Protection and repair of the injured spinal cord: a review of completed, ongoing, and planned clinical trials for acute spinal cord injury

2008 ◽  
Vol 25 (5) ◽  
pp. E14 ◽  
Author(s):  
Gregory W. J. Hawryluk ◽  
James Rowland ◽  
Brian K. Kwon ◽  
Michael G. Fehlings
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Clinical Trials ◽  
Phase Ii ◽  
Sodium Succinate ◽  
Thyrotropin Releasing Hormone ◽  
Acute Spinal Cord Injury ◽  
Releasing Hormone ◽  
Methylprednisolone Sodium Succinate ◽  
Cord Injury

Over the past 2 decades, advances in understanding the pathophysiology of spinal cord injury (SCI) have stimulated the recent emergence of several therapeutic strategies that are being examined in Phase I/II clinical trials. Ten randomized controlled trials examining methylprednisolone sodium succinate, tirilizad mesylate, monosialotetrahexosylganglioside, thyrotropin releasing hormone, gacyclidine, naloxone, and nimodipine have been completed. Although the primary outcomes in these trials were laregely negative, a secondary analysis of the North American Spinal Cord Injury Study II demonstrated that when administered within 8 hours of injury, methylprednisolone sodium succinate was associated with modest clinical benefits, which need to be weighed against potential complications. Thyrotropin releasing hormone (Phase II trial) and monosialotetrahexosylganglioside (Phase II and III trials) also showed some promise, but we are unaware of plans for future trials with these agents. These studies have, however, yielded many insights into the conduct of clinical trials for SCI. Several current or planned clinical trials are exploring interventions such as early surgical decompression (Surgical Treatment of Acute Spinal Cord Injury Study) and electrical field stimulation, neuroprotective strategies such as riluzole and minocycline, the inactivation of myelin inhibition by blocking Nogo and Rho, and the transplantation of various cellular substrates into the injured cord. Unfortunately, some experimental and poorly characterized SCI therapies are being offered outside a formal investigational structure, which will yield findings of limited scientific value and risk harm to patients with SCI who are understandably desperate for any intervention that might improve their function. Taken together, recent advances suggest that optimism for patients and clinicians alike is justified, as there is real hope that several safe and effective therapies for SCI may become available over the next decade.

scholarly journals A Clinical Practice Guideline for the Management of Patients With Acute Spinal Cord Injury: Recommendations on the Use of Methylprednisolone Sodium Succinate

2017 ◽  
Vol 7 (3_suppl) ◽  
pp. 203S-211S ◽  
Author(s):  
Michael G. Fehlings ◽  
Jefferson R. Wilson ◽  
Lindsay A. Tetreault ◽  
Bizhan Aarabi ◽  
Paul Anderson ◽  
...  
Keyword(s):  
Systematic Review ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Clinical Practice ◽  
Sodium Succinate ◽  
Acute Spinal Cord Injury ◽  
Adult Patients ◽  
High Dose ◽  
Methylprednisolone Sodium Succinate ◽  
Cord Injury

Introduction: The objective of this guideline is to outline the appropriate use of methylprednisolone sodium succinate (MPSS) in patients with acute spinal cord injury (SCI). Methods: A systematic review of the literature was conducted to address key questions related to the use of MPSS in acute SCI. A multidisciplinary Guideline Development Group used this information, in combination with their clinical expertise, to develop recommendations for the use of MPSS. Based on GRADE (Grading of Recommendation, Assessment, Development and Evaluation), a strong recommendation is worded as “we recommend,” whereas a weaker recommendation is indicated by “we suggest.” Results: The main conclusions from the systematic review included the following: (1) there were no differences in motor score change at any time point in patients treated with MPSS compared to those not receiving steroids; (2) when MPSS was administered within 8 hours of injury, pooled results at 6- and 12-months indicated modest improvements in mean motor scores in the MPSS group compared with the control group; and (3) there was no statistical difference between treatment groups in the risk of complications. Our recommendations were: (1) “We suggest not offering a 24-hour infusion of high-dose MPSS to adult patients who present after 8 hours with acute SCI”; (2) “We suggest a 24-hour infusion of high-dose MPSS be offered to adult patients within 8 hours of acute SCI as a treatment option”; and (3) “We suggest not offering a 48-hour infusion of high-dose MPSS to adult patients with acute SCI.” Conclusions: These guidelines should be implemented into clinical practice to improve outcomes and reduce morbidity in SCI patients.

Review of clinical trials of neuroprotection in acute spinal cord injury

1999 ◽  
Vol 6 (1) ◽  
pp. E10 ◽  
Author(s):  
Charles H. Tator ◽  
Michael G. Fehlings
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Clinical Trials ◽  
Treatment Time ◽  
Time Window ◽  
Current Knowledge ◽  
Acute Spinal Cord Injury ◽  
Randomized Controlled Studies ◽  
Cord Injury ◽  
Therapeutic Time Window

In this paper the authors review the clinical trials of neuroprotection that have been performed for the treatment of acute spinal cord injury (SCI). The biological rationale for the selection of each treatment modality is discussed with reference to current knowledge of the principles in the management of acute SCI as well as the primary and secondary injury mechanisms identified by experimental and clinical studies of the pathophysiology of acute SCI. The trials are evaluated with regard to the availability and use of accurate clinical outcome measures, and the methodologies of the trials are critically evaluated with an emphasis on prospective randomized controlled studies. A detailed description and critical analysis are provided of the results of the 10 clinical trials conducted to date in which a randomized prospective controlled design has been used. The issue of the therapeutic time window in acute SCI is discussed. To date, methylprednisolone is the only effective neuroprotective agent that has been established for use in human SCI, and the only therapeutic time window established in human SCI is a maximum trauma-to-treatment time of 8 hours.

Quantification of Thyrotropin-Releasing Hormone Changes and Serotonin Content Changes Following Graded Spinal Cord Injury

1995 ◽  
Vol 59 (3) ◽  
pp. 393-398 ◽  
Author(s):  
Scott Shapiro ◽  
Mike Kubek ◽  
Eric Siemers ◽  
Edward Daly ◽  
Jim Callahan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Thyrotropin Releasing Hormone ◽  
Serotonin Content ◽  
Releasing Hormone ◽  
Cord Injury

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

2017 ◽  
Vol 34 (3) ◽  
pp. 599-606 ◽  
Author(s):  
Ginette Thibault-Halman ◽  
Carly S. Rivers ◽  
Christopher S. Bailey ◽  
Eve C. Tsai ◽  
Brian Drew ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Clinical Trials ◽  
National Registry ◽  
Acute Spinal Cord Injury ◽  
Registry Data ◽  
Cord Injury ◽  
National Registry Data

Guidelines for the Management of Patients with Spinal Cord Injury: The Use of Methylprednisolone Sodium Succinate

2016 ◽  
Vol 16 (10) ◽  
pp. S215 ◽  
Author(s):  
Michael G. Fehlings ◽  
Jefferson Wilson ◽  
Bizhan Aarabi ◽  
Paul A. Anderson ◽  
Paul M. Arnold ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Sodium Succinate ◽  
Methylprednisolone Sodium Succinate ◽  
Cord Injury

scholarly journals A Clinical Practice Guideline for the Management of Acute Spinal Cord Injury: Introduction, Rationale, and Scope

2017 ◽  
Vol 7 (3_suppl) ◽  
pp. 84S-94S ◽  
Author(s):  
Michael G. Fehlings ◽  
Lindsay A. Tetreault ◽  
Jefferson R. Wilson ◽  
Brian K. Kwon ◽  
Anthony S. Burns ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Traumatic Event ◽  
Sodium Succinate ◽  
Well Being ◽  
Acute Spinal Cord Injury ◽  
Optimal Timing ◽  
Past Century ◽  
Cord Injury

Acute spinal cord injury (SCI) is a traumatic event that results in disturbances to normal sensory, motor, or autonomic function and ultimately affects a patient’s physical, psychological, and social well-being. The management of patients with SCI has drastically evolved over the past century as a result of increasing knowledge on injury mechanisms, disease pathophysiology, and the role of surgery. There still, however, remain controversial areas surrounding available management strategies for the treatment of SCI, including the use of corticosteroids such as methylprednisolone sodium succinate, the optimal timing of surgical intervention, the type and timing of anticoagulation prophylaxis, the role of magnetic resonance imaging, and the type and timing of rehabilitation. This lack of consensus has prevented the standardization of care across treatment centers and among the various disciplines that encounter patients with SCI. The objective of this guideline is to form evidence-based recommendations for these areas of controversy and outline how to best manage patients with SCI. The ultimate goal of these guidelines is to improve outcomes and reduce morbidity in patients with SCI by promoting standardization of care and encouraging clinicians to make evidence-informed decisions.

Sign in / Sign up

Export Citation Format

Share Document