JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

March 2023

N-T08

 

Slide A: Signalment (JPC #1372658): Pig; age, breed and gender unspecified

 

HISTORY: This is one of a group of pigs whose water had been turned off for 3 consecutive days; when the farmer noticed that the water had been turned off, he immediately turned it back on; later that day the farmer noticed that many of the pigs were depressed, down or dead.

 

HISTOPATHOLOGIC DESCRIPTION: Cerebrum: There is multifocal laminar cortical necrosis of the middle to deep cortical gray matter characterized by rarefaction, loss, and cavitation (liquefactive necrosis), including loss of neurons, with replacement by eosinophilic and karyorrhectic debris, many gitter cells, increased numbers of microglia, fewer reactive astrocytes, and a few scattered gemistocytes (gliosis). Within less affected areas of middle to deep cortical laminae, many neurons are hypereosinophilic, angular, and shrunken with pyknotic nuclei (necrosis) and are occasionally surrounded by glial cells (satellitosis). Blood vessels within the affected cortical neuropil are often prominent, lined by hypertrophic endothelium (reactive), and surrounded by variably dense cuffs of eosinophils, lymphocytes, and macrophages. Low numbers of similar inflammatory cells multifocally minimally extend into the leptomeninges. There is mild spongiosis within the cortical white matter.  

 

MORPHOLOGIC DIAGNOSIS: Cerebrum, gray matter: Laminar cortical necrosis, multifocal, moderate, with lymphoplasmacytic and eosinophilic perivascular encephalitis, and gliosis, breed unspecified, porcine

 

Slide B: Signalment (JPC #1619720): Sheep; age, breed, and gender unspecified

 

HISTORY: This sheep was given a large quantity of water after having no access to water for 48 hours.  

 

HISTOPATHOLOGIC DESCRIPTION: Cerebrum: There is multifocal liquefactive necrosis of the middle to deep cortical grey matter laminae characterized by vacuolation, rarefaction, and loss of neuropil with neuronal loss and replacement by increased numbers of hypertrophic microglia and astrocytes (gliosis). Within areas of necrosis, many neurons are hypereosinophilic, angular, and shrunken with pyknotic nuclei (necrosis) and are occasionally surrounded by a few glial cells (satellitosis). Virchow-Robin space is multifocally expanded by clear space and endothelial cells are often hypertrophic with swollen nuclei, and there are multifocal areas of mild hemorrhage, fibrin, and edema.

 

Cerebellum and brain stem: No significant findings.

 

MORPHOLOGIC DIAGNOSIS: Cerebrum, gray matter: Laminar cortical necrosis, multifocal, moderate, breed unspecified, ovine

 

ETIOLOGIC DIAGNOSIS: Hypernatremic polioencephalomalacia

 

CAUSE: Salt poisoning; water deprivation syndrome; sodium ion toxicosis

 

GENERAL DISCUSSION: 

• Caused by severe dehydration followed by rehydration (indirect toxicity) or by excessive intake of salt (direct toxicity)
• Does not occur when animals have free access to water with low salinity
• Occurs primarily in pigs and poultry, occasionally in ruminants, dogs, horses, NHPs, and sheep
• Sources of salt may include ingestion of brackish or tidal water, oil well sludge, and improperly mixed milk replacers
• Limitation of water intake may be due to freezing of trough or pipes, competition, debilitation, or distance to water source

 

PATHOGENESIS:

Indirect (Delayed): 

• Neurologic disease precipitated by consumption of high levels of salt with water deprivation followed by excessive water consumption
• Only proven to occur in swine; circumstantial evidence that it may occur in sheep and cattle
• Initially, hypernatremia pulls fluid from the brain causing brain shrinkage. 
• To minimize the difference in osmolality, the brain adapts by allowing movement of sodium and other ions into the parenchyma initially, and later (hours to days), the brain generates organic osmolytes. During rehydration, organic osmolytes cannot shift into vasculature and maintain high osmolality in neural parenchyma, drawing in fluid and causing brain swelling.
• Further pathogenesis is unclear, but character and distribution of lesions resemble those of anoxia.

 

Direct (Immediate): 

• Gastrointestinal and neurologic disease caused by excessive consumption of salt due to high salinity of water or after salt restriction
• Occurs primarily in cattle and poultry
• Pathogenesis of neurologic signs unknown

 

TYPICAL CLINICAL FINDINGS:

• Inappetence, dehydration, animals often found dead
• Indirect salt poisoning: blindness, deafness, unresponsive to external stimuli, head pressing, characteristic convulsions which cause pigs to walk backward and dog-sitting
• Direct salt poisoning in cattle: vomiting, diarrhea, abdominal pain, polyuria, ataxia, paresis, knuckling of fetlocks, and blindness

 

TYPICAL GROSS FINDINGS:

• Indirect salt poisoning: restricted to brain and inconsistently seen; cerebral/leptomeningeal congestion and edema; cerebrocortical laminar necrosis on transverse section
• Direct salt poisoning: congestion of abomasal mucosa in cattle

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Cerebrocortical laminar necrosis and astrocytic swelling
• Pigs: Eosinophilic infiltrates (perivascular, leptomeningeal) combined with laminar cortical necrosis is pathognomonic for salt toxicity
  1. Eosinophilic infiltrate is a non-specific finding on its own
  2. Chronic: Macrophage influx
  3. Edema of subcortical white matter
• Ruminants

• Arteriolar degeneration with neutrophilic infiltrate
• Cerebellar Purkinje cell necrosis
• Edema of basal nuclei, thalamus, midbrain
• Salt toxicity in ruminants does not consistently produce the characteristic cerebral eosinophilia seen in swine

 

ADDITIONAL DIAGNOSTIC TESTS:

• Serum, cerebral, CSF, and ocular sodium levels; however, these may decrease rapidly once given access to water/fluids
• Brain sodium is not uniformly distributed; homogenization of an entire brain hemisphere ensures accurate brain sodium concentration; brain sodium levels take longer to normalize than other samples after an animal has been fluid resuscitated (Romano J Vet Diagn Invest 2022) 

 

DIFFERENTIAL DIAGNOSIS:

• In swine, the combination of laminar cortical necrosis and eosinophilic meningeal and perivascular inflammation is pathognomonic for water deprivation/salt toxicity
• Other causes of encephalitis in swine:

• Mulberry heart disease (vitamin E deficiency) associated leukoencephalomalacia and other porcine encephalitides can cause eosinophilic infiltrates in meninges and perivascular spaces
• Pseudorabies/Aujeszky's disease (Herpesvirus suis, N-V07): Nonsuppurative meningoencephalomyelitis with ganglioneuritis, neuronal degeneration and necrosis, and intranuclear inclusion bodies; also multifocal necrosis in the liver, spleen and adrenal gland
• Bacterial meningoencephalitis (Streptococcus suis, Haemophilus parasuis)
• Teschen's disease (Porcine enterovirus, N-V04): Nonsuppurative polioencephalomyelitis
• Arsenic toxicity (D-T14): Cerebral edema and hemorrhage from vascular necrosis, but primarily degeneration of the spinal cord, peripheral and optic nerves; hemorrhagic gastroenteritis
• Porcine hemagglutinating encephalomyelitis virus (coronavirus): Nonsuppurative meningoencephalomyelitis and neuronal degeneration primarily within peripheral ganglia and the gray matter of the caudal brain stem and spinal cord
• Rabies (rhabdovirus, N-V06): Nonsuppurative encephalomyelitis with perivascular lymphocytic cuffing, gliosis and Negri bodies
• Edema disease (E. coli, N-B02): Shiga-like toxin damages endothelium, resulting in fibrinoid necrosis and vasculitis with secondary ischemic damage

• Cerebral laminar cortical necrosis in ruminants:  

• Thiamine deficiency (vitamin B1, N-T02B) 
• Lead poisoning (N-T05)
• Sulfur toxicity
• Hypoxia

 

COMPARATIVE PATHOLOGY:

 

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, Inc; 2016:314-315.
2. Miller AD, Zachary JF. Nervous system. In: Zachary JF, eds. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Mosby-Elsevier; 2022:853-854.
3. Romano MC, Higgs GE, Helm MN, Stefanovski D, Gaskill CL. Sodium distribution in the bovine brain. J Vet Diagn Invest. 2021; 33(2): 384-387.
4. Schmidt RE, Reavill DR, Phalen DN. Pathology of Pet and Aviary Birds. 2^nd ed. Ames, IO: John Wiley & Sons, Inc. 2015: 141.

 

 

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