Central Nervous System Flashcards
Function of gray matter
Generation of nerve impulses
Function of white matter
Conduction of nerve impulses
Axonal transport systems
- Synthesis/packaging of NT in rER and Golgi apparatus
- NT travelled through length of axon to synapse by kinesin
- NT released from vesicle at synapse
- Used vesicles returned along microtubule by dynein
Kinesin
Microtubules motor protein using energy from ATP hydrolysis to generate mechanical force to bind to/move NT along microtubule
Pathogens using NT transport system to enter / spread within CNS
Rabies virus
Listeria monocytogenes
Function of astrocytes
Maintain BBB
Regulate nutrients to neurons
Insulate synapses
Respond to industry (astrocytosis/gliosis)
Function of microglia
Resident macrophages of CNS (clean up white matter debris)
Respond to injury (microgliosis/gliosis)
Function of oligodendrocytes
Produce myelin
Ependymal cells
Cells linking ventricular system
Facilitate movement of CSF
Choroid plexus cells
Epithelial endothelial border (blood CSF barrier) of ventricular system
Make CSF
Meninges
Connective tissue of CNS
Carry blood vessels to cerebral cortex
Encloses/holds CSF in subarachnoid space
Function of CSF
Provides cushioning and nutrients
Blood brain barrier
Protects brain from pathogens/xenobiotics
Regulates diffusion of hormones / cytokines
Blood meninges barrier
Functions similar to BBB, but less restrictive
Also promotes immune response in injury/inflammation
Blood CSF barrier
Regulated movement of agents from blood to CSF
Choroid plexus epithelial cells with tight junction; fenestrated vessels in choroid stroma
General function of parietal lobe
Integration of sensory information
General function of temporal lobe
Behavior and hearing
General function of pyriform lobe
Olfaction
General function of caudate, claustrum, putamen, pallidum
Motor function
General function of septal nuclei
Emotion
Upper motor neurons
Entirely within CNS
Initiate voluntary movement
Lower motor neutrons
Cell bodies in spinal cord/Brainstem grey matter; axons to periphery
Innervate / activate skeletal muscle
Thiamine deficiency in dogs
Neuronal necrosis in posterior colliculi neuronal cell bodies
Copper deficiency
Oligodendroglia dysfunction in sheep
Diffuse cerebral white matter loss
Swayback, blind, in coordination; more commonly in lambs (congenital); sometimes delayed (kids) - Wallerian degeneration in dorsolateral/Ventromedial spinal cord tracts
Hydrocephalus
Ventricular dilation
Increase in CSF volume in ventricles
Several causes (i.e., congenital, obstruction, degeneration of parenchyma, lack of resorption, excess formation of CSF)
Histology of Atrophy
Loss of neurons and myelin with or without astrocytosis and astrocytosis sclerosis
Encephalomalacia
Necrosis of the brain
Polioencephalomalacia
Necrosis of the grey matter of the brain
Leukoencephalomalacia
Necrosis of white matter of the brain
Myelomalacia
Necrosis of the spinal cord
Poliomyelomalacia
Necrosis of the grey matter of the spinal cord
Leukomyelomalacia
Necrosis of the white matter of the spinal cord
Polioencephalomalacia of ruminants
Cortical necrosis (grey matter of brain) due to thiamine deficiency, high S diet, water deprivation
Clinical signs: facial twitching, grinding teeth, opisthotonos, convulsions, coma
Sequelae of brain hemorrhage
Elevated intracranial pressure
Gross path of brain edema
Swollen/flattened gyri
Widened, less distinct sulci
Brain compressed against calvaria
Pathogenesis of CNS lesions
Lesion occupies + expands adjacent neuroparenchyma —> inc brain volume —> inc intracranial pressure —> caudal herniations of cerebellum thru foramen magnum —> compression of CV and resp centers in medulla —> coma/death
Factors affecting susceptibility of neuron to damage
Level of metabolic activity
Length of axon
Histologic changes seen in grey matter
Chromatolysis
Neuronal swelling
Acute neuronal necrosis
Histologic changes in white matter
Spheroids
Digestion chambers
Neuronal ceroid lipofuscinosis
Accumulation of lipofuscin (oxidation of fatty acids)
Mitochondrial defect?
Transmissible spongiform encephalopathies
Spongiform change in histo (vacuolization)
Prions detectible by immunohistochemical staining
Hepatic encephalopathy
Ammonia toxicity
Cytotoxic/intracellular edema
Astrocytosis (Type II - arranged in pairs/small clusters)
Astrocyte response to injury
Hypertrophy (swelling of cytoplasm, increase in astrocytic fibers - glial scar)
Hyperplasia (astrocytosis, inc in number)
Microglia response to injury
Hypertrophy
Hyperplasia
Become activated —> glitter cells (macrophage behavior, foamy or lipid laden macrophages)
Gitter cells
Foamy, lipid-laden cells in area of necrosis of CNS (from microglia cells)
Neuronophagia
Accumulation of mononuclear cells, oligodendrocytes, microglia, and neutrophils or astrocytes around a neuronal cell body
Post necrotic healing of CNS
Neovascularization
Astrogliosis
Fibrillary astroglial scar
Primary demyelination
Leukodystrophies (genetic enzyme defects)
Rare!
Secondary demylination
Infectious (Canine distemper)
Nutritional (copper deficiency)
Toxin (bromethalin)
Trauma/compression
Clinical signs of demyelination
Limb ataxia
Paresis
Paralysis
Tremors
Seizure
Lysol-fast blue
Stain for myelin
Demylination
Loss of myelin caused by damage to oligodendrocytes (CNS) of Schwann cells (PNS)
Neural tube defects
Spectrum of congenital malformations due to abnormal development and/or closure of neural tube during development
- can also affect vertebrae, skull, skin, musculature
Agyria (lissencephaly)
Lack of the normal number and thickness of cerebral hemispheric gyri
Thickened cortex with reduction in underlaying white mater
*Normal in rodents, lagomorphs, birds
Seizures, cognitive dysfunction in some dogs
Caudal occipital malformation (COMS)
Small breed dogs (Cavalier King Charles)
Congenital malformation of caudal occipital region of skull —> overcrowding of caudal fossa —> compression of Brainstem/cerebellum at foramen magnum —> syringomyelia
Syringomyelia
Accumulation of fluid within the spinal cord
Cerebellar hypoplasia
Segmental absence of neurons
Occurs during fetal development (born abnormal)
Causes of cerebellar hypoplasia
Genetic
Viral (feline panleukopenia virus, BVDV, border disease virus, classical swine fever)
Cerebellar abiotrophy
Selective loss of neurons occurring early in life (animal born neuron) (accelerated degeneration)
Segmental absence of neurons
Causes of vascular obstruction / ischemic infarction in brain
Local disease —> vascular thrombosis
Embolization of external process
Atherosclerosis (not as common in animals as ppl)
Feline ischemic encephalopathy/myelopathy
Fibrocartilaginous embolism
Feline ischemic myelopathy and encephalopathy
Cause of ischemic infarction in cats
Hypertension, hypertrophic cardiomyopathy, chronic renal failure
Ventral spinal artery most commonly affected
Fibrocartilaginous embolism
Unknown pathogenesis - IVD gains access to vasculature??
Acute onset of clinical signs
Dogs/pigs with history of excessive exercise
Hansen type I herniation
IVDD with extrusion of nucleus purposes material into spinal canal —> spinal cord compression
Acute onset, small breed (dachshund); complete loss of voluntary movement of hind legs (paraplegia)
Factors: dehydration, degeneration, cartilage metaplasia of nuc pulp
Hansen type II herniation
IVDD: Protrusion of annulus fibrosis into spinal canal —> spinal cord compression
Older, large breed dogs
Slow and progressive; paraparesis —> paraplegia (waxing and waning)
Storage diseases
Congenital: Lysosomal storage disease; Neuronal ceroid lipofuscinosis; Lafora disease
Acquired: ingestion of plant with alkaloid enzyme inhibitors
Cervical stenotic myelopathy (Wobbler’s syndrome) : osseous form
compression of dorsal or dorsolateral spinal cord
1-3 yo large/giant breed dogs
Loss of proprioception, gait deficiency, ataxia
Clinical signs more pronounced in hind limbs
Cervical stenotic myelopathy (Wobbler’s) : disc-associated form
Hansen type II protrusion
Middle-aged large-breed dogs
Ventral spinal cord compression
Degenerative myelopathy
Common in old dogs (German Shepard, corgis)
Late onset, progressive
Weakness/ataxia due to spinal cord lesions
Spheroids/demyelination in funiculi
Neuroaxonal dystrophy
Axonal swelling, atrophy, degeneration = spheroids
Waxing and waning ataxia
Dogs/horses
Encephalitis
Inflammation of the brain
Polioencephalitis
Inflammation of grey matter of brain
Leukoencephalitis
Inflammation of white matter of brain
Myelitis
Inflammation of spinal cord
Portals of entry to nervous system
Hematogenous
Local extension (often severe otitis, severe nasal infection)
Direct penetration
Retrograde axonal flow (rabies, Listeria, herpesvirus, tetanospasmin)
Histological signs of viral infection in nervous system
Inflammation - local, disseminated perivascular cuffs
Neuronal degeneration / death
Inclusion bodies
Gliosis
Rabies histology
Perivascular cuffing
Intracytoplasmic inclusion bodies in neurons
Direct fluorescent antibody test - gold standard
Canine distemper virus histology
Intracytoplasmic and intranuclear inclusion bodies in astrocytes, neurons, choroid plexus epithelium
White matter: leukoencephalitis with demyelination
Grey matter: neuronal necrosis with gliosis + perivascular cuffing of lymphocytes/macs
IHC to confirm
Arboviruses
Equine encephalitis alpha viruses (EEE, WEE, VEE)
West Nile Virus
All produce similar lesion in brain/spinal cord —> immunohistochemistry to distinguish
Histology of arboviruses (agents of encephalitis)
Perivascular cuffing by lymphocytes and plasma cells
Neurophagia (glial nodules)
Caprine Arthritis and Ecephalitis virus
Lentivirus (retrovirus) - Nervous system disease in kids; lymphoproliferative synovitis/arthritis, pneumonia, mastitis in adult goats
Histopath of caprine arthritis and encephalitis virus
Caprine leukoencephalomyelitis
Perivascular cuffing by lymphocytes/Macs with malacia in white matter (subependymal cerebrum, Brainstem, beneath pia in spinal cord)
Pathological findings of feline infectious peritonitis
Hydrocephalus
Granulomatous meningitis
Choroid plexitis, ependymitis, vasculitis
Equine herpesviral myeloencephalopathy
Caused by Equine herpesvirus-1 and 4 (DNA viruses)
Clinical signs: ataxia, paresis, paralysis
Vasculitis with thrombosis, edema, hemorrhage —> secondary ischemia —> axonal spheroids
Manifestation of bacterial infection of nervous system
Inflammation - focal, mutlifocal, dissemination
Usually Suppurative, sometimes granulomatous
Regional destruction of neuroparenchyma
May or may not see organisms
Bacterial meningitis
Hematogenous spread, local extension, direct penetration
Inflammation of leptomeninges ; inflammation of dura mater (pachymeningitis)
Brain abscess
Center of pus encircled by neutrophils / fibrous capsule
Large > small animals
Hematogenous, local extension, direct penetration
Listeria
From contaminated silage
Break in oral mucosa —> local invasion —> trigeminal nerves —> retrograde travel to Brainstem —> Suppurative encephalitis with microabscesses
Infectious thrombotic meningoencephalitis (ITME)
Histophilus somni (affects cattle)
Hematogenous spread from RT —> apoptosis of endothelium (from bacterial virulence factor) —> vasculitis —> thrombosis —> hemorrage
Gross: multifocal random hemorrhages
Cryptococcus neoformans (C. gatii)
Yeast infection
Dogs, cats, (horses)
Suppurative to granulomatous meningoencephalitis with large areas of necrosis that contain numerous yeast
Protozoal infection in the CNS
Necrosis (obvious or subtle)
Multifocal granulomatous, (eosinophilic), necrotizing encephalitis
Widespread destruction, organism (usually) rare
Equine Protozoal myeloencephalitis
Sarcocystis neurona
Spinal cord most frequently affected
Serology / clinical signs to diagnose
Meningoencephalomyelitis of unknown origin
Cause unknown
Difficult to diagnose ante mortem
Categories:
- Granulomatous meningoencephalitis
- Necrotizing meningoencephalitis
-Necrotizing encephalitis
Granulomatous meningoencephalitis
White matter midbrain, Brainstem, spinal cord; disseminated or focal
Multifocal perivascular macrophages with lymphocytes and plasma cells
Necrotizing meningoencephalitis
Leukopoliomalacia and leukopolioencephalomyelitis of cerebral hemispheres
Necrotizing encephalitis
Leukomalacia and leukoencephalitis of cerebral hemispheres and Brainstem with perivascular lymphoplasmacytic cuffing and gemistocytic astrocytes
Salt toxicity
Indirect toxicity in pigs following excessive salt ingestion / water deprivation (brain edema upon re-introduction of water)
Laminar necrosis of cortical neurons/cortical malacia
Abundant eosinophils in meninges / around blood vessels
Bromethalin toxicity
Non-anticoagulant rotenticide, Uncouple oxidative phosphorylation in mintocondria
Cerebral edema, intramyelinic edema, myelin splitting, Axonal swelling (white matter vacuolation)
Lead poisoning
Pb interferes with glutamate/GABA release —> disrupts Ca homeostasis —> neuronal necrosis
Histopath of lead poisoning
Cytotoxic cerebral edema
Gliosis and astrocytic swelling
Ischemic neuronal necrosis in cerebral cortex
Bilateral symmetrical demyelination/axonal degeneration
Yellow star thistle toxicity
Bilaterally symmetrical malacia in substantia nigra / globes pallidus in horses
Equine nigropallidal encephalomalacia
Meningioma
Tumor of meninges
Most common intracranial neoplasm in cats/dogs (rare in horses/ruminants)
Compressive growth pattern; more rostral
Most benign
Subtypes of Grade I meningioma
Transitional
Meningothelial
Psammamatous
Fibrous
Glioma
Oligodendroglioma, Astrocytoma, High grade glioma (glioblastoma multiforme)
Brachycephalic dogs predisposed; also in cat, cattle, horses
Infiltrative histologically; grossly well demarcated
Intraventricular tumors
Choroid plexus tumors (papilloma or carcinoma) - Golden retriever
Ependymoma - uncommon tumors
Metastatic neoplasia in dogs
Hemangiosarcoma, carcinoma, malignant melanoma
Metastatic neoplasia in cats
Mammary adenocarcinoma, lymphoma
