Cerebrospinal Fluid Pressure Dynamics as a Bedside Test in Traumatic Spinal Cord Injury to Assess Surgical Spinal Cord Decompression: Safety, Feasibility, and Proof-of-Concept.

BACKGROUND: Sufficient and timely spinal cord decompression is a critical surgical objective for neurological recovery in spinal cord injury (SCI). Residual cord compression may be associated with disturbed cerebrospinal fluid pressure (CSFP) dynamics. OBJECTIVES: This study aims to assess whether intrathecal CSFP dynamics in SCI following surgical decompression are feasible and safe, and to explore the diagnostic utility. METHODS: Prospective cohort study. Bedside lumbar CSFP dynamics and cervical MRI were obtained following surgical decompression in N = 9 with mostly cervical acute-subacute SCI and N = 2 patients with non-traumatic SCI. CSFP measurements included mean CSFP, cardiac-driven CSFP peak-to-valley amplitudes (CSFPp), Valsalva maneuver, and Queckenstedt's test (firm pressure on jugular veins, QT). From QT, proxies for cerebrospinal fluid pulsatility curve were calculated (ie, relative pulse pressure coefficient; RPPC-Q). CSFP metrics were compared to spine-healthy patients. computer tomography (CT)-myelography was done in 3/8 simultaneous to CSFP measurements. RESULTS: Mean age was 45 ± 9 years (range 17-67; 3F), SCI was complete (AIS A, N = 5) or incomplete (AIS B-D, N = 6). No adverse events related to CSFP assessments. CSFP rise during QT was induced in all patients [range 9.6-26.6 mmHg]. However, CSFPp was reduced in 3/11 (0.1-0.3 mmHg), and in 3/11 RPPC-Q was abnormal (0.01-0.05). Valsalva response was reduced in 8/11 (2.6-23.4 mmHg). CSFP dynamics corresponded to CT-myelography. CONCLUSIONS: Comprehensive bedside lumbar CSFP dynamics in SCI following decompression are safe, feasible, and can reveal distinct patterns of residual spinal cord compression. Longitudinal studies are required to define critical thresholds of impaired CSFP dynamics that may impact neurological recovery and requiring surgical revisions.

Glial fibrillary acidic protein is a robust biomarker in cerebrospinal fluid and peripheral blood after traumatic spinal cord injury: a prospective pilot study.

PURPOSE: Biochemical biomarkers to determine the injury severity and the potential for functional recovery of traumatic spinal cord injury (TSCI) are highly warranted; however, it remains to be clarified whether cerebrospinal fluid (CSF) or peripheral blood (PB) is the ideal sample media. This study aims to measure and compare biomarker concentrations in CSF and PB and to explore associations between biomarker concentrations and injury severity, i.e., American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade, and biomarker concentrations and clinical outcome, i.e., AIS grade improvement and Spinal Cord Independent Measure version III (SCIM-III) score. METHODS: From 2018 to 2020, we conducted a single-center prospective pilot study of TSCI patients (n=15) and healthy controls (n=15). Sample collection and clinical outcome assessment were performed at median 13 h [IQR: 19], 9 days [IQR: 2], and 148 days [IQR: 49] after TSCI. Concentrations of neuron-specific enolase (NSE); glial fibrillary acid protein (GFAP); neurofilament light chain (NfL); interferon-γ (IFN-γ); interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, and IL-13; and tumor necrosis factor α (TNF-α) were measured and associated to clinical outcomes. RESULTS: The biomarker concentrations were higher in CSF than PB. CSF concentrations of GFAP, NSE, IFN-y, TNF-a, IL-2, IL-12p70, IL-4, IL-10, and IL-13 and PB concentrations of GFAP and IFN-y were significantly associated with AIS grade, but not with AIS grade improvement or SCIM-III score. CONCLUSIONS: Our results support GFAP as a potential diagnostic biomarker that may be measured in CSF as well as PB.

Evaluation of the involvement of Th17-cells in the pathogenesis of canine spinal cord injury.

Intervertebral disc herniation (IVDH) is a frequently occurring neurological disease of dogs and the most common reason for spinal cord injury (SCI). Clinical signs are variable thus a reliable prognosis is crucial for further treatment decisions. Currently, the prognosis of IVDH primarily depends on presence or absence of deep pain perception. The purpose of this study was to investigate if Th17-cells could serve as a potential, prognostic biomarker for IVDH. We investigated a possible role of the adaptive immune system in the pathophysiology of IVDH in dogs. The investigation was performed by analyzing the influence of Th17-cells in blood and cerebrospinal fluid (CSF) of sixty-two dogs suffering from IVDH. In addition, we examined if Th17-cells might influence the course of this disease. As controls, paired blood and CSF samples of ten healthy clinic-owned dogs were examined and the values were compared to those of the IVDH group. Isolated lymphocytes were analyzed after stimulation by using multicolour flow cytometry to measure the number of Th17-cells. IL-17 levels were measured in paired serum and CSF samples by Enzyme-linked Immunosorbent Assays (ELISA). Highly significant differences of stimulated Th17-cells in EDTA-blood samples could be determined between Th17-cell levels of dogs suffering from IVDH and the healthy control group and also between three sampling time points: preoperative, after clinical improvement and after six months. Preoperatively, Th17-cell levels were strongly decreased in contrast to the healthy controls. The decreased amount of Th17-cell levels recovered postoperatively so that Th17-cell levels of the last follow-up examinations were comparable to the control group after six months. At the same time IL-17 measured in serum preoperatively was significantly higher in dogs with IVDH than in healthy controls. However, there was no considerable difference of IL-17 measured in CSF between the groups. In conclusion, a high activity and consequent consumption of IL-17-producing Th17-cells is suspected in acute IVDH. These findings may indicate an involvement of Th17-cells in the pathogenesis of IVDH and emphasize that these cells might be involved in the interaction of pain, stress and immune reaction. However, based on the findings of this study the development of Th17-cells as a biomarker cannot be recommended, yet.

Proteomic Portraits Reveal Evolutionarily Conserved and Divergent Responses to Spinal Cord Injury.

Despite the emergence of promising therapeutic approaches in preclinical studies, the failure of large-scale clinical trials leaves clinicians without effective treatments for acute spinal cord injury (SCI). These trials are hindered by their reliance on detailed neurological examinations to establish outcomes, which inflate the time and resources required for completion. Moreover, therapeutic development takes place in animal models whose relevance to human injury remains unclear. Here, we address these challenges through targeted proteomic analyses of cerebrospinal fluid and serum samples from 111 patients with acute SCI and, in parallel, a large animal (porcine) model of SCI. We develop protein biomarkers of injury severity and recovery, including a prognostic model of neurological improvement at 6 months with an area under the receiver operating characteristic curve of 0.91, and validate these in an independent cohort. Through cross-species proteomic analyses, we dissect evolutionarily conserved and divergent aspects of the SCI response and establish the cerebrospinal fluid abundance of glial fibrillary acidic protein as a biochemical outcome measure in both humans and pigs. Our work opens up new avenues to catalyze translation by facilitating the evaluation of novel SCI therapies, while also providing a resource from which to direct future preclinical efforts.

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.

Lumbar Drains for Vascular Procedures: An Institutional Protocol Review and Guidelines.

BACKGROUND: Aortic disease requiring open or endovascular repair may result in spinal cord injury in approximately 2%-10% of patients. Cerebrospinal fluid diversion using lumbar drains (LDs) has been validated as a protective measure to mitigate this complication. METHODS: This single-institution retrospective study analyzed the implementation of a standardized protocol and subsequent educational intervention for LDs for aortic vascular procedures over a 4-year period. RESULTS: In 2016-2019, 45 patients had LDs placed for open or endovascular procedures; group 1 included 19 patients with LDs placed before protocol implementation, and group 2 included 26 patients with LDs placed as per the institutional protocol. Demographics and procedural details in both groups were similar. However, there was a significant difference in the number of patients who had emergent versus planned placement of the LD (group 1, 89.5%; group 2, 50%; P < 0.01), volume of cerebrospinal fluid drained (group 1, 453 mL; group 2, 197 mL; P < 0.01), and compliance with 10 mL/hour drainage recommendation (group 1, 68.4%; group 2, 100%; P < 0.01). In group 1, 5 (31.6%) patients experienced neurological complications compared with only 1 (3.8%) in group 2. LD-related complications occurred 3 patients (15.8%) in group 1, whereas none occurred in group 2. Survey results suggested increased health care worker protocol familiarity with educational interventions. CONCLUSIONS: Implementation of an institutional protocol for LDs for open or endovascular procedures is feasible and beneficial. Educational modules improve familiarity among all health care providers, which can improve patient care and complication avoidance.

Characterization of Cerebrospinal Fluid Ubiquitin C-Terminal Hydrolase L1 as a Biomarker of Human Acute Traumatic Spinal Cord Injury.

A major obstacle for translational research in acute spinal cord injury (SCI) is the lack of biomarkers that can objectively stratify injury severity and predict outcome. Ubiquitin C-terminal hydrolase L1 (UCH-L1) is a neuron-specific enzyme that shows promise as a diagnostic biomarker in traumatic brain injury (TBI), but has not been studied in SCI. In this study, cerebrospinal fluid (CSF) and serum samples were collected over the first 72-96 h post-injury from 32 acute SCI patients who were followed prospectively to determine neurological outcomes at 6 months post-injury. UCH-L1 concentration was measured using the Quanterix Simoa platform (Quanterix, Billerica, MA) and correlated to injury severity, time, and neurological recovery. We found that CSF UCH-L1 was significantly elevated by 10- to 100-fold over laminectomy controls in an injury severity- and time-dependent manner. Twenty-four-hour post-injury CSF UCH-L1 concentrations distinguished between American Spinal Injury Association Impairment Scale (AIS) A and AIS B, and AIS A and AIS C patients in the acute setting, and predicted who would remain "motor complete" (AIS A/B) at 6 months with a sensitivity of 100% and a specificity of 86%. AIS A patients who did not improve their AIS grade at 6 months post-injury were characterized by sustained elevations in CSF UCH-L1 up to 96 h. Similarly, the failure to gain >8 points on the total motor score at 6 months post-injury was associated with higher 24-h CSF UCH-L1. Unfortunately, serum UCH-L1 levels were not informative about injury severity or outcome. In conclusion, CSF UCH-L1 in acute SCI shows promise as a biomarker to reflect injury severity and predict outcome.

Early CSF Biomarkers and Late Functional Outcomes in Spinal Cord Injury. A Pilot Study.

Although, biomarkers are regarded as an important tool for monitoring injury severity and treatment efficacy, and for predicting clinical evolution in many neurological diseases and disorders including spinal cord injury, there is still a lack of reliable biomarkers for the assessment of clinical course and patient outcome. In this study, a biological dataset of 60 cytokines/chemokines, growth factorsm and intracellular and extracellular matrix proteins, analyzed in CSF within 24 h of injury, was used for correlation analysis with the clinical dataset of the same patients. A heat map was generated of positive and negative correlations between biomarkers and clinical rating scale scores at discharge, and between biomarkers and changes in clinical scores during the observation period. Using very stringent statistical criteria, we found 10 molecules which correlated with clinical scores at discharge, and five molecules, which correlated with changes in clinical scores. The proposed methodology may be useful for generating hypotheses regarding "predictive" and "treatment effectiveness" biomarkers, thereby suggesting potential candidates for disease-modifying therapies using a "bed-to-bench" approach.

Cerebrospinal fluid levels of GFAP and pNF-H are elevated in patients with chronic spinal cord injury and neurological deterioration.

BACKGROUND: Years after a traumatic spinal cord injury (SCI), a subset of patients may develop progressive clinical deterioration due to intradural scar formation and spinal cord tethering, with or without an associated syringomyelia. Meningitis, intradural hemorrhages, or intradural tumor surgery may also trigger glial scar formation and spinal cord tethering, leading to neurological worsening. Surgery is the treatment of choice in these chronic SCI patients. OBJECTIVE: We hypothesized that cerebrospinal fluid (CSF) and plasma biomarkers could track ongoing neuronal loss and scar formation in patients with spinal cord tethering and are associated with clinical symptoms. METHODS: We prospectively enrolled 12 patients with spinal cord tethering and measured glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1 (UCH-L1), and phosphorylated Neurofilament-heavy (pNF-H) in CSF and blood. Seven patients with benign lumbar intradural tumors and 7 patients with cervical radiculopathy without spinal cord involvement served as controls. RESULTS: All evaluated biomarker levels were markedly higher in CSF than in plasma, without any correlation between the two compartments. When compared with radiculopathy controls, CSF GFAP and pNF-H levels were higher in patients with spinal cord tethering (p ≤ 0.05). In contrast, CSF UCH-L1 levels were not altered in chronic SCI patients when compared with either control groups. CONCLUSIONS: The present findings suggest that in patients with spinal cord tethering, CSF GFAP and pNF-H levels might reflect ongoing scar formation and neuronal injury potentially responsible for progressive neurological deterioration.

Acute Spinal Cord Injury: Monitoring Lumbar Cerebrospinal Fluid Provides Limited Information about the Injury Site.

In some centers, monitoring lumbar cerebrospinal fluid (CSF) is used to guide management of patients with acute traumatic spinal cord injuries (TSCI) and draining lumbar CSF to improve spinal cord perfusion. Here, we investigate whether the lumbar CSF provides accurate information about the injury site and the effect of draining lumbar CSF on injury site perfusion. In 13 TSCI patients, we simultaneously monitored lumbar CSF pressure (CSFP) and intraspinal pressure (ISP) from the injury site. Using CSFP or ISP, we computed spinal cord perfusion pressure (SCPP), vascular pressure reactivity index (sPRx) and optimum SCPP (SCPPopt). We also assessed the effect on ISP of draining 10 mL CSF. Metabolites at the injury site were compared with metabolites in the lumbar CSF. We found that ISP was pulsatile, but CSFP had low pulse pressure and was non-pulsatile 21% of the time. There was weak or no correlation between CSFP versus ISP (R = -0.11), SCPP(csf) versus SCPP(ISP) (R = 0.39), and sPRx(csf) versus sPRx(ISP) (R = 0.45). CSF drainage caused no significant change in ISP in 7/12 patients and a significant drop of <5 mm Hg in 4/12 patients and of ∼8 mm Hg in 1/12 patients. Metabolite concentrations in the CSF versus the injury site did not correlate for lactate (R = 0.00), pyruvate (R = -0.12) or lactate-to-pyruvate ratio (R = -0.05) with weak correlations noted for glucose (R = 0.31), glutamate (R = 0.61), and glycerol (R = 0.56). We conclude that, after a severe TSCI, monitoring from the lumbar CSF provides only limited information about the injury site and that lumbar CSF drainage does not effectively reduce ISP in most patients.

Biomarkers in Traumatic Spinal Cord Injury-Technical and Clinical Considerations: A Systematic Review.

Objective. To examine (1) if serological or cerebrospinal fluid (CSF) biomarkers can be used as diagnostic and/or prognostic tools in patients with spinal cord injury (SCI) and (2) if literature provides recommendations regarding timing and source of biomarker evaluation. Data Sources. A systematic literature search to identify studies reporting on diagnostic and prognostic blood and/or CSF biomarkers in SCI was conducted in PubMed/MEDLINE, CINAHL, Science Direct, The Cochrane Library, ISI Web of Science, and PEDro. Study Selection. Clinical trials, cohort, and pilot studies on patients with traumatic SCI investigating at least one blood or CSF biomarker were included. Following systematic screening, 19 articles were included in the final analysis. PRISMA guidelines were followed to conduct this review. Data Extraction. Independent extraction of articles was completed by 2 authors using predefined inclusion criteria and study quality indicators. Data Synthesis. Nineteen studies published between 2002 and April 2019 with 1596 patients were included in the systematic review. In 14 studies, blood biomarkers were measured, 4 studies investigated CSF biomarkers, and 1 study used both blood and CSF samples. Conclusions. Serum/CSF concentrations of several biomarkers (S100b, IL-6, GFAP, NSE, tau, TNF-α, IL-8, MCP-1, pNF-H, and IP-10) following SCI are highly time dependent and related to injury severity. Future studies need to validate these markers as true biomarkers and should control for secondary complications associated with SCI. A deeper understanding of secondary pathophysiological events after SCI and their effect on biomarker dynamics may improve their clinical significance as surrogate parameters in future clinical studies.

Possible Strategies to Optimize a Biomarker Discovery Approach to Correlate with Neurological Outcome in Patients with Spinal Cord Injury: A Pilot Study.

The lack of reliable diagnostic and prognostic markers for spinal cord injured (SCI) patients is a severe obstacle in development and testing of new therapies, and it also impairs appropriate rehabilitation care. The sparse available data on the biochemical composition of cerebrospinal fluid (CSF) during the acute and/or chronic phase of the lesion provide, up until now, inconsistent results. In this pilot study, we then explored the possibility of combining a multi-parametric and bioinformatic analysis of CSF for its biological properties tested on different cells types, suitable for investigating inflammation and re-myelination. The patient enrollment was based on stringent inclusion criteria; that is, cervical and thoracic SCI trauma, CSF collection within 24 h of trauma, type of surgical approach for spine stabilization, and absence of steroid therapy before CSF collection. Eleven SCI patients and four healthy controls were included, and in three patients, CSF was also collected at 3 months after lesion. We identified 19 proteins among the 60 investigated cytokines, chemokines, growth factors, and structural biomarkers, which are transiently regulated 24 h after SCI. A bioinformatic analysis indicated that interleukin (IL)-6 and IL-10 are in the core of the interconnected net of activated proteins. Cell-based experiments indicate that CSF from SCI patients stimulates astroglia derivation from neural precursor cells, and an inverse correlation between IL-8 CSF level and oligodendrocyte precursor cells generated from neural stem cells was also observed. Results from this pilot study suggest that using a combined bioanalytic and biological approach to analyze SCI CSF at different times after injury could be a useful approach for identifying reliable diagnostic and prognostic markers in SCI.

Cerebrospinal Fluid Drainage During Endovascular Aortic Aneurysm Repair: A Systematic Review of the Literature and Treatment Recommendations.

INTRODUCTION: Spinal cord injury (SCI) is a known complication of aortic aneurysm repair. Previous reports indicate that cerebrospinal fluid drainage (CSFD) may reduce incidence of SCI during open aortic aneurysm repair but its utility in endovascular repair remains poorly understood. We performed a systematic review of the literature to examine the protocols and outcomes of CSFD in patients undergoing endovascular aortic aneurysm repair. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were utilized to conduct a systematic literature review. PubMed, Scopus, Ovid, Cochrane, and EMBASE were queried for articles published since 2016 using search terms "(cerebrospinal fluid diversion OR CSF diversion OR lumbar drain OR subarachnoid drain OR spinal) AND (aortic aneurysm AND thoracic AND endovascular OR TEVAR)." Ninety-two articles were identified and screened by 2 independent reviewers, and 23 studies met criteria for full-text review after initial screening. RESULTS: A total of 8 studies met full inclusion criteria for final analysis. Six studies reported incidence of SCI in patients with CSFD and 2 compared SCI incidence between patients with and without CSFD. Protocols for drainage most commonly included draining to a target pressure intra- and postoperatively, between 8 and 12 mm Hg. Incidence of SCI ranged from 0% to 17% in patients with CSFD, and from 0% to 50% in those without CSFD. Rates of CSFD-related complications ranged from <1% to 28%. CONCLUSION: There may be a protective benefit of CSFD in preventing SCI, but there remains significant variation in drain placement protocols. Significant potential bias exists in the reviewed data. Higher quality studies on the role of CSFD in endovascular aortic aneurysm repair are needed.

Neurochemical biomarkers in spinal cord injury.

STUDY DESIGN: This is a narrative review of the literature on neurochemical biomarkers in spinal cord injury (SCI). OBJECTIVES: The objective was to summarize the literature on neurochemical biomarkers in SCI and describe their use in facilitating clinical trials for SCI. Clinical trials in spinal cord injury (SCI) have been notoriously difficult to conduct, as exemplified by the paucity of definitive prospective randomized trials that have been completed, to date. This is related to the relatively low incidence and the complexity and heterogeneity of the human SCI condition. Given the increasing number of promising approaches that are emerging from the laboratory which are vying for clinical evaluation, novel strategies to help facilitate clinical trials are needed. METHODS: A literature review was conducted, with a focus on neurochemical biomarkers that have been described in human neurotrauma. RESULTS: We describe advances in our understanding of neurochemical biomarkers as they pertain to human SCI. The application of biomarkers from serum and cerebrospinal fluid (CSF) has been led by efforts in the human traumatic brain injury (TBI) literature. A number of promising biomarkers have been described in human SCI whereby they may assist in stratifying injury severity and predicting outcome. CONCLUSIONS: Several time-specific biomarkers have been described for acute SCI and for chronic SCI. These appear promising for stratifying injury severity and potentially predicting outcome. The subsequent application within a clinical trial will help to demonstrate their utility in facilitating the study of novel approaches for SCI.

Froin Syndrome After Spinal Cord Injury.

BACKGROUND: Froin syndrome is characterized by xanthochromia and hypercoagulability of the cerebrospinal fluid (CSF) due to elevated protein levels. This entity results from blockage of the spinal canal by a mass lesion leading to an isolated caudal CSF space. CASE DESCRIPTION: A 48-year-old male, who developed spasticity after a C6 spinal cord injury (SCI) 20 years earlier, presented with subobstruction of his intrathecal baclofen pump. A catheter access port aspiration revealed an extremely high protein concentration (38 g/L) with no signs of infection. Froin syndrome was confirmed when magnetic resonance imaging showed a complete obstruction of the spinal canal at the SCI level. CONCLUSIONS: We report the first case of Froin syndrome after SCI. Froin syndrome can impact intrathecal drug delivery and CSF diagnostics.

Mass Accuracy Check Using Common Background Peaks for Improving Metabolome Data Quality in Chemical Isotope Labeling LC-MS.

Chemical isotope labeling (CIL) LC-MS is a highly sensitive and quantitative method for metabolome analysis. Because of a large number of peaks detectable in a sample and the need of running many samples in a metabolomics project, any significant change in mass measurement accuracy during the whole period of running samples can adversely affect the downstream peak alignment and quantitative analysis. Herein, we report a rapid method to check the mass accuracy of individual spectra in each CIL LC-MS run in order to flag up any run containing spectra with accuracy drift that falls outside the expected error. The flagged run may be re-run or discarded before merging with other runs for peak alignment and analysis. This method is based on the observation that some background signals are commonly detected in almost all spectra collected in CIL LC-MS runs. A mass accuracy check (MAC) software program has been developed to first find the common background mass peaks and then use them as mass references to calculate any mass shifts over the course of multiple sample runs. Using a metabolome dataset of 324 human cerebrospinal fluid (CSF) samples and 35 quality control (QC) samples produced by CIL LC-MS, we show that this accuracy check method can streamline the initial raw data processing for downstream analysis in metabolomics.

MicroRNA Biomarkers in Cerebrospinal Fluid and Serum Reflect Injury Severity in Human Acute Traumatic Spinal Cord Injury.

Spinal cord injury (SCI) is a devastating condition with variability in injury mechanisms and neurologic recovery. Spinal cord impairment after SCI is measured and classified by a widely accepted standard neurological examination. In the very acute stages post-injury, however, this examination is extremely challenging (and often impossible) to conduct and has modest prognostic value in terms of neurological recovery. The lack of objective tools to classify injury severity and predict outcome is a barrier for clinical trials and thwarts development of therapies for those with SCI. Biological markers (biomarkers) represent a promising, complementary approach to these challenges because they represent an unbiased approach to classify injury severity and predict neurological outcome. Identification of a suitable panel of molecular biomarkers would comprise a fundamental shift in how patients with acute SCI are evaluated, stratified, and treated in clinical trials. MicroRNA are attractive biomarker candidates in neurological disorders for several reasons, including their stability in biological fluids, their conservation between humans and model mammals, and their tissue specificity. In this study, we used next-generation sequencing to identify microRNA associated with injury severity within the cerebrospinal fluid (CSF) and serum of human patients with acute SCI. The CSF and serum samples were obtained 1-5 days post-injury from 39 patients with acute SCI (24 American Spinal Injury Association Impairment Scale [AIS] A, 8 AIS B, 7 AIS C) and from five non-SCI controls. We identified a severity-dependent pattern of change in microRNA expression in CSF and identified a set of microRNA that are diagnostic of baseline AIS classification and prognostic of neurological outcome six months post-injury. The data presented here provide a comprehensive description of the CSF and serum microRNA expression changes that occur after acute human SCI. This data set reveals microRNA candidates that warrant further evaluation as biomarkers of injury severity after SCI and as key regulators in other neurological disorders.

Potential diagnostic and prognostic value of serum and cerebrospinal fluid biomarkers in traumatic spinal cord injury: A systematic review.

It remains unclear whether biomarkers in the serum or CSF can be used for diagnosis or prognosis of spinal cord injuries (SCI). Therefore, a systematic review was undertaken to evaluate the prognostic or diagnostic value of serum and CSF biomarkers in assessing the severity of SCI and the outcome of patients. Two independent reviewers summarized the human studies retrieved from the electronic databases of Medline, Embase, Scopus and ISI Web of Science until April 2018. Seventeen studies were included (1065 patients aged 16-94 years old). Although the findings of the included studies suggest that inflammatory and structural proteins may be useful in assessing the severity of SCI and prediction of neurological outcome, the level of evidence is generally low. Given limitations to the available evidence, further investigation in this field is required using large prospective data sets with rigorous analysis of sensitivity, specificity and prediction.

Protein Profiling in Serum and Cerebrospinal Fluid Following Complex Surgery on the Thoracic Aorta Identifies Biological Markers of Neurologic Injury.

Surgery on the arch or descending aorta is associated with significant risk of neurological complications. As a consequence of intubation and sedation, early neurologic injury may remain unnoticed. Biomarkers to aid in the initial diagnostics could prove of great value as immediate intervention is critical. Twenty-three patients operated in the thoracic aorta with significant risk of perioperative neurological injury were included. Cerebrospinal fluid (CSF) and serum were obtained preoperatively and in the first and second postoperative days and assessed with a panel of 92 neurological-related proteins. Three patients suffered spinal cord injury (SCI), eight delirium, and nine hallucinations. There were markers in both serum and CSF that differed between the affected and non-affected patients (SCI; IL6, GFAP, CSPG4, delirium; TR4, EZH2, hallucinations; NF1). The study identifies markers in serum and CSF that reflect the occurrence of neurologic insults following aortic surgery, which may aid in the care of these patients.