JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

April 2023

N-V20

 

Slide A: Signalment (JPC #2389731): 1 1/2-year-old male cockatoo

 

HISTORY: The bird was lethargic and anorexic for some time. It seemed to be wasting away and had been regurgitating food off and on for several weeks. Grossly, the proventriculus and ventriculus were dilated.

 

HISTOPATHOLOGIC DESCRIPTION: 

1.  Small intestine and mesentery: Multifocally there are infiltrates of moderate numbers of lymphocytes and plasma cells centered on the myenteric plexuses and ganglia that extend into the adjacent tunica muscularis. Within affected myenteric ganglia, there are decreased numbers of ganglion cells. Similar inflammatory cells are also present within peripheral nerves of the adjacent mesentery. There is diffuse mesenteric fat atrophy characterized by shrunken adipocytes with one or more variably sized intracytoplasmic lipid vacuoles, and blood vessels in close proximity to one another.

2.   Cerebrum: Multifocally there are perivascular infiltrates of low numbers of lymphocytes and plasma cells within the gray and white matter and the leptomeninges.

3.  Peripheral nerve: Multifocally infiltrating the endoneurium, perineurium, and surrounding epineurium are perivascular aggregates of low numbers of lymphocytes and plasma cells.

4.  Kidney: No significant findings.

 

MORPHOLOGIC DIAGNOSIS:

1.  Small intestine and mesentery: Ganglioneuritis and leiomyositis, lymphoplasmacytic, subacute, multifocal, mild, with ganglion cell loss, cockatoo, avian.

2.  Cerebrum: Meningoencephalitis, lymphoplasmacytic, subacute, multifocal, perivascular, mild.

3.  Peripheral nerve: Neuritis, lymphoplasmacytic, subacute, multifocal, mild.

4.  Adipose tissue, mesentery: Fat atrophy, diffuse, moderate.

5.  Kidney: Essentially normal tissue. 

 

Slide B: Signalment (JPC #2820183): Female psittacine

 

HISTORY: Chronic weight loss

 

HISTOPATHOLOGIC DESCRIPTION:

1.  Heart: Diffusely, nerves subjacent to the epicardium contain an infiltrate of low numbers of lymphocytes and plasma cells that occasionally extend into the surrounding connective tissue.

2.  Liver: Multifocally within portal areas, there is an infiltrate composed of low numbers of lymphocytes and plasma cells, and rare heterophils. Diffusely hepatocytes contain granular brown pigment (lipofuscin). 

 

MORPHOLOGIC DIAGNOSIS:

1.  Heart, epicardial nerves: Neuritis, lymphoplasmacytic, subacute, diffuse, moderate.

2.  Liver: Hepatitis, portal, lymphoplasmacytic and heterophilic, subacute, multifocal, mild.

 

ETIOLOGIC DIAGNOSIS: Bornaviral ganglioneuritis, leiomyositis, meningoencephalitis, neuritis, and hepatitis

 

CAUSE: Avian bornavirus (ABV) or Parrot bornavirus (PaBV)

 

CONDITION: Proventricular dilatation disease (PDD)

 

CONDITION SYNONYMS: Neuropathic gastric dilatation (NGD), avian ganglioneuritis, myenteric ganlgioneuritis, splanchnic neuropathy

 

GENERAL DISCUSSION:

• Proventricular dilatation disease (PDD) is a progressive, fatal, disease that results most commonly in neurologic and/or gastrointestinal signs 
• Caused by ABV/PaBV (Psittaciforme orthobornavirus 1 and 2; genus Orthobornavirus, family Bornaviridae), a neurotropic virus that infects and causes lymphoplasmacytic infiltrates within the central, peripheral and autonomic nervous systems, especially of the crop, proventriculus, and ventriculus 
• Affects a wide range of captive psittacines (esp African grey parrots, macaws, Amazon parrots, conures, and cockatoos) and nonpsittacine birds (ranging from red tailed hawks to Canada geese)

 

PATHOGENESIS: 

• There are 6 genotypes of avian bornavirus (PaBV 1, 2, 3, 4, 5, 7) which are involved in the development of disease, but avian bornavirus has also been isolated from clinically healthy psittacines 
• Mode of transmission, incubation time, and disease development largely unknown
  1. In birds experimentally infected with PaBV-2, clinical disease can be induced via intramuscular, intravenous, intracerebral or mixed routes of inoculation, but not with oculonasal or oral routes alone; in birds experimentally infected with PaBV-2 via an intramuscular route, virus spreads from the ventral horns of thoracic spinal cord to the brain (Araujo et al, Vet Pathol 2019)
• Occasionally causes blindness, but mechanism is unknown; it is capable of infecting multiple cells within the retina and infected birds often contain high virus particle titers, but no inflammation 
• Neurotropic virus, targeting neurons, glial cells, and ependymal cells, but a recent paper (Chenier et al, J Comp Pathol 2022) reported vascular tropism of PaBV-4 which resulted in fibrinoid vascular necrosis secondary to an immune-mediated reaction to the presence of PaBV-4
• A recent paper on the inflammatory infiltrate in cockatiels experimentally infected with PaBV-2 have a primarily T-cell infiltrate within the brain and proventriculus and mixed mononuclear infiltrate within the small intestine myenteric ganglia (Araujo et al, Vet Pathol 2022)

 

TYPICAL CLINICAL FINDINGS:

• Most common: Ileus, severe wasting with marked pectoral muscle and adipose atrophy, maldigestion and cloacal impaction (from lack of muscular grinding of feed) 
• Acute death (from heart lesions) 
• Blindness
• Hypoglycemia 

 

TYPICAL GROSS FINDINGS: 

• GI (most common): Flaccidity and dilation of any portion of the GI tract, esp proventriculus, ventriculus and crop are most affected; may be thin walled, ulcerated, and/or packed with feed; nerves on the serosal surface of affected organs may be enlarged 
• Heart (common): Cardiomegaly with occasionally with pale foci/streaks, slight ventricular dilation, hydropericardium 
• Adrenal glands (common): Slight adenomegaly with mild red-gray mottling 
• Birds with only neurologic signs or blindness may have no gross lesions at all 

 

TYPICAL LIGHT MICROSCOPIC FINDINGS: 

• GI: Segmental variable lymphoplasmacytic inflammation within the myenteric plexus +/- smooth muscle and nerves associated with of any part of the esophagus, crop, or gastrointestinal tract
• CNS/PNS: Lymphoplasmacytic infiltrates within the brain, spinal cord, peripheral nerves and ganglia; most severe within the brain stem and spinal cord +/- gliosis, neuronophagia, neuronal necrosis, perivascular lymphoplasmacytic cuffing, axonal and myelin degeneration 
• Heart: Multifocal lymphoplasmacytic inflammation within epicardial ganglia, epicardium, myocardium, and endocardium +/- myocyte necrosis, fibrosis, and lymphoplasmacytic infiltration of large cardiac vessels 
• Adrenal glands: Variable lymphoplasmacytic inflammation within medulla  
• Kidney: Rarely causes lymphoplasmacytic nephritis 
• Eye: Rarely causes lymphoplasmacytic uveitis and retinitis 
• Fibrinoid vascular necrosis and thrombosis within the pectoral muscles, myocardium, kidneys, air sacs, adrenal glands, pancreas, and thyroid gland (Chenier et al, J Comp Pathol 2022)

 

ADDITIONAL DIAGNOSTIC TESTS:

• Antemortem crop biopsy is effective in diagnosing 76% of cases; however, absence of lesions does not rule out PDD 
• rt-PCR for bornavirus; however, not all ABV positive birds have clinical disease 
• Serology 

 

DIFFERENTIAL DIAGNOSIS:

For gross finding of proventricular dilation:

• Post-mortem autolysis (most common) 
• Any disease that causes partial or complete obstruction of the intestines
• Infectious agents – Clostridial infections; gastric mycobacteriosis; fungal gastritis, peritonitis, and/or serositis; eastern equine encephalomyelitis; uncommon with Pacheco’s disease and poxvirus infections 
• Ulcerative or erosive gastritis 
• Lead poisoning (geese) 
• Finely ground diets (poultry, secondary to poor muscular development)

 

For lymphoplasmacytic meningoencephalitis in birds:

• Avian paramyxovirus type 1 (Newcastle disease virus, N-V10)
• EEE/WEE/VEE (alphavirus, N-V09)
• Avian encephalomyelitis virus (picornavirus, N-V03)
• Avian adenovirus
• Influenza A virus (D-V25)
• West Nile virus (flavivirus, N-V19)

 

COMPARATIVE PATHOLOGY:

 

REFERENCES: 

1. Araujo JL, Rech RR, Rodrigues-Hoffmann A, et al. Immunophenotype of the inflammatory response in the central and enteric nervous systems of cockatiels (Nymphicus hollandicus) experimentally infected with parrot bornavirus 2. Vet Pathol. 2022;59(3):493-497. 
2. Araujo RL, Rodrigues-Hoffmann A, Giaretta PR, et al. Distribution of viral antigen and inflammatory lesions in the central nervous system of cockatiels (Nymphicus hollandicus) experimentally infected with parrot bornavirus-2. Vet Pathol. 2019;56(1):106-117. 
3. Cantile C, Youssef S.  Nervous system.  Maxie MG ed. In: Jubb Kennedy and Palmer's Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA:  Elsevier Saunders; 2016:377-378.
4. Chenier S, DeLay J, Leacy A, et al. Vasculitis associated with parrot bornavirus 4 infection in a rose-crowend parakeet (Pyrrhurarhodocephala). J Comp Pathol. 2022;196:6-10. 
5. Leal de Araujo J, Hameed SS, Tizard I, et. al. Cardiac Lesions of Natural and Experimental Infection by Parrot Bornaviruses. J Comp Pathol. 2020;174:104-112. 
6. Reavill DR, Dorrestein G. Psittacines, Coliiformes, Musophagiformes, Cuculiformes. In: Terio KA, McAloose D, St. Leger J eds. Pathology of Wildlife and Zoo Animals. San Diego, CA:Elsevier. 2018: 788-789.
7. Schmidt RE, Reavill DR, Phalen DN, eds. Pathology of Pet and Aviary Birds. 2^nd ed. Ames, IA: Wiley Blackwell; 2015:4-5, 66, 69-70, 74-75, 78, 86, 132-133, 169, 223-224, 232-233, 272.
8. Shivapradsad HL. Miscellaneous diseases. In: Boulianne M, ed. Avian Disease Manual. 7^th ed. Jacksonville, FL: AAAP; 2013:199.

 

 

 

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