Publications

J Neuropsychiatry Clin Neurosci. 2024 Dec 4:appineuropsych20230055. doi: 10.1176/appi.neuropsych.20230055. Online ahead of print.

ABSTRACT

Memory impairments are common chronic and functionally important consequences of traumatic brain injury (TBI). Among patients with persistent verbal memory impairments due to TBI-related cholinergic deficits, donepezil (an acetylcholinesterase inhibitor) may improve these and related problems. The Multicenter Evaluation of Memory Remediation in TBI with Donepezil (MEMRI-TBI-D) study, a four-site, randomized, parallel-group, double-blind, placebo-controlled, 10-week clinical trial, evaluated the efficacy of donepezil on verbal memory impairments, co-occurring cognitive and noncognitive neuropsychiatric problems, and functional status among persons with severe, persistent, and functionally limiting verbal memory problems at least 6 months after mild, moderate, or severe TBI. Efficacy, safety, and tolerability measures were assessed. Seventy-five participants were randomly assigned to donepezil (N=37) and placebo (N=38) groups. In both modified intent-to-treat and per-protocol analyses, donepezil significantly improved memory (i.e., verbal learning, as measured by the Hopkins Verbal Learning Test-Revised Total Trials 1-3, the primary outcome measure) when compared with placebo. Treatment-responder rates in the donepezil and placebo groups were 42% and 18%, respectively, yielding a number needed to treat of 3.5. Among donepezil responders, delayed recall and processing speed also improved significantly. Treatment-emergent adverse event rates for donepezil and placebo were 46% and 8%, respectively, and mild or moderate (85%); diarrhea and nausea were significantly more common in the donepezil group, yielding a number needed to harm of 6.25 and a likelihood to be helped or harmed ratio of 1.79. These results suggest that donepezil is an efficacious treatment for severe, persistent memory impairments after predominantly severe TBI, with a relatively favorable safety and tolerability profile.

PMID:39628282 | DOI:10.1176/appi.neuropsych.20230055

Epilepsia. 2024 Nov 19. doi: 10.1111/epi.18181. Online ahead of print.

ABSTRACT

OBJECTIVE: An accurate evaluation of behavioral responsiveness during and after seizures in people with epilepsy is critical for diagnosis and management. Current methods for assessing behavioral responsiveness are characterized by substantial variation, subjectivity, and limited reliability and reproducibility in ambulatory and epilepsy monitoring unit settings. In this study, we aimed to develop and implement a novel mobile platform for deployment of automated responsiveness testing in epilepsy-the ARTiE Watch-to facilitate standardized, objective assessments of behavioral responsiveness during and after seizures.

METHODS: We prospectively recruited patients admitted to the epilepsy monitoring units for diagnostic evaluation and long-term video-electroencephalographic monitoring at Mayo Clinic and Yale New Haven Hospital. Participants wore the ARTiE Watch, a smartwatch paired with custom smartphone software integrated with cloud infrastructure allowing for remote activation of standardized assessment on the participants' smartwatches. The assessment consisted of 18 command prompts that test behavioral responsiveness across motor, language, and memory domains. Upon visually identifying an electrographic seizure during EMU monitoring, the BrainRISE platform was used to deploy the ARTiE Watch behavioral testing sequence. Responsiveness scoring was conducted on smartwatch files.

RESULTS: Eighteen of 56 participants had a total of 39 electrographic seizures assessed with the ARTiE Watch. The 18 subjects with ARTiE Watch-tested seizures had a total of 67 baseline (interictal) ARTiE Watch tests collected for analysis. The analysis showed distinct ARTiE Watch behavioral responsiveness phenotypes: (1) decreased responsiveness across all ARTiE Watch commands during seizure (ictal-postictal) periods compared (to baseline (p < .0001), (2) decreased responsiveness in bilateral tonic-clonic seizures compared to baseline (p < .0001) and compared to focal seizures (p < .0001), and (3) decreased responsiveness during focal impaired awareness seizures compared to baseline (p < .0001) and compared to focal aware seizures (p < .001).

SIGNIFICANCE: ARTiE Watch behavioral testing deployed utilizing a mobile cloud-based platform is feasible and can provide standardized, objective behavioral responsiveness assessments during seizures.

PMID:39559901 | DOI:10.1111/epi.18181

JMIR Form Res. 2024 Nov 8;8:e64540. doi: 10.2196/64540.

ABSTRACT

BACKGROUND: Concussions are common, particularly among young adults, and often are associated with persistent, debilitating, and hard-to-treat symptoms. Anxiety and concussion symptoms often amplify each other, and growing evidence indicates that anxiety plays a key role in symptoms persistence after concussion. Targeting anxiety early after concussion may be a promising means of helping prevent persistent concussion symptoms in this population. We developed the Toolkit for Optimal Recovery after Concussion (TOR-C), the first mind-body program tailored for young adults with a recent concussion and anxiety, aiming to prevent persistent concussion symptoms.

OBJECTIVE: This study aims to conduct an open pilot of TOR-C to test preliminary feasibility, signal of change in measures, and treatment perceptions.

METHODS: Five young adults (aged 18-24 years) attended 4 weekly one-on-one live video sessions with a clinician. Participants completed questionnaires measuring treatment targets (ie, pain catastrophizing, mindfulness, fear avoidance, limiting behaviors, and all-or-nothing behaviors) and outcomes (ie, postconcussive symptoms, physical function, anxiety, depression, and pain) at baseline, immediately following the intervention, and 3 months after intervention completion. At the conclusion of the program, participants attended a qualitative interview and provided feedback about the program to help optimize study content and procedures.

RESULTS: Feasibility markers were excellent for credibility and expectancy (5/5, 100% of participants scored above the credibility and expectancy scale midpoint), client satisfaction (4/5, 80% of participants scored above the Client Satisfaction Questionnaire midpoint), therapist adherence (97% adherence), acceptability of treatment (5/5, 100% of participants attended 3 or more sessions), adherence to homework (87% home practice completion), and feasibility of assessments (no measures fully missing). The feasibility of recruitment was good (5/7, 71% of eligible participants agreed to participate). There were preliminary signals of improvements from pre-post comparisons in treatment targets (d=0.72-2.20) and outcomes (d=0.41-1.38), which were sustained after 3 months (d=0.38-2.74 and d=0.71-1.63 respectively). Exit interviews indicated overall positive perceptions of skills and highlighted barriers (eg, busyness) and facilitators (eg, accountability) to engagement.

CONCLUSIONS: TOR-C shows preliminary feasibility, is associated with a signal of improvement in treatment targets and outcomes, and has the potential to support recovery from concussion. The quantitative findings along with the qualitative feedback obtained from the exit interviews will help optimize TOR-C in preparation for an upcoming randomized controlled trial of TOR-C versus an active control condition of health education for concussion recovery.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/25746.

PMID:39514283 | PMC:PMC11584528 | DOI:10.2196/64540

Arch Phys Med Rehabil. 2024 Nov 5:S0003-9993(24)01317-0. doi: 10.1016/j.apmr.2024.10.011. Online ahead of print.

ABSTRACT

OBJECTIVES: To assess the feasibility of the Toolkit for Optimal Recovery after Concussion (TOR-C), the first mind-body program aiming to prevent persistent concussion symptoms among young adults with anxiety, and an active control (Health Enhancement after Concussion [HE-C]). We also tested preliminary improvements in outcome measures and putative mechanistic targets.

DESIGN: Single-blind, 2-arm, randomized controlled trial (RCT).

SETTING: Academic medical center in the US Northeast.

PARTICIPANTS: Fifty young adults (aged 18-35 years) with a recent concussion (3-10 weeks prior) and anxiety (≥5 on the Generalized Anxiety Disorder-7 [GAD-7] questionnaire).

INTERVENTIONS: Both interventions consisted of four 45-minute 1:1 sessions with a clinician over Zoom. TOR-C (n=25) taught mind-body, cognitive-behavioral, and return-to-activity skills. HE-C (n=25) taught health education (eg, sleep, nutrition) without skills.

MAIN OUTCOME MEASURES: Primary: feasibility outcomes (eg, recruitment, credibility, expectancy, acceptability, safety, feasibility of assessments, fidelity, satisfaction, and TOR-C homework adherence) with a-priori-set benchmarks. Secondary: intervention outcomes were concussion symptoms (Post-Concussion Symptom Scale), physical function (World Health Organization Disability Assessment Scale), anxiety (GAD-7/anxiety subscale of the Hospital Anxiety and Depression Scale), depression (depression subscale of the Hospital Anxiety and Depression Scale) and pain (Numerical Rating Scale). TOR-C mechanistic targets were pain catastrophizing (Pain Catastrophizing Scale), mindfulness (Cognitive and Affective Mindfulness Scale-Revised), fear avoidance (Fear Avoidance Behavior after Traumatic Brain Injury), limiting behavior and all-or-nothing behavior (Behavioral Response to Illness Questionnaire).

RESULTS: Both interventions met all feasibility benchmarks and were associated with significant improvements in outcomes (concussion symptoms, physical function, anxiety, depression, and pain; d=0.44-1.21) and TOR-C mechanistic targets (pain catastrophizing, mindfulness, fear-avoidance, and limiting behavior; Cohen's d=0.41-1.24). Improvements in all-or-nothing behavior were only significant in TOR-C (d=0.52). Improvements in all mechanistic targets except all-or-nothing behavior after TOR-C were significantly associated with improvements in at least one outcome.

CONCLUSIONS: Findings provide strong support for the feasibility of TOR-C and HE-C, and preliminary evidence for improvements in mechanistic targets and outcomes. Findings inform a future fully-powered RCT testing efficacy of TOR-C versus HE-C.

PMID:39505248 | DOI:10.1016/j.apmr.2024.10.011

Lancet Reg Health Am. 2024 Oct 17;39:100915. doi: 10.1016/j.lana.2024.100915. eCollection 2024 Nov.

ABSTRACT

BACKGROUND: Contemporary surgical practices for traumatic brain injury (TBI) remain unclear. We describe the clinical profile of an 18-centre US TBI cohort with cranial surgery.

METHODS: The prospective, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (2014-2018; ClinicalTrials.gov #NCT02119182) enrolled subjects who presented to trauma centre and received head computed tomography within 24-h (h) post-TBI. We performed a secondary data analysis in subjects aged ≥17-years with hospitalisation. Clinical characteristics, surgery type/timing, hospital and six-month outcomes were reported.

FINDINGS: Of 2032 subjects (age: mean = 41.4-years, range = 17-89-years; male = 71% female = 29%), 260 underwent cranial surgery, comprising 65% decompressive craniectomy, 23% craniotomy, 12% other surgery. Subjects with surgery (vs. without surgery) presented with worse neurological injury (median Glasgow Coma Scale = 6 vs. 15; midline shift ≥5 mm: 48% vs. 2%; cisternal effacement: 61% vs. 4%; p < 0.0001). Median time-to-craniectomy/craniotomy was 1.8 h (interquartile range = 1.1-5.0 h), and 67% underwent intracranial pressure monitoring. Seventy-three percent of subjects with decompressive craniectomy and 58% of subjects with craniotomy had ≥3 intracranial lesion types. Decompressive craniectomy (vs. craniotomy) was associated with intracranial injury severity (median Rotterdam Score = 4 vs. 3, p < 0.0001), intensive care length of stay (median = 13 vs. 4-days, p = 0.0002), and six-month unfavourable outcome (62% vs. 30%; p = 0.0001). Earlier time-to-craniectomy was associated with intracranial injury severity.

INTERPRETATION: In a large representative cohort of patients hospitalised with TBI, surgical decision-making and time-to-surgery aligned with intracranial injury severity. Multifocal TBIs predominated in patients with cranial surgery. These findings summarise current TBI surgical practice across US trauma centres and provide the foundation for analyses in targeted subpopulations.

FUNDING: National Institute of Neurological Disorders and Stroke; US Department of Defense; Neurosurgery Research and Education Foundation.

PMID:39497836 | PMC:PMC11532273 | DOI:10.1016/j.lana.2024.100915

Neurol Clin Pract. 2025 Feb;15(1):e200390. doi: 10.1212/CPJ.0000000000200390. Epub 2024 Oct 25.

ABSTRACT

BACKGROUND: Cognitive motor dissociation (CMD) occurs when patients with severe brain injury follow commands on task-based functional MRI or EEG assessment despite demonstrating no behavioral evidence of language function. Recognizing the value of identifying patients with CMD, evidence-based guidelines published in the United States and Europe now recommend that these assessments are conducted as part of clinical care for select patients.

RECENT FINDINGS: We describe our institutionally supported approach for clinical assessment of CMD and report lessons learned so that other centers can more easily implement these evaluations. Among the key lessons are the need to consider ethical implications of CMD assessment; establish standardized local protocols for patient selection, data acquisition, analysis, and interpretation; and develop effective strategies for communication of test results.

IMPLICATIONS FOR PRACTICE: Independent validation of methods to assess CMD is not available. Our approach for clinical CMD assessment is intended to be flexible, allowing for iterative improvements as the evidence base grows.

PMID:39473967 | PMC:PMC11515113 | DOI:10.1212/CPJ.0000000000200390

Neurocrit Care. 2024 Oct 21. doi: 10.1007/s12028-024-02116-w. Online ahead of print.

ABSTRACT

Severe brain injury can result in disorders of consciousness (DoC), including coma, vegetative state/unresponsive wakefulness syndrome, and minimally conscious state. Improved emergency and trauma medicine response, in addition to expanding efforts to prevent premature withdrawal of life-sustaining treatment, has led to an increased number of patients with prolonged DoC. High-quality bedside care of patients with DoC is key to improving long-term functional outcomes. However, there is a paucity of DoC-specific evidence guiding clinicians on efficacious bedside care that can promote medical stability and recovery of consciousness. This Viewpoint describes the state of current DoC bedside care and identifies knowledge and practice gaps related to patient care with DoC collated by the Care of the Patient in Coma scientific workgroup as part of the Neurocritical Care Society's Curing Coma Campaign. The gap analysis identified and organized domains of bedside care that could affect patient outcomes: clinical expertise, assessment and monitoring, timing of intervention, technology, family engagement, cultural considerations, systems of care, and transition to the post-acute continuum. Finally, this Viewpoint recommends future research and education initiatives to address and improve the care of patients with DoC.

PMID:39433705 | DOI:10.1007/s12028-024-02116-w

medRxiv [Preprint]. 2024 Oct 10:2024.10.08.24314953. doi: 10.1101/2024.10.08.24314953.

ABSTRACT

Alpha (8-12 Hz) frequency band oscillations are among the most informative features in electroencephalographic (EEG) assessment of patients with disorders of consciousness (DoC). Because interareal alpha synchrony is thought to facilitate long-range communication in healthy brains, coherence measures of resting-state alpha oscillations may provide insights into a patient's capacity for higher-order cognition beyond channel-wise estimates of alpha power. In multi-channel EEG, global coherence methods may be used to augment standard spectral analysis methods by both estimating the strength and identifying the structure of coherent oscillatory networks. We performed global coherence analysis in 95 separate clinical EEG recordings (28 healthy controls and 33 patients with acute or chronic DoC, 25 of whom returned for follow-up) collected between two academic medical centers. We found that posterior alpha coherence is associated with recovery of higher-level cognition. We developed a measure of network organization, based on the distance between eigenvectors of the alpha cross-spectral matrix, that detects recovery of posterior alpha networks. In patients who have emerged from a minimally conscious state, we showed that coherence-based alpha networks are reconfigured prior to restoration of alpha power to resemble those seen in healthy controls. This alpha network measure performs well in classifying recovery from DoC (AUC = 0.78) compared to common representations of functional connectivity using the weighted phase lag index (AUC = 0.50 - 0.57). Lastly, we observed that activity within these alpha networks is suppressed during positive responses to task-based EEG command-following paradigms, supporting the potential utility of this biomarker to detect covert cognition. Our findings suggest that restored alpha networks may represent a sensitive early signature of cognitive recovery in patients with DoC. Therefore, network detection methods may augment the utility of EEG assessments for DoC.

PMID:39417105 | PMC:PMC11482980 | DOI:10.1101/2024.10.08.24314953

Neurocrit Care. 2024 Oct 15. doi: 10.1007/s12028-024-02098-9. Online ahead of print.

NO ABSTRACT

PMID:39407076 | DOI:10.1007/s12028-024-02098-9

Neurocrit Care. 2024 Oct 15. doi: 10.1007/s12028-024-02143-7. Online ahead of print.

ABSTRACT

Disorders of consciousness (DoC) resulting from severe acute brain injuries may prompt clinicians and surrogate decision makers to consider withdrawal of life-sustaining treatment (WLST) if the neurologic prognosis is poor. Recent guidelines suggest, however, that clinicians should avoid definitively concluding a poor prognosis prior to 28 days post injury, as patients may demonstrate neurologic recovery outside the acute time period. This practice may increase the frequency with which clinicians consider the option of delayed WLST (D-WLST), namely, WLST that would occur after hospital discharge, if the patient's recovery trajectory ultimately proves inconsistent with an acceptable quality of life. However acute care clinicians are often uncertain about what D-WLST entails and therefore find it difficult to properly counsel surrogates about this option. Here, we describe practical and theoretical considerations relevant to D-WLST. We first identify post-acute-care facilities to which patients with DoC are likely to be discharged and where D-WLST may be considered. Second, we describe how clinicians and surrogates may determine the appropriate timing of D-WLST. Third, we outline how D-WLST is practically implemented. And finally, we discuss psychosocial barriers to D-WLST, including the regret paradox, in which surrogates of patients who do not recover to meet preestablished goals frequently choose not to ultimately pursue D-WLST. Together, these practical, logistic, and psychosocial factors must be considered when potentially deferring WLST to the post-acute-care setting to optimize neurologic recovery for patients, avoid prolonged undue suffering, and promote informed and shared decision-making between clinicians and surrogates.

PMID:39407075 | DOI:10.1007/s12028-024-02143-7

Neurocrit Care. 2024 Oct 11. doi: 10.1007/s12028-024-02101-3. Online ahead of print.

NO ABSTRACT

PMID:39394544 | DOI:10.1007/s12028-024-02101-3

Neurocrit Care. 2024 Oct 1. doi: 10.1007/s12028-024-02096-x. Online ahead of print.

NO ABSTRACT

PMID:39354124 | DOI:10.1007/s12028-024-02096-x

J Head Trauma Rehabil. 2024 Sep 23. doi: 10.1097/HTR.0000000000000997. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine, in persons with traumatic brain injury (TBI), the association between cognitive change after inpatient rehabilitation discharge and 1-year participation and life satisfaction outcomes.

DESIGN: Secondary analysis of prospectively collected TBI Model Systems (TBIMS) data.

SETTING: Inpatient rehabilitation and community.

PARTICIPANTS: 499 individuals with TBI requiring inpatient rehabilitation who completed the Brief Test of Adult Cognition by Telephone (BTACT) at inpatient rehabilitation discharge (ie, baseline) and 1-year postinjury.

MAIN OUTCOME MEASURES: Participation Assessment with Recombined Tools-Objective (PART-O) and Satisfaction with Life Scale (SWLS).

RESULTS: Of 2,840 TBIMS participants with baseline BTACT, 499 met inclusion criteria (mean [standard deviation] age = 45 [19] years; 72% male). Change in BTACT executive function (EF) was not associated with 1-year participation (PART-O; β = 0.087, 95% CI [-0.004, 0.178], P = .061) when it was the sole model predictor. Change in BTACT episodic memory (EM) was associated with 1-year participation (β = 0.096, [0.007, 0.184], P = .035), but not after adjusting for demographic, clinical, and functional status covariates (β = 0.067, 95% CI [-0.010, 0.145], P = .089). Change in BTACT EF was not associated with life satisfaction total scores (SWLS) when it was the sole model predictor (β = 0.091, 95% CI [-0.001, 0.182], P = .0503). Change in BTACT EM was associated with 1-year life satisfaction before (β = 0.114, 95% CI [0.025, 0.202], P = .012) and after adjusting for covariates (β = 0.103, [0.014, 0.191], P = .023). In secondary analyses, change in BTACT EF was associated with PART-O Social Relations and Out and About subdomains before (Social Relations: β = 0.127, 95% CI [0.036, 0.217], P = .006; Out and About: β = 0.141, 95% CI [0.051, 0.232], P = .002) and after (Social Relations: β = 0.168, 95% CI [0.072, 0.265], P < .002; Out and About: β = 0.156, 95% CI [0.061, 0.252], P < .002) adjusting for functional status and further adjusting for covariates (Social Relations: β = 0.127, 95% CI [0.040, 0.214], P = .004; Out and About: β = 0.136, 95% CI [0.043, 0.229], P = .004). However, only the models adjusting for functional status remained significant after multiple comparison correction (ie, Bonferroni-adjusted alpha level = 0.002).

CONCLUSION: EF gains during the first year after TBI were related to 1-year social and community participation. Gains in EM were associated with 1-year life satisfaction. These results highlight the potential benefit of cognitive rehabilitation after inpatient rehabilitation discharge and the need for interventions targeting specific cognitive functions that may contribute to participation and life satisfaction after TBI.

PMID:39330921 | DOI:10.1097/HTR.0000000000000997

Am J Speech Lang Pathol. 2024 Nov 4;33(6):3129-3138. doi: 10.1044/2024_AJSLP-23-00495. Epub 2024 Sep 25.

ABSTRACT

PURPOSE: Therapeutic alliance (TA) is critical to rehabilitation outcomes for adults with acquired brain injuries (ABIs). The purpose of this viewpoint article is to review factors that contribute to TA and to suggest ways speech-language pathologists (SLPs) can integrate these factors into their ABI rehabilitation practice.

METHOD: We evaluated literature describing client and clinician factors shown to affect-or not affect-TA in ABI rehabilitation and mapped findings onto suggested practices that SLPs may use to actively promote TA with their clients. Informed by our findings and TA frameworks, we integrated findings into a novel clinician self-reflection tool: the Therapeutic Alliance Reflection Checklist.

CONCLUSIONS: TA is a key ingredient in ABI rehabilitation. We contend that SLPs can, and should, actively facilitate TA with clients; the self-reflection checklist can assist. We advocate for continued TA research and improved measurement across rehabilitation settings. We further contend that training in active TA-promoting skills is a critical component of speech-language pathology education.

PMID:39320322 | DOI:10.1044/2024_AJSLP-23-00495

Neurocrit Care. 2024 Sep 20. doi: 10.1007/s12028-024-02134-8. Online ahead of print.

NO ABSTRACT

PMID:39304560 | DOI:10.1007/s12028-024-02134-8

Neurocrit Care. 2024 Sep 5. doi: 10.1007/s12028-024-02094-z. Online ahead of print.

NO ABSTRACT

PMID:39237849 | DOI:10.1007/s12028-024-02094-z

Neurocrit Care. 2024 Aug 27. doi: 10.1007/s12028-024-02095-y. Online ahead of print.

NO ABSTRACT

PMID:39192103 | DOI:10.1007/s12028-024-02095-y

Neurocrit Care. 2024 Aug 26. doi: 10.1007/s12028-024-02100-4. Online ahead of print.

NO ABSTRACT

PMID:39187691 | DOI:10.1007/s12028-024-02100-4

Neurocrit Care. 2024 Aug 26. doi: 10.1007/s12028-024-02097-w. Online ahead of print.

NO ABSTRACT

PMID:39187690 | DOI:10.1007/s12028-024-02097-w

Neurocrit Care. 2024 Aug 21. doi: 10.1007/s12028-024-02099-8. Online ahead of print.

NO ABSTRACT

PMID:39168938 | DOI:10.1007/s12028-024-02099-8

Neurocrit Care. 2024 Oct;41(2):357-368. doi: 10.1007/s12028-024-02068-1. Epub 2024 Aug 14.

ABSTRACT

BACKGROUND: Clinical management of persons with disorders of consciousness (DoC) is dedicated largely to optimizing recovery. However, selecting a measure to evaluate the extent of recovery is challenging because few measures are designed to precisely assess the full range of potential outcomes, from prolonged DoC to return of preinjury functioning. Measures that are designed specifically to assess persons with DoC are often performance-based and only validated for in-person use. Moreover, there are no published recommendations addressing which outcome measures should be used to evaluate DoC recovery. The resulting inconsistency in the measures selected by individual investigators to assess outcome prevents comparison of results across DoC studies. The National Institute of Neurological Disorders and Stroke (NINDS) common data elements (CDEs) is an amalgamation of standardized variables and tools that are recommended for use in studies of neurologic diseases and injuries. The Neurocritical Care Society Curing Coma Campaign launched an initiative to develop CDEs specifically for DoC and invited our group to recommend CDE outcomes and endpoints for persons with DoCs.

METHODS: The Curing Coma Campaign Outcomes and Endpoints CDE Workgroup, consisting of experts in adult and pediatric neurocritical care, neurology, and neuroscience, used a previously established five-step process to identify and select candidate CDEs: (1) review of existing NINDS CDEs, (2) nomination and systematic vetting of new CDEs, (3) CDE classification, (4) iterative review and approval of panel recommendations, and (5) development of case report forms.

RESULTS: Among hundreds of existing NINDS outcome and endpoint CDE measures, we identified 20 for adults and 18 for children that can be used to assess the full range of recovery from coma. We also proposed 14 new outcome and endpoint CDE measures for adults and 5 for children.

CONCLUSIONS: The DoC outcome and endpoint CDEs are a starting point in the broader effort to standardize outcome evaluation of persons with DoC. The ultimate goal is to harmonize DoC studies and allow for more precise assessment of outcomes after severe brain injury or illness. An iterative approach is required to modify and adjust these outcome and endpoint CDEs as new evidence emerges.

PMID:39143375 | DOI:10.1007/s12028-024-02068-1

N Engl J Med. 2024 Aug 15;391(7):598-608. doi: 10.1056/NEJMoa2400645.

ABSTRACT

BACKGROUND: Patients with brain injury who are unresponsive to commands may perform cognitive tasks that are detected on functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). This phenomenon, known as cognitive motor dissociation, has not been systematically studied in a large cohort of persons with disorders of consciousness.

METHODS: In this prospective cohort study conducted at six international centers, we collected clinical, behavioral, and task-based fMRI and EEG data from a convenience sample of 353 adults with disorders of consciousness. We assessed the response to commands on task-based fMRI or EEG in participants without an observable response to verbal commands (i.e., those with a behavioral diagnosis of coma, vegetative state, or minimally conscious state-minus) and in participants with an observable response to verbal commands. The presence or absence of an observable response to commands was assessed with the use of the Coma Recovery Scale-Revised (CRS-R).

RESULTS: Data from fMRI only or EEG only were available for 65% of the participants, and data from both fMRI and EEG were available for 35%. The median age of the participants was 37.9 years, the median time between brain injury and assessment with the CRS-R was 7.9 months (25% of the participants were assessed with the CRS-R within 28 days after injury), and brain trauma was an etiologic factor in 50%. We detected cognitive motor dissociation in 60 of the 241 participants (25%) without an observable response to commands, of whom 11 had been assessed with the use of fMRI only, 13 with the use of EEG only, and 36 with the use of both techniques. Cognitive motor dissociation was associated with younger age, longer time since injury, and brain trauma as an etiologic factor. In contrast, responses on task-based fMRI or EEG occurred in 43 of 112 participants (38%) with an observable response to verbal commands.

CONCLUSIONS: Approximately one in four participants without an observable response to commands performed a cognitive task on fMRI or EEG as compared with one in three participants with an observable response to commands. (Funded by the James S. McDonnell Foundation and others.).

PMID:39141852 | DOI:10.1056/NEJMoa2400645

Front Dement. 2023 Sep 1;2:1254986. doi: 10.3389/frdem.2023.1254986. eCollection 2023.

ABSTRACT

With human life expectancy and proportion of older adults increasing, global use of evidence-supported preventative methods to minimize risk of brain-related disabilities such as Alzheimer's disease and other dementias-as well as interventions to slow rate of disease progression-is important. Sustained engagement in cognitive and physical exercise programs may prevent or delay dementia onset as well as maximize health and function of those with dementia. Despite awareness of the importance of cognitive and physical exercise to brain health, exercise program adherence by older adults is extremely challenging. In this Perspective article, we summarize what is known about contributors to exercise program adherence and strategies to promote it. We discuss our viewpoint on knowledge gaps regarding exercise adherence and research that needs to be conducted. We conclude by proposing a multi-dimensional exercise adherence assessment framework that includes portable neurophysiologic technologies to inform initial design and updating of individualized exercise programs that optimize sustained exercise program engagement and, ultimately, maximize brain health in older adults with and without mild cognitive impairment and dementia.

PMID:39081974 | PMC:PMC11285648 | DOI:10.3389/frdem.2023.1254986

Trauma Surg Acute Care Open. 2024 Jul 24;9(1):e001501. doi: 10.1136/tsaco-2024-001501. eCollection 2024.

ABSTRACT

OBJECTIVES: An estimated 14-23% of patients with traumatic brain injury (TBI) incur multiple lifetime TBIs. The relationship between prior TBI and outcomes in patients with moderate to severe TBI (msTBI) is not well delineated. We examined the associations between prior TBI, in-hospital mortality, and outcomes up to 12 months after injury in a prospective US msTBI cohort.

METHODS: Data from hospitalized subjects with Glasgow Coma Scale score of 3-12 were extracted from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (enrollment period: 2014-2019). Prior TBI with amnesia or alteration of consciousness was assessed using the Ohio State University TBI Identification Method. Competing risk regressions adjusting for age, sex, psychiatric history, cranial injury and extracranial injury severity examined the associations between prior TBI and in-hospital mortality, with hospital discharged alive as the competing risk. Adjusted HRs (aHR (95% CI)) were reported. Multivariable logistic regressions assessed the associations between prior TBI, mortality, and unfavorable outcome (Glasgow Outcome Scale-Extended score 1-3 (vs. 4-8)) at 3, 6, and 12 months after injury.

RESULTS: Of 405 acute msTBI subjects, 21.5% had prior TBI, which was associated with male sex (87.4% vs. 77.0%, p=0.037) and psychiatric history (34.5% vs. 20.7%, p=0.010). In-hospital mortality was 10.1% (prior TBI: 17.2%, no prior TBI: 8.2%, p=0.025). Competing risk regressions indicated that prior TBI was associated with likelihood of in-hospital mortality (aHR=2.06 (1.01-4.22)), but not with hospital discharged alive. Prior TBI was not associated with mortality or unfavorable outcomes at 3, 6, and 12 months.

CONCLUSIONS: After acute msTBI, prior TBI history is independently associated with in-hospital mortality but not with mortality or unfavorable outcomes within 12 months after injury. This selective association underscores the importance of collecting standardized prior TBI history data early after acute hospitalization to inform risk stratification. Prospective validation studies are needed.

LEVEL OF EVIDENCE: IV.

TRIAL REGISTRATION NUMBER: NCT02119182.

PMID:39081460 | PMC:PMC11287071 | DOI:10.1136/tsaco-2024-001501

medRxiv [Preprint]. 2024 Jun 25:2024.06.24.24309307. doi: 10.1101/2024.06.24.24309307.

ABSTRACT

Traumatic brain injury (TBI) is a risk factor for neurodegeneration and cognitive decline, yet the underlying pathophysiologic mechanisms are incompletely understood. This gap in knowledge is in part related to the lack of analytic methods to account for cortical lesions in prior neuroimaging studies. The objective of this study was to develop a lesion detection tool and apply it to an investigation of longitudinal changes in brain structure among individuals with chronic TBI. We identified 24 individuals with chronic moderate-to-severe TBI enrolled in the Late Effects of TBI (LETBI) study who had cortical lesions detected by T1-weighted MRI at two time points. Initial MRI scans were performed more than 1-year post-injury and follow-up scans were performed 3.1 (IQR=1.7) years later. We leveraged FreeSurfer parcellations of T1-weighted MRI volumes and a recently developed super-resolution technique, SynthSR, to identify cortical lesions in this longitudinal dataset. Trained raters received the data in a randomized order and manually corrected the automated lesion segmentation, yielding a final lesion mask for each scan at each timepoint. Lesion volume significantly increased between the two time points with a median volume change of 3.2 (IQR=5.9) mL (p<0.001), and the increases significantly exceeded the possible variance in lesion volume changes due to manual tracing errors (p < 0.001). Lesion volume significantly expanded longitudinally in 23 of 24 subjects, with all FDR corrected p-values ≤ 0.02. Inter-scan duration was not associated with the magnitude of lesion growth. We also demonstrated that the semi-automated tool showed a high level of accuracy compared to "ground truth" manual lesion segmentation. Semi-automated lesion segmentation is feasible in TBI studies and creates opportunities to elucidate mechanisms of post-traumatic neurodegeneration.

PMID:38978662 | PMC:PMC11230300 | DOI:10.1101/2024.06.24.24309307

J Head Trauma Rehabil. 2024 Nov-Dec 01;39(6):E532-E542. doi: 10.1097/HTR.0000000000000941. Epub 2024 May 24.

ABSTRACT

OBJECTIVES: To identify personal, clinical, and environmental factors associated with 4 previously identified distinct multidimensional participation profiles of individuals following traumatic brain injury (TBI).

SETTING: Community.

PARTICIPANTS: Participants ( n = 408) enrolled in the TBI Model Systems (TBIMS) Participation Module, all 1 year or more postinjury.

DESIGN: Secondary data analysis of cross-sectional data from participants in a multicenter TBIMS module study on participation conducted between May 2006 and September 2007. Participants provided responses to questionnaires via a telephone interview at their study follow-up (1, 2, 5, 10, or 15 years postinjury).

MAIN MEASURES: Participants provided responses to personal (eg, demographic), clinical (eg, function), environmental (eg, neighborhood type), and participation measures to create multidimensional participation profiles. Data from measures collected at the time of injury (preinjury questionnaire, injury characteristics) were also included. The primary outcome was assignment to one of 4 multidimensional participation profile groups based on participation frequency, importance, satisfaction, and enfranchisement. The measures used to develop the profiles were: Participation Assessment with Recombined Tools-Objective, Importance, and Satisfaction scores, each across 3 domains (Productivity, Social Relationships, Out and About in the Community) and the Enfranchisement Scale (contributing to one's community, feeling valued by the community, choice and control).

RESULTS: Results of the multinomial regression analysis, with 4 distinct participation profile groups as the outcome, indicated that education, current employment, current illicit drug use, current driving status, community type, and FIM Cognitive at follow-up significantly distinguished participation profile groups. Findings suggest a trend toward differences in participation profile groups by race/Hispanic ethnicity.

CONCLUSIONS: Understanding personal, clinical, and environmental factors associated with distinct participation outcome profiles following TBI may provide more personalized and nuanced guidance to inform rehabilitation intervention planning and/or ongoing clinical monitoring.

PMID:38833709 | DOI:10.1097/HTR.0000000000000941

J Neurotrauma. 2024 Oct;41(19-20):2336-2348. doi: 10.1089/neu.2024.0014. Epub 2024 May 13.

ABSTRACT

Among patients with severe traumatic brain injury (TBI), there is high prognostic uncertainty but growing evidence that recovery of independence is possible. Nevertheless, families are often asked to make decisions about withdrawal of life-sustaining treatment (WLST) within days of injury. The range of potential outcomes for patients who died after WLST (WLST+) is unknown, posing a challenge for prognostic modeling and clinical counseling. We investigated the potential for survival and recovery of independence after acute TBI in patients who died after WLST. We used Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) data and propensity score matching to pair participants with WLST+ to those with a similar probability of WLST (based on demographic and clinical characteristics), but for whom life-sustaining treatment was not withdrawn (WLST-). To optimize matching, we divided the WLST- cohort into tiers (Tier 1 = 0-11%, Tier 2 = 11-27%, Tier 3 = 27-70% WLST propensity). We estimated the level of recovery that could be expected in WLST+ participants by evaluating 3-, 6-, and 12-month Glasgow Outcome Scale-Extended (GOSE) and Disability Rating Scale outcomes in matched WLST- participants. Of 90 WLST+ participants (80% male, mean [standard deviation; SD] age = 59.2 [17.9] years, median [IQR] days to WLST = 5.4 [2.2, 11.7]), 80 could be matched to WLST- participants. Of 56 WLST- participants who were followed at 6 months, 31 (55%) died. Among survivors in the overall sample and survivors in Tiers 1 and 2, more than 30% recovered at least partial independence (GOSE ≥4). In Tier 3, recovery to GOSE ≥4 occurred at 12 months, but not 6 months, post-injury. These results suggest a substantial proportion of patients with TBI and WLST may have survived and achieved at least partial independence. However, death or severe disability is a common outcome when the probability of WLST is high. While further validation is needed, our findings support a more cautious clinical approach to WLST and more complete reporting on WLST in TBI studies.

PMID:38739032 | PMC:PMC11564834 | DOI:10.1089/neu.2024.0014

Sci Transl Med. 2024 May;16(745):eadj4303. doi: 10.1126/scitranslmed.adj4303. Epub 2024 May 1.

ABSTRACT

Consciousness is composed of arousal (i.e., wakefulness) and awareness. Substantial progress has been made in mapping the cortical networks that underlie awareness in the human brain, but knowledge about the subcortical networks that sustain arousal in humans is incomplete. Here, we aimed to map the connectivity of a proposed subcortical arousal network that sustains wakefulness in the human brain, analogous to the cortical default mode network (DMN) that has been shown to contribute to awareness. We integrated data from ex vivo diffusion magnetic resonance imaging (MRI) of three human brains, obtained at autopsy from neurologically normal individuals, with immunohistochemical staining of subcortical brain sections. We identified nodes of the proposed default ascending arousal network (dAAN) in the brainstem, hypothalamus, thalamus, and basal forebrain. Deterministic and probabilistic tractography analyses of the ex vivo diffusion MRI data revealed projection, association, and commissural pathways linking dAAN nodes with one another and with DMN nodes. Complementary analyses of in vivo 7-tesla resting-state functional MRI data from the Human Connectome Project identified the dopaminergic ventral tegmental area in the midbrain as a widely connected hub node at the nexus of the subcortical arousal and cortical awareness networks. Our network-based autopsy methods and connectivity data provide a putative neuroanatomic architecture for the integration of arousal and awareness in human consciousness.

PMID:38691619 | DOI:10.1126/scitranslmed.adj4303

Brain Inj. 2024 Aug 23;38(10):796-806. doi: 10.1080/02699052.2024.2347567. Epub 2024 Apr 29.

ABSTRACT

PURPOSE: To determine how life satisfaction changes across the first 10 years following traumatic brain injury (TBI).

METHODS: Participants included 1,941 individuals from the TBI Model Systems database with life satisfaction data at 1-, 5-, and 10-years post-TBI. Based on Satisfaction With Life Scale scores, individuals were characterized as having one of the five 10-year life satisfaction trajectories: 'Stable High,' 'Stable Low,' 'Increased to High,' 'Decreased to Low,' and 'Unstable.' These were analyzed for group differences in demographics and psychosocial and functional outcomes.

RESULTS: Sixty percent participants had 'Stable High' or 'Increasing to High' trajectories. Approximately 25% had "Stable Low' or 'Decreasing to Low' trajectories, and approximately 15% had unstable trajectories. Higher life satisfaction trajectories were associated with the best psychosocial and functional outcomes whereas lower trajectories were associated with the worst psychosocial and functional outcomes. Trajectories were indistinguishable based on demographics.

CONCLUSION: Life satisfaction over the first 10 years following TBI is dynamic, with most individuals reporting high life satisfaction by 10 years post-TBI. Examination of psychosocial and functional factors related to life satisfaction trajectories may inform community-based intervention recommendations, resources, and supports to maximize long-term satisfaction with life.

PMID:38682889 | DOI:10.1080/02699052.2024.2347567

Proc Natl Acad Sci U S A. 2024 May 7;121(19):e2313568121. doi: 10.1073/pnas.2313568121. Epub 2024 Apr 22.

ABSTRACT

United States (US) Special Operations Forces (SOF) are frequently exposed to explosive blasts in training and combat, but the effects of repeated blast exposure (RBE) on SOF brain health are incompletely understood. Furthermore, there is no diagnostic test to detect brain injury from RBE. As a result, SOF personnel may experience cognitive, physical, and psychological symptoms for which the cause is never identified, and they may return to training or combat during a period of brain vulnerability. In 30 active-duty US SOF, we assessed the relationship between cumulative blast exposure and cognitive performance, psychological health, physical symptoms, blood proteomics, and neuroimaging measures (Connectome structural and diffusion MRI, 7 Tesla functional MRI, [¹¹C]PBR28 translocator protein [TSPO] positron emission tomography [PET]-MRI, and [¹⁸F]MK6240 tau PET-MRI), adjusting for age, combat exposure, and blunt head trauma. Higher blast exposure was associated with increased cortical thickness in the left rostral anterior cingulate cortex (rACC), a finding that remained significant after multiple comparison correction. In uncorrected analyses, higher blast exposure was associated with worse health-related quality of life, decreased functional connectivity in the executive control network, decreased TSPO signal in the right rACC, and increased cortical thickness in the right rACC, right insula, and right medial orbitofrontal cortex-nodes of the executive control, salience, and default mode networks. These observations suggest that the rACC may be susceptible to blast overpressure and that a multimodal, network-based diagnostic approach has the potential to detect brain injury associated with RBE in active-duty SOF.

PMID:38648470 | PMC:PMC11087753 | DOI:10.1073/pnas.2313568121

J Neurotrauma. 2024 Aug;41(15-16):e1996-e2008. doi: 10.1089/neu.2023.0567. Epub 2024 May 10.

ABSTRACT

The purpose of this study was to differentiate clinically meaningful improvement or deterioration from normal fluctuations in patients with disorders of consciousness (DoC) following severe brain injury. We computed indices of responsiveness for the Coma Recovery Scale-Revised (CRS-R) using data from a clinical trial of 180 participants with DoC. We used CRS-R scores from baseline (enrollment in a clinical trial) and a 4-week follow-up assessment period for these calculations. To improve precision, we transformed ordinal CRS-R total scores (0-23 points) to equal-interval measures on a 0-100 unit scale using Rasch Measurement theory. Using the 0-100 unit total Rasch measures, we calculated distribution-based 0.5 standard deviation (SD) minimal clinically important difference, minimal detectable change using 95% confidence intervals, and conditional minimal detectable change using 95% confidence intervals. The distribution-based minimal clinically important difference evaluates group-level changes, whereas the minimal detectable change values evaluate individual-level changes. The minimal clinically important difference and minimal detectable change are derived using the overall variability across total measures at baseline and 4 weeks. The conditional minimal detectable change is generated for each possible pair of CRS-R Rasch person measures and accounts for variation in standard error across the scale. We applied these indices to determine the proportions of participants who made a change beyond measurement error within each of the two subgroups, based on treatment arm (amantadine hydrochloride or placebo) or categorization of baseline Rasch person measure to states of consciousness (i.e., unresponsive wakefulness syndrome and minimally conscious state). We compared the proportion of participants in each treatment arm who made a change according to the minimal detectable change and determined whether they also changed to another state of consciousness. CRS-R indices of responsiveness (using the 0-100 transformed scale) were as follows: 0.5SD minimal clinically important difference = 9 units, minimal detectable change = 11 units, and the conditional minimal detectable change ranged from 11 to 42 units. For the amantadine and placebo groups, 70% and 58% of participants showed change beyond measurement error using the minimal detectable change, respectively. For the unresponsive wakefulness syndrome and minimally conscious state groups, 54% and 69% of participants changed beyond measurement error using the minimal detectable change, respectively. Among 115 participants (64% of the total sample) who made a change beyond measurement error, 29 participants (25%) did not change state of consciousness. CRS-R indices of responsiveness can support clinicians and researchers in discerning when behavioral changes in patients with DoC exceed measurement error. Notably, the minimal detectable change can support the detection of patients who make a "true" change within or across states of consciousness. Our findings highlight that the continued use of ordinal scores may result in incorrect inferences about the degree and relevance of a change score.

PMID:38613812 | PMC:PMC11386986 | DOI:10.1089/neu.2023.0567

J Neurosurg. 2024 Mar 15;141(2):417-429. doi: 10.3171/2023.11.JNS231425. Print 2024 Aug 1.

ABSTRACT

OBJECTIVE: The International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) and Corticosteroid Randomization After Significant Head Injury (CRASH) prognostic models for mortality and outcome after traumatic brain injury (TBI) were developed using data from 1984 to 2004. This study examined IMPACT and CRASH model performances in a contemporary cohort of US patients.

METHODS: The prospective 18-center Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study (enrollment years 2014-2018) enrolled subjects aged ≥ 17 years who presented to level I trauma centers and received head CT within 24 hours of TBI. Data were extracted from the subjects who met the model criteria (for IMPACT, Glasgow Coma Scale [GCS] score 3-12 with 6-month Glasgow Outcome Scale-Extended [GOSE] data [n = 441]; for CRASH, GCS score 3-14 with 2-week mortality data and 6-month GOSE data [n = 831]). Analyses were conducted in the overall cohort and stratified on the basis of TBI severity (severe/moderate/mild TBI defined as GCS score 3-8/9-12/13-14), age (17-64 years or ≥ 65 years), and the 5 top enrolling sites. Unfavorable outcome was defined as GOSE score 1-4. Original IMPACT and CRASH model coefficients were applied, and model performances were assessed by calibration (intercept [< 0 indicated overprediction; > 0 indicated underprediction] and slope) and discrimination (c-statistic).

RESULTS: Overall, the IMPACT models overpredicted mortality (intercept -0.79 [95% CI -1.05 to -0.53], slope 1.37 [1.05-1.69]) and acceptably predicted unfavorable outcome (intercept 0.07 [-0.14 to 0.29], slope 1.19 [0.96-1.42]), with good discrimination (c-statistics 0.84 and 0.83, respectively). The CRASH models overpredicted mortality (intercept -1.06 [-1.36 to -0.75], slope 0.96 [0.79-1.14]) and unfavorable outcome (intercept -0.60 [-0.78 to -0.41], slope 1.20 [1.03-1.37]), with good discrimination (c-statistics 0.92 and 0.88, respectively). IMPACT overpredicted mortality and acceptably predicted unfavorable outcome in the severe and moderate TBI subgroups, with good discrimination (c-statistic ≥ 0.81). CRASH overpredicted mortality in the severe and moderate TBI subgroups and acceptably predicted mortality in the mild TBI subgroup, with good discrimination (c-statistic ≥ 0.86); unfavorable outcome was overpredicted in the severe and mild TBI subgroups with adequate discrimination (c-statistic ≥ 0.78), whereas calibration was nonlinear in the moderate TBI subgroup. In subjects ≥ 65 years of age, the models performed variably (IMPACT-mortality, intercept 0.28, slope 0.68, and c-statistic 0.68; CRASH-unfavorable outcome, intercept -0.97, slope 1.32, and c-statistic 0.88; nonlinear calibration for IMPACT-unfavorable outcome and CRASH-mortality). Model performance differences were observed across the top enrolling sites for mortality and unfavorable outcome.

CONCLUSIONS: The IMPACT and CRASH models adequately discriminated mortality and unfavorable outcome. Observed overestimations of mortality and unfavorable outcome underscore the need to update prognostic models to incorporate contemporary changes in TBI management and case-mix. Investigations to elucidate the relationships between increased survival, outcome, treatment intensity, and site-specific practices will be relevant to improve models in specific TBI subpopulations (e.g., older adults), which may benefit from the inclusion of blood-based biomarkers, neuroimaging features, and treatment data.

PMID:38489823 | PMC:PMC11010725 | DOI:10.3171/2023.11.JNS231425

J Head Trauma Rehabil. 2024 Jul-Aug 01;39(4):E190-E200. doi: 10.1097/HTR.0000000000000940. Epub 2024 Feb 27.

ABSTRACT

OBJECTIVE: To examine the association between participation and satisfaction with life at 1, 2, 5, and 10 years after traumatic brain injury (TBI) in older adults.

SETTING: Community.

PARTICIPANTS: Participants ( N = 2362) who sustained complicated mild to severe TBI, requiring inpatient rehabilitation, at age 60 years or older and had follow-up data on participation and satisfaction with life for at least 1 follow-up time point across 1, 2, 5, and 10 years. Age at each time period was categorized as 60 to 64 years, 65 to 75 years, and 75 years or older.

DESIGN: Secondary data analysis of a large multicenter database.

MAIN MEASURES: Three domains (Productivity, Social Relations, Out and About) of the Participation Assessment With Recombined Tools-Objective (PART-O); Satisfaction With Life Scale (SWLS).

RESULTS: SWLS increased over the 10 years after TBI and was significantly associated with greater frequency of participation across all domains. There was a significant interaction between age and PART-O Social Relations such that there was a weaker relationship between Social Relations and SWLS in the oldest group (75 years or older). There was no interaction between Productivity or Out and About and age, but greater participation in both of these domains was associated with greater life satisfaction across age groups.

CONCLUSIONS: These findings indicate that greater participation is associated with increased satisfaction with life in older adults, across all participation domains over the first 10 years postinjury, suggesting that rehabilitation should target improving participation even in older adults. The decreased association of social relations with satisfaction with life in the oldest age group suggests that frequency of social relations may not be as important for life satisfaction in the oldest adults, but quality may still be important.

PMID:38453629 | PMC:PMC11227408 | DOI:10.1097/HTR.0000000000000940

J Trauma Acute Care Surg. 2024 Sep 1;97(3):343-355. doi: 10.1097/TA.0000000000004305. Epub 2024 Mar 5.

ABSTRACT

Traumatic brain injury (TBI) represents a major cause of death and disability, significantly impacting the lives of 2.5 million people annually in the United States. Long-term natural history studies have clarified that functional recovery continues for up to a decade, even among those who sustain severe TBI. Despite these findings, nihilistic attitudes regarding prognosis persist among clinicians, highlighting the need for improved understanding of the natural history of recovery from TBI and the factors that influence outcome. Recent advances in neuroimaging technologies and blood-based biomarkers are shedding new light on injury detection, severity classification and the physiologic mechanisms underlying recovery and decline postinjury. Rehabilitation is an essential component of clinical management after moderate to severe TBI and can favorably influence mortality and functional outcome. However, systemic barriers, including healthcare policy, insurance coverage and social determinants of health often limit access to inpatient rehabilitation services. Posttraumatic amnesia and confusion contribute to morbidity after TBI; however, early initiation and sustained provision of rehabilitation interventions optimize long-term outcome. Evidence-based reviews have clearly shown that cognitive rehabilitation strategies can effectively restore or compensate for the cognitive sequelae of TBI when used according to existing practice guidelines. Neurostimulant agents are commonly employed off-label to enhance functional recovery, however, only amantadine hydrochloride has convincingly demonstrated effectiveness when used under tested parameters. Noninvasive brain stimulation procedures, including transcranial direct current stimulation and transcranial magnetic stimulation, have emerged as promising treatments in view of their ability to modulate aberrant neuronal activity and augment adaptive neuroplasticity, but assessment of safety and effectiveness during the acute period has been limited. Understanding the natural history of recovery from TBI and the effectiveness of available therapeutic interventions is essential to ensuring appropriate clinical management of this complex population.

PMID:38439156 | DOI:10.1097/TA.0000000000004305

Brain Commun. 2024 Jan 29;6(1):fcae022. doi: 10.1093/braincomms/fcae022. eCollection 2024.

ABSTRACT

Disorders of consciousness are neurological conditions characterized by impaired arousal and awareness of self and environment. Behavioural responses are absent or are present but fluctuate. Disorders of consciousness are commonly encountered as a consequence of both acute and chronic brain injuries, yet reliable epidemiological estimates would require inclusive, operational definitions of the concept, as well as wider knowledge dissemination among involved professionals. Whereas several manifestations have been described, including coma, vegetative state/unresponsive wakefulness syndrome and minimally conscious state, a comprehensive neurobiological definition for disorders of consciousness is still lacking. The scientific literature is primarily observational, and studies-specific aetiologies lead to disorders of consciousness. Despite advances in these disease-related forms, there remains uncertainty about whether disorders of consciousness are a disease-agnostic unitary entity with a common mechanism, prognosis or treatment response paradigm. Our knowledge of disorders of consciousness has also been hampered by heterogeneity of study designs, variables, and outcomes, leading to results that are not comparable for evidence synthesis. The different backgrounds of professionals caring for patients with disorders of consciousness and the different goals at different stages of care could partly explain this variability. The Prospective Studies working group of the Neurocritical Care Society Curing Coma Campaign was established to create a platform for observational studies and future clinical trials on disorders of consciousness and coma across the continuum of care. In this narrative review, the author panel presents limitations of prior observational clinical research and outlines practical considerations for future investigations. A narrative review format was selected to ensure that the full breadth of study design considerations could be addressed and to facilitate a future consensus-based statement (e.g. via a modified Delphi) and series of recommendations. The panel convened weekly online meetings from October 2021 to December 2022. Research considerations addressed the nosographic status of disorders of consciousness, case ascertainment and verification, selection of dependent variables, choice of covariates and measurement and analysis of outcomes and covariates, aiming to promote more homogeneous designs and practices in future observational studies. The goal of this review is to inform a broad community of professionals with different backgrounds and clinical interests to address the methodological challenges imposed by the transition of care from acute to chronic stages and to streamline data gathering for patients with disorders of consciousness. A coordinated effort will be a key to allow reliable observational data synthesis and epidemiological estimates and ultimately inform condition-modifying clinical trials.

PMID:38344653 | PMC:PMC10853976 | DOI:10.1093/braincomms/fcae022

Brain Inj. 2024 Mar 20;38(4):249-259. doi: 10.1080/02699052.2024.2309549. Epub 2024 Feb 8.

ABSTRACT

PRIMARY OBJECTIVE: This study aimed to verify the reliability and validity of the Japanese version of the Coma Recovery Scale-Revised (CRS-R).

METHODS: Subjects included 59 patients with disorders of consciousness (DOC) due to acquired brain injury. To validate test-retest reliability, Evaluator A assessed the CRS-R twice on the same day (A1, A2). To examine inter-rater reliability, Evaluators A (A2) and B (B) assessed the CRS-R without a time interval. To test concurrent validity, Evaluator A (A1) assessed the CRS-R, Japan Coma Scale (JCS), and the Glasgow Coma Scale (GCS) consecutively. To validate diagnostic accuracy, we evaluated the degree of agreement between A1 and A2 and between A2 and B in their diagnosis of DOC by CRS-R.

RESULTS: The test-retest (ρ = 0.92) and inter- (ρ = 0.98) reliability of CRS-R were excellent" and Concurrent validity of CRS-R with JCS (ρ = -0.82) and GCS (ρ = 0.92) were high. Results of DOC diagnosis were consistent for 48/59 cases (κ = 0.82) for A1 and A2 and for 54/59 cases (κ = 0.92) for A2 and B.

CONLCUSION: The Japanese version of the CRS-R may be as reliable and valid as the original English and other language versions.

PMID:38329043 | DOI:10.1080/02699052.2024.2309549

Neurosci Conscious. 2024 Feb 7;2024(1):niad026. doi: 10.1093/nc/niad026. eCollection 2024.

ABSTRACT

Historically, clinical evaluation of unresponsive patients following brain injury has relied principally on serial behavioral examination to search for emerging signs of consciousness and track recovery. Advances in neuroimaging and electrophysiologic techniques now enable clinicians to peer into residual brain functions even in the absence of overt behavioral signs. These advances have expanded clinicians' ability to sub-stratify behaviorally unresponsive and seemingly unaware patients following brain injury by querying and classifying covert brain activity made evident through active or passive neuroimaging or electrophysiologic techniques, including functional MRI, electroencephalography (EEG), transcranial magnetic stimulation-EEG, and positron emission tomography. Clinical research has thus reciprocally influenced clinical practice, giving rise to new diagnostic categories including cognitive-motor dissociation (i.e. 'covert consciousness') and covert cortical processing (CCP). While covert consciousness has received extensive attention and study, CCP is relatively less understood. We describe that CCP is an emerging and clinically relevant state of consciousness marked by the presence of intact association cortex responses to environmental stimuli in the absence of behavioral evidence of stimulus processing. CCP is not a monotonic state but rather encapsulates a spectrum of possible association cortex responses from rudimentary to complex and to a range of possible stimuli. In constructing a roadmap for this evolving field, we emphasize that efforts to inform clinicians, philosophers, and researchers of this condition are crucial. Along with strategies to sensitize diagnostic criteria and disorders of consciousness nosology to these vital discoveries, democratizing access to the resources necessary for clinical identification of CCP is an emerging clinical and ethical imperative.

PMID:38327828 | PMC:PMC10849751 | DOI:10.1093/nc/niad026

Neurocrit Care. 2024 Jun;40(3):865-878. doi: 10.1007/s12028-023-01899-8. Epub 2024 Jan 19.

ABSTRACT

The advent of neurotechnologies including advanced functional magnetic resonance imaging and electroencephalography to detect states of awareness not detectable by traditional bedside neurobehavioral techniques (i.e., covert consciousness) promises to transform neuroscience research and clinical practice for patients with brain injury. As these interventions progress from research tools into actionable, guideline-endorsed clinical tests, ethical guidance for clinicians on how to responsibly communicate the sensitive results they yield is crucial yet remains underdeveloped. Drawing on insights from empirical and theoretical neuroethics research and our clinical experience with advanced neurotechnologies to detect consciousness in behaviorally unresponsive patients, we critically evaluate ethical promises and perils associated with disclosing the results of clinical covert consciousness assessments and describe a semistructured approach to responsible data sharing to mitigate potential risks.

PMID:38243150 | PMC:PMC11147696 | DOI:10.1007/s12028-023-01899-8

NeuroRehabilitation. 2024;54(1):23-42. doi: 10.3233/NRE-230123.

ABSTRACT

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.

PMID:38217619 | PMC:PMC10898447 | DOI:10.3233/NRE-230123

Front Neurol. 2023 Dec 12;14:1308540. doi: 10.3389/fneur.2023.1308540. eCollection 2023.

ABSTRACT

INTRODUCTION: Mild traumatic brain injury (mTBI) is a heterogenous injury which can be difficult to characterize and manage. Using cross-sectional network analysis (NA) to conceptualize mTBI symptoms offers an innovative solution to identify how mTBI symptoms relate to each other. The centrality hypothesis of network theory posits that certain symptoms in a network are more relevant (central) or have above average influence over the rest of the network. However, no studies have used NA to characterize the interrelationships between symptoms in a cohort of patients who presented with mTBI to a U.S. Level 1 trauma center emergency department and how subacute central symptoms relate to long-term outcomes.

METHODS: Patients with mTBI (Glasgow Coma Scale = 13-15) evaluated across 18 U.S. Level 1 trauma centers from 2013 to 2019 completed the Rivermead Post-Concussion Symptoms Questionnaire (RPQ) at 2 weeks (W2) post-injury (n = 1,593) and at 3 months (M3), 6 months (M6), and 12 months (M12) post-injury. Network maps were developed from RPQ subscale scores at each timepoint. RPQ scores at W2 were associated with M6 and M12 functional and quality of life outcomes.

RESULTS: Network structure did not differ across timepoints, indicating no difference in symptoms/factors influence on the overall symptom network across time. The cognitive factor had the highest expected influence at W2 (1.761), M3 (1.245), and M6 (1.349). Fatigue had the highest expected influence at M12 (1.275). The emotional factor was the only other node with expected influence >1 at any timepoint, indicating disproportionate influence of emotional symptoms on overall symptom burden (M3 = 1.011; M6 = 1.076).

DISCUSSION: Several symptom factors at 2-weeks post-injury were more strongly associated with incomplete recovery and/or poorer injury-related quality of life at 6 and 12 months post-injury than previously validated demographic and clinical covariates. The network analysis suggests that emotional, cognitive, and fatigue symptoms may be useful treatment targets in this population due to high centrality and activating potential of the overall symptom network.

PMID:38148980 | PMC:PMC10750770 | DOI:10.3389/fneur.2023.1308540

Neurocrit Care. 2024 Feb;40(1):58-64. doi: 10.1007/s12028-023-01883-2. Epub 2023 Dec 12.

ABSTRACT

BACKGROUND: In patients with disorders of consciousness (DoC), laboratory and molecular biomarkers may help define endotypes, identify therapeutic targets, prognosticate outcomes, and guide patient selection in clinical trials. We performed a systematic review to identify common data elements (CDEs) and key design elements (KDEs) for future coma and DoC research.

METHODS: The Curing Coma Campaign Biospecimens and Biomarkers work group, composed of seven invited members, reviewed existing biomarker and biospecimens CDEs and conducted a systematic literature review for laboratory and molecular biomarkers using predetermined search words and standardized methodology. Identified CDEs and KDEs were adjudicated into core, basic, supplemental, or experimental CDEs per National Institutes of Health classification based on level of evidence, reproducibility, and generalizability across different diseases through a consensus process.

RESULTS: Among existing National Institutes of Health CDEs, those developed for ischemic stroke, traumatic brain injury, and subarachnoid hemorrhage were most relevant to DoC and included. KDEs were common to all disease states and included biospecimen collection time points, baseline indicator, biological source, anatomical location of collection, collection method, and processing and storage methodology. Additionally, two disease core, nine basic, 24 supplemental, and 59 exploratory biomarker CDEs were identified. Results were summarized and generated into a Laboratory Data and Biospecimens Case Report Form (CRF) and underwent public review. A final CRF version 1.0 is reported here.

CONCLUSIONS: Exponential growth in biomarkers development has generated a growing number of potential experimental biomarkers associated with DoC, but few meet the quality, reproducibility, and generalizability criteria to be classified as core and basic biomarker and biospecimen CDEs. Identification and adaptation of KDEs, however, contribute to standardizing methodology to promote harmonization of future biomarker and biospecimens studies in DoC. Development of this CRF serves as a basic building block for future DoC studies.

PMID:38087173 | DOI:10.1007/s12028-023-01883-2

Neurocrit Care. 2024 Feb;40(1):65-73. doi: 10.1007/s12028-023-01870-7. Epub 2023 Dec 7.

ABSTRACT

BACKGROUND: The fundamental gap obstructing forward progress of evidenced-based care in pediatric and neonatal disorders of consciousness (DoC) is the lack of defining consensus-based terminology to perform comparative research. This lack of shared nomenclature in pediatric DoC stems from the inherently recursive dilemma of the inability to reliably measure consciousness in the very young. However, recent advancements in validated clinical examinations and technologically sophisticated biomarkers of brain activity linked to future abilities are unlocking this previously formidable challenge to understanding the DoC in the developing brain.

METHODS: To address this need, the first of its kind international convergence of an interdisciplinary team of pediatric DoC experts was organized by the Neurocritical Care Society's Curing Coma Campaign. The multidisciplinary panel of pediatric DoC experts proposed pediatric-tailored common data elements (CDEs) covering each of the CDE working groups including behavioral phenotyping, biospecimens, electrophysiology, family and goals of care, neuroimaging, outcome and endpoints, physiology and big Data, therapies, and pediatrics.

RESULTS: We report the working groups' pediatric-focused DoC CDE recommendations and disseminate CDEs to be used in studies of pediatric patients with DoC.

CONCLUSIONS: The CDEs recommended support the vision of progressing collaborative and successful internationally collaborative pediatric coma research.

PMID:38062304 | DOI:10.1007/s12028-023-01870-7

Neurocrit Care. 2024 Feb;40(1):382-383. doi: 10.1007/s12028-023-01894-z.

NO ABSTRACT

PMID:38057543 | DOI:10.1007/s12028-023-01894-z

Nat Med. 2023 Dec;29(12):3162-3174. doi: 10.1038/s41591-023-02638-4. Epub 2023 Dec 4.

ABSTRACT

Converging evidence indicates that impairments in executive function and information-processing speed limit quality of life and social reentry after moderate-to-severe traumatic brain injury (msTBI). These deficits reflect dysfunction of frontostriatal networks for which the central lateral (CL) nucleus of the thalamus is a critical node. The primary objective of this feasibility study was to test the safety and efficacy of deep brain stimulation within the CL and the associated medial dorsal tegmental (CL/DTTm) tract.Six participants with msTBI, who were between 3 and 18 years post-injury, underwent surgery with electrode placement guided by imaging and subject-specific biophysical modeling to predict activation of the CL/DTTm tract. The primary efficacy measure was improvement in executive control indexed by processing speed on part B of the trail-making test.All six participants were safely implanted. Five participants completed the study and one was withdrawn for protocol non-compliance. Processing speed on part B of the trail-making test improved 15% to 52% from baseline, exceeding the 10% benchmark for improvement in all five cases.CL/DTTm deep brain stimulation can be safely applied and may improve executive control in patients with msTBI who are in the chronic phase of recovery.ClinicalTrials.gov identifier: NCT02881151 .

PMID:38049620 | PMC:PMC11087147 | DOI:10.1038/s41591-023-02638-4

Neurocrit Care. 2024 Feb;40(1):51-57. doi: 10.1007/s12028-023-01873-4. Epub 2023 Nov 29.

ABSTRACT

BACKGROUND: Over the past 30 years, there have been significant advances in the understanding of the mechanisms associated with loss and recovery of consciousness following severe brain injury. This work has provided a strong grounding for the development of novel restorative therapeutic interventions. Although all interventions are aimed at modulating and thereby restoring brain function, the landscape of existing interventions encompasses a very wide scope of techniques and protocols. Despite vigorous research efforts, few approaches have been assessed with rigorous, high-quality randomized controlled trials. As a growing number of exploratory interventions emerge, it is paramount to develop standardized approaches to reporting results. The successful evaluation of novel interventions depends on implementation of shared nomenclature and infrastructure. To address this gap, the Neurocritical Care Society's Curing Coma Campaign convened nine working groups and charged them with developing common data elements (CDEs). Here, we report the work of the Therapeutic Interventions Working Group.

METHODS: The working group reviewed existing CDEs relevant to therapeutic interventions within the National Institutes of Health National Institute of Neurological Disorders and Stroke database and reviewed the literature for assessing key areas of research in the intervention space. CDEs were then proposed, iteratively discussed and reviewed, classified, and organized in a case report form (CRF).

RESULTS: We developed a unified CRF, including CDEs and key design elements (i.e., methodological or protocol parameters), divided into five sections: (1) patient information, (2) general study information, (3) behavioral interventions, (4) pharmacological interventions, and (5) device interventions.

CONCLUSIONS: The newly created CRF enhances systematization of future work by proposing a portfolio of measures that should be collected in the development and implementation of studies assessing novel interventions intended to increase the level of consciousness or rate of recovery of consciousness in patients with disorders of consciousness.

PMID:38030874 | PMC:PMC11495790 | DOI:10.1007/s12028-023-01873-4

Phys Med Rehabil Clin N Am. 2024 Feb;35(1):15-33. doi: 10.1016/j.pmr.2023.06.011. Epub 2023 Jul 27.

ABSTRACT

In this article, we discuss the taxonomy associated with the four major disorders of consciousness (DoC): coma, vegetative state or unresponsive wakefulness syndrome, minimally conscious state, and post-traumatic confusional state. We briefly review the history of each disorder and then provide operational definitions and diagnostic criteria for each one. We rely heavily on recently released practice guidelines and, where appropriate, identify knowledge gaps and discuss future directions to advance DoC research and practice.

PMID:37993185 | PMC:PMC11465191 | DOI:10.1016/j.pmr.2023.06.011

J Neurotrauma. 2024 Feb;41(3-4):529-536. doi: 10.1089/neu.2023.0225.

ABSTRACT

We examined whether females with a history of traumatic brain injury (TBI) and intimate partner violence (IPV) have greater exposure to lifetime trauma relative to females with TBI but no IPV history. Further, we assessed the effects of lifetime trauma on psychological outcomes after TBI. Female participants (n = 70; age M [standard deviation-SD] = 50.5 [15.2] years) with TBI (time since injury median [interquartile range -IQR] = 10.2 [5.3-17.8] years) completed a structured assessment of lifetime history of TBI, including an IPV module to query head injuries from physical violence by an intimate partner. We characterized lifetime trauma exposure with the Adverse Childhood Experiences (ACEs) questionnaire and Survey of Exposure to Community Violence (CV). We evaluated psychological functioning with self-report questionnaires of post-traumatic stress disorder (PTSD), depression, and anxiety symptoms. Compared with those with no IPV history (n = 51), participants reporting IPV-related head injuries (n = 19; 27.1%) reported more ACEs (M[SD] IPV: 4.5[2.9]; No IPV: 1.6[1.8], p < 0.001, d = 1.08) and greater CV (IPV: 17.5[8.4]; No IPV: 7.6[6.1], p < .0001, d = 1.26). Within the full sample, ACEs (β = 0.21, 95% confidence interval [CI] = 0.04-0.39) and CV (β = 0.07, 95% CI = 0.01-0.13) predicted worse PTSD symptoms, while IPV alone did not. Exposure to all three sources of trauma (ACEs, CV, and IPV) was associated with worse PTSD symptoms relative to fewer traumas. The results highlight the scope of traumatic exposures among TBI survivors and the importance of considering IPV and other lifetime trauma exposure in assessing and managing TBI. Trauma-informed interventions that are modified for TBI-related impairment may offer improved outcomes in managing psychological symptoms.

PMID:37974411 | PMC:PMC10837032 | DOI:10.1089/neu.2023.0225

Neurocrit Care. 2024 Feb;40(1):384. doi: 10.1007/s12028-023-01874-3.

NO ABSTRACT

PMID:37923969 | DOI:10.1007/s12028-023-01874-3

Semin Neurol. 2022 Jun;42(3):e1. doi: 10.1055/s-0043-1775572. Epub 2023 Oct 30.

NO ABSTRACT

PMID:37903645 | DOI:10.1055/s-0043-1775572

J Spec Oper Med. 2023 Dec 29;23(4):47-56. doi: 10.55460/99QW-K0HG.

ABSTRACT

United States Special Operations Forces (SOF) personnel are frequently exposed to explosive blasts in training and combat. However, the effects of repeated blast exposure on the human brain are incompletely understood. Moreover, there is currently no diagnostic test to detect repeated blast brain injury (rBBI). In this "Human Performance Optimization" article, we discuss how the development and implementation of a reliable diagnostic test for rBBI has the potential to promote SOF brain health, combat readiness, and quality of life.

PMID:37851859 | DOI:10.55460/99QW-K0HG

JAMA Netw Open. 2023 Sep 5;6(9):e2335804. doi: 10.1001/jamanetworkopen.2023.35804.

ABSTRACT

IMPORTANCE: One traumatic brain injury (TBI) increases the risk of subsequent TBIs. Research on longitudinal outcomes of civilian repetitive TBIs is limited.

OBJECTIVE: To investigate associations between sustaining 1 or more TBIs (ie, postindex TBIs) after study enrollment (ie, index TBIs) and multidimensional outcomes at 1 year and 3 to 7 years.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included participants presenting to emergency departments enrolled within 24 hours of TBI in the prospective, 18-center Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study (enrollment years, February 2014 to July 2020). Participants who completed outcome assessments at 1 year and 3 to 7 years were included. Data were analyzed from September 2022 to August 2023.

EXPOSURES: Postindex TBI(s).

MAIN OUTCOMES AND MEASURES: Demographic and clinical factors, prior TBI (ie, preindex TBI), and functional (Glasgow Outcome Scale-Extended [GOSE]), postconcussive (Rivermead Post-Concussion Symptoms Questionnaire [RPQ]), psychological distress (Brief Symptom Inventory-18 [BSI-18]), depressive (Patient Health Questionnaire-9 [PHQ-9]), posttraumatic stress disorder (PTSD; PTSD Checklist for DSM-5 [PCL-5]), and health-related quality-of-life (Quality of Life After Brain Injury-Overall Scale [QOLIBRI-OS]) outcomes were assessed. Adjusted mean differences (aMDs) and adjusted relative risks are reported with 95% CIs.

RESULTS: Of 2417 TRACK-TBI participants, 1572 completed the outcomes assessment at 1 year (1049 [66.7%] male; mean [SD] age, 41.6 [17.5] years) and 1084 completed the outcomes assessment at 3 to 7 years (714 [65.9%] male; mean [SD] age, 40.6 [17.0] years). At 1 year, a total of 60 participants (4%) were Asian, 255 (16%) were Black, 1213 (77%) were White, 39 (2%) were another race, and 5 (0.3%) had unknown race. At 3 to 7 years, 39 (4%) were Asian, 149 (14%) were Black, 868 (80%) were White, 26 (2%) had another race, and 2 (0.2%) had unknown race. A total of 50 (3.2%) and 132 (12.2%) reported 1 or more postindex TBIs at 1 year and 3 to 7 years, respectively. Risk factors for postindex TBI were psychiatric history, preindex TBI, and extracranial injury severity. At 1 year, compared with those without postindex TBI, participants with postindex TBI had worse functional recovery (GOSE score of 8: adjusted relative risk, 0.57; 95% CI, 0.34-0.96) and health-related quality of life (QOLIBRI-OS: aMD, -15.9; 95% CI, -22.6 to -9.1), and greater postconcussive symptoms (RPQ: aMD, 8.1; 95% CI, 4.2-11.9), psychological distress symptoms (BSI-18: aMD, 5.3; 95% CI, 2.1-8.6), depression symptoms (PHQ-9: aMD, 3.0; 95% CI, 1.5-4.4), and PTSD symptoms (PCL-5: aMD, 7.8; 95% CI, 3.2-12.4). At 3 to 7 years, these associations remained statistically significant. Multiple (2 or more) postindex TBIs were associated with poorer outcomes across all domains.

CONCLUSIONS AND RELEVANCE: In this cohort study of patients with acute TBI, postindex TBI was associated with worse symptomatology across outcome domains at 1 year and 3 to 7 years postinjury, and there was a dose-dependent response with multiple postindex TBIs. These results underscore the critical need to provide TBI prevention, education, counseling, and follow-up care to at-risk patients.

PMID:37751204 | PMC:PMC10523170 | DOI:10.1001/jamanetworkopen.2023.35804

J Cereb Blood Flow Metab. 2024 Jan;44(1):50-65. doi: 10.1177/0271678X231197392. Epub 2023 Sep 20.

ABSTRACT

Early prediction of the recovery of consciousness in comatose cardiac arrest patients remains challenging. We prospectively studied task-relevant fMRI responses in 19 comatose cardiac arrest patients and five healthy controls to assess the fMRI's utility for neuroprognostication. Tasks involved instrumental music listening, forward and backward language listening, and motor imagery. Task-specific reference images were created from group-level fMRI responses from the healthy controls. Dice scores measured the overlap of individual subject-level fMRI responses with the reference images. Task-relevant responsiveness index (Rindex) was calculated as the maximum Dice score across the four tasks. Correlation analyses showed that increased Dice scores were significantly associated with arousal recovery (P < 0.05) and emergence from the minimally conscious state (EMCS) by one year (P < 0.001) for all tasks except motor imagery. Greater Rindex was significantly correlated with improved arousal recovery (P = 0.002) and consciousness (P = 0.001). For patients who survived to discharge (n = 6), the Rindex's sensitivity was 75% for predicting EMCS (n = 4). Task-based fMRI holds promise for detecting covert consciousness in comatose cardiac arrest patients, but further studies are needed to confirm these findings. Caution is necessary when interpreting the absence of task-relevant fMRI responses as a surrogate for inevitable poor neurological prognosis.

PMID:37728641 | PMC:PMC10905635 | DOI:10.1177/0271678X231197392

Neurocrit Care. 2024 Jun;40(3):909-917. doi: 10.1007/s12028-023-01844-9. Epub 2023 Sep 19.

ABSTRACT

BACKGROUND: The recent publication of practice guidelines for management of patients with disorders of consciousness (DoC) in the United States and Europe was a major step forward in improving the accuracy and consistency of terminology, diagnostic criteria, and prognostication in this population. There remains a pressing need for a more precise brain injury classification system that combines clinical semiology with neuroimaging, electrophysiologic, and other biomarker data. To address this need, the National Institute of Neurological Disorders and Stroke launched the Common Data Elements (CDEs) initiative to facilitate systematic collection of high-quality research data in studies involving patients with neurological disease. The Neurocritical Care Society's Curing Coma Campaign expanded this effort in 2018 to develop CDEs for DoC. Herein, we present CDE recommendations for behavioral phenotyping of patients with DoC.

METHODS: The Behavioral Phenotyping Workgroup used a preestablished, five-step process to identify and select candidate CDEs that included review of existing National Institute of Neurological Disorders and Stroke CDEs, nomination and systematic vetting of new CDEs, CDE classification, iterative review, and approval of panel recommendations and development of corresponding case review forms.

RESULTS: We identified a slate of existing and newly proposed basic, supplemental, and exploratory CDEs that can be used for behavioral phenotyping of adult and pediatric patients with DoC.

CONCLUSIONS: The proposed behavioral phenotyping CDEs will assist with international harmonization of DoC studies and allow for more precise characterization of study cohorts, favorably impacting observational studies and clinical trials aimed at improving outcome in this population.

PMID:37726548 | DOI:10.1007/s12028-023-01844-9

Neurocrit Care. 2023 Dec;39(3):600-610. doi: 10.1007/s12028-023-01796-0. Epub 2023 Sep 13.

ABSTRACT

BACKGROUND: To facilitate comparative research, it is essential for the fields of neurocritical care and rehabilitation to establish common data elements (CDEs) for disorders of consciousness (DoC). Our objective was to identify CDEs related to goals-of-care decisions and family/surrogate decision-making for patients with DoC.

METHODS: To achieve this, we formed nine CDE working groups as part of the Neurocritical Care Society's Curing Coma Campaign. Our working group focused on goals-of-care decisions and family/surrogate decision-makers created five subgroups: (1) clinical variables of surrogates, (2) psychological distress of surrogates, (3) decision-making quality, (4) quality of communication, and (5) quality of end-of-life care. Each subgroup searched for existing relevant CDEs in the National Institutes of Health/CDE catalog and conducted an extensive literature search for additional relevant study instruments to be recommended. We classified each CDE according to the standard definitions of "core", "basic", "exploratory", or "supplemental", as well as their use for studying the acute or chronic phase of DoC, or both.

RESULTS: We identified 32 relevant preexisting National Institutes of Health CDEs across all subgroups. A total of 34 new instruments were added across all subgroups. Only one CDE was recommended as disease core, the "mode of death" of the patient from the clinical variables subgroup.

CONCLUSIONS: Our findings provide valuable CDEs specific to goals-of-care decisions and family/surrogate decision-making for patients with DoC that can be used to standardize studies to generate high-quality and reproducible research in this area.

PMID:37704937 | DOI:10.1007/s12028-023-01796-0

Neurocrit Care. 2023 Dec;39(3):593-599. doi: 10.1007/s12028-023-01846-7. Epub 2023 Sep 13.

ABSTRACT

BACKGROUND: The implementation of multimodality monitoring in the clinical management of patients with disorders of consciousness (DoC) results in physiological measurements that can be collected in a continuous and regular fashion or even at waveform resolution. Such data are considered part of the "Big Data" available in intensive care units and are potentially suitable for health care-focused artificial intelligence research. Despite the richness in content of the physiological measurements, and the clinical implications shown by derived metrics based on those measurements, they have been largely neglected from previous attempts in harmonizing data collection and standardizing reporting of results as part of common data elements (CDEs) efforts. CDEs aim to provide a framework for unifying data in clinical research and help in implementing a systematic approach that can facilitate reliable comparison of results from clinical studies in DoC as well in international research collaborations.

METHODS: To address this need, the Neurocritical Care Society's Curing Coma Campaign convened a multidisciplinary panel of DoC "Physiology and Big Data" experts to propose CDEs for data collection and reporting in this field.

RESULTS: We report the recommendations of this CDE development panel and disseminate CDEs to be used in physiologic and big data studies of patients with DoC.

CONCLUSIONS: These CDEs will support progress in the field of DoC physiologic and big data and facilitate international collaboration.

PMID:37704934 | PMC:PMC10782548 | DOI:10.1007/s12028-023-01846-7

PLoS One. 2023 Aug 24;18(8):e0290290. doi: 10.1371/journal.pone.0290290. eCollection 2023.

ABSTRACT

Over the last 30 years, there has been a growing trend in clinical trials towards assessing novel interventions not only against the benchmark of statistical significance, but also with respect to whether they lead to clinically meaningful changes for patients. In the context of Disorders of Consciousness (DOC), despite a growing landscape of experimental interventions, there is no agreed standard as to what counts as a minimal clinically important difference (MCID). In part, this issue springs from the fact that, by definition, DOC patients are either unresponsive (i.e., in a Vegetative State; VS) or non-communicative (i.e., in a Minimally Conscious State; MCS), which renders it impossible to assess any subjective perception of benefit, one of the two core aspects of MCIDs. Here, we develop a novel approach that leverages published, international diagnostic guidelines to establish a probability-based minimal clinically important difference (pMCID), and we apply it to the most validated and frequently used scale in DOC: the Coma Recovery Scale-Revised (CRS-R). This novel method is objective (i.e., based on published criteria for patient diagnosis) and easy to recalculate as the field refines its agreed-upon criteria for diagnosis. We believe this new approach can help clinicians determine whether observed changes in patients' behavior are clinically important, even when patients cannot communicate their experiences, and can align the landscape of clinical trials in DOC with the practices in other medical fields.

PMID:37616196 | PMC:PMC10449161 | DOI:10.1371/journal.pone.0290290

Neurocrit Care. 2023 Dec;39(3):586-592. doi: 10.1007/s12028-023-01803-4. Epub 2023 Aug 23.

ABSTRACT

The convergence of an interdisciplinary team of neurocritical care specialists to organize the Curing Coma Campaign is the first effort of its kind to coordinate national and international research efforts aimed at a deeper understanding of disorders of consciousness (DoC). This process of understanding includes translational research from bench to bedside, descriptions of systems of care delivery, diagnosis, treatment, rehabilitation, and ethical frameworks. The description and measurement of varying confounding factors related to hospital care was thought to be critical in furthering meaningful research in patients with DoC. Interdisciplinary hospital care is inherently varied across geographical areas as well as community and academic medical centers. Access to monitoring technologies, specialist consultation (medical, nursing, pharmacy, respiratory, and rehabilitation), staffing resources, specialty intensive and acute care units, specialty medications and specific surgical, diagnostic and interventional procedures, and imaging is variable, and the impact on patient outcome in terms of DoC is largely unknown. The heterogeneity of causes in DoC is the source of some expected variability in care and treatment of patients, which necessitated the development of a common nomenclature and set of data elements for meaningful measurement across studies. Guideline adherence in hemorrhagic stroke and severe traumatic brain injury may also be variable due to moderate or low levels of evidence for many recommendations. This article outlines the process of the development of common data elements for hospital course, confounders, and medications to streamline definitions and variables to collect for clinical studies of DoC.

PMID:37610641 | DOI:10.1007/s12028-023-01803-4

Neurocrit Care. 2023 Dec;39(3):578-585. doi: 10.1007/s12028-023-01795-1. Epub 2023 Aug 22.

ABSTRACT

BACKGROUND: Electroencephalography (EEG) has long been recognized as an important tool in the investigation of disorders of consciousness (DoC). From inspection of the raw EEG to the implementation of quantitative EEG, and more recently in the use of perturbed EEG, it is paramount to providing accurate diagnostic and prognostic information in the care of patients with DoC. However, a nomenclature for variables that establishes a convention for naming, defining, and structuring data for clinical research variables currently is lacking. As such, the Neurocritical Care Society's Curing Coma Campaign convened nine working groups composed of experts in the field to construct common data elements (CDEs) to provide recommendations for DoC, with the main goal of facilitating data collection and standardization of reporting. This article summarizes the recommendations of the electrophysiology DoC working group.

METHODS: After assessing previously published pertinent CDEs, we developed new CDEs and categorized them into "disease core," "basic," "supplemental," and "exploratory." Key EEG design elements, defined as concepts that pertained to a methodological parameter relevant to the acquisition, processing, or analysis of data, were also included but were not classified as CDEs.

RESULTS: After identifying existing pertinent CDEs and developing novel CDEs for electrophysiology in DoC, variables were organized into a framework based on the two primary categories of resting state EEG and perturbed EEG. Using this categorical framework, two case report forms were generated by the working group.

CONCLUSIONS: Adherence to the recommendations outlined by the electrophysiology working group in the resting state EEG and perturbed EEG case report forms will facilitate data collection and sharing in DoC research on an international level. In turn, this will allow for more informed and reliable comparison of results across studies, facilitating further advancement in the realm of DoC research.

PMID:37606737 | DOI:10.1007/s12028-023-01795-1

Neurocrit Care. 2023 Dec;39(3):611-617. doi: 10.1007/s12028-023-01794-2. Epub 2023 Aug 8.

ABSTRACT

BACKGROUND: Over the past 5 decades, advances in neuroimaging have yielded insights into the pathophysiologic mechanisms that cause disorders of consciousness (DoC) in patients with severe brain injuries. Structural, functional, metabolic, and perfusion imaging studies have revealed specific neuroanatomic regions, such as the brainstem tegmentum, thalamus, posterior cingulate cortex, medial prefrontal cortex, and occipital cortex, where lesions correlate with the current or future state of consciousness. Advanced imaging modalities, such as diffusion tensor imaging, resting-state functional magnetic resonance imaging (fMRI), and task-based fMRI, have been used to improve the accuracy of diagnosis and long-term prognosis, culminating in the endorsement of fMRI for the clinical evaluation of patients with DoC in the 2018 US (task-based fMRI) and 2020 European (task-based and resting-state fMRI) guidelines. As diverse neuroimaging techniques are increasingly used for patients with DoC in research and clinical settings, the need for a standardized approach to reporting results is clear. The success of future multicenter collaborations and international trials fundamentally depends on the implementation of a shared nomenclature and infrastructure.

METHODS: To address this need, the Neurocritical Care Society's Curing Coma Campaign convened an international panel of DoC neuroimaging experts to propose common data elements (CDEs) for data collection and reporting in this field.

RESULTS: We report the recommendations of this CDE development panel and disseminate CDEs to be used in neuroimaging studies of patients with DoC.

CONCLUSIONS: These CDEs will support progress in the field of DoC neuroimaging and facilitate international collaboration.

PMID:37552410 | DOI:10.1007/s12028-023-01794-2

Biol Psychiatry Glob Open Sci. 2022 Mar 16;3(3):374-385. doi: 10.1016/j.bpsgos.2022.03.004. eCollection 2023 Jul.

ABSTRACT

BACKGROUND: Traumatic brain injury (TBI) can alter brain structure and lead to onset of persistent neuropsychological symptoms. This study investigates the relationship between brain injury and psychological distress after mild TBI using multimodal magnetic resonance imaging.

METHODS: A total of 89 patients with mild TBI from the TRACK-TBI (Transforming Research and Clinical Knowledge in Traumatic Brain Injury) pilot study were included. Subscales of the Brief Symptoms Inventory 18 for depression, anxiety, and somatization were used as outcome measures of psychological distress approximately 6 months after the traumatic event. Glasgow Coma Scale scores were used to evaluate recovery. Magnetic resonance imaging data were acquired within 2 weeks after injury. Perivascular spaces (PVSs) were segmented using an enhanced PVS segmentation method, and the volume fraction was calculated for the whole brain and white matter regions. Cortical thickness and gray matter structures volumes were calculated in FreeSurfer; diffusion imaging indices and multifiber tracts were extracted using the Quantitative Imaging Toolkit. The analysis was performed considering age, sex, intracranial volume, educational attainment, and improvement level upon discharge as covariates.

RESULTS: PVS fractions in the posterior cingulate, fusiform, and postcentral areas were found to be associated with somatization symptoms. Depression, anxiety, and somatization symptoms were associated with the cortical thickness of the frontal-opercularis and occipital pole, putamen and amygdala volumes, and corticospinal tract and superior thalamic radiation. Analyses were also performed on the two hemispheres separately to explore lateralization.

CONCLUSIONS: This study shows how PVS, cortical, and microstructural changes can predict the onset of depression, anxiety, and somatization symptoms in patients with mild TBI.

PMID:37519474 | PMC:PMC10382710 | DOI:10.1016/j.bpsgos.2022.03.004

bioRxiv [Preprint]. 2023 Jul 15:2023.07.13.548265. doi: 10.1101/2023.07.13.548265.

ABSTRACT

Consciousness is comprised of arousal (i.e., wakefulness) and awareness. Substantial progress has been made in mapping the cortical networks that modulate awareness in the human brain, but knowledge about the subcortical networks that sustain arousal is lacking. We integrated data from ex vivo diffusion MRI, immunohistochemistry, and in vivo 7 Tesla functional MRI to map the connectivity of a subcortical arousal network that we postulate sustains wakefulness in the resting, conscious human brain, analogous to the cortical default mode network (DMN) that is believed to sustain self-awareness. We identified nodes of the proposed default ascending arousal network (dAAN) in the brainstem, hypothalamus, thalamus, and basal forebrain by correlating ex vivo diffusion MRI with immunohistochemistry in three human brain specimens from neurologically normal individuals scanned at 600-750 μm resolution. We performed deterministic and probabilistic tractography analyses of the diffusion MRI data to map dAAN intra-network connections and dAAN-DMN internetwork connections. Using a newly developed network-based autopsy of the human brain that integrates ex vivo MRI and histopathology, we identified projection, association, and commissural pathways linking dAAN nodes with one another and with cortical DMN nodes, providing a structural architecture for the integration of arousal and awareness in human consciousness. We release the ex vivo diffusion MRI data, corresponding immunohistochemistry data, network-based autopsy methods, and a new brainstem dAAN atlas to support efforts to map the connectivity of human consciousness.

PMID:37502983 | PMC:PMC10369992 | DOI:10.1101/2023.07.13.548265

Ann Neurol. 2023 Nov;94(5):919-924. doi: 10.1002/ana.26740. Epub 2023 Aug 9.

ABSTRACT

We developed and validated an abbreviated version of the Coma Recovery Scale-Revised (CRS-R), the CRS-R For Accelerated Standardized Testing (CRSR-FAST), to detect conscious awareness in patients with severe traumatic brain injury in the intensive care unit. In 45 consecutively enrolled patients, CRSR-FAST administration time was approximately one-third of the full-length CRS-R (mean [SD] 6.5 [3.3] vs 20.1 [7.2] minutes, p < 0.0001). Concurrent validity (simple kappa 0.68), test-retest (Mak's ρ = 0.76), and interrater (Mak's ρ = 0.91) reliability were substantial. Sensitivity, specificity, and accuracy for detecting consciousness were 81%, 89%, and 84%, respectively. The CRSR-FAST facilitates serial assessment of consciousness, which is essential for diagnostic and prognostic accuracy. ANN NEUROL 2023;94:919-924.

PMID:37488068 | PMC:PMC10701693 | DOI:10.1002/ana.26740

J Neurotrauma. 2023 Nov;40(21-22):2449-2451. doi: 10.1089/neu.2023.0275. Epub 2023 Oct 12.

NO ABSTRACT

PMID:37476969 | PMC:PMC10649169 | DOI:10.1089/neu.2023.0275

Ann Neurol. 2023 Dec;94(6):1008-1023. doi: 10.1002/ana.26741. Epub 2023 Oct 5.

ABSTRACT

OBJECTIVE: It is not currently possible to predict long-term functional dependency in patients with disorders of consciousness (DoC) after traumatic brain injury (TBI). Our objective was to fit and externally validate a prediction model for 1-year dependency in patients with DoC ≥ 2 weeks after TBI.

METHODS: We included adults with TBI enrolled in TBI Model Systems (TBI-MS) or Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) studies who were not following commands at rehabilitation admission or 2 weeks post-injury, respectively. We fit a logistic regression model in TBI-MS and validated it in TRACK-TBI. The primary outcome was death or dependency at 1 year post-injury, defined using the Disability Rating Scale.

RESULTS: In the TBI-MS Discovery Sample, 1,960 participants (mean age 40 [18] years, 76% male, 68% white) met inclusion criteria, and 406 (27%) were dependent 1 year post-injury. In a TBI-MS held out cohort, the dependency prediction model's area under the receiver operating characteristic curve was 0.79 (95% CI 0.74-0.85), positive predictive value was 53% and negative predictive value was 86%. In the TRACK-TBI external validation (n = 124, age 40 [16] years, 77% male, 81% white), the area under the receiver operating characteristic curve was 0.66 (0.53, 0.79), equivalent to the standard IMPACT_{core + CT} score (p = 0.8).

INTERPRETATION: We developed a 1-year dependency prediction model using the largest existing cohort of patients with DoC after TBI. The sensitivity and negative predictive values were greater than specificity and positive predictive values. Accuracy was diminished in an external sample, but equivalent to the IMPACT model. Further research is needed to improve dependency prediction in patients with DoC after TBI. ANN NEUROL 2023;94:1008-1023.

PMID:37470289 | PMC:PMC10799195 | DOI:10.1002/ana.26741

J Neurotrauma. 2023 Oct 11. doi: 10.1089/neu.2023.0009. Online ahead of print.

ABSTRACT

We previously described five trajectories of insomnia (each defined by a distinct pattern of insomnia severity over 12 months following traumatic brain injury [TBI]). Our objective in the present study was to estimate the association between insomnia trajectory status and trajectories of mental health and neurocognitive outcomes during the 12 months after TBI. In this study, participants included N = 2022 adults from the Federal Inter-agency Traumatic Brain Injury Repository database and Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study. The following outcome measures were assessed serially at 2 weeks, and 3, 6, and 12 months post-injury: Insomnia Severity Index, Patient Health Questionnaire, Post-Traumatic Stress Disorder (PTSD) Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), Patient Reported Outcomes Measurement Information System-Pain, and Quality of Life After Brain Injury-Overall Scale. Neurocognitive performance was assessed at 2 weeks, and 6 and 12 months using the Wechsler Adult Intelligence Scales Processing Speed Index and the Trails Making Test Parts A and B. Results indicated that greater insomnia severity was associated with greater abnormality in mental health, quality of life, and neuropsychological testing outcomes. The pattern of insomnia over time tracked the temporal pattern of all these outcomes for all but a very small number of participants. Notably, severe insomnia at 3 or 6 months post-TBI was a risk factor for poor recovery at 12 months post-injury. In conclusion, in this well-characterized sample of individuals with TBI, insomnia severity generally tracked severity of depression, pain, PTSD, quality of life, and neurocognitive outcomes over 12 months post-injury. More intensive sleep assessment is needed to elucidate the nature of these relationships and to help inform best strategies for intervention.

PMID:37463057 | DOI:10.1089/neu.2023.0009

J Neurol Neurosurg Psychiatry. 2023 Dec;94(12):1012-1017. doi: 10.1136/jnnp-2023-331562. Epub 2023 Jun 27.

ABSTRACT

OBJECTIVES: Obesity is associated with chronic inflammation, which may impact recovery from mild traumatic brain injury (mTBI). The objective was to assess the role of obesity in recovery of symptoms, functional outcome and inflammatory blood biomarkers after mTBI.

METHODS: TRACK-TBI is a prospective study of patients with acute mTBI (Glasgow Coma Scale=13-15) who were enrolled ≤24 hours of injury at an emergency department of level 1 trauma centres and followed for 12 months. A total of 770 hospitalised patients who were either obese (body mass index (BMI) >30.0) or healthy mass (BMI=18.5-24.9) were enrolled. Blood concentrations of high-sensitivity C reactive protein (hsCRP), interleukin (IL) 6, IL-10, tumour necrosis factor alpha; Rivermead Post-Concussion Symptoms Questionnaire (RPQ), Quality of Life After Brain Injury and Glasgow Outcome Score-Extended reflecting injury-related functional limitations at 6 and 12 months were collected.

RESULTS: After adjusting for age and gender, obese participants had higher concentrations of hsCRP 1 day after injury (mean difference (MD)=0.65; 95% CI: 0.44 to 0.87, p<0.001), at 2 weeks (MD=0.99; 95% CI: 0.74 to 1.25, p<0.001) and at 6 months (MD=1.08; 95% CI: 0.79 to 1.37, p<0.001) compared with healthy mass participants. Obese participants had higher concentrations of IL-6 at 2 weeks (MD=0.37; 95% CI: 0.11 to 0.64, p=0.006) and 6 months (MD=0.42; 95% CI: 0.12 to 0.72, p=0.006). Obese participants had higher RPQ total score at 6 months (MD=2.79; p=0.02) and 12 months (MD=2.37; p=0.049).

CONCLUSIONS: Obesity is associated with higher symptomatology at 6 and 12 months and higher concentrations of blood inflammatory markers throughout recovery following mTBI.

PMID:37369556 | DOI:10.1136/jnnp-2023-331562

Neurology. 2023 Aug 15;101(7):e740-e753. doi: 10.1212/WNL.0000000000207501. Epub 2023 Jun 21.

ABSTRACT

BACKGROUND AND OBJECTIVES: Traumatic brain injury (TBI) may be a chronic condition carrying risk of future sequelae; few prospective studies examine long-term postinjury outcomes. We examined the prevalence of functional, cognitive, and psychiatric change outcomes from 1 to 7 years postinjury.

METHODS: Transforming Research and Clinical Knowledge in TBI LONG (TRACK-TBI LONG) participants were prospectively enrolled within 24 hours of injury and followed up to 1 year postinjury; a subset participated in long-term follow-up from 2 to 7 years postinjury. Reliable change thresholds for the Brief Test of Adult Cognition by Telephone General Composite (cognition) and Brief Symptom Inventory (BSI)-18 (psychiatric) were derived from orthopedic trauma controls (OTCs). Multiple assessments were completed (postinjury baseline assessment and 2 or 3 visits 2-7 years postinjury) within a sample subset. Change was assessed for functional outcome (Glasgow Outcome Scale-Extended [GOSE]) and self-report/informant report of decline. Prevalence ratios for outcomes classified as stable, improved, and declined were reported individually and collectively. The Fisher exact test and log-binomial regression models examined factors associated with decline and improvement.

RESULTS: Of the sample (N = 1,264; mild TBI [mTBI], Glasgow Coma Scale [GCS] 13-15, n = 917; moderate-to-severe TBI [msTBI], GCS 3-12, n = 193; or OTC n = 154), "stable" was the most prevalent outcome. Functional outcome showed the highest rates of decline, regardless of TBI severity (mild = 29%; moderate/severe = 23%). When measures were collectively considered, rates of decline included mTBI (21%), msTBI (26%), and OTC (15%). Age and preinjury employment status were associated with functional decline (per 10 years; relative risk [RR] 1.16, 95% CI 1.07-1.25, p < 0.001; higher in retired/disabled/not working vs full-time/part-time; RR 1.81, 95% CI 1.33-2.45, respectively) in the mTBI group. Improvement in functional recovery 2-7 years postinjury was associated with higher BSI scores (per 5 points; RR 1.11, 95% CI 1.04-1.18, p = 0.002) and GOSE score of 5-7 (GOSE = 8 as reference; RR 2.64, 95% CI 1.75-3.97, p < 0.001). Higher BSI scores and identifying as Black (RR 2.28, 95% CI 1.59-3.25, p < 0.001) were associated with a greater likelihood of improved psychiatric symptoms in mTBI (RR 1.21, 95% CI 1.14-1.29, p < 0.001). A greater likelihood of cognitive improvement was observed among those with higher educational attainment in msTBI (per 4 years; RR 2.61, 95% CI 1.43-4.79, p = 0.002).

DISCUSSION: Function across domains at 1-year postinjury, a common recovery benchmark, undergoes change across the subsequent 6 years. Results support consideration of TBI as a chronic evolving condition and suggest continued monitoring, rehabilitation, and support is required to optimize long-term independence and quality of life.

PMID:37344231 | PMC:PMC10437015 | DOI:10.1212/WNL.0000000000207501

PM R. 2024 Feb;16(2):174-189. doi: 10.1002/pmrj.13027. Epub 2023 Jul 25.

ABSTRACT

OBJECTIVE: To conduct a scoping review of models of care for chronic disease management to identify potentially effective components for management of chronic traumatic brain injury (TBI).

METHODS: Information sources: Systematic searches of three databases (Ovid MEDLINE, Embase, and Cochrane Database of Systematic Reviews) from January 2010 to May 2021.

ELIGIBILITY CRITERIA: Systematic reviews and meta-analyses reporting on the effectiveness of the Chronic Care Model (CCM), collaborative/integrated care, and other chronic disease management models.

DATA: Target diseases, model components used (n = 11), and six outcomes (disease-specific, generic health-related quality of life and functioning, adherence, health knowledge, patient satisfaction, and cost/health care use).

SYNTHESIS: Narrative synthesis, including proportion of reviews documenting outcome benefits.

RESULTS: More than half (55%) of the 186 eligible reviews focused on collaborative/integrated care models, with 25% focusing on CCM and 20% focusing on other chronic disease management models. The most common health conditions were diabetes (n = 22), depression (n = 16), heart disease (n = 12), aging (n = 11), and kidney disease (n = 8). Other single medical conditions were the focus of 22 reviews, multiple medical conditions of 59 reviews, and other or mixed mental health/behavioral conditions of 20 reviews. Some type of quality rating for individual studies was conducted in 126 (68%) of the reviews. Of reviews that assessed particular outcomes, 80% reported disease-specific benefits, and 57% to 72% reported benefits for the other five types of outcomes. Outcomes did not differ by the model category, number or type of components, or target disease.

CONCLUSIONS: Although there is a paucity of evidence for TBI per se, care model components proven effective for other chronic diseases may be adaptable for chronic TBI care.

PMID:37329557 | DOI:10.1002/pmrj.13027

Disabil Rehabil. 2024 Jun;46(11):2385-2395. doi: 10.1080/09638288.2023.2221900. Epub 2023 Jun 9.

ABSTRACT

Purpose. To characterize societal participation profiles after moderate-severe traumatic brain injury (TBI) along objective (Frequency) and subjective (Satisfaction, Importance, Enfranchisement) dimensions.Materials and Methods. We conducted secondary analyses of a TBI Model Systems sub-study (N = 408). Multiaxial assessment of participation included the Participation Assessment with Recombined Tools-Objective and -Subjective questionnaires (Participation Frequency and Importance/Satisfaction, respectively) and the Enfranchisement Scale. Participants provided responses via telephone interview 1-15 years post-injury. Multidimensional participation profiles (classes) were extracted using latent profile analysis.Results. A 4-class solution was identified as providing maximal statistical separation between profiles and being clinically meaningful based on profile demographic features. One profile group (48.5% of the sample) exhibited the "best" participation profile (High Frequency, Satisfaction, Importance, and Enfranchisement) and was also the most advantaged according to socioeconomic indicators. Other profile groups showed appreciable heterogeneity across participation dimensions. Age, race/ethnicity, education level, ability to drive, and urbanicity were features that varied between profiles.Conclusions. Societal participation is a critical, but inherently complex, TBI outcome that may not be adequately captured by a single index. Our data underscore the importance of a multidimensional approach to participation assessment and interpretation using profiles. The use of participation profiles may promote precision health interventions for community integration.Implications for RehabilitationOur study found unidimensional measures of societal participation in traumatic brain injury (TBI) populations that focus exclusively on frequency indicators may be overly simplistic and miss key subjective components of participationTaking a multidimensional perspective, we documented four meaningfully distinct participation subgroups (including both objective and subjective dimensions of societal participation) within the TBI rehabilitation populationMultidimensional profiles of participation may be used to group individuals with TBI into target groups for intervention (e.g., deeper goal assessment for individuals who do not rate standard participation activities as important, but also do not participate and do not feel enfranchised).

PMID:37296112 | DOI:10.1080/09638288.2023.2221900

JAMA. 2023 Jun 13;329(22):1934-1946. doi: 10.1001/jama.2023.8823.

ABSTRACT

IMPORTANCE: SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals.

OBJECTIVE: To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections.

DESIGN, SETTING, AND PARTICIPANTS: Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling.

EXPOSURE: SARS-CoV-2 infection.

MAIN OUTCOMES AND MEASURES: PASC and 44 participant-reported symptoms (with severity thresholds).

RESULTS: A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months.

CONCLUSIONS AND RELEVANCE: A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.

PMID:37278994 | PMC:PMC10214179 | DOI:10.1001/jama.2023.8823

Arch Phys Med Rehabil. 2023 Nov;104(11):1865-1871. doi: 10.1016/j.apmr.2023.04.017. Epub 2023 May 7.

ABSTRACT

OBJECTIVE: To investigate whether a functional decline in cognitive activities decades after moderate-to-severe traumatic brain injury (m-sTBI) might relate to injury features and/or lifetime health factors, some of which may emerge as consequences of the injury.

DESIGN: Secondary analysis of the TBI Model Systems National Database, a prospective, multi-center, longitudinal study of patients with m-sTBI.

SETTING: TBI Model Systems Centers.

PARTICIPANTS: Included were 732 participants rated on the cognitive subscale of the Functional Independence Measure (FIM Cognitive), a metric for everyday cognitive skills, across 3 time points out to 20 years (visits at 2-, 10-, and 20-year follow-ups; N=732).

INTERVENTIONS: Not applicable.

MAIN OUTCOME MEASURE(S): FIM Cognitive Scale. Injury characteristics such as timing and features pertaining to severity and health-related factors (eg, alcohol use, socioeconomic status) were examined to discriminate stable from declining participants on the FIM Cognitive Scale using logistic regression.

RESULTS: At 20 years post-injury, there was a low base rate of FIM Cognitive decline (11%, n=78), with most being stable or having meaningful improvement (89%, n=654). Older age at injury, longer duration of post-traumatic amnesia, and presence of repetitive seizures were significant predictors of FIM Cognitive decline in the final model (area under the curve=0.75), while multiple health-related factors that can represent independent co-morbidities or possible consequences of injury were not.

CONCLUSION(S): The strongest contributors to reported functional decline in cognitive activities later-in-life were related to acute characteristics of m-sTBI and experiencing post-traumatic seizures. Future studies are needed integrating functional with performance-based cognitive assessments to affirm conclusions and identify the timeline and trajectory of cognitive decline.

PMID:37160187 | PMC:PMC10966469 | DOI:10.1016/j.apmr.2023.04.017

Lancet Neurol. 2023 Jun;22(6):517-528. doi: 10.1016/S1474-4422(23)00065-0. Epub 2023 Apr 20.

ABSTRACT

Traumatic brain injury (TBI) is a global health priority, associated with substantial burden. Historically conceptualised as an injury event with finite recovery, TBI is now recognised as a chronic condition that can affect multiple domains of health and function, some of which might deteriorate over time. Many people who have had a TBI remain moderately to severely disabled at 5 years, are rehospitalised up to 10 years post-injury, and have a reduced lifespan relative to the general population. Understanding TBI as a chronic disease process can be highly informative for optimising care, which has traditionally focused on acute care. Chronic brain injury care models must be informed by a holistic understanding of long-term outcomes and the factors that can affect how care needs evolve over time. The United States Traumatic Brain Injury Model Systems of Care follows up individuals with moderate-to-severe TBI for over 30 years, allowing characterisation of the chronic (2-30 years or more post injury) functional, cognitive, behavioural, and social sequelae experienced by individuals who have had a moderate-to-severe TBI and the implications for their health and quality of life. Older age, social determinants of health, and lower acute functional status are associated with post-recovery deterioration, while younger age and greater functional independence are associated with risky health behaviours, including substance misuse and re-injury. Systematically collected data on long-term outcomes across multiple domains of health and function are needed worldwide to inform the development of models for chronic disease management, including the proactive surveillance of commonly experienced health and functional challenges.

PMID:37086742 | DOI:10.1016/S1474-4422(23)00065-0

Neurocrit Care. 2023 Jun;38(3):584-590. doi: 10.1007/s12028-023-01706-4. Epub 2023 Apr 8.

ABSTRACT

Early reemergence of consciousness predicts long-term functional recovery for patients with severe brain injury. However, tools to reliably detect consciousness in the intensive care unit are lacking. Transcranial magnetic stimulation electroencephalography has the potential to detect consciousness in the intensive care unit, predict recovery, and prevent premature withdrawal of life-sustaining therapy.

PMID:37029315 | PMC:PMC11421303 | DOI:10.1007/s12028-023-01706-4

medRxiv [Preprint]. 2023 Mar 15:2023.03.14.23287249. doi: 10.1101/2023.03.14.23287249.

ABSTRACT

IMPORTANCE: There are currently no models that predict long-term functional dependency in patients with disorders of consciousness (DoC) after traumatic brain injury (TBI).

OBJECTIVE: Fit, test, and externally validate a prediction model for 1-year dependency in patients with DoC 2 or more weeks after TBI.

DESIGN: Secondary analysis of patients enrolled in TBI Model Systems (TBI-MS, 1988-2020, Discovery Sample) or Transforming Research and Clinical Knowledge in TBI (TRACK-TBI, 2013-2018, Validation Sample) and followed 1-year post-injury.

SETTING: Multi-center study at USA rehabilitation hospitals (TBI-MS) and acute care hospitals (TRACK-TBI).

PARTICIPANTS: Adults with TBI who were not following commands at rehabilitation admission (TBI-MS; days post-injury vary) or 2-weeks post-injury (TRACK-TBI).

EXPOSURES: In the TBI-MS database (model fitting and testing), we screened demographic, radiological, clinical variables, and Disability Rating Scale (DRS) item scores for association with the primary outcome.

MAIN OUTCOME: The primary outcome was death or complete functional dependency at 1-year post-injury, defined using a DRS-based binary measure (DRS _Depend ), indicating need for assistance with all activities and concomitant cognitive impairment.

RESULTS: In the TBI-MS Discovery Sample, 1,960 subjects (mean age 40 [18] years, 76% male, 68% white) met inclusion criteria and 406 (27%) were dependent at 1-year post-injury. A dependency prediction model had an area under the receiver operating characteristic curve (AUROC) of 0.79 [0.74, 0.85], positive predictive value of 53%, and negative predictive value of 86% for dependency in a held-out TBI-MS Testing cohort. Within the TRACK-TBI external validation sample (N=124, age 40 [16], 77% male, 81% white), a model modified to remove variables not collected in TRACK-TBI, had an AUROC of 0.66 [0.53, 0.79], equivalent to the gold-standard IMPACT _core+CT score (0.68; 95% AUROC difference CI: -0.2 to 0.2, p=0.8).

CONCLUSIONS AND RELEVANCE: We used the largest existing cohort of patients with DoC after TBI to develop, test and externally validate a prediction model of 1-year dependency. The model’s sensitivity and negative predictive value were greater than specificity and positive predictive value. Accuracy was diminished in an external sample, but equivalent to the best-available models. Further research is needed to improve dependency prediction in patients with DoC after TBI.

PMID:36993195 | PMC:PMC10055467 | DOI:10.1101/2023.03.14.23287249

Cortex. 2023 May;162:136-139. doi: 10.1016/j.cortex.2023.01.003. Epub 2023 Mar 1.

NO ABSTRACT

PMID:36948917 | DOI:10.1016/j.cortex.2023.01.003

JAMA Netw Open. 2023 Mar 1;6(3):e233660. doi: 10.1001/jamanetworkopen.2023.3660.

ABSTRACT

IMPORTANCE: Many level I trauma center patients experience clinical sequelae at 1 year following traumatic brain injury (TBI). Longer-term outcome data are needed to develop better monitoring and rehabilitation services.

OBJECTIVE: To examine functional recovery, TBI-related symptoms, and quality of life from 1 to 5 years postinjury.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study enrolled trauma patients across 18 US level I trauma centers between 2014 and 2018. Eligible participants were enrolled within 24 hours of injury and followed up to 5 years postinjury. Data were analyzed January 2023.

EXPOSURES: Mild TBI (mTBI), moderate-severe TBI (msTBI), or orthopedic traumatic controls (OTC).

MAIN OUTCOMES AND MEASURES: Functional independence (Glasgow Outcome Scale-Extended [GOSE] score 5 or higher), complete functional recovery (GOSE score, 8), better (ie, lower) TBI-related symptom burden (Rivermead Post Concussion Symptoms Questionnaire score of 15 or lower), and better (ie, higher) health-related quality of life (Quality of Life After Brain Injury Scale-Overall Scale score 52 or higher); mortality was analyzed as a secondary outcome.

RESULTS: A total 1196 patients were included in analysis (mean [SD] age, 40.8 [16.9] years; 781 [65%] male; 158 [13%] Black, 965 [81%] White). mTBI and OTC groups demonstrated stable, high rates of functional independence (98% to 100% across time). While odds of independence were lower among msTBI survivors, the majority were independent at 1 year (72%), and this proportion increased over time (80% at 5 years; group × year, P = .005; independence per year: odds ratio [OR] for msTBI, 1.28; 95% CI, 1.03-1.58; OR for mTBI, 0.81; 95% CI, 0.64-1.03). For other outcomes, group differences at 1 year remained stable over time (group × year, P ≥ .44). Odds of complete functional recovery remained lower for persons with mTBI vs OTC (OR, 0.39; 95% CI, 0.28-0.56) and lower for msTBI vs mTBI (OR, 0.34; 95% CI, 0.24-0.48). Odds of better TBI-related symptom burden and quality of life were similar for both TBI subgroups and lower than OTCs. Mortality between 1 and 5 years was higher for msTBI (5.5%) than mTBI (1.5%) and OTC (0.7%; P = .02).

CONCLUSIONS AND RELEVANCE: In this cohort study, patients with previous msTBI displayed increased independence over 5 years; msTBI was also associated with increased mortality. These findings, in combination with the persistently elevated rates of unfavorable outcomes in mTBI vs controls imply that more monitoring and rehabilitation are needed for TBI.

PMID:36939699 | PMC:PMC10028488 | DOI:10.1001/jamanetworkopen.2023.3660

J Clin Med. 2023 Mar 3;12(5):2024. doi: 10.3390/jcm12052024.

ABSTRACT

INTRODUCTION: Neuroworsening may be a sign of progressive brain injury and is a factor for treatment of traumatic brain injury (TBI) in intensive care settings. The implications of neuroworsening for clinical management and long-term sequelae of TBI in the emergency department (ED) require characterization.

METHODS: Adult TBI subjects from the prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot Study with ED admission and disposition Glasgow Coma Scale (GCS) scores were extracted. All patients received head computed tomography (CT) scan <24 h post-injury. Neuroworsening was defined as a decline in motor GCS at ED disposition (vs. ED admission). Clinical and CT characteristics, neurosurgical intervention, in-hospital mortality, and 3- and 6-month Glasgow Outcome Scale-Extended (GOS-E) scores were compared by neuroworsening status. Multivariable regressions were performed for neurosurgical intervention and unfavorable outcome (GOS-E ≤ 3). Multivariable odds ratios (mOR) with [95% confidence intervals] were reported.

RESULTS: In 481 subjects, 91.1% had ED admission GCS 13-15 and 3.3% had neuroworsening. All neuroworsening subjects were admitted to intensive care unit (vs. non-neuroworsening: 26.2%) and were CT-positive for structural injury (vs. 45.4%). Neuroworsening was associated with subdural (75.0%/22.2%), subarachnoid (81.3%/31.2%), and intraventricular hemorrhage (18.8%/2.2%), contusion (68.8%/20.4%), midline shift (50.0%/2.6%), cisternal compression (56.3%/5.6%), and cerebral edema (68.8%/12.3%; all p < 0.001). Neuroworsening subjects had higher likelihoods of cranial surgery (56.3%/3.5%), intracranial pressure (ICP) monitoring (62.5%/2.6%), in-hospital mortality (37.5%/0.6%), and unfavorable 3- and 6-month outcome (58.3%/4.9%; 53.8%/6.2%; all p < 0.001). On multivariable analysis, neuroworsening predicted surgery (mOR = 4.65 [1.02-21.19]), ICP monitoring (mOR = 15.48 [2.92-81.85], and unfavorable 3- and 6-month outcome (mOR = 5.36 [1.13-25.36]; mOR = 5.68 [1.18-27.35]).

CONCLUSIONS: Neuroworsening in the ED is an early indicator of TBI severity, and a predictor of neurosurgical intervention and unfavorable outcome. Clinicians must be vigilant in detecting neuroworsening, as affected patients are at increased risk for poor outcomes and may benefit from immediate therapeutic interventions.

PMID:36902811 | PMC:PMC10004432 | DOI:10.3390/jcm12052024

J Head Trauma Rehabil. 2023 Nov-Dec 01;38(6):448-457. doi: 10.1097/HTR.0000000000000860. Epub 2023 Feb 28.

ABSTRACT

OBJECTIVE: To identify demographic, injury-related, and 1-year postinjury clinical and functional predictors of high and low life satisfaction at 10 years after moderate to severe traumatic brain injury (TBI) using an extreme phenotyping approach.

SETTING: Multicenter longitudinal database study.

PARTICIPANTS: A total of 3040 people from the National Institute on Disability, Independent Living, and Rehabilitation Research TBI Model Systems database with life satisfaction data at 10 years post-TBI.

DESIGN: Multicenter, cross-sectional, observational design.

MAIN MEASURES: Satisfaction With Life Scale (outcome), Glasgow Coma Scale, Disability Rating Scale, Functional Independence Measure, Participation Assessment with Recombined Tools-Objective, Patient Health Questionnaire-9, and General Anxiety Disorder-7 (standardized predictors).

RESULTS: Greater cognitive and motor independence, more frequent community participation, and less depressive symptoms 1 year post-moderate to severe TBI predicted extreme high life satisfaction 10 years later. Non-Hispanic White and Hispanic individuals were significantly more likely than Black individuals to have extreme high life satisfaction 10 years post-TBI.

CONCLUSIONS: Extreme phenotyping analysis complements existing knowledge regarding life satisfaction post-moderate to severe TBI. From a chronic disease management perspective, future studies are needed to examine the feasibility and impact of early postinjury medical and rehabilitative interventions targeting cognitive and motor function, community participation, and mood on the maintenance/enhancement of long-term life satisfaction post-TBI.

PMID:36854110 | PMC:PMC10460820 | DOI:10.1097/HTR.0000000000000860

J Head Trauma Rehabil. 2023 Jul-Aug 01;38(4):351-357. doi: 10.1097/HTR.0000000000000864. Epub 2023 Feb 28.

ABSTRACT

Functional magnetic resonance imaging (fMRI) now promises to improve diagnostic and prognostic accuracy for patients with disorders of consciousness, and accordingly has been endorsed by professional society guidelines, including those of the American Academy of Neurology, American College of Rehabilitation Medicine, National Institute on Disability, Independent Living, and Rehabilitation Research, and the European Academy of Neurology. Despite multiple professional society endorsements of fMRI in evaluating patients with disorders of consciousness following severe brain injury, insurers have yet to issue clear guidance regarding coverage of fMRI for this indication. Lack of insurer coverage may be a rate-limiting barrier to accessing this technique, which could uncover essential diagnostic and prognostic information for patients and their families. The emerging clinical and ethical case for harmonized insurer recognition and reimbursement of fMRI for vulnerable persons following severe brain injury with disorders of consciousness is explained and critically evaluated.

PMID:36854104 | PMC:PMC10329974 | DOI:10.1097/HTR.0000000000000864

Int J Environ Res Public Health. 2023 Jan 21;20(3):1988. doi: 10.3390/ijerph20031988.

ABSTRACT

College-aged individuals with anxiety are vulnerable to developing persistent concussion symptoms, yet evidence-based treatments for this population are limited. Understanding these individuals' perspectives is critical for developing effective interventions. We conducted qualitative interviews with 17 college-aged individuals (18-24 years old) with a recent (≤10 weeks) concussion and at least mild anxiety (≥5 on the GAD-7 questionnaire) to understand the life impact of their concussion. We identified 5 themes: (1) disruption to daily activities (e.g., reduced participation in hobbies and physical activity); (2) disruption to relationships (e.g., reduced social engagement, feeling dismissed by others, stigma, and interpersonal friction); (3) disruptions in school/work (e.g., challenges participating due to light sensitivity, cognitive or sleep disturbance, and related emotional distress); (4) changes in view of the self (e.g., feeling "unlike oneself", duller, or more irritable), and (5) finding "silver linings" after the injury (e.g., increased motivation). Concussions impact the lives of college-aged individuals with co-occurring anxiety in a broad range of domains, many of which remain largely neglected in standard concussion clinical assessment and treatment. Assessing and addressing these issues has the potential to limit the negative impact of concussion, promote recovery, and potentially help prevent persistent concussion symptoms in this at-risk population.

PMID:36767359 | PMC:PMC9915955 | DOI:10.3390/ijerph20031988

Arch Phys Med Rehabil. 2023 Jul;104(7):1062-1071. doi: 10.1016/j.apmr.2023.01.004. Epub 2023 Feb 2.

ABSTRACT

OBJECTIVE: To explore the factor structure of the Rehabilitation Needs Survey (RNS).

DESIGN: Secondary analysis of observational cohort study who were 5-years post-traumatic brain injury (TBI).

SETTING: Five Inpatient Rehabilitation Facilities.

PARTICIPANTS: Veterans enrolled in the TBI Model Systems longitudinal study who completed the RNS at 5-year follow-up (N=378).

MAIN OUTCOME MEASURE(S): RNS.

RESULTS: RNS factor structure was examined with exploratory factor analysis (EFA) with oblique rotation. Analyses returned 2- and 3-factor solutions with Cronbach alphas ranging from 0.715 to 0.905 and corrected item-total correlations that ranged from 0.279 to 0.732. The 2-factor solution accounted for 61.7% of the variance with ≥3 exclusively loading items on each factor with acceptable internal consistency metrics and was selected as the most parsimonious and clinically applicable model. Ad hoc analysis found the RNS structure per the EFA corresponded with elements of the International Classification of Functioning, Disability and Health (ICF) conceptual framework. All factors had adequate internal consistency (α≥0.70) and 20 of the 21 demonstrated good discrimination (corrected item-total correlations≥0.40).

CONCLUSIONS: The 2-factor solution of the RNS appears to be a useful model for enhancing its clinical interpretability. Although there were cross-loading items, they refer to complex rehabilitation needs that are likely influenced by multiple factors. Alternatively, there are items that may require alteration and redundant items that should be considered for elimination.

PMID:36736804 | DOI:10.1016/j.apmr.2023.01.004

Arch Phys Med Rehabil. 2023 Jul;104(7):1054-1061. doi: 10.1016/j.apmr.2023.01.007. Epub 2023 Feb 1.

ABSTRACT

OBJECTIVE: To explore the prognostic value of the Coma Recovery Scale-Revised (CRS-R) in predicting disability outcomes in patients with severe traumatic brain injury using the Disability Rating Scale (DRS).

DESIGN: Secondary analysis including linear and logistic regressions were performed.

SETTING: Data were collected in a previous clinical trial.

PARTICIPANTS: One hundred eighty-four participants across 3 countries (N=184).

MAIN OUTCOME MEASURES: Disability Rating Scales.

RESULTS: Analyses showed an inverse relation between CRS-R scores obtained at baseline and change in DRS scores at 6 weeks. Similarly, changes in CRS-R scores between baseline and 4 weeks were also found to have an inverse relation to change in DRS scores at 6 weeks.

CONCLUSIONS: This study generates a tool that can be used to predict the probability that a patient with severe traumatic brain injury lands in 1 of 3 disability categories. The CRS-R may be useful in prognostication of disability in patients with severe traumatic brain injury.

PMID:36736600 | PMC:PMC10404472 | DOI:10.1016/j.apmr.2023.01.007

J Head Trauma Rehabil. 2023 May-Jun 01;38(3):E186-E194. doi: 10.1097/HTR.0000000000000814. Epub 2022 Oct 14.

ABSTRACT

OBJECTIVE: The goal of this study is to describe national trends in inpatient rehabilitation facility (IRF) discharges for the most severely disabled cohort of patients with traumatic brain injury (TBI).

METHODS: Data from the Uniform Data System for Medical Rehabilitation for patients discharged from an IRF between January 1, 2002, and December 31, 2017, with a diagnosis of TBI and an admission Functional Independence Measure of 18, the lowest possible score, were obtained and analyzed.

RESULTS: Of the 252 112 patients with TBI discharged during the study period, 10 098 met the study criteria. From 2002 to 2017, the number of patients with an IRF admission Functional Independence Measure of 18 following TBI discharged from IRFs annually decreased from 649 to 488, modeled by a negative regression (coefficient = -2.97; P = .001), and the mean age (SD) increased from 43.0 (21.0) to 53.7 (21.3) years (coefficient = 0.70; P < .001). During the study period, the number of patients with the most severe disability on admission to IRF who were discharged annually as a proportion of total patients with TBI decreased from 5.5% to 2.5% (odds ratio = 0.95; P < .001) and their mean length of stay decreased from 41.5 (36.2) to 29.3 (24.9) days (coefficient = -0.83; P < .001].

CONCLUSION: The number and proportion of patients with the most severe disability on IRF admission following TBI who are discharged from IRFs is decreasing over time. This may represent a combination of primary prevention, early mortality due to withdrawal of life-sustaining treatment, alternative discharge dispositions, or changes in admitting and reimbursement practices. Furthermore, there has been a decrease in the duration of IRF level care for these individuals, which could ultimately lead to poorer functional outcomes, particularly given the importance of specialized rehabilitative care in this population.

PMID:36730991 | PMC:PMC10102246 | DOI:10.1097/HTR.0000000000000814

Transl Psychiatry. 2023 Jan 25;13(1):24. doi: 10.1038/s41398-023-02313-9.

ABSTRACT

Many patients with mild traumatic brain injury (mTBI) are at risk for mental health problems such as posttraumatic stress disorder (PTSD). The objective of this study was to determine whether the polygenic risk for PTSD (or for related mental health disorders or traits including major depressive disorder [MDD] and neuroticism [NEU]) was associated with an increased likelihood of PTSD in the aftermath of mTBI. We used data from individuals of European ancestry with mTBI enrolled in TRACK-TBI (n = 714), a prospective longitudinal study of level 1 trauma center patients. One hundred and sixteen mTBI patients (16.3%) had probable PTSD (PCL-5 score ≥33) at 6 months post-injury. We used summary statistics from recent GWAS studies of PTSD, MDD, and NEU to generate polygenic risk scores (PRS) for individuals in our sample. A multivariable model that included age, sex, pre-injury history of mental disorder, and cause of injury explained 7% of the variance in the PTSD outcome; the addition of the PTSD-PRS (and five ancestral principal components) significantly increased the variance explained to 11%. The adjusted odds of PTSD in the uppermost PTSD-PRS quintile was nearly four times higher (aOR = 3.71, 95% CI 1.80-7.65) than in the lowest PTSD-PRS quintile. There was no evidence of a statistically significant interaction between PTSD-PRS and prior history of mental disorder, indicating that PTSD-PRS had similar predictive utility among those with and without pre-injury psychiatric illness. When added to the model, neither MDD-PRS nor NEU-PRS were significantly associated with the PTSD outcome. These findings show that the risk for PTSD in the context of mTBI is, in part, genetically influenced. They also raise the possibility that an individual's PRS could be clinically actionable if used-possibly with other non-genetic predictors-to signal the need for enhanced follow-up and early intervention; this precision medicine approach needs to be prospectively studied.

PMID:36693822 | PMC:PMC9873804 | DOI:10.1038/s41398-023-02313-9

Neuroimage Clin. 2023;37:103294. doi: 10.1016/j.nicl.2022.103294. Epub 2022 Dec 13.

ABSTRACT

New techniques for individualized assessment of white matter integrity are needed to detect traumatic axonal injury (TAI) and predict outcomes in critically ill patients with acute severe traumatic brain injury (TBI). Diffusion MRI tractography has the potential to quantify white matter microstructure in vivo and has been used to characterize tract-specific changes following TBI. However, tractography is not routinely used in the clinical setting to assess the extent of TAI, in part because focal lesions reduce the robustness of automated methods. Here, we propose a pipeline that combines automated tractography reconstructions of 40 white matter tracts with multivariate analysis of along-tract diffusion metrics to assess the presence of TAI in individual patients with acute severe TBI. We used the Mahalanobis distance to identify abnormal white matter tracts in each of 18 patients with acute severe TBI as compared to 33 healthy subjects. In all patients for which a FreeSurfer anatomical segmentation could be obtained (17 of 18 patients), including 13 with focal lesions, the automated pipeline successfully reconstructed a mean of 37.5 ± 2.1 white matter tracts without the need for manual intervention. A mean of 2.5 ± 2.1 tracts resulted in partial or failed reconstructions and needed to be reinitialized upon visual inspection. The pipeline detected at least one abnormal tract in all patients (mean: 9.1 ± 7.9) and accurately discriminated between patients and controls (AUC: 0.91). The number and neuroanatomic location of abnormal tracts varied across patients and levels of consciousness. The premotor, temporal, and parietal sections of the corpus callosum were the most commonly damaged tracts (in 10, 9, and 8 patients, respectively), consistent with prior histopathological studies of TAI. TAI measures were not associated with concurrent behavioral measures of consciousness. In summary, we provide proof-of-principle evidence that an automated tractography pipeline has translational potential to detect and quantify TAI in individual patients with acute severe TBI.

PMID:36529035 | PMC:PMC9792957 | DOI:10.1016/j.nicl.2022.103294

Geriatrics (Basel). 2022 Oct 24;7(6):120. doi: 10.3390/geriatrics7060120.

ABSTRACT

Dog walking is a physical activity (PA) with many health benefits for older adults. Dog behavior issues can be a barrier to dog walking. This study piloted leash manners training as a PA intervention for dog owners ages 60+ years. Fourteen dog owners (mean age = 65 years, female = 71%) enrolled in a leash manners training course. Process evaluation data were collected to determine feasibility and acceptability of the intervention and study procedures. Twelve of fourteen enrolled participants (86%) completed the course, and most were highly engaged with the program, as evidenced by high class attendance (92% of participants who completed the course attended ≥5 of 6 classes) and a majority (64%) reporting frequent skills practice at home. Further, most participants (73%) reported their leash walking skills improved. The PA assessment protocol (7 days of 24 h data collection using activPAL monitors) was well tolerated, with all participants who completed assessments at each time point (pre-program, post-program, 4-week follow-up) providing ≥6 valid days of data. In sum, the intervention approach and study procedures were feasible and acceptable in this sample of older adults. More research is needed to determine the effectiveness of leash manners training for increasing PA in this population.

PMID:36412609 | PMC:PMC9680302 | DOI:10.3390/geriatrics7060120

Brain Commun. 2022 Oct 31;4(6):fcac280. doi: 10.1093/braincomms/fcac280. eCollection 2022.

ABSTRACT

Resting-state functional MRI is being used to develop diagnostic, prognostic and therapeutic biomarkers for critically ill patients with severe brain injuries. In studies of healthy volunteers and non-critically ill patients, prospective cardiorespiratory data are routinely collected to remove non-neuronal fluctuations in the resting-state functional MRI signal during analysis. However, the feasibility and utility of collecting cardiorespiratory data in critically ill patients on a clinical MRI scanner are unknown. We concurrently acquired resting-state functional MRI (repetition time = 1250 ms) and cardiac and respiratory data in 23 critically ill patients with acute severe traumatic brain injury and in 12 healthy control subjects. We compared the functional connectivity results from two approaches that are commonly used to correct cardiorespiratory noise: (i) denoising with cardiorespiratory data (i.e. image-based method for retrospective correction of physiological motion effects in functional MRI) and (ii) standard bandpass filtering. Resting-state functional MRI data in 7 patients could not be analysed due to imaging artefacts. In 6 of the remaining 16 patients (37.5%), cardiorespiratory data were either incomplete or corrupted. In patients (n = 10) and control subjects (n = 10), the functional connectivity results corrected with the image-based method for retrospective correction of physiological motion effects in functional MRI did not significantly differ from those corrected with bandpass filtering of 0.008-0.125 Hz. Collectively, these findings suggest that, in critically ill patients with severe traumatic brain injury, there is limited feasibility and utility to denoising the resting-state functional MRI signal with prospectively acquired cardiorespiratory data.

PMID:36382222 | PMC:PMC9665273 | DOI:10.1093/braincomms/fcac280

Front Rehabil Sci. 2022 Jul 22;3:908615. doi: 10.3389/fresc.2022.908615. eCollection 2022.

ABSTRACT

BACKGROUND: The return to participation in meaningful life roles for persons with acquired brain injury (pwABI) is a goal shared by pwABI, their families, clinicians, and researchers. Synthesizing how pwABI define participation will help to identify the aspects of participation important to pwABI and can inform a person-centered approach to participation outcome assessment. To-date, the qualitative synthesis approach has been used to explore facilitators and barriers of participation post-stroke, and views about participation among individuals with stroke in the UK.

OBJECTIVES: This paper's objectives are to (1) conduct a scoping review of qualitative literature that defines and characterizes participation from the perspective of pwABI of any type, (2) synthesize how pwABI define and categorize participation, and (3) link the themes identified in the qualitative synthesis to the International Classification of Functioning, Disability, and Health (ICF) using standardized linking rules to enhance the comparability of our findings to other types of health information, including standardized outcome measures.

METHODS: We completed a scoping review of qualitative literature. Our search included PubMed, APA PsychInfo, CINAHL, and Embase databases and included articles that (1) had qualitative methodology, (2) had a sample ≥50% pwABI, (3) had aims or research questions related to the meaning, definition, perception, or broader experience of participation, and (4) were in English. Qualitative findings were synthesized using Thomas and Harden's methodology and resultant themes were linked to ICF codes.

RESULTS: The search identified 2,670 articles with 2,580 articles excluded during initial screening. The remaining 90 article abstracts were screened, and 6 articles met the full inclusion criteria for the qualitative synthesis. Four analytical themes emerged: (1) Essential Elements of Participation (2) How pwABI Approach Participation, (3) Where pwABI Participate, and (4) Outcomes of Participation. Each overarching theme included multiple descriptive themes.

CONCLUSION: In this paper, we identified themes that illustrate key components of participation to pwABI. Our results provide insight into the complex perspectives about participation among pwABI and illustrate aspects of participation that should hold elevated importance for clinicians and researchers supporting participation of pwABI.

PMID:36188936 | PMC:PMC9397755 | DOI:10.3389/fresc.2022.908615

Lancet Neurol. 2022 Nov;21(11):1004-1060. doi: 10.1016/S1474-4422(22)00309-X. Epub 2022 Sep 29.

ABSTRACT

Traumatic brain injury (TBI) has the highest incidence of all common neurological disorders, and poses a substantial public health burden. TBI is increasingly documented not only as an acute condition but also as a chronic disease with long-term consequences, including an increased risk of late-onset neurodegeneration. The first Lancet Neurology Commission on TBI, published in 2017, called for a concerted effort to tackle the global health problem posed by TBI. Since then, funding agencies have supported research both in high-income countries (HICs) and in low-income and middle-income countries (LMICs). In November 2020, the World Health Assembly, the decision-making body of WHO, passed resolution WHA73.10 for global actions on epilepsy and other neurological disorders, and WHO launched the Decade for Action on Road Safety plan in 2021. New knowledge has been generated by large observational studies, including those conducted under the umbrella of the International Traumatic Brain Injury Research (InTBIR) initiative, established as a collaboration of funding agencies in 2011. InTBIR has also provided a huge stimulus to collaborative research in TBI and has facilitated participation of global partners. The return on investment has been high, but many needs of patients with TBI remain unaddressed. This update to the 2017 Commission presents advances and discusses persisting and new challenges in prevention, clinical care, and research.

In LMICs, the occurrence of TBI is driven by road traffic incidents, often involving vulnerable road users such as motorcyclists and pedestrians. In HICs, most TBI is caused by falls, particularly in older people (aged ≥65 years), who often have comorbidities. Risk factors such as frailty and alcohol misuse provide opportunities for targeted prevention actions. Little evidence exists to inform treatment of older patients, who have been commonly excluded from past clinical trials—consequently, appropriate evidence is urgently required. Although increasing age is associated with worse outcomes from TBI, age should not dictate limitations in therapy. However, patients injured by low-energy falls (who are mostly older people) are about 50% less likely to receive critical care or emergency interventions, compared with those injured by high-energy mechanisms, such as road traffic incidents.

Mild TBI, defined as a Glasgow Coma sum score of 13–15, comprises most of the TBI cases (over 90%) presenting to hospital. Around 50% of adult patients with mild TBI presenting to hospital do not recover to pre-TBI levels of health by 6 months after their injury. Fewer than 10% of patients discharged after presenting to an emergency department for TBI in Europe currently receive follow-up. Structured follow-up after mild TBI should be considered good practice, and urgent research is needed to identify which patients with mild TBI are at risk for incomplete recovery.

The selection of patients for CT is an important triage decision in mild TBI since it allows early identification of lesions that can trigger hospital admission or life-saving surgery. Current decision making for deciding on CT is inefficient, with 90–95% of scanned patients showing no intracranial injury but being subjected to radiation risks. InTBIR studies have shown that measurement of blood-based biomarkers adds value to previously proposed clinical decision rules, holding the potential to improve efficiency while reducing radiation exposure. Increased concentrations of biomarkers in the blood of patients with a normal presentation CT scan suggest structural brain damage, which is seen on MR scanning in up to 30% of patients with mild TBI. Advanced MRI, including diffusion tensor imaging and volumetric analyses, can identify additional injuries not detectable by visual inspection of standard clinical MR images. Thus, the absence of CT abnormalities does not exclude structural damage—an observation relevant to litigation procedures, to management of mild TBI, and when CT scans are insufficient to explain the severity of the clinical condition.

Although blood-based protein biomarkers have been shown to have important roles in the evaluation of TBI, most available assays are for research use only. To date, there is only one vendor of such assays with regulatory clearance in Europe and the USA with an indication to rule out the need for CT imaging for patients with suspected TBI. Regulatory clearance is provided for a combination of biomarkers, although evidence is accumulating that a single biomarker can perform as well as a combination. Additional biomarkers and more clinical-use platforms are on the horizon, but cross-platform harmonisation of results is needed. Health-care efficiency would benefit from diversity in providers.

In the intensive care setting, automated analysis of blood pressure and intracranial pressure with calculation of derived parameters can help individualise management of TBI. Interest in the identification of subgroups of patients who might benefit more from some specific therapeutic approaches than others represents a welcome shift towards precision medicine. Comparative-effectiveness research to identify best practice has delivered on expectations for providing evidence in support of best practices, both in adult and paediatric patients with TBI.

Progress has also been made in improving outcome assessment after TBI. Key instruments have been translated into up to 20 languages and linguistically validated, and are now internationally available for clinical and research use. TBI affects multiple domains of functioning, and outcomes are affected by personal characteristics and life-course events, consistent with a multifactorial bio-psycho-socio-ecological model of TBI, as presented in the US National Academies of Sciences, Engineering, and Medicine (NASEM) 2022 report. Multidimensional assessment is desirable and might be best based on measurement of global functional impairment. More work is required to develop and implement recommendations for multidimensional assessment. Prediction of outcome is relevant to patients and their families, and can facilitate the benchmarking of quality of care. InTBIR studies have identified new building blocks (eg, blood biomarkers and quantitative CT analysis) to refine existing prognostic models. Further improvement in prognostication could come from MRI, genetics, and the integration of dynamic changes in patient status after presentation.

Neurotrauma researchers traditionally seek translation of their research findings through publications, clinical guidelines, and industry collaborations. However, to effectively impact clinical care and outcome, interactions are also needed with research funders, regulators, and policy makers, and partnership with patient organisations. Such interactions are increasingly taking place, with exemplars including interactions with the All Party Parliamentary Group on Acquired Brain Injury in the UK, the production of the NASEM report in the USA, and interactions with the US Food and Drug Administration. More interactions should be encouraged, and future discussions with regulators should include debates around consent from patients with acute mental incapacity and data sharing. Data sharing is strongly advocated by funding agencies. From January 2023, the US National Institutes of Health will require upload of research data into public repositories, but the EU requires data controllers to safeguard data security and privacy regulation. The tension between open data-sharing and adherence to privacy regulation could be resolved by cross-dataset analyses on federated platforms, with the data remaining at their original safe location. Tools already exist for conventional statistical analyses on federated platforms, however federated machine learning requires further development. Support for further development of federated platforms, and neuroinformatics more generally, should be a priority.

This update to the 2017 Commission presents new insights and challenges across a range of topics around TBI: epidemiology and prevention (section 1); system of care (section 2); clinical management (section 3); characterisation of TBI (section 4); outcome assessment (section 5); prognosis (Section 6); and new directions for acquiring and implementing evidence (section 7). Table 1 summarises key messages from this Commission and proposes recommendations for the way forward to advance research and clinical management of TBI.

PMID:36183712 | PMC:PMC10427240 | DOI:10.1016/S1474-4422(22)00309-X

Neuropsychopharmacology. 2022 Dec;47(13):2332. doi: 10.1038/s41386-022-01466-3.

NO ABSTRACT

PMID:36180785 | PMC:PMC9630453 | DOI:10.1038/s41386-022-01466-3

Biol Psychiatry Cogn Neurosci Neuroimaging. 2024 Feb;9(2):164-175. doi: 10.1016/j.bpsc.2022.08.015. Epub 2022 Sep 21.

ABSTRACT

BACKGROUND: Adult patients with mild traumatic brain injury (mTBI) exhibit distinct phenotypes of emotional and cognitive functioning identified by latent profile analysis of clinical neuropsychological assessments. When discerned early after injury, these latent clinical profiles have been found to improve prediction of long-term outcomes from mTBI. The present study hypothesized that white matter (WM) microstructure is better preserved in an emotionally resilient mTBI phenotype compared with a neuropsychiatrically distressed mTBI phenotype.

METHODS: The present study used diffusion magnetic resonance imaging to investigate and compare WM microstructure in major association, projection, and commissural tracts between the two phenotypes and over time. Diffusion magnetic resonance images from 172 patients with mTBI were analyzed to compute individual diffusion tensor imaging maps at 2 weeks and 6 months after injury.

RESULTS: By comparing the diffusion tensor imaging parameters between the two phenotypes at global, regional, and voxel levels, emotionally resilient patients were shown to have higher axial diffusivity compared with neuropsychiatrically distressed patients early after mTBI. Longitudinal analysis revealed greater compromise of WM microstructure in neuropsychiatrically distressed patients, with greater decrease of global axial diffusivity and more widespread decrease of regional axial diffusivity during the first 6 months after injury compared with emotionally resilient patients.

CONCLUSIONS: These results provide neuroimaging evidence of WM microstructural differences underpinning mTBI phenotypes identified from neuropsychological assessments and show differing longitudinal trajectories of these biological effects. These findings suggest that diffusion magnetic resonance imaging can provide short- and long-term imaging biomarkers of resilience.

PMID:36152948 | PMC:PMC10065831 | DOI:10.1016/j.bpsc.2022.08.015

Brain Commun. 2022 Sep 1;4(5):fcac188. doi: 10.1093/braincomms/fcac188. eCollection 2022.

ABSTRACT

The epidemiology of coma is unknown because case ascertainment with traditional methods is difficult. Here, we used crowdsourcing methodology to estimate the incidence and prevalence of coma in the UK and the USA. We recruited UK and US laypeople (aged ≥18 years) who were nationally representative (i.e. matched for age, gender and ethnicity according to census data) of the UK and the USA, respectively, utilizing a crowdsourcing platform. We provided a description of coma and asked survey participants if they-'right now' or 'within the last year'-had a family member in coma. These participants (UK n = 994, USA n = 977) provided data on 30 387 family members (UK n = 14 124, USA n = 16 263). We found more coma cases in the USA (n = 47) than in the UK (n = 20; P = 0.009). We identified one coma case in the UK (0.007%, 95% confidence interval 0.00-0.04%) on the day of the survey and 19 new coma cases (0.13%, 95% confidence interval 0.08-0.21%) within the preceding year, resulting in an annual incidence of 135/100 000 (95% confidence interval 81-210) and a point prevalence of 7 cases per 100 000 population (95% confidence interval 0.18-39.44) in the UK. We identified five cases in the USA (0.031%, 95% confidence interval 0.01-0.07%) on the day of the survey and 42 new cases (0.26%, 95% confidence interval 0.19-0.35%) within the preceding year, resulting in an annual incidence of 258/100 000 (95% confidence interval 186-349) and a point prevalence of 31 cases per 100 000 population (95% confidence interval 9.98-71.73) in the USA. The five most common causes were stroke, medically induced coma, COVID-19, traumatic brain injury and cardiac arrest. To summarize, for the first time, we report incidence and prevalence estimates for coma across diagnosis types and settings in the UK and the USA using crowdsourcing methods. Coma may be more prevalent in the USA than in the UK, which requires further investigation. These data are urgently needed to expand the public health perspective on coma and disorders of consciousness.

PMID:36132425 | PMC:PMC9486895 | DOI:10.1093/braincomms/fcac188

Semin Neurol. 2022 Jun;42(3):249-258. doi: 10.1055/s-0042-1756298. Epub 2022 Sep 13.

ABSTRACT

Severe brain injury is associated with a period of impaired level of consciousness that can last from days to months and results in chronic impairment. Systematic assessment of level of function in patients with disorders of consciousness (DoC) is critical for diagnosis, prognostication, and evaluation of treatment efficacy. Approximately 40% of patients who are thought to be unconscious based on clinical bedside behavioral assessment demonstrate some signs of consciousness on standardized behavioral assessment. This finding, in addition to a growing body of literature demonstrating the advantages of standardized behavioral assessment of DoC, has led multiple professional societies and clinical guidelines to recommend standardized assessment over routine clinical evaluation of consciousness. Nevertheless, even standardized assessment is susceptible to biases and misdiagnosis, and examiners should consider factors, such as fluctuating arousal and aphasia, that may confound evaluation. We review approaches to behavioral assessment of consciousness, recent clinical guideline recommendations for use of specific measures to evaluate patients with DoC, and strategies for mitigating common biases that may confound the examination.

PMID:36100225 | PMC:PMC11529827 | DOI:10.1055/s-0042-1756298

J Neurotrauma. 2023 Feb;40(3-4):337-348. doi: 10.1089/neu.2022.0141. Epub 2022 Oct 14.

ABSTRACT

The effects of traumatic brain injury (TBI) are difficult to measure in longitudinal cohort studies, because disparate pre-injury characteristics and injury mechanisms produce variable impairment profiles and recovery trajectories. In preparation for the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study, which followed patients with injuries ranging from uncomplicated mild TBI to coma, we designed a multi-dimensional Flexible outcome Assessment Battery (FAB). The FAB relies on a decision-making algorithm that assigns participants to a Comprehensive (CAB) or Abbreviated Assessment Battery (AAB) and guides test selection across all phases of recovery. To assess feasibility of the FAB, we calculated the proportion of participants followed at 2 weeks (2w) and at 3, 6, and 12 months (3m, 6m, 12m) post-injury who completed the FAB and received valid scores. We evaluated utility of the FAB by examining differences in 6m and 12m Glasgow Outcome Scale-Extended (GOSE) scores between participant subgroups derived from the FAB-enabled versus traditional approach to outcome assessment applied at 2w. Among participants followed at 2w (n = 2094), 3m (n = 1871), 6m (n = 1736), and 12m (n = 1607) post-injury, 95-99% received valid completion scores on the FAB, in full or in part, either in person or by telephone. Level of function assessed by the FAB-enabled approach at 2w was associated with 6m and 12m GOSE scores (proportional odds p < 0.001). These findings suggest that the participant classification methodology afforded by the FAB may enable more effective data collection to improve detection of natural history changes and TBI treatment effects.

PMID:36097759 | PMC:PMC9902043 | DOI:10.1089/neu.2022.0141

Rehabil Psychol. 2022 Nov;67(4):535-545. doi: 10.1037/rep0000462. Epub 2022 Aug 18.

ABSTRACT

PURPOSE/OBJECTIVE: Traumatic brain injuries (TBIs) are increasingly common and a major cause of death and long-term disability. Many individuals experience chronic stressors and adverse health outcomes, emphasizing the importance of cultivating resilience, (defined herein as individual, social, and systemic components engaged in response to the stressors that allow individuals to "bounce back," or move forward adaptively after TBI). Patients' perceptions of factors influencing resilience are critical to guide interventions that meet their needs. Here we offer the first metasynthesis of factors influencing resilience after TBI using a Social Ecological model framework. Research Methods/Design: We preregistered our metasynthesis on PROSPERO (CRD42021233975) and followed PRISMA guidelines. We searched 4 electronic databases for qualitative studies from inception up until June 2021. We included qualitative studies detailing perspectives of individuals with a history of moderate-severe TBI. We excluded case studies and systematic reviews. After removal of duplicates, we identified 124 articles for screening. We reviewed 49 articles for full text eligibility and included 38 studies. We extracted study characteristics and data (e.g., author interpretations and relevant quotes) relating to factors influencing resilience.

RESULTS: We synthesized findings using a Social Ecological model framework to guide thematic analysis. Persons with TBI identified barriers and facilitators to resilience at individual (e.g., physical and cognitive challenges, coping behaviors), interpersonal, (e.g., stigma and isolation) and systemic (e.g., access to resources, rehabilitation support) levels.

CONCLUSIONS/IMPLICATIONS: Considering multifaceted factors at individual, interpersonal and systemic levels in clinical, research, and policy-setting contexts is important for cultivating resilience and optimizing recovery after TBI. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

PMID:35980702 | PMC:PMC11231693 | DOI:10.1037/rep0000462

Lancet Neurol. 2022 Sep;21(9):803-813. doi: 10.1016/S1474-4422(22)00256-3.

ABSTRACT

BACKGROUND: The prognostic value of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) as day-of-injury predictors of functional outcome after traumatic brain injury is not well understood. GFAP is a protein found in glial cells and UCH-L1 is found in neurons, and these biomarkers have been cleared to aid in decision making regarding whether brain CT should be performed after traumatic brain injury. We aimed to quantify their prognostic accuracy and investigate whether these biomarkers contribute novel prognostic information to existing clinical models.

METHODS: We enrolled patients from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) observational cohort study. TRACK-TBI includes patients 17 years and older who are evaluated for TBI at 18 US level 1 trauma centres. All patients receive head CT at evaluation, have adequate visual acuity and hearing preinjury, and are fluent in either English or Spanish. In our analysis, we included participants aged 17-90 years who had day-of-injury plasma samples for measurement of GFAP and UCH-L1 and completed 6-month assessments for outcome due to traumatic brain injury with the Glasgow Outcome Scale-Extended (GOSE-TBI). Biomarkers were analysed as continuous variables and in quintiles. This study is registered with ClinicalTrials.gov, NCT02119182.

FINDINGS: We enrolled 2552 patients from Feb 26, 2014, to Aug 8, 2018. Of the 1696 participants with brain injury and data available at baseline and at 6 months who were included in the analysis, 120 (7·1%) died (GOSE-TBI=1), 235 (13·9%) had an unfavourable outcome (ie, GOSE-TBI ≤4), 1135 (66·9%) had incomplete recovery (ie, GOSE-TBI <8), and 561 (33·1%) recovered fully (ie, GOSE-TBI=8). The area under the curve (AUC) of GFAP for predicting death at 6 months in all patients was 0·87 (95% CI 0·83-0·91), for unfavourable outcome was 0·86 (0·83-0·89), and for incomplete recovery was 0·62 (0·59-0·64). The corresponding AUCs for UCH-L1 were 0·89 (95% CI 0·86-0·92) for predicting death, 0·86 (0·84-0·89) for unfavourable outcome, and 0·61 (0·59-0·64) for incomplete recovery at 6 months. AUCs were higher for participants with traumatic brain injury and Glasgow Coma Scale (GCS) score of 3-12 than for those with GCS score of 13-15. Among participants with GCS score of 3-12 (n=353), adding GFAP and UCH-L1 (alone or combined) to each of the three International Mission for Prognosis and Analysis of Clinical Trials in traumatic brain injury models significantly increased their AUCs for predicting death (AUC range 0·90-0·94) and unfavourable outcome (AUC range 0·83-0·89). However, among participants with GCS score of 13-15 (n=1297), adding GFAP and UCH-L1 to the UPFRONT study model modestly increased the AUC for predicting incomplete recovery (AUC range 0·69-0·69, p=0·025).

INTERPRETATION: In addition to their known diagnostic value, day-of-injury GFAP and UCH-L1 plasma concentrations have good to excellent prognostic value for predicting death and unfavourable outcome, but not for predicting incomplete recovery at 6 months. These biomarkers contribute the most prognostic information for participants presenting with a GCS score of 3-12.

FUNDING: US National Institutes of Health, National Institute of Neurologic Disorders and Stroke, US Department of Defense, One Mind, US Army Medical Research and Development Command.

PMID:35963263 | PMC:PMC9462598 | DOI:10.1016/S1474-4422(22)00256-3

J Head Trauma Rehabil. 2023 May-Jun 01;38(3):249-258. doi: 10.1097/HTR.0000000000000806. Epub 2022 Jul 21.

ABSTRACT

OBJECTIVE: To identify early predictors of US high school and college graduation after moderate-to-severe traumatic brain injury (TBI).

SETTING: Inpatient rehabilitation and community.

PARTICIPANTS: TBI Model Systems participants, aged 16 to 24 years, enrolled as high school or college students at time of injury.

DESIGN: Prospective cohort study.

MAIN MEASURES: Successful graduation was defined as having a diploma (high school) or an associate/bachelor's degree (college) at 1-, 2-, or 5-year follow-up. Predictors were sex, race/ethnicity, urbanicity, preinjury substance abuse, primary rehabilitation payer, and functional independence at inpatient rehabilitation discharge.

METHOD: We descriptively characterized differences between those who did and did not graduate high school and college within the first 5 years postinjury and identified early predictors of successful high school and college graduation using 2 binomial logistic regressions.

RESULTS: Of those with known graduation status, 81.2% of high school and 41.8% of college students successfully graduated. Graduates in both groups were more often White than Black and had more functional independence at discharge. Among high school students, preinjury substance abuse was also a risk factor for not graduating, as was identifying as Hispanic or "other" race.

CONCLUSIONS: Sociodemographic factors and disability influence graduation outcomes, requiring structural, institutional, and personal interventions for success.

PMID:35862899 | DOI:10.1097/HTR.0000000000000806

Rehabil Psychol. 2022 Aug;67(3):344-355. doi: 10.1037/rep0000421. Epub 2022 Jul 14.

ABSTRACT

OBJECTIVE: In rehabilitation research and practice, participation is defined as involvement in life situations and most often measured as frequency of engaging in these life situations. This narrow measurement approach overlooks that individuals perceive importance of and satisfaction with participation in activities in various life areas differently. The purpose of this study was to determine differences in meaningful participation (perceived importance and satisfaction) after moderate to severe traumatic brain injury (TBI) across age groups and to identify predictors of participation satisfaction.

METHOD: Secondary data analysis of a TBI Model Systems substudy, including the Participation Assessment with Recombined Tools-Subjective (PART-S) that rates participation importance and satisfaction in 11 life areas that we grouped into three domains (i.e., productivity, social relations, out-and-about). We identified differences across age groups (i.e., 16 to 24 years, 25 to 44 years, 45 to 64 years, and 65 + years) and predictors of participation satisfaction.

RESULTS: Participation satisfaction in and importance of the 11 life areas varied across age groups. In all age groups, participants rated relationships as being of medium or high importance more often than other life areas. Older adults reported the highest participation satisfaction across life areas, despite having the lowest participation frequency. Consistent predictors of participation satisfaction were cognitive functioning and frequency of participation in the domain examined.

CONCLUSION: Participation importance, satisfaction, and frequency are related, yet distinct, dimensions of participation that should all be measured to adequately evaluate meaningful participation. Future research should explore interventions across the lifespan that target modifiable predictors, like functional cognition and access to frequent participation in important life activities. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

PMID:35834205 | DOI:10.1037/rep0000421

Front Aging. 2022 Feb 2;3:773944. doi: 10.3389/fragi.2022.773944. eCollection 2022.

ABSTRACT

Brain health is essential to successful aging, and exercise is essential to brain health. Evidence supports the benefits of regular physical and cognitive exercise in preventing or delaying progressin of mild cognitive impairment and dementia. Despite known benefits, motivation to initiate and adhere to an exercise program can be challenging to older adults. We propose that assessment of motivation in the older adult population be part of individualized physical and cognitive exercise program initial development and ongoing precision health coaching to facilitate initiation of-and adherence to-individualized multi-modal exercise programs and sustained exercise engagement. We suggest one published, physical exercise motivation questionnaire and present a new, psychometrically supported, parallel cognitive exercise questionnaire to do so. Needs for-and implications of-continued exercise motivation research using neurophysiologic and neuropsychologic metrics are discussed.

PMID:35821853 | PMC:PMC9261340 | DOI:10.3389/fragi.2022.773944

Semin Neurol. 2022 Jul 6. doi: 10.1055/a-1893-2875. Online ahead of print.

NO ABSTRACT

PMID:35793706 | DOI:10.1055/a-1893-2875

J Neurotrauma. 2022 Nov;39(21-22):1524-1532. doi: 10.1089/neu.2022.0113. Epub 2022 Jul 25.

ABSTRACT

More than 75% of patients presenting to level I trauma centers in the United States with suspicion of TBI sufficient to require a clinical computed tomography scan report injury-related symptoms 3 months later. There are currently no approved treatments, and few clinical trials have evaluated possible treatments. Efficient trials will require subject inclusion and exclusion criteria that balance cost-effective recruitment with enrolling individuals with a higher chance of benefiting from the interventions. Using data from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study, we examined the relationship of 3-month symptoms to pre-injury, demographic, and acute characteristics as well as 2-week symptoms and blood-based biomarkers to identify and evaluate factors that may be used for sample enrichment for clinical trials. Many of the risk factors for TBI symptoms reported in the literature were supported, but the effect sizes of each were small or moderate (< 0.5). The only factors with large effect sizes when predicting 3-month symptom burden were TBI-related (i.e., post-concussive) and post-traumatic stress symptom levels at 2 weeks (respective effect sizes 1.13 and 1.34). TBI severity was not significantly associated with 3-month symptom burden (p = 0.37). Using simulated data to evaluate the effect of enrichment, we showed that including only people with high symptom burden at 2 weeks would permit trials to reduce the sample size by half, with minimal increase in screening, as compared with enrolling an unenriched sample. Clinical trials aimed at reducing symptoms after TBI can be efficiently conducted by enriching the included sample with people reporting a high early symptom burden.

PMID:35754333 | PMC:PMC9689769 | DOI:10.1089/neu.2022.0113

Neuropsychopharmacology. 2022 Dec;47(13):2300-2308. doi: 10.1038/s41386-022-01359-5. Epub 2022 Jun 18.

ABSTRACT

Several proteins have proven useful as blood-based biomarkers to assist in evaluation and management of traumatic brain injury (TBI). The objective of this study was to determine whether two day-of-injury blood-based biomarkers are predictive of posttraumatic stress disorder (PTSD). We used data from 1143 individuals with mild TBI (mTBI; defined as admission Glasgow Coma Scale [GCS] score 13-15) enrolled in TRACK-TBI, a prospective longitudinal study of level 1 trauma center patients. Plasma glial fibrillary acidic protein (GFAP) and serum high sensitivity C-reactive protein (hsCRP) were measured from blood collected within 24 h of injury. Two hundred and twenty-seven (19.9% of) patients had probable PTSD (PCL-5 score ≥ 33) at 6 months post-injury. GFAP levels were positively associated (Spearman's rho = 0.35, p < 0.001) with duration of posttraumatic amnesia (PTA). There was an inverse association between PTSD and (log)GFAP (adjusted OR = 0.85, 95% CI 0.77-0.95 per log unit increase) levels, but no significant association with (log)hsCRP (adjusted OR = 1.11, 95% CI 0.98-1.25 per log unit increase) levels. Elevated day-of-injury plasma GFAP, a biomarker of glial reactivity, is associated with reduced risk of PTSD after mTBI. This finding merits replication and additional studies to determine a possible neurocognitive basis for this relationship.

PMID:35717463 | PMC:PMC9630517 | DOI:10.1038/s41386-022-01359-5

Neurocrit Care. 2022 Oct;37(2):608-609. doi: 10.1007/s12028-022-01536-w.

NO ABSTRACT

PMID:35715614 | PMC:PMC9519697 | DOI:10.1007/s12028-022-01536-w

Mol Psychiatry. 2022 Sep;27(9):3898-3903. doi: 10.1038/s41380-022-01646-z. Epub 2022 Jun 15.

ABSTRACT

Neuropsychiatric symptoms may persist following acute COVID-19 illness, but the extent to which these symptoms are specific to COVID-19 has not been established. We utilized electronic health records across 6 hospitals in Massachusetts to characterize cohorts of individuals discharged following admission for COVID-19 between March 2020 and May 2021, and compared them to individuals hospitalized for other indications during this period. Natural language processing was applied to narrative clinical notes to identify neuropsychiatric symptom domains up to 150 days following hospitalization, in addition to those reflected in diagnostic codes as measured in prior studies. Among 6619 individuals hospitalized for COVID-19 drawn from a total of 42,961 hospital discharges, the most commonly-documented symptom domains between 31 and 90 days after initial positive test were fatigue (13.4%), mood and anxiety symptoms (11.2%), and impaired cognition (8.0%). In regression models adjusted for sociodemographic features and hospital course, none of these were significantly more common among COVID-19 patients; indeed, mood and anxiety symptoms were less frequent (adjusted OR 0.72 95% CI 0.64-0.92). Between 91 and 150 days after positivity, most commonly-detected symptoms were fatigue (10.9%), mood and anxiety symptoms (8.2%), and sleep disruption (6.8%), with impaired cognition in 5.8%. Frequency was again similar among non-COVID-19 post-hospital patients, with mood and anxiety symptoms less common (aOR 0.63, 95% CI 0.52-0.75). Propensity-score matched analyses yielded similar results. Overall, neuropsychiatric symptoms were common up to 150 days after initial hospitalization, but occurred at generally similar rates among individuals hospitalized for other indications during the same period. Post-acute sequelae of COVID-19 may benefit from standard if less-specific treatments developed for rehabilitation after hospitalization.

PMID:35705635 | PMC:PMC9199464 | DOI:10.1038/s41380-022-01646-z

J Neurotrauma. 2022 Sep;39(17-18):1275-1276. doi: 10.1089/neu.2022.0268.

NO ABSTRACT

PMID:35699082 | PMC:PMC9422788 | DOI:10.1089/neu.2022.0268

J Head Trauma Rehabil. 2022 Nov-Dec 01;37(6):327-337. doi: 10.1097/HTR.0000000000000799. Epub 2022 Jun 9.

ABSTRACT

OBJECTIVE: To describe the self-reported needs of family caregivers of service members and veterans (SMVs) who sustained a traumatic brain injury (TBI) and to identify predictors of the unmet family caregiver needs.

SETTING: Five Department of Veterans Affairs (VA) Polytrauma Rehabilitation Centers (PRCs).

PARTICIPANTS: Family caregivers of SMVs enrolled in the VA PRC TBI Model Systems (TBIMS) national database who were within their first 5 years post-TBI ( n = 427).

DESIGN: Observational study.

MAIN OUTCOME MEASURE: The Family Needs Questionnaire-Revised (FNQ-R) was completed by each SMV's designated caregiver.

ANALYSES: Descriptive analyses were conducted on the FNQ-R responses at the item, domain, and total score levels. Unadjusted univariable and adjusted multivariable regression models were fitted to identify predictors of total unmet needs and unmet family need domains.

RESULTS: FNQ-R item-level and domain-level descriptive results indicated that health information was the most frequently met need domain. In contrast, emotional and instrumental support domains were the least often met. On average, family caregivers reported that 59.2% of the 37 FNQ-R needs were met at the time of the follow-up assessment. Regression models indicated that both the number of SMV-perceived environmental barriers and whether the SMV received mental health treatment within the past year predicted the number of unmet FNQ-R needs. SMV-reported environmental barriers predicted increased unmet needs in all 6 family caregiver domains, and SMV mental health treatment in the past year predicted more unmet family caregiver emotional support, community support, and professional support needs.

CONCLUSIONS: The current findings can be used to inform policy and programming for VA and Department of Defense to proactively address the specific needs of families and caregivers experienced in the first 5 years post-TBI.

PMID:35687889 | DOI:10.1097/HTR.0000000000000799

Am J Phys Med Rehabil. 2023 Feb 1;102(2):137-143. doi: 10.1097/PHM.0000000000002054. Epub 2022 Jun 8.

ABSTRACT

OBJECTIVE: The aim of the study was to predict suicidal ideation 1 yr after moderate to severe traumatic brain injury.

DESIGN: This study used a cross-sectional design with data collected through the prospective, longitudinal Traumatic Brain Injury Model Systems network at hospitalization and 1 yr after injury. Participants who completed the Patient Health Questionnaire-9 suicide item at year 1 follow-up ( N = 4328) were included.

RESULTS: A gradient boosting machine algorithm demonstrated the best performance in predicting suicidal ideation 1 yr after traumatic brain injury. Predictors were Patient Health Questionnaire-9 items (except suicidality), Generalized Anxiety Disorder-7 items, and a measure of heavy drinking. Results of the 10-fold cross-validation gradient boosting machine analysis indicated excellent classification performance with an area under the curve of 0.882. Sensitivity was 0.85 and specificity was 0.77. Accuracy was 0.78 (95% confidence interval, 0.77-0.79). Feature importance analyses revealed that depressed mood and guilt were the most important predictors of suicidal ideation, followed by anhedonia, concentration difficulties, and psychomotor disturbance.

CONCLUSIONS: Overall, depression symptoms were most predictive of suicidal ideation. Despite the limited clinical impact of the present findings, machine learning has potential to improve prediction of suicidal behavior, leveraging electronic health record data, to identify individuals at greatest risk, thereby facilitating intervention and optimization of long-term outcomes after traumatic brain injury.

PMID:35687765 | PMC:PMC9729434 | DOI:10.1097/PHM.0000000000002054

J Neurotrauma. 2022 Oct;39(19-20):1391-1407. doi: 10.1089/neu.2022.0030. Epub 2022 Jun 29.

ABSTRACT

Emerging evidence suggests that repeated blast exposure (RBE) is associated with brain injury in military personnel. United States (U.S.) Special Operations Forces (SOF) personnel experience high rates of blast exposure during training and combat, but the effects of low-level RBE on brain structure and function in SOF have not been comprehensively characterized. Further, the pathophysiological link between RBE-related brain injuries and cognitive, behavioral, and physical symptoms has not been fully elucidated. We present a protocol for an observational pilot study, Long-Term Effects of Repeated Blast Exposure in U.S. SOF Personnel (ReBlast). In this exploratory study, 30 active-duty SOF personnel with RBE will participate in a comprehensive evaluation of: 1) brain network structure and function using Connectome magnetic resonance imaging (MRI) and 7 Tesla MRI; 2) neuroinflammation and tau deposition using positron emission tomography; 3) blood proteomics and metabolomics; 4) behavioral and physical symptoms using self-report measures; and 5) cognition using a battery of conventional and digitized assessments designed to detect subtle deficits in otherwise high-performing individuals. We will identify clinical, neuroimaging, and blood-based phenotypes that are associated with level of RBE, as measured by the Generalized Blast Exposure Value. Candidate biomarkers of RBE-related brain injury will inform the design of a subsequent study that will test a diagnostic assessment battery for detecting RBE-related brain injury. Ultimately, we anticipate that the ReBlast study will facilitate the development of interventions to optimize the brain health, quality of life, and battle readiness of U.S. SOF personnel.

PMID:35620901 | PMC:PMC9529318 | DOI:10.1089/neu.2022.0030

J Neurotrauma. 2022 Oct;39(19-20):1318-1328. doi: 10.1089/neu.2021.0408. Epub 2022 Jul 18.

ABSTRACT

Diffusion tensor imaging (DTI) literature on single-center studies contains conflicting results regarding acute effects of mild traumatic brain injury (mTBI) on white matter (WM) microstructure and the prognostic significance. This larger-scale multi-center DTI study aimed to determine how acute mTBI affects WM microstructure over time and how early WM changes affect long-term outcome. From Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI), a cohort study at 11 United States level 1 trauma centers, a total of 391 patients with acute mTBI ages 17 to 60 years were included and studied at two weeks and six months post-injury. Demographically matched friends or family of the participants were the control group (n = 148). Axial diffusivity (AD), fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) were the measures of WM microstructure. The primary outcome was the Glasgow Outcome Scale Extended (GOSE) score of injury-related functional limitations across broad life domains at six months post-injury. The AD, MD, and RD were higher and FA was lower in mTBI versus friend control (FC) at both two weeks and six months post-injury throughout most major WM tracts of the cerebral hemispheres. In the mTBI group, AD and, to a lesser extent, MD decreased in WM from two weeks to six months post-injury. At two weeks post-injury, global WM AD and MD were both independently associated with six-month incomplete recovery (GOSE <8 vs = 8) even after accounting for demographic, clinical, and other imaging factors. DTI provides reliable imaging biomarkers of dynamic WM microstructural changes after mTBI that have utility for patient selection and treatment response in clinical trials. Continued technological advances in the sensitivity, specificity, and precision of diffusion magnetic resonance imaging hold promise for routine clinical application in mTBI.

PMID:35579949 | PMC:PMC9529303 | DOI:10.1089/neu.2021.0408

J Neurotrauma. 2022 Oct;39(19-20):1417-1428. doi: 10.1089/neu.2022.0095. Epub 2022 Jun 16.

ABSTRACT

This study aimed to empirically evaluate the hierarchical structure of the Coma Recovery Scale-Revised (CRS-R) rating scale categories and their alignment with the Aspen consensus criteria for determining disorders of consciousness (DoC) following a severe brain injury. CRS-R data from 262 patients with DoC following a severe brain injury were analyzed applying the partial credit Rasch Measurement Model. Rasch Analysis produced logit calibrations for each rating scale category. Twenty-eight of the 29 CRS-R rating scale categories were operationalized to the Aspen consensus criteria. We expected the hierarchical order of the calibrations to reflect Aspen consensus criteria. We also examined the association between the CRS-R Rasch person measures (indicative of performance ability) and states of consciousness as determined by the Aspen consensus criteria. Overall, the order of the 29 rating scale category calibrations reflected current literature regarding the continuum of neurobehavioral function: category 6 "Functional Object Use" of the Motor item was hardest for patients to achieve; category 0 "None" of the Oromotor/Verbal item was easiest to achieve. Of the 29 rating scale categories, six were not ordered as expected. Four rating scale categories reflecting the Vegetative State (VS)/Unresponsive Wakefulness Syndrome (UWS) had higher calibrations (reflecting greater neurobehavioral function) than the easiest Minimally Conscious State (MCS) item (category 2 "Fixation" of the Visual item). Two rating scale categories, one reflecting MCS and one not operationalized to the Aspen consensus criteria, had higher calibrations than the easiest eMCS item (category 2 "Functional: Accurate" of the Communication item). CRS-R person measures (indicating amount of neurobehavioral function) and states of consciousness, based on Aspen consensus criteria, showed a strong correlation (r_s = 0.86; p < 0.01). Our study provides empirical evidence for revising the diagnostic criteria for MCS to also include category 2 "Localization to Sound" of the Auditory item and for Emerged from Minimally Conscious State (eMCS) to include category 4 "Consistent Movement to Command" of the Auditory item.

PMID:35570725 | PMC:PMC9529298 | DOI:10.1089/neu.2022.0095

Cortex. 2022 Jul;152:136-152. doi: 10.1016/j.cortex.2022.04.007. Epub 2022 Apr 15.

ABSTRACT

Tools assaying the neural networks that modulate consciousness may facilitate tracking of recovery after acute severe brain injury. The ABCD framework classifies resting-state EEG into categories reflecting levels of thalamocortical network function that correlate with outcome in post-cardiac arrest coma. In this longitudinal cohort study, we applied the ABCD framework to 20 patients with acute severe traumatic brain injury requiring intensive care (12 of whom were also studied at ≥6-months post-injury) and 16 healthy controls. We tested four hypotheses: 1) EEG ABCD classifications are spatially heterogeneous and temporally variable; 2) ABCD classifications improve longitudinally, commensurate with the degree of behavioral recovery; 3) ABCD classifications correlate with behavioral level of consciousness; and 4) the Coma Recovery Scale-Revised arousal facilitation protocol yields improved ABCD classifications. Channel-level EEG power spectra were classified based on spectral peaks within pre-defined frequency bands: 'A' = no peaks above delta (<4 Hz) range (complete thalamocortical disruption); 'B' = theta (4-8 Hz) peak (severe thalamocortical disruption); 'C' = theta and beta (13-24 Hz) peaks (moderate thalamocortical disruption); or 'D' = alpha (8-13 Hz) and beta peaks (normal thalamocortical function). Acutely, 95% of patients demonstrated 'D' signals in at least one channel but exhibited within-session temporal variability and spatial heterogeneity in the proportion of different channel-level ABCD classifications. By contrast, healthy participants and patients at follow-up consistently demonstrated signals corresponding to intact thalamocortical network function. Patients demonstrated longitudinal improvement in ABCD classifications (p < .05) and ABCD classification distinguished patients with and without command-following in the subacute-to-chronic phase of recovery (p < .01). In patients studied acutely, ABCD classifications improved after the Coma Recovery Scale-Revised arousal facilitation protocol (p < .05) but did not correspond with behavioral level of consciousness. These findings support the use of the ABCD framework to characterize channel-level EEG dynamics and track fluctuations in functional thalamocortical network integrity in spatial detail.

PMID:35569326 | PMC:PMC9759728 | DOI:10.1016/j.cortex.2022.04.007

Int J Environ Res Public Health. 2022 May 7;19(9):5717. doi: 10.3390/ijerph19095717.

ABSTRACT

Objectives: To compare characteristics of caregivers of adults with acute traumatic brain injury (TBI) in the U.S. and Latin America (Mexico and Colombia). Design: Secondary data analysis of two cohorts. Cohort 1: English-speaking caregivers of adults with TBI in the U.S. (n = 80). Cohort 2: Spanish-speaking caregivers of adults with TBI in Mexico or Colombia (n = 109). Results: Similarities between the U.S. and Latin American caregiver groups, respectively, were: predominantly women (81.3%, 81.7%, respectively); spouses/domestic partners (45%, 31.2%); and motor vehicle accident (41.5%, 48.6%) followed by fall etiologies (40%, 21.1%). Differences between U.S. and Latin American caregivers were: age (49.5 years, 41.5 years, p < 0.001); employment status ((Χ52 = 59.63, p < 0.001), full-time employment (63.7%, 25.7%), homemaker (2.5%, 31.2%), and retired (17.5%, 1.8%)); violence-related etiology (2.5%, 15.6%); and severity of depressive symptoms (M = 7.9, SD = 5.8; M = 5.8, SD = 5.7; p = 0.014). Conclusions: TBI caregivers in the U.S. were older and employed full-time or retired more often than those in Latin America. Violence-related etiology was nearly five times more common in Latin America, raising concerns for potential implications of post-traumatic stress and family adjustment after injury. Although both groups likely could use mental health support, this was particularly true of the U.S. cohort, maybe due to differential demographics, mechanisms of injury, or family and community support.

PMID:35565112 | PMC:PMC9102876 | DOI:10.3390/ijerph19095717

Neurocrit Care. 2022 Aug;37(1):326-350. doi: 10.1007/s12028-022-01505-3. Epub 2022 May 10.

ABSTRACT

This proceedings article presents actionable research targets on the basis of the presentations and discussions at the 2nd Curing Coma National Institutes of Health (NIH) symposium held from May 3 to May 5, 2021. Here, we summarize the background, research priorities, panel discussions, and deliverables discussed during the symposium across six major domains related to disorders of consciousness. The six domains include (1) Biology of Coma, (2) Coma Database, (3) Neuroprognostication, (4) Care of Comatose Patients, (5) Early Clinical Trials, and (6) Long-term Recovery. Following the 1st Curing Coma NIH virtual symposium held on September 9 to September 10, 2020, six workgroups, each consisting of field experts in respective domains, were formed and tasked with identifying gaps and developing key priorities and deliverables to advance the mission of the Curing Coma Campaign. The highly interactive and inspiring presentations and panel discussions during the 3-day virtual NIH symposium identified several action items for the Curing Coma Campaign mission, which we summarize in this article.

PMID:35534661 | PMC:PMC9283342 | DOI:10.1007/s12028-022-01505-3

J Neurotrauma. 2022 Sep;39(17-18):1222-1230. doi: 10.1089/neu.2022.0076. Epub 2022 Jun 20.

ABSTRACT

Patients with disorders of consciousness (DoC) after traumatic brain injury (TBI) recover to varying degrees of functional dependency. Dependency is difficult to measure but critical for interpreting clinical trial outcomes and prognostic counseling. In participants with DoC (i.e., not following commands) enrolled in the TBI Model Systems National Database (TBIMS NDB), we used the Functional Independence Measure (FIM^®) as the reference to evaluate how accurately the Glasgow Outcome Scale-Extended (GOSE) and Disability Rating Scale (DRS) assess dependency. Using the established FIM-dependency cut-point of <80, we measured the classification performance of literature-derived GOSE and DRS cut-points at 1-year post-injury. We compared the area under the receiver operating characteristic curve (AUROC) between the DRS_Depend, a DRS-derived marker of dependency, and the data-derived optimal GOSE and DRS cut-points. Of 18,486 TBIMS participants, 1483 met inclusion criteria (mean [standard deviation (SD)] age = 38 [18] years; 76% male). The sensitivity of GOSE cut-points of ≤3 and ≤4 (Lower Severe and Upper Severe Disability, respectively) for identifying FIM-dependency were 97% and 98%, but specificities were 73% and 51%, respectively. The sensitivity of the DRS cut-point of ≥12 (Severe Disability) for identifying FIM-dependency was 60%, but specificity was 100%. The DRS_Depend had a sensitivity of 83% and a specificity of 94% for classifying FIM-dependency, with a greater AUROC than the data-derived optimal GOSE (≤3, p = 0.01) and DRS (≥10, p = 0.008) cut-points. Commonly used GOSE and DRS cut-points have limited specificity or sensitivity for identifying functional dependency. The DRS_Depend identifies FIM-dependency more accurately than the GOSE and DRS cut-points, but requires further validation.

PMID:35531895 | PMC:PMC9422782 | DOI:10.1089/neu.2022.0076

Radiology. 2022 Aug;304(2):385-394. doi: 10.1148/radiol.212181. Epub 2022 Apr 26.

ABSTRACT

Background After severe traumatic brain injury (sTBI), physicians use long-term prognostication to guide acute clinical care yet struggle to predict outcomes in comatose patients. Purpose To develop and evaluate a prognostic model combining deep learning of head CT scans and clinical information to predict long-term outcomes after sTBI. Materials and Methods This was a retrospective analysis of two prospectively collected databases. The model-building set included 537 patients (mean age, 40 years ± 17 [SD]; 422 men) from one institution from November 2002 to December 2018. Transfer learning and curriculum learning were applied to a convolutional neural network using admission head CT to predict mortality and unfavorable outcomes (Glasgow Outcomes Scale scores 1-3) at 6 months. This was combined with clinical input for a holistic fusion model. The models were evaluated using an independent internal test set and an external cohort of 220 patients with sTBI (mean age, 39 years ± 17; 166 men) from 18 institutions in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study from February 2014 to April 2018. The models were compared with the International Mission on Prognosis and Analysis of Clinical Trials in TBI (IMPACT) model and the predictions of three neurosurgeons. Area under the receiver operating characteristic curve (AUC) was used as the main model performance metric. Results The fusion model had higher AUCs than did the IMPACT model in the prediction of mortality (AUC, 0.92 [95% CI: 0.86, 0.97] vs 0.80 [95% CI: 0.71, 0.88]; P < .001) and unfavorable outcomes (AUC, 0.88 [95% CI: 0.82, 0.94] vs 0.82 [95% CI: 0.75, 0.90]; P = .04) on the internal data set. For external TRACK-TBI testing, there was no evidence of a significant difference in the performance of any models compared with the IMPACT model (AUC, 0.83; 95% CI: 0.77, 0.90) in the prediction of mortality. The Imaging model (AUC, 0.73; 95% CI: 0.66-0.81; P = .02) and the fusion model (AUC, 0.68; 95% CI: 0.60, 0.76; P = .02) underperformed as compared with the IMPACT model (AUC, 0.83; 95% CI: 0.77, 0.89) in the prediction of unfavorable outcomes. The fusion model outperformed the predictions of the neurosurgeons. Conclusion A deep learning model of head CT and clinical information can be used to predict 6-month outcomes after severe traumatic brain injury. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Haller in this issue.

PMID:35471108 | PMC:PMC9340242 | DOI:10.1148/radiol.212181

Brain Sci. 2022 Mar 24;12(4):429. doi: 10.3390/brainsci12040429.

ABSTRACT

Transcranial direct-current stimulation (tDCS) over the prefrontal cortex can improve signs of consciousness in patients in a minimally conscious state. Transcranial pulsed-current stimulation (tPCS) over the mastoids can modulate brain activity and connectivity in healthy controls. This study investigated the feasibility of tPCS as a therapeutic tool in patients with disorders of consciousness (DoC) and compared its neurophysiological and behavioral effects with prefrontal tDCS. This pilot study was a randomized, double-blind sham-controlled clinical trial with three sessions: bi-mastoid tPCS, prefrontal tDCS, and sham. Electroencephalography (EEG) and behavioral assessments were collected before and after each stimulation session. Post minus pre differences were compared using Kruskal-Wallis and Wilcoxon signed-rank tests. Twelve patients with DoC were included in the study (eight females, four traumatic brain injury, 50.3 ± 14 y.o., 8.8 ± 10.5 months post-injury). We did not observe any side-effects following tPCS, nor tDCS, and confirmed their feasibility and safety. We did not find a significant effect of the stimulation on EEG nor behavioral outcomes for tPCS. However, consistent with prior findings, our exploratory analyses suggest that tDCS induces behavioral improvements and an increase in theta frontal functional connectivity.

PMID:35447961 | PMC:PMC9031379 | DOI:10.3390/brainsci12040429

Neurohospitalist. 2022 Apr;12(2):280-284. doi: 10.1177/19418744211051459. Epub 2022 Jan 13.

ABSTRACT

Neuroprognostication following diffuse axonal injury (DAI) has historically relied on neuroimaging techniques with lower spatial resolution and contrast than techniques currently available in clinical practice. Since the initial studies of DAI classification and prognosis in the 1980s and 1990s, advances in neuroimaging have improved detection of brainstem microbleeds, a hallmark feature of Grade 3 DAI that has traditionally been associated with poor neurologic outcome. Here, we report clinical and radiologic data from two patients with severe traumatic brain injury and grade 3 DAI who recovered functional independence and returned to work within 4 months of injury. Importantly, both patients were scanned using 3 Tesla MRI protocols that included susceptibility-weighted imaging (SWI), a technique that provides enhanced sensitivity for detecting brainstem microbleeds. These observations highlight the importance of developing approaches to DAI classification and prognosis that better align with contemporary neuroimaging capabilities.

PMID:35419140 | PMC:PMC8995586 | DOI:10.1177/19418744211051459

Arch Phys Med Rehabil. 2022 Sep;103(9):1870-1873. doi: 10.1016/j.apmr.2022.03.010. Epub 2022 Apr 6.

ABSTRACT

OBJECTIVE: To determine whether consistent command-following (CCF) should be added to the diagnostic criteria for emergence from the minimally conscious state (eMCS).

DESIGN: Retrospective cohort study.

SETTING: Inpatient rehabilitation hospital.

PARTICIPANTS: Patients (N=214) with acquired brain injury resulting in disorders of consciousness (DoC) admitted to a specialized rehabilitation program.

MAIN OUTCOME MEASURES: Difference between time to recovery of CCF and time to recovery of functional object use (FOU) or functional communication (FC), the 2 existing criteria for eMCS as measured by the Coma Recovery Scale-Revised (CRS-R).

RESULTS: Of 214 patients (median age, 53 years [interquartile range {IQR}, 34-66 years], male: 134 [62.6%], traumatic etiology: 115 [53.7%], admission CRS-R total score: 10 [IQR, 7-13]) admitted to rehabilitation without CCF, FOU, or FC, 162 (75.7%) recovered CCF and FOU or FC during the 8-week observation period. On average, recovery of CCF, FOU, and FC was observed within 1 day of one another, approximately 46 days (IQR, 38.25-58 days) post injury. One hundred and sixteen patients (71.6%) recovered FOU or FC prior to or at the same time as CCF.

CONCLUSIONS: In patients recovering from DoC, CCF reemerges around the same time as FOU and FC. This finding may reflect the shared dependency of these behaviors on cognitive processes (eg, language comprehension, attention, motor control) that are essential for effective interpersonal interaction and social participation. Our results support the addition of CCF to the existing diagnostic criteria for eMCS, but further validation in an independent sample should be conducted.

PMID:35398046 | PMC:PMC9452458 | DOI:10.1016/j.apmr.2022.03.010

Nat Rev Neurol. 2022 Jul;18(7):419-427. doi: 10.1038/s41582-022-00644-7. Epub 2022 Mar 29.

ABSTRACT

Neuroprognostication, or the prediction of recovery from disorders of consciousness caused by severe brain injury, is as critical as it is complex. With profound implications for mortality and quality of life, neuroprognostication draws upon an intricate set of biomedical, probabilistic, psychosocial and ethical factors. However, the clinical approach to neuroprognostication is often unsystematic, and consequently, variable among clinicians and prone to error. Here, we offer a stepwise conceptual framework for reasoning through neuroprognostic determinations - including an evaluation of neurological function, estimation of a recovery trajectory, definition of goals of care and consideration of patient values - culminating in a clinically actionable formula for weighing the risks and benefits of life-sustaining treatment. Although the complexity of neuroprognostication might never be fully reducible to arithmetic, this systematic approach provides structure and guidance to supplement clinical judgement and direct future investigation.

PMID:35352033 | PMC:PMC9326772 | DOI:10.1038/s41582-022-00644-7

J Neurotrauma. 2022 Jun;39(11-12):870-878. doi: 10.1089/neu.2021.0421.

ABSTRACT

The Glasgow Outcome Scale-Extended (GOSE) is a functional outcome measure intended to place individuals with traumatic brain injury (TBI) into one of eight broad levels of injury-related disability. This simplicity is not always optimal, particularly when more granular assessment of individuals' injury recovery is desired. The GOSE, however, is customarily assessed using a multi-question interview that contains richer information than is reflected in the GOSE score. Using data from the multi-center Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study (N = 1544), we used item response theory (IRT) to evaluate whether rescoring the GOSE using IRT, which posits that a continuous latent variable (disability) underlies responses, can yield a more precise index of injury-related functional limitations. We fit IRT models to GOSE interview responses collected at three months post-injury. Each participant's level of functional limitation was estimated from the model (GOSE-IRT) and comparisons were made between IRT-based and standard (GOSE-Ordinal) scores. The IRT scoring resulted in 141 possible scores (vs. 7 GOSE-Ordinal scores in this sample of individuals with GOSE scores ranging between 2 and 8). Moreover, GOSE-IRT scores were significantly more strongly associated with measures of TBI-related symptoms, psychological symptoms, and quality of life. Our findings demonstrate that rescoring the GOSE interview using IRT yields more granular, meaningful measurement of injury-related functional limitations, while adding no additional respondent or examiner burden. This technique may have utility for many applications, such as clinical trials aiming to detect small treatment effects, and small-scale studies that need to maximize statistical efficiency.

PMID:35317604 | PMC:PMC9225413 | DOI:10.1089/neu.2021.0421

EBioMedicine. 2022 Mar;77:103933. doi: 10.1016/j.ebiom.2022.103933. Epub 2022 Mar 14.

ABSTRACT

BACKGROUND: Factors such as age, pre-injury health, and injury severity, account for less than 35% of outcome variability in traumatic brain injury (TBI). While some residual outcome variability may be attributable to genetic factors, published candidate gene association studies have often been underpowered and subject to publication bias.

METHODS: We performed the first genome- and transcriptome-wide association studies (GWAS, TWAS) of genetic effects on outcome in TBI. The study population consisted of 5268 patients from prospective European and US studies, who attended hospital within 24 h of TBI, and satisfied local protocols for computed tomography.

FINDINGS: The estimated heritability of TBI outcome was 0·26. GWAS revealed no genetic variants with genome-wide significance (p < 5 × 10^-8), but identified 83 variants in 13 independent loci which met a lower pre-specified sub-genomic statistical threshold (p < 10^-5). Similarly, none of the genes tested in TWAS met tissue-wide significance. An exploratory analysis of 75 published candidate variants associated with 28 genes revealed one replicable variant (rs1800450 in the MBL2 gene) which retained significance after correction for multiple comparison (p = 5·24 × 10^-4).

INTERPRETATION: While multiple novel loci reached less stringent thresholds, none achieved genome-wide significance. The overall heritability estimate, however, is consistent with the hypothesis that common genetic variation substantially contributes to inter-individual variability in TBI outcome. The meta-analytic approach to the GWAS and the availability of summary data allows for a continuous extension with additional cohorts as data becomes available.

FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

PMID:35301180 | PMC:PMC8927841 | DOI:10.1016/j.ebiom.2022.103933

Neurology. 2022 Apr 26;98(17):701-702. doi: 10.1212/WNL.0000000000200574. Epub 2022 Mar 11.

NO ABSTRACT

PMID:35277443 | DOI:10.1212/WNL.0000000000200574

Brain Sci. 2022 Feb 2;12(2):211. doi: 10.3390/brainsci12020211.

ABSTRACT

As the clinical trial landscape for patients with disorders of consciousness (DoC) expands, consideration of associated ethical challenges and opportunities is of ever-increasing importance. Responsible conduct of research in the vulnerable population of persons with DoC, including those with coma, vegetative state/unresponsive wakefulness syndrome (VS/UWS), minimally conscious state (MCS), covert cortical processing (CCP), and cognitive motor dissociation (CMD), demands proactive deliberation of unique ethical issues that may arise and the adoption of robust protections to safeguard patients, surrogates, and other key stakeholders. Here we identify and critically evaluate four central categories of ethical considerations in clinical trials involving participants with DoC: (1) autonomy, respect for persons and informed consent of individuals with liminal consciousness; (2) balancing unknown benefits and risks, especially considering the epistemological gap between behavior and consciousness that complicates ordinary ascription of subjective states; (3) disclosure to surrogates and clinical teams of investigational results pertaining to consciousness; and (4) justice considerations, including equitable access to clinical trial enrollment across communities and geographies. We outline guiding principles and research opportunities for clinicians, neuroethicists, and researchers engaged in DoC clinical trials to advance ethical study design and deployment in this complex yet crucial area of investigation.

PMID:35203974 | PMC:PMC8870384 | DOI:10.3390/brainsci12020211

Arch Phys Med Rehabil. 2022 Nov;103(11):2164-2173. doi: 10.1016/j.apmr.2022.01.159. Epub 2022 Feb 22.

ABSTRACT

OBJECTIVE: To identify correlates of life satisfaction at 10 years after moderate to severe traumatic brain injury (TBI) using an extreme phenotyping approach.

DESIGN: Effect sizes were calculated in this observational cohort study to estimate relationships of 10-year postinjury extremely high, extremely low, and moderate life satisfaction with (1) pre-injury demographics, injury-related factors, and functional characteristics at inpatient rehabilitation admission and discharge; and (2) postinjury demographics and clinical and functional measures at 10 years postinjury.

SETTING: Multicenter longitudinal database study.

PARTICIPANTS: People identified from the National Institute on Disability, Independent Living, and Rehabilitation Research TBI Database with life satisfaction data at 10 years post TBI (N=4800).

INTERVENTIONS: Not applicable.

MAIN OUTCOME MEASURE: Satisfaction With Life Scale.

RESULTS: Although few pre-injury factors or clinical and functional factors shortly after injury were associated with 10-year life satisfaction groups, the following 10-year postinjury factors were associated with extremely high vs extremely low life satisfaction group membership: greater independent functioning, less disability, more frequent community participation, being employed, and having fewer depressive and anxiety symptoms. Those with extremely high life satisfaction were distinctly different from those with moderate and extremely low satisfaction. Extremely high life satisfaction was underrepresented among non-Hispanic Black persons relative to non-Hispanic White persons. Relationships between life satisfaction and independent functioning, disability, and participation were attenuated among non-Hispanic Black persons.

CONCLUSIONS: Extreme phenotyping analysis complements existing knowledge regarding life satisfaction after moderate to severe TBI and may inform acute and postacute clinical service delivery by comparing extremely high and extremely low life satisfaction subgroups. Findings suggest little association among personal, clinical, and functional characteristics early post TBI and life satisfaction 10 years later. Contemporaneous correlates of extremely high life satisfaction exist at 10 years post TBI, although the positive relationship of these variables to life satisfaction may be attenuated for non-Hispanic Black persons.

PMID:35202582 | PMC:PMC9484051 | DOI:10.1016/j.apmr.2022.01.159

Resuscitation. 2022 Apr;173:103-111. doi: 10.1016/j.resuscitation.2022.01.033. Epub 2022 Feb 8.

ABSTRACT

BACKGROUND: Studies of neurologic outcomes have found conflicting results regarding differences between patients with substance-related cardiac arrests (SRCA) and non-SRCA. We investigate the effects of SRCA on severe cerebral edema development, a neuroimaging intermediate endpoint for neurologic injury.

METHODS: 327 out-of-hospital comatose cardiac arrest patients were retrospectively analyzed. Demographics and baseline clinical characteristics were examined. SRCA categorization was based on admission toxicology screens. Severe cerebral edema classification was based on radiology reports. Poor clinical outcomes were defined as discharge Cerebral Performance Category scores > 3.

RESULTS: SRCA patients (N = 86) were younger (P < 0.001), and more likely to have non-shockable rhythms (P < 0.001), be unwitnessed (P < 0.001), lower Glasgow Coma Scale scores (P < 0.001), absent brainstem reflexes (P < 0.05) and develop severe cerebral edema (P < 0.001) than non-SRCA patients (N = 241). Multivariable analyses found younger age (P < 0.001), female sex (P = 0.008), non-shockable rhythm (P = 0.01) and SRCA (P = 0.05) to be predictors of severe cerebral edema development. Older age (P < 0.001), non-shockable rhythm (P = 0.02), severe cerebral edema (P < 0.001), and absent pupillary light reflexes (P = 0.004) were predictors of poor outcomes. SRCA patients had higher proportion of brain deaths (P < 0.001) compared to non-SRCA patients.

CONCLUSIONS: SRCA results in higher rates of severe cerebral edema development and brain death. The absence of statistically significant differences in discharge outcomes or survival between SRCA and non-SRCA patients may be related to the higher rate of withdrawal of life-sustaining treatment (WLST) in the non-SRCA group. Future neuroprognostic studies may opt to include neuroimaging markers as intermediate measures of neurologic injury which are not influenced by WLST decisions.

PMID:35149137 | PMC:PMC9282938 | DOI:10.1016/j.resuscitation.2022.01.033

Brain Inj. 2022 Feb 23;36(3):415-423. doi: 10.1080/02699052.2022.2034190. Epub 2022 Feb 10.

ABSTRACT

OBJECTIVES: To evaluate associations between traumatic brain injury (TBI) and presence of health conditions, and to compare associations of health and cognition between TBI cases and controls.

METHODS: This matched case-control study used data from the TBI Model Systems National Database (TBI cases) and Midlife in the United States II and Refresher studies (controls). 248 TBI cases were age-, sex-, race-, and education-matched without replacement to three controls. Cases and controls were compared on prevalence of 18 self-reported conditions, self-rated health, composite scores from the Brief Test of Adult Cognition by Telephone.

RESULTS: The following conditions were significantly more prevalent among TBI cases versus controls: anxiety/depression (OR = 3.12, 95% CI: 2.20, 4.43, p < .001), chronic sleeping problems (OR = 2.76, 95% CI: 1.86, 4.10, p < .001), headache/migraine (OR = 2.61, 95% CI: 1.50, 4.54, p = .0007), and stroke (OR = 6.42, 95% CI: 2.93, 14.10, p < .001). The relationship between self-rated health and cognition significantly varied by TBI (p_interaction = 0.002).

CONCLUSION: Individuals with TBI have greater odds of selected neurobehavioral conditions compared to their demographically similar uninjured peers. Among persons with TBI there was a stronger association between poorer self-rated health and cognition than controls. TBI is increasingly conceptualized as a chronic disease; current findings suggest post-TBI health management requires cognitive supports.

PMID:35143349 | PMC:PMC9205640 | DOI:10.1080/02699052.2022.2034190

Neurocrit Care. 2022 Aug;37(1):47-59. doi: 10.1007/s12028-021-01425-8. Epub 2022 Feb 9.

ABSTRACT

BACKGROUND: Although coma is commonly encountered in critical care, worldwide variability exists in diagnosis and management practices. We aimed to assess variability in coma definitions, etiologies, treatment strategies, and attitudes toward prognosis.

METHODS: As part of the Neurocritical Care Society Curing Coma Campaign, between September 2020 and January 2021, we conducted an anonymous, international, cross-sectional global survey of health care professionals caring for patients with coma and disorders of consciousness in the acute, subacute, or chronic setting. Survey responses were solicited by sequential emails distributed by international neuroscience societies and social media. Fleiss κ values were calculated to assess agreement among respondents.

RESULTS: The survey was completed by 258 health care professionals from 41 countries. Respondents predominantly were physicians (n = 213, 83%), were from the United States (n = 141, 55%), and represented academic centers (n = 231, 90%). Among eight predefined items, respondents identified the following cardinal features, in various combinations, that must be present to define coma: absence of wakefulness (81%, κ = 0.764); Glasgow Coma Score (GCS) ≤ 8 (64%, κ = 0.588); failure to respond purposefully to visual, verbal, or tactile stimuli (60%, κ = 0.552); and inability to follow commands (58%, κ = 0.529). Reported etiologies of coma encountered included medically induced coma (24%), traumatic brain injury (24%), intracerebral hemorrhage (21%), and cardiac arrest/hypoxic-ischemic encephalopathy (11%). The most common clinical assessment tools used for coma included the GCS (94%) and neurological examination (78%). Sixty-six percent of respondents routinely performed sedation interruption, in the absence of contraindications, for clinical coma assessments in the intensive care unit. Advanced neurological assessment techniques in comatose patients included quantitative electroencephalography (EEG)/connectivity analysis (16%), functional magnetic resonance imaging (7%), single-photon emission computerized tomography (6%), positron emission tomography (4%), invasive EEG (4%), and cerebral microdialysis (4%). The most commonly used neurostimulants included amantadine (51%), modafinil (37%), and methylphenidate (28%). The leading determinants for prognostication included etiology of coma, neurological examination findings, and neuroimaging. Fewer than 20% of respondents reported routine follow-up of coma survivors after hospital discharge; however, 86% indicated interest in future research initiatives that include postdischarge outcomes at six (85%) and 12 months (65%).

CONCLUSIONS: There is wide heterogeneity among health care professionals regarding the clinical definition of coma and limited routine use of advanced coma assessment techniques in acute care settings. Coma management practices vary across sites, and mechanisms for coordinated and sustained follow-up after acute treatment are inconsistent. There is an urgent need for the development of evidence-based guidelines and a collaborative, coordinated approach to advance both the science and the practice of coma management globally.

PMID:35141860 | PMC:PMC9283177 | DOI:10.1007/s12028-021-01425-8

JAMA Netw Open. 2022 Jan 4;5(1):e2145310. doi: 10.1001/jamanetworkopen.2021.45310.

ABSTRACT

IMPORTANCE: Insomnia is common after traumatic brain injury (TBI) and contributes to morbidity and long-term sequelae.

OBJECTIVE: To identify unique trajectories of insomnia in the 12 months after TBI.

DESIGN, SETTING, AND PARTICIPANTS: In this prospective cohort study, latent class mixed models (LCMMs) were used to model insomnia trajectories over time and to classify participants into distinct profile groups. Data from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study, a longitudinal, multisite, observational study, were uploaded to the Federal Interagency Traumatic Brain Injury Repository (FITBIR) database. Participants were enrolled at 1 of 18 participating level I trauma centers and enrolled within 24 hours of TBI injury. Additional data were obtained directly from the TRACK-TBI investigators that will be uploaded to FITBIR in the future. Data were collected from February 26, 2014, to August 8, 2018, and analyzed from July 1, 2020, to November 15, 2021.

EXPOSURES: Traumatic brain injury.

MAIN OUTCOMES AND MEASURES: Insomnia Severity Index assessed serially at 2 weeks and 3, 6, and 12 months thereafter.

RESULTS: The final sample included 2022 participants (1377 [68.1%] men; mean [SD] age, 40.1 [17.2] years) from the FITBIR database and the TRACK-TBI study. The data were best fit by a 5-class LCMM. Of these participants, 1245 (61.6%) reported persistent mild insomnia symptoms (class 1); 627 (31.0%) initially reported mild insomnia symptoms that resolved over time (class 2); 91 (4.5%) reported persistent severe insomnia symptoms (class 3); 44 (2.2%) initially reported severe insomnia symptoms that resolved by 12 months (class 4); and 15 (0.7%) initially reported no insomnia symptoms but had severe symptoms by 12 months (class 5). In a multinomial logistic regression model, several factors significantly associated with insomnia trajectory class membership were identified, including female sex (odds ratio [OR], 1.65 [95% CI, 1.02-2.66]), Black race (OR, 2.36 [95% CI, 1.39-4.01]), history of psychiatric illness (OR, 2.21 [95% CI, 1.35-3.60]), and findings consistent with intracranial injury on computed tomography (OR, 0.36 [95% CI, 0.20-0.65]) when comparing class 3 with class 1.

CONCLUSIONS AND RELEVANCE: These results suggest important heterogeneity in the course of insomnia after TBI in adults. More work is needed to identify outcomes associated with these insomnia trajectory class subgroups and to identify optimal subgroup-specific treatment approaches.

PMID:35080600 | PMC:PMC8792888 | DOI:10.1001/jamanetworkopen.2021.45310

J Neurotrauma. 2022 Mar;39(5-6):358-370. doi: 10.1089/neu.2021.0348. Epub 2022 Feb 9.

ABSTRACT

Symptom endorsement after traumatic brain injury (TBI) is common acutely post-injury and is associated with other adverse outcomes. Prevalence of persistent symptoms has been debated, especially in mild TBI (mTBI). A cohort of participants ≥17 years with TBI (n = 2039), 257 orthopedic trauma controls (OTCs), and 300 friend controls (FCs) were enrolled in the TRACK-TBI study and evaluated at 2 weeks and 3, 6, and 12 months post-injury using the Rivermead Post-Concussion Symptoms Questionnaire (RPQ). TBI participants had significantly higher symptom burden than OTCs or FCs at all times, with average scores more than double. TBI cases showed significant decreases in RPQ score between each evaluation (p < 0.001), decreasing ∼1.7 points per month between 2 weeks and 3 months and 0.2 points per month after that. More than 50% of the TBI sample, including >50% of each of the mild and moderate/severe TBI subsamples, continued to endorse three or more symptoms as worse than pre-injury through 12 months post-injury. A majority of TBI participants who endorsed a symptom at 3 months or later did so at the next evaluation as well. Contrary to reviews that report symptom resolution by 3 months post-injury among those with mTBI, this study of participants treated at level 1 trauma centers and having a computed tomography ordered found that persistent symptoms are common to at least a year after TBI. Additionally, although symptom endorsement was not specific to TBI given that they were also reported by OTC and FC participants, TBI participants endorsed over twice the symptom burden compared with the other groups.

PMID:35078327 | PMC:PMC8892966 | DOI:10.1089/neu.2021.0348

Lancet Neurol. 2022 Feb;21(2):153-162. doi: 10.1016/S1474-4422(21)00374-4.

ABSTRACT

BACKGROUND: Frailty is known to be associated with poorer outcomes in individuals admitted to hospital for medical conditions requiring intensive care. However, little evidence is available for the effect of frailty on patients' outcomes after traumatic brain injury. Many frailty indices have been validated for clinical practice and show good performance to predict clinical outcomes. However, each is specific to a particular clinical context. We aimed to develop a frailty index to predict 6-month outcomes in patients after a traumatic brain injury.

METHODS: A cumulative deficit approach was used to create a novel frailty index based on 30 items dealing with disease states, current medications, and laboratory values derived from data available from CENTER-TBI, a prospective, longitudinal observational study of patients with traumatic brain injury presenting within 24 h of injury and admitted to a ward or an intensive care unit at 65 centres in Europe between Dec 19, 2014, and Dec 17, 2017. From the individual cumulative CENTER-TBI frailty index (range 0-30), we obtained a standardised value (range 0-1), with high scores indicating higher levels of frailty. The effect of frailty on 6-month outcome evaluated with the extended Glasgow Outcome Scale (GOSE) was assessed through a proportional odds logistic model adjusted for known outcome predictors. An unfavourable outcome was defined as death or severe disability (GOSE score ≤4). External validation was performed on data from TRACK-TBI, a prospective observational study co-designed with CENTER-TBI, which enrolled patients with traumatic brain injury at 18 level I trauma centres in the USA from Feb 26, 2014, to July 27, 2018. CENTER-TBI is registered with ClinicalTrials.gov, NCT02210221; TRACK-TBI is registered at ClinicalTrials.gov, NCT02119182.

FINDINGS: 2993 participants (median age was 51 years [IQR 30-67], 2058 [69%] were men) were included in this analysis. The overall median CENTER-TBI frailty index score was 0·07 (IQR 0·03-0·15), with a median score of 0·17 (0·08-0·27) in older adults (aged ≥65 years). The CENTER-TBI frailty index score was significantly associated with the probability of an increasingly unfavourable outcome (cumulative odds ratio [OR] 1·03, 95% CI 1·02-1·04; p<0·0001), and the association was stronger for participants admitted to hospital wards (1·04, 1·03-1·06, p<0·0001) compared with those admitted to the intensive care unit (1·02, 1·01-1·03 p<0·0001). External validation of the CENTER-TBI frailty index in data from the TRACK-TBI (n=1667) cohort supported the robustness and reliability of these findings. The overall median TRACK-TBI frailty index score was 0·03 (IQR 0-0·10), with the frailty index score significantly associated with the risk of an increasingly unfavourable outcome in patients admitted to hospital wards (cumulative OR 1·05, 95% CI 1·03-1·08; p<0·0001), but not in those admitted to the intensive care unit (1·01, 0·99-1·03; p=0·43).

INTERPRETATION: We developed and externally validated a frailty index specific to traumatic brain injury. Risk of unfavourable outcome was significantly increased in participants with a higher CENTER-TBI frailty index score, regardless of age. Frailty identification could help to individualise rehabilitation approaches aimed at mitigating effects of frailty in patients with traumatic brain injury.

FUNDING: European Union, Hannelore Kohl Stiftung, OneMind, Integra LifeSciences Corporation, NeuroTrauma Sciences, NIH-NINDS-TRACK-TBI, US Department of Defense.

PMID:35065038 | DOI:10.1016/S1474-4422(21)00374-4

JAMA Netw Open. 2021 Dec 1;4(12):e2140191. doi: 10.1001/jamanetworkopen.2021.40191.

ABSTRACT

IMPORTANCE: Posttraumatic epilepsy (PTE) is a recognized sequela of traumatic brain injury (TBI), but the long-term outcomes associated with PTE independent of injury severity are not precisely known.

OBJECTIVE: To determine the incidence, risk factors, and association with functional outcomes and self-reported somatic, cognitive, and psychological concerns of self-reported PTE in a large, prospectively collected TBI cohort.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter, prospective cohort study was conducted as part of the Transforming Research and Clinical Knowledge in Traumatic Brain Injury study and identified patients presenting with TBI to 1 of 18 participating level 1 US trauma centers from February 2014 to July 2018. Patients with TBI, extracranial orthopedic injuries (orthopedic controls), and individuals without reported injuries (eg, friends and family of participants; hereafter friend controls) were prospectively followed for 12 months. Data were analyzed from January 2020 to April 2021.

EXPOSURE: Demographic, imaging, and clinical information was collected according to TBI Common Data Elements. Incidence of self-reported PTE was assessed using the National Institute of Neurological Disorders and Stroke Epilepsy Screening Questionnaire (NINDS-ESQ).

MAIN OUTCOMES AND MEASURES: Primary outcomes included Glasgow Outcome Scale Extended, Rivermead Cognitive Metric (RCM; derived from the Rivermead Post Concussion Symptoms Questionnaire), and the Brief Symptom Inventory-18 (BSI).

RESULTS: Of 3296 participants identified as part of the study, 3044 met inclusion criteria, and 1885 participants (mean [SD] age, 41.3 [17.1] years; 1241 [65.8%] men and 644 [34.2%] women) had follow-up information at 12 months, including 1493 patients with TBI; 182 orthopedic controls, 210 uninjured friend controls; 41 patients with TBI (2.8%) and no controls had positive screening results for PTE. Compared with a negative screening result for PTE, having a positive screening result for PTE was associated with presenting Glasgow Coma Scale score (8.1 [4.8] vs.13.5 [3.3]; P < .001) as well as with anomalous acute head imaging findings (risk ratio, 6.42 [95% CI, 2.71-15.22]). After controlling for age, initial Glasgow Coma Scale score, and imaging findings, compared with patients with TBI and without PTE, patients with TBI and with positive PTE screening results had significantly lower Glasgow Outcome Scale Extended scores (mean [SD], 6.1 [1.7] vs 4.7 [1.5]; P < .001), higher BSI scores (mean [SD], 50.2 [10.7] vs 58.6 [10.8]; P = .02), and higher RCM scores (mean [SD], 3.1 [2.6] vs 5.3 [1.9]; P = .002) at 12 months.

CONCLUSIONS AND RELEVANCE: In this cohort study, the incidence of self-reported PTE after TBI was found to be 2.8% and was independently associated with unfavorable outcomes. These findings highlight the need for effective antiepileptogenic therapies after TBI.

PMID:34964854 | PMC:PMC8717106 | DOI:10.1001/jamanetworkopen.2021.40191

Am J Speech Lang Pathol. 2022 Jan 18;31(1):188-202. doi: 10.1044/2021_AJSLP-21-00129. Epub 2021 Dec 20.

ABSTRACT

PURPOSE: Return to work (RTW) is a major life participation metric used for persons with a traumatic brain injury (TBI). Speech-language pathologists (SLPs) have clinical expertise in the cognitive-communication aspects of TBI. This clinical focus article aims to support the clinical practice of SLPs by summarizing key interprofessional vocational rehabilitation (VR) models and illustrating the role of the SLP throughout the RTW process with a case study.

METHOD: This clinical focus article was written by the Academy of Neurologic Communication Disorders and Sciences TBI Research Group along with a VR expert. Authors engaged in deliberative, agenda-based discussions beginning with a literature review based on previous systematic studies. Discussions explored relevant VR and SLP practices.

RESULTS: This clinical focus article presents key VR models in parallel with SLP assessment and treatment to illustrate best practice patterns in an RTW field with a dearth of SLP-specific literature. We summarize general VR approaches and four evidence-supported VR models for adults with TBI. We highlight how a model of interprofessional assessment can assist with planning and communication of important work-related concerns. We illustrate how the chronological model of work return can assist with developing goals and planning treatment.

CONCLUSIONS: SLPs play an important role in identifying, managing, and collaborating with an RTW team following TBI. A working knowledge of VR models can assist with improving the dialogue between SLPs and VR professionals and can inform practice when working with persons with TBI who have work return as a goal.

PMID:34929113 | DOI:10.1044/2021_AJSLP-21-00129

Neurology. 2022 Jan 18;98(3):e315-e325. doi: 10.1212/WNL.0000000000013067. Epub 2021 Dec 3.

ABSTRACT

BACKGROUND AND OBJECTIVES: In patients with severe coronavirus disease 2019 (COVID-19), disorders of consciousness (DoC) have emerged as a serious complication. The prognosis and pathophysiology of COVID-DoC remain unclear, complicating decisions about continuing life-sustaining treatment. We describe the natural history of COVID-DoC and investigate its associated brain connectivity profile.

METHODS: In a prospective longitudinal study, we screened consecutive patients with COVID-19 at our institution. We enrolled critically ill adult patients with a DoC unexplained by sedation or structural brain injury and who were planned to undergo a brain MRI. We performed resting-state fMRI and diffusion MRI to evaluate functional and structural connectivity compared to healthy controls and patients with DoC resulting from severe traumatic brain injury (TBI). We assessed the recovery of consciousness (command following) and functional outcomes (Glasgow Outcome Scale Extended [GOSE] and the Disability Rating Scale [DRS]) at hospital discharge and 3 and 6 months after discharge. We also explored whether clinical variables were associated with recovery from COVID-DoC.

RESULTS: After screening 1,105 patients with COVID-19, we enrolled 12 with COVID-DoC. The median age was 63.5 years (interquartile range 55-76.3 years). After the exclusion of 1 patient who died shortly after enrollment, all of the remaining 11 patients recovered consciousness 0 to 25 days (median 7 [5-14.5] days) after the cessation of continuous IV sedation. At discharge, all surviving patients remained dependent: median GOSE score 3 (1-3) and median DRS score 23 (16-30). Ultimately, however, except for 2 patients with severe polyneuropathy, all returned home with normal cognition and minimal disability: at 3 months, median GOSE score 3 (3-3) and median DRS score 7 (5-13); at 6 months, median GOSE score 4 (4-5), median DRS score 3 (3-5). Ten patients with COVID-DoC underwent advanced neuroimaging; functional and structural brain connectivity in those with COVID-DoC was diminished compared to healthy controls, and structural connectivity was comparable to that in patients with severe TBI.

DISCUSSION: Patients who survived invariably recovered consciousness after COVID-DoC. Although disability was common after hospitalization, functional status improved over the ensuing months. While future research is necessary, these prospective findings inform the prognosis and pathophysiology of COVID-DoC.

TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov identifier: NCT04476589.

PMID:34862317 | PMC:PMC8792809 | DOI:10.1212/WNL.0000000000013067

J Neurotrauma. 2022 Jul;39(13-14):1010-1012. doi: 10.1089/neu.2021.0356. Epub 2021 Dec 22.

ABSTRACT

Traumatic brain injury (TBI) results in disparate outcomes ranging from persistent disorders of consciousness to symptom resolution. Despite the breadth and complexity of TBI recovery, most clinical trials dichotomize outcome by establishing an arbitrary cut-point, above and below which recovery is described as "favorable" and "unfavorable," respectively. For example, the widely used eight-level Glasgow Outcome Scale-Extended (GOSE) is typically collapsed into these two categories. Dichotomizing the GOSE into "favorable" and "unfavorable" outcome may limit detection of treatment effects in TBI clinical trials, contribute to imprecise prognostic counseling, and unduly influence decision-making with regard to withdrawal of life-sustaining therapy. We illustrate the lack of standardization in defining "unfavorable" and "favorable" TBI outcome on the GOSE by identifying the broad range of cut-points, from a score of 3 (part-time supervision in the home required) to 7 (presence of some residual of symptoms), that have been used to dichotomize the GOSE. We also highlight the ethical concerns related to characterizing TBI outcomes solely from the perspective of investigators and clinicians, rather than patients and caregivers. Finally, we suggest that a pragmatic, immediate solution to GOSE dichotomization is to report the likelihood of achieving each of the eight GOSE outcome levels and propose a study design for a new patient- and caregiver-centered TBI outcome metric.

PMID:34861770 | PMC:PMC9248332 | DOI:10.1089/neu.2021.0356

J Clin Psychol. 2022 May;78(5):877-891. doi: 10.1002/jclp.23282. Epub 2021 Nov 25.

ABSTRACT

OBJECTIVE: To identify group-based patterns in suicidal ideation (SI) over the first 10 years after traumatic brain injury (TBI).

METHODS: Participants included 9539 individuals in the TBI Model Systems National Database who responded to Patient Health Questionnaire-9 Item 9 assessing SI at 1, 2, 5, and/or 10 years post-injury. A k-means cluster analysis was conducted to determine group-based patterns of SI, and pre-injury variables were compared with ANOVAs and chi-square tests.

RESULTS: SI and attempts decreased over time. Four group-based patterns emerged: Low, increasing, moderate, and decreasing SI. The low SI group comprised 89% of the sample, had the highest pre-injury employment, fewer mental health vulnerabilities, least severe injuries, and were oldest. The increasing SI group had the most severe TBIs, were youngest, and disproportionately Black or Asian/Pacific Islander.

CONCLUSION: These findings reinforce the importance of mental health and suicide risk assessment during chronic recovery from TBI.

PMID:34825373 | DOI:10.1002/jclp.23282

Am J Health Syst Pharm. 2022 Feb 18;79(5):359-363. doi: 10.1093/ajhp/zxab420.

ABSTRACT

PURPOSE: To advance the implementation of consciousness-promoting therapies in patients with acute disorders of consciousness, the availability of potential therapeutic agents in formulations suitable for administration in hospitalized patients in the presence of complex comorbid conditions is paramount. The purpose of this study is to evaluate the long-term stability of extemporaneously prepared preservative-free methylphenidate hydrochloride (HCl) 5 mg/mL intravenous solution for experimental use.

METHODS: A methylphenidate 5 mg/mL solution was prepared under proper aseptic techniques with Methylphenidate Hydrochloride, USP, powder mixed in sterile water for solution. Methylphenidate HCl 5 mg/mL solution was sterilized by filtration technique under USP <797>-compliant conditions. Samples were stored refrigerated (2-8°C) and analyzed at approximately days 1, 30, 60, 90, 180, and 365. At each time point, chemical and physical stability were evaluated by visual inspection, pH measurement, membrane filtration procedure, turbidometric or photometric technique, and high-performance liquid chromatography analysis.

RESULTS: Over the 1-year study period, the samples retained 96.76% to 102.04% of the initial methylphenidate concentration. There was no significant change in the visual appearance, pH level, or particulate matter during the study period. The sterility of samples was maintained and endotoxin levels were undetectable throughout the 1-year stability period.

CONCLUSION: Extemporaneously prepared preservative-free methylphenidate 5 mg/mL intravenous solution was physically and chemically stable at 32, 61, 95, 186, and 365 days when stored in amber glass vials at refrigerated temperatures (2-8°C).

PMID:34788364 | PMC:PMC9013207 | DOI:10.1093/ajhp/zxab420

JAMA Neurol. 2021 Nov 1;78(11):1412-1413. doi: 10.1001/jamaneurol.2021.3430.

NO ABSTRACT

PMID:34605886 | DOI:10.1001/jamaneurol.2021.3430

J Neurotrauma. 2021 Dec;38(23):3295-3305. doi: 10.1089/neu.2021.0199.

ABSTRACT

In nearly all clinical and research contexts, the initial severity of a traumatic brain injury (TBI) is measured using the Glasgow Coma Scale (GCS) total score. The GCS total score however, may not accurately reflect level of consciousness, a critical indicator of injury severity. We investigated the relationship between GCS total scores and level of consciousness in a consecutive sample of 2455 adult subjects assessed with the GCS 69,487 times as part of the multi-center Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study. We assigned each GCS subscale score combination a level of consciousness rating based on published criteria for the following disorders of consciousness (DoC) diagnoses: coma, vegetative state/unresponsive wakefulness syndrome, minimally conscious state, and post-traumatic confusional state, and present our findings using summary statistics and four illustrative cases. Participants had the following characteristics: mean (standard deviation) age 41.9 (17.6) years, 69% male, initial GCS 3-8 = 13%; 9-12 = 5%; 13-15 = 82%. All GCS total scores between 4-14 were associated with more than one DoC diagnosis; the greatest variability was observed for scores of 7-11. Further, a wide range of total scores was associated with identical DoC diagnoses. Importantly, a diagnosis of coma was only possible with GCS total scores of 3-6. The GCS total score does not accurately reflect level of consciousness based on published DoC diagnostic criteria. To improve the classification of patients with TBI and to inform the design of future clinical trials, clinicians and investigators should consider individual subscale behaviors and more comprehensive assessments when evaluating TBI severity.

PMID:34605668 | PMC:PMC8917895 | DOI:10.1089/neu.2021.0199

Neurocrit Care. 2021 Dec;35(3):927. doi: 10.1007/s12028-021-01356-4.

NO ABSTRACT

PMID:34591257 | DOI:10.1007/s12028-021-01356-4

Brain Inj. 2021 Nov 10;35(12-13):1552-1562. doi: 10.1080/02699052.2021.1972455. Epub 2021 Sep 21.

ABSTRACT

PRIMARY OBJECTIVE: We hypothesized that, in patients with acute severe traumatic brain injury (TBI) who recover basic language function, speech-evoked blood-oxygen-level-dependent (BOLD) functional MRI (fMRI) responses within the canonical language network increase over the first 6 months post-injury.

RESEARCH DESIGN: We conducted a prospective, longitudinal fMRI pilot study of adults with acute severe TBI admitted to the intensive care unit. We also enrolled age- and sex-matched healthy subjects.

METHODS AND PROCEDURES: We evaluated BOLD signal in bilateral superior temporal gyrus (STG) and inferior frontal gyrus (IFG) regions of interest acutely and approximately 6 months post-injury. Given evidence that regions outside the canonical language network contribute to language processing, we also performed exploratory whole-brain analyses.

MAIN OUTCOMES AND RESULTS: Of the 16 patients enrolled, eight returned for follow-up fMRI, all of whom recovered basic language function. We observed speech-evoked longitudinal BOLD increases in the left STG, but not in the right STG, right IFG, or left IFG. Whole-brain analysis revealed increases in the right supramarginal and middle temporal gyri but no differences between patients and healthy subjects (n = 16).

CONCLUSION: This pilot study suggests that, in patients with severe TBI who recover llanguage function, speech-evoked responses in bihemispheric language-processing cortex reemerge by 6 months post-injury.

PMID:34546806 | PMC:PMC8678186 | DOI:10.1080/02699052.2021.1972455

Brain Inj. 2021 Aug 24;35(10):1284-1291. doi: 10.1080/02699052.2021.1972153. Epub 2021 Sep 13.

ABSTRACT

OBJECTIVE: Examine effects of age cohort on post-injury life satisfaction in elderly persons with TBIDesign: Retrospective cohortSetting: TBI Model Systems centers.

PARTICIPANTS: 5,109 elderly participants with TBI in the TBI Model Systems National DatabaseInterventions: Not applicableMain Outcome Measures: Demographics, injury characteristics and cause, outcomes, age at time of analysis, time to follow commands, maximum follow-up period, and scores on the Satisfaction With Life Scale (SWLS) and Participation Assessment with Recombined Tools-Objective (PART-O) scores at 1, 2, 5, or 10 years post-injury.

RESULTS: Life satisfaction post-TBI across groups increased with age. The young-old sub-group demonstrated the poorest life satisfaction outcomes, while the oldest sub-group experienced greatest life satisfaction. In contrast, participation decreased with age.

CONCLUSIONS: Findings show diversity in satisfaction with life following moderate to severe TBI for three elderly age-cohorts. Differences may be due to variations in generation-based lived experience, in perceived meaningfulness of participation, could echo prior evidence of greater resilience in the oldest group, or could reflect bias within the study sample. Further research into between- and within- differences for elderly TBI age cohorts is needed to more precisely meet their needs for physical and functional rehabilitation as well as psychological supports.

PMID:34516315 | DOI:10.1080/02699052.2021.1972153

J Neurotrauma. 2021 Dec;38(23):3352-3363. doi: 10.1089/neu.2020.7546. Epub 2021 Oct 18.

ABSTRACT

It is important to measure quality of life (QoL) after traumatic brain injury (TBI), yet limited studies have compared QoL inventories. In 2579 TBI patients, orthopedic trauma controls, and healthy friend control participants, we compared the Quality of Life After Brain Injury-Overall Scale (QOLIBRI-OS), developed for TBI patients, to the Satisfaction with Life Scale (SWLS), an index of generic life satisfaction. We tested the hypothesis that group differences (TBI and orthopedic trauma vs. healthy friend controls) would be larger for the QOLIBRI-OS than the SWLS and that the QOLIBRI-OS would manifest more substantial changes over time in the injured groups, demonstrating more relevance of the QOLIBRI-OS to traumatic injury recovery. (1) We compared the group differences (TBI vs. orthopedic trauma control vs. friend control) in QoL as indexed by the SWLS versus the QOLIBRI-OS and (2) characterized changes across time in these two inventories across 1 year in these three groups. Our secondary objective was to characterize the relationship between TBI severity and QoL. As compared with healthy friend controls, the QOLIBRI reflected greater reductions in QoL than the SWLS for both the TBI group (all time points) and the orthopedic trauma control group (2 weeks and 3 months). The QOLIBRI-OS better captured expected improvements in QoL during the injury recovery course in injured groups than the SWLS, which demonstrated smaller changes over time. TBI severity was not consistently or robustly associated with self-reported QoL. The findings imply that, as compared with the SWLS, the QOLIBRI-OS appears to identify QoL issues more specifically relevant to traumatically injured patients and may be a more appropriate primary QoL outcome measure for research focused on the sequelae of traumatic injuries.

PMID:34435894 | PMC:PMC8820285 | DOI:10.1089/neu.2020.7546

Expert Rev Neurother. 2021 Sep;21(9):1051-1058. doi: 10.1080/14737175.2021.1968299. Epub 2021 Aug 26.

ABSTRACT

OBJECTIVE: To determine minimally clinically important differences (MCIDs) for Disability Rating Scale (DRS), Fugl-Meyer Upper Extremity Subscale (FM-UE), Fugl-Meyer Lower Extremity Subscale (FM-LE), and Fugl-Meyer Motor Scale (FMMS) in patients with chronic motor deficits secondary to traumatic brain injury (TBI).

METHODS: Retrospective analysis from the 1-year, double-blind, randomized, surgical sham-controlled, Phase 2 STEMTRA trial (NCT02416492), in which patients with chronic motor deficits secondary to TBI (N = 61) underwent intracerebral stereotactic implantation of modified bone marrow-derived mesenchymal stromal (SB623) cells. MCIDs for DRS, FM-UE, FM-LE, and FMMS were triangulated with distribution-based, anchor-based, and Delphi panel estimates.

RESULTS: Triangulated MCIDs were: 1) -1.5 points for the Disability Rating Scale; 2) 6.2 points for the Fugl-Meyer Upper Extremity Subscale; 3) 3.2 points for the Fugl-Meyer Lower Extremity Subscale; and 4) 8.4 points for the Fugl-Meyer Motor Scale.

CONCLUSIONS: For the first time in the setting of patients with chronic motor deficits secondary to TBI, this study reports triangulated MCIDs for: 1) DRS, a measure of global outcome; and 2) Fugl-Meyer Scales, measures of motor impairment. These findings guide the use of DRS and Fugl-Meyer Scales in the assessment of global disability outcome and motor impairment in future TBI clinical trials.

PMID:34402352 | DOI:10.1080/14737175.2021.1968299

Am J Speech Lang Pathol. 2021 Sep 23;30(5):2329-2333. doi: 10.1044/2021_AJSLP-20-00145. Epub 2021 Aug 11.

ABSTRACT

Purpose The purpose of this article is to promote the viewpoint that speech-language pathologists (SLPs) are well positioned to actively encourage individuals with cognitive-communication disorders following acquired brain injury (ABI) to engage in ongoing, long-term, cognitive exercise post-therapy discharge. Method This viewpoint article draws on evidence from the well-researched area of physical exercise, reports findings of early-stage research in the much less studied area of cognitive exercise, and highlights relevant aspects of motivational theory informing exercise participation. Informed by these, an evidence-supported model of cognitive exercise engagement is offered to inform ABI-targeted cognitive wellness empowerment efforts, and a case study illustrates clinical application of the model. Conclusions Exercise provides an opportunity to sustain or improve long-term health, function, and quality of life outcomes. It is within SLP scope of practice to collaborate with family members and other caregivers to empower individuals post-ABI, especially those with decreased self-management skills, to engage in long-term computerized and noncomputerized cognitive exercise following SLP therapy discharge. Ongoing research will further inform the evidence supporting the scholarly opinion presented in this viewpoint.

PMID:34379514 | DOI:10.1044/2021_AJSLP-20-00145

Brain. 2021 Dec 16;144(11):3291-3310. doi: 10.1093/brain/awab290.

ABSTRACT

Neuroethical questions raised by recent advances in the diagnosis and treatment of disorders of consciousness are rapidly expanding, increasingly relevant and yet underexplored. The aim of this thematic review is to provide a clinically applicable framework for understanding the current taxonomy of disorders of consciousness and to propose an approach to identifying and critically evaluating actionable neuroethical issues that are frequently encountered in research and clinical care for this vulnerable population. Increased awareness of these issues and clarity about opportunities for optimizing ethically responsible care in this domain are especially timely given recent surges in critically ill patients with prolonged disorders of consciousness associated with coronavirus disease 2019 around the world. We begin with an overview of the field of neuroethics: what it is, its history and evolution in the context of biomedical ethics at large. We then explore nomenclature used in disorders of consciousness, covering categories proposed by the American Academy of Neurology, the American Congress of Rehabilitation Medicine and the National Institute on Disability, Independent Living and Rehabilitation Research, including definitions of terms such as coma, the vegetative state, unresponsive wakefulness syndrome, minimally conscious state, covert consciousness and the confusional state. We discuss why these definitions matter, and why there has been such evolution in this nosology over the years, from Jennett and Plum in 1972 to the Multi-Society Task Force in 1994, the Aspen Working Group in 2002 and the 2018 American and 2020 European Disorders of Consciousness guidelines. We then move to a discussion of clinical aspects of disorders of consciousness, the natural history of recovery and ethical issues that arise within the context of caring for people with disorders of consciousness. We conclude with a discussion of key challenges associated with assessing residual consciousness in disorders of consciousness, potential solutions and future directions, including integration of crucial disability rights perspectives.

PMID:34347037 | PMC:PMC8883802 | DOI:10.1093/brain/awab290

IEEE J Biomed Health Inform. 2022 Mar;26(3):1285-1296. doi: 10.1109/JBHI.2021.3099745. Epub 2022 Mar 7.

ABSTRACT

Prognoses of Traumatic Brain Injury (TBI) outcomes are neither easily nor accurately determined from clinical indicators. This is due in part to the heterogeneity of damage inflicted to the brain, ultimately resulting in diverse and complex outcomes. Using a data-driven approach on many distinct data elements may be necessary to describe this large set of outcomes and thereby robustly depict the nuanced differences among TBI patients' recovery. In this work, we develop a method for modeling large heterogeneous data types relevant to TBI. Our approach is geared toward the probabilistic representation of mixed continuous and discrete variables with missing values. The model is trained on a dataset encompassing a variety of data types, including demographics, blood-based biomarkers, and imaging findings. In addition, it includes a set of clinical outcome assessments at 3, 6, and 12 months post-injury. The model is used to stratify patients into distinct groups in an unsupervised learning setting. We use the model to infer outcomes using input data, and show that the collection of input data reduces uncertainty of outcomes over a baseline approach. In addition, we quantify the performance of a likelihood scoring technique that can be used to self-evaluate the extrapolation risk of prognosis on unseen patients.

PMID:34310331 | PMC:PMC8789941 | DOI:10.1109/JBHI.2021.3099745

Neurocrit Care. 2021 Oct;35(2):335-346. doi: 10.1007/s12028-021-01263-8. Epub 2021 Jul 26.

ABSTRACT

BACKGROUND: Traumatic brainstem injury has yet to be incorporated into widely used imaging classification systems for traumatic brain injury (TBI), and questions remain regarding prognostic implications for this TBI subgroup. To address this, retrospective data on patients from the multicenter prospective Transforming Research and Clinical Knowledge in TBI study were studied.

METHODS: Patients with brainstem and cerebrum injury (BSI+) were matched by age, sex, and admission Glasgow Coma Scale (GCS) score to patients with cerebrum injuries only. All patients had an interpretable head computed tomography (CT) scan from the first 48 hours after injury and a 6-month Glasgow Outcome Scale Extended (GOSE) score. CT scans were reviewed for brainstem lesions and, when present, characterized by location, size, and type (traumatic axonal injury, contusion, or Duret hemorrhage). Clinical, demographic, and outcome data were then compared between the two groups.

RESULTS: Mann-Whitney U-tests showed no significant difference in 6-month GOSE scores in patients with BSI+ (mean 2.7) compared with patients with similar but only cerebrum injuries (mean 3.9), although there is a trend (p = 0.10). However, subclassification by brainstem lesion type, traumatic axonal injury (mean 4.0) versus Duret hemorrhage or contusion (mean 1.4), did identify a proportion of BSI+ with significantly less favorable outcome (p = 0.002). The incorporation of brainstem lesion type (traumatic axonal injury vs. contusion/Duret), along with GCS into a multivariate logistic regression model of favorable outcome (GOSE score 4-8) did show a significant contribution to the prognostication of this brainstem injury subgroup (odds ratio 0.08, 95% confidence interval 0.00-0.67, p = 0.01).

CONCLUSIONS: These findings suggest two groups of patients with brainstem injuries may exist with divergent recovery potential after TBI. These data support the notion that newer CT imaging classification systems may augment traditional clinical measures, such as GCS in identifying those patients with TBI and brainstem injuries that stand a higher chance of favorable outcome.

PMID:34309784 | PMC:PMC8727027 | DOI:10.1007/s12028-021-01263-8

medRxiv [Preprint]. 2021 Jul 14:2021.07.09.21252353. doi: 10.1101/2021.07.09.21252353.

ABSTRACT

Neuropsychiatric symptoms may persist following acute COVID-19 illness, but the extent to which these symptoms are specific to COVID-19 has not been established. We utilized electronic health records across 6 hospitals in Massachusetts to characterize cohorts of individuals discharged following admission for COVID-19 between March 2020 and May 2021, and compared them to individuals hospitalized for other indications during this period. Natural language processing was applied to narrative clinical notes to identify neuropsychiatric symptom domains up to 150 days following hospitalization. Among 6,619 individuals hospitalized for COVID-19 drawn from a total of 42,961 hospital discharges, the most commonly documented symptom domains between 31 and 90 days after initial positive test were fatigue (13.4%), mood and anxiety symptoms (11.2%), and impaired cognition (8.0%). In models adjusted for sociodemographic features and hospital course, none of these were significantly more common among COVID-19 patients; indeed, mood and anxiety symptoms were less frequent (adjusted OR 0.72 95% CI 0.64-0.92). Between 91 and 150 days after positivity, most commonly-detected symptoms were fatigue (10.9%), mood and anxiety symptoms (8.2%), and sleep disruption (6.8%), with impaired cognition in 5.8%. Frequency was again similar among non-COVID-19 post-hospital patients, with mood and anxiety symptoms less common (aOR 0.63, 95% CI 0.52-0.75). Neuropsychiatric symptoms were common up to 150 days after initial hospitalization, but occurred at generally similar rates among individuals hospitalized for other indications during the same period. Post-acute sequelae of COVID-19 thus may benefit from standard if less-specific treatments developed for rehabilitation after hospitalization.

FUNDING: R01MH120227, R01MH116270 (Perlis).

PMID:34282420 | PMC:PMC8288151 | DOI:10.1101/2021.07.09.21252353

JAMA Neurol. 2021 Sep 1;78(9):1137-1148. doi: 10.1001/jamaneurol.2021.2120.

ABSTRACT

IMPORTANCE: A head computed tomography (CT) with positive results for acute intracranial hemorrhage is the gold-standard diagnostic biomarker for acute traumatic brain injury (TBI). In moderate to severe TBI (Glasgow Coma Scale [GCS] scores 3-12), some CT features have been shown to be associated with outcomes. In mild TBI (mTBI; GCS scores 13-15), distribution and co-occurrence of pathological CT features and their prognostic importance are not well understood.

OBJECTIVE: To identify pathological CT features associated with adverse outcomes after mTBI.

DESIGN, SETTING, AND PARTICIPANTS: The longitudinal, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study enrolled patients with TBI, including those 17 years and older with GCS scores of 13 to 15 who presented to emergency departments at 18 US level 1 trauma centers between February 26, 2014, and August 8, 2018, and underwent head CT imaging within 24 hours of TBI. Evaluations of CT imaging used TBI Common Data Elements. Glasgow Outcome Scale-Extended (GOSE) scores were assessed at 2 weeks and 3, 6, and 12 months postinjury. External validation of results was performed via the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Data analyses were completed from February 2020 to February 2021.

EXPOSURES: Acute nonpenetrating head trauma.

MAIN OUTCOMES AND MEASURES: Frequency, co-occurrence, and clustering of CT features; incomplete recovery (GOSE scores <8 vs 8); and an unfavorable outcome (GOSE scores <5 vs ≥5) at 2 weeks and 3, 6, and 12 months.

RESULTS: In 1935 patients with mTBI (mean [SD] age, 41.5 [17.6] years; 1286 men [66.5%]) in the TRACK-TBI cohort and 2594 patients with mTBI (mean [SD] age, 51.8 [20.3] years; 1658 men [63.9%]) in an external validation cohort, hierarchical cluster analysis identified 3 major clusters of CT features: contusion, subarachnoid hemorrhage, and/or subdural hematoma; intraventricular and/or petechial hemorrhage; and epidural hematoma. Contusion, subarachnoid hemorrhage, and/or subdural hematoma features were associated with incomplete recovery (odds ratios [ORs] for GOSE scores <8 at 1 year: TRACK-TBI, 1.80 [95% CI, 1.39-2.33]; CENTER-TBI, 2.73 [95% CI, 2.18-3.41]) and greater degrees of unfavorable outcomes (ORs for GOSE scores <5 at 1 year: TRACK-TBI, 3.23 [95% CI, 1.59-6.58]; CENTER-TBI, 1.68 [95% CI, 1.13-2.49]) out to 12 months after injury, but epidural hematoma was not. Intraventricular and/or petechial hemorrhage was associated with greater degrees of unfavorable outcomes up to 12 months after injury (eg, OR for GOSE scores <5 at 1 year in TRACK-TBI: 3.47 [95% CI, 1.66-7.26]). Some CT features were more strongly associated with outcomes than previously validated variables (eg, ORs for GOSE scores <5 at 1 year in TRACK-TBI: neuropsychiatric history, 1.43 [95% CI .98-2.10] vs contusion, subarachnoid hemorrhage, and/or subdural hematoma, 3.23 [95% CI 1.59-6.58]). Findings were externally validated in 2594 patients with mTBI enrolled in the CENTER-TBI study.

CONCLUSIONS AND RELEVANCE: In this study, pathological CT features carried different prognostic implications after mTBI to 1 year postinjury. Some patterns of injury were associated with worse outcomes than others. These results support that patients with mTBI and these CT features need TBI-specific education and systematic follow-up.

PMID:34279565 | PMC:PMC8290344 | DOI:10.1001/jamaneurol.2021.2120

Neurocrit Care. 2021 Jul;35(Suppl 1):4-23. doi: 10.1007/s12028-021-01260-x. Epub 2021 Jul 8.

ABSTRACT

Coma and disorders of consciousness (DoC) are highly prevalent and constitute a burden for patients, families, and society worldwide. As part of the Curing Coma Campaign, the Neurocritical Care Society partnered with the National Institutes of Health to organize a symposium bringing together experts from all over the world to develop research targets for DoC. The conference was structured along six domains: (1) defining endotype/phenotypes, (2) biomarkers, (3) proof-of-concept clinical trials, (4) neuroprognostication, (5) long-term recovery, and (6) large datasets. This proceedings paper presents actionable research targets based on the presentations and discussions that occurred at the conference. We summarize the background, main research gaps, overall goals, the panel discussion of the approach, limitations and challenges, and deliverables that were identified.

PMID:34236619 | PMC:PMC8264966 | DOI:10.1007/s12028-021-01260-x

JAMA Neurol. 2021 Aug 1;78(8):982-992. doi: 10.1001/jamaneurol.2021.2043.

ABSTRACT

IMPORTANCE: Moderate to severe traumatic brain injury (msTBI) is a major cause of death and disability in the US and worldwide. Few studies have enabled prospective, longitudinal outcome data collection from the acute to chronic phases of recovery after msTBI.

OBJECTIVE: To prospectively assess outcomes in major areas of life function at 2 weeks and 3, 6, and 12 months after msTBI.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study, as part of the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study, was conducted at 18 level 1 trauma centers in the US from February 2014 to August 2018 and prospectively assessed longitudinal outcomes, with follow-up to 12 months postinjury. Participants were patients with msTBI (Glasgow Coma Scale scores 3-12) extracted from a larger group of patients with mild, moderate, or severe TBI who were enrolled in TRACK-TBI. Data analysis took place from October 2019 to April 2021.

EXPOSURES: Moderate or severe TBI.

MAIN OUTCOMES AND MEASURES: The Glasgow Outcome Scale-Extended (GOSE) and Disability Rating Scale (DRS) were used to assess global functional status 2 weeks and 3, 6, and 12 months postinjury. Scores on the GOSE were dichotomized to determine favorable (scores 4-8) vs unfavorable (scores 1-3) outcomes. Neurocognitive testing and patient reported outcomes at 12 months postinjury were analyzed.

RESULTS: A total of 484 eligible patients were included from the 2679 individuals in the TRACK-TBI study. Participants with severe TBI (n = 362; 283 men [78.2%]; median [interquartile range] age, 35.5 [25-53] years) and moderate TBI (n = 122; 98 men [80.3%]; median [interquartile range] age, 38 [25-53] years) were comparable on demographic and premorbid variables. At 2 weeks postinjury, 36 of 290 participants with severe TBI (12.4%) and 38 of 93 participants with moderate TBI (41%) had favorable outcomes (GOSE scores 4-8); 301 of 322 in the severe TBI group (93.5%) and 81 of 103 in the moderate TBI group (78.6%) had moderate disability or worse on the DRS (total score ≥4). By 12 months postinjury, 142 of 271 with severe TBI (52.4%) and 54 of 72 with moderate TBI (75%) achieved favorable outcomes. Nearly 1 in 5 participants with severe TBI (52 of 270 [19.3%]) and 1 in 3 with moderate TBI (23 of 71 [32%]) reported no disability (DRS score 0) at 12 months. Among participants in a vegetative state at 2 weeks, 62 of 79 (78%) regained consciousness and 14 of 56 with available data (25%) regained orientation by 12 months.

CONCLUSIONS AND RELEVANCE: In this study, patients with msTBI frequently demonstrated major functional gains, including recovery of independence, between 2 weeks and 12 months postinjury. Severe impairment in the short term did not portend poor outcomes in a substantial minority of patients with msTBI. When discussing prognosis during the first 2 weeks after injury, clinicians should be particularly cautious about making early, definitive prognostic statements suggesting poor outcomes and withdrawal of life-sustaining treatment in patients with msTBI.

PMID:34228047 | PMC:PMC8261688 | DOI:10.1001/jamaneurol.2021.2043

Mult Scler Relat Disord. 2021 Aug;53:103051. doi: 10.1016/j.msard.2021.103051. Epub 2021 May 29.

ABSTRACT

BACKGROUND: Disease progression of multiple sclerosis (MS) is often monitored by ambulatory measures, but how non-ambulatory sensorimotor measures differentially associate to walking measures in MS subtypes is unknown. We determined whether there are characteristic differences between relapsing-remitting MS (RRMS), progressive MS (PMS), and non-MS controls in lower extremity sensorimotor function and clinical walking tasks and the sensorimotor associations with walking function in each group.

METHODS: 18 RRMS, 13 PMS and 28 non-MS control participants were evaluated in their plantar cutaneous sensitivity (vibration perception threshold, Volts), proprioception during ankle joint position-matching (|∆°| in dorsiflexion), motor coordination (rapid foot-tap count/10 s), and walking function with three tests: Timed 25-foot walk (T25FW) at preferred and fast speeds (s), and timed-up-and-go (TUG, s).

RESULTS: Foot-tapping (p = 0.039, Mean difference (MD)= 5.65 taps) and plantar cutaneous sensation (p = 0.026, MD= -10.30 V) differed between the MS subtypes. For the RRMS group faster walking was related to better proprioceptive function (preferred T25FW: p = 0.019, Root mean square error (RMSE)=1.94; fast T25FW: p = 0.004, RMSE=1.65; TUG: p = 0.001, RMSE=2.12) and foot-tap performance (preferred T25FW: p = 0.033, RMSE = 2.74; fast T25FW: p = 0.010, RMSE=2.02). These associations were not observed in the PMS group.

CONCLUSIONS: Foot-tap performance and plantar cutaneous sensitivity but not ankle proprioception differed between MS subtypes. Lower walking performance was associated with lower foot-tapping and plantar cutaneous sensitivity in the RRMS but not the PMS group. This result suggests a change in the relationship of lower extremity sensorimotor function to walking performance in the PMS subtype.

PMID:34139463 | DOI:10.1016/j.msard.2021.103051

J Abnorm Psychol. 2021 Jul;130(5):423-434. doi: 10.1037/abn0000672. Epub 2021 Jun 10.

ABSTRACT

Neuropsychiatric symptoms are common, comorbid, and often disabling for patients with traumatic brain injury (TBI). Identifying transdiagnostic symptom dimensions post-TBI may help overcome limitations of traditional psychiatric diagnoses and advance treatment development. We characterized the dimensional structure of neuropsychiatric symptoms at 2-weeks postinjury in n = 1,732 TBI patients and n = 238 orthopedic-injured trauma controls (OTC) from the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study. Symptoms were reported on the Brief Symptom Inventory-18, Patient Health Questionnaire-9 Depression checklist, PTSD Checklist for DSM-5, PROMIS Pain Intensity scale, and Insomnia Severity Index. We established a novel factor model of neuropsychiatric symptoms and evaluated how 3 TBI severity strata and OTC patients differed in symptom severity. The final factor model had 6 first-order factors subsumed by 2 second-order factors: Internalizing (encompassing Depression, Anxiety, and Fear) and Somatic symptoms (Sleep, Physical, Pain). Somatic symptoms fit better as a correlated factor of (vs. a lower-order factor within) Internalizing. All symptom dimensions except for Pain were more severe in 1 or more TBI subgroups, as compared to the OTC group. Milder brain injury was generally associated with more severe symptoms, whereas more general injury severity (higher level of care, e.g., emergency department, intensive care unit) was associated with more pain. The findings indicate a broad factor resembling the internalizing factor of general psychopathology in traumatically injured patients, alongside a distinct somatic symptom factor. Brain injury, especially milder brain injury, may exacerbate liabilities toward these symptoms. These neuropsychiatric dimensions may help advance more precision medicine research for TBI. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

PMID:34110838 | PMC:PMC8552293 | DOI:10.1037/abn0000672

J Neurotrauma. 2021 Oct 1;38(19):2706-2713. doi: 10.1089/neu.2021.0038. Epub 2021 Jul 20.

ABSTRACT

Understanding the effects of age on longitudinal traumatic brain injury (TBI) outcomes requires attention to both chronic and evolving TBI effects and age-related changes in health and function. The present study examines the independent and interactive effects of aging and chronicity on functional outcomes after TBI. We leveraged a well-defined cohort of individuals who sustained a moderate/severe TBI and received acute inpatient rehabilitation at specialized centers with high follow up rate as part of their involvement in the TBI Model Systems longitudinal study. We selected individuals at one of two levels of TBI chronicity (either 2 or 10 years post-injury) and used an exact matching procedure to obtain balanced chronicity groups based on age and other characteristics (N = 1993). We found that both older age and greater injury chronicity were related to greater disability, reduced functional independence, and less community participation. There was a significant age by chronicity interaction, indicating that the adverse effects of greater time post-injury were most pronounced among survivors who were age 75 or older. The inflection point at roughly 75 years of age was corroborated by post hoc analyses, dividing the sample by age at 75 years and examining the interaction between age group and chronicity. These findings point to a need for provision of rehabilitation services in the chronic injury period, particularly for those who are over 75 years old. Future work should investigate the underlying mechanisms of this interaction towards the goal of developing interventions and models of care to promote healthy aging with TBI.

PMID:34082606 | PMC:PMC8822416 | DOI:10.1089/neu.2021.0038

Brain Sci. 2021 May 21;11(6):672. doi: 10.3390/brainsci11060672.

ABSTRACT

Exercise self-efficacy, the confidence a person has in their ability to develop and meet exercise goals, is key to exercise motivation. The primary objective of this pilot study was to explore associations among cognitive exercise self-efficacy, cognitive exercise frequency, challenge, and enjoyment in older adults. A prospective, cross-sectional, observational study design was used with 133 community-dwelling individuals aged 55 years and older. Respondents completed a cognitive exercise self-efficacy scale and responded to cognitive exercise queries. Individuals who engaged in cognitive exercise demonstrated greater cognitive exercise self-efficacy. Cognitive exercise self-efficacy ratings were significantly different across challenge and enjoyment conditions (Pearson's χ² test, df = 9, N = 133, χ² = 123.49, p < 0.01), such that the greater the perception of each, the greater the cognitive exercise self-efficacy (p < 0.01). The comparative impact of perceived enjoyment on cognitive exercise self-efficacy was greater than the impact of perceived challenge. Study findings support positive associations among cognitive exercise self-efficacy, cognitive exercise frequency, challenge, and enjoyment. Consideration of these findings may inform design and sustained implementation of motivating cognitive exercise programs to maximize health and quality of life outcomes of healthy and neurologic older adult populations.

PMID:34063967 | PMC:PMC8224066 | DOI:10.3390/brainsci11060672

AJOB Neurosci. 2021 Apr-Sep;12(2-3):200-202. doi: 10.1080/21507740.2021.1904050.

NO ABSTRACT

PMID:33960894 | PMC:PMC8496492 | DOI:10.1080/21507740.2021.1904050

AJOB Neurosci. 2021 Apr-Sep;12(2-3):169-171. doi: 10.1080/21507740.2021.1904055.

NO ABSTRACT

PMID:33960891 | DOI:10.1080/21507740.2021.1904055

J Neurosurg Anesthesiol. 2022 Apr 1;34(2):233-237. doi: 10.1097/ANA.0000000000000772.

ABSTRACT

BACKGROUND: Traumatic brain injury (TBI) is a major global health problem. Little research has addressed extracranial organ dysfunction following TBI, particularly myocardial injury. Using a sensitive marker of myocardial injury-high sensitivity troponin (hsTn)-we examined the incidence of early myocardial injury following TBI and explored its association with neurological outcomes following moderate-severe TBI.

METHODS: We conducted a pilot cohort study of 133 adult (age above 17 y) subjects enrolled in the TRACK-TBI 18-center prospective cohort study. Descriptive statistics were used to examine the incidence of myocardial injury (defined as hsTn >99th percentile for a standardized reference population) across TBI severities, and to explore the association of myocardial injury with a 6-month extended Glasgow Outcome Score among patients with moderate-severe TBI.

RESULTS: The mean (SD) age of the participants was 44 (17) years, and 87 (65%) were male. Twenty-six patients (20%) developed myocardial injury following TBI; myocardial injury was present in 15% of mild TBI patients and 29% of moderate-severe TBI patients (P=0.13). Median (interquartile range) hsTn values were 3.8 ng/L (2.1, 9.0), 5.8 ng/L (4.5, 34.6), and 10.2 ng/L (3.0, 34.0) in mild, moderate, and severe TBI participants, respectively (P=0.04). Overall, 11% of participants with moderate-severe TBI and myocardial injury experienced a good outcome (6-mo extended Glasgow Outcome Score≥5) at 6 months, compared with 65% in the group that did not experience myocardial injury (P=0.01).

CONCLUSIONS: Myocardial injury is common following TBI, with a likely dose-response relationship with TBI severity. Early myocardial injury was associated with poor 6-month clinical outcomes following moderate-severe TBI.

PMID:33901061 | PMC:PMC8536798 | DOI:10.1097/ANA.0000000000000772

J Neurotrauma. 2021 Sep 1;38(17):2419-2434. doi: 10.1089/neu.2020.7528. Epub 2021 Apr 28.

ABSTRACT

The Glasgow Outcome Scale (GOS) in its original or extended (GOSE) form is the most widely used assessment of global disability in traumatic brain injury (TBI) research. Several publications have reported concerns about assessor scoring inconsistencies, but without documentation of contributing factors. We reviewed 6801 GOSE assessments collected longitudinally, across 18 sites in the 5-year, observational Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study. We recorded error rates (i.e., corrections to a section or an overall rating) based on site assessor documentation and categorized scoring issues, which then informed further training. In cohort 1 (n = 1261; February 2014 to May 2016), 24% of GOSEs had errors identified by central review. In cohort 2 (n = 1130; June 2016 to July 2018), acquired after curation of cohort 1 data, feedback, and further training of site assessors, the error rate was reduced to 10%. GOSE sections associated with the most frequent interpretation and scoring difficulties included whether current functioning represented a change from pre-injury (466 corrected ratings in cohort 1; 62 in cohort 2), defining dependency in the home and community (163 corrections in cohort 1; three in cohort 2) and return to work/school (72 corrections in cohort 1; 35 in cohort 2). These results highlight the importance of central review in improving consistency across sites and over time. Establishing clear scoring criteria, coupled with ongoing guidance and feedback to data collectors, is essential to avoid scoring errors and resultant misclassification, which carry potential to result in "failure" of clinical trials that rely on the GOSE as their primary outcome measure.

PMID:33832330 | PMC:PMC8390785 | DOI:10.1089/neu.2020.7528

JAMA Netw Open. 2021 Apr 1;4(4):e213046. doi: 10.1001/jamanetworkopen.2021.3046.

ABSTRACT

IMPORTANCE: Knowledge of differences in mild traumatic brain injury (mTBI) recovery by sex and age may inform individualized treatment of these patients.

OBJECTIVE: To identify sex-related differences in symptom recovery from mTBI; secondarily, to explore age differences within women, who demonstrate poorer outcomes after TBI.

DESIGN, SETTING, AND PARTICIPANTS: The prospective cohort study Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) recruited 2000 patients with mTBI from February 26, 2014, to July 3, 2018, and 299 patients with orthopedic trauma (who served as controls) from January 26, 2016, to July 27, 2018. Patients were recruited from 18 level I trauma centers and followed up for 12 months. Data were analyzed from August 19, 2020, to March 3, 2021.

EXPOSURES: Patients with mTBI (defined by a Glasgow Coma Scale score of 13-15) triaged to head computed tomography in 24 hours or less; patients with orthopedic trauma served as controls.

MAIN OUTCOMES AND MEASURES: Measured outcomes included (1) the Rivermead Post Concussion Symptoms Questionnaire (RPQ), a 16-item self-report scale that assesses postconcussion symptom severity over the past 7 days relative to preinjury; (2) the Posttraumatic Stress Disorder Checklist for the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (PCL-5), a 20-item test that measures the severity of posttraumatic stress disorder symptoms; (3) the Patient Health Questionnaire-9 (PHQ-9), a 9-item scale that measures depression based on symptom frequency over the past 2 weeks; and (4) the Brief Symptom Inventory-18 (BSI-18), an 18-item scale of psychological distress (split into Depression and Anxiety subscales).

RESULTS: A total of 2000 patients with mTBI (1331 men [67%; mean (SD) age, 41.0 (17.3) years; 1026 White (78%)] and 669 women [33%; mean (SD) age, 43.0 (18.5) years; 505 (76%) White]). After adjustment of multiple comparisons, significant TBI × sex interactions were observed for cognitive symptoms (B = 0.76; 5% false discovery rate-corrected P = .02) and somatic RPQ symptoms (B = 0.80; 5% false discovery rate-corrected P = .02), with worse symptoms in women with mTBI than men, but no sex difference in symptoms in control patients with orthopedic trauma. Within the female patients evaluated, there was a significant TBI × age interaction for somatic RPQ symptoms, which were worse in female patients with mTBI aged 35 to 49 years compared with those aged 17 to 34 years (B = 1.65; P = .02) or older than 50 years (B = 1.66; P = .02).

CONCLUSIONS AND RELEVANCE: This study found that women were more vulnerable than men to persistent mTBI-related cognitive and somatic symptoms, whereas no sex difference in symptom burden was seen after orthopedic injury. Postconcussion symptoms were also worse in women aged 35 to 49 years than in younger and older women, but further investigation is needed to corroborate these findings and to identify the mechanisms involved. Results suggest that individualized clinical management of mTBI should consider sex and age, as some women are especially predisposed to chronic postconcussion symptoms even 12 months after injury.

PMID:33822070 | PMC:PMC8025125 | DOI:10.1001/jamanetworkopen.2021.3046

PLoS One. 2021 Mar 31;16(3):e0248824. doi: 10.1371/journal.pone.0248824. eCollection 2021.

ABSTRACT

OBJECTIVE: To characterize the functional impairments of a cohort of patients undergoing inpatient rehabilitation after surviving severe COVID-19 illness, in order to better understand the ongoing needs of this patient population.

METHODS: This study consisted of a retrospective chart review of consecutive patients hospitalized for COVID-19 and admitted to a regional inpatient rehabilitation hospital from April 29th to May 22nd, 2020. Patient demographics, clinical characteristics and complications from acute hospitalization were examined. Measures of fall risk (Berg Balance Scale), endurance (6 Minute Walk Test), gait speed (10 Meter Walk Test), mobility (transfer and ambulation independence), cognition, speech and swallowing (American Speech and Hearing Association National Outcomes Measurement System Functional Communication Measures) were assessed at rehabilitation admission and discharge.

RESULTS: The study population included 29 patients and was 70% male, 58.6% white and with a mean age of 59.5. The mean length of acute hospitalization was 32.2 days with a mean of 18.7 days intubated. Patients spent a mean of 16.7 days in inpatient rehabilitation and 90% were discharged home. Patients demonstrated significant improvement from admission to discharge in measures of fall risk, endurance, gait speed, mobility, cognition, speech and swallowing, (p< 0.05). At discharge, a significant portion of the population continued to deficits in cognition (attention 37%; memory 28%; problem solving 28%), balance (55%) and gait speed (97%).

CONCLUSION: Patients admitted to inpatient rehabilitation after hospitalization with COVID-19 demonstrated deficits in mobility, cognition, speech and swallowing at admission and improved significantly in all of these domains by discharge. However, a significant number of patients exhibited residual deficits at discharge highlighting the post-acute care needs of this patient population.

PMID:33788876 | PMC:PMC8011729 | DOI:10.1371/journal.pone.0248824

JAMA Netw Open. 2021 Mar 1;4(3):e213467. doi: 10.1001/jamanetworkopen.2021.3467.

ABSTRACT

IMPORTANCE: Heterogeneity across patients with traumatic brain injury (TBI) presents challenges for clinical care and intervention design. Identifying distinct clinical phenotypes of TBI soon after injury may inform patient selection for precision medicine clinical trials.

OBJECTIVE: To investigate whether distinct neurobehavioral phenotypes can be identified 2 weeks after TBI and to characterize the degree to which early neurobehavioral phenotypes are associated with 6-month outcomes.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study included patients presenting to 18 US level 1 trauma centers within 24 hours of TBI from 2014 to 2019 as part of the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study. Data were analyzed from January 28, 2020, to January 11, 2021.

EXPOSURES: TBI.

MAIN OUTCOMES AND MEASURES: Latent profiles (LPs) were derived from common dimensions of neurobehavioral functioning at 2 weeks after injury, assessed through National Institutes of Health TBI Common Data Elements (ie, Brief Symptom Inventory-18, Patient Health Questionnaire-9 Depression checklist, Posttraumatic Stress Disorder Checklist for DSM-5, PROMIS Pain Intensity scale, Insomnia Severity Index, Rey Auditory Verbal Learning Test, Wechsler Adult Intelligence Scale-Fourth Edition Coding and Symbol Search subtests, Trail Making Test, and NIH Toolbox Cognitive Battery Pattern Comparison Processing Speed, Dimensional Change Card Sort, Flanker Inhibitory Control and Attention, and Picture Sequence Memory subtests). Six-month outcomes were the Satisfaction With Life Scale (SWLS), Quality of Life after Brain Injury-Overall Scale (QOLIBRI-OS), Glasgow Outcome Scale-Extended (GOSE), and Rivermead Post-Concussion Symptoms Questionnaire (RPQ).

RESULTS: Among 1757 patients with TBI included, 1184 (67.4%) were men, and the mean (SD) age was 39.9 (17.0) years. LP analysis revealed 4 distinct neurobehavioral phenotypes at 2 weeks after injury: emotionally resilient (419 individuals [23.8%]), cognitively impaired (368 individuals [20.9%]), cognitively resilient (620 individuals [35.3%]), and neuropsychiatrically distressed (with cognitive weaknesses; 350 individuals [19.9%]). Adding LP group to models including demographic characteristics, medical history, Glasgow Coma Scale score, and other injury characteristics was associated with significantly improved estimation of association with 6-month outcome (GOSE R2 increase = 0.09-0.19; SWLS R2 increase = 0.12-0.22; QOLIBRI-OS R2 increase = 0.14-0.32; RPQ R2 = 0.13-0.34).

CONCLUSIONS AND RELEVANCE: In this cohort study of patients with TBI presenting to US level-1 trauma centers, qualitatively distinct profiles of symptoms and cognitive functioning were identified at 2 weeks after TBI. These distinct phenotypes may help optimize clinical decision-making regarding prognosis, as well as selection and stratification for randomized clinical trials.

PMID:33783518 | PMC:PMC8010589 | DOI:10.1001/jamanetworkopen.2021.3467

J Neurotrauma. 2021 Sep 1;38(17):2435-2446. doi: 10.1089/neu.2020.7527. Epub 2021 Apr 6.

ABSTRACT

The Glasgow Outcome Scale-Extended (GOSE) has become one of the most widely used outcome instruments to assess global disability and recovery after traumatic brain injury. Achieving consistency in the application of the assessment remains a challenge, particularly in multi-center studies involving many assessors. We present a manual for the GOSE interview that is designed to support both single- and multi-center studies and promote inter-rater agreement. Many patients fall clearly into a particular category; however, patients may have outcomes that are on the borderline between adjacent categories, and cases can present other challenges for assessment. The Manual includes the general principles of assessment, advice on administering each section of the GOSE interview, and guidance on "borderline" and "difficult" cases. Finally, we discuss the properties of the GOSE, including strengths and limitations, and outline recommendations for assessor training, accreditation, and monitoring.

PMID:33740873 | PMC:PMC8390784 | DOI:10.1089/neu.2020.7527

JAMA Neurol. 2021 May 1;78(5):548-557. doi: 10.1001/jamaneurol.2021.0084.

ABSTRACT

IMPORTANCE: Traumatic brain injury (TBI) leads to 2.9 million visits to US emergency departments annually and frequently involves a disorder of consciousness (DOC). Early treatment, including withdrawal of life-sustaining therapies and rehabilitation, is often predicated on the assumed worse outcome of disrupted consciousness.

OBJECTIVE: To quantify the loss of consciousness, factors associated with recovery, and return to functional independence in a 31-year sample of patients with moderate or severe brain trauma.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed patients with TBI who were enrolled in the Traumatic Brain Injury Model Systems National Database, a prospective, multiyear, longitudinal database. Patients were survivors of moderate or severe TBI who were discharged from acute hospitalization and admitted to inpatient rehabilitation from January 4, 1989, to June 19, 2019, at 1 of 23 inpatient rehabilitation centers that participated in the Traumatic Brain Injury Model Systems program. Follow-up for the study was through completion of inpatient rehabilitation.

EXPOSURES: Traumatic brain injury.

MAIN OUTCOMES AND MEASURES: Outcome measures were Glasgow Coma Scale in the emergency department, Disability Rating Scale, posttraumatic amnesia, and Functional Independence Measure. Patient-related data included demographic characteristics, injury cause, and brain computed tomography findings.

RESULTS: The 17 470 patients with TBI analyzed in this study had a median (interquartile range [IQR]) age at injury of 39 (25-56) years and included 12 854 male individuals (74%). Of these patients, 7547 (57%) experienced initial loss of consciousness, which persisted to rehabilitation in 2058 patients (12%). Those with persisting DOC were younger; had more high-velocity injuries; had intracranial mass effect, intraventricular hemorrhage, and subcortical contusion; and had longer acute care than patients without DOC. Eighty-two percent (n = 1674) of comatose patients recovered consciousness during inpatient rehabilitation. In a multivariable analysis, the factors associated with consciousness recovery were absence of intraventricular hemorrhage (adjusted odds ratio [OR], 0.678; 95% CI, 0.532-0.863; P = .002) and intracranial mass effect (adjusted OR, 0.759; 95% CI, 0.595-0.968; P = .03). Functional improvement (change in total functional independence score from admission to discharge) was +43 for patients with DOC and +37 for those without DOC (P = .002), and 803 of 2013 patients with DOC (40%) became partially or fully independent. Younger age, male sex, and absence of intraventricular hemorrhage, intracranial mass effect, and subcortical contusion were associated with better functional outcome. Findings were consistent across the 3 decades of the database.

CONCLUSIONS AND RELEVANCE: This study found that DOC occurred initially in most patients with TBI and persisted in some patients after rehabilitation, but most patients with persisting DOC recovered consciousness during rehabilitation. This recovery trajectory may inform acute and rehabilitation treatment decisions and suggests caution is warranted in consideration of withdrawing or withholding care in patients with TBI and DOC.

PMID:33646273 | PMC:PMC7922241 | DOI:10.1001/jamaneurol.2021.0084

J Head Trauma Rehabil. 2021 May-Jun 01;36(3):196-204. doi: 10.1097/HTR.0000000000000641.

ABSTRACT

OBJECTIVE: To examine changes in functional memory, problem solving, comprehension, expression, and social communication over the first 2 years posttraumatic brain injury (TBI) and the ability of each to predict return to work (RTW) outcomes at 1 year and 5 years postinjury.

DESIGN: Secondary analysis of data from a multicenter longitudinal cohort study.

SETTING: Acute inpatient rehabilitation facilities and community follow-up.

PARTICIPANTS: A total of 3543 individuals between 16 and 60 years of age who were competitively employed at the time of TBI and had completed year 1, year 2, and year 5 postinjury follow-ups.

MAIN OUTCOME MEASURES: Year 1 and year 5 RTW status (± competitively employed) at the time of study completion.

RESULTS: Greater function across each of the 5 cognitive-communication abilities was associated with RTW success at 1 year and 5 years post-TBI. At discharge, these 5 abilities showed comparable odds of predicting later employment. At year 1 and year 2 follow-ups, independence with problem solving was the most predictive of employment 5 years post-TBI, followed by social interaction, memory, expression, and comprehension.

CONCLUSIONS: An increased rehabilitation focus on functional memory, problem solving, comprehension, expression, and social interaction post-TBI has the potential to improve RTW outcomes.

PMID:33528176 | PMC:PMC8327472 | DOI:10.1097/HTR.0000000000000641

JMIR Res Protoc. 2021 Jan 14;10(1):e25746. doi: 10.2196/25746.

ABSTRACT

BACKGROUND: Every year, approximately 42 million people sustain a mild traumatic brain injury (mTBI, also known as concussion), with particularly high rates among college-aged individuals. A substantial proportion of these people (44%-64%) develop persistent symptoms that are challenging to treat, costly, and associated with significant disability. Anxiety has emerged as a risk factor for progression from acute to persistent mTBI symptoms.

OBJECTIVE: This study aims to develop, adapt, and establish the feasibility of the Toolkit for Optimal Recovery after Concussions (TOR-C), an innovative mind-body program aimed at preventing persistent symptoms among young adults with mTBI and comorbid anxiety. Here, we describe the proposed study design, methodology, measurement, and treatment manuals.

METHODS: In phase 1, we will conduct individual, live video qualitative interviews (up to n=20) with college-aged individuals with mTBI and comorbid anxiety to inform adaptation of the intervention and study procedures. In phase 2, an open pilot of the live video TOR-C (n=5) with exit interviews will be conducted to explore the initial feasibility, acceptability, and credibility of the program and to refine the study procedures. Phase 3 will involve conducting a feasibility randomized controlled trial (N=50) of the TOR-C versus a health education control (Health Enhancement for Concussions; HE-C), both delivered via live video, to establish feasibility of recruitment procedures (screening, eligibility, and enrollment) and data collection; feasibility, credibility, and acceptability of the live video TOR-C and HE-C (adherence, retention, fidelity, and satisfaction) following prespecified benchmarks; and a signal of improvement in outcomes.

RESULTS: Phase 1 of the study has been approved by the Massachusetts General Hospital Institutional Review Board. Study completion is anticipated by early 2025.

CONCLUSIONS: We will develop and test the first mind-body intervention focused on prevention of persistent symptoms following mTBI in young adults with comorbid anxiety problems. This will allow us to establish feasibility markers in postconcussive symptoms, anxiety, disability, and fear avoidance to inform a future efficacy trial of the TOR-C versus HE-C.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/25746.

PMID:33443484 | PMC:PMC7843203 | DOI:10.2196/25746

J Neurotrauma. 2021 Jun 15;38(12):1620-1631. doi: 10.1089/neu.2020.7373. Epub 2021 Feb 18.

ABSTRACT

Diffusion tractography magnetic resonance imaging (MRI) can infer changes in network connectivity in patients with traumatic brain injury (TBI), but the pathological substrates of disconnected tracts have not been well defined because of a lack of high-resolution imaging with histopathological validation. We developed an ex vivo MRI protocol to analyze tract terminations at 750-μm isotropic resolution, followed by histopathological evaluation of white matter pathology, and applied these methods to a 60-year-old man who died 26 days after TBI. Analysis of 74 cerebral hemispheric white matter regions revealed a heterogeneous distribution of tract disruptions. Associated histopathology identified variable white matter injury with patchy deposition of amyloid precursor protein (APP), loss of neurofilament-positive axonal processes, myelin dissolution, astrogliosis, microgliosis, and perivascular hemosiderin-laden macrophages. Multiple linear regression revealed that tract disruption strongly correlated with the density of APP-positive axonal swellings and neurofilament loss. Ex vivo diffusion MRI can detect tract disruptions in the human brain that reflect axonal injury.

PMID:33412995 | PMC:PMC8165468 | DOI:10.1089/neu.2020.7373

Neuroimage Clin. 2020;28:102503. doi: 10.1016/j.nicl.2020.102503. Epub 2020 Nov 19.

ABSTRACT

BACKGROUND: It is not currently possible to predict which patients will develop chronic disorders of consciousness (DoC) after severe traumatic brain injury (TBI). Although the ascending arousal network (AAN) supports human consciousness, it is unknown which AAN pathways must be preserved for patients to recover consciousness.

METHODS: Sixteen patients with acute traumatic coma and 16 matched healthy controls were scanned with high angular resolution diffusion imaging (HARDI). All patients recovered consciousness (Recovery Cohort). Nine were scanned longitudinally: first in the ICU (Acute), then at ≥5 months post-injury (Follow-up). Six separate patients with post-traumatic DoC were scanned ≥5 months post-injury (Chronic DoC Cohort). For each AAN pathway, we computed the median relative change in Acute-to-Follow-up Connectivity Probability (CP) in the Recovery Cohort. We then used Wilcoxon tests with Bonferroni correction to compare CP in each AAN pathway in the Recovery Cohort at Follow-up versus the Chronic DoC Cohort. In an exploratory analysis, we used principal component analysis (PCA) to determine whether linear combinations of AAN CP values could separate the Chronic DoC Cohort from the Recovery Cohort and the healthy controls.

RESULTS: In the Recovery Cohort, the largest relative AAN CP changes were in the brainstem-to-thalamus (median [IQR] = 0.7 [0.09, 0.9]) and forebrain-to-occipital lobe (-0.8 [-0.9, -0.8]) pathways. The AAN connections that differed in the cross-sectional analysis between the Recovery Cohort at Follow-up and the Chronic DoC Cohort included brainstem-to-hypothalamus (W = 53, P_Bonf = 0.02), brainstem-to-temporal lobe (W = 52, P_Bonf = 0.04), and thalamus-to-temporal lobe (W = 54, P_Bonf = 0.009). Plotting the first two principal components of AAN connectivity resulted in a linear separation of Chronic DoC patients from other study groups.

CONCLUSIONS: We provide evidence for a longitudinal increase in brainstem-thalamic connectivity during recovery of consciousness after traumatic coma. Cross-sectional analyses revealed that brainstem-hypothalamus, brainstem-temporal lobe, and thalamus-temporal lobe connectivity differed between patients who recovered consciousness and those with a chronic DoC. These observations provide the basis for further investigation into AAN connectivity as a biomarker for recovery of consciousness after traumatic coma.

PMID:33395992 | PMC:PMC7724378 | DOI:10.1016/j.nicl.2020.102503

Biol Psychiatry Cogn Neurosci Neuroimaging. 2021 Mar;6(3):352-359. doi: 10.1016/j.bpsc.2020.10.008. Epub 2020 Oct 27.

ABSTRACT

BACKGROUND: Brain volumes in regions such as the hippocampus and amygdala have been associated with risk for the development of posttraumatic stress disorder (PTSD). The objective of this study was to determine whether a set of regional brain volumes, measured by magnetic resonance imaging at 2 weeks following mild traumatic brain injury, were predictive of PTSD at 3 and 6 months after injury.

METHODS: Using data from TRACK-TBI (Transforming Research and Clinical Knowledge in TBI), we included patients (N = 421) with Glasgow Coma Scale scores 13-15 assessed after evaluation in the emergency department and at 2 weeks, 3 months, and 6 months after injury. Probable PTSD diagnosis (PTSD Checklist for DSM-5 score, ≥33) was the outcome. FreeSurfer 6.0 was used to perform volumetric analysis of three-dimensional T1-weighted magnetic resonance images at 3T obtained 2 weeks post injury. Brain regions selected a priori for volumetric analyses were insula, hippocampus, amygdala, superior frontal cortex, rostral and caudal anterior cingulate, and lateral and medial orbitofrontal cortices.

RESULTS: Overall, 77 (18.3%) and 70 (16.6%) patients had probable PTSD at 3 and 6 months. A composite volume derived as the first principal component incorporating 73.8% of the variance in insula, superior frontal cortex, and rostral and caudal cingulate contributed to the prediction of 3-month (but not 6-month) PTSD in multivariable models incorporating other established risk factors.

CONCLUSIONS: Results, while needing replication, provide support for a brain reserve hypothesis of PTSD and proof of principle for how prediction of at-risk individuals might be accomplished to enhance prognostic accuracy and enrich clinical prevention trials for individuals at the highest risk of PTSD following mild traumatic brain injury.

PMID:33386283 | PMC:PMC7946719 | DOI:10.1016/j.bpsc.2020.10.008

PLoS One. 2020 Dec 14;15(12):e0242811. doi: 10.1371/journal.pone.0242811. eCollection 2020.

ABSTRACT

INTRODUCTION: The high failure rate of clinical trials in traumatic brain injury (TBI) may be attributable, in part, to the use of untested or insensitive measurement instruments. Of more than 1,000 clinical outcome assessment measures (COAs) for TBI, few have been systematically vetted to determine their performance within specific "contexts of use (COU)." As described in guidance issued by the U.S. Food and Drug Administration (FDA), the COU specifies the population of interest and the purpose for which the COA will be employed. COAs are commonly used for screening, diagnostic categorization, outcome prediction, and establishing treatment effectiveness. COA selection typically relies on expert consensus; there is no established methodology to match the appropriateness of a particular COA to a specific COU. We developed and pilot-tested the Evidence-Based Clinical Outcome assessment Platform (EB-COP) to systematically and transparently evaluate the suitability of TBI COAs for specific purposes.

METHODS AND FINDINGS: Following a review of existing literature and published guidelines on psychometric standards for COAs, we developed a 6-step, semi-automated, evidence-based assessment platform to grade COA performance for six specific purposes: diagnosis, symptom detection, prognosis, natural history, subgroup stratification and treatment effectiveness. Mandatory quality indicators (QIs) were identified for each purpose using a modified Delphi consensus-building process. The EB-COP framework was incorporated into a Qualtrics software platform and pilot-tested on the Glasgow Outcome Scale-Extended (GOSE), the most widely-used COA in TBI clinical studies.

CONCLUSION: The EB-COP provides a systematic methodology for conducting more precise, evidence-based assessment of COAs by evaluating performance within specific COUs. The EB-COP platform was shown to be feasible when applied to a TBI COA frequently used to detect treatment effects and can be modified to address other populations and COUs. Additional testing and validation of the EB-COP are warranted.

PMID:33315925 | PMC:PMC7735614 | DOI:10.1371/journal.pone.0242811

Arch Phys Med Rehabil. 2021 Feb;102(2):339-340. doi: 10.1016/j.apmr.2020.10.111. Epub 2020 Nov 21.

NO ABSTRACT

PMID:33234247 | DOI:10.1016/j.apmr.2020.10.111

J Neurotrauma. 2021 Apr 1;38(7):918-927. doi: 10.1089/neu.2020.7177. Epub 2020 Dec 28.

ABSTRACT

Systemic inflammation impacts outcome after traumatic brain injury (TBI), but most TBI biomarker studies have focused on brain-specific proteins. C-reactive protein (CRP) is a widely used biomarker of inflammation with potential as a prognostic biomarker after TBI. The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study prospectively enrolled TBI patients within 24 h of injury, as well as orthopedic injury and uninjured controls; biospecimens were collected at enrollment. A subset of hospitalized participants had blood collected on day 3, day 5, and 2 weeks. High-sensitivity CRP (hsCRP) and glial fibrillary acidic protein (GFAP) were measured. Receiver operating characteristic analysis was used to evaluate the prognostic ability of hsCRP for 6-month outcome, using the Glasgow Outcome Scale-Extended (GOSE). We included 1206 TBI subjects, 122 orthopedic trauma controls (OTCs), and 209 healthy controls (HCs). Longitudinal biomarker sampling was performed in 254 hospitalized TBI subjects and 19 OTCs. hsCRP rose between days 1 and 5 for TBI and OTC subjects, and fell by 2 weeks, but remained elevated compared with HCs (p < 0.001). Longitudinally, hsCRP was significantly higher in the first 2 weeks for subjects with death/severe disability (GOSE <5) compared with those with moderate disability/good recovery (GOSE ≥5); AUC was highest at 2 weeks (AUC = 0.892). Combining hsCRP and GFAP at 2 weeks produced AUC = 0.939 for prediction of disability. Serum hsCRP measured within 2 weeks of TBI is a prognostic biomarker for disability 6 months later. hsCRP may have utility as a biomarker of target engagement for anti-inflammatory therapies.

PMID:33161875 | PMC:PMC7987360 | DOI:10.1089/neu.2020.7177

J Neurotrauma. 2021 Apr 15;38(8):1048-1059. doi: 10.1089/neu.2020.7295. Epub 2020 Dec 14.

ABSTRACT

Our objective was to examine the construct validity of the Brief Test of Adult Cognition by Telephone (BTACT) and its relationship to traumatic brain injury (TBI) of differing severities. Data were analyzed on 1422 patients with TBI and 170 orthopedic trauma controls (OTC) from the multi-center Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study. Participants were assessed at 6 months post-injury with the BTACT and an in-person neuropsychological battery. We examined the BTACT's factor structure, factorial group invariance, convergent and discriminant validity, and relationship to TBI and TBI severity. Confirmatory factor analysis supported both a 1-factor model and a 2-factor model comprising correlated Episodic Memory and Executive Function (EF) factors. Both models demonstrated strict invariance across TBI severity and OTC groups. Correlations between BTACT and criterion measures suggested that the BTACT memory indices predominantly reflect verbal episodic memory, whereas the BTACT EF factor correlated with a diverse range of cognitive tests. Although the EF factor and other BTACT indices showed significant relationships with TBI and TBI severity, some group effect sizes were larger for more comprehensive in-person cognitive tests than the BTACT. The BTACT is a promising, brief, phone-based cognitive screening tool for patients with TBI. Although the BTACT's memory items appear to index verbal Episodic Memory, items that purport to assess EFs may reflect a broader array of cognitive domains. The sensitivity of the BTACT to TBI severity is lower than domain-specific neuropsychological measures, suggesting it should not be used as a substitute for comprehensive, in-person cognitive testing at 6 months post-TBI.

PMID:33107388 | PMC:PMC8054514 | DOI:10.1089/neu.2020.7295

J Neurotrauma. 2021 Mar;38(5):546-554. doi: 10.1089/neu.2020.7055. Epub 2020 Dec 14.

ABSTRACT

Identifying the principal determinants of life satisfaction following mild TBI (mTBI) may inform efforts to improve subjective well-being in this population. We examined life satisfaction among participants in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study who presented with mTBI (Glasgow Coma Scale [GCS] score = 13-15; n = 1152). An L1-regularization path algorithm was used to select optimal sets of baseline and concurrent symptom measures for prediction of scores on the Satisfaction with Life Scale (SWLS) at 2 weeks and 3, 6, and 12 months post-injury. Multi-variable linear regression models (all n = 744-894) were then fit to evaluate associations between the empirically selected predictors and SWLS scores at each follow-up visit. Results indicated that emotional post-TBI symptoms (all b = -1.27 to -0.77, all p < 0.05), anhedonia (all b = -1.59 to -1.08, all p < 0.01), and pain interference (all b = -1.38 to -0.89, all p < 0.001) contributed to the prediction of lower SWLS scores at all follow-ups. Insomnia predicted lower SWLS scores at 2 weeks, 3 months, and 6 months (all b = -1.11 to -0.83, all ps < 0.01); and negative affect predicted lower SWLS scores at 2 weeks, 3 months, and 12 months (all b = -1.38 to -0.80, all p < 0.005). Other post-TBI symptom domains and baseline socio-demographic, injury-related, and clinical characteristics did not emerge as robust predictors of SWLS scores during the year after mTBI. Efforts to improve satisfaction with life following mTBI may benefit from a focus on the detection and treatment of affective symptoms, pain, and insomnia. The results reinforce the need for tailoring of evidence-based treatments for these conditions to maximize efficacy in patients with mTBI.

PMID:33107371 | PMC:PMC7898402 | DOI:10.1089/neu.2020.7055

Arch Phys Med Rehabil. 2021 Jan;102(1):87-96. doi: 10.1016/j.apmr.2020.09.377. Epub 2020 Oct 3.

ABSTRACT

OBJECTIVE: To develop a measure of global functioning after moderate-severe TBI with similar measurement precision but a longer measurement range than the FIM.

DESIGN: Phase 1: retrospective analysis of 5 data sets containing FIM, Disability Rating Scale, and other assessment items to identify candidate items for extending the measurement range of the FIM; Phase 2: prospective administration of 49 candidate items from phase 1, with Rasch analysis to identify a unidimensional scale with an extended range.

SETTING: Six TBI Model System rehabilitation hospitals.

PARTICIPANTS: Individuals (N=184) with moderate-severe injury recruited during inpatient rehabilitation or at 1-year telephone follow-up.

INTERVENTIONS: Participants were administered the 49 assessment items in person or via telephone.

MAIN OUTCOME MEASURES: Item response theory parameters: item monotonicity, infit/outfit statistics, and Factor 1 variance.

RESULTS: After collapsing misordered rating categories and removing misfitting items, we derived the Brain Injury Functional Outcome Measure (BI-FOM), a 31-item assessment instrument with high reliability, greatly extended measurement range, and improved unidimensionality compared with the FIM.

CONCLUSIONS: The BI-FOM improves global measurement of function after moderate-severe brain injury. Its high precision, relative lack of floor and ceiling effects, and feasibility for telephone follow-up, if replicated in an independent sample, are substantial advantages.

PMID:33022273 | PMC:PMC9255898 | DOI:10.1016/j.apmr.2020.09.377

J Neurotrauma. 2021 Jan 15;38(2):196-209. doi: 10.1089/neu.2020.7074. Epub 2020 Oct 19.

ABSTRACT

The majority of traumatic brain injuries (TBIs) are categorized as mild, according to a baseline Glasgow Coma Scale (GCS) score of 13-15. Prognostic models that were developed to predict functional outcome and persistent post-concussive symptoms (PPCS) after mild TBI have rarely been externally validated. We aimed to externally validate models predicting 3-12-month Glasgow Outcome Scale Extended (GOSE) or PPCS in adults with mild TBI. We analyzed data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) project, which included 2862 adults with mild TBI, with 6-month GOSE available for 2374 and Rivermead Post-Concussion Symptoms Questionnaire (RPQ) results available for 1605 participants. Model performance was evaluated based on calibration (graphically and characterized by slope and intercept) and discrimination (C-index). We validated five published models for 6-month GOSE and three for 6-month PPCS scores. The models used different cutoffs for outcome and some included symptoms measured 2 weeks post-injury. Discriminative ability varied substantially (C-index between 0.58 and 0.79). The models developed in the Corticosteroid Randomisation After Significant Head Injury (CRASH) trial for prediction of GOSE <5 discriminated best (C-index 0.78 and 0.79), but were poorly calibrated. The best performing models for PPCS included 2-week symptoms (C-index 0.75 and 0.76). In conclusion, none of the prognostic models for early prediction of GOSE and PPCS has both good calibration and discrimination in persons with mild TBI. In future studies, prognostic models should be tailored to the population with mild TBI, predicting relevant end-points based on readily available predictors.

PMID:32977737 | DOI:10.1089/neu.2020.7074

Neuroimage Clin. 2020;28:102426. doi: 10.1016/j.nicl.2020.102426. Epub 2020 Sep 15.

ABSTRACT

BACKGROUND: Transcranial direct current stimulation (tDCS) may promote the recovery of severely brain-injured patients with disorders of consciousness (DOC). Prior tDCS studies targeted single brain regions rather than brain networks critical for consciousness recovery.

OBJECTIVE: Investigate the behavioral and electrophysiological effects of multifocal tDCS applied over the frontoparietal external awareness network in patients with chronic acquired DOC.

METHODS: Forty-six patients were included in this randomized double-blind sham-controlled crossover trial (median [interquartile range]: 46 [35 - 59] years old; 12 [5 - 47] months post injury; 17 unresponsive wakefulness syndrome, 23 minimally conscious state (MCS) and 6 emerged from the MCS). Multifocal tDCS was applied for 20 min using 4 anodes and 4 cathodes with 1 mA per electrode. Coma Recovery Scale-Revised (CRS-R) assessment and 10 min of resting state electroencephalogram (EEG) recordings were acquired before and after the active and sham sessions.

RESULTS: At the group level, there was no tDCS behavioral treatment effect. However, following active tDCS, the EEG complexity significantly increased in low frequency bands (1-8 Hz). CRS-R total score improvement was associated with decreased baseline complexity in those bands. At the individual level, after active tDCS, new behaviors consistent with conscious awareness emerged in 5 patients. Conversely, 3 patients lost behaviors consistent with conscious awareness.

CONCLUSION: The behavioral effect of multifocal frontoparietal tDCS varies across patients with DOC. Electrophysiological changes were observed in low frequency bands but not translated into behavioral changes at the group level.

PMID:32977212 | PMC:PMC7511767 | DOI:10.1016/j.nicl.2020.102426

Mult Scler J Exp Transl Clin. 2020 Aug 31;6(3):2055217320934835. doi: 10.1177/2055217320934835. eCollection 2020 Jul-Sep.

ABSTRACT

BACKGROUND: A sensitive test reflecting subtle sensorimotor changes throughout disease progression independent of mobility impairment is currently lacking in progressive multiple sclerosis.

OBJECTIVES: We examined non-ambulatory measures of upper and lower extremity sensorimotor function that may reveal differences between relapsing-remitting and progressive forms of multiple sclerosis.

METHODS: Cutaneous sensitivity, proprioception, central motor function and mobility were assessed in 32 relapsing-remitting and 31 progressive multiple sclerosis patients and 30 non-multiple sclerosis controls.

RESULTS: Cutaneous sensation differed between relapsing-remitting and progressive multiple sclerosis at the foot and to a lesser extent the hand. Proprioception function in the upper but not the lower extremity differed between relapsing-remitting and progressive multiple sclerosis, but was different for both upper and lower extremities between multiple sclerosis patients and non-multiple sclerosis controls. Foot-tap but not hand-tap speed was slower in progressive compared to relapsing-remitting multiple sclerosis, suggestive of greater central motor function impairment in the lower extremity in progressive multiple sclerosis. In addition, the non-ambulatory sensorimotor measures were more sensitive in detecting differences between relapsing-remitting and progressive multiple sclerosis than mobility assessed with the 25-foot walk test.

CONCLUSION: This study provides novel information about changes in sensorimotor function in progressive compared with relapsing-remitting forms of multiple sclerosis, and in particular the importance of assessing both upper and lower extremity function. Importantly, our findings showed loss of proprioceptive function in multiple sclerosis but also in progressive compared to relapsing-remitting multiple sclerosis.

PMID:32944271 | PMC:PMC7466899 | DOI:10.1177/2055217320934835

J Neurotrauma. 2021 Apr 1;38(7):858-869. doi: 10.1089/neu.2020.7287. Epub 2020 Nov 13.

ABSTRACT

Few studies have assessed the long-term functional outcomes of traumatic brain injury (TBI) in large, well-characterized samples. Using the Traumatic Brain Injury Model Systems cohort, this study assessed the maintenance of independence between years 5 and 15 post-injury and risk factors for decline. The study sample included 1381 persons with TBI who received inpatient rehabilitation, survived to 15 years post-injury, and were available for data collection at 5 or 10 years and 15 years post-injury. The Functional Independence Measure (FIM) and Disability Rating Scale (DRS) were used to measure functional outcomes. The majority of participants had no changes during the 10-year time frame. For FIM, only 4.4% showed decline in Self-Care, 4.9% declined in Mobility, and 5.9% declined in Cognition. Overall, 10.4% showed decline in one or more FIM subscales. Decline was detected by DRS Level of Function (24% with >1-point change) and Employability (6% with >1-point change). Predictors of decline factors across all measures were age >25 years and, across most measures, having less than or equal to a high school education. Additional predictors of FIM decline included male sex (FIM Mobility and Self-Care) and longer rehabilitation length of stay (FIM Mobility and Cognition). In contrast to studies reporting change in the first 5 years post-TBI inpatient rehabilitation, a majority of those who survive to 15 years do not experience functional decline. Aging and cognitive reserve appear to be more important drivers of loss of function than original severity of the injury. Interventions to identify those at risk for decline may be needed to maintain or enhance functional status as persons age with a TBI.

PMID:32907468 | DOI:10.1089/neu.2020.7287

J Neurotrauma. 2020 Dec 1;37(23):2460-2467. doi: 10.1089/neu.2020.7140. Epub 2020 Sep 14.

ABSTRACT

Glial fibrillary acidic protein (GFAP) is cleared by the Food and Drug Administration (FDA) to determine need for head computed tomography (CT) within 12 h after mild traumatic brain injury (TBI) (Glasgow Coma Score [GCS] 13-15); S100 calcium-binding protein B (S100B) serves this function in Europe. This phase 1 biomarker cohort analysis of the multi-center, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study compares GFAP's diagnostic performance, measured on a rapid point-of-care platform, against protein S100B to predict intracranial abnormalities on CT within 24 h post-injury across the spectrum of TBI (GCS 3-15). Head CT scan performed in TBI subjects and blood was collected for all consenting subjects presenting to 18 United States level 1 trauma centers. Plasma was analyzed on a point-of-care device prototype assay for GFAP and serum was analyzed for S100B. In 1359 patients with TBI (GCS 3-15), mean (standard deviation [SD]) age = 40.1 (17.0) years; 68% were male. Plasma GFAP levels were significantly higher in CT+ TBI subjects (median = 1358 pg/mL, interquartile range [IQR]: 472-3803) than in CT- TBI subjects (median = 116 pg/mL, IQR: 26-397) or orthopedic trauma controls (n = 122; median = 13 pg/mL, IQR: 7-20), p < 0.001. Serum S100B levels were likewise higher in CT+ TBI subjects (median = 0.17 μg/L, IQR: 0.09-0.38) than in CT- TBI subjects (median = 0.10 μg/L, IQR: 0.06-0.18), p < 0.001. Receiver operating characteristic curves were generated for prediction of intracranial injury on admission CT scan; area under the curve (AUC) for GFAP was significantly higher than for S100B in the same cohort (GFAP AUC - 0.85, 95% confidence interval [CI] 0.83-0.87; S100B AUC - 0.67, 95% CI 0.64-0.70; p < 0.001). GFAP, measured on a point-of-care platform prototype assay, has high discriminative ability to predict intracranial abnormalities on CT scan in patients with TBI across the full injury spectrum of GCS 3-15 through 24 h post-injury. GFAP substantially outperforms S100B.

PMID:32854584 | PMC:PMC7698990 | DOI:10.1089/neu.2020.7140

Conf Rec Asilomar Conf Signals Syst Comput. 2019 Nov;2019:240-244. doi: 10.1109/ieeeconf44664.2019.9048807. Epub 2020 Mar 30.

ABSTRACT

Dynamic functional connectivity (DFC) analysis involves measuring correlated neural activity over time across multiple brain regions. Significant regional correlations among neural signals, such as those obtained from resting-state functional magnetic resonance imaging (fMRI), may represent neural circuits associated with rest. The conventional approach of estimating the correlation dynamics as a sequence of static correlations from sliding time-windows has statistical limitations. To address this issue, we propose a multivariate stochastic volatility model for estimating DFC inspired by recent work in econometrics research. This model assumes a state-space framework where the correlation dynamics of a multivariate normal observation sequence is governed by a positive-definite matrix-variate latent process. Using this statistical model within a sequential Bayesian estimation framework, we use blood oxygenation level dependent activity from multiple brain regions to estimate posterior distributions on the correlation trajectory. We demonstrate the utility of this DFC estimation framework by analyzing its performance on simulated data, and by estimating correlation dynamics in resting state fMRI data from a patient with a disorder of consciousness (DoC). Our work advances the state-of-the-art in DFC analysis and its principled use in DoC biomarker exploration.

PMID:32801606 | PMC:PMC7425228 | DOI:10.1109/ieeeconf44664.2019.9048807

Neurocrit Care. 2020 Oct;33(2):364-375. doi: 10.1007/s12028-020-01062-7. Epub 2020 Aug 13.

ABSTRACT

There are currently no therapies proven to promote early recovery of consciousness in patients with severe brain injuries in the intensive care unit (ICU). For patients whose families face time-sensitive, life-or-death decisions, treatments that promote recovery of consciousness are needed to reduce the likelihood of premature withdrawal of life-sustaining therapy, facilitate autonomous self-expression, and increase access to rehabilitative care. Here, we present the Connectome-based Clinical Trial Platform (CCTP), a new paradigm for developing and testing targeted therapies that promote early recovery of consciousness in the ICU. We report the protocol for STIMPACT (Stimulant Therapy Targeted to Individualized Connectivity Maps to Promote ReACTivation of Consciousness), a CCTP-based trial in which intravenous methylphenidate will be used for targeted stimulation of dopaminergic circuits within the subcortical ascending arousal network (ClinicalTrials.gov NCT03814356). The scientific premise of the CCTP and the STIMPACT trial is that personalized brain network mapping in the ICU can identify patients whose connectomes are amenable to neuromodulation. Phase 1 of the STIMPACT trial is an open-label, safety and dose-finding study in 22 patients with disorders of consciousness caused by acute severe traumatic brain injury. Patients in Phase 1 will receive escalating daily doses (0.5-2.0 mg/kg) of intravenous methylphenidate over a 4-day period and will undergo resting-state functional magnetic resonance imaging and electroencephalography to evaluate the drug's pharmacodynamic properties. The primary outcome measure for Phase 1 relates to safety: the number of drug-related adverse events at each dose. Secondary outcome measures pertain to pharmacokinetics and pharmacodynamics: (1) time to maximal serum concentration; (2) serum half-life; (3) effect of the highest tolerated dose on resting-state functional MRI biomarkers of connectivity; and (4) effect of each dose on EEG biomarkers of cerebral cortical function. Predetermined safety and pharmacodynamic criteria must be fulfilled in Phase 1 to proceed to Phase 2A. Pharmacokinetic data from Phase 1 will also inform the study design of Phase 2A, where we will test the hypothesis that personalized connectome maps predict therapeutic responses to intravenous methylphenidate. Likewise, findings from Phase 2A will inform the design of Phase 2B, where we plan to enroll patients based on their personalized connectome maps. By selecting patients for clinical trials based on a principled, mechanistic assessment of their neuroanatomic potential for a therapeutic response, the CCTP paradigm and the STIMPACT trial have the potential to transform the therapeutic landscape in the ICU and improve outcomes for patients with severe brain injuries.

PMID:32794142 | PMC:PMC8336723 | DOI:10.1007/s12028-020-01062-7

J Head Trauma Rehabil. 2021 Jan-Feb 01;36(1):E30-E39. doi: 10.1097/HTR.0000000000000602.

ABSTRACT

OBJECTIVE: To identify risk factors for suicidal ideation (SI) following mild traumatic brain injury (mTBI).

SETTING: Eleven US level 1 trauma centers.

PARTICIPANTS: A total of 1158 emergency department patients with mTBI (Glasgow Coma Scale score = 13-15) enrolled in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study.

DESIGN: Prospective observational study; weights-adjusted multivariable logistic regression models (n's = 727-883) estimated associations of baseline factors and post-TBI symptoms with SI at 2 weeks and 3, 6, and 12 months postinjury.

MAIN MEASURES: Patient Health Questionnaire, Rivermead Post-Concussion Symptoms Questionnaire.

RESULTS: Preinjury psychiatric history predicted SI at all follow-ups (adjusted odds ratios [AORs] = 2.26-6.33, P values <.05) and history of prior TBI predicted SI at 2 weeks (AOR = 2.36, 95% confidence interval [CI] = 1.16-4.81, P = .018), 3 months (AOR = 2.62, 95% CI = 1.33-5.16, P = .005), and 6 months postinjury (AOR = 2.54, 95% CI = 1.19-5.42, P = .016). Adjusting for these baseline factors, post-TBI symptoms were strongly associated with SI at concurrent (AORs = 1.91-2.88 per standard deviation unit increase in Rivermead Post-Concussion Symptoms Questionnaire score; P values <.0005) and subsequent follow-up visits (AORs = 1.68-2.53; P values <.005). Most of the associations between post-TBI symptoms and SI were statistically explained by co-occurring depression.

CONCLUSION: Screening for psychiatric and prior TBI history may help identify patients at risk for SI following mTBI. Awareness of the strong associations of post-TBI symptoms with SI may facilitate interventions to prevent suicide-related outcomes in patients with mTBI.

PMID:32769835 | PMC:PMC10134479 | DOI:10.1097/HTR.0000000000000602

J Head Trauma Rehabil. 2021 Jan-Feb 01;36(1):E50-E60. doi: 10.1097/HTR.0000000000000586.

ABSTRACT

OBJECTIVES: To compare characteristics of those who do and do not sustain subsequent traumatic brain injuries (TBIs) following index TBI and to identify reinjury risk factors.

DESIGN: Secondary data analysis of an ongoing longitudinal cohort study.

SETTING: TBI Model Systems Centers.

PARTICIPANTS: In total, 11 353 individuals aged 16+ years.

MAIN OUTCOME MEASURES: Ohio State University TBI Identification Method.

RESULTS: In total, 7.9% of individuals reported sustaining a TBI post-index TBI. Twenty percent of reinjuries occurred within a year of the index TBI. Reinjury risk followed an approximate U-shaped distribution such that risk was higher in the first year, declined 2 to 10 years postinjury, and then increased after 10 years. A multivariable Weibull model identified predictors of reinjury: younger (<29 years) and middle-aged and older (50+ years) age at index TBI relative to middle age, pre-index TBI, pre-index alcohol and illicit drug use, incarceration history, and less severe index TBI.

CONCLUSIONS: A subset of individuals who receive inpatient rehabilitation for TBI are at an increased risk for reinjury, and an injury-prone phenotype may be characterized by engagement in risk behaviors. Factors associated with reinjury risk may differ for younger versus middle-aged and older adults. Findings underscore the need for empirically informed risk stratification models to identify TBI survivors at risk for reinjury.

PMID:32769829 | DOI:10.1097/HTR.0000000000000586

Arch Phys Med Rehabil. 2020 Nov;101(11):2041-2050. doi: 10.1016/j.apmr.2020.06.021. Epub 2020 Jul 29.

ABSTRACT

In response to the need to better define the natural history of emerging consciousness after traumatic brain injury and to better describe the characteristics of the condition commonly labeled posttraumatic amnesia, a case definition and diagnostic criteria for the posttraumatic confusional state (PTCS) were developed. This project was completed by the Confusion Workgroup of the American Congress of Rehabilitation Medicine Brain Injury Interdisciplinary Special Interest group. The case definition was informed by an exhaustive literature review and expert opinion of workgroup members from multiple disciplines. The workgroup reviewed 2466 abstracts and extracted evidence from 44 articles. Consensus was reached through teleconferences, face-to-face meetings, and 3 rounds of modified Delphi voting. The case definition provides detailed description of PTCS (1) core neurobehavioral features, (2) associated neurobehavioral features, (3) functional implications, (4) exclusion criteria, (5) lower boundary, and (6) criteria for emergence. Core neurobehavioral features include disturbances of attention, orientation, and memory as well as excessive fluctuation. Associated neurobehavioral features include emotional and behavioral disturbances, sleep-wake cycle disturbance, delusions, perceptual disturbances, and confabulation. The lower boundary distinguishes PTCS from the minimally conscious state, while upper boundary is marked by significant improvement in the 4 core and 5 associated features. Key research goals are establishment of cutoffs on assessment instruments and determination of levels of behavioral function that distinguish persons in PTCS from those who have emerged to the period of continued recovery.

PMID:32738198 | DOI:10.1016/j.apmr.2020.06.021

Neurology. 2020 Sep 15;95(11):e1538-e1553. doi: 10.1212/WNL.0000000000010256. Epub 2020 Jul 16.

ABSTRACT

OBJECTIVE: To develop and evaluate a model for staging cortical amyloid deposition using PET with high generalizability.

METHODS: Three thousand twenty-seven individuals (1,763 cognitively unimpaired [CU], 658 impaired, 467 with Alzheimer disease [AD] dementia, 111 with non-AD dementia, and 28 with missing diagnosis) from 6 cohorts (European Medical Information Framework for AD, Alzheimer's and Family, Alzheimer's Biomarkers in Daily Practice, Amsterdam Dementia Cohort, Open Access Series of Imaging Studies [OASIS]-3, Alzheimer's Disease Neuroimaging Initiative [ADNI]) who underwent amyloid PET were retrospectively included; 1,049 individuals had follow-up scans. With application of dataset-specific cutoffs to global standard uptake value ratio (SUVr) values from 27 regions, single-tracer and pooled multitracer regional rankings were constructed from the frequency of abnormality across 400 CU individuals (100 per tracer). The pooled multitracer ranking was used to create a staging model consisting of 4 clusters of regions because it displayed a high and consistent correlation with each single-tracer ranking. Relationships between amyloid stage, clinical variables, and longitudinal cognitive decline were investigated.

RESULTS: SUVr abnormality was most frequently observed in cingulate, followed by orbitofrontal, precuneal, and insular cortices and then the associative, temporal, and occipital regions. Abnormal amyloid levels based on binary global SUVr classification were observed in 1.0%, 5.5%, 17.9%, 90.0%, and 100.0% of individuals in stage 0 to 4, respectively. Baseline stage predicted decline in Mini-Mental State Examination (MMSE) score (ADNI: n = 867, F = 67.37, p < 0.001; OASIS: n = 475, F = 9.12, p < 0.001) and faster progression toward an MMSE score ≤25 (ADNI: n = 787, hazard ratio [HR]_stage1 2.00, HR_stage2 3.53, HR_stage3 4.55, HR_stage4 9.91, p < 0.001; OASIS: n = 469, HR_stage4 4.80, p < 0.001).

CONCLUSION: The pooled multitracer staging model successfully classified the level of amyloid burden in >3,000 individuals across cohorts and radiotracers and detects preglobal amyloid burden and distinct risk profiles of cognitive decline within globally amyloid-positive individuals.

PMID:32675080 | PMC:PMC7713745 | DOI:10.1212/WNL.0000000000010256

Neurology. 2020 Sep 15;95(11):e1488-e1499. doi: 10.1212/WNL.0000000000010254. Epub 2020 Jul 13.

ABSTRACT

OBJECTIVE: This international multicenter, prospective, observational study aimed at identifying predictors of short-term clinical outcome in patients with prolonged disorders of consciousness (DoC) due to acquired severe brain injury.

METHODS: Patients in vegetative state/unresponsive wakefulness syndrome (VS/UWS) or in minimally conscious state (MCS) were enrolled within 3 months from their brain injury in 12 specialized medical institutions. Demographic, anamnestic, clinical, and neurophysiologic data were collected at study entry. Patients were then followed up for assessing the primary outcome, that is, clinical diagnosis according to standardized criteria at 6 months postinjury.

RESULTS: We enrolled 147 patients (44 women; mean age 49.4 [95% confidence interval 46.1-52.6] years; VS/UWS 71, MCS 76; traumatic 55, vascular 56, anoxic 36; mean time postinjury 59.6 [55.4-63.6] days). The 6-month follow-up was complete for 143 patients (VS/UWS 70; MCS 73). With respect to study entry, the clinical diagnosis improved in 72 patients (VS/UWS 27; MCS 45). Younger age, shorter time postinjury, higher Coma Recovery Scale-Revised total score, and presence of EEG reactivity to eye opening at study entry predicted better outcome, whereas etiology, clinical diagnosis, Disability Rating Scale score, EEG background activity, acoustic reactivity, and P300 on event-related potentials were not associated with outcome.

CONCLUSIONS: Multimodal assessment could identify patients with higher likelihood of clinical improvement in order to help clinicians, families, and funding sources with various aspects of decision-making. This multicenter, international study aims to stimulate further research that drives international consensus regarding standardization of prognostic procedures for patients with DoC.

PMID:32661102 | PMC:PMC7713739 | DOI:10.1212/WNL.0000000000010254

Arch Phys Med Rehabil. 2020 Nov;101(11):1973-1979. doi: 10.1016/j.apmr.2020.05.026. Epub 2020 Jul 10.

ABSTRACT

OBJECTIVE: To examine heterogeneity in the temporal patterns of depression and participation over the first 2 years post traumatic brain injury (TBI).

DESIGN: Observational prospective longitudinal study.

SETTING: Inpatient rehabilitation centers, with 1- and 2-year follow-up conducted primarily by telephone.

PARTICIPANTS: Persons with TBI (N=2307) enrolled in the Traumatic Brain Injury Model Systems database, followed at 1 and 2 years post injury.

INTERVENTIONS: Not applicable.

MAIN OUTCOME MEASURE: Patient Health Questionnaire-9 (PHQ-9) and Participation Assessment With Recombined Tools-Objective (PART-O).

RESULTS: Using latent class modeling we examined heterogeneity in the longitudinal relationship between PHQ-9 and PART-O. The identified 6 classes were most distinct in terms of (1) level of PHQ-9 score and (2) association between the year 1 PART-O score and year 2 PHQ-9 score. For most participants, PART-O at year 1 predicted PHQ-9 at year 2 more than the reverse. However, there was a subgroup of participants that demonstrated the reverse pattern, PHQ-9 predicting later PART-O, who were on average, older and in the "other" employment category.

CONCLUSIONS: Results suggest that links between participation and depression are stronger for some people living with TBI than for others and that variation in the temporal sequencing of these 2 constructs is associated with demographic characteristics. These findings illustrate the value in accounting for population heterogeneity when evaluating temporal among outcome domains.

PMID:32653581 | DOI:10.1016/j.apmr.2020.05.026

Ann Neurol. 2020 Oct;88(4):851-854. doi: 10.1002/ana.25838. Epub 2020 Aug 6.

ABSTRACT

Many patients with severe coronavirus disease 2019 (COVID-19) remain unresponsive after surviving critical illness. Although several structural brain abnormalities have been described, their impact on brain function and implications for prognosis are unknown. Functional neuroimaging, which has prognostic significance, has yet to be explored in this population. Here we describe a patient with severe COVID-19 who, despite prolonged unresponsiveness and structural brain abnormalities, demonstrated intact functional network connectivity, and weeks later recovered the ability to follow commands. When prognosticating for survivors of severe COVID-19, clinicians should consider that brain networks may remain functionally intact despite structural injury and prolonged unresponsiveness. ANN NEUROL 2020;88:851-854.

PMID:32613682 | PMC:PMC7361474 | DOI:10.1002/ana.25838

Neurocrit Care. 2020 Aug;33(1):1-12. doi: 10.1007/s12028-020-01028-9.

ABSTRACT

Coma and disordered consciousness are common manifestations of acute neurological conditions and are among the most pervasive and challenging aspects of treatment in neurocritical care. Gaps exist in patient assessment, outcome prognostication, and treatment directed specifically at improving consciousness and cognitive recovery. In 2019, the Neurocritical Care Society (NCS) launched the Curing Coma Campaign in order to address the "grand challenge" of improving the management of patients with coma and decreased consciousness. One of the first steps was to bring together a Scientific Advisory Council including coma scientists, neurointensivists, neurorehabilitationists, and implementation experts in order to address the current scientific landscape and begin to develop a framework on how to move forward. This manuscript describes the proceedings of the first Curing Coma Campaign Scientific Advisory Council meeting which occurred in conjunction with the NCS Annual Meeting in October 2019 in Vancouver. Specifically, three major pillars were identified which should be considered: endotyping of coma and disorders of consciousness, biomarkers, and proof-of-concept clinical trials. Each is summarized with regard to current approach, benefits to the patient, family, and clinicians, and next steps. Integration of these three pillars will be essential to the success of the Curing Coma Campaign as will expanding the "curing coma community" to ensure broad participation of clinicians, scientists, and patient advocates with the goal of identifying and implementing treatments to fundamentally improve the outcome of patients.

PMID:32578124 | PMC:PMC7392933 | DOI:10.1007/s12028-020-01028-9

Am J Speech Lang Pathol. 2020 Aug 4;29(3):1735-1748. doi: 10.1044/2020_AJSLP-19-00020. Epub 2020 Jun 23.

ABSTRACT

Purpose Social communication is the set of abilities that allows individuals to achieve relevant social goals across contexts. Speech-language pathology evaluation and treatment of traumatic brain injury (TBI)-related social communication problems should be informed by evidence-supported theories of social communication. The primary purpose of this article is to summarize the results of a scoping review of theoretical models that speech-language pathologists may apply to the evaluation and treatment of social communication problems of adults with TBI. Method A scoping review was conducted of PubMed, PsycINFO, and Embase for sources published in English between 1989 and 2020 that described human social communication and participation. Resulting sources were systematically examined for social communication models. Results Nine theoretical models were identified that speech-language pathologists may apply to their assessment and treatment of social communication abilities of adults with TBI. Identified models were categorized thematically into one of three classes: cognitive models, social competence models, and pragmatic models. Using a framework developed for the purposes of this article, each identified model was evaluated, and one exemplar model in each class is described in depth. Conclusions Social communication problems in adults post-TBI are common. The existence of multiple models empowers speech-language pathologists to select individual-focused assessment and treatment approaches to maximize intervention outcomes.

PMID:32569483 | DOI:10.1044/2020_AJSLP-19-00020

Assessment. 2021 Sep;28(6):1656-1670. doi: 10.1177/1073191120913941. Epub 2020 Apr 24.

ABSTRACT

This study aimed to elucidate the structure of the Rivermead Postconcussion Symptoms Questionnaire (RPQ) and evaluate its longitudinal and group variance. Factor structures were developed and compared in 1,011 patients with mild traumatic brain injury (mTBI; i.e., Glasgow Coma Scale score 13-15) from the Transforming Research and Clinical Knowledge in TBI study, using RPQ data collected at 2 weeks, and 3, 6, and 12 months postinjury. A bifactor model specifying a general factor and emotional, cognitive, and visual symptom factors best represented the latent structure of the RPQ. The model evinced strict measurement invariance over time and across sex, age, race, psychiatric history, and mTBI severity groups, indicating that differences in symptom endorsement were completely accounted for by these latent dimensions. While highly unidimensional, the RPQ has multidimensional features observable through a bifactor model, which may help differentiate symptom expression patterns in the future.

PMID:32326739 | PMC:PMC7584771 | DOI:10.1177/1073191120913941

J Am Coll Surg. 2020 May;230(5):819-835. doi: 10.1016/j.jamcollsurg.2020.01.032. Epub 2020 Mar 19.

NO ABSTRACT

PMID:32201197 | DOI:10.1016/j.jamcollsurg.2020.01.032

J Neurol. 2020 May;267(5):1255-1259. doi: 10.1007/s00415-020-09760-0.

ABSTRACT

Following electronic publication of the above-referenced manuscript, we discovered that one of the three criteria we proposed to establish command-following in the MCS+ syndrome was inadvertently omitted in some parts of the manuscript.

PMID:32193597 | DOI:10.1007/s00415-020-09760-0

Mult Scler Relat Disord. 2020 Jun;41:102031. doi: 10.1016/j.msard.2020.102031. Epub 2020 Feb 27.

ABSTRACT

BACKGROUND: Rapid tapping tests have been shown to be reliable measures of upper motor neuron disease, and effectively examine motor function differences between multiple sclerosis (MS) and non-MS controls (CON), and between relapsing-remitting and progressive MS subtypes. To successfully perform rapid repetitive movements such as tapping, a person must be able to consistently turn on and off motor units to switch between the up and down movement phases. However, it is not clear which specific movement phase that occurs during tapping is different between MS subtypes. The objective of this study was to quantify and characterize performance differences during rapid hand- and foot-tapping tests between relapsing-remitting (RRMS) and progressive (PMS) forms of MS, as well as how both subtypes differ from non-MS controls.

METHODS: Participants in this study included 30 non-MS controls, 32 RRMS, and 31 PMS. Participants wore inertial sensors on all hands and feet and were instructed to tap as fast as possible for 10 s. Angular velocity from the gyroscope was used to quantify inter-tap interval (ms), coefficient of variation of inter-tap interval (COV), and up- and down-movement characteristics (duration (ms), COV, peak angular velocity (rad/s)). Differences between groups were examined with ANOVA and independent t-tests. Inter-tap interval was examined for its ability to distinguish between RRMS and PMS by a binary logistic regression analysis. Up-down movement characteristics were further evaluated for within-group directional differences (up- vs. down-phase movement components) with paired-sample t-tests.

RESULTS: Inter-tap interval for both hand- and foot-tapping differed between controls and MS, but only foot tapping was different between RRMS and PMS (RRMS = 286.7 ± 83.0 ms; PMS = 379.5 ± 170.9 ms; mean difference (d) = -92.8 ms). Logistic regression analysis showed foot-tap interval but not hand-tap interval has the potential to distinguish between RRMS and PMS (Area under the ROC = 0.71). Both up- and down-movement duration differences were consistent with the results for inter-tap interval, but up-movement duration showed larger mean group differences than down-movement differences. No significant group differences in overall inter-tap interval COV were detected for either hand- or foot-tapping; however, up-movement foot-tapping variation (CON = 18.7 ± 6.1; RRMS = 25.5 ± 11.2; PMS = 23.3 ± 8.6; CON vs RRMS d = -6.8; CON vs PMS d = -4.7), but not down-movement variation was different between controls and MS. Up- and down-peak angular velocity during foot-tapping were different between controls and PMS (CON Up = 1.4 ± 0.5 rad/s; PMS Up = 1.0 ± 0.4 rad/s; Up d = 0.4 rad/s; CON Down= 1.5 ± 0.6 rad/s; PMS Down = 1.2 ± 0.5 rad/s; Down d = 0.3 rad/s), and up-movement peak angular velocity differences showed larger mean group differences than the down-movement peak angular velocity between controls and PMS.

CONCLUSION: Foot-tapping differs between MS disease subtypes and has greater potential than hand-tapping to distinguish between subtypes. Performance in the up-movement showed larger group differences than the down-movement, suggesting that the anti-gravity up-movement during tapping may be more important diagnostically. Future studies should be conducted on the nature of the physiological mechanisms underlying impairments in anti-gravity movements in people with MS.

PMID:32172213 | DOI:10.1016/j.msard.2020.102031

Arch Phys Med Rehabil. 2020 Jul;101(7):1260-1264. doi: 10.1016/j.apmr.2020.01.015. Epub 2020 Feb 28.

ABSTRACT

OBJECTIVE: Characterize the temporal profile of recovery of communication after severe brain injury.

DESIGN: Retrospective cohort study.

SETTING: Inpatient rehabilitation hospital.

PARTICIPANTS: Patients with severe acquired brain injury and no evidence of communication on the Coma Recovery Scale-Revised (CRS-R) (N=175).

MAIN OUTCOME MEASURES: Time from injury to recovery of intentional communication (IC, inconsistent yes/no responses) and functional communication (FC, consistent and accurate yes/no responses) on the CRS-R Communication subscale.

RESULTS: Patients (N=175) were included in the primary observation period of the first 8 weeks of inpatient rehabilitation (median [interquartile range, IQR]: 48 [27-61] years old, 105 men, 28 [21-38] days postinjury, 100 traumatic etiology). Fifty-four patients (31%) did not recover IC or FC. Thirty patients (17%) recovered IC only (median [IQR] days from injury to IC= 40 [34-54]), 72 patients (41%) recovered IC followed by FC (days from injury to FC=50 [42-61]), and 19 patients (11%) recovered FC without first recovering IC (43 [32-63]). The patients who recovered neither IC nor FC within 8 weeks of admission were admitted to rehabilitation later than those who recovered IC and/or FC (P<.01). Sixteen patients who did not recover communication within 8 weeks of admission to rehabilitation subsequently recovered FC prior to discharge.

CONCLUSIONS: In patients with severe brain injury receiving inpatient rehabilitation, discernible yes-no responses emerged approximately 6 weeks postinjury and became reliable 1 week later. Approximately 1 in 3 patients did not demonstrate IC or FC within 8 weeks of admission to rehabilitation, although 33% of these individuals recovered communication prior to discharge. In total, 61% of patients recovered FC prior to discharge from rehabilitation.

PMID:32113971 | DOI:10.1016/j.apmr.2020.01.015

J Head Trauma Rehabil. 2020 Jul/Aug;35(4):254-261. doi: 10.1097/HTR.0000000000000566.

ABSTRACT

OBJECTIVE: To examine the association between social Internet use and real-world societal participation in survivors of moderate-severe traumatic brain injury.

DESIGN: Prospective cross-sectional observational study.

SETTING: Ten Traumatic Brain Injury Model Systems Centers.

PARTICIPANTS: A total of 331 participants in the Traumatic Brain Injury Model Systems, interviewed at any follow-up year between April 2014 and March 2015.

MAIN MEASURES: Survey on Internet use, including social media and other online socialization; Participation Assessment with Recombined Tools-Objective with separate analyses of Productivity, Social Relations, Out and About subscales; covariates included demographics, injury variables, and functional and emotional status at follow-up.

RESULTS: Participants were classified as social Internet users (N = 232) or nonusers (N = 99). Users had significantly higher Participation Assessment with Recombined Tools-Objective Social Relations scores than nonusers. A similar finding pertained to Out and About scores, with the between-group difference significantly greater for those with greater depressive symptoms severity. Users and nonusers did not differ significantly on Productivity subscale.

CONCLUSIONS: The positive association between social Internet use and real-world social participation suggests that people with traumatic brain injury do not use social media as an alternative to real-world socialization. Rather, it is likely that similar barriers and facilitators affect both online and real-world social participation following traumatic brain injury. Emotional function should be considered as a moderating factor in further studies.

PMID:32108716 | PMC:PMC8594140 | DOI:10.1097/HTR.0000000000000566

J Neurotrauma. 2020 Jul 15;37(14):1627-1636. doi: 10.1089/neu.2019.6893. Epub 2020 Apr 15.

ABSTRACT

The Glasgow Outcome Scale, Pediatric Revision (GOSE-P) is an assessment of "global outcome" designed as a developmentally appropriate version of the Glasgow Outcome Scale-Extended for use in clinical trials of children with traumatic brain injury (TBI). Initial testing describes validity across a wide age and injury severity spectrum, yet the GOSE-P's utility for monitoring children with milder injuries is less clear. We examined the level of agreement between the GOSE-P and the Health and Behavior Inventory (HBI), a TBI-related symptom checklist used to assess children with mild TBI for clinical and research purposes. Participants included children and adolescents 3-16 years of age (n = 50) who presented to two level 1 trauma centers within 24 h of injury, with a GCS of 13-15, who underwent clinical neuroimaging. Outcome was assessed 2 weeks and 3 months following injury. We examined the severity of TBI-related symptoms across disability categories identified using the GOSE-P, and the level of agreement between the two measures in identifying deficits 2 weeks following injury and improvement from 2 weeks to 3 months. Using the GOSE-P, 62% had deficits at 2 weeks, and 42% improved from 2 weeks to 3 months. Agreement between the GOSE-P and HBI was fair 2 weeks after TBI (k = 0.24-0.33), and poor for identifying subsequent improvement (k = 0.10-0.16). Modest agreement between the GOSE-P and the HBI may reflect restricted participation from diverse causes, including TBI, other bodily injuries, and prescribed activity restrictions, and highlights the need for multi-dimensional outcome batteries.

PMID:32106753 | PMC:PMC7339019 | DOI:10.1089/neu.2019.6893

Arch Phys Med Rehabil. 2020 Jun;101(6):1072-1089. doi: 10.1016/j.apmr.2020.01.013. Epub 2020 Feb 20.

ABSTRACT

Persons who have disorders of consciousness (DoC) require care from multidisciplinary teams with specialized training and expertise in management of the complex needs of this clinical population. The recent promulgation of practice guidelines for patients with prolonged DoC by the American Academy of Neurology, American Congress of Rehabilitation Medicine (ACRM), and National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) represents a major advance in the development of care standards in this area of brain injury rehabilitation. Implementation of these practice guidelines requires explication of the minimum competencies of clinical programs providing services to persons who have DoC. The Brain Injury Interdisciplinary Special Interest Group of the ACRM, in collaboration with the Disorders of Consciousness Special Interest Group of the NIDILRR-Traumatic Brain Injury Model Systems convened a multidisciplinary panel of experts to address this need through the present position statement. Content area-specific workgroups reviewed relevant peer-reviewed literature and drafted recommendations which were then evaluated by the expert panel using a modified Delphi voting process. The process yielded 21 recommendations on the structure and process of essential services required for effective DoC-focused rehabilitation, organized into 4 categories: diagnostic and prognostic assessment (4 recommendations), treatment (11 recommendations), transitioning care/long-term care needs (5 recommendations), and management of ethical issues (1 recommendation). With few exceptions, these recommendations focus on infrastructure requirements and operating procedures for the provision of DoC-focused neurorehabilitation services across subacute and postacute settings.

PMID:32087109 | DOI:10.1016/j.apmr.2020.01.013

J Neurotrauma. 2021 Sep 15;38(18):2514-2529. doi: 10.1089/neu.2019.6762. Epub 2020 Apr 1.

ABSTRACT

Recent biomarker innovations hold potential for transforming diagnosis, prognostic modeling, and precision therapeutic targeting of traumatic brain injury (TBI). However, many biomarkers, including brain imaging, genomics, and proteomics, involve vast quantities of high-throughput and high-content data. Management, curation, analysis, and evidence synthesis of these data are not trivial tasks. In this review, we discuss data management concepts and statistical and data sharing strategies when dealing with biomarker data in the context of TBI research. We propose that application of biomarkers involves three distinct steps-discovery, evaluation, and evidence synthesis. First, complex/big data has to be reduced to useful data elements at the stage of biomarker discovery. Second, inferential statistical approaches must be applied to these biomarker data elements for assessment of biomarker clinical utility and validity. Last, synthesis of relevant research is required to support practice guidelines and enable health decisions informed by the highest quality, up-to-date evidence available. We focus our discussion around recent experiences from the International Traumatic Brain Injury Research (InTBIR) initiative, with a specific focus on four major clinical projects (Transforming Research and Clinical Knowledge in TBI, Collaborative European NeuroTrauma Effectiveness Research in TBI, Collaborative Research on Acute Traumatic Brain Injury in Intensive Care Medicine in Europe, and Approaches and Decisions in Acute Pediatric TBI Trial), which are currently enrolling subjects in North America and Europe. We discuss common data elements, data collection efforts, data-sharing opportunities, and challenges, as well as examine the statistical techniques required to realize successful adoption and use of biomarkers in the clinic as a foundation for precision medicine in TBI.

PMID:32046588 | PMC:PMC8403188 | DOI:10.1089/neu.2019.6762