PURPOSE:The use of interventional pain management (IPM) modalities to alleviate chronic pain is increasing despite the lack of high-quality evidence. We undertook this survey to explore patterns, training, and attributes of IPM practice.METHODS:We administered a 32-item survey via seven Canadian physician member organizations, whose members were engaged in the management of chronic pain.RESULTS:Of 777 physicians contacted, 256 (33%) responded: 45 (6%) declined to participate and 211 (27%) agreed to participate; the number of participants answering any given question varied. One hundred and sixty-nine of 194 (87%) practiced IPM and 103 of 194 (53%) managed only non-cancer pain. Pain management training of ≥ six months was associated with higher odds of IPM training (odds ratio [OR], 2.98; 95% confidence interval [CI], 1.32 to 6.7), but not necessarily ongoing IPM practice (OR, 1.97; 95% CI, 0.74 to 5.3). A substantial percentage of physicians (108 of 168 [64%]) practiced IPM based only on training received during either their base residency program or courses. Only 48 of 186 (26%) felt that there were adequate opportunities for IPM training, and 69 of 186 (37%) believed that their colleagues practiced IPM in accordance with the best current evidence.CONCLUSIONS:Our survey indicates that IPM practice and training were not uniform, and that interventional therapies for chronic pain may not be performed in accordance with the best available evidence. Our survey highlights a lack of IPM training opportunities, which may result in substandard training. Concerted efforts involving physician organizations and regulators are needed to standardize IPM training and develop clinical guidelines to optimize evidence-based practice.

Study Design. Systematic review. Objective. To determine the validity of the Hoffmann sign for the detection of degenerative cervical myelopathy (DCM) for patients presenting with cervical complaints. Summary of Background Data. While physical examination maneuvers are often used to diagnose DCM, no previous review has synthesized diagnostic accuracy data. Methods. Medline, Embase, and HealthStar were searched for articles from January 1, 1947 to March 1, 2017 using the following terms: Spinal Cord Diseases, Spinal Cord Compression, Cervical Vertebrae, Signs and Symptoms, Physical Examination, Epidemiologic studies, Epidemiologic Research Design, Predictive Value of Tests, and Myelopathy. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) checklist was applied to determine the level of evidence. Articles included were published in English or French language, rated as QUADAS level 3 or higher with a minimum 10 patients presenting with cervical complaints having undergone the Hoffman sign. Excluded studies recruited patients with a nondegenerative type of cervical myelopathy, and/or no evaluation with magnetic resonance imaging. Results. A total of 589 articles were selected for review. Following the application of inclusion and exclusion criteria, 45 articles were analyzed using the QUADAS checklist. Only of three articles were of QUADAS quality 3 or higher. Analysis of combined data from 2/3 studies indicated that the Hoffman sign has a positive likelihood ratio of 2.2 (95% CI 1.5–3.3) and a negative likelihood ratio of 0.63 (95% CI 0.5–0.8). Conclusion. A positive Hoffman alone is unlikely to lead to more than a small change in estimated probability of DCM as compared with the gold standard test (magnetic resonance imaging). Variability in results across individual studies may result from differences in study design. There are insufficient data to support use of the Hoffman sign alone to confirm or refute a diagnosis of DCM. Level of Evidence: 1

Background: No drug treatment capable of restoring locomotor capabilities in patients suffering a motor-complete spinal cord injury (SCI) has ever been developed. We assessed the safety and efficacy of an activator of spinal locomotor neurons in humans, which were shown in paraplegic animals to elicit temporary episodes of involuntary walking.Methods: Single administration of buspirone/levodopa/carbidopa (Spinalon (TM)), levodopa/carbidopa (ratio 4: 1), and buspirone or placebo was performed using a dose-escalation design in 45 subjects placed in supine position who had had an SCI classified as complete (AIS A) or motor-complete/sensory incomplete (AIS B) for at least 3 months. Blood samples before and at regular intervals (15, 30, 60, 120, 240 min) after treatment were collected for hematological and pharmacokinetic (PK) analyses. Electromyographic (EMG) activity of eight muscles (four per leg) was monitored prior to and at several time points after drug administration.Results: Spinalon (TM) (10-35 mg buspirone/100-350 mg levodopa/25-85 mg carbidopa) displayed no sign of safety concerns - only mild nausea was found in 3 cases. At higher doses, 50 mg/500 mg/125 mg Spinalon (TM) was considered to have reached maximum tolerated dose (MTD) since 3 out of 4 subjects experienced related adverse events including vomiting. PK analyses showed comparable data between groups suggesting no significant drug-drug interaction with Spinalon (TM). Only the Spinalon (TM)-treated groups displayed significant EMG activity accompanied by locomotor-like characteristics - that is with rhythmic and bilaterally alternating bursts.Conclusion: Therefore, this study provides evidence of safety and preliminary efficacy following a single administration of Spinalon (TM) in subjects with SCI.

PURPOSE:To determine the clinical effect of antibiotic treatment for patients with low back pain and Modic 1 changes.METHODS:This is a retrospective case series of patients treated at the Canadian Forces Health Services Centre in Ottawa and the McGill University Health Centre. Where available, pain, functional, and imaging outcomes in 11 patients treated between 2013 and 2015 were analyzed to determine effect of antibiotic treatment for patients with low back pain and associated Modic 1 changes on magnetic resonance imaging.RESULTS:Conservatively, only 3 of 11 patients met the criteria for improvement for pain and/or function. While a larger proportion improved in the long term, outcomes were not thought to be temporally attributable to antibiotic treatment, as in most cases, ongoing therapy, medications, and/or injections were required. There did not appear to be a correlation between clinical improvement and associated end plate volume involvement for Modic changes.CONCLUSION:Antibiotics for the treatment of low back pain in the context of Modic changes on MRI did not generally provide significant improvement in pain and function for patients in this small cohort. Despite early excitement regarding this treatment, further research is required.

BACKGROUND:This prospective, randomized trial compared neurostimulation (NS) and ultrasound (US) guided lateral femoral cutaneous nerve (LFCN) block. We hypothesized that US would result in a shorter total anesthesia-related time (sum of performance and onset times).METHODS:Twenty-one volunteers were enrolled. The right lower limb was randomized to an NS- or US-guided LFCN block. The alternate technique was employed for the left lower limb. With NS, paresthesias were sought in the lateral thigh at a stimulatory threshold of 0.6 mA (pulse width=0.3 ms; frequency=2 Hz) or lower. With US, local anesthetic was deposited under the inguinal ligament, ventral to the iliopsoas muscle. In both groups, 5 mL of lidocaine 2% were used to anesthetize the nerve. During the procedure of the block, the performance time and number of needle passes were recorded. Subsequently, a blinded observer assessed sensory block in the lateral thigh every minute until 20 minutes. Success was defined as loss of pinprick sensation at a point midway between the anterior superior iliac spine and the lateral knee line. The blinded observer also assessed the areas of sensory block in the anterior, medial, lateral, and posterior aspects of the thigh and mapped this distribution onto a corresponding grid.RESULTS:Both modalities provided comparable success rates (76.2%-95.2%), performance times (162.1 to 231.3 seconds), onset times (300.0 to 307.5 seconds) and total anesthesia related-times (480.1 to 554.0 seconds). However US required fewer needle passes (3.2±2.9 vs 9.5±12.2; P=.009). There were no intergroup differences in terms of the distribution of the anesthetized cutaneous areas. However considerable variability was encountered between individuals and between the 2 sides of a same subject. The most common areas of sensory loss included the central lateral two-eighths anteriorly and the central antero-inferior three-eighths laterally.CONCLUSION:Ultrasound guidance and NS provide similar success rates and total anesthesia-related times for LFCN block. The territory of the LFCN displays wide inter- and intra-individual variability.

We describe a case of a 53-year-old man with type 2 diabetes mellitus in whom cervical-radiculoplexus neuropathy developed, with concomitant cranial and phrenic nerve involvement, occurring as a stepwise, monophasic course. The patient had a presumed remote history of idiopathic cervical-radiculoplexus neuropathy.

New treatments are being investigated for spinal cord injury (SCI), and any improvement may result in incremental cost savings. The objective of this study was to determine the direct costs of care 2 years after an SCI, stratifying for completeness and level of injury. A retrospective database analysis was carried out using data from the Quebec Trauma Registry, the Quebec Medical Insurance Board, and the Quebec Automobile Insurance Corporation between 1997 and 2007. Excluding individuals sustaining moderate or severe traumatic brain injuries, 481 individuals who sustained an SCI from motor vehicle accidents were identified. Individuals were classified as complete and incomplete in the following categories: C1–C7, C8–T6, T7–L1, L2–S5. Using data from governmental public healthcare organizations makes this study comprehensive. For C1–C7 complete and incomplete spinal cord injuries, the first-year cost was $157 718 and $56 505, respectively (2009 Canadian dollars calculated per patient). Similar differences between complete and incomplete spinal cord injuries were seen for the other groups. Furthermore, for complete injuries, costs were higher for higher levels of injury during both the first and the second year after injury. For incomplete lesions, costs did not differ significantly between groups during the first or the second year. Incomplete spinal cord injuries result in lower healthcare costs compared with complete injuries across all groups during the first 2 years after injury. As less severe levels of injury result in measurably lower costs, the funds spent to reduce the severity or level of SCI could at least partially be recouped through healthcare savings.

BACKGROUND A 55-year-old male presented with severe pain and functional limitations as a result of left hip osteoarthritis. He had failed multiple treatments while waiting for a hip arthroplasty, including physical therapy, medications, and various intra-articular injections. Thermal radiofrequency lesioning of the obturator and femoral articular branches to the hip joint was offered in the interim. OBJECTIVES To our knowledge, this is the first report to describe an inferior-lateral approach for lesioning the obturator branch, the clinical application of successive lesions to increase denervation area, and outcomes in a patient receiving a second treatment with previously good results. METHODS To discuss relevant and technical factors for this specific case, we reviewed previous literature on hip joint radiofrequency and critically evaluated previous anatomic studies in the context of radiofrequency. RESULTS The first treatment provided significant benefit for a period of 6 months. A second treatment was employed providing only mild to moderate benefit until his joint replacement surgery 4 months later. Literature review revealed studies of low quality secondary to small sample sizes, patient selection methodology, inclusion of patients with heterogenous etiologies for pain, variable needle placement techniques, and lack of measurement of functional outcomes. LIMITATIONS Case report and low quality studies in existing literature. CONCLUSIONS Hip joint radiofrequency denervation is a promising avenue for adjunctive treatment of hip pain. Further cadaveric studies are required to clarify a multitude of technical parameters. Once these are well defined, future clinical studies should consider pain, functional, and economic outcomes in their design.

Event Abstract Back to Event Kinetics of inflammatory markers following traumatic injuries to the spinal cord. Danuta Radzioch1, 2*, Gabriella Wojewodka1, 3, Samuel David1, 2, Ioli Makriyianni3, Mohan Radhakrishna1, 3, Stefan Parent4, 5 and Jean Ouellet1, 6 1 McGill University, Canada 2 Montreal General Hospital Research Institute, Canada 3 Montreal General Hospital, McGill University Health Center, Canada 4 Hôpital Sacré-Coeur de Montréal, Canada 5 Université de Montréeal, Canada 6 Shriners Hospital Canada, Canada ABSTRACT Inflammation following traumatic spinal cord injuries precedes the wound healing process, however, excessive inflammation may lead to irreversible neuronal damage. In this study we assessed whether there are differences in elevation of inflammatory markers in patients with spinal cord injuries (SCI) as compared to those with spinal fractures (SF) without CNS damage. Patients with SCI and SF were recruited to the study. Blood samples were collected at 1, 2, 3, 8-16, 25-49 days and 1-2 years post injury. We analyzed inflammatory markers in blood plasma (IL-1β, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IFNα2, IFNγ, and TNFα) and assessed the differences in their levels between patients with SCI and SF injuries. Here we report preliminary data on 7 SCI and 10 SF patients. IL-6 levels were higher in SCI than SF patients from days 1 to 3, whereas at 8-16 days post injury, IL-6 became significantly lower in SCI patients than SF (p = 0.0428). At day 2, IL-10 levels were significantly higher in SCI patients compared to SF (p = 0.0341). IFNγ levels were higher in SCI and SF patients at day 3 (p = 0.0216). At 8-16 days post injury , IL-17A and IL-8 were higher in SCI than SF patients (p = 0.0079 and p = 0.0033, respectively). SCI patients had significantly higher levels of inflammatory markers than SF patients from the first day of injury suggesting that SCI patients may benefit from therapies reducing systemic inflammation immediately following SCI injury. INTRODUCTION Injuries to the spinal cord may cause debilitating and permanent motor damage. The inflammatory process plays a crucial role in neuronal repair. Neutrophils are rapidly recruited following trauma to the spinal cord. They start appearing within 2 to 3 hours post injury and their peak concentration can be observed between 1 to 3 days (1). Macrophage recruitment follows neutrophil infiltration and the increased amount of macrophages may persist for months (1, 2). Unabated, the inflammatory process may impede neuronal repair leading to secondary tissue damage. Unlike spinal cord injuries, spinal fractures result in little CNS damage. We hypothesized that the expression of inflammatory markers following these two types of injuries have different kinetics, explaining in part the difference in patient recovery. In this report, we describe preliminary data from our study assessing the expression of cytokines following trauma causing spinal cord injury and spinal fracture. METHODS Study Protocol. Patients with an isolated spinal cord injury (SCI) or isolated spinal fracture (SF) were recruited from the Montreal Sacré-Coeur Hospital (Montreal, Qc, Canada) and the Montreal General Hospital (Montreal, Qc, Canada) emergency departments. Here we report preliminary data on 7 SCI and 10 SF patients. The study was approved by the institutional review boards for both study sites. Patients and family members were asked to give consent to participate in the study. The inclusion criteria for isolated SCI included: up to 65 years of age, complete American Spinal Injury Association (ASIA) A grade of injury, incomplete (ASIA) B, C or D. The inclusion criteria for isolated SF included: up to 65 years of age, ASIA E (no spinal cord deficit), cervical, thoracic, and lumbar burst fractures with no spinal cord injury that have had conservative treatment or surgical intervention. Exclusion criteria included: older than 65 years of age, presence of tumors, other major trauma such as in long bones (femur, tibia, fibula, humerus, ulna, radius), traumatic brain injury, Type B or C pelvic fractures, Cauda Equina Syndrome, pregnancy, metabolic diseases and more than 72 hours post injury. Sample collection and cytokine analysis. Blood samples were collected at 1, 2, 3, 8-16, 25-49 days and 1-2 years post injury in EDTA coated tubes. Samples were spun at 3000 rpm at 4°C for 10 min for plasma isolation. We analyzed inflammatory markers in blood plasma (IL-1β, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IFNα2, IFNγ, and TNFα) with the MILLIPLEX® Map multiplex assay (Millipore, Mississauga, ON, Canada) using the MAGPIX® multiplexing instrument (Millipore) according to manufacturer’s instructions. Data was analyzed with the MILLIPLEX® Analyst software, version 4.2 (Millipore). Statistical analysis. Data were analyzed using the GraphPad Prism 5 (GraphPad Software, LaJolla, CA, USA). The Mann-Whitney test was used to determine statistical differences between the two patient groups at each time point. Significance was set at p < 0.05. RESULTS AND DISCUSSION Inflammation plays an important role in tissue repair following any type of injury. In the case of spinal trauma, the timing of inflammatory cell influx and cytokine expression is sensitive (3). For instance, soon after spinal trauma, macrophages are polarized towards a M1 phenotype inducing the expression of pro-inflammatory cytokines. This is followed by a brief period of polarization towards M2 macrophages, which may have anti-inflammatory effects in spinal trauma. Eventually, the polarization returns to predominantly M1 macrophages, with minimal presence of M2 macrophages (4). Our analysis of the expression of inflammatory markers revealed differences between SCI and SF patient groups post spinal trauma (Figure 1). Within 24 hours of injury (day 1), there were no statistically significant differences between the two groups, although IL-6 had the tendency to be higher in SCI patients (Figure 1D). At day 2, IL-6 and IL-10 were higher in SCI patients than SF (Figure 1D and G). The higher levels of IL-10 suggest a brief shift towards anti-inflammatory mechanisms however not sustained at day 3. IFNγ levels in SCI patients were significantly higher in SCI patients as of day 3 (p = 0.0216, Figure 1B) which may induce prolonged activation of pro-inflammatory pathways. Significantly higher levels of IL-8 and IL-17A (p = 0.0033 and p = 0.0079, respectively) were observed in SCI patients at 8-16 days post-injury (Figure 1F and J). Interestingly, IL-17 was found to impair recovery from spinal contusions in mouse models and IL-17 knock-out mice had improved recovery of locomotor function compared to wild-type controls (5). Our previous studies using a mouse model of spinal cord injury demonstrated improved locomotor function recovery and reduced cytokine expression following treatment with fenretinide, a Vitamin A derivative (6). Our preliminary results suggest that SCI patients have higher levels of inflammatory markers following injury. Further studies are needed to determine whether they may benefit from anti-inflammatory therapies, such as fenretinide. CONCLUSION SCI patients had significantly higher levels of inflammatory markers than SF patients from the first day of injury. These could be a target for therapy immediately following SCI injury. FIGURE LEGEND Figure 1. Kinetics of inflammatory markers in SCI and SF patients. Blood plasma was analyzed from 7 SCI (red) and 10 SF (blue) patients at 1. 1 day (SCI n = 3; SF n = 8), 2. 2 days (SCI n = 7; SF n = 9), 3. 3 days (SCI n = 7; SF n = 10), 4. 8-16 days (SCI n = 7; SF n = 9), 5. 25-49 days (SCI n = 6; SF n = 5), 6. 1-2 years after trauma (SCI n = 2; SF n = 2). A) IFNα2 levels were higher in SCI patients than SF. B) IFNγ levels were higher in SCI and SF patients at day 3 (p = 0.0216). C) IL-1β levels were higher in SF patients than SCI patients on Day 1. D) IL-6 levels were higher in SCI than SF patients from days 1 to 3 whereas at 8-16 days post injury, IL-6 became significantly lower in SCI patients than SF (p = 0.0428). E) IL-7 levels were higher in SCI patients at later time points. F) At 8-16 days post injury, IL-8 was higher in SCI than SF patients (p = 0.0033). G) At day 2, IL-10 levels were significantly higher in SCI patients compared to SF (p = 0.0341). H) IL-12p70 levels were higher in SF patients on day 2, but were higher in SCI patients at later time points. I) IL-13 levels were barely detectable in all samples excepting high levels in one patient at 1-2 years post injury. J) At 8-16 days post injury, IL-17A was higher in SCI than SF patients (p = 0.0079). K) TNFα levels were similar in SCI and SF groups. Figure 1 References 1 Fleming JC, Norenberg MD, Ramsay DA, et al. The cellular inflammatory response in human spinal cords after injury Brain 2006;129:3249-69. 2 Chang HT Subacute human spinal cord contusion: few lymphocytes and many macrophages Spinal Cord 2007;45:174-82. 3 David S, Kroner A Repertoire of microglial and macrophage responses after spinal cord injury Nat Rev Neurosci 2011;12:388-99. 4 Kigerl KA, Gensel JC, Ankeny DP, et al. Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord J Neurosci 2009;29:13435-44. 5 Hill F, Kim CF, Gorrie CA, et al. Interleukin-17 deficiency improves locomotor recovery and tissue sparing after spinal cord contusion injury in mice Neurosci Lett 2011;487:363-7. 6 Lopez-Vales R, Redensek A, Skinner TA, et al. Fenretinide promotes functional recovery and tissue protection after spinal cord contusion injury in mice J Neurosci 2010;30:3220-6. Keywords: Spinal Cord Injuries, Inflammation, Cytokines, Spinal Fractures, Kinetics, Chemokines, clinical study Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Immune-mediated disease pathogenesis Citation: Radzioch D, Wojewodka G, David S, Makriyianni I, Radhakrishna M, Parent S and Ouellet J (2013). Kinetics of inflammatory markers following traumatic injuries to the spinal cord.. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.01182 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 31 Jul 2013; Published Online: 22 Aug 2013. * Correspondence: Prof. Danuta Radzioch, McGill University, Montreal, Canada, danuta.radzioch@mcgill.ca Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Danuta Radzioch Gabriella Wojewodka Samuel David Ioli Makriyianni Mohan Radhakrishna Stefan Parent Jean Ouellet Google Danuta Radzioch Gabriella Wojewodka Samuel David Ioli Makriyianni Mohan Radhakrishna Stefan Parent Jean Ouellet Google Scholar Danuta Radzioch Gabriella Wojewodka Samuel David Ioli Makriyianni Mohan Radhakrishna Stefan Parent Jean Ouellet PubMed Danuta Radzioch Gabriella Wojewodka Samuel David Ioli Makriyianni Mohan Radhakrishna Stefan Parent Jean Ouellet Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Event Abstract Back to Event Lipid profile analysis in spinal trauma patients shows severe distortion of AA/DHA after injury Danuta Radzioch1, 2*, Juan B. De Sanctis3, Gabriella Wojewodka1, 2, Mohan Radhakrishna1, 4, Ioli Makriyianni4, Stefan Parent5, 6, Jean Ouellet1, 7 and Samuel David1, 2 1 McGill University, Canada 2 Montreal General Hospital Research Institute, Canada 3 Central University of Venezuela, Venezuela 4 Montreal General Hospital, McGill University Hospital Center, Canada 5 Université de Montréal, Canada 6 Hôpital Sacré-Coeur de Montréal, Canada 7 Shriners Hospital Canada, Canada ABSTRACT Studies have shown fatty acid abnormalities in various neurological disorders with increased arachidonic acid (AA), an omega-6 pro-inflammatory fatty acid, and decreased levels of docosahexaenoic acid (DHA), an omega-3 fatty acid which reduces inflammation. Using a mouse model of spinal contusion injury, we previously showed rapid increases in AA/DHA ratio in the plasma and spinal cord of mice after spinal cord injuries. We found that treatment with the drug fenretinide corrected the fatty acid defects and improved recovery in mice. In this study, we hypothesized that AA and DHA may also be impaired in patients following trauma to the spine. Here we report preliminary results from our study including 23 spinal cord injury patients and 8 spinal fracture patients. Plasma samples were taken at various times post injury: 1, 2, 3, 8-16 and 25-49 days. We assessed the levels of AA, DHA and malondialdehyde (MDA), a marker of lipid peroxidation. The greatest changes in fatty acids occurred immediately after spinal cord trauma with increased AA and decreased DHA in both types of injuries. Thus the AA/DHA ratio was distorted towards a more pro-inflammatory status. Additionally, MDA increased after spinal cord injury which indicated higher levels of peroxidation. At later time points, the fatty acid levels returned to normal and peroxidation decreased as well. Our results provided confirmation for our hypothesis that AA/DHA ratio is distorted in the plasma immediately after spinal cord injuries and may be a factor in contributing to further neuronal damage. This is important as our data suggest that immediate application of fenretinide after a spinal injury in the rodent model might decrease secondary damage and improve neurological outcomes. INTRODUCTION Injury to the spinal cord leads to functional impairments due to loss of neurons, glia, myelin and the disruption of axonal pathways. This functional loss is permanent after spinal cord injury (SCI) because of the limited capacity of the CNS for regeneration and self-renewal (1). Several studies indicate that individuals with various neurological disorders have increased levels of arachidonic acid (AA), the omega-6 polyunsaturated fatty acid (PUFA) which causes inflammation, and decreased levels of docosahexaenoic acid (DHA), the omega-3 PUFA which reduces inflammation (2-4). These two fatty acids are also involved in many other biological functions in addition to inflammation. After SCI, PUFAs appear to be important regulators of the onset and resolution of the inflammatory response (5). AA is metabolized by cyclooxygenases and lypooxygenases giving rise to prostaglandins, thromboxanes and leukotrienes, which are potent pro-inflammatory mediators (6). Conversely, DHA, with its anti-inflammatory properties, plays a role in the resolution of inflammation by generating lipoxins, protectins and resolvins of the D series which actively terminate inflammation (7-9). In addition, DHA also has potent free radical scavenging and anti-oxidant properties (10). We hypothesized that the levels AA and DHA would be affected in patients with spinal traumas. METHODS Study Protocol. Patients with an isolated spinal cord injury (SCI) or isolated spinal fracture (SF) were recruited from the Montreal Sacré-Coeur Hospital (Montreal, Qc, Canada) and the Montreal General Hospital (Montreal, Qc, Canada) emergency departments. Here we report preliminary data on 23 SCI and 8 SF patients. The study was approved by the institutional review boards for both study sites. Patients and family members were asked to give consent to participate in the study. The inclusion criteria for isolated SCI included: up to 65 years of age, complete American Spinal Injury Association (ASIA) A grade of injury, incomplete (ASIA) B, C or D. The inclusion criteria for isolated SF included: up to 65 years of age, ASIA E (no spinal cord deficit), thoracic, cervical, and lumbar burst fractures with no spinal cord injury that have had conservative treatment or surgical intervention. Exclusion criteria included: older than 65 years of age, presence of tumors, other major trauma such as in long bones (femur, tibia, fibula, humerus, ulna, radius), traumatic brain injury, Type B or C pelvic fractures, Cauda Equina Syndrome, pregnancy, metabolic diseases and more than 72 hours post injury. Ten healthy volunteers were recruited and consented as controls for the fatty acid analysis. Sample collection and PUFA analysis. Blood samples were collected at 1, 2, 3, 8-16 and 25-49 days in EDTA coated tubes. Samples were spun at 3000 rpm at 4°C for 10 min for plasma isolation. For PUFA analysis, 100 µl of plasma was added to 900 µl of 1 mM butylated hydroxyanisole (BHA) in a 2:1 chloroform/methanol solution. Lipids were isolated according to the Folch method (11). AA and DHA were assessed by gas chromatography as previously described (12, 13). We assessed lipid peroxidation by indirectly measuring malondialdehyde (MDA) using the thiobarbituric acid reactive species (TBARS) assay (13). RESULTS AND DISCUSSION Using a mouse model of spinal contusions we previously demonstrated that spinal traumas have severe effects on PUFA levels. We found increases in AA and decreases in DHA localized to the spinal cord tissue which were also present systemically in blood plasma. When treated with the semi-synthetic retinoid fenretinide, the mice were protected from the changes in fatty acids and had better recovery of locomotor function (14). We found similar effects on PUFAs in our patient groups after spinal injury. In both SCI and SF patient groups, AA levels were higher than HC levels at day 1 (Figure 1A) and DHA levels were lower than normal values (Figure 1B). Overall, the AA/DHA ratios were also abnormally high. With time, the PUFA levels normalized at the 8 – 16 days post-injury time points. Lipid peroxidation was higher in both patient groups compared to HC values and normalized 1 to 2 weeks after injury, similar to PUFA kinetics. In general, patients were in a greater state of inflammation on day 1 with higher AA and MDA, and lower DHA values. Over time, these levels returned to normal due to the possible effect of current treatments on oxidative stress and improve the AA/DHA ratio to a more anti-inflammatory state. We did not observe any differences in fatty acids between SCI and SF patients thus far although MDA levels in SF patients tended to be higher on day 1 than in SCI patients. The pathway downstream of AA, namely the cyclooxygenase-2 enzyme that generates various eicosanoids, has been shown to contribute to the inflammation-induced secondary damage and functional loss after SCI. Inhibition of COX-2 results in improvement in functional recovery, reduced lesion size and an increase in viable tissue in mild forms of SCI (15, 16). Neuroinflammation was also shown to be modulated by various metabolites of phospholipase A2 (PLA2) affecting inflammation and demyelination. PLA2 enzymes catalyze the hydrolysis of fatty acids at the sn-2 position in phospholipids and thus give rise to the release of fatty acids, such as AA, and the production of lysophospholipids, such as lysophosphatidylcholine (LPC) and have been shown to play a role in SCI (17). PUFAs in general are susceptible to lipid peroxidation due to their high content of double bonds. DHA in particular, having more double bonds than AA, is affected by high states of oxidative stress (18). Reducing MDA, thus increases DHA levels, which was demonstrated by our results. As SCI and SF patients suffered from defects in PUFAs following spinal trauma, they may both benefit from therapies, such as fenretinide, to protect neurons from the consequences of initial PUFA imbalance which in case of SCI trauma frequently leads to irreversible damage of neurons and subsequently to paralysis. CONCLUSION Both SCI and SF patients suffer from defects in PUFAs and higher rates of lipid peroxidation following spinal trauma. The imbalances in the AA/DHA ratio return to normal after 1 to 2 weeks post-injury. Patients may benefit from anti-inflammatory and anti-oxidant therapies, such as fenretinide, to preserve PUFA levels and recover the balance between the levels of pro-inflammatory AA and the anti-inflammatory DHA. FIGURE LEGEND Figure 1. PUFA and lipid peroxidation levels in plasma following spinal trauma. PUFA and lipid peroxidation levels were measured in spinal cord injury patients (SCI, red) and spinal fracture (SF, blue). A) Arachidonic acid (AA) levels. Significant differences were observed in SCI patients between day 1 vs. 8 – 16 days, and vs. 25 – 49 days. For the SF group, day 1 values were significantly different from 8 – 16 days. SCI values at day 1 were significantly different from healthy controls (HC, grey shading) (ANOVA, p < 0.0001). B) Docosahexaenoic acid (DHA) levels. Significant differences were observed in SCI patients between day 1 vs. 8 – 16 days, and vs. 25 – 49 days (ANOVA, p < 0.0001). C) Arachidonic acid/docosahexaenoic acid ratios (AA/DHA). Significant differences (p < 0.05) were observed in the SCI group between day 1 vs. 8 – 16 days, and vs. 26 – 49 days. SF patients had significant differences between day 1 values vs. 8 – 16 days. At day 1, the AA/DHA ratio in the SCI group was significantly higher than HC (ANOVA, p < 0.0001). D) Malondialdehyde (MDA). Significant differences were found in SCI patients between day 1 vs. 8 – 16 days (ANOVA, p = 0.0065). Grey shading represents min and max ranges for HC values and the dotted horizontal line represents the mean of the HC group.* represents significant differences between the time point and day 1 within the patient group as per the ad hoc post-tests. † represents significant differences between the patient group at day 1 and HC as per the ad hoc post-tests. Statistical analysis was done using the Kruskal-Wallis non-parametric ANOVA. P values listed are for the overall ANOVA test. Figure 1 References 1 David S, Lacroix S Molecular approaches to spinal cord repair Annu Rev Neurosci 2003;26:411-40. 2 Richardson AJ Omega-3 fatty acids in ADHD and related neurodevelopmental disorders Int Rev Psychiatry 2006;18:155-72. 3 Orr SK, Bazinet RP The emerging role of docosahexaenoic acid in neuroinflammation Curr Opin Investig Drugs 2008;9:735-43. 4 Michael-Titus AT Omega-3 fatty acids and neurological injury Prostaglandins Leukot Essent Fatty Acids 2007;77:295-300. 5 Farooqui AA, Horrocks LA, Farooqui T Interactions between neural membrane glycerophospholipid and sphingolipid mediators: a recipe for neural cell survival or suicide J Neurosci Res 2007;85:1834-50. 6 David S, Greenhalgh AD, Lopez-Vales R Role of phospholipase A2s and lipid mediators in secondary damage after spinal cord injury Cell Tissue Res 2012;349:249-67. 7 Ariel A, Serhan CN Resolvins and protectins in the termination program of acute inflammation Trends Immunol 2007;28:176-83. 8 Serhan CN Novel chemical mediators in the resolution of inflammation: resolvins and protectins Anesthesiol Clin 2006;24:341-64. 9 Serhan CN, Yacoubian S, Yang R Anti-inflammatory and proresolving lipid mediators AnnuRevPathol 2008;3:279-312.:279-312. 10 Endres S, von Schacky C n-3 polyunsaturated fatty acids and human cytokine synthesis Curr Opin Lipidol 1996;7:48-52. 11 Folch J, Lees M, Sloane Stanely GH A simple method for the isolation and purification of total lipides from animal tissues J Biol Chem 1957;226:497-509. 12 Schlenk H, Gellerman J Esterification of Fatty Acids with Diazomethane on a Small Scale Anal Chem 1960;32:1412-14. 13 Oborna I, Wojewodka G, De Sanctis JB, et al. Increased lipid peroxidation and abnormal fatty acid profiles in seminal and blood plasma of normozoospermic males from infertile couples Hum Reprod 2010;25:308-16. 14 Lopez-Vales R, Redensek A, Skinner TA, et al. Fenretinide promotes functional recovery and tissue protection after spinal cord contusion injury in mice J Neurosci 2010;30:3220-6. 15 Lopez-Vales R, Garcia-Alias G, Guzman-Lenis MS, et al. Effects of COX-2 and iNOS inhibitors alone or in combination with olfactory ensheathing cell grafts after spinal cord injury Spine (Phila Pa 1976) 2006;31:1100-6. 16 O'Banion MK, Kyrkanides S, Olschowka JA Selective inhibition of cyclooxygenase-2 attenuates expression of inflammation-related genes in CNS injury Adv Exp Med Biol 2002;507:155-60. 17 Lopez-Vales R, Ghasemlou N, Redensek A, et al. Phospholipase A2 superfamily members play divergent roles after spinal cord injury FASEB J 2011;25:4240-52. 18 Halliwell B, Chirico S Lipid peroxidation: its mechanism, measurement, and significance Am J Clin Nutr 1993;57:715S-24S; discussion 24S-25S. Keywords: Polyunsaturated fatty acid (PUFA), Arachidonic Acid, docosahexaenoic acid, spinal cord injury (SCI), Spinal Fractures, Spinal Trauma, Malondialdehyde, Lipid Peroxidation, clinical study Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Immune-mediated disease pathogenesis Citation: Radzioch D, De Sanctis JB, Wojewodka G, Radhakrishna M, Makriyianni I, Parent S, Ouellet J and David S (2013). Lipid profile analysis in spinal trauma patients shows severe distortion of AA/DHA after injury. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.01183 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 31 Jul 2013; Published Online: 22 Aug 2013. * Correspondence: Prof. Danuta Radzioch, McGill University, Montreal, Canada, danuta.radzioch@mcgill.ca Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Danuta Radzioch Juan B De Sanctis Gabriella Wojewodka Mohan Radhakrishna Ioli Makriyianni Stefan Parent Jean Ouellet Samuel David Google Danuta Radzioch Juan B De Sanctis Gabriella Wojewodka Mohan Radhakrishna Ioli Makriyianni Stefan Parent Jean Ouellet Samuel David Google Scholar Danuta Radzioch Juan B De Sanctis Gabriella Wojewodka Mohan Radhakrishna Ioli Makriyianni Stefan Parent Jean Ouellet Samuel David PubMed Danuta Radzioch Juan B De Sanctis Gabriella Wojewodka Mohan Radhakrishna Ioli Makriyianni Stefan Parent Jean Ouellet Samuel David Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. 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Background: The personal and societal impact of chronic low back pain is considerable. The intervertebral disc is considered the etiologic source in up to 40% of patients, with considerable previous efforts directed at developing reliable and efficacious treatments. Recent publications, including a double-blind, randomized, placebo-controlled trial, using a one-time treatment of methylene blue, showed statistically significant, clinically relevant improvements in pain and function in the treatment groups. The postulated mechanism of action of methylene blue is denervation of small nociceptive fibers that grow into the annulus fibrosis, which are implicated in discogenic pain.Study Design: Retrospective case series.Setting: Academic pain management center.Objectives: To examine the outcomes for a cohort of patients treated with methylene blue for discogenic pain, discuss potential differences in selection and administration protocols and briefly review other proposed treatments for discogenic pain (e. g. intradiscal electrothermy therapy, intradiscal steroids, intradiscal biaccuplasty, rami communicans radiofrequency thermocoagulation, and chymopapain).Methods: This case series examines the pain and functional outcomes in 8 patients treated with a one-time administration of methylene blue for discogenic back pain. Follow-up information was available between 2 months and over one year, depending on the patient.Results: Application of this treatment for these 8 patients for discogenic pain diagnosed by provocation discography showed only one clinical success at our center. Four patients had a time-limited clinical response in pain and/or function between 2 weeks and 5 months. Patient specific data are outlined in detail herein.Conclusions: Low back pain ascribed to a discogenic source continues to be an elusive clinical entity to treat. We have reserved further treatment of methylene blue for discogenic pain until other controlled trials have been published.Limitations: A case series.

Magnetic resonance imaging (MRI) has become the gold standard for imaging neurological tissues including the spinal cord. The use of MRI for imaging in the acute management of patients with spinal cord injury has increased significantly. This paper used a vigorous literature review with Downs and Black scoring, followed by a Delphi vote on the main conclusions. MRI is strongly recommended for the prognostication of acute spinal cord injury. The sagittal T2 sequence was particularly found to be of value. Four prognostication patterns were found to be predictive of neurological outcome (normal, single-level edema, multi-level edema, and mixed hemorrhage and edema). It is recommended that MRI be used to direct clinical decision making. MRI has a role in clearance, the ruling out of injury, of the cervical spine in the obtunded patient only if there is abnormality of the neurological exam. Patients with cervical spinal cord injuries have an increased risk of vertebral artery injuries but the literature does not allow for recommendation of magnetic resonance angiography as part of the routine protocol. Finally, time repetition (TR) and time echo (TE) values used to evaluate patients with acute spinal cord injury vary significantly. All publications with MRI should specify the TR and TE values used.

The posterolateral knee region is made up of a complex of dynamic and static knee stabilizers, I of which is the popliteus. The popliteus is not commonly documented as causing acute knee problems. Clinicians do not have reliable or valid techniques to assess injuries of this type. We present the case of an isolated popliteus injury near the proximal musculotendinous junction in a professional football player and review pertinent anatomy and examination findings for the popliteus.

In North America, rehabilitation is often viewed as a process that is required after a distinct health-related event. Examples of such events, including musculoskeletal injury, stroke and spinal cord injury, are listed in our commentary.[1][1] Maulik Baxi presents the perspective of the developing

Medicine evolves to reflect the needs of society. This evolution is commonly viewed to be driven by scientific research advances. However, factors on a macroscopic, population level can be equally influential. Three such factors in the 20th century led to the creation of a new specialty, physical