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.
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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
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.