Neuro 3 - inflammation Flashcards
encephalitis
inflammation of the brain (doesn’t distinguish between gray and white matter involvement and therefore implies involvement of both compartments)
polioencephalitis
inflammation of gray matter of the brain
leukoencephalitis
inflammation of white matter of the brain
myelitis
inflammation of the spinal cord (poliomyelitis/leukomyelitis)
encephalomyelitis
inflammation of the brain/spinal cord
meningitis
inflammation of the meninges (in general usage, implies involvement of leptomeninges)
meningoencephalitis
inflammation of the meninges and brain
choroiditis
inflammation of the choroid plexus
neuritis
inflammation of a peripheral nerve
polyneuritis
inflammation of multiple peripheral nerve
radiculoneuritis
inflammation of a nerve root
suppurative exudate
- neutrophils
- bacterial infection
- may accompany tissue necrosis
- rarely neutrophilic exudates in viral infection
non-suppurative exudate
- lymphocytes +/- plasma cells, histiocytes
- viral infections, autoimmune conditions, certain protozoal/parasitic infections
granulomatous exudate
- focal accumulations of histiocytic cells
- mycoses (may be pyogranulomatous)
- certain bacteria (myco), protozoa, metazoa
- idiopathic
eosinophilic exudate
- certain parasitic infections
- may represent species-specific responses to certain categories of non-infectious disease
- porcine salt poisoning
fibrinous exudate
- reflects severe vascular insult which may suggest certain infectious agents (chlamydia, FIP)
- rare to just see this in the brain
what do you see in non-suppurative meningitis
- mostly lymphocytes, monocytes
- some histiocytes, neutrophils
what do you see in suppurative meningitis
neutrophils
pleocytosis
migration of leukocytes (especially neutrophils) across the BBB
perivascular cuffs
- general term for describing the accumulation of cells in the perivascular area of medium to small sized veins (space of virchow-robin) and may be the result of cellular efflux or influx
- infiltrating cells: lymphocytes/plasma cells, eosinophils, monocytes
what can the route of CNS infection affect
- distribution of lesions
- progression of clinical signs (depends on location)
portals of infection into the CNS
- hematogenous (most common)
- neural (viral diseases)
- direct extension from surrounding structures (trauma, abscess)
hematogenous route of infection
- sites seeded (wherever vascular density is high and vessel caliber is small): leptomeninges, choroid plexus, ependyma, neural parenchyma
- agents: bacteria, viruses, fungi, parasites, protozoa
neural route of infection
- retrograde axonal transport (rabies, human herpes-1)
- ascending neuritis from oral cavity (listeriosis)
direct extension from surrounding structures route of infection
- nasal turbinates (cryptococcosis)
- extension from otitis media/interna (actinomyces pyogenes)
once bacteria enter CNS through blood, what happens
multiple and induce the release of proinflammatory and toxic compounds, which lead to pleocytosis and increased BBB permeability –> bacterial meningitis
what is suppurative meningitis +/- choroiditis
- secondary to generalized bacteremia (septicemia)
- generally disease of young immunocompromised animals (FPT, e coli, strep)
- primary infection site may be difficult to find (hematogenous dissemination) –> synovial membranes, serosal membranes, kidneys, meninges, CNS lesions
lesions in suppurative meningitis +/- choroiditis
- cloudiness of meninges (dependent portions)
- when meninges are grossly altered by inflammatory exudate, process is generally suppurative (neutrophils, bacteria, exudate may be sterile)
- secondary changes (brain swelling/edema, secondary hydrocephalus)
meningoencephalitis
- similar pathogenesis as meningitis
- seeding of CNS structures by bacterial emboli (increased particle size) –> pasteurella, actinobacillus, coliforms, histophilus
- primary site of infection may be more readily defined
- extension to involve brain facilitated by capillary embolization/venous thrombosis
abscess formation
- hematogenous seeding –> often associated with larger septic emboli (endocarditis, strep)
- arterial embolization at cerebral gray-white junction and thalamus results in infarction
- infection does not spread beyond the devitalized tissue, and that tissue is walled off by fibrillary astrocytes
meningeal abscessation
may represent a sequel to bacterial meningoencephalitis
thromboembolic meningoencephalitis
- bacterial disease of cattle caused by histophilus somni
- localization in vessels of CNS –> multifocal vasculitis, thrombosis, malacia
- lesions of other organ systems (infection of endothelium, bacteria in macrophages)
- thrombosis in CNS –> malacia, hemorrhage
what is listeriosis and pathogenesis
- short gram + rod associated with abortion, septicemia, encephalitis
- inadequate fermentation of silage
- enters rami of trigeminal nerve from buccal mucosa, erupting teeth, exposed dental pulp (ascending neuritis)
- ascention to brainstem where encephalitis develops
brainstem lesions of listeriosis
- gross: meningeal congestion, turbid CSF, pinpoint yellow to red soft parenchymal foci
- microscopic: non-suppurative meningitis/perivacular cuffing, parenchymal microabscesses
- macroscopic hemorrhage, edema
what do you see with granulomatous meningoencephalitis
- center of necrosis
- surrounded by macrophages and lymphocytes
- can be caused by mycobacterium
hematogenous route of CNS viral infection
- virus carried by leukocytes across BBB
- virus infects endothelial cells followed by direct extension into neuropil
extension along nerve processes of CNS viral infection
- rabies, herpes
- retrograde axoplasmic transport from peripheral sites to paraspinal ganglia and ultimately the brainstem or spinal cord
direct virus-induced damage to CNS
-lytic infection: fulminant viral gene expression –> death of host cell
-persistent infection: low-level viral gene expression
-latent infection: no gene expression
(lytic –> PI –> latent)
viruses causing lytic infection of neurons or glia regardless of host age (7)
- canine distemper (neurons, astrocytes)
- pseudorabies (neurons, glia)
- herpex (neurons)
- rabies (n)
- polio (n)
- EEE/WEE/VEE (n)
- west nile (n)
viruses causing lyic infection of CNS cell types in fetuses or neonates (5)
- feline parvo
- canine herpes
- BVD
- akabane
- hog cholera
indirect viruses and CNS damage - induction of immunomediated response
- ex) caprine arthritis, FIV, HIV
- immunopathogenic mechanisms: infection of microglia by lentivirus
- highly inflammatory lesion –> demyelination with sparing of neurons
- productive infection of microglia, T lymphocyte interaction with macrophages (cytokines), antiviral antibodies
indirect viruses and CNS damage - induction of vascular lesions
- may result in CNS edema, hemorrhage, thrombosis, infarction
- may affect systemic vasculature (CNS included), or lesion may be prominently on CNS
- damage may be from lytic virus infection of vessel wall (herpes)
- damage to vessel may be immune mediated (malignant catarrhal fever, FIP)
- may reflect endothelial damage and infection of neural cells when hematogenous route used (hendra virus, nipah virus, west nile)
general microscopic features of virus-infected tissues
- non-suppurative meningeal and/or parenchymal perivascular infiltrates (non-suppurative meningoencephalitis) –> lymphocytes, plasma cells
- necrosis of specific cell types
- viral inclusion bodies
what are viral inclusion bodies
- accumulations of virus protein or nucleoprotein in the nucleus or cytoplasm
- formation of novel intranuclear structures
- nuclear bodies are derived from nucleoli and arise to supplement nucleolar function
- virus infection may induce these structures to support the increased metabolic demand placed upon cells by virus replication
4 things you see microscopically in virus-infected tissues
- lymphocytic perivascular cuff in CNS
- neuronal degeneration and necrosis
- stellitosis and neuroniophagia
- viral inclusion bodies (intranuclear, intracytoplasmic)
canine distemper virus info
- paramyxoviral multisystemic disease
- clinical signs may be referable to primary viral or secondary bacterial infection of resp or GI tract
- replication within CNS is very age-related
canine distemper pathogenesis steps
- initial replication in lymphoid tissue of upper respiratory tract (tonsils)
- viremia with seeding of lymphoid tissues of body (second viremia)
- virus replication within other tissues (lymphoid tissue, bronchiolar epithelium, intestinal/gastric, cutaneous, urinary, odontogenic, nervous tissue)
things that CDV causes (list 3)
- acute encephalopathy/acute encephalitis
- subacute encephalitis (most common)
- delayed onset encephalitis (old dog encephalitis - neuronal viral persistence)
acute encephalitis in CDV
- neuronal lytic infection
- infection of young dogs without protective immunity from colostrum
- neurons of these animals support high-level virus replication
- rapid spread through CNS neurons –> rapid death
- +/- structural evidence of CNS infection
subacute encephalitis in CDV
- glial lytic infection
- as CNS matures, neuronal support of virus replication declines –> infection of glia most apparent, progression through neuropil is protracted
- infection of non-neuronal tissues (systemic signs may be cause of death)
- white matter lesions in cerebellum, pons, mesencephalon, medulla, spinal cord
- lesions tend to be periventricular
lesions in CDV subacute encephalitis
- loss of myelin (astrocyte infection –> oligodendrocytes degenerate, variable inflammation, glial intranuclear inclusions, astrocyte fusion, malacia)
- CNS infection may be subclinical (virus persists in neurons)
what is rabies
rhabdoviral disease of nervous system in which virus infection of neurons results in neuronal degeneration and necrosis with formation of viral inclusion bodies
rabies pathogenesis
- virus introduced to host with initial viral replication at site of entry
- virus enters peripheral sensory nerve ending and ascends to associated ganglion (paravertebral/dorsal spinal) by retrograde axoplasmic transport
- spread to spinal cord and ascension within the cord using axoplasmic transporter
- axoplasmic transport of virus occurs as virus ascends spinal cord, infecting new populations of neurons
- fatality as virulent strains reach brain
how route of rabies entry affects replication and amplification
- aerosol: replication in neuroepithelial calls of nasal nuclsa
- bite: amplification in muscle cells and cells of sensory spindle apparatus
rabies in horse v cow
- horse: brain affected more
- cow: spinal cord affected more
histopath of rabies
- lymphocytic perivascular cuff in CNS and ganglioneurotis
- neuronal degeneration
- negri bodies
equine herpesvirus 1 subtype 1 info
- abortogenic strain
- encephalitogenic variants: propensity to cause CNS signs is function of tropism for endothelial cells of vessels of spinal cord white matter
insult in equine herpes
- viral lytic infection of endothelial cells and immune complex formation –> necrotizing vasulitis with hemorrhage
- lesions anywhere in CNS, mostly present in spinal cord and brainstem white matter
- mononuclear cells may accumulate in or around affected vessels
signifiance of changes in equine herpes
- resultant white matter ischemia
- wallerian degeneration
- longest fiber tracts will accumulate greatest number of hits –> posterior paresis
histopath of equine herpes
- involvement of cerebrospinal ganglia
- intranuclear inclusions NOT observed
- IHC will demonstrate viral antigen
FIP
- coronavirus infection of cats –> multisystemic necrotizing vascular disease
- affects vessels associated with choroid, meninges, ependyma
systemic mycoses
- hematogenous dissemination of fungal yeast forms results in seeding of leptomeninges (histoplasma, blasto, coccidio, crypto)
- type of inflammatory exudate may vary (granulomatous, pyogranulomatous, negligible)
opportunistic fungi
- debilitation or immunosuppression results in tissue invasion
- septic thromboemboli and mycelial forms which invade vessel walls result in infarctive lesions
- agents: aspergillus, mucor, rhizopus, candida
cryptococcus neoformans info
- cats especially
- entry may be hematogenous or by direct entension from nasal cavity
- most frequently encountered CNS mycosis, 50% exhibit CNS symptoms
- pathogenic variants have thick mucopolysaccharide capsule
CNS lesions in cryptococcus
- solid masses of organisms with minimal inflammatory response
- grossly this is unapparent or see cloudy leptomeninges +/- hemorrhage
protozoal infection overview
- DH and IH
- infection of DH is intestinal, often asymptomatic, sexual reproduction with shedding of infective oocysts
- infection of IH may be symptomatic, asexual replication within vascular endohelium
- replication within tissue parenchymal cells with encystment
- some degree of immunocompromise generally required
examples of protozoal infections (4)
- toxoplasma gondii
- neosporum caninum
- sarcocystis neurona
- encephalitozoon cuniculi
equine protozoal myeloencephalitis (EPM)
- sarcocystis neurona
- DH: opossum, IH: raccoon
- lesion: perivascular cuffs of lymphocytes/macrophages/multinucleated giant cells, eosinophils with edema, wallerian degeneration with malacia
- organisms may be associated with lesions, free, or encysted
- atrophy of peripheral nerves and corresponding musculature
toxoplasmosis info
- toxoplasma gondii
- DH: cat - IH: mouse, mole, squirrel, etc (humans)
- 1/3 involve CNS symptoms
- immune suppression predisposes to infection
- lesions: malacic foci, pseudocysts, histiocytic inflammation, granulomas
metazoan parasites - aberrant migration
- parasitic or verminous encephalomyelitis
- aberrant migration through or encystment in CNS by parasite that is normally localized to other tissues of affected host
- strongylus vulgaris, taenia solium, cuterebra
metazoan parasites - aberrant host
- parasitic or verminous encephalomyelitis
- migration through CNS by parasite not normally encountered in affected host
- parelaphostrongylus tenius (normal = deer, larval migrans in goats, sheep, camelids)
- baylisascaris procyonis (normal = raccoon, larval migrans in dogs)
parelaphostrongylus tenius
- normal = deer, larval migrans goats, sheep camelids
- moose circling in water
- meningeal worm
