Current Approaches to the Management of Acute Thoracolumbar Disc Extrusion in Dogs

Intervertebral disc extrusion (IVDE) is one of the most common neurologic problems encountered in veterinary clinical practice. The purpose of this manuscript is to provide an overview of the literature related to treatment of acute canine thoracolumbar IVDE to help construct a framework for standard care of acute canine thoracolumbar IVDE where sufficient evidence exists and to highlight opportunities for future prospective veterinary clinical research useful to strengthen care recommendations in areas where evidence is low or non-existent. While there exist a number of gaps in the veterinary literature with respect to standards of care for dogs with acute thoracolumbar IVDE, recommendations for standard care can be made in some areas, particularly with respect to surgical decompression where the currently available evidence supports that surgery should be recommended for dogs with nonambulatory paraparesis or worse. While additional information is needed about the influence on timing of decompression on outcome in dogs that are deep pain negative for longer than 48 h duration, there is no evidence to support treatment of the 48 h time point as a cut off beyond which it becomes impossible for dogs to achieve locomotor recovery. Surgical decompression is best accomplished by either hemilaminectomy or mini-hemilaminectomy and fenestration of, at a minimum, the acutely ruptured disc. Adjacent discs easily accessed by way of the same approach should be considered for fenestration given the evidence that this substantially reduces future herniation at fenestrated sites. Currently available neuroprotective strategies such as high does MPSS and PEG are not recommended due to lack of demonstrated treatment effect in randomized controlled trials, although the role of anti-inflammatory steroids as a protective strategy against progressive myelomalacia and the question of whether anti-inflammatory steroids or NSAIDs provide superior medical therapy require further evaluation

Classification of Intervertebral Disc Disease

Intervertebral disc disease (IVDD) has been recognized in dogs since the 1800s, when the first descriptions of extruded disc material within the vertebral canal were published. In the intervening time our understanding of intervertebral disc pathology in dogs and cats has increased dramatically, with many variations of IVDD described. Whilst the volume of literature and collective understanding of IVDD has expanded, there has also been scope for confusion as the definition of intervertebral disc disease, with its myriad different manifestations, becomes more complicated. A large volume of literature has aimed to combine the use of histopathology, diagnostic imaging and clinical findings to better understand the various ways in which IVDD can be classified. Much of this research has focused on the classification of mechanisms of intervertebral disc degeneration, centering around the differences between, and overlaps in, IVDD in chondrodystrophic and non-chondrodystrophic dog breeds. However, with the increasing availability of advanced imaging modalities allowing more accurate antemortem diagnosis, the concept of IVDD has expanded to include other clinical presentations that may not fit into traditional models of classification of IVDD. This review aims to provide an up to date overview of both historical and current systems of IVDD classification, highlighting the important findings and controversies underpinning them

The effect of electromagnetic fields on postoperative pain and locomotor recovery in dogs with acute, severe thoracolumbar intervertebral disc extrusion: a randomized placebo-controlled, prospective clinical trial.

Spinal cord injury (SCI) due to acute intervertebral disc extrusions (IVDE) is common in dogs and is treated by surgical decompression. Dogs with sensorimotor complete injuries have an incomplete recovery. Pulsed electromagnetic fields (PEMF) reduce postoperative pain through anti-inflammatory effects and there is growing evidence for neuroprotective effects. This randomized, controlled clinical trial evaluated the effect of PEMF on post-operative pain and neurologic recovery in dogs with surgically treated sensorimotor complete SCI due to acute IVDE. Sixteen dogs with surgically treated complete thoracolumbar SCI were randomized to receive PEMF (15 minutes every 2 hours for 2 weeks then twice daily for 4 weeks) or placebo starting immediately after diagnosis. The primary outcome was gait score at 2 weeks. Secondary measures of gait, pain perception and proprioceptive function were evaluated at 2 and 6 weeks. Plasma GFAP concentration was measured as a SCI biomarker. Post-operative pain was quantified by measuring mechanical sensory thresholds (MST) at control and surgical sites. There was no significant difference in demographics or GFAP concentration between the 2 groups at trial entry. There was no difference in primary outcome or in secondary measures of gait, but proprioceptive placing was significantly better at 6 weeks and GFAP concentrations were significantly lower at 2 weeks in the PEMF group. MSTs were significantly higher in the PEMF treated group. We conclude that PEMF reduced incision-associated pain in dogs following surgery for IVDE and may reduce extent of spinal cord injury and enhance proprioceptive placing. Larger clinical trials are warranted

How Long and Low Can You Go? Effect of Conformation on the Risk of Thoracolumbar Intervertebral Disc Extrusion in Domestic Dogs

Intervertebral disc extrusion (IVDE) is a common neurological disorder in certain dog breeds, resulting in spinal cord compression and injury that can cause pain and neurological deficits. Most disc extrusions are reported in chondrodystrophic breeds (e.g. Dachshunds, Basset Hounds, Pekingese), where selection for ‘long and low’ morphologies is linked with intervertebral discs abnormalities that predispose dogs to IVDE. The aim of this study was to quantify the relationship between relative thoracolumbar vertebral column length and IVDE risk in diverse breeds. A 14 month cross-sectional study of dogs entering a UK small animal referral hospital for diverse disorders including IVDE was carried out. Dogs were measured on breed-defining morphometrics, including back length (BL) and height at the withers (HW). Of 700 dogs recruited from this referral population, measured and clinically examined, 79 were diagnosed with thoracolumbar IVDE following diagnostic imaging ± surgery. The BL:HW ratio was positively associated with IVDE risk, indicating that relatively longer dogs were at increased risk, e.g. the probability of IVDE was 0.30 for Miniature Dachshunds when BL:HW ratio equalled 1.1, compared to 0.68 when BL:HW ratio equalled 1.5. Additionally, both being overweight and skeletally smaller significantly increased IVDE risk. Therefore, selection for longer backs and miniaturisation should be discouraged in high-risk breeds to reduce IVDE risk. In higher risk individuals, maintaining a lean body shape is particularly important to reduce the risk of IVDE. Results are reported as probabilities to aid decision-making regarding breed standards and screening programmes reflecting the degree of risk acceptable to stakeholders

Whole genome sequencing reveals a 7 base-pair deletion in DMD exon 42 in a dog with muscular dystrophy

Dystrophin is a key cytoskeletal protein coded by the Duchenne muscular dystrophy (DMD) gene located on the X-chromosome. Truncating mutations in the DMD gene cause loss of dystrophin and the classical DMD clinical syndrome. Spontaneous DMD gene mutations and associated phenotypes occur in several other species. The mdx mouse model and the golden retriever muscular dystrophy (GRMD) canine model have been used extensively to study DMD disease pathogenesis and show efficacy and side effects of putative treatments. Certain DMD gene mutations in high-risk, the so-called hot spot areas can be particularly helpful in modeling molecular therapies. Identification of specific mutations has been greatly enhanced by new genomic methods. Whole genome, next generation sequencing (WGS) has been recently used to define DMD patient mutations, but has not been used in dystrophic dogs. A dystrophin-deficient Cavalier King Charles Spaniel (CKCS) dog was evaluated at the functional, histopathological, biochemical, and molecular level. The affected dog’s phenotype was compared to the previously reported canine dystrophinopathies. WGS was then used to detect a 7 base pair deletion in DMD exon 42 (c.6051-6057delTCTCAAT mRNA), predicting a frameshift in gene transcription and truncation of dystrophin protein translation. The deletion was confirmed with conventional PCR and Sanger sequencing. This mutation is in a secondary DMD gene hotspot area distinct from the one identified earlier at the 5′ donor splice site of intron 50 in the CKCS breed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00335-016-9675-2) contains supplementary material, which is available to authorized users

Arachidonic acid pathway alterations in cerebrospinal fluid of dogs with naturally occurring spinal cord injury

BACKGROUND: Canine intervertebral disc πherniation causes a naturally-occurring spinal cord injury (SCI) that bears critical similarities to human SCI with respect to both injury pathomechanisms and treatment. As such, it has tremendous potential to enhance our understanding of injury biology and the preclinical evaluation of novel therapies. Currently, there is limited understanding of the role of arachidonic acid metabolites in canine SCI. RESULTS: The CSF concentrations of PLA2 and PGE2 were higher in SCI dogs compared to control dogs (p = 0.0370 and 0.0273, respectively), but CSF LCT4 concentration in SCI dogs was significantly lower than that in control dogs (p < 0.0001). Prostaglandin E2 concentration in the CSF was significantly and positively associated with increased severity of SCI at the time of sampling (p = 0.041) and recovery 42 days post-injury (p = 0.006), as measured by ordinal behavioral scores. CONCLUSION: Arachidonic acid metabolism is altered in dogs with SCI, and these data suggest that these AA metabolites reflect injury severity and recovery, paralleling data from other model systems