Infectious/Non-Infectious Inflammatory Diseases of the CNS

Question 1

blood brain barrier

Answer 1

tight junctions between capillary endothelial cells
inflammation can readily develop in the brain and spinal cord!!

Question 2

meningitis

Answer 2

leptomeningitis: inflammation of pia-arachnoid
pachymeningitis: inflammation of dura mater

Question 2

what are some examples of neurotropic agents?

Answer 2

1. rabies: neurons of the grey matter
2. prions: medulla
3. Listeria monocytogenes: Pons and medulla

Question 2

unique features of CNS inflammation

Answer 2

• once thru blood/CNS barrier, infection can spread readily
• once CNS infection occurs it persists: drainage of exudate is poor, difficult to treat because of poor penetration of BBB by drugs
• many agents have no neurotropism (ie CNS infx part of systemic infx)
• some agents are neurotropic

Question 3

encephalitis

Answer 3

inflammation of the brain

Question 4

myelitis

Answer 4

inflammation of the spinal cord

Question 5

leptomeningitis

Answer 5

inflammation of pia-arachnoid

Question 6

pachymeningitis

Answer 6

inflammation of dura mater

Question 7

what are the 4 routes by which infx can get to CNS?

Answer 7

1. direct extension/implantation
2. hematogenous (most common)
3. via peripheral nerves
4. leukocyte trafficking

Question 8

direct extension/implantation

Answer 8

• penetrating trauma: stab, gun, skull fracture
• middle/inner ear infx
• nasal cavity/sinus infx thru cribriform plate or along olfactory n
• osteomyelitis
• neoplasia

Question 9

hematogenous CNS infx

Answer 9

• most common
• localization within capillary beds of meninges or choroid plexus (ex neonatal speticemia)
  sepsis sees these things

Question 10

what is the most common route of CNS infection?

Answer 10

hematogenous

Question 11

peripheral nerve CNS infx

Answer 11

• retrograde axonal transport (From NMJ and up into CNS)
• axoplasmic flow from PNS to CNS: ex rabies and listeria monocytogenes

Question 12

leukocyte trafficking CNS infx

Answer 12

macrophages or lymphocytes containing microbes during their transit thru CNS
ex: retroviruses
less common

Question 13

you get called out to a pig farm where several piglets 5-8 weeks are having neurological signs. some have died suddenly. those with signs have swollen joints and cutaneous lesions, as well as incoordination, tremors, lateral recumbency, and paddling. on necropsy you see suppurative meningitis. what are some differentials for this morphologic diagnosis?

Answer 13

bacteria! major causes of meningitis in pigs:
- strep suis **
- glasserella parasuis (glasser’s disease) **
- mycoplasma hyorhinis (does not cause meningitis)
- other gram neg like salmonella

Question 14

what are the 2 big bacterial differentials that cause meningitis in pigs?

Answer 14

1. Streptococcus suis
2. Glasserella parasuis: glasser’s disease

Question 15

meningitis is most often part of ________ ________ infection

Answer 15

systemic bacterial infection (ie septicemia)
can also result from direct extension like fractures, otitis, sinusitis

Question 16

T/F: meningitis is a common finding in neonatal septicemia

Answer 16

true: especially in food animals

Question 17

what are gross lesions of meningitis

Answer 17

opaque leptomeninges: look at ventral aspect of brain! gravity causes exudate to sink down
hard to see grossly
occasionally get involvement of ventricles, also maybe other lesions of septic animals like pleuritis, peritonitis, etc

Question 18

what is the most common cause of neonatal septicemia?

Answer 18

coliforms!

Question 19

what is empyema?

Answer 19

pus accumulating within a cavity or space

Question 20

where is the big place we see empyema?

Answer 20

epidural: outside the dura mater, surrounded by bony encasement
once ifx gets there can accumulate focally, but more commonly diffuses across the whole area

Question 21

where are common locations to see empyema?

Answer 21

vertebral canal is most common: tail docking or other traumatic injuries
cranium is less common: secondary infx following skull fracture

Question 22

mechanisms of bacterial abscesses

Answer 22

• direct implantation in wounds
• hematogenous **
• direct extension from adjacent tissues **
• common bacterial isolates

Question 23

what are ways direct extension from adjacent tissues can lead to brain abscesses?

Answer 23

1. cribriform plate --> frontal abscess. ex oestrus ovis in sheep 2. thermal injury from dehorning --> frontal abscess 3. inner ear infx --> cerebellopontine abscesses

Question 24

what are common bacterial isolates from brain abscesses?

Answer 24

trueperella pyogenes, streptococcus sp, pasteurella sp

Question 25

you get a call from a producer with an adult ewe who is depressed, has a right sided head tilt and is stumbling and circling to the right. what is immediately on your differential list?

Answer 25

Listeria!!

Question 26

Listeria monocytogenes

Answer 26

- associated with feeding SPOILED SILAGE oral wound allows bacterial invasion of mucosa --> bacteria invade trigeminal nn (others possible) --> travels to brainstem via axons (retrograde)

Question 27

pathogenesis of listeria monocytogenes

Answer 27

oral wound allows bacterial invasion of mucosa. --> bacteria invade trigeminal nn (others possible) --> travels to brainstem via axons (retrograde)

Question 28

what is the primary histologic lesion with listeria monocytogenes?

Answer 28

microabscesses in brainstem (pons and medulla)

Question 29

microabscesses in brainstem (pons and medulla)

Answer 29

LISTERIA MONOCYTOGENES

Question 30

how do you diagnose listeria monocytogenes?

Answer 30

culture, IHC, gram stain

Question 31

histophilus somni causes what disease

Answer 31

septicemia, thrombotic meningoencephalitis

Question 32

histophilus somni

Answer 32

- normal genital and nasal flora of cattle and sheep - resp tract --> SEPTICEMIA --> THROMBOTIC MENINGOENCEPHALITIS (and lesions in other tissues like bronchopneumonia and myocarditis) - gross: multifocal hemorrhages and necrosis (malacia) - primary histo lesion: vasculitis --> thrombosis +/- infarcts

Question 33

pathogenesis of Histophilus somni

Answer 33

resp tract --> SEPTICEMIA --> THROMBOTIC MENINGOENCEPHALITIS (and lesions in other tissues like bronchopneumonia and myocarditis)

Question 34

what are the gross lesions of Histophilus somni?

Answer 34

multifocal hemorrhages and necrosis (malacia)

Question 35

botulism (limber neck) pathogenesis

Answer 35

- Clostridium botulinum (A B or C) in soil, most commonly in horses in America, botulinum toxin leads to flaccid paralysis, ascends to diaphragm, cannot breathe, death normally nerve at NMJ releases ACh, binds and causes muscle contraction. botulism prevents ACh from being released at NMJ = flaccid paralysis

Question 36

does botulinum lead to a flaccid or rigid paralysis?

Answer 36

flaccid paralysis

Question 37

T/F: botulism has no gross or microscopic lesions

Answer 37

true

Question 38

how do you diagnose botulism?

Answer 38

history + toxin detection in clinical samples collected for lab: intestinal contents, serum, liver, etc

Question 39

what bacterial disease prevents ACh from being released at the NMJ; which causes flaccid paralysis?

Answer 39

clostridium botulinum type A, B or C

Question 40

lockjaw

Answer 40

clostridium tetani

Question 41

clostridium tetani pathogenesis

Answer 41

clostridium tetani toxin goes to motor end plate, blocks release of an inhibitory neurotransmitter glycine, and causes stiffness/spasms/fever etc

Question 42

symptoms of tetanus/lockjaw

Answer 42

stiffness of jaw severe muscle spasms sweating fever stiffness of abdominal muscles difficulty swallowing

Question 43

T/F: tetanus does not have any gross or microscopic lesions

Answer 43

true, just like botulism

Question 44

important viral infections of the CNS in horses

Answer 44

1. West Nile Virus 2. Equine encephalitis viruses (Eastern, western, venezuelan encephalitis) 3. EQUINE HERPESVIRUS 1 (myeloencephalopathy): primarily causes vasculitis, and doesn't specifically target grey matter 4. Rabies virus

Question 45

what does EHV-1 cause

Answer 45

myeloencephalopathy primarily causes vasculitis, and does not specifically target grey matter

Question 46

what virus causes random asymmetrical foci of hemorrhage?

Answer 46

equine herpesvirus-1

Question 47

viral infections of nervous system general characteristics

Answer 47

- usually part of system infection (viremia) - usually no gross lesions, but when you do see them, see lesions in grey matter (viruses want a cell to replicate in, which are neurons, where the grey matter is)

Question 48

histopathologic lesions of viral infections of the nervous sytem

Answer 48

- non-suppurative inflammation: perivascular cuffs, mild meningitis - gliosis/glial nodules - injury to neurons with neuronophagia

Question 49

what viruses cause demyelination?

Answer 49

canine distemper virus and small ruminant lentiviruses (caprine arthritis-encephalitis virus and visna) immune mediated myelin destruction or viral infection of oligodendrocytes

Question 50

what virus causes meningitis/ventriculitis?

Answer 50

feline infectious peritonitis virus

Question 51

what virus causes viral inclusion bodies?

Answer 51

rabies: Negri bodies, canine distemper virus (intracytolpasmic and intranuclear), pseudorabies (herpesvirus, intranuclear)

Question 52

do viruses do primary or secondary de-myelination?

Answer 52

primary: they are directly killing the cell that either makes myelin or its myelin sheath

Question 53

what are the main viruses that do primary demyelination?

Answer 53

canine distemper virus and small ruminant lentiviruses (caprine arthritis-encephalitis virus and visna)

Question 54

what is the main virus that induces meningitis/ventriculitis?

Answer 54

feline infectious peritonitis

Question 55

what locations/viruses might you see viral inclusion bodies with?

Answer 55

1. rabies virus: intracytoplasmic Negri bodies 2. canine distemper virus: intracytoplasmic and intranuclear 3. pseudorabies/herpes virus: intranuclear

Question 56

where are rabies viral inclusion bodies located?

Answer 56

intracytoplasmic: negri bodies

Question 57

where are canine distemper virus viral inclusion bodies located?

Answer 57

intracytoplasmic and intranuclear

Question 58

where are pseudorabies/herpesvirus viral inclusion bodies located?

Answer 58

intranuclear

Question 59

main virus causing infx in CNS in dogs

Answer 59

canine distemper virus

Question 60

main virus causing infx in CNS in cats

Answer 60

feline infectious peritonitis virus

Question 61

main virus causing infx in CNS in sheep/goats

Answer 61

lentivirus: caprine arthritis-encephalitis virus in goats visna in sheep

Question 62

what lesions does FIP cause?

Answer 62

granulomatous/pyogranulomatous inflammation focused on meninges and ventricular system granulomatous is classic thing

Question 63

what lesions does canine distemper virus cause?

Answer 63

- grey matter lesions: similar to other viruses - white matter lesions: DEMYELINATION (primary) - intra-nuclear and cytoplasmic inclusion bodies spongy change = demyelination

Question 64

spongy change =

Answer 64

demyelination

Question 65

post-vaccinal distemper

Answer 65

1-2 weeks after vaccination - aggressive behavior, progressive ataxia, paresis and death within a few days (looks like furious form of RV) - disseminated lesions in grey matter (so don't see demyelinating lesin)

Question 66

old dog encephalitis

Answer 66

- rare manifestation: subclinical persistent infx? - lesoins in grey and white matter of prosencephalon

Question 67

you see an 8 year old lab with chronic myoclonus/twitching in the face. what immediately goes on your differential list?

Answer 67

canine distemper

Question 68

small ruminant lentiviruses

Answer 68

- caprine arthritis encephalitis virus: 2-4 month old kids - visna: sheep: usually >2 years old clinical signs: hindlimb lameness and ataxia with paresis progressing to paralysis. affects mainly spinal cord causes demyelinating leukoencephalomyelitis: myelitis very prominent.

Question 69

caprine arthritis encephalitis virus

Answer 69

2-4 month old kids small ruminant lentivirus hindlimb lameness and ataxia, demyelinating leukoencephalomyelitis

Question 70

visna lentivirus

Answer 70

sheep usually > 2 years old hindlimb lameness and ataxia, demyelinating leukoencephalomyelitis

Question 71

what are the clinical signs of small ruminant lentivirus?

Answer 71

hindlimb lameness and ataxia, demyelinating leukoencephalomyelitis

Question 72

fungal and algae infections of CNS

Answer 72

- mostly isolated and usually opportunistic infection in immunocompromised animals - most go hematogenously (Blastomyces dermatitidis) - the one that does extension is Cryptococcus: extension from nasal cavity thru cribriform plate

Question 73

what is 1 specific instance of a fungal infx going to CNS by direct extension?

Answer 73

Cryptococcus: direct extension from cribriform plate

Question 74

what fungal species spreads hematogenously?

Answer 74

Blastomyces

Question 75

what are the gross lesions of fungal and algae infections of the CNS

Answer 75

parenchymal discoloration or a "mass-like" lesion

Question 76

what are the histopathology findings of fungal and algae infections?

Answer 76

granulomatous to pyogranulomatous inflammation presence of organisms histologically

Question 77

phaeohyphomycosis

Answer 77

pigmented fungus, environmental. some are neurotropic and can see in aged patients

Question 78

feline cryptococcus

Answer 78

inhalation into nasal cavity leads to invasion thru cribriform plate or among olfactory nerve leads to meningoencephalitis. lesion can look gelatinous on the meninges see thick non-staining polysacchardie capsules on histology cryptococcus neoformans or gattii

Question 79

you have a necropsy of a cat and see gelatinous material thru the meninges and forming a mass. you do histopathology and see thick, non-staining polysaccharide capsules. what is your diagnosis?

Answer 79

feline cryptococcus: either cryptococcus neoformans or gattii (PNW)

Question 80

you have a 3 year old quarter horse mare that has been stumbling, knuckling and has progressivve unilateral muscle atrophy of right pelvic limb. you do a CSF tap and see eosinophilic pleocytosis. the owner mentions that they have seen an opossum around lately. what is your diagnosis?

Answer 80

EPM: equine protozoal myeloencephalitis

Question 81

sarcocystis neuron

Answer 81

- EPM: equine protozal myeloencephalitis - ataxia, limb weakness, lameness - typically spinal cord and brainstem - asymmetrical foci of hemorrhage and malacia

Question 81

what causes equine protozoal myeloencephalitis? (EPM)

Answer 81

sarcocystis neurona

Question 82

what are the gross lesions of EPM?

Answer 82

asymmetrical foci of hemorrhage and malacia

Question 82

what is the definitive host of EPM?

Answer 82

opossums

Question 82

Neospora caninum in dogs

Answer 82

- young dog infections in utero - lesions: polyradiculoneuritis (nerve roots) and polymyositis (multiple muscles) see young dog with weakness progressing to paralysis

Question 83

what are the histopathologic lesions with protozoal infections?

Answer 83

pyogranulomatous/granulomatous inflammation +/- eosinophils see organisms histologically

Question 84

where are the lesions of neospora caninum in dogs?

Answer 84

polyradiculoneuritis: nerve root inflammation polymyositis: muscles inflammation nerves CNS and muscle!!

Question 85

neospora caninum in cattle

Answer 85

- abortion (midterm) - lesions (encephalitis, myositis/myocarditis)

Question 86

parelaphostrongylus tenuis

Answer 86

- meningeal worm - definitive host: white tailed deer (typically no signs) - reside mostly in subdural space - camelids ingest infected mollusks (IH) which results in aberant migration in the CNS parenchyma

Question 87

what is the definitive host for parelaphostrongylus tenuis?

Answer 87

white tailed deer camelids ingest infected mollusks (IH) which results in migration in the CNS parenchyma

Question 88

what are the characteristic lesions with parasitic infections of the CNS?

Answer 88

granulomatous and/or eosinophilic inflammation - linear tracts of hemorrhage and necrosis - organisms: larva or adults

Question 89

insect larvae parasitic infections of the CNS examples (3)

Answer 89

- oestrus ovis: nasal cavity of sheep and penetrate cribriform plate - hypodermis bovis: spinal cord of cattle - cuterebra sp: feline ischemic encephalopathy

Question 90

you see a cat presenting with a pencil-sized hole on the side of its neck. you suspect that there is some sort of larvae inside. what is your ddx?

Answer 90

cuterebra. causes feline ischemic encephalopathy if they penetrate thru nasal cavity and wounds. rarely can migrate into CNS: causes ischemic infarct initially, and then with chronicity see collapse of brain parenchyma

Question 91

what are the 3 types of canine meningoencephalitis of unknown origin (MUO)

Answer 91

1. granulomatous meningoencephalitis (GME) 2. necrotizing meningoencephalitis (NME) 3. necrotizing leukocencephalitis (NLE)

Question 92

MUO characteristics

Answer 92

- canine meningoencephalitis of unknown origin - immune mediated mechanism? - most cases in young adults (6mo to 3 yrs) - various breeds, but more commonly small breeds - usually multifocal disease

Question 93

MUO signalment

Answer 93

young adults (6 mo to 3 yrs), small breeds more common multifocal disease

Question 94

what lesions are seen with necrotizing meningoencephalitis?

Answer 94

- gross: multifocal asymmetrical, bilateral regions of encephalitis or malacia - histo: multifocal non-suppurative inflammation involving meninges and grey and white matter (predominantly cerebrum) with necrosis

Question 95

necrotizing leukoencephalitis lesions

Answer 95

gross: large asymmetric malacic foci confined to deep white matter (brainstem, cerebrum) histo: necrosis with thick lymphocytic perivascular cuffs white matter specific disease!

Question 96

coonhound paralysis

Answer 96

idiopathic inflammatory dz: polyradiculoneuritis in dogs - ascending paresis/paralysis of limbs - lymphocytic inflammatory, demyelination/axonal degeneration of spinal nerve roots/peripheral nerves! - suspected immune-mediated reaction suspected? hypersensitivity reaction to raccoon saliva?

Question 97

polyradiculoneuritis in dogs

Answer 97

- coonhound paralysis - targets spinal nerve roots/peripheral nerves: lymphocytic inflammatory, demyelination/axonal degeneration

Question 98

steroid-responsive meningitis-arteritis

Answer 98

- "beagle pain syndrome" - idiopathic inflamm disease - young adult dogs: acute fever, neutrophilia, neck pain

Question 99

you see a 3 year old dog with acute fever, neutrophilia, and neck pain. what is your suspicion?

Answer 99

beagle pain syndrom: steroid responsive meningitis-arteritis - subarachnoid hemorrhage, meningitis and necrotizing arthritis give steroids!!

Question 100

polyneuritis equi

Answer 100

- neuritis of cauda equina - horse disease - autoimmune vs post infectious? - chronic progressive tail and sphincter paralysis, urinary and fecal incontinence, perineal paresthesia/analgesia - gross: swollen nerves with adhesions