Treatment with potassium bromide mitigates ataxia and reduces tremor in lambs with perennial ryegrass toxicosis.

Aims: To assess the use of potassium bromide (KBr) as a therapeutic intervention for perennial ryegrass toxicosis (PRGT) in lambs fed ryegrass seed containing lolitrem B. Methods: Male lambs aged 10-12 months (n = 43) were assigned to receive ryegrass seed containing lolitrem B, at a dose of 0.16 mg/kg/day (Groups 2, 3 and 4), or lucerne chaff and molasses (Groups 1 and 5). Lambs in Groups 2 and 3 were observed for clinical signs and gait changes until defined signs of PGRT were observed, when they were transferred, with lambs in Group 1, to the Testing phase of the trial. Lambs in Group 3 were then treated with a single oral dose of 300 mg/kg bromide. Lambs in Groups 4 and 5 received KBr daily from the start of the trial (540 mg/kg bromide over 3 days then 20 mg/kg daily) and were transferred to the Testing phase after 18 days. Clinical examination and gait assessment, and surface electromyography of the triceps muscle, measuring root-mean-square (RMS) voltages, were carried out on Days 0, 1 and 2 of the Testing phase followed by necropsy, histopathology, measurement of concentrations of bromide in serum and CSF and faecal cortisol metabolites (FCM). Results: In Group 3 lambs, mean composite gait scores decreased between Testing phase Day 0 and Days 1 and 2 (p < 0.001), but increased in lambs in Group 2 between Day 0 and Day 2 (p = 0.015). Scores for lambs in Group 3 on Day 2 were lower than for lambs in Group 2 (p < 0.001). Mean RMS voltages on Day 2 were higher in lambs in Group 2 than Group 3 (p = 0.045). Mean concentrations of bromide in serum were >800 µg/mL in lambs in Groups 3 and 4 on Day 2. Concentrations of FCM were higher in lambs from Group 2 than in Groups 1 or 5, but were similar in Groups 2, 3 and 4. Histopathological findings in the cerebellum of lambs from Groups 2, 3 and 4 were similar, showing pyknosis of neurons within the granular layer of the cerebellum and Purkinje neuron proximal axonal spheroid formation. Conclusions and clinical relevance: A single oral dose of 300 mg/kg bromide in lambs with neurological signs of PRGT resulted in reduced composite gait scores and reduced RMS voltages, indicating a significant improvement in clinical signs of ataxia, movement disorder and muscle tremor associated with the neurotoxic effects of lolitrem B.

Development of a model for investigation of perennial ryegrass toxicosis in sheep.

AIMS To develop a clinical model of perennial ryegrass toxicosis (PRGT) based on feeding a known dose of lolitrem B and ergotamine, and to produce a consistent clinical presentation for assessment of disease pathophysiology, neurological changes and neurohistopathology. METHODS Male lambs, aged between 10-12 months, were randomly assigned to either Treatment (n=9) or Control (n=9) groups. Lambs in the Treatment group received feed containing a novel endophyte-infested perennial ryegrass seed, commencing on Day 0 of the Feeding phase with a low induction dose, then increasing after 3 days to provide 0.16 mg/kg live bodywight (LBW)/day of lolitrem B and 0.054 mg/kg LBW/day ergotamine. Lambs were examined daily and when defined signs of PRGT were observed they were transferred to the Testing phase. Neurological examinations, assessment of gait, surface electromyography (EMG) and mechanosensory nociceptive threshold testing were carried out and blood samples collected during both phases of the trial, with a full necropsy, histopathological examination and measurement of faecal cortisol metabolites (FCM) performed on Day 2 of the Testing phase. RESULTS Typical clinical signs of PRGT, including ataxia of vestibulocerebellar origin leading to stumbling, were observed in all Treatment lambs. The median interval from the start of the Feeding phase to entry into the Testing phase was 21 (min 18, max 34) days. Histopathological characterisation of neurological lesions included the presence of Purkinje cell vacuolation, pyknotic granular layer neurons and proximal axonal Purkinje cell spheroids. Lesions were most apparent within the vestibulocerebellum. Mean root-mean-square voltages from triceps EMG increased in Treatment lambs between Feeding phase Day 0 and Testing phase Day 2 (p<0.001). Daily water intake during the Testing phase for the Treatment group was less than in Control group lambs (p=0.002), and concentrations of FCM at necropsy were higher in Treatment compared to Control lambs (p=0.02). CONCLUSIONS AND CLINICAL RELEVANCE Lolitrem B and ergotamine dosing in feed on a live weight basis combined with neurological/gait assessment provides an effective model for investigation of PRGT and potential therapeutics. Assessment of gait changes using defined criteria and RMS voltages from EMG appear to be useful tools for the assessment of the severity of neurological changes.

Prevalence of exon 11 internal tandem duplications in the C-KIT proto-oncogene in Australian canine mast cell tumours.

OBJECTIVE: To measure the prevalence of internal tandem duplications (ITDs) in exon 11 of the proto-oncogene C-KIT in a sample of Australian cutaneous canine mast cell tumours (MCTs) drawn from general practice and to evaluate relationships between tumour mutation status and prognostic factors including signalment, tumour histological grade, tumour anatomical location and tumour size. METHODS: C-KIT exon 11 ITDs were detected by PCR in DNA extracted from formalin-fixed, paraffin-embedded canine MCTs sourced from three veterinary diagnostic laboratories in Adelaide and Melbourne. Tumours were graded according to two different systems (Patnaik and Kiupel systems) by board-certified anatomical pathologists blinded to the PCR results. Relationships between tumour mutation status and prognostic factors were evaluated using a generalised binary logistic regression analysis. RESULTS: ITDs were identified in 13 of 74 cutaneous canine MCT samples, giving an overall prevalence of 17.6% (95% confidence interval: 8.9-26.2%). ITDs were detected in 10 of 18 Patnaik grade III MCTs (55.6%) and 11 of 22 Kiupel high-grade MCTs (50%). Wald chi-square analysis revealed that detection of tumour ITDs was significantly associated with both Patnaik's and Kiupel's histologic grading systems (each: P < 0.001). The presence of the ITDs in MCTs was not associated with signalment, tumour anatomical location or tumour size. CONCLUSION: The prevalence of C-KIT exon 11 ITDs in Australian canine MCTs is similar to the prevalence in overseas canine populations (overall prevalence in Australia approximately 18%). ITDs were more frequently identified in higher grade MCTs.

Hypovitaminosis A in extensively grazed beef cattle.

CASE REPORT: Vitamin A deficiency was diagnosed in a herd of 97 19-month-old Braford heifers in the Mitchell Grass Downs (Astrebla spp.) bioregion of Hughenden in north-western Queensland during November 2015. Two heifers died after a 48-h history of sternal recumbency and of the 19 that had neurological signs, 7 were blind. Histological changes in the optic nerves of the two necropsied cattle were consistent with vitamin A deficiency. This diagnosis was supported by vitamin A concentrations in fresh liver samples of 5 and 6 mg/kg wet tissue (reference range, 100-175 mg/kg) despite treatment of the cattle with twice the recommended dose of parenteral vitamin A 3 weeks prior to sampling. Rainfall on the property during the 2 years before the outbreak was less than the annual rainfall average of 464 mm, with a total of 281 mm in 2014 and 117 mm from January to November in 2015, most of this falling in January. CONCLUSION: Plant assays for both ß-carotene and crude protein concentrations in dry matter (DM) were less than the recommended dietary requirements for beef cattle (0.30 mg/kg DM and 56 g/kg, respectively).

Axonal Spheroid Accumulation In the Brainstem and Spinal Cord of A Young Angus Cow with Ataxia.

CASE REPORT: An 18-month-old Angus cow presented with rapidly developing ataxia and subsequently died. The finding of large numbers of axonal spheroids in brainstem nuclei and spinal cord grey matter, bilaterally symmetrical in distribution, was consistent with a histopathological diagnosis of neuroaxonal dystrophy (NAD). Most of the axonal swellings were immunopositive to amyloid precursor protein, suggesting that interruption to axonal flow was important in their genesis. CONCLUSIONS: The topographical distribution of axonal spheroids in the brain and spinal cord in this bovine case closely resembled that found in the ovine neurodegenerative disorder termed NAD, in which axonal swellings are the major pathological feature. This appears to be the first reported case of this type of NAD in cattle. The aetiology of the spheroidal aggregations in this case was not determined. There was no evidence from the case history or neuropathology to indicate whether the axonal spheroids in this case involved an acquired or heritable aetiology.

An outbreak of primary photosensitisation in lambs secondary to consumption of Biserrula pelecinus (biserrula).

CASE REPORT: An outbreak of photosensitisation affecting approximately 25% of a flock of 120 meat lambs that was grazing a monoculture of the pasture legume Biserrula pelecinus var. Casbah (biserrula) was investigated. Blood samples were taken from sheep with moderate to severe clinical signs, and from apparently normal animals, for a complete blood count and biochemistry; 5 affected animals were subjected to a full necropsy. Histopathological investigation showed lesions consistent with photosensitisation of the exposed unpigmented skin of the face and ears. No histopathological or clinical pathological abnormalities suggestive of a hepatopathy were detected in any of the cases, indicating that the lesions observed in this flock were caused by a primary photosensitising agent present in B. pelecinus. CONCLUSION: This is the first confirmation that photosensitisation caused by ingestion of biserrula is caused by a primary photosensitising agent.

Acute renal failure associated with Amaranthus species ingestion by lambs.

CASE REPORT: This report documents an outbreak of acute renal failure in a flock of 9-month-old White Suffolk-cross ewe lambs. The mortality rate was moderate but the morbidity was high. The lambs had grazed a wheat stubble paddock in which there were several weed species, including Amaranthus spp. CLINICAL SIGNIFICANCE: Renal failure in livestock has been reported internationally following the ingestion of Amaranthus spp. and although it has previously been suspected in Australia no cases have been documented. It is important for Australian veterinarians and farmers to realise the toxic potential of this group of plants.

Haemolytic anaemia associated with Theileria sp. in an orphaned platypus.

CASE REPORT: The clinical and laboratory findings in an orphaned juvenile female platypus (Ornithorhynchus anatinus) that presented with a severe anaemia and tick infestation are reported. The animal developed a terminal septicaemia and died. Antemortem clinical pathology, postmortem histopathology and 18S rDNA sequencing supported a diagnosis of extravascular haemolytic anaemia secondary to Theileria ornithorhynchi infection. CONCLUSION: Although T. ornithorhynchi infection is common in the platypus, this is the first case in which it has been shown to cause a haemolytic anaemia in this species and molecular characterisation of the organism has been described. A review of the previous literature concerning T. ornithorhynchi and possible treatment options for future cases are discussed.

Acquired proximal renal tubulopathy in dogs exposed to a common dried chicken treat: retrospective study of 108 cases (2007-2009).

BACKGROUND: Proximal renal tubulopathy was reported in Australian dogs with markedly increased frequency from September 2007. METHODS: Two veterinarian-completed surveys were launched in response to an increased incidence of acquired proximal renal tubulopathy in dogs. The selection criterion for inclusion was glucosuria with blood glucose < 10 mmol/L. Data collected included signalment, presenting signs, history of feeding treats, results of urinalysis and blood tests, treatment and time to resolution of clinical signs. RESULTS: A total of 108 affected dogs were studied. All had been fed the same brand of dried chicken treats, made in China, for a median of 12 weeks (range, 0.3-78 weeks). Small breeds (< 10 kg) accounted for 88% of cases. Common presenting signs included polyuria/polydipsia (76%), lethargy (73%), inappetence (65%) and vomiting (54%). Common biochemical findings included euglycaemia (74%; 71/96), hypoglycaemia (23%; 22/96), acidosis (77%; 20/26), hypokalaemia (45%; 38/84), hypophosphataemia (37%; 28/75) and azotaemia (27%; 23/85). In addition to discontinuation of treats, 64 dogs received medical treatment, including intravenous fluids (52%) and oral electrolyte, amino acid or vitamin supplements. Six dogs died or were euthanased. Two dogs were necropsied. Histopathological findings consisted of proximal tubular necrosis accompanied by regeneration. Time to resolution of clinical signs in 35 survivors available for follow-up was < 2 weeks (n = 8), 2-4 weeks (n = 2), 5-7 weeks (n = 5) and 2-6 months (n = 10). CONCLUSION: Of the 108 dogs with acquired proximal renal tubulopathy contemporaneous with chicken treat consumption, most survived but many required aggressive supportive care. The treats likely contained a toxin targeting the proximal renal tubules. Diet history and urinalysis were vital for diagnosis.

Congenital dyserythropoietic anaemia and dyskeratosis in Australian Poll Hereford calves.

Congenital dyserythropoietic anaemia (CDA) is a heterogeneous group of rare genetic disorders that in humans is characterised by ineffective haematopoiesis with morphological abnormalities in erythroid precursor cells and secondary iron overload. In the 1990s, a syndrome of CDA with dyskeratosis and progressive alopecia was reported in Poll Hereford calves in Canada and the USA. We report the clinical and pathological findings in two Poll Hereford calves with this syndrome from separate properties in South Australia. The animals had a variably severe anaemia, associated with abnormal nucleated red blood cells in peripheral blood, and large numbers of rubricytes and metarubricytes with a characteristic nuclear ultrastructure in the bone marrow. Both calves were born with a wiry hair coat and a progressively 'dirty-faced' appearance associated with hyperkeratosis and dyskeratosis (apoptosis).

A Rosenthal fiber encephalomyelopathy resembling Alexander's disease in 3 sheep.

We report an encephalomyelopathy in three 18-month-old Merino sheep with features of adult-onset Alexander's disease (AD), a human primary astrocytic disorder. The signature histologic finding was the presence of numerous hypereosinophilic, intra-astrocytic inclusions (Rosenthal fibers), mainly in perivascular, subpial, and subependymal sites, especially in the caudal brain stem and spinal cord. Although AD usually results from mutations in the glial fibrillary acidic protein (GFAP) gene, no such mutation was detected in these sheep. However, the annual clinical presentation of this disorder in a few sheep in the affected flock is suggestive of a familial pattern of occurrence.

Neuroaxonal dystrophy in Australian Merino lambs.

Neuroaxonal dystrophy (NAD) is a morphological abnormality in man and animals that is characterized by the occurrence of numerous axonal swellings (spheroids) in the nervous system. NAD has been described in Suffolk lambs in the USA, Merino lambs in Australia and several breeds of sheep in New Zealand. This paper describes the clinicopathological changes of only the second occurrence of NAD reported in Merino lambs. There were some features (myelin loss, gliosis and visual impairment) in these Australian cases that have not been reported previously in ovine NAD. Application of immunohistochemical markers of axonal transport suggested that disruption of this transport mechanism contributed to spheroid development.

Review of neurological diseases of ruminant livestock in Australia. VI: postnatal bovine, and ovine and caprine, neurogenetic disorders.

This paper, the last in a series of reviews of neurological diseases of ruminants in Australia, discusses a range of neurogenetic disorders of cattle, sheep and goats, including necrotising encephalomyelopathy, glycogen storage disorders, cerebellar abiotrophy and ß-mannosidosis. They are categorised by the species and breeds in which they occur.

Neurological diseases of ruminant livestock in Australia. I: general neurological examination, necropsy procedures and neurological manifestations of systemic disease, trauma and neoplasia.

Disease surveillance is an integral part of most veterinary practices in Australia. The aim of this series of invited reviews is to facilitate the differential and ultimately definitive diagnosis of some of the previously known, as well as the novel and emerging, neurological disorders of ruminant livestock, which is of particular importance in the surveillance for transmissible spongiform encephalopathies. General principles of a systematic neurological examination, necropsy procedures and the neurological manifestations of systemic disease, trauma and neoplasia are described here.

Neurological diseases of ruminant livestock in Australia. III: bacterial and protozoal infections.

Bacteria (including chlamydia) and protozoa can produce neurological disease in Australian ruminant livestock and the nature of the inflammatory and neuroparenchymal response is often suggestive of a particular aetiological agent. An overview of the clinicopathological features of infectious disease affecting the central nervous system (CNS) is followed by a discussion of important bacterial and protozoal infections in Australia. Each infectious disease is discussed in terms of classification and pathogenesis linked to clinical signs and gross and microscopic findings. The literature review is restricted to infectious conditions causing CNS disease in Australia. Sources include the Australian Veterinary Journal (over 50 years of articles), the quarterly newsletter of the National Animal Health Surveillance System and the Animal Health Surveillance Quarterly.

Squamous cell carcinoma with sarcomatous stroma in the nasal cavity of a dog.

This is a report of an unusual squamous cell carcinoma in the nasal cavity of a dog. A 13-year-old Golden Retriever was presented with a unilateral nasal and ocular discharge. Although a nasal tumour was suspected, initial diagnostic investigations were unrewarding, and, with worsening clinical signs, the dog was euthanatized. Necropsy examination confirmed the presence of a nasal tumour that was composed histologically of both a well-differentiated squamous cell carcinoma component blending with a predominant spindle cell component. Immunohistochemical staining with anti-human keratin/cytokeratin (AE1/AE3, CAM 5.2 and broad spectrum cytokeratin), Vimentin, Desmin, smooth muscle actin and S-100 protein supported a diagnosis of a squamous cell carcinoma with (pseudo) sarcomatous stroma.

Cervical hyperaesthesia in a Maltese Terrier with necrotising meningoencephalitis.

A 15-month-old female neutered Maltese Terrier was presented with a 12 hour history of low head carriage, reluctance to move and yelping when picked up. Physical examination was unremarkable apart from cervical hyperaesthesia. Twenty four hours after initial assessment there was significant clinical deterioration, with the dog exhibiting lateral cervical flexion and neurological abnormalities consistent with diffuse multifocal cerebral dysfunction. Cerebrospinal fluid analysis revealed a marked pleocytosis. Euthanasia was elected and gross necropsy findings included swelling of the right frontal cortex and a focal area of necrosis in the ventrolateral grey matter of the frontal cortex. Histological examination of the brain tissue revealed focal areas of necrosis and generalised non-suppurative inflammation consistent with a morphological diagnosis of necrotising encephalomyelitis.