JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

January 2026

N-B03

 

Signalment (JPC #1369469): Feedlot steer

 

HISTORY:  Several steers in a feedlot herd of about 500 head exhibited sudden profound central nervous system depression terminating in death. Among the lesions observed at necropsy were ulcerative laryngitis, multifocal hemorrhagic areas of necrosis in the brain, and polyserositis.

 

HISTOPATHOLOGIC DESCRIPTION: Cerebrum: Affecting approximately 70% of the white matter and extending into the grey matter, there are multifocal areas of rarefaction. Rarefied areas are either necrotic with a loss of white and grey matter architecture and replacement by fragmented eosinophilic cellular debris admixed with abundant gitter cells, neutrophils, hemorrhage, fibrin and edema (liquefactive necrosis) or edematous. Edema is predominantly extracellular with either variably sized, round to oval, clear vacuoles within the myelin sheaths or increased space between myelinated axons expanded by pale eosinophilic material (edema fluid). In the overlying leptomeninges, there is also perivascular edema, fibrin, and hemorrhage centered on affected vessels. Gitter cells have expanded foam cytoplasm with abundant phagocytosed eosinophilic cellular debris or frequent erythrophagocytosis. Within and adjacent to these areas of necrosis and edema, as well as within the overlying leptomeninges, many blood vessels have walls that are transmurally infiltrated by moderate numbers of neutrophils and are expanded by eosinophilic fibrinoid material and fragmented cellular debris (necrotizing vasculitis). Some vessel walls are almost totally replaced by polymerized fibrin (fibrinoid vasculitis) and the most severely affected blood vessels are lost and replaced by a nodule of neutrophils, gitter cells, and necrotic cellular debris in a region of hemorrhage (vascular necrosis). In few of the affected vessels there are fibrin thrombi that partially obscure the vessel lumen and are composed of eosinophilic polymerized fibrin with abundant enmeshed erythrocytes and inflammatory cells. Within areas of necrosis, neurons are frequently shrunken, angular, and hypereosinophilic with a pyknotic or karyorrhectic deeply basophilic nucleus (neuronal necrosis). In less affected adjacent grey matter, the perivascular space around small caliber vessels is diffusely expanded (vasogenic edema). 

 

MORPHOLOGIC DIAGNOSIS: Cerebrum: Vasculitis, fibrinoid and necrotizing, subacute, multifocal, severe, with fibrin thrombi, and necrohemorrhagic and suppurative meningoencephalitis, breed unspecified bovine.

 

ETIOLOGIC DIAGNOSIS: Meningocerebral histophilosis

 

CAUSE: Histophilus somni (formerly Haemophilus somnus, Haemophilus agni, or Histophilus ovis)

 

CONDITION: Infectious thrombotic meningoencephalitis (ITME); thrombotic meningoencephalitis (TME)

 

SYNONYMS: H. somni disease complex

 

GENERAL DISCUSSION: 

• H. somni is an important disease of feedlot cattle that causes multiple syndromes: TME, fibrinopurulent bronchopneumonia, myocarditis, necrotizing laryngotracheitis, and polyarthritis   
• Facultative anaerobic, fastidious, gram-negative coccobacillus
• Typically affects cattle 6-12 month of age
• Component of the bovine respiratory disease complex
• Commonly isolated from the respiratory and urogenital tracts of healthy animals

 

PATHOGENESIS:

• Subclinical infection in cattle is not uncommon; no breed/sex predilection
• Stress (weather, shipping, crowding) can precipitate clinical disease 
• Calves are infected by carrier cows early in life and later spread the infection at the feedlot  
• How the bacteria invades the blood stream is not known but is believed by the respiratory tract from aerosolized urine
• Circulatory invasion results in septicemia and localization in many tissues
• Respiratory tract is colonized initially > local bacterial replication > septicemia > deposition in any organ (CNS especially at the gray and white matter interface is particularly vulnerable to damage) > endothelial apoptosis > subendothelial collagen is exposed > initiating vasculitis and secondary thrombosis > ischemia 
• Differences in strain pathogenicity exist; some are encephalopathic while others are associated with pneumonia
• There is no clear evidence of embolic events (therefore syndrome renamed TME from TEME)
• Emboli can be simulated by intravascular proliferation of bacteria at sites of    thrombosis
• Virulence Factors: important virulence factors include: 
• Lipo-oligosaccharide (LOS): Triggers apoptosis of bovine endothelial cells by caspase-3 activation; LOS may also activate platelets to initiate endothelial cell apoptosis via caspases 8 and 9, induce endothelial cytokine secretion and expression of leukocyte adhesion molecules (I-CAM1, P-selectin, E-selectin), and promote ROS production
• Immunoglobulin Fc binding proteins:  Bacteria secretes immunoglobulin Fc binding proteins, including 3IgG2-binding proteins (immunoglobulin protein A, IbpA), which are associated with serum resistance as well as inhibiting phagocytosis and inducing cytotoxicity of bovine monocytes;  thus, degradation or binding of antibody and formation of a capsule are mechanisms by which these pathogens may evade the host antibody response
• Inhibition of oxygen radicals: H. somni is capable of inhibiting the oxidative burst in neutrophils and alveolar macrophages 
• Intracellular survival
• Formation of biofilm is described for H. somni although the functional role in resisting the host immune response during development of BRD has not been tested 

 

TYPICAL CLINICAL FINDINGS:

• Course can be rapid (clinical signs may go unnoticed) 
• Sudden death
• Can include depression, pyrexia, stiffness, cough, tachypnea, abortion
• Neurological signs are diverse and include ataxia, paresis, blindness, and seizures

 

TYPICAL GROSS FINDINGS:

• CNS:  
• Random soft red to brown hemorrhagic foci (infarcts) in the brain and spinal cord; lesions are random, but may be a predilection for the white-gray matter interface of the cerebrum and thalamus
• CSF can appear cloudy
• Other lesions:
• Necrotizing laryngotracheitis
• Fibrinous pleuropneumonia
• Myocarditis with abscesses (abscesses most common in the left ventricular free wall, particularly papillary muscles)
• Otitis media
• Septicemia
• Polyarthritis (atlanto-occipital joint)
• Retinal hemorrhages
• Endometritis-vaginitis (abortion) in adults
• Widespread evidence of inflammation and petechia on serosal surfaces and in skeletal muscle
• Mastitis
• Orchitis
• Conjunctivitis

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Necrotizing vasculitis and thrombosis, hemorrhage, inflammation, and necrosis in many tissues; neutrophilic inflammation extends into the surrounding parenchyma
• CNS: Cerebral thrombosis/hemorrhage/necrosis often with bacterial colonies; fibrinopurulent meningitis
• Other lesions: Myocarditis, pleuritis, polyserositis, fibrinopurulent bronchopneumonia

 

ADDITIONAL DIAGNOSTIC TESTS:

• CSF analysis: Neutrophils, increased protein
• Bacterial culture

 

DIFFERENTIAL DIAGNOSIS:

• Gross differentials
• Lead poisoning (N-T05): Neuronal necrosis (can be laminar)
• Polioencephalomalacia (N-T02): Random foci of necrosis limited primarily to the gray matter of the cerebral cortex (laminar cortical necrosis from thiamine deficiency)
• Microscopic differentials
• Listeria monocytogenes (N-B04):  Neutrophilic inflammation in the brain stem (microabscesses) +/- vasculitis, but usually not characterized by numerous thrombi like TME
• Rabies (Rhabdoviridae, N-V06): Differential for any ox with neurologic problems, perivascular cuffing; intracytoplasmic inclusions in neurons (Negri bodies)

 

COMPARATIVE PATHOLOGY:

• Histophilus somni in sheep: lambs die of acute septicemia (most common gross lesion: multiple hemorrhages throughout carcass) while older sheep develop fibrinopurulent polyarthritis, thrombotic (from bacterial emboli) meningoencephalitis and nephritis
• Abcense of pulmonary lesions in sheep allows differentiation from Mannheimia haemolytica  
• Also causes epididymitis in rams
• Glaesserella parasuis (P-B18):  In pigs, fibrinous polyserositis (Glasser's disease), leptomeningitis, and synovitis
• Avibacterium paragallinarum (formerly Haemophilus paragallinarum):  Infectious coryza in chickens, pheasants, and guinea fowl
• Other Haemophilus sp. cause disease in nonhuman primates, rats, and humans

 

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; 2016:364-365.
2. Craig LE, Dittmer KE, Thompson KG. Bones and joints. In: Maxie MG, ed. Jubb Kennedy and Palmer's Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO:  Elsevier; 2016:151-2.
3. Foster RA, Premanandan C. Male Reproductive System.  In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed., St. Louis, MO; Elsevier; 2022:1312, 1327, 1332, 1366.
4. Fulton RM.  Bacterial diseases.  In: Boulianne M., ed. Avian Disease Manual. 8^th ed. Jacksonville, FL: American Association of Avian Pathologists; 2019:88-90.
5. Gal A, Castillo-Alcala F. Cardiovascular System.  In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed., St. Louis, MO; Elsevier; 2022:688.
6. Lopez A, Martinson SA. Respiratory System.  In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed., St. Louis, MO; Elsevier; 2022:587, 592, 608-609, 611-612, 619.
7. Lowenstine LJ, Osborn KG. Respiratory System Disease of Nonhuman Primates. In: Bennett BT, Abee CR, and Henrickson R. Nonhuman Primates in Biomedical Research: Diseases. 2nd ed. London, UK: Academic Press; 2012:456.
8. Martinez MAJ, Gasper DJ, Mucino MCC, Terio KA. Ch. 8 Suidae and Tayassuidae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:219.
9. Miller AD, Porter BF. Nervous System.  In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed., St. Louis, MO; Elsevier; 2022:910, 914, 952, 968, 1086.
10. Stanton JB, Zachary JF. Mechanisms of Microbial Infections.  In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed., St. Louis, MO; Elsevier; 2022:233.
11. Van AJ, Brown DL. Hepatobiliary System and Exocrine Pancreas.  In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed., St. Louis, MO; Elsevier; 2022:516.

Click the slide to view.

---