Acute Spinal Cord Injury Study Research Articles

Protocol for the Chinese Real-World Evidence for Acute Spinal Cord Injury (ChiRES) study: a prospective, observational, multicentre cohort study of acute spinal cord injury

IntroductionSpinal cord injury (SCI) is a catastrophic event with devastating physical, social and occupational consequences for patients and their families. The number of patients with acute SCI in China continues...

Racial and Ethnical Discrepancies and Similarities in the Epidemiology, Survival, and Neurological Outcomes After Acute Traumatic Spinal Cord Injury: A Retrospective Cohort Study Using Data from the NASCIS-1 Trial.

Little is known about the impact of race/ethnicity on the clinical and neurological outcomes after acute traumatic spinal cord injury (tSCI). This study examined the influence of race/ethnicity on the individuals' survival and neurological recovery within the first year after tSCI. The 306 cases enrolled in the First National Acute Spinal Cord Injury Study (NASCIS-1) were grouped as African American individuals (n = 84), non-Hispanic White individuals (n = 159), and other races/ethnicities that included Hispanic individuals (n = 60) and Asian individuals (n = 3). Outcome measures included survival and neurological recovery within the first year after tSCI. Data analyses were adjusted for major potential confounders. There were 39 females and 267 males with mean age of 31 years who mostly sustained cervical severe tSCI after motor vehicle accidents or falls. The three groups were comparable regarding sex distribution, level and severity of tSCI, level of consciousness at admission, and total received dose of methylprednisolone. African American individuals were significantly older than non-Hispanic White individuals (p = .0238). African American individuals and individuals of other races/ethnicities more often had a tSCI with open wound caused by missile and water-related accidents than non-Hispanic White individuals (p < .0001). Survival rates within the first year after tSCI were comparable among the three groups (p = .3191). Among the survivors, there were no significant differences among the three groups regarding motor and pinprick and light-touch sensory recovery (p > .0500). The results of this study suggest that, while there were few differences among the racial/ethnical groups regarding the epidemiology of tSCI, race/ethnicity did not influence survival rate or neurological recovery within the first year post-tSCI.

An Introduction to the North American Clinical Trials Network for Spinal Cord Injury Special Edition: Reflections on Accomplishments and a Look to the Future.

The North American Clinical Trials Network (NACTN) has been established as a network of translational clinical research centers focused on traumatic spinal cord injury (SCI) with the goals of facilitating clinical translational research, promotion of enhanced clinical care protocols including the principle of early surgery for SCI, and improving outcomes for individuals with acute SCI. Since its foundation in 2004 by Dr. Robert Grossman, NACTN has evolved into a powerful multi-stakeholder consortium of eight neurosurgical department faculties at university-affiliated institutions in the United States and Canada, a data management center, and a pharmacological center. To date, high-quality data from more than 1000 patients have been prospectively collected, providing us with a strong body of evidence surrounding SCI epidemiology, the natural history, and complications of acute and subacute SCI management. Key accomplishments of NACTN are summarized in this Focus issue. They include the launch, in collaboration with AO Spine, of the international, multi-center, placebo-controlled, Phase III Riluzole in Acute Spinal Cord Injury Study (RISCIS) that recruited 192 patients. While the primary analyses did not achieve the predetermined endpoint of efficacy for Riluzole, likely related to insufficient power, pre-planned secondary analyses demonstrated that all subgroups of cervical SCI subjects (AIS grades A, B and C) treated with Riluzole showed significant gains in functional recovery. The Focus Issue also includes a detailed analysis of the pharmacokinetics and pharmacodynamics of riluzole in the setting of acute SCI (RISCIS-PK study). Additional achievements include key contributions to the evidence supporting the role of early surgery in acute SCI, and a better understanding of the impact of complications on the outcomes of SCI. Future directions of NACTN will build on past accomplishments and focus on enhanced collaborations with other SCI networks, advanced analytics to examine large datasets, and a greater focus on chronic SCI.

Safety and Efficacy of Riluzole in Acute Spinal Cord Injury Study (RISCIS): A Multi-Center, Randomized, Placebo-Controlled, Double-Blinded Trial.

Riluzole is a sodium-glutamate antagonist that attenuates neurodegeneration in amyotrophic lateral sclerosis (ALS). It has shown favorable results in promoting recovery in pre-clinical models of traumatic spinal cord injury (tSCI) and in early phase clinical trials. This study aimed to evaluate the efficacy and safety of riluzole in acute cervical tSCI. An international, multi-center, prospective, randomized, double-blinded, placebo-controlled, adaptive, Phase III trial (NCT01597518) was undertaken. Patients with American Spinal Injury Association Impairment Scale (AIS) A-C, cervical (C4-C8) tSCI, and <12 h from injury were randomized to receive either riluzole, at an oral dose of 100 mg twice per day (BID) for the first 24 h followed by 50 mg BID for the following 13 days, or placebo. The primary efficacy end-point was change in Upper Extremity Motor (UEM) scores at 180 days. The primary efficacy analyses were conducted on an intention to treat (ITT) and completed cases (CC) basis. The study was powered at a planned enrolment of 351 patients. The trial began in October 2013 and was halted by the sponsor on May 2020 (and terminated in April 2021) in the face of the global COVID-19 pandemic. One hundred ninety-three patients (54.9% of the pre-planned enrolment) were randomized with a follow-up rate of 82.7% at 180 days. At 180 days, in the CC population the riluzole-treated patients compared with placebo had a mean gain of 1.76 UEM scores (95% confidence interval: -2.54-6.06) and 2.86 total motor scores (CI: -6.79-12.52). No drug-related serious adverse events were associated with the use of riluzole. Additional pre-planned sensitivity analyses revealed that in the AIS C population, riluzole was associated with significant improvement in total motor scores (estimate: standard error [SE] 8.0; CI 1.5-14.4) and upper extremity motor scores (SE 13.8; CI 3.1-24.5) at 6 months. AIS B patients had higher reported independence, measured by the Spinal Cord Independence Measure score (45.3 vs. 27.3; d: 18.0 CI: -1.7-38.0) and change in mental health scores, measured by the Short Form 36 mental health domain (2.01 vs. -11.58; d: 13.2 CI: 1.2-24.8) at 180 days. AIS A patients who received riluzole had a higher average gain in neurological levels at 6 months compared with placebo (mean 0.50 levels gained vs. 0.12 in placebo; d: 0.38, CI: -0.2-0.9). The primary analysis did not achieve the predetermined end-point of efficacy for riluzole, likely related to insufficient power. However, on pre-planned secondary analyses, all subgroups of cervical SCI subjects (AIS grades A, B and C) treated with riluzole showed significant gains in functional recovery. The results of this trial may warrant further investigation to extend these findings. Moreover, guideline development groups may wish to assess the possible clinical relevance of the secondary outcome analyses, in light of the fact that SCI is an uncommon orphan disorder without an accepted neuroprotective treatment.

186 A Multi-Center, Randomized, Placebo-Controlled, Double-Blinded Trial of Efficacy and Safety of Riluzole in Acute Spinal Cord Injury Study (RISCIS)

INTRODUCTION: Riluzole, a sodium-glutamate antagonist which is FDA approved for ALS has shown promising pre-clinical results and is clinically safe in SCI patients. METHODS: The RISCIS trial is an international, multi-center, prospective, double-blinded, randomized, placebo-controlled Phase II/III trial. Patients with ASIA A-C, C4-C8 SCI and &lt;12 hours from injury were randomized between Riluzole, at an oral dose of 100mg BID for the first 24 hours followed by 50mg BID for the following 13 days, and placebo control. RESULTS: Due to the impact of the global COVID-19 pandemic this trial was terminated prior to completion. 193 patients were randomized with a follow-up rate of 82.7% at 180-days. No statistical difference was noted in the demographics and baseline injury characteristics between the two groups. At 6 months there was a median gain in total motor scores (TOTM) of 30.0 in the Riluzole group compared to 20.0 for the Placebo group. The improved motor outcomes did not reach statistical significance. Given the decreased sample size, additional sensitivity analyses were conducted. In the ASIA-C population, Riluzole was a significant improver of total motor scores (coefficient estimate: 14.10, p = 0.020) and upper motor scores (CE: 7.68, p = 0.040) at 6 months. ASIA B patients had higher reported independence, as measured by the SCIM score (45.3 vs. 27.3; p = 0.071) and change in mental health scores as measured by the SF-36 mental health domain (2.01 vs. -11.58; p: 0.0205) at 180 days. CONCLUSIONS: Despite the premature termination of the RISCIS trial due to the COVID-19 pandemic, 193 subjects were recruited into this trial. Primary analysis showed a 10-motor point gain in riluzole-treated subjects which did not reach significance. However, on secondary analysis, incomplete cervical SCI subjects (AIS B and C) showed significant gains in functional recovery.

Methylprednisolone in acute traumatic spinal cord injury: case-matched outcomes from the NASCIS2 and Sygen historical spinal cord injury studies with contemporary statistical analysis.

Methylprednisolone (MP) to treat acute traumatic spinal cord injury (ATSCI) remains controversial since the release of the second National Acute Spinal Cord Injury Study (NASCIS2) in 1990. As two historical studies, NASCIS2 and Sygen in ATSCI, used identical MP dosages, it was possible to construct a new case-level pooled ATSCI data set satisfying contemporary criteria and able to clarify the effect of MP. The new pooled data set was first modernized by excluding patients with injury levels caudal to T10, lower-extremity American Spinal Injury Association (ASIA) motor scores (LEMSs) ≥ 46, Glasgow Coma Scale scores ≤ 11, and age < 15 or > 75 years, and then standardized to the ASIA grading and scoring format. A new updated NASCIS2 data set from this pooled data set contained 31.6% fewer patients than the 1990 NASCIS2 data set. In the new pooled data set, recovery of LEMSs from baseline to 26 weeks, the primary outcome variable, was separated statistically into five different injury severity cohorts (p < 0.0001). The severity cohorts contained groups with severe floor (62.9%) and ceiling (10.7%) effects, which do not contribute to drug effects. The new NASCIS2 data set duplicated the p value for MP versus placebo in the sub-subgroup analysis of MP initiated ≤ 8 hours (the subgroup) and recovery of motor function on only the right side of the body (a further subgroup within the ≤ 8-hour subgroup), presented as the positive MP effect in the original NASCIS2 reporting. However, current statistical interpretation considers results seen only in post hoc sub-subgroups, without multi-test corrections, to be random effects without clinical significance. The combined case-level pooled data set from the NASCIS2 and Sygen studies increased the MP group from 106 to 431 patients, creating a new MP combined group. This new data set served as a surrogate for a contemporary MP study and found that administration of MP did not enhance ASIA motor score improvement in the lower extremities at 26 weeks. Secondary analysis of descending ASIA motor and sensory cervical neurological levels in cervical ATSCI patients at 26 weeks also found no MP drug effect. Analysis of both the new updated NASCIS2 data set and the new case-matched pooled data set from two historical ATSCI studies revealed that administration of MP after spinal cord injury did not demonstrate any enhancement in neurological recovery at 26 weeks. The results of this analysis warrant review by clinical guideline groups.

Intraoperative Sensory Signals Predict Prognosis for Patients with Traumatic Cervical Spinal Cord Injury

In patients with traumatic cervical spinal cord injury (tCSCI), the potential role of intraoperative neuromonitoring as a prognostic tool has been insufficiently studied. This study aimed to determine if detectable signals during intraoperative neuromonitoring portend a greater likelihood of recovery for patients with tCSCI. Patients who underwent decompression and surgical fixation following tCSCI were retrospectively reviewed through previously prospectively collected data from the Surgical Timing in Acute Spinal Cord Injury Study. Improvement in American Spinal Injury Association (ASIA) motor score and ASIA Impairment Scale grade conversion rates at final follow-up were compared between patients with detectable intraoperative neuromonitoring somatosensory evoked potential (SSEP) signals and those without detectable signals. Forty-nine patients had intraoperative neuromonitoring. Patients with incomplete tCSCI had detectable lower extremity SSEPs more often than patients with complete tCSCI (56.3% vs. 23.5%, P= 0.028). There was no difference in detectable upper extremity SSEPs between complete and incomplete tCSCI (65.6% vs. 58.8%, P= 0.638). Of the 17 patients with complete tCSCI, patients with detectable lower extremity SSEPs had ASIA motor scores similar to the nondetectable cohort on admission (21.5 vs. 16.2, P= 0.609) but higher ASIA motor scores at final follow-up (57.5 vs. 27.1, P= 0.041). Of the 32 patients with incomplete spinal cord injury, there was no difference in grade conversion or motor scores between detectable and nondetectable SSEP cohorts. The presence of upper extremity SSEP signals in patients who present with complete tCSCI portends greater improvement in ASIA motor scores and likelihood of American Spinal Injury Association Impairment Scale grade conversion at final follow-up.

Systemic Administration of Allogeneic Cord Blood Mononuclear Cells in Adults with Severe Acute Contusion Spinal Cord Injury: Phase 1/2a Pilot Clinical Study–Safety and Primary Efficacy Evaluation

Phase 1 of the SUBSCI I/IIa (Systemic Umbilical Cord Blood Administration in Patients with Acute Severe Contusion Spinal Cord Injury) study focused on safety and primary efficacy of multiple systemic infusions of allogeneic unrelated human umbilical cord blood mononuclear cells in patients with severe acute spinal cord contusion having severe neurologic deficit. The primary end point was safety. The secondary end point was the restoration of motor and sensory function in lower limbs within a 1-year period. Ten patients with acute contusion spinal cord injury (SCI) and American Spinal Injury Association (ASIA) level A/B deficit were enrolled into phase 1. Patients were treated with 4 infusions of group-matched and rhesus-matched cord blood samples after primary surgery within 3 days after SCI. All patients were followed up for 12 months after SCI. Safety was assessed using adverse events classification depending on severity and relation to cell therapy. Primary efficacy was assessed using dynamics of deficit (ASIA scale). The overall number of adverse events reached 419 in 10 patients. Only 2 were estimated as possibly related to cell therapy, and the remaining 417 were definitely unrelated. Both adverse events were mild and clinically insignificant. No signs of immunization were found in participants. Analysis of clinical outcomes also showed that cell therapy promotes significant functional restoration of motor function. The data obtained suggest that systemic administration of allogeneic, non-human leukocyte antigen-matched human umbilical cord blood is safe and shows primary efficacy in adults with severe acute contusion SCI and ASIA level A/B deficit.

Effects of age on survival and neurological recovery of individuals following acute traumatic spinal cord injury.

Retrospective cohort study. To evaluate the effects of older age at the time of injury on the individuals' survival and neurological recovery within the first year after acute traumatic spinal cord injury (tSCI). United States. This study included all participants enrolled into the First National Acute Spinal Cord Injury Study (NASCIS-1). Outcome measures included survival and neurological recovery (as assessed using the NASCIS motor and sensory scores) within the first year after tSCI. Data analyses of neurological recovery were adjusted for major potential confounders. The study included 39 females and 267 males with overall mean age of 31 years who mostly sustained cervical severe tSCI after motor vehicle accidents or falls. Survival rates among older individuals are significantly lower than among younger individuals within the first year following tSCI (p < 0.0001). Among who survived the first year of tSCI, there were no statistically significant difference between older survivors and younger survivors regarding motor and sensory recovery in the multiple regression analyses adjusted for major potential confounders. The results of this retrospective study suggest that older age at the injury onset is associated with lower survival rate within the first year following tSCI. However, older individuals have similar potential to recover from their initial neurological impairment to younger individuals after tSCI. The results of this study combined to the recent literature underline the need for multidisciplinary team approach to the management of the elderly with acute SCI is essential to maximize their recovery.

Journal Club: High-dose methylprednisolone for acute traumatic spinal cord injury: A meta-analysis.

Methylprednisolone is a corticosteroid medication used in acute traumatic spinal cord injury (SCI) to tackle secondary injury cascades. Its use in acute SCI has been the subject of controversy for over 30 years. The second National Acute Spinal Cord Injury Study (NASCIS-2) demonstrated a small benefit of methylprednisolone,1 though this conclusion was derived from a post hoc subgroup analysis.2 Studies that followed did not reach the same conclusion and reported potential adverse effects of the drug.3 However, the 2017 AOSpine guideline continues to recommend high-dose methylprednisolone within 8 hours postinjury,4 based on a meta-analysis with rigid inclusion criteria.5 This Journal Club article reports on a study from Liu et al.,6 who have attempted to resolve this controversy. The study provides an elegant example of meta-analytic methods and has important implications for neurologic clinical practice.

Is there any gender or age-related discrepancy in the waiting time for each step in the surgical management of acute traumatic cervical spinal cord injury?

Context/Objective: Prior studies indicate that patient’s gender and age can influence treatment choices during spine disease management. This study examines whether individual’s gender and age at injury onset influence the waiting time for each step in the surgical management of patients with acute traumatic cervical spinal cord injury (atcSCI).Design: Retrospective cohort study.Setting: Quaternary spine trauma center.Participants: This study included consecutive individuals with atcSCI admitted from August/2002 to October/2008 who were enrolled in the Surgical Trial in Acute Spinal Cord Injury Study (STASCIS).Interventions: Spinal cord decompression.Outcome Measures: Data on the periods of time for each step in the surgical management were analyzed to explore the potential effects of gender and age at injury onset.Results: There were 64 individuals with atcSCI (17 women, 47 men; age range: 18–78 years; mean age: 50.5 ± 2.1 years). Older age was associated with longer stay in the acute spine center, but this association was cofounded by major pre-existing medical co-morbidities. Age did not significantly affect the waiting time for each step in the surgical management of these individuals with atcSCI. Women underwent surgical assessment earlier than men. Gender did not influence other key steps in the surgical management.Conclusion: The study results suggest that older age at injury onset was associated with longer stay in the acute spine care center, and women had a shorter waiting time for surgical assessment than men. Nevertheless, no other age or gender bias was identified in the waiting times for the steps in the management of atcSCI.

Association of Pneumonia, Wound Infection, and Sepsis with Clinical Outcomes after Acute Traumatic Spinal Cord Injury.

Pneumonia, wound infections, and sepsis (PWS) are the leading causes of acute mortality after traumatic spinal cord injury (SCI). However, the impact of PWS on neurological and functional outcomes is largely unknown. The present study analyzed participants from the prospective North American Clinical Trials Network (NACTN) registry and the Surgical Timing in Acute SCI Study (STASCIS) for the association between PWS and functional outcome (assessed as Spinal Cord Independence Measure subscores for respiration and indoor ambulation) at 6 months post-injury. Neurological outcome was analyzed as a secondary end-point. Among 1299 participants studied, 180 (14%) developed PWS during the acute admission. Compared with those without PWS, participants with PWS were mostly male (76% vs. 86%; p = 0.007), or presented with mostly American Spinal Injury Association Impairment Scale (AIS) grade A injury (36% vs. 61%; p < 0.001). There were no statistical differences between participants with or without PWS with respect to time from injury to surgery, and administration of steroids. Dominance analysis showed injury level, baseline AIS grade, and subject pre-morbid medical status collectively accounted for 77.7% of the predicted variance of PWS. Regression analysis indicated subjects with PWS demonstrated higher odds for respiratory (odds ratio [OR] 3.91, 95% confidence interval [CI]: 1.42-10.79) and ambulatory (OR 3.94, 95% CI: 1.50-10.38) support at 6 month follow-up in adjusted analysis. This study has shown an association between PWS occurring during acute admission and poorer functional outcomes following SCI.

Worldwide Steroid Prescription for Acute Spinal Cord Injury.

Study Design:Cross-sectional study.Objectives:To continue the line of a previous publication using steroid for acute spinal cord injury (SCI) by spine surgeons from Latin America (LA) and assess the current status of methylprednisolone (MP) prescription in Europe (EU), Asia Pacific (AP), North America (NA), and Middle East (ME) to determine targets for educational activities suitable for each region.Methods:The English version of a previously published questionnaire was used to evaluate opinions about MP administration in acute SCI in LA, EU, AP, NA, and ME. This Internet-based survey was conducted by members of AOSpine. The questionnaire asked about demographic features, background with management of spine trauma patients, routine administration of MP in acute SCI, and reasons for MP administration.Results:A total of 2659 responses were obtained for the electronic questionnaire from LA, EU, AP, NA, and ME. The number of spine surgeons that treat SCI was 2206 (83%). The steroid was used by 1198 (52.9%) surgeons. The uses of MP were based predominantly on the National Acute Spinal Cord Injury Study III study (n = 595, 50%). The answers were most frequently given by spine surgeons from AP, ME, and LA. These regions presented a statistically significant difference from North America (P < .001). The number of SCI patients treated per year inversely influenced the use of MP. The higher the number of patients treated, the lower the administration rates of MP observed.Conclusions:The study identified potential targets for educational campaigns, aiming to reduce inappropriate practices of MP administration.

A Critical Examination of Subgroup Analyses: The National Acute Spinal Cord Injury Studies and Beyond.

The use of high-dose methylprednisolone for acute spinal cord injury continues to be a topic of debate. This controversy largely stems from fundamental issues in statistical interpretation of trial data, most notably subgroup analyses. The purpose of this review is to discuss important examples of improper subgroup analysis and encourage better practices in future research.

Traumatic optic neuropathy: Surgical intervention improves vision and color perception

The most common cause of traumatic optic neuropathy (TON) is indirect injury to the optic nerve, which is thought to be the result of transmitted shock from an orbital impact to the intracanalicular portion of optic nerve. Direct TON can result from penetrating injury or from bony fragments in the optic canal or orbit piercing the optic nerve. Orbital hemorrhage and optic nerve sheath hematoma can also cause TON by direct compression. There may be optic nerve avulsion and transection also. Trauma to the optic nerve rarely improves vision with best of the management. The diagnosis of TON is made clinically based on history and ophthalmic signs along with neurological investigations. The management of indirect optic nerve injury is controversial. Experimental studies of optic nerve injury have employed Corticosteroid Randomization After Significant Head injury study, National Acute Spinal Cord Injury Study (NASCIS 2 and 3) and optic canal depression surgery. Most of the therapeutic regimens have been extrapolated from the NASCIS II, which showed a statistically significant improvement in neurologic outcome (motor and sensory) in a subgroup analysis of acute spinal cord injury patients receiving a methylprednisolone 30 mg/kg bolus within 8 h of injury, followed by 5.4 mg/kg/h for 23 h, but sometimes have high death rates and other complications. Based on the studies, good results can be obtained if interventions are made within 8 h of incident and observation thereafter.

Translational Advances in the Management of Acute Spinal Cord Injury

Translational Advances in the Management of Acute Spinal Cord Injury

Efficacy and Safety of Methylprednisolone Sodium Succinate in Acute Spinal Cord Injury: A Systematic Review.

Study Design:Systematic review and meta-analysis.Objective:The objective of this study was to conduct a systematic review to assess the comparative effectiveness and safety of high-dose methylprednisolone sodium succinate (MPSS) versus no pharmacological treatment in patients with traumatic spinal cord injury (SCI).Methods:A systematic search was performed in PubMed and the Cochrane Collaboration Library for literature published between January 1956 and June 17, 2015. Included studies were critically appraised, and Grades of Recommendation Assessment, Development and Evaluation methods were used to determine the overall quality of evidence for primary outcomes. Previous systematic reviews on this topic were collated and evaluated using the Assessment of Multiple Systematic Reviews scoring system.Results:The search yielded 723 citations, 13 of which satisfied inclusion criteria. Among these, 6 were primary research articles and 7 were previous systematic reviews. Based on the included research articles, there was moderate evidence that the 24-hour NASCIS II (National Acute Spinal Cord Injury Studies) MPSS regimen has no impact on long-term neurological recovery when all postinjury time points are considered. However, there is also moderate evidence that subjects receiving the same MPSS regimen within 8 hours of injury achieve an additional 3.2 points (95% confidence interval = 0.10 to 6.33; P = .04) of motor recovery compared with patients receiving placebo or no treatment.Conclusion:Although safe to administer, a 24-hour NASCIS II MPSS regimen, when all postinjury time points are considered, has no impact on indices of long-term neurological recovery. When commenced within 8 hours of injury, however, a high-dose 24-hour regimen of MPSS confers a small positive benefit on long-term motor recovery and should be considered a treatment option for patients with SCI.

Predicting Recruitment Feasibility for Acute Spinal Cord Injury Clinical Trials in Canada Using National Registry Data.

Traumatic spinal cord injury (SCI) represents a significant burden of illness, but it is relatively uncommon and heterogeneous, making it challenging to achieve sufficient subject enrollment in clinical trials of therapeutic interventions for acute SCI. The Rick Hansen Spinal Cord Injury Registry (RHSCIR) is a national SCI Registry that enters patients with SCI from acute-care centers across Canada. To predict the feasibility of conducting clinical trials of acute SCI within Canada, we have applied the inclusion/exclusion criteria of six previously conducted SCI trials to the RHSCIR data set and generated estimates of how many Canadian persons would have been eligible theoretically for enrollment in these studies. Data for SCI cases were prospectively collected for RHSCIR at 18 acute and 13 rehabilitation sites across Canada. RHSCIR patients enrolled between 2009-2013 who met the following key criteria were included: non-penetrating traumatic SCI; received acute care at a RHSCIR site; age more than 18, less than 75 years, and had complete admission single neurological level of injury data. Inclusion and exclusion criteria for the Minocycline in Acute Spinal Cord injury (Minocycline), Riluzole, Surgical Timing in Acute Spinal Cord Injury Study (STASCIS), Cethrin, Nogo antibody study (NOGO), and Sygen studies were applied retrospectively to this data set. The numbers of patients eligible for each clinical trial were determined. There were 2166 of the initial 2714 patients (79.8%) who met the key criteria and were included in the data set. Projected annual numbers of eligible patients for each trial were: Minocycline, 117; Riluzole, 62; STASCIS, 109; Cethrin, 101; NOGO, 82; and Sygen, 70. An additional 8.0% of the sample had a major head injury (Glasgow Coma Scale [GCS] score ≤12) and would have been excluded from the trials. RHSCIR provides a comprehensive national data set that may serve as a useful tool in the planning of multicenter clinical SCI trials.

Recent advances in managing a spinal cord injury secondary to trauma.

Traumatic spinal cord injuries (SCIs) affect 1.3 million North Americans, producing devastating physical, social, and vocational impairment. Pathophysiologically, the initial mechanical trauma is followed by a significant secondary injury which includes local ischemia, pro-apoptotic signaling, release of cytotoxic factors, and inflammatory cell infiltration. Expedient delivery of medical and surgical care during this critical period can improve long-term functional outcomes, engendering the concept of “Time is Spine”. We emphasize the importance of expeditious care while outlining the initial clinical and radiographic assessment of patients. Key evidence-based early interventions (surgical decompression, blood pressure augmentation, and methylprednisolone) are also reviewed, including findings of the landmark Surgical Timing in Acute Spinal Cord Injury Study (STASCIS). We then describe other neuroprotective approaches on the edge of translation such as the sodium-channel blocker riluzole, the anti-inflammatory minocycline, and therapeutic hypothermia. We also review promising neuroregenerative therapies that are likely to influence management practices over the next decade including chondroitinase, Rho-ROCK pathway inhibition, and bioengineered strategies. The importance of emerging neural stem cell therapies to remyelinate denuded axons and regenerate neural circuits is also discussed. Finally, we outline future directions for research and patient care.

Traumatic Spinal Cord Injury: the Impact of Timing. A Prospective Cohort Study to Evaluate Outcomes after Early Surgery (and Reasons for Delays)

IntroductionTraumatic spinal cord injury (tSCI) is a devastating condition affecting mostly young adults.1 Unfortunately, to date there are no standardized guidelines for treating these patients in the early phase and initial management can vary widely.2 Surgical decompression is considered to be a valid approach, however conclusive data regarding the best timing to perform it are still missing.3 The STASCIS trial evaluated the effect of surgical decompression pre- or 24 hours post-injury,4 however some aspects of its design have been criticized. The clinical study SCI-POEM aims to fill the gap of missing evidence by comparing the effect of early (<12 hour after injury) versus delayed (12 hour to 14 days after injury) surgical treatment.5 Material and MethodsThis is a prospective, multicenter, cohort study to test the superiority of early versus late surgery measured by the American Spinal Injury Association (ASIA) lower extremity motor score (ASIALEMS) pre-surgery and after 1 year. Inclusion criteria: Patients > 18 years old with tSCI, AIS grade A-D and indication of surgical management by the treating physician. To detect 6 points of difference in ASIALEMS with a power of 80%, a total of 300 patients are planned to be recruited in 17 clinics in 12 European countries within 3 years, assuming a 1:2 ratio of early vs delayed surgeries. Secondary outcome measures include different functional outcome scores and adverse events. Details about work, injury, main reason associated with a delayed surgery and steroid use are also collected. ResultsThe study started recruitment in March 2013 and until August 2015, 137 eligible patients had been enrolled: 112 (81.8%) men and 25 (18.2%) woman with ages ranging from 18 to 89. Mechanism of injury was low energy trauma in 42 (30.7%) cases and high energy trauma in 95 (69.3%) cases. In 67 (48.9%) patients, traumatic lesion occurred at a single level. One third of cases suffered a complete spinal cord injury (ASIA A, postsurgery measurement). About 50% of decompression surgeries were performed within 12 hour after injury. Unwanted delays for tSCI treatment (as judged by the local investigator) occurred in 36 (26.3%) cases, of which 25 (69.5%) were caused by logistical issues (bed or imaging availability, transfer, etc) and 11 (30.5%) were due to medical reasons. ConclusionIn our study, nearly two third of the cases had an incomplete spinal cord lesion (ASIA B-D), which highlights the relevance of appropriate and timely treatment to improve this situation. Strikingly, the actual rate of early vs delayed surgery is better than the anticipated 1:2 ratio. Even though 50% of the patients underwent early decompression, there was a considerable number of unwanted delays in the treatment of tSCI patients. The reasons for these delays are in most cases due to circumstances beyond the physician's control, such as time for transfer, availability of material resources or the medical condition of the patient. This information is important for future resource planning and suggests that improvements in material resources are needed across Europe.ReferencesLopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJL. Global Burden of Disease and Risk Factors. New York: Oxford University Press; 2006Fransen BL, Hosman AJ, van Middendorp JJ, Edwards M, van Grunsven PM, van de Meent H. Pre-hospital and acute management of traumatic spinal cord injury in the Netherlands: survey results urge the need for standardisation. Spinal Cord 2016;54(1):34–38van Middendorp JJ, Hosman AJ, Doi SA. The effects of the timing of spinal surgery after traumatic spinal cord injury: a systematic review and meta-analysis. J Neurotrauma 2013;30(21):1781–1794Fehlings MG, Vaccaro A, Wilson JR, et al. Early versus delayed decompression for traumatic cervical spinal cord injury: results of the Surgical Timing in Acute Spinal Cord Injury Study (STASCIS). PLoS ONE 2012;7(2):e32037van Middendorp JJ, Barbagallo G, Schuetz M, Hosman AJ. Design and rationale of a Prospective, Observational European Multicenter study on the efficacy of acute surgical decompression after traumatic Spinal Cord Injury: the SCI-POEM study. Spinal Cord 2012;50(9):686–694