Clinical Use of Bedside Portable Ultra-Low-Field Brain Magnetic Resonance Imaging in Patients on Extracorporeal Membrane Oxygenation: Results From the Multicenter SAFE MRI ECMO Study.

BACKGROUND: Early detection of acute brain injury (ABI) at the bedside is critical in improving survival for patients with extracorporeal membrane oxygenation (ECMO) support. We aimed to examine the safety of ultra-low-field (ULF; 0.064-T) portable magnetic resonance imaging (pMRI) in patients undergoing ECMO and to investigate the ABI frequency and types with ULF-pMRI. METHODS: This was a multicenter prospective observational study (SAFE MRI ECMO study [Assessing the Safety and Feasibility of Bedside Portable Low-Field Brain Magnetic Resonance Imaging in Patients on ECMO]; NCT05469139) from 2 tertiary centers (Johns Hopkins, Baltimore, MD and University of Texas-Houston) with specially trained intensive care units. Primary outcomes were safety of ULF-pMRI during ECMO support, defined as completion of ULF-pMRI without significant adverse events. RESULTS: Of 53 eligible patients, 3 were not scanned because of a large head size that did not fit within the head coil. ULF-pMRI was performed in 50 patients (median age, 58 years; 52% male), with 34 patients (68%) on venoarterial ECMO and 16 patients (32%) on venovenous ECMO. Of 34 patients on venoarterial ECMO, 11 (22%) were centrally cannulated and 23 (46%) were peripherally cannulated. In venovenous ECMO, 9 (18%) had single-lumen cannulation and 7 (14%) had double-lumen cannulation. Of 50 patients, adverse events occurred in 3 patients (6%), with 2 minor adverse events (ECMO suction event; transient low ECMO flow) and one serious adverse event (intra-aortic balloon pump malfunction attributable to electrocardiographic artifacts). All images demonstrated discernible intracranial pathologies with good quality. ABI was observed in 22 patients (44%). Ischemic stroke (36%) was the most common type of ABI, followed by intracranial hemorrhage (6%) and hypoxic-ischemic brain injury (4%). Of 18 patients (36%) with both ULF-pMRI and head computed tomography within 24 hours, ABI was observed in 9 patients with a total of 10 events (8 ischemic, 2 hemorrhagic events). Of the 8 ischemic events, pMRI observed all 8, and head computed tomography observed only 4 events. For intracranial hemorrhage, pMRI observed only 1 of them, and head computed tomography observed both (2 events). CONCLUSIONS: Our study demonstrates that ULF-pMRI can be performed in patients on ECMO across different ECMO cannulation strategies in specially trained intensive care units. The incidence of ABI was high, seen in 44% of ULF-pMRI studies. ULF-pMRI imaging appears to be more sensitive to ABI, particularly ischemic stroke, compared with head computed tomography.

Improving Outcomes After Post-Cardiac Arrest Brain Injury: A Scientific Statement From the International Liaison Committee on Resuscitation.

This scientific statement presents a conceptual framework for the pathophysiology of post-cardiac arrest brain injury, explores reasons for previous failure to translate preclinical data to clinical practice, and outlines potential paths forward. Post-cardiac arrest brain injury is characterized by 4 distinct but overlapping phases: ischemic depolarization, reperfusion repolarization, dysregulation, and recovery and repair. Previous research has been challenging because of the limitations of laboratory models; heterogeneity in the patient populations enrolled; overoptimistic estimation of treatment effects leading to suboptimal sample sizes; timing and route of intervention delivery; limited or absent evidence that the intervention has engaged the mechanistic target; and heterogeneity in postresuscitation care, prognostication, and withdrawal of life-sustaining treatments. Future trials must tailor their interventions to the subset of patients most likely to benefit and deliver this intervention at the appropriate time, through the appropriate route, and at the appropriate dose. The complexity of post-cardiac arrest brain injury suggests that monotherapies are unlikely to be as successful as multimodal neuroprotective therapies. Biomarkers should be developed to identify patients with the targeted mechanism of injury, to quantify its severity, and to measure the response to therapy. Studies need to be adequately powered to detect effect sizes that are realistic and meaningful to patients, their families, and clinicians. Study designs should be optimized to accelerate the evaluation of the most promising interventions. Multidisciplinary and international collaboration will be essential to realize the goal of developing effective therapies for post-cardiac arrest brain injury.

Microvascular Network Remodeling in the Ischemic Mouse Brain Defined by Light Sheet Microscopy.

BACKGROUND: Until now, the analysis of microvascular networks in the reperfused ischemic brain has been limited due to tissue transparency challenges. METHODS: Using light sheet microscopy, we assessed microvascular network remodeling in the striatum from 3 hours to 56 days post-ischemia in 2 mouse models of transient middle cerebral artery occlusion lasting 20 or 40 minutes, resulting in mild ischemic brain injury or brain infarction, respectively. We also examined the effect of a clinically applicable S1P (sphingosine-1-phosphate) analog, FTY720 (fingolimod), on microvascular network remodeling. RESULTS: Over 56 days, we observed progressive microvascular degeneration in the reperfused striatum, that is, the lesion core, which was followed by robust angiogenesis after mild ischemic injury induced by 20-minute middle cerebral artery occlusion. However, more severe ischemic injury elicited by 40-minute middle cerebral artery occlusion resulted in incomplete microvascular remodeling. In both cases, microvascular networks did not return to their preischemic state but displayed a chronically altered pattern characterized by higher branching point density, shorter branches, higher unconnected branch density, and lower tortuosity, indicating enhanced network connectivity. FTY720 effectively increased microvascular length density, branching point density, and volume density in both models, indicating an angiogenic effect of this drug. CONCLUSIONS: Utilizing light sheet microscopy together with automated image analysis, we characterized microvascular remodeling in the ischemic lesion core in unprecedented detail. This technology will significantly advance our understanding of microvascular restorative processes and pave the way for novel treatment developments in the stroke field.

Not So Transient?: A Narrative Review on Cognitive Impairment After Transient Ischemic Attack.

Transient ischemic attack (TIA) is traditionally viewed as a self-resolving episode of neurological change without persistent impairments and without evidence of acute brain injury on neuroimaging. However, emerging evidence suggests that TIA may be associated with lingering cognitive dysfunction. Cognitive impairment is a prevalent and disabling sequela of ischemic stroke, but the clinical relevance of this phenomenon after TIA is less commonly recognized. We performed a literature search of observational studies of cognitive function after TIA. There is a consistent body of literature suggesting that rates of cognitive impairment following TIA are higher than healthy controls, but the studies included here are limited by heterogeneity in design and analysis methods. We go on to summarize recent literature on proposed pathophysiological mechanisms underlying the development of cognitive impairment following TIA and finally suggest future directions for further research in this field.

Head Injury and Risk of Incident Ischemic Stroke in Community-Dwelling Adults.

BACKGROUND: While stroke is a recognized short-term sequela of traumatic brain injury, evidence about long-term ischemic stroke risk after traumatic brain injury remains limited. METHODS: The Atherosclerosis Risk in Communities Study is an ongoing prospective cohort comprised of US community-dwelling adults enrolled in 1987 to 1989 followed through 2019. Head injury was defined using self-report and hospital-based diagnostic codes and was analyzed as a time-varying exposure. Incident ischemic stroke events were physician-adjudicated. We used Cox regression adjusted for sociodemographic and cardiovascular risk factors to estimate the hazard of ischemic stroke as a function of head injury. Secondary analyses explored the number and severity of head injuries; the mechanism and severity of incident ischemic stroke; and heterogeneity within subgroups defined by race, sex, and age. RESULTS: Our analysis included 12 813 participants with no prior head injury or stroke. The median follow-up age was 27.1 years (25th-75th percentile=21.1-30.5). Participants were of median age 54 years (25th-75th percentile=49-59) at baseline; 57.7% were female and 27.8% were Black. There were 2158 (16.8%) participants with at least 1 head injury and 1141 (8.9%) participants with an incident ischemic stroke during follow-up. For those with head injuries, the median age to ischemic stroke was 7.5 years (25th-75th percentile=2.2-14.0). In adjusted models, head injury was associated with an increased hazard of incident ischemic stroke (hazard ratio [HR], 1.34 [95% CI, 1.12-1.60]). We observed evidence of dose-response for the number of head injuries (1: HR, 1.16 [95% CI, 0.97-1.40]; ≥2: HR, 1.94 [95% CI, 1.39-2.71]) but not for injury severity. We observed evidence of stronger associations between head injury and more severe stroke (National Institutes of Health Stroke Scale score ≤5: HR, 1.31 [95% CI, 1.04-1.64]; National Institutes of Health Stroke Scale score 6-10: HR, 1.64 [95% CI, 1.06-2.52]; National Institutes of Health Stroke Scale score ≥11: HR, 1.80 [95% CI, 1.18-2.76]). Results were similar across stroke mechanism and within strata of race, sex, and age. CONCLUSIONS: In this community-based cohort, head injury was associated with subsequent ischemic stroke. These results suggest the importance of public health interventions aimed at preventing head injuries and primary stroke prevention among individuals with prior traumatic brain injuries.

A neurophysiological profiling of the heartbeat-evoked potential in severe acquired brain injuries: A focus on unconsciousness.

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.

Uncovering the hidden effects of repetitive subconcussive head impact exposure: A mega-analytic approach characterizing seasonal brain microstructural changes in contact and collision sports athletes.

Repetitive subconcussive head impacts (RSHI) are believed to induce sub-clinical brain injuries, potentially resulting in cumulative, long-term brain alterations. This study explores patterns of longitudinal brain white matter changes across sports with RSHI-exposure. A systematic literature search identified 22 datasets with longitudinal diffusion magnetic resonance imaging data. Four datasets were centrally pooled to perform uniform quality control and data preprocessing. A total of 131 non-concussed active athletes (American football, rugby, ice hockey; mean age: 20.06 ± 2.06 years) with baseline and post-season data were included. Nonparametric permutation inference (one-sample t tests, one-sided) was applied to analyze the difference maps of multiple diffusion parameters. The analyses revealed widespread lateralized patterns of sports-season-related increases and decreases in mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) across spatially distinct white matter regions. Increases were shown across one MD-cluster (3195 voxels; mean change: 2.34%), one AD-cluster (5740 voxels; mean change: 1.75%), and three RD-clusters (817 total voxels; mean change: 3.11 to 4.70%). Decreases were shown across two MD-clusters (1637 total voxels; mean change: -1.43 to -1.48%), two RD-clusters (1240 total voxels; mean change: -1.92 to -1.93%), and one AD-cluster (724 voxels; mean change: -1.28%). The resulting pattern implies the presence of strain-induced injuries in central and brainstem regions, with comparatively milder physical exercise-induced effects across frontal and superior regions of the left hemisphere, which need further investigation. This article highlights key considerations that need to be addressed in future work to enhance our understanding of the nature of observed white matter changes, improve the comparability of findings across studies, and promote data pooling initiatives to allow more detailed investigations (e.g., exploring sex- and sport-specific effects).

Incidence of brain injuries in a large cohort of very preterm and extremely preterm infants at term-equivalent age: results of a single tertiary neonatal care center over 10 years.

OBJECTIVES: Cerebral magnetic resonance imaging (cMRI) at term-equivalent age (TEA) can detect brain injury (BI) associated with adverse neurological outcomes in preterm infants. This study aimed to assess BI incidences in a large, consecutive cohort of preterm infants born < 32 weeks of gestation, the comparison between very (VPT, ≥ 28 + 0 to < 32 + 0 weeks of gestation) and extremely preterm infants (EPT, < 28 + 0 weeks of gestation) and across weeks of gestation. METHODS: We retrospectively analyzed cMRIs at TEA of VPT and EPT infants born at a large tertiary center (2009-2018). We recorded and compared the incidences of BI, severe BI, intraventricular hemorrhage (IVH), periventricular hemorrhagic infarction (PVHI), cerebellar hemorrhage (CBH), cystic periventricular leukomalacia (cPVL), and punctate white matter lesions (PWML) between VPTs, EPTs, and across weeks of gestation. RESULTS: We included 507 preterm infants (VPT, 335/507 (66.1%); EPT, 172/507 (33.9%); mean gestational age (GA), 28 + 2 weeks (SD 2 + 2 weeks); male, 52.1%). BIs were found in 48.3% of the preterm infants (severe BI, 12.0%) and increased with decreasing GA. IVH, PVHI, CBH, cPVL, and PWML were seen in 16.8%, 0.8%, 10.5%, 3.4%, and 18.1%, respectively. EPT vs. VPT infants suffered more frequently from BI (59.3% vs. 42.7%, p < 0.001), severe BI (18.6% vs. 8.7%, p = 0.001), IVH (31.9% vs. 9.0%, p < 0.001), and CBH (18.0% vs. 6.6%, p < 0.001). CONCLUSION: Brain injuries are common cMRI findings among preterm infants with a higher incidence of EPT compared to VPT infants. These results may serve as reference values for clinical management and research. CLINICAL RELEVANCE STATEMENT: Our results with regard to gestational age might provide valuable clinical insights, serving as a key reference for parental advice, structured follow-up planning, and enhancing research and management within the Neonatal Intensive Care Unit. KEY POINTS: • Brain injury is a common cMRI finding in preterm infants seen in 48.3% individuals. • Extremely preterm compared to very preterm infants have higher brain injury incidences driven by brain injuries such as intraventricular and cerebellar hemorrhage. • Reference incidence values are crucial for parental advice and structured follow-up planning.

'Knock down the brain': a nonlinear analysis of electroencephalography to study the effects of sub-concussion in boxers.

BACKGROUND AND PURPOSE: Boxing is associated with a high risk of head injuries and increases the likelihood of chronic traumatic encephalopathy. This study explores the effects of sub-concussive impacts on boxers by applying both linear and nonlinear analysis methods to electroencephalogram (EEG) data. METHODS: Twenty-one boxers were selected (mean ± SD, age 28.38 ± 5.5 years; weight 67.55 ± 8.90 kg; years of activity 6.76 ± 5.45; education 14.19 ± 3.08 years) and divided into 'beginner' and 'advanced' groups. The Montreal Cognitive Assessment and the Frontal Assessment Battery were administered; EEG data were collected in both eyes-open (EO) and eyes-closed (EC) conditions during resting states. Analyses of EEG data included normalized power spectral density (nPSD), power law exponent (PLE), detrended fluctuation analysis and multiscale entropy. Statistical analyses were used to compare the groups. RESULTS: Significant differences in nPSD and PLE were observed between the beginner and advanced boxers, with advanced boxers showing decreased mean nPSD and PLE (nPSD 4-7 Hz, p = 0.013; 8-13 Hz, p = 0.003; PLE frontal lobe F3 EC, p = 0.010). Multiscale entropy analysis indicated increased entropy at lower frequencies and decreased entropy at higher frequencies in advanced boxers (F3 EC, p = 0.024; occipital lobe O1 EO, p = 0.029; occipital lobe O2 EO, p = 0.036). These changes are similar to those seen in Alzheimer's disease. CONCLUSION: Nonlinear analysis of EEG data shows potential as a neurophysiological biomarker for detecting the asymptomatic phase of chronic traumatic encephalopathy in boxers. This methodology could help monitor athletes' health and reduce the risk of future neurological injuries in sports.

Drugs, Delirium, and Trauma: Substance Use and Incidence of Delirium After Traumatic Brain Injury.

INTRODUCTION: There is a paucity of data on the effect of preinjury substance (alcohol, drugs) abuse on the risk of delirium in patients with traumatic brain injury (TBI). This study aimed to assess the incidence of delirium among patients with blunt TBI in association with different substances. METHODS: We analyzed the 2020 American College of Surgeons-Trauma Quality Improvement Program. We included all adult (≥18 y) patients with blunt TBI who had a recorded substance (drugs and alcohol) screening. Our primary outcome was the incidence of delirium. RESULTS: A total of 72,901 blunt TBI patients were identified. The mean (standard deviation) age was 56 (20) years and 68.0% were males. The median (interquartile range) injury severity score was 17 (10-25). Among the study population, 23.1% tested positive for drugs (Stimulants: 3.0%; Depressants: 2.9%, hallucinogens: 5.1%, Cannabinoids: 13.4%, TCAs: 0.1%), and 22.8% tested positive for Alcohol. Overall, 1856 (2.5%) experienced delirium. On univariate analysis, patients who developed delirium were more likely to have positive drug screening results. On multivariable regression analyses, positive screen tests for isolated stimulants (adjusted odds ratio [aOR]: 1.340, P = 0.018), tricyclic antidepressants (aOR: 3.107, P = 0.019), and cannabinoids (aOR: 1.326, P ≤ 0.001) were independently associated with higher odds of developing delirium. CONCLUSIONS: Nearly one-fourth of adult patients with blunt TBI had an initial positive substance screening test. Patients with positive results for isolated stimulants, tricyclic antidepressants, and cannabinoids were at a higher risk of developing delirium, whereas this association was not evident with other drugs and alcohol-positive tests. These findings emphasize the need for early drug screening in TBI patients and close monitoring of patients with positive screening tests.

National Analysis of Outcomes for Adult Trauma Patients With Isolated Severe Blunt Traumatic Brain Injury Following Venous Thromboembolism Prophylaxis.

INTRODUCTION: We aim to evaluate the association of early versus late venous thromboembolism (VTE) prophylaxis on in-hospital mortality among patients with severe blunt isolated traumatic brain injuries. METHODS: Data from the American College of Surgeons Trauma Quality Program Participant Use File for 2017-2021 were analyzed. The target population included adult trauma patients with severe isolated traumatic brain injury (TBI). VTE prophylaxis types (low molecular weight heparin and unfractionated heparin) and their administration timing were analyzed in relation to in-hospital complications and mortality. RESULTS: The study comprised 3609 patients, predominantly Caucasian males, with an average age of 48.5 y. Early VTE prophylaxis recipients were younger (P < 0.01) and more likely to receive unfractionated heparin (P < 0.01). VTE prophylaxis later than 24 h was associated with a higher average injury severity score and longer intensive care unit stays (P < 0.01). Logistic regression revealed that VTE prophylaxis later than 24 h was associated with significant reduction of in-hospital mortality by 38% (odds ratio 0.62, 95% confidence interval 0.40-0.94, P = 0.02). Additionally, low molecular weight heparin use was associated with decreased mortality odds by 30% (odds ratio 0.70, 95% confidence interval 0.55-0.89, P < 0.01). CONCLUSIONS: VTE prophylaxis later than 24 h is associated with a reduced risk of in-hospital mortality in patients with severe isolated blunt TBI, as opposed to VTE prophylaxis within 24 h. These findings suggest the need for timely and appropriate VTE prophylaxis in TBI care, highlighting the critical need for a comprehensive assessment and further research concerning the safety and effectiveness of VTE prophylaxis in these patient populations.

Comparing neuropsychological, typical, and ADNI criteria for the diagnosis of mild cognitive impairment in Vietnam-era veterans.

OBJECTIVE: Neuropsychological criteria for mild cognitive impairment (MCI) more accurately predict progression to Alzheimer's disease (AD) and are more strongly associated with AD biomarkers and neuroimaging profiles than ADNI criteria. However, research to date has been conducted in relatively healthy samples with few comorbidities. Given that history of traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) are risk factors for AD and common in Veterans, we compared neuropsychological, typical (Petersen/Winblad), and ADNI criteria for MCI in Vietnam-era Veterans with histories of TBI or PTSD. METHOD: 267 Veterans (mean age = 69.8) from the DOD-ADNI study were evaluated for MCI using neuropsychological, typical, and ADNI criteria. Linear regressions adjusting for age and education assessed associations between MCI status and AD biomarker levels (cerebrospinal fluid [CSF] p-tau181, t-tau, and Aß42) by diagnostic criteria. Logistic regressions adjusting for age and education assessed the effects of TBI severity and PTSD symptom severity simultaneously on MCI classification by each criteria. RESULTS: Agreement between criteria was poor. Neuropsychological criteria identified more Veterans with MCI than typical or ADNI criteria, and were associated with higher CSF p-tau181 and t-tau. Typical and ADNI criteria were not associated with CSF biomarkers. PTSD symptom severity predicted MCI diagnosis by neuropsychological and ADNI criteria. History of moderate/severe TBI predicted MCI by typical and ADNI criteria. CONCLUSIONS: MCI diagnosis using sensitive neuropsychological criteria is more strongly associated with AD biomarkers than conventional diagnostic methods. MCI diagnostics in Veterans would benefit from incorporation of comprehensive neuropsychological methods and consideration of the impact of PTSD.

Recovery trajectories of IQ after pediatric TBI: A latent class growth modeling analysis.

OBJECTIVE: To identify latent trajectories of IQ over time after pediatric traumatic brain injury (TBI) and examine the predictive value of risk factors within and across recovery trajectories. METHOD: 206 children ages 3-7 years at injury were included: 87 TBI (23 severe, 21 moderate, 43 complicated mild) and 119 orthopedic injury (OI). We administered intelligence tests shortly after injury (1½ months), 12 months, and 6.8 years postinjury. Latent class growth modeling was used to identify latent subgroups. Separate models examined verbal and nonverbal IQ recovery trajectories following TBI versus OI. Variables included: age at injury, sex, race, socioeconomic status, injury severity, quality of the home environment, family functioning, and parenting style. RESULTS: Both the TBI and OI analyses yielded different growth models for nonverbal (k = 3) and verbal IQ (k = 3). Although all models resulted in 3 latent classes (below average, average, and aboveaverage performance); trajectory shapes, contributors to class membership, and performance within each class varied by injury group and IQ domain. TBI severity was associated with class membership for nonverbal IQ, with less severe injuries associated with higher IQ scores; however, TBI severity did not influence verbal IQ class membership. Parenting style had a more prominent effect on verbal and nonverbal IQ within the TBI than OI trajectories. CONCLUSIONS: Findings suggest TBI severity is related to recovery trajectories for nonverbal but not verbal IQ and parenting style has stronger effects on recovery in TBI than OI. Results highlight the importance of parental factors on long-term recovery after TBI.

Exposure to Sedation and Analgesia Medications: Short-term Cognitive Outcomes in Pediatric Critical Care Survivors With Acquired Brain Injury.

Background/Objective: Pediatric intensive care unit (PICU) survivors risk significant cognitive morbidity, particularly those with acquired brain injury (ABI) diagnoses. Studies show sedative and analgesic medication may potentiate neurologic injury, but few studies evaluate impact on survivor outcomes. This study aimed to evaluate whether exposures to analgesic and sedative medications are associated with worse neurocognitive outcome. Methods: A retrospective cohort study was conducted of 91 patients aged 8 to 18 years, undergoing clinical neurocognitive evaluation approximately 1 to 3 months after PICU discharge. Electronic health data was queried for sedative and analgesic medication exposures, including opioids, benzodiazepines, propofol, ketamine, and dexmedetomidine. Doses were converted to class equivalents, evaluated by any exposure and cumulative dose exposure per patient weight. Cognitive outcome was derived from 8 objective cognitive assessments with an emphasis on executive function skills using Principal Components Analysis. Then, linear regression was used to control for baseline cognitive function estimates to calculate a standardized residualized neurocognitive index (rNCI) z-score. Multivariable linear regression evaluated the association between rNCI and medication exposure controlling for covariates. Significance was defined as P < .05. Results: Most (n = 80; 88%) patients received 1 or more study medications. Any exposure and higher cumulative doses of benzodiazepine and ketamine were significantly associated with worse rNCI in bivariate analyses. When controlling for Medicaid, preadmission comorbid conditions, length of stay, delirium, and receipt of other medication classes, receipt of benzodiazepine was associated with significantly worse rNCI (ß-coefficient = -0.48, 95% confidence interval = -0.88, -0.08). Conclusions: Exposure to benzodiazepines was independently associated with worse acute phase cognitive outcome using objective assessments focused on executive function skills when controlling for demographic and illness characteristics. Clinician decisions regarding medication regimens in the PICU may serve as a modifiable factor to improve outcomes. Additional inquiry into associations with long-term cognitive outcome and optimal medication regimens is needed.

Mild Traumatic Brain Injury Characteristics and Symptoms in Preschool Children: How Do They Differ to School Age Children? A Multicenter Prospective Observational Study.

OBJECTIVE: To investigate if preschool children differ to school age children with mild traumatic brain injury (TBI) with respect to injury causes, clinical presentation, and medical management. DESIGN: A secondary analysis of a dataset from a large, prospective and multisite cohort study on TBI in children aged 0-18 years, the Australian Paediatric Head Injury Rules Study. SETTING: Nine pediatric emergency departments (ED) and 1 combined adult and pediatric ED located across Australia and New Zealand. PARTICIPANTS: 7080 preschool aged children (2-5 years) were compared with 5251 school-age children (6-12 years) with mild TBI (N= (N=12,331) MAIN OUTCOME MEASURES: Clinical report form on medical symptoms, injury causes, and management. RESULTS: Preschool children were less likely to be injured with a projectile than school age children (P<.001). Preschool children presented with less: loss of consciousness (P<.001), vomiting (P<.001), drowsiness (P=.002), and headache (P<.001), and more irritability and agitation (P=.003), than school-age children in the acute period after mild TBI. Preschool children were less likely to have neuroimaging of any kind (P<.001) or to be admitted for observation than school age children (P<.001). CONCLUSIONS: Our large prospective study has demonstrated that preschool children with mild TBI experience a different acute symptom profile to older children. There are significant clinical implications with symptoms post-TBI used in medical management to aid decisions on neuroimaging and post-acute intervention.

Head Control Contributes to Prediction of Emergence From the Minimally Conscious State in Children Admitted to Inpatient Rehabilitation.

OBJECTIVE: To examine the utility of head and trunk control, assessed using the Physical Abilities and Mobility Scale, for predicting emergence from a minimally conscious state (eMCS) among children with acquired brain injury admitted to inpatient rehabilitation in a disorder of consciousness (DoC). DESIGN: Retrospective study. SETTING: Pediatric inpatient rehabilitation hospital. PARTICIPANTS: Forty patients (2-21 years-old) directly admitted from acute care to pediatric inpatient brain injury rehabilitation in a DoC (average length of stay=85 days; N=40). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: State of consciousness (eMCS vs not) at discharge from inpatient rehabilitation. RESULTS: Forty-five percent of patients emerged from a minimally conscious state during inpatient rehabilitation. Admission state of consciousness and head control (but not trunk control) were significantly associated with eMCS and provided complementary prognostic information. Admission state of consciousness (ie, admitting in a vegetative state/unresponsive wakefulness syndrome) afforded the greatest negative predictive value (93.8%), whereas admission head control ability afforded the greatest positive predictive value (81.8% for any independent head control; 100% for maintaining head-up position for >30 seconds). Fifty percent of patients who emerged during the inpatient stay did not have independent head control at admission, highlighting the importance of exploring head control as a prognostic marker in conjunction with indicators with greater sensitivity (eg, state of consciousness at admission). CONCLUSIONS: A brief measure of head control at admission may contribute to identification of a subgroup of patients who are likely to emerge.

Factors Related to the Quality and Stability of Partner Relationships After Stroke: A Systematic Literature Review.

OBJECTIVE: To provide an overview of the current state of knowledge on factors related to relationship quality and relationship stability after stroke. DATA SOURCES: Cumulative Index to Nursing and Allied Health (CINAHL), Embase, MEDLINE, Psychology and Behavioral Sciences Collection, APA PsycINFO, and PubMed were searched on November 15, 2022, for literature on factors associated with (1) relation quality and (2) relation stability after stroke. STUDY SELECTION: English quantitative and qualitative studies investigating factors associated with relation quality and/or stability after stroke were included. Three reviewers independently assessed eligibility. Consensus meetings were held in case of divergent opinions. A total of 44 studies were included. DATA EXTRACTION: Information regarding study objectives and characteristics, participant demographics, independent and dependent variables, and main findings was extracted. Study quality was rated using the Joanna Briggs Institute Checklist for Analytical Cross-Sectional Studies and/or the Critical Appraisal Skills Programme Checklist for Qualitative Research. Both were administered by the lead reviewer and checked by the second reviewer. Identified factors are described and presented according to the domains of the International Classification of Functioning, Disability, and Health model. DATA SYNTHESIS: Thirty-seven factors related to relationship quality after stroke were identified, covering the domains of body functions and structures (eg, cognitive problems), activities (eg, decrease in physical intimacy), participation (eg, being socially active), environment (eg, medication side effects), and personal factors (eg, hypervigilance). Eight factors related to relationship stability were identified, covering the domains of participation (agreement on reciprocal roles) and personal factors (eg, quality of prestroke relation). CONCLUSIONS: Relationship quality and stability after stroke are related to a multitude of factors. Future research should confirm the relevance of factors found in a few studies of suboptimal quality; explore possible associations between relationship stability and factors falling in the domains of body functions and structure, activity, and environmental factors; and explicitly explore potential positive effects of stroke on relationships.

Longitudinal Investigation of Alexithymia as a Predictor of Empathy, Emotional Functioning, Resilience, and Life Satisfaction 2 Years After Brain Injury.

OBJECTIVE: To examine the unique contribution of alexithymia at 1 year after traumatic brain injury (TBI) to the prospective prediction of emotional and social health outcomes at 2 years after injury. DESIGN: Multicenter, longitudinal cohort study. SETTING: Data were collected during year 1 and year 2 postinjury follow-up interviews across 4 TBI Model System centers. PARTICIPANTS: Persons with TBI (N=175; 134 men and 41 women) who had English fluency and were capable of providing self-reported data. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Primary independent variable was the Toronto Alexithymia Scale-20. Outcome measures included the Interpersonal Reactivity Index, National Institute of Health Toolbox Emotion Battery Anger, Difficulty with Emotion Regulation Scale, Connor-Davidson Resilience Scale, Posttraumatic Stress Disorder Checklist - Civilian, Satisfaction with Life Scale, General Anxiety Disorder-7, Patient Health Questionnaire 9, suicidal ideation, and problematic substance use. RESULTS: Simple adjusted models demonstrated that after controlling for the specific outcome at year 1, Toronto Alexithymia Scale-20 scores significantly predicted year 2 scores for perspective-taking, physical aggression, emotional dysregulation, resilience, anxiety, depression, and suicidal ideation. All of these predictive findings except for physical aggression were maintained in the fully adjusted models that also controlled for age, sex, education level, number of prior TBIs, and motor and cognitive functioning. CONCLUSIONS: Compared with those with lower alexithymia scores, persons with TBI who had higher alexithymia scores at 1 year after injury reported poorer emotional health at 2 years after TBI, even after controlling for year 1 outcome scores, sociodemographic characteristics, and injury-related factors. These results support the need to assess for elevated alexithymia and to provide interventions targeting alexithymia early in the TBI recovery process.

Traumatic Brain Injury and Its Risk Factors in a Homeless Population.

OBJECTIVE: To characterize the traumatic brain injury (TBI) profile and its associated risk factors in homeless individuals in Santa Clara County, CA. DESIGN: Observational cohort study. SETTING: Two homeless shelter health clinics in Santa Clara County, CA. PARTICIPANTS: Currently or recently homeless individuals seeking health care at 2 homeless shelter health clinics between August 2013 and May 2014. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Demographics, TBI incidence and characteristics. RESULTS: The findings indicate that TBI history in the homeless population was higher (79.7%) than in the general population (12%). Almost half of the population (49.2%) reported that their TBI occurred before the age of 18. Of the participants, 68.2% reported sustaining a TBI with loss of consciousness. TBI caused by violence (60%) was lower in this cohort than other homeless cohorts but was the main cause of injury regardless of age. Alcoholism was a risk factor for having more TBIs. No differences in TBI profile were found between sexes. CONCLUSIONS: Our findings underscore the need for more research on the lifetime risk factors associated with TBI to prevent and reduce the number of brain injuries in homeless populations.

Attention Training After Moderate-to-Severe Traumatic Brain Injury in Adults: A Systematic Review.

OBJECTIVE: To determine the extent and efficacy of attentional training as a form of neuropsychological rehabilitation to ameliorate attention deficits in adults with moderate-to-severe traumatic brain injury. DATA SOURCES: Articles published in Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, PubMed, PsycINFO, Scopus, and Web of Science were searched between January 17, and February 27, 2021. STUDY SELECTION: Two reviewers blindly assessed studies for eligibility according to the following criteria: any article evaluating the efficacy of any type of behavioral intervention that targeted attention (by means of cognitive rehabilitative, psychoeducational, or neuropsychological strategies, at either an individual or group level) in adults who had sustained a formally documented moderate-to-severe traumatic brain injury. DATA EXTRACTION: Methodological quality of each article was blindly assessed by 2 reviewers. Data were extracted from each study, including study type, sample size, sample characteristics, summary of intervention, measures used to assess attention, statistical outcomes and results, effect size, conclusion, and limitations. DATA SYNTHESIS: 7314 articles were retrieved from databases, 4325 articles remained after duplicate removal, and finally 21 articles met eligibility criteria and were included in this review. Articles represented varied methodological quality in group or single subject design. Irrespective of the heterogeneity regarding intervention types and attentional outcome measures used across the studies, overall findings suggest that attentional gains can be made in this sample, irrespective of time since injury, age, and injury severity. Further, a growing interest in technology-based interventions is frequently used and holds promise to bettering rehabilitation efforts. However, there is still limited evidence supporting the ecological validity of attentional training interventions (eg, the transfer of treatment effects to daily activities). CONCLUSIONS: This article plays a crucial role in informing ongoing rehabilitation practices, guiding clinicians with evidence-based strategies and shaping future research directions for more effective attentional training guidelines.