Advertisement
Review Article| Volume 40, ISSUE 5, P929-950, September 2010

Canine Degenerative Myelopathy

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribers receive full online access to your subscription and archive of back issues up to and including 2002.

      Content published before 2002 is available via pay-per-view purchase only.

      Subscribe:

      Subscribe to Veterinary Clinics: Small Animal Practice
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Averill D.R.
        Degenerative myelopathy in the aging German shepherd dog: clinical and pathologic findings.
        J Am Vet Med Assoc. 1973; 162: 1045-1051
        • Griffiths I.R.
        • Duncan I.D.
        Chronic degenerative radiculomyelopathy in the dog.
        J Small Anim Pract. 1975; 16: 461-471
        • Braund K.G.
        • Vandevelde M.
        German shepherd dog myelopathy—a morphologic and morphometric study.
        Am J Vet Res. 1978; 39: 1309-1315
        • Coates J.R.
        • March P.A.
        • Oglesbee M.
        • et al.
        Clinical characterization of a familial degenerative myelopathy in Pembroke Welsh Corgi dogs.
        J Vet Intern Med. 2007; 21: 1323-1331
        • Awano T.
        • Johnson G.S.
        • Wade C.M.
        • et al.
        Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis.
        Proc Natl Acad Sci U S A. 2009; 106: 2794-2799
        • Johnston P.E.J.
        • Barrie J.A.
        • McCulloch M.C.
        • et al.
        Central nervous system pathology in 25 dogs with chronic degenerative radiculomyelopathy.
        Vet Rec. 2000; 146: 629-633
        • Kathmann I.
        • Cizinauskas S.
        • Doherr M.G.
        • et al.
        Daily controlled physiotherapy increases survival time in dogs with suspected degenerative myelopathy.
        J Vet Intern Med. 2006; 20: 927-932
        • Bichsel P.
        • Vandevelde M.
        • Lang J.
        • et al.
        Degenerative myelopathy in a family of Siberian husky dogs.
        J Am Vet Med Assoc. 1983; 183: 998-1000
        • Matthews N.S.
        • de Lahunta A.
        Degenerative myelopathy in an adult miniature poodle.
        J Am Vet Med Assoc. 1985; 186: 1213-1215
        • Miller A.D.
        • Barber R.
        • Porter B.F.
        • et al.
        Degenerative myelopathy in two boxer dogs.
        Vet Pathol. 2009; 46: 684-687
        • March P.A.
        • Coates J.R.
        • Abyad R.J.
        • et al.
        Degenerative myelopathy in 18 Pembroke Welsh Corgi dogs.
        Vet Pathol. 2009; 46: 241-250
        • Long S.N.
        • Henthorn P.S.
        • Serpell J.
        • et al.
        Degenerative myelopathy in Chesapeake Bay retrievers.
        J Vet Intern Med. 2009; 23: 401-402
        • Polizopoulou Z.S.
        • Koutinas A.F.
        • Patsikas M.N.
        • et al.
        Evaluation of a proposed therapeutic protocol in 12 dogs with tentative degenerative myelopathy.
        Acta Vet Hung. 2008; 56: 293-301
        • Levine J.M.
        • Hillman R.B.
        • Erb H.N.
        • et al.
        The influence of age on patellar reflex response in the dog.
        J Vet Intern Med. 2002; 16: 244-246
        • Braund K.G.
        Hip dysplasia and degenerative myelopathy: making the distinction in dogs.
        Vet Med. 1987; 82: 782-789
        • Kneller S.K.
        • Oliver J.E.
        • Lewis R.E.
        Differential diagnosis of progressive caudal paresis in an aged German shepherd dog.
        J Am Anim Hosp Assoc. 1975; 11: 414-417
        • Hoerlein B.F.
        Intervertebral disc disease.
        in: Oliver J.E. Hoerlein B.F. Mayhew I.G. Veterinary neurology. W.B. Saunders, Philadelphia1987: 321-341
        • Summers B.A.
        • Cummings J.F.
        • de Lahunta A.
        Veterinary neuropathology.
        Mosby, St. Louis (MO)1995 (p. 189–207)
        • Cork L.C.
        • Troncoso J.C.
        • Price D.L.
        • et al.
        Canine neuroaxonal dystrophy.
        J Neuropathol Exp Neurol. 1983; 42: 286-296
        • Chrisman C.L.
        • Cork L.C.
        • Gamble D.A.
        Neuroaxonal dystrophy of Rottweiler dogs.
        J Am Vet Med Assoc. 1984; 184: 464-467
        • Bruijn L.I.
        • Miller T.M.
        • Cleveland D.W.
        Unraveling the mechanisms involved in motor neuron degeneration in ALS.
        Annu Rev Neurosci. 2004; 27: 723-749
        • Boillee S.
        • Vande Velde C.
        • Cleveland D.W.
        ALS: a disease of motor neurons and their nonneuronal neighbors.
        Neuron. 2006; 52: 39-59
        • Olby N.
        Motor neuron disease: inherited and acquired.
        Vet Clin North Am Small Anim Pract. 2004; 34: 1403-1418
        • Barclay K.B.
        • Haines D.M.
        Immunohistochemical evidence for immunoglobulin and complement deposition in spinal cord lesions in degenerative myelopathy in German shepherd dogs.
        Can J Vet Res. 1994; 58: 20-24
        • Caulkins S.E.
        • Purinton P.T.
        • Oliver J.E.
        Arterial supply to the spinal cord of dogs and cats.
        Am J Vet Res. 1989; 50: 425-430
        • de Lahunta A.
        • Glass E.
        Veterinary neuroanatomy and clinical neurology.
        Saunders Elsevier, St. Louis (MO)2009
        • Grant G.
        • Rexed B.
        Dorsal spinal afferents to Clarke's column.
        Brain. 1958; 81: 567-576
        • Al-Chaer E.D.
        • Lawand N.B.
        • Westlund K.N.
        • et al.
        Pelvic visceral input into the nucleus gracilis is largely mediated by the postsynaptic dorsal column pathway.
        J Neurophysiol. 1996; 76: 2675-2690
        • Shelton G.D.
        • Johnson G.C.
        • Johnson G.S.
        • et al.
        Peripheral nerve pathology in canine degenerative myelopathy with mutation in superoxide dismutase 1 gene.
        J Vet Intern Med. 2009; 23: 710-711
        • Griffiths I.R.
        • Duncan I.D.
        Age changes in the dorsal and ventral lumbar nerve roots of dogs.
        Acta Neuropathol. 1975; 32: 75-85
        • Cavanagh J.B.
        The significance of the “dying back” process in experimental and human neurological disease.
        Int Rev Exp Pathol. 1964; 3: 219-267
        • Spencer P.S.
        • Schaumburg H.H.
        Central peripheral distal axonopathy—the pathology of dying-back polyneuropathies.
        Prog Neuropathol. 1976; 3: 253-295
        • Waxman F.J.
        • Clemmons R.M.
        • Johnson G.
        • et al.
        Progressive myelopathy in older German shepherd dogs. I. Depressed response to thymus-dependent mitogens.
        J Immunol. 1980; 124: 1209-1215
        • Waxman F.J.
        • Clemmons R.M.
        • Hinrichs D.J.
        Progressive myelopathy in older German shepherd dogs. II. Presence of circulating suppressor cells.
        J Immunol. 1980; 124: 1216-1222
      1. Williams DA, Sharp NJH, Batt RM. Enteropathy associated with degenerative myelopathy in German shepherd dogs. In: Proceedings of the First ACVIM Forum. 1983. p. 40.

        • Williams D.A.
        • Batt R.M.
        • Sharp N.J.H.
        Degenerative myelopathy in German shepherd dogs: an association with mucosal biochemical changes and bacterial overgrowth in the small intestine.
        Clin Sci. 1984; 66: 25
      2. Williams DA, Prymak C, Baughan J. Tocopherol (vitamin E) status in canine degenerative myelopathy. In: Proceedings 3rd ACVIM Forum. 1985. p. 154.

        • Fechner H.
        • Johnston P.E.
        • Sharp N.J.H.
        • et al.
        Molecular genetic and expression analysis of alpha-tocopherol transfer protein mRNA in German shepherd dogs with degenerative myelopathy.
        Berl Munch Tierarztl Wochenschr. 2003; 11: 631-636
        • Johnston P.E.J.
        • Knox K.
        • Gettinby G.
        • et al.
        Serum α-tocopherol concentrations in German shepherd dogs with chronic degenerative radiculomyelopathy.
        Vet Rec. 2001; 148: 403-407
        • Sheahan B.J.
        • Caffrey J.F.
        • Gunn H.M.
        • et al.
        Structural and biochemical changes in a spinal myelinopathy in twelve English foxhounds and two harriers.
        Vet Pathol. 1991; 28: 117-124
        • Olby N.J.
        • Sharp N.J.H.
        • Muñana K.R.
        • et al.
        Chronic and acute compressive spinal cord lesions in dogs are associated with increased lumbar CSF glutamate levels.
        J Vet Intern Med. 1999; 13: 240
        • Appel S.H.
        CD4+ T cells mediate cytotoxicity in neurodegenerative diseases.
        J Clin Invest. 2009; 119: 13-15
        • Blythe L.L.
        • Craig A.M.
        • Lassen E.D.
        • et al.
        Serially determined plasma α-tocopherol concentrations and results of the oral vitamin E absorption test in clinically normal horses and in horses with degenerative myeloencephalopathy.
        Am J Vet Res. 1991; 52: 908-911
        • Cummings J.F.
        • de Lahunta A.
        • Mohammed H.O.
        • et al.
        Equine motor neuron disease: a new neurologic disorder.
        Equine Pract. 1991; 13: 15-18
        • Divers T.J.
        • Cummings J.E.
        • de Lahunta A.
        • et 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: 120-126
        • Flegel T.
        • Sharp N.
        • Olby N.
        • et al.
        Analysis of the canine αTTP gene—a candidate gene for degenerative myelopathy?.
        J Vet Intern Med. 1999; 13: 240
        • Clemmons R.M.
        • Cheeseman J.A.
        • Kamishina H.
        • et al.
        Genetic analysis of a spontaneous canine model of primary multiple sclerosis.
        FASEB J. 2006; 20: A1417
        • Clark L.A.
        • Tsai K.L.
        • Murphy K.E.
        Alleles of DLA-DRB1 are not unique in German shepherd dogs having degenerative myelopathy.
        Anim Genet. 2008; 39: 332
        • Karlsson E.K.
        • Baranowska I.
        • Wade C.M.
        • et al.
        Efficient mapping of mendelian traits in dogs through genome-wide association.
        Nat Genet. 2007; 39: 1321-1328
        • Lindblad-Toh K.
        • Wade C.M.
        • Mikkelsen T.S.
        • et al.
        Genome sequence, comparative analysis and haplotype structure of the domestic dog.
        Nature. 2005; 438: 803-819
        • Divers T.J.
        • Mohammed H.O.
        • Cummings J.F.
        • et al.
        Equine motor neuron disease: findings in 28 horses and proposal of a pathophysiological mechanism for the disease.
        Equine Vet J. 1994; 26: 409-415
        • Valentine B.A.
        • de Lahunta A.
        • George C.
        • et al.
        Acquired equine motor neuron disease.
        Vet Pathol. 1994; 31: 130-138
        • de la Rúa-Domenèch R.
        • Wiedmann M.
        • Mohammed H.O.
        • et al.
        Equine motor neuron disease is not linked to Cu/Zn superoxide dismutase mutations: sequence analysis of the equine Cu/Zn superoxide dismutase cDNA.
        Gene. 1996; 178: 83-88
        • Rosen D.R.
        • Siddique T.
        • Patterson D.
        • et al.
        Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis.
        Nature. 1993; 362: 59-62
        • Dion P.A.
        • Daoud H.
        • Rouleau G.A.
        Genetics of motor neuron disorders: new insights into pathogenic mechanisms.
        Nat Rev Genet. 2009; 10: 769-782
        • Rakhit R.
        • Chakrabartty A.
        Structure, folding, and misfolding of Cu, Zn superoxide dismutase in amyotrophic lateral sclerosis.
        Biochim Biophys Acta. 2006; 1762: 1025-1037
        • Bruijn L.I.
        • Houseweart M.K.
        • Kato S.
        • et al.
        Aggregation and motor neuron toxicity of an ALS-linked SOD1 mutant independent from wild-type SOD1.
        Science. 1998; 281: 1851-1854
        • Green S.L.
        • Tolwani R.J.
        • Varma S.
        • et al.
        Structure, chromosomal location, and analysis of the canine Cu/Zn superoxide dismutase (SOD1) gene.
        J Hered. 2002; 93: 119-124
        • Boissinot M.
        • Karnas S.
        • Lepock J.R.
        • et al.
        Function of the Greek key connection analysed using circular permutants of superoxide dismutase.
        EMBO J. 1997; 16: 2171-2178
        • Deng H.X.
        • Hentati A.
        • Tainer J.A.
        • et al.
        Amyotrophic lateral sclerosis and structural defects in Cu, Zn superoxide dismutase.
        Science. 1993; 261: 1047-1051
        • Sandelin E.
        • Nordlund A.
        • Andersen P.M.
        • et al.
        Amyotrophic lateral sclerosis-associated copper/zinc superoxide dismutase mutations preferentially reduce the repulsive charge of the proteins.
        J Biol Chem. 2007; 282: 21230-21236
        • Shaw B.F.
        • Valentine J.S.
        How do ALS-associated mutations in superoxide dismutase 1 promote aggregation of the protein?.
        Trends Biochem Sci. 2007; 32: 78-85
        • Jonsson P.A.
        • Ernhill K.
        • Andersen P.M.
        • et al.
        Minute quantities of misfolded mutant superoxide dismutase-1 cause amyotrophic lateral sclerosis.
        Brain. 2004; 127: 1-88
        • Wang J.
        • Slunt H.
        • Gonzales V.
        • et al.
        Copper-binding-site-null SOD1 causes ALS in transgenic mice: aggregates of non-native SOD1 delineate a common feature.
        Hum Mol Genet. 2003; 12: 2753-2764
        • Hirano A.
        • Kurland L.T.
        • Sayre G.P.
        Familial amyotrophic lateral sclerosis. A subgroup characterized by posterior and spinocerebellar tract involvement and hyaline inclusions in the anterior horn cells.
        Arch Neurol. 1967; 16: 232-243
        • Kato S.
        • Hayashi H.
        • Nakashima K.
        • et al.
        Pathological characterization of astrocytic hyaline inclusions in familial amyotrophic lateral sclerosis.
        Am J Pathol. 1997; 151: 611-620
        • Charcot J.-M.
        • Joffroy A.
        Deux cas d'atrophie musculaire progressive avec lésions de l substance grise et de faisceaux antérolatéraux de la moelle épinière.
        Arch Physiol Norm Pathol. 1869; I: 354-357
        • Leigh P.N.
        Amyotrophic lateral sclerosis.
        in: Eisen A.A. Shaw P.J. Motor neuron disorders and related diseases. vol. 82. Elsevier, Amsterdam2007: 249-268
        • Wijesekera L.C.
        • Leigh P.N.
        Amyotrophic lateral sclerosis.
        Orphanet J Rare Dis. 2009; 4 (Available at: http://www.orjrd.com/content/4/1/3. Accessed May 18, 2010): 1-22
        • Magnus T.
        • Beck M.
        • Giess R.
        • et al.
        Disease progression in amyotrophic lateral sclerosis: predictors of survival.
        Muscle Nerve. 2002; 25: 709-714
        • Andersen P.M.
        Amyotrophic lateral sclerosis associated with mutations in the CuZn superoxide dismutase gene.
        Curr Neurol Neurosci Rep. 2006; 6: 37-46
        • Wilson C.M.
        • Grace G.M.
        • Munoz D.G.
        • et al.
        Cognitive impairment in sporadic ALS: a pathologic continuum underlying a multisystem disorder.
        Neurology. 2001; 57: 651-657
        • Jones J.C.
        • Inzana K.D.
        • Rossmeisl J.H.
        • et al.
        CT myelography of the thoraco-lumbar spine in 8 dogs with degenerative myelopathy.
        J Vet Sci. 2005; 6: 341-348
        • Pradat P.F.
        • Dib M.
        Biomarkers in amyotrophic lateral sclerosis: facts and future horizons.
        Mol Diag Ther. 2009; 13: 115-125
        • Turner M.R.
        • Kiernan M.C.
        • Leigh P.N.
        • et al.
        Biomarkers in amyotrophic lateral sclerosis.
        Lancet Neurol. 2009; 8: 94-109
        • Ruaux C.G.
        • Coates J.R.
        • March P.A.
        • et al.
        Analysis of oligoclonal banding in CSF and serum from dogs with degenerative myelopathy.
        J Vet Intern Med. 2003; 17: 401
        • Kamishina H.
        • Oji T.
        • Cheeseman J.A.
        • et al.
        Detection of oligoclonal bands in cerebrospinal fluid from German shepherd dogs with degenerative myelopathy by isoelectric focusing and immunofixation.
        Vet Clin Pathol. 2008; 37: 217-220
        • Oji T.
        • Kamishina H.
        • Cheeseman J.A.
        • et al.
        Measurement of myelin basic protein in the cerebrospinal fluid of dogs with degenerative myelopathy.
        Vet Clin Pathol. 2007; 36: 281-284
        • Clemmons R.M.
        Degenerative myelopathy.
        in: Kirk R.W. Current veterinary therapy X. Small animal practice. W.B. Saunders Company, Philadelphia1989: 830-833
      3. Clemmons RM. Therapeutic considerations for degenerative myelopathy of German shepherds. In: Proceedings 9th ACVIM Forum. New Orleans (LA), 1991. p. 773–5.

        • Clemmons R.M.
        Degenerative myelopathy.
        Vet Clin North Am Small Anim Pract. 1992; 22: 965-971
        • Sherman J.
        • Olby N.J.
        Nursing and rehabilitation of the neurological patient.
        in: Platt S.R. Olby N.J. BSAVA manual of canine and feline neurology. 3rd edition. BSAVA, Gloucester (UK)2004: 394-407
        • Bensimon G.
        • Lacomblez L.
        • Meininger V.
        A control trial of riluzole.
        N Engl J Med. 1994; 330: 585-591
        • Van Damme P.
        • Robberecht W.
        Recent advances in motor neuron disease.
        Curr Opin Neurol. 2009; 22: 486-492
        • Smith R.A.
        • Miller T.M.
        • Yamanaka K.
        • et al.
        Antisense oligonucleotide therapy for neurodegenerative disease.
        J Clin Invest. 2006; 116: 2290-2296
        • Nayak M.S.
        • Kim Y.S.
        • Goldman M.
        • et al.
        Cellular therapies in motor neuron diseases.
        Biochim Biophys Acta. 2006; 1762: 1128-1138
        • Urushitani M.
        • Ezzi S.A.
        • Julien J.P.
        Therapeutic effects of immunization with mutant superoxide dismutase in mice models of amyotrophic lateral sclerosis.
        Proc Natl Acad Sci U S A. 2007; 104: 2495-2500
        • Turner B.J.
        • Talbot K.
        Transgenics, toxicity and therapeutics in rodent models of mutant SOD1-mediated familial ALS.
        Prog Neurobiol. 2008; 85: 94-134
        • Benatar M.
        Lost in translation: treatment trials in the SOD1 mouse and in human ALS.
        Neurobiol Dis. 2007; 26: 1-13
        • DiBernardo A.B.
        • Cudkowicz M.E.
        Translating preclinical insights into effective human trials in ALS.
        Biochim Biophys Acta. 2006; 1762: 1139-1149
        • Ellinwood N.M.
        • Vite C.H.
        • Haskin M.E.
        Gene therapy for lysosomal storage diseases: the lessons and promise of animal models.
        J Gene Med. 2004; 6: 481-506
        • Rakhit R.
        • Cunningham P.
        • Furtos-Matei A.
        • et al.
        Oxidation-induced misfolding and aggregation of superoxide dismutase and its implications for amyotrophic lateral sclerosis.
        J Biol Chem. 2002; 277: 47551-47556
        • Wong P.C.
        • Pardo C.A.
        • Borchelt D.R.
        • et al.
        An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria.
        Neuron. 1995; 14: 1105-1116
        • Paoloni M.
        • Khanna C.
        Translation of new cancer treatments from pet dogs to humans.
        Nat Rev Cancer. 2008; 8: 147-156