Utility and repeatability of quantitative outcome measures to assess recovery after canine spinal cord injury Thesis Presented in Partial Fulfillment of the Requirements for the Degree Master of Science in the Graduate School of The Ohio State University By Rachel Baek Song, VMD Graduate Program in Comparative Veterinary Medicine The Ohio State University 2015 Master’s Examination Committee: Professor Sarah A. Moore, Advisor Professor Ronaldo C. da Costa Professor D. Michele Basso Copyrighted by Rachel Baek Song 2015 Abstract Intervertebral disc extrusion (IVDE) is the most common cause of acute spinal cord injury (SCI) in dogs, and chondrodystrophic breeds such as the dachshund are commonly represented in the literature. The high incidence of spontaneous SCI in dogs makes them an important large animal model for human SCI. Clinical evaluation of dogs with SCI has historically focused on locomotor scoring and only a crude assessment of the ‘presence’ or ‘absence’ of nociception. The development of repeatable, sensitive and objective outcomes measures are of immense importance in establishing dogs with spontaneous SCI as a successful model for human SCI. Clearly defined outcome measures would allow for the identification of potential interventional therapy that may progress into clinical trials in humans. The goals of this study were to (1) identify differences in sensory threshold (ST) values between normal dogs and dogs with spontaneous IVDE and (2) to identify differences in footprint parameters between normal dogs and dogs with spontaneous IVDE to be used as outcome measures from SCI. Twenty normal dogs and 29 dogs with 30 discrete incidences of spontaneous SCI due to acute IVDE were prospectively enrolled for both studies. Sensory threshold (ST) was measured using an electric von Frey anesthesiometer (VFA) in all limbs of normal dogs at three separate time points and SCI-affected dogs at day 3, 10 and 30 following decompressive surgery. ST values were compared between groups and correlated with locomotor recovery in SCI-affected dogs. ST values were significantly higher (consistent ii with hypoalgesia) in the pelvic limbs of SCI-affected dogs at day 3, day 10 and day 30 when compared to normal dogs while no significant difference in thoracic limb ST values was observed between groups. A progressive decrease in pelvic limb ST values occurred in SCI-affected dogs over time, consistent with improvement toward normal sensation or development of allodynia. This finding correlated inversely with locomotor score. A significant overall decline in ST values across testing sessions was observed for all limbs of normal and SCI-affected dogs. This finding may be related to patient acclimation, operator training effect, or effect of analgesic medications. Footprint parameters of stride length (SL), base-of-support (BS) and coefficients of variance (COV) were made using a simple ‘finger painting’ technique in all limbs of the same 20 normal dogs and 29 dogs with 30 discrete incidences of IVDE. Measurements were made at three separate time points in normal dogs and on day 3, 10 and 30 following decompressive surgery in dogs with SCI. Values for SL and BS were compared between groups at each time point. Mean SL in all limbs was significantly lower in SCI-affected dogs at day 3, 10 and 30 compared to normal dogs. The COV of SL was significantly higher in both thoracic limbs and one pelvic limb in SCI-affected dogs only at day 3 following surgery compared to normal dogs. Additionally, BS in the thoracic limbs was found to be significantly higher in SCI-affected dogs at day 3 and day 30 following surgery compared to normal dogs. BS-PL was not significantly different between SCI-affected dogs and normal dogs. iii To my grandfathers Lee Eun Chul and Baek Myung Ik. Thank you for your teachings on life, love, and perseverance. iv Acknowledgments I would like to thank my advisor, Dr. Sarah A. Moore for her guidance and support throughout this process. I would also like to thank my examination committee for their encouragement and advice. I would especially like to thank Lesley Fisher, who was instrumental in data analysis and manuscript preparation. I would like to thank Amanda Disher and Heather Myers in their assistance with data collection. Additionally, I would like to thank the entire Neurology and Surgery service for their help in case recruitment. I would additionally like to thank the OSU Neurology service including Dr. Laurie Cook, Dr. Michele Provencher, Dr. Ronaldo da Costa, Dr. Sarah Moore, Amanda Disher and Heather Myers for their constant encouragement through tough times. Thank you to all my past and present mentors, who have touched my life and shaped me in immeasurable ways. Thank you to my family for making me to be the person I am. Thank you to my husband Moses Song, for being my emotional support and rock throughout the years and allowing me to pursue my dreams. v Vita June 2003 .......................................................Ridgewood High School 2007 ...............................................................B.A. Biological Sciences, Cornell University 2011................................................................V.M.D. University of Pennsylvania 2011-2012 .....................................................Small Animal Rotating Intern, Red Bank Veterinary Hospital 2012 to present ..............................................Graduate Teaching Associate, Department of Veterinary Clinical Sciences, The Ohio State University 2012 to present ..............................................Residency in Neurology and Neurosurgery, Veterinary Medical Center, The Ohio State University vi Publications 1. Song RB, Vitullo C, da Costa RC, Daniels JB. Long term survival in a dog with meningocencephalitis and epidural abscessation due to Actinomyces sp. Journal of Veterinary Diagnostic Investigation. 2015;27. Accepted April 17, 2015. In press. 2. Song RB, Kent M, Glass EN, Castro F, de Lahunta A. Dyke-Davidoff-Masson like syndrome in a cat. Australian Veterinary Journal. Accepted Apr 13, 2015. 3. Himmel LE, Song RB, da Costa RC, Oglesbee MJ. Pathology in Practice: Primitive neuroectodermal tumor. Journal of the American Veterinary Medical Association. Accepted Dec 2, 2014. 4. Song RB, Glass EN, Kent M, Sanchez MD, Smith DM, de Lahunta A. Surgical correction of a sacral meningomyelocele in a dog. Journal of the American Animal Hospital Assocation. 2014;50:436-443. 5. Song RB, Cross JR, Bradley CW, Vite C. Retrospective postmortem evaluation of 435 cases of canine intracranial neoplasia: relationship of neoplasm to breed, age, and body weight (1986-2010). Journal of Veterinary Internal Medicine. 2013;27:1143-1152. 6. Song RB, Cross JR, Golder FS, Callan MB. Chronic urinary and bowel dysfunction in a cat following epidural morphine analgesia. Journal of Feline Medicine and Surgery. 2011;13:602-605. vii 7. Song RB, Basso DM, da Costa RC, Fisher LC, Mo X, Moore SA. von Frey anesthesiometry to assess sensory impairment after acute spinal cord injury caused by thoracolumbar intervertebral disc extrusion in dogs. The Veterinary Journal. Submitted Jan 12, 2015. 8. Song RB, Oldach M, Basso DM, da Costa RC, Fisher LC, Mo X, Moore SA. A simplified method of walking track analysis to assess locomotor recovery after acute spinal cord injury caused by thoracolumbar intervertebral disc extrusion in dogs. The Veterinary Journal. Submitted April 8, 2015. Fields of Study Major Field: Comparative Veterinary Medicine viii Table of Contents Abstract ............................................................................................................................... ii Acknowledgments............................................................................................................... v Vita ..................................................................................................................................... vi Publications ....................................................................................................................... vii Fields of Study ................................................................................................................. viii Table of Contents ............................................................................................................... ix List of Tables .................................................................................................................... xii List of Figures .................................................................................................................. xiv List of Abbreviations ....................................................................................................... xvi Chapter 1 Introduction ....................................................................................................... 1 Chapter 2 Literature Review .............................................................................................. 4 2.1 Canine spinal cord injury .......................................................................................... 4 2.1.1 Causes ................................................................................................................. 4 2.1.2 Pathophysiology of injury .................................................................................. 6 2.2 Clinical trials in canine models of spinal cord injury.............................................. 13 2.3 Behavioral tests as outcome measures ...................................................................