JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

February 2017

N-M19

 

Signalment (JPC #1852981):  A 4-year-old Rhesus macaque

 

HISTORY:  After a week of water deprivation, this animal drank water heavily but ate poorly.  Over the course of a week, it became depressed and died despite supportive care.

 

HISTOPATHOLOGICAL DESCRIPTION:  Cerebrum, cortex:  Diffusely in the meninges and multifocally in the white and gray matter, veins are dilated up to 1mm and congested and often contain thrombi.  Occasionally, the walls of the thrombosed veins are expanded by hyalinized fibrin and edema (fibrinoid change).  Multifocally, the endothelium lining affected vessels is moderately hypertrophied (reactive).  Multifocally within the white matter surrounding affected veins, there are moderate numbers of gemistocytes, increased numbers of microglial cells (microgliosis), and hemosiderin-laden macrophages admixed with hemorrhage.  There is mild vacuolation in the adjacent white matter (edema).  Rare axons are swollen, rounded, and eosinophilic (spheroid). 

 

MORPHOLOGIC DIAGNOSIS:  Cerebrum, vessels:  Thrombosis, venous, multifocal, moderate, with congestion, vascular fibrinoid change, hemorrhage, hemosiderosis, gemistocytosis, and rare spheroids, rhesus macaque, nonhuman primate.

 

CONDITION:  Idiopathic cerebral venous thrombosis

 

GENERAL DISCUSSION:

·       Cerebral venous thrombosis is a recognized entity in humans and rarely occurs in macaques

 

PATHOGENESIS:

·       The etiology is unknown but it has been reported with diseases leading to hypercoagulability such as diarrhea and water deprivation; it can also be an incidental finding at necropsy

·       Hypovolemia/endotoxemia from colitis > vasodilatation, vascular stasis, and elaboration of inflammatory cytokines (TNF and IL-1) > activation of the clotting cascade and thrombosis >venous occlusion > perivascular edema > demyelinating lesion

·       Proposed that degenerate axonal terminals in center of lesion release excessive amounts of neurotransmitter glutamate leading to injury of still viable neurons on periphery; glutamate binds to viable neuron > calcium flows into cell > cell death

·       Neurons (especially Purkinje cells) and oligodendroglia are most sensitive to ischemia; astrocytes are moderately resistant; microglia and blood vessels are most resistant

·       Gray matter and deeper lamina are more sensitive to ischemia than white matter and superficial lamina due to higher metabolic rate and dependence on oxygen

 

TYPICAL CLINICAL FINDINGS:

·       Signs reflect the primary disease present and the location and extent of injury; can range from nonexistent to moderate

·       CNS signs include depression, ataxia, loss of reflexes or proprioception, and seizures; diarrhea common

·       CSF usually normal

 

TYPICAL GROSS FINDINGS:

·       Abundance of lipid and lack of fibrous connective tissue in CNS causes gross lesions to become soft due to liquefactive necrosis; gray matter lesions tend to be hemorrhagic and white matter lesions tend to be soft due to less dense capillary meshwork

·       Multifocal congestion, thrombi, hemorrhage, and malacia occurs primarily in the white matter of the cerebrum and may rarely occur in the cerebellum

·       Typically bilateral, but not always symmetrical

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

·       Common to see acute and chronic lesions

·       Major CNS lesions include multiple cerebral and dural thrombi, hemorrhage, fibrin, perivascular demyelination, reactive gemistocytic astrocytes

·       It is not uncommon to have chronic lesions characterized by recanalization of thrombi adjacent to acute lesions

 

DIFFERENTIAL DIAGNOSIS:

·       Venous infarcts have more extensive hemorrhage and affect the white matter; arterial infarcts usually affect the gray matter due to its high metabolic rate

 

COMPARATIVE PATHOLOGY:

·       Horse

o   Equine herpesvirus 1:  "Strokes" secondary to necrotizing vasculitis and thrombosis

o   Neonatal maladjustment syndrome:  Lesions range from perivascular and petechial hemorrhage throughout the brain to ischemic laminar necrosis of the cerebral cortex with necrosis in paired grey nuclei of brainstem; etiology is unknown

·       Dog

o  Cerebral infarction due to aberrant migration of Dirofilaria immitis

o  Amyloid degeneration of meningeal and cerebral vessels occurs in aged dogs

o  Fibrocartilaginous embolism primary affects spinal cord

o  Atherosclerosis secondary to hypothyroidism or diabetes mellitus

o  Vasculitis associated with systemic lupus erythematosis or Rocky Mountain spotted fever (Rickettsia rickettsii)

o  Steroid-responsive meningo-arteritis (polyarteritis nodosa) has a predilection for spinal arteries

 

·       Cat

o   Feline ischemic encephalopathy: Cerebral infarction due to Cuterebra sp. migration

o   More severe lesions tend to be around the middle cerebral artery

·       Pig

o   Organomercurial poisoning: Hyaline necrosis of meningeal vessels

o   Polyarteritis nodosa: Predilection for the cerebral arteries

o   Edema disease (Shiga-like toxin producing Escherichia coli): important cause of cerebrospinal angiopathy

·       Cattle

o   Noninflammatory thrombosis of the cranial dural sinuses occurs in polioencephalomalacia and head injuries

o   Thrombotic meningoencephalitis (Histophilus somni): Vasculitis, thrombosis and neutrophilic inflammation

 

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. St. Louis, MO: Elsevier; 2016:296-301.

2.      Fahey MA, Westmoreland SV. Nervous system disorders of nonhuman primates and research models. In: Abee CR, Mansfield K, Tardif S, et al., eds. Nonhuman Primates in Biomedical Research: Diseases. Vol 2. 2nd ed. London, UK: Elsevier; 2012:756-757.

3.      Harber ES, O’Sullivan MG, Jayo MJ, et al. Cerebral infarction in two cynomolgus macaques (Macaca fascicularis) with hypernatremia. Vet Pathol. 1996;33(4):431-434.

4.      Kumar V, Abbas AK, Aster JC. Hemodynamic disorders, thromboembolic disease, and shock. In: Kumar V, Abbas AK, Aster JC. eds. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Philadelphia, PA: Elsevier Saunders; 2015:127-131.

5.      Lewis AD, Colgin LMA. Pathology of noninfectious diseases of the laboratory primate. In: Wolfe-Coote S, ed. The Laboratory Primate. London, England: Elsevier Limited; 2005:61-62.

6.      Miller AD, Zachary JF. Nervous system. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017: 822-825.

7.      Musio F, Older SA, Jenkins T, et al. Case report: Cerebral venous thrombosis as a manifestation of acute ulcerative colitis. Am J Med Scien. 1993;305(1):28-35.

8.      Sheffield WD, Squire RA, Strandberg JD. Cerebral venous thrombosis in the rhesus monkey. Vet Pathol. 1981;18(3):326-334.

9.      Swayne DE, Tyler DE, Batker J. Cerebral infarction with associated venous thrombosis in a dog. Vet Pathol. 1988;25(4):317-320.

 


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