Neuroaxonal dystrophy

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Abnormal morphology associated with neuroaxonal dystrophy. A - ventral view of a puppy showing invariant and locked position of limbs. B - showing partially dissected cervical to lower lumbar segments of spinal cord lying in the scoliotic vertebral column[1]

Neuroaxonal dystrophy is an autosomal-recessive genetic disease of dogs characterized by neurodegenerative pathology of the central and/or peripheral nervous system.

A number of breeds appear predisposed to this condition, including the Papillon[2], Chihuahua-cross[3], Rottweiler[4], Collie[5], Dachshund[6] and Jack Russell Terrier[7].

In dogs, this condition appears as local swellings (spheroids) and atrophy of axons[1]. This condition is caused by a mutation in the mitofusin 2 gene.

A neonate form manifests as fetal akinesia late in gestation and respiratory failure at birth, both due to lower motor neuron dysfunction, and is accompanied by cerebellar hypoplasia. Affected newborn pups usually present with acute respiratory distress, stereotypical positioning of limbs, scoliosis, arthrogryposis, pulmonary hypoplasia and respiratory failure.

Some dogs have delayed onset, with symptoms appearing in adult life or at old age[8] with a slow-onset of neurological signs such as ataxia, intention tremors[9], hypermetria and laryngeal paralysis[10].

Diagnosis is made difficult by the fact that neuroaxonal dystrophy and cerebellar abiotrophy have similar clinical, neurological and MRI features[11].

Postmortem examination usually reveals swollen axons/spheroids throughout thebrainstem, spinal cord and peripheral nerves. Cerebellar hypoplasia is a feature of this condition with degeneration of Purkinje cells and neurons prevalent throughout deep cerebellar nuclei. Segmental swellings of axons may also be evident with axonal swelling filled with membrane bound fragments filled with neurofilaments[12].

Immunohistochemical staining with alpha-synuclein in the dystrophic axons is a feature of this condition[13].

A differential diagnosis would include include cerebellar abiotrophy and ceroid lipofuscinosis[14] as well as causes of peripheral neuropathy such as vitamin E deficiency[15], diabetes mellitus, normal aging, and exposure to certain toxins[16][17].

References

  1. 1.0 1.1 Fyfe JC et al (2010) Inherited neuroaxonal dystrophy in dogs causing lethal, fetal-onset motor system dysfunction and cerebellar hypoplasia. J Comp Neurol 518:3771–3784
  2. Franklin RJ et al (1995) Neuroaxonal dystrophy in a litter of papillon pups. J Small Anim Pract 36:441–444
  3. Nibe K 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
  4. Chrisman CL et al (1984) Neuroaxonal dystrophy of Rottweiler dogs. J Am Vet Med Assoc 184:464–467
  5. Clark RG et al (1982) Suspected inherited cerebellar neuroaxonal dystrophy in collie sheep dogs. N Z Vet J 30(7):102-103
  6. Duncan ID et al (1982) The pathology of a sensory neuropathy affecting Long Haired Dachshund dogs. Acta Neuropathol 58(2):141-151
  7. Sacre BJ et al (1993) Neuroaxonal dystrophy in a Jack Russell terrier pup resembling human infantile neuroaxonal dystrophy. Cornell Vet 83(2):133-142
  8. Sisó S et al (2001) Juvenile neuroaxonal dystrophy in a Rottweiler: accumulation of synaptic proteins in dystrophic axons. Acta Neuropathol 102(5):501-504
  9. Evans MG et al (1988) Neuroaxonal dystrophy in a rottweiler pup. J Am Vet Med Assoc 192(11):1560-1562
  10. Bennett PF & Clarke RE (1997) Laryngeal paralysis in a rottweiler with neuroaxonal dystrophy. Aust Vet J 75(11):784-786
  11. deLahunta A (1990) Abiotrophy in domestic animals: review. Can J Vet Res 54:65–76
  12. Fyfe JC et al (2011) A novel mitofusin 2 mutation causes canine fetal-onset neuroaxonal dystrophy. Neurogenetics 12(3):223-232
  13. Nibe K et al (2009) Immunohistochemical features of dystrophic axons in Papillon dogs with neuroaxonal dystrophy. Vet Pathol 46(3):474-483
  14. Nibe K et al (2010) Comparative study of cerebellar degeneration in canine neuroaxonal dystrophy, cerebellar cortical abiotrophy, and neuronal ceroid-lipofuscinosis. J Vet Med Sci 72(11):1495-1499
  15. McLellan GJ et al (2003) Clinical and pathological observations in English cocker spaniels with primary metabolic vitamin E deficiency and retinal pigment epithelial dystrophy. Vet Rec 153(10):287-292
  16. Schmidt RE et al (1991) Differential effect of chronic vitamin E deficiency on the development of neuroaxonal dystrophy in rat gracile/cuneate nuclei and prevertebral sympathetic ganglia. Neurosci Lett 123:102–106
  17. Schmidt RE et al (1997) Dystrophic axonal swellings develop as a function of age and diabetes in human dorsal root ganglia. Neuropathol Exp Neurol 56:1028–1043