JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

March 2023

N-T11

 

Signalment (JPC #2038191): Age and breed unspecified horse

 

HISTORY: This horse had hypertonia of the lips, tongue, and facial muscles causing the animal to have a fixed or wooden expression. The horse died after an acute inability to eat or drink.

 

HISTOPATHOLOGIC DESCRIPTION: Mesencephalon, level of the substantia nigra, pineal gland, and subcommissural organ: Within the substantia nigra there is a focal, well demarcated, 5 mm diameter area of cavitation with complete loss of neuropil and replacement by numerous gitter cells and abundant clear space (liquefactive necrosis). The area of cavitation contains few scattered thin strands of pre-existing eosinophilic fibrillar material and pre-existing vessels lined by reactive endothelium. Multifocally, within the surrounding neuropil and white matter, there are moderately increased numbers of glial cells (gliosis), moderate numbers of dilated myelin sheaths containing brightly eosinophilic 15-20 µm diameter swollen axons (spheroids), and few scattered degenerate and necrotic neurons. Blood vessels within the leptomeninges and neuroparenchyma are mildly congested.

 

MORPHOLOGIC DIAGNOSIS: Mesencephalon, substantia nigra: Necrosis, liquefactive, focally extensive, with cavitation, gliosis, and spheroids, breed unspecified, equine.

 

CAUSE: Yellow star thistle (Centaurea solstitialis), Russian knapweed (Centaurea repens), or purple star thistle (Centaurea calcitropa)

 

CONDITION: Nigropallidal encephalomalacia (NPE); Toxic Equine Parkinsonism

 

CONDITION SYNONYMS: "Chewing disease"

 

GENERAL DISCUSSION:

• Caused by prolonged ingestion of yellow star thistle (Centaurea solstitialis) or Russian knapweed (Centaurea repens)
• Occurs in the summer when most plants are dried and thistle remains green and palatable as forage
• Disease is similar to Parkinson’s disease in humans; proposed as a model for experimental studies, but equine disease is not associated with the abnormal cytoplasmic accumulation of α-synuclein as is seen in Parkinson’s disease

 

PATHOGENESIS:

• Exact mechanism is unknown; caused by a neurotoxin called repin; repin is a principle sesquiterpene lactone present in the aerial (above ground) parts of the plant
• Repin causes glutathione (major antioxidant) depletion, increase in ROS and oxidative damage, mitochondrial dysfunction, membrane damage in PC12 cells (pheochromocytoma cell line) and mouse astrocytes, and neuronal cell death
  1. Repin also inhibits dopamine release in the rat striatum which may contribute to clinical signs
• Onset of disease is sudden and may occur as early as 1 month after initial exposure to start thistle
• Death is a result of starvation and dehydration
• Dopaminergic strionigral tract (striatum and substantia nigra) is a target area; proposed that the high concentration of monoamine oxidase involved in dopamine metabolism could render these areas of the brain more susceptible to oxidative damage

 

TYPICAL CLINICAL FINDINGS:

• Idle drowsiness, persistent chewing movements, and difficulty in prehension; sensation and reflexes are normal
• Lip and tongue paralysis with reduced jaw tone are early clinical signs

 

TYPICAL GROSS FINDINGS:

• Usually both the globus pallidus and substantia nigra are symmetrically involved, but can involve only one structure; affected areas are slightly bulging, yellow, gelatinous foci that progress rapidly to a sharply demarcated pseudocystic cavity
  1. Pallidal foci involve the rostral portion of the globus pallidus, are lenticular in form, and 1-1.5 cm in size
  2. Substantia nigra contains a core of necrotic tissue that is ~0.5 cm in diameter and extends from the mammillary bodies to the point of emergence of the oculomotor nerve

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

 

DIFFERENTIAL DIAGNOSIS:

• Rabies virus (N-V06) induces perivascular cuffing and gliosis with eosinophilic cytoplasmic inclusion bodies (Negri bodies)
• Leukoencephalomalacia due to fumonisin B1 intoxication (N-T10) Fusarium verticillioides and F. proliferatum (formerly grouped together as Fusarium moniliforme contaminated corn) produces bilateral but unequal encephalomalacia of the white matter tracts of the cerebrum
• Hepatoencephalopathy due to hepatotoxic plants (Crotalaria, Senecio)
• Other causes of necrosis (not typically bilaterally symmetrical or confined to the globus pallidus and substantia nigra): Equine protozoal myelitis (N-P01), EHV-1, etc.

 

COMPARATIVE PATHOLOGY:

Centaurea sp. toxicosis in other species:

• The plants do not appear to be toxic to ruminants, rodents, other small laboratory animals, monkeys, or dogs; sheep do well on sole diets of these plants
• Other plants with sesquiterpene lactones include Chrysanthemum spp. (contact dermatitis) and Geigeria, Helenium and Hymenoxys spp. that produce regurgitation, salivation, dysphagia, and coughing in cattle

 

REFERENCES:

1. Cantile C, Youssef S. The nervous system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA: Elsevier Limited; 2016:314.
2. Miller AD, Porter BF. Nervous system. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier, Inc.; 2022:956-966.

 

 

 

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