Early Surgery for Traumatic Spinal Cord Injury: Where Are We Now?

Study Design: Narrative review. Objective: There is a strong biological rationale to perform early decompression after traumatic spinal cord injury (SCI). With an enlarging clinical evidence base, most spine surgeons internationally now favor early decompression for the majority of SCI patients; however, a number of pertinent questions remain surrounding this therapy. Methods: A narrative review evaluating the status of early surgery for SCI. In particular, we addressed the following questions: (1) Which patients stand to benefit most from early surgery? 2) What is the most appropriate time threshold defining early surgery? Results: Although heterogeneity exists, the evidence generally seems to support early surgery. While the best evidence exists for cervical SCI, there is insufficient data to support a differential effect for early surgery depending on neurological level or injury severity. When comparing thresholds to define early versus late surgery-including a later threshold (48-72 hours), an earlier threshold (24 hours), and an ultra-early threshold (8-12 hours)-the 2 earlier time points seem to be associated with the greatest potential for improved outcomes. However, existing prehospital and hospital logistics pose barriers to early surgery in a significant proportion of patients. An overview of recommendations from the recent AOSpine guidelines is provided. Conclusion: In spite of increasing acceptance of early surgery post SCI, further research is needed to (1) identify subgroups of patients who stand to derive particular benefit-in particular to develop more evidence-based approaches for central cord syndrome and (2) investigate the efficacy and feasibility of ultra-early surgery targeting more aggressive timelines

Guidelines for the management of degenerative cervical myelopathy and spinal cord injury: an introduction to a focus issue

Study Design: Introduction to a guidelines project. Objectives: The objective of this focus issue is to present guidelines that outline how to best manage patients with degenerative cervical myelopathy (DCM) and spinal cord injury (SCI). Topics addressed in this focus issue include: 1) management strategies for patients with mild, moderate and severe DCM; and 2a) timing of surgical decompression; b) the use of methylprednisolone sodium succinate; c) the type and timing of anticoagulation strategies; d) the role of magnetic resonance imaging in clinical decision making and outcome prediction; and e) the type and timing of rehabilitation in patients with SCI. Methods: Systematic reviews were conducted to address key clinical questions and to synthesize the current body of evidence. A multidisciplinary guideline development group used the results of these reviews, along with their clinical expertise, to develop clinical practice guidelines, in a process that adhered to methodology proposed by the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) Working Group. Results: The multidisciplinary guideline development group combined the systematic review findings with their clinical expertise and opinions to formulate recommendations on how to manage patients with DCM and SCI. Conclusions: These guidelines will serve as tools to assist clinicians in their decision making by offering a perspective that combines the available evidence, expertise from a variety of clinicians, and patient values

Efficacy and safety of methylprednisolone sodium succinate in acute spinal cord injury: a systematic review

Study Design: Systematic review and meta-analysis. Objective: The objective of this study was to conduct a systematic review to assess the comparative effectiveness and safety of high-dose methylprednisolone sodium succinate (MPSS) versus no pharmacological treatment in patients with traumatic spinal cord injury (SCI). Methods: A systematic search was performed in PubMed and the Cochrane Collaboration Library for literature published between January 1956 and June 17, 2015. Included studies ere critically appraised, and Grades of Recommendation Assessment, Development and Evaluation methods were used to determine the overall quality of evidence for primary outcomes. Previous systematic reviews on this topic were collated and evaluated using the Assessment of Multiple Systematic Reviews scoring system. Results: The search yielded 723 citations, 13 of which satisfied inclusion criteria. Among these, 6 were primary research articles and 7 were previous systematic reviews. Based on the included research articles, there was moderate evidence that the 24-hour NASCIS II (National Acute Spinal Cord Injury Studies) MPSS regimen has no impact on long-term neurological recovery when all postinjury time points are considered. However, there is also moderate evidence that subjects receiving the same MPSS regimen within 8 hours of injury achieve an additional 3.2 points (95% confidence interval = 0.10 to 6.33; P = .04) of motor recovery compared with patients receiving placebo or no treatment. Conclusion: Although safe to administer, a 24-hour NASCIS II MPSS regimen, when all postinjury time points are considered, has no impact on indices of long-term neurological recovery. When commenced within 8 hours of injury, however, a high-dose 24-hour regimen of MPSS confers a small positive benefit on long-term motor recovery and should be considered a treatment option for patients with SCI

A phase I/IIa clinical trial of a recombinant Rho protein antagonist in acute spinal cord injury.

Multiple lines of evidence have validated the Rho pathway as important in controlling the neuronal response to growth inhibitory proteins after central nervous system (CNS) injury. A drug called BA-210 (trademarked as Cethrin(®)) blocks activation of Rho and has shown promise in pre-clinical animal studies in being used to treat spinal cord injury (SCI). This is a report of a Phase I/IIa clinical study designed to test the safety and tolerability of the drug, and the neurological status of patients following the administration of a single dose of BA-210 applied during surgery following acute SCI. Patients with thoracic (T2-T12) or cervical (C4-T1) SCI were sequentially recruited for this dose-ranging (0.3 mg to 9 mg Cethrin), multi-center study of 48 patients with complete American Spinal Injury Association assessment (ASIA) A. Vital signs; clinical laboratory tests; computed tomography (CT) scans of the spine, head, and abdomen; magnetic resonance imaging (MRI) of the spine, and ASIA assessment were performed in the pre-study period and in follow-up periods out to 1 year after treatment. The treatment-emergent adverse events that were reported were typical for a population of acute SCI patients, and no serious adverse events were attributed to the drug. The pharmacokinetic analysis showed low levels of systemic exposure to the drug, and there was high inter-patient variability. Changes in ASIA motor scores from baseline were low across all dose groups in thoracic patients (1.8±5.1) and larger in cervical patients (18.6±19.3). The largest change in motor score was observed in the cervical patients treated with 3 mg of Cethrin in whom a 27.3±13.3 point improvement in ASIA motor score at 12 months was observed. Approximately 6% of thoracic patients converted from ASIA A to ASIA C or D compared to 31% of cervical patients and 66% for the 3-mg cervical cohort. Although the patient numbers are small, the observed motor recovery in this open-label trial suggests that BA-210 may increase neurological recovery after complete SCI. Further clinical trials with Cethrin in SCI patients are planned, to establish evidence of efficacy

Pattern of neurological recovery in persons with an acute cervical spinal cord injury over the first 14 days post injury

IntroductionFollowing a traumatic spinal cord injury (SCI) it is critical to document the level and severity of injury. Neurological recovery occurs dynamically after injury and a baseline neurological exam offers a snapshot of the patient's impairment at that time. Understanding when this exam occurs in the recovery process is crucial for discussing prognosis and acute clinical trial enrollment. The objectives of this study were to: (1) describe the trajectory of motor recovery in persons with acute cervical SCI in the first 14 days post-injury; and (2) evaluate if the timing of the baseline neurological assessment in the first 14 days impacts the amount of motor recovery observed.MethodsData were obtained from the Rick Hansen Spinal Cord Injury Registry (RHSCIR) site in Vancouver and additional neurological data was extracted from medical charts. Participants with a cervical injury (C1–T1) who had a minimum of three exams (including a baseline and discharge exam) were included. Data on the upper-extremity motor score (UEMS), total motor score (TMS) and American Spinal Injury Association (ASIA) Impairment Scale (AIS) were included. A linear mixed-effect model with additional variables (AIS, level of injury, UEMS, time, time2, and TMS) was used to explore the pattern and amount of motor recovery over time.ResultsTrajectories of motor recovery in the first 14 days post-injury showed significant improvements in both TMS and UEMS for participants with AIS B, C, and D injuries, but was not different for high (C1–4) vs. low (C5–T1) cervical injuries or AIS A injuries. The timing of the baseline neurological examination significantly impacted the amount of motor recovery in participants with AIS B, C, and D injuries.DiscussionTiming of baseline neurological exams was significantly associated with the amount of motor recovery in cervical AIS B, C, and D injuries. Studies examining changes in neurological recovery should consider stratifying by severity and timing of the baseline exam to reduce bias amongst study cohorts. Future studies should validate these estimates for cervical AIS B, C, and D injuries to see if they can serve as an “adjustment factor” to control for differences in the timing of the baseline neurological exam

Differential Histopathological and Behavioral Outcomes Eight Weeks after Rat Spinal Cord Injury by Contusion, Dislocation, and Distraction Mechanisms

The objective of this study was to compare the long-term histological and behavioral outcomes after spinal cord injury (SCI) induced by one of three distinct biomechanical mechanisms: dislocation, contusion, and distraction. Thirty male Sprague-Dawley rats were randomized to incur a traumatic cervical SCI by one of these three clinically relevant mechanisms. The injured cervical spines were surgically stabilized, and motor function was assessed for the following 8 weeks. The spinal cords were then harvested for histologic analysis. Quantification of white matter sparing using Luxol fast blue staining revealed that dislocation injury caused the greatest overall loss of white matter, both laterally and along the rostrocaudal axis of the injured cord. Distraction caused enlarged extracellular spaces and structural alteration in the white matter but spared the most myelinated axons overall. Contusion caused the most severe loss of myelinated axons in the dorsal white matter. Immunohistochemistry for the neuronal marker NeuN combined with Fluoro Nissl revealed that the dislocation mechanism resulted in the greatest neuronal cell losses in both the ventral and dorsal horns. After the distraction injury mechanism, animals displayed no recovery of grip strength over time, in contrast to the animals subjected to contusion or dislocation injuries. After the dislocation injury mechanism, animals displayed no improvement in the grooming test, in contrast to the animals subjected to contusion or distraction injuries. These data indicate that different SCI mechanisms result in distinct patterns of histopathology and behavioral recovery. Understanding this heterogeneity may be important for the future development of therapeutic interventions that target specific neuropathology after SCI

Interventions to Optimize Spinal Cord Perfusion in Patients With Acute Traumatic Spinal Cord Injury: An Updated Systematic Review

STUDY DESIGN: Systematic review update. OBJECTIVES: Interventions that aim to optimize spinal cord perfusion are thought to play an important role in minimizing secondary ischemic damage and improving outcomes in patients with acute traumatic spinal cord injuries (SCIs). However, exactly how to optimize spinal cord perfusion and enhance neurologic recovery remains controversial. We performed an update of a recent systematic review (Evaniew et al, J. Neurotrauma 2020) to evaluate the effects of Mean Arterial Pressure (MAP) support or Spinal Cord Perfusion Pressure (SCPP) support on neurological recovery and rates of adverse events among patients with acute traumatic SCI. METHODS: We searched PubMed/MEDLINE, EMBASE and ClinicalTrials.gov for new published reports. Two reviewers independently screened articles, extracted data, and evaluated risk of bias. We implemented the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach to rate confidence in the quality of the evidence. RESULTS: From 569 potentially relevant new citations since 2019, we identified 9 new studies for inclusion, which were combined with 19 studies from a prior review to give a total of 28 studies. According to low or very low quality evidence, the effect of MAP support on neurological recovery is uncertain, and increased SCPP may be associated with improved neurological recovery. Both approaches may involve risks for specific adverse events, but the importance of these adverse events to patients remains unclear. Very low quality evidence failed to yield reliable guidance about particular monitoring techniques, perfusion ranges, pharmacological agents, or durations of treatment. CONCLUSIONS: This update provides an evidence base to support the development of a new clinical practice guideline for the hemodynamic management of patients with acute traumatic SCI. While avoidance of hypotension and maintenance of spinal cord perfusion are important principles in the management of an acute SCI, the literature does not provide high quality evidence in support of a particular protocol. Further prospective, controlled research studies with objective validated outcome assessments are required to examine interventions to optimize spinal cord perfusion in this setting

Establishing Diagnostic Criteria for Degenerative Cervical Myelopathy [AO Spine RECODE-DCM Research Priority Number 3].

STUDY DESIGN: Narrative review. OBJECTIVES: To discuss the importance of establishing diagnostic criteria in Degenerative Cervical Myelopathy (DCM), including factors that must be taken into account and challenges that must be overcome in this process. METHODS: Literature review summarising current evidence of establishing diagnostic criteria for DCM. RESULTS: Degenerative Cervical Myelopathy (DCM) is characterised by a degenerative process of the cervical spine resulting in chronic spinal cord dysfunction and subsequent neurological disability. Diagnostic delays lead to progressive neurological decline with associated reduction in quality of life for patients. Surgical decompression may halt neurologic worsening and, in many cases, improves function. Therefore, making a prompt diagnosis of DCM in order to facilitate early surgical intervention is a clinical priority in DCM. CONCLUSION: There are often extensive delays in the diagnosis of DCM. Presently, no single set of diagnostic criteria exists for DCM, making it challenging for clinicians to make the diagnosis. Earlier diagnosis and subsequent specialist referral could lead to improved patient outcomes using existing treatment modalities

Sensorimotor plasticity after spinal cord injury: a longitudinal and translational study

Objective The objective was to track and compare the progression of neuroplastic changes in a large animal model and humans with spinal cord injury. Methods A total of 37 individuals with acute traumatic spinal cord injury were followed over time (1, 3, 6, and 12 months post-injury) with repeated neurophysiological assessments. Somatosensory and motor evoked potentials were recorded in the upper extremities above the level of injury. In a reverse-translational approach, similar neurophysiological techniques were examined in a porcine model of thoracic spinal cord injury. Twelve Yucatan mini-pigs underwent a contusive spinal cord injury at T10 and tracked with somatosensory and motor evoked potentials assessments in the fore- and hind limbs pre- (baseline, post-laminectomy) and post-injury (10 min, 3 h, 12 weeks). Results In both humans and pigs, the sensory responses in the cranial coordinates of upper extremities/forelimbs progressively increased from immediately post-injury to later time points. Motor responses in the forelimbs increased immediately after experimental injury in pigs, remaining elevated at 12 weeks. In humans, motor evoked potentials were significantly higher at 1-month (and remained so at 1 year) compared to normative values. Conclusions Despite notable differences between experimental models and the human condition, the brain's response to spinal cord injury is remarkably similar between humans and pigs. Our findings further underscore the utility of this large animal model in translational spinal cord injury research

Establishing Diagnostic Criteria for Degenerative Cervical Myelopathy [AO Spine RECODE-DCM Research Priority Number 3].

STUDY DESIGN: Narrative review. OBJECTIVES: To discuss the importance of establishing diagnostic criteria in Degenerative Cervical Myelopathy (DCM), including factors that must be taken into account and challenges that must be overcome in this process. METHODS: Literature review summarising current evidence of establishing diagnostic criteria for DCM. RESULTS: Degenerative Cervical Myelopathy (DCM) is characterised by a degenerative process of the cervical spine resulting in chronic spinal cord dysfunction and subsequent neurological disability. Diagnostic delays lead to progressive neurological decline with associated reduction in quality of life for patients. Surgical decompression may halt neurologic worsening and, in many cases, improves function. Therefore, making a prompt diagnosis of DCM in order to facilitate early surgical intervention is a clinical priority in DCM. CONCLUSION: There are often extensive delays in the diagnosis of DCM. Presently, no single set of diagnostic criteria exists for DCM, making it challenging for clinicians to make the diagnosis. Earlier diagnosis and subsequent specialist referral could lead to improved patient outcomes using existing treatment modalities