JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

April 2026

N-V02 (NP)

Signalment (JPC #1446702): Two near-term ovine fetuses

HISTORY: Both of these animals were from a flock in which adults of both sexes were ill and there had been several deaths. Abortions had occurred, and many ewes had given birth to small weak lambs.

HISTOPATHOLOGIC DESCRIPTION: Cerebrum: Diffusely, gyri are markedly thinned, and multifocally the white matter and deep gray matter are lost, often f of lymphocytes and plasma cells (perivascular cuffing).

Tongue: Essentially normal tissue.

MORPHOLOGIC DIAGNOSIS:

1. Cerebral cortex, white and deep gray matter: Necrosis and loss, acute, multifocal, marked, with gliosis and mild perivascular lymphoplasmacytic cuffing, breed unspecified, ovine.
2. Tongue: No significant lesions.

ETIOLOGIC DIAGNOSIS: Orbiviral encephalopathy

CAUSE: Ovine orbivirus; Bluetongue virus (BTV)

CONDITION: Bluetongue; Sore muzzle

GENERAL DISCUSSION:

• Bluetongue is a vector-borne viral hemorrhagic fever disease of ruminants, particularly sheep, that causes hydranencephaly and porencephaly in lambs and calves
  • Hydranencephaly = missing large portions of the brain, specifically the cerebral hemispheres
    • considered a severe form of porencephaly
  • Porencephaly = cysts or fluid filled cavities form inside the brain
    • Typically a single cavity in a cerebral hemisphere that typically communicates with the subarachnoid space, but it can also communicate with a lateral ventricle
  • Goats and adult cattle are largely asymptomatic
• Family Reoviridae, genus Orbivirus, nonenveloped, double stranded RNA virus; over 26 recognized serotypes with considerable genetic variation among strains

PATHOGENESIS:

• Biting midges (Culicoides sp.) are the main biological vector; vertical and oral transmission rarely occur
• Culicoides sp. (biting midge, gnat) ingests infected blood meal > virus replicates and infects salivary glands 10-15 days post-ingestion > Culicoides sp. bites sheep > virus replicates in regional lymph nodes > infects and travels within monocyte/macrophage system > viremia > virus infects and replicates in endothelial cells throughout body > endothelial cell damage > vasculitis > hemorrhage, edema, thrombosis > infarction, necrosis, and ulceration of mucosal surfaces
  • Necrosis of the precursor cells in the subventricular zone, which are essential in the formation of the cerebral cortical white matter > cavitation
• Two attachment proteins, capsid structural proteins VP2 and VP5, bind glycosaminoglycans in target cell membranes and facilitate attachment and penetration of virus into macrophages
• Congenital bluetongue occurs in lambs and calves when the dam receives a live, attenuated bluetongue virus vaccine or contracts bluetongue infection during pregnancy
• Type of congenital CNS anomaly depends on fetal age at time of inoculation or infection

TYPICAL CLINICAL FINDINGS:

• Lethargy, circling, head pressing, blindness-loss of normal pupillary light reflexes
• Hypermetria and spasticity if cerebellum is affected

TYPICAL GROSS FINDINGS:

• Congenital anomalies (lambs) vary with stage of gestation that the dam is infected:
  • < 50 days: Fetal absorption or abortion
  • 50 - 55 days: Hydranencephaly and retinodysplasia
  • 75 days: Porencephalic cysts (no ocular lesions)
  • > 100 days: Mild focal meningoencephalitis
• Bluetongue viral infection of fetal calves can cause hydranencephaly
• Systemic bluetongue: Focal hemorrhage of the tunica media at the base of the pulmonary artery, hemorrhage of the ruminal pillars, tongue cyanosis, erosions and ulcers of oral mucosa, laminitis, coronitis, skeletal and cardiac muscle hemorrhage, edema and necrosis

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Lambs infected at 50 - 55 days gestation: Severe necrotizing encephalopathy and retinopathy
• At 75 days gestation: Multifocal encephalitis, vacuolation of white matter, formation of a porous cavity lined by astrocytes and hemosiderin-laden macrophages
• At 100 days gestation: Focal mild meningoencephalitis
• Systemic: Vasculitis, myofiber necrosis, and hemorrhage

ULTRASTRUCTURAL FINDINGS:

• Virions in the cytosol are icosahedral, nonencapsulated, approximately 75 nms in diameter; inner electron-dense core of 45 nms surrounded by an inner shell

ADDITIONAL DIAGNOSTIC TESTS:

• ELISA, AGID, complement fixation, PCR

DIFFERENTIAL DIAGNOSIS:

Causes of hydrancephaly and porencephaly in sheep:

• Border disease virus (Flaviviridae, Pestivirus): Hypomyelinogenesis, porencephaly, hydranencephaly, cerebellar hypoplasia, microencephaly of lambs and goat kids
• Cache valley virus (Bunyaviridae, Otrhobunyavirus): Hydranencephaly, microencephaly, cerebellar hypoplasia, absent ventral horn neurons in spinal cord of lambs in U.S.
• Copper deficiency (N-T04, Swayback, enzootic ataxia): Can cause porencephaly in lambs
• Akabane disease (Bunyaviridae, Orthobunyavirus): Porencephaly, hydranencephaly, ventral horn neuronal degeneration in spinal cord of ruminants; Japan, Australia, and Israel
• Rift valley fever virus (D-V18, Bunyaviridae, Phlebovirus): Hydranencephaly of lambs in Africa
• Wesselsbron disease (Flaviviridae, Flavivirus): Hydranencephaly of lambs in Africa
• Schmallenberg virus (Bunyaviridae, Orthobunyavirus): Hydranencephaly, porencephaly, hydrocephalus, cerebellar hypoplasia, and micromyelia in calves, goat kids, and lambs
• Deer, antelope, elk: Epizootic hemorrhagic disease virus (EHDV, C-V03) (Reoviridae, Orbivirus): Causes lesions similar to bluetongue, but often does not result in coronitis

COMPARATIVE PATHOLOGY:

• Numerous domestic livestock (cattle, goats) and wildlife species are serologically positive for BTV yet are usually subclinical or have minimal clinical signs
• Cervid orbiviruses include BTV and EHDV – Hemorrhage at the base of the pulmonary artery is a near-pathognomonic lesion for these viral infections
• Captive Eurasian lynx - BTV serotype 8 has been associated with disease in lynx fed stillborn or aborted fetuses from BTV-infected farms; lesions include those of vasculitis; free-ranging felids have evidence of infection but not disease

References:

1. Cantile C, Miller AD, Youssef S. Nervous System. In: Maxie MG, ed. Jubb, Kennedy & Palmer's Pathology of Domestic Animals. Vol 1. 7th ed. St. Louis, MO: Elsevier; 2026:273, 280.
2. Cheville NF, et al. Cytopathology of Viral Diseases. In: Cheville NF, ed. Ultrastructural Pathology: The Comparative Cellular Basis of Disease. 2nd ed. Ames, IA: Wiley-Blackwell; 2009:377.
3. Howerth EW, Nemeth NM, Ryser-Degiorgis, M. Cervidae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. Cambridge, MA: Elsevier; 2018:159-161.
4. Jones, MEB, Gasper DJ, Mitchell E. Bovidae, Antilocapridae, Giraffidae, Tragulidae, Hippopotamidae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. Cambridge, MA: Elsevier; 2018:128.
5. Terio KA, McAloose D, Mitchell E. Felidae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. Cambridge, MA: Elsevier; 2018:274.
6. Vandevelde M, et al. Veterinary Neuropathology. Ames, IA: Wiley-Blackwell; 2012:97, 98.
7. Zachary JF. Mechanisms of microbial infections. In: Zachary JF, eds. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Mosby Elsevier; 2022:920.

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