis A -> optic nerve hypoplasia or congenital copper deficiency in lambs leads to white matter necrosis/ cavitation)
3) Toxins: eg steroidal alkaloid from veratrum californicum (skunk cabbage) in hseep at day 14 gestation -> synopthalia (failure of the 2 eye globes to separate and holoprosencephaly)
4) Virus e.g feline panleukopenia lead to cerebellar hypoplasia
or VBDV leads to cerebellar hypoplasia, hydranencephaly, porencephaly
Hypovitaminosis A during gestation leads to
optic nerve hypoplasia
Congenital copper deficiency in lambs leads to
Swayback
white matter necrossi and cavitation
Ingestion of Steroidal alkaloid from Veratrum californicum (skunk cabbage) at day 14 leads to________ in sheep
synopthalia (failure of the 2 eye globes to separate and holoprosencephaly
What what day of gestation does ingestion of Veratrum californicum (skunk cabbage) lead to synopthalia and holoprosencephaly in sheep
Day 14
Veratrum californicum **
Skunk cabbage that when ingested at day 14 of gestation in sheep leads to synopthalia and holoprosencephaly
Feline panleukopenia virus causes newborns to have
cerebellar hypoplasia
BVDV causes newborns to have
cerebellar hypoplasia
Hydrancephaly
Porencephaly
Synophthalmia
failure of the 2 eye globes to separate
-idiopathic
-veratrum californicum
Holoprosencephaly
where the two hemispheres of the brain do not separate
-idiopathic
-veratrum californicum
Most congenital malformations of the CNS occur immediately after birth or within the first week of life. When might they not
some may occur later in life (ie Lysosomal storage diseases)
*also some malformations are obvious externally while others require sectioning brain/spinal cord
Cranium bifidum
cranioschisis
-midline bony defect in the cranium
may be accompanied by
a) Meningocele (sac like protrusion of meninges through defect
b) Meingocephalocele (sac-like protrision of meninges and brain parenchyma through defect)
-midline bony defect in the cranium
may be accompanied by
a) Meningocele (sac like protrusion of meninges through defect
b) Meingocephalocele (sac-like protrision of meninges and brain parenchyma through defect)
Cranium bifidum (cranioschisis)
What might accompany Cranium bifidum
a) Meningocele (sac like protrusion of meninges through defect
b) Meingocephalocele (sac-like protrision of meninges and brain parenchyma through defect)
What are the different neural tube closure defects
1) Cranium bifidum (Cranioschisis)
2) Spina bifida
midline bony defect in vertebral column
usually involves lumbar, sacral or caudal vertebrae
ranging from failure of closure of vertebral arches (most common) to agenesis of vertebrae
may be accompanied by meningocele, meningomyelocele, or myelodysplasia
Spina bifida
What vertebrae does spina bifida most commonly affect
lumbar, sacral or caudal vertebrae
What may accompany spina bifida (midline bony defect in vertebral column leading to failure of vertebral arches to close or agenesis)
meningocele, meningomyelocele, or myelodysplasia
What results in interference with normal migration of neurons during development
genetic defects
What is Lissencephaly
agyria- cerebrum has smooth surface without gyri and sulci
due to a genetic defect resulting in interference of normal migration of neurons during development
What causes Lissencephaly
agyria- cerebrum has smooth surface without gyri and sulci
due to a genetic defect resulting in interference of normal migration of neurons during development
You see a rat with a smooth brain upon necropsy. You are thinking lissencephaly (agyri). What is significant?
Lissencephaly is genetic defect resulting in interference with normal migration of neurons during development leading to no gyri and sulci
Rats, Mice, and Rabbits normally have a smooth brain so this is not signficiant
formation of fluid filled cavities in brain reuslting from destruction of immature neuroblasts preventing appropriate migration and development
-usually occurs in utero
Encephaloclastic defects
a) Porencephaly: smaller cavities in cerebral hemispheres
b) Hydranencephaly: more severe destructive event resulting in massive cerebrocortical necrosis (gray and/whte matter) with almost complete loss of pre-existing tissue -> compensatory expansion of the lateral ventricles
Porencephaly
smaller fluid-filled cavities in cerebral hemispheres resulting from destruction of immature neuroblasts preventing appropriate migration and development, usually in utero
Hydranencephaly
more severe destructive event resulting in massive cerebrocortical necrosis (gray and/whte matter) with almost complete loss of pre-existing tissue -> compensatory expansion of the lateral ventricles
due to destruction of immature neuroblasts preventing appropriate migration and development
Encephaloclastic defects
formation of fluid filled cavities in brain reuslting from destruction of immature neuroblasts preventing appropriate migration and development
-usually occurs in utero
can be Porencephaly or Hydranencephaly
Encephaloclastic defects are often associated with
utero viral infections (eg. BVDV, bluetongue virus, Border disease virus)
You see several lambs from a flock of sheep in Germany were aborted or stillborn with several neuromuscular congenital malformations. You note porencephaly and arthrogryposis. What are some potential causes
Schmallenberg Virus *
Other possible causes:
Akabane Virus
Cache Valley Virus
Bluetongue Virus
What are the fetal teratogenic effects of feline panleukopenia virus (parvovirus)
Cerebellar hypoplasia, dysplasia
Purkinje cell loss
Hydranencephaly
What are the fetal teratogenic effects of Classical Swine Fever Virus (Pestivirus)
Dysmyelinogenesis, cerebellar hypoplasia
What are the fetal teratogenic effects of BVDV
Hydrocephalus, cerebellar hypo- and aplasia, prosencephaly in calves; hypomyelination ,orencephaly in lambs
excessive accumulation of cerebrospinal fluid leading to expansion of ventricular system +/- Subarachnoid spaces
Hydrocephalus
What is the most common congenital malformation in Vet med
Hydrocephalus
With hydrocephalus there is excessive accumulation of CSF leading to expansion of the
ventricular system +/- subarachnoid spaces
What are the different types of Hydrocephalus
1) Non-communicating (most common): fluid within ventricular system, obstruction anterior to lateral apertures of 4th ventricle and (mesencephalic aqueduct)
2) Communicating (rare): excess fluid in ventricular system and subarachnoid spaces leading to malformation of arachnoid villi
3) Hydrocephalus Ex vacuo: loss of brain tissue (eg hydranencephaly) leading to dilation of ventricular system
What is the most common site of obstruction in non-communicating hydrocephalus *
Mesencephalic aqueduct
Hydrocephalus Ex vacuo
loss of brain tissue (eg hydranencephaly) leading to dilation of ventricular system
What are the sequelae to hydrocephalus
1) dilation of ventricles- secondary compression atrophy of white matter
2) May have flattened gyri and shallow sulci
3) Possible herniation through foramen magnum (depending on how rapid obstruction occurs)
What breeds is congenital hydrocephalus most common in
toy and bracycephalic breeds of dogs
and
calves
Congenital hydrocephalus is most commonly a malformation of the _____________ **
mesencephalic aqueduct
congenital hydrocephalus
associated with enlargement of cranium (doming) and open fontanelles
most commonly a malformation of mesencephalic aqueduct
most common in toy and brachycephalic breeds and calves
How might an animal get acquired hydrocephalus
obstruction of CSF flow due to inflammation, neoplasia or other compressive lesions
-location varies
obstruction of CSF flow due to inflammation, neoplasia or other compressive lesions
-location varies
acquired hydrocephalus
abnormal dilation of central canal of spinal cord
hydromyelia
What is the most appropriate term for dilation of the ventricular system secondary to an encephaloclastic defect such as hydranencephaly
non-communicating hydrocephalus
Hydromyelia
abnormal dilation of central canal of spinal cord
-most are congenital (genetic or infectious)
-acquired are rare (similar causes to acquired hydrocephalus)
which of the following locations of stenosis is most commonly found in congenital hydrocephalus
Mesencephalic aqueduct
Syringomyelia
cystic fluid filled tubular cavity (syrinx) within the spinal cord that is not lined by ependyma
-congenital or acquired (rupture of ependyma with secondary cavitation)
Dogs and calves; Weimaraner and CKCS -associated with Chiari-like malformation)
cystic fluid filled tubular cavity (syrinx) within the spinal cord that is not lined by ependyma
Syringomyelia
What breeds is syringomyelia most common in
Dogs and calves; Weimaraner and CKCS -associated with Chiari-like malformation)
Syringomyelia can be congenital or acquired. How might it be acquired
rupture of the ependyma with secondary cavitation leads to a cystic lfuid-filled tubular cavity (syrinx) within the spinal cord
What will you see microscopically in a patient with cerebellar hypoplasia
the cerebellum is decreased in size but microscopically you will see decreased Purkinje cells and granular layer cells- destruction of mitotically active external granular cells
What are the causes of cerebellar hypoplasia
1) Viral infections: parvoviruses (feline panleukopenia and canine parvovirsu) or Pestiviruses (BVDV at fetal 100-150 days gestation or classical swine fever, or border disease virus)
2) Inherited genetic defect
3) Toxins: piglets from sows treated with organophsophate insecticide during second half of gestation
piglets from sows treated with organophsophate insecticide during second half of gestation will develop
cerebellar hypoplasia
At what time frame of gestation do fetal infections of BVDV result in cerebellar hypoplasia
between days 100-150
What is cerebellar cortical abiotrophy (CCA)
the lack of vital, nutritive substance necessary for normal cell lifespan
-premature degeneration/ necrosis and loss of Purkinje cells and granular layer cells (cerebullum can be smaller or normal size)
-Intrinsic metabolic defect susepcted (most autosomal recessive)
early onset and progressive (but not as borth) -> cerebllar ataxia with head tremor, truncal ataxia, symmetrical hypermetria, spasticity and broad-based stnace
-premature degeneration/ necrosis and loss of Purkinje cells and granular layer cells (cerebullum can be smaller or normal size)
-Intrinsic metabolic defect susepcted (most autosomal recessive)
Cerebellar cortical abiotrophy (CCA)
How do you differentiate cerebellar hypoplasia from cerebellar cortical abiotrophy *
CCA is early onset and progressive (NOT present at birth)
cerebellar ataxia with head tremor, truncal ataxia, symmetrical hypermetria, spasticity and broad-based stanace
CCA is inherited in the breeds_______
dogs (Airdale, border collie, gorden setter
horses (arabian*, gotland pony
cattle (holstein, hereford, angus)
sheep (merine, coriedale)
pigs (Yorkshire)
What breeds get Chiari-like malformations
Cavalier King Charles Spaniel
What is Chiari-like malformation
when there is a mismatch between the caudal fossa volume and the brain parenchyma mass leading to caudal herniation of cerebellar vermis and brainstem into the foramen magnum
leading to
-Alteration in CSF flow between intracranial and spinal compartments and reduced craniospinal compliance can lead to springomyelia
common in CKCS
when there is a mismatch between the caudal fossa volume and the brain parenchyma mass leading to caudal herniation of cerebellar vermis and brainstem into the foramen magnum
leading to
-Alteration in CSF flow between intracranial and spinal compartments and reduced craniospinal compliance can lead to springomyelia
common in CKCS
Chiari-like malformation
what leads to syringomyelia in CKCS that hav chiari-like malformation
when they have chairi-like malformation there is a mismatch between caudal fossa volume and brain parenchyma mass leading to caudal herniation of cerebllar vermis and brainstem into foramen magnum
this creates alteration in CSF flow between intracrnail and spinal compartments and the reduced craniospinal compliances leads to syringomyelia
most biochemical defects are
lysosomal storage diseases
usually autosomal recessive (homozygotes manifest disease, heterozygotes are phenotypically normal by 50% have norma enzume activity
Do homozygotes or heterozygotes get lysosomal storage diseases
it is autosomal recessive
often gene dose dependent
homozygotes- manifest disease while heterozygotes are phenotypically normal but have 50% of normal enzyme activity
What do you see histologically of patients with lysosomal storage diseases
neurons +/- other cell types such as glial cells, macrophages, hepatocytes, renal tubular epithelium) with finely vacuolated cytoplasm
Ceroid lipofuscinosis
clinical signs are usually seen 1-2 years of age
widespread sotrage: moost severe/damaging to neurons of cerebral cortex, retina, and cerebellar Purkinje cells
leading to dementia blindness, ataxia
Atrophied regions may have brown tinge
*Only storage disease with gross lesions
What is the only storage disease with gross lesions
Ceroid lipofuscinosis
-atrophied regions may be brown tingue
widespread storage to severe/damaging to neurons of cerebral cortex, retina and cerebllar Purkinje cells
leaves atrophied regions with brown tingue *
Ceroid lipofuscinosis
When are the clincial signs of Ceroid lipofuscinosis apparent
typically 1-2 years of age
What plants do you see acquired/ induced storage disease due to Swainsonine toxicity
Astragalus and Oxytropis (locoweeds)
What happens when sheep, cattle, and horses eat Astragalus and Oxytropis (locoweeds)
1) Indolizidine alkaloid: inhibitor of a-mannosidase enzyme
2) get microscopic lesions idenditcal to genetic alpha-mannosidosis (finely vacuolated cytoplasm)
3)Storage disease
*Can be transfered to the fetus if pregnant animals consume it
T/F: if animal eats Astragalus and Oxytropis (locoweeds), the storage disease can be transferred to the fetus
True
you have a 6yo MN greyhound with peracute (sudden) onset of disorientation behavior changes and head pressing
Clinicalsigns after initial onset have no progressed and possibly improved over time. What is ths likely
Stroke or Neoplasia
What is the typical clinical presentation of cerebrovascular disease (stroke)
peracute/acute onset of neuro signs (usually indicating a focal lesion) which typically do not progress and may ablate with time
the outcome of thrombosis and infarction to nervous system depends on
-Type and size of obstructed vessel
-Rapidly of onset of ischemia (gradual to sudden obstruction)
-Vulnerability of the area of brain or spinal cord to hypoxia
(Neurons > Oligodendrocytes > astorcytes > microglia > vascular endothelial cells
What are the susceptibility levels of different cells in the CNS to hypoxia
Neurons > Oligodendrocytes > Astrocytes > Microglia > Vascular endothelial cells
What are the two different types of infarcts to the nervous system *
1) Ischemic infarcts: Thrombus or Thromboembolism leading to well circumscribed area of tan to yellow discolaration and softening (malacia), gray matter more susceptible, with chronicity- cavitation (if large region of injury)
2) Hemorrhagic infarct: vascular damage/ rupture leading to leakage of RBCs (venous thrombosis)
gross lesion: regional area of parenchymal hemorrhage
What gross lesion will you see with ischemic infarcts to the nervous system*
Thrombus or Thromboembolism leading to well circumscribed area of tan to yellow discolaration and softening (malacia), gray matter more susceptible, with chronicity- cavitation (if large region of injury)
What gross lesion will you see with a hemorrhagic infarct to the nervous system *
vascular damage/ rupture leading to leakage of RBCs (venous thrombosis)
gross lesion: regional area of parenchymal hemorrhage
Is gray or white matter more susceptible to ischemic infarcts
gray matter- more vasculature and susceptible cells (neurons)
Ischemic infarcts are due to _____________ while hemorrhagic infarcts are due to ___________
vascular (artery/arterioles) obstruction- thrombus or thromboembolism
Vascular damage/ rupture leading to leakage of RBCs (venous thrombosis
Why might a dog get atherosclerosis
secondary to hypothyroidism
you see multifocal acute hemorrhages on a canine brain. What might be the cause
Septicemia
Neoplasia
common in dogs
peracute (usually lateralized) spinal signs without pain
exact mechanism is unknown but herniation herniation of degenerative disk material (nucleus pulposus) Hansen type I -> vasculature -> occlusive emboli -> ischemic injury
Fibrocartilaginous emboli
Fibrocartilaginous emboli
common in dogs
peracute (usually lateralized) spinal signs without pain
exact mechanism is unknown but herniation herniation of degenerative disk material (nucleus pulposus) Hansen type I -> vasculature -> occlusive emboli -> ischemic injury
Although unknown, why might a dog get fibrocartilaginous emboli
herniation of degenerative disk material (nucleus pulposus) Hansen type I -> vasculature -> occlusive emboli -> ischemic injury
excess fluid accumulation in the CNS parenchyma
can be associated with most CNS disease processes
Edema
What are the types of cerebral edema
1) Vasogenic: most common type, due to increased vascular permeability -> extracellular fluid accumulation. White matter is most affected (spongiosis)
common causes- neoplasia, inflammation, trauma, and some toxic/metabolic conditions
2) Cytotoxic Edema: altered cellular metabolism -> intracellular fluid accumulation
Low O2 -> interference with ATP dependent Na/K pump in cell membrane leading to swelling of neurons, glial and endothelial cells (gray and white matter)
common causes are hypoxia, neoplasia, toxic/ metabolic conditions (ie salt poisoning in pigs, hepatic encephalopathy)
3) Interstitial edema (hydrostatic): accumulation of fluid in the periventricular white matter associated with increased ventricular pressure (hydrocephalus or hydromyelia)
4) Hypo-osmotic edema: osmotic imbalances associated with water intoxication
What is the most common type of cerebral edema
Vasogenic edema
most common type, due to increased vascular permeability -> extracellular fluid accumulation. White matter is most affected (spongiosis)
common causes- neoplasia, inflammation, trauma, and some toxic/metabolic conditions
How does vasogenic edema occur *
increased vascular permeability leading to extracellular fluid accumulation
white matter is most affected (spongiosis)
cause: neoplasia, inflammation, trauma
How does cytotoxic edema occur*
altered cellular metabolism -> intracellular fluid accumulation
Low O2 -> interference with ATP dependent Na/K pump in cell membrane leading to swelling of neurons, glial and endothelial cells (gray and white matter)
common causes are hypoxia*, neoplasia, toxic/ metabolic conditions (ie salt poisoning in pigs, hepatic encephalopathy)
How does hypo-osmotic edema occur
osmotic imbalances associated with water intoxication
How does interstitial edema occur
(hydrostatic): accumulation of fluid in the periventricular white matter associated with increased ventricular pressure (hydrocephalus or hydromyelia)
What gross lesions do you see with CNS edema
-flattened gyri and shallow sulci
-clear, watery fluid in leptomeninges
-posterior shifting of brain (herniation through foramen magnum)
-White matter may be soft, wet, pale yellow
edema may cause
herniation
1) through the foramen magnum (foramenal herniation)
2) Under tentorium cerebelli (transtentorial herniation)
3) Under the falx cerebri (falcine herniation)
4) Through defect in skull (eg. fracture) calvarial herniation
Clostridium perfringens type D (epsilon) may cause ____________ in sheep
focal symmetrical (hemorrhagic) encephalomalacia (internal capsule)
What causes focal symmetrical (hemorrhagic) encephalomalacia (internal capsule) in sheep
Clostridium perfringens type D (epsilon)
As the brain swells it can herniate. What are common locations for this to occur
1) through the foramen magnum (foramenal herniation of cerebellar vermis)
2) Under tentorium cerebelli (transtentorial herniation)
3) Under the falx cerebri (falcine herniation)
4) Through defect in skull (eg. fracture) calvarial herniation
caudal displacement of the parahippocampal gyri caused by sudden swelling of the brain from severe blunt trauma to head
transtentoral herniation
forces that are external to the body (HBC, kicks to head, falls ,gunshot wounds, bites)
external injury
what might be cause of intrinsic physical disturbances to the nervous system
disc extrusion,vertebral abscesses, neoplasia, congenital malformations causing compression
primary traumatic injuries
from the direct trauma (fractures, hemorrhage, edema, and direct injury to the parenchyma from forces acting on the brain
(acceleration/deceleration and rotational forces)
How do acceleration/deceleration forces differ from rotational forces in context of traumatic brain injuries
Acceleration/deceleration- superficial gray matter (hemorrhages, contusion, and tearing of neuronal tissue)
Rotational forces- deeper white matter (causing concussive injuries and axonal damage)
What is second injury to trauma
series of events that can lead to continued injury to the neurons/glial cells
Major mediators- oxygen free radicles, excitatory amino acids, nitric oxide
series of events that can lead to continued injury to the neurons/glial cells
Major mediators- oxygen free radicles, excitatory amino acids, nitric oxide
What is second injury to trauma
What is seen in acceleration/ deceleration trauma
Acceleration/deceleration- superficial gray matter (hemorrhages, contusion, and tearing of neuronal tissue)
What is seen in rotational trauma
Rotational forces- deeper white matter (causing concussive injuries and axonal damage)
diffuse but transient brain injury associated with temporary loss of consciousness
typically no gross lesions
uncommon in animals
Concussion
focal brain injury which may (but not usually) results in unconsciousness
usually a grossly detectible, superficial area of brain hemorrhage
often associated with skull fracture
Contusion
How does concussion differ from contusion
Concussion: diffuse but transient brain injury associated with temporary loss of consciousness
typically no gross lesions
uncommon in animals
Contusion: focal brain injury which may (but not usually) results in unconsciousness
usually a grossly detectible, superficial area of brain hemorrhage
often associated with skull fracture
Coup contusion
the inside of the cranial vault strikes the stationary brain at the point of impact
Contrecoup contusion
lesion occurs on the opposite side due to stretching and tearing of vessels or the brain struck by inside of cranial vault, on opposite side from blow, where there is reduced CSF buffer present
How does Coup differ from contrecoup
Coup: the inside of the cranial vault strikes the stationary brain at the point of impact
Contrecoup:
What is the most common place you see hemorrhage following cranial trauma? **
The subarachnoid space
What are the causes of brain hemorrhage
1) Trauma
2) DIC
3) Damage to vessels/ vasculitis (viruses, septicemia, immune complex, neoplasia, parasites)
What fractures are common with horses that rear over backwards
fracture of basisphenoid bone
displaced bone lacerates large vessels at the base of the brain
hemorrhage becomes the dominant lesion
Fracture of what bone in horses leads to laceration of large vessels at the base of the brain leading to hemorrhage *
basisphenoid bone
The extradural space is greatest in the
cervical vertebral column, cranial thoracic, and caudal lumbar region
spinal cord compression is less likely
There is a lower risk of intervertebral disc extrusion at the
intercapital ligaments (T2-T10)
What does T2- T10 have a lower risk of intervertebral disc extrusion
intercapital ligaments (T2-T10)
What might lead to contusion to the spinal cord
Focal hemorrhage associated with fracture, luxation, subluxation, or disc herniation
What might lead to compression of the spinal cord *
extramedullary pressures (disc herniation, vertebral/ meningeal neoplasia, vertebral fracture/ subluxation, vertebral malformation
What is seen microscopically with spinal cord trauma*
hemorrhage (more prominent in gray matter)
axonal/myelin degeneration at site of compression
degeneration of axon and myelin sheath distal to site of injury (Wallerian degeneration)
Acute spinal cord compression
1) sudden direct impact to spinal cord (contusion)
2) Hypoxia caused by direct injury to vessels leading to hemorrhage or thrombosis
compression of vessels without vascular injury (blood stasis)
release of local neurotransmitters (norepinephrine) -> vasospasm and vasoconstriction
ex: Hansen type I intervertebral disc extrusion
acute extrusion of nucleus pulposus through annulus fibrosus and into the canal
-usually associated with “chondroid” degeneration/metaplasia of nucleous pulposus
genetically programmed and starts early (6months)
Chondrodystrophic breeds
Hansen type I disc extrusion, leads to acute compression (contusion)
Hansen type I disc extrusion
acute extrusion of nucleus pulposus through annulus fibrosus and into the canal
-usually associated with “chondroid” degeneration/metaplasia of nucleous pulposus
genetically programmed and starts early (6months)
Chondrodystrophic breeds
chronic spinal cord compression that is slowly developing
Low grade hypoxia due to compression of vessels leading to reduced perfusion, vascular stasis, and increased hydrostatic pressure leading to edema
Hansen type II intervertebral disc protusion
or
cervical vertebral stenotic myelopathy
bulging of disc material into the vertebral canal associated with fibrous degeneration of annulus (usually around 8-10 years of age)
More common in non-chondrodystrophic dogs
Hansen type II disc protrusion
Hansen type II disc protrusion
bulging of disc material into the vertebral canal associated with fibrous degeneration of annulus (usually around 8-10 years of age)
More common in non-chondrodystrophic dogs
acute and chronic spinal cord compression can lead to
ascending/ descending hemorrhagic myelomalacia
more common in type I IVDD
12-24 hours after injury
high-velocity-low volume disc extrusion
acute non-compressive nucleus pulpsosus extrusion
What is Wobbler’s syndrome
cervical vertebral stenotic myelopathy
What can be the causes of Wobbler’s Syndrome
Cervical Vertebral Stenotic myelopathy caused by:
1) Osseous (young adults) where vertebral malformations often associated with degeneration of facet joint (osteochondrosis dissecans)
can be complicated/ exacerbated by hypertrophy of ligamentum flavum or synovial cysts
2) Disc-associated in adult dogs born with congenital vertebral canal stenosis: prone to cord compression because smaller extradural space with secondary hypertrophy of dorsal longitudinal ligament and annulus fibrosis
C5-C6 and C6-C7
What is the osseous form of cervical vertebral stenotic myelopathy
Cervical Vertebral Stenotic myelopathy caused by:
1) Osseous (young adults) where vertebral malformations often associated with degeneration of facet joint (osteochondrosis dissecans)
can be complicated/ exacerbated by hypertrophy of ligamentum flavum or synovial cysts
What causes the osseous form cervical vertebral stenotic myelopathy
vertebral malformation -degeneration of facet joints (osteochondrossis dissecans)
What is the difference between static vs dynamic Wobbler’s syndrome in horses
Static >1 year of age - compression regardless of neck position (C5-C6 and C6-C7)
Dynamic (typically 8-18 months): flexed neck: C3-C4 and C4-C5
Glioma
neoplasia of glial cell origin
most common type of primary intra-axial CNS neoplasia in dogs and cats (dogs more frequent)
major types:
Astrocytoma
Oligodendroglioma
Undefined glioma (both phenotypes in high proportions >30-40%)
What is an undefined glioma
when there is both phenotypes (astrocytoma and oligodendroglioma) at high proportions >30-40%
What CNS neoplasia are brachycephalic breeds predisposed for
Astrocytoma
Oligodendroglioma
Where are astrocytomas most commonly located in
temporal and piriform lobes
What is the gross appearance of astrocytomas *
firm and tan-gray with indistinct boundaries
high grade tumors have more distinct mass with hemorrhage and necrosis
What is the gross appearance of oligodendroglioma *
well-demarcated with gelatinous or mucoid texture
Where are oligodendrogliomas typically located
Cerebrum- olfactory bulbs and front, temporoal, and piriform lobes
How do you diagnose gliomas
immunohistochem
A) Glial fibrillary acidic protein (GFAP) for cytoplasm of astrocytes
B) Oligodendrocyte lineage transcription factor 2 (Olig2) - labels nucleus of all gliomas
C) 2,3’ cyclic nucleotide 3’- phosphodiesterase (CNPase): fairly specific of oligodendroglioma (cytoplasmic)
Where are choroid plexus tumors located *
Ventnricular location
-Hydrocephalus: obstructive or increased CSF production
Choroidplexus can lead to
Hydrocephalus: obstructive or increased CSF production
How do you classify choroid plexus tumors
Papilloma
Atypical papilloma
Carcinoma
Where are Ependymoma located*
ventricular system (lateral and third most common) or extraventricular
lead to obstructive (acquired) hydrocephalus
What is sequela of ependymoma
lead to obstructive (acquired) hydrocephalus
What are the classification of Ependymoma
1) Ependymoma
2) Anaplastic (malignant_ ependymoma
What is the most common primary CNS tumor of cats and dogs*
Meningioma
what are the common sites for meningioma in dogs and cats
Dogs: frontal lobes and olfactory lobes
Cats: usually solitary (can have multiple) and supratentoral; associated with tela choridea of third ventricle
*extra neuronal metastasis is rate
What are the gross lesions of meningioma
extra-axial, well circumscribed +/- secondary pressure necrosis of parenchyma
commonly amenable to surgical excision
Meningiomas are (intra/extra) axial
extra axial
neoplasm derived from neuronal precursor cells in olfactory mucosa
in the caudal aspect of nasal cavity
Olfactory neuroblastoma
(Esthesioneuroblastoma)
Esthesioneuroblastoma
Olfactory neuroblastoma
neoplasm derived from neuronal precursor cells in olfactory mucosa
in the caudal aspect of nasal cavity
Olfactory neuroblastoma
Esthesioneuroblastoma
neoplasm derived from neuronal precursor cells in olfactory mucosa
in the caudal aspect of nasal cavity
Neoplasm of undifferentiated cells of cerebellum
often congenital (calves and young dogs)
originate from external granular cell layer
Medullobastoma
(a primitive neuroectodermal tumor- PNET)
Where do Medulloblastomas originate from
a primitive neuroectodermal tumor- PNET
Neoplasm of undifferentiated cells of cerebellum
often congenital (calves and young dogs)
originate from external granular cell layer
Spinal Nephroblastoma *
thoracolumbar spinal cord tumor of young dogs
Between T10-L2
Young <1 year
2 cell populations (embryonic blastemal cells and epithelial cells)
Where does spinal nephroblastoma typically occur *
T10-L2 in young dogs (<1yr)
thoracolumbar spinal cord tumor of young dogs
What age of dog does spinal nephroblastoma typically affect *
T10-L2 in young dogs (<1yr)
thoracolumbar spinal cord tumor of young dogs
What are the cells of origins of nerve sheath tumors
1) Schwannoma- Schwann cells
2) Neurofibroma- fibroblasts
3) Perineurioma- perineural cells
4) Malignant nerve sheath tumor
What are the common sites of nerve sheath tumors in dogs, cattle, horses, and cats
Dog:
brachial plexus»_space; lumbosacral plexus
distal peripheral nerves/skin
trigeminal (most common cranial nerve)
Cattle:
Multicentric (Neurofubromatosis): ANS, heart, mediastinum, 8th cranial nerve, intercostal nerves, brachial plexus
Horses/Cats: Skin
What do nerve sheath tumors look like grossly
nodular subcutaneous mass or thickening of nerves
fusion with adjacent nerves
What is the most common spinal cord tumor and second most common intracranial tumor in cats
Multicentric lymphoma
Leukocytic tumors (lymphoma) in canine and feline are mostly (B or T cell)
T cell lymphoma (90%)
What causes lymphoma in cattle **
Bovine leukemia virus associated (intradural and extramedullary in caudal equina)
Where in the nervous system is bovine leukemia virus associated with *
intradural and extramedullary in caudal equina
What is Cholesteatoma
a tumor like lesion that is common in 15-20% of old horses
suspected chronic intermittent hemorrhage or congestion/edema of choroid plexus
usually incidental (unless large)
a tumor like lesion that is common in 15-20% of old horses
suspected chronic intermittent hemorrhage or congestion/edema of choroid plexus
usually incidental (unless large)
Cholesteatoma
A cholesteatoma in older horses is thought to be due to _________________ of the _____________
chronic intermittent hemorrhage or congestion/edema of choroid plexus
Secondary tumors of the CNS are ________ common than primary tumors
less
How might an animal get secondary tumors of the CNS
1) Direct extension:
a) bony tumors of cranium or vertebrae (osteoma, osteosarcoma, osteochondrosarcoma, multiple myeloma)
b) Carcinomas of nasal and paranasal sinuses
c) Ocular tumor
2) Hematogenous metastasis: mammary and pulmonary tumors, melanoma, hemangiosarcoma, and multicentric lymphoma
What tumors might spread hematogenously to the CNS
Hematogenous metastasis: mammary and pulmonary tumors, melanoma, hemangiosarcoma, and multicentric lymphoma
What tumors might spread via direct extension to the CNS
a) bony tumors of cranium or vertebrae (osteoma, osteosarcoma, osteochondrosarcoma, multiple myeloma)
b) Carcinomas of nasal and paranasal sinuses
c) Ocular tumor
What is the blood brain barrier
tight junctions between capillary endothelial cells
*inflammation can readily develop in the brain and spinal cord
-cytokines or local mast cells products (eg histamine) -> increase permeability of vascular endothelium
What will a dog with multilobular osteochondrosarcoma look like
a large lump on they head
how might the capillary endothelial cells become leaky
-cytokines or local mast cells products (eg histamine) -> increase permeability of vascular endothelium
Once CNS infection occurs __________
it tends to persist
-drainage of exudate from CSF is poor (lack of lymphatic vessels in CNS)
-diffucult to treat because of poor penetration of blood brain barrier by drugs
Why does CNS infection typically persist
-drainage of exudate from CSF is poor (lack of lymphatic vessels in CNS)
-difficult to treat because of poor penetration of blood brain barrier by drugs
-No fibroblasts to wall off the area
Many agents have no neurotropism and you really only see brain involvement with systemic infection but what are some agents that are neurotropic
Rabies- neurons of grey mater
Prions- medulla
Listeria monocytogenes- Pons and medulla
Rabies targets neurons of (white/grey) matter
grey matter
Most viruses target the (white/grey) matter
grey matter
Where do you sample for prions disease
obex of the medulla (dorsal motor nucleus of the vagas nerve)
inflammation of the brain
encephalitis
inflammation of the spinal cord
myelitis
inflammation of the pia-arachnoid *
leptomeningitis
inflammation of the dura mater*
pachymeningitis
pachymeningitis
inflammation of the dura mater
inflammation of the ependyma
ependymitis
inflammation of the choroid plexus
choroiditis
inflammation of the ventricles
ventriculitis
What are the different routes of CNS infection *
1) Direct extension/implantation- penetrating trauma (stab wound, gun shot, skull fracture), middle/inner ear infections, nasal cavity/sinus infections through the cribriform plate along olfactory nerve, osteomyelitis, neoplasia
2) Hematogenous- localization within capillary beds of meninges or choroid plexus (eg. neonatal septicemia)
3) Via peripheral nerves (retrograde axonal transport) via axoplasmic flow from PNS to CNS (rabies virus and Listeria monocytogenes)
4) Leukocyte trafficking- macrophages or lymphocytes containing microbes during their transit through CNS (retroviruses)
What virus infects the ventricles of the brain
FIP- feline infectious peritionitis virus
How might the CNS get infected through direct extension
1) penetrating trauma (stab wound, gun shot, skull fracture), 2) middle/inner ear infections
3) nasal cavity/sinus infections through the cribriform plate along olfactory nerve
4) osteomyelitis
5) neoplasia
How might a sheep get a frontal lobe abscess from direct extension from the nasal cavity
Oestrus ovus (nasal bot)
or dehorning
What is the most common route of CNS infection
Hematogenous- localization within capillary beds of meninges or choroid plexus (eg. neonatal septicemia)
What are examples of pathogens that infect the CNS via retrograde axonal transport
Via peripheral nerves (retrograde axonal transport) via axoplasmic flow from PNS to CNS (rabies virus and Listeria monocytogenes)
What is a common site to see CNS infection through hematogenous spread
pituitary abscess
you have several piglets (5-8 weeks), some sudden deaths that are all paddling.
some develop neurologic abnormalties, swollen joints or cutaneous lesions- incoordination, tremors, lateral recumbency, padlding, and opisthonos. Upon necropsy you see suppurative meningitis. What might have causes this
Major causes of meningitis in pigs (as part of polyserotis)
1) Steptococcus suis
2) Glasseurella parasios (Glasser’s disease)
3) Mycoplasma hyorhinis (does not cause meningitis)
4) Other gram negative septicemia (e.g Salmonella)
What are major causes of meningitis in pigs (as part of polyserositis)
Major causes of meningitis in pigs (as part of polyserotis)
1) Steptococcus suis
2) Glasseurella parasios (Glasser’s disease)
3) Mycoplasma hyorhinis (does not cause meningitis)
4) Other gram negative septicemia (e.g Salmonella)
Meningitis is most often ____ *
part of systemic bacterial infection (septicemia)
also can result from direct extension (ie. fractures, otitis, sinusitis)
a common finding in neonatal septicemia
What are the gross lesions of meningitis *
*Opaque leptomeninges (look at ventral aspect of brain)
+/- thickening of choroid plexus and roughening of ependymal surface
+/- other lesions of septic animals - peritonitis, pericarditis, endophthalmitis, polyarthritis
Why do you need to look at the ventral aspect of the brain when necropsy of an animal with menigitis *
*Opaque leptomeninges (look at ventral aspect of brain)
What is the possible causes of bovine neonatal septicemia that can lead to CNS infection
*Coliforms
Strep
Pasteurella
Salmonella
Klebsiella
Staphyococcus
Actinpbacillus equi (foals)
Where in the nervous system do you typically see empyema
epidural
-vertebral canal (tail docking or other traumatic injuries
-cranium (secondary to infection following skull fracture
Oestrus ovis infection in sheep can lead to *
direct extension through cribiform plate to cause a frontal abscess of the brain
What can thermal injury from dehorning result in?
frontal abscess
What can inner ear infection result in
cerebellopontine abscesses from direct extension from adjacent tissues
What are common isolates of bacterial abscesses to nervous system
Trueperella pyogenes
Streptococcus
Pasteurella
What might cause chronic cerebral abscess in sheep
Corynebacterium pseudotuberculosis
Direct extension of bacteria from middle/inner ear can lead to
cerebellopontine abscess (look at the ears/ typanic bullae
What is the most common cause of middle/inner ear infections in cattle leading to cerebellopontine abscess *
Mycoplasma bovis
_____________ in the middle/inner ear of cattle can lead to __________ via direct extension *
Mycoplasma bovis ; cerebellopontine abscess
you have a circling adult ewe, depressed, right sided head tilt, stumbling/circling to the right, right sided facial paresis, several animals affected. What might be the differential
Listeria monocytogenes
or
Inner ear infection
Listeria monocytogenes is associated with *
spoiled silage
What is the pathogenesis of Listeria monocytogenes *
1) Spoiled silage
2) Oral wound allows bacterial invasion of mucosa
3) Bacteria invade trigeminal (other nerves possible)
4) Travel to brainstem via axons (retrograde)
5) Gross lesions typically absent but causes microabscesses in brainstem (pons and medulla)
What are the typical gross lesions you see with Listeria monocytogenes infection *
Gross lesions typically absent but causes microabscesses in brainstem (pons and medulla)
How do you diagnose Listeria monocytogenes
culture, IHC, Gram stain
What will you see on histology of animal with Listeria *
**microabscesses in brainstem (pons and medulla)
What nerve does listeria invade
tirgeminal and travels to the brainstem via axons (retrograde)
What is the pathogenesis of Histophilus somni
1) Normal genital and nasal flora of cattle and sheep
2) Respiratory tract -> septicemia
3) Thrombotic meningoencephalitis (and lesions in other tissues such as bronchopneumonia and myocarditis)
How does Histophilus somni cause multifocal hemorrhages and necrosis (malacia) *
Septicemia leads to thrombotic meningoencephalitis
gross lesions: multifocal hemorrhages and necrosis (malacia)- brain and spinal cord
Primary histological lesion
-Vasculitis -> thrombosis +/- infarcts with gram positive bacteria within thrombi and vessel walls
What lesions do you see with Histophilus somni infection
gross lesions: multifocal hemorrhages and necrosis (malacia)- brain and spinal cord
Primary histological lesion
-Vasculitis -> thrombosis +/- infarcts with gram positive bacteria within thrombi and vessel walls
What is the primary lesion you see with Histophilus somni
multifocal hemorrhages and necrosis (malacia)- brain and spinal cord caused by thrombotic and vasculitis
What causes focal symmetrical encephalomalacia
Clostridium perfringens type D
epsilon toxin
What is the pathogenesis of Clostridium type D leading focal symmetrical encephalomalacia (FSE) *
1) Food animals eat lots of highly fermented carbs
2) Overgrowth of Clostridium perfringes type D producing epsilon toxin
3) Degeneration of vascular endothelial tight junctions
4) Swelling and rupture of perivascular astrocyte processes
5) Leakage of fluid and increased intracerebral pressure
6) Parenchymal necrosis
How does epsilon toxin cause focal symmetrical encephalomalacia
1) Degeneration of vascular endothelial tight junctions
2) Swelling and rupture of perivascular astrocyte processes
3) Leakage of fluid and increased intracerebral pressure
4) Parenchymal necrosis
Sheep: thalamus, cerebellar peduncles,internal capsule with acute protein rich perivascular edema
Goats: can be acute or chronic fibrinohemorrhagic colitis)
What is the pathogenesis of botulism (limber neck)
1) Clostridium botulinum (type A, B or C) in soul
2) Botulinum toxin blocks the release of acetylcholine, inhibiting contraction
3) Flaccid paralysis
4) Diaphragm -> death
*NO gross or microscopic lesions
What lesions do you see with botulism
no gross of microscopic lesions
diagnosis: history plus toxin detection in clinical samples collected for lab analysis
(intestinal contents, serum, liver)
What is the pathogenesis of tetanus (lockjaw)
1) Clostridium tetani toxin
2) Motor end plate, blocks release of glycine (inhibitory neurotransmitter)
3) Symptoms: stiffness of jaw, severe muscle spasms, sweating, fever, stiffness of abdominal muscles, difficulty swallowing
*No gross of microscopic lesions
What lesions do you see with tetanus
No gross of microscopic lesions
What is the mechanism of action of tetanus toxin?
binds to the motor end and blocks the release of glycine (inhibitory neurotransmitter)
leading to rigid paralysis (lockjaw, severe muscle spasms, fever, sweating)
you have a 10yo gelding that is ataxic, fever, and depression, headpressing, muscle fasciculations, hind limb weakness, progression to parlaysis, convulsions and death
prior to death, CSF showed mononuclear pleocytosis with predominance of lymphocytes
upon necropsy, grey matter is affected, neuronal necrosis, glial nodules, and non-suppurative perivascular cuffs.
What might be the cause
Viral infections of the CNS in horses
1) West Nile Virus
2) Equine Encephalitis Virus (Eastern- neutrophils), Western, and Venezuelan encephalitis
3) Equine herpesvirus -1 (myeloencephalopathy)- primarily causes vasculitis (does not specifically target gray matter)
4) Rabies virus
What are the different viral infections of the CNS in the horse
1) West Nile Virus
2) Equine Encephalitis Virus (Eastern- neutrophils), Western, and Venezuelan encephalitis
3) Equine herpesvirus -1 (myeloencephalopathy)- primarily causes vasculitis (does not specifically target gray matter)
4) Rabies virus
Eastern Equine Encephalitis virus causes
neutrophilic infiltration- dies fast enough where neutrophils do not go away)
How does Equine herpesvirus-1 cause myeloencephalopathy
primary causes vasculitis (does not specifically target gray matter)
What are important viral infections of the CNS in dog
1) Canine distemper *
2) Rabies virus
3) Canine adenovirus- vascultis
4) Canine herpesvirus-1
What are characteristic lesions of viral infections of the nervous system *
usually no gross lesions
Histopathology: lesions most prominent in the gray matter (polioencephalitis)
1) Nonsuppurative inflamamtion (lymphocytes and plasma cells) - perivascular cuffs, mild meningitis)
2) Gliosis/ glial nodules
3) Injury to neurons (chromatolysis and necrosis) with neurophagia
other viral associated lesions: demyelination (immune destruction), meningitis/ventriculitis (FIP)
viral inclusion bodies
When might you see intracytoplasmic negri bodies
Rabies virus
when might you see both intracytoplasmic and intranuclear inclusion bodies
Canine distemper virus
What kind of inclusion bodies do you see with pseudorabies
it is a herpesvirus so you will see intranuclear
What virus can cause ventriculitis
feline infectious peritionitis virus
What viruses can cause demyelination through immune destruction or viral infection of oligodendrocytes
Canine distemper virus or small ruminant lentiviruses (caprine arthritis- encephalitis virus and vesna)
What are important viral infections of the CNS in cats
1) FIP
2) Rabies virus
What are the important viral infections of the CNS in cattle
1) Bovine herpesvirus-5 (and less commonly BHV-1)
2) Malignant catarrhal fever (MCF)- vasculitis
3) Rabies virus
4) West Nile Virus
What are the important viral infections of the CNS in sheep/goats
1) Lentivirus (Caprine arthritis- encephalitis virus in goats, visna in sheep)
2) Rabies virus
3) West NIle Virus
What causes granulomatous/ pyogranulomatous inflammation focused on meninges and ventricular system
Feline Infectious Peritonitis virus
Feline Infectious Peritonitis virus causes
granulomatous/ pyogranulomatous inflammation focused on meninges and ventricular system
Which of the following is the primary histologic lesion seen with locoweed toxicity?
Neurons with large discrete intracytoplasmic vacuoles
Neurons with finely vacuolated cytoplasm
Acute neuronal necrosis
Lipofuscin accumulation in the cytoplasm of neurons
Neurons with finely vacuolated cytoplasm
Which of the following conditions exhibits autofluorescence of the neuropil when examined under a black light?
Polioencephalomalacia
Which of the following is a cause of polioencephalomalacia in ruminants?
A) Thiamine deficiency
B) Sulfur deficiency
C) Moldy corn poisoning
D) Selenium toxicity
A) Thiamine deficiency
Which of the following is a cause of cerebellar aplasia or hypoplasia in pigs?
Classical swine fever
What lesion is shown in the nucleus pulposus of the image and what type of intervertebral disc disease would this patient be predisposed to develop?
Chondroid degeneration/metaplasia; Hansen type I disc extrusion
What is the most common location of stenosis with congenital hydrocephalus?
Mesencephalic aqueduct
Which of the following would cause an ischemic infarct (and not a hemorrhagic infarct)?
A) Thrombus of an artery
B) Thrombus of a vein
C) Traumatic rupture of a blood vessel
D) Vasculitis leading to leakage of RBCs
A) Thrombus of an artery
What type of hydrocephalus can occur following in utero destruction of the cerebrocortical parenchyma (i.e., hydranencephaly)
Hydrocephalus ex vacuo
exposure to organic and inorganic compounds- pesticides, heavy metals, plants, microbial products, etc.
Intoxication
inadequate levels of minerals, vitamins, metabolites
deficiency
What are the clinical features of toxic/ metabolic CNS disease
peracute to acute (headpressing, disorientation, recumbency, tonic-clonic seizures, partial seizures)
age is not a generalized feature- certain toxins/deficiencies do express predilections
commonly an outbreak
Know this: Toxic and Metabolic Diseases are of often (bilateral/unilateral) and (symmetrical/asymmetrical) *
Bilateral and Symmetrical
True/False: Toxic and Metabolic Disease of the CNS target specific anatomic areas and cell types of the CNS *
true
it is dependent on vascular geography and concentration of receptors
Why do toxic and metabolic diseases of the CNS target specific anatomic areas and cell types of the central nervous system *
1) Vascular geography
2) Concentration of receptors
What are the major patterns of toxic/metabolic disease
1) Malacia (softening- common pathway) +/- hemorrhage
2) Selective necrosis- neurons, axons, myelin
3) Spongiform state (status spongiosis- irregular cavities within the neuropil secondary to neuronal loss
irregular cavities within the neuropil secondary to neuronal loss
Spongiform state (status spongiosis-
What are the 4 causes polioencephalomalacia in large animals *
1) Sulfur toxicity
2) Thiamine deficiency
3) Water deprivation encephalopathy
4) Lead toxicity
Polioencephalomalacia in large animals
cerebrocortical necrosis (CCN) to the cerebral cortex- basal/thalamic nuclei, colliculi, and cerebellar cortex
caused by:
1) Sulfur toxicity
2) Thiamine deficiency
3) Water deprivation encephalopathy
4) Lead toxicity
Diagnosis: postmortem: gross and histological findings
What does sulfur toxicity in large animals lead to *
Polioencephalomalacia
What does thiamin (B1) deficiency in large animals lead to
Polioencephalomalacia
What is the pathogenesis of sulfur toxicity in ruminants
1) Sulfur ingested in excess (feed or water)
2) Rumen microbes produce excess hydrogen sulfied (H2S) where it accumulates in ruminal gas cap and
3) soluble hydrosulfide anions accumulate in ruminal fluid and diffuse across the rumen wall
3) H2S decreases mitochondrial respiration- inhibits cytochrome oxidases *
4) Brain has a high demand for oxygen, glucose, and energy metabolites and leads to neuronal dysfunction, degneration, and necrosis
5) Polioencephalomalacia
What do the soluble hydrosulfide anions (H2S gas) that accumulate in ruminal fluid due in cattle with sulfur toxicity **
they diffuse across the rumen wall and decrease mitochondrial respiration via inhibiting cytochrome oxidases
causing neuronal dysfunction, degeneration, and necrosis
How does sulfur toxicity cause polioencephalomalacia *
H2S diffuses across rumen wall decrease mitochondrial respiration via inhibiting cytochrome oxidases
causing neuronal dysfunction, degeneration, and necrosis
What is the pathogenesis of thiamin deficiency in cattle *
1) High carbohydrate diets lead to overgrowth of thiaminase producing bacteria (Cl. sprogenes and Bacillus thiaminoolyticus) or grazing of thiaminase containing plants (Bracken fern, Nardoo) or Amprolium
2) Insufficient thiamine leads to neuronal dysfunction, degeneration, and necrosis
a vitamin that is a crucial cofactor for glucose metabolism and glial-neuronal membrane interactions
Thiamin (B1)
What diet causes cattle to develop a thiamin deficiency *
High carbohydrate diet-
overgrowth of thiaminase producing bacteria (Cl. sprogenes and Bacillus thiaminoolyticus) or grazing of thiaminase containing plants (Bracken fern, Nardoo) or Amprolium
How might cattle get thiamin deficiency *
1)High carbohydrate diet-
overgrowth of thiaminase producing bacteria (Cl. sprogenes and Bacillus thiaminoolyticus) *
2) Thiaminase containing plants (Bracken fern, Nardoo)
3) Amprolium
What are gross findings of polioencephalomalacia in large animals
1) Gyri are flattened
2) Sulci are less sistinct
3) Multifocal to coalescing yellow foci (necrosis)
4) Cerebellar hemorrhage suggestive of herniation
5) Deep laminar necrosis resulting in perisulci cystic cavities ***
6) Tan to yellow discolored cortex with shrunken to absent grey matter
Deep laminar necrosis resulting in perisulci cystic cavities is seen in_________ **
polioencephalomalacia in large animals
What tool on necropsy floor can you use to diagnose polioencephalomalacia **
UV/Woods lamp
*autofluorescent of the necrotic areas
when neurons die they release lipofuscin and the macrophages pick that up
What do you see on histology in large animals with polioencephalomalacia *
1) Spongy change (edematous)
2) Neuronal necrosis- band like “Pseudo laminar” ***
3) Gliosis- reactive astrocytes, increased microglia
4) Vascular proliferation
5) Infiltration of the neuropil by macrophages with phagocytic ability “Gitter cells”
How does neuronal necrosis with polioencephalomalacia present itself on histology **
In a band like “pseudolaminar” form
How do carnivores get thiamin
through dietary intake
ruminants have bacteria to rpduce it
How is the topography of thiamin deficiency in carnivores different from ruminants *
In carnivores: caudal colliculi, medial vestibular nuclei and lateral geniculate bodies (often hemorrhagic) *
What are the etiologies of thiamin deficiency in carnivores *
1) Starvation (cats)
2) Raw fish
3) Thiamin inactivation - thiamin levels are measured and addressed in commerical dog foods
What are the most commonly affected regions in thiamin deficiency in carnivores *
caudal colliculi, medial vestibular nuclei and lateral geniculate bodies (often hemorrhagic)
Bilateral and symmetrical
How are water deprivation encephalopathies caused
1) Pigs fed a high salt ration
2) occurs in other animals as a result of water deprivation. arid environments, broken water pipes, frozen water, neglect
*Pathogenesis revolves around osmotic gradients between the blood stream and CNS
*PEM/CCN lesions
What species is salt toxicity common in? *
Pigs
What is the pathogenesis of salt toxicity (common in pigs) *
1) Water intake restriction in pigs being fed a high salt diet
2) Blood becomes hypernatremia
3) Following osmotic gradient, fluid from brain moves into vessels
4) Brain becomes dehydrated
5) Equilibration of NaCl between plasma and extracellular space if the CNS is slow
6) Development of PEM is unclear but not hypothesized to be secondary to compression and anorexia
*When water is provided the blood becomes hypotonic in comparison to the brain. Excess fluid from blood moves into the dehydrated brain
What lesions do you see on necropsy of an animal with salt toxicity
Gross: Tonsillar Cerebellar Herniation
Histologic: Perivascular infiltrate of eosinophils is essentially pathognomonic
Water Toxicity
Causes PEM/CCN
excess water consumption following deprivation following the osmotic gradient, IV fluid moves into brain
Similar necropsy findings but eosinophilic perivascular infiltrates are not a feature
Salt toxicity has similar necropsy findings from water toxicity. What is not seen in water toxicity but is seen in salt toxicity
Eosinophilic perivascular infiltrates on histology
Lead toxicity
Causes PEM/CN
young animals: milk substitutes, paint, plumbing, batteries
birds: leadshot, fishing, coin
oxidative stress leads to erythrocytic and vascular damage-> generating edema
can occur with other heavy metals
What causes Equine Nigropallidalencephalomalacia *
Ingestion of the yellow star thistle or Russian knapweed
-dry summer pastures
-chronic exposure, acute onset of disease
*Repin is suspected toxic compound
What plants cause Nigropallidalencephalomalacia *
Yellow Star Thistle (Centaurea solstitalis)
Russian Knapweed (C. repens)
What is Equine Nigropallidalencephalomalacia *
caused by Yellow Star Thistle or Russian knapweed (dry summer pastures and chronic exposure with acute onset)
Signs: Abnormal tongue movement, difficulty with prehension, swallowing, and drinking
Gross/Histologic lesions- bilaterally symmetrical malacia of substantia nigra and globus pallidus effecting conscious proprioception and movement
*Pseudolaminar necrosis is not a feature
What causes Equine Leukoencephalomalacia
Mycotoxic (Moldy corn disease) producing Fumoninsin B1*
acute onset with chronic exposure
What is the pathogenesis of Moldy Corn Disease *
1) Ingestion of moldy corn contamined with Fusarium moniliforme
2) Fumonisin B1 causes vascular damage selectively in the white matter with secondary encephalomalacia
3) Bilateral asymmetrical, centrum semiovale, corona radiata
*Leukoencephalomalacia
may also cause concurrent hepatic necrosis
Fumoninsin B1 *
produced by Fusarium moniliforme that grows in moldy corn
causes vascular damage selectively in the white matter with secondary encephalomalacia
Causes Equine Leukoencephalomalacia
What lesions do Fumoninsin B1 from Fusarium moniliforme cause
Bilateral asymmetrical * damage to the centrum semiovale and corona radiata
(occasionally in the brainstem and cerebellar white matter) via vascular damage to white matter with secondary encephalomalacia
Equine Leukoencephalomalacia
What are the general characterisics of degenerative disease
1) Selective degeneration and loss of cells or cell components
2) Bilaterally symmetric
3) Individual animals
How are degenerative diseases named?
by their main cellular target and/or lesion patterns
What are major patterns with degenerative disease
-Loss of neurons, axons and/or myelin. compare with normal animal, swollen axons (primary axonal pathology)
-Pallor of white matter
-Spongy state
-Intracellular storage: most easily recognizable, accumulatio of abnormal material, malacia
Degeneration of neurons is often
degeneration and loss of neurons in a specific anatomic structure
often polyphasic
can lead to anterograde or retrograde axonal lesions
What is one of the most common and important degenerative diseases (neuronal)
Motor Neuronal Diseases
-Hereditary Canine Spinal Muscular Atrophy
-Bovine Motor Neuron Disease with neurofilamentous accumulation
Clinical: weakness of limb, spinal and head muscles with progressive atrophy and eventual paresis and paralysis
Spongiform Encephalopathies
Transmissible degenerative diseases
1) TSEs
2) Prions
Normal prion protein exposed to scrapie related protein (abnormally conformed prior protein) serves as a template to influence a geometric conformation change in exposed animal
Disease examples: BSE, FSE, Scrapie, SWD, Creutzfeldt-Jakobs Disease, fatal insomnia
What is the pathogenesis of Spongiform Encephalopathies *
Normal prion protein exposed to scrapie related protein (abnormally conformed prior protein) serves as a template to influence a geometric conformation change in exposed animal
What are the clinical signs of Spongiform Encephalopathies
slowly progressive deteriration
long incubation period (years) -> disease of adult animals
almost always fatal
changes in behavioral or temperament
progressive ataxia (+ other neurologic signs) and weight loss
Where do you submit samples for prion diseases/ chronic wasting disease *
Medulla oblongata - obex
What is the etiology of equine degenerative myeloencephalopathy *
hereditary defect that predisposed to pathology related to environmental or nutritional factors
-Vitamin E deficiency has been demonstrated **
Equine Degenerative myeloencephalopathy *
occurs sporadically in many breeds
hereditary defect that predisposed to pathology related to environmental or nutritional factors
Vitamin E deficiency
Clinical: onset at around 6 months, ataxia and tetraparesis
Pathology: Dystrophic axons and neuronal degernation, lipofiscin accumulation in endothelial cells, neurons, and macrophages in affected nuclei
Does normally the dry or wet form of FIP affect the CNS and eyes
dry form
FIP causes:
granulomatous and exudative ventriculitis and periventricular encephalitis
obstructive lesion with secondary hydroencephalus
Does canine distemper virus cause grey or white matter lesions
BOTH
grey matter- similar to other viruses
but also white matter (more common)- causing demyelination (primary)
Distemper causes
1) White matter lesions -primary demyelination leading to spongy changes that can progress to necrosis
2) Intranuclear and intracytoplasmic inclusion bodies
Post-vaccinal distemper
occurs 1-2 weeks after vaccination
aggressive behavior, progressive ataxia, paresis and death within a few days
*Disseminated lesions in gray matter
associated with MLV
old dog encephalitis
rare manifestation- thought to be subclinical persistent infection of canine distemper infections
lesions in gray and white matter of forebrain (including demyelination)
What age does caprine arthritis encephalitis virus typically affect
2-4 month old kids
What is the pathology of small ruminant lentiviruses like CAEV and Visna *
Demyelinating leukoencephalomyelitis
CAEV: 2-4 month old kids
Visna: sheep >2 years old
What age of visna typically affect sheep
usually older animals >2 years
What might cause demyelinating leukoencephalomyelitis in small ruminants
Caprine arthritis encephalitis virus or visna
10 yo MC cat with several week history of sneezing, nasal discharge and firm swelling over bridge of nose. 2 day history of depression, disorientation, and seizures.
What additional diagnostic tests would you perform?
Advanced imaging to rule out some sort of mass
Cytology
Fungal and algae infections of the CNS
mostly isolated occurences and often opportunisitc infection in immunocompromised animals
pathogenesis:
1) mostly hematogenous (systemic) - Blastomyces dermatitidis
2) Extension from nasal cavity- Cryptococcus sp.- direct extension through the cribiform plate
Gross legions: regions of parenchymas discoloration or a mass like lesion
Histopathology: granulomatous to pyogranulomatous inflammation with organisms histologically
What lesions do you see with fungal and algae infections of the CNS
Gross legions: regions of parenchymas discoloration or a mass like lesion
Histopathology: granulomatous to pyogranulomatous inflammation with organisms histologically
How does Cryptococcus sp. typically infect the CNS
through direct extension through the cribiform plate
How does Blastomyces dermatitidis typically infect the CNS
mostly hematogenous (systemic)
How does fungi and algae infect CNS
1) mostly hematogenous (systemic) - Blastomyces dermatitidis
2) Extension from nasal cavity- Cryptococcus sp.- direct extension through the cribiform plate
What is the pathogenesis of Feline Cryptococcosis
1) Inhalation into nasal cavity
2) Invasion through cribiform plate or along olfactory nerve
3) Meningoencephalitis - granulomatous to pyogranulomatous inflammation with regions of parenchymal discoloration in a mass like lesion
You have a 3yo QH mare with chronic history of gait abnormalities (ataxia, knuckling, crossing over) and progressive unilateral muscle atrophy of right pelvic limb
Upon CSF you see eosinophilic pleocytosis. What might have caused this?
EPM
Infarction
EHV-1
Parasite
Equine protozoal myeloencephalitis (EPM)
Asymmetrical foci of hemorrhage and malacia caused by Sarcocystis neurona
have a distribution of lesion- typically the spinal cord +/- brainstem
predilection for cervical and lumbar intumescences
What causes Equine Protozoal Myeloencephalitis
Sarcocystic neurona
What protozoa has a predilection for the CNS of horses
Sarcocystic neurona - asymmetrical foci of hemorrhage and malacia
What gross lesions are seen with Equine protozoal myeloencephalitis (EPM) *
asymmetrical foci of hemorrhage and malacia
What protozoa cause CNS signs due to sludging of parasitized erythrocytes in the cerebral capillaries
Babesia sp infection in cattle, dogs and horses
Trypanosoma sp in cattle
What lesions are seen with protozoal infections of the NS *
Gross: random regions of parenchymal discolaration and malacia
Histo: Pyogranulomatous/ granulomatous inflammation +/- eosinophils in a random pattern (asymmetrical)
Necrosis
see organisms histologically
What protozoa cause midterm abortion in cattle
Neospora caninum
Neospora caninum affct what two species
Dogs- young dogs infected in-utero leading to polyradiculoneuritis, polymyositis, and meningoencephalomyeltis
Cattle- abortion (midterm) with lesions in the fetus of encephalitis, myositis/myocarditis
How are dogs typically infected with Neospora caninum
in-utero
cause polyradiculoneuritis, polymyositis, and meningoencephalomyeltis
What is the typical signalment of dogs with neospora caninum
young puppies (infected in utero) with weakness progressing to paralysis
What lesions are seen in Neospora caninum infection of puppies *
1) Polyradiculoneuritis - inflammation of multiple nerves and spinal nerve roots
2) Polymyositis- inflammation of multiple muscles
3) Meningoencephalomyelitis
*Granulomatous and eosinophilic encephalitis
you have a 2.5 yo female llama from indiana with a two week history of dragging the left pelvic limb. the clinical signs progressed to ataxia and tetraparesis with loss of superficial pain in the pelvic limbs.
bright and alert with normal appetite
CSF- elevated protein content and an increased white blood cell count with a predominance of eosinohphils. What classes of organisms would you suspect
Parasite - Parelaphostrongylus tenuis
What lesions do you see with cattle with neospora caninum
Abortion (midterm)
lesions: encephalitis and myositis/myocarditis of the fetus
Parelaphostrongylus tenuis
Meningeal worm
Definitive host: White tailed deer- typically no clinical signs (reside in subdural space)
Camelids: ingest infected mollusks (intermediate host) which result in aberrant migration in the CNS parenchyma
*Granulomatous and/or eosinophilic inflammation with linear tracts of hemorrhage and necrosiss
can see organisms (larva or adults)
What lesions do you see with parasitic infections of the CNS*
Granulomatous and/or eosinophilic inflammation with linear tracts of hemorrhage and necrosiss
can see organisms (larva or adults)
What species do you typically see Parelaphostrongylus tenuis in
Camelids- ingest infected mollusks (intermediate host) which results in aberrant migration in the CNS parenchyma
insect larvae live in nasal cavity of sheep and penetrate the cribriform plate
Oestrus ovis
insect that affects the spinal cord of cattle
Hypodermis bovis
insect that causes feline ischemic encephalopathy
Cuterebra sp.
What does Cuterebra cause
feline ischemic encephalopathy- regionally extensive encephalomalacia with cuterebra larva
Cestode infection of the CNS*
Adults (intestine of final host)- larva can infect CNS of intermediate host*
Pathology: Single or multiple cysts (space occupying mass)*
Coenurus cerebralis (Taenia multiceps- dogs) sheep
Cysticercus cellulosae (Taenia solium- humans) pigs and dogs
What are the different types of canine meningoencephalitis of unknown origin (MUO) *
1) Granulomatous meningoencephalitis (GME)
2) Necrotizing meningoencephalitis (NME)
3) Necrotizing leukoencephalitis (NLE)
What is canine meningoencephalitis of unknown origin (MUO) *know this to memory
1) Granulomatous meningoencephalitis (GME) - angiocentric granulomatous inflammation of white matter
2) Necrotizing meningoencephalitis (NME)
3) Necrotizing leukoencephalitis (NLE)- gross large asymmetric malacic foci confined to deep white matter
immune mediated mechanism?
Most cases in young adults (6 months to 3 years)
usually multifocal disease
What age of dog does MUO typically affect
young adult dogs (6 months to 3 years)
Is MUO focal or multifocal disease? *
Multifocal disease
Coonhound paralysis
polyradiculoneuritis in dogs that affects spinal nerve roots/ peripheral nerves
ascending paresis- paralysis of limbs
suspected immune mediated reaction suspected (hypersensitivity to raccoon saliva)
polyneuritis equi
neuritis of the cauda equina
autoimmune or post infectious?
see swollen nerves with adhesions (can see cranial nerve involvement)
chronic progressive tail and sphincter paralysis, urinary incontinence, fecal retention, perineal paresthesia/ analagesia
Beagle pain syndrome *
Steroid-responsive meningitis arteritis that occurs in young adult dogs
acute fever, neutrophilia, neck pain
see subarachnoid hemorrhage in the brainstem/cervical spinal cord
Histologically: meningitis and necrotizing arteritis
