Background

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.

Objective

To evaluate outcomes through 24 months postimplantation.

Methods

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.

Results

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.

Conclusion

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.

Background and objectives

Traumatic spinal cord injury (SCI) remains a devastating condition with no proven effective treatment options available. In a prior single-arm study of patients with thoracic complete SCI (INSPIRE; ClinicalTrials.gov, NCT02138110), acute implantation of an investigational bioresorbable polymer scaffold (Neuro-Spinal Scaffold [NSS]) appeared to be safe through 24 months postimplantation and was associated with an American Spinal Injury Association Impairment Scale (AIS) conversion rate that exceeded historical controls. Here, we evaluated whether NSS implantation demonstrates probable benefit for safety and neurological recovery in patients with thoracic complete SCI vs standard-of-care spine surgery.

Methods

INSPIRE 2.0 was a randomized, controlled, parallel, multicenter study conducted at Level I trauma centers in the United States (ClinicalTrials.gov, NCT03762655; funded by InVivo Therapeutics Corporation). Patients with AIS grade A, thoracic (T2-T12), nonpenetrating SCI requiring spine surgery ≤7 days postinjury were randomized (1:1, computer-generated allocation) to undergo NSS implantation or spine surgery alone (control group). Patients and follow-up International Standards for Neurological Classification of SCI assessors were blinded. A predefined study success criterion required the proportion of patients with improvement of ≥1 AIS grade at 6 months postsurgery (primary endpoint) to be ≥20% higher in the NSS group than in the control group.

Results

Target enrollment was reached (N = 20) with 10 patients randomized and analyzed in each group. At 6 months postsurgery, an improvement in the AIS grade was reported in 2 NSS patients (20%; both to AIS C) and 3 control group patients (30%; to AIS B [n = 2] or AIS C [n = 1]). No serious or unanticipated adverse device effects were reported. The study was closed to further follow-up because of not meeting its primary endpoint.

Conclusion

In this small group of patients with thoracic complete (AIS A) SCI, implantation of an intraparenchymal bioresorbable scaffold did not produce probable clinical benefit. However, this study provides evidence that surgical intervention in an injured spinal cord parenchyma may be performed safely.

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.

STUDY DESIGN: Systematic review. OBJECTIVES: The correlation between pre-operative diffusion tensor imaging (DTI) metrics and post-operative clinical outcomes in patients with degenerative cervical myelopathy (DCM) has been widely investigated with different studies reporting varied findings. We conducted a systematic review to determine the association between DTI metric and clinical outcomes after surgery. METHODS: We identified relevant articles that investigated the relationship between pre-operative DTI indices and post-operative outcome in DCM patients by searching PubMed/MEDLINE, Web of Science, Scopus, and EMBASE from inception until October 2023. In addition, quantitative synthesis and meta-analyses were performed. RESULTS: FA was significantly correlated with postoperative JOA or mJOA across all age and follow up subgroups, changes observed in JOA or mJOA from preoperative to postoperative stages (Δ JOA or Δ mJOA) in subgroups aged 65 and above and in those with a follow-up period of 6 months or more, as well as recovery rate in all studies pooled together and also in the under-65 age bracket. Additionally, a significant correlation was demonstrated between recovery rate and ADC across all age groups. No other significant correlations were discovered between DTI parameters (MD, AD, and ADC) and post-operative outcomes. CONCLUSION: DTI is a quantitative noninvasive evaluation tool that correlates with severity of DCM. However, the current evidence is still elusive regarding whether DTI metric is a validated tool for predicting the degree of post-operative recovery, which could potentially be useful in patient selection for surgery.

Study design

Narrative Review.

Objectives

The objective of this review is to provide a stepwise approach to the assessment of patients with potential symptoms of degenerative cervical myelopathy (DCM).

Methods

N/A.

Results

DCM is an overarching term used to describe progressive compression of the cervical spinal cord by age-related changes to the spinal axis. These alterations to normal anatomy narrow the spinal canal, reduce the space available for the spinal cord, and may ultimately compress the ascending and descending neural tracts. Patients with DCM present with a wide range of symptoms that can significantly impact quality of life, including bilateral hand numbness and paresthesia, gait impairment, motor weakness of the upper and lower extremities, and bladder and bowel dysfunction. Unfortunately, DCM is often misdiagnosed, resulting in delayed assessment and management by the appropriate specialist. The proper evaluation of a patient with suspected DCM includes obtaining a detailed patient history, conducting a comprehensive neurological examination, and ordering appropriate tests to rule in or out other diagnoses.

Conclusion

This review summarizes a stepwise approach to the diagnosis of patients with DCM.

Study design

Narrative review.

Objective

The current review aimed to describe the role of existing techniques and emerging methods of imaging and electrophysiology for the management of degenerative cervical myelopathy (DCM), a common and often progressive condition that causes spinal cord dysfunction and significant morbidity globally.

Methods

A narrative review was conducted to summarize the existing literature and highlight future directions.

Results

Anatomical magnetic resonance imaging (MRI) is well established in the literature as the key imaging tool to identify spinal cord compression, disc herniation/bulging, and inbuckling of the ligamentum flavum, thus facilitating surgical planning, while radiographs and computed tomography (CT) provide complimentary information. Electrophysiology techniques are primarily used to rule out competing diagnoses. However, signal change and measures of cord compression on conventional MRI have limited utility to characterize the degree of tissue injury, which may be helpful for diagnosis, prognostication, and repeated assessments to identify deterioration. Early translational studies of quantitative imaging and electrophysiology techniques show potential of these methods to more accurately reflect changes in spinal cord microstructure and function.

Conclusion

Currently, clinical management of DCM relies heavily on anatomical MRI, with additional contributions from radiographs, CT, and electrophysiology. Novel quantitative assessments of microstructure, perfusion, and function have the potential to transform clinical practice, but require robust validation, automation, and standardization prior to uptake.

STUDY DESIGN: Literature Review. OBJECTIVE: Myelopathy affecting the thoracic spinal cord can arise secondary to several aetiologies which have similar presentation and management. Consequently, there are many uncertainties in this area, including optimal terminology and definitions. Recent collaborative cervical spinal research has led to the proposal and subsequent community adoption of the name degenerative cervical myelopathy(DCM), which has facilitated the establishment of internationally-agreed research priorities for DCM. We put forward the case for the introduction of the term degenerative thoracic myelopathy(DTM) and degenerative spinal myelopathy(DSM) as an umbrella term for both DCM and DTM. METHODS: Following PRISMA guidelines, a systematic literature search was performed to identify degenerative thoracic myelopathy literature in Embase and MEDLINE. RESULTS: Conditions encompassed within DTM include thoracic spondylotic myelopathy, ossification of the posterior longitudinal ligament, ossification of the ligamentum flavum, calcification of ligaments, hypertrophy of ligaments, degenerative disc disease, thoracic osteoarthritis, intervertebral disc herniation, and posterior osteophytosis. The classic presentation includes girdle pain, gait disturbance, leg weakness, sensory disturbance, and bladder or bowel dysfunction, often with associated back pain. Surgical management is typically favoured with post-surgical outcomes dependent on many factors, including the causative pathology, and presence of additional stenosis. CONCLUSION: The clinical entities encompassed by the term DTM are interrelated, can manifest concurrently, and present similarly. Building on the consensus adoption of DCM in the cervical spine and the recent proposal of degenerative cervical radiculopathy(DCR), extending this common nomenclature framework to the terms degenerative spinal myelopathy and degenerative thoracic myelopathy will help improve recognition and communication.

Acute traumatic spinal cord injury (SCI) can result in severe, lifelong neurological deficits. After SCI, Rho activation contributes to collapse of axonal growth cones, failure of axonal regeneration, and neuronal loss. This randomized, double-blind, placebo-controlled phase 2b/3 study evaluated the efficacy and safety of Rho inhibitor VX-210 (9 mg) in patients after acute traumatic cervical SCI. The study enrolled patients 14-75 years of age with acute traumatic cervical SCIs, C4-C7 (motor level) on each side, and American Spinal Injury Association Impairment Scale (AIS) Grade A or B who had spinal decompression/stabilization surgery commencing within 72 h after injury. Patients were randomized 1:1 with stratification by age (<30 vs. ≥30 years) and AIS grade (A vs. B with sacral pinprick preservation vs. B without sacral pinprick preservation). A single dose of VX-210 or placebo in fibrin sealant was administered topically onto the dura over the site of injury during decompression/stabilization surgery. Patients were evaluated for medical, neurological, and functional changes, and serum was collected for pharmacokinetics and immunological analyses. Patients were followed up for up to 12 months after treatment. A planned interim efficacy-based futility analysis was conducted after ∼33% of patients were enrolled. The pre-defined futility stopping rule was met, and the study was therefore ended prematurely. In the final analysis, the primary efficacy end-point was not met, with no statistically significant difference in change from baseline in upper-extremity motor score at 6 months after treatment between the VX-210 (9-mg) and placebo groups. This work opens the door to further improvements in the design and conduct of clinical trials in acute SCI.

STUDY DESIGN: Clinical practice guideline development following the GRADE process. OBJECTIVES: Hemodynamic management is one of the only available treatment options that likely improves neurologic outcomes in patients with acute traumatic spinal cord injury (SCI). Augmenting mean arterial pressure (MAP) aims to improve blood perfusion and oxygen delivery to the injured spinal cord in order to minimize secondary ischemic damage to neural tissue. The objective of this guideline was to update the 2013 AANS/CNS recommendations on the hemodynamic management of patients with acute traumatic SCI, acknowledging that much has been published in this area since its publication. Specifically, we sought to make recommendations on 1. The range of mean arterial pressure (MAP) to be maintained by identifying an upper and lower MAP limit; 2. The duration of such MAP augmentation; and 3. The choice of vasopressor. Additionally, we sought to make a recommendation on spinal cord perfusion pressure (SCPP) targets. METHODS: A multidisciplinary guideline development group (GDG) was formed that included health care professionals from a wide range of clinical specialities, patient advocates, and individuals living with SCI. The GDG reviewed the 2013 AANS/CNS guidelines and voted on whether each recommendation should be endorsed or updated. A systematic review of the literature, following PRISMA standards and registered in PROSPERO, was conducted to inform the guideline development process and address the following key questions: (i) what are the effects of goal-directed interventions to optimize spinal cord perfusion on extent of neurological recovery and rates of adverse events at any time point of follow-up? and (ii) what are the effects of particular monitoring techniques, perfusion ranges, pharmacological agents, and durations of treatment on extent of neurological recovery and rates of adverse events at any time point of follow-up? The GDG combined the information from this systematic review with their clinical expertise in order to develop recommendations on a MAP target range (specifically an upper and lower limit to target), the optimal duration for MAP augmentation, and the use of vasopressors or inotropes. Using methods outlined by the GRADE working group, recommendations were formulated that considered the balance of benefits and harms, financial impact, acceptability, feasibility and patient preferences. RESULTS: The GDG suggested that MAP should be augmented to at least 75-80 mmHg as the lower limit, but not actively augmented beyond an upper limit of 90-95 mmHg in order to optimize spinal cord perfusion in acute traumatic SCI. The quality of the evidence around the target MAP was very low, and thus the strength of this recommendation is weak. For duration of hemodynamic management, the GDG suggested that MAP be augmented for a duration of 3-7 days. Again, the quality of the evidence around the duration of MAP support was very low, and thus the strength of this recommendation is also weak. The GDG felt that a recommendation on the choice of vasopressor or the use of SCPP targets was not warranted, given the dearth of available evidence. CONCLUSION: We provide new recommendations for blood pressure management after acute SCI that acknowledge the limitations of the current evidence on the relationship between MAP and neurologic recovery. It was felt that the low quality of existing evidence and uncertainty around the relationship between MAP and neurologic recovery justified a greater range of MAP to target, and for a broader range of days post-injury than recommended in previous guidelines. While important knowledge gaps still remain regarding hemodynamic management, these recommendations represent current perspectives on the role of MAP augmentation for acute SCI.

STUDY DESIGN: A modified Delphi study. OBJECTIVE: To assess current practice patterns in the management of cervical spinal cord injury (SCI) and develop a simplified, practical classification system which offers ease of use in the acute setting, incorporates modern diagnostic tools and provides utility in determining treatment strategies for cervical SCI. METHODS: A three-phase modified Delphi procedure was performed between April 2020 and December 2021. During the first phase, members of the AOSpine SCI Knowledge forum proposed variables of importance for classifying and treating cervical SCI. The second phase involved an international survey of spine surgeons gauging practices surrounding the role and timing of surgery for cervical SCI and opinions regarding factors which most influence these practices. For the third phase, information obtained from phases 1 and 2 were used to draft a new classification system. RESULTS: 396 surgeons responded to the survey. Neurological status, spinal stability and cord compression were the most important variables influencing decisions surrounding the role and timing of surgery. The majority (>50%) of respondents preferred to perform surgery within 24 hours post-SCI in clinical scenarios in which there was instability, severe cord compression or severe neurology. Situations in which <50% of respondents were inclined to operate early included: SCI with mild neurological impairments, with cord compression but without instability (with or without medical comorbidities), and SCI without cord compression or instability. CONCLUSIONS: Spinal stability, cord compression and neurological status are the most important variables influencing surgeons practices surrounding the surgical management of cervical SCI. Based on these results, a simplified classification system for acute cervical SCI has been proposed.