Risk Of Adverse Neurological Outcomes Research Articles

RADT-12. CLINICAL RELEVANCE OF RADIATION-INDUCED CAVERNOUS MALFORMATIONS

Abstract BACKGROUND Radiation-induced cavernous malformations (RICMs) are delayed complications of brain irradiation during childhood. The prevalence of cavernomas in the general population was found to be 0.5% in a large prospective study. However, the exact incidence of RICM in children and the mechanisms of the development of RICM remain largely unknown since the cumulative incidence of RICM is underreported. Recent systemic review revealed 113 children with RICM after treatment of brain tumors and leukemias. 67% were asymptomatic and 21% showed signs of hemorrhage. In this review, the average dose of radiation was 50Gy and the mean time to detection was 9.2 years. METHODS We conducted a retrospective review of RICM in children who underwent total body irradiation (TBI) for bone marrow transplant. Our study goals were to better understand the incidence and patterns of RICMs and to develop a risk stratification for monitoring. Between 9/2000-1/2023, 161 patients underwent TBI. Of 47 patients who had post-transplant brain MR imaging done, 15 patients had MRIs available for review. RESULTS Of 15 reviewed MRIs, 11 (73.3%) had RICMs identified. 6 cases had >5 small (<3mm) RICMs. Most RICMs were in the frontal lobes. MRIs were obtained an average of 64 months from TBI. Radiation doses ranged from 200-2760cGy with an average of 1144cGy. There was 1 case of microhemorrhage due to RICM. None of our patients deceased as a result of their RICM. CONCLUSIONS Our cohort showed a high incidence (73.3%) of RICM despite low doses of radiation. Due to their typically small size and lack of clinical symptoms, RICM is often underreported. Although the outcome of cavernous malformation is favorable, it is important to understand the incidence and risk of adverse neurologic outcomes posed by RICMs. By performing regular surveillance, complications related to RICMs may be intervened with preventative procedures such as microsurgery.

Relation of MRI-Visible Perivascular Spaces and Other MRI Markers of Cerebral Small Vessel Disease.

Perivascular spaces (PVS) visible on brain MRI signal cerebral small vessel disease (CSVD). The coexistence of PVS with other CSVD manifestations likely increases the risk of adverse neurological outcomes. We related PVS to other CSVD manifestations and brain volumes that are markers of vascular brain injury and neurodegeneration. Framingham Heart Study (FHS) participants with CSVD ratings on brain MRI were included. PVS were rated in the basal ganglia (BG) and centrum semiovale (CSO) into grades I-IV and a category reflecting high burden in single or mixed CSO-BG regions. We related PVS to covert brain infarcts (CBI), white matter hyperintensities (WMH), cerebral microbleeds (CMB), total brain, hippocampal, and cortical gray matter volumes using adjusted multivariable regression analyses. In 2454 participants (mean age 54 ± 12 years), we observed that higher PVS burden in both BG and CSO was related to CMB in lobar and deep brain regions and increased WMH. Greater CSO PVS burden was associated with decreased total cortical gray volumes. PVS are associated with ischemic markers of CSVD and neurodegeneration markers. Further studies should elucidate the causality between PVS and other CSVD manifestations.

Smart ICV™ versus VOCAL™ in fetal brain volume assessment: Can we begin to trust artificial intelligence in clinical practice?

This paper is a commentary about an interesting research conducted with the aim of testing the agreement between manual versus automatic technique in measuring fetal brain volume. Given the high degree of reliability between the two techniques, we hope that the new automatic software can become useful tools in identifying fetuses with reduced brain volume at high risk of adverse neurological outcome.

Bedside monitoring of hypoxic ischemic brain injury using low-field, portable brain magnetic resonance imaging after cardiac arrest

BackgroundAssessment of brain injury severity is critically important after survival from cardiac arrest (CA). Recent advances in low-field MRI technology have permitted the acquisition of clinically useful bedside brain imaging. Our objective was to deploy a novel approach for evaluating brain injury after CA in critically ill patients at high risk for adverse neurological outcome. MethodsThis retrospective, single center study involved review of all consecutive portable MRIs performed as part of clinical care for CA patients between September 2020 and January 2022. Portable MR images were retrospectively reviewed by a blinded board-certified neuroradiologist (S.P.). Fluid-inversion recovery (FLAIR) signal intensities were measured in select regions of interest. ResultsWe performed 22 low-field MRI examinations in 19 patients resuscitated from CA (68.4% male, mean [standard deviation] age, 51.8 [13.1] years). Twelve patients (63.2%) had findings consistent with HIBI on conventional neuroimaging radiology report. Low-field MRI detected findings consistent with HIBI in all of these patients. Low-field MRI was acquired at a median (interquartile range) of 78 (40–136) hours post-arrest. Quantitatively, we measured FLAIR signal intensity in three regions of interest, which were higher amongst patients with confirmed HIBI. Low-field MRI was completed in all patients without disruption of intensive care unit equipment monitoring and no safety events occurred. ConclusionIn a critically ill CA population in whom MR imaging is often not feasible, low-field MRI can be deployed at the bedside to identify HIBI. Low-field MRI provides an opportunity to evaluate the time-dependent nature of MRI findings in CA survivors.

The Impact of Different Degrees of Intraventricular Hemorrhage on Mortality and Neurological Outcomes in Very Preterm Infants: A Prospective Cohort Study.

ObjectiveIntraventricular hemorrhage (IVH) is a common complication in preterm infants and is related to neurodevelopmental outcomes. Infants with severe IVH are at higher risk of adverse neurological outcomes and death, but the effect of low-grade IVH remains controversial. The purpose of this study was to evaluate the impact of different degrees of IVH on mortality and neurodevelopmental outcomes in very preterm infants.MethodsPreterm infants with a gestational age of <30 weeks admitted to neonatal intensive care units were included. Cerebral ultrasound was examined repeatedly until discharge or death. All infants were followed up to 18–24 months of corrected age. The impact of different grades of IVH on death and neurodevelopmental disability was assessed by multiple logistic regression.ResultsA total of 1,079 preterm infants were included, and 380 (35.2%) infants had grade I-II IVH, 74 (6.9%) infants had grade III-IV IVH, and 625 (57.9%) infants did not have IVH. The mortality in the non-IVH, I-II IVH, and III-IV IVH groups was 20.1, 19.7, and 55.2%, respectively (p < 0.05), and the incidence of neurodevelopmental disabilities was 13.9, 16.1, and 43.3%, respectively (p < 0.05), at 18–24 months of corrected age. After adjusting for confounding factors, preterm infants with III-IV IVH had higher rates of cerebral palsy [26.7 vs. 2.4%, OR = 6.10, 95% CI (1.840–20.231), p = 0.003], disability [43.3 vs. 13.9%, OR = 2.49, 95% CI (1.059–5.873), p = 0.037], death [55.2 vs. 20.1%, OR = 3.84, 95% CI (2.090–7.067), p < 0.001], and disability + death [73.7 vs. 28.7%, OR = 4.77, 95% CI (2.518–9.021), p < 0.001] compared to those without IVH. However, the mortality and the incidence of neurodevelopmental disability in infants with I-II IVH were similar to those without IVH (p > 0.05).ConclusionsSevere IVH but not mild IVH increased the risk of mortality and neurodevelopmental disability in very preterm infants.

Call to action: long‐term neurodevelopment in monochorionic twins

Call to action: long‐term neurodevelopment in monochorionic twins

Amplitude integrated EEG: how much it helps in prognostication in neonatal encephalopathy?

Introduction Neonatal encephalopathy (NE) is associated with a high risk of adverse neurological outcomes. Several neurodiagnostic tests have been evaluated to predict the prognosis. Amplitude integrated Electroencephalogram (aEEG) is now being commonly used for bedside evaluation of cerebral function. There is limited data on the role of aEEG for prognostication in NE, from resource-limited settings. Objective To evaluate the predictive ability of aEEG for abnormal neurological outcomes in neonatal encephalopathy or neonates with encephalopathy. Methods Neonates above 35 weeks of gestation admitted to NICU in a tertiary care hospital with a diagnosis of encephalopathy were enrolled. Clinical characteristics severity of encephalopathy and seizures were recorded. Amplitude integrated recording was started at admission and continued till recovery of trace to normal or for 10 days. The primary outcome was death or abnormal neurological status at 3–6 months of age. The study was registered in the Clinical Trial Registry of India (CTRI/2013/05/003612) Results The incidence of NE was 6% of total admission. Moderate and severe encephalopathy occurred in 58 and 39% of babies respectively. Hypoxic-ischemic encephalopathy was the most common cause. Clinical seizures occurred in 91% of cases. An abnormal aEEG trace was observed in 51 (76.1%) infants with NE. For adverse neurological outcomes at an age average of 4.5 months of age, aEEG had a sensitivity, specificity, NPV, and PPV of 100, 54.2, 100, and 77.5, respectively. Conclusions Clinical staging and aEEG has good predictive ability to detect an adverse neurological outcome. aEEG improves the ability to predict abnormal outcome in babies with moderate encephalopathy. Early recovery of aEEG abnormality correlates with better neurodevelopmental outcomes. KEY MESSAGES What’s known: aEEG is a useful modality to assess neurodevelopmental outcomes however data from developing countries is lacking. What’s new: aEEG monitoring in babies in neonatal encephalopathy may improve the prediction of abnormal neurological outcomes in babies with moderate encephalopathy.

Safety and feasibility of a factory-calibrated continuous glucose monitoring system in term and near-term infants at risk of hypoglycemia.

Hypoglycemia increases the risk of adverse neurological outcomes in neonates. Adequate glucose monitoring requires repetitive and painful blood sampling. We aimed to evaluate the feasibility and accuracy of a continuous glucose monitoring system (CGMS) using factory-calibrated sensors to improve glucose monitoring and decrease the frequency of blood samples in neonates. A methodological study was conducted to investigate a correlation of CGMS values with blood glucose measurements. Factory-calibrated CGMS sensors were placed on 21 infants at risk of hypoglycemia after delivery. CGMS values were compared with blood glucose concentrations. Thirty-seven pairs of CGMS and blood glucose values were obtained. There was a good correlation between CGMS and blood glucose values (R=0.67, p<0.01) with a mean difference (2 standard deviations) of 9.78 (-24.68 to 44.25) mg/dL. The mean differences at <3 hours and ≥3 hours after sensor placement were 17.35 (-4.54 to 39.21) mg/dL and 0.88 (-37.62 to 39.38) mg/dL, respectively. CGMS values were significantly higher than blood glucose concentration at <3 hours after sensor placement (p<0.01), whereas no significant differences in glucose values were observed between the CGMS and blood glucose values at ≥3 hours after sensor placement (p=0.852). The factory-calibrated CGMS was a safe and feasible modality for glucose monitoring. However, it has a tendency to overestimate the blood glucose concentrations. Therefore, this system should be used cautiously for neonates at risk of hypoglycemia, especially within 3 hours after sensor placement.

Understanding the Relationship Between Maternal Thyroid Hormones and Neurodevelopmental Outcomes

Background: In utero exposures to endocrine disrupting chemicals can impact a range of health outcomes for the offspring. Specifically, when considering potential disruptions to proper maternal thyroid functioning due to chemical exposures there is increasing concern that adverse neurodevelopmental outcomes may occur in the offspring. A preclinical outcome, hypothyroxinemia (low free thyroxine and thyroid stimulating hormone within the reference rage) is being recognized as a potential outcome of interest in understanding alterations in maternal thyroid functioning. Methods: A literature review on the associations between maternal thyroid hormone levels, including maternal hypothyroxinemia and offspring neurodevelopmental outcomes was conducted. Studies were categorized if the main analysis presented evaluated the risk of adverse neurological outcomes as a result of incremental changes in maternal fT4 or the categorical outcome of yes/no hypothyroxinemia. Results: We found that altered free thyroxine (fT4) in early pregnancy has the most evidence regarding the relationship between altered maternal thyroid hormone homeostasis and adverse neurodevelopmental outcomes in offspring. We will present multiple approaches to utilize data from the literature to evaluate the magnitude of impact from altered maternal fT4 levels on offspring neurodevelopment. These approaches consist of both evaluating dose-response relationships between maternal fT4 and offspring neurodevelopment and examining how shifts in distributions of thyroid hormone levels may place additional proportions of a population at risk. Conclusions: The presented methods can be used to assess the potential neurodevelopmental impacts on the fetus of a pregnant mother exposed to a chemical that may potentially alter homeostatic thyroid functioning (e.g., PCBs, perchlorate, PBDEs, PFAs, BPA)

Brain inflammation and injury at 48 h is not altered by human amnion epithelial cells in ventilated preterm lambs.

Mechanical ventilation of preterm neonates is associated with neuroinflammation and an increased risk of adverse neurological outcomes. Human amnion epithelial cells (hAECs) have anti-inflammatory and regenerative properties. We aimed to determine if intravenous administration of hAECs to preterm lambs would reduce neuroinflammation and injury at 2 days of age. Preterm lambs were delivered by cesarean section at 128-130 days' gestation (term is ~147 days) and either ventilated for 48 h or humanely killed at birth. Lambs received 3 mL surfactant (Curosurf) via endotracheal tube prior to delivery (either with or without 90 × 106 hAECs) and 3 mL intravenous phosphate-buffered saline (with or without 90 × 106 hAECs, consistent with intratracheal treatment) after birth. Ventilation increased microglial activation, total oligodendrocyte cell number, cell proliferation and blood-brain barrier permeability (P < 0.05, PBS + ventilation and hAEC + ventilation vs. control), but did not affect numbers of immature and mature oligodendrocytes. Ventilation reduced astrocyte and neuron survival (P < 0.05, PBS + ventilation and hAEC + ventilation vs. control). hAEC administration did not alter markers of neuroinflammation or injury within the white or gray matter. Mechanical ventilation for 48 h upregulated markers of neuroinflammation and injury in preterm lambs. Administration of hAECs did not affect markers of neuroinflammation or injury. Mechanical ventilation of preterm lambs for 48 h, in a manner consistent with contemporary neonatal intensive care, causesneuroinflammation, neuronal loss and pathological changes in oligodendrocyte and astrocyte survival consistent with evolving neonatal brain injury.Intravenous administration of hAECs immediately after birth did not affect neonatal cardiorespiratory function and markers of neuroinflammation or injury.Reassuringly, our findings in a translational large animal model demonstrate that intravenous hAEC administration to the preterm neonate is safe.Considering that hAECs are being used in phase 1 trials for the treatment of BPD in preterm infants, with future trials planned for neonatal neuroprotection, we believe these observations are highly relevant.

Prognostic value of amplitude-integrated EEG in neonates with high risk of neurological sequelae.

ObjectiveTo determine the efficacy and the prognostic value of amplitude‐integrated electroencephalography (aEEG) in term and near‐term neonates with high risk of neurological sequelae.MethodsInfants of ≥35 weeks of gestation diagnosed with neonatal encephalopathy or with high risk of brain injury were included. All eligible infants underwent aEEG within 6 h after clinical assessment. The infants were followed up 12 months to evaluate neurological development.ResultsA total of 250 infants were eligible, of which 85 had normal aEEG, 81 had mildly abnormal aEEG, and 84 had severely abnormal aEEG. Of these infants, 168 were diagnosed with different neonatal encephalopathies, 27 with congenital or metabolic diseases, and 55 with high risk of brain injury. In all, 22 infants died, 19 were lost to follow‐up, and 209 completed the follow‐up at 12 months, of which 62 were diagnosed with a neurological disability. Statistical analysis showed that severely abnormal aEEG predicted adverse neurological outcome with a sensitivity of 70.2%, a specificity of 87.1%, a positive predictive value of 75.6%, and a negative predictive value of 83.7%.InterpretationaEEG can predict adverse outcomes in high‐risk neonates and is a useful method for monitoring neonates with high risk of adverse neurological outcomes.

Independent role of neonatal seizures in subsequent neurological outcomes: a population-based study.

This population-based study aimed to estimate the impact of neonatal seizures on subsequent neurological outcomes, regardless of underlying etiology. We performed a retrospective cohort study (1st January 2009-31st December 2014), using a USA nationwide claims database. Newborn infants enrolled in 2009 were followed for up to 6years. Neonatal seizures were identified by combining the International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code of 779.0 (convulsions in newborn), procedure codes of electroencephalogram and brain imaging, and antiepileptic drugs claims. Cox regression models were built to estimate the independent impact of neonatal seizures on developing epilepsy, intellectual disability, psychiatric/behavioral disorders, and headache. Out of 490071 newborn infants (251850 males [51.4%], 238221 females [48.6%]), 800 neonatal seizure cases were identified. After controlling for sex, birthweight, preterm birth status, and underlying etiology, neonates with seizures were more likely to have epilepsy (hazard ratio=32.7; 95% confidence interval [CI]=27.7-38.7; p<0.001), intellectual disability (hazard ratio=2.0; 95% CI=1.8-2.3; p<0.001), and headache (hazard ratio=1.6; 95% CI=1.1-2.2; p=0.013) than those without seizures. Observed covariates being equal, seizures in neonates appeared to play a significant role in developing epilepsy, intellectual disability, and headache. The findings showed a detrimental impact of the event in the very early life on neurological outcomes in later life. Seizures had their own impact on the development of adverse neurological outcomes. The magnitude of impact was quite large in epilepsy.

Fetal intracranial hemorrhage. Prenatal diagnosis and postnatal outcomes

Objective: To present our experience with 14 cases of fetal intracranial hemorrhage (ICH).Methods: Cases of fetal ICH detected in our institution between 2005 and 2016 by ultrasonography. Maternal characteristics, ultrasound and MRI findings, and postnatal outcome were noted.Results: Twelve cases (86.7%) were identified during a third trimester routine scan at a median gestational age of 30.6 weeks. The ICH was classified as Grade 2 in two cases, Grade 3 in three cases, and Grade 4 in nine cases. Nine cases were bilateral and five were unilateral (four left/one right). The 11 MRI available confirmed grade and location and, in six cases (54.5%), added new findings. There were six terminations of pregnancy, one intrauterine fetal death and seven babies born alive. These were followed up for 28 months (range 3–96). Some grade of neurologic impairment was observed in five children (71.4%, one Grade 3/four Grade 4), mainly mild to moderate motor sequelae.Conclusion: Diagnosis of fetal ICH is amenable to antenatal US. Most of the cases identified are of high grade and usually detected during the third trimester. MRI is a valuable complementary tool in evaluating ICH. Conversely to that previously reported, postnatal survival is high but it entails the risk of adverse neurologic outcome in most neonates.

Does growth restriction increase the vulnerability to acute ventilation-induced brain injury in newborn lambs? Implications for future health and disease.

Fetal growth restriction (FGR) and preterm birth are frequent co-morbidities, both are independent risks for brain injury. However, few studies have examined the mechanisms by which preterm FGR increases the risk of adverse neurological outcomes. We aimed to determine the effects of prematurity and mechanical ventilation (VENT) on the brain of FGR and appropriately grown (AG, control) lambs. We hypothesized that FGR preterm lambs are more vulnerable to ventilation-induced acute brain injury. FGR was surgically induced in fetal sheep (0.7 gestation) by ligation of a single umbilical artery. After 4 weeks, preterm lambs were euthanized at delivery or delivered and ventilated for 2 h before euthanasia. Brains and cerebrospinal fluid (CSF) were collected for analysis of molecular and structural indices of early brain injury. FGRVENT lambs had increased oxidative cell damage and brain injury marker S100B levels compared with all other groups. Mechanical ventilation increased inflammatory marker IL-8 within the brain of FGRVENT and AGVENT lambs. Abnormalities in the neurovascular unit and increased blood-brain barrier permeability were observed in FGRVENT lambs, as well as an altered density of vascular tight junctions markers. FGR and AG preterm lambs have different responses to acute injurious mechanical ventilation, changes which appear to have been developmentally programmed in utero.

Continuous subcutaneous glucose monitoring is accurate in term and near-term infants at risk of hypoglycaemia.

Postnatal hypoglycaemia increases the risk of adverse neurological outcomes in newborn infants, and adequate glucose control requires repetitive and painful blood sampling. This study evaluated a continuous glucose monitoring system (CGMS) that aims to improve glucose control and decrease the frequency of blood samples taken from neonates. CGMS sensors, which measure glucose values every five minutes and require calibration twice a day, were placed on 20 infants at risk of hypoglycaemia. The infants also underwent blood glucose sampling, and the blood glucose values were compared with CGMS values six times during the first 30 minutes after sampling. We used 97/264 (37%) of the blood glucose values taken for the CGMS calibration. The highest accuracy, a mean of 0.22 (95% confidence interval 0.13-0.30 mmol/L), was found 15-19 minutes after sampling, due to the calibration process. No significant subcutaneous glucose time lag was detectable. The CGMS system was an accurate and feasible method for glucose control, provided earlier detection of hypoglycaemia in newborn infants and reduced their exposure to procedural pain. The delay in calibration in infants was a new finding and needs to be taken into account when comparing CGMS readings to blood glucose values.

Low levels of mannose-binding lectin at admission increase the risk of adverse neurological outcome in preterm infants: a 1-year follow-up study

Objective: The aim of this study was to explore the association between serum levels of mannose-binding lectin (MBL) at admission and neurodevelopmental outcomes in a group of Chinese preterm infants, observed prospectively, until 1-year of corrected age (CA).Methods: All preterm infants used in this study were received from the neonatal intensive care unit (NICU) of our Hospital between 1 January 2012 and 31 August 2013. Serum levels of MBL and clinical data were obtained at the time of admission. The influence of MBL levels on neurological outcome was assessed by logistic regression analysis. Clinical follow-up was performed at 1 year.Results: The study cohort consisted of 175 neonates at baseline and 105 finished the 1-year follow-up. The mean serum MBL levels at the time of admission were significantly lower in children with adverse neurological outcomes as compared with children with no adverse [0.53 (SD = 0.09) μg/ml versus 0.80 (SD = 0.17) μg/ml, respectively; t = 8.342, p < 0.0001]. In multivariate analysis, there was an increased risk of adverse neurological outcomes associated with MBL ≤ 0.68 μg/ml [odds ratios (OR) = 12.11, 95% confidence interval (CI): 2.31–30.32; p < 0.0001] after adjusting for possible factors.Conclusion: Preterm infants who had low levels of MBL at admission are exposed to an increased risk of adverse neurological outcomes.

Impact of time to return of spontaneous circulation on neuroprotective effect of targeted temperature management at 33 or 36 degrees in comatose survivors of out-of hospital cardiac arrest

AimTime to Return of Spontaneous Circulation (ROSC) has a plausible relation to severity of hypoxic injury before and during resuscitation in Out-of-Hospital Cardiac Arrest (OHCA), and has consistently been associated with adverse outcome. The effect of Targeted Temperature Management (TTM) may not be similar over the full spectrum of time to ROSC. This study investigated the possible beneficial effect of targeting 33°C over 36°C on the prognostic importance of time to ROSC. MethodsIn predefined sub-study of the TTM-trial (NEJM 2013) we investigated the relationship between time to ROSC, level of TTM and mortality and neurological outcome as assessed by the Cerebral Performance Category (CPC) scale and modified Rankin Scale (mRS) after 180 days. ResultsProlonged time to ROSC was significantly associated with increased mortality with a hazard ratio (HR) of 1.02 per minute (95% CI 1.01–1.02). Level of TTM did not modify the association of time to ROSC and mortality, pinteraction=0.85. Prolonged time to ROSC was associated with reduced odds of surviving with a favorable neurological outcome for CPC (p=0.008 for CPC 1–2) and mRS (p=0.17, mRS 0–3) with no significant interaction with level of TTM. ConclusionTime to ROSC remains a significant prognostic factor in comatose OHCA patients with regards to risk of death and risk of adverse neurological outcome. For any time to ROSC, targeting 33°C in TTM was not associated with benefit with regards to reducing mortality or risk of adverse neurological outcome compared to targeting 36°C.

Abstract 14644: Impact of Time to Return of Spontaneous Circulation on Neuro-protective Effect of Target Temperature Management at 33 and 36 Degrees in Comatose Survivors of Out of Hospital Cardiac Arrest

Introduction: Prolonged time to Return of Spontaneous Circulation (ttROSC) after Out of Hospital Cardiac Arrest (OHCA) has consistently been associated with adverse outcome by a plausible direct relation to severity of anoxic injury. Hypothesis: Target temperature management (TTM) is assumed effective against anoxic brain injury and we hypothesized that TTM at 33 degrees would be more beneficial with prolonged time to ROSC compared to 36 degrees. Methods: In a post hoc analysis of the TTM trial, which showed no overall benefit of targeting 33 °C over 36 in 939 patients (NEJM 2013), we investigated the relation of time to ROSC and mortality and neurological outcome as assessed by the Cerebral Performance Category (CPC) and Modified Ranking Scale (mRS) after 180 days. Results: Prolonged ttROSC was significantly and independently associated with increased mortality, p&lt;0.001 (figure), with Hazard Ratio (HR) of 1.02 (95% CI 1.01-1.02, p&lt;0.001) per minute increase and level of TTM did not modify this association, p interaction =0.85. In survivors prolonged ttROSC was associated with increased odds of surviving with an unfavorable neurological outcome for CPC (p=0.008 for CPC 3-4) and a similar trend, albeit not statistically significant was observed for mRS (p=0.17, mRS 4-5). Odds for unfavorable neurological outcome (CPC&gt;2, mRS&gt;3) was not modified by levels of TTM overall. Conclusion: Time to ROSC remains a significant prognostic factor in comatose patients resuscitated from OHCA with regards to risk of death and risk of adverse neurological outcome in survivors. TTM at 33 degrees offers no advantage over targeting 36 degrees with regards to mortality or neurological outcome in patients with prolonged time to ROSC. Figure: Mortality rates stratified by quartiles of tome to ROSC and by TTM level. Differences tested by log rank test in between TTM in strata

The Breadth and Type of Systemic Inflammation and the Risk of Adverse Neurological Outcomes in Extremely Low Gestation Newborns

BackgroundWe hypothesized that the risk of brain damage in extremely preterm neonates increases with the breadth and type of systemic inflammation, indexed by the number of elevated inflammation-related proteins and the number of functional categories of inflammation-related proteins exhibiting an elevated concentration. MethodsIn blood from 881 infants born before 28 weeks gestation, we measured the concentrations of 25 inflammation-related proteins, representing six functional categories (cytokines, chemokines, growth factors, adhesion molecules, metalloproteinases, and liver-produced acute phase reactant proteins) on postnatal days 1, 7, and 14. We evaluated associations between the number and type of proteins whose concentrations were elevated on two separate occasions a week apart and the diagnoses of ventriculomegaly as a neonate, and at 2 years, microcephaly, impaired early cognitive functioning, cerebral palsy, and autism risk as assessed with the Modified Checklist for Autism in Toddlers screen, and in a subset of these children from 12 of 14 sites (n = 826), an attention problem identified with the Child Behavior Checklist. ResultsThe risk of abnormal brain structure and function overall was increased among children who had recurrent and/or persistent elevations of the 25 proteins. The risk for most outcomes did not rise until at least four proteins in at least two functional categories were elevated. When we focused our analysis on 10 proteins previously found to be associated consistently with neurological outcomes, we found the risk of low Mental Development Index on the Bayley Scales of Infant Development-II, microcephaly, and a Child Behavior Checklist-defined attention problem increased with higher numbers of these recurrently and/or persistently elevated proteins. InterpretationIncreasing breadth of early neonatal inflammation, indexed by the number of protein elevations or the number of protein functional classes elevated, is associated with increasing risk of disorders of brain structure and function among infants born extremely preterm.

OP19.06: Outcome in isolated posterior fossa malformations: a systematic review and meta‐analysis

The aim of this meta-analysis was to explore the outcome of isolated posterior fossa malformations diagnosed pre-natally. This review was performed according to a protocol designed a priori and recommended for systematic reviews and meta-analysis (MOOSE). The posterior fossa anomalies included in this review are Dandy-Walker malformation (DWM), vermian hypoplasia (VH), megacisterna magna (MCM) and Blake's pouch cyst (BPC). Only studies with a clear definition of the posterior fossa malformation analysed and a confirmed post-natal diagnosis were considered suitable for inclusion. The outcomes observed were chromosomal abnormalities, development of ventriculomegaly before or after birth, need for shunt associated abnormalities detected only at prenatal MRI and missed at the scan, associated abnormalities detected only after birth and missed prenatally and neurodevelopmental outcome, including neurological, motor, cognitive, intellectual and socio-behavioural assessment. Twenty studies included 434 fetuses were included in the analysis. Posterior fossa abnormalities were isolated in 35.3% (154/434) of the cases. The incidence of the different outcomes explored in this review are reported in table 1. OP19.06: Table 1. Outcome in isolated posterior fossa anomalies The incidence of abnormal neurodevelopmental outcome in fetuses with isolated DWM is sensibly lower than previously reported. Fetuses with MCM, BPC and VH are at very low risk of chromosomal abnormalities and neurocognitive deficits. Future studies should investigate potential markers to identify those fetuses at higher risk of adverse neurological outcome.