Unfavorable Neurological Outcome Research Articles

Association between low pH and unfavorable neurological outcome among out-of-hospital cardiac arrest patients treated by extracorporeal CPR: a prospective observational cohort study in Japan

BackgroundWe aimed to identify the association of pH value in blood gas assessment with neurological outcome among out-of-hospital cardiac arrest (OHCA) patients treated by extracorporeal cardiopulmonary resuscitation (ECPR).MethodsWe retrospectively analyzed the database of a multicenter prospective observational study on OHCA patients in Osaka prefecture, Japan (CRITICAL study), from July 1, 2012 to December 31, 2016. We included adult OHCA patients treated by ECPR. Patients with OHCA from external causes such as trauma were excluded. We conducted logistic regression analysis to identify the odds ratio (OR) and 95% confidence interval (CI) of the pH value for 1 month favorable neurological outcome adjusted for potential confounders including sex, age, witnessed by bystander, CPR by bystander, pre-hospital initial cardiac rhythm, and cardiac rhythm on hospital arrival.ResultsAmong the 9822 patients in the database, 260 patients were finally included in the analysis. The three groups were Tertile 1: pH ≥ 7.030, Tertile 2: pH 6.875–7.029, and Tertile 3: pH < 6.875. The adjusted OR of Tertiles 2 and 3 compared with Tertile 1 for 1 month favorable neurological outcome were 0.26 (95% CI 0.10–0.63) and 0.24 (95% CI 0.09–0.61), respectively.ConclusionsThis multi-institutional observational study showed that low pH value (< 7.03) before the implementation of ECPR was associated with 1 month unfavorable neurological outcome among OHCA patients treated with ECPR. It may be helpful to consider the candidate for ECPR.

High early phase hemoglobin level is associated with favorable neurological outcome in patients with severe traumatic brain injury.

The appropriate hemoglobin (Hb) level threshold for the early phase (i.e. from Emergency Department to ICU admission) in patients with severe traumatic brain injury (TBI) is still unknown. Therefore, we aimed to examine the association between Hb levels during the early phase and neurological outcomes in patients with severe TBI using data from the Brain Hypothermia (B-HYPO) Study Group. We performed a post-hoc analysis of the B-HYPO study (a prospective, multicenter, randomized controlled trial on patients with severe TBI who received either mild therapeutic hypothermia [MTH; 32.0°C-34.0°C] or fever control [35.5°C-37.0°C]). We calculated Hb levels during early phase by the formula: (admission Hb+Hb on day 1)/2. The primary outcome was the association between during early phase Hb levels and 6-month neurological outcome after the TBI based on the Glasgow Outcome Scale scores (a measure of functional recovery defined as moderate disability or good recovery). We reviewed data from 130 patients and found favorable neurological outcomes in 48.5% of them. We found significant differences between the favorable and unfavorable neurological outcome groups in terms of their Hb levels on admission and on day 1. But, we found no Hb level differences after day 3 (including 1day after rewarming). Our multivariable analysis showed that Hb levels during early phase were significantly associated with favorable neurological outcomes (odds ratio, 1.387; 95% confidence interval, 1.057-1.858; P=0.018). High early phase Hb levels are associated with favorable neurological outcomes after severe TBI.

Targeted temperature management and emergent coronary angiography are associated with improved outcomes in patients with prehospital return of spontaneous circulation

Whether targeted temperature management (TTM) and emergent coronary angiography (CAG) remain associated with better outcomes in patients with prehospital return of spontaneous circulation (ROSC) was unknown. This retrospective cohort study enrolled 81 adult, nontraumatic out-of-hospital cardiac arrest patients who had good pre-arrest neurological function and achieved prehospital ROSC during 2012 to August 2017. The outcomes were survival-to-discharge and neurological recovery at discharge. Fifty-five patients (67.9%) survived to hospital discharge (the survivor group) and twenty-six (32.1%) failed (the non-survivor group). A total of 47 patients (58.0%) presented favorable neurological outcomes [Cerebral Performance Category (CPC) score=1-2, the favorable group], and 34 patients (42.0%) presented unfavorable neurological outcomes (CPC score=3-5, the poor group). The survivor group had more patients with TTM (45.5% vs. 19.2%, p=0.023) and emergent CAG (76.4% vs. 19.2%, p<0.001) than the non-survivor group, and similar findings were noted in the neurological outcomes (TTM: 44.7% vs. 26.5%, p=0.094; CAG: 80.9% vs. 26.5%, p<0.001). TTM remained associated with increased survival-to-discharge [odds ratio (OR)=14.635, 95% confidence interval (CI)=1.296-165.305, p = 0.030] and a trend toward good neurological recovery (OR=4.551, 95%CI=0.963-21.517, p=0.056). After excluding patients with rapid neurological recovery after ROSC (n=70), TTM was associated with good neurological outcomes (OR=4.534, 95% CI=1.075-19.127, p=0.040). Emergent CAG had the trend associated with survival-to-discharge (OR = 9.599, 95%CI = 0.764-120.634, p = 0.080) and was significantly associated with good neurological outcomes (OR=21.785, 95%CI=2.004-236.836, p=0.011). In patients with prehospital ROSC, both TTM and emergent CAG were associated to improved survival and neurological outcomes.

Predictors of mortality and neurological function in ICU patients recovering from cardiac arrest: A Spanish nationwide prospective cohort study.

To identify predictors of mortality and neurological function in adult ICU patients recovering from cardiac arrest. A prospective cohort multicenter study was carried out. Forty-six polyvalent ICUs. A total of 595 patients recovering from out-of-hospital cardiac arrest (OHCA, n=285) or in-hospital cardiac arrest (IHCA, n=310). Survival and recovery of neurological function. The mean cardiopulmonary resuscitation time was 18min (range 10-30). Moderate hypothermia was used in 197 patients, and 150 underwent percutaneous coronary intervention (PCI). Return of spontaneous circulation (ROSC) was achieved within 20min in 370 patients. Variables associated to mortality (ICU and in-hospital) were age (odds ratio [OR]=1.0, 95%CI 1.0-1.0 per year), non-cardiac origin of cardiac arrest (OR=2.16, 95%CI 1.38-3.38; P=0.001) and ROSC >20min (OR=3.07, 95%CI 1.97-4.78; P<0.001), whereas PCI and the presence of shockable rhythm exhibited a protective effect. Favorable neurological outcome was associated to shockable rhythm, ROSC <20min, and cardiac origin of arrest. Hypothermia did not affect survival or neurological outcome in the multivariate analysis. Age, non-cardiac origin of cardiac arrest and ROSC >20min were predictors of mortality. In contrast, cardiac arrest of cardiac origin, ROSC <20min, and defibrillable rhythms were associated to unfavorable neurological outcomes.

Early outcome prediction with quantitative pupillary response parameters after out-of-hospital cardiac arrest: A multicenter prospective observational study​.

We aimed to determine the characteristics of quantitative pupillary response parameters other than amplitude of pupillary light reflex (PLR) early after return of spontaneous circulation (ROSC) and their implications for predicting neurological outcomes early after cardiac arrest (CA). Fifty adults resuscitated after non-traumatic out-of-hospital CA from four emergency hospitals were enrolled. Pupil diameters, PLR, constriction velocity (CV), maximum CV (MCV), dilation velocity (DV), latency of constriction, and Neurological Pupil index (NPi) were quantitatively measured at 0, 6, 12, 24, 48, and 72 h post-ROSC using an automated pupillometer. Change over time of each parameter was compared between favorable (Cerebral Performance Category [CPC] 1 or 2) and unfavorable neurological outcome (CPC 3-5) groups. Prognostic values of 90-day favorable outcome by these parameters and when combined with clinical predictors (witness status, bystander cardiopulmonary resuscitation, initial shockable rhythm, implementation of target temperature management) were tested. Thirteen patients achieved favorable outcome. CV, MCV, DV (P < 0.001), and NPi (P = 0.005) were consistently greater in the favorable group than in the unfavorable outcome group. Change over time was not statistically different between the groups in all parameters. CV, MCV, DV (ρ = 0.96 to 0.97, P < 0.001, respectively), and NPi (ρ = 0.65, P < 0.001) positively correlated with PLR. The prognostic value of 0-hour CV (area under the curve, AUC [95% confidence interval]: 0.92 [0.80-1.00]), DV (0.84 [0.68-0.99]), and NPi (0.88 [0.74-1.00]) was equivalent to that of PLR (0.84 [0.69-0.98]). Prognostic values improved to AUC of 0.95-0.96 when 0-hour PLR, CV, DV, or NPi was combined with clinical predictors. The 0-hour CV, MCV, and NPi showed equivalent prognostic values to PLR alone/in combination with clinical predictors. Using PLR among several quantitative pupillary response parameters for early neurological prognostication of post-CA patients is a simple and effective strategy.

Oxygen and carbon dioxide levels in patients after cardiac arrest

BackgroundThe relationship of PaO2 and PaCO2 levels with outcome after cardiac arrest (CA) is controversial. Few studies have analysed both PaO2 and PaCO2 in this setting and the overall exposure to different PaO2 and PaCO2 levels has not been taken into account. MethodsWe reviewed blood gas data obtained within the first 24 h from all comatose adult patients who were admitted to the intensive care unit after successful resuscitation from CA. Exposure times to different PaO2 and PaCO2 thresholds were reported as areas under the curve (AUC) and the time above these thresholds was then calculated. The primary outcome measure was neurological outcome assessed using the Cerebral Performance Category (CPC) score at 3 months. An unfavourable outcome was defined as a CPC of 3–5 and a favourable outcome as a CPC of 1–2. ResultsA total of 356 patients were studied, with a median number of 9 [6–11] blood gas measurements within the first 24 h after admission. The highest and lowest PaO2 and PaCO2 were similar in patients with unfavourable and favourable neurological outcomes. There were no differences in the AUCs or times over different thresholds of PaO2 and PaCO2 in the two groups. In a multivariable analysis, high blood lactate concentrations on admission, presence of shock and a non-shockable initial rhythm were significantly associated with unfavourable outcome. ConclusionsThere was no association between exposure to various levels of PaO2 and PaCO2 and neurological outcome after cardiac arrest.

The characteristics of patients with bilateral absent evoked potentials after post-anoxic brain damage: A multicentric cohort study

ObjectivesPatients with bilateral absence of cortical response (N20ABS) to somatosensory evoked potentials (SSEPs) have poor neurological outcome after cardiac arrest (CA). However, SSEPs are not available in all centers. The aim of this study was to identify predictors of N20ABS. MethodsRetrospective analysis of institutional databases (2008–2015) in three ICUs including all adult admitted comatose patients undergoing SSEPs between 48 and 72 h after CA. We collected clinical (i.e. absence of pupillary reflexes, PLR, myoclonus and absent or posturing motor response and myoclonus on day 2–3), electroencephalographic (EEG; i.e. unreactive to painful stimuli; presence of a highly malignant patterns, such as burst-suppression or flat tracings) findings during the first 48 h, and the highest NSE levels on the first 3 days after CA. Unfavorable neurological outcome (UO) was assessed at 3 months using the Cerebral Performance Categories of 3–5. ResultsWe studied 532 patients with SSEPs, including 143 (27%) without N20ABS; UO was observed in 334 (63%) patients. Median time to SSEPs was 72 [48–72] h after CA. No patient with absent PLR and myoclonus during the ICU stay had N20 present; similar results were observed with the combination of absent PLR, myoclonus and any EEG pattern (i.e. unreactive or highly malignant). Similar results were observed in the subgroup of patients where NSE was available (n = 303). In a multivariate logistic regression, non-cardiac etiology of arrest, unreactive EEG to painful stimuli, absence of pupillary reflexes and posturing motor response, were independent predictors of N20ABS. When available, the highest NSE was also an independent predictor of N20ABS. ConclusionsClinical and EEG findings predicting patients with N20ABS, confirm that N20ABS reflects a severe and permanent cerebral damage after CA.

Transverse Myelitis in Systemic Lupus Erythematosus: Clinical Features and Prognostic Factors in a Large Cohort of Latin American Patients.

Acute transverse myelitis (ATM) is an infrequent but severe complication of systemic lupus erythematosus (SLE). The purpose of study was to describe clinical features and prognostic factors of patients with SLE-related ATM. In this medical records review study, data were collected from 60 patients from 16 centers seen between 1996 and 2017 who met diagnostic criteria for SLE and myelitis as defined by the American College of Rheumatology/Systemic International Collaborating Clinics and the Working Group of the Transverse Myelitis Consortium, respectively. Objective neurological impairment was measured with American Spinal Injury Association Impairment Scale (AIS) and European Database for Multiple Sclerosis Grade Scale (EGS). Among patients included, 95% (n = 57) were female, and the average age was 31.6 ± 9.6 years. Myelitis developed after diagnosis of SLE in 60% (n = 36). Symmetrical paraparesis with hypoesthesia, flaccidity, sphincter dysfunction, AIS = A/B, and EGS ≥ 8 was the most common presentation. Intravenous methylprednisolone was used in 95% (n = 57), and 78.3% (n = 47) received intravenous cyclophosphamide. Sensory/motor recovery at 6 months was observed in 75% (42 of 56), but only in 16.1% (9 of 56) was complete. Hypoglycorrhachia and EGS ≥ 7 in the nadir were associated with an unfavorable neurological outcome at 6 months (p < 0.05). A relapse rate during follow-up was observed in 30.4% (17 of 56). Hypoglycorrhachia and hypocomplementemia seem to be protective factors for relapse. Intravenous cyclophosphamide was associated with time delay to relapse. Systemic lupus erythematosus-related ATM may occur at any time of SLE course, leading to significant disability despite treatment. Relapses are infrequent and intravenous cyclophosphamide seems to delay it. Hypoglycorrhachia, hypocomplementemia, and EGS at nadir are the most important prognostic factors.

Abstract TMP19: MRI Characteristics and Predictors of Diffusion Weighted Hyperintense Lesions After Spontaneous Intracerebral Hemorrhage: A Secondary Analysis of MISTIE-III

Introduction: Mechanisms of diffusion weighted hyperintense lesions (DWIHL) after spontaneous intracerebral hemorrhage (ICH) are controversial. We evaluated mechanism and outcome of DWIHL. Methods: Protocolized MRI scans within 7 days from ICH were reviewed from MISTIE-III trial. Imaging analysis included DWIHL, leukoariosis (Fazekas score), enlarged perivascular space (EPVS), and cerebral microbleeds. Multivariable logistic regression analysis was performed to assess predictors and outcomes of having DWIHLs. Favorable outcome was defined as modified Rankin Score 0-3 at 12 months. Results: Of 499 patients, 300 underwent DWI studies (62% lobar ICH; 38% deep ICH) and 178 (59%) had acute DWIHLs (66% lobar; 34% deep). DWIHL locations were perihematomal in 140 (79%); and remote in 96 (54%). In multivariable regression analysis, DWIHLs were associated with initial mean arterial pressure [MAP] (odds ratio [OR]: 1.004; 95% confidence interval [CI]: 1.002-1.01), initial ICH volume (OR: 1.004; 95%CI: 1.001-1.01), NIHSS at randomization (OR: 1.01; 95%CI: 1.01-1.02), hypertension history (OR: 1.41; 95%CI: 1.04-1.93), and Fazekas score (OR: 1.04; 95%CI: 1.01-1.08). Patients with DWIHLs were less likely to have favorable outcome (66% vs. 50%; OR: 0.89; 95%CI: 0.81-0.99) after adjusting for ICH severity; however, the presence of DWIHLs did not confer an independent mortality risk at 12 months. In addition, perihematomal DWIHLs were associated with ICH volume (OR: 1.003; 95%CI: 1.00-1.01), NIHSS (OR: 1.01; 95%CI: 1.00-1.02), deep location (OR: 1.25; 95%CI: 1.10-1.42), and centrum semiovale EPVS score (OR: 0.99; 95% CI: 0.99-1.00). Remote DWIHLs were associated with Fazekas score (OR: 1.17; 95%CI: 1.06-1.29), centrum semiovale EPVS score (OR: 1.01; 95%CI: 1.00-1.01), atrial fibrillation (OR: 1.40; 95%CI: 1.04-1.90), and maximal ΔMAP on first 24 hours (OR: 1.004; 95%CI: 1.001-1.006). Conclusions: DWIHLs were common (59%) in patients after spontaneous ICH, predominantly in lobar locations and were associated with unfavorable neurologic outcome. While perihematomal DWIHLs were associated with ICH severity, remote DWIHLs suggested different mechanisms including acute blood pressure reduction, cardiac emboli, and white matter disease severity.

Electrocardiographic changes during therapeutic hypothermia: observational data from a single centre.

Therapeutic hypothermia is recommended to reduce the risk of hypoxic brain damage and improve short-term survival after cardiac arrest. It also temporarily affects the cardiac conduction system. The aim of this study was to evaluate electrocardiographic changes during therapeutic hypothermia and their impact on the outcome. This retrospective analysis involved 26 patients who underwent therapeutic hypothermia after cardiac arrest in Vilnius University Hospital Santaros Klinikos from 2011 to 2015. During cooling, a significant reduction in the heart rate (p = 0.013), shortening of QRS complex duration (p = 0.041), and prolongation of the QTc interval (p < 0.001) were observed. During the cooling period, five patients had subtle Osborn waves, which disappeared after rewarming. The association between electrocardiographic changes during cooling and unfavourable neurological outcome or in-hospital mortality was non-significant. Therapeutic hypothermia after cardiac arrest causes reversible electrocardiographic changes that do not increase the risk of in-hospital mortality or unfavourable neurological outcomes.

Prognostic Significance of the Difference Between Mixed and Jugular Venous Oxygen Saturation After Severe Traumatic Brain Injury: A Post Hoc Analysis of the Brain Hypothermia Study

In patients postcardiac arrest, it has been reported that the small value of the difference between mixed venous oxygen saturation (Svo2) and jugular venous oxygen saturation (Sjvo2) is associated with poor neurologic outcome. However, the importance of the difference between mixed venous oxygen saturation and jugular venous oxygen saturation (ΔSo2 [v- jv]) remains unknown in severe traumatic brain injury (TBI). The aim of this study was to examine whether ΔSo2 (v- jv) is associated with neurologic outcome and mortality in patients with severe TBI. We conducted post hoc analyses of the Brain Hypothermia Study, a multicenter randomized controlled trial of mild therapeutic hypothermia for the treatment of severe TBI. The value of ΔSo2(v- jv) on day 1 and day 3 was compared between survivors (n= 65) and nonsurvivors (n= 25) or between patients with favorable (n= 47) and unfavorable (n= 43) neurologic outcomes. The reduction in ΔSo2 (v- jv) on day 3 was-2.0% (range,-6.9% to 6.5%) in the nonsurvivor group and 6.3% (range,-2.5% to 16.7%) in the survivor group. The difference was statistically significant (P=0.03). The same tendencies were observed in the nonsurvivor group on day 1 and in the unfavorable neurologic outcome group on day 1 and day 3, but the difference was not significant. The reduction in ΔSo2(v- jv) on day 3 was associated with high mortality in patients with severe TBI.

Association of Cerebral Oximetry with Outcomes after Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) is associated with neurologic morbidity and mortality. We investigated whether cerebral regional oxygen saturation (rSO2) is associated with neurologic outcomes and survival in children on ECMO. This was a retrospective observational study of children aged 1day to 20years who underwent ECMO with routine cerebral rSO2 monitoring in the pediatric intensive care unit at a single academic center between February 2008 and September 2014. We collected all serial rSO2 values recorded in the electronic medical record during the ECMO course. Favorable outcome was defined as survival with Pediatric Cerebral Performance Category (PCPC) ≤ 2 at hospital discharge or no decline from baseline PCPC. We reviewed data from 153 patients who underwent 156 ECMO runs. The median age was 12.5days (interquartile range [IQR], 2days-15months). Ninety-nine (64%) patients survived to hospital discharge, and 82/99 (83%) survivors had favorable neurologic outcome by discharge PCPC. Neuroimaging studies were obtained in 135 (87%) patients, 59 (44%) of which showed abnormal findings. Ninety-two (59%) patients had any rSO2 ≤ 50%, 60 (38%) had any rSO2 decline > 20% from baseline, and 26 (17%) had any rSO2 decline > 20% from the reading 1h prior. Any rSO2 ≤ 50% and any rSO2 decline > 20% from baseline were each associated with unfavorable outcome at hospital discharge (multivariable-adjusted odds ratio [OR], 2.82 [95% CI 1.10-7.25] and 4.52 [95% CI 1.76-11.58], respectively). rSO2 decline > 20% from the reading 1h prior was not significantly associated with the outcomes. Among children in one institution who underwent routine clinical rSO2 monitoring during ECMO, rSO2 decline was associated with unfavorable short-term neurologic outcome and death after adjusting for potential confounders. The effectiveness of initiating early preventative measures in these high-risk patients needs further study.

Serum Magnesium Levels and Neurological Outcomes in Patients Undergoing Targeted Temperature Management After Cardiac Arrest

IntroductionMagnesium plays a neuroprotective role at the physiologic level, but its neuroprotective role in patients undergoing targeted temperature management for cardiac arrest is not well established. We performed multiple logistic regression analysis to evaluate whether magnesium levels can predict neurological outcomes in patients undergoing targeted temperature management after cardiac arrest. MethodsWe retrospectively investigated data on 86 patients who had undergone targeted temperature management after cardiac arrest between December 2015 and November 2017. The primary outcome was to determine whether magnesium levels predict unfavorable neurological outcomes for patients with return of spontaneous circulation after targeted temperature management. Cerebral Performance Category 3, 4, or 5 indicated unfavorable neurological outcomes. We performed multiple logistic regression to evaluate the primary outcome, adjusting for the time to return of spontaneous circulation, motor score of the Glasgow Coma Scale, first-recorded cardiac rhythm, pH, and magnesium levels. ResultsOf the 86 patients, 58 had unfavorable neurological outcomes. The mean hospital stay was 19 days. Multivariable analysis indicated that magnesium levels were not associated with an unfavorable neurological outcome. In contrast, a time to return of spontaneous circulation greater than 30 minutes and Glasgow Coma Scale motor score of 1 were significantly associated with an unfavorable neurological outcome. DiscussionMagnesium levels were not associated with an unfavorable neurological outcome according to multivariable analysis. We found that a time to return of spontaneous circulation greater than 30 minutes and Glasgow Coma Scale motor score of 1 might predict an unfavorable neurological outcome.

Posterior reversible encephalopathy syndrome as an underlying cause for encephalopathy in a sepsis patient in the intensive care unit: case report

Posterior reversible encephalopathy (PRES) is a clinical and radiological syndrome characterized by neurological findings and vasogenic edema in the posterior regions of the cerebral hemispheres. Sepsis and septic shock have recently been recognized as an etiological factor in PRES. In this case report, we are presenting a patient with intraabdominal sepsis and PRES followed in the intensive care unit with an unfavorable neurological outcome. Wider recognition of PRES as a cause of encephalopathy in sepsis patients is necessary.

Predictive value of an early amplitude-integrated electroencephalogram for short-term neurologic outcomes in preterm infants.

The aim of this study was to compare serial scores of amplitude-integrated electroencephalography (aEEG) in preterm infants with favorable neurologic outcome compared with those with unfavorable neurologic outcome and to evaluate whether aEEG in the early days of life has predictive value for short-term neurologic outcome in preterm infants. This prospective observational study included infants born at ≤32 weeks of gestational age and ≤1,500 g of birth weight. On the basis of brain ultrasonography findings, the infants were divided into two groups (favorable and unfavorable outcome group) at 36 weeks of corrected age or at discharge. aEEG was performed at 12-14 h (day-1), 46-48 h (day-2), 70-72 h (day-3), and 1 week (day-7) of life. The aEEG recordings were analyzed using the criteria described by Burdjalov et al.23 and the serial scores of aEEG were compared between the two groups. Thirty five infants were enrolled and 18 infants and 17 infants were identified into both groups, respectively. Infants in the favorable outcome group showed high scores in almost all parameters and the score of all parameters increased over time. However, the scores of all components decreased in day-2 compared with those of day 1 in the unfavorable outcome group. The total score less than 3 of day-2 has predictive value of 70.6% of sensitivity and 72.2% of specificity for unfavorable outcome. We found that aEEG is a useful predictor for short-term neurologic outcome in preterm infants.

Locked-In Syndrome after Traumatic Basilar Artery Entrapment within a Clivus Fracture: A Case Report and Review of the Literature.

We report the case of a 58-year-old male with a rare vascular complication after traumatic head injury: entrapment of the basilar artery into a fracture of the clivus, ultimately leading to a locked-in syndrome due to brainstem infarction. Review of the literature revealed 19 earlier published cases of basilar artery entrapment within traumatic longitudinal clival fractures. In the majority of these patients there is an unfavorable neurological outcome.

Ability of Fibrin Monomers to Predict Progressive Hemorrhagic Injury in Patients with Severe Traumatic Brain Injury.

Progressive hemorrhagic injury (PHI) is common in patients with severe traumatic brain injury (TBI) and is associated with poor outcomes. TBI-associated coagulopathy is frequent and has been described as risk factor for PHI. This coagulopathy is a dynamic process involving hypercoagulable and hypocoagulable states either one after the other either concomitant. Fibrin monomers (FMs) are a direct marker of thrombin action and thus reflect coagulation activation. This study sought to determine the ability of FM to predict PHI after severe TBI. We conducted a prospective, observational study including all severe TBI patients admitted in the trauma center. Between September 2011 and September 2016, we enrolled patients with severe TBI into the derivation cohort. Between October 2016 and December 2018, we recruited the validation cohort on the same basis. Study protocol included FM measurements and standard coagulation test at admission and two computed tomography (CT) scans (upon arrival and at least 6h thereafter). A PHI was defined by an increment in size of initial lesion (25% or more) or the development of a new hemorrhage in the follow-up CT scan. Multivariate logistic regression analysis was applied to identify predictors of PHI. Overall, 106 patients were included in the derivation cohort. Fifty-four (50.9%) experienced PHI. FM values were higher in these patients (151 [136.8-151] vs. 120.5 [53.3-151], p < 0.0001). The ROC curve demonstrated that FM had a fair accuracy to predict the occurrence of PHI with an area under curve of 0.7 (95% CI [0.6-0.79]). The best threshold was determined at 131.7μg/ml. In the validation cohort of 54 patients, this threshold had a negative predictive value of 94% (95% CI [71-100]) and a positive predictive value of 49% (95% CI [32-66]). The multivariate logistic regression analysis identified 2 parameters associated with PHI: FM ≥ 131.7 (OR 6.8; 95% CI [2.8-18.1]) and Marshall category (OR 1.7; 95% CI [1.3-2.2]). Coagulopathy was not associated with PHI (OR 1.3; 95% CI [0.5-3.0]). The proportion of patients with an unfavorable functional neurologic outcome at 6-months follow-up was higher in patients with positive FM: 59 (62.1%) versus 16 (29.1%), p < 0.0001. FM levels at admission had a fair accuracy to predict PHI in patients with severe TBI. FM values ≥ 131.7μg/ml are independently associated with the occurrence of PHI.

Transcranial Doppler ultrasound findings in children with moderate-to-severe traumatic brain injury following abusive head trauma.

PurposeAbusive head trauma (AHT) is the leading cause of fatal head injuries for children under 2 years. The objective was to evaluate, using transcranial Doppler ultrasound (TCD), whether children with AHT have a similar neurovascular response to injury compared with children without AHT.MethodsRetrospective sub-analysis of previously prospectively acquired data in a pediatric intensive care unit in a level 1 trauma hospital. TCD was performed daily until hospital day 8, discharge, or death. Neurologic outcome was assessed using the Glasgow Outcome Scale Extended (GOS-E Peds) at 1 month from initial injury.ResultsSixty-nine children aged 1 day to 17 years with moderate-to-severe traumatic brain injury were enrolled. Fifteen children suffered AHT and 54 had no suspicion for AHT. Fifteen children with AHT underwent 80 serial TCD examinations; 54 children without AHT underwent 308 exams. After standardization for age and gender normative values, there was no statistically significant difference in mean cerebral blood flow velocity of the middle cerebral artery (VMCA) between children with and without AHT. There was no difference in the incidence of extreme cerebral blood flow velocity (CBFV, greater or less than 2 standard deviations from normative value) between groups. Within the AHT group, there were no statistically significant differences in VMCA between children with a favorable (GOS-E Peds 1–4) versus unfavorable neurologic outcome (GOS-E Peds 5–8).ConclusionChildren with AHT have no significant differences in VMCA or percentage of extreme CBFV in the middle cerebral artery compared to with those without AHT.

Abstract 475: Association Between Bystander Delay in Activating the Emergency Response System and Outcomes Following Out-Of-Hospital Cardiac Arrest: All-Japan National Utstein Registry

Introduction: An emphasis on the chain of survival has contributed to improved outcomes of out-of-hospital cardiac arrest (OHCA). Although immediate recognition of cardiac arrest (CA) and activation of the emergency response system are the first links in the chain of survival, their impact on outcomes is unclear. Hypothesis: Delayed time from collapse to activation of the emergency response system (bystander delay) is associated with an unfavorable neurological outcome after adult OHCA. Methods: Data from the prospective, nationwide, population-based All-Japan Utstein Registry of the Fire and Disaster Management Agency between January 1, 2012 and December 31, 2016 were analyzed. Of the 625,916 eligible cases, 164,256 adult, non-traumatic, witnessed OHCA including bystander delay times (age, 79 [IQR, 67-86] years; 60% male) were studied. The primary outcome measure was favorable neurological outcome 1 month after an OHCA, defined as a score of 1 or 2 on the Cerebral Performance Category Scale. Results: The median bystander delay time of 2.0 [1.0-4.0] min was shorter among patients who achieved a favorable outcome as compared to 3.0 [1.0-6.0] min (P &lt; 0.001) for patients with an unfavorable outcome. In multivariable logistic regression analyses, bystander delay had an OR for favorable neurological outcome of 0.94 [95% CI, 0.93-0.97] after adjusting for age, sex, etiology of arrest, first documented rhythm, provision of bystander CPR, use of public access automated external defibrillator, epinephrine administration, time intervals of activation of the emergency response system and hospital arrival, and collapse to initiation of CPR, and regional location. Similarly, bystander delay was independently associated with reduced neurologically favorable survival among patients who received bystander CPR within one minute of collapse (adjusted OR, 0.97 [0.97-0.98]). Conclusions: Bystander delay was independently associated with decreased odds of neurologically favorable survival, even among patients for whom bystander CPR was immediately performed.

Life-long epigenetic programming of cortical architecture by maternal 'Western' diet during pregnancy.

The evolution of human diets led to preferences toward polyunsaturated fatty acid (PUFA) content with 'Western' diets enriched in ω-6 PUFAs. Mounting evidence points to ω-6 PUFA excess limiting metabolic and cognitive processes that define longevity in humans. When chosen during pregnancy, ω-6 PUFA-enriched 'Western' diets can reprogram maternal bodily metabolism with maternal nutrient supply precipitating the body-wide imprinting of molecular and cellular adaptations at the level of long-range intercellular signaling networks in the unborn fetus. Even though unfavorable neurological outcomes are amongst the most common complications of intrauterine ω-6 PUFA excess, cellular underpinnings of life-long modifications to brain architecture remain unknown. Here, we show that nutritional ω-6 PUFA-derived endocannabinoids desensitize CB1 cannabinoid receptors, thus inducing epigenetic repression of transcriptional regulatory networks controlling neuronal differentiation. We found that cortical neurons lose their positional identity and axonal selectivity when mouse fetuses are exposed to excess ω-6 PUFAs in utero. Conversion of ω-6 PUFAs into endocannabinoids disrupted the temporal precision of signaling at neuronal CB1 cannabinoid receptors, chiefly deregulating Stat3-dependent transcriptional cascades otherwise required to execute neuronal differentiation programs. Global proteomics identified the immunoglobulin family of cell adhesion molecules (IgCAMs) as direct substrates, with DNA methylation and chromatin accessibility profiling uncovering epigenetic reprogramming at >1400 sites in neurons after prolonged cannabinoid exposure. We found anxiety and depression-like behavioral traits to manifest in adult offspring, which is consistent with genetic models of reduced IgCAM expression, to suggest causality for cortical wiring defects. Overall, our data uncover a regulatory mechanism whose disruption by maternal food choices could limit an offspring's brain function for life.