Neuropath Lecture 3

Question 1

describe hypomelinogenesis

Answer 1

1. not enough myelin forms
2. described in many dog breeds; puppies develop tremors between 10 days and 8 weeks of age
3. due to in utero viral infections
   -border disease: sheep
   -hog cholera: pigs
   -BVD: calves

Question 2

describe leukodystrophies

Answer 2

1. disorders of myelin synthesis and maintenance
2. also called demyelinating diseases
3. typically heritable, early onset, lack of inflammation, symmetrical lesions, qualitative defect in myelin

example is globoid cell leukodystrophy

Question 3

describe globoid cell leukodystrophy (Krabbe’s disease)

Answer 3

1. lysosomal storage disease
2. deficiency of galactocerebroside beta-galactosidase
3. globoid cells (like gitter cells but bigger because can’t break anything down) accumulate in CNS and PNS
4. diagnose via nerve biopsy

Question 4

describe demyelination

Answer 4

1. removal of structurally normal myelin
2. primary/true demyelination:
   -removal of myelin is the primary lesion, axon sparing, may see status spongiosus on report
   -often in inflammatory setting
   -causes:
   –coonhound paralysis
   –viral diseases: canine distemper, CAE
3. secondary:
   -removal of myelin following axonal damage (wallerian degeneration)
   -subsequent degeneration and removal of myelin
   -will see: spheroids, swollen myelin sheaths (clear vacuoles), and digestion chambers from macrophages coming in to clean up

Question 5

what are the 6 types of inflammation we see in neural tissue?

Answer 5

1. suppurative/purulent/neutrophilic: bacterial, eastern equine encephalitis virus, or west nile virus
2. lymphoplasmacytic: viral or immune-mediated
3. granulomatous:
   -protozoa and metazoan parasites
   -mycobacterial
   -fungal
4. eosinophilic (+/- granulomatous): helminths and other metazoan parasites
5. pyogranulomatous (neutrophils + granulomatous):
   -fungal
   -FIP
6. idiopathic:
   -granulomatous, lymphoplasmacytic, necrotizing

Question 6

what are the 4 routes of bacterial disease in neural tissue?

Answer 6

1. hematogenous
2. direct extension from adjacent structure: erosion of bone or along nerves
3. via peripheral nerves (listeria encephalitis)
4. implantation via penetrating wound

Question 7

describe listeria encephalitis

Answer 7

organism: gram + rods

pathogenesis:
enter peripheral nerve fibers (V and VII) via oral/nasal abrasion, travels to caudal brain stem to V/VII nuclei, causes inflammation via perivascular cuffs, microabscesses, neuronopahagia)

3. moves via actin polymerization

diagnostic confirmation: microscopic plus fluoroscopic antibody, IHC, culture, PCR

clinical signs:
1. unilateral cranial nerve signs: circling, head tilt
2. bilateral lesions in the CAUDAL brainstem!!
3. primarily a winter-spring disease of feedlot or houses ruminants
4. less acidic pH of spoiled silage enhances multiplication of L. monocytogenes

Question 8

what are the two routes of origin of viral infections?

Answer 8

1. via blood: most common
   -EEE
   -WNV
   -canine distemper
2. via nerves:
   -lyssaviruses
   -herpesviruses

Question 9

what are 4 general and 3 specific features of viral infections?

Answer 9

general features:
1. mononuclear cells (primarily lymphocytes)
2. MNCs form perivascular cuff
3. glial response (primarily microglia)
4. milk meningeal inflammation

specific features:
1. neuronal degeneration (neuronophagia): WNV, BVD, listeria
2. viral inclusion bodies: rabies, canine distemper
3. demyelination: canine distemper

Question 10

describe rabies (3)

Answer 10

1. enters/spreads via nerves
2. salient/most important feature: Negri bodies (intracellular inclusions in neurons)
3. confirmatory testing: FA is gold
   standard but need correct area of fresh brain tissue

Question 11

describe canine distemper (5)

Answer 11

1. immune response:
   -prompt: subclinical disease
   -none: fatal encephalomyelitis
   -delayed: chronic inflammatory white matter disease
2. age:
   -young/juvenile: primary GRAY matter disease
   -mature: primarily WHITE matter disease
3. viral strain: some strains primarily cause gray matter disease, some primarily cause white matter disease
4. salient features:
   -lymphoplasmacytic meningoencephalitis
   -intranuclear and inctracellular inclusions: mostly in astrocytes
   -demyelination
5. ancillary testing:
   -FA: fresh tissue
   -IHC: formalin fixed
   -PCR: fresh tissue/CSF

Question 12

describe Feline Infectious Peritonitis (FIP)

Answer 12

1. salient features:
   -surface oriented leptomeninges, choroid plexus, ependyma (ratty edges)
   -pyogranulomatous, lymphoplasmacytic, fibrinous
2. ancillary testing:
   -FA: fresh
   -PCR: typically fresh
   -IHC: formalin fixed
3. immune-complexed mediated disease, where pre-existing antibodies accelerate the disease and virus infected macrophages disseminate the disease
4. cell mediated immunity determines outcome:
   -effusive FIP: produce antibodies but fail to generate effective cell-mediated immunity response
   -noneffusive FIP: partially protective cell-mediated immunity response that is unable to contain the virus

Question 13

describe EEE and West Nile Virus (5)

Answer 13

1. seasonal, mosquito borne virus
2. hyperexcitability and restlessness, developing to lethargy and depression and cortical blindness
3. may be primarily neutrophilic response that progresses to lymphoplasmacytic
4. infects neurons resulting in neuronophagia
5. diagnostic confirmation: IHC, serology (IgM), VI PCR

Question 14

describe CAE

Answer 14

1. lentivirus transmitted by colostrum and milk, +/- direct contact
2. immune-mediated, virus replicates in macrophages
3. encephalitis occurs in younger animals, unlike other lentiviral infections
4. in kids, lesions are most severe in the brainstem and spinal cord and asymmetrical
5. will see leukoencephalomyelitis with demyelination

Question 15

describe 3 yeast fungal diseases

Answer 15

1. blastomycosis:
   -surface related
   -broad based budding
2. cryptococcosis:
   -surface related
   -narrow-base budding
3. coccidioidomycosis:
   -out west mostly
   -endosporulation

Question 16

generally describe 2 types of hyphal fungal disease

Answer 16

1. phaeohyphomycosis:
   -cladosporium/cladophialophora
   -large discolored areas of necrosis
   -cats
2. apsergillosis:
   -angiophilic, necrotizing
   -secondary to gastroenteritis

Question 17

describe 2 metazoan parasite diseases

Answer 17

1. parelaphostringylosis:
   -P. tenius: meningeal worm of deer
   -affects small ruminants and camelids
   -spinal cord: necrosis and hemorrhage
   –larvae tunnel in spinal cords and form tracks
   -will see eosinophilic inflammation but need to localize lesion to make diagnosis!
2. halicephalobus gingivalus: horses
   -encephalomyelitis, nephritis, posthitis, osteomyelitis
   -granulomatous, multinodular
   -larvae and female adults parthenogenic

Question 18

describe equine protozoal myelitis

Answer 18

1. sarcocystis neurona
2. variable signs; often asymmetric
3. usually no gross lesions, but if present: multifocal necrosis and hemorrhage anywhere, more commonly spinal cord
4. ancillary testing: IHC, PLEASE localize lesion locally

Question 19

what are 3 types of protozoal encephalitis

Answer 19

1. toxoplasmosis: many species
2. neosporosis: affect dogs, cattle, horses
3. sarcocystis: horses and dogs

ancillary testing: IHC, PCR

Question 20

describe transmissible spongiform encephalopathies

Answer 20

1. prion diseases; NOT viruses, are devoid of nucleic acids
2. disorders of protein conformation
3. result in neuronal and neuropil (axons and dendrites) vacuolation
4. examples include: scrapie, BSE, chronic wasting disease