AFIP SYSTEMIC PATHOLOGY

JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

April 2014

N-V04(NP)

 

SIGNALMENT (JPC #213899):  An age and breed unspecified pig

 

HISTORY:  A group of pigs developed high fever (105 degrees F), anorexia, lassitude, depression, and rear limb incoordination.

 

HISTOPATHOLOGIC DESCRIPTION: 

Slide A: Spinal cord and meninges:  Multifocally, mildly expanding the meninges, Virchow-Robin spaces, and the adjacent grey matter is a cellular infiltrate composed of lymphocytes, histiocytes, and fewer plasma cells. Within the grey matter, predominantly in the ventral horns, are multifocal aggregates of oligodendrocytes, astrocytes, and microglia (glial nodules).  Vessels throughout the tissue are frequently lined by hypertrophied endothelium.  

 

Slide B: Cerebellum and brain stem:   Diffusely expanding the meninges and Virchow-Robin space and occasionally extending into the cerebellar molecular layer are moderate numbers of lymphocytes and macrophages with fewer plasma cells.  Moderate numbers of Purkinje cells as well as scattered neurons within the brain stem are shrunken and angular with hypereosinophilic cytoplasm and pyknotic nuclei (necrosis). Necrotic neurons occasionally are surrounded by oligodendroglial cells (satellitosis).  Within the molecular layer of the cerebellum and adjacent to necrotic neurons within the pons, there are rare multifocal aggregates of oligodendroglial cells and astrocytes (glial nodules).  Vessels throughout the section often are lined by hypertrophied (reactive) endothelium.

 

MORPHOLOGIC DIAGNOSIS:  

Spinal cord and meninges:  Meningopoliomyelitis, lymphohistiocytic (nonsuppurative), subacute, multifocal, moderate, breed unspecified, porcine.

 

Cerebellum and brain stem:  Meningoencephalitis, lymphohistiocytic (nonsuppurative), subacute, diffuse, moderate, with neuronal and Purkinje cell necrosis, breed unspecified, porcine.

 

ETIOLOGIC DIAGNOSIS:  Teschoviral meningoencephalitis

 

CAUSE:  Porcine teschovirus (porcine enterovirus)

 

CONDITION:  Teschen disease, Talfan disease 

 

CONDITION SYNONYMS:  Poliomyelitis suum, benign enzootic paresis, Ontario encephalomyelitis, polioencephalomyelitis

 

GENERAL DISCUSSION:

·       Porcine enterovirus serotypes 1-7 and 11-13 have been reclassified as porcine teschovirus 1-7, 11-13, genus Teschovirus, family Picornaviridae, non-enveloped ssRNA viruses

·       Porcine enterovirus A (PEV-A), porcine enterovirus B (PEV-B), and porcine teschovirus all cause polioencephalomyelitis; they are closely related but do not confer cross protection

·       Infection is most common post-weaning due to waning maternal immunity and mixing of pigs from different sources

·       Teschen disease, caused by porcine teschovirus 1, is the acute, severe form that is recognized in Europe and sporadically in Africa; it has high morbility and mortality and affects pigs of all ages

·       Talfan disease, caused by less virulent strains, is a subacute or less severe manifestation; it is more common and occurs worldwide; it usually affects 6-10 week-old pigs with low morbidity and mortality

 

PATHOGENESIS:

·       Fecal-oral infection or indirect fomite exposure > viral replication in tonsils (large amounts of virus in 24 hours) and intestinal epithelium (especially ileum and colon), clinically asymptomatic phase with minimal tissue change > viremia (porcine teschovirus 1) > CNS invasion of specific neuronal populations > lower motor neuron paralysis

·       CNS involvement is dependent on the virulence of the strain and the age of the pig

·       Viremia by some serotypes may lead to localization in the pregnant uterus resulting in death of fetuses

·       Infection can also be transmitted by aerosolization, with viral replication occurring in the respiratory tract

 

TYPICAL CLINICAL FINDINGS:

·       Most infections are asymptomatic

·       CNS signs as soon as 6 days after exposure, including ataxia and flaccid paralysis

·       Virulent form (Teschen disease):

o   Convulsions, opisthotonos, nystagmus, coma, stiffness of the extremities, inability to stand, anorexia; death commonly occurs in 3-4 days

o   Survivors may have residual paralysis

·       Mild form (Talfan disease):

o   Primarily asymptomatic

o   Paresis and ataxia that seldom progresses to paralysis

 

TYPICAL GROSS FINDINGS:

·       None

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

·       Neuronal necrosis with glial nodules and neuronophagia

·       Nonsuppurative polioencephalomyelitis: Extends throughout the cerebrospinal axis from the olfactory bulbs to the lumbar spinal cord; most severe in the brainstem from the hypothalamus through the medulla, decreasing in intensity down the spinal cord, with relative sparing of the cerebral and cerebellar cortices

·       Spinal cord lesions include nonsuppurative myelitis and neuronal degeneration and necrosis (neuronal swelling, chromatolysis, satellitosis, neuronophagia) are largely confined to grey matter, particularly the ventral horns

·       Mild lymphocytic meningitis, typically overlying areas of cerebral parenchymal injury

·       Marked lymphocytic meningitis, typically overlying areas of cerebellar molecular layer inflammatory lesions, in older pigs with a more prolonged disease course

·       Ganglioneuritis within the dorsal root and trigeminal ganglia

 

ULTRASTRUCTURAL FINDINGS:

·       Intracytoplasmic paracrystalline arrays of 25-30nm diameter, non-enveloped viral particles within neurons, endothelium, astrocyte foot processes, glial processes

·       Disrupted structure of rough endoplasmic reticulum - ribosomes separate from the endoplasmic reticulum, and there is progressive dilation of endoplasmic reticulum and a loss of Nissl body clusters

 

ADDITIONAL DIAGNOSTIC TESTS: 

·       Diagnosis is based on virus isolation, immunohistochemistry, PCR

 

DIFFERENTIAL DIAGNOSIS:

·       Hemagglutinating encephalomyelitis virus (coronavirus):  Causes two different syndromes- vomiting and wasting disease and an acute nonsuppurative encephalomyelitis that appears almost identical to Teschen disease

·       Pseudorabies (porcine herpesvirus):  Intranuclear inclusions within degenerate neurons                               

·       Rabies (rhabdovirus):  Rare in swine; presence of Negri bodies and absence of spinal cord involvement        

·       Classical swine fever (pestivirus) (Hog cholera)/African swine fever (asfarvirus): Similar clinically but are characterized by vasculitis, perivascular cuffing, and lack of neuronal necrosis                       

·       Salt poisoning:  This causes similar CNS signs, but the characteristic cerebral edema and eosinophilic meningoencephalitis with laminar cortical necrosis allows differentiation

 

COMPARATIVE PATHOLOGY:

·       Swine vesicular disease (picornavirus, enterovirus):  Disease only of swine that causes lesions similar to foot and mouth disease (aphthovirus)

·       Chickens:  Polioencephalomyelitis (enterovirus) in young birds (avian encephalomyelitis; epidemic tremor)

·       Mice:  Theiler’s disease (enterovirus) causes polioencephalomyelitis with resultant flaccid paralysis

 

References:

1.      Alexandersen S, Knowles NJ, Dekker A, Belsham GJ, Zhang Z, Koenen F.  Picornaviruses.  In:  Diseases of Swine.  10th ed.  Ames, IA: Wiley, Inc.; 2012: 610-614.

2.      Cantile C., Youssef S. Nervous system. In: Maxie, MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals, Vol I. 6th ed. Philadelphia, PA: Elsevier Ltd; 2016:372-373.

3.      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: 1283-1286.

4.      Deng MY, et al.  Diagnosis of Porcine teschovirus encephalomyelitis in the Republic of Haiti.  J Vet Diagn Invest  2012;24(4):671-678.

5.      MacLachlan, NJ, Dubovi EJ. Fenners’s Veterinary Virology. 4th ed. Burlington, MA: Academic Press; 2011:437.

6.      Summers BA, Cummings JF, de Lahunta A. Veterinary Neuropathology. St. Louis, MO: Mosby, Inc; 1995:123-125.

7.      Vandevelde M, Higgins RJ, Oevermann, A.  Veterinary neuropathology: essentials of theory and practice, 1st ed.  Ames, IA: Wiley-Blackwell; 2012:50, 66-67.

8.      Yamada M, Miyazaki A, Yamamoto Y, Nakamura K, Ito M, Tsunemitsu H, Narita M.  Experimental teschovirus encephalomyelitis in gnotobiotic pigs.  J Comp Path.  2014;150(2-3): 276-286.


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