TY - JOUR
T1 - Neurophysiological Changes in the First Year After Cell Transplantation in Sub-acute Complete Paraplegia
AU - Santamaria, Andrea J.
AU - Benavides, Francisco D.
AU - Saraiva, Pedro M.
AU - Anderson, Kimberly D.
AU - Khan, Aisha
AU - Levi, Allan D.
AU - Dietrich, W. Dalton
AU - Guest, James D.
N1 - Funding Information:
We would like to acknowledge all of the team members that contributed to the trial, including James Adcock, Gagani Athauda, Adrianna Brooks, Mary Barlett Bunge, Diana Cardenas, Rosie Curiel, Kevin Dalal, Marine Dididze, Maxwell Donaldson, Katie Gant, Shelly Garcia, Barth Green, Anil Lalwani, Efrat Saraf-Lavi, Damien Pearse, Alberto Martinez-Arizala, Katie Nagle, Risset Silvera, Steven Vanni, Michael Wang, Patrick Wood, Eva Widerstr?m-Noga, and Lloyd Zucker. Trial oversight was provided by external Data Safety Monitoring Board members (Drs. Robert Grossman, Howard Landy, Steve Kirshblum, and Nick Boulis) and External Advisory Board members (Drs. Dan Lammertse, Mark Tuszynski, and James Fawcett). We extend special thanks to the participants and their families for their willingness to participate in the study. Funding. The Miami Project to Cure Paralysis Clinical Trials Initiative and the Buoniconti Fund to Cure Paralysis at the University of Miami, Miller School of Medicine, as well as the Bryon Riesch Paralysis Foundation, Peacock Foundation, the Norman & Bettina Roberts Foundation, and the Katie Samson Foundation.
Publisher Copyright:
© Copyright © 2021 Santamaria, Benavides, Saraiva, Anderson, Khan, Levi, Dietrich and Guest.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/1/18
Y1 - 2021/1/18
N2 - Neurophysiological testing can provide quantitative information about motor, sensory, and autonomic system connectivity following spinal cord injury (SCI). The clinical examination may be insufficiently sensitive and specific to reveal evolving changes in neural circuits after severe injury. Neurophysiologic data may provide otherwise imperceptible circuit information that has rarely been acquired in biologics clinical trials in SCI. 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. Here, we report longitudinal electrophysiological assessments conducted during the trial. 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. We found several notable signals not detectable by clinical exam. In all six participants, thoracoabdominal motor connectivity was detected below the clinically assigned neurological level defined by sensory preservation. Additionally, small voluntary activations of leg and foot muscles or positive lower extremity MEPs were detected in all participants. Voluntary EMG was most sensitive to detect leg motor function. The recorded MEP amplitudes and latencies indicated a more caudal thoracic level above which amplitude recovery over time was observed. In contrast, further below, amplitudes showed less improvement, and latencies were increased. 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. As an open-label study, we can establish no clear link between these observations and cell transplantation. This neurophysiological characterization may be of value to detect therapeutic effects in future controlled studies.
AB - Neurophysiological testing can provide quantitative information about motor, sensory, and autonomic system connectivity following spinal cord injury (SCI). The clinical examination may be insufficiently sensitive and specific to reveal evolving changes in neural circuits after severe injury. Neurophysiologic data may provide otherwise imperceptible circuit information that has rarely been acquired in biologics clinical trials in SCI. 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. Here, we report longitudinal electrophysiological assessments conducted during the trial. 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. We found several notable signals not detectable by clinical exam. In all six participants, thoracoabdominal motor connectivity was detected below the clinically assigned neurological level defined by sensory preservation. Additionally, small voluntary activations of leg and foot muscles or positive lower extremity MEPs were detected in all participants. Voluntary EMG was most sensitive to detect leg motor function. The recorded MEP amplitudes and latencies indicated a more caudal thoracic level above which amplitude recovery over time was observed. In contrast, further below, amplitudes showed less improvement, and latencies were increased. 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. As an open-label study, we can establish no clear link between these observations and cell transplantation. This neurophysiological characterization may be of value to detect therapeutic effects in future controlled studies.
KW - Schwann cell (SC)
KW - level of injury
KW - neurophysiology
KW - spinal cord injury
KW - transplantation
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UR - http://www.scopus.com/inward/citedby.url?scp=85100553195&partnerID=8YFLogxK
U2 - 10.3389/fneur.2020.514181
DO - 10.3389/fneur.2020.514181
M3 - Article
AN - SCOPUS:85100553195
VL - 11
JO - Frontiers in Neurology
JF - Frontiers in Neurology
SN - 1664-2295
M1 - 514181
ER -