AFIP SYSTEMIC PATHOLOGY

JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

April 2017

N-V09

 

Signalment (JPC #2841678):  4-year-old Tennessee walking horse gelding

 

HISTORY:  This horse exhibited severe lethargy that rapidly progressed to recumbency.

 

HISTOPATHOLOGIC DESCRIPTION:  Cerebrum:  Multifocally, Virchow Robin space is moderately expanded by lymphocytes, plasma cells, and fewer neutrophils admixed with moderate edema.  This inflammatory infiltrate and numerous glial cells (gliosis) often extend into the surrounding neuropil.  The leptomeninges are expanded up to 3 times normal by a similar inflammatory infiltrate admixed with scant eosinophilic cellular and karyorrhectic debris, eosinophilic fibrillar material (fibrin), mild hemorrhage, and increased clear space (edema). Inflammatory cells often surround individual neurons (satellitosis) which are either degenerate with central chromatolysis and vacuolation of the perikaryon, or are necrotic with shrunken, angular, eosinophilic cytoplasm and pyknosis.  Rarely, necrotic neurons are phagocytized by inflammatory cells (neuronophagia).   Within the white matter, there is mild spongiosis as well as rare swollen axons within dilated myelin sheaths (spheroids). Multifocally endothelium is hypertrophied (reactive) and there is margination of neutrophils in smaller vessels.

 

MORPHOLOGIC DIAGNOSIS:  Cerebrum:  Meningoencephalitis, perivascular, lymphoplasmacytic and neutrophilic, multifocal, moderate, with neuronal necrosis, satellitosis, and neuronophagia, Tennessee walking horse, equine. 

 

ETIOLOGIC DIAGNOSIS:  Alphaviral meningoencephalitis

 

CAUSE:  Eastern equine encephalitis virus

 

CONDITION:  Eastern equine encephalitis

 

GENERAL DISCUSSION:

·       Venezuelan, eastern, and western equine encephalitis viruses (VEE, EEE, WEE) are in the virus family Togaviridae, genus Alphavirus and transmitted between mosquitoes, birds, and rodents The virus cycles between reservoir hosts, water birds (EEE), wild birds (primarily passerines) (WEE), and rodents (VEE); horses and humans are incidental, dead end hosts that may develop encephalitis when infected

·       Outbreaks may involve humans only, horses only or both and may be limited to inapparent systemic infection or lethal encephalitis

·       Generally, WEE is less virulent for horses while EEE is often acutely fatal; VEE commonly occurs in epizootics that reoccur at approximately 10 year intervals

·       Target cell in the CNS is the neuron

 

PATHOGENESIS:

·       EEE:  Mosquito Culiseta melanura (ornithophilic species i.e. feeds on birds only)      > waterfowl; Aedes sp., Coquillettidia sp., Ochlerotatus sp.(bridge vectors) > horse and human transmission

·       WEE:  Mosquito Culex tarsalis (indiscriminate feeder) > primarily passerine birds

·       VEE:  Avirulent endemic form that cycles between Culex sp. mosquitoes and small rodents, birds and horses (titers not reached to infect vector mosquitoes) > disease produced after mutation of the virus > virulent epidemic strain causes disease >mutated strain reaches high titers in horses > become a major amplifying host in epizootics

·       Pathogenesis:  Initial viral replication in regional lymph nodes and blood vessels > primary viremia > secondary viremia with replication in muscle and lymph nodes > high viral titer > hematogenous dissemination > neuronal invasion, presumed to be via invasion of exposed nerve endings or neuromuscular junctions

 

TYPICAL CLINICAL FINDINGS:

·       Infections are more common in late summer and fall (mosquito season)

·       Young horses are more susceptible than old

·       Infection may be subclinical or consist of fever and mild depression

·       Neurologic disease occurs suddenly after a 1-3 week incubation period with rapid progression to profound depression, impaired vision, circling, head pressing, recumbency, paralysis, occasionally seizures and death within 2-4 days

 

TYPICAL GROSS FINDINGS:

·       There are no pathognomonic gross lesions

·       When present, gross lesions are asymmetrical and best appreciated in the gray matter of the spinal cord and include congestion, hemorrhage, and often malacia 

·       Cerebral hyperemia, edema, petechiation and focal necrosis may be seen

·       EEE may cause small intestinal lesions that include multifocal myonecrosis and lymphomonocytic infiltration the muscular layer

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

·       Lesions are confined to gray matter with more severe lesions in the cerebral cortex, especially in the frontal, rhinoencephalic and occipital areas with lesions of lesser intensity in the pyriform lobes; severe lesions may also be present in the thalamus and hypothalamus; lesions are typically less severe caudally

·       Microscopic lesions are characterized by:  Perivascular cuffing with lymphocytes, macrophages, and neutrophils with neuronal degeneration, necrosis, neuronophagia, microgliosis, perivascular edema and hemorrhage

·       In early stages (2 days) of EEE there is a prominent neutrophilic perivascular infiltration with neutrophils found in scattered malacic foci; neutrophils may also be present in cases of VEE

·       Necrotizing vasculitis, thrombosis and cerebrocortical necrosis are particularly evident in VEE but also reported in EEE

·       Rare intranuclear inclusions have been described

·       In horses, EEE may cause small intestinal lesionsthat include multifocal myonecrosis and lymphomonocytic infiltration the muscular layer and focal mild perivascular lymphocytic infiltration in the submucosal

·       Horses with EEE may develop bone marrow depletion and lymphocytolysis in the spleen and lymph nodes

 

ULTRASTRUCTURAL FINDINGS:

·       Virions are spherical, enveloped, with a icosahedral nucleocapsid

·       Replication occurs in the cytoplasm with budding from the plasma membrane

 

ADDITIONAL DIAGNOSTIC TESTS:

·       Serology is used for antemortem diagnosis

·       RT-PCR and immunohistochemistry of CNS tissue are used for postmortem diagnosis

·       Isolation and identification by neutralization or partial sequencing is especially important in VEE, which occurs in avirulent endemic and virulent epidemic types

 

DIFFERENTIAL DIAGNOSIS:

·       West Nile virus:  Mosquito transmitted flavivirus, is maintained in a mosquito to bird cycle; horses and humans are aberrant, dead-end hosts; severe polioencephalomyelitis with lymphocytic and histiocytic perivascular infiltrate, multifocal microgliosis, and neuronophagia; primarily affects gray matter of lower brainstem and thoracolumbar spinal cord

·       Japanese encephalitis virus:  Mosquito transmitted flavivirus confined to Asia, produces lesions indistinguishable from EEE and similarly affect humans; pigs serve as a major amplification host

·       Equine herpes virus 1:  Alphaherpesvirus causing sporadic outbreaks of neurologic disease, respiratory disease or abortion; virus causes endothelial cell damage leading to necrotizing vasculitis, thrombosis and infarction; affects both white and gray matter

·       Borna disease virus:  Genus Bornavirus, family Bornaviridae, causes viral encephalitis in horses in Europe; severe encephalomyelitis with lymphoplasmacytic perivascular cuffing without neuronal necrosis; eosinophilic intranuclear inclusions

·       Equine protozoal myelitis:  Apicomplexan coccidian parasite (Sacrocystis neurona) causes multifocal, asymmetric hemorrhages, malacia, and discoloration in white matter of the spinal cord; brainstem is more frequently affected than other parts of the brain, but less affected than cervical and lumbar spinal cord; affects both white Matter (WM) and gray matter (GM)

 

Gross DDx

·       EPM- both/either GM and WM

·       Post anesthetic hemorrhagic myelopathy-GM entire length of spinal cord

·       Rabies- GM

·       EHV1-GM or WM

·       WNV- GM thoracolumbar

 

COMPARATIVE PATHOLOGY:

·       Alphaviruses are an important cause of epidemic encephalitis in humans and    lesions are similar to those of the horse 

·       EEE researched as potential biological weapon capable of aerosolization

·       Some bird species are highly susceptible to EEE and have high mortality (commercial pheasant flocks, red-winged blackbirds, cardinals, sparrows, and cedar waxwings); deaths have been reported for domestic fowl, broilers, emus and whooping cranes; lesions include multifocal necrosis of heart and liver, lymphoid depletion and necrosis in the thymus, spleen and bursa of Fabricius

·       EEE has been reported in cattle, dogs, white-tailed deer, camilids, and mourning doves

·       Pigs may develop myocarditis from EEE

·       Guinea pigs and white mice are highly susceptible

 

References:

1.      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; 2016:376-7.

2.      Kiupel, M, Fitzgerald SD, Pennick KE, et al. Distribution of eastern equine encephalomyelitis viral protein and nucleic acid within central nervous tissue lesions in white-tailed deer (Odocoileus virginianus ) Vet Pathol. 2013;50:1058-1062.

3.      MacLachlan JN, Dubovi E. Fenner’s Veterinary Virology. 4th ed. San Diego CA: Academic Press; 2011:458-463.

4.      Miller AD, Zachary JF: Nervous system. In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Mosby Elsevier; 2017:876-7.

5.      Reed DS, Lackemeyer MG, Garza NL, et al. Severe encephalitis in cynomolgus macaques exposed to aerosolized eastern equine encephalitis virus. J Infect Dis. 2007;196:441-450.

6.      Schmitt SM, Cooley TJ, Fitzgerald SD, et al. An outbreak of eastern equine encephalitis virus in free-ranging white-tailed deer in Michigan. J Wildl Dis. 2007;43(4):635-644.

7.      Steele KE, Twenhafel NA. REVIEW PAPER: Pathology of animal models of alphavirus encephalitis. Vet Pathol. 2010;47:790

8.      Summers BA, Cummings JF, de Lahunta A. Veterinary Neuropathology. St. Louis, MO: Mosby; 1995:144-149.

9.      Young DS, Kramer LD, Maffei JG, et al. Molecular epidemiology of eastern equine encephalitis virus, New York. Emerg Infect Dis. 2008;14(3):454-460.

 

 


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