Patients' Perspectives on Life and Recovery 1 Year After COVID-19 Hospitalization.

BACKGROUND: Many patients hospitalized for COVID-19 experience prolonged symptoms months after discharge. Little is known abou t patients' personal experiences recovering from COVID-19 in the United States (US), where medically underserved populations are at particular risk of adverse outcomes. OBJECTIVE: To explore patients' perspectives on the impact of COVID-19 hospitalization and barriers to and facilitators of recovery 1 year after hospital discharge in a predominantly Black American study population with high neighborhood-level socioeconomic disadvantage. DESIGN: Qualitative study utilizing individual, semi-structured interviews. PARTICIPANTS: Adult patients hospitalized for COVID-19 approximately 1 year after discharge home who were engaged in a COVID-19 longitudinal cohort study. APPROACH: The interview guide was developed and piloted by a multidisciplinary team. Interviews were audio-recorded and transcribed. Data were coded and organized into discrete themes using qualitative content analysis with constant comparison techniques. KEY RESULTS: Of 24 participants, 17 (71%) self-identified as Black, and 13 (54%) resided in neighborhoods with the most severe neighborhood-level socioeconomic disadvantage. One year after discharge, participants described persistent deficits in physical, cognitive, or psychological health that impacted their current lives. Repercussions included financial suffering and a loss of identity. Participants reported that clinicians often focused on physical health over cognitive and psychological health, an emphasis that posed a barrier to recovering holistically. Facilitators of recovery included robust financial or social support systems and personal agency in health maintenance. Spirituality and gratitude were common coping mechanisms. CONCLUSIONS: Persistent health deficits after COVID-19 resulted in downstream consequences in participants' lives. Though participants received adequate care to address physical needs, many described persistent unmet cognitive and psychological needs. A more comprehensive understanding of barriers and facilitators for COVID-19 recovery, contextualized by specific healthcare and socioeconomic needs related to socioeconomic disadvantage, is needed to better inform intervention delivery to patients that experience long-term sequelae of COVID-19 hospitalization.

Adherence to Established Blood Pressure Targets and Associated Complications in Patients Presenting with Acute Intracerebral Hemorrhage.

BACKGROUND: Conflicting evidence exists surrounding systolic blood pressure (SBP) control in patients with acute intracerebral hemorrhage (ICH). The 2022 American Heart Association and American Stroke Association guidelines recommend targeting a SBP of 140 mm Hg while maintaining the range of 130-150 mm Hg. The current practice at our health system is to titrate antihypertensives to a SBP goal of < 160 mm Hg, which aligns with previous recommendations. We hypothesized that the prior lack of guidance to a specific SBP target range predisposed patients to hypotension leading to an increased risk of brain and renal adverse events. METHODS: This retrospective, multicenter, single health system cohort study included adults admitted to the neurointensive care unit or intermediate unit with acute ICH from June 2019 to June 2021. The primary objective evaluated the frequency of time within SBP range (140-160 mm Hg) in the first 48 h. Secondary and safety end points included the frequency of time above and below the established SBP range, episodes of hypotension (defined as a decrease in SBP < 140 mm Hg prompting discontinuation in antihypertensive[s] or the initiation of vasopressor[s]), the incidence of new brain or renal adverse events within 7 days, and modified Rankin Scale at discharge. RESULTS: A total of 80 patients (59% men; median age 62 years) were included. The majority of ICHs in this cohort were intraparenchymal (70%). Nearly one third were attributed to systemic hypertension (31%). During the first 48 h of admission, the frequency of time spent above, within, and below the target SBP range were 6 h (12%), 16 h (34%), and 26 h (54%), respectively. Hypotension was associated with renal adverse events (odds ratio [OR] 3.36, 95% confidence interval [CI] 1.10-11.44, p = 0.023). A relative SBP reduction > 20% in the first 48 h was associated with renal adverse events (OR 8.99, 95% CI 2.57-35.25, p < 0.001), brain ischemia (OR 22.5, 95% CI 1.92-300.11, p = 0.005), and an increased odd of a modified Rankin Scale of 4-6 at discharge (OR 11.79, 95% CI 2.79-57.02, p < 0.001). CONCLUSIONS: In individuals with nontraumatic/nonaneurysmal ICH, SBP measurements were observed to be < 140 mm Hg for > 50% of the initial 48 h following admission. Hypotension and relative SBP reduction > 20% were also independent predictors of renal adverse events. SBP reduction > 20% was also an independent predictor of brain ischemia. These data indicate that intensive SBP reduction following ICH predispose patients to secondary organ injury that may impact long-term outcomes. Our data suggest that a more modest lowering of the SBP within 48 h, as recommended in the most recent guidelines, may minimize the risk of further adverse events.

Neurotrauma.

PURPOSE OF REVIEW: This review will highlight the latest research relevant to the clinical care of traumatic brain injury (TBI) patients over the last 2 years while underscoring the implications of these advances in the understanding of diagnosis, treatment, and prognosis of TBI. RECENT FINDINGS: Brain tissue oxygenation monitoring can identify hypoperfusion as an adjunct to intracerebral pressure monitoring. Multiple biomarker assays are now available to help clinicians screen for mild TBI and biomarker elevations correlate with the size of intracranial injury. Beta-blocker exposure following TBI has demonstrated a survival benefit in those with TBI though the mechanism for this remains unknown. The optimal timing for venous thromboembolism prophylaxis for TBI patients is still uncertain. SUMMARY: The current characterization of TBI as mild, moderate, or severe fails to capture the complexity of the disease process and helps little with prognostication. Molecular biomarkers and invasive monitoring devices including brain tissue oxygenation and measures of cerebral autoregulation are being utilized more commonly and can help guide therapy. Extracranial complications following TBI are common and include infection, respiratory failure, coagulopathy, hypercoagulability, and paroxysmal sympathetic hyperactivity.

Molecular biomarkers in the neurological ICU: is there a role?

PURPOSE OF REVIEW: The aim of the article is to summarize recent advances in the field of molecular biomarkers in neurocritical care. RECENT FINDINGS: Advances in ultrasensitive immunoassay technology have made it possible to measure brain-derived proteins that are present at subfemtomolar concentrations in blood. These assays have made it possible to measure neurofilament light chain (NfL) in serum or plasma, and early studies indicate that NfL is a promising prognostic and pharmacodynamic biomarker across a broad range of neurologic disorders, including cardiac arrest and traumatic brain injury. However, as acquired brain injury is a complex and heterogeneous disorder, it is likely that assays of panels of biomarkers will ultimately be needed to maximally impact practice. Micro-RNAs are a novel but exciting class of molecules that also show potential to provide clinically actionable information. SUMMARY: Although not yet ready for adoption into routine clinical practice, several molecular biomarkers are on the cusp of clinical validation. The availability of such tests likely will revolutionize the practice of neurocritical care.

Long-Term Outcomes After Extracorporeal Life Support for Acute Respiratory Failure.

OBJECTIVE: This study aims to determine the prevalence of functional and psychological impairment in survivors of extracorporeal life support (ECLS) and assess the needs of survivors to guide development of an effective follow-up program. DESIGN: This mixed-methods outcomes study used quantitative assessment via standardized instruments (Katz Index of Independence of Activities of Daily Living [Katz ADL], the Lawton Instrumental Activities of Daily Living [Lawton IADL], Hospital Anxiety and Depression Scale, and the Post Traumatic Growth Inventory) and qualitative interview to identify challenges experienced by survivors. SETTING: A single institutional experience in an academic medical center in the United States. PATIENTS: Patient selection targeted patients who underwent veno-venous ECLS for acute respiratory failure between January 1, 2015, and April 1, 2017. Forty-two patients (21 male, 21 female; median age of 49 years; interquartile range 36-57 years) completed the interview a median of 14.6 (interquartile range 7.7-21.1) months after ECLS decannulation. INTERVENTIONS: This was an observational follow-up study for which no intervention was made. MEASUREMENTS AND MAIN RESULTS: The Katz ADL and Lawton IADL revealed high independence and functionality in 62% of patients (26 of 42). Clinically significant anxiety was present in 48% (20 of 42) of patients and depression in 26% (11 of 42). There was a correlation between the number of ADL and IADL deficiencies and depression (rho 0.61, p < 0.001) and anxiety (rho 0.29, p = 0.033) subscales of the Hospital Anxiety and Depression Scale. High levels of posttraumatic growth were noted in 50% (21 of 42) of patients. Nearly all survivors noted that a clinic designed for post-ECLS follow-up would be beneficial. Patients desired access to education, improved coordination of care, and additional mental health resources. CONCLUSIONS: This study demonstrated persistent physical and psychological impairments in survivors of ECLS. Patients consistently expressed a desire to debrief on their hospital course and receive education on possible long-term effects. Study findings suggest that structured follow-up may allow for early identification of psychological and physical impairments to improve outcomes. Future studies should focus on investigating the effect of rehabilitation and follow-up clinics in preventing these issues.

Elevated Red Cell Distribution Width is Associated with Cerebral Infarction in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Elevated red blood cell distribution width (RDW) has been associated with thrombotic disorders including myocardial infarction, venous thromboembolism, and ischemic stroke, independent of other inflammatory and coagulation biomarkers. The purpose of this study was to determine whether elevated RDW is associated with cerebral infarction and poor outcome after aneurysmal subarachnoid hemorrhage (aSAH). METHODS: In this retrospective single-center cohort of aSAH patients (October 2009-September 2014), elevated RDW was defined as a mean RDW >14.5 % during the first 14 days after aSAH. Outcomes included cerebral infarction (CI) by any mechanism and poor functional outcome, defined as discharge modified Rankin Scale (mRS) >4, indicating severe disability or death. RESULTS: Of 179 patients, 27 % had a high Hunt-Hess grade (IV-V), and 76 % were women. Twenty-four patients (13.4 %) underwent red blood cell (RBC) transfusion and compared to patients with normal RDW, patients with an elevated RDW were at greater odds of RBC transfusion (OR 2.56 [95 % CI, 1.07-6.11], p = 0.035). In univariate analysis, more patients with elevated RDW experienced CI (30.8 vs. 13.7 %, p = 0.017). In the multivariable model, elevated RDW was significantly associated with CI (OR 3.08 [95 % CI, 1.30-7.32], p = 0.011), independent of known confounders including but not limited to age, sex, race, high Hunt-Hess grade, and RBC transfusion. In multivariable analysis, RDW elevation was also associated with poor functional outcome (mRS > 4) at discharge (OR 2.59 [95 % CI, 1.04-629], p = 0.040). CONCLUSIONS: RDW elevation is associated with cerebral infarction and poor outcome after aSAH. Further evaluation of this association is warranted as it may shed light on mechanistic relations between anemia, inflammation, and thrombosis after aSAH.

Clinical Outcomes after Traumatic Brain Injury.

Traumatic brain injury (TBI) is a major cause of death and disability that often affects young people. After injury, the degree of recovery can be highly variable, with some people regaining near complete function while others remain severely disabled. Understanding what factors influence recovery is important for counseling patients and families in the acute period after injury and can help guide therapeutic decisions in the acute period following injury. In this review, prognostic algorithms useful for clinicians are discussed. Tools for grading patient outcomes, their role in clinical care and research studies, and their limitations are reviewed. Ongoing work focusing on the development of biomarkers to track TBI recovery and the refinement of clinical outcome metrics is summarized.

Sleep Features on Continuous Electroencephalography Predict Rehabilitation Outcomes After Severe Traumatic Brain Injury.

OBJECTIVE: Sleep characteristics detected by electroencephalography (EEG) may be predictive of neurological recovery and rehabilitation outcomes after traumatic brain injury (TBI). We sought to determine whether sleep features were associated with greater access to rehabilitation therapies and better functional outcomes after severe TBI. METHODS: We retrospectively reviewed records of patients admitted with severe TBI who underwent 24 or more hours of continuous EEG (cEEG) monitoring within 14 days of injury for sleep elements and ictal activity. Patient outcomes included discharge disposition and modified Rankin Scale (mRS). RESULTS: A total of 64 patients underwent cEEG monitoring for a mean of 50.6 hours. Status epilepticus or electrographic seizures detected by cEEG were associated with poor outcomes (death or discharge to skilled nursing facility). Sleep characteristics were present in 19 (30%) and associated with better outcome (89% discharged to home/acute rehabilitation; P = .0002). Lack of sleep elements on cEEG correlated with a poor outcome or mRS > 4 at hospital discharge (P = .012). Of those patients who were transferred to skilled nursing/acute rehabilitation, sleep architecture on cEEG associated with a shorter inpatient hospital stay (20 days vs 27 days) and earlier participation in therapy (9.8 days vs 13.2 days postinjury). Multivariable analyses indicated that sleep features on cEEG predicted functional outcomes independent of admission Glasgow Coma Scale and ictal-interictal activity. CONCLUSION: The presence of sleep features in the acute period after TBI indicates earlier participation in rehabilitative therapies and a better functional recovery. By contrast, status epilepticus, other ictal activity, or absent sleep architecture may portend a worse prognosis. Whether sleep elements detected by EEG predict long-term prognosis remains to be determined.

Proteinuria, but Not eGFR, Predicts Stroke Risk in Chronic Kidney Disease: Chronic Renal Insufficiency Cohort Study.

BACKGROUND AND PURPOSE: Chronic kidney disease is associated with an increased risk of cardiovascular events. However, the impact of chronic kidney disease on cerebrovascular disease is less well understood. We hypothesized that renal function severity would be predictive of stroke risk, independent of other vascular risk factors. METHODS: The study population included 3939 subjects enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study, a prospective observational cohort. Stroke events were reported by participants and adjudicated by 2 vascular neurologists. Cox proportional hazard models were used to compare measures of baseline renal function with stroke events. Multivariable analysis was performed to adjust for key covariates. RESULTS: In 3939 subjects, 143 new stroke events (0.62 events per 100 person-years) occurred over a mean follow-up of 6.4 years. Stroke risk was increased in subjects who had worse baseline measurements of renal function (estimated glomerular filtration rate and total proteinuria or albuminuria). When adjusted for variables known to influence stroke risk, total proteinuria or albuminuria, but not estimated glomerular filtration rate, were associated with an increased risk of stroke. Treatment with blockers of the renin-angiotensin system did not decrease stroke risk in individuals with albuminuria. CONCLUSIONS: Proteinuria and albuminuria are better predictors of stroke risk in patients with chronic kidney disease than estimated glomerular filtration rate. The impact of therapies targeting proteinuria/albuminuria in individuals with chronic kidney disease on stroke prevention warrants further investigation.

Change in Enlarged Perivascular Spaces over Time and Associations with Outcomes After Traumatic Brain Injury.

Enlarged perivascular spaces (EPVs) can be seen on magnetic resonance imaging (MRI) scans in various neurological diseases, including traumatic brain injury (TBI). EPVs have been associated with cognitive dysfunction and sleep disturbances; however, their clinical significance remains unclear. The goal of this study was to identify MRI burden of EPVs over time following TBI and to explore their relationship with postinjury outcomes. Individuals with TBI underwent postinjury data collection at Day 1 (blood), 2 weeks (blood, MRI, outcomes), and 6 months (blood, MRI, outcomes). EPV burden was assessed using T1 and FLAIR sequences on representative slices in the centrum semiovale, basal ganglia, and midbrain. Serum blood was assayed to measure concentrations of neurofilament light (NfL) and glial fibrillary acidic protein (GFAP). Thirty-two participants with TBI were included (mean age 36.8 years, 78% male, 50% White). Total EPVs count did not significantly change from 2 weeks (23.5 [95% confidence interval or CI = 22.0-32.0]) to 6 months (26.0 [95% CI = 22.0-30.0], p = 0.16). For self-reported measures of sleep, there were no significant associations between EPVs count and Insomnia Severity Index (2 weeks: ß = -0.004; 95% CI = -0.094, 0.086; 6 months: ß = 0.002; 95% CI = -0.122, 0.125) or the subset of sleep questions on the Rivermead Post-Concussion Symptoms Questionnaire (2 weeks: ß = -0.005; 95% CI = -0.049, 0.039; 6 months: ß = -0.019; 95% CI = -0.079, 0.042). Functional outcome, determined by 6 months incomplete recovery (Glasgow Outcome Scale-Extended [GOS-E < 8]) versus complete recovery (GOS-E = 8), was significantly associated with a higher number of EPVs at 2 weeks (odds ratio = 0.94, 95% CI = 0.88-0.99). Spearman correlations showed no significant relationship between EPVs count and GFAP or NfL. This study used commonly acquired MRI sequences to quantify EPVs and investigated their utility as a potential imaging biomarker in TBI. Given the minimal change in EPVs over time, this period may not be long enough for potential recovery or may indicate that EPVs are structural findings that do not significantly change over time.

Imaging Approach to Concussion.

The acute and long-term neurobiological sequelae of concussion (mild traumatic brain injury [mTBI]) and sub-concussive head trauma have become increasingly apparent in recent decades in part due to neuroimaging research. Although imaging has an established role in the clinical management of mTBI for the identification of intracranial lesions warranting urgent interventions, MR imaging is increasingly employed for the detection of post-traumatic sequelae which carry important prognostic significance. As neuroimaging research continues to elucidate the pathophysiology of TBI underlying prolonged recovery and the development of persistent post-concussive symptoms, there is a strong motivation to translate these techniques into clinical use for improved diagnosis and therapeutic monitoring.

Clinical Updates in Mild Traumatic Brain Injury (Concussion).

Traumatic brain injury (TBI) affects > 3 million people in the United States annually. Although the number of deaths related to severe TBIs has stabalized, mild TBIs, often termed concussions, are increasing. As evidence indicates that a significant proportion of these mild injuries are associated with long-lasting functional deficits that impact work performance, social integration, and may predispose to later cognitive decline, it is important that we (a) recognize these injuries, (b) identify those at highest risk of poor recovery, and (c) initiate appropriate treatments promptly. We discuss the epidemiology of TBI, the most common persistent symptoms, and treatment approaches.

Assessment of Resident Physician Comfort in Screening for Social Determinants of Health in a Specialty Clinic Population.

Through qualitative surveys, a team of law students, law professors, physicians, and residents explored the perceptions of neurology residents towards referral to appropriate legal resources in an academic training program. Respondents reported feeling uncomfortable screening their patients for health-harming legal needs, which many attributed to a lack of training in this area. These findings indicate that neurology residents would benefit from training on screening for social factors that may be impacting their patients' health.

Associations of Microvascular Injury-Related Biomarkers With Traumatic Brain Injury Severity and Outcomes: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Pilot Study.

Traumatic brain injury (TBI) is characterized by heterogeneity in terms of injury severity, mechanism, outcome, and pathophysiology. A single biomarker alone is unlikely to capture the heterogeneity of even one injury subtype, necessitating the use of panels of biomarkers. Herein, we focus on traumatic cerebrovascular injury and investigate associations of a panel of 16 vascular injury-related biomarkers with indices of TBI severity and outcomes using data from 159 participants in the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) Pilot Study. Associations of individual biomarkers and clusters of biomarkers identified using non-linear principal components analysis with TBI severity and outcomes were assessed using logistic regression models and Spearman's correlations. As individual biomarkers, higher levels of thrombomodulin, angiopoietin (Ang)-2, von Willebrand factor, and P-selectin were associated with more severe injury; higher levels of Ang-1, Tie2, vascular endothelial growth factor (VEGF)-C, and basic fibroblast growth factor (bFGF) were associated with less severe injury (all p < 0.05 in age-adjusted models). After false discovery rate correction for multiple comparisons, higher levels of Ang-2 remained associated with more severe injury and higher levels of Ang-1, Tie2, and bFGF remained associated with less severe injury at a p < 0.05 level. In principal components analysis, principal component (PC)1, comprised of Ang1, bFGF, P-selectin, VEGF-C, VEGF-A, and Tie2, was associated with less severe injury (age-adjusted odds ratio [OR]: 0.63, 95% confidence interval [CI]: 0.44-0.88 for head computer tomography [CT] positive vs. negative) and PC2 (Ang-2, E-selectin, Flt-1, placental growth factor, thrombomodulin, and vascular cell adhesion protein 1) was associated with greater injury severity (age-adjusted OR: 2.29, 95% CI: 1.49-3.69 for Glasgow Coma Scale [GCS] 3-12 vs. 13-15 and age-adjusted OR 1.59, 95% CI: 1.11-2.32 for head CT positive vs. negative). Neither individual biomarkers nor PCs were associated with outcomes in adjusted models (all p > 0.05). In conclusion, in this trauma-center based population of acute TBI patients, biomarkers of microvascular injury were associated with TBI severity.

Longitudinal Abnormalities in White Matter Extracellular Free Water Volume Fraction and Neuropsychological Functioning in Patients with Traumatic Brain Injury.

Traumatic brain injury is a global public health problem associated with chronic neurological complications and long-term disability. Biomarkers that map onto the underlying brain pathology driving these complications are urgently needed to identify individuals at risk for poor recovery and to inform design of clinical trials of neuroprotective therapies. Neuroinflammation and neurodegeneration are two endophenotypes potentially associated with increases in brain extracellular water content, but the nature of extracellular free water abnormalities after neurotrauma and its relationship to measures typically thought to reflect traumatic axonal injury are not well characterized. The objective of this study was to describe the relationship between a neuroimaging biomarker of extracellular free water content and the clinical features of a cohort with primarily complicated mild traumatic brain injury. We analyzed a cohort of 59 adult patients requiring hospitalization for non-penetrating traumatic brain injury of all severities as well as 36 healthy controls. Patients underwent brain magnetic resonance imaging (MRI) at 2 weeks (n = 59) and 6 months (n = 29) post-injury, and controls underwent a single MRI. Of the participants with TBI, 50 underwent clinical neuropsychological assessment at 2 weeks and 28 at 6 months. For each subject, we derived a summary score representing deviations in whole brain white matter extracellular free water volume fraction (VF) and free water-corrected fractional anisotropy (fw-FA). The summary specific anomaly score (SAS) for VF was significantly higher in TBI patients at 2 weeks and 6 months post-injury relative to controls. SAS for VF exhibited moderate correlation with neuropsychological functioning, particularly on measures of executive function. These findings indicate abnormalities in whole brain white matter extracellular water fraction in patients with TBI and are an important step toward identifying and validating noninvasive biomarkers that map onto the pathology driving disability after TBI.

Plasma von Willebrand Factor Is Elevated Hyperacutely After Mild Traumatic Brain Injury.

Each year in the United States, ∼2.7 million persons seek medical attention for traumatic brain injury (TBI), of which ∼85% are characterized as being mild brain injuries. Many different cell types in the brain are affected in these heterogeneous injuries, including neurons, glia, and the brain vasculature. Efforts to identify biomarkers that reflect the injury of these different cell types have been a focus of ongoing investigation. We hypothesized that von Willebrand factor (vWF) is a sensitive biomarker for acute traumatic vascular injury and correlates with symptom severity post-TBI. To address this, blood was collected from professional boxing athletes (n = 17) before and within 30 min after competition. Plasma levels of vWF and neuron-specific enolase were measured using the Meso Scale Discovery, LLC. (MSD) electrochemiluminescence array-based multi-plex format (MSD, Gaithersburg, MD). Additional symptom and outcome data from boxers and patients, such as the Rivermead symptom scores (Rivermead Post Concussion Symptoms Questionnaire [RPQ-3]), were collected. We found that, subsequent to boxing bouts, there was a 1.8-fold increase in vWF levels within 30 min of injury (p < 0.0009). Moreover, fold-change in vWF correlates moderately (r = 0.51; p = 0.03) with the number of head blows. We also found a positive correlation (r = 0.69; p = 0.002) between fold-change in vWF and self-reported post-concussive symptoms, measured by the RPQ-3. The receiver operating curve analysis of vWF plasma levels and RPQ-3 scoring yielded a sensitivity of 94.12% and a specificity of 76.5% with an area under the curve of 83% for boxers after a fight compared to the pre-bout baseline. This study suggests that vWF is a potential blood biomarker measurable in the hyperacute period after blunt mild TBI. This biomarker may prove to be useful in diagnosing and monitoring traumatic vascular injury.

Dynamic contrast enhanced MRI for characterization of blood-brain-barrier dysfunction after traumatic brain injury.

BACKGROUND AND PURPOSE: Dysfunction of the blood-brain-barrier (BBB) is a recognized pathological consequence of traumatic brain injury (TBI) which may play an important role in chronic TBI pathophysiology. We hypothesized that BBB disruption can be detected with dynamic contrast-enhanced (DCE) MRI not only in association with focal traumatic lesions but also in normal-appearing brain tissue of TBI patients, reflecting microscopic microvascular injury. We further hypothesized that BBB integrity would improve but not completely normalize months after TBI. MATERIALS AND METHODS: DCE MRI was performed in 40 adult patients a median of 23 days after hospitalized TBI and in 21 healthy controls. DCE data was analyzed using Patlak and linear models, and derived metrics of BBB leakage including the volume transfer constant (Ktrans) and the normalized permeability index (NPI) were compared between groups. BBB metrics were compared with focal lesion distribution as well as with contemporaneous measures of symptomatology and cognitive function in TBI patients. Finally, BBB metrics were examined longitudinally among 18 TBI patients who returned for a second MRI a median of 204 days postinjury. RESULTS: TBI patients exhibited higher mean Ktrans (p = 0.0028) and proportion of suprathreshold NPI voxels (p = 0.001) relative to controls. Tissue-based analysis confirmed greatest TBI-related BBB disruption in association with focal lesions, however elevated Ktrans was also observed in perilesional (p = 0.011) and nonlesional (p = 0.044) regions. BBB disruption showed inverse correlation with quality of life (rho = -0.51, corrected p = 0.016). Among the subset of TBI patients who underwent a second MRI several months after the initial evaluation, metrics of BBB disruption did not differ significantly at the group level, though variable longitudinal changes were observed at the individual subject level. CONCLUSIONS: This pilot investigation suggests that TBI-related BBB disruption is detectable in the early post-injury period in association with focal and diffuse brain injury.

Six-Month Impairment in Cognition, Mental Health, and Physical Function Following COVID-19-Associated Respiratory Failure.

To determine the prevalence and extent of impairments impacting health-related quality of life among survivors of COVID-19 who required mechanical ventilation, 6 months after hospital discharge. DESIGN: Multicenter, prospective cohort study, enrolling adults 18 years old or older with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection who received mechanical ventilation for 48 hours or more and survived to hospital discharge. Eligible patients were contacted 6 months after discharge for telephone-based interviews from March 2020 to December 2020. Assessments included: Montreal Cognitive Assessment-Blind, Hospital Anxiety and Depression Scale, Impact of Event Scale-6, EuroQOL 5 domain quality-of-life questionnaire, and components of the Multidimensional Dyspnea Profile. SETTING: Two tertiary academic health systems. PATIENTS: Of 173 eligible survivors, a random sample of 63 were contacted and 60 consented and completed interviews. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Mean age was 57 + 13 years and mean duration of invasive mechanical ventilation was 14 + 8.2 days. Six months post-discharge, 48 patients (80%; 95% CI, 68-88%) met criteria for post-intensive care syndrome (PICS), with one or more domains impaired. Among patients with PICS, 28 (47%; 95% CI, 35-59%) were impaired in at least 2 domains, and 12 (20%; 95% CI, 12-32%) impaired in all three domains. Significant symptoms of post-traumatic stress were present in 20 patients (33%; 95% CI, 23-46%), anxiety in 23 (38%; 95% CI, 27-51%), and depression in 25 (42%; 95% CI, 30-54%). Thirty-three patients (55%; 95% CI, 42-67%) had impairments in physical activity; 25 patients (42%; 95% CI, 30-54%) demonstrated cognitive impairment. CONCLUSIONS: Eighty percent of COVID-19 survivors who required mechanical ventilation demonstrated PICS 6 months after hospital discharge. Patients were commonly impaired in multiple PICS domains as well as coexisting mental health domains.

Imaging biomarkers of vascular and axonal injury are spatially distinct in chronic traumatic brain injury.

Traumatic Brain Injury (TBI) is associated with both diffuse axonal injury (DAI) and diffuse vascular injury (DVI), which result from inertial shearing forces. These terms are often used interchangeably, but the spatial relationships between DAI and DVI have not been carefully studied. Multimodal magnetic resonance imaging (MRI) can help distinguish these injury mechanisms: diffusion tensor imaging (DTI) provides information about axonal integrity, while arterial spin labeling (ASL) can be used to measure cerebral blood flow (CBF), and the reactivity of the Blood Oxygen Level Dependent (BOLD) signal to a hypercapnia challenge reflects cerebrovascular reactivity (CVR). Subjects with chronic TBI (n = 27) and healthy controls (n = 14) were studied with multimodal MRI. Mean values of mean diffusivity (MD), fractional anisotropy (FA), CBF, and CVR were extracted for pre-determined regions of interest (ROIs). Normalized z-score maps were generated from the pool of healthy controls. Abnormal ROIs in one modality were not predictive of abnormalities in another. Approximately 9-10% of abnormal voxels for CVR and CBF also showed an abnormal voxel value for MD, while only 1% of abnormal CVR and CBF voxels show a concomitant abnormal FA value. These data indicate that DAI and DVI represent two distinct TBI endophenotypes that are spatially independent.