The Integrated Neurological Change Score Is a Sensitive Neurological Composite Measure to Evaluate Cervical Spinal Cord Injury Trials

The Integrated Neurological Change Score (INCS) combines changes in sensory and motor subscores from the International Standards for Spinal Cord Injury Classification (ISNCSCI) into a composite measure. We evaluated the INCS sensitivity to therapeutic outcomes, robustness against ceiling effects, and association to functional improvement in patients with acute cervical spinal cord injury (SCI). To this end, we conducted a retrospective analysis of data from the Nogo Inhibition in Spinal Cord Injury (NISCI) clinical trial alongside a matched cohort from the European Multicenter Study about Spinal Cord Injury (EMSCI). The NISCI trial assessed the safety and efficacy of the anti-Nogo-A antibody (NG-101) in acute cervical SCI, reporting a potential therapeutic effect in motor incomplete patients. Our findings show that the sensitivity of INCS to the effect of NG-101 is comparable to that obtained employing the changes in the Upper Extremity Motor Score (the primary outcome in the NISCI trial). Moreover, the INCS is less susceptible to ceiling effects compared to measures of upper and lower extremity or total motor scores, as observed in the NISCI trial and in the matched EMSCI cohort. This robustness may facilitate the design of more inclusive clinical trials without compromising statistical power. Finally, INCS correlates strongly with functional outcomes in self-care and walking ability, outperforming ISNCSCI motor scores. In conclusion, the INCS represents a sensitive measure of neurological change corroborating the value of ISNCSCI standards for use in SCI trials.