Clinical and genetic characterisation of dystrophin-deficient muscular dystrophy in a family of Miniature Poodle dogs

Four full-sibling intact male Miniature Poodles were evaluated at 4–19 months of age. One was clinically normal and three were affected. All affected dogs were reluctant to exercise and had generalised muscle atrophy, a stiff gait and a markedly elevated serum creatine kinase activity. Two affected dogs also showed poor development, learning difficulties and episodes of abnormal behaviour. In these two dogs, investigations into forebrain structural and metabolic diseases were unremarkable; electromyography demonstrated fibrillation potentials and complex repetitive discharges in the infraspinatus, supraspinatus and epaxial muscles. Histopathological, immunohistochemical and immunoblotting analyses of muscle biopsies were consistent with dystrophin-deficient muscular dystrophy. DNA samples were obtained from all four full-sibling male Poodles, a healthy female littermate and the dam, which was clinically normal. Whole genome sequencing of one affected dog revealed a >5 Mb deletion on the X chromosome, encompassing the entire DMD gene. The exact deletion breakpoints could not be experimentally ascertained, but we confirmed that this region was deleted in all affected males, but not in the unaffected dogs. Quantitative polymerase chain reaction confirmed all three affected males were hemizygous for the mutant X chromosome, while the wildtype chromosome was observed in the unaffected male littermate. The female littermate and the dam were both heterozygous for the mutant chromosome. Forty-four Miniature Poodles from the general population were screened for the mutation and were homozygous for the wildtype chromosome. The finding represents a naturally-occurring mutation causing dystrophin-deficient muscular dystrophy in the dog

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

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

Somatosensory and motor evoked potentials in dogs with chronic severe thoracolumbar spinal cord injury

ome dogs that become paraplegic after severe spinal cord injury regain ambulation on the pelvic limbs despite permanent loss of pelvic limb sensation, a phenomenon termed ‘spinal walking’. Plastic changes in spinal cord circuitry are thought to mediate this form of recovery but the precise circumstances that favor its development are not known. More information on this phenomenon would be helpful because it might be possible to coax more function in chronically paraplegic animals so improving their, and their owners’, quality of life. We analysed the correlation of ‘spinal walking’ and pelvic limb pain sensation with recordings of scalp and spinal somatosensory and transcranial magnetic motor evoked potentials. We prospectively examined 94 paraplegic dogs (including 53 Dachshunds) that had sustained T10 to L3 spinal cord injury (including 78 dogs with acute intervertebral disc herniation) at a median time of 12.0 months from injury. Nine dogs exhibited ‘spinal walking’ and nine other individuals had intact pelvic limb pain sensation. Of 34 tested, 12 dogs had recordable scalp somatosensory evoked potentials. Fifty-three of 59 tested dogs had recordable spinal somatosensory evoked potentials, but only six had recordable potentials cranial to the lesion. Twenty-two of 94 tested dogs had recordable transcranial magnetic motor evoked potentials in the pelvic limb(s). There was no apparent association between intact evoked potential recording and either spinal walking or intact pain sensation. We conclude that factors other than influence, or lack of influence, of input carried by spinal cord long tracts mediate recovery of spinal walking