Focal compression of the cervical spinal cord alone does not indicate high risk of neurological deterioration in patients with a diagnosis of mild degenerative cervical myelopathy.

Degenerative Cervical Myelopathy (DCM) is the functional derangement of the spinal cord resulting from vertebral column spondylotic degeneration. Typical neurological symptoms of DCM include gait imbalance, hand/arm numbness, and upper extremity dexterity loss. Greater spinal cord compression is believed to lead to a higher rate of neurological deterioration, although clinical experience suggests a more complex mechanism involving spinal canal diameter (SCD). In this study, we utilized machine learning clustering to understand the relationship between SCD and different patterns of cord compression (i.e. compression at one disc level, two disc levels, etc.) to identify patient groups at risk of neurological deterioration. 124 MRI scans from 51 non-operative DCM patients were assessed through manual scoring of cord compression and SCD measurements. Dimensionality reduction techniques and k-means clustering established patient groups that were then defined with their unique risk criteria. We found that the compression pattern is unimportant at SCD extremes (≤14.5 mm or > 15.75 mm). Otherwise, severe spinal cord compression at two disc levels increases deterioration likelihood. Notably, if SCD is normal and cord compression is not severe at multiple levels, deterioration likelihood is relatively reduced, even if the spinal cord is experiencing compression. We elucidated five patient groups with their associated risks of deterioration, according to both SCD range and cord compression pattern. Overall, SCD and focal cord compression alone do not reliably predict an increased risk of neurological deterioration. Instead, the specific combination of narrow SCD with multi-level focal cord compression increases the likelihood of neurological deterioration in mild DCM patients.

Advanced MRI metrics improve the prediction of baseline disease severity for individuals with degenerative cervical myelopathy.

BACKGROUND CONTEXT: Degenerative cervical myelopathy (DCM) is the most common form of atraumatic spinal cord injury globally. Degeneration of spinal discs, bony osteophyte growth and ligament pathology results in physical compression of the spinal cord contributing to damage of white matter tracts and grey matter cellular populations. This results in an insidious neurological and functional decline in patients which can lead to paralysis. Magnetic resonance imaging (MRI) confirms the diagnosis of DCM and is a prerequisite to surgical intervention, the only known treatment for this disorder. Unfortunately, there is a weak correlation between features of current commonly acquired MRI scans ("community MRI, cMRI") and the degree of disability experienced by a patient. PURPOSE: This study examines the predictive ability of current MRI sequences relative to "advanced MRI" (aMRI) metrics designed to detect evidence of spinal cord injury secondary to degenerative myelopathy. We hypothesize that the utilization of higher fidelity aMRI scans will increase the effectiveness of machine learning models predicting DCM severity and may ultimately lead to a more efficient protocol for identifying patients in need of surgical intervention. STUDY DESIGN/SETTING: Single institution analysis of imaging registry of patients with DCM. PATIENT SAMPLE: A total of 296 patients in the cMRI group and 228 patients in the aMRI group. OUTCOME MEASURES: Physiologic measures: accuracy of machine learning algorithms to detect severity of DCM assessed clinically based on the modified Japanese Orthopedic Association (mJOA) scale. METHODS: Patients enrolled in the Canadian Spine Outcomes Research Network registry with DCM were screened and 296 cervical spine MRIs acquired in cMRI were compared with 228 aMRI acquisitions. aMRI acquisitions consisted of diffusion tensor imaging, magnetization transfer, T2-weighted, and T2*-weighted images. The cMRI group consisted of only T2-weighted MRI scans. Various machine learning models were applied to both MRI groups to assess accuracy of prediction of baseline disease severity assessed clinically using the mJOA scale for cervical myelopathy. RESULTS: Through the utilization of Random Forest Classifiers, disease severity was predicted with 41.8% accuracy in cMRI scans and 73.3% in the aMRI scans. Across different predictive model variations tested, the aMRI scans consistently produced higher prediction accuracies compared to the cMRI counterparts. CONCLUSIONS: aMRI metrics perform better in machine learning models at predicting disease severity of patients with DCM. Continued work is needed to refine these models and address DCM severity class imbalance concerns, ultimately improving model confidence for clinical implementation.

Mobilizing registry data for quality improvement: A convergent mixed-methods analysis and application to spinal cord injury.

Introduction: The rising prevalence of complex chronic conditions and growing intricacies of healthcare systems emphasizes the need for interdisciplinary partnerships to advance coordination and quality of rehabilitation care. Registry databases are increasingly used for clinical monitoring and quality improvement (QI) of health system change. Currently, it is unclear how interdisciplinary partnerships can best mobilize registry data to support QI across care settings for complex chronic conditions. Purpose: We employed spinal cord injury (SCI) as a case study of a highly disruptive and debilitating complex chronic condition, with existing registry data that is underutilized for QI. We aimed to compare and converge evidence from previous reports and multi-disciplinary experts in order to outline the major elements of a strategy to effectively mobilize registry data for QI of care for complex chronic conditions. Methods: This study used a convergent parallel-database variant mixed design, whereby findings from a systematic review and a qualitative exploration were analyzed independently and then simultaneously. The scoping review used a three-stage process to review 282 records, which resulted in 28 articles reviewed for analysis. Concurrent interviews were conducted with multidisciplinary-stakeholders, including leadership from condition-specific national registries, members of national SCI communities, leadership from SCI community organizations, and a person with lived experience of SCI. Descriptive analysis was used for the scoping review and qualitative description for stakeholder interviews. Results: There were 28 articles included in the scoping review and 11 multidisciplinary-stakeholders in the semi-structured interviews. The integration of the results allowed the identification of three key learnings to enhance the successful design and use of registry data to inform the planning and development of a QI initiative: enhance utility and reliability of registry data; form a steering committee lead by clinical champions; and design effective, feasible, and sustainable QI initiatives. Conclusion: This study highlights the importance of interdisciplinary partnerships to support QI of care for persons with complex conditions. It provides practical strategies to determine mutual priorities that promote implementation and sustained use of registry data to inform QI. Learnings from this work could enhance interdisciplinary collaboration to support QI of care for rehabilitation for persons with complex chronic conditions.

Variation in surgical treatment of degenerative spondylolisthesis in Canada: surgeon assessment of stability and impact on treatment.

INTRODUCTION: Controversy exists regarding the optimal surgical treatment of degenerative lumbar spondylolisthesis (DS). Not all DS patients are the same, and the degree to which inherent stability may dictate treatment is unknown. The purpose of this study was to determine the variability in surgical approach relative to surgeon classified stability. The secondary objective was to compare patient-reported outcomes (PROs) across different surgical techniques and grades of stability. METHODS: Patients prospectively enrolled from eleven tertiary care institutions and followed from 2015 to 2019. The surgical technique was at the surgeon's discretion. Surgeons were asked to grade the degree of instability based on the degenerative spondylolisthesis instability classification system (DSIC). DSIC categorizes three different types (I-stable, II-potentially unstable, and III-unstable). One-year changes in PROs were compared between each group. Multivariable regression was used to identify any characteristics that explained variability in treatment. RESULTS: There were 323 patients enrolled in this study. Surgeons' stability classification versus procedure [decompression alone (D)/decompression and posterolateral fusion (D-PL)/and decompression with posterior/transforaminal lumbar interbody fusion (D-PLIF/TLIF)] were as follows: type I (n = 91): D-41%/D-PL-13%/D-PLIF/TLIF-46%; type II (n = 175): D-23%/D-PL-17%/D-PLIF/TLIF-60%; and type III (n = 57):(D-0%/D-PL-14%/D-PLIF/TLIF-86%). Type I patients undergoing D-PL had some improvements in EQ-5D and NRS versus those undergoing D-PLIF/TLIF but otherwise there were no other significant differences between groups. Regression analysis demonstrated advanced age (OR = 1.06, CI 1.02-10.12) and type I (OR = 2.61, CI 1.17-5.81) were associated with receiving decompression surgery alone. CONCLUSIONS: There exists considerable variation in surgical management of DS in Canada. Given similar PROs in two of the three groups, there is potential to tailor surgical intervention and improve resource utilization.

The Damaged Spinal Cord Is a Suitable Target for Stem Cell Transplantation.

Background. Given individuals with spinal cord injury (SCI) approaching 2 million, viable options for regenerative repair are desperately needed. Human central nervous system stem cells (HuCNS-SC) are self-renewing, multipotent adult stem cells that engraft, migrate, and differentiate in appropriate regions in multiple animal models of injured brain and spinal cord. Preclinical improved SCI locomotor function provided rationale for the first-in-human SCI clinical trial of HuCNS-SC cells. Evidence of feasibility and long-term safety of cell transplantation into damaged human cord is needed to foster translational progression of cellular therapies. Methods. A first-ever, multisite phase I/IIa trial involving surgical transplantation of 20 million HuCNS-SC cells into the thoracic cord in 12 AIS A or B subjects (traumatic, T2-T11 motor-complete, sensory-incomplete), aged 19 to 53 years, demonstrated safety and preliminary efficacy. Six-year follow-up data were collected (sensory thresholds and neuroimaging augmenting clinical assessments). Findings. The study revealed short- and long-term surgical and medical safety (well-tolerated immunosuppression in population susceptible to infections). Preliminary efficacy measures identified 5/12 with reliable sensory improvements. Unfortunately, without thoracic muscles available for manual muscle examination, thoracic motor changes could not be measured. Lower limb motor scores did not change during the study. Cervical cord imaging revealed, no tumor formation or malformation of the lesion area, and secondary supralesional structural changes similar to SCI control subjects. Interpretation. Short- and long-term safety and feasibility support the consideration of cell transplantation for patients with complete and incomplete SCI. This report is an important step to prepare, foster, and maintain the therapeutic development of cell transplantation for human SCI.

Opioid use trends in patients undergoing elective thoracic and lumbar spine surgery.

Background: Opioid use in North America has increased rapidly in recent years. Preoperative opioid use is associated with several negative outcomes. Our objectives were to assess patterns of opioid use over time in Canadian patients who undergo spine surgery and to determine the effect of spine surgery on 1-year postoperative opioid use. Methods: A retrospective analysis was performed on prospectively collected data from the Canadian Spine Outcomes and Research Network for patients undergoing elective thoracic and lumbar surgery. Self-reported opioid use at baseline, before surgery and at 1 year after surgery was compared. Baseline opioid use was compared by age, sex, radiologic diagnosis and presenting complaint. All patients meeting eligibility criteria from 2008 to 2017 were included. Results: A total of 3134 patients provided baseline opioid use data. No significant change in the proportion of patients taking daily (range 32.3%-38.2%) or intermittent (range 13.7%-22.5%) opioids was found from pre-2014 to 2017. Among patients who waited more than 6 weeks for surgery, the frequency of opioid use did not differ significantly between the baseline and preoperative time points. Significantly more patients using opioids had a chief complaint of back pain or radiculopathy than neurogenic claudication (p < 0.001), and significantly more were under 65 years of age than aged 65 years or older (p < 0.001). Approximately 41% of patients on daily opioids at baseline remained so at 1 year after surgery. Conclusion: These data suggest that additional opioid reduction strategies are needed in the population of patients undergoing elective thoracic and lumbar spine surgery. Spine surgeons can be involved in identifying patients taking opioids preoperatively, emphasizing the risks of continued opioid use and referring patients to appropriate evidence-based treatment programs.

Contexte: En Amérique du Nord, l'utilisation d'opioïdes a augmenté rapidement dans les dernières années. La prise d'opioïdes en période préopératoire est associée à plusieurs issues négatives. Cette étude visait à évaluer l'évolution des tendances dans l'utilisation d'opioïdes des patients canadiens ayant subi une chirurgie spinale, et de déterminer les effets de la chirurgie sur leur utilisation 1 an après l'opération. Méthodes: Une analyse rétrospective a été réalisée à partir de données recueillies de manière prospective par le Canadian Spine Outcomes and Research Network pour les patients ayant subi une chirurgie thoracique ou une chirurgie spinale élective. On a comparé l'utilisation autodéclarée d'opioïdes au début du suivi, avant la chirurgie et 1 an après la chirurgie. L'utilisation d'opioïdes au départ a été comparée selon le sexe, l'âge, le diagnostic radiologique et le motif de consultation. Entre 2008 et 2017, tous les patients satisfaisant aux critères d'admissibilités ont été inclus dans l'étude. Résultats: Au total, 3134 patients ont fourni des données sur leur prise d'opioïdes au début du suivi. Il n'y avait pas de changement significatif dans la proportion de patients utilisant quotidiennement (32,3 % à 38,2 %) ou occasionnellement (13,7 % à 22,5 %) des opioïdes entre les patients à l'étude avant 2014 et ceux à l'étude de 2014 à 2017. Parmi les patients qui ont attendu plus de 6 semaines avant la chirurgie, la fréquence de la prise d'opioïdes n'a pas changé de manière significative entre le début du suivi et la rencontre préopératoire. Une proportion significativement plus grande de patients qui utilisaient des opioïdes consultaient principalement pour des douleurs au dos ou une radiculopathie que pour une claudication neurogène (p < 0,001), et il y avait une proportion significativement plus grande de patients de moins de 65 ans qui utilisaient des opioïdes que de patients de 65 ans ou plus (p < 0,001). Environ 41 % des patients qui prenaient quotidiennement des opioïdes au départ le faisaient aussi 1 an après la chirurgie. Conclusion: Ces données suggèrent que des stratégies supplémentaires de réduction de l'utilisation d'opioïdes sont nécessaires pour les patients qui subissent une chirurgie thoracique ou une chirurgie spinale élective. Il est possible de demander aux chirurgiens spécialisés dans ce domaine de repérer les patients qui prennent des opioïdes avant l'opération, puisque l'utilisation prolongée comporte des risques, et de les aiguiller vers un programme de traitement adéquat et fondé sur des données probantes.

The impact of machine learning on patient care: A systematic review.

BACKGROUND: Despite the expanding use of machine learning (ML) in fields such as finance and marketing, its application in the daily practice of clinical medicine is almost non-existent. In this systematic review, we describe the various areas within clinical medicine that have applied the use of ML to improve patient care. METHODS: A systematic review was performed in accordance with the PRISMA guidelines using Medline(R), EBM Reviews, Embase, Psych Info, and Cochrane Databases, focusing on human studies that used ML to directly address a clinical problem. Included studies were published from January 1, 2000 to May 1, 2018 and provided metrics on the performance of the utilized ML tool. RESULTS: A total of 1909 unique publications were reviewed, with 378 retrospective articles and 8 prospective articles meeting inclusion criteria. Retrospective publications were found to be increasing in frequency, with 61 % of articles published within the last 4 years. Prospective articles comprised only 2 % of the articles meeting our inclusion criteria. These studies utilized a prospective cohort design with an average sample size of 531. CONCLUSION: The majority of literature describing the use of ML in clinical medicine is retrospective in nature and often outlines proof-of-concept approaches to impact patient care. We postulate that identifying and overcoming key translational barriers, including real-time access to clinical data, data security, physician approval of "black box" generated results, and performance evaluation will allow for a fundamental shift in medical practice, where specialized tools will aid the healthcare team in providing better patient care.

Cerebrospinal Fluid Biomarkers in Human Spinal Cord Injury from a Phase II Minocycline Trial.

Inflammatory changes after spinal cord injury (SCI) have been reported in animal models, but human studies are relatively limited. We examined cerebrospinal fluid (CSF) collected from subjects enrolled in a phase II placebo-controlled trial of minocycline for evidence of inflammatory and structural changes after acute human SCI. CSF was collected from 29 subjects every 6 h for 7 days and investigated for eight molecules. CSF from 6 normal subjects (lumbar microdiscectomy patients without central nervous system pathology) was also examined for comparison. Cumulative levels of CSF molecules were compared between patients with motor complete and motor incomplete injury, between those receiving minocycline or placebo, and correlated to neurological outcome at 1 year (alpha = 0.05). We found that levels of C-C motif chemokine ligand 2 (monocyte chemoattractant), C-X-C motif chemokine 10 (CXCL10; T-cell chemoattractant), interleukin-1ß (IL-1ß), matrix metalloproteinase-9 (MMP-9), neurofilament heavy chain (NfH), and heme oxygenase-1 (HO-1) were significantly elevated after SCI. Neural cell adhesion molecule and nitric oxide oxidation products (NOx) were not significantly altered. Levels of IL-1ß, MMP-9, and HO-1 were higher in subjects with more severe motor impairment. Higher cumulative levels of IL-1ß, MMP-9, and CXCL10 exhibited moderate, but significant, correlation with worse motor recovery at 12 months. Only HO-1 and NfH appeared to vary with minocycline treatment; HO-1 lacked a later peak compared to placebo-treated subjects while NfH did not manifest its early peak with treatment. These analyses of CSF biomarkers imply a pathophysiological role for particular molecules and suggest mechanistic targets for minocycline in human traumatic SCI.

Serum Albumin Predicts Long-Term Neurological Outcomes After Acute Spinal Cord Injury.

BACKGROUND: There is a need to identify reliable biomarkers of spinal cord injury recovery for clinical practice and clinical trials. OBJECTIVE: Our objective was to correlate serum albumin levels with spinal cord injury neurological outcomes. METHODS: We performed a secondary analysis of patients with traumatic spinal cord injury (n = 591) participating in the Sygen clinical trial. Serum albumin concentrations were obtained as part of routine blood chemistry analysis, at trial entry (24-72 hours), 1, 2, and 4 weeks after injury. The primary outcomes were "marked recovery" and lower extremity motor scores, derived from the International Standards for the Neurological Classification of Spinal Cord Injury. Data were analyzed with multivariable logistic and linear regression to adjust for potential confounders. RESULTS: Serum albumin was significantly associated with spinal cord injury neurological outcomes. Higher serum albumin concentrations at 1, 2, and 4 weeks were associated with higher 52-week lower extremity motor score. Similarly, the odds of achieving "marked neurological recovery" was greater for individuals with higher serum albumin concentrations. The association between serum albumin concentrations and neurological outcomes was independent of initial injury severity, treatment with GM-1, and polytrauma. CONCLUSIONS: In spinal cord injury, serum albumin is an independent marker of long-term neurological outcomes. Serum albumin could serve as a feasible biomarker for prognosis at the time of injury and stratification in clinical trials.

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.

Timing of Decompression in Patients With Acute Spinal Cord Injury: A Systematic Review.

STUDY DESIGN: Systematic review. OBJECTIVE: To conduct a systematic review and synthesis of the literature to assess the comparative effectiveness, safety, and cost-effectiveness of early (≤24 hours) versus late decompression (>24 hours) in adults with acute spinal cord injury (SCI). METHODS: A systematic search was conducted of Medline, EMBASE, the Cochrane Collaboration Library, and Google Scholar to identify studies published through November 6, 2014. Studies published in any language, in humans, and with an abstract were considered for inclusion. Included studies were critically appraised and the overall strength of evidence was determined using methods proposed by the Grading of Recommendation Assessment, Development and Evaluation working group. RESULTS: The search yielded 449 potentially relevant citations. Sixteen additional primary studies were identified through other sources. Six studies met inclusion criteria. All but 2 studies were considered to have moderately high risk of bias. Across studies and injury levels, the impact of early surgical decompression (≤24 hours) on clinically important improvement in neurological status was variable. Isolated studies reported statistically significant and clinically important improvements at 6 months (cervical injury, low strength of evidence) and following discharge from inpatient rehabilitation (all levels, very low strength of evidence) but not at other time points; another study observed a statistically significant 6 point improvement in ASIA Impairment Scale (AIS) among patients with AIS B, C, or D, but not for those with AIS A (very low strength of evidence). In one study of acute central cord syndrome without instability, a clinically and statistically meaningful improvement in total motor scores was reported at 6 and 12 months in patients treated early (versus late). There were, however, no significant differences in AIS improvement between early and late surgical groups at 6- or 12-months (very low strength of evidence). One of 3 studies found a shorter length of hospital stay associated with early surgical decompression. Of 3 studies reporting on safety, no significant differences in rates of complications (including mortality, neurologic deterioration, pneumonia or pressure ulcers) were noted between early and late decompression groups. CONCLUSIONS: Results surrounding the efficacy of early versus late decompressive surgery, as well as the quality of evidence available, were variable depending on the level of SCI, timing of follow-up, and specific outcome considered. Existing evidence supports improved neurological recovery among cervical SCI patients undergoing early surgery; however, evidence regarding remaining SCI populations and clinical outcomes was inconsistent.

Neurons Export Extracellular Vesicles Enriched in Cysteine String Protein and Misfolded Protein Cargo.

The fidelity of synaptic transmission depends on the integrity of the protein machinery at the synapse. Unfolded synaptic proteins undergo refolding or degradation in order to maintain synaptic proteostasis and preserve synaptic function, and buildup of unfolded/toxic proteins leads to neuronal dysfunction. Many molecular chaperones contribute to proteostasis, but one in particular, cysteine string protein (CSPα), is critical for proteostasis at the synapse. In this study we report that exported vesicles from neurons contain CSPα. Extracellular vesicles (EV's) have been implicated in a wide range of functions. However, the functional significance of neural EV's remains to be established. Here we demonstrate that co-expression of CSPα with the disease-associated proteins, polyglutamine expanded protein 72Q huntingtinex°n1 or superoxide dismutase-1 (SOD-1G93A) leads to the cellular export of both 72Q huntingtinex°n1 and SOD-1G93A via EV's. In contrast, the inactive CSPαHPD-AAA mutant does not facilitate elimination of misfolded proteins. Furthermore, CSPα-mediated export of 72Q huntingtinex°n1 is reduced by the polyphenol, resveratrol. Our results indicate that by assisting local lysosome/proteasome processes, CSPα-mediated removal of toxic proteins via EVs plays a central role in synaptic proteostasis and CSPα thus represents a potential therapeutic target for neurodegenerative diseases.

The impact of specialized centers of care for spinal cord injury on length of stay, complications, and mortality: a systematic review of the literature.

Specialized centers of care for spinal cord injury (SCI) were first established in 1944 in England. The objective of these centers is to improve care and neurological recovery of patients suffering from a spinal cord injury. An interdisciplinary group of experts composed of medical and surgical specialists treating patients with SCI formulated the following questions: (1) Is there any evidence to suggest that specialized centers of care in SCI decrease the length of patient stay? and (2) Is there evidence that specialized centers of care for SCI reduce mortality and secondary complications? A systematic review of the current evidence was performed using multiple databases to answer these two specific questions. Two independent reviewers graded each paper using the Black and Downs method. Recommendations were then formulated based on the evidence available and were reviewed by a panel of experts using a modified Delphi approach. Two recommendations were formulated and both received complete agreement from a panel of experts. The first recommendation is "Early transfer of a patient with traumatic SCI to a specialized center of care should be done promptly to decrease overall length of stay." The second recommendation is "Early transfer of patients with traumatic SCI to an integrated multidisciplinary specialized center of care decreases overall mortality, and the number and severity of complications."

Inflammatory and structural biomarkers in acute traumatic spinal cord injury.

The paralysis of an acute spinal cord injury (SCI) remains a catastrophic condition for which there are currently no effective treatments. While the diagnosis of acute traumatic SCI is typically quite easy to make, distinguishing the exact degree of severity and prognosticating the extent of neurologic recovery are challenging. Functional neurologic measures are currently used to stratify injury severity and predict neurologic outcome. However, these measures are often impossible to determine in acutely injured patients. Additionally, for patients deemed to be of a specific injury severity, the variability in spontaneous neurologic recovery is high. Both of these issues severely impair the ability to perform clinical trials in novel therapies for SCI. Biomarkers that could more precisely define the severity of injury and better predict neurologic outcome would be extremely valuable. Furthermore, biological surrogate outcomes measures would be very useful in small preliminary clinical trials of novel therapies if they could inform decisions around the therapeutic regimen for subsequent larger clinical trials. This review highlights our ongoing work in establishing biomarkers for SCI using cerebrospinal fluid samples from acutely injured patients.

Clinical predictors of recovery after blunt spinal cord trauma: systematic review.

Several clinical, imaging, and therapeutic factors affecting recovery following spinal cord injury (SCI) have been described. A systematic review of the topic is still lacking. Our primary aim was to systematically review clinical factors that may predict neurological and functional recovery following blunt traumatic SCI in adults. Such work would help guide clinical care and direct future research. Both Medline and Embase (to April 2008) were searched using index terms for various forms of SCI, paraplegia, or quadri/tetraplegia, and functional and neurological recovery. The search was limited to published articles that were in English and included human subjects. Article selection included class I and II evidence, blunt traumatic SCI, injury level above L1-2, baseline assessment within 72 h of injury, use of American Spinal Injury Association (ASIA) scoring system for clinical assessment, and functional and neurological outcome. A total of 1526 and 1912 citations were located from Medline and Embase, respectively. Two surgeons reviewed the titles, abstracts, and full text articles for each database. Ten articles were identified, only one of which was level 1 evidence. Age and gender were identified as two patient-related predictors. While motor and functional recovery decreased with advancing age for complete SCI, there was no correlation considering incomplete ones. Therefore, treatment should not be restructured based on age in incomplete SCI. Among injury-related predictors, severity of SCI was the most significant. Complete injuries correlated with increased mortality and worse neurological and functional outcomes. Other predictors included SCI level, energy transmitted by the injury, and baseline electrophysiological testing.

Manipulation or microdiskectomy for sciatica? A prospective randomized clinical study.

OBJECTIVE: The purpose of this study was to compare the clinical efficacy of spinal manipulation against microdiskectomy in patients with sciatica secondary to lumbar disk herniation (LDH). METHODS: One hundred twenty patients presenting through elective referral by primary care physicians to neurosurgical spine surgeons were consecutively screened for symptoms of unilateral lumbar radiculopathy secondary to LDH at L3-4, L4-5, or L5-S1. Forty consecutive consenting patients who met inclusion criteria (patients must have failed at least 3 months of nonoperative management including treatment with analgesics, lifestyle modification, physiotherapy, massage therapy, and/or acupuncture) were randomized to either surgical microdiskectomy or standardized chiropractic spinal manipulation. Crossover to the alternate treatment was allowed after 3 months. RESULTS: Significant improvement in both treatment groups compared to baseline scores over time was observed in all outcome measures. After 1 year, follow-up intent-to-treat analysis did not reveal a difference in outcome based on the original treatment received. However, 3 patients crossed over from surgery to spinal manipulation and failed to gain further improvement. Eight patients crossed from spinal manipulation to surgery and improved to the same degree as their primary surgical counterparts. CONCLUSIONS: Sixty percent of patients with sciatica who had failed other medical management benefited from spinal manipulation to the same degree as if they underwent surgical intervention. Of 40% left unsatisfied, subsequent surgical intervention confers excellent outcome. Patients with symptomatic LDH failing medical management should consider spinal manipulation followed by surgery if warranted.

Reduction of PrP(C) in human cerebrospinal fluid after spinal cord injury.

It has been estimated that cerebrospinal fluid (CSF) contains approximately 80 proteins that significantly increase or decrease in response to various clinical conditions. Here we have evaluated the CSF protein PrP(C) (cellular prion protein) for possible increases or decreases following spinal cord injury. The physiological function of PrP(C) is not yet completely understood; however, recent findings suggest that PrP(C) may have neuroprotective properties. Our results show that CSF PrP(C) is decreased in spinal cord injured patients 12 h following injury and is absent at 7 days. Given that normal PrP(C) has been proposed to be neuroprotective we speculate that the decrease in CSF PrP(C) levels may influence neuronal cell survival following spinal cord injury.