What are clinical indicators
This is the second of a 2-part review of spinal cord injury. The focus herein is to highlight recent findings regarding prognostic indicators used for spinal cord injury (SCI) in dogs, promote an awareness of the current recommendations of standard of care for traumatic spinal cord injury in veterinary medicine, and highlight the findings of clinical trials of therapies for spinal cord injury in dogs. This 2-part review provides information that will assist general and specialty veterinary practitioners in evidence-based veterinary medical practice in an area that has become particularly specialized.
Lésions de la moelle épinière II. Indicateurs de pronostic, normes de soins et essais cliniques. Le présent document représente la deuxième partie d’une revue en 2 parties sur les lésions de la moelle épinière (LME). L’objet du présent article consiste à souligner les constatations récentes concernant les indicateurs de pronostic utilisés pour les LME chez les chiens, à promouvoir la sensibilisation à l’égard des recommandations actuelles pour les normes de soins en médecine vétérinaire relativement aux traumatismes de la moelle épinière et à mettre en lumière les constatations d’essais cliniques réalisés pour traiter les blessures de LME chez les chiens. Cette revue en 2 parties fournit des renseignements qui aideront les omnipraticiens et les spécialistes vétérinaires dans la pratique factuelle de la médecine vétérinaire pour un domaine qui est devenu particulièrement spécialisé.
(Traduit par Isabelle Vallières)
Traumatic spinal cord injury (SCI) is a disease with devastating effects in dogs, including paresis or paralysis and/or urinary and fecal incontinence. The most common causes of spinal cord injury in dogs include trauma induced by prolapsed intervertebral discs and exogenous sources of trauma such as motor vehicle accidents (1 –3 ). The pathophysiological consequences of SCI are brought about by primary and secondary injury mechanisms. Primary SCI results from the direct mechanical injury to the spinal cord. For example, extruded intervertebral disc material can cause both contusion and compression causing mechanical injury to the vasculature and neural and supporting tissue of the spinal cord. Primary injury may also take the form of laceration, shearing, and traction. Secondary SCI causes physical expansion of the primary injury and results from a variety of biochemical and vascular events. Regardless of the mechanism of injury, spinal cord tissue [neurons and supporting cells (glia)] is destroyed and connections between brain-spinal cord and spinal cord-spinal cord neurons are lost.
The way in which the central nervous system heals is unique and the local environment within the injured spinal cord is inhibitory to neuronal regeneration. Basic, translational, and clinical research aim to treat SCI using a variety of strategies.
Current therapies for SCI, experimentally and/or clinically, include: 1) preventing secondary injury, 2) promoting regeneration and/or sprouting of remaining axons, 3) enhancing the purposeful function of remaining neural circuitry, 4) replacing destroyed spinal cord tissue, and 5) a combination of these approaches.
Prognostic indicators for traumatic spinal cord injury
One of the common questions owners of SCI dogs have is “Will my dog be able to walk again?” or “What is the likelihood that my dog will not have any more back pain?” Several attempts to describe surrogate markers or prognostic indicators of recovery following SCI have been made. Herein, we review the clinical signs and advanced imaging that have been studied as prognostic indicators in animals with naturally occurring SCI.
Temporal aspects of onset and duration of clinical signs have been investigated as prognostic indicators, with variable results, for dogs with SCI resulting from intervertebral disc herniation. The rapidity of development of clinical signs does not seem to affect outcome for dogs with intact pain perception (4 ). One study, examining the rates of recovery for dogs without perception of pain caudal to the level of the SCI, and undergoing surgical decompression, found that animals that were unable to locomote within 1 h from the onset of clinical signs were less likely to satisfactorily recover (regain pain perception, locomotor ability and voluntary micturition) compared with animals that took more than 1 h to lose the ability to locomote (5 ). This is likely because of the more peracute severity of the concussive force by which the spinal cord was impacted by the intervertebral disc material. In another study, however, the rapidity of developing clinical signs could not be used to predict whether or not an animal would regain locomotor ability (6 ). In both studies, duration of paraplegia prior to a dog receiving decompressive surgery was not important in predicting whether or not the animal would be able to recover locomotor ability.
Traditionally, loss of pain perception caudal to the level of the SCI has been used as a poor prognostic indicator for recovery from SCI. A relatively recent retrospective study of dogs
with severe SCI identified that pain perception as a prognostic indicator depends on 1) the type of traumatic event causing the SCI, and 2) the rapidity with which pain perception returns (6 ). In particular, 2 of 9 paraplegic dogs without pain perception and having SCI resulting from exogenous trauma and vertebral fractures and/or spinal luxations, treated medically or surgically, were eventually able to locomote. None of these 9 dogs regained pain perception and the 2 that regained the ability to locomote had periodic urinary and fecal incontinence (6 ). In the same study, dogs with severe SCI, resulting from intervertebral disc herniation, and loss of pain perception and having undergone decompressive surgery were investigated. The authors found that 68% of paraplegic dogs without pain perception caudal to the level of the SCI, and having undergone decompressive surgery, regained the ability to walk. Interestingly, all dogs that regained pain perception were eventually able to locomote. Seventy-eight percent of the dogs regaining pain perception did so within 2 wk after decompressive surgery, and 97% had regained pain perception by 1 mo after decompressive surgery. Interestingly, 7 of 18 dogs that did not regain pain perception were able to locomote (range of time to walk 16–72 wk after decompressive surgery), though they never regained fecal or urinary continence. Consequently, waiting for 1 mo in animals lacking pain perception caudal to the level of the SCI, will aid in prognosticating whether or not the animal will regain the ability to locomote. Importantly, approximately 40% of animals that regained pain perception caudal to the level of the SCI, and the ability to locomote had mild intermittent urinary and fecal incontinence. Another interesting finding from this study was that for paraplegic dogs lacking pain perception, and resulting from intervertebral disc herniation, recovery of locomotor ability occured more quickly for younger and small-breed dogs. This is interesting given that recent studies have shown that elderly rats have greater spinal cord demyelination and impaired re-myelinating abilities following SCI (7 ,8 ). Importantly, however, a dog’s physical stature does not appear to matter for prognostication for dogs with thoracolumbar SCI resulting from intervertebral disc herniation (type I disc disease) and intact pain perception (9 –11 ).
The rationale behind using advanced imaging as a prognostic tool for SCI stems from pathophysiological processes that ensue after injury to the spinal cord. As mentioned in part I of this review, contusion, concussion, and compression of the spinal cord and vascular tissue cause inflammation, hemorrhage, ischemia, edema, and direct mechanical damage to the spinal cord. These pathological changes can be visualized with advanced imaging techniques, especially magnetic resonance (MR) imaging.
Several retrospective studies using advanced imaging findings as prognostic indicators for recovery have recently been published. From these studies, it appears that the degree of spinal cord compression, based upon MR imaging, is not predictive of recovery (12 ,13 ). However, it appears that dogs with an area of hyperintensity of the spinal cord (on T2-weighted images) at least as long as the L2 vertebral body, preoperatively, have a poor prognosis for recovery after thoracolumber disc herniation (14 ). It should be noted, however, that successful recovery was defined as regaining the ability to locomote unaided and with or without mild neurologic deficits, including absent or mild urinary and fecal incontinence (12 ,14 ).
At a very intuitive level, animals having undergone complete or nearly complete transection of their spinal cords, albeit rare, have a poor prognosis for satisfactory recovery. This is evident from the findings of Olby et al (6 ), where only 2 of 9 dogs with severe traumatic SCIs regained the ability to walk in the absence of regaining pain perception. Although it appears that only 10% of descending axons are required for successful locomotion (15 ), we know that not all descending spinal tracts contribute equally to locomotion and that there is redundancy in some of these pathways (16 –20 ). Consequently, it is likely that the answer to the question “what is spared?” is highly relevant to predicting recovery after SCI. At first, identifying what particular pathways are spared may seem an impossible task; however, recent developments in diffusion MR imaging make these tasks possible. Diffusion MR imaging methods are based upon measuring the diffusion of water within the microenvironment of living tissue. A particular diffusion MR imaging method, known as diffusion tensor imaging, measures the restricted diffusion of water along, for example, neural tracts. When diffusion tensor imaging is used to specifically image white matter tracts, this is termed tractography. Given that tractography ( Figure 1 ) is possible, even after spinal cord injury, in the future we will undoubtedly be able to better identify what particular white matter tracts are affected and therefore prognosticate the likelihood of recovery (21 ).Source: www.ncbi.nlm.nih.gov