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CASE NOTES


Ovine segmental axonopathy

Leah Johnson1,2, Katie Eager1,2, Brendon O'Rourke1 and Imke Tammen2

1. Elizabeth Macarthur Agricultural Institute, Menangle, Department of Primary Industries, Menangle, NSW
2. Sydney School of Veterinary Science, The University of Sydney, Camden, NSW

Posted Flock and Herd November 2024

Ovine segmental axonopathy ('Murrurundi disease') is an autosomal recessive inherited disorder in Merino sheep presenting as progressive hindlimb ataxia. Cases have been identified in both Australia and New Zealand (Hartley & Loomis 1981, Harper et al. 1986 & Jolly et al. 2006). Sheep typically present with clinical signs between one to five years of age. Affected sheep have hindlimb ataxia and toe knuckling or dragging of hind feet, often progressing to collapse or dog sitting (Harper et al. 1986). On physical exam, sheep may have hindlimb muscle weakness, normal or increased patella reflex and reduced hind limb withdrawal reflex, while cranial nerve exam is usually unremarkable (Harper et al. 1986). Tremors are not observed (Harper et al. 1986, Jolly et al. 2006).

Post-mortem examination is typically unremarkable except for hindlimb muscle atrophy (Harper et al. 1986). On histopathology, there are large axonal swellings and empty vacuoles throughout white matter within the brain and spinal cord. Areas often affected within the brain include the cerebellar peduncles, dorsolateral thalamic tracts, cuneate fasciculus, longitudinal medial fasciculus, corticospinal tracts, at the roots of the abducens, facial and sensory portion of the trigeminal nerves, and sometimes within the brainstem nuclei and cerebral cortex (Harper et al. 1986). In the spinal cord, axonal swellings are present in cervical, thoracic and lumbar spinal cord, particularly in the dorsal rootlets and dorsal white matter tracts, and sometimes ventral and lateral white matter tracts (Harper et al. 1986 and Jolly et al. 2006). Variable amounts of Wallerian degeneration may be concurrently present (Harper et al. 1986 and Jolly et al. 2006). Peripheral nerves are also affected, although axonal swellings are sparse (Jolly et al. 2006 and Windsor 2006). Electron microscopy of the axonal swellings has shown accumulation of membrane bound vesicles +/- mitochondria, electron dense bodies and larger vacuoles (Jolly et al. 2006 and Windsor 2006).

Differential diagnoses for hindlimb ataxia in sheep may include:

Signalment, history, concurrent clinical signs, clinical pathology and post-mortem findings (if performed) are essential in determining most likely differentials. Absence/presence of central neurologic deficits, tremors and convulsions, and determining the presence of limb paresis with or without concurrent knuckling can be useful differentiating factors (Bourke 1995). Primary myopathies present with paresis or weakness in the absence of knuckling and have not been included in this list (although can sometimes appear similar to 'ataxia'). Similarly, various metabolic conditions may cause weakness or a similar presentation to hindlimb ataxia, for example hypocalcaemia, pregnancy toxaemia and heat stress/hyperthermia.

A retrospective analysis was conducted on submissions at Elizabeth Macarthur Agricultural Institute (EMAI) Menangle. Records were reviewed from 2011 for cases in which histopathology had led to a diagnosis of axonopathy or in which segmental axonopathy was considered in the differential diagnoses by the pathologist based on histopathology. Cases were retrospectively assessed on signalment, history, clinical signs and histopathology to determine if segmental axonopathy was the likely diagnosis. These results were compared with genetic testing, for which a likely causative variant has recently been identified. Comparison with genetic testing confirmed that histopathology was very useful in diagnosing segmental axonopathy, with all cases predicted as likely affected on histopathology confirmed to be segmental axonopathy on genetic testing.

Summary of segmental axonopathy cases at EMAI

History











  • Clinical signs from one year onwards
  • Fine wool Merinos
  • Males and females affected
  • Affected animals typically identified on the property for several previous years, sometimes noticed to be increasing in frequency over time
  • Clinically affected animals noticed at times of yarding, shearing
  • Progressive clinical signs requiring euthanasia. Progress to recumbency
  • Showing signs of collapse, progressing to euthanasia or dying with wasting or dying from misadventure (one investigation describes progression of signs over six months)
  • No response to treatments trialled, no improvement in signs
  • In one case, change in ram selection coincided with onset of clinical signs. In a second case, there was no recent change with rams sourced from home-bred rams.
  • One report of faster growing weaners/hoggets affected
Clinical signs and examination






  • Exacerbated by stress, exercise, mustering, shearing
  • Hindlimb ataxia, uncoordinated, staggering, stumbling, walking with swaying hindlimbs, hopping hindlimb gait, hindlimbs collapsing underneath, dog-sitting, falling with difficulty rising, collapsing when pushed or trying to turn, falling to one side, recumbency, circling (pivoting on forelimbs with hindlimb hopping)
  • Forelimbs unaffected
  • Vision unaffected
  • Sensation present in feet
  • No tremors
  • Bright, alert, responsive. Normal mentation.
Post-mortem findings
  • Often no significant findings on gross post-mortem

As segmental axonopathy has a later onset of clinical signs, which are primarily neurologic, many submissions are received as part of the National TSE Surveillance Program (NTSEP).

Distribution of lesions in segmental axonopathy is well established, as previously described by Harper et al. (1986) and Jolly et al. (2006). Examining the key sites is important in determining presence or absence of diagnostic features. Therefore, if segmental axonopathy is suspected, and a post-mortem is done, submitting formalin-fixed brain and spinal cord (ideally cervical, thoracic and lumbar spinal cord segments individually identified) is ideal for both diagnosis of segmental axonopathy and investigation of differential diagnoses. Submitting small samples of fresh brain and spinal cord is also recommended if there is any possibility that ancillary diagnostics may be needed, for example culture or PCR.

Segmental axonopathy has been confirmed in a flock most recently in 2024, confirming the ongoing presence of segmental axonopathy in Merino sheep flocks in NSW. The availability of an accessible, ante-mortem genetic test will allow a more thorough assessment of how widespread segmental axonopathy is, as well as guide breeding management to assist in reducing clinical cases.

Segmental axonopathy genetic testing is now available through the Biotechnology department of EMAI (DNA test was developed in collaboration with K. Dittmer, R. Jolly and M. Littlejohn from Massey University). Preferred sample types include Allflex TSU samples or EDTA blood. Testing of other sample types such as semen, fresh tissue or formalin-fixed, paraffin-embedded tissue is possible, however DNA extraction charges may apply. Please contact for further information. The authors also welcome the chance to promote the Anstee Hub for Inherited Diseases in Animals (AHIDA) ahida.sydney.edu.au, recently launched by the University of Sydney. We encourage veterinarians and producers to report suspected inherited diseases to the database to facilitate the development of diagnostic genetic tests.

References

  1. Bourke CA (1995) The clinical differentiation of nervous and muscular locomotor disorders of sheep in Australia Australian Veterinary Journal 1995 Jun 72(6):228-34
  2. Harper PA, Duncan DW, Plant JW, Smeal MG (1986) Cerebellar abiotrophy and segmental axonopathy: two syndromes of progressive ataxia of Merino sheep Australian Veterinary Journal 1986 Jan 63(1):18-21
  3. Hartley WJ, Loomis LN (1981) Murrurundi disease: an encephalopathy of sheep Australian Veterinary Journal 1981 Aug 57(8):399-400
  4. Jolly RD, Johnstone AC, Williams SD, Zhang K and Jordan TW (2006) Segmental axonopathy of Merino sheep in New Zealand New Zealand Veterinary Journal 2006 Oct 54(5):210-7
  5. Windsor PA (2006) Ultrastructural findings in ovine segmental axonopathy of Merino sheep Australian Veterinary Journal 2006 May 84(5):169-72

Acknowledgements

The authors would like to acknowledge the submitting veterinarians for case material. The authors also thank the specimen receival, histology, biotechnology and pathology departments at EMAI for their assistance with cases at EMAI. The authors would like to acknowledge Patrick Staples for conducting the search of EMAI records.

 


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