ISSN 2398-2969      

Neuroaxonal dystrophy

icanis

Synonym(s): NAD


Introduction

  • Fatal, progressive neurodegenerative disorder.
  • Cerebellar-like clinical signs.
  • Hereditary or congenital in young Jack Russell terriers, Papillons, Chihuahuas, Collie Sheep dogs, Rottweilers, Boxers and German Shepherds.
  • No treatment.

Pathogenesis

Etiology

  • Several reports have suggested an autosomal recessive inheritance.
  • In the Spanish Water dog Spanish Water dog the disease is caused by a mutation in the tectonin beta-propeller repeat-containing protein 2 (TECPR2) gene which is involved in the autophagic pathways, axonal transport, and mitochondrial metabolism.
  • In the Papillon, the disease is caused by a mutation in the PLA2G6 gene. The precise mechanism of how dysfunction of PLA2G6 leads to axonal degeneration still remains unclear.

Pathophysiology

  • Current concepts of pathogenesis of both, inherited and physiologic, NADs in dogs suggest a disruption of the axonal transport system leading to a functional transsection of the nerve fiber.
  • The mechanisms by which spheroids develop in NAD are only partly known, but immunohistochemical methods have shown that NAD entails an accumulation of synapse-associated proteins, cytoskeletal proteins and other axonal markers, this suggesting an axonal transport deficit as the underlying cause of spheroid formation.

Timecourse

  • NAD is a monophasic and progressive disease.
  • The velocity of deterioration differs among the affected breeds. In Rottweilers the clinical picture gradually worsens over a time period up to several years; whereas in Jack Russell terriers, Papillons, Chihuahuas and Collie Sheep dogs a more rapid progression usually demands euthanasia within several weeks after presentation.

Diagnosis

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Treatment

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Prevention

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Outcomes

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Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Degl’Innocenti S, Asiag N, Zeira O et al (2017) Neuroaxonal dystrophy and cavitating leukocencephalopathy of Chihuahua dogs. Vet Pathol 54 (5), 832-837 PubMed.
  • Tsuboi M, Watanabe M, Nibe K et al (2017) Identification of the PLA2G6 c.1579G>A missense mutation in Papillon dog neuroaxonal dystrophy using whole exome sequencing analysis. PLoS One 12 (1), e0169002 PubMed.
  • Pintus D, Cancedda MG, Macciocu S et al (2016) Pathological findings in a Dachshund-cross dog with neuroaxonal dystrophy. Acta Vet Scand 58 (1), 37 PubMed.
  • Hahn K, Rohdin C, Jagannathan V et al (2015) TECPR2 associated neuroaxonal dystrophy in Spanish water dogs.  PLoS One 10 (11), e0141824 PubMed.
  • Fyfe J C, Al-Tamimi R A, Castellani R J et al (2010) Inherited neuroaxonal dystrophy in dogs causing lethal, fetal-onset motor system dysfunction and cerebellar hypoplasia.  J Comp Neurol 518 (18), 3771-3784 PubMed.
  • Nibe K, Nakayama H, Uchida K (2009) Immunohistochemical features of dystrophic axons in Papillon dogs with neuroaxonal dystrophy. Vet Pathol 46 (3), 474-483 PubMed.
  • Nibe K, Kita C, Morozumi M et al (2007) Clinicopathological features of canine neuroaxonal dystrophy and cerebellar cortical abiotrophy in Papillon and Papillon-related dogs. J Vet Med Sci 69 (10), 1047-1052 PubMed.
  • Diaz V J, Dunque C, Geisel R (2007) Neuroaxonal dystrophy in dogs: case report in 2 litters of Papillon puppies. J Vet Intern Med 21 (3), 531-534 PubMed.
  • Tamura S, Tamura Y, Uchida K (2007) Magnetic resonance imaging findings in neuroaxonal dystrophy in a papillon puppy. J Small Anim Pract 48 (8), 458-461 PubMed.
  • Sisó S, Ferrer I, Pumarola M (2001) Juvenile neuroaxonal dystrophy in a Rottweiler: accumulation of synaptic proteins in dystrophic axons. Acta Neuropathol 102 (5), 501-504 PubMed.
  • Bennett P F, Clarke R E (1997) Laryngeal paralysis in a rottweiler with neuroaxonal dystrophy. Aust Vet J  75 (11), 784-786 PubMed.
  • Boersma A, Zonnevylle H, Sanchez M  A et al (1995) Progressive ataxia in a Rottweiler dog. Vet Q 17 (3), 108-109 PubMed.
  • Franklin R J, Jefferey N D, Ramsey I K (1995) Neuroaxonal dystrophy in a litter of papillon pups. J Small Anim Pract 36 (10), 441-444 PubMed.
  • Sacre B J, Cummings J F, De Lahunta A (1993) Neuroaxonal dystrophy in a Jack Russell terrier pup resembling human infantile neuroaxonal dystrophy. Cornell Vet 83 (2), 133-142 PubMed.
  • Chrisman C L (1992) Neurological diseases of rottweilers: neuroaxonal dystrophy and leukoencephalopathy. J Small Anim Pract 33 (10), 500-504 Wiley Online Library.
  • Evans M G, Mullaney T P, Lowrie C T (1988) Neuroaxonal dystrophy in a rottweiler pup. J Am Vet Med Assoc 192 (11), 1560-1562 PubMed.
  • Blakemore W F, Palmer A C (1985) Nervous disease in the chihuahua characterised by axonal swellings. Vet Rec 117 (19), 498-499 PubMed.
  • Chrisman C L, Cork L C, Gamble D A (1984) Neuroaxonal dystrophy of Rottweiler dogs. J Am Vet Med Assoc 184 (4), 464-467 PubMed.
  • Cork L C, Troncoso J C, Price D L et al (1983) Canine neuroaxonal dystrophy. J Neuropathol Exp Neurol 42 (3), 286-296 PubMed.
  • Clark R G, Hartley W J, Burgess G S et al (1982) Suspected inherited cerebellar neuroaxonal dystrophy in collie sheep dogs. N Z Vet J 30 (7), 102-103 PubMed.

Other sources of information

  • Braund KG (2003) Degenerative disorders of the central nervous system. In: Braund KG (ed)Clinical neurology in small animals localization, diagnosis and treatment. International Veterinary Information Service (www.ivis.org), Ithaca, New York.
  • Lowe J S, Leigh P (2002) Disorders of movement and system degenerations. In: Graham D, Lantos P (eds)Greenfield's neuropathology. 7th edn, Arnold, London, pp 281-366.
  • Ackerman L (1999) The genetic condition: a guide to health problems in purebred dogs. AAHA Press, Lakewood, Colorado, pp 140-141.
  • Summers B A, Cummings J F, De Lahunta A (1995) Veterinary neuropathology. Mosby, St Louis, pp 315-317.

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