AFIP SYSTEMIC PATHOLOGY

JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

April 2017

N-V07

 

Signalment (JPC #1178019):  Feeder pig

 

HISTORY (Case A):  This was one of 193 feeder pigs from a Midwest stockyard. Slight coughing was observed in the group. Three days later 123 gilts were sick with an influenza-like disease. The signs noted were coughing, anorexia, vomiting, shaking of the head, frequent getting up and down and convulsions. The next day, several were found dead and 20 others were sick. The findings at necropsy were edema and congestion of the lungs, pleural and pericardial effusion, epicardial petechiation, empty congested stomach, congestion of the intestine, liver, and spleen, and marked congestion of the meningeal vessels. Bacteriologic examination was negative.

 

HISTOPATHOLOGIC DESCRIPTION:  Cerebellum, cerebrum, brain stem:  Multifocally in the cerebellum, brain stem, and cerebrum, Purkinje cells and scattered neurons are shrunken, and hypereosinophilic with pyknotic nuclei (necrosis), and are multifocally surrounded by nodular aggregates of glial cells (satellitosis). Rare Purkinje cells contain poorly discernible, round, 4-6 um, oval, eosinophilic to amphophilic, homogenous, intranuclear viral inclusion bodies which marginate the chromatin. In all sections, there is multifocal scattered and nodular gliosis in the white and grey matter.  Multifocally vessel walls and Virchow-robin spaces are expanded by lymphocytes and plasma cells (perivascular cuffing).  Meninges are expanded by cellular infiltrates composed of numerous lymphocytes, fewer histiocytes, plasma cells, hemorrhage, and fibrin.

 

MORPHOLOGIC DIAGNOSIS:  Cerebellum, cerebrum, brain stem: Meningoencephalitis, nonsuppurative, multifocal, moderate, with neuronal necrosis, gliosis and neuronal eosinophilic intranuclear viral inclusion bodies, mixed-breed, porcine.

 

Signalment (JPC #2015639):  Yearling Hereford crossbred steer

 

HISTORY (Case B):  This steer exhibited hyperesthesia, pruritus, excessive salivation, ataxia, and paralysis.

 

HISTOPATHOLOGIC DESCRIPTION:  Spinal cord:  Multifocally there is mild gliosis in the grey matter that occasionally extends as nodular aggregates (glial nodules) into the white matter. Multifocally within the grey matter, rare shrunken angular, hypereosinophilic neurons (necrosis) contain poorly discernible, round, 4-6 um, eosinophilic to amphophilic intranuclear viral inclusion bodies. Multifocally within the grey and white matter, low numbers of lymphocytes and fewer plasma cells expand Virchow-Robin space (perivascular cuffing).

 

MORPHOLOGIC DIAGNOSIS:  Spinal cord:  Myelitis, nonsuppurative, perivascular, multifocal, mild, with glial nodules, rare neuronal necrosis and intranuclear viral inclusion bodies, Hereford crossbred, bovine.

 

ETIOLOGIC DIAGNOSIS:  Alphaherpesviral encephalitis / poliomyelitis

 

CAUSE:  Porcine herpesvirus-1 (Herpesvirus suis, pseudorabies virus)

 

CONDITION:  Pseudorabies

 

CONDITION SYNONYMS:  Aujeszky’s disease, Mad itch

 

GENERAL DISCUSSION:

·       ds DNA virus; Suid herpesvirus 1; genus Varicellovirus; Herpesviridae

·       Neurons are primary target: results in polioencephalitis or polioencephalomyelitis

·       Pseudorabies is a worldwide, sporadic disease of domestic swine

·       The pig is the only natural host for this virus as it is the only species able to survive a productive infection; brown rat is suspected host in wild

·       Other species serve as dead end hosts with peracute, fulminant disease

·       Species affected include:  Bovine, ovine, canine, feline

 

PATHOGENESIS:

·       Route of natural infection in pigs – intranasal, pharyngeal, tonsillar, or pulmonary by direct contact, fomites, or aerosolization, followed by reproduction of virus in epithelial cells of the upper respiratory tract

·       Virus then travels to the tonsil and local lymph nodes by way of the lymph vessels

·       Virus replicates in the epithelium of the upper respiratory tract and invades sensory nerve endings and is transported in axoplasm via the trigeminal ganglion and olfactory bulb to the brain

·       Centripetal invasion of local peripheral nervescauses nerve cell damage, which leads to clinical sign of intense pruritis

·       In latently infected pigs, the oronasal epithelium can be recurrently infected by virus spreading from the nervous system, followed by its excretion in the oronasal fluid

·       Transplacental infections occur in pigs causing abortion in about 50% of sows pregnant in the first month, and the delivery of macerated, mummified, and normal fetuses when infection occurs at later stages of gestation

·       Direct or indirect contact with pigs, ingestion of infected pork (usual source for dogs and cats) results in infection of dead end hosts; the pathogenesis is similar

·       Virulence factors:  Virus-encoded enzymes involved in nucleic acid metabolism determine herpesvirus virulence; glycoprotein gE is involved in spread within nervous system for PRV

·       Virus is fairly strictly neurotropic, in species other than pigs

 

TYPICAL CLINICAL FINDINGS:

Age related susceptibility in swine:

·       Newborn piglets: Severe, highly fatal

·       Young piglets:  Pyrexia, ataxia, congenital tremors, recumbency, generalized seizures, and variable respiratory signs; possibly high mortality

·       Postweaning and older pigs:  Infection may be mild or inapparent and consist primarily of respiratory signs

·       Susceptible pregnant sows:  Early embryonic death, abortion, and mummified fetuses; necrotic placentitis

o   Intense pruritus is not typically seen in swine

Non-porcine species:

·       There is little age-related susceptibility; signs include intense pruritus (“mad itch”), fever, salivation, excitement, convulsions, paralysis; generally fatal within 48 hours

 

TYPICAL GROSS FINDINGS:

·       Piglets:  Tonsillar necrosis; multifocal necrosis in the liver, spleen, lymph nodes, adrenal glands, and lungs; pneumonia; congestion of the leptomeninges

·       Non-porcine species:  Cutaneous trauma associated with itching, pulmonary congestion and hemorrhage

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

·       Reflect neutrotropic and epitheliotropic nature of the virus

·       Epitheliotrophic lesions: Young, aborted piglets

·       Neutrotrophilc lesions: Ruminants and carnivores

·       Nonsuppurative ganglioneuritis and meningoencephalomyelitis

·       Microgliosis (patchy, around necrotic neurons), neuronal and parenchymal necrosis

·       Intranuclear inclusion bodies – found in neurons, oligodendrocytes, astrocytes, and endothelial cells; also affected epithelium (liver, tonsil, lung, spleen, placenta, adrenal glands)

o   Swine:  Solid and amphophilic

o   Other species:  Granular, small and multiple in the affected nucleus

·       Cerebellar cortex:  Leptomeningitis, Purkinje and granule cell necrosis, glial shrubbery (clustering of microglial cells around necrotic Purkinje cells or their dendrites)

·       Affects primarily the cerebral and cerebellar cortices; lesions anywhere in the brain and to a lesser degree the spinal cord

·       Perivascular cuffing with lymphocytes and plasma cells

·       Epitheliotropic lesions: Tiny areas of coagulative or lytic necrosis in liver, tonsil, lung, spleen, placenta, adrenals

·       Multifocal necrosis and inflammation of visceral and lymphoid organs in young pigs and aborted fetuses

 

ULTRASTRUCTURAL FINDINGS:

·       Nucleocapsid: 105-110 nm in diameter; enveloped nucleocapsid:150-180 nm in diameter, icosahedral

 

ADDITIONAL DIAGNOSTIC TESTS:

·       Serum neutralization, ELISA, fluorescent antibody

·       Immunochromatographic strips using glycoprotein gB

 

DIFFERENTIAL DIAGNOSIS: 

For histological lesions:

Swine:

·       Rabies (rhabdovirus):  Rare in pigs; perivascular cuffing, Negri bodies

·       Viral encephalomyelitis of pigs (Teschen disease) (Picornaviridae, teschovirus):  No gross lesions; nonsuppurative encephalomyelitis of predominantly the gray matter

·       Classical swine fever (Flaviviridae, pestivirus): Splenic infarction, hemorrhagic lymph nodes, tonsillar necrosis, renal petechial and ecchymotic hemorrhages, subcutaneous and serosal hemorrhage

·       African swine fever (Asfarviridae):  Vasculitis, edema, and hemorrhage

·       Bacterial:  Streptococcus suis and Haemophilus parasuis (Glasser's disease)

·       Salt poisoning:  Abundant eosinophils expanding the meninges and Virchow-Robin space

·       Porcine hemagglutinating encephalomyelitis virus (Coronaviridae):  Nonsuppurative meningoencephalomyelitis, neuronal degeneration

 

Cattle:

·       Rabies:  Negri bodies in cytoplasm of Purkinje cells

·       Polioencephalomalacia :  Prominent cerebral cortical necrosis

·       Lead toxicity:  Laminar cortical necrosis

 

COMPARATIVE PATHOLOGY:

·       Feral swine: in U.S., 18% positive for Ab; in 25 of 35 states in 2012

·       Dog and cat:  Clinically similar to cattle; ptyalism; sudden death without premonitory signs or following a brief clinical course

·       Herpesviruses associated with encephalitides include:  Equine herpesvirus-1, Bovine herpsesvirus-1 and 5, and Canine herpesvirus

·       Simian herpesvirus B (cercopithecine herpesvirus-1) can cause fatal encephalitis in humans, rabbits, and some mice

·       The rabbit is the most sensitive laboratory animal and is often used for virus identification via subcutaneous inoculation and subsequent development of intense local pruritis

 

References:

1.      Ardans A. Herpesviridae. In: Hirsch D, Zee Y eds., Veterinary Microbiology.  Malden, MA: Blackwell Science; 1999:350-363.

2.      Cantile C, Youssef S. Nervous system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA: Elsevier Saunders; 2016:370-372.

3.      Cramer SD, Campbell GA, Njaa BL, et al.  Pseudorabies virus infection in Oklahoma hunting dogs.  J Vet Diagn Invest. 23(5):915-923.

4.      Knowles DP. Herpesvirales. In: MacLachlan NJ, Dubovi EJ, eds. Fenner’s Veterinary Virology. 4th ed. San Diego, CA: Academic Press; 2011:193-195.

5.      Miller AD, Zachary JF. Nervous system. In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Mosby Elsevier; 2016:889.

6.      Pedersen K,Bevins SN,Baroch JA, Cumbee JC. et al. Pseudorabies in feral swine in the United States, 2009-2012, J Wildl Dis. 2013; 49(3): 709-713.

7.      Pejsak Z, Truszczynski M. Aujeszky’s disease (Pseudorabies). In: Straw B, Zimmerman J, D'Allaire S, Taylor D, eds. Diseases of Swine. 9th ed. Ames, IA: Blackwell Publishing; 2006:419-433.

8.      Radostits OM, Gay CC, Constable PD, Hinchcliff KW. Veterinary Medicine. 9th ed. Philadelphia, PA: Elsevier; 2007:1394-1404.

9.      Schoeniger S, Klose K, Werner H, Schwarz B.-A, Mueller T, and Schoon H.-A.  Nonsuppurative encephalitis in a dog.  Vet Pathol 2012;49(4):731-734.

10.   Summers B, Cummings J, de Lahunta A. Veterinary Neuropathology. St. Louis, MO: Mosby; 1995:99-100.

11.   Xiujie L, Yaning S, Suzhen Y,Yinbiao W, et al. Development of an immunochormatographic strip for antibody detection of pseudorabies virus in swine. J Vet Diagn Invest. 2015, 27(6): 739-742.

12.   Zachary JF.  Mechanisms of microbial infections.  In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Mosby Elsevier; 2017:224-225.

 

 

 


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