There is convincing preclinical evidence that early decompression in the setting of spinal cord injury (SCI) improves neurologic outcomes. However, the effect of early surgical decompression in ...patients with acute SCI remains uncertain. Our objective was to evaluate the relative effectiveness of early (<24 hours after injury) versus late (≥ 24 hours after injury) decompressive surgery after traumatic cervical SCI.
We performed a multicenter, international, prospective cohort study (Surgical Timing In Acute Spinal Cord Injury Study: STASCIS) in adults aged 16-80 with cervical SCI. Enrolment occurred between 2002 and 2009 at 6 North American centers. The primary outcome was ordinal change in ASIA Impairment Scale (AIS) grade at 6 months follow-up. Secondary outcomes included assessments of complications rates and mortality.
A total of 313 patients with acute cervical SCI were enrolled. Of these, 182 underwent early surgery, at a mean of 14.2(± 5.4) hours, with the remaining 131 having late surgery, at a mean of 48.3(± 29.3) hours. Of the 222 patients with follow-up available at 6 months post injury, 19.8% of patients undergoing early surgery showed a ≥ 2 grade improvement in AIS compared to 8.8% in the late decompression group (OR = 2.57, 95% CI:1.11,5.97). In the multivariate analysis, adjusted for preoperative neurological status and steroid administration, the odds of at least a 2 grade AIS improvement were 2.8 times higher amongst those who underwent early surgery as compared to those who underwent late surgery (OR = 2.83, 95% CI:1.10,7.28). During the 30 day post injury period, there was 1 mortality in both of the surgical groups. Complications occurred in 24.2% of early surgery patients and 30.5% of late surgery patients (p = 0.21).
Decompression prior to 24 hours after SCI can be performed safely and is associated with improved neurologic outcome, defined as at least a 2 grade AIS improvement at 6 months follow-up.
Although there is a strong biological rationale for early decompression of the injured spinal cord, the influence of the timing of surgical decompression for acute spinal cord injury (SCI) remains ...debated, with substantial variability in clinical practice. We aimed to objectively evaluate the effect of timing of decompressive surgery for acute SCI on long-term neurological outcomes.
We did a pooled analysis of individual patient data derived from four independent, prospective, multicentre data sources, including data from December, 1991, to March, 2017. Three of these studies had been published; of these, only one study previously specifically analysed the effect of the timing of surgical decompression. These four datasets were selected because they were among the highest quality acute SCI datasets available and contained highly granular data. Individual patient data were obtained by request from study authors. All patients who underwent decompressive surgery for acute SCI within these datasets were included. Patients were stratified into early (<24 h after spinal injury) and late (≥24 h after spinal injury) decompression groups. Neurological outcomes were assessed by American Spinal Injury Association (ASIA), or International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), examination. The primary endpoint was change in total motor score from baseline to 1 year after spinal injury. Secondary endpoints were ASIA Impairment Scale (AIS) grade and change in upper-extremity motor, lower-extremity motor, light touch, and pin prick scores after 1 year. One-stage meta-analyses were done by hierarchical mixed-effects regression adjusting for baseline score, age, mechanism of injury, AIS grade, level of injury, and administration of methylprednisolone. Effect sizes were summarised by mean difference (MD) for sensorimotor scores and common odds ratio (cOR) for AIS grade, with corresponding 95% CIs. As a secondary analysis, change in total motor score was regressed against time to surgical decompression (h) as a continuous variable, using a restricted cubic spline with adjustment for the same covariates as in the primary analysis.
We identified 1548 eligible patients from the four datasets. Outcome data at 1 year after spinal injury were available for 1031 patients (66·6%). Patients who underwent early surgical decompression (n=528) experienced greater recovery than patients who had late decompression surgery (n=1020) at 1 year after spinal injury; total motor scores improved by 23·7 points (95% CI 19·2–28·2) in the early surgery group versus 19·7 points (15·3–24·0) in the late surgery group (MD 4·0 points 1·7–6·3; p=0·0006), light touch scores improved by 19·0 points (15·1–23·0) vs 14·8 points (11·2–18·4; MD 4·3 1·6–7·0; p=0·0021), and pin prick scores improved by 18·3 points (13·7–22·9) versus 14·2 points (9·8–18·6; MD 4·0 1·5–6·6; p=0·0020). Patients who had early decompression also had better AIS grades at 1 year after surgery, indicating less severe impairment, compared with patients who had late surgery (cOR 1·48 95% CI 1·16–1·89; p=0·0019). When time to surgical decompression was modelled as a continuous variable, there was a steep decline in change in total motor score with increasing time during the first 24–36 h after injury (p<0·0001); and after 36 h, change in total motor score plateaued.
Surgical decompression within 24 h of acute SCI is associated with improved sensorimotor recovery. The first 24–36 h after injury appears to represent a crucial time window to achieve optimal neurological recovery with decompressive surgery following acute SCI.
None.
Abstract
BACKGROUND: Traumatic spinal cord injuries (SCI) have devastating consequences for the physical, financial, and psychosocial well-being of patients and their caregivers. Expediently ...delivering interventions during the early postinjury period can have a tremendous impact on long-term functional recovery.
PATHOPHYSIOLOGY: This is largely due to the unique pathophysiology of SCI where the initial traumatic insult (primary injury) is followed by a progressive secondary injury cascade characterized by ischemia, proapoptotic signaling, and peripheral inflammatory cell infiltration. Over the subsequent hours, release of proinflammatory cytokines and cytotoxic debris (DNA, ATP, reactive oxygen species) cyclically adds to the harsh postinjury microenvironment. As the lesions mature into the chronic phase, regeneration is severely impeded by the development of an astroglial-fibrous scar surrounding coalesced cystic cavities. Addressing these challenges forms the basis of current and upcoming treatments for SCI.
MANAGEMENT: This paper discusses the evidence-based management of a patient with SCI while emphasizing the importance of early definitive care. Key neuroprotective therapies are summarized including surgical decompression, methylprednisolone, and blood pressure augmentation. We then review exciting neuroprotective interventions on the cusp of translation such as Riluzole, Minocycline, magnesium, therapeutic hypothermia, and CSF drainage. We also explore the most promising neuroregenerative strategies in trial today including Cethrin™, anti-NOGO antibody, cell-based approaches, and bioengineered biomaterials. Each section provides a working knowledge of the key preclinical and patient trials relevant to clinicians while highlighting the pathophysiologic rationale for the therapies.
CONCLUSION: We conclude with our perspectives on the future of treatment and research in this rapidly evolving field.
Based on 6-month data from the InVivo Study of Probable Benefit of the Neuro-Spinal Scaffold for Safety and Neurological Recovery in Patients with Complete Thoracic Spinal Cord Injury (INSPIRE) study ...(NCT02138110), acute implantation of an investigational bioresorbable polymer device (Neuro-Spinal Scaffold NSS) appeared to be safe in patients with complete thoracic spinal cord injury (SCI) and was associated with an ASIA Impairment Scale (AIS) conversion rate that exceeded historical controls.
To evaluate outcomes through 24 months postimplantation.
INSPIRE was a prospective, open-label, multicenter, single-arm study. Eligible patients had traumatic nonpenetrating SCI with a visible contusion on MRI, AIS A classification, neurological level of injury at T2-T12, and requirement for open spine surgery ≤96 hours postinjury.
Nineteen patients underwent NSS implantation. Three patients had early death determined by investigators to be unrelated to the NSS or its implantation procedure. Seven of 16 evaluable patients (44%) had improvement of ≥1 AIS grade at 6 months (primary end point) to AIS B (n = 5) or AIS C (n = 2). Three patients with AIS B at 6 months had further neurological improvement to AIS C by 12 (n = 2) and 24 (n = 1) months, respectively; none have deteriorated per latest available follow-up. No unanticipated or serious adverse device effects were reported.
In this small group of patients with complete thoracic SCI, acute NSS implantation within the spinal cord appeared to be safe with no long-term neurological issues identified during the 24-month follow-up. Patients remain stable, with additional AIS conversions observed in some patients at 12 months and beyond. These data further support the safety and probable benefit of NSS implantation in this patient population.
Abstract
BACKGROUND
Human central nervous system stem cells (HuCNS-SC) are multipotent adult stem cells with successful engraftment, migration, and region-appropriate differentiation after spinal ...cord injury (SCI).
OBJECTIVE
To present data on the surgical safety profile and feasibility of multiple intramedullary perilesional injections of HuCNS-SC after SCI.
METHODS
Intramedullary free-hand (manual) transplantation of HuCNS-SC cells was performed in subjects with thoracic (n = 12) and cervical (n = 17) complete and sensory incomplete chronic traumatic SCI.
RESULTS
Intramedullary stem cell transplantation needle times in the thoracic cohort (20 M HuCNS-SC) were 19:30 min and total injection time was 42:15 min. The cervical cohort I (n = 6), demonstrated that escalating doses of HuCNS-SC up to 40 M range were well tolerated. In cohort II (40 M, n = 11), the intramedullary stem cell transplantation needle times and total injection time was 26:05 ± 1:08 and 58:14 ± 4:06 min, respectively. In the first year after injection, there were 4 serious adverse events in 4 of the 12 thoracic subjects and 15 serious adverse events in 9 of the 17 cervical patients. No safety concerns were considered related to the cells or the manual intramedullary injection. Cervical magnetic resonance images demonstrated mild increased T2 signal change in 8 of 17 transplanted subjects without motor decrements or emerging neuropathic pain. All T2 signal change resolved by 6 to 12 mo post-transplant.
CONCLUSION
A total cell dose of 20 M cells via 4 and up to 40 M cells via 8 perilesional intramedullary injections after thoracic and cervical SCI respectively proved safe and feasible using a manual injection technique.
Acute spinal cord injury (SCI) is a traumatic event that results in disturbances to normal sensory, motor, or autonomic function and ultimately affects a patient’s physical, psychological, and social ...well-being. The management of patients with SCI has drastically evolved over the past century as a result of increasing knowledge on injury mechanisms, disease pathophysiology, and the role of surgery. There still, however, remain controversial areas surrounding available management strategies for the treatment of SCI, including the use of corticosteroids such as methylprednisolone sodium succinate, the optimal timing of surgical intervention, the type and timing of anticoagulation prophylaxis, the role of magnetic resonance imaging, and the type and timing of rehabilitation. This lack of consensus has prevented the standardization of care across treatment centers and among the various disciplines that encounter patients with SCI. The objective of this guideline is to form evidence-based recommendations for these areas of controversy and outline how to best manage patients with SCI. The ultimate goal of these guidelines is to improve outcomes and reduce morbidity in patients with SCI by promoting standardization of care and encouraging clinicians to make evidence-informed decisions.
Abstract
Degenerative cervical myelopathy (DCM) is a common cause of spinal cord dysfunction that confronts clinicians on a daily basis. Research performed over the past few decades has provided ...improved insight into the diagnosis, evaluation, and treatment of this disorder. We aim to provide clinicians with an update regarding the state of the art in DCM, focusing on more recent research pertaining to pathophysiology, natural history, treatment, consideration of the minimally symptomatic patient, surgical outcome prediction, and outcome measurement. Current concepts of pathophysiology focus on the combination of static and dynamic elements leading to breakdown of the blood–spinal cord barrier at the site of compression resulting in local inflammation, cellular dysfunction, and apoptosis. With respect to treatment, although there is a dearth of high-quality studies comparing surgical to nonoperative treatment, several large prospective studies have recently associated surgical management with clinically and statistically significant improvement in functional, disability, and quality of life outcome at long-term follow-up. When selecting the specific surgical intervention for a patient with DCM, anterior (discectomy, corpectomy, hybrid discectomy/corpectomy), posterior (laminectomy and fusion, laminoplasty), and combined approaches may be considered as options depending on the specifics of the patient in question; evidence supporting each of these approaches is reviewed in detail. Recently developed clinical prediction models allow for accurate forecasting of postoperative outcomes, permitting enhanced communication and management of patient expectations in the preoperative setting. Finally, an overview of outcome measures recommended for use in the assessment of DCM patients is provided.
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