Intraoperative Neuromonitoring for Spines at Risk During Nonspine Surgery: A 9-Year Review.

BACKGROUND: Patients with certain spinal anomalies are at risk for rare but devastating spinal cord injuries under anesthesia. We created a Spine at Risk (SAR) program to evaluate and recommend precautions for such patients, including intraoperative neuromonitoring (IONM) use for the highest-risk patients. We aimed to review all monitored nonspine procedures to determine rate of potential spinal cord injuries avoided in those who would otherwise have been unmonitored. METHODS: We performed a retrospective review of our institutional SAR program from 2011 to 2019 to analyze the number of nonspine anesthetized procedures that were done under IONM, the characteristics of those that had an IONM alert; and the clinical outcomes. RESULTS: Of the 3,453 patients flagged for SAR review, 1121 (33%) received a precaution recommendation, and 359 (10% of all flagged) were given IONM recommendations. Of those, 57 patients (16% of recommendations, 2% of all flagged) had a total of 102 nonspine anesthetized procedures done under IONM. Seven patients had a total of 10 cases with IONM alerts. Two cases were aborted when improved signals could not be obtained after working through a checklist; one of these patients woke with transient neurological deficits. Signals improved to baseline in 7 cases by working through a signal loss checklist. One case was aborted preoperatively when monitorable baseline signals could not be obtained. CONCLUSIONS: In the highest-risk spinal anomaly patients, we monitored an average of 11.7 nonspine cases per year, with a 10% rate of IONM alerts, and no permanent neurological deficits. Although the majority of patients remain safe during procedures, in the most critical patients IONM allowed the team to identify and react to alerts that may have otherwise led to permanent neurological injury. This is the largest series of spinal cord-monitored nonspine pediatric cases. It is important for pediatric orthopedic surgeons to evaluate at-risk patients and recommend IONM where appropriate, to protect both patients and our procedural colleagues. LEVEL OF EVIDENCE: Case series, level IV.

Comparison of Landmark-Guided Versus Fluoroscopy-Guided Cerebrospinal Fluid Drain-Related Complications After Aortic Repairs.

OBJECTIVE: Cerebrospinal fluid drains (CSFDs) are efficacious in preventing spinal cord injury after thoracic or thoracoabdominal aortic repair with extensive coverage. Increasingly, fluoroscopy is used to guide placement instead of the traditional landmark-based approach, but it is unknown which approach is associated with fewer complications. DESIGN: A retrospective cohort study. SETTING: In the operating room. PARTICIPANTS: Patients having undergone thoracic or thoracoabdominal aortic repair with a CSFD over a 7-year period at a single center. INTERVENTIONS: No intervention. MEASUREMENTS AND MAIN RESULTS: Groups were reviewed and statistically compared with respect to baseline characteristics, ease of CSFD placement, and major and minor complications directly related to placement. A total of 150 CSFDs were placed with landmark guidance as opposed to 95 with fluoroscopy guidance. Compared to the landmark group, patients with fluoroscopy-guided CSFDs were older (p < 0.008), had lower American Society of Anesthesiologists physical status scores (p = 0.008), required fewer CSFD placement attempts (p = 0.011), had the CSFD in place for longer duration (p < 0.001), and had a similar incidence of CSFD-related complications (p > 0.999). Composites of both major (4.5% of cases) and minor CSFD-related complications (6.1% of cases), the primary outcomes of the study, occurred with similar incidences between the 2 groups (p > 0.999 for both comparisons) after adjusting potential confounders. CONCLUSIONS: In patients undergoing thoracic or thoracoabdominal aortic repairs, there were no significant differences in the risk of major and minor CSFD-related complications between fluoroscopic guidance and the landmark approach. Although the authors' institution is a high-volume center for this type of procedure, the study was limited by a small sample size. Hence, regardless of the technique used for the placement of CSFD, the risks related to the placement should be balanced carefully against the potential benefits resulting from spinal cord injury prevention. Fluoroscopy-aided insertion of CSFD requires fewer attempts and, hence, may be better tolerated by patients.

Assessment of increased knowledge about traffic accidents prevention, one month after a presentation included in the program "it can happen to you" of AESLEME.

Road traffic accidents are a real pandemic and incur expenses amounting to 1-2% of every country's GDP. AESLEME (Association for the Study of Spinal Cord Injuries) has celebrated its 30th anniversary here in Spain. AESLEME's instructors are health workers and people with spinal cord injuries caused by road accidents: their presentations-teaching road safety and sharing information on irreversible injuries-are enhanced by personal stories that help schoolchildren to acquire knowledge on this matter. STUDY DESIGN: Pre and post-quasi-experimental study. OBJECTIVE: To assess the increase in knowledge about road safety following a school-based road safety campaign. METHODS: Two multiple-choice tests were given to each of the 8106 students taking part, who were 12-14 years old. Of the four possible answers, only one of them was correct. The first multiple-choice test was taken before the presentation and the second was taken one month later. RESULTS: After assessing the answers, there was a change in the tendency of the number of correct before/after answers for the multiple-choice test, and the number of correct ones rose one month after the presentation. This increase is statistically significant (p < 0.01) and represents a national increase of 61% in the probability of correct answers, although this varies from 8% to 278% depending on the region. CONCLUSIONS: The assessment, involving over 8000 people, showed that there has been an improvement in road safety knowledge thanks to education provided by AESLEME's instructors, and a statistically significant increase was obtained throughout Spain and different regions.

Could extended laminectomy effectively prevent spinal cord injury due to spinal shortening after 3-column osteotomy?

OBJECTIVE: To explore whether the laminectomy extension can effectively prevent spinal cord injury (SCI) due to spinal shortening after 3-column osteotomy in goat models. METHODS: A total of twenty healthy goats were included and done with 3-column osteotomy of T13 and L1 under the somatosensory evoked potential (SSEP) monitoring. The samples were divided into two groups. The first group underwent regular laminectomy while the second group underwent an extended laminectomy with an extra 10 mm-lamina cranial to L2. The SSEP measured after 3-column osteotomy was set as the baseline, and the SSEP decreased by 50% from the baseline amplitude and/or delayed by 10% relative to the baseline peak latency was set as positive results, which indicated spinal cord injury. The vertebral column was gradually shortened until the SSEP monitoring just did not show a positive result. The height of the initial osteotomy gap (the distance from the lower endplate of T12 to the upper endplate of L2), the shortened distance (△H), the number of spinal cord angulated and the changed angle of the spinal cord (△α) were measured and recorded in each group. Neurological function was evaluated by the Tarlov scores on day 2 postoperatively. RESULTS: All the goats except one of the first group due to changes in the SSEP during the osteotomy were included and analyzed. In the first group, the height of the initial osteotomy segment and the safe shortening distances were 61.6 ± 2.6 mm and 35.2 ± 2.6 mm, respectively; the spinal cord of 5 goats was angulated (46.4 ± 6.6°), the other four goats were kinked and not angulated. In the second group, the height of the initial osteotomy segment and the safe shortening distances were 59.8 ± 1.5 mm and 43.3 ± 1.2 mm, respectively, and the spinal cord of ten goats were angulated (97.6 ± 7.2°). There was no significant difference in the height of the initial osteotomy segment between the two groups by using Independent-Samples T-Test, P = 0.095 (P > 0.05); there were significant difference in the safe shortening distance and the changed angle of the spinal cord between the two groups by using Independent-Samples T-Test (both [Formula: see text]H and [Formula: see text]α of P < 0.001), the difference between their mean were 8.1 mm and 51.2°. Significant difference was found in the number of spinal cord angulation between the two groups through Fisher's exact test (5/9 vs. 10/10, P = 0.033). CONCLUSIONS: An additional resection of 10 mm-lamina cranial to L2 showed the satisfactory effect in alleviating SCI after 3-column osteotomy. Timely and appropriate extend laminectomy could be a promising therapeutic strategy for SCI attributable to facilitating spinal cord angulation rather than spinal cord kinking and increasing the safe shortening distance.

Spinal cord protection in open and endovascular approaches to thoracoabdominal aortic aneurysms.

Despite advancements in surgical and postoperative management, spinal cord injury has been a persistent complication of both open and endovascular repair of thoracoabdominal and descending thoracic aortic aneurysm. Spinal cord injury can be explained with an ischemia-infarction model which results in local edema of the spinal cord, damaging its structure and leading to reversible or irreversible loss of its function. Perfusion of the spinal cord during aortic procedures can be enhanced by several adjuncts which have been described with a broad variety of evidence in their support. These adjuncts include systemic hypothermia, cerebrospinal fluid drainage, extracorporeal circulation and distal aortic perfusion, segmental arteries reimplantation, left subclavian artery revascularization, and staged aortic repair. The Authors here reviewed and discussed the role of such adjuncts in preventing spinal cord injury from occurring, pinpointing current evidence and outlining future perspectives.

Spinal drain for aortic aneurysm repairs: tool or toy?

PURPOSE OF REVIEW: Spinal cord injury (SCI) is one of the biggest complications in open and endovascular aortic repairs. Historically, cerebrospinal fluid drains (CSFD) have been one of the most effective modalities in reducing SCI and one of the most studied. CSFD placement also carries its' own set of procedural risks. This editorial intends to evaluate recent literature to determine whether CSFDs remain a valuable tool in aortic repair. RECENT FINDINGS: As the surgical management of thoracic aortic aneurysms has evolved, there has been an increasing number of endovascular repairs. Current recommendations emphasize prophylactic CSFD placement in endovascular repair cases deemed 'high risk.' However, several meta-analyses differ on whether prophylactic CSFD placement reduced the risk of SCI. The incidence of SCI decreased between 2014 and 2018, despite a similar rate of prophylactic CSFD placement suggesting other techniques are being performed and may be effective in spinal cord protection as well. SUMMARY: There has been conflicting data on whether CSFDs have a role in reducing the risk of SCI in endovascular aortic repair. Some studies suggest that there is no benefit to placement while others suggest that routine prophylactic drains should be placed for all endovascular cases. Despite this, efforts have been made to selectively place CSFDs in those patients deemed at 'high risk' for SCI. CSFDs also remain a part of rescue treatment for postoperative SCI. This suggests that CSFDs continue to be a valuable tool that we need to better comprehend. Future research is necessary to better understand how patient risk factors can be balanced with perioperative management to help identify patients who may benefit from CSFD placement.

[Prevention and Treatment of Ischemic Spinal Cord Injury].

In recent years, the widespread use of thoracic/thoracoabdominal stent grafting and a better understanding of spinal cord blood supply have led to quite a few change in measures to prevent spinal cord injury. It is essential to understand the characteristics of spinal cord blood flow, which is complicated by collateral pathways, and to strive to maintain spinal cord blood flow during surgery. It is also important to plan staged repair as much as possible in any treatment modality. Particular attention must be paid to the prevention of second attacks, especially after thoracic/thoracoabdominal endovascular aortic repair without segmental artery reconstruction. Systemic circulatory and respiratory management, improvement of anemia, and cerebrospinal fluid drainage with attention to drainage rates, may be effective as preventive and therapeutic measures for spinal cord injury.

Prospective Assessment of a Protocol Using Neuromonitoring, Early Limb Reperfusion, and Selective Temporary Aneurysm Sac Perfusion to Prevent Spinal Cord Injury During Fenestrated-branched Endovascular Aortic Repair.

OBJECTIVE: The aim of this study was to analyze the outcomes of a standardized protocol using routine CSFD, neuromonitoring, LL reperfusion, and selective TASP to prevent SCI during F-BEVAR. BACKGROUND: SCI is to be the most devastating complication for the patient, family, and surgeon, with impact on patient's quality of life and long-term prognosis. An optimal standardized protocol may be used to improve outcomes. METHODS: Patients enrolled in a prospective, nonrandomized single-center study between 2013 and 2018. A SCI prevention protocol was used for TAAAS or complex abdominal aneurysms with ≥5-cm supraceliac coverage including CSFD, neuromonitoring, LL reperfusion, and selective TASP. Endpoints included mortality and rates of SCI. RESULTS: SCI prevention protocol was used in 170 of 232 patients (73%) treated by F-BEVAR. Ninety-one patients (55%) had changes in neuromonitoring, which improved with maneuvers in all except for 9 patients (10%) who had TASP. There was one 30-day or in-hospital mortality (0.4%). Ten patients (4%) developed SCIs including in 1% (1/79) of patients with normal neuromonitoring and 10% (9/91) of those who had decline in neuromonitoring ( P = 0.02). Permanent paraplegia occurred in 2 patients (1%). Factors associated with SCI included total operating time (odds ratio 1.5, 95% confidence interval 1.1-2.2, P = 0.02) and persistent changes in neuromonitoring requiring TASP (odds ratio 15.7, 95% confidence interval 2.9-86.2, P = 0.001). CONCLUSION: This prospective nonrandomized study using a standardized strategy to prevent SCI was associated with low incidence of the SCI during F-BEVAR. Permanent paraplegia occurred in 1%.

Spinal drainage complications after aortic surgery.

OBJECTIVE/BACKGROUND: Spinal drain (SD) placement is an adjunct used in open and endovascular aortic surgery to mitigate the risk of spinal cord injury. SD placement can lead to subdural hematoma and intracranial hemorrhage (SDH/ICH). Previous studies have highlighted a correlation between incidence of SDH/ICH and amount of cerebrospinal fluid (CSF) drained. We have two philosophies of SD management in our institution. One protocol allows fluid removal for pressure >10 cm H2O with no volume restriction. A second, similar protocol restricts CSF drainage to <25 mL/h. We examined SD complications and the influence of volume restriction. METHODS: Patients were identified according to the Current Procedure Terminology codes for SD placement, thoracic endovascular aortic repair, fenestrated/branched endovascular aortic repair, endovascular abdominal aortic repair, and open thoracic or thoracoabdominal aortic repair between January 1, 2012, and December 31, 2015. Patients' demographics included age, gender, race, body mass index, and comorbidities such as hypertension, chronic obstructive pulmonary disease, stroke, transient ischemic attack, diabetes mellitus, bleeding disorder, and connective tissue disorders. Management protocol was classified as volume independent (VI) or volume dependent (VD) by physician order. Postoperative complications related to the SD were noted. RESULTS: We identified 948 patients who had an SD placed during the study period; 473 were done before aortic surgeries. A total of 364 patients (77%) underwent endovascular aortic surgery. The mean age at the time of procedure was 67.2 years, and 66% of patients were male. Thirty-nine patients (8.3%) were noted to have connective tissue disorders. Bloody SD placement occurred in 14 patients (3.1%) requiring rescheduling of the operation. SDH/ICH occurred in 11 patients (2.3%), postoperative blood tinged SD output in 94 patients (19.9 %), and 22 patients (4.7 %) had a CSF leak after SD removal. The incidence of SDH/ICH was not affected by the management protocol (2.6% VI vs 2.0% VD, P = .66), whereas the incidence of postoperative blood tinged SD output was significantly higher in the VI group (25.1% VI vs 15.0% VD, P = .006). Perioperative low-dose aspirin (81 mg) and prophylactic subcutaneous heparin did not increase the incidence of SDH/ICH. Postoperative thrombocytopenia was found to be associated with higher incidence of SDH/ICH (median 86,000 vs 113,000, P = .002). CONCLUSIONS: Severe complications of SD placement (SDH/ICH) occur in 2.3% of SD patients undergoing aortic surgery, and the risk is higher in the setting of postoperative thrombocytopenia. SD volume limitation, blood tinged drainage, antiplatelet medication, and low-dose heparin do not affect the risk of SDH/ICH. The risks of spinal drains for aortic surgery should be balanced against potential benefits.

Trends in the use of cerebrospinal drains and outcomes related to spinal cord ischemia after thoracic endovascular aortic repair and complex endovascular aortic repair in the Vascular Quality Initiative database.

BACKGROUND: Spinal cord ischemia (SCI) is a dreaded complication of thoracic and complex endovascular aortic repair (TEVAR/cEVAR). Controversy exists surrounding cerebrospinal fluid drain (CSFD) use, especially preoperative prophylactic placement, owing to concerns regarding catheter-related complications. However, these risks are balanced by the widely accepted benefits of CSFDs during open repair to prevent and/or rescue patients with SCI. The importance of this issue is underscored by the paucity of data on CSFD practice patterns, limiting the development of practice guidelines. Therefore, the purpose of the present analysis was to evaluate the differences between patients who developed SCI despite preoperative CSFD placement and those treated with therapeutic postoperative CSFD placement. METHODS: All elective TEVAR/cEVAR procedures for degenerative aneurysm pathology in the Society for Vascular Surgery Vascular Quality Initiative from 2014 to 2019 were analyzed. CSFD use over time, the factors associated with preoperative prophylactic vs postoperative therapeutic CSFD placement in patients with SCI (transient or permanent), and outcomes were evaluated. Survival differences were estimated using the Kaplan-Meier method. RESULTS: A total of 3406 TEVAR/cEVAR procedures met the inclusion criteria, with an overall SCI rate of 2.3% (n = 88). The SCI rate decreased from 4.55% in 2014 to 1.43% in 2018. Prophylactic preoperative CSFD use was similar over time (2014, 30%; vs 2018, 27%; P = .8). After further exclusions to evaluate CSFD use in those who had developed SCI, 72 patients were available for analysis, 48 with SCI and prophylactic CSFD placement and 24 with SCI and therapeutic CSFD placement. Specific to SCI, the patient demographics and comorbidities were not significantly different between the prophylactic and therapeutic groups, with the exception of previous aortic surgery, which was more common in the prophylactic CSFD cohort (46% vs 23%; P < .001). The SCI outcome was significantly worse for the therapeutic group because 79% had documented permanent paraplegia at discharge compared with 54% of the prophylactic group (P = .04). SCI patients receiving a postoperative therapeutic CSFD had had worse survival than those with a preoperative prophylactic CSFD (50% ± 10% vs 71% ± 9%; log-rank P = .1; Wilcoxon P = .05). CONCLUSIONS: Prophylactic CSFD use with TEVAR/cEVAR remained stable during the study period. Of the SCI patients, postoperative therapeutic CSFD placement was associated with worse sustained neurologic outcomes and overall survival compared with preoperative prophylactic CSFD placement. These findings highlight the need for a randomized clinical trial to examine prophylactic vs therapeutic CSFD placement in association with TEVAR/cEVAR.

Risk factors for spinal cord injury and complications of cerebrospinal fluid drainage in patients undergoing fenestrated and branched endovascular aneurysm repair.

OBJECTIVE: Spinal cord injury (SCI) is one of the most devastating complications of thoracoabdominal aortic aneurysm (TAAA) repair. Cerebrospinal fluid drainage (CSFD) is routinely used to prevent and to treat SCI during open TAAA repair. However, the risks and benefits of CSFD during fenestrated-branched endovascular aneurysm repair (F/B-EVAR) are unclear. This study aimed to determine the risk of SCI after F/B-EVAR and to assess the risks and benefits of CSFD. METHODS: We analyzed 106 consecutive patients with TAAAs treated with F/B-EVAR from 2014 to 2019 in a prospective physician-sponsored investigational device exemption study (G130193). Data were collected prospectively and audited by an independent external monitor. All patients were treated with Cook manufactured patient-specific F/B-EVAR devices or the Cook t-Branch devices (Cook Medical, Bloomington, Ind). CSFD was used at the discretion of the principal investigator. Risk factors for SCI were identified, and CSFD complications were assessed. RESULTS: Prophylactic CSFD was used in 78 patients (73.6%), and 28 patients (26.4%) underwent F/B-EVAR without CSFD. Four patients (3.8%) with prophylactic CSFD developed SCI, including two patients (1.9%) with permanent paraplegia (Tarlov grade 1-2) and two patients (1.9%) with paraparesis (Tarlov grade 3). Multivariate analysis revealed that greater extent of thoracic aortic coverage (odds ratio, 1.06; 95% confidence interval, 1.00-1.11; P = .02) and intraoperative blood loss (odds ratio, 1.00; 95% confidence interval, 1.00-1.002; P = .04) were the significant risk factors for SCI. Six patients (7.6% [6/78]) experienced major CSFD-related complications, including subarachnoid hemorrhage in 2.6% (2), spinal hematoma in 2.6% (2), cerebellar hemorrhage in 1.3% (1), and spinal drain fracture requiring surgical laminectomy in 1.3% (1). Minor CSFD-related complications occurred in 20 patients (25.6% [20/78]), including paresthesia during CSFD insertion (10), minimal bloody cerebrospinal fluid (7), drain malfunction (2), and reflex hypotension (1). Technical difficulties during CSFD catheter placement were noted in seven patients (9.0%). Excluding four patients with SCI, intensive care unit stay was 3.3 ± 4.0 days in the CSFD group vs 1.2 ± 0.9 days in the no-CSFD group (P = .007). Total hospital length of stay was 6.0 ± 4.9 days in the CSFD group vs 3.5 ± 1.9 days in the no-CSFD group (P = .01). CONCLUSIONS: The incidence of SCI after F/B-EVAR with selective CSFD was low, and risk factors for SCI were greater with extent of thoracic aortic coverage and intraoperative blood loss. However, the incidence of major CSFD-related complications exceeded the incidence of SCI, and CSFD significantly increased both intensive care unit and total hospital length of stay. Therefore, routine prophylactic CSFD may not be justified, and a prospective randomized trial of CSFD in patients undergoing F/B-EVAR seems appropriate.

Ketone Metabolite ß-Hydroxybutyrate Ameliorates Inflammation After Spinal Cord Injury by Inhibiting the NLRP3 Inflammasome.

Ketogenic diet (KD) has been shown to be beneficial in a range of neurological disorders, with ketone metabolite ß-hydroxybutyrate (ßOHB) reported to block the nucleotide oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome in bone marrow-derived macrophages. In this study, we show that pretreatment with KD or in situ ßOHB suppressed macrophages/microglia activation and the overproduction of inflammatory cytokines, while KD downregulated the expression of NLRP3 inflammasome. Moreover, KD promoted macrophages/microglia transformation from the M1 phenotype to the M2a phenotype following spinal cord injury (SCI) in the in vivo study. Rats in the KD group demonstrated improved behavioral and electrophysiological recovery after SCI when compared to those rats in the standard diet group. The in vitro study performed on BV2 cells indicated that ßOHB inhibited an LPS+ATP-induced inflammatory response and decreased NLRP3 protein levels. Our data demonstrated that pretreatment with KD attenuated neuroinflammation following SCI, probably by inhibiting NLRP3 inflammasome and shifting the activation state of macrophages/microglia from the M1 to the M2a phenotype. Therefore, the ketone metabolite ßOHB might provide a potential future therapeutic strategy for SCI.

Intubation Biomechanics: Clinical Implications of Computational Modeling of Intervertebral Motion and Spinal Cord Strain during Tracheal Intubation in an Intact Cervical Spine.

BACKGROUND: In a closed claims study, most patients experiencing cervical spinal cord injury had stable cervical spines. This raises two questions. First, in the presence of an intact (stable) cervical spine, are there tracheal intubation conditions in which cervical intervertebral motions exceed physiologically normal maximum values? Second, with an intact spine, are there tracheal intubation conditions in which potentially injurious cervical cord strains can occur? METHODS: This study utilized a computational model of the cervical spine and cord to predict intervertebral motions (rotation, translation) and cord strains (stretch, compression). Routine (Macintosh) intubation force conditions were defined by a specific application location (mid-C3 vertebral body), magnitude (48.8 N), and direction (70 degrees). A total of 48 intubation conditions were modeled: all combinations of 4 force locations (cephalad and caudad of routine), 4 magnitudes (50 to 200% of routine), and 3 directions (50, 70, and 90 degrees). Modeled maximum intervertebral motions were compared to motions reported in previous clinical studies of the range of voluntary cervical motion. Modeled peak cord strains were compared to potential strain injury thresholds. RESULTS: Modeled maximum intervertebral motions occurred with maximum force magnitude (97.6 N) and did not differ from physiologically normal maximum motion values. Peak tensile cord strains (stretch) did not exceed the potential injury threshold (0.14) in any of the 48 force conditions. Peak compressive strains exceeded the potential injury threshold (-0.20) in 3 of 48 conditions, all with maximum force magnitude applied in a nonroutine location. CONCLUSIONS: With an intact cervical spine, even with application of twice the routine value of force magnitude, intervertebral motions during intubation did not exceed physiologically normal maximum values. However, under nonroutine high-force conditions, compressive strains exceeded potentially injurious values. In patients whose cords have less than normal tolerance to acute strain, compressive strains occurring with routine intubation forces may reach potentially injurious values.

Design and development of 1,3,5-triazine derivatives as protective agent against spinal cord injury in rat via inhibition of NF-ĸB.

Spinal cord injury (SCI) is a chronic disease causing motor and sensory loss in the affected individuals. The SCI has a huge impact on the lives of patients that makes them susceptible to life-long disability. However, the current clinical modalities are ineffective to cope the aftermath of SCI. Thus, in the present study, we aimed to develop a series of 1,3,5-triazine derivatives as a protective agent against SCI. The molecules were developed by facile synthetic route and obtained in excellent yield. The compounds were tested for their efficacy to inhibit the transcription of NF-κB in RAW 264.7 cells, where they displayed mild to potent activity. Compound 8a was identified as most potent NF-κB inhibitor among the tested analogues. The effect of compound 8a was further scrutinized against the SCI injury in rats induced by contusion injury. It has been found that compound 8a improves motor function of rats together with reduction in inflammation and edema in spinal cord of rats. It also showed to inhibit oxidative stress and inflammation in the SCI rats. In a western blot analysis, after SCI induction, compound 8a inhibited NF-κB and its upstream regulator TLR4 in a dose-dependent manner. Collectively, our study provides a novel class of agent that provide protective action against SCI.

The effect of the perfluorocarbon emulsion Oxycyte™ in an ovine model of severe decompression illness.

Background: The treatment of decompression sickness (DCS) with hyperbaric oxygen (HBO2) serves to decrease intravascular bubble size, increase oxygen (O2) delivery to tissue and enhance the elimination of inert gas. Emulsified perfluorocarbons (PFC) combined with breathing O2 have been shown to have similar effects animal models. We studied an ovine model of severe DCS treated with the intravenous PFC Oxycyte™ while breathing O2 compared to saline control also breathing O2. Methods: Juvenile male sheep (N=67; weight 24.4±2.10kg) were compressed to 257 feet of sea water (fsw) in our multiple large-animal chamber where they remained under pressure for 31 minutes. Animals then were decompressed to surface pressure and randomized to receive either Oxycyte at 5mL/kg intravenously (IV) or 5mL/kg saline IV (both receiving 100% O2) 10 minutes after reaching surface pressure. Mortality was recorded at two hours, four hours, and 24 hours after receiving the study drug. Surviving animals underwent perfusion fixation and harvesting of the spinal cord at 24 hours. Spinal cord sections were assessed for volume of lesion area and compared. Results: There was no significant difference in survival at two hours (p=0.2737), four hours (p=0.2101), or 24 hours (p=0.3171). Paralysis at 24 hours was not significantly different. However, spinal cord lesion area was significantly smaller in the Oxycyte group as compared to the saline group, with median spinal cord lesion areas 0.65% vs. 0.94% (p=0.0107). Conclusion: In this ovine model of severe DCS the intravenous PFC Oxycyte did not reduce mortality but did ameliorate spinal cord injury when used after the onset of DCS.

Cerebrospinal fluid drainage to prevent postoperative spinal cord injury in thoracic aortic repair.

BACKGROUND: Cerebrospinal fluid drainage (CSFD) is recommended as a spinal cord protective strategy in open and endovascular thoracic aortic repair. Although small studies support the use of CSFD, systematic reviews have not suggested definite conclusion and a large-scale study is needed. Therefore, we reviewed medical records of patients who had undergone descending and thoracoabdominal aortic repair (both open and endovascular repair) at multiple institutions to assess the association between CSFD and postoperative motor deficits. METHODS: Patients included in this study underwent descending or thoracoabdominal aortic repair between 2000 and 2013 at 12 hospitals belonging to the Japanese Association of Spinal Cord Protection in Aortic Surgery. We conducted a retrospective study to investigate whether motor-evoked potential monitoring is effective in reducing motor deficits in thoracic aortic aneurysm repair. We use the same dataset to examine whether CSFD reduces motor deficits after propensity score matching. RESULTS: We reviewed data from 1214 patients [open surgery, 601 (49.5%); endovascular repair, 613 (50.5%)]. CSFD was performed in 417 patients and not performed in the remaining 797 patients. Postoperative motor deficits were observed in 75 (6.2%) patients at discharge. After propensity score matching (n = 700), mixed-effects logistic regression performed revealed that CSFD is associated with postoperative motor deficits at discharge [adjusted odds ratio (OR), 3.87; 95% confidence interval (CI), 2.30-6.51]. CONCLUSION: CSFD may not be effective for postoperative motor deficits at discharge.

Inhibiting HMGB1-RAGE axis prevents pro-inflammatory macrophages/microglia polarization and affords neuroprotection after spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) favors a persistent pro-inflammatory macrophages/microglia-mediated response with only a transient appearance of anti-inflammatory phenotype of immune cells. However, the mechanisms controlling this special sterile inflammation after SCI are still not fully elucidated. It is known that damage-associated molecular patterns (DAMPs) released from necrotic cells after injury can trigger severe inflammation. High mobility group box 1(HMGB1), a ubiquitously expressed DNA binding protein, is an identified DAMP, and our previous study demonstrated that reactive astrocytes could undergo necroptosis and release HMGB1 after SCI in mice. The present study aimed to explore the effects and the possible mechanism of HMGB1on macrophages/microglia polarization, as well as the neuroprotective effects by HMGB1 inhibition after SCI. METHODS: In this study, the expression and the concentration of HMGB1 was determined by qRT-PCR, ELISA, and immunohistochemistry. Glycyrrhizin was applied to inhibit HMGB1, while FPS-ZM1 to suppress receptor for advanced glycation end products (RAGE). The polarization of macrophages/microglia in vitro and in vivo was detected by qRT-PCR, immunostaining, and western blot. The lesion area was detected by GFAP staining, while neuronal survival was examined by Nissl staining. Luxol fast blue (LFB) staining, DAB staining, and western blot were adopted to evaluate the myelin loss. Basso-Beattie-Bresnahan (BBB) scoring and rump-height Index (RHI) assay was applied to evaluate locomotor functional recovery. RESULTS: Our data showed that HMGB1 can be elevated and released from necroptotic astrocytes and HMGB1 could induce pro-inflammatory microglia through the RAGE-nuclear factor-kappa B (NF-κB) pathway. We further demonstrated that inhibiting HMGB1 or RAGE effectively decreased the numbers of detrimental pro-inflammatory macrophages/microglia while increased anti-inflammatory cells after SCI. Furthermore, our data showed that inhibiting HMGB1 or RAGE significantly decreased neuronal loss and demyelination, and improved functional recovery after SCI. CONCLUSIONS: The data implicated that HMGB1-RAGE axis contributed to the dominant pro-inflammatory macrophages/microglia-mediated pro-inflammatory response, and inhibiting this pathway afforded neuroprotection for SCI. Thus, therapies designed to modulate immune microenvironment based on this cascade might be a prospective treatment for SCI.

The green tea polyphenolic catechin epigallocatechin gallate and neuroprotection.

Epigallocatechin gallate is the most abundant composition of the tea catechins and is thought to be responsible for the majority of biological activity of green tea extracts such as antioxidant, anti-inflammatory, and antiapoptotic effects. Meanwhile, EGCG has been shown to be some of the neuroprotective effects against neural injuries and neurodegenerative diseases. This paper summarizes current knowledge on neuroprotective effects of EGCG and their molecular mechanisms responsible for the neuroprotection in various models of neurodegenerative and neural injury.

Spinal needle size and traumatic neonatal lumbar puncture: an observational study (neo-LP).

The incidence of 'traumatic' lumbar puncture (LP; CSF red cells > 500/mm) has been reported to be 35-46% in the neonatal period. A traumatic LP incurs challenges in diagnosis and management of the underlying condition and increases the risk of complications. We aimed to assess the benefits of a smaller outer diameter, larger gauge 25G needle in reducing the incidence of traumatic LPs compared with the standard 22G LP needle. This prospective observational study compared data from two consecutive epochs. Epoch 1 (Control, April 2016-October 2016), 22G needle for LP as standard practice. Epoch 2 (Intervention, November 2016-October 2017) 25G needle used for LP. Primary outcome was the incidence of traumatic LP. Multiple logistic regression analyses were conducted adjusting for corrected gestational age (CGA) at LP, proceduralist experience and need for ventilation as an indicator of illness. There were 240 LPs during the study period involving 361 attempts (22G, n = 228; 25G, n = 133). Median gestation at birth (P = 0.617) and CGA at LP (P = 0.163) were comparable. Multivariate analysis revealed lower incidence of traumatic LP using 25G needle (P < 0.001). Incidence of obtaining a successful CSF sample was similar between groups (P = 0.944). Proceduralist experience (P = 0.189) and neonatal illness (P = 0.801) were not significant factors.Conclusion: Our results showed that traumatic LPs were ~ 50% less common with 25G vs 22G needles while retaining a comparable success rate. Dry taps were more likely among the 25G group.What is Known:• The incidence of neonatal 'traumatic' lumbar puncture (CSF red cells > 500/mm) has been reported to be 35-46%.• A traumatic lumbar puncture incurs challenges in diagnosis and management of the underlying condition and increases the risk of complications.What is New:• Multivariate analysis revealed lower incidence of traumatic lumbar puncture using 25G needle (vs 22G).• Incidence of obtaining a successful CSF sample was similar between groups.

Protective effect of Oxymatrine against acute spinal cord injury in rats via modulating oxidative stress, inflammation and apoptosis.

The present study was performed to examine the effect of oxymatrine (OMT) on motor functions and histopathologic changes after spinal cord injury and the mechanism underlying its neuroprotective effects. Results suggested that, OMT causes regain of lost motor function near to normal via attenuating oxidative stress, inflammatory response and cellular apoptosis. These observations were further supported by histological examination of spinal cord of rats. It also showed to regulate pro-inflammatory cytokines, Bcl2 family proteins and reduces the level of toll like receptor (TLR-4) and nuclear factor-kappa B (NF-ĸB) in concentration dependent manner. The mitogen-activated protein kinase (MAPK) pathway was also regulated by OMT after SCI. It has been suggested that, OMT promotes the recovery of motor function after SCI in rats via multiple mechanism, and this effect may be related to its anti-oxidant, anti-inflammatory and anti-apoptotic effects.