JPC SYSTEMIC PATHOLOGY
NERVOUS SYSTEM
April 2023
N-V16 (NP)
Signalment (JPC #1902458): Weaner pig
HISTORY: These pigs were purchased for rearing. Seven days after arrival on the farm, 27 of the pigs had high fever, anorexia, and cutaneous hyperemia. Most of the pigs died 7-12 days later.
HISTOPATHOLOGIC DESCRIPTION: Cerebrum and diencephalon: Multifocally, blood vessels within the gray matter, white matter, meninges, and the choroid plexus are surrounded by moderate numbers of lymphocytes, macrophages, plasma cells, and a small amount of karyorrhectic and cellular debris (necrosis) that occasionally extends into surrounding neuroparenchyma. Frequently these vessels are characterized by discontinuity of the endothelium and expansion of the tunica media by fibrillar eosinophilic material (fibrin), previously described inflammatory cells, and a mild amount of necrotic debris (vasculitis). These vessels are also surrounded by increased clear space (edema). There are multifocal glial nodules (gliosis) within both grey and white matter, and increased numbers of reactive astrocytes (astrocytosis). Less affected blood vessels are often lined by hypertrophied (reactive) endothelium.
MORPHOLOGIC DIAGNOSIS: Cerebrum and diencephalon: Meningoencephalitis, lymphoplasmacytic and histiocytic, perivascular, multifocal, mild, with vasculitis, gliosis, and glial nodules, breed not specified, porcine.
ETIOLOGIC DIAGNOSIS: Pestiviral meningoencephalitis
CAUSE: Porcine pestivirus
CONDITION: Classical swine fever, hog cholera
CONDITION SYNONYMS: Schweinpest, peste du porc, peste svina
GENERAL DISCUSSION:
- A highly contagious, fatal hemorrhagic disease caused by a small, enveloped ssRNA virus belonging to the genus Pestivirus (Flaviviridae)
- Peracute, acute, subacute, chronic, and persistently infected forms, as well as teratogenic effects in fetal piglets
- Morbidity and mortality ranges from almost none to 100% depending on strain virulence, which varies widely
- High, moderate, or low virulence strains
PATHOGENESIS:
- Virus is transmitted by direct contact with infected animals, usually by the oronasal route, or indirect contact with food, feces, carcasses, and arthropods
- Virus is eliminated in urine, feces, lacrimal and oronasal secretions, and in semen of infected boars
- Highly virulent strains of CSFV in small populations of wild boars can be self-limiting
- Naïve populations are infected by indirect or direct contact with infected domestic pigs or wild boars
- Prime viral targets are monocytes and macrophages, but also epithelial cells, endothelial cells, lymphocytes, neutrophils, fibroblasts and megakaryocytes
- Pathogenesis is incompletely understood, but involves cytopathic effects of virus on the lymphoreticular cells and macrophages, the vascular endothelium, and epithelial cells
- Virus enters through mucous membranes, replicates in tonsillar epithelium & macrophages > spreads to cervical lymph nodes > release of chemical mediators > tissue damage (lymphoid depletion, epithelial necrosis, etc.)
- Necrosis of endothelium > thrombocytopenia and consumption coagulopathy > DIC and hemorrhage
- Persistent infection can occur (similar to BVDV)
- Teratogenic effects if piglets are infected in utero in days 10-97 of gestation due to selective inhibition of cell division
- Hypoplasia and dysplasia of cerebellum and CNS hypomyelinogenesis – “congenital tremor syndrome”
- Microencephaly
TYPICAL CLINICAL FINDINGS:
- Acute – Sudden death, depression, anorexia, lethargy, fever, leukopenia, thrombocytopenia, vomiting, diarrhea, cutaneous erythema and hemorrhage, nervous signs, conjunctivitis
- Subacute and chronic – Emaciation, cutaneous erythema and hemorrhage, alopecia, dermatitis, diarrhea
- In utero infections may result in abortion, stillbirth or mummified fetuses, or congenital tremors type A1 (due to cerebellar hypoplasia and hypomyelinogenesis)
TYPICAL GROSS FINDINGS:
- Acute
- Hemorrhages in peripheral lymph nodes
- Renal petechia
- Splenic infarction
- Subacute and chronic
- "Button ulcers" within the intestinal tract, lymphoid depletion, hemorrhage and petechiation
- Necrotizing and ulcerative enteritis, suppurative rhinitis, pneumonia
- In utero infection
- Cerebellar hypoplasia, other congenital abnormalities
- Abortion, stillbirths, and mummified fetuses
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Central nervous system
- Nonsuppurative meningoencephalitis with vasculitis and perivasculitis
- Perivascular cuffs
- Other tissues
- Fibrinoid necrosis, vasculitis, hemorrhage (primarily vessels in lymph nodes)
- Fibrin thrombi and infarction (commonly spleen)
- Lymphoid necrosis and depletion
ULTRASTRUCTURAL FINDINGS:
- Virions bud from the membranes of the endoplasmic reticulum and are spheroidal, enveloped, and 40-50 nm in diameter
- There are fringelike projections of 6-8 nm on the virion surface
ADDITIONAL DIAGNOSTIC TESTS:
- The direct immunofluorescence test in frozen tissue sections (usually tonsil)
- Neutralization peroxidase-linked assay, fluorescent antibody virus neutralization, and ELISA
- CSFV antigen can be detected in formalin-fixed tissue by semi-nested RT-PCR or in situ hybridization
- RT-PCR can be used to detect CSFV antigen in serum from live pigs, and meat juice and skeletal muscle from both live and dead pigs (lower diagnostic sensitivity than serum)
DIFFERENTIAL DIAGNOSIS:
For microscopic findings (non-suppurative meningoencephalitis in pigs):
- African swine fever (asfarvirus) - Similar lesion to those of porcine pestivirus
- Pseudorabies/Aujeszky's disease (N-V07, porcine herpesvirus type 1) – Non-suppurative meningoencephalomyelitis with ganglioneuritis, usually has intranuclear inclusion bodies
- Water deprivation/salt toxicity (N-T08) – Laminar cerebrocortical neuronal necrosis with perivascular eosinophilic cuffs in the leptomeninges
- Teschen disease (N-V04, porcine enterovirus) – Non-suppurative polioencephalomyelitis
- Porcine hemagglutinating encephalomyelitis virus (porcine coronavirus) –Non-suppurative meningoencephalomyelitis and neuronal degeneration
- Rabies (N-V06, rhabdovirus) – Non-suppurative encephalomyelitis with perivascular lymphocytic cuffing, gliosis and Negri bodies
- Swine vesicular disease (porcine enterovirus) – Non-suppurative encephalomyelitis; vesicles on hoofs, snout, and oral cavity
- Encephalomyocarditis virus (C-V02, picornavirus) – Usually sudden death due to myocarditis; a minority of pigs will also have non-suppurative meningoencephalitis
For gross finding, intestinal button ulcers:
- Salmonella Cholerasuis – infection is often closely associated with CSF, recovered from 10-50% of cases of CSF
COMPARATIVE PATHOLOGY:
- Other Pestiviruses – Bovine viral diarrhea (N-V01, bovine pestivirus) and border disease (ovine pestivirus) also can cause in utero infection, persistent viremia, and congenital abnormalities
References:
- Stanton JB, Zachary JF. Mechanisms of Microbial Infections. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:261-262.
- Martinez MAJ, Gasper DJ, Mucino MCC, Terio KA. Suidae and Tayassuidae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:213.
- Miller AD, Porter, BF. Nervous System. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:925.e2, 946.
- Robinson WF, Robinson NA. Cardiovascular system. In: Maxie MF, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol. 3, 6th ed. St. Louis, MO: Elsevier; 2016:77-78.
- Uzal FA, Plattner BL, Hostetter JM. Alimentary system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. Philadelphia, PA: Elsevier Saunders; 2016:170-173.
- Valli VEO, Kiupel M, Bienzle D. Hematopoietic system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol. 3, 6th ed. St. Louis, MO: Elsevier; 2016:178-181.