Early Surgery for Traumatic Spinal Cord Injury: Where Are We Now?

Study Design: Narrative review. Objective: There is a strong biological rationale to perform early decompression after traumatic spinal cord injury (SCI). With an enlarging clinical evidence base, most spine surgeons internationally now favor early decompression for the majority of SCI patients; however, a number of pertinent questions remain surrounding this therapy. Methods: A narrative review evaluating the status of early surgery for SCI. In particular, we addressed the following questions: (1) Which patients stand to benefit most from early surgery? 2) What is the most appropriate time threshold defining early surgery? Results: Although heterogeneity exists, the evidence generally seems to support early surgery. While the best evidence exists for cervical SCI, there is insufficient data to support a differential effect for early surgery depending on neurological level or injury severity. When comparing thresholds to define early versus late surgery-including a later threshold (48-72 hours), an earlier threshold (24 hours), and an ultra-early threshold (8-12 hours)-the 2 earlier time points seem to be associated with the greatest potential for improved outcomes. However, existing prehospital and hospital logistics pose barriers to early surgery in a significant proportion of patients. An overview of recommendations from the recent AOSpine guidelines is provided. Conclusion: In spite of increasing acceptance of early surgery post SCI, further research is needed to (1) identify subgroups of patients who stand to derive particular benefit-in particular to develop more evidence-based approaches for central cord syndrome and (2) investigate the efficacy and feasibility of ultra-early surgery targeting more aggressive timelines

Altered intra-nuclear organisation of heterochromatin and genes in ICF syndrome.

The ICF syndrome is a rare autosomal recessive disorder, the most common symptoms of which are immunodeficiency, facial anomalies and cytogenetic defects involving decondensation and instability of chromosome 1, 9 and 16 centromeric regions. ICF is also characterised by significant hypomethylation of the classical satellite DNA, the major constituent of the juxtacentromeric heterochromatin. Here we report the first attempt at analysing some of the defining genetic and epigenetic changes of this syndrome from a nuclear architecture perspective. In particular, we have compared in ICF (Type 1 and Type 2) and controls the large-scale organisation of chromosome 1 and 16 juxtacentromeric heterochromatic regions, their intra-nuclear positioning, and co-localisation with five specific genes (BTG2, CNN3, ID3, RGS1, F13A1), on which we have concurrently conducted expression and methylation analysis. Our investigations, carried out by a combination of molecular and cytological techniques, demonstrate the existence of specific and quantifiable differences in the genomic and nuclear organisation of the juxtacentromeric heterochromatin in ICF. DNA hypomethylation, previously reported to correlate with the decondensation of centromeric regions in metaphase described in these patients, appears also to correlate with the heterochromatin spatial configuration in interphase. Finally, our findings on the relative positioning of hypomethylated satellite sequences and abnormally expressed genes suggest a connection between disruption of long-range gene-heterochromatin associations and some of the changes in gene expression in ICF. Beyond its relevance to the ICF syndrome, by addressing fundamental principles of chromosome functional organisation within the cell nucleus, this work aims to contribute to the current debate on the epigenetic impact of nuclear architecture in development and disease

Efficacy, Safety, and Timing of Anticoagulant Thromboprophylaxis for the Prevention of Venous Thromboembolism in Patients With Acute Spinal Cord Injury: A Systematic Review

Study Design: Systematic review. Objectives: The objective of this study was to answer 5 key questions: What is the comparative effectiveness and safety of (1a) anticoagulant thromboprophylaxis compared to no prophylaxis, placebo, or another anticoagulant strategy for preventing deep vein thrombosis (DVT) and pulmonary embolism (PE) after acute spinal cord injury (SCI)? (1b) Mechanical prophylaxis strategies alone or in combination with other strategies for preventing DVT and PE after acute SCI? (1c) Prophylactic inferior vena cava filter insertion alone or in combination with other strategies for preventing DVT and PE after acute SCI? (2) What is the optimal timing to initiate and/or discontinue anticoagulant, mechanical, and/or prophylactic inferior vena cava filter following acute SCI? (3) What is the cost-effectiveness of these treatment options? Methods: A systematic literature search was conducted to identify studies published through February 28, 2015. We sought randomized controlled trials evaluating efficacy and safety of antithrombotic strategies. Strength of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Results: Nine studies satisfied inclusion criteria. We found a trend toward lower risk of DVT in patients treated with enoxaparin. There were no significant differences in rates of DVT, PE, bleeding, and mortality between patients treated with different types of low-molecular-weight heparin or between low-molecular-weight heparin and unfractionated heparin. Combined anticoagulant and mechanical prophylaxis initiated within 72 hours of SCI resulted in lower risk of DVT than treatment commenced after 72 hours of injury. Conclusion: Prophylactic treatments can be used to lower the risk of venous thromboembolic events in patients with acute SCI, without significant increase in risk of bleeding and mortality and should be initiated within 72 hours. © 2017, © The Author(s) 2017

The impact of riluzole on neurobehavioral outcomes in preclinical models of traumatic and nontraumatic spinal cord injury: results from a systematic review of the literature

Study Design:Systematic review.Objective:To evaluate the impact of riluzole on neurobehavioral outcomes in preclinical models of nontraumatic and traumatic spinal cord injury (SCI).Methods:An extensive search of the literature was conducted in Medline, EMBASE, and Medline in Process. Studies were included if they evaluated the impact of riluzole on neurobehavioral outcomes in preclinical models of nontraumatic and traumatic SCI. Extensive data were extracted from relevant studies, including sample characteristics, injury model, outcomes assessed, timing of evaluation, and main results. The SYRCLE checklist was used to assess various sources of bias.Results:The search yielded a total of 3180 unique citations. A total of 16 studies were deemed relevant and were summarized in this review. Sample sizes ranged from 14 to 90, and injury models included traumatic SCI (n = 9), degenerative cervical myelopathy (n = 2), and spinal cord-ischemia (n = 5). The most commonly assessed outcome measures were BBB (Basso, Beattie, Besnahan) locomotor score and von Frey filament testing. In general, rats treated with riluzole exhibited significantly higher BBB locomotor scores than controls. Furthermore, riluzole significantly increased withdrawal thresholds to innocuous stimuli and tail flick latency following application of radiant heat stimuli. Finally, rats treated with riluzole achieved superior results on many components of gait assessment.Conclusion:In preclinical models of traumatic and nontraumatic SCI, riluzole significantly improves locomotor scores, gait function, and neuropathic pain. This review provides the background information necessary to interpret the results of clinical trials on the impact of riluzole in traumatic and nontraumatic SCI

Development and implementation of clinical practice guidelines: An update and synthesis of the literature with a focus in application to spinal conditions

Study Design:Review.Objectives:The objectives of this review are to (a) summarize the role of clinical practice guidelines (CPGs), (b) outline the methodology involved in formulating CPGs, (c) provide an illustration of these principles using a CPG developed for degenerative cervical myelopathy, and (d) highlight the importance of knowledge translation.Methods:A review of the literature was conducted to summarize current standards in CPG development and implementation.Results:CPGs are systematically developed statements intended to affect decisions made by health care providers, policy makers, and patients. The main objectives of CPGs are to synthesize and translate evidence into recommendations, optimize patient outcomes, standardize care, and facilitate shared decision making among physicians, patients, and their caregivers. The main steps involved in the development of CPGs include defining the clinical problem, assembling a multidisciplinary guideline development group and systematic review team, conducting a systematic review of the literature, translating the evidence to recommendations, critically appraising the CPG and updating the document when new studies arise. The final step in developing a CPG is to implement it into clinical practice; this step requires an assessment of the barriers to implementation and the formulation of effective dissemination strategies.Conclusion:CPGs are an important component in the teaching and practice of medicine and are available for a wide spectrum of diseases. CPGs, however, can only be used to influence clinical practice if the recommendations are informed by a systematic review of the literature and developed using rigorous methodology. The opportunity to transform clinical management of spinal conditions is an attractive outcome of the application of high-quality CPGs

How large should whales be?

The evolution and distribution of species body sizes for terrestrial mammals is well-explained by a macroevolutionary tradeoff between short-term selective advantages and long-term extinction risks from increased species body size, unfolding above the 2g minimum size induced by thermoregulation in air. Here, we consider whether this same tradeoff, formalized as a constrained convection-reaction-diffusion system, can also explain the sizes of fully aquatic mammals, which have not previously been considered. By replacing the terrestrial minimum with a pelagic one, at roughly 7000g, the terrestrial mammal tradeoff model accurately predicts, with no tunable parameters, the observed body masses of all extant cetacean species, including the 175,000,000g Blue Whale. This strong agreement between theory and data suggests that a universal macroevolutionary tradeoff governs body size evolution for all mammals, regardless of their habitat. The dramatic sizes of cetaceans can thus be attributed mainly to the increased convective heat loss is water, which shifts the species size distribution upward and pushes its right tail into ranges inaccessible to terrestrial mammals. Under this macroevolutionary tradeoff, the largest expected species occurs where the rate at which smaller-bodied species move up into large-bodied niches approximately equals the rate at which extinction removes them.Comment: 7 pages, 3 figures, 2 data table

Efficacy and safety of methylprednisolone sodium succinate in acute spinal cord injury: a systematic review

Study Design: Systematic review and meta-analysis. Objective: The objective of this study was to conduct a systematic review to assess the comparative effectiveness and safety of high-dose methylprednisolone sodium succinate (MPSS) versus no pharmacological treatment in patients with traumatic spinal cord injury (SCI). Methods: A systematic search was performed in PubMed and the Cochrane Collaboration Library for literature published between January 1956 and June 17, 2015. Included studies ere critically appraised, and Grades of Recommendation Assessment, Development and Evaluation methods were used to determine the overall quality of evidence for primary outcomes. Previous systematic reviews on this topic were collated and evaluated using the Assessment of Multiple Systematic Reviews scoring system. Results: The search yielded 723 citations, 13 of which satisfied inclusion criteria. Among these, 6 were primary research articles and 7 were previous systematic reviews. Based on the included research articles, there was moderate evidence that the 24-hour NASCIS II (National Acute Spinal Cord Injury Studies) MPSS regimen has no impact on long-term neurological recovery when all postinjury time points are considered. However, there is also moderate evidence that subjects receiving the same MPSS regimen within 8 hours of injury achieve an additional 3.2 points (95% confidence interval = 0.10 to 6.33; P = .04) of motor recovery compared with patients receiving placebo or no treatment. Conclusion: Although safe to administer, a 24-hour NASCIS II MPSS regimen, when all postinjury time points are considered, has no impact on indices of long-term neurological recovery. When commenced within 8 hours of injury, however, a high-dose 24-hour regimen of MPSS confers a small positive benefit on long-term motor recovery and should be considered a treatment option for patients with SCI

Recovery priorities in degenerative cervical myelopathy: a cross-sectional survey of an international, online community of patients.

OBJECTIVES: To establish the recovery priorities of individuals suffering with degenerative cervical myelopathy (DCM). DESIGN: A cross-sectional, observational study. SETTING: Patients from across the world with a diagnosis of DCM accessed the survey over an 18-month period on Myelopathy.org, an international myelopathy charity. PARTICIPANTS: 481 individuals suffering from DCM completed the online survey fully. MAIN OUTCOME MEASURES: Functional recovery domains were established through qualitative interviews and a consensus process. Individuals were asked about their disease characteristics, including limb pain (Visual Analogue Scale) and functional disability (patient-derived version of the modified Japanese Orthopaedic Association score). Individuals ranked recovery domains (arm and hand function, walking, upper body/trunk function, sexual function, elimination of pain, sensation and bladder/bowel function) in order of priority. Priorities were analysed as the modal first priority and mean ranking. The influence of demographics on selection was analysed, with significance p<0.05. RESULTS: Of 659 survey responses obtained, 481 were complete. Overall, pain was the most popular recovery priority (39.9%) of respondents, followed by walking (20.2%), sensation (11.9%) and arm and hand function (11.5%). Sexual function (5.7%), bladder and bowel (3.7%) and trunk function (3.5%) were chosen less frequently. When considering the average ranking of symptoms, while pain remained the priority (2.6±2.0), this was closely followed by walking (2.9±1.7) and arm/hand function (3.0±1.4). Sensation ranked lower (4.3±2.1). With respect to disease characteristics, overall pain remained the recovery priority, with the exception of patients with greater walking impairment (p<0.005) who prioritised walking, even among patients with lower pain scores. CONCLUSIONS: This is the first study investigating patient priorities in DCM. The patient priorities reported provide an important framework for future research and will help to ensure that it is aligned with patient needs.NIHR Welcome Trus

Influenza pandemic: perception of risk and individual precautions in a general population. Cross sectional study

BACKGROUND: An influenza pandemic may have considerable impact on health and societal functioning. The aim of this study was to explore people's reflections on the consequences of a pandemic. METHODS: Cross-sectional web-based survey of 1,168 Norwegians aged 16–82 years. The main outcome measures were answers to questions about a potential pandemic ("serious influenza epidemic"): statements about personal precautions including stockpiling Tamiflu(®), the perceived number of fatalities, the perceived effects of Tamiflu(®), the sources of information about influenza and trust in public information. RESULTS: While 80% of the respondents stated that they would be "careful about personal hygiene", only a few would stay away from work (2%), or move to an isolated place (4%). While 27% of respondents were uncertain about the number of fatalities during an influenza pandemic, 48% thought it would be lower than the estimate of Norwegian health authorities (0.05%–1%) and only 3% higher. At least half of the respondents thought that Tamiflu(® )might reduce the mortality risk, but less than 1% had personally purchased the drug. The great majority had received their information from the mass media, and only 9% directly from health authorities. Still the majority (65%) trusted information from the authorities, and only 9% reported overt distrust. CONCLUSION: In Norway, considerable proportions of people seem to consider the mortality risk during a pandemic less than health authorities do. Most people seem to be prepared to take some, but not especially disruptive, precautions