April 2017



Signalment (JPC 2332604):  Four-month-old male pygmy goat


HISTORY:  This goat presented afebrile with posterior paresis and ataxia.  The paresis progressed to the front limbs.


HISTOPATHOLOGIC DESCRIPTION:  Brainstem, mesencephalon:  Multifocally affecting the submeningeal white matter and, to a lesser extent, the paraventricular region with multifocal disruption of the ependymal lining, are foci of necrosis with loss of neuropil and replacement by numerous gitter cells, reactive astrocytes, few lymphocytes, many variably sized acicular cholesterol clefts, and scattered eosinophilic cellular and karyorrhectic debris.  Myelin sheaths are multifocally lost, dilated and empty, or contain eosinophilic debris and degenerate macrophages (digestion chambers).  Adjacent Virchow-Robin spaces are moderately expanded by mononuclear inflammatory infiltrate composed of lymphocytes and macrophages, and to a lesser extent, the meninges are multifocally expanded a similar inflammatory infiltrate.  Adjacent capillaries are lined by reactive endothelium.


MORPHOLOGIC DIAGNOSIS:  Brainstem, mesencephalon:  Leukoencephalitis, necrotizing, lymphohistiocytic, paraventricular and submeningeal, multifocal, moderate, with demyelination, reactive astrocytosis, and gliosis, pygmy goat, caprine.


ETIOLOGIC DIAGNOSIS:  Lentiviral leukoencephalitis


CAUSE: Small ruminant lentivirus (caprine arthritis-encephalitis virus)


CONDITION:  Caprine arthritis-encephalitis



·       Caprine arthritis encephalitis virus (CAEV) of goats and visna-maedi virus (VISNA) of sheep are small-ruminant lentiviruses (SRLV)in the family Retroviridae; enveloped, single-stranded RNA; some strains of virus affect both species and there is viral overlap especially in gag and pol genes

O       Lentiviruses are nononcogenic retroviruses that cause chronic progressive disease with long incubation periods and persistent infection; SRLVs do not cause immunosuppression like other lentiviral infections

O       CAEV is SRLV subgroup B

O       VISNA is SRLV subgroup A

·       SRLVs have the following viral genes:

O       pol – encodes reverse transcriptase and other enzymes

O       gag – encodes for group-specific nucleocapsid & matrix glycoproteins; detected by antibody-based tests

O       env – encodes for surface glycoprotein that mediates receptor binding and virus entry into cells; target for neutralizing antibody

O       vif, rev, and tat – encodes for regulatory proteins

·       The virus causes four clinical syndromes; a single animal can show multiple forms but typically one syndrome predominates in endemic situations:

1.     Arthritis: In many herds this is the only clinical manifestation of infection; typically affects adult goats (see M-V02)

2.     Encephalomyelitis: Occurs in young goats 2-4 months old; visna in sheep (affects sheep over 2 years old)

3.     Mastitis:  Frequent subclinical lesion, not typically clinical

4.     Interstitial pneumonia: Maedi, or ovine progressive pneumonia (see P-V18)

·       Nervous and articular forms are typically observed in goats

·       Pulmonary, mammary, and nervous forms are the most common in sheep

·       Young goats (<4-6 months):  Neurological disease with ascending paralysis and nonsuppurative leukoencephalomyelitis and often interstitial pneumonia

·       Adult goats:  Animals that survive the initial infection later develop chronic, nonsuppurative arthritis and synovitis (most common presentation), mastitis (usually subclinical), and chronic interstitial pneumonia (usually subclinical)



·       Transmission: 1) to kids via infected macrophages in milk and colostrum (most common), 2) adult to adult aerosol spread (less common in goats; more common in Maedi-Visna of sheep), and 3) in utero transmission (rare/never) à virus likely infects mucosal dendritic cells à virus to regional lymph node àvirus enters macrophages likely via mannose receptor àspread to monocyte precursor cells in the bone marrow àmigration to regional lymph nodes and hematogenous dissemination mainly to lung, mammary gland, CNS, and joints à dysregulation of cytokines produced by infected macrophages and lymphocytes results in lymphoid recruitment (IL-16 expression increased; TNF alpha, IL-1 beta, IL-6, and IL-12 expression are all reduced)

·       The virus can infect a variety of cell types including choroid plexus, mammary epithelium, fibroblasts, endothelial cells, and monocytes; however, it only replicates well in mature macrophages; the virus is activated when monocytes mature into macrophages

·       Clinical disease often doesn’t become apparent until several years later

·       Persistent viral infection of macrophages, microglia, monocytes, and dendritic cells

·       Most goats naturally infected with CAEV are asymptomatic but remain life-long carriers, excreting virus into the environment via colostrum, milk, and respiratory secretions

·       Proinflammatory cytokines from concurrent infection with other pathogens hasten disease onset

·       Altered organ function is due to the immunoinflammatory response rather than direct viral effect



·       Most infected goats are asymptomatic

·       CNS disease occurs in young goats (<4 month old) and is frequently fatal

·       Neurologic signs are due to motor spinal dysfunction without signs of cerebral disease, i.e. initial hindlimb lameness and ataxia with paresis that progresses to paralysis over several weeks

·       Mature adults:

O       Arthritis:  Lameness, joint effusion, enlarged carpal joints, high prevalence of carpal hygromas

O       Interstitial pneumonia:  Dyspnea and coughing, cachexia

O       Mastitis:  Udder firm, swollen; reduced milk production

·       CSF lymphocytosis, pleocytosis, increased protein; clinical course corresponds to degree of CSF lymphocytosis



CNS lesions:

·       Typically no gross lesions

·       If present: foci of yellow-white malacia distributed at random in the CNS, especially the spinal cord

Other lesions:

·       Joints:  Chronic proliferative arthritis/synovitis of carpal, stifle, hock joints

·       Lung:  Interstitial pneumonia most severe in caudal lobes

·       Mammary gland:  Indurative mastitis (“hard udder”), agalactia



For CNS lesions:

·       Chronic inflammation and demyelination primarily involving the white matter (unlike other neurotropic viruses)

·       Early inflammatory CNS lesions:

O       Intense mononuclear/lymphohistiocytic inflammation of the white matter  (leukoencephalomyelitis) with mononuclear perivascular cuffing (more prominent in kids than sheep) and gliosis; mononuclear infiltrates may form tertiary lymphoid follicles in the choroid plexus

O       Lesions begin in and just beneath the ependyma

O       Myelin remains relatively intact even within inflammatory foci at this time

O       Spinal cord grey matter may have irregular but intense nonsuppurative inflammation

·       Later inflammatory CNS lesions, in paralytic and terminal animals:

O       Periventricular destruction of white matter of cerebrum and cerebellum; almost all white matter may be destroyed, leaving the grey matter relatively free of lesions

O       Inflammatory lesions may persist for years in goats that survive

·       Demyelination leading to malacia: 

O       Mild to severe myelin destruction principally involving the white matter  especially of the spinal cord (most severe from mesencephalon caudally), resulting in “myelinoclastic lesions”

O       Patchy, asymmetrical, characteristically peripheral, triangular shaped demyelinated plaques with base on the pia mater; contain numerous reactive astrocytes and microglia

O       Spinal nerve roots also affected

O       Evidence of remyelination can be found

O       Not caused by progressive spread of pericentral inflammation

Other lesions:

·       Joints:  Lymphoplasmacytic arthritis, synovial cell hyperplasia, villus hypertrophy

·       Lung:  Interstitial pneumonia, diffuse in sheep but multifocal well demarcated in goats, with pronounced lymphoid hyperplasia that may form lymphoid nodules with germinal centers, type II pneumocyte hyperplasia (mild in sheep, marked in goats), filling of alveoli with proteinaceous material

·       Mammary gland:  Lymphocytic infiltrates and follicles, plasma cells, and macrophages in the mammary interstitium



·       Demyelination with macrophages stripping myelin from axons



·       Serology (AGID or ELISA): useful for herd-level diagnosis; can be performed on bulk tank milk

·       Immunohistochemistry: antigen is typically within macrophages in lesions

·       PCR of blood, milk, or tissue

·       Virus isolation



Other CNS disease in goats:

·       Copper deficiency (enzootic ataxia, swayback):  Axonal degeneration and demyelination of lateral (dorsal aspect) and ventral (ventromedial aspect) funiculi of spinal cord

·       Rabies (lyssavirus):  Nonsuppurative encephalomyelitis; Negri bodies

·       Listeria monocytogenes:  Affinity for brainstem; microabscesses, vasculitis

·       Neuronal vacuolar degeneration of Angora goats:  Scrapie-like neuronopathy in young Angora goats in Australia



·       Other Lentiviruses:

O       Equine infectious anemia virus (EIA)

O       Feline immunodeficiency virus (FIV)

O       Bovine immunodeficiency virus (BIV)

O       Simian immunodeficiency virus (SIV)

O       Human immunodeficiency virus (HIV)



1.      Barrero Dominguez BB, Luque I, Maldonado A, Huerta B, Sanchez M, Gomez Laguna J, Astorga R.  Seroprevalence and risk factors of exposure to caprine arthritis-encephalitis virus in southern Spain.  Vet Record.  2017;180(9):226.

2.      Cantile C, Youssef S. Nervous system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier; 2016:378-379.

3.      Caswell JL, Williams KJ. Respiratory system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier; 2016:558-560.

4.      Constable PD, Hinchcliff KW, Done SH, Grunberg W.  Veterinary Medicine:  A Textbook of the Diseases of Cattle, Horses, Sheep, Pigs, and Goats, Vol 2.  11th ed.  St. Louis, MO: Elsevier; 2017: 1252-1256.

5.      Craig LE, Dittmer KE, Thompson KG. Bones and joints. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier; 2016:154-155.

6.      Foster, R.  Female reproductive system and mammae.  In:  Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Mosby, Inc.; 2017:1175, 1187.

7.      López A, Martinson SA.  Respiratory system, mediastinum, and pleurae.  In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Mosby, Inc.; 2017:537-538.

8.      Nagel-Alne GE, Valle PS, Krontveit R, Solverod LS.  Caprine arthritis encephalitis and caseous lymphadenitis in goats: use of bulk tank milk ELISAs for herd-level surveillance.  Vet Record.  2014;176(7):173.

9.      Patton KM, Bildfell RJ, Anderson ML, Cebra CK, Valentine BA. Fatal Caprine arthritis encephalitis virus-like infection in 4 Rocky Mountain goats (Oreamnos americanus). J Vet Diagn Invest. 2012;24(2):392-396.

10.   Pérez M, Biescas E, Reina R, Glaria I, Marin B, 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.

11.   Smith GW.  Weakness and/or depressed mentation.  In:  Manifestations and management of disease in neonatal ruminants.  In: Smith BP, ed.  Large Animal Internal Medicine, 5th ed.  St. Louis, MO: Elsevier-Mosby; 2015: 308

12.   Vandevelde M, Higgins RJ, Oevermann, A.  Veterinary neuropathology: essentials of theory and practice, 1st ed.  Ames, IA: Wiley-Blackwell; 2012:50, 58-59.

13.   Washburn K.  Caprine arthritis-encephalitis virus.  In:  Disorders of the organ systems.  In:  Smith BP, ed.  Large Animal Internal Medicine, 5th ed.  St. Louis, MO: Elsevier-Mosby; 2015:1100-1102.

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

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