JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

January 2023

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 occluded by mats 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, increased pallor (edema), and multifocal vacuolation of the neuropil (spongiosis). 

 

MORPHOLOGIC DIAGNOSIS: Cerebrum and diencephalon: Meningitis, ependymitis, and ventriculitis, fibrinous, 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 clear space (edema) and eosinophilic flocculant material (fibrin). There is increased clear space in the underlying neuropil and low levels of the previously described inflammatory cells. Leptomeningeal vessels and underlying neuropil are lined by plump endothelial cells with round nuclei (reactive endothelium) and frequently contain transmigrating 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
  1. Normal flora of the upper respiratory tract in many species
  2. Important cause of pneumonia and meningitis in guinea pigs, humans, NHPs
  3. 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) à  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 à 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
  1. May be easily overlooked since it is the same color as the brain and it accumulates in the arachnoid spaces; 
  2. May obscure vessels and nerves on dependent aspect of brain
  3. 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, lympoplasmacytic, 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
  1. Also causes fibrinous pleuropneumonia (P-B07), septicemia, polyserositis, conjunctivitis/panophthalmitis, peritonitis, sudden death
  2. Stress, viral infection, waning neonatal passive immunity predispose
  3. In a recent study in baboons, Streptococcus spp. infection was associated with fibrinosuppurative inflammation in the lungs (most common site), CNS (second most common), spleen, and soft tissues; S. pneumoniae was most common isolate in lungs
• Rat: Outbreaks rare in well-managed facilities; organism carried in nasal turbinates and tympanic bullae of normal rats; typically opportunistic invader 
  1. as in guinea pigs, some serotypes isolated from sick rats are the same as those from human cases (zoonotic hazard)
  2. 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
• 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 
  1. Calves: Streptococcus spp. asspoicated with leptomeningitis, synovitis, ophthalmitis; other causes E. coli, Pasteurella, Mannheimia
  2. Foals: Streptococcus spp. associated with leptomeningitis, polyserositis, synovitis, other causes include E. coli, Salmonella typhimurium
  3. 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.
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3. Davis KL, Gonzalez O, Jumar S, Dick EG. Pathology Associated with Streptococcus spp. Infection in Baboons (Papio spp.). Vet Pathol. 2020; 57:714-722.
4. 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.
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6. 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.
7. 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.
8. 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.
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