CASE NOTES


Ovine Segmental Axonopathy in Two Fine Wool Merino Flocks

Petrea Wait1, Katherine Loring2, Patrick Shearer3, Tom Westermann3 & Erika Bunker3, Peter Windsor4

District Veterinarian, Cooma1; 5th year veterinary student, Charles Sturt University2; State Veterinary Diagnostic Laboratory, EMAI, Menangle3; Professor Emeritus and Specialist Veterinarian (Pathbiol., Small Ruminant Health Management), University of Sydney4

Posted Flock & Herd August 2017

Introduction

Ovine Segmental Axonopathy (OSA) was identified in  1962, although the aetiology was not described at this time1. After further investigations on the same property in 1981, the  condition was named  “Murrurundi Disease.” It was characterised as an encephalopathy that resulted in spheroid vacuolation of the axons of the white matter in the cerebellum and spinal cord. This farm reported that clinical signs only developed in sheep aged 2-5 years1. Murrurundi Disease is often considered to be an early reported case of OSA, and the names are sometimes used interchangeably6,7,10.

Cases of OSA are reported sporadically and incidence within affected flocks and age of affected animals varies in the literature1, 7. However, all cases are reported to be progressive, occur in adult fine wool merinos and cause hindlimb paresis, resulting in ataxia and recumbency. In all reported cases with histopathology included, ballooning of the axons of the white matter in the cerebellum and spinal cord was identified. The resulting spheroid vacuoles contain eosinophilic granular material. This is differentiated from spongiform encephalopathies, in which vacuolation occurs primarily in the grey matter10.

OSA can be easily confused with other neurological conditions of sheep11. Field differentiation can be difficult, as it is based solely on presenting clinical signs and  history.

Case Studies

Farm 1

History

A District Veterinarian (DV) for the South East Local Land Services (LLS) was called to investigate neurological signs in young merino sheep. The producer switched from medium to fine wool merino blood lines approximately 15 years ago and since the change has found that a small number of sheep develop nervous signs at around 12 months of age. These sheep become progressively weaker in the hindlimbs over a period of approximately six months and were eventually unable to stand.

Previous investigations by other veterinarians have ruled out nutritional and toxic aetiologies.

Affected sheep are identified by the producer at their first shearing. An affected sheep is one that displays hind limb weakness, manifesting as a bunny hopping gait, slowness to rise, difficulty keeping up with the mob when being moved and stumbling or falling, while mentation and the forelimbs are unaffected. The producer noticed that the sheep are often more affected after handling and were far more difficult to move after shearing.

No rams, either stud bought or home bred (bred from stud rams) have developed hindlimb paresis.

Clinical Findings

A group of affected sheep were presented for examination. They ranged in age from 12 to 24 months old and displayed clinical signs of varying severity. The younger sheep mainly displayed a bunny hopping gait, hindquarter swaying, knuckling of hind fetlocks and stumbling when stressed (see Figure 1), while the older, more severely affected animals exhibited a ‘dog-sitting’ posture with the forelimbs pivoting around the hindquarters, hind limb swaying and staggered when walking (see Figure 2). Animals at this stage of disease progression had difficulty rising without assistance and would thus, be euthanised on welfare grounds.

No older stock are affected and no rams, either purchased or bred on farm, are showing signs of the condition. The producer was unable to identify which lambs were from which ewes and could not, therefore, be traced back to particular sires.

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Figure 1. Video of an affected sheep of 12 month of age, early stage disease.
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Figure 2. Video of an affected sheep of 24 months of age, late stage disease

Post-mortem and Pathology

Two of the most severely affected sheep were humanely euthanised on farm and post-mortem examinations were conducted. No abnormalities were identified grossly in either animal and whole blood, brain and spinal cord were collected from both sheep. The brain and spinal cord were submitted for TSE surveillance as well as histopathology to identify a cause of the hindlimb paresis.

Findings

Both sheep were found to be TSE negative on the basis of immunohistochemistry. 

Mild to marked vacuolation of the white matter tracts was identified at standard sites 1-3 in the cerebellum, as well as in all examined portions of the spinal cord (cervical, thoracic and lumbar sections). The vacuoles were of varying size and shape and contained fine granular eosinophilic spheroids. In longitudinal histopathology sections, the vacuoles appear to be arranged in chains.

Histopathology and presentation are consistent with Ovine Segmental Axonopathy

Further Diagnostics

Blood was collected in EDTA from all 33 rams used on the property. These were submitted for inclusion into a molecular investigation aimed at identifying heritability of the disease.

Farm 2

History

Farm 2 is a fine wool merino property that has noticed a slow increase in the number of sheep with hindlimb paresis over the last 20 years. The producer has noticed  that the sheep become weak in the hind legs at around 12 months of age and that this weakness greatly increases after  handling. The weakness progresses over the next 6 months, often to the point where sheep are unable to rise. The producer is not currently supplementing with cobalt and reduces the risk of phalaris staggers through pasture and stock management as they have experienced  phalaris staggers in the past.

Clinical findings

The producer identified a mob of approximately 25 sheep of mixed sex that had difficulty keeping up when the mob was being moved down a laneway. Most of these sheep showed signs of hindlimb weakness, including stumbling, falling, bunny-hopping, poorly coordinated movements, dropped hocks and tight circling (pivoting on the hindlegs). The producer identified two animals for euthanisia as they were unable to walk and had to be carried in to the yards.

Both sheep, a ewe and a wether, were 18 months old and had been recently shorn. They were able to stand only with assistance, but would subsequently fall over with any rapid movements. There was physical evidence of prolonged recumbency on the wether (grass and faecal staining on one side) and both sheep could drag themselves around the yard using their forelegs. Mentation of the animals appeared to be unaffected.

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Figure 3: Video of an affected sheep of 18 months of age.

Post-mortem and Pathology

Both the wether and the ewe were humanely euthanised and necropsied. st-  No gross lesions were detected  and the brain and spine were  removed for for submission for TSE surveillance and histopathological examination.

Findings

Histopathological examination found no lesions consistent with TSE. 

Sections of brain and spinal cord of both sheep exhibited mild random multifocal vacuolation in white matter tracts and multifocal dilated myelin sheaths, occasionally containing swollen, eosinophilic axons (spheroids), or fine eosinophilic granular material (suggestive of degrading spheroid) (figures 4 and 5). These findings are consistent with Ovine Segmental Axonopathy.

Figure 4: Trigeminal tract from wether
Figure 5:  Spinal cord from wether

Additional histopathological findings in the ewe from Farm 2 included moderate intracytoplasmic accumulation of dark brown, coarse granular pigment often perinuclear and occurring in single or multiple aggregates primarily within neurons and consistent with phalaris intoxication.

Discussion

Many  conditions cause  ataxia in sheep and differentiation between these is often difficult. These conditions may be a result of intoxication, infection, metabolic disturbance, vitamin or mineral deficiency, or a genetic defect6. Ovine segmental axonopathy (OSA) is presumed  to be a genetic condition, found only in fine wool merino sheep of a single but well distributed bloodline (P. Windsor, personal communication). The antemortem investigation may lead to a presumptive diagnosis, but histopathology of the cerebellum and spinal cord is currently required for definitive diagnosis.

Typical histological findings in the central and peripheral nervous system include widespread axonal ballooning forming spheroids and large vacuoles, mainly involving myelinated tracts, accompanied by Wallerian degeneration. The axonal swellings are large round to oval structures containing fine granular eosinophilic material or are empty, forming multiple vacuoles. All areas of the nervous system are affected, with the most striking pathology found in the trigeminal radix 10. Windsor who first described the ultrastructural findings in this condition  considered these findings to be pathognomonic  (P. Windsor, personal communication)).

The widespread vacuolation of the white matter is suggestive of a spongiform leukoencephalopathy, and occasional vacuoles in neurones resemble those found in transmissible spongiform encephalopathies. The signs of a progressive neurological disease are also consistent with a TSE, and so is an important differential for this condition.

Many neurological conditions can present in similar ways and field diagnosis will often rely on clinical findings and history of exposure to possible toxins1-4. OSA and phalaris staggers, which were found concurrently in one of the sampled animals, have different, but overlapping clinical signs and some of these are inherently subjective. Factors such as the cause of instability when walking (paresis vs. equilibrium disturbance6) is difficult to determine and other signs such as tremors or convulsions may be intermittent and possibly missed during a short examination. In an extensive production system, these may be overlooked as the animals.. 

Despite exhaustive history, observation and clinical exam, many differentials remain to be distinguishable only via histopathology of the brain and spinal cord. Clinically, OSA, cerebellar abiotrophy and neuroaxonal dystrophy present nearly identically, however, histologically, cerebellar abiotrophy is characterised by a loss of Purkinje cells within the cerebellum8, 9, and has been identified in breeds other than merinos. Neuroaxonal dystrophy presents in much the same way as OSA and involves the enlargement of axons, although the cause and location of the enlargement differs10.

Recently investigated cases of OSA4, 9 reported that cases were typically seen in animals aged 1 – 2 years of age, while older investigations noted that clinical signs were identified in animals aged 2-5 years5, 6. On both properties visited during this investigation, the majority of cases were first noted at 12 months of age and progressed over the next six months. Farm 2 reported a greater variation in the age of onset and progression of clinical signs. This is one of the antemortem indications that the disease process on this farm was not only OSA. Onset of clinical signs of phalaris staggers can be highly variable making the connection of exposure to the disease difficult5. In noting this, exposure to phalaris was, in this case, thought to be minimal and insignificant. 

References

  1. Alden R, Hackney B, Weston L, Quinn J. Phalaris Toxicoses in Australian Livestock Production Systems: Prevalence, Aetiology and Toxicology. J Toxins 2014;1:7
  2. Bourke C. The clinical differentiation of nervous and muscular locomotor disorders of sheep in Australia. Aust Vet Jl 1995;72:228-234
  3. Bourke C, Carrigan M, Dixon R. The pathogenesis of the nervous syndrome of Phalaris aquatica toxicity in sheep. AustVet Jl 1990;67:356-358
  4. Bourke C, Rendell D, Colegate S. Clinical observations and differentiation of the peracute Phalaris aquatica poisoning syndrome in sheep known as Polioencephalo‐malacia‐like sudden death'. Aust Vet J 2003;81:698-700
  5. Hartley W, Loomis L. Murrurundi disease: an encephalopathy of sheep. Aust Vet Jl 1981;57:399-400
  6. Harper PAW, Duncan DW, Plant JW, Smeal MG. Cerebellar abiotrophy and segmental axonopathy: two syndromes of progressive ataxia of Merino sheep. Aust Vet Jl 1986;63:18-21
  7. Jolly R, Johnstone A, Williams S, Zhang K, Jordan T. Segmental axonopathy of Merino sheep in New Zealand. NZ Vet Jl 2006;54:210-217
  8. Johnstone A, Johnson C, Malcolm K, Jolly R. Cerebellar cortical abiotrophy in Wiltshire sheep. NZ Vet Jl 2005;53:242-245
  9. Watt B, Carr M, Spiers Z, Dawood K. Two cases of neurogenetic progressive ataxia in merino sheep: Segmental axonopathy and cerebellar abiotrophy. Flock and Herd 2011
  10. Windsor P. Ultrastructural findings in ovine segmental axonopathy of Merino sheep. Aust Vet J 2006;84:169-172
  11. Windsor PA, Kessell AE, Finnie JW. Review of neurological diseases of ruminant livestock in Australia. VI: postnatal bovine, and ovine and caprine, neurogenetic disorders. Aust Vet J 2011;89:432-438

 


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