Clinical and Neurophysiological Changes after Targeted Intrathecal Injections of Bone Marrow Stem Cells in a C3 Tetraplegic Subject

• Published in: Journal of neurotrauma Vol. 36; no. 3; pp. 500 - 516
• Main Authors: Santamaría, Andrea J., Benavides, Francisco D., DiFede, Darcy L., Khan, Aisha, Pujol, Marietsy V., Dietrich, W. Dalton, Marttos, Antonio, Green, Barth A., Hare, Joshua M., Guest, James D.
• Format: Journal Article
• Language: English
• Published: United States Mary Ann Liebert, Inc 01.02.2019
• Subjects: Adult; Autonomic nervous system; Bone marrow; Cerebrospinal fluid; Cytokines; Electromyography; Electrophysiology; Evoked Potentials, Motor - physiology; Evoked Potentials, Somatosensory - physiology; Female; Humans; Immunomodulation; Injections, Spinal; Interdisciplinary aspects; International standards; Magnetic resonance imaging; Medicine; Mesenchymal Stem Cells; Motor evoked potentials; Motor neurons; Muscles; Neural networks; Neurophysiology; Ostomy; Pain; Paralysis; Patients; Quadriplegia - etiology; Quadriplegia - physiopathology; Quadriplegia - therapy; Respiration; Respiratory function; Skin; Somatosensory evoked potentials; Spinal cord injuries; Spinal Cord Injuries - complications; Spinal Cord Injuries - physiopathology; Spinal Cord Injuries - therapy; Stem cells; Treatment Outcome; Ventilators; Weaning; Florida; United States > US; intrathecal; SCI; phrenic; BMSC; electrophysiology
• ISSN: 0897-7151; 1557-9042; 1557-9042
• DOI: 10.1089/neu.2018.5716

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.