Treatment Effects of Intra-Articular Allogenic Mesenchymal Stem Cell Secretome in an Equine Model of Joint Inflammation

Background: Allogenic mesenchymal stem cell (MSC) secretome is a novel intra-articular therapeutic that has shown promise in in vitro and small animal models and warrants further investigation. Objectives: To investigate if intra-articular allogenic MSC-secretome has anti-inflammatory effects using an equine model of joint inflammation. Study Design: Randomized positively and negatively controlled experimental study. Method: In phase 1, joint inflammation was induced bilaterally in radiocarpal joints of eight horses by injecting 0.25 ng lipopolysaccharide (LPS). After 2 h, the secretome of INFy and TNFα stimulated allogeneic equine MSCs was injected in one randomly assigned joint, while the contralateral joint was injected with medium (negative control). Clinical parameters (composite welfare scores, joint effusion, joint circumference) were recorded, and synovial fluid samples were analyzed for biomarkers (total protein, WBCC; eicosanoid mediators, CCL2; TNFα; MMP; GAGs; C2C; CPII) at fixed post-injection hours (PIH 0, 8, 24, 72, and 168 h). The effects of time and treatment on clinical and synovial fluid parameters and the presence of time-treatment interactions were evaluated. For phase 2, allogeneic MSC-secretome vs. allogeneic equine MSCs (positive control) was tested using a similar methodology. Results: In phase 1, the joint circumference was significantly (p < 0.05) lower in the MSC-secretome treated group compared to the medium control group at PIH 24, and significantly higher peak synovial GAG values were noted at PIH 24 (p < 0.001). In phase 2, no significant differences were noted between the treatment effects of MSC-secretome and MSCs. Main Limitations: This study is a controlled experimental study and therefore cannot fully reflect natural joint disease. In phase 2, two therapeutics are directly compared and there is no negative control. Conclusions: In this model of joint inflammation, intra-articular MSC-secretome injection had some clinical anti-inflammatory effects. An effect on cartilage metabolism, evident as a rise in GAG levels was also noted, although it is unclear whether this could be considered a beneficial or detrimental effect. When directly comparing MSC-secretome to MSCs in this model results were comparable, indicating that MSC-secretome could be a viable off-the-shelf alternative to MSC treatment

Dystonia in veterinary neurology

Dystonia is a clinical sign and main feature of many movement disorders in humans as well as veterinary species. It is characterized by sustained or intermittent involuntary muscle contractions causing abnormal (often repetitive) movements, postures, or both. This review discusses the terminology and definition of dystonia, its phenomenology, and its pathophysiology, and provides considerations regarding the diagnosis and treatment of dystonia in dogs and cats. In addition, currently recognized or reported disorders in dogs and cats in which dystonia is a particular or main feature are discussed and comparisons are made between disorders featuring dystonia in humans and animals. We suggest that when describing the phenomenology of dogs and cats with dystonia, if possible the following should be included: activity being performed at onset (e.g., resting or running or exercise-induced), body distribution, duration, responsiveness (subjective), severity, temporal pattern (i.e., paroxysmal or persistent, severity at onset and at later stages), presence or absence of autonomic signs (e.g., salivation), presence or absence of preceding signs (e.g., restlessness), presence or absence of signs after dystonia subsides (e.g., sleepiness), coexistence of other movement disorders, any other neurological manifestations, and possible links to administered medications, intoxications or other associated factors. We also suggest that dystonia be classified based on its etiology as either structural genetic, suspected genetic, reactive, or unknown

Chiari malformatie en syringomyelie: veel voorkomende aandoeningen bij de toybreeds

Kleine hondjes, zoals de Chihuahua en Dwergkees (Pommeriaantje), zijn tegenwoordig zeer populair. Wat veel – potentiële - eigenaren niet weten, is dat deze hondjes dikwijls chronische of aanvalsgewijze pijn hebben. Dit is vaak het gevolg van chiari malformatie en/of syringomyelie. We zien deze aandoeningen ook bij andere kleine rassen met een relatief breed maar kort hoofd. Neuroloog Paul Mandigers, ziet deze hondjes dagelijks in zijn praktijk

Surgical osteochondral defect repair in the horse—a matter of form or function?

Focal cartilaginous and osteochondral lesions can have traumatic or chondropathic degenerative origin. The fibrocartilaginous repair tissue that forms naturally, eventually undergoes fibrillation and degeneration leading to further disruption of joint homeostasis. Both types of lesion will therefore eventually lead to activity‐related pain, swelling and decreased mobility and will frequently progress to osteoarthritis. Most attempts at realising cartilage regeneration have so far resulted in cartilage repair (and not regeneration). The aim of this article was to review experimental research on surgical cartilage restoration techniques performed so far in equine models. Currently available surgical options for treatment of osteochondral lesions in the horse are summarised. The experimental validity of equine experimental models is addressed and finally possible avenues for further research are discussed

Rater agreement for assessment of equine back mobility at walk and trot compared to quantitative gait analysis

Background Lameness assessment in horses is still predominantly performed using subjective methods. Visual assessment is known to have moderate to good intra-rater agreement but relatively poor inter-rater agreement. Little is known about inter- and intra-rater agreement on the evaluation of back motion, for which no objective measurement technique in a clinical setting is available thus far. Objectives To describe inter- and intra-rater agreement of visual evaluation of equine back mobility. Study design Rater reliability study using a fully crossed design in which all horses are rated by all observers. This data is compared with objective gait analysis. Methods Seventy equine professionals (veterinarians and physiotherapists) and veterinary students evaluated videos of 12 healthy horses at walk and trot on a hard, straight line. Nine parameters related to back mobility were scored: general mobility, thoracic, lumbar, lumbosacral flexion and extension and left and right thoracolumbar latero-flexion. All parameters were compared with simultaneously measured quantitative motion parameters. After 1 month, six randomly chosen horses were re-evaluated by 57 observers. Results For each parameter inter- and intra-rater agreements were calculated using intra-class correlation coefficients. For all parameters, inter-rater agreement was very poor (<0.2). The mean intra-rater agreement of all observers and for all parameters was poor (~0.4) but varied between 0.0 and 0.96 for individual observers. There was no correlation between the visual subjective scoring and objective gait analysis measurements. Main limitations Horses were scored from videos and by lack of any existing (semi-) quantitative system, a custom-made system had to be used. Conclusions The poor inter- and intra-rater agreements of visual scoring of mobility of the equine back and the disagreement between subjective and objective gait analysis data, demonstrate the need for the development and introduction of objective, quantitative and repeatable techniques to assess equine back motion

Responses of the healthy equine carpal joint to treadmill exercise

We investigated the effects of treadmill exercise on synovial fluid (SF) biomarkers and range of motion (ROM) of the carpal joints in healthy Shetland ponies. Seven ponies (age 3-6y; acclimatised to treadmill), were trained five days/week for five weeks, complemented with 30 min (30’) daily walking exercise. Training consisted of 4’ trot (16 km/h), 2’ canter (21 km/h), 2’ trot (preceded and completed by 5’ walking at 4.4 km/h). SF was collected from left (LF) and right (RF) middle carpal joints three days before the first and 24 h after the last training session (Day33), and additionally from the left side at Day11, -12, -32 and -52. Cartilage metabolism markers CPII, C2C and GAG, and inflammatory markers PGE2.D2, CCL2, and MMP were measured. Carpal ROM was measured using 3D optical motion capture (Proreflex 240, Qualisys, framerate 200 Hz), on the treadmill at Day2 and Day25. Linear mixed models were used for statistical analysis, with significance set at

Is Encephalitozoon cuniculi of Significance in Young Dogs With Neurological Signs?

Encephalitozoon cuniculi is a microsporidium belonging to the phylum Microspora. A few reports have described the clinical significance of E. cuniculi infection in young dogs. In American and Japanese household dog populations, the seroprevalence was found to be 21%, indicating its wide-spread existence. To evaluate the clinical significance of E. cuniculi in a cohort of young dogs with neurological signs, the presence of the organism and possible response to treatment were studied. Over a 1-year period, all young dogs (100) and/or if an EDTA-blood sample and/or urine sample tested positive by polymerase chain reaction (PCR). Sixteen dogs with various neurological signs were included in this study. Additional work-up included magnetic resonance imaging and cerebrospinal fluid analysis, but these revealed no abnormalities or indication of infection. All dogs were treated with fenbendazole for 10-30 days. Neurological signs disappeared completely in five dogs, 11 dogs continued to show neurological signs, and five dogs deteriorated and were euthanized, after which necropsy was performed in three. At necropsy no evidence of an E. cuniculi infection was found. We concluded that, although IgM titers and PCR indicated an E. cuniculi infection, it is most likely of limited clinical significance in young dogs

Epileptic seizures triggered by eating in dogs

Background: Seizures triggered by eating (STE) behavior are very rare in humans and have not been documented previously in dogs. Objectives: To document the occurrence of STE in dogs and describe their clinical features. Animals: Ten client-owned dogs with STE diagnosed at 5 European referral centers. Methods: A call for suspected cases of STE was made online. This call was followed by a retrospective review of medical records, combined with a questionnaire to be completed by both the owner and the board-certified neurologist who made the diagnosis. Cases were included if >50% of the seizures that occurred were related to eating and if a minimum diagnostic evaluation for seizures had been performed. Results: Four cases only had STE and 6 cases had both STE and spontaneous seizures. Four of the dogs were retrievers. The most common seizure type was focal epileptic seizures evolving to become generalized. Nine dogs were diagnosed with idiopathic epilepsy. One dog had a presumptive diagnosis of glioma involving the margins of the parietal, temporal, and frontal cortex (the perisylvian region), an area known to have a key role in eating-associated epilepsy in people. Treatment strategies included a combination of pharmacological management and eating habit changes. Conclusions and Clinical Importance: We have identified a form of reflex epilepsy in dogs, with STE behavior. Further studies are warranted to improve the characterization and management of STE

A knockout mutation associated with juvenile paroxysmal dyskinesia in Markiesje dogs indicates SOD1 pleiotropy

A juvenile form of paroxysmal dyskinesia segregated in the Markiesje dog breed. Affected pups exhibited clinical signs of a severe tetraparesis, dystonia, cramping and falling over when trying to walk. In most cases, the presentation deteriorated within weeks and elective euthanasia was performed. Pedigree analysis indicated autosomal recessive inheritance. Genome-wide association and homozygosity mapping of 5 affected dogs from 3 litters identified the associated locus on chromosome 31 in the region of SOD1. The DNA sequence analysis of SOD1 showed that the patients were homozygous for a frameshift mutation in the fourth codon. None of the other analyzed dogs of the breed was homozygous for the mutation, indicating full penetrance of the genetic defect. Mutations in SOD1 are known to cause recessive degenerative myelopathy in middle-aged dogs with low penetrance and dominant amyotrophic lateral sclerosis in humans with variable age of onset. Our findings are similar to recent observations in human patients that a loss of function mutation in SOD1 leads to a juvenile neurologic disease distinct from amyotrophic lateral sclerosis