JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

January 2026

N-B08

SLIDE A:

Signalment (JPC# 2319642): Guinea pig

HISTORY: None

HISTOPATHOLOGIC DESCRIPTION: Cerebrum at the level of the hippocampus and thalamus: Multifocally expanding the leptomeninges of the third ventricle up to 150µm and obscuring ependymal cells is a dense inflammatory infiltrate composed of numerous macrophages, lymphocytes, and heterophils admixed with eosinophilic flocculant beaded material (fibrin) and proteinaceous fluid (edema). Inflammatory cells often transmigrate or obscure vessel walls. Multifocally vessels within the leptomeninges and underlying neuropil are congested and often exhibit hypertrophied (reactive) endothelium and vessel lumens are infrequently partially or completely obscured by aggregates of eosinophilic fibrillar material adhered to the endothelium (fibrin thrombi). Periventricular thalamic gray matter has increased numbers of glial cells (gliosis), infiltration by rare heterophils, vacuolation and increased pallor (edema).

MORPHOLOGIC DIAGNOSIS: Cerebrum and diencephalon: Meningitis, ependymitis, and ventriculitis, heterophilic and lymphohistiocytic, subacute, multifocal, moderate, guinea pig, Cavia porcellus.

SLIDE B:

Signalment (JPC #2319638): Monkey

HISTORY: None

HISTOPATHOLOGIC DESCRIPTION: Cerebrum, site unspecified. The leptomeninges are diffusely expanded up to 120µm by a dense inflammatory infiltrate composed of abundant lymphocytes, neutrophils, and macrophages, with fewer eosinophils, admixed with lakes of eosinophilic fluid (edema) and fibrin. Leptomeningeal vessels and underlying neuropil are lined by plump endothelial cells with round nuclei (reactive endothelium) and frequently contain transmigrating inflammatory cells. There is mild vacuolation of the underlying neuropil and low numbers of the previously described inflammatory cells.

MORPHOLOGIC DIAGNOSIS: Cerebrum: Meningitis, fibrinosuppurative and lymphohistiocytic, subacute, diffuse, moderate, monkey, species unspecified.

ETIOLOGIC DIAGNOSIS: Streptococcal (pneumococcal) meningitis

CAUSE: Streptococcus pneumoniae

ETIOLOGY SYNONYMS: Pneumonococcus pneumoniae, Diplococcus pneumoniae

GENERAL DISCUSSION:

• Streptococcus pneumoniae is a Gram positive 1-2µm heavily encapsulated alpha-hemolytic cocci that occurs in pairs (diplococci) and short chains
  • Normal flora of the upper respiratory tract in many species
  • Important cause of pneumonia and meningitis in guinea pigs, humans, NHPs
  • Capsular polysaccharide types 4 and 19 most frequently isolated from guinea pigs; serotypes identical to humans, interspecies transmission not proven
• Streptococcus spp. classified by their actions on blood agar (turn agar green = alpha hemolytic; completely lyse agar = beta hemolytic) or their carbohydrate antigens (Lancefield groups)
• Guinea pigs can also be infected by:
  • S. equi subsp. zooepidemicus: beta-hemolytic; Lancefield group B; causes cervical lymphadenitis (“lumps”, H-B02)
  • S. pyogenes: beta-hemolytic, Lancefield group A
  • Streptococcus equi, Streptococcus equisimilis: Lancefield group C

PATHOGENESIS:

• Predisposing factors: Stress (transportation, temperature change), pregnancy, poor husbandry, inadequate nutrition (hypovitaminosis C), waning passive immunity, immunosuppression, concurrent viral infection
• Aerosol transmission > colonizes nasopharynx > ear or lung infection > bacteremia > invades CNS > leptomeninges (little resistance to spread in meningeal spaces, CSF an excellent nutrient source for bacteria) > meningitis
• Virulence factors:
  • Does not produce toxins
  • Polysaccharide capsule resists phagocytosis and hides bacteria from antibodies and complement proteins
  • Several serotypes activate the alternative complement pathway 🡪 this may stimulate early tissue damage
• Leptomeningitis may lead to choroiditis, ependymitis, and internal hydrocephalus due to obstruction of the aqueduct
• Leptomeningeal vasculitis is common; however thrombosis is uncommon and typically hits the smallest vessels with a slow onset that allows for development of collateral circulation

TYPICAL CLINICAL FINDINGS:

• Epizootics typically occur in winter
• Young animals/pregnant sows at risk
• Weakness, ataxia, lethargy, anorexia, muscle tremors, flaccid paralysis, clonic seizures, constricted pupils, delayed light reflexes, nystagmus, torticollis
• Dyspnea, nasal/ocular discharge
• Abortion, stillbirth
• Sudden death

TYPICAL GROSS FINDINGS:

• Meninges are opaque and/or hyperemic with accumulation of grayish-yellow fibrinopurulent exudate
  • May be easily overlooked since it is the same color as the brain and it accumulates in the arachnoid spaces;
  • May obscure vessels and nerves on dependent aspect of brain
  • Localizes to fissures (most space in the arachnoid), spares the surface of the gyri on the dorsal aspect of the brain
• Fibrinopurulent pleuritis, pericarditis, peritonitis, conjunctivitis, lung consolidation with abscessation and hemorrhage, and otitis media

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Diffuse fibrinous exudate, Gram positive paired cocci, heterophilic, lymphoplasmacytic, histiocytic inflammation
• Fibrinopurulent meningitis
• Acute bronchopneumonia with fibrin and polymorphonuclear cell infiltration; elongated/fusiform infiltrating cells forming palisading patterns in airways and alveoli
  • +/- Thrombosis of pulmonary vessels in acute cases
• Splenitis, metritis, ovarian abscessation, hepatic necrosis, lymphadenitis
• Suppurative arthritis and osteomyelitis reported in guinea pigs with borderline vitamin C deficiency (M-M07)

ADDITIONAL DIAGNOSTIC TESTS:

• Gram stain on direct smears of exudate or histologic sections
• Culture of tissue or nasal passage wash

DIFFERENTIAL DIAGNOSIS:

• For histologic finding of meningitis in guinea pigs:
  • Bordetella bronchiseptica (P-B09): Gram negative; typically causes suppurative bronchopneumonia, but may see meningitis if septicemic
  • Streptococcus equi subsp. zooepidemicus (H-B02): Gram positive; typically causes suppurative lymphadenitis but meningitis may be seen if septicemic
  • Lymphocytic choriomeningitis (N-V18, arenavirus): Rare; lymphocytic inflammation of the meninges, ependyma, and choroid plexus

COMPARATIVE PATHOLOGY:

• NHPs: S. pneumoniae is the most common cause of fibrinopurulent meningitis and meningoencephalitis
  • Also causes fibrinous pleuropneumonia (P-B07), septicemia, polyserositis, conjunctivitis/panophthalmitis, peritonitis, sudden death
  • Stress, viral infection, waning neonatal passive immunity predispose
• Rat: Outbreaks rare in well-managed facilities; organism carried in nasal turbinates and tympanic bullae of normal rats; typically opportunistic invader
  • as in guinea pigs, some serotypes isolated from sick rats are the same as those from human cases (zoonotic hazard)
  • Fibrinopurulent polyserositis, pleuropneumonia, pericarditis, peritonitis, meningitis, rhinitis, and otitis media +/- embolic suppurative lesions in liver, spleen, kidney
• Hamster: S. pneumonia has been associated with upper respiratory disease, otitis and bronchopneumonia
• Otters: S. lutetiensis sp. nov. causes a fatal meningoencephalitis, endocarditis, septicemia in northern sea otters; major cause of death (30% of a 600 animals in a 6 year study); S. phocae causes meningoencephalitis in Southern sea otters
• Cats: a recent review found that Streptococcus canis is the main bacterial cause of meningoencephalitis; associated with intensively housed young cats; P. multocida is another differential (de Cecco, J Vet Diagn Invest 2021)
• Dogs: recent retrospective of 28 dogs with confirmed diagnosis of sepsis with neurologic involvement had positive bacterial culture growth with 6 cases of Streptococcus canis, 5 cases of E. coli, and 3 cases of Staphylococcus intermedius (Elbert, J Vet Diagn Invest 2022)
  • Gross: leptomeningeal hemorrhages in 10 cases
  • Histo: neutrophilic and/or fibrinous meningoencephalitis with hemorrhage, vasculitis, thrombosis, and neuronal necrosis, with intracellular bacteria
• Mink: Two outbreaks of septicemia with meningoencephalitis in farmed mink recently reported, with Streptococcus bovis/Streptococcus equinus complex identified by bacterial culture from brain and liver (Crawford, J Vet Diagn Invest 2025)
• Horses:
  • Streptococcus pluranimalium identified as cause of meningoencephalitis in 3-year-old quarter horse with acute onset of neurologic signs and sudden death (Fu, J Vet Diagn Invest 2021)
  • A recent retrospective found bacterial cause in 14 of 171 cases (8%) of meningoencephalomyelitis in US horses between 1996-2023; bacteria were cultured in 4 cases, including Streptococcus equi subsp. Zooepidemicus (2), Klebsiella pneumoniae, and Salmonella sp. Borrelia burgdorferi was identified by PCR and FISH in one case. (Countrymann, J Vet Diagn Invest 2026)
• Acute meningitis in neonates commonly caused by neonatal septicemia, especially in ruminants and pigs; also known as neonatal bacterial suppurative meningitis (NBSM); frequently manifests as combination of polyarthritis, purulent leptomeningitis, choroiditis
  • Calves: Streptococcus spp. associated with leptomeningitis, synovitis, ophthalmitis; other causes E. coli, Pasteurella, Mannheimia
  • Foals: Streptococcus spp. associated with leptomeningitis, polyserositis, synovitis, other causes include E. coli, Salmonella typhimurium
  • Piglets: Streptococcus suis type I and II associated with leptomeningitis, choroiditis, ependymitis, cranial neuritis, myelitis; other causes include Glasserella parasuis, Salmonella cholerasuis, E. coli

REFERENCES:

1. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents & Rabbits. 4th ed. Ames, IA: Blackwell Publishing Ltd; 2016:144-145,186,230.
2. 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: Saunders Elsevier; 2016:353-355.
3. Countrymann K, Ruby R, Miller AD. A retrospective study of 171 cases of equine meningoencephalomyelitis in the United States, 1996-2023. J Vet Diagn Invest. 2026;38(1):100-111.
4. Crawford MJ, Sebastian KN, Elsmo E, Clarke LL, Tsoi MF. Recurrent outbreak of Streptococcus bovis/Streptococcus equinus complex-associated meningoencephalitis in farmed mink. J Comp Pathol. 2025; 219:78-81.
5. De Cecco BS, Carossino M, Del Piero F, et al. Meningoencephalomyelitis in domestic cats: 3 cases of Pasteurella multocida infection and literature review. J Vet Diagn Invest. 2021; 33(6):1156-1162.
6. Elbert JA, Rissi DR. Neuropathologic changes associated with systemic bacterial infection in 28 dogs. J Vet Diagn Invest. 2022;34(4):752-756.
7. Fu D, Ramachandran A, Miller C. Streptococcus pluranimalium meningoencephalitis in a horse. J Vet Diagn Invest. 2021;33(5):956-960.
8. Lowenstine LJ, McManamon R, Terio KA. Apes. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018:387, 392.
9. Matz-Rensing K, Lowenstine LJ. New world and old-world monkeys. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018:363, 364.
10. Miller AD, Porter BF. Nervous system. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7^th ed. St. Louis, MO: Mosby Elsevier; 2022:924-925.
11. Simmons J and Gibson S. Bacterial and mycotic diseases in nonhuman primates. In: Abee CR, Mansfield K, Tardif S, Morris T, eds. Nonhuman Primates in Biomedical Research: Diseases. 2^nd ed. London, UK: Academic Press; 2012:107-109.
12. Williams BH, Huntington KAB, Miller M. Mustelids. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018:297-298.

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