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.
Charles H. Tator and Michael G. Fehlings
Michael G. Fehlings and Charles H. Tator
The authors conducted an evidence-based review of the literature to evaluate critically the rationale and indications for and the timing of decompressive surgery for the treatment of acute, nonpenetrating spinal cord injury (SCI).
The experimental and clinical literature concerning the role of, and the biological rationale for surgical decompression for acute SCI was reviewed. Clinical studies of nonoperative management of SCI were also examined for comparative purposes. Evidence from clinical trials was categorized as Class I (well-conducted randomized prospective trials), Class II (well-designed comparative clinical studies), or Class III (retrospective studies).
Studies in which animal models of SCI were used consistently demonstrated a beneficial effect of early surgical decompression, although it is difficult to apply these data directly to the clinical setting. The clinical studies provided suggestive (Class III and limited Class II) evidence that decompressive procedures improve neurological recovery after SCI. However, no clear consensus can be inferred from the literature as to the optimum timing of decompressive surgery. Many authors have advocated delayed treatment to avoid medical complications, although there is good evidence from recent Class II trials that early decompressive surgery can be performed safely without added morbidity or mortality.
There is biological evidence from experimental studies in animals that early surgical decompression may improve neurological recovery after SCI, although the relevant interventional timing in humans remains unclear. To date, the role of surgical decompression in patients with SCI is only supported by Class III and limited Class II evidence. Accordingly, decompressive surgery for SCI can only be considered a practice option. Furthermore, analysis of the literature does not allow definite conclusions to be drawn regarding appropriate timing of intervention. Hence, there is a need to conduct well-designed experimental and clinical studies of the timing and neurological results of surgical decompression for the treatment of acute SCI.
W. Bradley Jacobs and Michael G. Fehlings
✓ Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease that primarily affects the vertebral column and sacroiliac joints. Over time, the disease process promotes extensive remodeling of the spinal axis via ligamentous ossification, vertebral joint fusion, osteoporosis, and kyphosis. These pathological changes result in a weakened vertebral column with increased susceptibility to fractures and spinal cord injury (SCI). Spinal cord injury is often exacerbated by the highly unstable nature of vertebral column fractures in AS. A high incidence of missed fractures in the ankylosed spine as well as an increased incidence of spinal epidural hematoma also worsens the severity of SCI. Spinal cord injury in AS is a complex problem associated with high morbidity and mortality rates, which can be attributed to the severity of the injury, associated medical comorbidities, and the advanced age of most patients with AS who suffer an SCI. In this paper the authors outline the factors that increase the incidence of vertebral column fractures and SCI in AS and discuss the management of SCI in patients with AS. Primary prevention strategies for SCI in patients with AS are outlined as well.
Michael G. Fehlings and Allyson Tighe
Spinal cord injury (SCI) is a condition with devastating consequences for the patient, family, and society. Although effective treatments for SCI remain limited, there have been many advances in recent years, which have promise for the future from a clinical translational perspective. This issue of Neurosurgical Focus explores some of the current basic science, preclinical, and clinical research directed towards this goal. Clinical investigations are also discussed with regard to the treatment and management of different types of SCI and of SCI in different populations. The issue concludes with a review of the current, ongoing, and planned clinical trials, providing a glimpse of the promising new therapies being developed for the treatment of SCI.
Michael G. Fehlings, Lindsay Tetreault, Patrick C. Hsieh, Vincent Traynelis and Michael Y. Wang
Eftekhar Eftekharpour, Soheila Karimi-Abdolrezaee and Michael G. Fehlings
✓ Despite advances in medical and surgical care, the current clinical therapies for spinal cord injury (SCI) are largely ineffective. During the last 2 decades, the search for new therapies has been revolutionized by the discovery of stem cells, which has inspired scientists and clinicians to search for a stem cell–based reparative approaches to many diseases, including neurotrauma. In the present study, the authors briefly summarize current knowledge related to the pathophysiology of SCI, including the concepts of primary and secondary injury and the importance of posttraumatic demyelination. Key inhibitory obstacles that impede axonal regeneration include the glial scar and a number of myelin inhibitory molecules including Nogo. Recent advancements in cell replacement therapy as a therapeutic strategy for SCI are summarized. The strategies include the use of pluripotent human stem cells, embryonic stem cells, and a number of adult-derived stem and progenitor cells such as mesenchymal stem cells, Schwann cells, olfactory ensheathing cells, and adult-derived neural precursor cells. Although current strategies to repair the subacutely injured cord appear promising, many obstacles continue to render the treatment of chronic injuries challenging. Nonetheless, the future for stem cell–based reparative strategies for treating SCI appears bright.
Henry Ahn and Michael G. Fehlings
In this report, the authors suggest evidence-based approaches to minimize the chance of perioperative spinal cord injury (POSCI) and optimize outcome in the event of a POSCI.
A systematic review of the basic science and clinical literature is presented.
Authors of clinical studies have assessed intraoperative monitoring to minimize the chance of POSCI. Furthermore, preoperative factors and intraoperative issues that place patients at increased risk of POSCI have been identified, including developmental stenosis, ankylosing spondylitis, preexisting myelopathy, and severe deformity with spinal cord compromise. However, no studies have assessed methods to optimize outcomes specifically after POSCIs. There are a number of studies focussed on the pathophysiology of SCI and the minimization of secondary damage. These basic science and clinical studies are reviewed, and treatment options outlined in this article.
There are a number of treatment options, including maintenance of mean arterial blood pressure > 80 mm Hg, starting methylprednisolone treatment preoperatively, and multimodality monitoring to help prevent POSCI occurrence, minimize secondary damage, and potentially improve the clinical outcome of after a POSCI. Further prospective cohort studies are needed to delineate incidence rate, current practice patterns for preventing injury and minimizing the clinical consequences of POSCI, factors that may increase the risk of POSCI, and determinants of clinical outcome in the event of a POSCI.
Pascal Jabbour, Michael Fehlings, Alexander R. Vaccaro and James S. Harrop
In this paper the authors review spine trauma and spinal cord injury (SCI) in the geriatric population. The information in this study was compiled through a literature review of clinical presentation and management of SCI in the elderly population. This was done to define, identify, and specify treatment algorithms and management strategies in this unique patient population.
Charles H. Tator, Michael Fehlings, Kevin Thorpe and Wayne Taylor
A multicenter retrospective study was performed in 36 participating North American centers to examine the use and timing of surgery in the treatment of acute spinal cord injury (SCI). The study was conducted to obtain information required for the planning of a randomized controlled trial of early compared with late decompressive surgery.
The records of all patients aged 16 to 75 years with acute SCI who were admitted to the 36 centers within 24 hours of injury over a 9-month period (August 1994 to April 1995) were examined to obtain data on admission variables, methods of diagnosis, use of traction, and surgical variables including type and timing of surgery.
A total of 585 patients with acute SCI or cauda equina injury were admitted to these centers, although approximately half were ultimately excluded because they did not meet inclusion criteria. Common causes for exclusion were late admission, age, gunshot wound, and an absence of spinal cord compression demonstrated on imaging studies. Thus, only approximately 50% of acute SCI patients would be eligible for inclusion in a study of acute decompressive procedures. Although 100% of patient underwent computerized tomography (CT) scaning, only 54% underwent magnetic resonance imaging, and CT myelography was performed in only 6%. Complete neurological injuries (American Spinal Injury Association Grade A) were present in 57.8%. Traction was applied in only 47% of patients with cervical injuries, of which only 42% demonstrated successful decompression by traction. Neurological deterioration occurred in 8.1% of patients after traction. Surgery was performed in 65.4% of patients. The timing of surgery varied widely: less than 24 hours in 23.5% of patients; 25 to 48 hours in 15.8%; 48 to 96 hours in 19.0%; and 5 days or longer in 41.7% of patients.
These data indicate that whereas surgery is commonly performed in patients with acute SCI, one-third of the cases are managed nonoperatively, and there is very little agreement on the optimum timing of surgical treatment. The results of this study confirm the need for a randomized controlled trial to determine the optimum timing of surgical decompressive procedures in patients with SCI.