Their neurological level of injury (NLI) was defined conventionally as the last dermatome with normal sensation. In this study, we enrolled six thoracic AIS A complete paraplegics with subacute SCI into a dose-escalation safety study of autologous Schwann cell transplantation (aSC) ( 7). Whereas, standard outcome measures ( 5) may fail to detect changes in circuit connectivity ( 6), neurophysiologic findings may inform development in a therapeutics program. Drug and biologics development is costly ( 3), and a lack of an apparent signal of an effect may cause a program to be terminated ( 4). Clinical trials have limitations on costs, the available time for study assessments, and the acceptable research burden to participants ( 2). Changes in neural connectivity can provide an important “biomarker” when there is a lack of clinically apparent therapeutic effects. Despite the primary outcome of safety, efficacy signals are sought to inform future product development. However, the thoracic NLI is based on a sensory exam with no motor component ( 1). In early Phase clinical trials of biological therapeutics for SCI, the emphasis is on safety for thoracic injuries, this is usually considered to be the maintenance of a stable neurological level of injury (NLI). This neurophysiological characterization may be of value to detect therapeutic effects in future controlled studies. As an open-label study, we can establish no clear link between these observations and cell transplantation. Intercostal spasms observed with EMG may also indicate this thoracic “motor level.” Galvanic skin testing revealed autonomic dysfunction in the hands above the injury levels. In contrast, further below, amplitudes showed less improvement, and latencies were increased. The recorded MEP amplitudes and latencies indicated a more caudal thoracic level above which amplitude recovery over time was observed. Voluntary EMG was most sensitive to detect leg motor function. Additionally, small voluntary activations of leg and foot muscles or positive lower extremity MEPs were detected in all participants. In all six participants, thoracoabdominal motor connectivity was detected below the clinically assigned neurological level defined by sensory preservation. We found several notable signals not detectable by clinical exam. Six participants underwent neurophysiology screening pre-transplantation with three post-transplantation neurophysiological assessments, focused on the thoracoabdominal region and lower limbs, including MEPs, SSEPs, voluntarily triggered EMG, and changes in GSR. Here, we report longitudinal electrophysiological assessments conducted during the trial. We reported a Phase 1 study of autologous purified Schwann cell suspension transplantation into the injury epicenter of participants with complete subacute thoracic SCI, observing no clinical improvements. Neurophysiologic data may provide otherwise imperceptible circuit information that has rarely been acquired in biologics clinical trials in SCI. The clinical examination may be insufficiently sensitive and specific to reveal evolving changes in neural circuits after severe injury. Neurophysiological testing can provide quantitative information about motor, sensory, and autonomic system connectivity following spinal cord injury (SCI). 3Miller School of Medicine, The Interdisciplinary Stem Cell Institute, The University of Miami, Miami, FL, United States.2The Department of Neurological Surgery, Miller School of Medicine, The University of Miami, Miami, FL, United States.1The Miami Project to Cure Paralysis, Miller School of Medicine, The University of Miami, Miami, FL, United States.
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