In the United States alone, there are more than 200,000 individuals living with a chronic spinal cord injury (SCI). Healthcare for these individuals creates a significant economic burden for the country, not to mention the physiological, psychological, and social suffering these people endure everyday. Regaining partial function can lead to greater independence, thereby improving quality of life. To ascertain what functions are most important to the SCI population, in regard to enhancing quality of life, a novel survey was performed in which subjects were asked to rank seven functions in order of importance to their quality of life. The survey was distributed via email, postal mail, the internet, interview, and word of mouth to the SCI community at large. A total of 681 responses were completed. Regaining arm and hand function was most important to quadriplegics, while regaining sexual function was the highest priority for paraplegics. Improving bladder and bowel function was of shared importance to both injury groups. A longitudinal analysis revealed only slight differences between individuals injured <3 years compared to those injured >3 years. The majority of participants indicated that exercise was important to functional recovery, yet more than half either did not have access to exercise or did not have access to a trained therapist to oversee that exercise. In order to improve the relevance of research in this area, the concerns of the SCI population must be better known and taken into account. This approach is consistent with and emphasized by the new NIH roadmap to discovery.

Background/Objective: The end goal of clinical care and clinical research involving spinal cord injury (SCI) is to improve the overall ability of persons living with SCI to function on a daily basis. Neurologic recovery does not always translate into functional recovery. Thus, sensitive outcome measures designed to assess functional status relevant to SCI are important to develop. Method: Evaluation of currently available SCI functional outcome measures by a multinational work group. Results: The 4 measures that fit the prespecified inclusion criteria were the Modified Barthel Index (MBI), the Functional Independence Measure (FIM), the Quadriplegia Index of Function (QIF), and the Spinal Cord Independence Measure (SCIM). The MBI and the QIF were found to have minimal evidence for validity, whereas the FIM and the SCIM were found to be reliable and valid. The MBI has little clinical utility for use in the SCI population. Likewise, the FIM applies mainly when measuring burden of care, which is not necessarily a reflection of functional recovery. The QIF is useful for measuring functional recovery but only in a subpopulation of people with SCI, and substantial validity data are still required. The SCIM is the only functional recovery outcome measure designed specifically for SCI. Conclusions: The multinational work group recommends that the latest version of the SCIM (SCIM III) continue to be refined and validated and subsequently implemented worldwide as the primary functional recovery outcome measure for SCI. The QIF may continue to be developed and validated for use as a supplemental tool for the nonambulatory tetraplegic population.

Study design: Review by the spinal cord outcomes partnership endeavor (SCOPE), which is a broadbased international consortium of scientists and clinical researchers representing academic institutions, industry, government agencies, not-for-profit organizations and foundations. Objectives: Assessment of current and evolving tools for evaluating human spinal cord injury (SCI) outcomes for both clinical diagnosis and clinical research studies. Methods: a framework for the appraisal of evidence of metric properties was used to examine outcome tools or tests for accuracy, sensitivity, reliability and validity for human SCI. Results: Imaging, neurological, functional, autonomic, sexual health, bladder/bowel, pain and psychosocial tools were evaluated. Several specific tools for human SCI studies have or are being developed to allow the more accurate determination for a clinically meaningful benefit (improvement in functional outcome or quality of life) being achieved as a result of a therapeutic intervention. Conclusion: Significant progress has been made, but further validation studies are required to identify the most appropriate tools for specific targets in a human SCI study or clinical trial.

The RNA-binding protein HuD binds to a regulatory element in the 3Ј untranslated region (3Ј UTR) of the GAP-43 mRNA. To investigate the functional significance of this interaction, we generated PC12 cell lines in which HuD levels were controlled by transfection with either antisense (pDuH) or sense (pcHuD) constructs. pDuH-transfected cells contained reduced amounts of GAP-43 protein and mRNA, and these levels remained low even after nerve growth factor (NGF) stimulation, a treatment that is normally associated with protein kinase C (PKC)-dependent stabilization of the GAP-43 mRNA and neuronal differentiation. Analysis of GAP-43 mRNA stability demonstrated that the mRNA had a shorter half-life in these cells. In agreement with their deficient GAP-43 expression, pDuH cells failed to grow neurites in the presence of NGF or phorbol esters. These cells, however, exhibited normal neurite outgrowth when exposed to dibutyryl-cAMP, an agent that induces outgrowth independently from GAP-43. We observed opposite effects in pcHuD-transfected cells. The GAP-43 mRNA was stabilized in these cells, leading to an increase in the levels of the GAP-43 mRNA and protein. pcHuD cells were also found to grow short spontaneous neurites, a process that required the presence of GAP-43. In conclusion, our results suggest that HuD plays a critical role in PKC-mediated neurite outgrowth in PC12 cells and that this protein does so primarily by promoting the stabilization of the GAP-43 mRNA. INTRODUCTIONIn addition to transcriptional factors, RNA-binding proteins play a critical role in the developmental control of gene expression. Among these is ELAV (embryonic lethal abnormal vision), an RNA-binding protein identified in Drosophila, where the gene is required for normal development and maintenance of the nervous system (Campos et al., 1985;Robinow et al., 1988). In higher vertebrates and mammals, four members of the ELAV-like family have been identified. These are also referred to as Hu proteins, namely HuR (also known as HuA), HuB (Hel-N1), HuC, and HuD, because these are targets of anti-Hu antibodies present in the sera of patients with paraneoplastic encephalomyelitis (Dalmau et al., 1992). HuR is ubiquitously expressed (Ma et al., 1996), while HuB, HuC, and HuD are expressed uniquely in the nervous system. Recent studies indicate that overexpression of neural ELAV-like proteins is sufficient to induce neuronal differentiation in vitro and in vivo (Wakamatsu and Weston, 1997; Akamatsu et al., 1999;Antic et al., 1999;Kasashima et al., 1999). While the exact function and targets of ELAV/Hu proteins remain to be fully elucidated, it seems likely that this family of RNA-binding proteins controls neuronal differentiation by selectively modulating the expression of neural-specific, growth-associated genes.The growth-associated protein GAP-43 is expressed in neurons primarily during the initial establishment and regeneration of neural connections (Skene, 1989;Benowitz and Routtenberg, 1997 Eggen et al., 1995;Chiaramello et al., 1996;Kinney et ...

Study Design: Secure, web-based survey. Objectives: Obtain information from the spinal cord injured (SCI) population regarding sexual dysfunctions, with the aim of developing new basic science and clinical research and eventual therapies targeting these issues. Setting: Worldwide web. Methods: Individuals 18 years or older living with SCI. Participants obtained a pass-code to enter a secure website and answered survey questions. A total of 286 subjects completed the survey. Results: The majority of participants stated that their SCI altered their sexual sense of self and that improving their sexual function would improve their quality of life (QoL). The primary reason for pursuing sexual activity was for intimacy need, not fertility. Bladder and bowel concerns during sexual activity were not strong enough to deter the majority of the population from engaging in sexual activity. However, in the subset of individuals concerned about bladder and/or bowel incontinence during sexual activity, this was a highly significant issue. In addition, the occurrence of autonomic dysreflexia (AD) during typical bladder or bowel care was a significant variable predicting the occurrence and distress of AD during sexual activity. Conclusion: Sexual function and its resultant impact on QoL is a major issue to an overwhelming majority of people living with SCI. This certainly constitutes the need for expanding research in multiple aspects to develop future therapeutic interventions for sexual health and SCI.

The rationale for implantation of autologous human Schwann cells (SCs) in persons with subacute spinal cord injury (SCI) is based on evidence that transplanted SCs are neuroprotective, support local axonal plasticity, and are capable of myelinating axons. A Phase I clinical trial was conducted to evaluate the safety of autologous human SC transplantation into the injury epicenter of six subjects with subacute SCI. The trial was an open-label, unblinded, non-randomized, non-placebo controlled study with a dose escalation design and standard medical rehabilitation. Participants were paraplegics with neurologically complete, trauma-induced spinal lesions. Autologous SCs were cultured in vitro from a sural nerve harvested from each participant and injected into the epicenter of the spinal lesion. Outcome measures for safety were protocol compliance, feasibility, adverse events, stability of neurological level, absence of detectable mass lesion, and the emergence of clinically significant neuropathic pain or muscle spasticity no greater than expected for a natural course cohort. One year post-transplantation, there were no surgical, medical, or neurological complications to indicate that the timing or procedure for the cell transplantation was unsafe. There were no adverse events or serious adverse events related to the cell therapy. There was no evidence of additional spinal cord damage, mass lesion, or syrinx formation. We conclude that it is feasible to identify eligible candidates, appropriately obtain informed consent, perform a peripheral nerve harvest to obtain SCs within 5-30 days of injury, and perform an intra-spinal transplantation of highly purified autologous SCs within 4-7 weeks of injury.

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