Objectives for NS 3:

1. Objectives for NS 3: You should be able to define, describe pathogenesis, list lesions and know how to diagnose the following conditions:

2. Infectious diseases of CNS Portal of entry Blood Nerves Paracranial and paravertebral infections (sinuses, ear, bones et cet)

3. Meningitis • Et: E. coli, Streptococcus, HaemophilusCryptococcus, FIP virus etc. • Most common in young animals (Bo, Po) • Often as part of polyserositis • Lesions: inflammatory exudate • Diagnosis: • Gross (impression smear) and histology • Bacterial/fungal culture

4. Encephalomyelitis There are many infectious agents • Viral • Bacterial • Mycotic • Protozoal • Parasitic (nematodes) • Prion

5. Bacterial infections - H. somnus Infectious thrombotic (thromboembolic) meningoencephalitis • Et: Haemophilus somnus • Pneumonia, arthritis, heart abscess….in Bo • Pathogenesis: H. somnus invades circulation Damages endothelium of CNS venules Subendothelial collagen exposed Thrombosis, infarction, & vasculitis CNS hemorrhage, necrosis and inflammation

6. Bacterial infections - H. somnus Diagnosis • Gross and histologic lesions • Bacterial culture

7. Bacterial infections - Listeriosis Listeriosis • Et: Listeria monocytogenes • Abortion, septicemia, CNS in Bo, Ov, (Ho) • Pathogenesis: • Invasion of oral mucosa • Cetnripetal intraaxonal migration • Infection of Trigeminal gang. and brainsteam • Multifocal suppurative meningoencephalitis

8. Bacterial infections - Listeriosis Diagnosis • Histologic lesions (with Gr + bacteria) • Bacterial culture

9. TSE Transmissible spongiform encephalopathy • Unique and very unusual dz!!!??? • Scrapie in sheep and goats • Bovine Spongiform Encephalopathy in cattle • Chronic Wasting Disease in elk, white-tailed deer, black-tailed deer and mule deer • Transmissible Mink Encephalopathy • Several forms in humans • Recent reports in other species

10. TSE Pathogenesis • Normal prion protein PrPc is present in • neurons and it has helix conformation • Abnormal prion protein PrPres or PrPsc has •  sheet conformation • PrPres can induce conformational change in • PrPc to become PrPres • Accumulation of PrPres in neurons causes dz. • Interspecies transmission depends on in each • PrPc species

11. TSE Inoculation Transmission Mutation Inheritance PrPc PrPc PrPc PrPres PrPres PrPc Conformational change PrPres PrPres

12. TSE What to do if …? • Submit the animal to a diagnostic lab and indicate that it is “TSE suspect” • If diagnostic lab is far away: • Wear double gloves, mask and eye protection • Decapitate the animal and send the head Diagnosis • Histology • IHC

13. Viral infections - Rabies Rabies • Rabies viruscan infect all mammals • Maintained in nature in reservoir host • (skunks (prairies); foxes (ON), raccoons, bats) • Pathogenesis: • Transmitted by bite • Centripetal intraaxonal migration to CNS • Infects many neurons incl. Lymbic system • Centrifugal migration to salivary gl. • Death is due to progressive paralysis

14. Viral infections - Rabies Lesions • Clin. phases: prodromal, excitatory (furious or dumb form), & paralytic • Non suppurative encephalitis • and ganglioneuritis • Intracytoplasmatic inclusion bodies Diagnosis • Fluorescence antibody test • Mouse or tissue culture inoculation • Histology & IHC

15. Viral infections - Rabies What to do if…? • Label: “RABIES SUSPECT” and submit • to diagnostic lab • If you are doing necropsy yourself: • Should be vaccinated against rabies • Use double gloves, mask and eye protection • Never use power tools for brain removal • Avoid, contact with saliva, brain and CSF • Submit half brain (frozen) to CFIA • Other half in formalin

16. Viral infections - Distemper Distemper • Distemper virus, morbillivirus, Paramyxov. • Dogs, fox, wolf, hyena, ferret, raccoons, etc • Rarely seen in dogs due to vaccination • Multisystemic dz (lung, skin, CNS, urinary,lymphoid tissue immunosuppression)

17. Viral infections - Distemper Pathogenesis Infection (inhalation) Replication in tonsils/lungs Other lymphoid tissues >> immunosuppression CNS & Epithelia (~ 8-9 days after infection) Death due to Severe viral infection +/- 2o bacterial infect. Recovery CNS infection 1o demyelination due to direct viral damage 2o demyelination due to inflammatory reaction

18. Viral infections - Distemper Lesions in CNS: Demyelination (primary and secondary) Non suppurative encephalitis with I/N and I/C inclusion bodies Diagnosis • Histology • IHC

19. Viral infections - WNV West Nile Virus • Arthropod-borne flavivirus in birds, Eq, Ho • Usually no clinical signs in birds • However, fatal CNS dz. WAS PRESENT in various birds in the recent US outbreak. • Lesions: non suppurative encephalitis • Diagnosis: IHC, PCR, • Serology in live

20. Viral infections - in utero In utero viral infections • Cerebellar hypoplasia • Feline panleukopniavirus • Cerebellar hypoplasia, hydranencephaly and/or hypomyelination • Bovine viral diarrhea virus • Hog cholera virus • Blue tongue virus • Border disease virus

21. Protozoal infections • Equine protozoal encephalomyelitis • Sarcocysis neurona (defin. host - opasum) • Lesions: necrosis/malacia, inflammation most frequently in the spinal cord • Diagnosis: • Histological lesions • IHC

22. Neoplasia Neoplasia • Meningioma • Astorcytoma • Oligodendroglioma • Ependymoma Diagnosis Histology