Jefferson R. Wilson

Early versus Delayed Decompression for Traumatic Cervical Spinal Cord Injury: Results of the Surgical Timing in Acute Spinal Cord Injury Study (STASCIS)

Background There is convincing preclinical evidence that early decompression in the setting of spinal cord injury (SCI) improves neurologic outcomes. However, the effect of early surgical decompression in patients with acute SCI remains uncertain. Our objective was to evaluate the relative effectiveness of early (<24 hours after injury) versus late (≥24 hours after injury) decompressive surgery after traumatic cervical SCI. Methods We performed a multicenter, international, prospective cohort study (Surgical Timing in Acute Spinal Cord Injury Study: STASCIS) in adults aged 16–80 with cervical SCI. Enrolment occurred between 2002 and 2009 at 6 North American centers. The primary outcome was ordinal change in ASIA Impairment Scale (AIS) grade at 6 months follow-up. Secondary outcomes included assessments of complications rates and mortality. Findings A total of 313 patients with acute cervical SCI were enrolled. Of these, 182 underwent early surgery, at a mean of 14.2(±5.4) hours, with the remaining 131 having late surgery, at a mean of 48.3(±29.3) hours. Of the 222 patients with follow-up available at 6 months post injury, 19.8% of patients undergoing early surgery showed a ≥2 grade improvement in AIS compared to 8.8% in the late decompression group (OR = 2.57, 95% CI:1.11,5.97). In the multivariate analysis, adjusted for preoperative neurological status and steroid administration, the odds of at least a 2 grade AIS improvement were 2.8 times higher amongst those who underwent early surgery as compared to those who underwent late surgery (OR = 2.83, 95% CI:1.10,7.28). During the 30 day post injury period, there was 1 mortality in both of the surgical groups. Complications occurred in 24.2% of early surgery patients and 30.5% of late surgery patients (p = 0.21). Conclusion Decompression prior to 24 hours after SCI can be performed safely and is associated with improved neurologic outcome, defined as at least a 2 grade AIS improvement at 6 months follow-up.

Efficacy and safety of surgical decompression in patients with cervical spondylotic myelopathy: results of the AOSpine North America prospective multi-center study.

BACKGROUND Cervical spondylotic myelopathy is the leading cause of spinal cord dysfunction worldwide. The objective of this study was to evaluate the impact of surgical decompression on functional, quality-of-life, and disability outcomes at one year after surgery in a large cohort of patients with this condition. METHODS Adult patients with symptomatic cervical spondylotic myelopathy and magnetic resonance imaging evidence of spinal cord compression were enrolled at twelve North American centers from 2005 to 2007. At enrollment, the myelopathy was categorized as mild (modified Japanese Orthopaedic Association [mJOA] score ≥ 15), moderate (mJOA = 12 to 14), or severe (mJOA < 12). Patients were followed prospectively for one year, at which point the outcomes of interest included the mJOA score, Nurick grade, Neck Disability Index (NDI), and Short Form-36 version 2 (SF-36v2). All outcomes at one year were compared with the preoperative values with use of univariate paired statistics. Outcomes were also compared among the severity classes with use of one-way analysis of variance. Finally, a multivariate analysis that adjusted for baseline differences among the severity groups was performed. Treatment-related complication data were collected and the overall complication rate was calculated. RESULTS Eighty-five (30.6%) of the 278 enrolled patients had mild cervical spondylotic myelopathy, 110 (39.6%) had moderate disease, and 83 (29.9%) had severe disease preoperatively. One-year follow-up data were available for 222 (85.4%) of 260 patients. There was a significant improvement from baseline to one year postoperatively (p < 0.05) in the mJOA score, Nurick grade, NDI score, and all SF-36v2 health dimensions (including the mental and physical health composite scores) except general health. With the exception of the change in the mJOA, the degree of improvement did not depend on the severity of the preoperative symptoms. These results remained unchanged after adjusting for relevant confounders in the multivariate analysis. Fifty-two patients experienced complications (prevalence, 18.7%), with no significant differences among the severity groups. CONCLUSIONS Surgical decompression for the treatment of cervical spondylotic myelopathy was associated with improvement in functional, disability-related, and quality-of-life outcomes at one year of follow-up for all disease severity categories. Furthermore, complication rates observed in the study were commensurate with those in previously reported cervical spondylotic myelopathy series.

Emerging therapies for acute traumatic spinal cord injury

There are currently about 85 000 Canadians living with spinal cord injuries, more than half of which are secondary to trauma.[1][1] As the population ages, the incidence and prevalence of traumatic spinal cord injury are expected to increase, primarily as a result of fall-related injuries among

A prospective, multicenter, phase I matched-comparison group trial of safety, pharmacokinetics, and preliminary efficacy of riluzole in patients with traumatic spinal cord injury.

A prospective, multicenter phase I trial was undertaken by the North American Clinical Trials Network (NACTN) to investigate the pharmacokinetics and safety of, as well as obtain pilot data on, the effects of riluzole on neurological outcome in acute spinal cord injury (SCI). Thirty-six patients, with ASIA impairment grades A-C (28 cervical and 8 thoracic) were enrolled at 6 NACTN sites between April 2010 and June 2011. Patients received 50 mg of riluzole PO/NG twice-daily, within 12 h of SCI, for 14 days. Peak and trough plasma concentrations were quantified on days 3 and 14. Peak plasma concentration (Cmax) and systemic exposure to riluzole varied significantly between patients. On the same dose basis, Cmax did not reach levels comparable to those in patients with amyotrophic lateral sclerosis. Riluzole plasma levels were significantly higher on day 3 than on day 14, resulting from a lower clearance and a smaller volume of distribution on day 3. Rates of medical complications, adverse events, and progression of neurological status were evaluated by comparison with matched patients in the NACTN SCI Registry. Medical complications in riluzole-treated patients occurred with incidences similar to those in patients in the comparison group. Mild-to-moderate increase in liver enzyme and bilirubin levels were found in 14-70% of patients for different enzymes. Three patients had borderline severe elevations of enzymes. No patient had elevated bilirubin on day 14 of administration of riluzole. There were no serious adverse events related to riluzole and no deaths. The mean motor score of 24 cervical injury riluzole-treated patients gained 31.2 points from admission to 90 days, compared to 15.7 points for 26 registry patients, a 15.5-point difference (p=0.021). Patients with cervical injuries treated with riluzole had more-robust conversions of impairment grades to higher grades than the comparison group.

Early versus late surgery for traumatic spinal cord injury: the results of a prospective Canadian cohort study

Study design:A multicenter Canadian cohort study.Objectives:The objective of this study is to evaluate the impact of early versus late surgical decompression on motor neurological recovery after traumatic spinal cord injury (SCI).Setting:Canadian acute care and SCI rehabilitation facilities.Methods:A prospective cohort study of patients within the Ontario Spinal Cord Injury Registry program was performed. We considered SCI patients with an admission American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade of A through D, with magnetic resonance imaging-confirmed spinal cord compression. Grouped analysis was performed comparing the cohort of patients who received early surgery (<24 h after SCI) to those receiving delayed surgery (⩾24 h after SCI). The primary outcome was the change in ASIA motor score (AMS) occurring between hospital admission and rehabilitation discharge.Results:A total of 35 (41.7%) patients underwent early surgery and 49 (58.3%) underwent late surgery. At admission, there was a greater proportion of patients within the early surgery group with more severe AIS grade A injuries. Of the 55 patients with neurological exam available at rehabilitation discharge, a greater proportion had at least a two-grade AIS improvement in the early-surgery group (P=0.01). The mean improvement in AMS at rehabilitation discharge was 20 points amongst early-surgery patients and 15 points amongst late-surgery patients (P=0.46). In the analysis investigating AMS improvement, adjusted for preoperative status and neurological level, there was a positive effect estimate for early surgical therapy that was statistically significant (P=0.01).Conclusion:The results here add weight to the growing body of literature, which supports the principle of early intervention in the setting of spinal trauma and SCI.

Traumatic spinal cord injury

Traumatic spinal cord injury (SCI) has devastating consequences for the physical, social and vocational well-being of patients. The demographic of SCIs is shifting such that an increasing proportion of older individuals are being affected. Pathophysiologically, the initial mechanical trauma (the primary injury) permeabilizes neurons and glia and initiates a secondary injury cascade that leads to progressive cell death and spinal cord damage over the subsequent weeks. Over time, the lesion remodels and is composed of cystic cavitations and a glial scar, both of which potently inhibit regeneration. Several animal models and complementary behavioural tests of SCI have been developed to mimic this pathological process and form the basis for the development of preclinical and translational neuroprotective and neuroregenerative strategies. Diagnosis requires a thorough patient history, standardized neurological physical examination and radiographic imaging of the spinal cord. Following diagnosis, several interventions need to be rapidly applied, including haemodynamic monitoring in the intensive care unit, early surgical decompression, blood pressure augmentation and, potentially, the administration of methylprednisolone. Managing the complications of SCI, such as bowel and bladder dysfunction, the formation of pressure sores and infections, is key to address all facets of the patients injury experience.

Clinical predictors of neurological outcome, functional status, and survival after traumatic spinal cord injury: a systematic review

OBJECT The object of this study was to identify, by means of a systematic review of the literature, the acute clinical predictors of neurological outcome, functional outcome, and survival after traumatic spinal cord injury (SCI). METHODS A comprehensive computerized literature review search was performed, using MEDLINE, PubMed, EMBASE, CINAHL, and the Cochrane Database of Systematic Reviews. Selected articles were classified according to their level of evidence. Articles were then stratified into one of 3 domains depending on whether the primary focus was clinical prediction of 1) neurological outcome, 2) functional status, or 3) survival. For each study selected, clinical predictors related to patient demographic characteristics, injury mechanism, or neurological examination findings were extracted, and the individual relationship to outcome was defined. RESULTS The initial search resulted in 376 citations. After application of the inclusion and exclusion criteria and study review, 51 relevant articles were identified and graded. Of these, 25 provided predictors for neurological outcome, 22 for functional outcome, and 15 for survival, with several of the articles providing information on more than one type of outcome. All of the included studies were designated as providing Class I, II, or III levels of evidence. The severity of neurological injury (as measured by admission Americal Spinal Injury Association Impairment Scale grade, Frankel grade, or injury completeness), level of injury, and the presence of a zone of partial preservation were consistent predictors of neurological outcome. Severity of neurological injury, level of injury, reflex pattern, and age were consistent predictors of functional outcome. Finally, severity of neurological injury, level of injury, age, and the presence of multisystem trauma seen with higher-energy injury mechanisms were consistent predictors of survival. CONCLUSIONS On the basis on this review, the authors have identified a constellation of acute clinical features that may help to define an individuals profile for recovery and survival after SCI. This study will help to facilitate communication in the clinical realm and assist in classifying subsets of patients within future clinical studies.

The effects of intrathecal injection of a hyaluronan-based hydrogel on inflammation, scarring and neurobehavioural outcomes in a rat model of severe spinal cord injury associated with arachnoiditis

Traumatic spinal cord injury (SCI) comprises a heterogeneous condition caused by a complex array of mechanical forces that damage the spinal cord - making each case somewhat unique. In addition to parenchymal injury, a subset of patients experience severe inflammation in the subarachnoid space or arachnoiditis, which can lead to the development of fluid-filled cavities/syringes, a condition called post-traumatic syringomyelia (PTS). Currently, there are no therapeutic means to address this devastating complication in patients and furthermore once PTS is diagnosed, treatment is often prone to failure. We hypothesized that reducing subarachnoid inflammation using a novel bioengineered strategy would improve outcome in a rodent model of PTS. A hydrogel of hyaluronan and methyl cellulose (HAMC) was injected into the subarachnoid space 24 h post PTS injury in rats. Intrathecal injection of HAMC reduced the extent of fibrosis and inflammation in the subarachnoid space. Furthermore, HAMC promoted improved neurobehavioural recovery, enhanced axonal conduction and reduced the extent of the lesion as assessed by MRI and histomorphometric assessment. These findings were additionally associated with a reduction in the post-traumatic parenchymal fibrous scar formation as evidenced by reduced CSPG deposition and reduced IL-1α cytokine levels. Our data suggest that HAMC is capable of modulating inflammation and scarring events, leading to improved functional recovery following severe SCI associated with arachnoiditis.

Systematic review of magnetic resonance imaging characteristics that affect treatment decision making and predict clinical outcome in patients with cervical spondylotic myelopathy.

Study Design. Systematic review. Objective. To determine whether there are magnetic resonance imaging (MRI) characteristics in patients with cervical spondylotic myelopathy that affect treatment decisions or predict postsurgical outcomes or adverse events. Summary of Background Data. Although the role of MRI in confirming the clinical diagnosis of cervical spondylotic myelopathy and directing surgical management is well established, its potential value as a prognostic tool is largely unknown. Methods. A systematic search was conducted using PubMed and the Cochrane Collaboration Library for articles published between January 1, 1956, and November 20, 2012. The overall body of evidence with respect to each clinical question was determined on the basis of precepts outlined by the Grading of Recommendation Assessment, Development and Evaluation Working Group and recommendations made by the Agency for Healthcare Research and Quality. Results. The initial search yielded 268 citations. Twenty publications met all inclusion criteria and were included in the review. Three of these assessed MRI predictors of clinical deterioration in the case of conservative treatment and 17 evaluated MRI anatomic or cord characteristics that could predict surgical outcome or adverse events. There is low evidence suggesting that a high signal intensity (SI) grade on T2WI is not associated with patient deterioration during conservative treatment. High SI grade on T2WI, along with compression ratio and canal diameter, was not an important predictor of outcome. There is low evidence identifying number of high SI segments on T2WI, low SI segments on T1WI, combined T1/T2 SI, and SI ratio as important negative predictors of surgical outcome. Conclusion. On the basis of this review and on low-quality evidence, we have identified 3 important negative predictors of surgical outcome: number of high SI segments on T2WI, combined T1/T2 signal change, and SI ratio. Evidence-Based Clinical Recommendations. Recommendation 1. We suggest that when clinically feasible, surgeons rely on MRI to confirm the diagnosis of CSM and rely on clinical history and examination to determine progression and severity of disease. Overall Strength of Evidence. Low Strength of Recommendation. Weak Recommendation 2. T2 signal may be a useful prognostic indicator when used in combination with low SI change on T1WI, or as a ratio comparing compressed with noncompressed segments, or as a ratio of T2 compared with T1WI. We suggest that if surgeons use MRI signal intensity to estimate the risk of a poor outcome after surgery, they use high SI change on T2WI in combination with other signal intensity parameters, and not in isolation. Overall Strength of Evidence: Low Strength of Recommendation: Weak

Frequency, timing, and predictors of neurological dysfunction in the nonmyelopathic patient with cervical spinal cord compression, canal stenosis, and/or ossification of the posterior longitudinal ligament.

Study Design. Systematic review and survey. Objective. To perform an evidence synthesis of the literature and obtain information from the global spine care community assessing the frequency, timing, and predictors of symptom development in patients with radiographical evidence of cervical spinal cord compression, spinal canal narrowing, and/or ossification of posterior longitudinal ligament (OPLL) but no symptoms of myelopathy. Summary of Background Data. Evidence for a marker to predict symptom development remains sparse, and there is controversy surrounding the management of asymptomatic patients. Methods. We conducted a systematic review of the English language literature and an international survey of spine surgeons to answer the following key questions in patients with radiographical evidence of cervical spinal cord compression, spinal canal narrowing, and/or OPLL but no symptoms of myelopathy: (1) What are the frequency and timing of symptom development? (2) What are the clinical, radiographical, and electrophysiological predictors of symptom development? (3) What clinical and/or radiographical features influence treatment decisions based on an international survey of spine care professionals? Results. The initial literature search yielded 388 citations. Applying the inclusion/exclusion criteria narrowed this to 5 articles. Two of these dealt with the same population. For patients with spinal cord compression secondary to spondylosis, one study reported the frequency of myelopathy development to be 22.6%. The presence of symptomatic radiculopathy, cervical cord hyperintensity on magnetic resonance imaging, and prolonged somatosensory- and motor-evoked potentials were reported in one study as significant independent predictors of myelopathy development. In contrast, the lack of magnetic resonance imaging hyperintensity was found to be a positive predictor of early myelopathy development (⩽12-mo follow-up). For subjects with OPLL, frequency of myelopathy development was reported in 3 articles and ranged from 0.0% to 61.5% of subjects. One of these studies reported canal stenosis of 60% or more, lateral deviated OPLL, and increased cervical range of motion as significant predictors of myelopathy development. In a survey of 774 spine surgeons, the majority deemed the presence of clinically symptomatic radiculopathy to predict progression to myelopathy in nonmyelopathic patients with cervical stenosis. Survey responses pertaining to 3 patient case vignettes are also presented and discussed in the context of the current literature. Conclusion. On the basis of these results, we provide a series of evidence-based recommendations related to the frequency, timing, and predictors of myelopathy development in asymptomatic patients with cervical stenosis secondary to spondylosis or OPLL. Future prospective studies are required to refine our understanding of this topic. Evidence-Based Clinical Recommendations. Recommendation. Patients with cervical canal stenosis and cord compression secondary to spondylosis, without clinical evidence of myelopathy, and who present with clinical or electrophysiological evidence of cervical radicular dysfunction or central conduction deficits seem to be at higher risk for developing myelopathy and should be counseled to consider surgical treatment. Overall Strength of Evidence. Moderate Strength of Recommendation. Strong Summary Statements.Statement 1: On the basis of the current literature, for patients with cervical canal stenosis and cord compression secondary to spondylosis, without clinical evidence of myelopathy, approximately 8% at 1-year follow-up and 23% at a median of 44-months follow-up develop clinical evidence of myelopathy.Statement 2: For patients with cervical canal stenosis and cord compression secondary to spondylosis, without clinical evidence of myelopathy, the absence of magnetic resonance imaging intramedullary T2 hyperintensity has been shown to predict early myelopathy development (<12-mo follow-up) and the presence of such signal has been shown to predict late myelopathy development (mean 44-mo follow-up). In light of this discrepancy, no definite recommendation can be made surrounding the utility of this finding in predicting myelopathy development.Statement 3: For patients with OPLL but without myelopathy, no recommendation can be made regarding the incidence or predictors of progression to myelopathy.