Test 4: 2: neuropath Flashcards
order of the ventricular system of the CNS
gray matter in the CNS is organized
laminae or nuceli
found on the outside of the brain
inside of the spinal cord
made of neuronal cell bodies and dendrites
white matter of the CNS is organized
into tracts
conduction of nerve impulse from grey matter(nuclei or laminae)
made of neuronal axons surrounded by myelin
on inside of brain, outside of spinal cord
nissel substance in the neuron is made from
rough ER
where neurotransmitters are being processed into vesicles
golgi
what makes up grey matter
neuronal cell bodies
dendrites
glial cells
what makes up white matter
axons
axon terminals/synaptic end bulbs
used for conduction of impulse
three type of CNS glial cells
astrocytes
microglia
oligodendrocytes
astrocytes maintain —, regulate —, — synapses and can respond to injury
blood brain barrier
nutrients
insulate
astrocytosis/gliosis
microglia are the resident — of the CNS, help regulate —
macrophage- phagocytosis and antigen presenting
neuron function
microgliosis/gliosis
oligodendrocytes make —, one cell insulates —, can respond to myelin injury by —
myelin
one cell- multiple neurons
OPC regeneration
schwann vs oligodendrocytes
many schwann one neuron
one oligo= many neurons
makes myelin
— cells make CSF
chroid plexus cells
Epithelial-endothelial
border (Blood CSF Barrier)
— cells line the ventricles and move CSF
ependymal cells
pachymeniges are the —
dura mater
leptomeninges are the —
arachnoid mater
subarachnoid space
pia mater
3 components of the blood brain barrier
Specialized vascular endothelial cells
Tight junctions and unique basement membranes
Astrocyte foot processes
some functions of the blood brain barrier
Protects the brain from pathogens and xenobiotics
Regulates diffusion of hormones and cytokines
Contributes to sustain the delicate CNS homeostasis
2 components of the blood meningeal barrier
Specialized vascular endothelial cells
Tight junctions and basement membrane
function of the blood meningeal barrier
Same properties as BBB but less restrictive and promote immune responses during injury/infection
3 components of the blood CSF barrier
Choroid plexus epithelial cells with tight junctions
Vessels in choroidal stroma are fenestrated
Arachnoid membrane
function of the blood CSF barrier
Regulates movement of agents from blood to CSF
upper vs lower motor neuron
upper do not leave CNS (come from the motor cortex or nuceli in the brain stem and will synapse will lower motor neuron in the spinal cord, activates skeletal muscle
what caused this
thiamine deficiency in carnivore
neuronal necrosis
posterior colliculi neuronal cell bodies
what caused this
copper deficiency
oligodendroglia dysfunction
diffuse cerebral white mater loss
leukoencephalomalacia: necrosis of the white matter of the brain
another name for necrosis in brain
malacia
what type of neoplasm
meningioma
cause atrophy of the brain
encephalomalacia
encephalomalacia: necrosis of the brain
polioencephalomalacia
necrosis of the grey matter of the brain
leukoencephalomalacia:
necrosis of the white matter of the brain
myelomalacia
necrosis of the spinal cord
poliomyelomalacia
necrosis of the grey matter of the spinal cord
leukomyelomalacia
leukomyelomalacia: necrosis of the white matter of the spinal cord
thiamine deficiency in ruminants will do what to the brain
Polioencephalomalacia of ruminants: necrosis of the grey matter of the brain
laminar cortical necrosis
Clinical signs: facial twitching, grinding teeth, opisthotonos, convulsions, coma
Causes: thiamine deficiency, high sulfur diets, water deprivation
Polioencephalomalacia of ruminants-necrosis of the grey matter of the brain
- Laminar cortical necrosis
- Clinical signs: facial twitching, grinding teeth, opisthotonos, convulsions, coma
- Causes: thiamine deficiency, high sulfur diets, water deprivation
what can cause ventricular dilation (hydrocephalus)
Excessive formation of CSF
Obstruction of CSF flow within ventricular system or subarachnoid space
Lack of resorption
Focal or diffuse loss of parenchyma → ventricles expand and CSF fills the space
( hydrocephalus ex-vacuo)
hydrocephalus (ventricular dilation)
what causes this
cerebellar herniation with compression of brainstem breathing centers leading to death
hemorrhage or edema or tumor can cause this
what happens during neuronal degeneration
chromatolysis
peripheralization of nucelus
neuronal swelling
increased glial cells
what happen to neurons during acute neuronal necorsis
shrunken
angular
pink (hypereosion)
increased glial cells
what happens during degeneration of axons
swelling and spheroid formation
digestion chambers (phagocytosis of axon debris)
what disease
neuronal ceroid lipofuscinosis
Accumulation of lipofuscin (oxidation of fatty acids)
- Likely mitochondrial defect (not lysosomal defect)
storage disease
what disease in the brain that causes neuronal vacuolization
Transmissible spongiform encephalopathies
(mad cow= bovine spongiform encephalopathy)
Accumulation of misfolded prion proteins (PrP)
what causes this neuronal vacuolization
Hepatic encephalopathy
Ammonia toxicity: changes in transport of amino acids and electrolytes into neurons
disrupting function and causing cytoxic/intracellular edema
Astrocytosis (Type II, aka Alzheimer’s type II – arranged in pairs and small clusters)
What are some things that cause necrosis of neurons
ischemia, hypoglycemia, seizures, viral infection, or toxins
hypertrophy and hyperplasia of astrocytes is called
astrocytosis
astrocytes can respond to injury by laying down —
astrocytic fibers
glial scars
(fibrosis like)
Neuronophagia
glial nodules
glial cells surround dying neuron
accumulation of mononuclear cells, oligodendrocytes,
microglia, and neutrophils or astrocytes, around or at the site of a neuronal cell body
what common infection causes secondary demyelination
canine distemper
why are primary demyelination rare
deadly
Leukodystrophies (genetic enzyme defects; rare)
what is happening
demyelination (white mater)
(luxol-fast blue stain)
Caused by damage to the oligodendrocytes (CNS) or Schwann cells (PNS)
Remyelination is very poor in the CNS, but usually successful in the PNS
what neural tube defect
spina bifida
what neural tube defect
meningeocele
Agyria (lissencephaly)
Complete lack of the normal number and thickness of
cerebral hemispheric gyri
similar to Chiari type I malformation in people
Caudal occipital malformation (COMS)
common in Small breed dogs (Cavalier King Charles Spaniels)
Congenital malformation of caudal occipital region of skull → overcrowding of caudal fossa →
compression of the brainstem and cerebellum at the level of the foramen magnum (arrowhead)
→ Syringomyelia: accumulation of fluid within the spinal cord (aka syrinx) (arrow)
Syringomyelia:
accumulation of fluid within the spinal cord (aka syrinx)
can be caused by Caudal occipital malformation (COMS)
what went wrong?
c
cerebellar hypoplasia
congenital defect
or
Viral: Feline panleukopenia virus, bovine viral diarrhea virus, border disease virus, and classical swine fever virus.
what virus can cause cerebellar hypoplasia
Feline panleukopenia virus, bovine viral diarrhea virus, border disease virus, and classical swine fever virus.
brain= what is this showing
cerebellar hypoplasia
loss of purkinje and granular cells
caused by genetic or viral ( feline panleukopenia virus, bovine viral diarrhea virus, border disease virus, and classical swine fever virus.
cerebellar abiotrophy is caused by —
genetic or idiopathic
born normal then losses purkinje cells and granular cells
accelerated degeneration
cerebellar abiotrophy vs cerebellar hypoplasia
both are loss of purkinje and granular cells in the brain
hypoplasia: caused by virus- born abnormal
abiotrophy: unknown cause- born normal then accelerated degeneration
atherosclerosis in animals is related to —
hypothyroidism and DM
Mini Schnauzers predisposed
Feline ischemic myelopathy and encephalopathy is associated with
Hypertension, Hypertrophic cardiomyopathy, Chronic renal failure
ventral spinal artery most common
Fibrocartilaginous embolism (FCE) is caused by
Intervertebral disc emboli (fibrocartilaginous emboli) → occlusion of small blood vessels → infarct → necrosis (myelomalacia) → Macrophages remove necrotic debris
history: dogs very active then acute onset of disuse of back legs
vascular anomalies
Hemangiomas, arteriovenous malformations
benign but can rupture and squish things around it
intervertebral discs
Nucleus pulposus (NP): central
gelatinous proteoglycan-rich substance
Annulus fibrosus (AF):
surrounding concentric fibrous lamellae comprised of collagen and elastin
hansen type I herniation
Extrusion of nucleus pulposus material into the
spinal canal, resulting in spinal cord compression
acute causes full paralysis
hansen type II herniation
Protrusion of the annulus fibrosus into the spinal
canal, resulting in spinal cord compression
patients with IVDD usually have hansen type —. Will often present with impaired motor function or complete loss of voluntary movement in both hind limbs (—)
type 1
paraplegia
acute onset
small dogs (Dachshund, Lhasa Apso, Shih Tzu)
IVDD caused by hansen type — leads to onset of symptoms that is slow and progressive
type II
paraparesis→ paraplegia
storage disease
Cellular catabolism: degradation of macromolecules
in vesicular compartments (i.e. —) to smaller molecules to be reused or excreted (aka: —)
lysosomes
autophagy
storage disease is caused by problem with enzymes caused by
genetic mutation resulting in dysfunctional enzyme
ingestion of substance that interferes with enzyme function (swainsonine- plant with alkaloid enzyme inhibitor)
Degenerative Myelopathy occurs in what type of dogs
german shepherd
corgi
Degenerative Myelopathy causes —
Late onset (≥7 years), progressive Weakness and ataxia due to spinal cord lesions
Spheroids and demyelination in dorsal funiculi
- SOD1 mutation has been found in corgis (and other breeds)
corgis with SOD1 mutation get —
degenerative myelopathy
neuroaxonal dystrophy
neuroaxonal dystrophy affects — dogs and — horses
Rottweilers, Papillons, Chihuahuas, Collie sheepdogs,
Jack Russell Terriers
Quarterhorse (and others: Morgans, Appaloosa,
Lusitano, Haflinger…)
what part of the CNS does neuroaxonal dystrophy attack
Brainstem (cuneate and gracilis nuclei),
Thoracic spinal cord nuclei
forms spheroids
leads to intermittent weakness of hind legs
encephalitis
inflammation of the brain
polioencephalitis:
inflammation of the grey matter of the brain
leukoencephalitis:
inflammation of the white matter of the brain
myelitis:
inflammation of the spinal cord
4 ways for infection to get into nervous system
blood
local extension
direct penetration
retrograde axonal flow (listeria, rabies, herpes)
rabies is caused by —
Lyssavirus (Rhabdoviridae)
rabies cellular tropsim is for —
neurons
uses retrograde axonal flow to travel to brain through nerves
how to test for rabies
Direct fluorescent antibody test (dFA, IF)
rabies histo will show perivascular —, — inclusion bodies in the neurons
cuffing
intracytoplasmic (negri bodies)
canine distemper virus is caused by
Morbillivirus (Paramyxoviridae)
how to transmit canine distemper
respiratory secretions
what cells do canine distemper attack
epithelium(conjunctiva), lymphoid (macrophages and lymphocytes)
clinical signs of canine distemper virus
respiratory: Conjunctivitis, rhinitis, and bronchopneumonia
GI:Diarrhea and vomiting
CNS: nervous, Seizures, cerebellar or vestibular ataxia
histo of canine distemper virus shows — inclusion bodies in — cells
Intracytoplasmic AND intranuclear
astrocytes, neurons, choroid plexus epithelium
what happens to the white matter with canine distemper virus
demyelination of the cerebellum, midbrain, brainstem, optic nerves, spinal cord
leukoencephalitis
canine distemper does what to gray matter
Neuronal necrosis with gliosis and perivascular cuffing of lymphocytes and macrophages
histo of arbovirus such as EEE
Pe rivascular cuffing by lymphocytes and plasma cells And neutrophils!
with glial nodules (neuronophagia)
caprine arthritis and encephalitis virus is spread by
direct contact
through milk leading to persistent infection
what cells does caprine arthritis and encephalitis virus attack
macrophages
clinical signs of caprine arthritis and encephalitis virus in young goats
Nervous system disease = hind limb lameness and ataxia with
paresis that progresses over several weeks to paralysis
* Usually fatal
clinical signs of caprine arthritis and encephalitis virus in adult goats
arthritis
pneumonia
encephalomyelitis
caprine arthritis and encephalitis virus histo shows
Perivascular cuffing by lymphocytes and macrophages with malacia particularly in the white matter of the subependymal cerebrum, brainstem, and beneath the pia in spinal cord
FIP is caused by —
enteric coronavirus is mutated inside a cat to feline infectious peritonitis virus
how is FIP spread
fecal oral
most common in young cats
FIP attacks what cell types
intestinal epithelium and macrophages
clinical signs of FIP
varied (aggression, rage, hiding/withdrawal), convulsive disorders, nystagmus, head tilt or circling
Pathological findings: Hydrocephalus, granulomatous meningitis, choroid plexitis, ependymitis, and vasculitis (immune complex)
— is a DNA virus that causes vasculitis leading to thrombosis in horses
Equine herpesviral myeloencephalopathy
Equine herpesvirus-1 and 4 (Alphaherpesvirinae)
what type of cells do equine herpes attack
epithelium, endothelium and neurons
lives forever in neurons- waiting
equine herpesviral myeloencephalopathy is caused by vasculitis with — leading to secondary ischemia and axonal —.
thrombosis, edema and hemorrhage
spheroids
most common cause of bacterial meningitis
E. coli, Streptococccus spp.
* Plus Pasteurella, Salmonella in young large animals
pachymeningitis
Inflammation of dura mater
pachymeninges is another name for dura mater
how does listeria cause encephalitis
large animal eats food containimated with Listeria monocytogenes
Break in oral mucosa → invasion of Listeria locally and into trigeminal nerves → travel retrograde up axon to the brainstem→ suppurative encephalitis with microabscesses in the brainstem
can cause abortion and mastitis
Infectious thrombotic meningoencephalitis (ITME) is caused by —
Histophilus somni
Cattle
how does Histophilus somni in cattle cause Infectious thrombotic meningoencephalitis (ITME)
toxin from bacteria causes pneumonia that leads to vasculitis then thrombosis and hemorrhage
grossly causing multifocal random hemorrhage
cat brain
Cryptococcus neoformans (and C. gatii)
yeast
can infect dogs,cats and horses
causes suppurative to granulomatous meningoencephalitis with large areas of necrosis (“pseudocysts”) that contain numerous yeast
Cryptococcus neoformans (and C. gatii) will cause the formation of — meningoencephalitis with areas of —
suppurative to granulomatous
necrosis (“pseudocysts”) that contain numerous yeast
— is an good example of local extension from the nose into the brain in cats
Cryptococcus neoformans (and C. gatii)
causes nose deformaty and then Suppurative to granulomatous meningoencephalitis with large areas of necrosis (“pseudocysts”) that contain numerous yeast
three protozoa that cause infections in the CNS
Toxoplasma gondii
* Can infect nearly any mammalian species
* Definitive host is cat
Neospora caninum
* Disease in dogs, cattle, deer
* Definitive host is dog
Sarcocystis neurona
* Equine Protozoal Myeloencephalitis (EPM)
* Definitive host is opossum, other wildlife
Equine Protozoal Myeloencephalitis (EPM)
is causes by
Sarcocystis neurona
a protozoa, definitive host opossum
protozoal infection of the brain will present as —
organism moving through tissue will cause necrosis
Multifocal granulomatous, (eosinophilic), necrotizing encephalitis
can rarely see the organism surrounded by glial cells
EPM can look similar to
equine herpes virus
weakness and acute ataxia
EPM is caused by sarcocystic neurona and has no long lasting infection
three types of meningoencephalomyelitis of unknown origin (MUO)
Granulomatous meningoencephalomyelitis (GME)- any breed, caudal CNS- brainstem and spinal cord
necrotizing meningoencephalomyelitis (NME)- small dogs, cerebral
necrotizing encephalitis (NE)- small dogs, cerebral
Bromethalin toxicity attacks the —
attacks electron transport chain
Uncouples oxidative phosphorylation in mitochondria
leads to edema
Decreased ATP synthesis and dysfunction of ATP-dependent Na/K pump → accumulation of Na (and water) in cells → cytotoxic cerebral edema → cerebral edema, including intramyelinic edema, myelin splitting, and axonal swelling (white matter vacuolation)
type of nonanticoagulant rodenticide
Bromethalin toxicity will cause — in the brain
white matter edema
rodent killer that attacks electron transport chain
yellowstar thistle toxicity in horses will cause malacia in the — and the —
pastures containing Centaurea solstitialis (yellow star thistle) or C. repens (Russian knapweed)
— deficiency will lead to malacia of the caudal colliculi or the rostal midbrain/caudal brainstem nuceli and cerebral cortex in carnivores
thiamine
in ruminants will attack the grey matter
deficiency in — will cause this in lambs and kids
copper
swayback
Bilaterally symmetrical cavitation of the cerebral white matter
(congenital)
Wallerian degeneration in
dorsolateral and ventromedial tracts of spinal cord (delayed)
— are tumor of meninges
meningiomas
most common intracranial tumor in cats and dogs, rare in horses
more common rostrally
most benign Grade 1, grade III very rare
meningiomas are most common in
Most common intracranial neoplasm in cats and dogs
- Very rare in horses and ruminants
usually benign but cause compression of brain
4 subtypes of meningioma tumors
histologically different but behave similarly- benign
tumor of gilial cells are
Astrocytomas Oligodendrogliomas
short faced breeds some cat, cattle and horses
Grossly well demarcated BUT infiltrative histologically
— type of brain cancer is Grossly well demarcated BUT infiltrative
histologically
glioma
Astrocytomas Oligodendrogliomas
what type of tumor
intraventricular tumor
Choroid plexus tumors
* Papilloma or Carcinoma
* Golden retriever predisposed
* Reported sporadically in horses and cattle
what type of intraventricular tumor is common in golden retrievers
choroid plexus tumor
type of intraventricular tumor
Ependymoma
* Uncommon tumors in dogs, cats,
horses, cattle
name some metastatic neoplasia in brain of dog
Hemangiosarcoma, carcinoma, malignant melanoma
common metastatic brain cancers of cats
Mammary adenocarcinoma, lymphoma
paraparetic
partial paralysis of the lower limbs.
You perform a physical exam and you find dimpling of the skin overlying the lumbar region of the spinal column (image), an easily expressed bladder, absent anal sphincter tone, and analgesia to the skin of the perineum.
Given the signalment of the patient and the location of the lesion, what do you think is the most likely disease process —
, most likely specific type of disease —?
congenital
neural tube defect
On histologic examination of the spinal cord you see the changes depicted below:
What area of the spinal cord does this represent —?
What characteristic pathologic change to neurons are the arrows pointing to?
white matter
axonal swelling (spheroids)
What is the pathogenesis of this lesion?
Degeneration of the nucleus pulposus, annulus fibrosis and/or dorsal longitudinal ligament —> extrusion or herniation of disc material into spinal canal –> trauma to spinal cord and occlusion of blood vessels –> demyelination –> leukomalacia, hemorrhage (and poliomalacia if severe enough)
What is the name of this disease?
IVDD
Intervertebral disc disease
What serologic test(s) will you submit with the serum sample you collected antemortem, given the nature and distribution of the gross lesions in the spinal cord?
Equine herpes virus 1 and 4
Sarcocytis neurona
Equine Eastern Encephalitis virus
West Nile virus
Equine herpes virus 1 and 4
Sarcocytis neurona
a six year old thoroughbred gelding presents to you with signs of weakness over the past week that have now progressed to severe ataxia
On histologic examination of the spinal cord you find the changes below:
What etiologic agent is responsible for this disease?
What is the disease called?
Sarcocystis neurona
Equine protozoal myeloencephalitis (EPM)
What disease process do you suspect this represents?
what neoplasm does this most likely represent?
neoplasia
Peripheral nerve sheath tumor
Anatomic location and Gross: Multiple masses arising at the spinal nerve roots
Histology: Slender, fusiform cells arranged in bundles and plexiform nodules with bland oval nuclei.
