Read-Only Case Details Reviewed: Feb 2008

JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

January 2023

N-M07

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: Bilaterally and symmetrically within the dorsal brainstem, primarily within the lateral and medial (accessory) cuneate nuclei, there are moderate numbers of swollen eosinophilic axons, up to 60 µm in diameter, with homogenous granular axoplasm (spheroids) and occasional dilated myelin sheaths. Multifocally, neurons within affected areas are shrunken and hypereosinophilic with loss of Nissl substance and nuclear pyknosis or karyolysis (neuronal necrosis) or are swollen with central dispersion of Nissl substance and peripheralized nuclei (central chromatolysis). Within the affected areas, there are mildly increased numbers of astrocytes (astrocytosis) that are often hypertrophied (reactive; astrogliosis), and there are occasional scattered macrophages that contain a yellow-brown, lipofuscin-like, granular intracytoplasmic pigment.

MORPHOLOGIC DIAGNOSIS: Brainstem, lateral and medial cuneate nuclei: Axonal degeneration (spheroids), bilaterally symmetrical, moderate, with astrogliosis, neuronal necrosis and myelin sheath dilation, Welsh cob, equine.

CONDITION: Equine degenerative myeloencephalopathy (EDM)

SYNONYMS: Neuroaxonal dystrophy

GENERAL DISCUSSION:

Chronically progressive, irreversible syndrome of symmetrical ataxia in young horses (6-24 months of age)
Wallerian degeneration in white matter of spinal cord funiculi and brainstem
Simultaneous involvement in multiple cord segments of ascending and descending tracts
Reported in a variety of purebred and mixed breed horses, and a similar disease exists in zebras.
1. May be a familial predisposition in Appaloosa, Standardbred, Paso Fino, and Lusitano horses. Also seen in Morgan and Quarter horse breeds
Considered an advanced form of neuroaxonal dystrophy

PATHOGENESIS:

Unknown; appears to be a combination of genetic predisposition and environmental risk factors (specifically diets low in α-tocopherol (vitamin E)
1. Vitamin E deficiency may play a role in the disease process since supplementation reduces the severity of clinical deficits as well as decreased incidence at farms with high prevalence of EDM
2. Oxidative damage and lipid peroxidation of cell membranes > accumulation of lipopigment
3. Other risk factors that may play a role: Copper deficiency, toxins (insecticides or wood preservatives), inadequate access to green pasture
Disruption of axonal transport likely plays a crucial role in the pathogenesis of dystrophic axons in EDM.

TYPICAL CLINICAL FINDINGS:

Slowly progressive course with proprioceptive and upper motor neuron deficits in a young horse
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:

Bilateral axonal degeneration affecting all funiculi throughout the spinal cord and brain stem (ongoing Wallerian degeneration and post-Wallerian astrogliosis); degenerate and necrotic neurons
1. Loss of myelinated axons and dense reactive gliosis
2. Spheroids (swellings filled with amorphous debris, membranous profiles, and effete organelles)
3. Astrocytosis
4. Accumulation of lipofuscin-like pigment in macrophages, endothelial cells, and neurons; degenerate and necrotic neurons
Lesions predominate in the sensory axons and are most dramatic in the mid-thoracic and anterior cervical segments in the ascending dorsolateral (spinocerebellar) and descending ventromedial (motor) tracts
1. Chromatolytic and necrotic neurons in Clarke’s column in Clarke’s column (the nucleus of the dorsal spinocerebellar tract)
2. Spheroids have been described in the nucleus gracilis, medial and lateral cuneate nuclei of the terminal brainstem, and thoracic nucleus of the spinal cord
Similar but mild changes are noted in myelinated tracts of the caudal medulla and caudal cerebellar peduncle

ADDITIONAL DIAGNOSTIC TESTS:

Bloodwork: Plasma alpha-tocopherol levels

DIFFERENTIAL DIAGNOSIS:

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 (N-M02, Wobbler syndrome): Axonal degeneration and demyelination (Wallerian degeneration); more common in older horses (1-4 years); histologic findings vary based on location in relation to site of compression
Equine protozoal myeloencephalitis (N-P01, Sarcocystis neurona): Necrotizing, nonsuppurative myeloencephalitis, axonal degeneration, schizonts and merozoites
Cauda equina syndrome (N-M18, idiopathic polyradiculoneuritis): Granulomatous inflammation around cauda equine
Equine herpesvirus-1 (EHV-1, alphaherpesvirus) myeloencephalopathy: Vasculitis and necrosis in spinal cord and brain; often accompanies or follows respiratory disease and abortions
Perinneal rye grass staggers (N-T12, Lolium perenne): No specific pathologic changes; can have axonal swelling, especially in Purkinje cells (torpedoes)
Parasite migration: Strongylus spp., Hypoderma spp.

COMPARATIVE PATHOLOGY:

Neuroaxonal dystrophy (including EDM) are disorders associated with axonal swellings (axonal spheroids) and have a species/breed association and usually early onset (<1 year of age (4 weeks-3 years))
1. Described in many species, most common in dogs and horses
2. Characterized by prominent axonal swellings in various nuclei (often sensory) in the brainstem, cerebellum, and spinal cord
3. Loss of cerebellar Purkinje and granule cells reported in Rottweilers and cats, loss of brainstem neurons in cats
Other neuropathies in which Vitamin E plays a role:
1. Equine motor neuron disease (EMND): Clinically similar syndrome to EDM with degenerative changes in the brainstem; older horses; associated with a vitamin E deficiency but lacks genetic component; affects ventral and intermediate gray columns of the spinal cord; a lower motor neuron disease
2. Zebras and Mongolian wild horses (Equus przewalskii): Disease similar to EDM, associated with hypovitaminosis E
3. Spontaneous hemorrhagic necrosis (SHN) in fetal hamsters, with symmetrical, subependymal vascular degeneration and intraventricular hemorrhage
4. Encephalomalacia in Guinea Pigs
5. Encephalomalacia (Crazy Chick Disease) in poultry: Ataxia, loss of balance, prostration; cerebellum often contains yellow or congested, hemorrhagic, or necrotic areas visible on the surface, usually within the first month of life
6. Avians with hypovitaminosis E may have degeneration and loss of Purkinje cells and a spongiform degeneration of the white matter of the cerebellum and, in severe cases, of the cerebrum
7. - Prominent myocardial and skeletal muscle lesions are also present in these birds
Hypovitaminosis E/ Vitamin E deficiency leads to:
1. Yellow fat disease/nutritional panniculitis, in multiple mammalian and reptilian species
2. Nutritional myopathy (M-M11) or cardiomyopathy (C-M06) in a number of mammals, avian species, and fish
3. Intestinal ceroidosis (AKA leiomyometaplasia, brown dog gut) in dogs
4. Neuropathies

References:

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