Spinal cord injury (SCI) is a devastating event resulting in permanent loss of neurological function. To date, effective therapies for SCI have not been established. With recent progress in neurobiology, however, there is hope that drug administration could improve outcomes after SCI. Riluzole is a benzothiazole anticonvulsant with neuroprotective effects. It has been approved by the U.S. Food and Drug Administration as a safe and well-tolerated treatment for patients with amyotrophic lateral sclerosis. The mechanism of action of riluzole involves the inhibition of pathologic glutamatergic transmission in synapses of neurons via sodium channel blockade. There is convincing evidence that riluzole diminishes neurological tissue destruction and promotes functional recovery in animal SCI models. Based on these results, a phase I/IIa clinical trial with riluzole was conducted for patients with SCI between 2010 and 2011. This trial demonstrated significant improvement in neurological outcomes and showed it to be a safe drug with no serious adverse effects. Currently, an international, multi-center clinical trial (Riluzole in Acute Spinal Cord Injury Study: RISCIS) in phase II/III is in progress with riluzole for patients with SCI (clinicaltrials.gov, registration number NCT01597518). This article reviews the pharmacology and neuroprotective mechanisms of riluzole, and focuses on existing preclinical evidence, and emerging clinical data in the treatment of SCI.

Object: Postoperative C-5 palsy is a significant complication resulting from cervical decompression procedures. Moreover, when cervical degenerative diseases are treated with a combination of decompression and posterior instrumented fusion, patients are at increased risk for C-5 palsy. However, the clinical and radiological features of this condition remain unclear. Therefore, the purpose of this study was to clarify the risk factors for developing postoperative C-5 palsy. Methods: Eighty-four patients (mean age 60.1 years) who had undergone posterior instrumented fusion using cervical pedicle screws to treat nontraumatic lesions were independently reviewed. The authors analyzed the medical records of some of these patients who developed postoperative C-5 palsy, paying particular attention to their plain radiographs, MRI studies, and CT scans. Risk factors for postoperative C-5 palsy were assessed using multivariate logistic regression analysis. The cutoff values for the pre- and postoperative width of the intervertebral foramen (C4–5) were determined by receiver operating characteristic curve analysis. Results: Ten (11.9%) of 84 patients developed postoperative C-5 palsy. Seven patients recovered fully from the neurological complications. The pre- and postoperative C4–5 angles showed significant kyphosis in the C-5 palsy group. The pre- and postoperative diameters of the C4–5 foramen on the palsy side were significantly smaller than those on the opposite side in the C-5 palsy group and those bilaterally in the non–C5 palsy group. Risk factors identified by multivariate logistic regression analysis were as follows: 1) ossification of the posterior longitudinal ligament (relative risk [RR] 7.22 [95% CI 1.03–50.55]); 2) posterior shift of the spinal cord (C4–5) (RR 1.73 [95% CI 1.00–2.98]); and 3) postoperative width of the C-5 intervertebral foramen (RR 0.33 [95% CI 0.14–0.79]). The cutoff values of the pre- and postoperative widths of the C-5 intervertebral foramen for C-5 palsy were 2.2 and 2.3 mm, respectively. Conclusions: Patients with preoperative foraminal stenosis, posterior shift of the spinal cord, and additional iatrogenic foraminal stenosis due to cervical alignment correction were more likely to develop postoperative C-5 palsy after posterior instrumentation with fusion. Prophylactic foraminotomy at C4–5 might be useful when preoperative foraminal stenosis is present on CT. Furthermore, it might be useful for treating postoperative C-5 palsy. To prevent excessive posterior shift of the spinal cord, the authors recommend that appropriate kyphosis reduction should be considered carefully.

Object: The cervical pedicle screw (PS) provides strong stabilization but poses a potential risk to the neurovascular system, which may be catastrophic. In particular, vertebrae with degenerative changes complicate the process of screw insertion, and PS misplacement and subsequent complications are more frequent. The purpose of this study was to evaluate the peri- and postoperative complications of PS fixation for nontraumatic lesions and to determine the risk factors of each complication. Methods: Eighty-four patients who underwent cervical PS fixation for nontraumatic lesions were independently reviewed to identify associated complications. The mean age of the patients was 60.1 years, and the mean follow-up period was 4.1 years (range 6–168 months). Pedicle screw malpositioning was classified on postoperative CT scans as Grade I (< 50% of the screw outside the pedicle) or Grade II (≥ 50% of the screw outside the pedicle). Risk factors of each complication were evaluated using a multivariate analysis. Results: Three hundred ninety cervical PSs and 24 lateral mass screws were inserted. The incidence of PS misplacement was 19.5% (76 screws); in terms of malpositioning, 60 screws (15.4%) were classified as Grade I and 16 (4.1%) as Grade II. In total, 33 complications were observed. These included postoperative neurological complications in 11 patients in whom there was no evidence of screw misplacement (C-5 palsy in 10 and C-7 palsy in 1), implant failure in 11 patients (screw loosening in 5, broken screws in 4, and loss of reduction in 2), complications directly attributable to screw insertion in 5 patients (nerve root injury by PS in 3 and vertebral artery injury in 2), and other complications in 6 patients (pseudarthrosis in 2, infection in 1, transient dyspnea in 1, transient dysphagia in 1, and adjacent-segment degeneration in 1). The multivariate analysis showed that a primary diagnosis of cerebral palsy was a risk factor for postoperative implant failure (HR 10.91, p = 0.03) and that the presence of preoperative cervical spinal instability was a risk factor for both Grade I and Grade II screw misplacement (RR 2.12, p = 0.03), while there were no statistically significant risk factors for postoperative neurological complications in the absence of evidence of screw misplacement or complications directly attributable to screw insertion. Conclusions: In the present study, misplacement of cervical PSs and associated complications occurred more often than in previous studies. The rates of screw-related neurovascular complications and neurological deterioration unrelated to PSs were high. Insertion of a PS for nontraumatic lesions is surgically more challenging than that for trauma; consequently, experienced surgeons should use PS fixation for nontraumatic cervical lesions only after thorough preoperative evaluation of each patient's cervical anatomy and after considering the risk factors specified in the present study.

Study Design: Narrative review. Objectives: To discuss the current understanding of the natural history of degenerative cervical myelopathy (DCM). Methods: Literature review summarizing current evidence pertaining to the natural history and risk factors of DCM. Results: DCM is a common condition in which progressive arthritic disease of the cervical spine leads to spinal cord compression resulting in a constellation of neurological symptoms, in particular upper extremity dysfunction and gait impairment. Anatomical factors including cord-canal mismatch, congenitally fused vertebrae and genetic factors may increase individuals’ risk for DCM development. Non-myelopathic spinal cord compression (NMSCC) is a common phenomenon with a prevalence of 24.2% in the healthy population, and 35.3% among individuals >60 years of age. Clinical radiculopathy and/or electrophysiological signs of cervical cord dysfunction appear to be risk factors for myelopathy development. Radiological progression of incidental Ossification of the Posterior Longitudinal Ligament (OPLL) is estimated at 18.3% over 81-months and development of myelopathy ranges between 0-61.5% (follow-up ranging from 40 to 124 months between studies) among studies. In patients with symptomatic DCM undergoing non-operative treatment, 20-62% will experience neurological deterioration within 3-6 years. Conclusion: Current estimates surrounding the natural history of DCM, particularly those individuals with mild or minimal impairment, lack precision. Clear predictors of clinical deterioration for those treated with non-operative care are yet to be identified. Future studies are needed on this topic to help improve treatment counseling and clinical prognostication.

Study Design: Clinical practice guideline development. Objectives: Acute spinal cord injury (SCI) can result in devastating motor, sensory, and autonomic impairment; loss of independence; and reduced quality of life. Preclinical evidence suggests that early decompression of the spinal cord may help to limit secondary injury, reduce damage to the neural tissue, and improve functional outcomes. Emerging evidence indicates that “early” surgical decompression completed within 24 hours of injury also improves neurological recovery in patients with acute SCI. The objective of this clinical practice guideline (CPG) is to update the 2017 recommendations on the timing of surgical decompression and to evaluate the evidence with respect to ultra-early surgery (in particular, but not limited to, <12 hours after acute SCI). Methods: A multidisciplinary, international, guideline development group (GDG) was formed that consisted of spine surgeons, neurologists, critical care specialists, emergency medicine doctors, physical medicine and rehabilitation professionals, as well as individuals living with SCI. A systematic review was conducted based on accepted methodological standards to evaluate the impact of early (within 24 hours of acute SCI) or ultra-early (in particular, but not limited to, within 12 hours of acute SCI) surgery on neurological recovery, functional outcomes, administrative outcomes, safety, and cost-effectiveness. The GRADE approach was used to rate the overall strength of evidence across studies for each primary outcome. Using the “evidence-to-recommendation” framework, recommendations were then developed that considered the balance of benefits and harms, financial impact, patient values, acceptability, and feasibility. The guideline was internally appraised using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool. Results: The GDG recommended that early surgery (≤24 hours after injury) be offered as the preferred option for adult patients with acute SCI regardless of level. This recommendation was based on moderate evidence suggesting that patients were 2 times more likely to recover by ≥ 2 ASIA Impairment Score (AIS) grades at 6 months (RR: 2.76, 95% CI 1.60 to 4.98) and 12 months (RR: 1.95, 95% CI 1.26 to 3.18) if they were decompressed within 24 hours compared to after 24 hours. Furthermore, patients undergoing early surgery improved by an additional 4.50 (95% 1.70 to 7.29) points on the ASIA Motor Score compared to patients undergoing surgery after 24 hours post-injury. The GDG also agreed that a recommendation for ultra-early surgery could not be made on the basis of the current evidence because of the small sample sizes, variable definitions of what constituted ultra-early in the literature, and the inconsistency of the evidence. Conclusions: It is recommended that patients with an acute SCI, regardless of level, undergo surgery within 24 hours after injury when medically feasible. Future research is required to determine the differential effectiveness of early surgery in different subpopulations and the impact of ultra-early surgery on neurological recovery. Moreover, further work is required to define what constitutes effective spinal cord decompression and to individualize care. It is also recognized that a concerted international effort will be required to translate these recommendations into policy.

Mini: On magnetic resonance imaging, indirect decompression using lateral lumbar interbody fusion and posterior fixation was confirmed immediately after surgery and also continuously progressed after surgery, particularly during the first 6 months. Thecal sac enlargement was also confirmed, and is suspected to be caused by the atrophy of the ligamentum flavum and the disc. Study Design.: A prospective cohort study. Objective.: The aim of this study was to investigate radiographical changes related to indirect decompression using lateral lumbar interbody fusion (LLIF) with posterior fixation. Summary of Background Data.: Indirect lumbar decompression via LLIF is used to treat degenerative lumbar diseases requiring neural decompression. Although evidence suggests that thecal sac enlargement follows shortly after surgery, few studies have described the postoperative changes on MRIs. Methods.: This study involved 102 patients who underwent indirect decompression at 136 levels, with LLIF and posterior fixation. Magnetic resonance imaging (MRIs) were collected preoperatively and several times postoperatively (over a 2-year period starting immediately after surgery). We then quantified the cross-sectional areas of the thecal sac and ligamentum flavum, as well as the anteroposterior diameter of disc bulging, and qualitatively assessed lumbar spinal stenosis according to a modified version of Schizas’ classification [Grades A (mild) to C (severe)]. The Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) was used for the assessment of the clinical symptoms. Results.: All changes were observable immediately after surgery, progressed over time, and were significantly different statistically at 2 years after surgery. The thecal sac was significantly larger (189% of preoperative; P < 0.0001), while the ligamentum flavum and disc bulge were significantly smaller [58.9% and 67.3% of preoperative (P < 0.001), respectively]. The number of patients with grade C (severe) lumbar stenosis also dropped significantly (preoperative, 17.6%; 2 years postoperative, 0%). There were no significant differences in JOABPEQ results at 6 months, 1 year, and 2 years postsurgery. Conclusion.: Indirect decompression produces immediate positive results that continue to improve over time. The cross-sectional area of the thecal sac doubled by 2 years after surgery, and the ligamentum flavum cross-sectional area and disc bulging both shrank significantly. At the same time, however, postoperative radiographical improvements do not appear to correlate with clinical symptoms. Level of Evidence: 3