Hereditary myelopathies in dogs
Keywords:
degenerative disease myelodystrophy myelopathy
Abstract
The purpose of the current review is to summarize data regarding hereditary myelopathies in dogs. Canine degenerative myelopathy (DM) is a progressive disease prevalent in senior (≥8 years old), large breed-dogs, predominating in German shepherd dog. Neurolocalization indicates a thoracolumbar, upper motor neuron, lesion; it can progress to the thoracic limbs and later to lower motor neurons of all limbs resembling human amyotrophic lateral sclerosis (ALS). Tentative diagnosis is based on ruling out other progressive myelopathies. Clinical similarities between ALS and DM made superoxide dismutase 1 gene (SOD1) a viable candidate gene as an etiopathogenic factor. Α E40K missense mutation of the SOD1 has been linked to DM. A genetic test for DM exists, which will aid breeding programs to eliminate the disease. Exercise and physiotherapy are important to slow the progression of DM. Long-term prognosis is poor as dogs become non-ambulatory within 4-6 months from the time of diagnosis. Dystrophic myelopathies include Afgan hound myelopathy/hereditary necrotizing myelopathy in Kooikerhondje dogs, leukoencephalomyelopathy and neuroaxonal dystrophy in Rottweilers and spongiform leukoencephalomyelopathy. A similar myelopathy is Jack Russell and Fox terrier hereditary ataxia. Their etiology is suspected to be hereditary and they appear at a young age. They are diagnosed solely postmortem with histopathological examination. There is no etiologic treatment and the prognosis is poor except for Rottweiler neuroaxonal dystrophy and Jack Russel ataxia due to the extremely slow progression of symptoms. Syringomyelia is characterized by the formation of fluid filled cavities within the spinal cord and outside the central canal that may communicate with the central canal and it is caused mainly due to Chari-like malformation (CLM). The most important clinical sign is neuropathic pain and is localized in the cervical region of the spinal cord. Progression of the disease varies, there are severe disabilities due to pain or it can be an incidental finding. CT and MRI are the preferable ways to detect the lesions. For CLM, therapy includes surgical and medical management. Drugs can be divided into analgesics (non-steroidal anti-inflammatory, gabapentin, pregabalin, tramadol), drugs reducing cerebrospinal fluid (CSF) production (omeprazole, acetazolamide, furosemide) and corticosteroids. Medical therapy diminishes the severity of clinical signs but never succeeds full resolution.
Article Details
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Baka, R., & POLIZOPOULOU, Z. (2021). Hereditary myelopathies in dogs. Journal of the Hellenic Veterinary Medical Society, 72(1), 2583–2594. https://doi.org/10.12681/jhvms.26740
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- Vol. 72 No. 1 (2021)
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- Review Articles
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References
Averill DR, Bronson RT (1977) Inheriting necrotizing myelopathy of afghan hounds, J Neuropathol Exp Neurol 36 (4): 734-747.
Awano T, Johnson GS, Wade CM, Katz ML, Johnson GC, Taylor JF, Perloski M, Biagi T, Baranowska I, Long S, March PA, Olby NJ, Shelton GD, Khan S, O’Brien DP, Lindblad-Toh K, Coates JR (2009) Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis. PNAS 106 (8): 2794-2799.
Barclay KB, Haines DM (1994) Immunohistochemical evidence for immunoglobin and complement deposition in spinal cord lesions in degenerative myelopathy in German shepherd dogs. Can Vet J Res 58:20-24.
Bichsel P, Vandevelde M, Lang J, Kull-Hächler S(1983) Degenerative myelopathy in a family of Siberian Husky dogs. J Am Vet Med Assoc 183 (9): 998-1000.
Björck G, Dyrendahl S, Olsson SE (1957) Hereditary ataxia in Smooth-Haired Fox Terriers. Vet Rec 69: 871-876.
Boersma A , Zonnevylle H, Sánchez MA, Espiñeira MD (1995) Progressive ataxia in a Rottweiler dog. Vet Q 17: 108-109.
Borrett D, Becker LE (1985) Alexander’s disease: a disease of astrocytes. Brain 108: 367-385.
Braund KG, Vandevelde M (1978) German Shepherd dog myelopathy- a morphologic and morphometric study. Am J Vet Res 39(8): 1309-1315.
Capucchio MT, Spalenza V, Biasibetti E, Bottero MT, Rasero R, Dalmasso A, Sacchi P (2014) Degenerative myelopathy in German Shepherd dog: comparison of two molecular assays for the identification of the SOD1:c.118G>A mutation. Mol Biol Rep 41: 665-670.
Carrion E, Hertzog JH, Medlock MD, Hauser GJ, Dalton HJ (2001) Use of acetazolamide to decrease cerebrospinal fluid production in chronically ventilated patients with ventriculopleural shunts. Arch Dis Child 84: 68-71.
Cauzinille L, KornegayJN (1992) Acquired syringomyelia in a dog. J Am Vet Med Assoc 201 (8): 1225-1228.
Chang H-S, Kamishina H, Mizukami K, Momoi Y, Katayama M, Rahman MM, Uddin MM, Yabuki A, Koyiama M, Yamato O (2013) Genotyping assay for the Canine Degenerative Myelopathy- Associated c.118G>A (p.E40K) Mutation of the SOD1 Gene using conventional and Real-Time PCR Methods: A high prevalence in the Pembroke Welsh Corgi Breed in Japan. J Vet Med Sci 75(6): 795-798.
Child G, Higgins RJ, Cuddon PA (1986) Acquired scoliosis associated with hydromyelia and syringomyelia in two dogs. J Am Vet Med Assoc 189 (8): 909-912.
Christman CL (1991) Hemiplegia, hemiparesis, quadriplegia,quadriparesis, ataxia of all four limbs, andepisodic weakness. In: Problems in Small Animal Neurology, 2nd ed, Lea & Febiger, Philadelphia:pp 337-396.
Chrisman CL (1992) Neurological diseases of Rottweilers: Neuroaxonal dystrophy and leukoencephalomalacia. J Small Anim Pract 33: 500-504.
Chuma A, Kitahara H, Minami S, Goto S, Takaso M, Moriya H (1997) Structural scoliosis model in dogs with experimentally induced syringomyelia. SPINE 22 (6): 589-595.
Churcher RK, Child G (2000) Chiari 1/Syringomyelia complex in a Cavalier King Charles Spaniel. Aust Vet J 78 (2): 92-95.
Clemmons RM (1992) Degenerative myelopathy. Vet Clin North Am Small Anim Pract 22 (4): 965-971.
Coates JR, March PA, Oglesbee M, Ruaux CG, Olby NJ, Berghaus RD, O’Brien DP, Keating JH, Johnson GS, Williams DA (2007) Clinical characterization of a familial degenerative myelopathy in Pembroke Welsh Corgi Dogs. J Vet Intern Med 21: 1323-1331.
Cork LC, Troncoso JC, Price DL, Stanley EF, Griffin JW (1983) Canine Neuroaxonal Dystrophy. J Neuropathol Exp Neurol 42 (3): 286-296.
Crisp MJ, Beckett J, Coates JR, Miller TM (2014) Canine Degenerative Myelopathy: Biochemical characterization of superoxide dismutase 1 in the first naturally occurring non-human amyotrophic lateral sclerosis model. Exp Neurol available in PMC, 1-20.
Cummings JF,De Lahunta A (1978) Hereditary myelopathy of Afghan Hounds, a myelinolytic disease. Acta Neuropath 42: 173-181.
Davies DR, Irwin PJ (2003) Degenerative neurological and neuromuscular disease in young Rottweilers. J Small Anim Pract 44: 388-394.
Yin W, Tibbs R, Aoki K, Badr A, Zhang J (2001) Metabolic alterations in cerebrospinal fluid from double hemorrhage model of dogs. Neurol Res 23(1): 87-92.
Dewey CW, Da Costa RC (2016) Myelopathies: Disorders of the Spinal Cord. In: Practical guide to canine and feline neurology, 3rd ed, Wiley Blackwell, Singapore: 358-369.
Evans MG, Mullaney TP, Lowrie CT (1988) Neuroaxonal dystrophy in a Rottweiler pup. J Am Vet Med Assoc192: 1560-1562.
Forman OP, De Risio L, Mellersh CS (2013) Missense mutation in CAPN1 is associated with spinocerebellar ataxia in the Parson Russell Terrier dog breed. PLoS One8 (5) e64627.
Furneaux RW, Doige CE, Kaye MM (1973) Syringomyelia and Spina Bifida Occulta in a Samoyed Dog. Can Vet Jour 14 (2): 317-321.
Gamble DA, Chrisman CL (1984) A leukoencephalomyelopathy of Rottweiler dogs. Vet Pathol 21: 274-280.
Geib LW, Bistner SI (1967) Spinal cord dysraphismin a dog.J Am Vet Med Assoc 150: 618-620.
Gilliam D, O’Brien DP, Coates JR, Johnson GS, Johnson GC, Mhlanga-Mutangadura T, Hansen L, Taylor JF, Schnabel RD (2014) A homozygous KCNJ10 mutation in Jack RussellTerriers and related breeds with spinocerebellar ataxia with myokymia, seizures or both. J Vet Intern Med28: 871-877.
Granger N, Neeves J (2015) Developing objective measures of gait abnormalities in dogs with degenerative myelopathy. Vet Rec 176: 290.
Griffiths IR, Duncan ID (1975) Chronic degenerative radiculomyelopathy in the dog. J Small Anim Pract 16: 461-471.
Hartley WJ (1973) Ataxia in Jack Russell Terriers. Acta Neuropath 26:71-74.
Hirschvogel K, Matiasek K, Flatz K, Drögemüller M, Drögemüller C, Reiner B, Fischer A (2013) Magnetic Resonance Imaging and genetic investigation of a case of Rottweiler leukoencephalomyelopathy. Vet Res 9: 57.
Holder AL, Price JA, Adams JP, Volk HA, Catchpole B (2014) A retrospective study of the prevalence of the canine degenerative myelopathy associated superoxidase dismutase 1 mutation (SOD1:c.118G>A) in a referral population of German Shepherd Dogs from the UK. Canine Genet Epidemiol 1: 10.
Itoh T, Nishimura R, Matsunaga S, Kadosawa T, Mochizuki M, Sasaki N(1996) Syringomyelia and hydrocephalus in a dog. J Am Vet Med Assoc 209 (5): 934-936.
Ivansson EL, Megquier K, Kozyrev SV, Murén E, Baranowska Körberg I,Swofford R, Koltookian M, Tonomura N, Zeng R, Kolicheski AL, Hansen L, Katz ML, Johnson GC, Johnson GS, Coates JR, Lindblad-Toh K (2016) Variants within the SP110 nuclear body protein modify risk of canine degenerative myelopathy. PNAS: 3091-3100.
Javaheri S, Corbett WS, Simbartl LA, Mehta S, Khosla A (1997) Different effects of omeprazole and Sch 28080 on canine cerebrospinal fluid production. Brain Res 754:321-324.
Johnston PEJ, Barrie JA, McCulloch MC, Anderson TJ, Griffiths IR (2000) Central nervous system pathology in 25 dogs with chronic degenerative radiculomyelopathy. Vet Rec 146: 629-633.
Jones JC, Inzana KD, Rossmeisl JH, Bergman RL, Wells T, Butler K (2005) CT-myelopathy of the thoraco-lumbar spine in 8 dogs with degenerative myelopathy. J Vet Sci 6: 341-348.
Kathmann I, Cizinauskas S, Doherr MG, Steffen F, Jaggy A (2006) Daily controlled physiotherapy increases survival time in dogs with suspected degenerative myelopathy. J Vet Intern Med 20: 927-932.
Kirberger RM, Jacobson LS, Davies JV, Engela J (1997) Hydromyelia in a dog. Vet Radiol Ultrasound 38 (1): 30-38.
Kobatake Y, Sakai H, Tsukui T, Yamato O, Kohyama M, Sasaki J, Kato S, Urushitani M, Maeda S, Kamishina H (2016) Localization of a mutation SOD1 protein in E40K- heterozygous dogs: Implications of anon-cell-autonomous pathogenesis of degenerative myelopathy. JNeurolScihttp://dx.doi.org/10.1016/j.jns.2016.10.034
Lee BCP, Zimnicrman RD, Manning JJ, Dcck MDF (1985) MR imaging of syringomyclia and hydromyelia. AJNR 6: 221-228.
Levendoglu F, Ogun CO, Ozerbil O, Ogun TC, Ugurlu H (2004) Gabapentin is a first line drug for the treatment of neuropathic pain in spinal cord injury. Spine 29:743-751.
Lindvall-Axelsson M, Nilsson C, Owman C, Winbladh B (1992) Inhibition of cerebrospinal fluid formation by omeprazole. Exp Neurol 115: 394-399.
Löbert V (2003) Etablierung von laktat- und pyruvatmessung im plasma und liquor cerebrospinalis zur diagnostik von mitochondrialen erkrankungen beim hund. Inaugural-dissertation. University of veterinary medicine Hannover: Department of Small Animal Medicine and Surgery.
Long SN, Henthorn P, Serpell J, Van Winkle T, Coates JR (2009) Degenerative myelopathy in a Chesapeake Bay Retrievers. J Vet Intern Med 23: 396-416.
Longhofer SL, Duncan ID, Messing A (1990) A degenerative myelopathy in young German shepherd dogs. J Small Anim Pract 31: 199-203.
Lu D, Lamb CR, Pfeiffer DU, Targett MP (2003) Neurological signs and results of magnetic resonance imaging in 40 cavalier King Charles Spaniels with Chiari type 1 like malformations. Vet Rec 153: 260-263.
McClarty B, Suthcrland S. Bertram EG (1990) The Spine. In: Kucharczyk W MRI: Central Nervous System. Raven Press, Philadelphia: 19.
Mc Grath JT (1960) Neurologic Examination of the Dog. In: Neurological examination of the dog with clinicopathologic observations. 2nd Ed, Lea & Febiger, Philadelphia: 200-211.
Mandigers PJJ, Van Nes JJ, Knol BW, Ubbink GJ, Gruys E (1993) Hereditary necrotizing myelopathy in Kooiker dogs. Res Vet Sience 54:118-123.
March PA, Coates JR, Abyad RJ, Williams DA, O’ Brien DP, Olby NJ, Keating JH, Oglesbee M (2009) Degenerative myelopathy in 18 Pembroke Welsh Corgi dogs. Vet Pathol 46: 241-250.
Martin-Vaquero P, Da Costa RC, Simmons JK, Beamer GL, Ja¨ derlund KH, Oglesbee MJ (2012) A novel spongiform leukoencephalomyelopathy in Border Terrier Puppies. J Vet Intern Med 26: 402-406.
Mesfin GM, Kusewitt D, Parker A (1980) Degenerative myelopathy in a cat. J Am Vet Med Assoc 176 (1): 62-64.
Miller AD, Barber R, Porter BF, Peters RM, Kent M, Platt SR, Schatzberg SJ (2009) Degenerative myelopathy in two boxer dogs. Vet Pathol 46: 684-687.
Moretto G, Sparaco M, Monaco S, Bonetti B, Rizzuto N (1993) Cytoskeletal changes and ubiquitin expression in dystrophic axons of Seitelberger’s disease. Clin neuropathol 12: 34-37.
Nakamae S, Kobatake Y, Suzuki R, Tsukui T, Kato S, Yamato O, Sakaki H, Urushitani M, Maeda S, Kaminisha H (2015) Accumulation and aggregate formation of mutatnt superoxidase 1 in canine degenerative myelopathy. Neuroscience 303: 229-240.
Nakamura M, Chiba K, Nishizawa T, Maruiwa H, Matsumoto M, Toyama Y (2004) Retrospective study of surgery-related outcomes in patients with syringomyelia associated with Chiari I malformation: Clinical significance ofchanges in the size and localization of syrinx on pain relief. JNeurosurg 3 (l): 241-244.
Norman D (1987) MR of the spine. In: Brant-Zawadzki M, Norman D, eds. Magnetic restinance imaging of the central nervous system. Raven Press,New York: 311-314.
Oldfield EH, Muraszko K, Shawker TH,Patronas NJ (1994) Pathophysiology of syringomyelia associated with Chiari 1 malformation of the cerebellar tonsils. Implications for diagnosis and treatment. Neurosurg 80: 3-15.
Polizopoulou ZS, Koutinas AF, Patsikas MN, Soubasis N ( 2008) Evaluation of a proposed therapeutic protocol in 12 dogs with tentative degenerative myelopathy. Acta veterinaria Hungarica 56 (3): 293-301.
Richardson JA, Tang K, Burns DK (1991) Myeloencephalopathy withRosenthal fiber formation in a miniature poodle. Vet Pathol 28: 536-538.
Rohdin C, Lüdtke L, Wohlsein P, Jäderlund KH (2010) New aspects of hereditary ataxia in smooth-haired fox terriers. Vet Rec 166 (18): 557-560.
Rohdin C, Gilliam D, O’Leary CA, O’Brien DP, Coates JR, Johnson GS, Hultin Jäderlund K (2015) A KCNJ10 mutation previously identified in the Russell group of terriers also accurs in Smooth-haired Fox Terrierswith hereditary ataxia and in related breeds. Acta Veterinaria Scandinavica 57 (26): 1-4.
Rusbridge C, MacSweeny JE, Davies JV, Chandler K, Fitzmaurice SN, Dennis R, Cappello R, Wheeler SJ (2000) Syringohydromyelia in Cavalier King Charles Spaniels. J Am Anim Hosp Assoc 36 (1): 34-41.
Rusbridge C, Knowler SP (2004) Inheritance of occipital bone hypoplasia (Chiari type I malformation) in Cavalier King Charles Spaniels. J Vet Intern Med 18: 673-678.
Rusbridge C, Greitz D, Iskandar BJ (2006) Syringomyelia: current concepts in pathogenesis, diagnosis and treatment. J Vet Intern Med 20:469-479.
Rusbridge C, Carruthers H, Dube M-P, Holmes M,Jeffery ND (2007) Syringomyelia in Cavalier King Charles Spaniels: the relationship between syrinx dimension and pain. J Small Anim Pract 48: 432-436.
Schmahl W, Kaiser E (1984) Hydrocephalus, Syringomyelia and Spinal cord angiodysgenesis in a Lhasa-apso dog. Vet Pathol 21: 252-254.
Shinnar S, Gammon K, Bergman EW Jr, Epstein M, Freeman JM (1985) Management of hydrocephalus in infancy: Use of acetazolamide and furosemide to avoid cerebrospinal fluid shunts. J Pediatr 107: 31-37.
Siso S, Ferrer I, Pumarola M (2001) Juvenile neuroaxonal dystrophy ina Rottweiler: accumulation of synaptic proteins in dystrophic axons. Acta Neuropathol 102: 501-504.
Slocombe RF, Mitten R, Mason TA (1989) Leykoencephalomyelopathy in Australian Rottweiler dogs. Austr Vet J 66 (5): 147-150.
Summers BA, Cummings JF, De Lahunta A (1995) Textbook of Veterinary Neuropathology. MO: Mosby, St Louis: pp 321-322.
Tagaki S, Kadosawa T, Ohsaki T, Hoshino Y, Okumura M, Fujinaga T (2005) Hindbrain decompression in a dog with scoliosis associated with syringomyelia. J Am Vet Med Assoc 226 (8): 1359- 1363.
Todor DR, Harrison TM, Millport TH (2000) Pain and syringomyelia: review. Neurosurg Focus 8: 1-6.
Vogh BP (1980) The relation of choroid plexus carbonic anhydrase activity to cerebrospinal fluid formation: Study of three inhibitors in cat with extrapolation to man. J Pharmacol Exp Ther 213: 321-331.
Wessmann A, Goedde T, Fischer A, Wohlsein P, Hamann H, Distl O, Tipold A (2004) Hereditary Ataxia in the jack Russell terrier – Clinical and Genetic Investigations. J Vet Intern Med 18: 515-521.
Wisoff JH, Epstein F (1989) Management of hydromyelia. Neurosurgery 25: 562-571.
Wouda W, van Nes JJ (1986) Progressive ataxia due to central demyelination in Rottweiler dogs. Vet Q 8 (2): 89-97.
