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Aneurysmal subarachnoid hemorrhage (aSAH) not only causes neurological deficits but also influences extracerebral organ functions. The Logistic Organ Dysfunction System (LODS) reliably captures organ dysfunctions and predicts mortality of critically ill patients. This study investigated LODS in the setting of aSAH as a surrogate marker for early brain injury (EBI). Patients with aSAH treated between 2012 and 2020 were retrospectively analyzed. LODS was calculated within 24 h upon admission applying functional parameters for each organ system. The EBI was evaluated based on 1-persistent loss of consciousness, 2-global cerebral edema, and 3-intracranial blood burden. The outcome was assessed with the modified Rankin scale (mRS) at 3-months after ictus (mRS > 2 = unfavorable outcome). A total of 324 patients with a mean age of 55.9 years were included. Severe EBI (EBI grade ≥ 3) was found in 38% (124/324) of patients. Higher LODS score correlated with severe EBI (p < 0.0001) and poor outcome (p < 0.0001). LODS with a cutoff of 7 allowed a reliable discrimination (AUC 78%, p < 0.0001) of patients with severe from those with mild EBI. The LODS-calculation as an early risk stratification and prognostic tool reliably reflected the severity of EBI after aSAH and correlated with outcome., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethics approval This study was performed in line with the principles of the 1964 Helsinki declaration and its later amendments. This is an observational study. The study was approved by the Ethics Committee of the University Medical Center Göttingen (No. 16/9/20). Due to the retrospective study design informed consent was waived by the Ethics Committee of the University Medical Center Göttingen., (© 2024. The Author(s).)

Objective: This study aims to analyze the risk factors for early postoperative brain injury in patients undergoing cardiovascular surgery and explore the predictive value of transcranial color Doppler (TCCD) and regional cerebral oxygen saturation (rSO 2 ) for detecting early postoperative brain injury in cardiovascular surgery patients., Methods: A total of 55 patients undergoing cardiovascular surgery with cardiopulmonary bypass in Changzhou No.2 The People's Hospital of Nanjing Medical University were included in this study. Neuron-specific enolase (NSE) concentration was measured 24 h after operation. Patients were divided into brain injury (NSE ≥ 16.3 ng/mL) and normal (0 < NSE < 16.3 ng/mL) groups according to the measured NSE concentration. The clinical outcomes between the two groups were compared, including decreased rSO 2 and cerebral blood flow (as measured by TCCD) levels. The risk factors of early postoperative brain injury were analyzed by multivariate logistic regression analysis, and the significant variables were analyzed by receiver operating characteristic (ROC) analysis., Results: A total of 50 patients were included in this study, with 20 patients in the brain injury group and 30 patients in the normal group. Cardiopulmonary bypass time (min) (107 ± 29 vs. 90 ± 28, P = 0.047) and aortic occlusion time (min) (111 (IQR 81-127) vs. 87 (IQR 72-116), P = 0.010) were significantly longer in the brain injury group than in the normal group. Patients in the brain injury group had greater decreased rSO 2 (%) (27.0 ± 7.3 vs. 17.5 ± 6.1, P < 0.001) and cerebral blood flow (%) (44.9 (IQR 37.8-69.2) vs. 29.1 (IQR 12.0-48.2), P = 0.004) levels. Multivariate logistic regression analysis suggested that decreased rSO 2 and cerebral blood flow levels, aortic occlusion time, and history of atrial fibrillation were independent risk factors for early postoperative brain injury (P < 0.05). ROC analysis reported that the best cutoff values for predicting early postoperative brain injury were 21.4% and 37.4% for decreased rSO 2 and cerebral blood flow levels, respectively (P < 0.05)., Conclusion: The decreased rSO 2 and cerebral blood flow levels, aorta occlusion time, and history of atrial fibrillation were independent risk factors for early postoperative brain injury. TCCD and rSO 2 could effectively monitor brain metabolism and cerebral blood flow and predict early postoperative brain injury., (© 2024. The Author(s).)

This study explores the perspectives of intimate partner violence (IPV) survivors and staff of brain injury (BI) screening, and the neuropsychological evaluation (NPE) process. We gathered qualitative data from 17 participants - 10 IPV survivors, at risk for a BI, who had received BI screening and a NPE and a total of 7 staff in IPV-serving organizations. Interviews were recorded, transcribed verbatim and analysed for key themes using thematic analysis. Survivors were over 18 years of age; the majority were between 19 and 45 years old, unemployed, unmarried, and had children. Survivors were angry, scared, and embarrassed to learn that they might have an IPV-related BI. They were thankful to have an explanation for some of their cognitive symptoms, which disrupted their daily activities, social relationships, and overall quality of life. Staff were pleased to be able to provide valuable information to their clients that could have a positive impact on their wellbeing. Overall, screening for a BI and participation in the NPE were well tolerated by IPV survivors with a possible BI. Inclusion of the perspectives of IPV survivors and support staff is an essential first step to better understanding their needs so interventions can be developed to aid their recovery.

Background: Trauma-related deaths and posttraumatic sequelae are a global health concern, necessitating a deeper understanding of the pathophysiology to advance trauma therapy. Proteomics offers insights into identifying and analyzing plasma proteins associated with trauma and inflammatory conditions; however, current proteomic methods have limitations in accurately measuring low-abundance plasma proteins. This study compared plasma proteomics profiles of patients from different acute trauma subgroups to identify new therapeutic targets and devise better strategies for personalized medicine., Methods: This prospective observational single-center cohort study was conducted between August 2020 and September 2021 in the intensive care unit of Osaka University Hospital in Japan. Enrolling 59 consecutive patients with blunt trauma, we meticulously analyzed plasma proteomics profiles in participants with torso or head trauma, comparing them with those of controls (mild trauma). Using the Olink Explore 3072 instrument (Olink Proteomics AB, Uppsala, Sweden), we identified five endotypes (α-ε) via unsupervised hierarchical clustering., Results: The median time from injury to blood collection was 47 minutes [interquartile range, 36-64 minutes]. The torso trauma subgroup exhibited 26 unique proteins with significantly altered expression, while the head trauma subgroup showed 68 unique proteins with no overlap between the two. The identified endotypes included α (torso trauma, n = 8), β (young patients with brain injury, n = 5), γ (severe brain injury postsurgery, n = 8), δ (torso or brain trauma with mild hyperfibrinolysis, n = 18), and ε (minor trauma, n = 20). Patients with torso trauma showed changes in blood pressure, smooth muscle adaptation, hypermetabolism, and hypoxemia. Patients with traumatic brain injury had dysregulated blood coagulation and altered nerves regeneration and differentiation., Conclusion: This study identified unique plasma protein expression patterns in patients with torso trauma and traumatic brain injury, helping categorize five distinct endotypes. Our findings may offer new insights for clinicians, highlighting potential strategies for personalized medicine and improved trauma-related care., Level of Evidence: Prognostic and Epidemiological; Level III., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Surgery of Trauma.)

Preterm infants are a high-risk group for brain injury, and it is important to evaluate the neurological recovery of preterm infants. Therefore, this paper evaluates the neurological recovery in preterm infants at high risk of brain injury by amplitude-integrated EEG and GMs scale. The study collected basic information on preterm infants and performed amplitude integrated EEG examination and GMs scale evaluation. Amplitude integrated EEG examination attaches electrodes using multielectrode arrays onto specific areas of the premature head to record brain wave activity to monitor electrical activity in the preterm brain in real time and amplify and process through the signals received by the electrodes to obtain more detailed EEG data. The GMs scale evaluates the developmental and functional status of the child and allows an objective assessment of the development and recovery of neurological function by observing their performance in motor, language, cognition, and social interaction. Analysis of the data by statistical processing. The results showed that early brain injury was evident in high-risk infants. Amplitude integrated EEG parameters can have some predictive value for brain injury. There were also differences in GMs scale assessment between brain injury and non-brain injury. Amplitude integrated EEG combined with GMs scale has certain value in predicting brain injury and can provide an important basis for early intervention in children with preterm brain injury and help to improve their neurodevelopmental outcome., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interests regarding the publication of this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background The Box and Block Test (BBT) is a highly recommended outcome measure to assess unilateral gross motor activity of the upper limbs. The BBT has not previously been available in a version adapted to the Spanish context. Thus, this study aimed to cross-culturally adapt and translate the BBT's instructions and pilot test the Spanish version of BBT in adults with acquired brain injury (ABI). Methods The BBT was translated and cross-culturally adapted following standard procedures. An expert committee approved the final Spanish version of BBT and it was conceptually validated by four therapists with expertise in ABI. The tool was tested on 14 adults with ABI. Results The Spanish version of BBT included a new section of materials for the test and a record to count the number of blocks transferred from one compartment of the box to the other. Following the pilot study, a modification in terminology was implemented for referring to the dominant and non-dominant hands. Conclusions Our results suggest that the Spanish version of BBT is suitable for assessing manual dexterity in Spanish-speaking adults with ABI.

For patients who may lack capacity, the Mental Capacity Act 2005 requires capacity to be assessed for each decision at the time that treatment is offered, but this is not practical for every element of basic care and intervention delivered to patients undergoing rehabilitation following acquired brain injury, especially if their needs are changing. In this quality improvement project, we introduced a system for screening Mental Capacity and documentation to identify patients with a) largely intact cognition for whom capacity may be reasonably be presumed, and b) those in prolonged disorders of consciousness who clearly lacked capacity for all decisions. This enabled the multidisciplinary team to concentrate on evaluation of capacity in the third group who had more nuanced ability and required detailed assessment or support for decision-making. Two rounds of audit demonstrated that implementation improved the consistency of assessment and documentation. Multicentre roll-out of this approach is now required., Competing Interests: Declaration of competing interest There are no personal or financial conflicts of interest. All authors are employed by Northwick Park Hospital, King's College London, or University College London Hospitals NHS Foundation Trust, which may cite this article as part of their quality improvement and development programmes. We do not consider that any of these relationships or activities have influenced the submitted work., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: For critically ill patients with acute severe brain injuries, consciousness may reemerge before behavioral responsiveness. The phenomenon of covert consciousness (i.e., cognitive motor dissociation) may be detected by advanced neurotechnologies such as task-based functional MRI (fMRI) and electroencephalography (EEG) in patients who appear unresponsive on the bedside behavioral examination. In this narrative review, we summarize the state-of-the-science in ICU detection of covert consciousness. Further, we consider the prognostic and therapeutic implications of diagnosing covert consciousness in the ICU, as well as its potential to inform discussions about continuation of life-sustaining therapy for patients with severe brain injuries., Data Sources: We reviewed salient medical literature regarding covert consciousness., Study Selection: We included clinical studies investigating the diagnostic performance characteristics and prognostic utility of advanced neurotechnologies such as task-based fMRI and EEG. We focus on clinical guidelines, professional society scientific statements, and neuroethical analyses pertaining to the implementation of advanced neurotechnologies in the ICU to detect covert consciousness., Data Extraction and Data Synthesis: We extracted study results, guideline recommendations, and society scientific statement recommendations regarding the diagnostic, prognostic, and therapeutic relevance of covert consciousness to the clinical care of ICU patients with severe brain injuries., Conclusions: Emerging evidence indicates that covert consciousness is present in approximately 15-20% of ICU patients who appear unresponsive on behavioral examination. Covert consciousness may be detected in patients with traumatic and nontraumatic brain injuries, including patients whose behavioral examination suggests a comatose state. The presence of covert consciousness in the ICU may predict the pace and extent of long-term functional recovery. Professional society guidelines now recommend assessment of covert consciousness using task-based fMRI and EEG. However, the clinical criteria for patient selection for such investigations are uncertain and global access to advanced neurotechnologies is limited., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Cognitive deficits are common after brain injury and can be measured in various ways. Many neuropsychological tests are designed to measure specific cognitive deficits, and self-report questionnaires capture cognitive complaints. Measuring cognition in daily life is important in rehabilitating the abilities required to undertake daily life activities and participate in society. However, assessment of cognition in daily life is often performed in a non-standardized manner. In this opinion paper we discuss the various types of assessment of cognitive functioning and their associated instruments. Drawing on existing literature and evidence from experts in the field, we propose a framework that includes seven dimensions of cognition measurement, reflecting a continuum ranging from controlled test situations through to measurement of cognition in daily life environments. We recommend multidimensional measurement of cognitive functioning in different categories of the continuum for the purpose of diagnostics, evaluation of cognitive rehabilitation treatment, and assessing capacity after brain injury.

This study critically reviews prognostication, brings into focus its "refinement" over the decades, and provides a template for clinicians who must judge the functioning of patients who awaken. This includes the use of diagnostic tests, including neuroimaging, electrophysiology, and laboratory testing that may aid in evaluating neurologic recovery. The article reviews recent guidelines and provides advice informed by many years of clinical experience., Competing Interests: Disclosure The author has nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: The assessment of mood after brain injury is more challenging when people have ongoing severe cognitive and receptive communication impairments. There is no gold standard on how these assessments should be undertaken. This study aimed to reach a consensus on this among specialists working with this population., Design: Focus groups were completed using a structured nominal group technique. Groups were compared for overlapping themes and agreed processes., Participants: Five focus groups with a total of 14 participants who work with the population of interest were completed. Participants included 12 clinical psychologists, one psychiatrist and one consultant in rehabilitation medicine., Results: Each of the five groups reached a consensus on a process for assessing mood in this population. Results overlapped and were combined into a proposed circular and iterative model of assessment that includes: (pre) information gathering, (peri) assessment processes, and (post) treatment; with formulation being seen as a vital part of the process. Standardised measures were not recommended for use with this population. Beyond the consensus processes, three implicit themes were identified: (1) depression is different after severe brain injury, (2) overlapping tasks and roles, and (3) looking at the bigger picture., Conclusions: A good level of consensus was achieved across the five groups on processes to follow when assessing mood when people have ongoing cognitive and receptive communication impairments after severe brain injury. We recommend that this formulation-based model be followed when assessing people in this clinical population., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose of Review: Critically ill children are at risk of neurologic dysfunction and acquiring primary and secondary brain injury. Close monitoring of cerebral function is crucial to prevent, detect, and treat these complications., Recent Findings: A variety of neuromonitoring modalities are currently used in pediatric and neonatal ICUs. These include noninvasive modalities, such as electroencephalography, transcranial Doppler, and near-infrared spectroscopy, as well as invasive methods including intracranial pressure monitoring, brain tissue oxygen measurement, and cerebral microdialysis. Each modality offers unique insights into neurologic function, cerebral circulation, or metabolism to support individualized neurologic care based on a patient's own physiology. Utilization of these modalities in ICUs results in reduced neurologic injury and mortality and improved neurodevelopmental outcomes., Summary: Monitoring of neurologic function can significantly improve care of critically ill children. Additional research is needed to establish normative values in pediatric patients and to standardize the use of these modalities., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Electrocencephalography (EEG) is a tool to assess cerebral cortical activity. We investigated the indications and results of routine EEG recordings in neurocritical care patients and corresponding changes in anti-seizure medication (ASM)., Materials and Methods: This was a single-center, retrospective cohort study. We included all adult Intensive Care Unit (ICU) patients with severe acute brain injury who received a routine EEG (30-60 min). Indications, background patterns, presence of rhythmic and periodic patterns, seizures, and adjustments in ASM were documented., Results: A total of 109 patients were included. The EEGs were performed primarily to investigate the presence of (non-convulsive) status epilepticus ((NC)SE) and/or seizures. A (slowed) continuous background pattern was present in 94%. Low voltage, burst-suppression and suppressed background patterns were found in six patients (5.5%). Seizures were diagnosed in two patients and (NC)SE was diagnosed in five patients (6.4%). Based on the EEG results, ASM was changed in 47 patients (43%). This encompassed discontinuation of ASM in 27 patients (24.8%) and initiation of ASM in 20 patients (18.3%)., Conclusions: All EEGs were performed to investigate the presence of (NC)SE or seizures. A slowed, but continuous background pattern was found in nearly all patients and (NC)SE and seizures were rarely diagnosed. Adjustments in ASM were made in approximately half of the patients., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Unconsciousness in severe acquired brain injury (sABI) patients occurs with different cognitive and neural profiles. Perturbational approaches, which enable the estimation of proxies for brain reorganization, have added a new avenue for investigating the non-behavioural diagnosis of consciousness. In this prospective observational study, we conducted a comparative analysis of the topological patterns of heartbeat-evoked potentials (HEP) between patients experiencing a prolonged disorder of consciousness (pDoC) and patients emerging from a minimally consciousness state (eMCS). A total of 219 sABI patients were enrolled, each undergoing a synchronous EEG-ECG resting-state recording, together with a standardized consciousness diagnosis. A number of graph metrics were computed before/after the HEP (Before/After) using the R-peak on the ECG signal. The peak value of the global field power of the HEP was found to be significantly higher in eMCS patients with no difference in latency. Power spectrum was not able to discriminate consciousness neither Before nor After. Node assortativity and global efficiency were found to vary with different trends at unconsciousness. Lastly, the Perturbational Complexity Index of the HEP was found to be significantly higher in eMCS patients compared with pDoC. Given that cortical elaboration of peripheral inputs may serve as a non-behavioural determinant of consciousness, we have devised a low-cost and translatable technique capable of estimating causal proxies of brain functionality with an endogenous, non-invasive stimulus. Thus, we present an effective means to enhance consciousness assessment by incorporating the interaction between the autonomic nervous system (ANS) and central nervous system (CNS) into the loop., (© 2024 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Competing Interests: VN is supported by a National Institute for Health and Care Health Research (NIHR) Rosetrees Trust Advanced Fellowship (NIHR302544), which is funded in partnership by the NIHR and Rosetrees Trust. The views expressed are those of the author and not necessarily those of the NIHR, Rosetrees Trust, or the Department of Health and Social Care. VN also holds a researcher-led grant with Roche Pharmaceuticals, unrelated to this Comment.

Objectives: We hypothesized that neuropsychological testing and history of falls would be associated with difficulty resume driving after acute acquired brain injury (ABI). This study aimed to analyze ABI facing difficulties in resuming driving in the acute phase., Methods: We retrospectively analyzed 63 patients receiving assistance in driving-resumption after ABI. Patients were categorized into two groups: driving-resumption-possible and driving-resumption-difficult. Discriminant analysis delineated characteristics of patients experiencing driving-resumption difficulty. Additionally, significant predictors were analyzed using ROC curves., Results: 42 patients were able to resume driving, and 21 experienced difficulties in driving resumption. Factors predicting difficulty returning to driving were age, history of falls, TMT Part B, and ROCF. Furthermore, cut-off values for each were 72 years, 148 seconds for TMT Part B, and 29.5 points for ROCF., Conclusions: Patients with advanced age, history of falls, delayed TMT Part B, and poor ROCF outcomes may face challenges in resuming driving after ABI. These factors may serve as a valuable metric to assess driving resumption difficulties after ABI., Competing Interests: Declaration of competing interest This manuscript has not been published or presented elsewhere in part or in entirety and is not under consideration by another journal. All study participants provided informed consent, and the study design was approved by the appropriate ethics review board. We have read and understood your journal's policies, and we believe that neither the manuscript nor the study violates any of these. There are no conflicts of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Intracranial hypertension (IH) is a life-threating condition especially for the brain injured patient. In such cases, an external ventricular drain (EVD) or an intraparenchymal bolt are the conventional gold standard for intracranial pressure (ICPi) monitoring. However, these techniques have several limitations. Therefore, identifying an ideal screening method for IH is important to avoid the unnecessary placement of ICPi and expedite its introduction in patients who require it. A potential screening tool is the ICP wave morphology (ICPW) which changes according to the intracranial volume-pressure curve. Specifically, the P2/P1 ratio of the ICPW has shown promise as a triage test to indicate normal ICP. In this study, we propose evaluating the noninvasive ICPW (nICPW-B4C sensor) as a screening method for ICPi monitoring in patients with moderate to high probability of IH. This is a retrospective analysis of a prospective, multicenter study that recruited adult patients requiring ICPi monitoring from both Federal University of São Paulo and University of São Paulo Medical School Hospitals. ICPi values and the nICPW parameters were obtained from both the invasive and the noninvasive methods simultaneously 5 min after the closure of the EVD drainage. ICP assessment was performed using a catheter inserted into the ventricle and connected to a pressure transducer and a drainage system. The B4C sensor was positioned on the patient's scalp without the need for trichotomy, surgical incision or trepanation, and the morphology of the ICP waves acquired through a strain sensor that can detect and monitor skull bone deformations caused by changes in ICP. All patients were monitored using this noninvasive system for at least 10 min per session. The area under the curve (AUC) was used to describe discriminatory power of the P2/P1 ratio for IH, with emphasis in the Negative Predictive value (NPV), based on the Youden index, and the negative likelihood ratio [LR-]. Recruitment occurred from August 2017 to March 2020. A total of 69 patients fulfilled inclusion and exclusion criteria in the two centers and a total of 111 monitorizations were performed. The mean P2/P1 ratio value in the sample was 1.12. The mean P2/P1 value in the no IH population was 1.01 meanwhile in the IH population was 1.32 (p < 0.01). The best Youden index for the mean P2/P1 ratio was with a cut-off value of 1.13 showing a sensitivity of 93%, specificity of 60%, and a NPV of 97%, as well as an AUC of 0.83 to predict IH. With the 1.13 cut-off value for P2/P1 ratio, the LR- for IH was 0.11, corresponding to a strong performance in ruling out the condition (IH), with an approximate 45% reduction in condition probability after a negative test (ICPW). To conclude, the P2/P1 ratio of the noninvasive ICP waveform showed in this study a high Negative Predictive Value and Likelihood Ratio in different acute neurological conditions to rule out IH. As a result, this parameter may be beneficial in situations where invasive methods are not feasible or unavailable and to screen high-risk patients for potential invasive ICP monitoring.Trial registration: At clinicaltrials.gov under numbers NCT05121155 (Registered 16 November 2021-retrospectively registered) and NCT03144219 (Registered 30 September 2022-retrospectively registered)., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Walking impairment is a common disability post acquired brain injury (ABI), with visually evident arm movement abnormality identified as negatively impacting a multitude of psychological factors. The International Classification of Functioning, Disability and Health (ICF) qualifiers scale has been used to subjectively assess arm movement abnormality, showing strong intra-rater and test-retest reliability, however, only moderate inter-rater reliability. This impacts clinical utility, limiting its use as a measurement tool. To both automate the analysis and overcome these errors, the primary aim of this study was to evaluate the ability of a novel two-level machine learning model to assess arm movement abnormality during walking in people with ABI., Methods: Frontal plane gait videos were used to train four networks with 50%, 75%, 90%, and 100% of participants (ABI: n = 42, healthy controls: n = 34) to automatically identify anatomical landmarks using DeepLabCut ™ and calculate two-dimensional kinematic joint angles. Assessment scores from three experienced neurorehabilitation clinicians were used with these joint angles to train random forest networks with nested cross-validation to predict assessor scores for all videos. Agreement between unseen participant (i.e. test group participants that were not used to train the model) predictions and each individual assessor's scores were compared using quadratic weighted kappa. One sample t-tests (to determine over/underprediction against clinician ratings) and one-way ANOVA (to determine differences between networks) were applied to the four networks., Results: The machine learning predictions have similar agreement to experienced human assessors, with no statistically significant (p < 0.05) difference for any match contingency. There was no statistically significant difference between the predictions from the four networks (F = 0.119; p = 0.949). The four networks did however under-predict scores with small effect sizes (p range = 0.007 to 0.040; Cohen's d range = 0.156 to 0.217)., Conclusions: This study demonstrated that machine learning can perform similarly to experienced clinicians when subjectively assessing arm movement abnormality in people with ABI. The relatively small sample size may have resulted in under-prediction of some scores, albeit with small effect sizes. Studies with larger sample sizes that objectively and automatically assess dynamic movement in both local and telerehabilitation assessments, for example using smartphones and edge-based machine learning, to reduce measurement error and healthcare access inequality are needed., (© 2024. The Author(s).)

Acquired brain injury is an urgent situation that requires rapid diagnosis and treatment. Magnetic resonance imaging (MRI) and computed tomography (CT) are required for accurate diagnosis. However, these methods are costly and require substantial infrastructure and specialized staff. Circulatory biomarkers of acute brain injury may help in the management of patients with acute cerebrovascular events and prevent poor outcome and mortality. The purpose of this review is to provide an overview of the development of potential biomarkers of brain damage to increase diagnostic possibilities. For this purpose, we searched the PubMed database of studies on the diagnostic potential of brain injury biomarkers. We also accessed information from Clinicaltrials.gov to identify any clinical trials of biomarker measurements for the diagnosis of brain damage. In total, we present 41 proteins, enzymes and hormones that have been considered as biomarkers for brain injury, of which 20 have been studied in clinical trials. Several microRNAs have also emerged as potential clinical biomarkers for early diagnosis. Combining multiple biomarkers in a panel, along with other parameters, is yielding promising outcomes., (© 2024. The Author(s).)

Background: Population-based data regarding the associations between prior concussion or brain injury symptoms/diagnosis and mental/social well-being is lacking for U.S. children., Methods: Associations between prior concussion or brain injury symptoms/diagnosis (reported by parents of children ages 5-17 from the 2020 National Health Interview Survey) and current mental/social well-being were determined in multivariable models., Results: Amongst 2020 US children, 8.7% and 5.3% had previous symptoms and diagnosis of concussion/brain injury, respectively. 23% of children with symptoms were never checked for a concussion/brain injury, with younger children at higher risk of not getting checked after symptomatic head trauma. Prior concussion or brain injury symptoms/diagnosis was associated with a higher likelihood of current depressive symptoms (odds ratio [OR] = 1.60; 95% CI = 1.21-2.14; p  < 0.001), anxiety (OR = 2.07; 95% CI = 1.52-2.82; p  < 0.001), difficulty making friends (OR = 1.57; 95% = 1.06-2.33; p  = 0.03), use of medications for mental/social/behavioral issues (OR = 1.69; CI = 1.21-2.36; p  = 0.002), and mental health therapy/counseling (OR = 1.52; 95% CI = 1.13-2.04; p  = 0.006)., Conclusion: U.S. children with prior concussion or brain injury symptoms/diagnosis have a higher rate of mental and social disturbances and a more frequent need for mental health services. Nearly one-quarter of children with significant symptoms after head trauma are never checked for a concussion/brain injury; routine concussion evaluation after head trauma should be emphasized especially in younger children.

Objectives: We sought to investigate the value of combining intrauterine cerebral blood flow changes with brain electrical activity examination in evaluating the prognosis of brain injury., Methods: A total of 90 preterm infants were enrolled and divided into 2 groups: the brain damaged preterm infants group (n = 55) and the nonbrain damaged preterm infants group (n = 35). The diagnostic efficacy of combining intrauterine cerebral blood flow changes with electroencephalogram (EEG) activity examination in predicting the prognosis of preterm infants with brain injury was evaluated using T-test. Pearson linear correlation was applied to analyze the relationship between fetal intrauterine cerebral blood flow changes combined with electrical activity examination and the prognosis of brain injury., Results: Significant differences were seen in pulse index, the ratio of peak systolic velocity to end diastolic velocity ratio, and other indexes between the 2 groups (P < 0.05). The combined approach of intrauterine cerebral blood flow changes with EEG activity examination demonstrated significantly higher values for area under the curve, sensitivity and negative predictive value compared to using intrauterine cerebral blood flow changes or EEG activity examination alone (P < 0.05). A positive correlation was found between fetal intrauterine cerebral blood flow and electrical activity examination (P < 0.05)., Conclusions: Combining the assessment of intrauterine cerebral blood flow changes with cerebral electrical activity examination proved beneficial in diagnosing the prognosis of brain injury and provided an important reference for early clinical intervention., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Seizure disorders have often been found to be associated with corpus callosum injuries, but in most cases, they remain undiagnosed. Understanding the clinical, electrographic, and neuroradiological alternations can be crucial in delineating this entity., Objective: This systematic review aims to analyze the effects of corpus callosum injuries on seizure semiology, providing insights into the neuroscientific and clinical implications of such injuries., Methods: Adhering to the PRISMA guidelines, a comprehensive search across multiple databases, including PubMed/Medline, NIH, Embase, Cochrane Library, and Cross-ref, was conducted until September 25, 2023. Studies on seizures associated with corpus callosum injuries, excluding other cortical or sub-cortical involvements, were included. Machine learning (Random Forest) and deep learning (1D-CNN) algorithms were employed for data classification., Results: Initially, 1250 articles were identified from the mentioned databases, and additional 350 were found through other relevant sources. Out of all these articles, 41 studies met the inclusion criteria, collectively encompassing 56 patients The most frequent clinical manifestations included generalized tonic-clonic seizures, complex partial seizures, and focal seizures. The most common callosal injuries were related to reversible splenial lesion syndrome and cytotoxic lesions. Machine learning and deep learning analyses revealed significant correlations between seizure types, semiological parameters, and callosal injury locations. Complete recovery was reported in the majority of patients post-treatment., Conclusion: Corpus callosum injuries have diverse impacts on seizure semiology. This review highlights the importance of understanding the role of the corpus callosum in seizure propagation and manifestation. The findings emphasize the need for targeted diagnostic and therapeutic strategies in managing seizures associated with callosal injuries. Future research should focus on expanding the data pool and exploring the underlying mechanisms in greater detail., Competing Interests: Declaration of Competing Interest None of the authors have any financial or personal relationships that could inappropriately influence or bias the work presented in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: There is a crucial need for reliable tools to measure impaired self-awareness (ISA) in patients with acquired brain injury (ABI) across cognitive-functional domains. The aim of this study was to assess the psychometric properties of the Cog-Awareness ADL Scale, which is a novel self-proxy discrepancy method for measuring ISA in both basic and instrumental activities of daily living. Methods: This multicenter study included 54 patients (no-low ISA n  = 33; severe ISA, n  = 21) from four outpatient rehabilitation units in Málaga-Granada, Spain, and 51 healthy controls. The participants and proxy raters completed the Cog-Awareness ADL Scale and the Patient Competency Rating Scale (PCRS). Agreement between both scales was assessed using Spearman's correlations and the Bland-Altman plot. Group comparisons were made on measures of SA, cognitive abilities and demographic variables. Sensitivity and specificity were analysed by ROC curve analysis. Results: Convergent validity was supported by strong correlations with the PCRS and its subscales (rho's ranging from 0.51 to 0.80, p  < 0.01 for all). The Bland-Altman plot confirmed measurement agreement (only 3.70% of the scores were outside the 95% limits). External validity was demonstrated by effectively discriminating between healthy controls and ABI patients with no-low and severe ISA on each discrepancy index while controlling for cognitive/demographic variables. The Cog-Awareness ADL Scale showed optimal diagnostic accuracy (AUC = 0.95, sensitivity = 0.90, specificity = 0.90). Conclusions: The Cog-Awareness ADL Scale proved to be a feasible, valid, and clinical tool to assess ISA across different cognitive-functional domains, in Spanish ABI-patients.

Objectives: Surrogate decision-making by family caregivers for patients with severe brain injury is influenced by the availability and understanding of relevant information and expectations for future rehabilitation. We aimed to compare the consistency of family caregivers' perceptions with clinical diagnoses and to inform their expectation of prognosis in the future., Methods: The Coma Recovery Scale-Revised was used to assess the diagnosis of inpatients with severe brain injury between February 2019 and February 2020. A main family caregiver was included per patient. The family caregiver's perception of the patient's consciousness and expectations of future recovery were collected through questionnaires and compared consistently with the clinical diagnosis., Results: The final sample included 101 main family caregivers of patients (57 UWS, unresponsive wakefulness syndrome, 37 MCS, minimally conscious state, 7 EMCS, emergence from MCS) with severe brain injury. Only 57 family caregivers correctly assessed the level of consciousness as indicated by the CRS-R, showing weak consistency (Kappa = 0.217, P = 0.002). Family caregivers' demographic characteristics and CRS-R diagnosis influenced the consistency between perception and clinical diagnosis. Family caregivers who provided hands-on care to patients showed higher levels of consistent perception (AOR = 12.24, 95% CI = 2.06-73.00, P = 0.006). Compared to UWS, the family caregivers of MCS patients were more likely to have a correct perception (OR = 7.68, 95% CI = 1.34-44.06). Family caregivers had positive expectations for patients' recovery in terms of both communication and returning to normal life., Conclusion: Nearly half of family caregivers have inadequate understanding of their relative's level of consciousness, and most of them report overly optimistic expectations that do not align with clinical diagnosis. Providing more medical information to family caregivers to support their surrogate decision-making process is essential., (© 2024. The Author(s).)

Objective: This article synthesizes the current literature on prognostication in neurocritical care, identifies existing challenges, and proposes future research directions to reduce variability and enhance scientific and patient-centered approaches to neuroprognostication., Latest Developments: Patients with severe acute brain injury often lack the capacity to make their own medical decisions, leaving surrogate decision makers responsible for life-or-death choices. These decisions heavily rely on clinicians' prognostication, which is still considered an art because of the previous lack of specific guidelines. Consequently, there is significant variability in neuroprognostication practices. This article examines various aspects of neuroprognostication. It explores the cognitive approach to prognostication, highlights the use of statistical modeling such as Bayesian models and machine learning, emphasizes the importance of clinician-family communication during prognostic disclosures, and proposes shared decision making for more patient-centered care., Essential Points: This article identifies ongoing challenges in the field and emphasizes the need for future research to ameliorate variability in neuroprognostication. By focusing on scientific methodologies and patient-centered approaches, this research aims to provide guidance and tools that may enhance neuroprognostication in neurocritical care., (Copyright © 2024 American Academy of Neurology.)

The utilization of Artificial Intelligence (AI) and Machine Learning (ML) is paving the way for significant strides in patient diagnosis, treatment, and prognostication in neurocritical care. These technologies offer the potential to unravel complex patterns within vast datasets ranging from vast clinical data and EEG (electroencephalogram) readings to advanced cerebral imaging facilitating a more nuanced understanding of patient conditions. Despite their promise, the implementation of AI and ML faces substantial hurdles. Historical biases within training data, the challenge of interpreting multifaceted data streams, and the "black box" nature of ML algorithms present barriers to widespread clinical adoption. Moreover, ethical considerations around data privacy and the need for transparent, explainable models remain paramount to ensure trust and efficacy in clinical decision-making.This article reflects on the emergence of AI and ML as integral tools in neurocritical care, discussing their roles from the perspective of both their scientific promise and the associated challenges. We underscore the importance of extensive validation in diverse clinical settings to ensure the generalizability of ML models, particularly considering their potential to inform critical medical decisions such as withdrawal of life-sustaining therapies. Advancement in computational capabilities is essential for implementing ML in clinical settings, allowing for real-time analysis and decision support at the point of care. As AI and ML are poised to become commonplace in clinical practice, it is incumbent upon health care professionals to understand and oversee these technologies, ensuring they adhere to the highest safety standards and contribute to the realization of personalized medicine. This engagement will be pivotal in integrating AI and ML into patient care, optimizing outcomes in neurocritical care through informed and data-driven decision-making., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Optic nerve sheath diameter (ONSD) is a promising, noninvasive invasive intracranial pressure (ICP) measurement method. This study aims to analyze the differences in ONSD between the left and right eyeballs and the differences in ultrasonic measurement between the transverse and sagittal planes., Methods: Data from a total of 50 eligible patients with various types of brain injury who were admitted to our hospital from May 2019 to June 2021 were analyzed. An ONSD assessment was then performed using Philips B-mode ultrasound, measuring ONSD 3 mm posterior to the eyeballs. The left and right ONSDs in the transverse and sagittal planes were measured. Intraparenchymal fiber optic sensors and catheters were inserted into the ventricles and connected to an external pressure transducer to measure ICP., Results: A total of 164 sonographic measurements of ONSD were performed in 50 patients with brain injury in a prospective observational study. Statistically significant differences were found in ONSD between the transverse and sagittal planes. The difference in the left ONSD between the transverse and sagittal planes was 0.007 ± 0.030 cm ( P = 0.003). The Spearman rank correlation test showed that the correlation coefficient between ICP and left/right ONSD in the transverse/sagittal planes was 0.495 vs 0.546 and 0.559 vs 0.605, respectively. The results showed that the areas under the curve of ONSD in the transverse and sagittal planes were 0.843 and 0.805, respectively. Medcalc software was used to compare the areas under the receiver operator characteristic curve, and the results showed that ONSD in the sagittal plane is generally better than in the transverse plane ( P = 0.0145)., Conclusions: This study found that ONSD in the sagittal plane is superior to the transverse plane regarding the comprehensive efficacy of ICP, and unilateral measurement is sufficient., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by North American Neuro-Ophthalmology Society.)

In this two-center prospective cohort study of children on ECMO, we assessed a panel of plasma brain injury biomarkers using exploratory factor analysis (EFA) to evaluate their interplay and association with outcomes. Biomarker concentrations were measured daily for the first 3 days of ECMO support in 95 participants. Unfavorable composite outcome was defined as in-hospital mortality or discharge Pediatric Cerebral Performance Category > 2 with decline ≥ 1 point from baseline. EFA grouped 11 biomarkers into three factors. Factor 1 comprised markers of cellular brain injury (NSE, BDNF, GFAP, S100β, MCP1, VILIP-1, neurogranin); Factor 2 comprised markers related to vascular processes (vWF, PDGFRβ, NPTX1); and Factor 3 comprised the BDNF/MMP-9 cellular pathway. Multivariable logistic models demonstrated that higher Factor 1 and 2 scores were associated with higher odds of unfavorable outcome (adjusted OR 2.88 [1.61, 5.66] and 1.89 [1.12, 3.43], respectively). Conversely, higher Factor 3 scores were associated with lower odds of unfavorable outcome (adjusted OR 0.54 [0.31, 0.88]), which is biologically plausible given the role of BDNF in neuroplasticity. Application of EFA on plasma brain injury biomarkers in children on ECMO yielded grouping of biomarkers into three factors that were significantly associated with unfavorable outcome, suggesting future potential as prognostic instruments., (© 2024. The Author(s).)

Background: The evaluation of impaired self-awareness (ISA) after brain injury is not widespread in Japan, and there is a lack of Japanese assessments of self-awareness., Objectives: To translate the original version of the Awareness Questionnaire (AQ), an instrument for assessing ISA, into Japanese using a validated method and examine its reliability and validity in inpatients with stroke., Methods: This cross-sectional, prospective study enrolled 130 participants. The double-translation process was used to develop the Japanese version of the AQ., Results: Data were collected from 120 patients. High intra-rater reliability was observed for the patient (Cronbach's α = 0.824) and clinician samples (Cronbach's α = 0.933). High intra- and inter-rater reliability were found for all AQ items [interclass coefficient (ICC) (1, 1) = 0.828, ICC (2, 1) = 0.852, ICC (3, 1) = 0.848]; however, the sub-item analysis revealed only moderate reliability. Validity assessment revealed a low but significant positive correlation ( r  = 0.209; p  < 0.05) between the Japanese version of the AQ and the Japanese version of the Self-Regulation Skills Interview and a low but significant negative correlation ( r  = 0.197; p  < 0.05) between the Japanese version of the AQ and the Mini-Mental State Examination., Conclusions: The Japanese version of the AQ was developed and applied to stroke patients, but the concept of post-stroke ISA may differ from ISA after traumatic brain injury, highlighting the need for a stroke-specific version of the AQ.

Neonatal brain injury (NBI) is a critical condition for preterm neonates with potential long-term adverse neurodevelopmental outcomes. This prospective longitudinal case-control study aimed at investigating the levels and prognostic value of serum neuron-specific enolase (NSE) during the first 3 days of life in preterm neonates (<34 weeks) that later developed brain injury in the form of either periventricular leukomalacia (PVL) or intraventricular hemorrhage (IVH) during their hospitalization. Participants were recruited from one neonatal intensive care unit, and on the basis of birth weight and gestational age, we matched each case ( n = 29) with a neonate who had a normal head ultrasound scan ( n = 29). We report that serum NSE levels during the first three days of life do not differ significantly between control and preterm neonates with NBI. Nevertheless, subgroup analysis revealed that neonates with IVH had significantly higher concentrations of serum NSE in comparison to controls and neonates with PVL on the third day of life ( p = 0.014 and p = 0.033, respectively). The same pattern on the levels of NSE on the third day of life was also observed between (a) neonates with IVH and all other neonates (PVL and control; p = 0.003), (b) neonates with II-IV degree IVH and all other neonates ( p = 0.003), and (c) between control and the five ( n = 5) neonates that died from the case group ( p = 0.023). We conclude that NSE could be an effective and useful biomarker on the third day of life for the identification of preterm neonates at high risk of developing severe forms of IVH.

Purpose of Review: We selectively review emerging noninvasive neuromonitoring techniques and the evidence that supports their use in the ICU setting. The focus is on neuromonitoring research in patients with acute brain injury., Recent Findings: Noninvasive intracranial pressure evaluation with optic nerve sheath diameter measurements, transcranial Doppler waveform analysis, or skull mechanical extensometer waveform recordings have potential safety and resource-intensity advantages when compared to standard invasive monitors, however each of these techniques has limitations. Quantitative electroencephalography can be applied for detection of cerebral ischemia and states of covert consciousness. Near-infrared spectroscopy may be leveraged for cerebral oxygenation and autoregulation computation. Automated quantitative pupillometry and heart rate variability analysis have been shown to have diagnostic and/or prognostic significance in selected subtypes of acute brain injury. Finally, artificial intelligence is likely to transform interpretation and deployment of neuromonitoring paradigms individually and when integrated in multimodal paradigms., Summary: The ability to detect brain dysfunction and injury in critically ill patients is being enriched thanks to remarkable advances in neuromonitoring data acquisition and analysis. Studies are needed to validate the accuracy and reliability of these new approaches, and their feasibility and implementation within existing intensive care workflows., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The presence of abnormal electrocardiograms in individuals without known organic heart disease is one of the most common manifestations of cardiac dysfunction occurring during acute non traumatic brain injury. The primary goal of the present review is to provide an overview of the available data and literature regarding the presence of new-onset electrocardiographic (ECG) alterations in acute non traumatic brain injury. The secondary aim is to identify the incidence of ECG alterations and consider the prognostic significance of new-onset ECG changes in this setting. To do so, English language articles from January 2000 to January 2022 were included from PubMed using the following keywords: "electrocardiogram and subarachnoid hemorrhage", "electrocardiogram and intracranial hemorrhage", "Q-T interval and subarachnoid hemorrhage ", "Q-T interval and intracranial bleeding ", "Q-T interval and intracranial hemorrhage", and "brain and heart- interaction in stroke". Of 3162 papers, 27 original trials looking at electrocardiogram alterations in acute brain injury were included following the PRISMA guideline. ECG abnormalities associated with acute brain injury could potentially predict poor patient outcomes. They could even herald the future development of neurogenic pulmonary edema (NPE), delayed cerebral ischemia (DCI), and even in-hospital death. In particular, patients with SAH are at increased risk of having severe ventricular dysrhythmias. These may contribute to a high mortality rate and to poor functional outcome at 3 months. The current data on ECG QT dispersion and mortality appear less clearly associated. While some patients demonstrated poor outcomes, others showed no relationship with poor outcomes or increased in-hospital mortality. Observing ECG alterations carefully after cerebral damage is important in the critical care of these patients as it can expose preexisting myocardial disease and change prognosis., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Neonatal Encephalopathy (NE) is a major cause of lifelong disability and neurological complications in affected infants. Identifying novel diagnostic biomarkers in this population may assist in predicting MRI injury and differentiate neonates with NE from those with low-cord pH or healthy neonates and may help clinicians make real-time decisions. To compare the microRNA (miRNA) profiles between neonates with NE, healthy controls, and neonates with low cord pH. Moreover, miRNA concentrations were compared to brain injury severity in neonates with NE. This is a retrospective analysis of miRNA profiles from select samples in the biorepository and data registry at the University of Florida Health Gainesville. The Firefly miRNA assay was used to screen a total of 65 neurological miRNA targets in neonates with NE (n = 36), low cord pH (n = 18) and healthy controls (n = 37). Multivariate statistical techniques, including principal component analysis and orthogonal partial least squares discriminant analysis, and miRNA Enrichment Analysis and Annotation were used to identify miRNA markers and their pathobiological relevance. A set of 10 highly influential miRNAs were identified, which were significantly upregulated in the NE group compared to healthy controls. Of these, miR-323a-3p and mir-30e-5p displayed the highest fold change in expression levels. Moreover, miR-34c-5p, miR-491-5p, and miR-346 were significantly higher in the NE group compared to the low cord pH group. Furthermore, several miRNAs were identified that can differentiate between no/mild and moderate/severe injury in the NE group as measured by MRI. MiRNAs represent promising diagnostic and prognostic tools for improving the management of NE., (© 2024. The Author(s).)

Introduction: The aim of this study was to observe the validity, diagnostic capacity, and reliability of the thermographic technique in the analysis of sensitive and motor sequelae in patients with chronic brain damage., Method: A longitudinal descriptive observational study was performed. Forty-five people with impairment in at least one anatomical region participated in and completed this study. All patients who had become infected by SARS-CoV-2 in the past year were excluded. Thermographic measurement was conducted, and the Modified Ashworth Scale and Pressure Pain Threshold was analyzed., Results: A high correlation between two times of thermography data was observed. The Spearman correlations obtained between the Ashworth score on each leg and the temperature given by thermography were all significant., Discussion and Conclusions: Despite the above, the Spearman correlations obtained between the PPT in each leg and the temperature offered by thermography were not significant in any of the measurements. For this reason, thermography is a potential tool for the diagnosis and assessment of neuromuscular motor sequelae, but not for sensitive sequelae, after brain injury. Nevertheless, for the time being, no statistical relationship has been observed between the data reported by thermography and PPT; thus, future studies are needed to further investigate these results.

Background: Population-level administrative data provides a cost-effective means of monitoring health outcomes and service needs of clinical populations. This study aimed to present a method for case identification of non-traumatic brain injury in population-level data and to examine the association with sociodemographic factors., Methods: An estimated resident population of youth aged 0-24 years was constructed using population-level datasets within the New Zealand Integrated Data Infrastructure. A clinical consensus committee reviewed the International Classification of Diseases Ninth and Tenth Editions codes and Read codes for inclusion in a case definition. Cases were those with at least one non-traumatic brain injury code present in the five years up until 30 June 2018 in one of four databases in the Integrated Data Infrastructure. Rates of non-traumatic brain injury were examined, both including and excluding birth injury codes and across age, sex, ethnicity, and socioeconomic deprivation groups., Results: Of the 1 579 089 youth aged 0-24 years on 30 June 2018, 8154 (0.52%) were identified as having one of the brain injury codes in the five-years to 30 June 2018. Rates of non-traumatic brain injury were higher in males, children aged 0-4 years, Māori and Pacific young people, and youth living with high levels of social deprivation., Conclusion: This study presents a comprehensive method for case identification of non-traumatic brain injury using national population-level administrative data., (© 2024. The Author(s).)

Objective: Current methods used to measure incidence of traumatic brain injury (TBI) underestimate its true public health burden. The use of self-report surveys may be an approach to improve these estimates. An important step in public health surveillance is to define a public health problem using a case definition. The purpose of this article is to outline the process that the Centers for Disease Control and Prevention undertook to refine a TBI case definition to be used in surveillance using a self-report survey., Setting: Survey., Participants: A total of 10 030 adults participated via a random digit-dial telephone survey from September 2018 to September 2019., Main Measures: Respondents were asked whether they had sustained a hit to the head in the preceding 12 months and whether they experienced a series of 12 signs and symptoms as a result of this injury., Design: Head injuries with 1 or more signs/symptoms reported were initially categorized into a 3-tiered TBI case definition (probable TBI, possible TBI, and delayed possible TBI), corresponding to the level of certainty that a TBI occurred. Placement in a tier was compared with a range of severity measures (whether medical evaluation was sought, time to symptom resolution, self-rated social and work functioning); case definition tiers were then modified in a stepwise fashion to maximize differences in severity between tiers., Results: There were statistically significant differences in the severity measure between cases in the probable and possible TBI tiers but not between other tiers. Timing of symptom onset did not meaningfully differentiate between cases on severity measures; therefore, the delayed possible tier was eliminated, resulting in 2 tiers: probable and possible TBI., Conclusion: The 2-tiered TBI case definition that was derived from this analysis can be used in future surveillance efforts to differentiate cases by certainty and from noncases for the purpose of reporting TBI prevalence and incidence estimates. The refined case definition can help researchers increase the confidence they have in reporting survey respondents' self-reported TBIs as well as provide them with the flexibility to report an expansive (probable + possible TBI) or more conservative (probable TBI only) estimate of TBI prevalence., Competing Interests: Dr Corrigan's effort was supported in part by a grant from the National Institute on Disability, Independent Living, and Rehabilitation Research to Ohio State University (Grant 90DPTB0026). NIDILRR is a Center within the Administration for Community Living (ACL), Department of Health and Human Services (HHS). The contents of this publication do not necessarily represent the policy of NIDILRR, ACL, or HHS, and you should not assume endorsement by the Federal Government. For the remaining authors, no conflicts of interest were declared.

Introduction: Single-pulse transcranial magnetic stimulation (TMS) has many applications for pediatric clinical populations, including infants with perinatal brain injury. As a noninvasive neuromodulation tool, single-pulse TMS has been used safely in infants and children to assess corticospinal integrity and circuitry patterns. TMS may have important applications in early detection of atypical motor development or cerebral palsy., Areas Covered: The authors identified and summarized relevant studies incorporating TMS in infants, including findings related to corticospinal development and circuitry, motor cortex localization and mapping, and safety. This special report also describes methodologies and safety considerations related to TMS assessment in infants, and discusses potential applications related to diagnosis of cerebral palsy and early intervention., Expert Opinion: Single-pulse TMS has demonstrated safety and feasibility in infants with perinatal brain injury and may provide insight into neuromotor development and potential cerebral palsy diagnosis. Additional research in larger sample sizes will more fully evaluate the utility of TMS biomarkers in early diagnosis and intervention. Methodological challenges to performing TMS in infants and technical/equipment limitations require additional consideration and innovation toward clinical implementation. Future research may explore use of noninvasive neuromodulation techniques as an intervention in younger children with perinatal brain injury to improve motor outcomes.

Objective: Severe brain injuries can result in disorders of consciousness, such as the Minimally Conscious State (MCS), where individuals display intermittent yet discernible signs of conscious awareness. The varied levels of responsiveness and awareness observed in this state have spurred the progressive delineation of two subgroups within MCS, termed "plus" (MCS+) and "minus" (MCS-). However, the clinical validity of these classifications remains uncertain. This study aimed to investigate and compare the likelihood of emergence from MCS, as well as the functional independence after emergence, in individuals categorized as in MCS+ and MCS-., Methods: Demographic and behavioral data of 80 participants, admitted as either in MCS+ (n = 30) or MCS- (n = 50) to a long-term neurorehabilitation unit, were retrospectively analyzed. The neurobehavioral condition of each participant was evaluated weekly until discharge, demise, or emergence from MCS. The functional independence of those participants who emerged from MCS was assessed 6 months after emergence., Results: While only about half of the individuals classified as in MCS- (n = 24) emerged from the MCS, all those admitted as in MCS+ did, and in a shorter postinjury period. Despite these differences, all individuals who emerged from the MCS demonstrated similar high disability and low functional independence 6 months after emergence, regardless of their state at admission., Interpretation: Individuals classified as MCS+ exhibited a higher likelihood of emergence and a shorter time to emergence compared to those in MCS-. However, the level of functional independence 6 months after emergence was found to be unrelated to the initial state at admission., (© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Changes in arterial partial pressure of carbon dioxide (Pa co2 ) may alter cerebral perfusion in critically ill patients with acute brain injury. Consequently, international guidelines recommend normocapnia in mechanically ventilated patients with acute brain injury. The measurement of end-tidal capnography (Et co2 ) allows its approximation. Our objective was to report the agreement between trends in Et co2 and Pa co2 during mechanical ventilation in patients with acute brain injury., Methods: Retrospective monocenter study was conducted for 2 years. Critically ill patients with acute brain injury who required mechanical ventilation with continuous Et co2 monitoring and with 2 or more arterial gas were included. The agreement was evaluated according to the Bland and Altman analysis for repeated measurements with calculation of bias, and upper and lower limits of agreement. The directional concordance rate of changes between Et co2 and Pa co2 was evaluated with a 4-quadrant plot. A polar plot analysis was performed using the Critchley methods., Results: We analyzed the data of 255 patients with a total of 3923 paired ΔEt co2 and ΔPa co2 (9 values per patient in median). Mean bias by Bland and Altman analysis was -8.1 (95 CI, -7.9 to -8.3) mm Hg. The directional concordance rate between Et co2 and Pa co2 was 55.8%. The mean radial bias by polar plot analysis was -4.4° (95% CI, -5.5 to -3.3) with radial limit of agreement (LOA) of ±62.8° with radial LOA 95% CI of ±1.9°., Conclusions: Our results question the performance of trending ability of Et co2 to track changes in Pa co2 in a population of critically ill patients with acute brain injury. Changes in Et co2 largely failed to follow changes in Pa co2 in both direction (ie, low concordance rate) and magnitude (ie, large radial LOA). These results need to be confirmed in prospective studies to minimize the risk of bias., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2023 International Anesthesia Research Society.)

Methods evaluating the status of the injured brain have evolved over the past 63 years since Lundberg first reported clinical measurement of intracranial pressure (ICP) to evaluate the status of the injured brain (Lundberg, Acta Psychiatr Scand Suppl. 36:1-193, 1960). Subsequent evaluation involved measurement of the autoregulatory capacity of the brain by measuring cerebral blood flow (CBF) with decreasing mean arterial pressure (MAP) to define the critical CPP where the vasodilatory capacity of the cerebral circulation is exceeded and CBF begins to fall (CPP of 50 mmHg). A seminal advance was made by Marmarou (Marmarou et al., J Neurosurg. 48:332-344, 1978) who measured brain compliance by injecting a bolus of saline into the intracranial catheter while measuring the rise in intracranial pressure (ICP) otherwise known as induced pressure reactivity (iPRx). Seeking to utilise continuous measurement of iPRx in traumatic brain injury (TBI) patients with continuous monitoring of ICP, the ICP response to arterial pulsations was developed to evaluate the optimal CPP patients with raised ICP by the arterial pulsations-based iPRx. A similar approach was made with Doppler measurement of CBF with arterial pulsations for iCVRx to guide optimal CPP (CPPopt). Both iPRx and iCVRx are associated with microvascular shunts (MVS) and can accurately measure the critical CPP, whereas the CBF autoregulation curve by decreasing MAP does not. Sophisticated continuous multimodal monitoring established with ICM+ algorithms successfully identifies CPPopt for ICP control and identifies CBF dysregulation as related to outcome, but does not provide insights into the mechanisms involved in the loss of CBF autoregulation as related to increased ICP and potentially effective treatments (Froese et al., Neurocrit Care. 34:325-335, 2021)., (© 2024. Oxygen Transport to Tissue International.)

Recently, the usefulness of near-infrared spectroscopy-based cerebral oximetry in extremely preterm infants to prevent death or severe brain injury was evaluated in a study called SafeBoosC-III (N = 1601). In this study, the incidence of both outcomes was similar between the cerebral oximetry and the control group. In a previous smaller study called SafeBoosC-II (N = 166), there was a borderline significant advantage for cerebral oximetry. There is therefore a highly significant (p = 0.010) difference between the two outcomes. What could be the reason for the difference? One major difference was that many centres were not familiar with cerebral oximeters in the new study compared with the old study. This could be a reason for the discrepancy. We conclude that cerebral oximetry should not be disregarded as a method of neuromonitoring in neonatology., (© 2024. Oxygen Transport to Tissue International.)

Introduction: At present, neurodevelopmental abnormalities are the most frequent type of complication in school-aged children with congenital heart disease (CHD). We analysed the incidence of acute neurologic events (ANEs) in patients with operated CHD and the usefulness of neuromarkers for the prediction of neurodevelopment outcomes., Methods: Prospective observational study in infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. We assessed the following variables: (1) serum biomarkers of brain injury (S100B, neuron-specific enolase) in cord blood and preoperative blood samples; (2) clinical and laboratory data from the immediate postnatal and perioperative periods; (3) treatments and complications; (4) neurodevelopment (Bayley-III scale) at age 2 years., Results: the study included 84 infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. Seventeen had univentricular heart, 20 left ventricular outflow obstruction and 10 genetic syndromes. The postoperative mortality was 5.9% (5/84) and 10.7% (9/84) patients experienced ANEs. The mean overall Bayley-III scores were within the normal range, but 31% of patients had abnormal scores in the cognitive, motor or language domains. Patients with genetic syndromes, ANEs and univentricular heart had poorer neurodevelopmental outcomes. Elevation of S100B in the immediate postoperative period was associated with poorer scores., Conclusions: children with a history of cardiac surgery for CHD in the first year of life are at risk of adverse neurodevelopmental outcomes. Patients with genetic syndromes, ANEs or univentricular heart had poorer outcomes. Postoperative ANEs may contribute to poorer outcomes. Elevation of S100B levels in the postoperative period was associated with poorer neurodevelopmental outcomes at 2 years. Studies with larger samples and longer follow-ups are needed to define the role of these biomarkers of brain injury in the prediction of neurodevelopmental outcomes in patients who undergo surgery for management of CHD., (Copyright © 2023 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Impairment of executive functions is a frequent and disabling consequence of brain injury. In 1991, Shallice and Burgess elaborated the Multiple Errand Test (MET) to assess everyday troubles associated with this impairment., Objective: Our first aim was to create a generic version of MET (MET-G) readily adaptable to different settings and for retesting. The second aim was to validate the revised version to detect executive impairment in individuals with severe ABI., Methods: An inter-professional team of experts in neurorehabilitation created a revised version of MET. Twenty-one patients with sABI (severe Acquired Brain Injury) and a control group of 20 neurologically healthy subjects, took part in the testing of MET-G., Results: MET-G clearly distinguished people with sABI from healthy controls based on Total error score, task completion, and rule breaking. The test showed good inter-rater reliability and internal consistency., Conclusions: The new, generic version of MET was able to differentiate adults with sABI from controls and proved to be a good tool for evaluating executive functions in these patients in daily-life contexts. Indications on how to adapt the test to different contexts and different scoring modalities are provided.

Background Although individuals with acquired brain injury (ABI) may be vulnerable to cyberscams, the lack of existing measures documenting cybersafety behaviours in people with ABI limits our understanding of ABI-specific risk factors, the frequency of this problem, and the ability to evaluate evidence-based interventions. The CyberABIlity Scale was developed to assess vulnerability in people with ABI via self-rated statements and practical scam-identification tasks. This study aimed to develop and refine The CyberABIlity Scale through feedback from clinicians and people with ABI. Methods Scale feedback was collected via three rounds of clinician surveys (n  = 14) using Delphi methods and two rounds of cognitive interviews with participants with ABI (n  = 8). Following each round, feedback was quantitatively and qualitatively summarised, and revisions were made accordingly. Results Key revisions included removing 12 items deemed irrelevant. Instructions and rating scales were revised to improve clarity. Cognitive interviews identified 15 comprehension errors, with further revisions made to support response clarity for participants with ABI. Clinicians and participants with ABI endorsed the content and face validities of The CyberABIlity Scale . Conclusions Following further validation, The CyberABIlity Scale has the potential to be an effective screening measure for online vulnerability for people with ABI within clinical and research settings.

Fetal growth restriction (FGR) and small for gestational age (SGA) infants have increased risk of mortality and morbidity. Although both FGR and SGA infants have low birthweights for gestational age, a diagnosis of FGR also requires assessments of umbilical artery Doppler, physiological determinants, neonatal features of malnutrition, and in utero growth retardation. Both FGR and SGA are associated with adverse neurodevelopmental outcomes ranging from learning and behavioral difficulties to cerebral palsy. Up to 50% of FGR, newborns are not diagnosed until around the time of birth, yet this diagnosis lacks further indication of the risk of brain injury or adverse neurodevelopmental outcomes. Blood biomarkers may be a promising tool. Defining blood biomarkers indicating an infant's risk of brain injury would provide the opportunity for early detection and therefore earlier support. The aim of this review was to summarize the current literature to assist in guiding the future direction for the early detection of adverse brain outcomes in FGR and SGA neonates. The studies investigated potential diagnostic blood biomarkers from cord and neonatal blood or serum from FGR and SGA human neonates. Results were often conflicting with heterogeneity common in the biomarkers examined, timepoints, gestational age, and definitions of FGR and SGA used. Due to these variations, it was difficult to draw strong conclusions from the results. The search for blood biomarkers of brain injury in FGR and SGA neonates should continue as early detection and intervention is critical to improve outcomes for these neonates., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Objective: This commentary seeks to evaluate existing knowledge about the relationship between brain injury (BI) and overdose (OD), to unify distant bodies of literature, and to enhance prevention and treatment for opioid OD among individuals with BI., Background: There is a hidden epidemic of undiagnosed BI in the United States. Due to lack of screening, the vast majority of BI sufferers do not know they have a BI. Not only are those with BI at elevated risk for opioid use, misuse, and opioid use disorder, but also they are at elevated risk for OD. Conversely, those with OUD and those who experienced an OD, are more likely to sustain BI. Key Findings/Conclusions: The existing literature suggests that primary strategies to reduce ABI (Acquired Brain Injury)/TBI (Traumatic Brain Injury) harms involve addressing: screening, stigma, racial disparities, and popular misconceptions about OD. The association between TBI and OD is an underexamined public health issue, exacerbated by the bidirectional nature of the relationship. Not only is TBI a risk factor for opioid OD; opioid OD was also found to be a major cause of ABI, which can have lifelong effects similar to Alzheimer's disease. Screening tools for BI were underutilized and inconsistently implemented across reviewed studies. Enhanced screening population wide is a promising intervention, complemented with expanded treatment and research. Black individuals face worse outcomes in BI and treatment outcomes. Anti-racist strategies must fight inequity while addressing social and structural drivers of overdose and BI within the opioid and opioid overdose crises.

Traumatic brain injury (TBI) remains a major cause of morbidity and death among the pediatric population. Timely diagnosis, however, remains a complex task because of the lack of standardized methods that permit its accurate identification. The aim of this study was to determine whether serum levels of brain injury biomarkers can be used as a diagnostic and prognostic tool in this pathology. This prospective, observational study collected and analyzed the serum concentration of neuronal injury biomarkers at enrollment, 24h and 48h post-injury, in 34 children ages 0-18 with pTBI and 19 healthy controls (HC). Biomarkers included glial fibrillary acidic protein (GFAP), neurofilament protein L (NfL), ubiquitin-C-terminal hydrolase (UCH-L1), S-100B, tau and tau phosphorylated at threonine 181 (p-tau181). Subjects were stratified by admission Glasgow Coma Scale score into two categories: a combined mild/moderate (GCS 9-15) and severe (GCS 3-8). Glasgow Outcome Scale-Extended (GOS-E) Peds was dichotomized into favorable (≤4) and unfavorable (≥5) and outcomes. Data were analyzed utilizing Prism 9 and R statistical software. The findings were as follows: 15 patients were stratified as severe TBI and 19 as mild/moderate per GCS. All biomarkers measured at enrollment were elevated compared with HC. Serum levels for all biomarkers were significantly higher in the severe TBI group compared with HC at 0, 24, and 48h. The GFAP, tau S100B, and p-tau181 had the ability to differentiate TBI severity in the mild/moderate group when measured at 0h post-injury. Tau serum levels were increased in the mild/moderate group at 24h. In addition, NfL and p-tau181 showed increased serum levels at 48h in the aforementioned GCS category. Individual biomarker performance on predicting unfavorable outcomes was measured at 0, 24, and 48h across different GOS-E Peds time points, which was significant for p-tau181 at 0h at all time points, UCH-L1 at 0h at 6-9 months and 12 months, GFAP at 48h at 12 months, NfL at 0h at 12 months, tau at 0h at 12 months and S100B at 0h at 12 months. We concluded that TBI leads to increased serum neuronal injury biomarkers during the first 0-48h post-injury. A biomarker panel measuring these proteins could aid in the early diagnosis of mild to moderate pTBI and may predict neurological outcomes across the injury spectrum.

Aims: To examine whether accelerometry can quantitate asymmetry of upper limb activity in infants aged 3-12 months at risk for developing unilateral spastic cerebral palsy (USCP)., Method: A prospective study was performed in 50 infants with unilateral perinatal brain injury at high risk of developing USCP. Triaxial accelerometers were worn on the ipsilateral and contralesional upper limb during the Hand Assessment for Infants (HAI). Infants were grouped in three age intervals (3-5 months, 5-7.5 months and 7.5 until 12 months). Each age interval group was divided in a group with and without asymmetrical hand function based on HAI cutoff values suggestive of USCP., Results: In a total of 82 assessments, the asymmetry index for mean upper limb activity was higher in infants with asymmetrical hand function compared to infants with symmetrical hand function in all three age groups (ranging from 41 to 51% versus - 2-6%, p  < 0.01), while the total activity of both upper limbs did not differ., Conclusions: Upper limb accelerometry can identify asymmetrical hand function in the upper limbs in infants with unilateral perinatal brain injury from 3 months onwards and is complementary to the Hand Assessment for Infants.