JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

April 2023

N-V12 (NP)

 

Signalment (JPC #2359294): An adult seal 

 

HISTORY: This animal was found dead along the shore. Gross inspection revealed severe bronchopneumonia.

 

HISTOPATHOLOGIC DESCRIPTION: Cerebrum: Multifocally within the gray matter, there are multiple small, up to 200 µm diameter, foci of liquefactive necrosis characterized by spongiosis and neuropil loss with replacement by minimal eosinophilic debris, microglia, and astrocytes variably forming glial nodules. Multifocally neurons are degenerate (swollen and round with central chromatolysis) or necrotic (shrunken, hypereosinophilic cytoplasm with pyknotic nuclei). There is occasional satellitosis and rare multinucleated syncytial cells. There are few gemistocytes (astrocytes with abundant eosinophilic cytoplasm with eccentric nuclei). Rarely, neurons and astrocytes contain round to oval, 1-5 µm diameter, eosinophilic intranuclear or intracytoplasmic inclusion bodies. Multifocally within the white matter, myelin sheaths are dilated and contain a round, swollen, hypereosinophilic axon (spheroids). In more severely affected areas, blood vessels are occasionally lined by hypertrophied reactive endothelial cells and surrounded by mild hemorrhage, fibrin and edema. Diffusely, there is mild expansion of Virchow Robin space by few lymphocytes, plasma cells, and rare macrophages (perivascular cuffing). The meninges contain a similar but milder inflammatory infiltrate.

 

MORPHOLOGIC DIAGNOSIS: Cerebrum: Encephalitis, necrotizing and lymphohistiocytic, multifocal, moderate, with spongiosis, gliosis, perivascular cuffing, neuronal degeneration, syncytia, and neuronal and glial intranuclear and intracytoplasmic eosinophilic inclusion bodies, seal, pinniped.

 

ETIOLOGIC DIAGNOSIS: Morbilliviral encephalitis

 

CAUSE: Phocine morbillivirus [Phocine distemper virus (PDV)]

 

GENERAL DISCUSSION: 

• Family Paramyxoviridae, genus Morbillivirus; single-stranded, enveloped, RNA viruses
• PDV is closely related to Canine distemper virus (CDV) and has a wide host range including all terrestrial carnivores; has also caused epidemics among pinnipeds
• PDV is a highly contagious aerosolized virus that causes epizootics in naive populations (multiple, very large, well-documented epizootics resulting in >20,000 deaths per outbreak in European seals); evidence also suggests transmission by direct and indirect contact due to sociable behavior of pinnipeds
• Clinical signs and lesions in lung, CNS, and lymphoid tissue are comparable to CDV
• Serologic surveys have detected anti-morbilliviral antibodies from pinnipeds from the Antarctic to the Canadian artic
• Secondary bacterial infections can be common: Bordetella bronchiseptica and Streptococcus equi subsp. zooepidemicus were significantly associated with the seal die-offs from phocine distemper in 2002 

 

PATHOGENESIS:

• Proposed similarity to CDV: Inhalation à Virus replicates in lymphoid tissue à Viremia 5-12 days post-infection à Lymphocytolysis and lymphoid depletion à Dissemination to multiple tissues, including respiratory, GI tract, CNS, and lymphoid tissues à Immunosuppression à Increased susceptibility to secondary infections
• CNS white matter demyelination following the direct spread of virus into cerebrospinal fluid

 

TYPICAL CLINICAL FINDINGS:

• Abortion, sudden death
• Lethargy, weakness, ventral pressure sores, severe edematous conjunctivitis, serous to mucopurulent oculonasal discharge, cutaneous lesions, gastroenteritis, neurologic signs
• Pneumonia, anorexia, respiratory distress, cyanosis, coughing terminally

 

TYPICAL GROSS FINDINGS:

• CNS: No gross lesions
• Respiratory: Bronchointerstitial pneumonia, pulmonary edema and congestion, atelectasis, emphysema, occasionally exudative pleuritis

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Intranuclear and/or intracytoplasmic viral inclusion bodies are single to multiple, eosinophilic, distinct, round to oval, and up to 20 um in diameter
• Multinucleated “Warthin-Finkeldey” syncytial cells in bronchi, and bronchiolar and alveolar lumina, which often contain inclusion bodies
• CNS: Non-suppurative demyelinating meningoencephalitis, neuronal and glial necrosis, perivascular cuffing, gliosis, neuronophagia, and inclusion bodies within astrocytes, neurons, and ependymal cells
• Respiratory: Bronchointerstitial pneumonia, edema, congestion, and interlobular, subpleural and mediastinal emphysema; intracytoplasmic and intranuclear (less frequent) inclusion bodies in respiratory epithelium, alveolar macrophages, and type II pneumocytes
• Lymphoid tissue: Lymphocytolysis, lymphoid depletion of lymph nodes, spleen, gut-associated lymphoid tissue, and thymus; rare intracytoplasmic inclusion bodies
• Other tissues: Intracytoplasmic inclusion bodies can be found within epithelium of the urinary tract including urinary bladder and renal pelvis, and the gastrointestinal tract including biliary and pancreatic ductules

 

ULTRASTRUCTURAL FINDINGS:

 

ADDITIONAL DIAGNOSTIC TESTS:  

• Reverse transcriptase polymerase chain reaction (RT-PCR)
• Immunohistochemistry
• Immunofluorescence

 

DIFFERENTIAL DIAGNOSIS:

 

COMPARATIVE PATHOLOGY:

Other morbilliviruses:

• Cetacean morbillivirus: Bronchointerstitial pneumonia, lymphoid depletion, syncytial cells, 3-8 um diameter eosinophilic intranuclear or intracytoplasmic inclusion bodies of lung, lymph node, spleen, epidermis and urinary bladder; demyelination is NOT recognized in CMV-infected cetaceans; poses a significant risk to endangered species of aquatic mammals
• Rinderpest (D-V28): Infects ruminants and wild ungulates, dehydration, diarrhea, depression and death, oral/esophageal erosion and ulceration, inflammation and necrosis of gastrointestinal tract, Peyer's patch necrosis; currently classified as eradicated
• Canine distemper virus (N-V11, I-V12, P-V01, U-V07): Infects animals of the families Ailuridae (red panda), Canidae (fox, wolf), Hyaenidae (hyena), Mustelidae (ferret, mink), Procyonidae (raccoon, panda), Ursidae (bear), Viverridae (civet, mongoose), and Felidae (exotic felids including lions, tigers, and leopards) are susceptible; causes bronchointerstitial pneumonia with syncytia, inclusion bodies, lymphoid depletion, optic neuritis, retinal degeneration, anterior uveitis, defective enamel development, hyperkeratosis, demyelination, neuronal degeneration and perivascular cuffs in CNS
• Peste des petits ruminants: Infects sheep and goats, acute onset, inflammation and necrosis of mouth and gastrointestinal tract, and inconsistent involvement of the respiratory tract
• Measles (rubeola) virus (P-V02): Infectious disease of primates characterized by blotchy red-brown rash, and sometimes pneumonia, diarrhea, keratitis, blindness, encephalitis, and hemorrhage
• Free ranging polar bears: Many have serologic evidence of exposure to phocine distemper virus and/or dolphin morbillivirus (a strain of cetacean morbillivirus)  

 

References:

1. Colegrove KM, Burek-Huntington KA, Roe W, Siebert U. Pinnipediae. In: Terio KA, McAloose D, St. Leger J eds. Pathology of Wildlife and Zoo Animals. San Diego:Elsevier. 2018: 578-579.
2. Duignan PJ, Van Bressem MF, Baker JD, et al. Phocine Distemper Virus: Current Knowledge and Future Directions. Viruses. 2014; 6:5093-5134.
3. Keel MK, Terio KA, McAloose D. Canidae, Ursidae, and Ailuridae. In: Terio KA, McAloose D, St. Leger J eds. Pathology of Wildlife and Zoo Animals. San Diego:Elsevier. 2018:241.
4. Lopez A, Martinson SA. Respiratory System, Thoracic Cavities, Mediastinum, and Pleurae. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:633-634.
5. MacLachlan NJ, Dubovi EJ.  Paramyxoviridae and Pneumoviridae. In: MacLachlan NJ, Dubovi EJ, eds. Fenner’s Veterinary Virology, 5th ed. San Diego, CA: Academic Press, Elsevier; 2017:327-349.
6. Miller AD, Porter, BF. Nervous System. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:975.
7. Peste des petits ruminants. In: Committee on Foreign Animal Diseases of the United States Animal Health Association. Foreign Animal Diseases, 7th Ed. Boca Raton, FL: Boca Publications Group, Inc.; 2008:357-363.
8. Rinderpest. In: Committee on Foreign Animal Diseases of the United States Animal Health Association. Foreign Animal Diseases, 7th Ed. Boca Raton, FL: Boca Publications Group, Inc.; 2008:377-382.
9. Siebert U, Rademaker M, Ulrich SA, et al. Bacterial microbiota in harbor seals (Phoca vitulina) from the North Sea of Schleswig-Holstein, Germany, around the time of morbillivirus and influenza epidemics. J Wildl Dis. 2017;53(2):201-214.

Click the slide to view.

---