AFIP SYSTEMIC PATHOLOGY

JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

January 2020

N-B04

 

Signalment (JPC #2239642): 5-year-old Holstein cow

 

HISTORY: This cow exhibited anorexia and mental confusion followed by recumbency and nervous signs. The animal was sick for two days.

 

HISTOPATHOLOGIC DESCRIPTION: Brainstem: There is a focally extensive, 7mm X 10 mm area of rarefaction, predominantly affecting the gray matter, characterized by loss of neuropil and abundant clear space (edema). This focus is infiltrated by abundant degenerate and nondegenerate neutrophils, fewer gitter cells, lymphocytes, and abundant cellular and karyorrhectic debris (necrosis). Within surrounding, less affected areas are numerous nodules of viable and degenerate neutrophils that occasionally are centered on a focus of lytic necrosis (microabscesses), spongiosis, and swollen axons within dilated myelin sheaths (spheroids). Multifocally, vascular endothelial cells are hypertrophied and vessel walls are transmurally expanded by neutrophils, fibrin, and cellular and karyorrhectic debris (necrotizing vasculitis). Multifocally, Virchow-Robin space and to a lesser extent the leptomeninges are expanded up to three times normal by lymphocytes, plasma cells, and macrophages with few neutrophils.

 

MORPHOLOGIC DIAGNOSIS: Brainstem: Meningoencephalitis, necrosuppurative, subacute, multifocal, moderate, with necrotizing vasculitis, microabscesses, and mononuclear perivascular cuffing, Holstein, bovine.

 

ETIOLOGIC DIAGNOSIS: Listerial meningoencephalitis

 

CAUSE: Listeria monocytogenes

 

CONDITION: Listeriosis, “Circling disease”

 

GENERAL DISCUSSION:

·        Gram-positive, motile, facultatively intracellular, facultative anaerobic bacillus with more than 11 serotypes

·      Almost all animal infections are caused by serotypes 1/2a, 1/2b, and 4b (while food borne illness strains belong to serotype 1/2c)

·        Ubiquitous in the environment, especially temperate zones

·        Resistant to harsh environmental conditions

·        Sporadic disease in a variety of animals, including man

·        Economically important in ruminants; seasonal occurrence (winter)

·        Associated with poorly preserved silage (improper fermentation with silage pH >5), big-bale silage, moist feed

·        Commonly isolated from tissues of normal animals (e.g. lymphoid tissues) and in large numbers in the feces of ruminants

·        Intracellular pathogen within macrophages, neutrophils, and epithelial cells

 

PATHOGENESIS:

·        Three main distinct disease syndromes in animals (syndrome seldom overlap; likely separate pathogeneses):

·      Encephalitis: disease of adult ruminants; associated with heavy feeding of silage

·      Bacterial invasion through wounds in oral mucosa (pathologic or physiologic) > invade the trigeminal nerves and travel centripetally via retrograde axonal transport to the brain (medulla oblongata) > spreads rostrally and caudally, affecting parenchyma then meninges

·      Affinity for brainstem; lesions most severe in the medulla and pons

·      Commonly, extensive tissue destruction associated with suppurative inflammation

·      Abortion:

·      Hematogenous spread to gravid uterus > organisms penetrate placenta and spread to fetal liver > focal hepatic necrosis

·      Can cause third trimester abortion

·      Retention of fetal membranes causes clinical illness

·      Septicemia: more common form in monogastrics

·      Transported by macrophages

·      Liver: multifocal necrosis or miliary microabscesses; rarely heart and other tissues

·      Principally in neonates as a continuation of the fetal infection

·      Enteric:

·      Extremely rare; reported in humans, cattle, and sheep

·      Severe congestion of entire digestive tract with prominent muscularis mucosa neutrophilic inflammation, mucosal necrosis, and villous blunting

·        Virulence factors:

·      Listeriolysin O (LLO) is a pore-forming cytolysin that lyses phagocytic cell phagosomes, allowing escape into cytoplasm where the organism multiplies

·      Internalin internalizes via E-cadherin; required to overcome intestinal, placental, and blood-brain barriers

·      Utilizes cholesterol-binding hemolysin to lyse phagocytic cell phagosomes and escape into the host cytoplasm

·      One of the few organisms known to co-opt host cell actin using ActA protein, allowing cell-to-cell transfer

·        Recent report of brainstem encephalitis (rhombencephalitis) in pastured bull (not fed silage); one isolate of L. monocytogenes found in pasture, serotype 4b, and positive for internalins A, C, and J (Matto, J Vet Diagn Invest 2017)

 

TYPICAL CLINICAL FINDINGS:

·      Encephalitic form:

·      Mental confusion and depression, head pressing, turning or twisting of head to one side (without rotation), walking in circles (“circling disease”)

·      Unilateral facial nerve (CN VII) paralysis causing drooping eyelid, ear, lips

·      Paralysis of masticatory muscles and pharynx leading to drooling

·      Strabismus, nystagmus, hemiparesis, decreased rumenal motility

·        Purulent endophthalmitis, usually unilateral

 

TYPICAL GROSS FINDINGS:

·        Gross brain lesions are rare; parenchymal lesions occur initially (microabscesses), then meningeal lesions

·        Occasionally, medullary meninges thickened by greenish gelatinous material

·        Occasionally, gray foci of softening (malacia) in cross sections of medulla (caused by inflammatory cells/thrombi occluding vessels)

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

·        Microabscesses and glial nodules infiltrated by neutrophils and gitter cells that may contain bacteria and have a center of liquefactive necrosis (rhombencephalitis)

·        The parenchyma surrounding microabscesses and glial nodules may be minimally affected, or may be edematous and rarefied with areas of malacia and prominently swollen axons

·        Acute vasculitis with fibrin exudation in the white matter near inflammatory foci, secondary to drainage of the parenchymal foci into the Virchow-Robin space

·        Mononuclear leptomeningitis and densely cellular mononuclear perivascular cuffs (lymphocytes and histiocytes with fewer neutrophils and eosinophils)

·        Neuronal necrosis

·        Cranial nerves may have intrafascicular and perineural accumulations of inflammatory cells (lymphocytes, macrophages, plasma cells, and neutrophils)

ADDITIONAL DIAGNOSTIC TESTS:

·        Gram-positive intrahistiocytic or intraneutrophilic bacilli in tissue, in association with typical light microscopic findings, is pathognomonic

·        CSF analysis: protein concentration greater than 40ug/dL and WBC count greater than 12 mononuclear cells per uL (mononuclear pleocytosis) with consistent clinical signs is suggestive of listeriosis

·        Culture

·        PCR

·        Immunohistochemistry: bacteria in axons, neurons, and microabscesses

 

DIFFERENTIAL DIAGNOSIS:

·        Clinical signs:

·      Nervous ketosis in cattle

·      Middle ear disease

·      Malignant catarrhal fever (purulent endophthalmitis; D-V15, S-V01)

·      Cerebral theileriosis (N-P08): “turning sickness” or “East Coast Fever”; present in Kenya, Tanzania, and India; caused by piroplasm Theileria annulata and Theileria parva

·        Microscopic:

·      Polioencephalomalacia (N-T02; thiamine deficiency): marked laminar cerebral cortical necrosis

·      Malignant catarrhal fever (ovine herpesvirus 2; D-V15, S-V01): perivascular edema, nonsuppurative meningoencephalomyelitis, lymphocytic perivascular cuffing

·      Thrombotic meningoencephalitis (Histophilus somni; N-B03): fibrinonecrotic vasculitis with fibrin thrombi; meningoencephalitis, neutrophilic inflammation, bacterial colonies

·      Rabies (Rhabdoviridae: Lyssavirus; N-V06): nonsuppurative polioencephalomyelitis with ganglionitis, Negri bodies in Purkinje cells

 

 

COMPARATIVE PATHOLOGY:

·        Same triad of syndromes in many mammals and birds

    • Sheep and goats: common
    • Horses, swine, dogs, and rodents: less common
      • Horses: abortion in mares; septicemia in foals
      • Dogs: encephalitis
    • Backyard poultry: L. monocytogenes has been reported as a cause of infectious mortality in backyard poultry within 8 states in the US (Cadmus, J Vet Diagn Invest 2019)

·        Rabbits: abortion (very susceptible), sudden death in does in advanced pregnancy; tropism for gravid uterus (adult bucks and nonpregnant does are resistant); histologic lesions include hepatic necrosis, cerebral and cerebellar microabscesses, mononuclear leptomeningitis with prominent perivascular cuffs; report in Canadian wild hares include necrotizing and fibrinosuppurative transmural metritis and septicemia (Pathology of Wildlife and Zoo Animals 2018)

·        Guinea pigs: used as a model of human maternal-fetal listeriosis; rarely occurs naturally

·        Humans/nonhuman primates: causes septicemia, meningitis, and abortion; one of the most common causes of meningitis in humans

·      New World and Old World Monkeys: clinical disease uncommon; typically, signs include reproductive failure (abortion, stillbirth, neonatal death due to septicemia or cerebral complications); the mother displays absent to mild clinical symptoms; lesions most often include diffuse fibrinopurulent placentitis, and multifocal hepatic and lung necrosis of the fetus (Pathology of Wildlife and Zoo Animals 2018)

·        Monotremes and marsupials: reported in several species; in the antechinus (Australian marsupial), often associated with postmating die off of males secondary to physiological exhaustion, with multifocal pinpoint hepatic (primarily), and myocardial and adrenal necrosis, splenic lymphoid depletion (Pathology of Wildlife and Zoo Animals 2018)

·      Sugar glider: single case report; necrotizing and suppurative hepatitis with associated splenitis and lymphadenitis (Bates, J Am Vet Med Assoc 2017)

·        Camelids: septicemic listeriosis with meningoencephalitis (with microabscesses) reported in two neonatal llamas from the same herd, associated lesions included hepatic necrosis in both animals, splenic lymphoid depletion in one animal; few case reports in South American domestic llamas and alpacas (Hawkins, J Vet Diagn Invest 2017)

·        Brushtail possum (Trichosurus vulpecula) and two common ringtail possums (Pseudocheirus peregrinus): a report of 3 animals with both the encephalitic and septicemic forms (Sangster, Vet Pathol 2016)

 

REFERENCES:

  1. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Wiley-Blackwell; 2016:203, 226-227, 280-281.
  2. Bates MC, Righton AK, Singh K. Pathology in practice. Jour Am Vet Med Assoc. 2017;250(10):1109-1111.
  3. Cadmus KJ, Mete A, Harris M, et al. Causes of mortality in backyard poultry in eight states in the United States. Jour Vet Diagn Invest. 2019;31(3):318-326.
  4. Cantile C, Youssef S. Nervous system. In: Maxie, MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals, Vol I. 6th ed. Philadelphia, PA: Elsevier Ltd; 2016:362-363.
  5. Fairley RA, Pesavento PA, Clark RG. Listeria monocytogenes infection of the alimentary tract (enteric listeriosis) of sheep in New Zealand. Jour Comp Pathol. 2012;146(4): 308-313.
  6. Garcia JA, Michelous JF, Campero CM, Morrell EL, Odriozola ER, Moriera AR. Enteric listeriosis in grazing steers supplemented with spoiled silage. Jour Vet Diag Invest. 2016;28(1): 65-69.
  7. Hawkins IK, Ilha M, Anis E, Wilkes RP. Septicemia and meningoencephalitis caused by Listeria monocytogenes in two neonatal llamas. Jour Vet Diagn Invest. 2017;59(5):700-703.
  8. Mackay RJ, Van Metre DC, eds. Diseases of the nervous system. In: Smith BP, ed. Large Animal Internal Medicine, 5th ed. St. Louis, MO: Elsevier-Mosby; 2015: 952-953, 969-971.

9.    Matto C, Varela G, Mota MI, Fianneechini R, Rivero R. Rhombencephalitis caused by Listeria monocytogenes in a pastured bull. Jour Vet Diagn Invest. 2017;29(2):228-231.

10. Miller AD and Zachary JF: Nervous system. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Mosby, Inc.; 2016:881-882.

  1. Ossibof RJ. Serpentes. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018: 362, 469, 493, 509.
  2. Sangster CR. Multisystemic listeriosis in a common brushtail possum (Trichosurus vulpecula) and two common ringtail possums (Pseudocheirus peregrinus). Vet Pathol. 2016;53(3): 677-681.
  3. Sanjeev N. Listeria. In: McVey DS, Kennedy M, Chengpapa MM, eds. Veterinary Microbiology, 3rd ed. Ames, IA: Wiley-Blackwell; 2013:223-227.


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