JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

March 2023

N-V03

 

Signalment (#D86-608): 12-day old chick

 

HISTORY: This chick had paralysis beginning at 10 days of age.

 

HISTOPATHOLOGIC DESCRIPTION:  

Slide A: Multiple sections of brain including optic lobe, cerebellum and multiple sections of cerebrum:

 

Cerebrum: Predominately within the superficial cortex and rarely in the deeper cortex, there are moderate numbers of necrotic neurons that are hypereosinophilic, shrunken, and angular with nuclear pyknosis or karyolysis, and fewer degenerate neurons with central chromatolysis, admixed with many astrocytes and glial cells that often surround affected neurons (satellitosis). Multifocally, predominately within the gray matter, are few glial nodules and gliosis characterized by focal aggregates and overall increased numbers of glial cells, respectively. Multifocally Virchow-Robin spaces and the meninges are mildly expanded by few lymphocytes, macrophages, and plasma cells that multifocally extend into the surrounding parenchyma. The choroid plexus is focally infiltrated by few heterophils. 

 

Cerebellum: Many Purkinje cells are hypereosinophilic and shrunken with karyolysis (necrosis) and are often surrounded or replaced by few glial cells and rare lymphocytes and plasma cells. Within the molecular layer are few glial nodules. Multifocally within cerebellar gray and white matter, vessels are surrounded by few lymphocytes and plasma cells, that often extend into the adjacent parenchyma. Multifocally, the meninges are infiltrated by low numbers of lymphocytes, macrophages, and plasma cells.

 

Slide B: Proventriculus (2 sections), ventriculus, small intestine (2 sections), pancreas, mesentery, heart (2 sections):

 

Proventriculus: The tunica muscularis is expanded by moderate numbers of multifocal nodular aggregates of lymphocytes.  There are few nodular aggregates of lymphocytes expanding the lamina propria (GALT).

 

Ventriculus: Myocytes of the tunica muscularis are multifocally surrounded and separated by often perivascular mild lymphoplasmacytic cellular infiltrates. 

 

Heart: Multifocally the myocardium is infiltrated by low to moderate numbers of lymphocytes, plasma cells, and few macrophages and heterophils. Few myocardial fibers are hypereosinophilic with loss of cross-striations and nuclear pyknosis (necrosis) or rarely, pale, swollen, and vacuolated with loss of cross striations (degeneration). Pericardial adipose tissue contains similar inflammatory infiltrates.

 

Pancreas: Multifocally there are perivascular, nodular infiltrates of low to moderate numbers of lymphocytes.

 

Small intestine: The lamina propria of few blunted and fused villi is multifocally markedly expanded by abundant lymphocytes and histiocytes with frequent mitotic figures, and fewer heterophils, that surround and separate tortuous, hyperplastic crypts. Crypt hyperplasia is characterized by increased numbers of mitotic figures and piling up of the epithelium. Multifocally within the epithelium are few degenerate heterophils.

 

MORPHOLOGIC DIAGNOSIS: 

1. Brain, cerebrum: Meningoencephalitis, lymphoplasmacytic, multifocal, mild, with neuronal degeneration and necrosis, gliosis, and mild heterophilic choroiditis, breed unspecified, chicken.

2. Brain, cerebellum: Purkinje cell necrosis, multifocal, moderate, with gliosis and mild lymphoplasmacytic meningoencephalitis.

3. Proventriculus and ventriculus, tunica muscularis: Lymphoid aggregates, nodular, multifocal, mild to moderate.

4. Heart: Myocarditis, lymphohistiocytic and heterophilic, multifocal, mild, with multifocal cardiomyocyte necrosis and degeneration.  

5. Pancreas: Pancreatitis, perivascular, lymphocytic, multifocal, mild.

6. Small intestine: Enteritis, lymphohistiocytic and heterophilic, focal, moderate, with crypt hyperplasia.

 

ETIOLOGIC DIAGNOSIS: Picornaviral encephalomyelitis

 

CAUSE: Avian encephalomyelitis virus (AE)

 

CONDITION: Infectious avian encephalomyelitis

 

CONDITION SYNONYMS: Epidemic tremor

 

GENERAL DISCUSSION:  

• Avian encephalomyelitis virus (Picornaviridae, sole virus in genus Tremovirus) - Single-stranded RNA virus
• Worldwide viral infection of young (usually 1-3 weeks old) chickens, turkeys, pheasants, and quail resulting in ataxia that can progress to paralysis and tremors of head and neck
• Largely controlled in commercial flocks by vaccinating breeders

 

PATHOGENESIS:  

• Mode of transmission to commercial layer flocks (i.e., adults) is unknown, but believed to be through infected people or fomites; multiage facilities are at greater risk of infection than single age
• Horizontal infection results in viral replication in intestinal mucosa and lymphoid tissue resulting in viremia and dissemination to many other tissues (skeletal muscle, pancreas, other viscera) and finally the brain
• Severity of disease depends on age and immunologic status of bird; birds younger than 3-5 weeks and immunocompromised animals are more severely affected
• Virus shed in feces of infected birds and survives in the environment for at least 4 weeks; resistant to ether, chloroform, and various environmental conditions
• Infected adult layers transmit the virus vertically, surviving chicks transmit the virus horizontally in the feces
• Only young birds without maternal antibodies or those that are not immunocompetent develop life-long CNS signs; after 6-weeks of age, birds are usually protected via immunocompetence and protective humoral response

 

TYPICAL CLINICAL FINDINGS:  

• Neurologic signs: Ataxia, incoordination, fine tremors of the head and neck may develop (accentuated if startled); adults are usually asymptomatic whereas chicks are often born symptomatic or develop clinical signs by 2-3 weeks of age
• Adult infection results in decreased egg production and hatchability detectable with good record keeping; duration of decline is typically <2 weeks 
• Morbidity in chicks may reach 60%; mortality rates are 25-50%
• Symptomatic chicks that survive rarely recover completely; may exhibit stunted growth, poor egg production, and/or develop bluish lens opacity (i.e., cataracts) around 18-20 weeks of age with visual impairment

 

TYPICAL GROSS FINDINGS:  

• Often none
• Pale areas in ventriculus muscle due to masses of infiltrating lymphocytes

           

TYPICAL LIGHT MICROSCOPIC FINDINGS:  

CNS:

• Central chromatolysis of neurons in the nuclei in the midbrain and cerebellum
• Disseminated non-suppurative encephalomyelitis; neuronal satellitosis
• Perivascular infiltration of small lymphocytes in brain and spinal cord except the cerebellum where lesions are confined to the nucleus cerebralis
• Nodular and diffuse microgliosis predominately in cerebellar molecular layer
• Degeneration of Purkinje cells 
• Ganglionitis of dorsal nerve root ganglia

Viscera:

• Dense nodules of lymphocytes within muscular wall of gastrointestinal tract, especially proventriculus and ventriculus
• Multifocal nodular lymphoid infiltration within the pancreas and myocardium (esp. atrium) 

 

ULTRASTRUCTURAL FINDINGS:  

• Neuronal degeneration: Vacuolization of granular endoplasmic reticulum, loss of attached and free ribosomes, destruction of Golgi cisternae, vacuolization of mitochondria and loss of cristae
• Virus ~25 nm hexagonal; forms paracrystalline arrays

 

ADDITIONAL DIAGNOSTIC TESTS:  

• History, age, and typical clinical CNS signs suggest AE
• Virus isolation from brain tissue is confirmatory
• Serology: ELISA, immunodiffusion test, virus neutralization test, passive hemagglutinin test, and indirect fluorescent antibody test; Ab present between 4 days at least 28 months post infection; rising sequential titers is highly suggestive of active infection

 

DIFFERENTIAL DIAGNOSIS:  

Gross:

 

Microscopic:

• Marek’s disease (N-V08, alphaherpesvirus, Herpesviridae): Lymphoid infiltrates in the peripheral nerves and lymphomatosis of viscera
• Newcastle disease (N-V10, rubulavirus, Paramyxoviridae): Neuronal peripheral chromatolysis 
• Avian influenza (D-V25, Influenza virus type A, Orthomyxoviridae): Brain lesions of edema, congestion, hemorrhage, perivascular lymphoid cuffing; also associated lesions of necrosis and inflammation of dermis with hydropic degeneration and bulla formation in the epidermis and wattles
• Eastern equine encephalitis virus (N-V09, alphavirus, Togaviridae): Non-suppurative myocarditis is predominant lesion in chickens; +/- cerebral necrosis and mild lymphoid perivascular cuffing; hepatosplenic necrosis; thymic and bursal lymphoid depletion
• West Nile Virus: Hemorrhage in cerebellar folia, cerebrum, brain stem, cervical spinal cord; Degeneration and necrosis of cerebellar molecular layer and Purkinje cells; lymphoplasmacytic meningoencephalitis; perivascular cuffing; gliosis
• Vitamin E deficiency (N-M28): Swollen cerebellum with congestion, hemorrhage, and necrosis
• Riboflavin deficiency: Myelin degeneration, Schwann cell proliferation

 

COMPARATIVE PATHOLOGY:  

 

Genera of Picornaviridae: 

• Aphthovirus:    
  • Foot and mouth disease (D-V17)
  • Equine rhinitis A virus (formerly equine rhinovirus 1)
  • Bovine rhinitis B virus
• Avihepatovirus: Duck hepatitis A virus
• Cardiovirus: 
  • Swine, elephants: Encephalomyocarditis virus (C-V02)
  • Mice: Poliomyelitis (mouse encephalomyelitis, Theiler’s disease)
• Enterovirus
  • Pigs: Swine vesicular disease (SVD); Porcine enterovirus A & B
  • Bovine: Bovine enterovirus infection
  • Duck: Duck hepatitis virus
  • Primates: Poliomyelitis
• Hepatovirus: Human & simian hepatitis A virus
• Teschovirus: Porcine teschovirus (N-V04, formerly porcine enterovirus-1) 

 

References:  

1. Crespo R, Franca MS, Fenton H, Shivaprasad HL. Galliformes and Columbiformes. In: Terio KA, McAloose D, St. Leger J eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier. 2018; 757-758.
2. Gal A, Castillo-Alcala F. Cardiovascular System, Pericardial Cavity, and Lymphatic Vessels. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:655.
3. Gough RE, McNulty MA. Picornaviridae. In: Pattison M, McMullin PF, Bradbury JM, Alexander DJ eds. Poultry Diseases. 6th ed. Philadelphia, PA: Saunders Elsevier; 2008:350-354. 
4. Ingram DR, Miller DL, et al. Serologic survey of wild turkeys (Meleagris gallopavo) and evidence of exposure to avian encephalomyelitis virus in Georgia and Florida, USA. J Wildl Dis. 2015; 51(2):374-379.
5. Schmidt R, Reavill DR, Phalen DN. Pathology of Pet and Aviary Birds. 2nd ed. Ames, IA: John Wiley & Sons, Inc.; 2015:221.
6. Ojkic D, Brash ML, Jackwood MW, Shivaprasad HL. Viral Diseases. In: Boulianne M ed. Avian Disease Manual. 7^th ed. Madison, WI: Omnipress; 2013:16-24, 40-43.
7. Senties-Cue CG, Gallardo RA, et al. Avian encephalomyelitis in layer pullets associated with vaccination. Avian Dis. 2016; 60(2):511-515. 
8. Suarez DL. Avian encephalomyelitis. In: Swayne DE ed. Diseases of Poultry. 14th ed. Hoboken, NJ: John Wiley and Sons, Inc.; 2020:520-527.
9. Swayne DE, Barnes JH, Abdul-Aziz T, Fletcher OJ. Nervous system. In: Avian Histopathology. 4^th ed. Jacksonville, FL: AAAP; 2016:473-474, 505-507.
10. Todd D, Weston JH, Mawhinney KA, Laird C. Characterization of the genome of avian encephalomyelitis virus with cloned cDNA fragments. Avian Dis. 1999; 43:219-226.

 

 

 

 

 

 

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