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.

The relationship of the posterior iliac interval and the S1 screw trajectory.

INTRODUCTION: Surgical fixation is widely practised in the management of spinal deformity. S1 screws are commonly incorporated in lumbosacral fusions and can be performed in both open and percutaneous techniques. However, their entry point is determined by the position of the pedicle as well as the posterior iliac interval (PII), as it creates an impedance for screw angulation. A wider angle screw has the potential to achieve a greater length and thus strength versus a narrow screw angle insertion due to risk of anterior breach. METHODS: A retrospective analysis of 50 consecutive patients between July 2018 andDecember 2021 undergoing lumbo-sacral fusion with include S1 screw insertion from a single institution and surgeon. The age, screw angles, and the posterior iliac intervals were measured. RESULTS: The patients ranged from age 27 to 83 years old (mean 64.7) with a posterior iliac interval (PII) ranging from 7.76 to 12.62 cm (mean 10.24) and the average S1 screw angle on the right was 76.01 degrees (range 59.37 to 88.48) and on the left 74.37 degrees (range 59.75 to 87.47 degrees). Applying the Pearson Correlation co-efficient, a wider PII correlated with a more angulated screw entry (P < 0.05). CONCLUSION: As expected, a wider PPI is significantly associated with a more angulated S1 screw trajectory and may have implication on patient biomechanics in lumbo-sacral fusion constructs.

A geospatial examination of specialist care accessibility and impact on health outcomes for patients with acute traumatic spinal cord injury in New South Wales, Australia: a population record linkage study.

BACKGROUND: Timely treatment is essential for achieving optimal outcomes after traumatic spinal cord injury (TSCI), and expeditious transfer to a specialist spinal cord injury unit (SCIU) is recommended within 24 h from injury. Previous research in New South Wales (NSW) found only 57% of TSCI patients were admitted to SCIU for acute post-injury care; 73% transferred within 24 h from injury. We evaluated pre-hospital and inter-hospital transfer practices to better understand the post-injury care pathways impact on patient outcomes and highlight areas in the health service pathway that may benefit from improvement. METHODS: This record linkage study included administrative pre-hospital (Ambulance), admissions (Admitted Patients) and costs data obtained from the Centre for Health Record Linkage, NSW. All patients aged ≥16 years with incident TSCI in NSW (2013-2016) were included. We investigated impacts of geographical disparities on pre-hospital and inter-hospital transport decisions from injury location using geospatial methods. Outcomes assessed included time to SCIU, surgery and the impact of these variables on the experience of inpatient complications. RESULTS: Inclusion criteria identified 316 patients, geospatial analysis showed that over half (53%, n = 168) of all patients were injured within 60 min road travel of a SCIU, yet only 28.6% (n = 48) were directly transferred to a SCIU. Patients were more likely to experience direct transfer to a SCIU without comorbid trauma (p < 0.01) but higher ICISS (p < 0.001), cervical injury (p < 0.01), and transferred by air-ambulance (p < 0.01). Indirect transfer to SCIU was more likely with two or more additional traumatic injuries (p < 0.01) or incomplete injury (p < 0.01). Patients not admitted to SCIU at all were older (p = 0.05) with lower levels of injury (p < 0.01). Direct transfers received earlier operative intervention (median (IQR) 12.9(7.9) hours), compared with patients transferred indirectly to SCIU (median (IQR) 19.5(18.9) hours), and had lower risk of complications (OR 3.2 v 1.4, p < 0.001). Complications included pressure injury, deep vein thrombosis, urinary infection, among others. CONCLUSIONS: Getting patients with acute TSCI patients to the right place at the right time is dependent on numerous factors; some are still being triaged directly to non-trauma services which delays specialist and surgical care and increases complication risks. The higher rates of complication following delayed transfer to a SCIU should motivate health service policy makers to investigate reasons for this practice and consent to improvement strategies. More stringent adherence to recommended guidelines would prioritise direct SCIU transfer for patients injured within 60 min radius, enabling the benefits of specialised care.

Heterogeneous emergency department management of published recommendation defined hypotension in patients with acute traumatic spinal cord injury: A multi-centre overview.

OBJECTIVE: Evidence-based management for patients with acute traumatic spinal cord injury (TSCI) in the ED has a critical impact on long-term outcomes. Acute hypotension post-injury may compromise spinal cord perfusion and extend neurological damage. Published guidelines recommend mean arterial blood pressure (BP) maintenance between 85 and 90 mmHg for 7 days post-injury; the extent to which this is followed in Australia is unknown. METHODS: Prospective observational study of patients ≥16 years with TSCI, treated at 48 hospitals across two Australian states. Mean arterial BPs were recorded in the Ambulance, and ED arrival and discharge. Patients' medical records documented treatment provided (intravenous fluids, vasopressors or both) for BP augmentation. Hypotension was defined as mean arterial BP <85 mmHg, per the American Association of Neurological Surgeons guidelines. RESULTS: The 208 patients with TSCI in the present study were more likely to receive BP augmentation if they experienced direct transport to a Spinal Cord Service hospital (OR 5.57, 95% CI 2.32-10.11), had a cervical level injury (OR 2.32, 95% CI 1.01-5.5) or were hypotensive on ED arrival (OR 2.42, 95% CI 1.34-4.39). Of the 112 patients who were hypotensive, 71 (63.4%) received treatment for this; however, the majority (76%) remained hypotensive on discharge. CONCLUSION: Hypotensive patients' post-TSCI experienced heterogeneous ED care discordant with published guidelines; varying by hospital type. Specialist care and more severe injury increased likelihood of guideline adherence. Lack of adherence may influence patient outcomes. Level 1 evidence is needed along with consistent guideline implementation and clinician training to likely improve TSCI management and outcomes.

How Does Cage Lordosis Influence Postoperative Segmental Lordosis in Lumbar Interbody Fusion.

BACKGROUND: Consideration of sagittal alignment is an integral part of spinal fusion surgery correlating with superior outcomes. Segmental lordosis is an important contributor to sagittal alignment. This study assessed surgical factors influencing segmental lordosis in a 360° fusion model, including cage dimensions, anterior longitudinal ligament resection, facetectomy, and posterior compression. METHODS: Six L3-4 synthetic spinal motion segments were used in a repeated measures design. Each sample was sequentially instrumented with lateral cages of increasing height and angle. Lordosis was assessed from lateral radiographs of intact and each instrumented condition. The effect of anterior longitudinal ligament resection, posterior compression with pedicle screws, and bilateral facetectomy was additionally examined. RESULTS: A linear relationship between segmental lordosis and cage height was found. This effect was greater with the anterior longitudinal ligament divided. In cages of the same anterior height, increased intrinsic cage lordosis did not result in increased segmental lordosis; cages with no intrinsic lordosis resulted in the highest segmental lordosis. In examining this finding, it was shown that posterior cage height had a larger influence on segmental lordosis. Posterior compression with pedicle screws and bilateral facetectomy increased the segmental lordosis by a further 3.4° and 2.6°, respectively. CONCLUSIONS: Cage height was a key factor, with posterior compression further increasing lordosis. The finding that 0° cages results in the most segmental lordosis was an unexpected finding and highlights the importance of appropriate sizing on resulting lordosis. These findings are relevant to cage selection but require further study prior to applying to clinical practice and may influence future cage design.

Emergency and acute care management of traumatic spinal cord injury: a survey of current practice among senior clinicians across Australia.

BACKGROUND: To describe pre-hospital, emergency department and acute care assessment and management practices of senior clinicians for patients with acute traumatic spinal cord injury (TSCI) across Australia; and to describe clinical practice variation. METHODS: We used a descriptive, cross-sectional study design to survey senior clinicians (greater than 10 years practice in this field) caring for patients with acute TSCI. The assessment, management and referral practices of prehospital, emergency department/trauma and surgical expert clinicians, across prehospital, early hospital care, diagnostic imaging and haemodynamic management were surveyed. RESULTS: We invited 95 eligible senior clinicians; the response rate was 75%. Survey findings demonstrated overall lack of awareness or consistent use of evidence based published guidelines; many clinicians following 'locally written' or 'no particular' guideline. Practitioners were conflicted across multiple areas including patient assessment and diagnosis, treatment and transport decisions. Reported spinal immobilisation practices differed substantially, as did target setting for blood pressure; the majority of clinicians actively monitored risk of respiratory deterioration. Specialist care consult and specialist service bed availability was reported as problematic by more than one third of clinicians. CONCLUSIONS: Unwarranted clinical practice variation is known to contribute to different health outcomes for patients with similar etiologies. Clinical practice guidelines offer evidence based, best practice standards, however are only effective if adopted throughout the healthcare system. Wide variability in acute care practices, pathways and timing to specialist centres for TSCI was evidenced by this survey despite seniority among clinicians. This devastating injury requires prompt, consistent, evidence based care from the moment of first responder. Improved outcomes for patients with TSCI would be more likely with standardised care across pre-hospital, emergency and acute care phases of care.

The Morel-Lavallée lesion in thoracolumbar spine trauma-two index cases.

The Morel-Lavallée lesion (MLL) is a closed degloving injury caused by traumatic separation of the subcutaneous tissue from the underlying fascia, without a break in the overlying skin. We present two cases that demonstrate a previously unrecognised association of the MLL with thoracolumbar spine fractures. The lesion is frequently missed, or its significance is overlooked, on initial evaluation. Awareness of this injury should allow tailored strategies to decrease the high risk of wound complications.

Idiopathic intradural dorsal thoracic arachnoid cysts: A case series and review of the literature.

BACKGROUND: Spinal intradural arachnoid cysts (SIAC) are cerebrospinal fluid (CSF) filled sacs formed by arachnoid membranes and may be either idiopathic or acquired. Idiopathic cysts represent a separate entity and their aetiology remains uncertain. By far the most difficult differential diagnosis is distinguishing between idiopathic anterior spinal cord herniation (IASCH) and dorsal thoracic intradural arachnoid cysts (TIAC), due to their similarity in radiological appearance. Cine-mode (SSFP) is emerging as a novel technique in the diagnosis and operative planning of SIAC. METHOD: Retrospective analysis of patients with idiopathic TIACs that were surgically managed at Royal North Shore Hospital and North Shore Private Hospital between November 2000 and November 2015. RESULTS: Ten patients were included in this study. Age ranged from 20 to 77years with a mean age of 60years and a female preponderance. The most common clinical features were progressive gait ataxia and lower limb myelopathy. Radicular pain tends to improve following surgery, however gait ataxia may not. DISCUSSION: While there are circumstances in which the distinction between dorsal thoracic intradural arachnoid cysts and idiopathic anterior spinal cord herniation are radiologically obvious, in cases where the appearances are less clear, cine-mode SSFP MRI imaging can provide an invaluable tool to differentiate these pathologies and lead the clinician towards the correct diagnosis and management. The mainstay of surgical management for dorsal TIACs is laminectomy and cyst excision or fenestration. Surgery for gait ataxia should be aimed towards preventing deterioration, while maintaining the potential for symptomatic improvement, whereas surgery for radicular pain should be curative.

Improving care standards for patients with spinal trauma combining a modified e-Delphi process and stakeholder interviews: a study protocol.

INTRODUCTION: Around 300 people sustain a new traumatic spinal cord injury (TSCI) in Australia each year; a relatively low incidence injury with extremely high long-term associated costs. Care standards are inconsistent nationally, lacking in consensus across important components of care such as prehospital spinal immobilisation, timing of surgery and timeliness of transfer to specialist services. This study aims to develop 'expertly defined' and agreed standards of care across the majority of disciplines involved for these patients. METHODS AND ANALYSIS: A modified e-Delphi process will be used to gain consensus for best practice across specific clinical early care areas for the patient with TSCI; invited participants will include clinicians across Australia with relevant and significant expertise. A rapid literature review will identify available evidence, including any current guidelines from 2005 to 2015. Level and strength of evidence identified, including areas of contention, will be used to formulate the first round survey questions and statements. Participants will undertake 2-3 online survey rounds, responding anonymously to questionnaires regarding care practices and indicating their agreement or otherwise with practice standard statements. Relevant key stakeholders, including patients, will also be interviewed face to face. ETHICS AND DISSEMINATION: Ethics approval for this study was obtained by the NSW Population & Health Services Research Ethics Committee on 14 January 2016 (HREC/12/CIPHS/74). Seeking comprehensive understanding of how the variation in early care pathways and treatment can be addressed to achieve optimal patient outcomes and economic costs; the overall aim is the agreement to a consistent approach to the triage, treatment, transport and definitive care of acute TSCI victims. The agreed practice standards of care will inform the development of a Clinical Pathway with practice change strategies for implementation. These standards will offer a benchmark for state-wide and potentially national policy.

Cervical spine immobilization in the elderly population.

BACKGROUND: Immobilization of the cervical spine is a cornerstone of spinal injury management. In the context of suspected cervical spine injury, patients are immobilized in a 'neutral position' based on the head and trunk resting on a flat surface. It is hypothesized that the increased thoracic kyphosis and loss of cervical lordosis seen in elderly patients may require alternative cervical immobilization, compared with the 'neutral position'. METHODS: To investigate this, an audit of pan-scan CT performed on consecutive major trauma patients aged over 65 years was carried out over a 6-month period. Utilizing the pan-CT's localizing scout film, a novel measurement, the 'chin-brow horizontal' angle was independently measured by a senior spine surgeon (RJM) and a neurosurgeon (PJR) with the gantry used as a horizontal zero- degree reference. The benefit of the 'chin-brow horizontal' angle in the trauma setting is it can be assessed from the bedside whilst the patient is immobilized against a flat surface. RESULTS: During the 6-month study period, 58 patients were identified (30 male, 28 female), with an average age of 77.6 years (minimum 65, maximum 97). Results showed that 'chin-brow horizontal' angles varied widely, between +15.8 degrees in flexion to -30.5 degrees in extension (mean -12.4 degrees in extension, standard deviation 9.31 degrees. The interobserver correlation was 0.997 (95% CI: 0.995-0.998). CONCLUSIONS: These findings suggest that, due to degenerative changes commonly seen in elderly patients, the routine use of the 'neutral position' adopted for cervical spine immobilization may not be appropriate in this population. We suggest that consideration be taken in cervical spine immobilization, with patients assessed on an individual basis including the fracture morphology, to minimize the risk of fracture displacement and worsened neurological deficit.

Interspinous process spacers versus traditional decompression for lumbar spinal stenosis: systematic review and meta-analysis.

BACKGROUND: Interspinous spacers are used in selected patients for the treatment of lumbar spinal stenosis. The uses of interspinous devices are still debated, with reports of significantly higher reoperation rates and unfavourable cost-effectiveness compared to traditional decompression techniques. METHODS: Six electronic databases were searched from their date of inception to December 2015. Relevant studies were identified using specific eligibility criteria and data was extracted and analyzed based on predefined primary and secondary endpoints. RESULTS: Eleven comparative studies were obtained for qualitative and quantitative assessment, data extraction and analysis. There was no significant difference in VAS back pain, leg pain or ODI scores for standalone interspinous process device (IPD) vs. bony decompression. However, standalone IPD was associated with lower surgical complications (4% vs. 8.7%, P=0.03) but higher long-term reoperation rates (23.7% vs. 8.5%, P<0.00001). IPD as an adjunct to decompression had comparable patient-reported scores, complications and reoperation rates to decompression alone. CONCLUSIONS: Current evidence indicates no superiority for mid- to long-term patient-reported outcomes for IPD compared with traditional bony decompression, with lesser surgical complications but at the risk of significantly higher reoperation rates and costs.

Biomechanical evaluation of a biomimetic spinal construct.

BACKGROUND: Laboratory spinal biomechanical tests using human cadaveric or animal spines have limitations in terms of disease transmission, high sample variability, decay and fatigue during extended testing protocols. Therefore, a synthetic biomimetic spine model may be an acceptable substitute. The goal of current study is to evaluate the properties of a synthetic biomimetic spine model; also to assess the mechanical performance of lateral plating following lateral interbody fusion. METHODS: Three L3/4 synthetic spinal motion segments were examined using a validated pure moment testing system. Moments (±7.5 Nm) were applied in flexion-extension (FE), lateral bending (LB) and axial rotation (AR) at 1Hz for total 10000 cycles in MTS Bionix. An additional test was performed 12 hours after 10000 cycles. A ±10 Nm cycle was also performed to allow provide comparison to the literature. For implantation evaluation, each model was tested in the 4 following conditions: 1) intact, 2) lateral cage alone, 3) lateral cage and plate 4) anterior cage and plate. Results were analysed using ANOVA with post-hoc Tukey's HSD test. RESULTS: Range of motion (ROM) exhibited logarithmic growth with cycle number (increases of 16%, 37.5% and 24.3% in AR, FE and LB respectively). No signification difference (p > 0.1) was detected between 4 cycles, 10000 cycles and 12 hour rest stages. All measured parameters were comparable to that of reported cadaveric values. The ROM for a lateral cage and plate construct was not significantly different to the anterior lumbar interbody construct for FE (p = 1.00), LB (p = 0.995) and AR (p = 0.837). CONCLUSIONS: Based on anatomical and biomechanical similarities, the synthetic spine tested here provides a reasonable model to represent the human lumbar spine. Repeated testing did not dramatically alter biomechanics which may allow non-destructive testing between many different procedures and devices without the worry of carry over effects. Small intra-specimen variability and lack of biohazard makes this an attractive alternative for in vitro spine biomechanical testing. It also proved an acceptable surrogate for biomechanical testing, confirming that a lateral lumbar interbody cage and plate construct reduces ROM to a similar degree as anterior lumbar interbody cage and plate constructs.

Porcine small intestine submucosa matrix (Surgisis) for esophageal perforation.

We present a case of traumatic cervical esophageal perforation complicated by delayed diagnosis and foreign body presence successfully repaired with acellular matrix biomaterial made from porcine submucosa (Surgisis mesh [Wilson-Cook, Winston-Salem, NC]). With metal plating eroding into the esophagus from a spinal fixation procedure, the mesh was applied to the defect just under the cricopharyngeus. The patient re-commenced oral intake after 7 days, and an endoscopy at 4 weeks revealed a well-incorporated mesh in an intact esophagus with normal caliber. In this case, Surgisis mesh (Wilson-Cook) proved effective in providing temporary esophageal integrity to allow healing in an infected field where diversion was impossible.

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.

Chiari malformation, cervical disc prolapse and syringomyelia--always think twice.

We present the case of a 36-year-old man with neck pain and parasthesia of both upper limbs. Magnetic resonance imaging demonstrated a cervical disc protrusion with spinal cord compression, a Chiari I malformation and cervical syringomyelia. On clinical grounds it was suspected that the cervical stenosis was the symptomatic pathology and an anterior cervical decompression was performed, followed by arthroplasty. Post-operative imaging demonstrated adequate canal decompression, preserved cervical mobility and near-complete resolution of the syrinx. Syringomyelia has a multitude of causes and synchronous pathology can occur. Cervical spondylosis is infrequently associated with syringomyelia. Chiari I malformations are increasingly incidentally detected and asymptomatic. This first report of arthroplasty for cervical spondylosis associated with syringomyelia adds to the growing body of experience with this new technology.

Operative steps in management of benign nerve sheath tumors.

Benign peripheral nerve sheath tumors include the neurofibroma, schwannoma, and their plexiform variants. Operative management begins with an assessment of the relative risks associated with surgery compared with observation. The risks of observation include the risk of malignancy, the progression of symptoms, risk of delayed surgery, and ongoing patient suffering. The risks of surgery include anesthetic problems, wound complications, and neurological injury. New neurological deficits have been reported to occur in approximately 10 to 15% of surgically treated cases. In general, surgery is recommended for symptomatic or progressive lesions. Although the surgical approach will vary depending on the location, type, and extent of tumor, adherence to certain principles will facilitate success. Adequate visualization and successful removal will be achieved with detailed anatomical knowledge, an adequate extensile exposure to visualize the proximal and distal tumor extent, circumferential dissection of the tumor, microsurgical dissection under appropriate magnification, and meticulous hemostasis throughout the procedure.