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      Olfactory Mucosal Autografts and Rehabilitation for Chronic Traumatic Spinal Cord Injury

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          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.

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          Autologous olfactory ensheathing cell transplantation in human paraplegia: a 3-year clinical trial

          Olfactory ensheathing cells show promise in preclinical animal models as a cell transplantation therapy for repair of the injured spinal cord. This is a report of a clinical trial of autologous transplantation of olfactory ensheathing cells into the spinal cord in six patients with complete, thoracic paraplegia. We previously reported on the methods of surgery and transplantation and the safety aspects of the trial 1 year after transplantation. Here we address the overall design of the trial and the safety of the procedure, assessed during a period of 3 years following the transplantation surgery. All patients were assessed at entry into the trial and regularly during the period of the trial. Clinical assessments included medical, psychosocial, radiological and neurological, as well as specialized tests of neurological and functional deficits (standard American Spinal Injury Association and Functional Independence Measure assessments). Quantitative test included neurophysiological tests of sensory and motor function below the level of injury. The trial was a Phase I/IIa design whose main aim was to test the feasibility and safety of transplantation of autologous olfactory ensheathing cells into the injured spinal cord in human paraplegia. The design included a control group who did not receive surgery, otherwise closely matched to the transplant recipient group. This group acted as a control for the assessors, who were blind to the treatment status of the patients. The control group also provided the opportunity for preliminary assessment of the efficacy of the transplantation. There were no adverse findings 3 years after autologous transplantation of olfactory ensheathing cells into spinal cords injured at least 2 years prior to transplantation. The magnetic resonance images (MRIs) at 3 years showed no change from preoperative MRIs or intervening MRIs at 1 and 2 years, with no evidence of any tumour of introduced cells and no development of post-traumatic syringomyelia or other adverse radiological findings. There were no significant functional changes in any patients and no neuropathic pain. In one transplant recipient, there was an improvement over 3 segments in light touch and pin prick sensitivity bilaterally, anteriorly and posteriorly. We conclude that transplantation of autologous olfactory ensheathing cells into the injured spinal cord is feasible and is safe up to 3 years of post-implantation, however, this conclusion should be considered preliminary because of the small number of trial patients.
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            Effects of repetitive motor training on movement representations in adult squirrel monkeys: role of use versus learning.

            Current evidence indicates that repetitive motor behavior during motor learning paradigms can produce changes in representational organization in motor cortex. In a previous study, we trained adult squirrel monkeys on a repetitive motor task that required the retrieval of food pellets from a small-diameter well. It was found that training produced consistent task-related changes in movement representations in primary motor cortex (M1) in conjunction with the acquisition of a new motor skill. In the present study, we trained adult squirrel monkeys on a similar motor task that required pellet retrievals from a much larger diameter well. This large-well retrieval task was designed to produce repetitive use of a limited set of distal forelimb movements in the absence of motor skill acquisition. Motor activity levels, estimated by the total number of finger flexions performed during training, were matched between the two training groups. This experiment was intended to evaluate whether simple, repetitive motor activity alone is sufficient to produce representational plasticity in cortical motor maps. Detailed analysis of the motor behavior of the monkeys indicates that their retrieval behavior was highly successful and stereotypical throughout the training period, suggesting that no new motor skills were learned during the performance of the large-well retrieval task. Comparisons between pretraining and posttraining maps of M1 movement representations revealed no task-related changes in the cortical area devoted to individual distal forelimb movement representations. We conclude that repetitive motor activity alone does not produce functional reorganization of cortical maps. Instead, we propose that motor skill acquisition, or motor learning, is a prerequisite factor in driving representational plasticity in M1. Copyright 2000 Academic Press.
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              Anatomical changes in human motor cortex and motor pathways following complete thoracic spinal cord injury.

              A debilitating consequence of complete spinal cord injury (SCI) is the loss of motor control. Although the goal of most SCI treatments is to re-establish neural connections, a potential complication in restoring motor function is that SCI may result in anatomical and functional changes in brain areas controlling motor output. Some animal investigations show cell death in the primary motor cortex following SCI, but similar anatomical changes in humans are not yet established. The aim of this investigation was to use voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) to determine if SCI in humans results in anatomical changes within motor cortices and descending motor pathways. Using VBM, we found significantly lower gray matter volume in complete SCI subjects compared with controls in the primary motor cortex, the medial prefrontal, and adjacent anterior cingulate cortices. DTI analysis revealed structural abnormalities in the same areas with reduced gray matter volume and in the superior cerebellar cortex. In addition, tractography revealed structural abnormalities in the corticospinal and corticopontine tracts of the SCI subjects. In conclusion, human subjects with complete SCI show structural changes in cortical motor regions and descending motor tracts, and these brain anatomical changes may limit motor recovery following SCI.
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                Author and article information

                Journal
                Neurorehabilitation and Neural Repair
                Neurorehabil Neural Repair
                SAGE Publications
                1545-9683
                1552-6844
                January 12 2010
                January 2010
                September 30 2009
                January 2010
                : 24
                : 1
                : 10-22
                Affiliations
                [1 ]Hospital de Egas Moniz, Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal,
                [2 ]Hospital de Egas Moniz, Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal
                [3 ]Hospital de S. Sebastião, Feira, Portugal
                [4 ]Centro Giusti, Instituto di Medicina Fisica e Riabilitazione, Firenze, Italy
                [5 ]Centro de Medicina de Reabilitação da Região Centro, Rovisco Pais, Tocha, Cantanhede, Portugal
                [6 ]Wayne State University Medical School, Detroit, Michigan, USA
                Article
                10.1177/1545968309347685
                19794133
                931833e3-8c59-4776-b387-4c1cce15d4ff
                © 2010

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