Safety and Efficacy of Riluzole in Acute Spinal Cord Injury Study (RISCIS): A Multi-Center, Randomized, Placebo-Controlled, Double-Blinded Trial.

Riluzole is a sodium-glutamate antagonist that attenuates neurodegeneration in amyotrophic lateral sclerosis (ALS). It has shown favorable results in promoting recovery in pre-clinical models of traumatic spinal cord injury (tSCI) and in early phase clinical trials. This study aimed to evaluate the efficacy and safety of riluzole in acute cervical tSCI. An international, multi-center, prospective, randomized, double-blinded, placebo-controlled, adaptive, Phase III trial (NCT01597518) was undertaken. Patients with American Spinal Injury Association Impairment Scale (AIS) A-C, cervical (C4-C8) tSCI, and <12 h from injury were randomized to receive either riluzole, at an oral dose of 100 mg twice per day (BID) for the first 24 h followed by 50 mg BID for the following 13 days, or placebo. The primary efficacy end-point was change in Upper Extremity Motor (UEM) scores at 180 days. The primary efficacy analyses were conducted on an intention to treat (ITT) and completed cases (CC) basis. The study was powered at a planned enrolment of 351 patients. The trial began in October 2013 and was halted by the sponsor on May 2020 (and terminated in April 2021) in the face of the global COVID-19 pandemic. One hundred ninety-three patients (54.9% of the pre-planned enrolment) were randomized with a follow-up rate of 82.7% at 180 days. At 180 days, in the CC population the riluzole-treated patients compared with placebo had a mean gain of 1.76 UEM scores (95% confidence interval: -2.54-6.06) and 2.86 total motor scores (CI: -6.79-12.52). No drug-related serious adverse events were associated with the use of riluzole. Additional pre-planned sensitivity analyses revealed that in the AIS C population, riluzole was associated with significant improvement in total motor scores (estimate: standard error [SE] 8.0; CI 1.5-14.4) and upper extremity motor scores (SE 13.8; CI 3.1-24.5) at 6 months. AIS B patients had higher reported independence, measured by the Spinal Cord Independence Measure score (45.3 vs. 27.3; d: 18.0 CI: -1.7-38.0) and change in mental health scores, measured by the Short Form 36 mental health domain (2.01 vs. -11.58; d: 13.2 CI: 1.2-24.8) at 180 days. AIS A patients who received riluzole had a higher average gain in neurological levels at 6 months compared with placebo (mean 0.50 levels gained vs. 0.12 in placebo; d: 0.38, CI: -0.2-0.9). The primary analysis did not achieve the predetermined end-point of efficacy for riluzole, likely related to insufficient power. However, on pre-planned secondary analyses, all subgroups of cervical SCI subjects (AIS grades A, B and C) treated with riluzole showed significant gains in functional recovery. The results of this trial may warrant further investigation to extend these findings. Moreover, guideline development groups may wish to assess the possible clinical relevance of the secondary outcome analyses, in light of the fact that SCI is an uncommon orphan disorder without an accepted neuroprotective treatment.

Survival Model of Thoracic Contusion Spinal Cord Injury in the Domestic Pig.

Spinal cord injury (SCI) frequently results in motor, sensory, and autonomic dysfunction for which there is currently no cure. Recent pre-clinical and clinical research has led to promising advances in treatment; however, therapeutics indicating promise in rodents have not translated successfully in human trials, likely due, in part, to gross anatomical and physiological differences between the species. Therefore, large animal models of SCI may facilitate the study of secondary injury processes that are influenced by scale, and may assist the translation of potential therapeutic interventions. The aim of this study was to characterize two severities of thoracic contusion SCI in female domestic pigs, measuring motor function and spinal cord lesion characteristics, over 2 weeks post-SCI. A custom-instrumented weight-drop injury device was used to release a 50 g impactor from 10 cm (n = 3) or 20 cm (n = 7) onto the exposed dura, to induce a contusion at the T10 thoracic spinal level. Hind limb motor function was assessed at 8 and 13 days post-SCI using a 10-point scale. Volume and extent of lesion-associated signal hyperintensity in T2-weighted magnetic resonance (MR) images were assessed at 3, 7, and 14 days post-injury. Animals were transcardially perfused at 14 days post-SCI and spinal cord tissue was harvested for histological analysis. Bowel function was retained in all animals and transient urinary retention occurred in one animal after catheter removal. All animals displayed hind limb motor deficits. Animals in the 10-cm group demonstrated some stepping and weight-bearing and scored a median 2-3 points higher on the 10-point motor function scale at 8 and 13 days post-SCI, than did the 20-cm group. Histological lesion volume was 20% greater, and 30% less white matter was spared, in the 20-cm group than in the 10-cm group. The MR signal hyperintensity in the 20-cm injury group had a median cranial-caudal extent approximately 1.5 times greater than the 10-cm injury group at all three time-points, and median volumes 1.8, 2.5, and 4.5 times greater at day 3, 7, and 14 post-injury, respectively. Regional differences in axonal injury were observed between groups, with amyloid precursor protein immunoreactivity greatest in the 20-cm group in spinal cord sections adjacent to the injury epicenter. This study demonstrated graded injuries in a domestic pig strain, with outcome measures comparable to miniature pig models of contusion SCI. The model provides a vehicle for the study of SCI and potential treatments, particularly where miniature pig strains are not available and/or where small animal models are not appropriate for the research question.

Prehospital Cardiovascular Autoregulatory Disturbances Correlate With the Functional Neuroanatomy of Acute Spinal Cord Injury.

STUDY DESIGN: Retrospective study. OBJECTIVE: The importance of attenuating the cardiovascular autoregulatory disturbances accompanying acute spinal cord injury (SCI) has long been recognized. This report assembles SCI emergency service data and correlates cardiovascular parameters to preserved functional neuroanatomy. SUMMARY OF BACKGROUND DATA: The nascent nature of evidence-based reporting of prehospital cardiovascular autoregulatory disturbances in SCI indicates the need to assemble more information. MATERIALS AND METHODS: SCI data for <24 hours were extracted from ambulance and hospital records. The mean arterial pressure (MAP) was calculated. The International Standard for Neurological Classification of SCI (ISNCSCI) evaluates the primary outcome of motor incomplete injury (grades C/D) at acute presentation. Logistic regression was adjusted for multiple confounders that were expected to influence the odds of grade C/D. RESULTS: A cohort of 99 acute SCI cases was retained; mean (SD) age 40.7±20.5 years, 88 male, 84 tetraplegic, 65 grades A/B (motor complete injury), triage time 2±1.6 hours. The lowest recorded prehospital MAP [mean (SD): 77.9±19, range: 45-145 mm Hg] approached the nadir for adequate organ perfusion. Thirty-four (52%) grade A/B and 10 (30%) C/D cases had MAP readings <85 mm Hg. In data adjusted for age, injury level, and triage time a 5 mm Hg increase in the lowest MAP value was associated with a 34% increase in the odds of having motor incomplete injury at acute presentation (adjusted odds ratio=1.34; 95% CI: 1.11-1.61; P =0.002). CONCLUSION: An important observation with implications for timely and selective cardiovascular resuscitation during SCI prehospital care involves significant negative associations between the depth of systemic hypotension and preserved functional neuroanatomy. Regardless of the mechanism, our confounder-adjusted logistic regression model extends in-hospital evidence and provides a conceptual bedside-bench framework for future investigations.

Persistently Raised Serum Titanium Levels After Spinal Instrumentation in Children.

STUDY DESIGN: Prospective study of patients undergoing elective spinal deformity surgery with repeated testing for circulating metal ions including preoperative levels acting as controls. OBJECTIVE: The aim was to determine if levels of particular circulating metal ions are maintained to two years postsurgery including different implant systems and rods. SUMMARY OF BACKGROUND DATA: Adults having hip replacements, especially metal-on-metal bearings, may develop high metal ion levels. Pediatric spinal implants are known to cause circulating metal ions, notably titanium, chromium, cobalt, and nickel. MATERIALS AND METHODS: Fifty-six children having spinal deformity surgery were studied with repeated testing for circulating metal ions, using high-resolution inductively coupled plasma mass spectrometry. Linear mixed-effects models adjusting for repeated measurements over time were used to analyze levels of titanium, cobalt, chromium, and nickel. RESULTS: Titanium levels showed a rapid increase by seven days and a peak at 30 days that was essentially maintained at the two-year assay. At two years, titanium levels were 5.14 times greater compared with the presurgery control level (P<0.0001). Cobalt levels were shown to gradually rise to a peak at 30 days and then slowly decline but remained 1.74 times above mean baseline level at two years (P=0.0004), with a declining trajectory. Chromium and nickel levels rose immediately postoperatively and then steadily declined to baseline by six months and remained at baseline at two years. The five implant systems tested had generally equivalent results. CONCLUSION: The persistent and rising levels of titanium, in a predominantly female population, is concerning. Titanium is known to cross the placental barrier and enter the circulation of the fetus in rodents and humans, and to accumulate in solid organs especially the liver, spleen, heart, and lymph nodes in humans. This potentially exposes the offspring of mothers with spinal implants to titanium, with potential teratogenic effects.

Local Bone Grafting Is Sufficient for Instrumented Adolescent Idiopathic Scoliosis Surgery: A Preliminary Study.

BACKGROUND: Several options for grafting exist; iliac crest bone grafting, allografts, and bone substitutes. Local bone graft (LBG) offers high-quality bone graft and no commercial cost. The aim of this study was to assess the clinical and radiologic results of adolescent idiopathic scoliosis (AIS) surgery with posterior instrumentation and fusion (PIF) in patients using only LBG and to measure the quantities harvested. METHODS: A total of 218 AIS patients who underwent pedicle screw PIF surgery using only LBG with a minimum 1-year follow-up were reviewed. Bone was harvested during surgery from the excised facet joints, spinous processes (not from the end instrumented vertebrae) and decortication of laminae and transverse processes in the operative field. The harvested bone graft weight of 127 patients was recorded prospectively and then computed to graft weight per kilogram body weight (GWPK) and graft weight per motion segment (GWPMS). RESULTS: The median follow-up time was 24.7 months (12.1 to 133 mo) with 128 of the 218 patients having over 2 years follow-up. A total of 280 curves were fused. One hundred fifty-six of the patients had single curve instrumentation and 62 had double curve surgery. The median preoperative primary Cobb angle was 57.0 (31 to 100) degrees and postoperatively was 20.0 (0 to 66) degrees, indicating a median correction of 65.3% (17.5% to 100%). The median graft weight was 30 g (14 to 62 g), GWPK was 0.54 g/kg (0.24 to 1.29 g/kg) and GWPMS was 3.3 g/motion segments (2.3 to 10.0 g/kg). Twelve of 218 patients (5.5%) required subsequent surgery. Only 2 patients developed pseudarthrosis (0.91%), noting that modern segmental instrumentation warrants longer follow-up for increased confidence of complete fusion. CONCLUSIONS: LBG achieved successful fusion in over 99% of patients undergoing PIF for AIS. The described terms GWPK and GWPMS can be insightful for future studies. LBG offers a safe and low-cost solution for bone grafting in AIS surgery. LEVEL OF EVIDENCE: Level IV.

Investigating the Effect of Axial Compression and Distraction on Cervical Facet Mechanics During Supraphysiologic Anterior Shear.

Bilateral cervical facet dislocation (BFD) with facet fracture (Fx) often causes tetraplegia but is rarely recreated experimentally, possibly due to a lack of muscle replication. Intervertebral axial compression (due to muscle activation) or distraction (due to inertial loading), when combined with excessive anterior translation, may influence interfacet contact or separation and the subsequent production of BFD with or without Fx. This paper presents a methodology to produce C6/C7 BFD+Fx using anterior shear motion superimposed with 300 N compression or 2.5 mm distraction. The effect of these superimposed axial conditions on six-axis loads, and C6 inferior facet deflections and surface strains, was assessed. Twelve motion segments (70 ± 13 yr) achieved 2.19 mm of supraphysiologic anterior shear without embedding failure (supraphysiologic shear analysis point; SSP), and BFD+Fx was produced in all five specimens that reached 20 mm of shear. Linear mixed-effects models (α = 0.05) assessed the effect of axial condition. At the SSP, the compressed specimens experienced higher axial forces, facet shear strains, and sagittal facet deflections, compared to the distracted group. Facet fractures had similar radiographic appearance to those that are observed clinically, suggesting that intervertebral anterior shear motion contributes to BFD+Fx.

Lumbar spine loads are reduced for activities of daily living when using a braced arm-to-thigh technique.

PURPOSE: To evaluate the effect of the braced arm-to-thigh technique (BATT) (versus self-selected techniques) on three-dimensional trunk kinematics and spinal loads for three common activities of daily living (ADLs) simulated in the laboratory: weeding (gardening), reaching for an object in a low cupboard, and car egress using the two-legs out technique. METHODS: Ten young healthy males performed each task using a self-selected technique, and then using the BATT. The pulling action of weeding was simulated using a magnet placed on a steel plate. Cupboard and car egress tasks were simulated using custom apparatus representing the dimensions of a kitchen cabinet and a medium-sized Australian car, respectively. Three-dimensional trunk kinematics and L4/L5 spinal loads were estimated using the Lifting Full-Body OpenSim model and compared between techniques. Paired t-tests were used to compare peak values between methods (self-selected vs BATT). RESULTS: The BATT significantly reduced peak extension moments (13-51%), and both compression (27-45%) and shear forces (31-62%) at L4/L5, compared to self-selected techniques for all three tasks (p < 0.05). Lateral bending angles increased with the BATT for weeding and cupboard tasks, but these changes were expected as the BATT inherently introduces asymmetric trunk motion. CONCLUSION: The BATT substantially reduced L4/L5 extension moments, and L4/L5 compression and shear forces, compared to self-selected methods, for three ADLs, in a small cohort of ten young healthy males without prior history of back pain. These study findings can be used to inform safe procedures for these three ADLs, as the results are considered representative of a mature population.

Chromium Metal Ion Release During Instrumented Spinal Surgery in Children: The Effects of Electrosurgery.

STUDY DESIGN: Prospective 2-year study with operative sampling and in-vitro analysis of chromium ions following spinal surgery in children. OBJECTIVES: To measure metal ion levels at preoperative, intraoperative, and postoperative times to determine patterns of metal ion release during instrumented spinal surgery. SUMMARY OF BACKGROUND DATA: Raised serum metal ion levels are reported following instrumented spinal fusion in adolescent idiopathic scoliosis. The authors noted raised chromium levels in patients receiving implants that did not contain chromium. This prompted further work to establish the source. The electrosurgery tips used were discovered to contain 17% chromium. METHODS: Chromium, cobalt, and titanium levels were measured before, during, and after surgery in serum and local intraoperative fluid samples in 11 children undergoing posterior instrumentation for scoliosis. Administered drugs, cell-saver fluids, and intraoperative fluids, both local and intravenous, were investigated to exclude these as sources of chromium ions. An in-vitro study was also performed to elucidate sources of intraoperative chromium ions. RESULTS: High chromium levels were detected in all samples from the wound irrigation fluid prior to insertion of metal implants. Immediate postoperative chromium serum ion levels were also elevated and returned to baseline by day 30. In-vitro sampling of fluids from test models using electrosurgery revealed high levels of chromium ions CONCLUSION.: This finding of high chromium metal ion concentrations in intraoperative and early postoperative samples provides evidence of chromium release during the dissection phase of spinal surgery. This challenges existing beliefs that metal ion release occurs solely due to implants and now implicates the electrosurgery electrode tips as a source of raised chromium ion levels. Thorough irrigation of the operative site after the dissection phase of surgery to both dilute and reduce the intraoperative chromium ion load is suggested. Alternative electrosurgery electrode tips or other methods to coagulate during surgery could be considered. LEVEL OF EVIDENCE: 2.

Do Children With Spinal Deformity Who Have Metal Implants and Frequent Exposure to X-Rays Increase Their Risk of Cancer?

STUDY DESIGN: Spinal surgery cohort. OBJECTIVE: The authors assess the risk of cancer in children who have undergone frequent radiographs and have metal implants for the treatment of spinal deformity. SUMMARY OF BACKGROUND DATA: Concerns have been raised regarding the cancer risk to children exposed to repeated radiological examinations as part of routine surveillance to monitor progression of spinal deformity. Additionally, there are reports of increased cancer risk in adults having joint replacement with metal implants causing raised metal ion levels in the blood. METHODS: A large number of consecutive children undergoing instrumented spinal surgery since 1979 were examined for their development of malignancy. High quality data on all invasive cancers from the South Australian Cancer Registry and deaths were linked to the spinal surgery cohort with the calculation of standardized incidence ratios (SIRs) using the Quinquinquennium method. RESULTS: The study cohort was formed by 865 children. The average follow-up time from date of surgery to either death or censoring date was 18 years with a maximum of 36 years. A total of 15,921 person years were examined. There was no increased rate of cancer in these patients. For the total cohort, the SIR was 1.00 (95% confidence interval [CI] 0.50-1.79). For females the SIR was 0.83 (95% CI 0.33-1.70) and for males the SIR was 1.33 (95% CI 0.36-3.40). The male SIR reflected an expected cancer incidence of three cases, when four cases were observed, and was not statistically significant. CONCLUSION: This study has found that radiation exposure and possible exposure to circulating metal ions as a result of routine instrumented spine surgery in children since 1979 is not associated with an increased risk of cancer in up to 36 years of follow up. LEVEL OF EVIDENCE: 2.

A braced arm-to-thigh (BATT) lifting technique reduces lumbar spine loads in healthy and low back pain participants.

Despite the common use of one-handed lifting techniques for activities of daily living, these techniques have received little attention in the biomechanics literature. The braced arm-to-thigh technique (BATT) is a one-handed lifting method in which the dominant hand picks up objects, while the free hand braces the trunk on the ipsilateral thigh. The aim of this study was to compare the BATT to two-handed or unsupported one-handed lifting techniques with loads of 2 and 10 kg, by evaluating trunk motion and spine loading at L4/L5. Twenty healthy participants (30-70 years old) matched in age and sex to 18 participants with low back pain were recruited to the study. A three-axis load cell secured to the distal anterior thigh measured the bracing forces applied by the hand. The OpenSim Lifting Full-Body model was used to estimate trunk kinematics and spinal loading at L4/L5. Linear mixed-effects models were developed to compare trunk angles and L4/L5 moments and forces between lifting techniques. Trunk flexion angles were significantly reduced for the BATT lift compared to one-handed and two-handed stoop lifts (9-20%). However, the BATT also increased asymmetric trunk kinematics and moments at L4/L5. The BATT produced significantly lower moments (28-38%), and compressive (25-32%) and antero-posterior shear (25-45%) forces at L4/L5, compared to unsupported lifting techniques. Bracing the hand on the thigh to support the trunk can substantially reduce low back loading during lifting tasks of 2 to 10 kg.

Cauda Equina Syndrome Core Outcome Set (CESCOS): An international patient and healthcare professional consensus for research studies.

BACKGROUND: Cauda Equina Syndrome (CES) is an emergency condition that requires acute intervention and can lead to permanent neurological deficit in working age adults. A Core Outcome Set (COS) is the minimum set of outcomes that should be reported by a research study within a specific disease area. There is significant heterogeneity in outcome reporting for CES, which does not allow data synthesis between studies. The hypothesis is that a COS for CES can be developed for future research studies using patients and healthcare professionals (HCPs) as key stakeholders. METHODS AND FINDINGS: Qualitative semi-structured interviews with CES patients were audio-recorded, transcribed and analysed using NVivo to identify the outcomes of importance. These were combined with the outcomes obtained from a published systematic literature review of CES patients. The outcomes were grouped into a list of 37, for rating through two rounds of an international Delphi survey according to pre-set criteria. The Delphi survey had an overall response rate of 63% and included 172 participants (104 patients, 68 HCPs) from 14 countries who completed both rounds. Thirteen outcomes reached consensus at the end of the Delphi survey and there was no attrition bias detected. The results were discussed at an international consensus meeting attended by 34 key stakeholders (16 patients and 18 HCPs) from 8 countries. A further three outcomes were agreed to be included. There was no selection bias detected at the consensus meeting. There are 16 outcomes in total in the CESCOS. DISCUSSION: This is the first study in the literature that has determined the core outcomes in CES using a transparent international consensus process involving healthcare professionals and CES patients as key stakeholders. This COS is recommended as the most important outcomes to be reported in any research study investigating CES outcomes and will allow evidence synthesis in CES.

Mechanisms of Failure Following Simulated Repetitive Lifting: A Clinically Relevant Biomechanical Cadaveric Study.

STUDY DESIGN: A biomechanical analysis correlating internal disc strains and tissue damage during simulated repetitive lifting. OBJECTIVE: To understand the failure modes during simulated safe and unsafe repetitive lifting. SUMMARY OF BACKGROUND DATA: Repetitive lifting has been shown to lead to lumbar disc herniation (LDH). In vitro studies have developed a qualitative understanding of the effect of repetitive loading on LDH. However, no studies have measured internal disc strains and subsequently correlated these with disc damage. METHODS: Thirty human cadaver lumbar functional spinal units were subjected to an equivalent of 1 year of simulated repetitive lifting under safe and unsafe levels of compression, in combination with flexion (13-15°), and right axial rotation (2°) for 20,000 cycles or until failure. Safe or unsafe lifting were applied as a compressive load to mimic holding a 20 kg weight either close to, or at arm's length, from the body, respectively. Maximum shear strains (MSS) were measured, and disc damage scores were determined in nine regions from axial post-test magnetic resonance imaging (MRI) and macroscopic images. RESULTS: Twenty percent of specimens in the safe lifting group failed before 20,000 cycles due to endplate failure, compared with 67% in the unsafe group. Over half of the specimens in the safe lifting group failed via either disc protrusion or LDH, compared with only 20% via protrusion in the unsafe group. Significant positive correlations were found between MRI and macroscopic damage scores in all regions (rs > 0.385, P < 0.049). A significant positive correlation was observed in the left lateral region for MSS versus macroscopic damage score (rs = 0.486, P < 0.037) and MSS versus failure mode (rs = 0.724, P = 0.018, only specimens with disc failure). Pfirrmann Grade 3 discs were strongly associated with subsequent LDH (P = 0.003). CONCLUSION: Increased shear strains were observed in the contralateral side to the applied rotation as disc injury progressed from protrusion to LDH. Larger compressive loads applied to simulate unsafe lifting led to frequent early failure of the endplate, however, smaller compressive loads at similar flexion angles applied under safe lifting led to more loading cycles before failure, where the site of failure was more likely to be the disc. Our study demonstrated that unsafe lifting leads to greater risk of injury compared with safe lifting, and LDH and disc protrusion were more common in the posterior/posterolateral regions. LEVEL OF EVIDENCE: N/A.

Does nanoscale porous titanium coating increase lumbar spinal stiffness of an interbody fusion cage? An in vivo biomechanical analysis in an ovine model.

BACKGROUND: Quantitative objective measures to determine fusion achievement further enable the comparison of new technologies, such as interbody cage surface enhancement. Our aims were to compare in vivo biomechanical responses of ovine L4/5 lumbar motion segments with two cages: 1) Polyetheretherketone or 2) Polyetheretherketone with a nanosurfaced titanium porous scaffold from Nanovis, Inc. METHODS: Fourteen Merino sheep randomly received either 1) standard Polyetheretherketone cage or 2) Nanocoated Polyetheretherketone cage at L4/L5 with autologous bone graft. At baseline and one-year follow-up, dynamic spinal stiffness was quantified in vivo using a validated mechanical assessment at 2 Hz, 6 Hz, and 12 Hz. The dorsoventral secant stiffness (ky = force/displacement, N/mm) and L4-L5 accelerations were determined at each frequency. A repeated measures analysis of variance with Bonferonni correction was used to evaluate within and between group differences among the biomechanical variables. FINDINGS: Both implants increased spinal stiffness at 2 Hz (21 and 39%, respectively, p < .005), and at 6 Hz (12 and 27%, p < .0001). Significantly greater spinal stiffness was observed with Nanocoated Polyetheretherketone at one-year for both frequencies (p < .05). No significant differences were observed at 12 Hz within or between groups. L4-L5 dorsoventral accelerations were significantly decreased one year following cage placement only with Nanocoated Polyetheretherketone (p < .05) and greater reductions in acceleration were observed with Nanocoated Polyetheretherketone compared to standard Polyetheretherketone (p < .05). INTERPRETATION: Both cages increased spinal stiffness, yet, nanosurfaced cages resulted in greater spinal stiffness changes and decreases in L4-L5 accelerations. These findings may assist in clinical decision making and post-operative recovery strategies.

Validation of an OpenSim full-body model with detailed lumbar spine for estimating lower lumbar spine loads during symmetric and asymmetric lifting tasks.

There is currently no validated full-body lifting model publicly available on the OpenSim modelling platform to estimate spinal loads during lifting. In this study, the existing full-body-lumbar-spine model was adapted and validated for lifting motions to produce the lifting full-body model. Back muscle activations predicted by the model closely matched the measured erector spinae activation patterns. Model estimates of intradiscal pressures and in vivo measurements were strongly correlated. The same spine loading trends were observed for model estimates and reported vertebral body implant measurements. These results demonstrate the suitability of this model to evaluate changes in lumbar loading during lifting.

The effect of axial compression and distraction on cervical facet mechanics during anterior shear, flexion, axial rotation, and lateral bending motions.

The subaxial cervical facets are important load-bearing structures, yet little is known about their mechanical response during physiological or traumatic intervertebral motion. Facet loading likely increases when intervertebral motions are superimposed with axial compression forces, increasing the risk of facet fracture. The aim of this study was to measure the mechanical response of the facets when intervertebral axial compression or distraction is superimposed on constrained, non-destructive shear, bending and rotation motions. Twelve C6/C7 motion segments (70 ±â€¯13 yr, nine male) were subjected to constrained quasi-static anterior shear (1 mm), axial rotation (4°), flexion (10°), and lateral bending (5°) motions. Each motion was superimposed with three axial conditions: (1) 50 N compression; (2) 300 N compression (simulating neck muscle contraction); and, (3) 2.5 mm distraction. Angular deflections, and principal and shear surface strains, of the bilateral C6 inferior facets were calculated from motion-capture data and rosette strain gauges, respectively. Linear mixed-effects models (α = 0.05) assessed the effect of axial condition. Minimum principal and maximum shear strains were largest in the compressed condition for all motions except for maximum principal strains during axial rotation. For right axial rotation, maximum principal strains were larger for the contralateral facets, and minimum principal strains were larger for the left facets, regardless of axial condition. Sagittal deflections were largest in the compressed conditions during anterior shear and lateral bending motions, when adjusted for facet side.

The Biomechanics of the Inter-Lamellar Matrix and the Lamellae During Progression to Lumbar Disc Herniation: Which is the Weakest Structure?

While microstructural observations have improved our understanding of possible pathways of herniation progression, no studies have measured the mechanical failure properties of the inter-lamellar matrix (ILM), nor of the adjacent lamellae during progression to herniation. The aim of this study was to employ multiscale, biomechanical and microstructural techniques to evaluate the effects of progressive induced herniation on the ILM and lamellae in control, pre-herniated and herniated discs (N = 7), using 2 year-old ovine spines. Pre-herniated and herniated (experimental) groups were subjected to macroscopic compression while held in flexion (13°), before micro-mechanical testing. Micro-tensile testing of the ILM and the lamella from anterior and posterolateral regions was performed in radial and circumferential directions to measure failure stress, modulus, and toughness in all three groups. The failure stress of the ILM was significantly lower for both experimental groups compared to control in each of radial and circumferential loading directions in the posterolateral region (p < 0.032). Within each experimental group in both loading directions, the ILM failure stress was significantly lower by 36% (pre-herniation), and 59% (herniation), compared to the lamella (p < 0.029). In pre-herniated compared to control discs, microstructural imaging revealed significant tissue stretching and change in orientation (p < 0.003), resulting in a loss of distinction between respective lamellae and ILM boundaries.

Quantitative evaluation of facet deflection, stiffness, strain and failure load during simulated cervical spine trauma.

Traumatic cervical facet dislocation (CFD) is often associated with devastating spinal cord injury. Facet fractures commonly occur during CFD, yet quantitative measures of facet deflection, strain, stiffness and failure load have not been reported. The aim of this study was to determine the mechanical response of the subaxial cervical facets when loaded in directions thought to be associated with traumatic bilateral CFD - anterior shear and flexion. Thirty-one functional spinal units (6 × C2/3, C3/4, C4/5, and C6/7, 7 × C5/6) were dissected from fourteen human cadaver cervical spines (mean donor age 69 years, range 48-92; eight male). Loading was applied to the inferior facets of the inferior vertebra to simulate the in vivo inter-facet loading experienced during supraphysiologic anterior shear and flexion motion. Specimens were subjected to three cycles of sub-failure loading (10-100 N, 1 mm/s) in each direction, before being failed in a randomly assigned direction (10 mm/s). Facet deflection, surface strains, stiffness, and failure load were measured. Linear mixed-effects models (α = 0.05; random effect of cadaver) accounted for variations in specimen geometry and bone density. Specimen-specific parameters were significantly associated with most outcome measures. Facet stiffness and failure load were significantly greater in the simulated flexion loading direction, and deflection and surface strains were higher in anterior shear at the non-destructive analysis point (47 N applied load). The sub-failure strains and stiffness responses differed between the upper and lower subaxial cervical regions. Failure occurred through the facet tip during anterior shear loading, while failure through the pedicles was most common in flexion.

Predictive Factors for the Outcome of Surgical Treatment of Lumbar Spondylolysis in Young Sporting Individuals.

STUDY DESIGN: Retrospective consecutive case series. OBJECTIVES: Only few sporting individuals with symptomatic lumbar pars injuries require surgical repair and it is often difficult to predict the outcome following surgery. The factors that predict the outcome after direct repair of lumbar pars defect was evaluated clinically and statistically. The preoperative background variables both subjective and objective as well as radiological evaluation were used in a multiple regression model to find the strong predictors of postoperative outcome as measured by VAS (visual analogue scores), ODI (Oswestry Disability Index) and SF-36 (Short Form). METHODS: Fifty-two consecutive young sporting individuals with a mean age of 19 years (range 8-30 years) were treated surgically for lumbar pars defect confirmed on imaging studies (ie, single-photon emission computed tomography, computed tomography, and magnetic resonance imaging). Fifty patients completed the VAS, ODI, and SF-36 questionnaires as a part of their assessment. Preoperative background variables were used in a multiple regression model to find the strongest predictor of postoperative outcome as measured by ODI. Ethical approval was taken by the institutional review board. RESULTS: Buck's screw repair of the pars defect was carried out in 44 patients (33 males, 11 female): unilateral in 8 patients (7 males, 1 female) and bilateral in 36 patients (26 males, 10 females). Although age at surgery showed linear colinearity (ρ = 0.32, P < .05), it was not significant in the model. The most consistent association with the preoperative VAS score were the pre- and postoperative ODI scores, that is, ρ = 0.51 (P < .01) and ρ = 0.33 (P < .05), respectively. In the bilateral group, with Buck's repair at a single level, that is, 33 of 36 (93%) patients had returned to sports at a mean time of 7.5 months (range 6-12 months). Overall, 44 of 52 (84%) individuals had returned to their sports with posttreatment ODI score of <10. The stepwise regression modeling suggested 6 independent factors (preoperative ODI, preoperative SF-36 physical component summary (PCS), Buck's repair, multiple operations, professionalism, and pars defect at L3), as the determinants of the outcome (ie, postoperative ODI) in 80.9% patients (R2 = 0.809). CONCLUSIONS: The outcome after direct repair of pars defect in those younger than 25 years runs a predictable course. Professionalism in sports has a high impact on the outcome. Preoperative ODI and SF-36 PCS scores are significant predictors of good functional outcome. The regression equation can predict the outcome in 80.9% sporting individuals undergoing Buck's repair.

Acute Thoracolumbar Spinal Cord Injury: Relationship of Cord Compression to Neurological Outcome.

BACKGROUND: Spinal cord injury in the cervical spine is commonly accompanied by cord compression and urgent surgical decompression may improve neurological recovery. However, the extent of spinal cord compression and its relationship to neurological recovery following traumatic thoracolumbar spinal cord injury is unclear. The purpose of this study was to quantify maximum cord compression following thoracolumbar spinal cord injury and to assess the relationship among cord compression, cord swelling, and eventual clinical outcome. METHODS: The medical records of patients who were 15 to 70 years of age, were admitted with a traumatic thoracolumbar spinal cord injury (T1 to L1), and underwent a spinal surgical procedure were examined. Patients with penetrating injuries and multitrauma were excluded. Maximal osseous canal compromise and maximal spinal cord compression were measured on preoperative mid-sagittal computed tomography (CT) scans and T2-weighted magnetic resonance imaging (MRI) by observers blinded to patient outcome. The American Spinal Injury Association (ASIA) Impairment Scale (AIS) grades from acute hospital admission (≤24 hours of injury) and rehabilitation discharge were used to measure clinical outcome. Relationships among spinal cord compression, canal compromise, and initial and final AIS grades were assessed via univariate and multivariate analyses. RESULTS: Fifty-three patients with thoracolumbar spinal cord injury were included in this study. The overall mean maximal spinal cord compression (and standard deviation) was 40% ± 21%. There was a significant relationship between median spinal cord compression and final AIS grade, with grade-A patients (complete injury) exhibiting greater compression than grade-C and D patients (incomplete injury) (p < 0.05). Multivariate logistic regression identified mean spinal cord compression as independently influencing the likelihood of complete spinal cord injury (p < 0.01). CONCLUSIONS: Traumatic thoracolumbar spinal cord injury is commonly accompanied by substantial cord compression. Greater cord compression is associated with an increased likelihood of severe neurological deficits (complete injury) following thoracolumbar spinal cord injury. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Traumatic subaxial cervical facet subluxation and dislocation: epidemiology, radiographic analyses, and risk factors for spinal cord injury.

BACKGROUND CONTEXT: Distractive flexion injuries (DFIs) of the subaxial cervical spine are major contributors to spinal cord injury (SCI). Prompt assessment and early intervention of DFIs associated with SCI are crucial to optimize patient outcome; however, neurologic examination of patients with subaxial cervical injury is often difficult, as patients commonly present with reduced levels of consciousness. Therefore, it is important to establish potential associations between injury epidemiology and radiographic features, and neurologic involvement. PURPOSE: The aims of this study were to describe the epidemiology and radiographic features of DFIs presenting to a major Australian tertiary hospital and to identify those factors predictive of SCI. The agreement and repeatability of radiographic measures of DFI severity were also investigated. STUDY DESIGN/SETTING: This is a combined retrospective case-control and reliability-agreement study. PATIENT SAMPLE: Two hundred twenty-six patients (median age 40 years [interquartile range = 34]; 72.1% male) who presented with a DFI of the subaxial cervical spine between 2003 and 2013 were reviewed. OUTCOME MEASURES: The epidemiology and radiographic features of DFI, and risk factors for SCI were identified. Inter- and intraobserver agreement of radiographic measurements was evaluated. METHODS: Medical records, radiographs, and computed tomography and magnetic resonance imaging scans were examined, and the presence of SCI was evaluated. Radiographic images were analyzed by two consultant spinal surgeons, and the degree of vertebral translation, facet apposition, spinal canal occlusion, and spinal cord compression were documented. Multivariable logistic regression models identified epidemiology and radiographic features predictive of SCI. Intraclass correlation coefficients (ICCs) examined inter- and intraobserver agreement of radiographic measurements. RESULTS: The majority of patients (56.2%) sustained a unilateral (51.2%) or a bilateral facet (48.8%) dislocation. The C6-C7 vertebral level was most commonly involved (38.5%). Younger adults were over-represented among motor-vehicle accidents, whereas falls contributed to a majority of DFIs sustained by older adults. Greater vertebral translation, together with lower facet apposition, distinguished facet dislocation from subluxation. Dislocation, bilateral facet injury, reduced Glasgow Coma Scale, spinal canal occlusion, and spinal cord compression were predictive of neurologic deficit. Radiographic measurements demonstrated at least a "moderate" agreement (ICC>0.4), with most demonstrating an "almost perfect" reproducibility. CONCLUSIONS: This large-scale cohort investigation of DFIs in the cervical spine describes radiographic features that distinguish facet dislocation from subluxation, and associates highly reproducible anatomical and clinical indices to the occurrence of concomitant SCI.