Surgery For Spinal Cord Injury Research Articles

Single-cell RNA sequencing integrated with bulk RNA sequencing analysis reveals the protective effects of lactate-mediated lactylation of microglia-related proteins on spinal cord injury.

Spinal cord injury (SCI) results in significant neurological deficits, and microglia play the critical role in regulating the immune microenvironment and neurological recovery. Protein lactylation has been found to modulate the function of immune cells. Therefore, this study aimed to elucidate the effects of glycolysis-derived lactate on microglial function and its potential neuroprotective mechanisms via lactylation after SCI. Single-cell RNA sequencing (scRNA-seq) data were obtained from figshare to analyze cellular and molecular alterations within the spinal cord post-SCI, further focusing on the expression of microglia-related genes for cell sub-clustering, trajectory analysis, and glycolysis function analysis. We also evaluated the expression of lactylation-related genes in microglia between day 7 after SCI and sham group. Additionally, we established the mice SCI model and performed the bulk RNA sequencing in a time-dependent manner. The expression of glycolysis- and lactylation-related genes was evaluated, as well as the immune infiltration analysis based on the lactylation-related genes. Then, we investigated the bio-effects of lactate on the inflammation and polarization phenotype of microglia. Finally, adult male C57BL/6 mice were subjected to exercise first to increase lactate level, before SCI surgery, aiming to evaluate the protective effects of lactate-mediated lactylation of microglia-related proteins on SCI. scRNA-seq identified a subcluster of microglia, recombinant chemokine C-X3-C-motif receptor 1+ (CX3CR1+) microglia, which is featured by M1-like phenotype and increased after SCI. KEGG analysis revealed the dysfunctional glycolysis in microglia after SCI surgery, and AUCell analysis suggested that the decreased glycolysis an increased oxidative phosphorylation in CX3CR1+ microglia. Differential gene analysis suggested that several lactylation-related genes (Fabp5, Lgals1, Vim, and Nefl) were downregulated in CX3CR1+ microglia at day 7 after SCI, further validated by the results from bulk RNA sequencing. Immunofluorescence staining indicated the expression of lactate dehydrogenase A (LDHA) in CX3CR1+ microglia also decreased at day 7 after SCI. Cellular experiments demonstrated that the administration of lactate could increase the lactylation level and inhibit the pro-inflammatory phenotype in microglia. Functionally, exercise-mediated lactate production resulted in improved locomotor recovery and decreased inflammatory markers in SCI mice compared to SCI alone. In the subacute phase of SCI, metabolic remodeling in microglia may be key therapeutic targets to promote nerve regeneration, and lactate contributed to neuroprotection after SCI by influencing microglial lactylation and inflammatory phenotype, which offered a novel approach for therapeutic intervention.

Timing of surgical intervention after firearm-related spinal cord injury

Context Surgical management of firearm-related spinal cord injury (SCI) remains controversial, and there are no clear guidelines. Time to surgery, surgical indications, and patient characteristics on initial presentation in this group are not well understood, and these factors may impact the potential for neurologic recovery after operative intervention. Objective To understand the timing and factors affecting the timing of operative intervention after firearm-related SCI Methods In a retrospective cohort study, patients with traumatic SCI from July 2012 to July 2022 (n = 1569) were identified from our level 1 trauma center Trauma Registry. Data was obtained from the trauma registry and chart review. Rates and timing of surgical intervention, initial injury severity measures, and general hospital outcomes were compared between firearm-related SCI and blunt trauma SCI. Results Patients with firearm-related SCI were less likely to undergo surgery compared to other etiologies (24.3% vs. 70.2%, P < 0.0001). Time to surgery for firearm-related SCI was longer than for other etiologies (49.2 ± 92.9 vs. 30.6 h ± 46.0, P = 0.012). Multiple measures of initial injury severity, including Injury Severity Score, Glasgow Coma Score, and emergency department disposition demonstrated more severe injury among patients with firearm-related SCI, and these patients often required other emergent surgeries prior to spine surgery (52%). Conclusions There was a longer time to spine surgery among patients with firearm-related SCI compared to blunt trauma SCI, and patients with firearm-related SCI were more severely injured on initial presentation. Further research is needed to understand the complex relationship between patient injury severity, surgical intervention, surgical timing, and outcomes after firearm-related SCI.

254 Initiation of Low Molecular Weight Heparin Within 24 Hours Is Safe and Effective for VTE Prophylaxis in Spinal Cord Injury Patients

INTRODUCTION: Venous thromboembolism (VTE) following traumatic spinal cord injury (SCI) is a major clinical concern. Current guidelines recommend initiation of chemical prophylaxis within 72 hours of injury or surgery. Given the high reported incidence of VTE in this population, the safety and efficacy of earlier initiation is an important clinical question. METHODS: We analyzed prospectively collected data in a cohort of 162 SCI patients from a single quaternary center. Demographic and clinical data were recorded. Univariate and multivariate logistic regression analyses were performed to identify predictors of VTE in SCI patients treated with LMWH within 24 hours of injury or surgery. RESULTS: Mean age was 56.9 years (28% females). One hundred and thirty (87.8%) patients underwent SCI surgery. There was an extremity fracture in 18.2% and lumbar drain was placed in 22.3%. DVT occurred in 7.4%, PE in 6.1%, and any VTE in 12.2%. A multivariable regression model including age, sex, race, injury severity score, level of SCI, SCI surgery status, admission lower extremity motor score, and extremity fracture showed that only lower extremity motor score (OR 0.94, p=0.03) was significantly associated with VTE. There were 1.5% patients with post-SCI surgery-related bleeds requiring surgery takeback. There were 5.6% non-surgery related bleeds, and 1.2% wound dehiscence. CONCLUSIONS: Initiation of LMWH within 24 hours of injury or surgery maintained the incidence of any VTE event within the lower end of previously reported ranges with 1.5% of patients who underwent SCI surgery requiring surgery takeback due to bleeding complications. Admission lower extremity motor score was the sole predictor of VTE in this patient cohort.

AO Spine/Praxis Clinical Practice Guidelines for the Management of Acute Spinal Cord Injury: An Introduction to a Focus Issue.

Narrative overview and summary. The objective of this introductory manuscript is to provide an overview of the effort that was undertaken to establish clinical practice guidelines for a number of important topics in spinal cord injury (SCI). These topics included: 1. The role and timing of surgical decompression after acute traumatic SCI; 2. The hemodynamic management of acute traumatic SCI; and 3. The definition, diagnosis, and management of intra-operative SCI. Here, we introduce the rationale for the guidelines, the methodology utilized, and summarize how the topics are addressed within various manuscripts of this Focus Issue. The key clinical questions were defined using the PICO format for treatment reviews (patient; intervention; comparison; outcomes) or PPO format (patient, prognostic factor, outcomes) for risk factor review. Multi-disciplinary, international guideline development groups (GDGs) were established to evaluate and collate the available evidence in a rigorous, systematic manner, followed by a review of systematically obtained evidence within the framework of the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) criteria and application of the Evidence to Decision process. Consensus meetings, using a modified Delphi approach, were held with the multidisciplinary, international GDGs using online video-conferencing technology and anonymous voting to develop the final recommendations for each of the topics addressed. All systematic review protocols followed PRISMA standards and were registered on PROSPERO; all potential conflicts were vetted in an open and transparent manner. The funders (AO Spine and Praxis Spinal Cord Institute) had no influence over editorial content or the guidelines process). Updated guidelines were established for the timing of surgical decompression after acute SCI, with surgical decompression within 24hours of injury now "recommended" as a treatment option. Updated guidelines were also established for hemodynamic management, with an expanded target range for mean arterial pressure (MAP) of 75-80 to 90-95mmHg for between 3 to 7days post-injury now "suggested" as a treatment option. The available literature mandated scoping and systematic reviews on the topic of intra-operative SCI, and this resulted in manuscripts to address the definition, frequency, and risk factors, to define the role of intra-operative neuromonitoring, and to suggest an evidence-based care pathway for management. A rigorous process following GRADE standards was undertaken to review the available evidence and establish guideline recommendations around the role and timing of surgery in acute SCI, optimal hemodynamic management of acute SCI and the prevention, diagnosis and management of intraoperative SCI. This effort also identified key knowledge gaps and future directions for study, which will serve to refine these recommendations in the future.

Epidemic Preventive Management during the Coronavirus Disease 2019 Pandemic Is a Risk Factor for Delirium after Spinal Cord Injury Surgery

Epidemic Preventive Management during the Coronavirus Disease 2019 Pandemic Is a Risk Factor for Delirium after Spinal Cord Injury Surgery

Liver-Derived Ketogenesis via Overexpressing HMGCS2 Promotes the Recovery of Spinal Cord Injury.

The liver is the major ketogenic organ of the body, and ketones are reported to possess favorable neuroprotective effects. This study aims to elucidate whether ketone bodies generated from the liver play a critical role in bridging the liver and spinal cord. Mice model with a contusive spinal cord injury (SCI) surgery is established, and SCI induces significant histological changes in mice liver. mRNA-seq of liver tissue shows the temporal changes of ketone bodies-related genes, β-hydroxybutyrate dehydrogenase (BDH1) and solute carrier family 16 (monocarboxylic acid transporters), member 6 (SLC16A6). Then, an activated ketogenesis model is created with adult C57BL/6 mice receiving the tail intravenous injection of GPAAV8-TBG-Mouse-Hmgcs2-CMV- mCherry -WPRE (HMGCS2liver ) and mice receiving equal AAV8-Null being the control group (Vectorliver ). Then, the mice undergo either a contusive SCI or sham surgery. The results show that overexpression of HMG-CoA synthase (Hmgcs2) in mice liver dramatically alleviates SCI-mediated pathological changes and promotes ketogenesis in the liver. Amazingly, liver-derived ketogenesis evidently alleviates neuron apoptosis and inflammatory microglia activation and improves the recovery of motor function of SCI mice. In conclusion, a liver-spinal cord axis can be bridged via ketone bodies, and enhancing the production of the ketone body within the liver has neuroprotective effects on traumatic SCI.

Electroacupuncture Inhibits Neuroinflammation Induced by Astrocytic Necroptosis Through RIP1/MLKL/TLR4 Pathway in a Mouse Model of Spinal Cord Injury.

Astrocytic necroptosis plays an essential role in the progression and regression of neurological disorders, which contributes to the neuroinflammation and disrupts neuronal regeneration and remyelination of severed axons. Electroacupuncture (EA), an effective therapeutic efficacy against spinal cord injury (SCI), has been proved to reduce neuronal cell apoptosis, inhibit inflammation, and prompt neural stem cell proliferation and differentiations. However, there have been few reports on whether EA regulate astrocytic necroptosis in SCI model. To investigate the effects of EA on astrocytic necroptosis and the mechanisms involved in the inhibition of astrocytic necroptosis after SCI in mice by EA, 8-week-old female C57BL/6 mice were subjected to SCI surgery and randomly divided into EA and SCI groups. Mice receiving sham surgery were included as sham group. "Jiaji" was selected as points for EA treatment, 10min/day for 14days. The invitro data revealed that EA treatment significantly improved the nervous function and pathological changes after SCI. EA also reduced the number of GFAP/P-MLKL, GFAP/MLKL, GFAP/HMGB1, and Iba1/HMGB1 co-positive cells and inhibited the expressions of IL-6, IL-1β, and IL-33. The results indicate a significant reduction in inflammatory reaction and astrocytic necroptosis in mice with SCI by EA. Additionally, the expressions of RIP1, MLKL, and TLR4, which are associated with necroptosis, were found to be downregulated by EA. In this study, we confirmed that EA can inhibit neuroinflammation by reducing astrocytic necroptosis through downregulation of RIP1/MLKL/TLR4 pathway in mice with SCI.

Safety and comparative efficacy of initiating low-molecular-weight heparin within 24 hours of injury or surgery for venous thromboembolism prophylaxis in patients with spinal cord injury: a prospective TRACK-SCI registry study.

Venous thromboembolism (VTE) following traumatic spinal cord injury (SCI) is a significant clinical concern. This study sought to determine the incidence of VTE and hemorrhagic complications among patients with SCI who received low-molecular-weight heparin (LMWH) within 24 hours of injury or surgery and identify variables that predict VTE using the prospective Transforming Research and Clinical Knowledge in SCI (TRACK-SCI) database. The TRACK-SCI database was queried for individuals with traumatic SCI from 2015 to 2022. Primary outcomes of interest included rates of VTE (including deep vein thrombosis [DVT] and pulmonary embolism [PE]) and in-hospital hemorrhagic complications that occurred after LWMH administration. Secondary outcomes included intensive care unit and hospital length of stay, discharge location type, and in-hospital mortality. The study cohort consisted of 162 patients with SCI. Fifteen of the 162 patients withdrew from the study, leading to loss of data for certain variables for these patients. One hundred thirty patients (87.8%) underwent decompression and/or fusion surgery for SCI. DVT occurred in 11 (7.4%) of 148 patients, PE in 9 (6.1%) of 148, and any VTE in 18 (12.2%) of 148 patients. The analysis showed that admission lower-extremity motor score (p = 0.0408), injury at the thoracic level (p = 0.0086), admission American Spinal Injury Association grade (p = 0.0070), and younger age (p = 0.0372) were significantly associated with VTE. There were 3 instances of postoperative spine surgery-related bleeding (2.4%) in the 127 patients who had spine surgery with bleeding complication data available, with one requiring return to surgery (0.8%). Thirteen (8.8%) of 147 patients had a bleeding complication not related to spine surgery. There were 2 gastrointestinal bleeds associated with nasogastric tube placement, 3 cases of postoperative non-spine-related surgery bleeding, and 8 cases of other bleeding complications (5.4%) not related to any surgery. Initiation of LMWH within 24 hours was associated with a low rate of spine surgery-related bleeding. Bleeding complications unrelated to SCI surgery still occur with LMWH administration. Because neurosurgical intervention is typically the limiting factor in initializing chemical DVT prophylaxis, many of these bleeding complications would have likely occurred regardless of the protocol.

An Introduction to the North American Clinical Trials Network for Spinal Cord Injury Special Edition: Reflections on Accomplishments and a Look to the Future.

The North American Clinical Trials Network (NACTN) has been established as a network of translational clinical research centers focused on traumatic spinal cord injury (SCI) with the goals of facilitating clinical translational research, promotion of enhanced clinical care protocols including the principle of early surgery for SCI, and improving outcomes for individuals with acute SCI. Since its foundation in 2004 by Dr. Robert Grossman, NACTN has evolved into a powerful multi-stakeholder consortium of eight neurosurgical department faculties at university-affiliated institutions in the United States and Canada, a data management center, and a pharmacological center. To date, high-quality data from more than 1000 patients have been prospectively collected, providing us with a strong body of evidence surrounding SCI epidemiology, the natural history, and complications of acute and subacute SCI management. Key accomplishments of NACTN are summarized in this Focus issue. They include the launch, in collaboration with AO Spine, of the international, multi-center, placebo-controlled, Phase III Riluzole in Acute Spinal Cord Injury Study (RISCIS) that recruited 192 patients. While the primary analyses did not achieve the predetermined endpoint of efficacy for Riluzole, likely related to insufficient power, pre-planned secondary analyses demonstrated that all subgroups of cervical SCI subjects (AIS grades A, B and C) treated with Riluzole showed significant gains in functional recovery. The Focus Issue also includes a detailed analysis of the pharmacokinetics and pharmacodynamics of riluzole in the setting of acute SCI (RISCIS-PK study). Additional achievements include key contributions to the evidence supporting the role of early surgery in acute SCI, and a better understanding of the impact of complications on the outcomes of SCI. Future directions of NACTN will build on past accomplishments and focus on enhanced collaborations with other SCI networks, advanced analytics to examine large datasets, and a greater focus on chronic SCI.

Recombinant Neorudin for the Prevention of Deep-Vein Thrombosis After Spinal-Cord Injury.

Whether anticoagulant therapy should be used after spinal-cord injury (SCI) surgery was controversial. The anticoagulation characteristics of a newly developed anticoagulant, recombinant neorudin (EPR-hirudin (EH)), were explored using a rat model of SCI to provide a basis for clinical anticoagulation therapy of SCI. A rat model of SCI was developed by Allen's method. Then, thrombosis in the inferior vena cava was induced by ligation. The low-bleeding characteristics of EH were explored by investigating dose-response and time-effect relationships, as well as multiple administration of EH, on thrombus formation complicated with SCI. EH inhibited thrombosis in a dose-dependent manner by reducing the wet weight and dry weight of the thrombus. An inhibiting action of EH on thrombosis was most evident in the group given EH 2 h after SCI. After multiple intravenous doses of EH, thrombosis inhibition was improved to that observed with low molecular weight heparin (LMWH) (87% vs 90%). EH administration after SCI neither increased bleeding in the injured spine nor damaged to nerve function. Bleeding duration and activated partial thromboplastin time were increased in the high-dose EH group compared with that in the normal-saline group, but were lower than those in the LMWH group. EH can reduce thrombus formation in a rat model of SCI, and bleeding is decreased significantly compared with that using LMWH. EH may prevent thrombosis after SCI or spinal surgery.

Complications Associated with Preventive Management to Reduce the Risk of COVID-19 Spread After Surgery for Spinal Cord Injury.

Preventive management to reduce the risk of coronavirus disease-2019 (COVID-19) spread led to delays in active rehabilitation, which may have negatively impacted the outcomes of patients with traumatic spinal cord injury (SCI). Therefore, the aim of this study was to clarify the influence of preventive management on the rate of perioperative complications after surgical treatment for SCI. This single-center retrospective study examined the cases of 175 patients who had SCI surgery between 2017 and 2021. We could not continue early rehabilitation interventions starting on April 30, 2020, because of our preventive management to reduce the risk of COVID-19 spread. Using a propensity score-matched model, we adjusted for age, sex, American Spinal Injury Association impairment scale score at admission, and risk factors for perioperative complications described in previous studies. Perioperative complication rates were compared between the COVID-19 pandemic and prepandemic groups. Of the 175 patients, 48 (the pandemic group) received preventive management. The preliminary analysis revealed significant differences between the unmatched pandemic and prepandemic groups with respect to age (75.0 versus 71.2 years, respectively; p = 0.024) and intraoperative estimated blood loss (152 versus 227 mL; p = 0.013). The pandemic group showed significant delays in visiting the rehabilitation room compared with the prepandemic group (10 versus 4 days from hospital admission; p < 0.001). There were significant differences between the pandemic and prepandemic groups with respect to the rates of pneumonia (31% versus 16%; p = 0.022), cardiopulmonary dysfunction (38% versus 18%; p = 0.007), and delirium (33% versus 13%; p = 0.003). With a propensity score-matched analysis (C-statistic = 0.90), 30 patients in the pandemic group and 60 patients in the prepandemic group were automatically selected. There were significant differences between the matched pandemic and prepandemic groups with respect to the rates of cardiopulmonary dysfunction (47% versus 23%; p = 0.024) and deep venous thrombosis (60% versus 35%; p = 0.028). Even with early surgical intervention, late mobilization and delays in active rehabilitation during the COVID-19 pandemic increased perioperative complications after SCI surgery. Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

193 Expansile Duraplasty Improves Motor Outcomes After Acute Traumatic Spinal Cord Injury

INTRODUCTION: Traumatic spinal cord injury (SCI) can lead to debilitating motor weakness. Early surgical decompression and optimization of spinal cord perfusion have emerged as potential therapies to prevent secondary injury caused by edema, ischemia, and inflammation. Expansile duraplasty extends decompression to the intrathecal space to optimize spinal cord perfusion. There remains a paucity of data on whether this provides a clinical benefit. METHODS: We included patients who underwent decompression and stabilization surgery for traumatic SCI from February 2017 to June 2021 at our level 1 trauma center. In duraplasty patients, a 1.5cm x3.5cm acellular, expansile patch was sutured into the dura at the injury site. We collected demographics, injury type, surgery performed, and American Spinal Injury Association (ASIA) motor scores (range 0-100) pre-operatively and at the time of hospital and inpatient rehabilitation discharge. RESULTS: 101 patients were included: 12 treated with expansile duraplasty and 89 without duraplasty. The mean pre-operative motor score was 48.7 ± 29.3 for all patients, 50.5 ± 19.7 for non-duraplasty and 35.7 ± 23.0 for expansile duraplasty (p = 0.06). At rehabilitation discharge, mean change in motor score from pre-operative exam was significantly higher in duraplasty patients (19.9 ± 11.0 for duraplasty vs. 10.9 ± 13.4 for non-duraplasty, p = 0.02). There were no wound complications in the duraplasty group. CONCLUSIONS: In this single-center, retrospective study, SCI patients undergoing expansile duraplasty had significantly greater improvement in ASIA motor scores at rehabilitation discharge compared to non-duraplasty controls. There was no increase in wound complications nor CNS infection. These data present an independent validation of preliminary data from international centers in favor of expansile duraplasty. Further prospective studies are warranted to assess whether this technique is efficacious in treating acute traumatic SCI.

Targeting of MALT1 May Improve Functional Recovery and Attenuate Microglia M1 Polarization-Mediated Neuroinflammation During Spinal Cord Injury.

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is involved in neural injury, neuroinflammation, microglia activation, and polarization, while its function in spinal cord injury (SCI) remains unclear. Thus, this study aimed to evaluate the role of MALT1 modification on SCI recovery and its underlying mechanism. SCI surgery or sham surgery was performed in Sprague-Dawley rats. Then, MALT1 knockdown or negative control lentivirus was injected into SCI rats. Subsequently, MALT1 expression, locomotor capability, neural injury, markers for microglia activation and polarization, inflammatory cytokine expressions, and nuclear factor (NF)-κB pathway were detected. SCI rats exhibited higher MALT1 expression, microglia activation and M1 polarization, neuroinflammation, and NF-κB pathway activation, while worse locomotor capacity compared to sham rats (all P < 0.05). In SCI rats, MALT1 knockdown alleviated Basso, Beattie, and Bresnahan score from 10 to 28days and attenuated HE staining reflected neural injury (all P < 0.05). Besides, MALT1 knockdown declined the number of IBA1+ cells, IBA1+ iNOS+ cells, and IBA1+ CD86+ cells, while enhanced the number of IBA1+ Arg1+ cells and IBA1+ CD206+ cells in SCI rats (all P < 0.05). Meanwhile, MALT1 knockdown declined the expressions of IL-1β, IL-6, and TNF-α in SCI (all P < 0.05), but did not affect IL-10 expression (P > 0.05). Furthermore, MALT1 knockdown suppressed NF-κB pathway activation validated by immunofluorescence staining and western blot assays (all P < 0.05). MALT1 knockdown improves functional recovery, attenuates microglia activation, M1 polarization, and neuroinflammation via inhibiting NF-κB pathway in SCI.

Retracted: Analysis of the Curative Effect and Prognostic Factors of Anterior Cervical Surgery for Spinal Cord Injury without Radiographic Abnormalities.

[This retracts the article DOI: 10.1155/2022/6836966.].

Risk Factors for Postoperative Complications and In-Hospital Mortality Following Surgery for Cervical Spinal Cord Injury.

Background and objective The operative priority in the setting of traumatic cervical spinal cord injury (SCI) is to decompress the injured spinal cord and stabilize the vertebral column. Currently, there is a relative paucity of evidence regarding associations of patient and surgical factors with in-hospital mortality following traumatic SCI. In light of this, the aim of this study was to investigate the correlation of injury, patient, and surgical factors with in-hospital morbidity and mortality. Methods The study was designed as a retrospective cohort study. The electronic medical records (EMR) at a single tertiary centre in Australia were retrospectively reviewed over a five-year period (2016-2021). All adults who were admitted to undergoemergency surgery for cervical SCI were identified and reviewed for patient factors (age, sex, comorbidities), injury factors [injury severity score (ISS), American Spinal Cord Injury Association (ASIA) classification], and surgical factors (anterior/posterior/360 instrumentation, greater than five levels instrumented, operative time). Factors were correlated to in-hospital complications (infection, pressure injury, ventilator dependency, venous thromboembolism, stroke) and in-hospital mortality by using univariate analysis and multivariable logistic regression models. Results A total of 92 patients were identified from the EMR. The median patient age was 54.5years [interquartile range (IQR): 2.5];77(82.2%) of the participants were male. The median ASIA classification was C4 ASIA C. In-hospital mortality following surgery was 6.5% (n=6). Of these patients, the primary cause of death was respiratory failure in 83.3% (n=5). In-hospital mortality was associated with anticoagulation (p=0.01), coronary disease (p=0.012), complete injury (p=0.011), and ventilator dependency (p<0.001). Postoperative pneumonia was associated with complete injury (p=0.009) and polytrauma (p=0.002). Ventilator dependency was associated with complete injuries (p<0.001) and polytrauma (p<0.001). A logistic regression analysis found complete neurological injury to be significant in predicting in-hospital mortality [odds ratio (OR): 184.53, 95% confidence interval (CI): 2.41-14106.65, p=0.018, R2=0.58]. Conclusion To improve surgical outcomes in patients with traumatic cervical SCI, a concerted effort must be made to prevent postoperative complications. Cardiovascular comorbidities present significant risk factors for patients. Patient age appears to insignificantly influence postoperative complication rates; however, this finding may have been influenced by selection bias. Postoperative respiratory complications, especially in patients with complete neurological deficits, can be particularly devastating.

Time is spine: What's over the horizon

The overarching theme in the early treatment of acute spinal cord injury (SCI) is to reduce the extent of secondary damage to facilitate early neurological and functional recovery. Although multiple studies have brought us innovative and potential new therapies to treat SCI, ameliorating neural damage remains a formidable challenge. Knowledge translation of clinical and basic research studies has shown that surgical intervention is a valuable treatment modality; however, the role, timing and optimal technique in surgery remains a topic of great controversy. While evidence to support the concept of ultra-early surgery for acute SCI continues to emerge, current protocols and international guidelines that encourage reducing time from trauma to surgery support the concept of “Time is Spine”. The present article provides a critical narrative review of the current best practice, with a particular focus on the timing of surgical intervention, which shapes our understanding of how time is of the essence in the management of acute SCI.

Low-intensity pulsed ultrasound partially reversed the deleterious effects of a severe spinal cord injury-induced bone loss and osteoporotic fracture healing in paraplegic rats.

To evaluate the effects of low-intensity pulsed ultrasound (LIPUS) on the quality of femoral fracture callus formation in rats with severe osteoporosis secondary to spinal cord injury (SCI). Forty-five male rats were equally divided into three groups: the Sham group underwent sham surgery for SCI followed by surgery for femoral fracture on day ten post-spine surgery; the SCI group sustained a complete transection of the spinal cord and a femoral fracture ten days post-SCI; and the SCI group treated with ultrasound (SCI + US), which also sustained a femoral fracture on day ten post-SCI, concomitant with daily application of LIPUS at the fracture site. At the non-fractured tibias, LIPUS counteracted the SCI-induced bone loss by normalizing the osteoblastic-related gene expression, decreasing resorptive area, increasing trabecular area, and decreasing RANK and RANK-L-positive areas, which resulted in higher cortical volume and stronger tibias. Likewise, LIPUS was effective at restoring bone fracture healing in SCI rats; by promoting endochondral ossification, increasing collagen deposition and OPG-positive-area, decreasing resorptive area, which led to higher density and improved microarchitecture, ultimately resulting in stronger fracture callus. At the tibias, LIPUS counteracted the SCI-induced bone loss effects by simultaneously increasing bone formation and decreasing bone resorption. We also evidenced the osteogenic effects of LIPUS at partially restoring the endochondral ossification during callus formation, leading to a newly formed tissue with improved microarchitecture and mechanical integrity. Therefore, LIPUS may be an efficient and non-invasive approach to prevent bone loss and osteoporotic fracture in SCI individuals.

A Practical Classification System for Acute Cervical Spinal Cord Injury Based on a Three-Phased Modified Delphi Process From the AOSpine Spinal Cord Injury Knowledge Forum.

A modified Delphi study. 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. 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. 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 24hours 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. 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.

Clinical electrodiagnostic evaluation for nerve transfer surgery in spinal cord injury: a new indication and clinical pearls.

In this review, we highlight the important role of the clinical electrodiagnostic (EDX) evaluation after cervical spinal cord injury (SCI). Our discussion focuses on the need for timely, frequent, and accurate EDX evaluations in the context of nerve transfer surgery to restore critical upper limb functions, including elbow extension, hand opening, and hand closing. The EDX evaluation is crucial to define the extent of lower motor neuron lesions and determine candidacy for surgery. We also discuss the important role of the postoperative EDX evaluation in determining prognosis and supporting rehabilitation. We propose a practical framework for EDX evaluation in this clinical setting.

Preoperative electrodiagnostic planning for upper limb peripheral nerve transfers in cervical spinal cord injury: A narrative review.

Peripheral nerve transfer (PNT) to improve upper limb function following cervical spinal cord injury (SCI) involves the transfer of supralesional donor nerves under voluntary control to intralesional or sublesional lower motor neurons not under voluntary control. Appropriate selection of donor and recipient nerves and surgical timing affect functional outcomes. Although the gold standard of nerve selection is intraoperative nerve stimulation, preoperative electrodiagnostic (EDX) evaluation may help guide surgical planning. Currently there is no standardized preoperative EDX protocol. This study reviews the EDX workup preceding PNT surgery in cervical SCI and proposes an informed EDX protocol to assist with surgical planning. The PICO (Population, Intervention, Comparison, Outcome) framework was used to formulate relevant Medical Subject Headings (MeSH) terms and identify published cases of PNT in cervical SCI in Medline, Embase, CINAHL, and Emcare databases in the last 10 years. The EDX techniques evaluating putative donor nerves, recipient nerve branches, time sensitivity of nerve transfer and other electrophysiological parameters were summarized to guide creation of a preoperative EDX protocol. Needle electromyography (EMG) was the most commonly used EDX technique to identify healthy donor nerves. Although needle EMG has also been used on recipient nerves, compound muscle action potential amplitudes may provide a more accurate determination of recipient nerve health and time sensitivity for nerve transfer. Although there has been progress in presurgical EDX evaluation, EMG and nerve conduction study approaches are variable, and each has limitations in their utility for preoperative planning. There is need for standardization in the EDX evaluation preceding PNT surgery to assist with donor and recipient nerve selection, surgical timing and to optimize outcomes. Based on results of this review, herein we propose the PreSCIse (PRotocol for Electrodiagnosis in SCI Surgery of the upper Extremity) preoperative EDX panel to achieve said goals through an interdisciplinary and patient-centered approach.