Pamela Johnston

Osteoarthritis in the cat 1. How common is it and how easy to recognise

Practical relevance Osteoarthritis (OA) is very common, particularly in older cats, but its clinical significance has largely gone unrecognised until recently. As in other species, OA is often painful and appropriate treatment is required to improve the animal’s quality of life. Most cases appear to be primary or idiopathic. It is important for the clinician to actively seek these cases in the practice population. Clinical challenges The recognition of chronic arthritic pain is a major challenge since most cats will not exhibit lameness. The main features of feline OA are changes in behaviour and lifestyle, which develop gradually and which owners tend to interpret as simply being the effects of old age. A meaningful physical orthopaedic examination can be difficult to achieve. A lack of familiarity with feline joint radiographs, and the fact that major cartilage pathology can be present in the absence of any bony change, mean that radiographic identification of OA in the cat can also be problematic. Client questionnaire The recognition of chronic arthritic pain in the cat is based on owner questionnaires designed to elicit information about changes in mobility, activity levels, grooming habits and general demeanour. Evidence base Several publications now report on the significance of behavioural and lifestyle changes as indicators of chronic arthritic pain in the cat. However, there is not as yet a fully validated owner-based questionnaire for recognising chronic pain in the cat. Furthermore, the aetiopathogenesis of feline OA still requires detailed investigation. Such studies are likely to make a major contribution to comparative rheumatology, since feline OA, more so than the canine disease, shows many similarities with human OA.

The skin is a significant but overlooked anatomical reservoir for vector-borne African trypanosomes

The role of mammalian skin in harbouring and transmitting arthropod-borne protozoan parasites has been overlooked for decades as these pathogens have been regarded primarily as blood-dwelling organisms. Intriguingly, infections with low or undetected blood parasites are common, particularly in the case of Human African Trypanosomiasis caused by Trypanosoma brucei gambiense. We hypothesise, therefore, the skin represents an anatomic reservoir of infection. Here we definitively show that substantial quantities of trypanosomes exist within the skin following experimental infection, which can be transmitted to the tsetse vector, even in the absence of detectable parasitaemia. Importantly, we demonstrate the presence of extravascular parasites in human skin biopsies from undiagnosed individuals. The identification of this novel reservoir requires a re-evaluation of current diagnostic methods and control policies. More broadly, our results indicate that transmission is a key evolutionary force driving parasite extravasation that could further result in tissue invasion-dependent pathology. DOI: http://dx.doi.org/10.7554/eLife.17716.001

Osteoarthritis in the cat: 2. How should it be managed and treated?

Practical relevance Osteoarthritis (OA) is very common in the cat and in many cases is associated with significant long-term pain, which limits mobility and activity, and severely compromises the animal’s quality of life. Clinical challenges The treatment of chronic arthritic pain is a major challenge and many analgesic drugs used in other species are not licensed, not available or not tested for use in the cat. Many older cats with painful OA have some degree of chronic kidney disease (CKD) and many clinicians are reluctant to use non-steroidal anti-inflammatory drugs (NSAIDs) in these animals because of the potential for nephrotoxicity. Evidence base There are several publications that show that meloxicam is an effective NSAID for the cat and can be used long-term. It is easy to administer and there is published evidence that meloxicam can actually slow the progression of CKD in this species. Many other drugs are used to treat chronic pain in the cat but there is no documented evidence of their efficacy in OA. Unlike the dog, there is limited evidence for the effectiveness of omega-3 fatty acid-rich diets in managing feline OA and further work is required. There is no published data as yet for the usefulness or otherwise of nutraceuticals (glucosamine and chondroitin) in managing feline OA; studies in the authors’ clinic suggest some pain-relieving effect. Research into environmental enrichment as a way of improving quality of life in cats with painful OA is lacking, but it is an approach worth using where possible. Modifications to the environment (eg, provision of comfortable bedding and ramps) are also important.

Central nervous system pathology in 25 dogs with chronic degenerative radiculomyelopathy

The neuropathology of 20 German shepherd dogs and five German shepherd dog crosses with chronic degenerative radiculomyelopathy were analysed by conventional techniques, immunocytochemistry and electron microscopy. There were previously unrecognised changes in brain nuclei. In the spinal cord, both motor and sensory tracts were involved, principally in their more distal regions. Wallerian degeneration affected the corticorubrospinal pathways in the lateral columns and the ventral funiculi, predominantly in the caudal thoracic and lumbar segments, although more cranial involvement was also observed. The dorsal columns were affected in the caudal lumbar region and the cervical fasciculus gracilis. The regional distribution was variable between cases. Within the brain, abnormalities, including chromatolysis, gliosis and neuronal loss were observed in the red nucleus, lateral vestibular nucleus and, occasionally, in the dentate nucleus. The changes in brain nuclei were compared with those found in dogs at various times after a focal spinal injury. The neuronal changes in the brain may be related to the primary site of damage, and possible aetiological mechanisms are discussed.

Serum α-tocopherol concentrations in German shepherd dogs with chronic degenerative radiculomyelopathy

The concentration of serum α-tocopherol was measured in German shepherd dogs with chronic degenerative radiculomyopathy, and in German shepherd dogs and dogs of other breeds unaffected by the condition. The mean concentration was significantly higher in German shepherd dogs with the condition than in other breeds of dog unaffected by it, but it was not significantly higher than in unaffected German shepherd dogs. Estimates of components of variance indicated that the concentration varied more widely in individual affected dogs than in unaffected dogs, irrespective of breed. These results suggest that chronic degenerative radiculomyopathy in German shepherd dogs is unlikely to be due to uncomplicated vitamin E deficiency.

Histology in recovered cases of grass sickness.

more about whether the diagnosis of grass sickness made on clinical grounds supplemented by laboratory tests, but without histology, is accurate. A team in Edinburgh suggests that an accurate diagnosis without histological evidence is possible and, in the few difficult cases, which usually resemble acute surgical colic, the diagnosis can be made at laparotomy before histological evidence is available. The opposite view (Scholes and others 1993) is that histological evidence, by ileal biopsy, is essential for a correct antemortem diagnosis. These two differing views cannot be commented on further without access to histological evidence from horses diagnosed clinically as having chronic grass sickness which subsequently recovered following treatment and then died at

The chaperone protein clusterin may serve as a cerebrospinal fluid biomarker for chronic spinal cord disorders in the dog

Chronic spinal cord dysfunction occurs in dogs as a consequence of diverse aetiologies, including long-standing spinal cord compression and insidious neurodegenerative conditions. One such neurodegenerative condition is canine degenerative myelopathy (DM), which clinically is a challenge to differentiate from other chronic spinal cord conditions. Although the clinical diagnosis of DM can be strengthened by the identification of the Sod1 mutations that are observed in affected dogs, genetic analysis alone is insufficient to provide a definitive diagnosis. There is a requirement to identify biomarkers that can differentiate conditions with a similar clinical presentation, thus facilitating patient diagnostic and management strategies. A comparison of the cerebrospinal fluid (CSF) protein gel electrophoresis profile between idiopathic epilepsy (IE) and DM identified a protein band that was more prominent in DM. This band was subsequently found to contain a multifunctional protein clusterin (apolipoprotein J) that is protective against endoplasmic reticulum (ER) stress-mediated apoptosis, oxidative stress, and also serves as an extracellular chaperone influencing protein aggregation. Western blot analysis of CSF clusterin confirmed elevated levels in DM compared to IE (p < 0.05). Analysis of spinal cord tissue from DM and control material found that clusterin expression was evident in neurons and that the clusterin mRNA levels from tissue extracts were elevated in DM compared to the control. The plasma clusterin levels was comparable between these groups. However, a comparison of clusterin CSF levels in a number of neurological conditions found that clusterin was elevated in both DM and chronic intervertebral disc disease (cIVDD) but not in meningoencephalitis and IE. These findings indicate that clusterin may potentially serve as a marker for chronic spinal cord disease in the dog; however, additional markers are required to differentiate DM from a concurrent condition such as cIVDD.

Proof of concept and feasibility studies examining the influence of combination ribose, adenine and allopurinol treatment on stroke outcome in the rat

Background: Cerebral ischaemia results in a rapid and profound depletion of adenosine triphosphate (ATP), the energy currency of the cell. This depletion leads to disruption of cellular homeostasis and cell death. Early replenishment of ATP levels might therefore have a neuroprotective effect in the injured brain. We have previously shown that the ATP precursors, D-ribose and adenine (RibAde), restored the reduced ATP levels in rat brain slices to values similar to those measured in the intact rodent brain. The aim of this study was to assess whether RibAde, either alone or in combination with the xanthine oxidase inhibitor allopurinol (RibAdeAll; to further increase the availability of ATP precursors), could improve outcome in an in vivo rodent model of transient cerebral ischaemia. Methods: After 60 min occlusion of the middle cerebral artery, and upon reperfusion, rats were administered saline, RibAde, or RibAdeAll for 6 h. Baseline lesion volume was determined by diffusion-weighted MRI prior to reperfusion and final infarct volume determined by T2-weighted MRI at Day 7. Neurological function was assessed at Days 1, 3 and 7. Results: Ischaemic lesion volume decreased between Days 1 and 7: a 50% reduction was observed for the RibAdeAll group, 38% for the RibAde group and 18% in the animals that received saline. Reductions in lesion size in treatment groups were accompanied by a trend for faster functional recovery. Conclusion: These data support the potential use of ribose, adenine and allopurinol in the treatment of cerebral ischaemic injury, especially since all compounds have been used in man.

Optimisation and validation of a PCR for Antigen Receptor Rearrangement (PARR) assay to detect clonality in canine lymphoid malignancies

Highlights • Ten primer sets detected clonality with high specificity and sensitivity.• Four extra primer sets may detect clonality in samples with equivocal results.• Knowledge of sample quality is needed for interpretation of results.• Samples generating dominant peaks require careful interpretation.

Acute motor and sensory polyganglioradiculoneuritis in a cat: clinical and histopathological findings

Polyneuropathies can have a variety of clinical presentations and tend to be rare in cats. In this report we describe a 6-year-old domestic shorthair cat with an acute and rapidly progressive onset of lower motor neuron and sensory signs affecting the spinal and cranial nerves. Histopathological examination revealed moderate-to-severe multifocal inflammatory infiltrates at the ventral and dorsal nerve roots, and dorsal spinal ganglia at the level of the L4 and cauda equina. The type and severity of inflammation varied between nerve roots, being composed of mainly neutrophils in some and mainly lymphocytes and macrophages in others. Immunohistochemistry showed a combination of neutrophils, macrophages and lymphocytes infiltrating the nerve roots and ganglia. The majority of the lymphocytes were T lymphocytes; only a few B lymphocytes were seen. Neurons within the affected ganglia showed central chromatolysis and necrosis. Wallerian-like degeneration and demyelination were observed in the nerve roots. A sensory and motor polyganglioradiculoneuritis was diagnosed. An autoimmune process similar to the acute motor and sensory neuropathy subtype of Guillain–Barré syndrome in humans or an infection by an unidentified agent were considered most likely.