JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

March 2023

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 forming areas of cavitation (liquefactive necrosis). Adjacent to areas of cavitation, small caliber blood vessels are closely apposed (stromal collapse) and surrounded by vacuolated, fragmented neuroparenchyma and high numbers of glial cells, including reactive astrocytes (gemistocytes) and moderate numbers of microglial cells (gliosis). At the periphery of the cavitated areas, the gray matter contains scattered shrunken neurons with hypereosinophilic cytoplasm and karyolysis or nuclear loss (necrosis). Multifocally, Virchow-Robins space is mildly expanded by low numbers 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; Soremuzzle

 

GENERAL DISCUSSION:

• Bluetongue is a vector-borne viral hemorrhagic fever disease of ruminants, particularly sheep, that causes hydranencephaly and porencephaly in lambs and calves
  • 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) varies 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:

 

ADDITIONAL DIAGNOSTIC TESTS:  

 

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
  • Recent report in cattle; placentitis and PI calves (Fernandez, Vet Pathol. 2018) 
• 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
  • Recent report of an outbreak in young lambs in South Africa in which the only CNS lesion was mild to moderate edema (hydranencephaly not reported); the most striking lesion was diffuse necrotizing hepatitis with foci of liquefactive hepatic necrosis; other characteristic lesions in spleen, kidney, and lungs (Odendaal, Vet Pathol. 2020)
• 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
  • Recent report of an outbreak of EHDV serotype 6 in cattle in Israel (Golender, J Vet Diagn Invest. 2017)

 

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. Allen AJ, et al. Bluetongue disease and seroprevalence in South American camelids from the northwestern region of the United States. J Vet Diagn Invest. 2015;27(2):226-230.
2. Anjaneya A, Singh, KP, Cherian S, et al. Comparative neuropathology of Major Indian Bluetongue virus serotypes in neonatal BALB/c muse model. J Comp Pathol. 2018;162:18-28. 
3. Cantile C, et al.  Nervous system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6^th ed. Philadelphia, PA: Elsevier Saunders; 2016:281. 
4. 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.
5. Fernandez M, Braun U, Frei S, Schweizer M, Hilbe M.   Border disease virus infection of bovine placentas.  Vet Pathol. 2018;55(3):425-433.
6. Golender N, Khinich Y, Gorohov A, Abramovitz I, Bumbarov V.  Epizootic hemorrhagic disease virus serotype 6 outbreak in Israeli cattle in 2015.  J Vet Diagn Invest. 2017;29(6):885-888.
7. 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.
8. 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. 
9. Laguardia-Nascimento M, et al. Detection of multiple viral infections in cattle and buffalo with suspected vesicular disease in Brazil. J Vet Diagn Invest. 2016; 28(4):377-381.
10. Odendaal L, Davis AS, Fosgate GT, Clift SJ.   Lesions and cellular tropism of natural Rift Valley Fever Virus infection in young lambs.  Vet Pathol. 2020;57(1):66-81.
11. 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.
12. Vandevelde M, et al. Veterinary Neuropathology. Ames, IA: Wiley-Blackwell; 2012: 97, 98.
13. Vinueza R, Cruz M, Breard E, Viarouge C, Zanella G. Bluetongue virus and epizootic hemorrhage disease virus survey in cattle of Galapagos Islands. J Vet Diagn Invest.2019;31(2):271-275.
14. 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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