JPC SYSTEMIC PATHOLOGY
Signalment (JPC # 2287965): Three-year-old Welsh cob mare
HISTORY: This mare had a one-year history of ataxia. No abnormalities were seen on cervical radiographs taken 3-months before euthanasia.
HISTOPATHOLOGIC DESCRIPTION: Brainstem: Within the dorsal brainstem there are bilaterally symmetrical areas of neuronal degeneration (characterized by swollen, vacuolated pale cytoplasm with loss of Nissl substance), necrosis (characterized by shrunken, angular, hypereosinophilic cytoplasm), and loss affecting the lateral and medial (accessory) cuneate nuclei. There are moderate numbers of swollen eosinophilic axons, up to 60um in diameter, with homogenous granular axoplasm (spheroids) and occasional dilated myelin sheaths. Within the affected nuclei, there are mildly increased numbers of hypertrophied (reactive) astrocytes (astrogliosis) and scattered macrophages that contain a yellow-brown, granular intracytoplasmic pigment (presumed lipofuscin).
MORPHOLOGIC DIAGNOSIS: Brainstem, cuneate nuclei: Neuroaxonal degeneration and necrosis, bilaterally symmetrical, moderate, with spheroids, Welsh cob, equine.
CONDITION: Equine degenerative myeloencephalopathy
· Chronically progressive, irreversible syndrome of symmetrical ataxia of unknown cause in young horses (6-24 months of age)
· Demyelination in white matter of spinal cord funiculi and brainstem
· May be a familial predisposition in Appaloosa, standardbred, Paso Fino and Lusitano horses
· Underdiagnosed entity due to clinical overlap with cervical vertebral compressive myelopathy and subtle histological findings
· Considered an advanced form of neuroaxonal dystrophy
· Sensory tracts affected include: spinocuneocerebellar (involved in unconscious proprioception - forelimbs), dorsal column-medial lemniscal (involved in conscious proprioception) and dorsal spinocerebellar tracts (involved in unconscious proprioception - hindlimbs)
· Simultaneous involvement in multiple cord segments of ascending and descending tracts
· Vitamin E deficiency may play a rolein the disease process since supplementation reduces the severity of clinical deficits
o Oxidative damage and lipid peroxidation of cell membranes > accumulation of lipopigment
· Other risk factors that may play a role: Copper deficiency, toxins (insecticides or wood preservatives), inadequate access to green pasture
· Recent studies indicated that a defect in axonal transport of proteins, particularly certain proteins vital to synaptic function, may be a key mechanism in the pathogenesis
TYPICAL CLINICAL FINDINGS:
· Slowly progressive course
· Proprioceptive and upper motor neuron deficits
· Spastic gait, knuckling, stumbling, circumduction, abduction, hypermetria
· All limbs may be equally affected, or may be more pronounced in the rear limbs
TYPICAL GROSS FINDINGS:
· No gross lesions
TYPICAL LIGHT MICROSCOPIC FINDINGS:
· Axonal loss, demyelination and astrogliosis
· Ongoing Wallerian degeneration and post-Wallerian astrogliosis in all funiculi throughout the spinal cord
o Most dramatic in the mid-thoracic and anterior cervical segments in the ascending dorsolateral (spinocerebellar) and descending ventromedial (motor) tracts
o Similar but mild changes are noted in myelinated tracts of the caudal medulla and caudal cerebellar peduncle
· Loss of myelinated axons and dense reactive gliosis
· Additional lesions: Spheroids, astrocytosis, degenerate and necrotic neurons, accumulation of lipofuscin-like pigment in macrophages, endothelial cells and neurons
ADDITIONAL DIAGNOSTIC TESTS:
· Luxol-fast blue to demonstrate demyelination
o 3-nitrotyrosine (3-NT) and 4-hydroxynonenol (4-HNE) to show oxidative damage
o Increases in neurons with oxidative stress
· Moderate neuronal apoptosis
· Calretinin staining of spheroids can identify neural tracts affected by the disease
· GFAP can highlight glial scarring due to degeneration and loss of axons
· Equine motor neuron disease- clinically similar syndrome to EDM with degenerative changes in the brainstem; older horses; slightly different anatomic locations affected; vitamin E deficiency may play a role in the disease
· Cervical stenotic myelopathy (Wobbler syndrome) – axonal degeneration and demyelination
· Equine protozoal myeloencephalitis (Sarcocystis neurona) – necrotizing, nonsuppurative myeloencephalitis, axonal degeneration, schizonts and merozoites
· Cauda equina syndrome (idiopathic polyradiculoneuritis) – granulomatous inflammation around cauda equine
· Equine herpesvirus-1 (alphaherpesvirus) myeloencephalopathy – vasculitis and necrosis in spinal cord and brain; often accompanies or follows respiratory disease and abortions
· Perinneal rye grass staggers (Lolium perenne) – no specific pathologic changes; can have axonal swelling, especially in Purkinje cells (torpedoes)
· Parasite migration – Strongylus sp., Hypoderma sp.
· Neuroaxonal dystrophy in Morgan horses: Clinically similar syndrome to EDM with degenerative changes in the brainstem; vitamin E deficiency may play a role in the disease
· Zebras and Mongolian wild horses (Equus przewalskii): Have a syndrome clinically and pathologically similar to equine degenerative myeloencephalopathy
· German shepherd dogs: Degenerative myelopathy – spinal cord demyelination and vacuolation, axonal degeneration and loss
· Welsh Corgi: Axonal loss (complete loss of recognizable fiber cylinders); degeneration (distended myelin cylinders with empty or degenerating axon profiles) with lesion severity greatest at spinal cord segment T12, but similar patterns of axonal loss and degeneration identified at all levels
1. Finno CJ, Valber SJ, Shivers J, D’Ameida E, Armien AG. Evidence of the primary afferent tracts undergoing neurodegeneration in horses with equine degenerative myeloencephalopathy based on calretinin immunohistochemical localization. Vet Pathol. 2016; 53(1):77-86.
2. Gandini G, Fatzer R, Mariscoli M, Spadari A, Cipone M, Jaggy A. Equine degenerative myelopathy in five quarter horses: Clinical and neuropathological findings. Equine Vet J. 2004:36(1):83-85.
3. Jahns H, Callanan JJ, McElroy MC, Sammin DJ, Bassett HF. Age-related and non-age-related changes in 100 surveyed horse brains. Vet Pathol. 2006:43(5):740-750.
4. LeCouteur RA, Grandy JL. Diseases of the spinal cord. In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine. 6th ed. St. Louis, MO: Elsevier Saunders; 2005:856-857.
5. 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; 2016:322-324.
6. Mackay RJ, Van Metre DC. Diseases of the nervous system. In: Smith BP, ed. Large Animal Internal Medicine. 5th ed. St. Louis, MO: Mosby Elsevier; 2015:988-989.
7. March PA, Coates JR, Abyad RA, Williams DA, O'Brien DP, Olby NJ, Keating JH, and Oglesbee M. Degenerative myelopathy in 18 Pembroke Welsh corgi dogs. Vet Pathol. 2009;46:241.
8. Miller AD, Zachary JF: The nervous system. In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Mosby Inc.; 2017:878-879.
9. Naylor RJ, Priestnall SL, Turk AC, Summers BA, Schoniger S, Piercy RJ. Equine degenerative myeloencephalopathy in a horse in the UK. Vet Rec. 2010;167(10):380-381.
10. Radostits OM, Gay CC, Hinchcliff KW, Constable PD. Diseases of the spinal cord. In: Radostits OM, Gay CC, Hinchcliff KW, Constable PD, eds. Veterinary Medicine a Textbook of the Diseases of Cattle, Horses, Sheep Pigs and Goats. 10th ed. Philadelphia, PA: Saunders Elsevier; 2007:617.
11. Summers BA, Cummings JF, de Lahunta A. Veterinary Neuropathology. St. Louis, MO: Mosby-Year Book Inc; 1995:167-169,317-319.
12. Wong DM, Ghosh A, Fales-Williams AJ, Haynes, Kanthasamy AG. Evidence of oxidative injury of the spinal cord in 2 Horses with equine degenerative myeloencephalopathy Vet Pathol. 2012;49(6):1049-1053.