[Show abstract][Hide abstract] ABSTRACT: Basic science advances in spinal cord injury (SCI) are leading to novel clinical approaches. The authors report a prospective, uncontrolled pilot study of the safety and outcomes of implanting olfactory mucosal autografts (OMA) in 20 patients with chronic, sensorimotor complete or motor complete SCI.
Seven paraplegic and 13 tetraplegic subjects (17 men and 3 women; 19-37 years old) who sustained a traumatic SCI 18 to 189 months previously (mean = 49 months) were enrolled. Preoperative rehabilitation that emphasized lower extremity stepping using either overground walking training or a robotic weight-supported treadmill training was provided for 25 to 39 hours per week for a median of 4 months at 3 sites. No change in ASIA Impairment Scale (AIS) motor scores for the lower extremities or AIS grades of completeness was found. OMAs were transplanted into 1.3- to 4-cm lesions at C4-T12 neurological levels after partial scar removal. Therapy was continued postoperatively. Preoperative and postoperative assessments included AIS scores and classification, electromyography (EMG) of attempted voluntary contractions, somatosensory evoked potentials (SSEP), urodynamic studies with sphincter EMG, spinal cord magnetic resonance imaging (MRI), and otolaryngology and psychology evaluations. The Functional Independence Measure (FIM) and Walking Index for Spinal Cord Injury (WISCI) were obtained in 13 patients.
All patients survived and recovered olfaction. One patient was rehospitalized for aseptic meningitis. Minor adverse events occurred in 4 others. The mean duration of follow-up was 27.7 months (range = 12-45 months). By MRI, the lesion site was filled in all patients with no neoplastic overgrowth or syringomyelia. AIS grades improved in 11 of 20 patients, 6 (A --> C), 3 (B --> C), and 2 (A --> B), and declined in 1 (B --> A). Improvements included new voluntary EMG responses (15 patients) and SSEPs (4 patients). Scores improved in the FIM and WISCI (13/13 tested), and urodynamic responses improved in 5 patients.
OMA is feasible, relatively safe, and possibly beneficial in people with chronic SCI when combined with postoperative rehabilitation. Future controlled trials may need to include a lengthy and intensive rehabilitation arm as a control.
[Show abstract][Hide abstract] ABSTRACT: To explore the feasibility of performing percutaneous endoscopic cellular transplantation into the lumbar spinal cord of pigs to create intramedullary cellular trails.
The lumbar subarachnoid space was accessed using a 10-gauge needle inserted between L5 and L6. A 12.5-French flexible introducer sheath was fed over the needle into the subarachnoid space. A 3.2-mm-diameter flexible, steerable endoscope was then directed intradurally through the sheath. The thecal space was distended by saline infusion. A microcatheter with an attached needle then was advanced through the working channel into the dorsal surface of the lumbar spinal cord. Five microliters of Hoechst-labeled fibroblasts were injected while the catheter was withdrawn slowly to create a trail of cells within the spinal cord. The spinal canal then was perfused with fixative. The injected spinal cord segment was removed and studied histologically. Endoscopic video was analyzed offline.
The endoscope could be navigated under visual guidance. The sacral and lumbar rootlets, the spinal cord, and associated vessels were visualized. In fixed sagittal sections, a linear trail of fluorescent fibroblasts could be seen within the lumbar spinal cord in each specimen.
Percutaneous endoscopic cellular injection may be useful for cellular transplantation, may reduce surgical and anesthetic time, may be compatible with local anesthesia, may eliminate the need to disrupt spinal instrumentation and bone grafts, and may allow greater flexibility in the respective timing of spinal fixation and cellular transplantation after spinal cord injury. This is the first report of the use of endoscopic intraspinal cellular transplantation.
[Show abstract][Hide abstract] ABSTRACT: Intraspinal transplantation of olfactory glial cells (OGC) has produced well-defined beneficial effects in experimental rodent models of spinal cord injury (SCI) and therefore has considerable promise as a treatment for severe SCI in human patients. In this study, we used clinical canine cases of severe SCI to determine whether derivation and transplantation of OGC from an autologous source was feasible. From the nerve fiber layer of a single olfactory bulb, we were able to generate 5 x 10(6) cells from each patient within 3 weeks. Of this population, 72% were p75(+) OGC, 20% were meningeal cells, and the remainder mainly astrocytes. Intraspinal transplantation was not associated with any observable long- or short-term complications.
Journal of Neurotrauma 12/2005; 22(11):1282-93. DOI:10.1089/neu.2005.22.1282 · 3.71 Impact Factor
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