TY - JOUR
T1 - Clinical and neurophysiological changes after targeted intrathecal injections of bone marrow stem cells in a C3 tetraplegic subject
AU - Santamaría, Andrea J.
AU - Benavides, Francisco D.
AU - Difede, Darcy L.
AU - Khan, Aisha
AU - Pujol, Marietsy V.
AU - Dietrich, W. Dalton
AU - Marttos, Jr, Antonio
AU - Green, Barth A.
AU - Hare, Joshua M.
AU - Guest, James D.
N1 - Funding Information:
We thank The Miami Project to Cure Paralysis, The Buoniconti Fund, and The Interdisciplinary Stem Cell Institute at the University of Miami, Miller School of Medicine, for supporting this study. Drs. C. Bowie, B. Snelling, M. Elhammady and E. Peterson also participated in the infusion procedures, and Dr. W. Jermako-wicz assisted with the subject’s care. Dr. O. Moraes facilitated a high-resolution MRI at the Hospital Sírio-Libanês, Sao Paulo, Brazil. Rebecca Safon served as study coordinator during part of the study. Deena Cilien, Vianca Caridad Diaz, and George Jim-sheleishvili assisted with testing. Vania Almeida assisted with translation. We extend special thanks to the subject and her family for their willingness to actively participate in the study.
Publisher Copyright:
© Copyright 2019, Mary Ann Liebert, Inc., publishers 2019.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2019/2/1
Y1 - 2019/2/1
N2 - High-level quadriplegia is a devastating condition with limited treatment options. Bone marrow derived stem cells (BMSCs) are reported to have immunomodulatory and neurotrophic effects in spinal cord injury (SCI). We report a subject with complete C2 SCI who received three anatomically targeted intrathecal infusions of BMSCs under a single-patient expanded access investigational new drug (IND). She underwent intensive physical therapy and was followed for >2 years. At end-point, her American Spinal Injury Association Impairment Scale (AIS) grade improved from A to B, and she recovered focal pressure touch sensation over several body areas. We conducted serial neurophysiological testing to monitor changes in residual connectivity. Motor, sensory, and autonomic system testing included motor evoked potentials (MEPs), somatosensory evoked potentials (SSEPs), electromyography (EMG) recordings, F waves, galvanic skin responses, and tilt-table responses. The quality and magnitude of voluntary EMG activations increased over time, but remained below the threshold of clinically obvious movement. Unexpectedly, at 14 months post-injury, deep inspiratory maneuvers triggered respiratory-like EMG bursting in the biceps and several other muscles. This finding means that connections between respiratory neurons and motor neurons were newly established, or unmasked. We also report serial analysis of MRI, International Standards for Neurological Classification of SCI (ISNCSCI), pulmonary function, pain scores, cerebrospinal fluid (CSF) cytokines, and bladder assessment. As a single case, the linkage of the clinical and neurophysiological changes to either natural history or to the BMSC infusions cannot be resolved. Nevertheless, such detailed neurophysiological assessment of high cervical SCI patients is rarely performed. Our findings indicate that electrophysiology studies are sensitive to define both residual connectivity and new plasticity.
AB - High-level quadriplegia is a devastating condition with limited treatment options. Bone marrow derived stem cells (BMSCs) are reported to have immunomodulatory and neurotrophic effects in spinal cord injury (SCI). We report a subject with complete C2 SCI who received three anatomically targeted intrathecal infusions of BMSCs under a single-patient expanded access investigational new drug (IND). She underwent intensive physical therapy and was followed for >2 years. At end-point, her American Spinal Injury Association Impairment Scale (AIS) grade improved from A to B, and she recovered focal pressure touch sensation over several body areas. We conducted serial neurophysiological testing to monitor changes in residual connectivity. Motor, sensory, and autonomic system testing included motor evoked potentials (MEPs), somatosensory evoked potentials (SSEPs), electromyography (EMG) recordings, F waves, galvanic skin responses, and tilt-table responses. The quality and magnitude of voluntary EMG activations increased over time, but remained below the threshold of clinically obvious movement. Unexpectedly, at 14 months post-injury, deep inspiratory maneuvers triggered respiratory-like EMG bursting in the biceps and several other muscles. This finding means that connections between respiratory neurons and motor neurons were newly established, or unmasked. We also report serial analysis of MRI, International Standards for Neurological Classification of SCI (ISNCSCI), pulmonary function, pain scores, cerebrospinal fluid (CSF) cytokines, and bladder assessment. As a single case, the linkage of the clinical and neurophysiological changes to either natural history or to the BMSC infusions cannot be resolved. Nevertheless, such detailed neurophysiological assessment of high cervical SCI patients is rarely performed. Our findings indicate that electrophysiology studies are sensitive to define both residual connectivity and new plasticity.
KW - BMSC
KW - SCI
KW - electrophysiology
KW - intrathecal
KW - phrenic
UR - http://www.scopus.com/inward/record.url?scp=85060436544&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85060436544&partnerID=8YFLogxK
U2 - 10.1089/neu.2018.5716
DO - 10.1089/neu.2018.5716
M3 - Article
C2 - 29790404
AN - SCOPUS:85060436544
VL - 36
SP - 500
EP - 516
JO - Central Nervous System Trauma
JF - Central Nervous System Trauma
SN - 0897-7151
IS - 3
ER -