Letter to editor: Brain tissue oxygen partial pressure monitoring and prognosis of patients with traumatic brain injury: a meta-analysis of published cases.

This critique evaluates a letter to the editor discussing the role of brain tissue oxygen partial pressure (PbtO2) monitoring in the prognosis of patients with traumatic brain injury (TBI). The meta-analysis aims to synthesize existing evidence, highlighting the potential of PbtO2 monitoring as an early indicator of cerebral hypoxia and its correlation with improved patient outcomes. Despite these promising findings, the analysis is constrained by significant methodological variability among the included studies, potential publication bias, and the practical challenges of implementing PbtO2 monitoring widely. The letter emphasizes the need for standardized protocols and further research to solidify the clinical utility of PbtO2 monitoring and integrate it with other monitoring strategies for comprehensive TBI management.

Neurological Impact of Slower Rewarming during Bypass Surgery in Infants.

BACKGROUND: Hypothermia is a neuroprotective strategy during cardiopulmonary bypass. Rewarming entailing a rapid rise in cerebral metabolism might lead to secondary neurological sequelae. In this pilot study, we aimed to validate the hypothesis that a slower rewarming rate would lower the risk of cerebral hypoxia and seizures in infants. METHODS: This is a prospective, clinical, single-center study. Infants undergoing cardiac surgery in hypothermia were rewarmed either according to the standard (+1°C in < 5 minutes) or a slow (+1°C in > 5-8 minutes) rewarming strategy. We monitored electrocortical activity via amplitude-integrated electroencephalography (aEEG) and cerebral oxygenation by near-infrared spectroscopy during and after surgery. RESULTS: Fifteen children in the standard rewarming group (age: 13 days [5-251]) were cooled down to 26.6°C (17.2-29.8) and compared with 17 children in the slow-rewarming group (age: 9 days [4-365]) with a minimal temperature of 25.7°C (20.1-31.4). All neonates in both groups (n = 19) exhibited suppressed patterns compared with 28% of the infants > 28 days (p < 0.05). During rewarming, only 26% of the children in the slow-rewarming group revealed suppressed aEEG traces (vs. 41%; p = 0.28). Cerebral oxygenation increased by a median of 3.5% in the slow-rewarming group versus 1.5% in the standard group (p = 0.9). Our slow-rewarming group revealed no aEEG evidence of any postoperative seizures (0 vs. 20%). CONCLUSION: These results might indicate that a slower rewarming rate after hypothermia causes less suppression of electrocortical activity and higher cerebral oxygenation during rewarming, which may imply a reduced risk of postoperative seizures.

Background EEG Suppression Ratio for Early Detection of Cerebral Injury in Pediatric Cardiac Arrest.

BACKGROUND: Our objective was to assess the utility of the 1-h suppression ratio (SR) as a biomarker of cerebral injury and neurologic prognosis after cardiac arrest (CA) in the pediatric hospital setting. METHODS: Prospectively, we reviewed data from children presenting after CA and monitored by continuous electroencephalography (cEEG). Patients aged 1 month to 21 years were included. The SR, a quantitative measure of low-voltage cEEG (≤ 3 µV) content, was dichotomized as present or absent if there was > 0% suppression for one continuous hour. A multivariate logistic regression analysis was performed including age, sex, type of CA (i.e., in-hospital or out-of-hospital), and the presence of SR as a predictor of global anoxic cerebral injury as confirmed by magnetic resonance imaging (MRI). RESULTS: We included 84 patients with a median age of 4 years (interquartile range 0.9-13), 64% were male, and 49% (41/84) had in-hospital CA. Cerebral injury was seen in 50% of patients, of whom 65% had global injury. One-hour SR presence, independent of amount, predicted cerebral injury with 81% sensitivity (95% confidence interval (CI) (66-91%) and 98% specificity (95% CI 88-100%). Multivariate logistic regression analyses indicated that SR was a significant predictor of both cerebral injury (ß = 6.28, p < 0.001) and mortality (ß = 3.56, p < 0.001). CONCLUSIONS: The SR a sensitive and specific marker of anoxic brain injury and post-CA mortality in the pediatric population. Once detected in the post-CA setting, the 1-h SR may be a useful threshold finding for deployment of early neuroprotective strategies prior or for prompting diagnostic neuroimaging.

Effective method of monitoring cerebral tissue oxygen saturation in cardiac surgery patients by combined use of tNIRS-1 and bispectral index.

To continuously and noninvasively monitor the cerebral tissue oxygen saturation (StO2) and hemoglobin concentration (gasHb) in cardiac surgery patients, a method combining the use of a cerebral tissue oximeter using near infrared time-resolved spectroscopy (tNIRS-1) and the bispectral index (BIS) was developed in this study. Moreover, the correlation between the estimated hemoglobin concentration (estHb), measured via tNIRS-1, and the hemoglobin concentration (gasHb), analyzed using a blood gas analyzer, were compared. The relationship between the BIS and gasHb was also examined. Through the comparison of BIS and StO2 (r1), and estHb and gasHb (r2), the correlation between the two was clarified with maximum r1 and r2 values of 0.617 and 0.946, respectively. The relationship between BIS and gasHb (r3), showed that there was a favorable correlation with a maximum r3 value of 0.969. There was also a continuous correlation between BIS and StO2 in patients undergoing cardiac surgery. In addition, a strong correlation was found between estHb and gasHb, and between BIS and gasHb. It was therefore concluded that the combined use of BIS and tNIRS-1 is useful to evaluate cerebral hypoxia, allowing for quick response to cerebral hypoxia and reduction of hemoglobin concentration during the operation.

EEG patterns and their correlations with short- and long-term mortality in patients with hypoxic encephalopathy.

OBJECTIVE: To analyze the association between electroencephalographic (EEG) patterns and overall, short- and long-term mortality in patients with hypoxic encephalopathy (HE). METHODS: Retrospective, mono-center analysis of 199 patients using univariate log-rank tests (LR) and multivariate cox regression (MCR). RESULTS: Short-term mortality, defined as death within 30-days post-discharge was 54.8%. Long-term mortality rates were 69.8%, 71.9%, and 72.9%, at 12-, 24-, and 36-months post-HE, respectively. LR revealed a significant association between EEG suppression (SUP) and short-term mortality, and identified low voltage EEG (LV), burst suppression (BSP), periodic discharges (PD) and post-hypoxic status epilepticus (PSE) as well as missing (aBA) or non-reactive background activity (nrBA) as predictors for overall, short- and long-term mortality. MCR indicated SUP, LV, BSP, PD, aBA and nrBA as significantly associated with overall and short-term mortality to varying extents. LV and BSP were significant predictors for long-term mortality in short-term survivors. Rhythmic delta activity, stimulus induced rhythmic, periodic or ictal discharges and sharp waves were not significantly associated with a higher mortality. CONCLUSION: The presence of several specific EEG patterns can help to predict overall, short- and long-term mortality in HE patients. SIGNIFICANCE: The present findings may help to improve the challenging prognosis estimation in HE patients.

Prediction of encephalopathy in perinatal asphyxia score: reaching the unreached.

OBJECTIVES: Neonates who develop moderate to severe encephalopathy following perinatal asphyxia will benefit from therapeutic hypothermia. Current National Institute of Child Health and Human Development (NICHD) criteria for identifying encephalopathic neonates needing therapeutic hypothermia has high specificity. This results in correctly identifying neonates who have already developed moderate to severe encephalopathy but miss out many potential beneficiaries who progress to develop moderate to severe encephalopathy later. The need is therefore not just to diagnose encephalopathy, but to predict development of encephalopathy and extend the therapeutic benefit for all eligible neonates. The primary objective of the study was to develop and validate the statistical model for prediction of moderate to severe encephalopathy following perinatal asphyxia and compare with current NICHD criteria. METHODS: The study was designed as prospective observational study. It was carried out in a single center Level 3 perinatal unit in India. Neonates>35 weeks of gestation and requiring resuscitation at birth were included. Levels of resuscitation and blood gas lactate were used to determine the pre-test probability, Thompson score between 3 and 5 h of life was used to determine post-test probability of developing encephalopathy. Primary outcome measure: Validation of Prediction of Encephalopathy in Perinatal Asphyxia (PEPA) score by Holdout method. RESULTS: A total of 55 babies were included in the study. The PEPA score was validated by Holdout method where the fitted receiver-operating characteristic (ROC) area for the training and test sample were comparable (p=0.758). The sensitivity and specificity of various PEPA scores for prediction of encephalopathy ranged between 74 and 100% in contrast to NICHD criteria which was 42%. PEPA score of 30 had a best combination of sensitivity and specificity of 95 and 89% respectively. CONCLUSIONS: PEPA score has a higher sensitivity than NICHD criteria for prediction of Encephalopathy in asphyxiated neonates.

Argyrophilic nucleolar organizer regions as a promising biomarker for the detection of brain hypoxia levels caused by different doses of carbon monoxide poisoning.

OBJECTIVES: The purpose of the study is to investigate whether there is any relationship between mean argyrophilic nucleolar organizing regions (AgNOR) number and total AgNOR area/total nuclear area (TAA/TNA) ratio and the levels of brain hypoxia after exposure to different acute doses of carbon monoxide (CO) gas. METHODS: Each experimental group was exposed to CO gas (concentrations of 1,000, 3,000 and 5,000 ppm). Then, the rats were anesthetized, and blood samples were taken from the right jugular vein for carboxyhemoglobin levels detection. The rats were sacrificed on seventh day. AgNOR staining was applied to brain tissues. TAA/TNA and mean AgNOR number were detected for each nucleus. RESULTS: Significant differences were detected among all groups for TAA/TNA ratio, mean AgNOR number and carboxyhemoglobin level. According to a double comparison of groups, the differences between control and 1,000 ppm, control and 3,000 ppm, control and 5,000 ppm, and between 1,000 and 5,000 ppm were significant for TAA/TNA ratio. When mean AgNOR number was considered, significant differences were detected between control and 1,000 ppm, control and 3,000 ppm, control and 5,000 ppm, and between 1,000 and 3,000 ppm. CONCLUSION: AgNOR proteins may be used for early detection of the duration, intensity, and damage of brain injury caused by CO poisoning. Thus, effective treatment strategies can be developed for the prevention of hypoxic conditions.

OBJETIVOS: El objetivo del estudio es investigar si existe alguna relación entre el número medio de regiones organizadoras nucleolares argirófilas (AgNOR) y la proporción de área total de AgNOR/área nuclear total (TAA/TNA) y los niveles de ­hipoxia cerebral en la exposición a diferentes dosis agudas de gas monóxido de carbono (CO). MÉTODOS: Cada grupo experimental fue expuesto a gas CO (concentraciones de 1,000, 3,000 y 5,000 ppm). Luego las ratas fueron anestesiadas, se tomaron muestras de sangre de la vena yugular derecha para la detección de los niveles de carboxihemoglobina. Las ratas se sacrificaron el séptimo día. Se aplicó tinción con AgNOR en los tejidos cerebrales. Se detectaron el TAA/TNA y el número medio de AgNOR para cada núcleo. RESULTADOS: Se detectaron diferencias significativas entre todos los grupos para la relación TAA/TNA, el número medio de AgNOR y el nivel de carboxihemoglobina. Según la doble comparación de grupos, las diferencias entre control y 1,000 ppm, control y 3,000 ppm, control y 5,000 ppm y 1,000 y 5,000 ppm fueron significativas para la relación TAA/TNA. Cuando se consideró el número de AgNOR medio, se detectaron diferencias significativas entre control y 1,000ppm, control y 3,000ppm, control y 5,000 ppm y 1,000 y 3,000 ppm. CONCLUSIÓN: Las proteínas AgNOR pueden usarse para la detección temprana de la duración, intensidad y daño de la lesión cerebral causada por la intoxicación por CO. Por lo tanto, se pueden desarrollar estrategias de tratamiento efectivas para la prevención de condiciones hipóxicas.

Fetal Cerebral Oxygenation Is Impaired in Congenital Heart Disease and Shows Variable Response to Maternal Hyperoxia.

Background Impairments in fetal oxygen delivery have been implicated in brain dysmaturation seen in congenital heart disease (CHD), suggesting a role for in utero transplacental oxygen therapy. We applied a novel imaging tool to quantify fetal cerebral oxygenation by measuring T2* decay. We compared T2* in fetuses with CHD with controls with a focus on cardiovascular physiologies (transposition or left-sided obstruction) and described the effect of brief administration of maternal hyperoxia on T2* decay. Methods and Results This is a prospective study performed on pregnant mothers with a prenatal diagnosis of CHD compared with controls in the third trimester. Participants underwent a fetal brain magnetic resonance imaging scan including a T2* sequence before and after maternal hyperoxia. Comparisons were made between control and CHD fetuses including subgroup analyses by cardiac physiology. Forty-four mothers (CHD=24, control=20) participated. Fetuses with CHD had lower total brain volume (238.2 mm3, 95% CI, 224.6-251.9) compared with controls (262.4 mm3, 95% CI, 245.0-279.8, P=0.04). T2* decay time was faster in CHD compared with controls (beta=-14.4, 95% CI, -23.3 to -5.6, P=0.002). The magnitude of change in T2* with maternal hyperoxia was higher in fetuses with transposition compared with controls (increase of 8.4 ms, 95% CI, 0.5-14.3, P=0.01), though between-subject variability was noted. Conclusions Cerebral tissue oxygenation is lower in fetuses with complex CHD. There was variability in the response to maternal hyperoxia by CHD subgroup that can be tested in future larger studies. Cardiovascular physiology is critical when designing neuroprotective clinical trials in the fetus with CHD.

Neurocognitive outcomes in adults following cerebral hypoxia: A systematic literature review.

BACKGROUND: Hypoxic ischemic brain injury (HIBI) occurs as a result of complete or partial disruption of cerebral oxygen supply. The physical and cognitive sequelae of adults following hypoxia varies widely. OBJECTIVE: To systematically review studies exploring the neuropsychological outcomes following hypoxic brain insult in adults. METHODS: Data was sourced using six databases (CINAHL, Cochrane, Embase, Medline, PsycInfo and Web of Science). Initial MESH terms identified 2,962 articles. After a three-stage independent review process, 18 articles, 9 case studies and 9 group studies were available for data synthesis from 1990-2012. Case study data was converted to standardised scores and compared to available test norms. Cohen's d was calculated to permit group data interpretation. RESULTS: Intellectual decrement was observed in some studies although difficult to delineate given the lack of use of measures of premorbid ability. Cognitive sequelae varied albeit with predominant disturbance in verbal memory, learning ability and executive function observed across studies. Wechsler Memory Scale Revised (WMS-R) visual memory was comparable to normative data. Impaired Rey Osterrieth Complex Figure (ROCFT) performance was found among group studies. Across visuo-constructional and attention domains, performance varied, although no significant difference relative to reported means was observed. CONCLUSIONS: Future studies should consider the use of standardised assessment protocols, which include measures of premorbid functioning and performance validity.

Neonatal neuron specific enolase, a sensitive biochemical marker of neuronal damage, is increased in preeclampsia: A retrospective cohort study.

BACKGROUND: Preeclampsia leads to chronic intrauterine hypoxia by interfering with placental blood supply. We aimed to investigate whether preeclampsia exposure has an influence on central nervous system of infants, as evaluated by analyzing neonatal serum neuron specific enolase (NSE). METHODS: This was a retrospective study including infants born in Nanfang hospital between Jan 2018 and Feb 2019 without asphyxia. They were divided into normotensive control group and preeclampsia group to compare the NSE levels. Furthermore, PE group was divided into five subgroups by lipstick of urine protein from 0 to 4+ to examine the relationship between urine protein and neonatal NSE. RESULTS: Of the 86 selected neonates, there were 40 in control group and 46 in preeclampsia group. The NSE levels were significantly higher in infants with preeclampsia exposure compared to those infants in control group (45.504 ± 17.926 vs 30.690 ± 4.475, P < 0.0001). Multiple regression analyses revealed that the preeclampsia (ß coef = 0.394, p = 0.041), 4+ proteinuria (ß coef = 0.558, p < 0.0001) and 3+ proteinuria (ß coef = 0.356, p = 0.005) were significant independent variables predicting elevated serum NSE concentration. CONCLUSION: For the first time, this research has suggested the increase of neonatal NSE in preeclampsia, and the quantity of maternal proteinuria may be able to predict neonatal NSE elevation. Long-term neurodevelopmental follow-up and targeted preventive strategies are advised for this underrecognized high-risk population.

Comparison of wavelet and correlation indices of cerebral autoregulation in a pediatric swine model of cardiac arrest.

Existing cerebrovascular blood pressure autoregulation metrics have not been translated to clinical care for pediatric cardiac arrest, in part because signal noise causes high index time-variability. We tested whether a wavelet method that uses near-infrared spectroscopy (NIRS) or intracranial pressure (ICP) decreases index variability compared to that of commonly used correlation indices. We also compared whether the methods identify the optimal arterial blood pressure (ABPopt) and lower limit of autoregulation (LLA). 68 piglets were randomized to cardiac arrest or sham procedure with continuous monitoring of cerebral blood flow using laser Doppler, NIRS and ICP. The arterial blood pressure (ABP) was gradually reduced until it dropped to below the LLA. Several autoregulation indices were calculated using correlation and wavelet methods, including the pressure reactivity index (PRx and wPRx), cerebral oximetry index (COx and wCOx), and hemoglobin volume index (HVx and wHVx). Wavelet methodology had less index variability with smaller standard deviations. Both wavelet and correlation methods distinguished functional autoregulation (ABP above LLA) from dysfunctional autoregulation (ABP below the LLA). Both wavelet and correlation methods also identified ABPopt with high agreement. Thus, wavelet methodology using NIRS may offer an accurate vasoreactivity monitoring method with reduced signal noise after pediatric cardiac arrest.

Sensitivity of a Next-Generation NIRS Device to Detect Low Mixed Venous Oxyhemoglobin Saturations in the Single Ventricle Population.

Regional cerebral oxygenation index (rSO2) based on near-infrared spectroscopy (NIRS) is frequently used to detect low venous oxyhemoglobin saturation (ScvO2). We compared the performance of 2 generations of NIRS devices. Clinically obtained, time-matched cerebral rSO2 and ScvO2 values were compared in infants monitored with the FORE-SIGHT (n = 73) or FORE-SIGHT ELITE (n = 47) by linear regression and Bland-Altman analyses. In both devices, cerebral rSO2 correlated poorly with measured ScvO2 (FORE-SIGHT partial correlation 0.50 [95% confidence interval {CI}, 0.40-0.58]; FORE-SIGHT ELITE partial correlation 0.47 [0.39-0.55]) and mean bias was +8 (standard deviation [SD] 13.2) for FORE-SIGHT and +14 (SD 12.5) for FORE-SIGHT ELITE. When ScvO2 was <30%, rSO2 was <40 in 8% of FORE-SIGHT ELITE readings. Future NIRS should be validated in more hypoxic cohorts.

Forehead electrodes sufficiently detect propofol-induced slow waves for the assessment of brain function after cardiac arrest.

In a recent study, we proposed a novel method to evaluate hypoxic ischemic encephalopathy (HIE) by assessing propofol-induced changes in the 19-channel electroencephalogram (EEG). The study suggested that patients with HIE are unable to generate EEG slow waves during propofol anesthesia 48 h after cardiac arrest (CA). Since a low number of electrodes would make the method clinically more practical, we now investigated whether our results received with a full EEG cap could be reproduced using only forehead electrodes. Experimental data from comatose post-CA patients (N = 10) were used. EEG was recorded approximately 48 h after CA using 19-channel EEG cap during a controlled propofol exposure. The slow wave activity was calculated separately for all electrodes and four forehead electrodes (Fp1, Fp2, F7, and F8) by determining the low-frequency (< 1 Hz) power of the EEG. HIE was defined by following the patients' recovery for six months. In patients without HIE (N = 6), propofol substantially increased (244 ± 91%, mean ± SD) the slow wave activity in forehead electrodes, whereas the patients with HIE (N = 4) were unable to produce such activity. The results received with forehead electrodes were similar to those of the full EEG cap. With the experimental pilot study data, the forehead electrodes were as capable as the full EEG cap in capturing the effect of HIE on propofol-induced slow wave activity. The finding offers potential in developing a clinically practical method for the early detection of HIE.

Detailed statistical analysis plan for the SafeBoosC III trial: a multinational randomised clinical trial assessing treatment guided by cerebral oxygenation monitoring versus treatment as usual in extremely preterm infants.

BACKGROUND: Infants born extremely preterm are at high risk of dying or suffering from severe brain injuries. Treatment guided by monitoring of cerebral oxygenation may reduce the risk of death and neurologic complications. The SafeBoosC III trial evaluates the effects of treatment guided by cerebral oxygenation monitoring versus treatment as usual. This article describes the detailed statistical analysis plan for the main publication, with the aim to prevent outcome reporting bias and data-driven analyses. METHODS/DESIGN: The SafeBoosC III trial is an investigator-initiated, randomised, multinational, pragmatic phase III trial with a parallel group structure, designed to investigate the benefits and harms of treatment based on cerebral near-infrared spectroscopy monitoring compared with treatment as usual. Randomisation will be 1:1 stratified for neonatal intensive care unit and gestational age (lower gestational age (< 26 weeks) compared to higher gestational age (≥ 26 weeks)). The primary outcome is a composite of death or severe brain injury at 36 weeks postmenstrual age. Primary analysis will be made on the intention-to-treat population for all outcomes, using mixed-model logistic regression adjusting for stratification variables. In the primary analysis, the twin intra-class correlation coefficient will not be considered. However, we will perform sensitivity analyses to address this. Our simulation study suggests that the inclusion of multiple births is unlikely to significantly affect our assessment of intervention effects, and therefore we have chosen the analysis where the twin intra-class correlation coefficient will not be considered as the primary analysis. DISCUSSION: In line with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines, we have developed and published this statistical analysis plan for the SafeBoosC III trial, prior to any data analysis. TRIAL REGISTRATION: ClinicalTrials.org, NCT03770741. Registered on 10 December 2018.

Association of antiepileptic drugs with resolution of epileptiform activity after cardiac arrest.

INTRODUCTION: We tested the impact of antiepileptic drug (AED) administration on post-cardiac arrest epileptiform electroencephalographic (EEG) activity. METHODS: We studied an observational cohort of comatose subjects treated at a single academic medical center after cardiac arrest from September 2010 to January 2018. We aggregated the observed EEG patterns into 5 categories: suppressed; discontinuous background with superimposed epileptiform activity; discontinuous background without epileptiform features; continuous background with epileptiform activity; and continuous background without epileptiform activity. We calculated overall probabilities of transitions between EEG states in a multistate model, then used Aalen's additive regression to test if AEDs or hypothermia are associated with a change in these probabilities. RESULTS: Overall, 828 subjects had EEG-monitoring for 42,840 h with a median of 40 [IQR 23-64] h per subject. Among patients with epileptiform findings on initial monitoring, 50% transitioned at least once to a non-epileptiform, non-suppressed state. By contrast, 19% with non-epileptiform initial activity transitioned to an epileptiform state at least once. Overall, 568 (78%) patients received at least one AED. Among patients with continuous EEG background activity, valproate, levetiracetam and lower body temperature were each associated with an increased probability of transition from epileptiform states to non-epileptiform states, where patients with discontinuous EEG background activity no agent linked to an increased probability of transitioning from epileptiform states. CONCLUSION: After cardiac arrest, the impact of AEDs may depend on the presence of continuous cortical background activity. These data serve to inform experimental work to better define the opportunities to improve neurologic care post-cardiac arrest.

Injury Patterns in Near-Hanging Patients: How Much Workup Is Really Needed?

Survivors of near-hangings suffer anoxic brain injuries, but it remains uncertain whether the incidence of associated injuries warrants extensive workup or trauma activation. An 11-year retrospective review was conducted on adult patients with a hanging mechanism who underwent trauma workup and management. The majority of patients (n = 98) were white (88.8%) males (75.5%) with an average age of 30 ± 12.3 years. Two-hundred fifty-four CT and magnetic resonance scans were performed and eight injuries were uncovered: three thyroid cartilage/hyoid fractures; three vertebral injuries; and two cervical vascular injuries. Anoxic brain injury was diagnosed clinically in 35 patients (35.7%) and was present in all 19 patients (19.4%) who died. Only one patient had intra-abdominal injury requiring surgical intervention. Injuries were more likely in patients with abnormal Glasgow Coma Scale (GCS) versus normal GCS (55% vs 10.5%, respectively). Patients who present after near-hanging have a low incidence of associated injuries. Workup can be restricted to patients with abnormal GCS scores and for specific signs and symptoms or high-risk energy mechanisms. The trauma team can be activated for signs of trauma.

Tuberous sclerosis complex presenting as convulsive status epilepticus followed by hypoxic cerebropathy: A case report.

RATIONALE: Tuberous sclerosis complex (TSC) is a relatively rare, autosomal dominant, and progressive neurocutaneous disorder involving multiple organs. Heterozygous mutations in the TSC1 gene located on chromosome 9 (9q34.13) or the TSC2 gene located on chromosome 16 (16p13.3) have been shown to be responsible for this disorder. The most common clinical manifestations are abnormalities of the skin, brain, kidney, heart, and lungs. Although all seizure types have been observed in TSC patients, the present case is the first in the literature to present with convulsive status epilepticus followed by hypoxic cerebropathy. PATIENT CONCERNS: A 33-month-old girl presented with fever and seizure followed by unconsciousness for 6 hours. Physical examination showed 4 hypopigmented macules with diameters exceeding 5 mm. Initial magnetic resonance imaging of the brain revealed diffuse edema in the bilateral cerebral cortex, cortical tubers, and subependymal nodules. Video electroencephalography showed no epileptiform activity, but diffuse slow waves intermixed with small fast waves were seen for all leads. Computed tomography brain scanning revealed bilateral cortex edema and calcified subependymal nodules. DIAGNOSIS: Combined with her clinical presentation, the patient was diagnosed with TSC after molecular analysis revealed she had inherited the TSC2 c.1832G>A (p.R611Q) mutation from her mother. INTERVENTIONS: The patient received anti-infection therapy, mannitol dehydration, hyperbaric oxygen treatment, and topiramate. OUTCOMES: One month later, the patient was in a decorticate state, presenting with unconsciousness and bilateral arm flexion and leg extension. At 6 weeks, repeated electroencephalography was normal. LESSONS: In addition to the present case report, rare studies have reported cases of TSC presenting as convulsive status epileticus followed by hypoxic cerebropathy, which may be strongly associated with a poor prognosis. Patients with the characteristic skin lesions and epilepsy should be carefully evaluated for the possible diagnosis of TSC.

Quantitative EEG predicts outcomes in children after cardiac arrest.

OBJECTIVE: To determine whether quantitative EEG (QEEG) features predict neurologic outcomes in children after cardiac arrest. METHODS: We performed a single-center prospective observational study of 87 consecutive children resuscitated and admitted to the pediatric intensive care unit after cardiac arrest. Full-array conventional EEG data were obtained as part of clinical management. We computed 8 QEEG features from 5-minute epochs every hour after return of circulation. We developed predictive models utilizing random forest classifiers trained on patient age and 8 QEEG features to predict outcome. The features included SD of each EEG channel, normalized band power in alpha, beta, theta, delta, and gamma wave frequencies, line length, and regularity function scores. We measured outcomes using Pediatric Cerebral Performance Category (PCPC) scores. We evaluated the models using 5-fold cross-validation and 1,000 bootstrap samples. RESULTS: The best performing model had a 5-fold cross-validation accuracy of 0.8 (0.88 area under the receiver operating characteristic curve). It had a positive predictive value of 0.79 and a sensitivity of 0.84 in predicting patients with favorable outcomes (PCPC score of 1-3). It had a negative predictive value of 0.8 and a specificity of 0.75 in predicting patients with unfavorable outcomes (PCPC score of 4-6). The model also identified the relative importance of each feature. Analyses using only frontal electrodes did not differ in prediction performance compared to analyses using all electrodes. CONCLUSIONS: QEEG features can standardize EEG interpretation and predict neurologic outcomes in children after cardiac arrest.

Serum tau fragments as predictors of death or poor neurological outcome after out-of-hospital cardiac arrest.

Background: Anoxic brain injury is the primary cause of death after resuscitation from out-of-hospital cardiac arrest (OHCA) and prognostication is challenging. The aim of this study was to evaluate the potential of two fragments of tau as serum biomarkers for neurological outcome. Methods: Single-center sub-study of 171 patients included in the Target Temperature Management (TTM) Trial randomly assigned to TTM at 33 °C or TTM at 36 °C for 24 h after OHCA. Fragments (tau-A and tau-C) of the neuronal protein tau were measured in serum 24, 48 and 72 h after OHCA. The primary endpoint was neurological outcome. Results: Median (quartile 1 - quartile 3) tau-A (ng/ml) values were 58 (43-71) versus 51 (43-67), 72 (57-84) versus 71 (59-82) and 76 (61-92) versus 75 (64-89) for good versus unfavourable outcome at 24, 48 and 72 h, respectively (pgroup = 0.95). Median tau C (ng/ml) values were 38 (29-50) versus 36 (29-49), 49 (38-58) versus 48 (33-59) and 48 (39-59) versus 48 (36-62) (pgroup = 0.95). Tau-A and tau-C did not predict neurological outcome (area under the receiver-operating curve at 48 h; tau-A: 0.51 and tau-C: 0.51). Conclusions: Serum levels of tau fragments were unable to predict neurological outcome after OHCA.