Risk factors for postoperative urinary retention after deep brain stimulation surgery: the role of the subthalamic nucleus.

OBJECTIVE: Deep brain stimulation (DBS) is a common procedure in neurosurgery used for the treatment of Parkinson's disease (PD) and essential tremor (ET) among other disorders. Lower urinary tract dysfunction is a common complication in PD, and this study aimed to evaluate the risk factors of postoperative urinary retention (POUR) after DBS surgery in patients with PD compared with patients with ET. Understanding the risk factors associated with this complication may help in the development of strategies to minimize its occurrence and improve patient outcomes. METHODS: The study was a retrospective analysis of patients who underwent DBS surgery for PD and ET at the University of Florida between 2010 and 2021. The surgical technique used has been described in previous articles and included a two-stage procedure, with stage 1 involving burr hole placement, microelectrode recording, and electrode implantation and stage 2 involving the placement of an implantable pulse generator (IPG). Data were collected on patient characteristics and surgical details and analyzed using univariate and mixed-linear models. Post hoc propensity score matching was used to confirm the association between subthalamic nucleus (STN)-DBS and POUR. RESULTS: The study included 350 patients (153 with PD and 197 with ET) who underwent 1086 DBS surgeries (lead implantations, IPG placement, and IPG replacements). The POUR rates were 16.6% (79/477), 5.2% (19/363), and 0.4% (1/246) for stage 1, stage 2, and IPG replacement procedures, respectively. Optimal mixed-effects logistic modeling revealed history of urinary retention (OR 9.3, p = 0.004), male sex (OR 2.7, p = 0.011), having an electrode placed or connected for the first time (OR 2.2, p = 0.014), anesthesia time (OR 1.5 for each 30-minute increase, p < 0.0001), preoperative opioid use (OR 1.4 for each additional 10 morphine milligram equivalents, p = 0.032), and Charlson Comorbidity Index (OR 1.4 per comorbidity, p = 0.017) to be significant risk factors for POUR. Having an electrode in the STN was found to be protective of POUR (propensity score-matched analysis: OR 0.2, p = 0.010). CONCLUSIONS: Most risk factors found to increase the risk of POUR in DBS are not modifiable but are still important to consider in preoperative planning. Opioid use reduction and shorter anesthesia time may be modifiable risk factors to weigh against their alternative. Targeting the STN during DBS may result in decreased rates of POUR. This highlights the potential for STN-targeted DBS in reducing POUR risk in PD and ET patients.

Pre-operative prediction of post-operative urinary retention in lumbar surgery: a prospective validation of machine learning model.

PURPOSE: Predicting urinary retention is difficult. The aim of this study is to prospectively validate a previously developed model using machine learning techniques. METHODS: Patients were recruited from pre-operative clinic. Prediction of urinary retention was completed pre-operatively by 4 individuals and compared to ground truth POUR outcomes. Inter-rater reliability was calculated with intercorrelation coefficient (2,1). RESULTS: 171 patients were included with age 63 ± 14 years, 58.5% (100/171) male, BMI 30.4 ± 5.9 kg/m2, American Society of Anesthesiologists class 2.6 ± 0.5, 1.7 ± 1.0 levels, 56% (96/171) fusions. The observed rate of POUR was 25.7%. The model's performance was found to be 0.663 (0.567-0.759). With a regression model probability cutoff of 0.24 and a neural network cutoff of 0.23, the following predictive power was achieved: specificity 90.6%, sensitivity 22.7%, negative predictive value 77.2%, positive predictive value 45.5%, and accuracy 73.1%. Intercorrelation coefficient for the regression aspect of the model was found to be 0.889 and intercorrelation coefficient for the neural network aspect of the model was found to be 0.874. CONCLUSIONS: This prospective study confirms performance of the prediction model for POUR developed with retrospective data, showing great correlation. This supports the use of machine learning techniques in the prediction of postoperative complications such as urinary retention.

Chronic thoracic pain after cardiac surgery: role of inflammation and biomechanical sternal stability.

Introduction: The pathogenesis of chronic chest pain after cardiac surgery has not been determinate. If left untreated, postoperative sternal pain reduces the quality of life and patient satisfaction with cardiac surgery. The purpose of the study was to examine the effect of chest inflammation on postoperative pain, risk factors for chronic pain after cardiac surgery and to explore how chest reconstruction was associated with the intensity of pain. Methods: The authors performed a study of acute and chronic thoracic pain after cardiac surgery in patients with and without sternal infection and compared different techniques for chest reconstruction. 42 high-risk patients for the development of mediastinitis were included. Patients with mediastinitis received chest reconstruction (group 1). Their demographics and risk factors were matched with no-infection patients with chest reconstruction (group 2) and subjects who underwent conventional sternal closure (group 3). Chronic pain was assessed by the numeric rating scale after surgery. Results: The assessment of the incidence and intensity of chest pain at 3 months post-surgery demonstrated that 14 out of 42 patients across all groups still experienced chronic pain. Specifically, in group 1 with sternal infection five patients had mild pain, while one patient experienced mild pain in group 2, and eight patients in group 3. Also, follow-up results indicated that the highest pain score was in group 3. While baseline levels of cytokines were increased among patients with sternal infection, at discharge only the level of interleukin 6 remained high compared to no infection groups. Compared to conventional closure, after chest reconstruction, we found better healing scores at 3-month follow-up and a higher percentage of patients with the complete sternal union. Conclusions: Overall, 14 out of 42 patients have chronic pain after cardiac surgery. The intensity of the pain in mediastinitis patients significantly decreased at 3 months follow-up after chest reconstruction. Thus, post-surgery mediastinitis is not a determining factor for development the chronic chest pain. There is no correlation between cytokines levels and pain score except interleukin 6 which remains elevated for a long time after treatment. Correlation between sternal healing score and chronic chest pain was demonstrated.

2023 Guideline for the Management of Patients With Aneurysmal Subarachnoid Hemorrhage: A Guideline From the American Heart Association/American Stroke Association.

AIM: The "2023 Guideline for the Management of Patients With Aneurysmal Subarachnoid Hemorrhage" replaces the 2012 "Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage." The 2023 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with aneurysmal subarachnoid hemorrhage. METHODS: A comprehensive search for literature published since the 2012 guideline, derived from research principally involving human subjects, published in English, and indexed in MEDLINE, PubMed, Cochrane Library, and other selected databases relevant to this guideline, was conducted between March 2022 and June 2022. In addition, the guideline writing group reviewed documents on related subject matter previously published by the American Heart Association. Newer studies published between July 2022 and November 2022 that affected recommendation content, Class of Recommendation, or Level of Evidence were included if appropriate. Structure: Aneurysmal subarachnoid hemorrhage is a significant global public health threat and a severely morbid and often deadly condition. The 2023 aneurysmal subarachnoid hemorrhage guideline provides recommendations based on current evidence for the treatment of these patients. The recommendations present an evidence-based approach to preventing, diagnosing, and managing patients with aneurysmal subarachnoid hemorrhage, with the intent to improve quality of care and align with patients' and their families' and caregivers' interests. Many recommendations from the previous aneurysmal subarachnoid hemorrhage guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

Utility of evoked potentials during anterior cerebral artery and anterior communicating artery aneurysm clipping.

Objective: To investigate the optimal combination of somatosensory- and transcranial motor-evoked potential (SSEP/tcMEP) modalities and monitored extremities during clip reconstruction of aneurysms of the anterior cerebral artery (ACA) and its branches. Methods: A retrospective review of 104 cases of surgical clipping of ruptured and unruptured aneurysms was performed. SSEP/tcMEP changes and postoperative motor deficits (PMDs) were assessed from upper and lower extremities (UE/LE) to determine the diagnostic accuracy of each modality separately and in combination. Results: PMDs were reported in 9 of 104 patients; 7 LE and 8 UE (3.6% of 415 extremities). Evoked potential (EP) monitoring failed to predict a PMD in 8 extremities (1.9%). Seven of 8 false negatives had subarachnoid hemorrhage. Sensitivity and specificity in LE were 50% and 97% for tcMEP, 71% and 98% for SSEP, and 83% and 98% for dual-monitoring of both tcMEP/SSEP. Sensitivity and specificity in UE were 38% and 99% for tcMEP, and 50% and 97% for tcMEP/SSEP, respectively. Conclusions: Combined tcMEP/SSEP is more accurate than single-modality monitoring for LE but is relatively insensitive for UE PMDs. Significance: During ACA aneurysm clipping, multiple factors may confound the ability of EP monitoring to predict PMDs, especially brachiofacial hemiparesis caused by perforator insufficiency.

What are we measuring? A refined look at the process of disrupted autoregulation and the limitations of cerebral perfusion pressure in preventing secondary injury after traumatic brain injury.

The cerebral perfusion pressure (CPP) and its relationship between intracranial pressure and mean arterial pressure is a concept ubiquitous in caring for the critically ill patient. CPP is often used as a surrogate measure for cerebral blood flow (CBF); however, this view fails to account for changes in cerebral vascular resistance (CVR). Changes in CVR occur due to cerebral autoregulation, which has classically been taught on a sigma shaped curve with a decline and increase at either end of a plateau. Historically, the conceptualized regulation maintains careful homeostatic levels despite external or internal dynamic changes; however, moderate and severe traumatic brain injury (TBI) has been postulated to bring about cerebral autoregulation dysfunction. We review the current application of CPP is limited by the dynamic changes in cerebral autoregulation after TBI. This review highlights CPP's role as a surrogate measure for CBF and the inherent limitations of current clinical management, due to the lack of monitoring capable of capture continuous variables to assist real-time decision making. This review evaluates the known literature and introduces topics for discussion that warrant further investigation via pre-clinical and clinical experimentation.

Predicting Clinical Outcomes 7-10 Years after Severe Traumatic Brain Injury: Exploring the Prognostic Utility of the IMPACT Lab Model and Cerebrospinal Fluid UCH-L1 and MAP-2.

BACKGROUND: Severe traumatic brain injury (TBI) is a major contributor to disability and mortality in the industrialized world. Outcomes of severe TBI are profoundly heterogeneous, complicating outcome prognostication. Several prognostic models have been validated for acute prediction of 6-month global outcomes following TBI (e.g., morbidity/mortality). In this preliminary observational prognostic study, we assess the utility of the International Mission on Prognosis and Analysis of Clinical Trials in TBI (IMPACT) Lab model in predicting longer term global and cognitive outcomes (7-10 years post injury) and the extent to which cerebrospinal fluid (CSF) biomarkers enhance outcome prediction. METHODS: Very long-term global outcome was assessed in a total of 59 participants (41 of whom did not survive their injuries) using the Glasgow Outcome Scale-Extended and Disability Rating Scale. More detailed outcome information regarding cognitive functioning in daily life was collected from 18 participants surviving to 7-10 years post injury using the Cognitive Subscale of the Functional Independence Measure. A subset (n = 10) of these participants also completed performance-based cognitive testing (Digit Span Test) by telephone. The IMPACT lab model was applied to determine its prognostic value in relation to very long-term outcomes as well as the additive effects of acute CSF ubiquitin C-terminal hydrolase-L1 (UCH-L1) and microtubule associated protein 2 (MAP-2) concentrations. RESULTS: The IMPACT lab model discriminated favorable versus unfavorable 7- to 10-year outcome with an area under the receiver operating characteristic curve of 0.80. Higher IMPACT lab model risk scores predicted greater extent of very long-term morbidity (ß = 0.488 p = 0.000) as well as reduced cognitive independence (ß = - 0.515, p = 0.034). Acute elevations in UCH-L1 levels were also predictive of lesser independence in cognitive activities in daily life at very long-term follow-up (ß = 0.286, p = 0.048). Addition of two CSF biomarkers significantly improved prediction of very long-term neuropsychological performance among survivors, with the overall model (including IMPACT lab score, UCH-L1, and MAP-2) explaining 89.6% of variance in cognitive performance 7-10 years post injury (p = 0.008). Higher acute UCH-L1 concentrations were predictive of poorer cognitive performance (ß = - 0.496, p = 0.029), whereas higher acute MAP-2 concentrations demonstrated a strong cognitive protective effect (ß = 0.679, p = 0.010). CONCLUSIONS: Although preliminary, results suggest that existing prognostic models, including models with incorporation of CSF markers, may be applied to predict outcome of severe TBI years after injury. Continued research is needed examining early predictors of longer-term outcomes following TBI to identify potential targets for clinical trials that could impact long-ranging functional and cognitive outcomes.

Preoperative prediction of postoperative urinary retention in lumbar surgery: a comparison of regression to multilayer neural network.

OBJECTIVE: Postoperative urinary retention (POUR) is a common complication after spine surgery and is associated with prolongation of hospital stay, increased hospital cost, increased rate of urinary tract infection, bladder overdistention, and autonomic dysregulation. POUR incidence following spine surgery ranges between 5.6% and 38%; no reliable prediction tool to identify those at higher risk is available, and that constitutes an important gap in the literature. The objective of this study was to develop and validate a preoperative risk model to predict the occurrence of POUR following routine elective spine surgery. METHODS: The authors conducted a retrospective chart review of consecutive adults who underwent lumbar spine surgery between June 1, 2017, and June 1, 2019. Patient characteristics, preexisting ICD-10 codes, preoperative pain and opioid use, preoperative alpha-1 blocker use, details of surgical planning, development of POUR, and management strategies were abstracted from electronic medical records. A binomial logistic model and a multilayer perceptron (MLP) were optimized using training and validation sets. The models' performance was then evaluated on model-naïve patients (not a part of either cohort). The models were then stacked to take advantage of each model's strengths and to avoid their weaknesses. Four additional models were developed from previously published models adjusted to include only relevant factors (i.e., factors known preoperatively and applied to the lumbar spine). RESULTS: Overall, 891 patients were included in the cohort, with a mean of 59.6 ± 15.5 years of age, 52.7% male, BMI 30.4 ± 6.4, American Society of Anesthesiologists class 2.8 ± 0.6, and a mean of 5.6 ± 5.7 comorbidities. The rate of POUR was found to be 25.9%. The two models were comparable, with an area under the curve (AUC) of 0.737 for the regression model and 0.735 for the neural network. By combining the two models, an AUC of 0.753 was achieved. With a regression model probability cutoff of 0.24 and a neural network cutoff of 0.23, maximal sensitivity and specificity were achieved, with specificity 68.2%, sensitivity 72.9%, negative predictive value 88.2%, and positive predictive value 43.4%. Both models individually outperformed previously published models (AUC 0.516-0.645) when applied to the current data set. CONCLUSIONS: This predictive model can be a powerful preoperative tool in predicting patients who will be likely to develop POUR. By using a combination of regression and neural network modeling, good sensitivity, specificity, and NPV are achieved.

"Carpe Diem" Professor - In Memoriam of Francis Robicsek (1925-2020).

Francis Robicsek was an outstanding cardiothoracic and vascular surgeon, anthropologist, biomedical engineer, philanthropist, art lover, and collector. During a career of almost 55 years, he managed to influence almost every aspect of cardiothoracic and vascular surgery. He is best known for his novel approach to the treatment of sternal instability, the Robicsek weave, which is currently the reference standard. His accomplishments include over 35,000 surgical interventions, 672 medical publications, 734 lectures, 4 textbooks on Mayan culture, and approximately 100 pupils. His remains one of the most fascinating stories in modern surgery.

Perioperative Care of Patients at High Risk for Stroke During or After Non-cardiac, Non-neurological Surgery: 2020 Guidelines From the Society for Neuroscience in Anesthesiology and Critical Care.

Perioperative stroke is associated with considerable morbidity and mortality. Stroke recognition and diagnosis are challenging perioperatively, and surgical patients receive therapeutic interventions less frequently compared with stroke patients in the outpatient setting. These updated guidelines from the Society for Neuroscience in Anesthesiology and Critical Care provide evidence-based recommendations regarding perioperative care of patients at high risk for stroke. Recommended areas for future investigation are also proposed.

Blood-Related Toxicity after Traumatic Brain Injury: Potential Targets for Neuroprotection.

Emergency visits, hospitalizations, and deaths due to traumatic brain injury (TBI) have increased significantly over the past few decades. While the primary early brain trauma is highly deleterious to the brain, the secondary injury post-TBI is postulated to significantly impact mortality. The presence of blood, particularly hemoglobin, and its breakdown products and key binding proteins and receptors modulating their clearance may contribute significantly to toxicity. Heme, hemin, and iron, for example, cause membrane lipid peroxidation, generate reactive oxygen species, and sensitize cells to noxious stimuli resulting in edema, cell death, and increased morbidity and mortality. A wide range of other mechanisms such as the immune system play pivotal roles in mediating secondary injury. Effective scavenging of all of these pro-oxidant and pro-inflammatory metabolites as well as controlling maladaptive immune responses is essential for limiting toxicity and secondary injury. Hemoglobin metabolism is mediated by key molecules such as haptoglobin, heme oxygenase, hemopexin, and ferritin. Genetic variability and dysfunction affecting these pathways (e.g., haptoglobin and heme oxygenase expression) have been implicated in the difference in susceptibility of individual patients to toxicity and may be target pathways for potential therapeutic interventions in TBI. Ongoing collaborative efforts are required to decipher the complexities of blood-related toxicity in TBI with an overarching goal of providing effective treatment options to all patients with TBI.

Temporal Profile of Microtubule-Associated Protein 2: A Novel Indicator of Diffuse Brain Injury Severity and Early Mortality after Brain Trauma.

This study compared cerebrospinal fluid (CSF) levels of microtubule-associated protein 2 (MAP-2) from adult patients with severe traumatic brain injury (TBI) with uninjured controls over 10 days, and examined the relationship between MAP-2 concentrations and acute clinical and radiologic measures of injury severity along with mortality at 2 weeks and over 6 months. This prospective study, conducted at two Level 1 trauma centers, enrolled adults with severe TBI (Glasgow Coma Scale [GCS] score ≤8) requiring a ventriculostomy, as well as controls. Ventricular CSF was sampled from each patient at 6, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 h following TBI and analyzed via enzyme-linked immunosorbent assay for MAP-2 (ng/mL). Injury severity was assessed by the GCS score, Marshall Classification on computed tomography (CT), Rotterdam CT score, and mortality. There were 151 patients enrolled-130 TBI and 21 control patients. MAP-2 was detectable within 6 h of injury and was significantly elevated compared with controls (p < 0.001) at each time-point. MAP-2 was highest within 72 h of injury and decreased gradually over 10 days. The area under the receiver operating characteristic curve for deciphering TBI versus controls at the earliest time-point CSF was obtained was 0.96 (95% CI 0.93-0.99) and for the maximal 24-h level was 0.98 (95% CI 0.97-1.00). The area under the curve for initial MAP-2 levels predicting 2-week mortality was 0.80 at 6 h, 0.81 at 12 h, 0.75 at 18 h, 0.75 at 24 h, and 0.80 at 48 h. Those with Diffuse Injury III-IV had much higher initial (p = 0.033) and maximal (p = 0.003) MAP-2 levels than those with Diffuse Injury I-II. There was a graded increase in the overall levels and peaks of MAP-2 as the degree of diffuse injury increased within the first 120 h post-injury. These data suggest that early levels of MAP-2 reflect severity of diffuse brain injury and predict 2-week mortality in TBI patients. These findings have implications for counseling families and improving clinical decision making early after injury and guiding multidisciplinary care. Further studies are needed to validate these findings in a larger sample.

Role of Interleukin-10 in Acute Brain Injuries.

Interleukin-10 (IL-10) is an important anti-inflammatory cytokine expressed in response to brain injury, where it facilitates the resolution of inflammatory cascades, which if prolonged causes secondary brain damage. Here, we comprehensively review the current knowledge regarding the role of IL-10 in modulating outcomes following acute brain injury, including traumatic brain injury (TBI) and the various stroke subtypes. The vascular endothelium is closely tied to the pathophysiology of these neurological disorders and research has demonstrated clear vascular endothelial protective properties for IL-10. In vitro and in vivo models of ischemic stroke have convincingly directly and indirectly shown IL-10-mediated neuroprotection; although clinically, the role of IL-10 in predicting risk and outcomes is less clear. Comparatively, conclusive studies investigating the contribution of IL-10 in subarachnoid hemorrhage are lacking. Weak indirect evidence supporting the protective role of IL-10 in preclinical models of intracerebral hemorrhage exists; however, in the limited number of clinical studies, higher IL-10 levels seen post-ictus have been associated with worse outcomes. Similarly, preclinical TBI models have suggested a neuroprotective role for IL-10; although, controversy exists among the several clinical studies. In summary, while IL-10 is consistently elevated following acute brain injury, the effect of IL-10 appears to be pathology dependent, and preclinical and clinical studies often paradoxically yield opposite results. The pronounced and potent effects of IL-10 in the resolution of inflammation and inconsistency in the literature regarding the contribution of IL-10 in the setting of acute brain injury warrant further rigorously controlled and targeted investigation.

Lateral Ventricle Volume Asymmetry Predicts Midline Shift in Severe Traumatic Brain Injury.

Midline shift following severe traumatic brain injury (sTBI) detected on computed tomography (CT) scans is an established predictor of poor outcome. We hypothesized that lateral ventricular volume (LVV) asymmetry is an earlier sign of developing asymmetric intracranial pathology than midline shift. This retrospective analysis was performed on data from 84 adults with blunt sTBI requiring a ventriculostomy who presented to a Level I trauma center. Seventy-six patients underwent serial CTs within 3 h and an average of three scans within the first 10 d of sTBI. Left and right LVVs were quantified by computer-assisted manual volumetric measurements. LVV ratios (LVR) were determined on the admission CT to evaluate ventricular asymmetry. The relationship between the admission LVR value and subsequent midline shift development was tested using receiver operating characteristic (ROC) analysis, and odds ratio (OR) and relative risk tests. Sixty patients had no >5 mm midline shift on the initial admission scan. Of these, 15 patients developed it subsequently (16 patients already had >5 mm midline shift on admission scans). For >5 mm midline shift development, admission LVR of >1.67 was shown to have a sensitivity of 73.3% and a specificity of 73.3% (area under the curve=0.782; p<0.0001). LVR of >1.67 as exposure yielded an OR of 7.56 (p<0.01), and a risk ratio of 4.42 (p<0.01) for midline shift development as unfavorable outcome. We propose that LVR captures LVV asymmetry and is not only related to, but also predicts the development of midline shift already at admission CT examination. Lateral ventricles may have a higher "compliance" than midline structures to developing asymmetric brain pathology. LVR analysis is simple, rapidly accomplished and may allow earlier interventions to attenuate midline shift and potentially improve ultimate outcomes.

Biomarkers improve clinical outcome predictors of mortality following non-penetrating severe traumatic brain injury.

OBJECTIVE: This study assessed whether early levels of biomarkers measured in CSF within 24-h of severe TBI would improve the clinical prediction of 6-months mortality. METHODS: This prospective study conducted at two Level 1 Trauma Centers enrolled adults with severe TBI (GCS ≤8) requiring a ventriculostomy as well as control subjects. Ventricular CSF was sampled within 24-h of injury and analyzed for seven candidate biomarkers (UCH-L1, MAP-2, SBDP150, SBDP145, SBDP120, MBP, and S100B). The International Mission on Prognosis and Analysis of Clinical Trials in TBI (IMPACT) scores (Core, Extended, and Lab) were calculated for each patient to determine risk of 6-months mortality. The IMPACT models and biomarkers were assessed alone and in combination. RESULTS: There were 152 patients enrolled, 131 TBI patients and 21 control patients. Thirty six (27 %) patients did not survive to 6 months. Biomarkers were all significantly elevated in TBI versus controls (p < 0.001). Peak levels of UCH-L1, SBDP145, MAP-2, and MBP were significantly higher in non-survivors (p < 0.05). Of the seven biomarkers measured at 12-h post-injury MAP-2 (p = 0.004), UCH-L1 (p = 0.024), and MBP (p = 0.037) had significant unadjusted hazard ratios. Of the seven biomarkers measured at the earliest time within 24-h, MAP-2 (p = 0.002), UCH-L1 (p = 0.016), MBP (p = 0.021), and SBDP145 (0.029) had the most significant elevations. When the IMPACT Extended Model was combined with the biomarkers, MAP-2 contributed most significantly to the survival models with sensitivities of 97-100 %. CONCLUSIONS: These data suggest that early levels of MAP-2 in combination with clinical data provide enhanced prognostic capabilities for mortality at 6 months.

Perioperative care of patients at high risk for stroke during or after non-cardiac, non-neurologic surgery: consensus statement from the Society for Neuroscience in Anesthesiology and Critical Care*.

Perioperative stroke can be a catastrophic outcome for surgical patients and is associated with increased morbidity and mortality. This consensus statement from the Society for Neuroscience in Anesthesiology and Critical Care provides evidence-based recommendations and opinions regarding the preoperative, intraoperative, and postoperative care of patients at high risk for the complication.

Human traumatic brain injury induces autoantibody response against glial fibrillary acidic protein and its breakdown products.

The role of systemic autoimmunity in human traumatic brain injury (TBI) and other forms of brain injuries is recognized but not well understood. In this study, a systematic investigation was performed to identify serum autoantibody responses to brain-specific proteins after TBI in humans. TBI autoantibodies showed predominant immunoreactivity against a cluster of bands from 38-50 kDa on human brain immunoblots, which were identified as GFAP and GFAP breakdown products. GFAP autoantibody levels increased by 7 days after injury, and were of the IgG subtype predominantly. Results from in vitro tests and rat TBI experiments also indicated that calpain was responsible for removing the amino and carboxyl termini of GFAP to yield a 38 kDa fragment. Additionally, TBI autoantibody staining co-localized with GFAP in injured rat brain and in primary rat astrocytes. These results suggest that GFAP breakdown products persist within degenerating astrocytes in the brain. Anti-GFAP autoantibody also can enter living astroglia cells in culture and its presence appears to compromise glial cell health. TBI patients showed an average 3.77 fold increase in anti-GFAP autoantibody levels from early (0-1 days) to late (7-10 days) times post injury. Changes in autoantibody levels were negatively correlated with outcome as measured by GOS-E score at 6 months, suggesting that TBI patients with greater anti-GFAP immune-responses had worse outcomes. Due to the long lasting nature of IgG, a test to detect anti-GFAP autoantibodies is likely to prolong the temporal window for assessment of brain damage in human patients.

Clinical utility of serum levels of ubiquitin C-terminal hydrolase as a biomarker for severe traumatic brain injury.

BACKGROUND: Brain damage markers released in cerebrospinal fluid (CSF) and blood may provide valuable information about diagnosis and outcome prediction after traumatic brain injury (TBI). OBJECTIVE: To examine the concentrations of ubiquitin C-terminal hydrolase-L1 (UCH-L1), a novel brain injury biomarker, in CSF and serum of severe TBI patients and their association with clinical characteristics and outcome. METHODS: This case-control study enrolled 95 severe TBI subjects (Glasgow Coma Scale [GCS] score, 8). Using sensitive UCH-L1 sandwich ELISA, we studied the temporal profile of CSF and serum UCH-L1 levels over 7 days for severe TBI patients. RESULTS: Comparison of serum and CSF levels of UCH-L1 in TBI patients and control subjects shows a robust and significant elevation of UCH-L1 in the acute phase and over the 7-day study period. Serum and CSF UCH-L1 receiver-operating characteristic curves further confirm strong specificity and selectivity for diagnosing severe TBI vs controls, with area under the curve values in serum and CSF statistically significant at all time points up to 24 hours (P < .001). The first 12-hour levels of both serum and CSF UCH-L1 in patients with GCS score of 3 to 5 were also significantly higher than those with GCS score of 6 to 8. Furthermore, UCH-L1 levels in CSF and serum appear to distinguish severe TBI survivors from nonsurvivors within the study, with nonsurvivors having significantly higher and more persistent levels of serum and CSF UCH-L1. Cumulative serum UCH-L1 levels > 5.22 ng/mL predicted death (odds ratio, 4.8). CONCLUSION: Serum levels of UCH-L1 appear to have potential clinical utility in diagnosing TBI, including correlating to injury severity and survival outcome.

Biokinetic analysis of ubiquitin C-terminal hydrolase-L1 (UCH-L1) in severe traumatic brain injury patient biofluids.

Ubiquitin C-terminal hydrolase-L1 (UCH-L1) is a neuron-specific enzyme that has been identified as a potential biomarker of traumatic brain injury (TBI). The study objectives were to determine UCH-L1 exposure and kinetic metrics, determine correlations between biofluids, and assess outcome correlations in severe TBI patients. Data were analyzed from a prospective, multicenter study of severe TBI (Glasgow Coma Scale [GCS] score ≤ 8). Cerebrospinal fluid (CSF) and serum data from samples taken every 6 h after injury were analyzed by enzyme-linked immunosorbent assay (ELISA). UCH-L1 CSF and serum data from 59 patients were used to determine biofluid correlations. Serum samples from 86 patients and CSF from 59 patients were used to determine outcome correlations. Exposure and kinetic metrics were evaluated acutely and up to 7 days post-injury and compared to mortality at 3 months. There were significant correlations between UCH-L1 CSF and serum median concentrations (r(s)=0.59, p<0.001), AUC (r(s)=0.3, p=0.027), Tmax (r(s)=0.68, p<0.001), and MRT (r(s)=0.65, p<0.001). Outcome analysis showed significant increases in median serum AUC (2016 versus 265 ng/mL*min, p=0.006), and Cmax (2 versus 0.4 ng/mL, p=0.003), and a shorter Tmax (8 versus 19 h, p=0.04) in those who died versus those who survived, respectively. In the first 24 h after injury, there was a statistically significant acute increase in CSF and serum median Cmax((0-24h)) in those who died. This study shows a significant correlation between UCH-L1 CSF and serum median concentrations and biokinetics in severe TBI patients, and relationships with clinical outcome were detected.