AFIP SYSTEMIC PATHOLOGY

JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

February 2017

N-M24

 

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)

 

GENERAL DISCUSSION:

·       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

 

PATHOGENESIS:

·       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

 

ULTRASTRUCTURAL FINDINGS:

·       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

 

DIFFERENTIAL DIAGNOSIS:

·       Equine degenerative myeloencephalopathy and cervical stenotic myelopathy

·       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

·       Rabies

·       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

 

COMPARATIVE PATHOLOGY:

·       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

Humans: 

·       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

 

References:

1.      Bedford HE, Valberg SJ, Firshman AM, et al.  Histopathologic findings in the sacrocaudalis dorsalis medialis muscle of horses with vitamin E-responsive muscle atrophy and weakness.  J Am Vet Med Assoc. 2013;242(8):1127-1137.

2.      Davidson MG, Geoly FJ, Gilger BC, McLellan GJ, Whitley W. Retinal degeneration associated with vitamin E deficiency in hunting dogs. J Am Vet Med Assoc. 1998;213:645-651.

3.      Divers TJ, Cummings JE, de Lahunta A, Hintz HF, Mohammed HO. Evaluation of the risk of motor neuron disease in horses fed a diet low in vitamin E and high in copper and iron. Am J Vet Res 2006;67(1):120-126.

4.      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; 2016:330-332.

  1. Mohammed HO, Divers TJ, Kwak J, Omar AH, White ME, de Lahunta A. Association of oxidative stress with motor neuron disease in horses.  Am J Vet Res. 2012;73(12):1957-1962.
  2. Mohammed HO, Divers TJ, Summers BA, de Lahunta A. Vitamin E deficiency and risk of equine motor neuron disease. Acta Vet Scand. 2007;49:17.

7.      Polack EW, King JM, Cummings JF, Mohammed HO, Birch M, Cronin T. Concentrations of trace minerals in the spinal cord of horses with equine motor neuron disease. Am J Vet Res. 2000;61:609-611.

8.      Riis RC, Jackson C, Rebhun W, Katz ML, Loew E, Summers B, Cummings J, de Lahunta A, Divers T, Mohammed H. Ocular manifestations of equine motor neuron disease. Equine Vet J. 31:99-110, 1999

  1. Sasaki N, Yamada M, Morita Y, Furuoka H, Itoh M, Satoh M, Yamada H. A case of equine motor neuron disease (EMND). J Vet Med Sci. 2006;68(12):1367-1369.

10.   Summers BA, Cummings JF, De Lehunta A. Veterinary Neuropathology. St. Louis, MO: Mosby; 1995:309-312.

11.   Valentine BA, De Lahunta A, George C, Summers BA, Cummings JF, Divers TJ, Mohammed HO:  Acquired equine motor neuron disease. Vet Pathol. 1994;31:130-138.

  1. van der Kolk JH, Rijnen KE, Rey F, de Graaf-Roelfsema E, Grinwis GC, Wijnberg ID. Evaluation of glucose metabolism in three horses with lower motor neuron degeneration. Am J Vet Res. 2005;66(2):271-6

13.   Zachary JF. Nervous system. In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:905, 940.


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