Prognostic Factors in Canine Acute Intervertebral Disc Disease

The International Campaign for Cures of Spinal Cord Injury Paralysis (ICCP) supported an international panel tasked with reviewing the methodology for clinical trials in spinal cord injury (SCI), and making recommendations on the conduct of future trials. This is the first of four papers. Here, we examine the spontaneous rate of recovery after SCI and resulting consequences for achieving statistically significant results in clinical trials. We have reanalysed data from the Sygen trial to provide some of this information. Almost all people living with SCI show some recovery of motor function below the initial spinal injury level. While the spontaneous recovery of motor function in patients with motor-complete SCI is fairly limited and predictable, recovery in incomplete SCI patients (American spinal injury Association impairment scale (AIS) C and AIS D) is both more substantial and highly variable. With motor complete lesions (AIS A/AIS B) the majority of functional return is within the zone of partial preservation, and may be sufficient to reclassify the injury level to a lower spinal level. The vast majority of recovery occurs in the first 3 months, but a small amount can persist for up to 18 months or longer. Some sensory recovery occurs after SCI, on roughly the same time course as motor recovery. Based on previous data of the magnitude of spontaneous recovery after SCI, as measured by changes in ASIA motor scores, power calculations suggest that the number of subjects required to achieve a significant result from a trial declines considerably as the start of the study is delayed after SCI. Trials of treatments that are most efficacious when given soon after injury will therefore, require larger patient numbers than trials of treatments that are effective at later time points. As AIS B patients show greater spontaneous recovery than AIS A patients, the number of AIS A patients requiring to be enrolled into a trial is lower. This factor will have to be balanced against the possibility that some treatments will be more effective in incomplete patients. Trials involving motor incomplete SCI patients, or trials where an accurate assessment of AIS grade cannot be made before the start of the trial, will require large subject numbers and/or better objective assessment methods.

It would be helpful to have factors that could identify patients who will, or will not, benefit from treatment with specific therapies. Ideally, these should be molecular-based factors. When results with molecular-based factors are disappointing, physicians often use clinical characteristics to make treatment decisions. Several characteristics have been suggested to predict sensitivity to epidermal growth factor receptor inhibitors in patients with non-small lung cancer, including gender, histology, smoking history. This report demonstrates that gender and histology are actually prognostic, rather than predictive factors. Before biomarkers or clinical characteristics are included in guidelines for selecting patients for specific treatments, it is imperative that the prognostic effects of these factors are distinguished from their ability to predict a differential clinical benefit from the specific treatment.

To assess whether the Pfirrmann system for grading lumbar intervertebral disk (IVD) degeneration in humans can also be used in dogs. 202 dogs. Magnetic resonance imaging was used to obtain images of vertebral segments from dogs, which were reviewed separately by 3 observers who graded the extent of degeneration in each visible IVD by use of the Pfirrmann classification system used for grading lumbar IVD degeneration in humans. Grading was validated against 2 factors associated with the extent of disk degeneration: type of dog (chondrodystrophic or nonchondrodystrophic breeds) and age. Interobserver and intraobserver agreement for Pfirrmann grading of IVD degeneration were good (κ scores, 0.81 to 0.93). An increase in the extent of disk degeneration was positively correlated with increases in age and with chondrodystrophic breed. The Pfirrmann system was reliably used to grade IVD degeneration in dogs of various breeds and ages. An increase in the extent of IVD degeneration was positively correlated with increases in age and with chondrodystrophic-type dogs.