JPC SYSTEMIC PATHOLOGY
Signalment (JPC # 2414304): 11-year-old male standardbred horse
HISTORY: This horse had a three-week history of weight loss but with good appetite, trembling, increased periods of time in sternal recumbency and abnormal stance.
HISTOPATHOLOGIC DESCRIPTION: Spinal cord: Within the ventral horns numerous neuronal cell bodies are swollen, rounded, with loss of Nissl substance and a pale, eosinophilic cytoplasm (chromatolysis). Nuclei are often faded, with dispersed chromatin or are rarely karyorrhectic (neuronal necrosis); occasionally necrotic neurons are surrounded by small aggregates of glial cells (satellitosis). Within the white matter, few myelin sheaths are dilated and contain clear space, swollen, eosinophilic axons (spheroids), or cellular debris and gitter cells with foamy cytoplasm (ellipsoids). On longitudinal section the dilated axonal sheaths coalesce to form linear arrangements (ellipsoids or digestion chambers).
MORPHOLOGIC DIAGNOSIS: Spinal cord, ventral motor neurons: Degeneration, multifocal, moderate, with mild axonal degeneration, standardbred, equine.
ETIOLOGIC DIAGNOSIS: Idiopathic motor neuron degeneration
CONDITION: Equine motor neuron disease (EMND)
· Acquired neuromuscular disease of horses characterized by degeneration of type I lower motor neurons in the ventral horns of the spinal cord and in brain stem nuclei that manifests as weakness, atrophy of type I myofibers, weight loss, and muscle fasciculation
· Affected breeds include standardbred, thoroughbred, quarter horse and Arab breeds
· Affects both sexes; age range from 15 months to 25 years with a peak at 16 years
· The progression can slow or stop but the horse will be left with permanent disabilities; most horses are euthanized because of the clinical signs
· Multifactorial disease
· Major contributing/predisposing factor: Diet deficient in vitamin E > decreased antioxidant capacity > accumulation of free radicals > oxidative damage to the somatic ventral motor neuron cells
· Increased rate of glucose metabolism may contribute, due to increased vitamin E use within the cell secondary to mitochondrial oxidative phosphorylation
TYPICAL CLINICAL FINDINGS:
· Progressive weakness, muscle fasciculations, muscle wasting and atrophy; and weight loss
· Characteristic stance with feet positioned well under the body and lowered head; frequent shifting of weight from limb to limb
· Pigmentary retinopathy: Ophthalmoscopic exam reveals a mosaic pattern of pigment deposition in the tapetal zone coupled with a horizontal band of pigment at the junction of the tapetum and nontapetum; corresponds with histologic changes
· Decreased plasma glucose curve after oral glucose tolerance testing in 50% of horses with EMND
TYPICAL GROSS FINDINGS:
· Marked muscle wasting with grossly apparent discoloration (pale red to yellow-red), most evident in the medial heads of the triceps brachii and vastus intermedius muscles
TYPICAL LIGHT MICROSCOPIC FINDINGS:
· Degeneration and loss of motor neurons in spinal cord ventral horns and in some brainstem nuclei (trigeminal, facial, hypoglossal, and the nucleus ambiguus)
· Motor neurons are swollen, chromatolytic and contain karyolytic nuclei
· Eosinophilic cytoplasmic inclusions are often present in the perikarya
· Wallerian degeneration and formation of Bungner"s bands (proliferating Schwann cells) may be seen in myelinated motor axons of ventral spinal roots and peripheral nerves
· Skeletal muscle: Histologic findings in skeletal are characteristic of denervation atrophy
· Angular atrophied fibers; atrophy of small and large groups of fibers
· Eye: Pigmentary retinopathy: Accumulation of dark brown/black to yellow brown pigment (ceroid-lipofuscin) in the retinal pigmented epithelium (RPE) and retina (similar to lesions in hunting dogs with chronic vitamin E deficiency), and congestion of the RPE
· Outer segments of peripheral photoreceptors contain an unusually high proportion of polyunsaturated fatty acids in their lipids making them extremely susceptible to autooxidative damage
· Affected neurons contain bundles of neurofilaments filling the perikaryon
· Focal aggregates of membranous vesicles correspond in location and size to eosinophilic inclusions seen in light microscopy
· Endothelial cell accumulation of lipopigment granules
ADDITIONAL DIAGNOSTIC TESTS:
· Low serum and skeletal concentration of a-tocopherol (vitamin E) (<1 mg/mL)
· Serum creatine kinase and lumbosacral CSF protein levels may be mildly elevated
· Antemortem diagnosis: Surgical biopsy of the nerve branch of cranial nerve XI that innervates the sternocephalicus muscle; surgical biopsy of sacrocaudalis dorsalis medialis muscle and immunohistochemistry with NADH-Tr stain showing disruption of mitochondrial staining (moth-eaten mitochondrial staining pattern)
· Ocular manifestations aid greatly in diagnosis
· Present clinically as ataxia and paresis; younger horses; slightly different anatomic locations affected
· Affects white matter; simultaneous involvement in multiple cord segments of ascending and descending tracts
· Vitamin E deficiency may also play a role
· Protozoal encephalomyelitis (Sarcocystis neurona)
· Typically necrotizing; may cause focal or multifocal degeneration of motor neurons and degeneration of brain and spinal cord white matter
· May see merozoites and schizonts
· Resulting LMN weakness is localized and often asymmetric
· May initially present with signs suggestive of lower motor neuron disease however other neurologic signs will follow due to the diffuse, rapid spread of the lesion
· Equine herpesvirus type 1 encephalomyelopathy
· Vasculitis within the brain, spinal cord, leptomeninges, and spinal ganglia
· Motor neuron degenerative conditions have been described in Brittany spaniels, Swedish Lapland dogs, rottweilers, domestic shorthair cats, Yorkshire and Hampshire pigs, and in brown Swiss, Danish red, Piedmont, and Holstein calves
· Amyotrophic lateral sclerosis (ALS) is the most common progressive motor neuron disease in humans
· Neuron degeneration in ALS involves both upper and lower motor neurons
· EMND differs from classical ALS in that upper motor neuron pyramidal tracts are not involved
· Point mutation of superoxide dismutase (SOD1) gene is involved in pathogenesis of familial ALS, similar mutations have not been reported in equine
· EMND more closely resembles progressive spinal muscle atrophy (PSMA), a variant of ALS
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