Dataset Information

Ambulation in Dogs With Absent Pain Perception After Acute Thoracolumbar Spinal Cord Injury.

ABSTRACT: Acute thoracolumbar spinal cord injury (SCI) is common in dogs frequently secondary to intervertebral disc herniation. Following severe injury, some dogs never regain sensory function to the pelvic limbs or tail and are designated chronically "deep pain negative." Despite this, a subset of these dogs develop spontaneous motor recovery over time including some that recover sufficient function in their pelvic limbs to walk independently without assistance or weight support. This type of ambulation is commonly known as "spinal walking" and can take up to a year or more to develop. This review provides a comparative overview of locomotion and explores the physiology of locomotor recovery after severe SCI in dogs. We discuss the mechanisms by which post-injury plasticity and coordination between circuitry contained within the spinal cord, peripheral sensory feedback, and residual or recovered supraspinal connections might combine to underpin spinal walking. The clinical characteristics of spinal walking are outlined including what is known about the role of patient or injury features such as lesion location, timeframe post-injury, body size, and spasticity. The relationship between the emergence of spinal walking and electrodiagnostic and magnetic resonance imaging findings are also discussed. Finally, we review possible ways to predict or facilitate recovery of walking in chronically deep pain negative dogs. Improved understanding of the mechanisms of gait generation and plasticity of the surviving tissue after injury might pave the way for further treatment options and enhanced outcomes in severely injured dogs.

SUBMITTER: Lewis MJ

PROVIDER: S-EPMC7479830 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Ambulation in Dogs With Absent Pain Perception After Acute Thoracolumbar Spinal Cord Injury.

Lewis Melissa J MJ Jeffery Nick D ND Olby Natasha J NJ

Frontiers in veterinary science 20200826

Acute thoracolumbar spinal cord injury (SCI) is common in dogs frequently secondary to intervertebral disc herniation. Following severe injury, some dogs never regain sensory function to the pelvic limbs or tail and are designated chronically "deep pain negative." Despite this, a subset of these dogs develop spontaneous motor recovery over time including some that recover sufficient function in their pelvic limbs to walk independently without assistance or weight support. This type of ambulation ...[more]

PMID: 33062648

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Project description:Background:Glyburide (also known as glibenclamide) is effective in reducing the severity of tissue destruction and improving functional outcome after experimental spinal cord injury in rodents and so has promise as a therapy in humans. There are many important differences between spinal cord injury in experimental animals and in human clinical cases, making it difficult to introduce new therapies into clinical practice. Spinal cord injury is also common in pet dogs and requires new effective therapies, meaning that they can act as a translational model for the human condition while also deriving direct benefits from such research. In this study we investigated the pharmacokinetics and safety of glyburide in dogs with clinical spinal cord injury. Methods:We recruited dogs that had incurred an acute thoracolumbar spinal cord injury within the previous 72 h. These had become acutely non-ambulatory on the pelvic limbs and were admitted to our veterinary hospitals to undergo anesthesia, cross sectional diagnostic imaging, and surgical decompression. Oral glyburide was given to each dog at a dose of 75 mcg/kg. In five dogs, we measured blood glucose concentrations for 10 h after a single oral dose. In six dogs, we measured serum glyburide and glucose concentrations for 24 h and estimated pharmacokinetic parameters to estimate a suitable dose for use in a subsequent clinical trial in similarly affected dogs. Results:No detrimental effects of glyburide administration were detected in any participating dog. Peak serum concentrations of glyburide were attained at a mean of 13 h after dosing, and mean apparent elimination half-life was approximately 7 h. Observed mean maximum plasma concentration was 31 ng/mL. At the glyburide dose administered there was no observable association between glyburide and glucose concentrations in blood. Discussion:Our data suggest that glyburide can be safely administered to dogs that are undergoing anesthesia, imaging and surgery for treatment of their acute spinal cord injury and can attain clinically-relevant serum concentrations without developing hazardous hypoglycemia. Serum glyburide concentrations achieved in this study suggest that a loading dose of 150 mcg/kg followed by repeat doses of 75 mcg/kg at 8-hourly intervals would lead to serum glyburide concentrations of 25-50 ng/mL within an acceptably short enough period after oral administration to be appropriate for a clinical trial in canine spinal cord injury.

Project description:Deep Learning based Convolutional Neural Networks (CNNs) are the state-of-the-art machine learning technique with medical image data. They have the ability to process large amounts of data and learn image features directly from the raw data. Based on their training, these networks are ultimately able to classify unknown data and make predictions. Magnetic resonance imaging (MRI) is the imaging modality of choice for many spinal cord disorders. Proper interpretation requires time and expertise from radiologists, so there is great interest in using artificial intelligence to more quickly interpret and diagnose medical imaging data. In this study, a CNN was trained and tested using thoracolumbar MR images from 500 dogs. T1- and T2-weighted MR images in sagittal and transverse planes were used. The network was trained with unremarkable images as well as with images showing the following spinal cord pathologies: intervertebral disc extrusion (IVDE), intervertebral disc protrusion (IVDP), fibrocartilaginous embolism (FCE)/acute non-compressive nucleus pulposus extrusion (ANNPE), syringomyelia and neoplasia. 2,693 MR images from 375 dogs were used for network training. The network was tested using 7,695 MR images from 125 dogs. The network performed best in detecting IVDPs on sagittal T1-weighted images, with a sensitivity of 100% and specificity of 95.1%. The network also performed very well in detecting IVDEs, especially on sagittal T2-weighted images, with a sensitivity of 90.8% and specificity of 98.98%. The network detected FCEs and ANNPEs with a sensitivity of 62.22% and a specificity of 97.90% on sagittal T2-weighted images and with a sensitivity of 91% and a specificity of 90% on transverse T2-weighted images. In detecting neoplasms and syringomyelia, the CNN did not perform well because of insufficient training data or because the network had problems differentiating different hyperintensities on T2-weighted images and thus made incorrect predictions. This study has shown that it is possible to train a CNN in terms of recognizing and differentiating various spinal cord pathologies on canine MR images. CNNs therefore have great potential to act as a "second eye" for imagers in the future, providing a faster focus on the altered image area and thus increasing workflow in radiology.

Dataset Information

Ambulation in Dogs With Absent Pain Perception After Acute Thoracolumbar Spinal Cord Injury.

Publications

Ambulation in Dogs With Absent Pain Perception After Acute Thoracolumbar Spinal Cord Injury.

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