AFIP SYSTEMIC PATHOLOGY

JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

April 2017

N-V13

 

Signalment (JPC: 1366104):  2.5‑year‑old Corriedale ewe

 

HISTORY:  Prior to death, a ewe from a small flock in Connecticut had a two-month history of a unilateral head tilt.

 

HISTOPATHOLOGIC DESCRIPTION: Cerebrum, thalamus:  Multifocally there are extensive areas of rarefaction and loss of neuropil (necrosis) within the periventricular white matter, with moderate numbers of gitter cells, lymphocytes, rare plasma cells and minimal hemorrhage. Multifocally myelin sheaths are lost with replacement by gitter cells (demyelination), or are markedly dilated (spongiosis) and contain swollen axons with hypereosinophilic axoplasm (spheroids). Adjacent gray matter contains increased numbers of astrocytes and microglial cells (reactive gliosis) and numerous vessels with hypertrophic endothelium (reactive) that are surrounded by variable numbers of macrophages, lymphocytes, and plasma cells expanding Virchow-Robin space (perivascular cuffing).  Multifocally within the gray matter and subependymal neuropil, there are few glial nodules, occasionally surrounding swollen or vacuolated (degenerate) neurons (satellitosis).  Moderate numbers of lymphocytes and plasma cells expand the subependymal neuropil and choroid plexus.

 

MORPHOLOGIC DIAGNOSIS:  Cerebrum, thalamus, white matter:  Demyelination and necrosis, multifocal, with gliosis, periventricular glial nodules, and choroiditis, Corriedale, ovine.

 

ETIOLOGIC DIAGNOSIS:  Lentiviral encephalitis

 

CAUSE:  Ovine lentivirus; Visna virus (VISNA)

 

CONDITION:  Visna-maedi disease complex

 

GENERAL DISCUSSION: 

·       Visna, a disease of sheep, is the neurological manifestation of visna-

maedi disease complex; visna almost always occurs with maedi

·       Visna (Icelandic for wasting) is an uncommon, insidious, fatal disease

·       Visna is caused by a small ruminant lentivirus (SRLV) of the family Retroviridae causing chronic encephalomyelitis in sheep

·       Highly variable positive-ssRNA viruses with genes:  gag (encodes nucleocapsid and matrix glycoproteins), pol (reverse transcriptase), env (surface glycoprotein that mediates receptor binding and entry into cells) and regulatory proteins encoded by vif, rev, tat genes

·       Viral infection is persistent and lifelong

·       Maedi-visna virus is closely related to caprine arthritis-encephalitis virus (CAEV) in goats which affects the nervous system of kids (2-4 months of age), frequently fatal; adult goats develop proliferative synovitis and mastitis; both young and old animals may develop an interstitial pneumonia

·       Maedi-visna disease complex causes any of the following in any combination:

·       Interstitial pneumonia (maedi and ovine progressive pneumonia)

·       Encephalomyelitis (visna of sheep)

·       Arthritis

·       Mastitis

 

PATHOGENESIS: 

·       Transmission primarily via colostrum, milk (ingestion) and respiratory droplets (inhalation)

  • Ovine lentivirus infects choroid plexus epithelium, fibroblasts, endothelial cells,  monocytes, and oligodendrocytes; circulating monocytes are the primary viral target; complete viral replication only occurs in mature macrophages
  • Viral antigenic drift enables evasion of host immune response

·       Prolonged incubation (up to 2 years)

  • Two basic lesions:

·       Inflammation which is not proportionate to the severity of clinical signs

·       Demyelination of brain and spinal cord, which is related to paresis; primary demyelination due to oligodendrocyte destruction

  • Lesions have been shown to be at least partially immune-mediated as well as due to direct destructive effect of virus

 

TYPICAL CLINICAL FINDINGS: 

·       Earliest signs: Caudal ataxia and trembling of the lips

·       Afebrile; progressive posterior ataxia and extensor paralysis and tetraplegia

·       Death from starvation (wasting) or secondary infection

·       Once paralytic signs develop, death is certain

·       Marked lymphocytosis within the CSF

·       Elevated protein in the CNS

 

TYPICAL GROSS FINDINGS: 

·       Often no gross CNS lesions

 

TYPICAL LIGHT MICROSCOPIC FINDINGS: 

·       Patchy demyelinating encephalomyelitis involving primarily the white matter

·       Early lesions are intensely inflammatory with perivascular cuffing and gliosis

·       Mononuclear cerebrospinal meningitis

·       In terminal stages of the disease, the periventricular destruction of the white matter in the cerebrum and cerebellum is extensive; in some sections of the brain, especially in the cerebellum, almost all white matter is destroyed leaving the gray matter free

·       The demyelinated plaques are characteristically peripheral and triangular in shape with a base on the pia mater

·       Dorsal and lateral tracts are most often involved; yet there is no selectivity for particular fiber tracts and no symmetry

·       Germinal centers may form in the choroid plexus

 

ULTRASTRUCTURAL FINDINGS: 

·       Difficult to identify virus particles via EM (most of the virus is present as a provirus)

 

ADDITIONAL DIAGNOSTIC TESTS: 

·       ELISA (most sensitive)

·       AGID (agar-gel immunodiffusion), IF (immunofluorescence), CF (complement fixation)

 

DIFFERENTIAL DIAGNOSIS: 

Progressive ataxia:

·       Rabies: Presence of cytoplasmic Negri bodies

·       Pseudorabies: Intranuclear inclusion bodies in neurons and astroglia

·       Scrapie: Demonstration of scrapie prion by immunostaining; no pleocytosis of cells in the CNS; spongiform encephalopathy

·       Copper deficiency (enzootic ataxia, swayback): Demyelinating disease of young lambs

 

COMPARATIVE PATHOLOGY: 

Other lentiviruses of the family Retroviridae:

·       CAEV (caprine arthritis encephalitis virus)

·       HIV, SIV, FIV, BIV (human/simian/feline/bovine immunodeficiency virus)

·       EIA (equine infectious anemia virus)

 

References: 

1.      Brellou GD, et al. Detection of maedi-visna virus in the liver and heart of naturally infected sheep. J Comp Pathol. 2007;136(1):27-35

2.      Cantile C, et al.  Nervous system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA: Elsevier Saunders; 2016: 378-380.

3.      Hudachek SF, et al. Lung tumor development and spontaneous regression in lambs coinfected with Jaagsiekte sheep retrovirus and ovine lentivirus. Vet Pathol. 2010;47:162.  

4.      Masters NJ, et al. Tragulidae, moschidae, and cervidae. In: Miller RE, et al, eds. Fowler’s Zoo and Wild Animal Medicine. Vol 8. St. Louis, MO: Elsevier Saunders; 2015: 617-620.

5.      Middleton JR. Cerebral disorders of the adult ruminant. Vet Clin Food Anim. 2017; 33: 43-57

6.      Pérez M, et al. Small ruminant lentivirus-induced arthritis: Clinicopathologic findings in sheep infected by a highly replicative SRLV B2 genotype. Vet Pathol. 2015; 52(1):132-139.

7.      Pinczowski P, et al. Small ruminant lentiviruses in sheep. Vet Pathol. 2017; doi: 10.1177/0300985816688742.

8.      Polledo L, et al. Patterns of lesion and local host cellular immune response in natural cases of ovine maedi-visna. J Comp Pathol. 2012; 147(1): 1-10.

9.      Vandevelde M, et al. Veterinary Neuropathology. Ames, IA: Wiley-Blackwell; 2012: 59, 63.

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

 


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