JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

January 2017

N-B02

 

Slide A

Signalment (JPC #1822362):  3-year-old, Yorkshire sow

 

HISTORY:  This sow presented with a history of recent loss of condition, posterior weakness and neuromuscular tics.

 

HISTOPATHOLOGIC DESCRIPTION:  Cerebrum and midbrain:  Multifocally, affecting small arteries and arterioles within the leptomeninges, cerebrum, midbrain and hippocampus, infiltrating the tunica media and adventitia and filling Virchow-Robin space are moderate numbers of lymphocytes and plasma cells admixed with small amounts of proteinaceous fluid (edema) and scant fibrin. Diffusely the leptomeninges are expanded by edema and ectatic lymphatics, congested vessels, and few hemosiderin laden macrophages. Multifocally, typically centered on vessels within the hippocampus and midbrain, there are small foci with rarefaction, edema and vacuolation of the neuropil. 

 

MORPHOLOGIC DIAGNOSIS:  Meningitis, lymphoplasmacytic, perivascular, multifocal, moderate, with neuropil rarefaction, and perivascular and meningeal edema, Yorkshire, porcine.

 

Slide B

Signalment (JPC #M0 4932):  3-week-old pig

 

HISTORY:  This pig presented with clinical signs of a CNS disturbance.

 

HISTOPATHOLOGIC DESCRIPTION:  Cerebrum:  Within the gray matter there are multiple foci of rarefaction up to 2 mm in diameter, characterized by pale staining, increased clear space (edema), vacuolated neuropil (spongiosis) and few shrunken, angular, hypereosinophilic necrotic neurons.   Multifocally, capillaries are lined by hypertrophied endothelial cells, and surrounded by edema and few lymphocytes and plasma cells that occasionally infiltrate the vessel walls and fill Virchow-Robin space. Rarely, the vessel walls of small arteries and arterioles are expanded/infiltrated by proteinaceous fluid, fibrin, and scant cellular debris (necrotizing vasculitis). The leptomeninges are minimally expanded by low numbers of lymphocytes and plasma cells and mild edema.

MORPHOLOGIC DIAGNOSIS:  Cerebrum:  Vasculitis, necrotizing and lymphoplasmacytic, multifocal, mild, with neuropil rarefaction, spongiosis, neuronal necrosis, perivascular and meningeal edema, Yorkshire, porcine.

 

ETIOLOGIC DIAGNOSIS:  Verotoxic meningitis

 

CAUSE:  Shiga-like toxin type IIe (verotoxin) producing Escherichia coli (VTEC)

 

CONDITION:  Edema disease

 

SYNONYM:  Enterotoxemic colibacillosis; cerebrospinal angiopathy

 

GENERAL DISCUSSION:

·       Generally occurs after weaning (piglets 6-14 weeks of age) or after a change in diet

·       Disorder of rapidly growing, healthy feeder pigs being fed high energy ration

·       Morbidity around 30%, with mortality approaching 100% of affected animals

·       Results in sudden death or nervous signs

 

PATHOGENESIS

·       Enterohemorrhagic (ETEC) E. coli (O serotypes) colonization of the small intestine > Shiga-like toxin enters blood stream > toxin damages endothelium and tunica muscularis (angiotoxin)> affinity for vessels in CNS and facial subcutis > edema and encephalomalacia

·       Spread via aerosols, direct contact, feed and other vehicles

·       Colonization of the small intestine by O serotypes of E. coli (O138, O139, O140)

·       E. coli epithelial colonization (jejunum / ileum) is mediated by F18ab fimbriae

·       Genetic susceptibility depends on the ability of E. coli to adhere to the intestine; receptors for E. coli (ie. F18) are not present in all pigs

·       Diarrhea is not a common feature of edema disease, although some strains produce a secretory enterotoxin that causes diarrhea

·       Enterotoxin (Shiga-like toxin type IIe[Stx2e] or verotoxin 2e)

·       Causes necrosis, not apoptosis, of endothelial and smooth muscle cells in blood vessels (disrupts protein synthesis leading to vascular permeability changes and cell lysis)

·       Endothelial cell sensitivity to Shiga-like toxin depends on the amount of Shiga-like toxin receptor (globotriaosyl ceramide and globotetraosyl ceramide)

·       Exposure of endothelial cells to lipopolysaccharides or cytokines (TNF-alpha, IL-1) increases sensitivity of some endothelial cells to the cytotoxic effects of Stx2e

·       Shiga-like toxin/verotoxin induces production of IL-8 > attracts neutrophils > spread toxin throughout body

 

TYPICAL CLINICAL FINDINGS:

·       Subcutaneous edema, primarily of the eyelids, forehead, nose, throat and lips

·       Nervous signs: Ataxia, convulsions, paralysis, aimless wandering and muscle tremors

 

TYPICAL GROSS FINDINGS:

·       CNS: Bilateral symmetrical areas of malacia; tan-grayish discoloration in the brainstem that may extend into the basal nuclei

·       Alimentary: Gastric edema, mesentery of the spiral colon, and gallbladder

·       Pulmonary: Edema with multifocal sublobular congestion; pleural effusions with white strands of fibrin

·       Cardiac: Epicardial and endocardial petechiae; pericardial effusion

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

·       Degenerative angiopathy/vasculitis affecting small arteries and arterioles (not a prominent feature in this case)

·       Early:  Perivascular edema with protein-rich, eosinophillic droplets

·       Late: Fibrinoid vascular necrosis is accompanied by infiltration of the tunica adventitia with neutrophils, lymphocytes, plasma cells and macrophages, resulting in endothelial hypertrophy of adventitial and medial layers

·       Thrombosis is usually not a feature (endothelium usually remains intact)

·       Most frequent and most severe in brainstem (caudal medulla to diencephalon) and in cerebral and cerebellar meninges

·       Focal encephalomalacia in brainstem

 

ADDITIONAL DIAGNOSTIC TESTS:

·       Serology

·       PCR

 

DIFFERENTIAL DIAGNOSIS:

For ataxia and recumbency in swine

·       Pseudorabies/Aujeszky's Disease (porcine herpesvirus-1):  Nonsuppurative meningoencephalomyelitis with ganglioneuritis, neuronal degeneration,  necrosis, and eosinophilic or basophilic intranuclear inclusion bodies 

·       Bacterial meningoencephalitis (Streptococcus suis, Haemophilus parasuis)

·       Water deprivation/salt toxicity: Laminar cerebrocortical neuronal necrosis, with swollen astrocytes and perivascular eosinophilic cuffs in the leptomeninges

·       Teschen's disease (Porcine enterovirus):  Nonsuppurative polioencephalomyelitis

·       Arsenic Toxicity:  Cerebral edema and hemorrhage from vascular necrosis,  but primarily degeneration of the peripheral and optic nerves, and the spinal cord, and a hemorrhagic gastroenteritis

·       Dietary microangiopathy of swine (Vitamin E-selenium deficiency): Fibrinoid necrosis of small arteries and arterioles with fibrin thrombi; primary lesions include hydropericardium and cardiac hemorrhage (Mulberry heart disease) and massive hepatic necrosis (hepatosis dietetica)

·       Porcine hemagglutinating encephalomyelitis virus (coronavirus): This disease affects pigs less than a week old; nonsuppurative meningoencephalomyelitis and neuronal degeneration primarily within the gray matter of the caudal brain stem and spinal cord

·       Rabies (rhabdovirus): Nonsuppurative encephalomyelitis with perivascular lymphocytic cuffing, gliosis and Negri bodies

 

COMPARATIVE PATHOLOGY:

·       In humans, shiga-like toxin producing O157:H7 E. coli causes hemorrhagic colitis and hemolytic uremic syndrome, characterized by acute renal failure, thrombocytopenia and microangiopathic hemolytic anemia

 

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. Philadelphia, PA: Elsevier Saunders; 2016: 297.

2.      Fairbrother JM, Gyles CL. Colibacillosis. In: Zimmerman JJ, Karriker LA, Ramirez A, Schwartz KJ, Stevenson GW, eds. Diseases of Swine. 10th ed. Ames, IA: Wiley-Blackwell; 2012:735.

3.      Gyles C, Boerlin P. Horizontally transferred genetic elements and their role in pathogenesis of bacterial disease. Vet Pathol. 2014; 51(2):328-340.

4.      Miller AD, Zachary JF. Nervous system. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Mosby Elsevier; 2016: 888-890.

5.      Uzal FA, Plattner BL, Hostetter JM.  Alimentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA: Elsevier Saunders; 2016: 162.

6.      Vandevelde M, Higgins RJ, Oevermann A. Veterinary Neuropathology. Ames, IA: Wiley-Blackwell; 2012: 117-118.

7.      Zachary JF. Mechanisms of microbial infections. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Mosby Elsevier; 2016: 157, 179, 189. 

 

 


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