Definitions of recovery and reintegration across the first year: A qualitative study of perspectives of persons with spinal cord injury and caregivers.

STUDY DESIGN: Longitudinal, qualitative cohort study. OBJECTIVES: To understand how people with newly acquired spinal cord injury (PWS) and their support person (SP) define recovery and successful community reintegration (CR) across the first 12 months post-injury (mpi) and their satisfaction with the rate of recovery and reintegration experienced. SETTING: Academic and Veterans hospitals in Midwest USA. METHODS: In-depth, semi-structured interviews were conducted in two cohorts of PWS and SP during the initial inpatient rehabilitation stay, at 6 mpi, and at 12 mpi. Recordings were transcribed; four authors independently undertook line-by-line coding. The team discussed codes to reach consensus and synthesize into broader themes within the International Classification of Function, Disability, and Health and Transformative frameworks. RESULTS: Data are reported on 23 PWS and 21 SP. PWS and SP are similar in defining recovery as gaining motor function and achieving independence. However, SP more frequently define recovery in terms of maintaining positivity and emotional recovery. At 12 mpi both groups shift to define recovery according to progress. Social roles, being active, and employment are persistent themes of how PWS and SP define successful CR. However, SP also frequently define successful CR as reestablishing identity and emotional adjustment. Veterans with SCI less frequently defined successful CR as employment. CONCLUSIONS: This study is the first to reveal how PWS and SP define recovery and reintegration during the first 12 mpi. Given decreasing lengths of stay, this information can be used to tailor rehabilitation strategies during the critical first year of injury to optimize recovery.

Factors Influencing Incidence of Wheelchair Repairs and Consequences Among Individuals with Spinal Cord Injury.

OBJECTIVE: To investigate the frequency and consequences of wheelchair repairs, looking at the relationship to usage, components, out-of-pocket costs, number of days affecting the user, and factors associated with the need for repairs or consequences. DESIGN: Survey, cross-sectional. SETTING: Nine spinal cord injury (SCI) Model Systems centers. PARTICIPANTS: Wheelchair users with SCI (N=533). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Cost and incidence of wheelchair repairs and consequences and wheelchair usage within the past 6 months. RESULTS: A total of 310 participants (56%) reported repairs, 127 (42%) of whom experienced at least 1 adverse consequence lasting a median of 5 days (interquartile range [IQR], 2-17.3 days). Repair rates were highest for the seating system, electronics, and tires. Participants were most often stranded at home or forced to use a backup chair. Median out-of-pocket costs were $150 (IQR, $50-$620). Active users, based on type of mobility and terrain, experienced more repairs and consequences than less active users. Repairs were more common among those who were Black (odds ratio [OR], 2.42) or power wheelchair (PWC) users (OR, 1.84), whereas consequences were more common among those who were Black (OR, 2.27), PWC (OR, 2.08) or power assist users (OR, 2.76), and those who had public insurance (OR, 1.70). CONCLUSIONS: Wheelchair repairs continue to affect more than 50% of wheelchair users with significant financial and personal cost. High repair rates limited participation inside and outside of the home. Consequences lasted longer than 2 weeks for many and may be minimized by a working backup chair. Disparities exist based on participant and wheelchair factors; repairs and adverse consequences appear to hit those most vulnerable with the least financial resources. Costs may be a barrier to repair completion for some individuals. This ongoing problem of high repair rates and their associated effects requires action such as higher standards, access to quicker service, and better training of users on wheelchair maintenance and repair.

Comprehensive and person-centred approach in research: what is missing?

The concept of a comprehensive and person-centred approach in healthcare is not new and it is the basic principle that is embedded in the International Classification of Functioning, Disability and Health (ICF) framework. However, the implementation of a comprehensive and person-centred approach has not been fully translated into research development in people living with spinal cord injuries (SCI). This approach in research is important as the perspectives of persons living with SCI should be equally valued drivers in any research intended to provide a direct or indirect outcome to people living with a SCI. This perspective paper will discuss some of the limiting factors and provide some examples of previous and current successful steps being taken towards the worldwide implementation of this approach. Finally, this paper will suggest some of the steps needed to implement this person-centred model in research in people with SCI.

Equitable partnerships between scientists and persons living with spinal cord injury will strengthen research scope, quality, and outcomes.

PURPOSE OF REVIEW: Partnerships across all stakeholders in the research process strengthen the outcomes and ultimate usability of research. The purpose of this review is to discuss the current level of inclusion of people living with spinal cord injury (SCI) in the research process, the science of engagement and benefits of partnerships in research, and emerging resources available to help promote ethical and effective partnerships in SCI research. RECENT FINDINGS: Significant strides have been made in interacting with people living with SCI to help identify the problem(s) that are important to study (i.e. the first step in the research process). The SCI research field is lagging in partnering with people living with SCI throughout the rest of the research process despite a plethora of evidence-based principles and strategies for effective partnerships in the broader context of research. There are several emerging resources specific to SCI to help researchers and the community begin to build meaningful partnerships throughout the entire cycle of research. SUMMARY: The SCI research field already values partnerships with clinicians and promotes the concept of 'bench-to-bedside and back again'. Now is the time to take it a step further to 'bench-to-bedside-to-community and back again'.

Barriers and Facilitators to Optimal Neuropathic Pain Management: SCI Consumer, Significant Other, and Health Care Provider Perspectives.

OBJECTIVE: Persistent neuropathic pain is a common and often severe consequence of spinal cord injury (SCI). There is a critical need to better understand how to overcome barriers and promote facilitators to optimal pain management. The present study was designed to identify, from the perspectives of persons living with SCI, their significant others, and SCI health care professionals, the barriers and facilitators to optimal pain management for intense neuropathic pain. DESIGN: Qualitative interviews. SETTING: University laboratory. SUBJECTS: People with SCI who had experienced intense neuropathic pain for a minimum of a year (N = 15), their significant others (N = 15), and SCI health care providers (N = 15). METHODS: Qualitative interviews were recorded, transcribed, and analyzed based on grounded theory using ATLAS.ti software. RESULTS: Inadequate access to care, information, or pain management expertise were frequently perceived barriers to optimal pain management across all three groups. Another major barrier was SCI stakeholders' concerns regarding the risks of adverse effects and addiction to pain medication. Facilitators included having a better understanding of pain and available treatment options, effective patient-provider communication, resilience, and access to nonpharmacological treatment options. CONCLUSIONS: Managing intense neuropathic pain poses significant challenges after SCI. SCI stakeholders felt that accessible treatment options were limited and primarily focused on pain medications with minimal benefit but with significant risks for addiction and adverse effects. Actionable facilitators to optimal pain management after SCI include education regarding neuropathic pain and treatment options for all stakeholders, better communication regarding neuropathic pain among stakeholders, and improved patient access to nonpharmacological treatment options.

Replication and novel analysis of age and sex effects on the neurologic and functional value of each spinal segment in the US healthcare setting.

STUDY DESIGN: Replication of previously developed prognostic model. OBJECTIVES: In motor complete injuries at admission to rehabilitation, perform; (1) replication analyses of the relationships between ISNCSCI motor level and motor scores and SCIM and (2) novel analyses to determine if age and/or sex moderate relationship between neurological impairment and function. SETTING: Admission to initial inpatient rehabilitation in the United States. METHODS: Post-Hoc analyses of data collected as part of a separate study. Replication analyses: (1) Pearson's correlation assessed relationship strength between neurologic impairment and function. (2) Multiple linear regression assessed if center or age influenced functional outcome. Novel analyses: (1) Moderated multiple regression assessed if age and/or sex moderated the lesion level-function relationship. RESULTS: Of the 406 datasets, 161 were motor complete injuries, and included in the analyses. Median time post injury at admission to rehabilitation was 19 days. Our replication analyses confirmed the neurologic and functional value of each spinal segment reported by the EM-SCI group (all p ≤ 0.018). We failed to confirm their reported age effect (p = 0.05) and non-effect of center (p = 0.037). Our novel analyses indicated that age coded as above/below 50 moderated the relationship between neurologic impairment and function (p = 0.038) in cervical injuries only, but that age coded as above/below 35 (all p ≥ 0.510) and sex (all p ≥ 0.465) did not. CONCLUSIONS: The neurological and functional value of each segment is consistent across very different healthcare settings in early and late sub-acute stages and minimally impacted by age and sex. Differences related to centers and age may confound efficacy trials. SPONSORSHIP: The Miami Project to Cure Paralysis; The Craig H. Neilsen Foundation (83492).

Imaging characteristics of chronic spinal cord injury identified during screening for a cell transplantation clinical trial.

OBJECTIVEIn cell transplantation trials for spinal cord injury (SCI), quantifiable imaging criteria that serve as inclusion criteria are important in trial design. The authors' institutional experience has demonstrated an overall high rate of screen failures. The authors examined the causes for trial exclusion in a phase I, open-lab clinical trial examining the role of autologous Schwann cell intramedullary transplantation. Specifically, they reviewed the imaging characteristics in people with chronic SCI that excluded applicants from the trial, as this was a common cause of screening failures in their study.METHODSThe authors reviewed MRI records from 152 people with chronic (> 1 year) SCI who volunteered for intralesional Schwann cell transplantation but were deemed ineligible by prospectively defined criteria. Rostral-caudal injury lesion length was measured along the long axis of the spinal cord in the sagittal plane on T2-weighted MRI. Other lesion characteristics, specifically those pertaining to lesion cavity structure resulting in trial exclusion, were recorded.RESULTSImaging records from 152 potential participants with chronic SCI were reviewed, 42 with thoracic-level SCI and 110 with cervical-level SCI. Twenty-three individuals (55%) with thoracic SCI and 70 (64%) with cervical SCI were not enrolled in the trial based on imaging characteristics. For potential participants with thoracic injuries who did not meet the screening criteria for enrollment, the average rostral-caudal sagittal lesion length was 50 mm (SD 41 mm). In applicants with cervical injuries who did not meet the screening criteria for enrollment, the average sagittal lesion length was 34 mm (SD 21 mm).CONCLUSIONSWhile screening people with SCI for participation in a cell transplantation clinical trial, lesion length or volume can exclude potential subjects who appear appropriate candidates based on neurological eligibility criteria. In planning future cell-based therapy trials, the limitations incurred by lesion size should be considered early due to the screening burden and impact on candidate selection.

Considerations and recommendations for selection and utilization of upper extremity clinical outcome assessments in human spinal cord injury trials.

STUDY DESIGN: This is a focused review article. OBJECTIVES: This review presents important features of clinical outcomes assessments (COAs) in human spinal cord injury research. Considerations for COAs by trial phase and International Classification of Functioning, Disability and Health are presented as well as strengths and recommendations for upper extremity COAs for research. Clinical trial tools and designs to address recruitment challenges are identified. METHODS: The methods include a summary of topics discussed during a two-day workshop, conceptual discussion of upper extremity COAs and additional focused literature review. RESULTS: COAs must be appropriate to trial phase and particularly in mid-late-phase trials, should reflect recovery vs. compensation, as well as being clinically meaningful. The impact and extent of upper vs. lower motoneuron disease should be considered, as this may affect how an individual may respond to a given therapeutic. For trials with broad inclusion criteria, the content of COAs should cover all severities and levels of SCI. Specific measures to assess upper extremity function as well as more comprehensive COAs are under development. In addition to appropriate use of COAs, methods to increase recruitment, such as adaptive trial designs and prognostic modeling to prospectively stratify heterogeneous populations into appropriate cohorts should be considered. CONCLUSIONS: With an increasing number of clinical trials focusing on improving upper extremity function, it is essential to consider a range of factors when choosing a COA. SPONSORS: Craig H. Neilsen Foundation, Spinal Cord Outcomes Partnership Endeavor.

First human experience with autologous Schwann cells to supplement sciatic nerve repair: report of 2 cases with long-term follow-up.

OBJECTIVE Long-segment injuries to large peripheral nerves present a challenge to surgeons because insufficient donor tissue limits repair. Multiple supplemental approaches have been investigated, including the use of Schwann cells (SCs). The authors present the first 2 cases using autologous SCs to supplement a peripheral nerve graft repair in humans with long-term follow-up data. METHODS Two patients were enrolled in an FDA-approved trial to assess the safety of using expanded populations of autologous SCs to supplement the repair of long-segment injuries to the sciatic nerve. The mechanism of injury included a boat propeller and a gunshot wound. The SCs were obtained from both the sural nerve and damaged sciatic nerve stump. The SCs were expanded and purified in culture by using heregulin ß1 and forskolin. Repair was performed with sural nerve grafts, SCs in suspension, and a Duragen graft to house the construct. Follow-up was 36 and 12 months for the patients in Cases 1 and 2, respectively. RESULTS The patient in Case 1 had a boat propeller injury with complete transection of both sciatic divisions at midthigh. The graft length was approximately 7.5 cm. In the postoperative period the patient regained motor function (Medical Research Council [MRC] Grade 5/5) in the tibial distribution, with partial function in peroneal distribution (MRC Grade 2/5 on dorsiflexion). Partial return of sensory function was also achieved, and neuropathic pain was completely resolved. The patient in Case 2 sustained a gunshot wound to the leg, with partial disruption of the tibial division of the sciatic nerve at the midthigh. The graft length was 5 cm. Postoperatively the patient regained complete motor function of the tibial nerve, with partial return of sensation. Long-term follow-up with both MRI and ultrasound demonstrated nerve graft continuity and the absence of tumor formation at the repair site. CONCLUSIONS Presented here are the first 2 cases in which autologous SCs were used to supplement human peripheral nerve repair in long-segment injury. Both patients had significant improvement in both motor and sensory function with correlative imaging. This study demonstrates preliminary safety and efficacy of SC transplantation for peripheral nerve repair.

Rehabilitation Professionals' Perspectives on Human Rights, Disability, and Science: A Qualitative Study.

Objective: To investigate the attitudes and knowledge of rehabilitation professionals concerning human rights within the context of disability, science, and technology access. Design: A qualitative study using in-depth semi-structured interviews. Setting: A large, urban, academically-affiliated rehabilitation research center. Participants: We conducted semi-structured interviews with rehabilitation professionals who specialize in spinal cord injury (SCI) care, including 6 physicians, 3 physical therapists, 2 occupational therapists, 2 nurses, 1 rehabilitation engineer, and 1 rehabilitation psychologist (N=15). Participants were purposively recruited through e-mail letters to members of the American Spinal Injury Association. Efforts were made to recruit a diverse cohort of rehabilitation professionals based on profession, sex, age, and race. Interviews were conducted in person during the 2018 annual meeting or by phone after the meeting. Interventions: Not applicable. Main Outcome Measures: Interviews were recorded, transcribed verbatim, and coded to identify emerging themes within and across participants' content. Results: Primary findings show that most respondents were unaware of disability-relevant human rights doctrine. None was aware of the right to science as articulated in Article 15 of the International Covenant on Economic, Social, and Cultural Rights. Only 2 respondents had previously considered injustices experienced by their clients as human rights violations, yet nearly all were intrigued by framing access difficulties within the right to science paradigm. Overall, participants reported they would find value in implementing human rights in their work. Conclusions: Rehabilitation professionals are receptive to a human rights framework. Further research is needed to identify actionable steps for implementing principles of human rights to increase access to technology by individuals with SCI.

Priorities, needs and willingness of use of nerve stimulation devices for bladder and bowel function in people with spinal cord injury (SCI): an Australian survey.

STUDY DESIGN: Anonymous online survey OBJECTIVES: To investigate the priorities, needs and willingness to adopt nerve stimulation devices for managing neurogenic bladder and bowel function in people with spinal cord injury (SCI) living in Australia. SETTING: Online survey of people living with SCI in Australia. METHODS: This anonymous online survey used Qualtrics and was advertised via standard communication channels, such as advocacy groups representing the SCI community in Australia, social media, attending SCI sporting events and by word-of-mouth. RESULTS: Responses from 62 individuals (32% female, 68% male) were included. Bladder emptying through urethra without catheter was the highest priority for bladder function. Reducing time required for bowel routines and constipation were the top priorities regarding bowel function. The highest concern for internal/implanted devices was the 4% chance of device surgical removal, while wearing wires under the clothes was the main concern for external devices. 53% of respondents were willing to trial an implanted nerve stimulation device, while 70% would trial an external device to improve and gain independence in bladder and bowel function. CONCLUSION: The findings of this study highlighted the potential role in which nerve stimulation can have in addressing bladder and bowel dysfunction in people with SCI, and have also identified that there was a need for Australian physiotherapists to evaluate their role in bladder and bowel dysfunction. Results from this study can help guide further research in nerve stimulation devices for bladder and bowel dysfunction in people with SCI. SPONSORSHIP: n/a.

Perspectives of people with spinal cord injury on a pain education resource.

Introduction: Spinal cord injury (SCI) often leads to neuropathic pain that negatively affects quality of life. Several qualitative research studies in individuals with SCI who experience neuropathic pain indicate the lack of adequate information about pain. We previously developed an educational resource, the SeePain, based on scientific literature and a series of qualitative interviews of people with SCI, their significant others/family members, and SCI healthcare providers. Methods: However, to quantitatively evaluate the utility of this educational resource in a larger sample, we examined the agreement and usefulness ratings of statements regarding clarity/comprehensibility, content, and format of the SeePain, derived from the thematic analysis of our previous qualitative interviews. Participants completed a survey that provided a digital version of the SeePain and then rated their agreement/usefulness with the statements using numerical rating scales. Results: There were overall high perceived agreement and usefulness ratings regarding the SeePain's clarity, content, and format. A factor analysis reduced the agreement and usefulness ratings into 4 components (content, clarity, format, and delivery medium). Group comparisons showed that individuals with higher education were more likely to endorse electronic and website formats, and the usefulness of a shorter version of the SeePain; females and younger individuals showed greater endorsement for clarity. Finally, higher pain intensity ratings were associated with greater agreement and usefulness of the content of the SeePain. Discussion: Overall, these results support the utility of the SeePain as a source of information regarding pain that may facilitate communication about pain and its management following SCI.

Reliability of the International Spinal Cord Injury Physical Therapy-Occupational Therapy Basic Data Set.

In interventional clinical trials for persons with spinal cord injury (SCI), the influence of experimental biological, pharmacological, or device-related interventions must be differentiated from that of physical and occupational therapy interventions, as rehabilitation influences motor-related outcomes. The International Spinal Cord Injury (ISCI) Physical Therapy-Occupational Therapy Basic Data Set (PT-OT BDS) was developed with the intent to track the content and time of rehabilitation interventions that are delivered concurrently with experimental interventions. We assessed the reliability of the PT-OT BDS based on agreement between users. Following an online training session, physical therapists (PTs) and occupational therapists (OTs) from 10 SCI clinical centers across 7 countries participated. At each center, pairs of therapists (a treating therapist and an observing therapist; PT/PT, OT/OT, or PT/OT) used the PT-OT BDS to record the content and time of therapy sessions for 20 patients. Data were analyzed to determine agreement between therapist pairs regarding the content of the therapy session. The influence of therapist characteristics (professional discipline [PT/OT], years of experience working with individuals with SCI), patient characteristics (level [tetraplegia/paraplegia] and severity [complete/incomplete] of injury), setting (inpatient/outpatient), and whether the center was U.S.- versus non-U.S.-based were also analyzed. There was high agreement for five of seven categories and medium agreement for the remaining two categories. For six of the seven intervention categories, there were no significant differences between the treating and the observing therapists in the percentage of instances that a specific category was selected. Characteristics of the therapists, characteristics of the patient, therapy setting, and global location of the center had no meaningful influence on level of agreement between therapist pairs. The BDS is reliable for use across settings, countries, and with patients of various impairment levels. The study also helped identify additional areas where refinement of the syllabus would be of value.

Including People with Spinal Cord Injury in Research as Participants, Partners, and Personnel.

Individuals with disabilities are significantly underrepresented in research and are often not included in discussions on diversity, equity, inclusion, and accessibility. The Advisory Committee to the National Institutes of Health Director Working Group on Diversity formed an ad hoc Subgroup on Individuals with Disabilities to develop recommendations on how to enhance the inclusion of people with disabilities in the scientific workforce as well as throughout the research ecosystem. The article summarizes those recommendations and how they came about, then contextualizes them for the spinal cord injury (SCI) research field. Other fields that do not typically include individuals with disabilities in research can learn from the strong history of including people with SCI as research participants. There has been a growing drive within our field to enhance the inclusion of people living with SCI as research partners, but how are we doing with promoting their inclusion in the scientific workforce?

Multi-center, single-blind randomized controlled trial comparing functional electrical stimulation therapy to conventional therapy in incomplete tetraplegia.

Background: Loss of upper extremity function after tetraplegia results in significant disability. Emerging evidence from pilot studies suggests that functional electrical stimulation (FES) therapy may enhance recovery of upper extremity function after tetraplegia. The aim of this trial was to determine the effectiveness of FES therapy delivered by the Myndmove stimulator in people with tetraplegia. Methods: A multi-center, single-blind, parallel-group, two-arm, randomized controlled trial was conducted comparing FES to conventional therapy in adults (≥18 years) with C4-C7 traumatic incomplete tetraplegia between 4 and 96 months post-injury, and with a baseline spinal cord injury independence measure III -self-care (SCIM III-SC) score of ≤10. Participants were enrolled at four SCI-specialized neurorehabilitation centers in the U.S. and Canada. Participants were stratified by center and randomized in a 1:1 ratio to receive either 40 sessions of FES or conventional therapy targeting upper extremities over a 14-week period. Blinded assessors measured SCIM III, Toronto Rehabilitation Institute Hand Function Test, and Graded Redefined Assessment of Strength, Sensibility, and Prehension at baseline, after 20th session, after 40th session or 14 weeks after 1st session, and at 24 weeks after 1st session. The primary outcome measure was change in SCIM III-SC from baseline to end of the treatment. Based on the primary outcome measure, a sample size of 60 was calculated. Seventeen participants' progress in the study was interrupted due to the COVID-19 lockdown. The protocol was modified for these participants to allow them to complete the study. Results: Between June 2019 to August 2021, 51 participants were randomized to FES (n = 27) and conventional therapy (n = 24). Both groups gained a mean of 2 points in SCIM-SC scores at the end of treatment, which was a clinically meaningful change. However, there was no statistically significant difference between the groups on any outcomes. Conclusion: Forty sessions of FES therapy delivered by the MyndMove stimulator are as effective as conventional therapy in producing meaningful functional improvements that persist after therapy is completed. Limitations of this study include the impact of COVID-19 limiting the ability to recruit the target sample size and per-protocol execution of the study in one-third of the participants. Registration: This trial is registered at www.ClinicalTrials.gov, NCT03439319.

Feasibility of gabapentin as an intervention for neurorecovery after an acute spinal cord injury: Protocol.

Introduction: This protocol is describing the first ever prospective, mock-efficacy, dose exploration trial design testing the feasibility of administering gabapentin in the acute setting as an intervention for neurorecovery. Gabapentin is an FDA-approved medication for treating seizures and postherpetic neuralgia and is used broadly off-label for neuropathic pain management for many conditions, including spinal cord injury. Emerging data suggests that when given early after spinal cord injury onset and in low-medium doses, gabapentin may have properties that promote recovery of neurological function. The objective of this trial is to assess the feasibility of conducting an efficacy trial in which gabapentin is started early after injury, is restricted in its dose, and is not used for pain management. Methods and analysis: Forty-two people aged 18 years or older with any level and any severity of spinal cord injury induced by a trauma will be enrolled, randomized, and have the first dose of study medication by 120 h post-injury onset. Participants will be randomly assigned to one of three groups: 600, 1,800 mg/day gabapentin, or placebo. Study medication will be given for a 90-day duration. Blinded assessments will be obtained at 7 days post-injury (baseline), 30 days post-injury (interim), after the 90-day treatment duration/approximately 3 months post-injury (end of treatment), and at 6 months post-injury (end of study). The key analysis parameters will evaluate feasibility of recruitment of target population, delivery of drug treatment protocol, maintenance of blinding, and retention of participants. Discussion: Outputs from this trial will inform research and clinical practice on the effects of manipulating gabapentin for non-pain management purposes in the acute setting and will guide the development of a properly powered efficacy trial of gabapentin as an intervention for neurorecovery in spinal cord injury. Ethics and dissemination: The study was approved by the MetroHealth Institutional Review Board (IRB21-00609) and registered at clinicaltrials.gov prior to enrolling any participants. Dissemination will include peer-reviewed publications, presentations at professional conferences and in the community, and through other healthcare and public venues. Clinical trial registration: www.ClinicalTrials.gov, identifier: NCT05302999; protocol version 1.1 approved 05/23/2022. Trial funding: National Institute on Disability, Independent Living and Rehabilitation Research.

Scalable culture techniques to generate large numbers of purified human Schwann cells for clinical trials in human spinal cord and peripheral nerve injuries.

OBJECTIVE: Schwann cells (SCs) have been shown to play an essential role in axon regeneration in both peripheral nerve injuries (PNIs) and spinal cord injuries (SCIs). The transplantation of SCs as an adjunctive therapy is currently under investigation in human clinical trials due to their regenerative capacity. Therefore, a reliable method for procuring large quantities of SCs from peripheral nerves is necessary. This paper presents a well-developed, validated, and optimized manufacturing protocol for clinical-grade SCs that are compliant with Current Good Manufacturing Practices (CGMPs). METHODS: The authors evaluated the SC culture manufacturing data from 18 clinical trial participants who were recruited for autologous SC transplantation due to subacute SCI (n = 7), chronic SCI (n = 8), or PNIs (n = 3). To initiate autologous SC cultures, a mean nerve length of 11.8 ± 3.7 cm was harvested either from the sural nerve alone (n = 17) or with the sciatic nerve (n = 1). The nerves were digested with enzymes and SCs were isolated and further expanded in multiple passages to meet the dose requirements for transplantation. RESULTS: An average yield of 87.2 ± 89.2 million cells at P2 and 150.9 ± 129.9 million cells at P3 with high viability and purity was produced. Cell counts and rates of expansion increased with each subsequent passage from P0 to P3, with the largest rate of expansion between P2 and P3. Larger harvest nerve lengths correlated significantly with greater yields at P0 and P1 (p < 0.05). In addition, a viability and purity above 90% was sustained throughout all passages in nearly all cell products. CONCLUSIONS: This study presents reliable CGMP-compliant manufacturing methods for autologous SC products that are suitable for regenerative treatment of patients with SCI, PNI, or other conditions.

Phase 1 Safety Trial of Autologous Human Schwann Cell Transplantation in Chronic Spinal Cord Injury.

A phase 1 open-label, non-randomized clinical trial was conducted to determine feasibility and safety of autologous human Schwann cell (ahSC) transplantation accompanied by rehabilitation in participants with chronic spinal cord injury (SCI). Magnetic resonance imaging (MRI) was used to screen eligible participants to estimate an individualized volume of cell suspension to be implanted. The trial incorporated standardized multi-modal rehabilitation before and after cell delivery. Participants underwent sural nerve harvest, and ahSCs were isolated and propagated in culture. The dose of culture-expanded ahSCs injected into the chronic spinal cord lesion of each individual followed a cavity-filling volume approach. Primary outcome measures for safety and trend-toward efficacy were assessed. Two participants with American Spinal Injury Association Impairment Scale (AIS) A and two participants with incomplete chronic SCI (AIS B, C) were each enrolled in cervical and thoracic SCI cohorts (n = 8 total). All participants completed the study per protocol, and no serious adverse events related to sural nerve harvest or ahSC transplantation were reported. Urinary tract infections and skin abrasions were the most common adverse events reported. One participant experienced a 4-point improvement in motor function, a 6-point improvement in sensory function, and a 1-level improvement in neurological level of injury. Follow-up MRI in the cervical (6 months) and thoracic (24 months) cohorts revealed a reduction in cyst volume after transplantation with reduced effect over time. This phase 1 trial demonstrated the feasibility and safety of ahSC transplantation combined with a multi-modal rehabilitation protocol for participants with chronic SCI.

A Randomized Controlled Trial of Local Delivery of a Rho Inhibitor (VX-210) in Patients with Acute Traumatic Cervical Spinal Cord Injury.

Acute traumatic spinal cord injury (SCI) can result in severe, lifelong neurological deficits. After SCI, Rho activation contributes to collapse of axonal growth cones, failure of axonal regeneration, and neuronal loss. This randomized, double-blind, placebo-controlled phase 2b/3 study evaluated the efficacy and safety of Rho inhibitor VX-210 (9 mg) in patients after acute traumatic cervical SCI. The study enrolled patients 14-75 years of age with acute traumatic cervical SCIs, C4-C7 (motor level) on each side, and American Spinal Injury Association Impairment Scale (AIS) Grade A or B who had spinal decompression/stabilization surgery commencing within 72 h after injury. Patients were randomized 1:1 with stratification by age (<30 vs. ≥30 years) and AIS grade (A vs. B with sacral pinprick preservation vs. B without sacral pinprick preservation). A single dose of VX-210 or placebo in fibrin sealant was administered topically onto the dura over the site of injury during decompression/stabilization surgery. Patients were evaluated for medical, neurological, and functional changes, and serum was collected for pharmacokinetics and immunological analyses. Patients were followed up for up to 12 months after treatment. A planned interim efficacy-based futility analysis was conducted after ∼33% of patients were enrolled. The pre-defined futility stopping rule was met, and the study was therefore ended prematurely. In the final analysis, the primary efficacy end-point was not met, with no statistically significant difference in change from baseline in upper-extremity motor score at 6 months after treatment between the VX-210 (9-mg) and placebo groups. This work opens the door to further improvements in the design and conduct of clinical trials in acute SCI.

A Primary Care Provider's Guide to Pain After Spinal Cord Injury: Screening and Management.

Individuals with spinal cord injury (SCI) often experience chronic pain as a secondary complication. It can significantly impair mental health, sleep, mood, and overall quality of life. It is important for providers within a primary care setting to recognize the different types of pain such as nociceptive and neuropathic. Various assessment tools are available to guide proper classification and subsequent management. Providers need to have a good knowledge base, structure, and patient focus when managing care. Nonpharmacological interventions are just as important and should be explored prior to or along with pharmacological interventions. Treatment modalities such as physical therapy, exercise, acupuncture, and cognitive behavioral therapy should be tailored to the individual to the greatest extent possible. Gabapentin, pregabalin, and amitriptyline have been studied extensively and are the first-line pharmacological agents for neuropathic pain. It is important to involve patients as equal stakeholders in any pain intervention with adequate lifelong follow-up. The aim of this article is to offer an overview of pain assessment, information, patient interaction, and treatment options available. Although chronic pain has remained difficult to treat successfully, primary care providers can play an integral role in delivering evidence-based and patient-centered care for managing chronic pain among individuals with SCI.