JPC SYSTEMIC PATHOLOGY
NERVOUS SYSTEM
January 2023
N-B05 (NP)
Signalment (JPC #1143949): Young calf
HISTORY: This calf was from Oklahoma. The animal experienced a sudden onset of disease characterized by high fever, anorexia, depression, decreased activity, excessive salivation with drooling, and nasal discharge. These signs were followed by dyspnea, cough, and severe diarrhea. Towards the end of the illness, the calf had difficulty walking and exhibited stiffness and knuckling in the fetlock joints. The animal was seen to move aimlessly in circles, stagger and fall with the head extended in opisthotonus. In the final stages, the limbs appeared weak or paralyzed, and death occurred 7 days after the onset of signs.
HISTOPATHOLOGIC DESCRIPTION: Brainstem: Multifocally expanding Virchow-Robin space, extending into the perivascular neuropil, and to a lesser extent expanding the leptomeninges are moderate numbers of lymphocytes and macrophages with fewer neutrophils and scant to moderate amounts of necrotic debris. Affected small caliber blood vessels are lined by hypertrophied (reactive) endothelial cells and vessel walls are often obscured by previously described inflammatory cells admixed with small amounts of necrotic debris and fibrin (necrotizing vasculitis). There is multifocal spongiosis within the neuropil adjacent to affected vessels. Within the white matter myelin sheaths are often dilated (ellipsoid) and contain swollen hypereosinophilic axons (spheroids) up to 30µm in diameter or rarely contain gitter cells (digestion chambers). Within the gray matter there are rare neurons with angular borders, hypereosinophilic cytoplasm, and pyknotic or karyolytic nuclei (neuronal necrosis) and rare neurons central chromatolysis (degeneration).
MORPHOLOGIC DIAGNOSIS: Brainstem: Meningoencephalitis, lymphohistiocytic and neutrophilic, multifocal, moderate, with necrotizing vasculitis, breed unspecified, bovine.
CAUSE: Chlamydia pecorum
ETIOLOGIC DIAGNOSIS: Chlamydial meningoencephalitis
CONDITION: Sporadic bovine encephalomyelitis
CONDITION SYNONYMS: Buss disease, transmissible serositis
GENERAL DISCUSSION:
· Chlamydia pecorum is an obligate intracellular gram-negative coccobacillus associated with abortion, conjunctivitis, encephalitis, enteritis, pneumonia, and polyarthritis in ruminants
· Chlamydiaceae are incapable of autonomous survival and replication and rely on host mitochondrial ATP for metabolic functions
· A publication (Borel, Vet Pathol 2018) clarified Chlamydial nomenclature: currently, the family Chlamydiaceae contains only ONE genus, Chlamydia (Chlamydophila is now considered an obsolete genus), with 11 species: C. abortus, C. avium, C. caviae, C.felis, C. gallinacea, C. muridarum, C. pecorum, C. pneumoniae, C. psittaci, C. suis, and C. trachomatis
PATHOGENESIS:
· Chlamydia exists in two forms (biphasic lifecycle): Elementary bodies and reticulate bodies
· Elementary bodies: small (0.3um) particles with rigid cell walls that can survive outside the host cell but are metabolically inactive and incapable of replication; they are the infectious form; attach to the host cell by adhesins on their surface and enter the host cell via phagocytosis
· Reticulate bodies: elementary bodies shed their cell wall and grow larger (0.6-1.5um), forming reticulate bodies that replicate by binary fission; this form is metabolically active, utilizing ATP from host mitochondria; reticulate bodies are incapable of infecting other cells; reticulate bodies condense and reform infectious elementary bodies that are released during cell lysis
· Chlamydiae persist as commensal flora on the conjunctiva and respiratory, GI, and genitourinary mucosae, often with no clinical signs
· They are shed in saliva, milk, urine, and feces
· The disease does not seem to be highly transmissible and mild or inapparent cases can occur; the incubation period varies from 4-27 days
· The organism has a tropism for blood vessels, mesenchymal tissue, and serous membranes; replication in serous membranes and vascular endothelium leads to serofibrinous serositis and vasculitis
· Encephalitis is secondary to vasculitis
· Detection of different strains in different tissues suggest differences in pathogenic potential (Borel, Vet Pathol 2018)
TYPICAL CLINICAL FINDINGS:
· Typically affects calves less than 6-months of age; 5-50% morbidity (highest in calves) and 31% mortality (highest in adults)
· Sudden onset of high fever, depression
· Catarrhal nasal discharge, excessive salivation and drooling, dyspnea, and cough
· Diarrhea
· Stiff gait, staggering, knuckling, circling, falling, muscle tremors
· Affected animals initially are ataxic but terminally become recumbent and develop opisthotonos
· No neurologic sequelae in survivors
TYPICAL GROSS FINDINGS:
· When present, are limited to active hyperemia and edema of the leptomeninges
· Serofibrinous polyserositis and synovitis with congestion and petechiation
· Approximately 50% of fatal cases also have pleuritis and pericarditis
· Meningoencephalomyelitis
· Leptomeningeal congestion and edema
· Exudative meningitis especially on ventral surface of brain stem
TYPICAL LIGHT MICROSCOPIC FINDINGS:
· Fibrinous serositis of pleural, peritoneal, pericardial cavities
· Vasculitis +/- endothelial proliferation in many organs
· Severe, diffuse mononuclear meningoencephalitis especially affecting medulla and cerebellum
· Degeneration and necrosis of the grey matter may be severe and are believed to be secondary to vascular lesions
· Elementary bodies in cytoplasm of mononuclear cells of affected tissues and exudates; NOT numerous
· IHC: antigen detected in cytoplasm of endothelium and macrophages of the brain, spleen, lung, mesothelium (Borel, Vet Pathol 2018)
ULTRASTRUCTURAL FINDINGS:
· Elementary bodies are round and dark with a bilayered cell wall and a unique dense core of condensed chromatin (nucleoid)
· Reticulate bodies are larger with more dispersed chromatin
· Intermediate forms (intermediate body) resemble reticulate bodies but contain a central electron dense core
· All three forms occur together, within membrane-bound vacuoles (phagosomes); host mitochondria are closely associated with these vacuoles
ADDITIONAL DIAGNOSTIC TESTS:
· Histochemical stains: Giemsa, Castaneda, Gimenez, and Macchiavello stain reticulate and elementary bodies
· Neutralizing antibody and complement fixation tests
· PCR and In Situ hybridization are available
DIFFERENTIAL DIAGNOSIS:
· For histologic findings:
· Histophilus somni (TME, N-B03): Diffuse severe vasculitis with more hemorrhage and thrombi, may see bacteria in vessels
· Listeria monocytogenes (N-B04): Localized signs; facial paralysis and circling; encephalitis with perivascular cuffs and microabscesses
· Alcelaphine herpesvirus 1, ovine herpesvirus 2 (MCF; D-V15, S-V01): No serositis; higher mortality; ocular and mucosal lesions; necrotizing arteritis; plasma exudation into Virchow-Robins space; lymphocytic inflammation
· Bovine herpes virus type 5: Encephalitis with perivascular cuffs and neuronal necrosis
· Other causes of bovine neurological disease:
· Rabies (Lyssavirus, Rhabdoviridae; N-V06): Negri bodies, mild perivascular cuffs
· Lead toxicity (N-T05): Absence of fever, severe motor disease, lead inclusions, cortical laminar necrosis
· Other causes of respiratory disease (without encephalitis)
· Pasteurella multocida: Similar lung lesions
COMPARATIVE PATHOLOGY:
· Chlamydia pecorum causes polyarthritis and abortion in sheep; meningoencephalitis, vasculitis, and abortion in cattle
· Chlamydia pneumoniae is a human pathogen causing bronchitis and pneumonia in marsupials and horses; affects also frogs and snakes
· Chlamydia psittaci (Psittacosis, D-B12) is a common avian pathogen causing conjunctivitis, pneumonia, enteritis, hepatitis; zoonotic
· Chlamydia abortus (R-B08) is endemic in ruminants causing abortion, especially in ewes; affects swine, rabbit, guinea pig, mice and human; zoonotic
· Chlamydia felis is endemic in cats, producing conjunctivitis and rhinitis; zoonotic
· Chlamydia caviae is pathogen of guinea pigs; zoonotic
· Affects guinea pigs 4-8 weeks old
· Transmitted via direct contact
· Causes inclusion body conjunctivitis, rhinitis, urogenital tract infections, abortions and pneumonia
· Cytology: diagnostic intracytoplasmic inclusions within epithelium in Geimsa-stained conjunctival smears
· Chlamydia trachomatis is a human pathogen causing trachoma, sexually transmitted disease and arthritis
· Chlamydia muridarum causes pneumonia in mice and hamsters
· Chlamydia suis causes conjunctivitis, enteritis and pneumonia in swine; zoonotic
· Chlamydia avium possibly causes enteritis and respiratory in birds
· Chlamydia gallinacea: in birds, no apparent pathology yet described
References:
1. Borel N, Polkinghorne A, Pospischil A. A Review on Chlamydial Diseases in Animals: Still a Challenge for Pathologists? Vet Pathol. 2018; 55(3): 374-390.
2. Barthold SW, Griffey SM, Percy DH. Guinea Pig. In: Pathology of Laboratory Rodents and Rabbits. 4th ed., Ames, IA: John Wiley & Sons, Inc.; 2016:224.
3. Cantile C, Youssef S. The nervous system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed., Philadelphia, PA: Elsevier Ltd.; 2016:391-392.
4. Miller AD and Porter BF. Nervous system. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022: 677-678, 688, 925 e.1-e.2.
5. Ostfeld N, Islam MM, Jelocnik M, Hilbe M, Sydler T, Hartnack S, Jacobson C, Clune T, Marsh I, Sales N, Polkinghorne A, Borel N. Chlamydia pecorum-Induced Arthritis in Experimentally and Naturally Infected Sheep. Vet Pathol. 2021;58(2):346-360.
6. Struthers JD, Lim A, Ferguson S, Lee JK, Chako C, Okwumabua O, Cuneo M, Valle AM, Brower A. Meningoencephalitis, Vasculitis, and Abortions Caused by Chlamydia pecorum in a Herd of Cattle. Vet Pathol. 2021;58(3):549-557.
7. Westermann T, Jenkins C, Onizawa E, Gestier S, McNally J, Kirkland P, Zhang J, Bogema D, Manning LK, Walker K, Pinczowski P. Chlamydia pecorum-Associated Sporadic Ovine Abortion. Vet Pathol. 2021;58(1):114-122.
