A Systematic Review of Safety Reporting in Acute Spinal Cord Injury Clinical Trials: Challenges and Recommendations.

Accurate safety information in published clinical trials guides the assessment of risk-benefit, as well as the design of future clinical trials. Comprehensive reporting of adverse events, toxicity, and discontinuations from acute spinal cord injury clinical trials is an essential step in this process. Here, we sought to assess the degree of "satisfactoriness" of reporting in past clinical trials in spinal cord injury. A review of citations from MEDLINE and EMBASE identified eligible clinical trials in acute (within 30 days) spinal cord injury. English language studies, published between 1980 and 2020, with sensory, motor, or autonomic neurological assessments as the primary outcome measure were eligible for inclusion. Criteria were then established to qualify the safety reporting as satisfactory (i.e., distinguished severe/life-threatening events), partially satisfactory, or unsatisfactory (i.e., only mentioned in general statements, or reported but without distinguishing severe events). A total of 40 trials were included. Satisfactory reporting for clinical adverse events was observed in 30% of trials; partially satisfactory was achieved by 10% of the trials, and the remaining 60% were unsatisfactory. The majority of trials were determined to be unsatisfactory for the reporting of laboratory-defined toxicity (82.5%); only 17.5% were satisfactory. Discontinuations were satisfactorily reported for the majority of trials (80%), with the remaining partially satisfactory (5%) or unsatisfactory (15%). Reporting of safety in clinical trials for acute spinal cord injury is suboptimal. Due to the complexities of acute spinal cord injury (e.g., polytrauma, multiple systems affected), tailored and specific standards for tracking adverse events and safety reporting should be established.

Lower extremity outcome measures: considerations for clinical trials in spinal cord injury.

STUDY DESIGN: This is a focused review article. OBJECTIVES: To identify important concepts in lower extremity (LE) assessment with a focus on locomotor outcomes and provide guidance on how existing outcome measurement tools may be best used to assess experimental therapies in spinal cord injury (SCI). The emphasis lies on LE outcomes in individuals with complete and incomplete SCI in Phase II-III trials. METHODS: This review includes a summary of topics discussed during a workshop focusing on LE function in SCI, conceptual discussion of corresponding outcome measures and additional focused literature review. RESULTS: There are a number of sensitive, accurate, and responsive outcome tools measuring both quantitative and qualitative aspects of LE function. However, in trials with individuals with very acute injuries, a baseline assessment of the primary (or secondary) LE outcome measure is often not feasible. CONCLUSION: There is no single outcome measure to assess all individuals with SCI that can be used to monitor changes in LE function regardless of severity and level of injury. Surrogate markers have to be used to assess LE function in individuals with severe SCI. However, it is generally agreed that a direct measurement of the performance for an appropriate functional activity supersedes any surrogate marker. LE assessments have to be refined so they can be used across all time points after SCI, regardless of the level or severity of spinal injury. SPONSORS: Craig H. Neilsen Foundation, Spinal Cord Outcomes Partnership Endeavor.

Dorsal root entry zone microcoagulation for spinal cord injury-related central pain: operative intramedullary electrophysiological guidance and clinical outcome.

OBJECT: Surgically created lesions of the spinal cord dorsal root entry zone (DREZ) to relieve central pain after spinal cord injury (SCI) have historically resulted in modest outcomes. A review of the literature indicates that fair to good relief of pain is achieved in approximately 50% of patients when an empirical procedure is performed. This study was undertaken to determine if intramedullary electrical guidance in DREZ lesioning could improve outcomes in patients with SCI-induced central pain. Additionally, electrical data were used to determine if the spinal cord could be somatotopically mapped with regard to this pain of central origin. METHODS: Forty-one patients with traumatic SCI and intractable central pain underwent DREZ lesioning in which intramedullary electrical guidance was conducted. In nine patients, recording of DREZ-related spontaneous electrical hyperactivity guided the lesioning process. In 32 patients, recording of DREZ-induced evoked electrical hyperactivity during transcutaneous C-fiber stimulation (TCS) additionally guided lesioning. The follow-up period ranged from 1 to 7 years. The analyzed electrical data allowed for somatotopic mapping of the spinal cord. CONCLUSIONS: Intramedullary electrical guidance of DREZ lesioning substantially improves pain outcomes in patients with traumatic SCI-induced central pain, compared with an empiric technique. The best outcome occurs when DREZ-related spontaneous electrical hyperactivity and evoked hyperactivity during TCS are both used to guide the DREZ lesioning procedure. With such guidance, 100% relief of pain was achieved in 84% of patients and 50 to 100% relief of pain in 88%. Somatotopic mapping of the electrical data led to a proposed pain mechanism for below-level pain, implicating the sympathetic nervous system.