AFIP SYSTEMIC PATHOLOGY

JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

January 2017

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 that is separated by abundant clear space and is infiltrated by large numbers of degenerate and nondegenerate neutrophils, fewer gitter cells, lymphocytes, and abundant cellular and karyorrhectic debris (necrosis).  Within surrounding, less affected areas are numerous microabscesses composed of nodules of viable and degenerate neutrophils that occasionally have a central area of lytic necrosis.  Adjacent to the area of rarefaction there is spongiosis and multiple cross-sections (spheroids) and longitudinal-sections of swollen axons within dilated myelin sheaths. Multifocally, vascular endothelial cells and vessel walls are 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

                      

CAUSEListeria monocytogenes

 

CONDITION:  Listeriosis, “Circling disease”

 

GENERAL DISCUSSION

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

o   Almost all animal infections are caused by serotypes 1/2a, 1/2b, and 4b (food borne illness strains belong to 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 (seldom overlap; likely separate pathogeneses):

·       Encephalitis: Disease of adult ruminants, associated with heavy feeding of silage

o   Bacterial invasion through wounds in oral mucosa (pathologic of 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

o   Affinity for brainstem, lesions most severe in the medulla and pons

o   Extensive tissue destruction associated with suppurative inflammation is common

·       Abortion

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

o   Can cause third trimester abortion

o   Retention of fetal membranes causes clinical illness

·       Septicemia:  More common form in monogastrics

o   Transported by macrophages

o   Liver, heart:  Multifocal necrosis or miliary microabscesses, rarely other tissues

o   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: 

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

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

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

 

TYPICAL CLINICAL FINDINGS

  • Encephalitic form: 

o   Mental confusion and depression, head pressing, turning or twisting of head to one side, walking in circles

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

o   Paralysis of masticatory muscles and pharynx leading to drooling

o   Strabismus, nystagmus, hemiparesis, decreased rumenal motility

  • Purulent endophthalmitis, usually unilateral

 

TYPICAL GROSS FINDINGS

  • Gross brain lesions are rare
  • Occasionally, medullary meninges may be thickened by greenish gelatinous material
  • Occasionally there are gray foci of softening (malacia) in cross sections of the medulla

 

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
  • Parenchyma surrounding microabscesses and glial nodules may be minimally affected or 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 (rhombencephalitis) 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:

o   Nervous ketosis in cattle

o   Middle ear disease

o   Malignant catarrhal fever (purulent endophthalmitis)

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

  • Microscopic:

o   Polioencephalomalacia (thiamine deficiency): Marked laminar cerebral cortical necrosis

o   Malignant catarrhal fever (ovine herpesvirus 2):  Perivascular edema, nonsuppurative meningoencephalomyelitis, lymphocytic perivascular cuffing

o   Thrombotic meningoencephalitis (Histophilus somni):  Fibrinonecrotic vasculitis with fibrin thrombi; meningoencephalitis, neutrophilic inflammation, bacterial colonies

o   Rabies (Rhabdoviridae: Lyssavirus): Nonsuppurative polioencephalomyelitis with ganglionitis, Negri bodies in Purkinje cells

 

COMPARATIVE PATHOLOGY

  • Same triad of syndromes in many mammals and birds
  • Sheep and goats, commonly
  • Horses, swine and rodents, less common
  • Rabbits: Abortion, sudden death in does in advanced pregnancy; tropism for gravid uterus (adult bucks and nonpregnant does are resistant)
  • 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
  • Bushy-tailed jirds (Sekeetamys calurus): a report of a natural outbreak of the systemic form in which affected animals died acutely without prior clinical signs
  • Brushtail possum (Trichosurus vulpecula) and two common ringtail possums (Pseudocheirus peregrinus):  a report of 3 animals with both the encephalitic and septicemic forms

 

References:

  1. Barthold SW, Griffey SM, Perch DH.  Pathology of Laboratory Rodents and Rabbits.  4th ed.  Ames, IA: Wiley-Blackwell; 2016:203, 226-227, 280-281.
  2. 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.
  3. Fairley RA, Pesavento PA, Clark RG.  Listeria monocytogenes infection of the alimentary tract (enteric listeriosis) of sheep in New Zealand.  J Comp Pathol.  2012;146(4): 308-313.
  4. Garcia JA, Michelous JF, Campero CM, Morrell EL, Odriozola ER, Moriera AR.  Enteric listeriosis in grazing steers supplemented with spoiled silage.  J Vet Diag Invest. 2016;28(1): 65-69.
  5. 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.
  6. 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.
  7. Radostits OM. Diseases caused by bacteria. In: Radostits OM, Gay DC, Blood DC, Hinchcliff KW eds. Veterinary Medicine. 10th ed. Philadelphia, PA: WB Saunders Co., Ltd.; 2010:805-810. 
  8. 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.
  9. Sanjeev N.  Listeria.  In:  McVey DS, Kennedy M, Chengpapa MM, eds. Veterinary Microbiology, 3rd ed.  Ames, IA: Wiley-Blackwell; 2013:223-227.
  10. Summers BA. Inflammatory diseases of the central nervous system. In: Cummings JF, de Lahunta A, eds. Veterinary Neuropathology. St. Louis, MO: Mosby-Year Book, Inc.; 1995:134-135.
  11. Vandevelde M, Higgins RJ, Oevermann, A.  Veterinary neuropathology: essentials of theory and practice, 1st ed.  Ames, IA: Wiley-Blackwell; 2012:50, 66-67.

 


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