Co-developing 'The CyberABIlity Scale' to assess vulnerability to cyberscams for people with acquired brain injury: Delphi and cognitive interviews with clinicians and people with acquired brain injury.

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.

Thermography Sensor to Assess Motor and Sensitive Neuromuscular Sequels of Brain Damage.

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.

MicroRNAs as biomarkers of brain injury in neonatal encephalopathy: an observational cohort study.

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.

Distance horizontal fusional facility (DFF): A new diagnostic vergence test for the acquired brain injury (ABI) population

Purpose To report the retrospectively-based, clinical diagnostic findings for the horizontal, distance, fusional facility (DFF) test in the non-TBI (traumatic brain inury), ABI (acquired brain injury) population. Methods The DFF test (4 pd base-out/2 pd base-in) was assessed and compared retrospectively in the first author's optometric practice in three clinical populations: (1) post-mTBI, visually-symptomatic (n = 52), (2) post-ABI, non-mTBI, visually-symptomatic (n = 34), and (3) visually-normal, visually asymptomatic (n = 44). Results The DFF values in each group were significantly different from each other (p < 0.05). The mean non-TBI, ABI group value was significantly lower than found in the mTBI group, and both were significantly lower than the mean found in the normal cohort (p < 0.05). There was a significant reduction in DFF with increased age (p < 0.001). ROC values for the AUC ranged from excellent to acceptable (0.94–0.74). Conclusion The DFF test is a new and useful way to assess horizontal, distance, dynamic, fusional facility in those with presumed non-mTBI, ABI neurological conditions to assist in its diagnosis. (AU)

Neuromonitoring in the ICU - what, how and why?

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.

Case identification of non-traumatic brain injury in youth using linked population data.

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, Maori 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.

Minimally conscious state plus versus minus: Likelihood of emergence and long-term functional independence.

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.

Single-pulse transcranial magnetic stimulation for assessment of motor development in infants with early brain injury.

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.

Single pulse transcranial magnetic stimulation (TMS) is a safe and noninvasive way to study brain activity in infants and children who have experienced brain injuries around the time of birth. Infants who have had an early brain injury may develop cerebral palsy, a developmental disability that affects movement. TMS uses a device that gives single pulses of energy to activate specific areas of the brain. This can be used to study how the brain connects to the muscles in the body through paths or 'tracts.' TMS helps researchers understand the development of the tracts and the potential need for therapy. This article reviews research studies that used TMS in infants and explains how TMS can be used to assess brain development. It also reviews safety considerations and challenges related to using TMS in infants. TMS could be a valuable tool for early diagnosis of cerebral palsy and could also help guide treatments for infants with brain injuries. However, more research is needed, using larger groups of infants, to potentially expand the use of TMS in clinical practice. Future directions include developing infant-specific research tools and using noninvasive brain stimulation to improve recovery for infants with brain injuries.

Covert consciousness.

Covert consciousness is a state of residual awareness following severe brain injury or neurological disorder that evades routine bedside behavioral detection. Patients with covert consciousness have preserved awareness but are incapable of self-expression through ordinary means of behavior or communication. Growing recognition of the limitations of bedside neurobehavioral examination in reliably detecting consciousness, along with advances in neurotechnologies capable of detecting brain states or subtle signs indicative of consciousness not discernible by routine examination, carry promise to transform approaches to classifying, diagnosing, prognosticating and treating disorders of consciousness. Here we describe and critically evaluate the evolving clinical category of covert consciousness, including approaches to its diagnosis through neuroimaging, electrophysiology, and novel behavioral tools, its prognostic relevance, and open questions pertaining to optimal clinical management of patients with covert consciousness recovering from severe brain injury.

Neurodevelopmental outcomes in congenital heart disease: Usefulness of biomarkers of brain injury.

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.

Detecting Asymmetry of Upper Limb Activity with Accelerometry in Infants at Risk for Unilateral Spastic Cerebral Palsy.

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.

Trending Ability of End-Tidal Capnography Monitoring During Mechanical Ventilation to Track Changes in Arterial Partial Pressure of Carbon Dioxide in Critically Ill Patients With Acute Brain Injury: A Monocenter Retrospective Study.

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.

Prognostic and Diagnostic Utility of Serum Biomarkers in Pediatric Traumatic Brain Injury.

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.

Unravelling the current shortfalls, challenges, and opportunities in traumatic brain injury.

The brain is the control centre of the human body. Injury to the brain can have diverse and disabling effects. Yet there remain important unanswered questions for clinicians, those affected and their families. This special collection aims to advance understanding of how we can better diagnose, treat and support those affected by brain injury across the severity spectrum.

Follow-up after PICU discharge for patients with acquired brain injury: the role of an abbreviated neuropsychological evaluation and a return-to-school program.

Objective: To present the results of an abbreviated testing protocol used to screen for neurocognitive and psychological sequelae of critical illness among pediatric intensive care unit (PICU) survivors with acquired brain injury in our post-discharge follow-up programs, and describe our process for facilitating this population's return to academic life. Design: Retrospective cohort study. Setting: Neurocritical care follow-up programs at two U.S. academic, tertiary medical/surgical PICUs. Patients: Children age > 4 years enrolled in the neurocritical care follow-up programs (n=289) at these institutions who underwent neurocognitive and psychological testing between 2017-2021. Interventions: None. Measurements and Main Results: One month after discharge from the hospital, nearly half of the children and/or their parents (48%) in our neurocritical care follow-up programs identified some type of emotional or behavioral concern compared to their premorbid state, and 15% reported some type of cognitive concern. On evaluation, 35% of the children were given a new neurocognitive diagnosis. Neurocognitive domains regulated by the executive functioning system were the most commonly affected, including attention (54%), memory (31%) and processing speed (27%). One-quarter of the children were given a new psychological diagnosis, most commonly post-traumatic stress disorder (PTSD) or stress-related symptoms (12%). Over 80% of patients in the programs were given new recommendations for school, for both new academic services and new classroom accommodations. Over half of children (57%) were referred for comprehensive follow-up neuropsychological evaluation. Conclusions: Abbreviated neurocognitive and psychological evaluation successfully identifies the same deficits commonly found among PICU survivors who undergo longer, more complete testing protocols. When combined with services aimed at successfully re-integrating PICU survivors back to school, this focused evaluation can provide an effective and efficient means of screening for cognitive and emotional deficits among PICU survivors, and establish a rationale for early academic support upon the child's return to school.

A biosensor for S100B detection based on PSS-MA-GoldMag-LFIA in early clinical diagnosis of brain damage.

S100B is an essential biomarker in the early diagnosis and treatment monitoring of brain injury. However, the traditional clinical diagnostic assay for S100B detection requires a complex operation or large equipment, which limits its application for rapid point-of-care tests (POCT). This study aimed to establish a lateral-flow immunoassay (LFIA) strip test system for S100B determination. PSS-MA-GoldMag nanoparticles were conjugated with anti-S100B antibodies as probes. Using this antibody-nanoparticle composite, an LFIA system based on magnetic quantification was established for S100B detection. For the evaluation of the performance of this LFIA system in clinical practice, 216 clinical samples were assayed using the LFIA test system and a commercial ECLI kit. Using the LFIA system, reliable results could be obtained in 30 min with a detection limit of 0.05 ng mL-1. The coefficient of variation (CV) was <13.8% and <14.03% for intra- and inter-assay precision, respectively. The recoveries were between 95.1 and 107.3%. The relative deviation of the interference experiments was <10%. In the analysis of clinical samples, the result indicated that the sera level of S100B in the detection group did not correlate with gender (p = 0.564 > 0.05) or age (p = 0.083 > 0.05). There is a good correlation between the novel method and the Elecsys®, with a determination coefficient of R2 0.9566, p > 0.05. The Bland-Altman analysis between the two ways shows that the 95% confidence bands between the two methods in measuring S100B were -0.27 ng mL-1 to +0.29 ng mL-1 with a mean difference of +0.006 ng mL-1. These results indicated that the novel LFIA system could be a simple, rapid, convenient, and accurate method for S100B determination.

Social workers and acquired brain injury: A systematic review of the current evidence-base.

Social work plays an important role in the assessment and treatment of people with acquired brain injury. Acquired brain injury is a complex and highly prevalent condition which can impact on cognitive, emotional and social domains. As acquired brain injury is a hidden disability it can be misdiagnosed or classified as another condition entirely. We sought to systematically explore the evidence base to examine how social workers have been prepared to work with their clients with brain injury. Employing six electronic databases (Social Policy & Practice, Web of Science, Scopus, PubMed, PsycINFO, CINAHL Plus) we reviewed 1071 papers. After applying eligibility criteria 17 papers were included in this review. We utilised standardised data extraction and quality appraisal tools to assess all included papers. Following appraisal, 9 papers were judged as possessing high methodological quality whilst 8 were judged as medium. Employing narrative synthesis, we identified four themes which captured the key findings of these papers. Themes were named as (i) advocacy and social work (ii) training and multidisciplinary team working (iii) inclusion of social networks and (iv) societal barriers. In order to meet their statutory responsibilities to practice safely, social workers must receive training in how to identify ABI and develop understanding of its consequences and subsequent need for provision. Social workers are also in a unique position to advocate for their clients and should make every effort to ensure their needs are met.

Raman Spectroscopy Spectral Fingerprints of Biomarkers of Traumatic Brain Injury.

Traumatic brain injury (TBI) affects millions of people of all ages around the globe. TBI is notoriously hard to diagnose at the point of care, resulting in incorrect patient management, avoidable death and disability, long-term neurodegenerative complications, and increased costs. It is vital to develop timely, alternative diagnostics for TBI to assist triage and clinical decision-making, complementary to current techniques such as neuroimaging and cognitive assessment. These could deliver rapid, quantitative TBI detection, by obtaining information on biochemical changes from patient's biofluids. If available, this would reduce mis-triage, save healthcare providers costs (both over- and under-triage are expensive) and improve outcomes by guiding early management. Herein, we utilize Raman spectroscopy-based detection to profile a panel of 18 raw (human, animal, and synthetically derived) TBI-indicative biomarkers (N-acetyl-aspartic acid (NAA), Ganglioside, Glutathione (GSH), Neuron Specific Enolase (NSE), Glial Fibrillary Acidic Protein (GFAP), Ubiquitin C-terminal Hydrolase L1 (UCHL1), Cholesterol, D-Serine, Sphingomyelin, Sulfatides, Cardiolipin, Interleukin-6 (IL-6), S100B, Galactocerebroside, Beta-D-(+)-Glucose, Myo-Inositol, Interleukin-18 (IL-18), Neurofilament Light Chain (NFL)) and their aqueous solution. The subsequently derived unique spectral reference library, exploiting four excitation lasers of 514, 633, 785, and 830 nm, will aid the development of rapid, non-destructive, and label-free spectroscopy-based neuro-diagnostic technologies. These biomolecules, released during cellular damage, provide additional means of diagnosing TBI and assessing the severity of injury. The spectroscopic temporal profiles of the studied biofluid neuro-markers are classed according to their acute, sub-acute, and chronic temporal injury phases and we have further generated detailed peak assignment tables for each brain-specific biomolecule within each injury phase. The intensity ratios of significant peaks, yielding the combined unique spectroscopic barcode for each brain-injury marker, are compared to assess variance between lasers, with the smallest variance found for UCHL1 (σ2 = 0.000164) and the highest for sulfatide (σ2 = 0.158). Overall, this work paves the way for defining and setting the most appropriate diagnostic time window for detection following brain injury. Further rapid and specific detection of these biomarkers, from easily accessible biofluids, would not only enable the triage of TBI, predict outcomes, indicate the progress of recovery, and save healthcare providers costs, but also cement the potential of Raman-based spectroscopy as a powerful tool for neurodiagnostics.

Clinical Grading Scales and Neuroprognostication in Acute Brain Injury.

Prediction of neurological clinical outcome after acute brain injury is critical because it helps guide discussions with patients and families and informs treatment plans and allocation of resources. Numerous clinical grading scales have been published that aim to support prognostication after acute brain injury. However, the development and validation of clinical scales lack a standardized approach. This in turn makes it difficult for clinicians to rely on prognostic grading scales and to integrate them into clinical practice. In this review, we discuss quality measures of score development and validation and summarize available scales to prognosticate outcomes after acute brain injury. These include scales developed for patients with coma, cardiac arrest, ischemic stroke, nontraumatic intracerebral hemorrhage, subarachnoid hemorrhage, and traumatic brain injury; for each scale, we discuss available validation studies.