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.
Lindsay Tetreault, Ahmed Ibrahim, Pierre Côté, Anoushka Singh and Michael G. Fehlings
Although generally safe and effective, surgery for the treatment of cervical spondylotic myelopathy (CSM) is associated with complications in 11%–38% of patients. Several predictors of postoperative complications have been proposed but few are used to detect high-risk patients. A standard approach to identifying “at-risk” patients would improve surgeons’ ability to prevent and manage these complications. The authors aimed to compare the complication rates between various surgical procedures used to treat CSM and to identify patient-specific, clinical, imaging, and surgical predictors of complications.
The authors conducted a systematic review of the literature and searched MEDLINE, MEDLINE in Process, EMBASE, and Cochrane Central Register of Controlled Trials from 1948 to September 2013. Cohort studies designed to evaluate predictors of complications and intervention studies conducted to compare different surgical approaches were included. Each article was critically appraised independently by 2 reviewers, and the evidence was synthesized according to the principles outlined by the Grading of Recommendation Assessment, Development and Evaluation (GRADE) Working Group.
A total of 5472 citations were retrieved. Of those, 60 studies met the inclusion criteria and were included in the review. These studies included 36 prognostic cohort studies and 28 comparative intervention studies. High evidence suggests that older patients are at a greater risk of perioperative complications. Based on low evidence, other clinical factors such as body mass index, smoking status, duration of symptoms, and baseline severity score, are not predictive of complications. With respect to surgical factors, low to moderate evidence suggests that estimated blood loss, surgical approach, and number of levels do not affect rates of complications. A longer operative duration (moderate evidence), however, is predictive of perioperative complications and a 2-stage surgery is related to an increased risk of major complications (high evidence). In terms of surgical techniques, higher rates of neck pain were found in patients undergoing laminoplasty compared with anterior spinal fusion (moderate evidence). In addition, with respect to laminoplasty techniques, there was a lower incidence of C-5 palsy in laminoplasty with concurrent foraminotomy compared with nonforaminotomy (low evidence).
The current review suggests that older patients are at a higher risk of perioperative complications. A longer operative duration and a 2-stage surgery both reflect increased case complexity and can indirectly predict perioperative complications.
Nardin Samuel, Christina L. Goldstein, Carlo Santaguida and Michael G. Fehlings
Spinal cord herniation is a relatively rare but increasingly recognized clinical entity, with fewer than 200 cases reported in the literature to date. The etiology of this condition remains unknown, and surgery is used as the primary treatment to correct the herniation and consequent spinal cord compromise. Some patients without clinical progression have been treated with nonoperative measures, including careful follow-up and symptomatic physical therapy. To date, however, there has been no published report on the resolution of spinal cord herniation without surgical intervention.
The patient in the featured case is a 58-year-old man who presented with mild thoracic myelopathy and imaging findings consistent with idiopathic spinal cord herniation. Surprisingly, updated MRI studies, obtained to better delineate the pathology, showed spontaneous resolution of the herniation. Subsequent MRI 6 months later revealed continued resolution of the previous spinal cord herniation.
This is the first report of spontaneous resolution of a spinal cord herniation in the literature. At present, the treatment of this disorder is individualized, with microsurgical correction used in patients with progressive neurological impairment. The featured case highlights the potential variability in the natural history of this condition and supports considering an initial trial of nonoperative management for patients with mild, nonprogressive neurological deficits.