Potential diagnostic and prognostic value of serum and cerebrospinal fluid biomarkers in traumatic spinal cord injury: A systematic review

It remains unclear whether biomarkers in the serum or CSF can be used for diagnosis or prognosis of spinal cord injuries (SCI). Therefore, a systematic review was undertaken to evaluate the prognostic or diagnostic value of serum and CSF biomarkers in assessing the severity of SCI and the outcome of patients. Two independent reviewers summarized the human studies retrieved from the electronic databases of Medline, Embase, Scopus and ISI Web of Science until April 2018. Seventeen studies were included (1065 patients aged 16�94 years old). Although the findings of the included studies suggest that inflammatory and structural proteins may be useful in assessing the severity of SCI and prediction of neurological outcome, the level of evidence is generally low. Given limitations to the available evidence, further investigation in this field is required using large prospective data sets with rigorous analysis of sensitivity, specificity and prediction. (Figure presented.). © 2018 International Society for Neurochemistr

Neurological recovery following traumatic spinal cord injury: A systematic review and meta-analysis

OBJECTIVE Predicting neurological recovery following traumatic spinal cord injury (TSCI) is a complex task considering the heterogeneous nature of injury and the inconsistency of individual studies. This study aims to summarize the current evidence on neurological recovery following TSCI by use of a meta-analytical approach, and to identify injury, treatment, and study variables with prognostic significance. METHODS A literature search in MEDLINE and EMBASE was performed, and studies reporting follow-up changes in American Spinal Injury Association (ASIA) Impairment Scale (AIS) or Frankel or ASIA motor score (AMS) scales were included in the meta-analysis. The proportion of patients with at least 1 grade of AIS/Frankel improvement, and point changes in AMS were calculated using random pooled effect analysis. The potential effect of severity, level and mechanism of injury, type of treatment, time and country of study, and follow-up duration were evaluated using meta-regression analysis. RESULTS A total of 114 studies were included, reporting AIS/Frankel changes in 19,913 patients and AMS changes in 6920 patients. Overall, the quality of evidence was poor. The AIS/Frankel conversion rate was 19.3 (95 CI 16.2�22.6) for patients with grade A, 73.8 (95 CI 69.0�78.4) for those with grade B, 87.3 (95 CI 77.9�94.8) for those with grade C, and 46.5 (95 CI 38.2�54.9) for those with grade D. Neurological recovery was significantly different between all grades of SCI severity in the following order: C > B > D > A. Level of injury was a significant predictor of recovery; recovery rates followed this pattern: lumbar > cervical and thoracolumbar > thoracic. Thoracic SCI and penetrating SCI were significantly more likely to result in complete injury. Penetrating TSCI had a significantly lower recovery rate compared to blunt injury (OR 0.76, 95 CI 0.62�0.92; p = 0.006). Recovery rate was positively correlated with longer follow-up duration (p = 0.001). Studies with follow-up durations of approximately 6 months or less reported significantly lower recovery rates for incomplete SCI compared to studies with long-term (3�5 years) follow-ups. CONCLUSIONS The authors� meta-analysis provides an overall quantitative description of neurological outcomes associated with TSCI. Moreover, they demonstrated how neurological recovery after TSCI is significantly dependent on injury factors (i.e., severity, level, and mechanism of injury), but is not associated with type of treatment or country of origin. Based on these results, a minimum follow-up of 12 months is recommended for TSCI studies that include patients with neurologically incomplete injury. ©AANS 2019, except where prohibited by US copyright la

Axonal degeneration and demyelination following traumatic spinal cord injury: A systematic review and meta-analysis

The pathophysiology of spinal cord injury (SCI) related processes of axonal degeneration and demyelination are poorly understood. The present systematic review and meta-analysis were performed such to establish quantitative results of animal studies regarding the role of injury severity, SCI models and level of injury on the pathophysiology of axon and myelin sheath degeneration. 39 related articles were included in the analysis. The compiled data showed that the total number of axons, number of myelinated axons, myelin sheath thickness, axonal conduction velocity, and internode length steadily decreased as time elapsed from the injury (P for trend <0.0001). The rate of axonal retrograde degeneration was affected by SCI model and severity of the injury. Axonal degeneration was higher in injuries of the thoracic region. The SCI model and the site of the injury also affected axonal retrograde degeneration. The number of myelinated axons in the caudal region of the injury was significantly higher than the lesion site and the rostral region. The findings of the present meta-analysis show that the pathophysiology of axons and myelin sheath differ in various phases of SCI and are affected by multiple factors related to the injury. © 2019 Elsevier B.V

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

OnlinePublRiluzole 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.Michael G. Fehlings, Ali Moghaddamjou, James S. Harrop, Ralph Stanford, Jonathon Ball, Bizhan Aarabi, Brian J. C. Freeman, Paul M. Arnold, James D. Guest, Shekar N. Kurpad, James M. Schuster, Ahmad Nassr, Karl M. Schmitt, Jefferson R. Wilson, Darrel S. Brodke, Faiz U. Ahmad, Albert Yee, Wilson Z. Ray, Nathaniel P. Brooks, Jason Wilson, Diana S-L Chow, Elizabeth G. Toups, and Branko Kopja