JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

January 2023

N-M02

 

Signalment (JPC #2020918): Two-year-old thoroughbred gelding

 

HISTORY: This horse’s clinical presentation varied from nearly normal to severe incoordination. Necropsy revealed no gross lesions in the spinal cord or brain. When the neck was flexed, the anterior end of the vertebral body of C5 protruded into the spinal canal, resulting in an approximately 50% reduction in the canal diameter. Less pronounced protrusions were noted at C3-C4 and C5-C6. Specimens submitted were from C6-C7.

 

HISTOPATHOLOGIC DESCRIPTION: Spinal cord, cervical (C6-C7 per contributor): Within the lateral and ventral funiculi, and most prominently in the white matter around the ventromedian fissure, there is multifocal moderate spongiosis. In these regions, approximately 25% of axons exhibit axonal (Wallerian) degeneration characterized by myelin sheaths that are dilated up to 5 times normal and which contain glassy, eosinophilic, swollen axons up to 30µm diameter (spheroids) or fragmented myelin debris (ellipsoids) admixed with single to multiple foamy macrophages which are occasionally multinucleated (gitter cells). There are increased numbers of gemistocytic astrocytes in areas of spongiosis. There is multifocal hemorrhage throughout the grey matter. 

 

MORPHOLOGIC DIAGNOSIS: Spinal cord, cervical, white matter: Axonal degeneration, ventral and lateral funiculi, moderate, with dilated myelin sheaths, spheroids, and ellipsoids (Wallerian degeneration), thoroughbred, equine.

 

ETIOLOGIC DIAGNOSIS: Spinal cord compression

 

CAUSE: Cervical vertebral stenosis

 

CONDITION: Cervical vertebral stenotic myelopathy

 

CONDITION SYNONYMS: Cervical vertebral malformation-malarticulation, cervical compressive myelopathy, wobbler syndrome, equine incoordination, equine sensory ataxia

 

GENERAL DISCUSSION:  

• Occurs in young, rapidly growing horses
• May be caused by dynamic (more common, termed cervical vertebral instability) or static (termed cervical vertebral stenosis) compression
• Spinal cord compression results in progressive spinal cord injury, ataxia and paresis (“wobbler” in wobbler syndrome refers to the ataxia)

 

PATHOGENESIS:

• Unknown cause; likely multifactorial 
• Affected horses are rapidly growing and on a high nutritional plane
• Hereditary and nutritional factors (oversupplementation) are postulated
• Dietary copper (low), zinc (high), carbohydrates (high) thought to play a role
• Osteochondrosis may encroach on the spinal canal or result in vertebral malalignment due to asymmetric articular facets

 

TYPICAL CLINICAL FINDINGS:

• Horses are rapidly growing, generally 6 months – 3 years of age 

• Cervical vertebral instability (dynamic): 8 – 18 months of age
• Cervical static stenosis: 1 – 4 years of age

• Thoroughbreds, warm bloods, Tennessee walking horses, quarter horses
• Males more common than females
• Gradual onset (though hard exercise may precipitate acute disease)
• Nervous signs: ataxia and paresis; generally symmetric; pelvic limbs more affected than the thoracic limbs
• Signs may improve with rest, remain static, or worsen
• Forced flexion of the neck may exacerbate clinical signs

 

TYPICAL GROSS FINDINGS:  

• Cervical vertebral instability (dynamic): most commonly caused by malarticulation and most commonly at C3-C5 (more mobile); may be caused by osteochondrosis of articular facets or abnormally large cranial vertebral epiphysis (Olsen 2022); compression may not be evident unless neck is flexed and may require parasagittal sectioning of vertebral column to visualize
• Cervical static stenosis: malformation of the spinal canal most commonly at C5-C7 (less mobile); primarily due to thickening of ligamentum flavum and dorsal lamina which may be developmental or may be secondary to mechanical trauma (quarter horses) (Olsen 2022); also due to osteophytes or osteochondrosis of articular facets 
• No gross lesions in the cord; may have rare foci of hemorrhage or malacia 

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Findings vary based on where the section is compared to the site of compression/stenosis 

• Cranial to compression site: Wallerian degeneration in ascending fibers, most of which are in the dorsal and lateral funiculi 
• At the compression site: Extensive axonal degeneration, secondary demyelination, and accompanying mild to moderate microglial proliferation; hemorrhage and necrotic foci in gray matter in severe cases; +/-retrograde chromatolysis of neurons
• Caudal to compression site: Wallerian degeneration in descending fibers, most of which are in the ventral and lateral funiculi 

• Static stenosis: the ligamentum flavum and dorsal lamina may have excess disorganized fibrocartilage, bone proliferation, and siderophages 

 

DIFFERENTIAL DIAGNOSIS:

• Other spinal cord degeneration in horses:

• Occipitoatlantoaxial malformation: inheritable malformation of the occipital bone, atlas, and axis; most frequently seen in Arabian horses
• Equine degenerative myeloencephalopathy (N-M07): Idiopathic disease of young horses; degeneration and demyelination of white matter tracts of the spinal cord and degenerative lesions of spinal and brain stem nuclei
• Intervertebral disk herniation: Herniated disk present at lesion site; reported rarely in horses in cervical spine, similar to Hansen type II disk herniation (see N-M27)

• Other causes of hind limb ataxia and paresis:

• Equine herpesvirus-1 myeloencephalitis: Vasculitis with necrosis and thrombosis of spinal cord and brain
• Neuritis of the cauda equina (N-M18): Severe granulomatous epidural inflammation of the cauda equina; cause unknown
• Rabies: (Lyssavirus, family Rhabdoviridae (N-V06)): Perivascular mononuclear perivascular cuffs and Negri bodies
• Protozoal myelitis (Sarcocystis neurona, N-P01): Necrotizing nonsuppurative myelitis or encephalitis with extensive mononuclear perivascular cuffs
• Intervertebral disk herniation (N-M27): Herniated disk present

 

COMPARATIVE PATHOLOGY:

• Dogs: Cervical vertebral malformation-malarticulation typically occurs at C5-C7; typically larger breeds at 8 months to one year of age (great Dane, Doberman pinscher, Saint Bernard, Irish setter, fox terrier, basset hound, Rhodesian ridgeback, Old English Sheepdog); males overrepresented; C3 affected in Basset hounds
• Uncommon in other domestic animals; lesions have been reported in calves, sheep, goats, and mink

 

References:

1. 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; 2016:303, 322-323.
2. Craig LE, Dittmer KE, Thompson KG.  Bones and joints. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA: Elsevier; 2016:136. 
3. Janes JG, Garrett KS, McQuerry KJ, et al. Cervical vertebral lesions in equine stenotic myelopathy. Vet Pathol. 2015; 52(5):919-927. 
4. Miller AD, Porter BF. Nervous system. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022: 953-954.
5. Olson EJ, Dykstra JA, Armstrong AR, Carlson CS. Bones, joints, tendons, and ligaments. In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier Mosby; 2022:1064.
6. Smith BP. Large Animal Internal Medicine. 5th ed. St. Louis, MO: Mosby Press; 2015:985-988.
7. Summers BA, Cummings JC, de Lahunta A. Veterinary Neuropathology. St. Louis, MO:   Mosby; 1995:193-202.

 

Click the slide to view.

---