• 1. Divers TJMohammed HOCummings JF. Equine motor neuron disease. Vet Clin North Am Equine Pract 1997 13 97105.

  • 2. Mohammed HODivers TJSummers BAet al. Vitamin E deficiency and risk of equine motor neuron disease. Acta Vet Scand 2007 49 17.

  • 3. Divers TJMohammed HOCummings JFet al. Equine motor neuron disease: findings in 28 horses and proposal of a pathophysiological mechanism for the disease. Equine Vet J 1994 26 409415.

    • Search Google Scholar
    • Export Citation
  • 4. Rua-Domenech RMohammed HOCummings JFet al. Association between plasma vitamin E concentration and the risk of equine motor neuron disease. Vet J 1997 154 203213.

    • Search Google Scholar
    • Export Citation
  • 5. Valentine BAde Lahunta AGeorge Cet al. Acquired equine motor neuron disease. Vet Pathol 1994 31 130138.

  • 6. Divers TValentine BJackson CAet al. Simple practical muscle biopsy test for equine motor neuron disease Proceedings1996 180181.

  • 7. Jackson CADe Lahunta ACummings JFet al. Spinal accessory nerve biopsy as an antemortem diagnostic test for equine motor neuron disease. Equine Vet J 1996 28 215219.

    • Search Google Scholar
    • Export Citation
  • 8. Divers TMohammed H. Equine motor neuron disease. In: Robinson NESprayberry KA, eds. Current therapy in equine medicine 6th ed. St Louis: Saunders Elsevier, 2009 615617.

    • Search Google Scholar
    • Export Citation
  • 9. Divers TJCummings JEde Lahunta Aet al. 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 120126.

    • Search Google Scholar
    • Export Citation
  • 10. Lindholm APiehl K. Fibre composition, enzyme activity and concentrations of metabolites and electrolytes in muscles of Standardbred horses. Acta Vet Scand 1974 15 287309.

    • Search Google Scholar
    • Export Citation
  • 11. Cumming WJKFulthorpe JJHudgson Pet al. Color atlas of muscle pathology London: Mosby-Wolfe, 1994.

  • 12. De La Corte FDValberg SJMacLeay JMet al. Glucose uptake in horses with polysaccharide storage myopathy. Am J Vet Res 1999 60 458462.

    • Search Google Scholar
    • Export Citation
  • 13. Green SLBouley DMPinter MJet al. Canine motor neuron disease: clinicopathologic features and selected indicators of oxidative stress. J Vet Intern Med 2001 15 112119.

    • Search Google Scholar
    • Export Citation
  • 14. Kleopa KAKyriacou KZamba-Papanicolaou Eet al. Reversible inflammatory and vacuolar myopathy with vitamin E deficiency in celiac disease. Muscle Nerve 2005 31 260265.

    • Search Google Scholar
    • Export Citation
  • 15. Pillai SRTraber MGKayden HJet al. Concomitant brainstem axonal dystrophy and necrotizing myopathy in vitamin E-deficient rats. J Neurol Sci 1994 123 6473.

    • Search Google Scholar
    • Export Citation
  • 16. Kennedy SRice DA. Histopathologic and ultrastructural myocardial alterations in calves deficient in vitamin E and selenium and fed polyunsaturated fatty acids. Vet Pathol 1992 29 129138.

    • Search Google Scholar
    • Export Citation
  • 17. Lofstedt J. White muscle disease of foals. Vet Clin North Am Equine Pract 1997 13 169185.

  • 18. Ferrans VJVan Vleet JF. Cardiac lesions of selenium-vitamin E deficiency in animals. Heart Vessels Suppl 1985 1 294297.

  • 19. Wilson TMMorrison HAPalmer NCet al. Myodegeneration and suspected selenium/vitamin E deficiency in horses. J Am Vet Med Assoc 1976 169 213217.

    • Search Google Scholar
    • Export Citation
  • 20. Owen RRMoore JNHopkins JBet al. Dystrophic myodegeneration in adult horses. J Am Vet Med Assoc 1977 171 343349.

  • 21. Mayhew IGBrown CMStowe HDet al. Equine degenerative myeloencephalopathy: a vitamin E deficiency that may be familial. J Vet Intern Med 1987 1 4550.

    • Search Google Scholar
    • Export Citation
  • 22. Baumgartner WFrese KElmadfa I. Neuroaxonal dystrophy associated with vitamin E deficiency in two Haflinger horses. J Comp Pathol 1990 103 114119.

    • Search Google Scholar
    • Export Citation
  • 23. Banker BQEngel AG. Basic reactions of muscle. In: Engel AGFranzini-Armstrong C, eds. Myology 2nd ed. New York: McGraw-Hill, 1994 832888.

    • Search Google Scholar
    • Export Citation
  • 24. Larsson BBjork JKadi Fet al. Blood supply and oxidative metabolism in muscle biopsies of female cleaners with and without myalgia. Clin J Pain 2004 20 440446.

    • Search Google Scholar
    • Export Citation
  • 25. Thomas PKCooper JMKing RHet al. Myopathy in vitamin E deficient rats: muscle fibre necrosis associated with disturbances of mitochondrial function. J Anat 1993 183 451461.

    • Search Google Scholar
    • Export Citation
  • 26. Palencia PQuiroz-Rothe ERivero JL. New insights into the skeletal muscle phenotype of equine motor neuron disease: a quantitative approach. Acta Neuropathol (Berl) 2005 109 272284.

    • Search Google Scholar
    • Export Citation
  • 27. Ferreiro AEstournet BChateau Det al. Multi-minicore disease—searching for boundaries: phenotype analysis of 38 cases. Ann Neurol 2000 48 745757.

    • Search Google Scholar
    • Export Citation
  • 28. Mitsuhashi SNonaka IWu Set al. Distal myopathy in multi-minicore disease. Intern Med 2009 48 17591762.

  • 29. Pietrini VMarbini AGalli Let al. Adult onset multi/minicore myopathy associated with a mutation in the RYR1 gene. J Neurol 2004 251 102104.

    • Search Google Scholar
    • Export Citation
  • 30. Buttriss JLDiplock AT. The relationship between alpha-tocopherol and phospholipid fatty acids in rat liver subcellular membrane fractions. Biochim Biophys Acta 1988 962 8190.

    • Search Google Scholar
    • Export Citation
  • 31. Oliveira MMWeglicki WBNason Aet al. Distribution of alpha-tocopherol in beef heart mitochondria. Biochim Biophy Acta 1969 180 98113.

    • Search Google Scholar
    • Export Citation
  • 32. Bonetti ENovello F. Distribution of H3-tocopherol in rat tissues and subcellular particles. Int J Vitam Nutr Res 1976 46 244247.

  • 33. Boveris AOshino NChance B. The cellular production of hydrogen peroxide. Biochem J 1972 128 617630.

  • 34. Sewell DAHarris RCMarlin DJ. Skeletal muscle characteristics in 2 year-old race-trained Thoroughbred horses. Comp Biochem Physiol Comp Physiol 1994 108 8796.

    • Search Google Scholar
    • Export Citation
  • 35. Valberg SJCarlson GPCardinet GH IIIet al. Skeletal muscle mitochondrial myopathy as a cause of exercise intolerance in a horse. Muscle Nerve 1994 17 305312.

    • Search Google Scholar
    • Export Citation
  • 36. DiMauro SBonilla E. Mitochondrial encephalomyopathies. In: Engel AGFranzini-Armstrong C, eds. Myology: basic and clinical 3rd ed. New York: McGraw-Hill, 2004 16231662.

    • Search Google Scholar
    • Export Citation
  • 37. Tyynismaa HCarroll CJRaimundo Net al. Mitochondrial myopathy induces a starvation-like response. Hum Mol Genet 2010 19 39483958.

    • Search Google Scholar
    • Export Citation
  • 38. National Research Council Nutrient requirements of horses 6th ed. Washington, DC: National Academies Press, 2007.

  • 39. Thafvelin BOksanen HE. Vitamin E and linolenic acid content of hay as related to different drying conditions. J Dairy Sci 1966 49 282286.

    • Search Google Scholar
    • Export Citation
  • 40. Lennox M. Hard to find nutrients for ration evaluations: filling in the holes Nottingham, Nottinghamshire, England: Nottingham University Press, 2001 135141.

    • Search Google Scholar
    • Export Citation
  • 41. Craig AMBlythe LLRowe KEet al. Variability of alpha-tocopherol values associated with procurement, storage, and freezing of equine serum and plasma samples. Am J Vet Res 1992 53 22282234.

    • Search Google Scholar
    • Export Citation
  • 42. Maenpaa PHKoskinen TKoskinen E. Serum profiles of vitamins A, E and D in mares and foals during different seasons. J Anim Sci 1988 66 14181423.

    • Search Google Scholar
    • Export Citation
  • 43. Blackley BRBell RJ. The Vitamin A and E status of horses raised in Alberta and Saskatchewan. Can Vet J 2011 35 297300.

  • 44. Steiss JETraber MGWilliams MAet al. Alpha tocopherol concentrations in clinically normal adult horses. Equine Vet J 1994 26 417419.

    • Search Google Scholar
    • Export Citation
  • 45. Craig AMBlythe LLLassen EDet al. Variations of serum vitamin E, cholesterol, and total serum lipid concentrations in horses during a 72-hour period. Am J Vet Res 1989 50 15271531.

    • Search Google Scholar
    • Export Citation
  • 46. Mardones PStrobel PMiranda Set al. Alpha-tocopherol metabolism is abnormal in scavenger receptor class B type I (SRBI)-deficient mice. J Nutr 2002 132 443449.

    • Search Google Scholar
    • Export Citation
  • 47. Fiorellino NMLamprecht EDWilliams CA. Absorption of different formulations of natural vitamin E in horses. J Equine Vet Sci 2009 29 100105.

    • Search Google Scholar
    • Export Citation

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Histopathologic findings in the sacrocaudalis dorsalis medialis muscle of horses with vitamin E–responsive muscle atrophy and weakness

Holly E. Bedford DVM, MS, DACVIM1, Stephanie J. Valberg DVM, PhD, DACVIM, DACVSMR2, Anna M. Firshman PhD, DACVIM, DACVSMR3, Michelle Lucio BS4, Mary K. Boyce DVM, PhD, DACVS5, and Troy N. Trumble DVM, PhD, DACVS6
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  • 1 Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN 55108.
  • | 2 Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN 55108.
  • | 3 Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN 55108.
  • | 4 Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN 55108.
  • | 5 Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN 55108.
  • | 6 Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN 55108.

Abstract

Objective—To characterize clinical findings, outcomes, muscle characteristics, and serum or muscle concentrations of α-tocopherol for horses with vitamin E–responsive signs of muscle atrophy and weakness consistent with signs of equine motor neuron disease (EMND).

Design—Retrospective case-control study.

Animals—8 affected (case) adult horses with acute (n = 3) or chronic (5) gross muscle atrophy that improved with vitamin E treatment and 14 clinically normal (control) adult horses with adequate (within reference range; 8) or low (6) muscle concentrations of α-tocopherol.

Procedures—Medical records were reviewed, serum and muscle concentrations of α-tocopherol were measured, and frozen biopsy specimens of sacrocaudalis dorsalis medialis muscle and gluteal muscle were histologically evaluated for pathological changes. Fiber type composition and fiber diameters were assessed in gluteal muscle specimens.

Results—A myopathy that was histologically characterized by redistribution of mitochondrial enzyme stain (moth-eaten appearance) and anguloid atrophy of myofibers was evident in sacrocaudalis dorsalis medialis muscle fibers of the 8 affected horses that had low serum (6/8) or skeletal muscle (5/5) concentrations of α-tocopherol; these histopathologic changes were not found in muscle specimens of control horses with low or adequate muscle concentrations of α-tocopherol. All affected horses regained strength and muscle mass within 3 months after initiation of vitamin E treatment and dietary changes.

Conclusions and Clinical Relevance—A vitamin E–deficient myopathy characterized histologically by a moth-eaten appearance in the mitochondria and anguloid myofiber atrophy in frozen sections of sacrocaudalis dorsalis medialis muscle biopsy specimens was found in horses with clinical signs of EMND that were highly responsive to vitamin E treatment. This myopathy may be a specific syndrome or possibly precede the development of neurogenic muscle fiber atrophy typical of EMND.

Abstract

Objective—To characterize clinical findings, outcomes, muscle characteristics, and serum or muscle concentrations of α-tocopherol for horses with vitamin E–responsive signs of muscle atrophy and weakness consistent with signs of equine motor neuron disease (EMND).

Design—Retrospective case-control study.

Animals—8 affected (case) adult horses with acute (n = 3) or chronic (5) gross muscle atrophy that improved with vitamin E treatment and 14 clinically normal (control) adult horses with adequate (within reference range; 8) or low (6) muscle concentrations of α-tocopherol.

Procedures—Medical records were reviewed, serum and muscle concentrations of α-tocopherol were measured, and frozen biopsy specimens of sacrocaudalis dorsalis medialis muscle and gluteal muscle were histologically evaluated for pathological changes. Fiber type composition and fiber diameters were assessed in gluteal muscle specimens.

Results—A myopathy that was histologically characterized by redistribution of mitochondrial enzyme stain (moth-eaten appearance) and anguloid atrophy of myofibers was evident in sacrocaudalis dorsalis medialis muscle fibers of the 8 affected horses that had low serum (6/8) or skeletal muscle (5/5) concentrations of α-tocopherol; these histopathologic changes were not found in muscle specimens of control horses with low or adequate muscle concentrations of α-tocopherol. All affected horses regained strength and muscle mass within 3 months after initiation of vitamin E treatment and dietary changes.

Conclusions and Clinical Relevance—A vitamin E–deficient myopathy characterized histologically by a moth-eaten appearance in the mitochondria and anguloid myofiber atrophy in frozen sections of sacrocaudalis dorsalis medialis muscle biopsy specimens was found in horses with clinical signs of EMND that were highly responsive to vitamin E treatment. This myopathy may be a specific syndrome or possibly precede the development of neurogenic muscle fiber atrophy typical of EMND.

Contributor Notes

Presented in abstract form at the 2010 American College of Veterinary Internal Medicine Forum, Anaheim, Calif, June 2010.

Address correspondence to Dr. Bedford (hollybedforddvm@hotmail.com).