Predicting outcome following mild traumatic brain injury: protocol for the longitudinal, prospective, observational Concussion Recovery (CREST) cohort study.
Ontology highlight
ABSTRACT: Introduction
Mild traumatic brain injury (mTBI) is a complex injury with heterogeneous physical, cognitive, emotional and functional outcomes. Many who sustain mTBI recover within 2 weeks of injury; however, approximately 10%-20% of individuals experience mTBI symptoms beyond this 'typical' recovery timeframe, known as persistent post-concussion symptoms (PPCS). Despite increasing interest in PPCS, uncertainty remains regarding its prevalence in community-based populations and the extent to which poor recovery may be identified using early predictive markers.Objective
(1) Establish a research dataset of people who have experienced mTBI and document their recovery trajectories; (2) Evaluate a broad range of novel and established prognostic factors for inclusion in a predictive model for PPCS.Methods and analysis
The Concussion Recovery Study (CREST) is a prospective, longitudinal observational cohort study conducted in Perth, Western Australia. CREST is recruiting adults aged 18-65 from medical and community-based settings with acute diagnosis of mTBI. CREST will create a state-wide research dataset of mTBI cases, with data being collected in two phases. Phase I collates data on demographics, medical background, lifestyle habits, nature of injury and acute mTBI symptomatology. In Phase II, participants undergo neuropsychological evaluation, exercise tolerance and vestibular/ocular motor screening, MRI, quantitative electroencephalography and blood-based biomarker assessment. Follow-up is conducted via telephone interview at 1, 3, 6 and 12 months after injury. Primary outcome measures are presence of PPCS and quality of life, as measured by the Post-Concussion Symptom Scale and the Quality of Life after Brain Injury questionnaires, respectively. Multivariate modelling will examine the prognostic value of promising factors.Ethics and dissemination
Human Research Ethics Committees of Royal Perth Hospital (#RGS0000003024), Curtin University (HRE2019-0209), Ramsay Health Care (#2009) and St John of God Health Care (#1628) have approved this study protocol. Findings will be published in peer-reviewed journals and presented at scientific conferences.Trial registration number
ACTRN12619001226190.
SUBMITTER: Gozt AK
PROVIDER: S-EPMC8126315 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:ImportanceOne traumatic brain injury (TBI) increases the risk of subsequent TBIs. Research on longitudinal outcomes of civilian repetitive TBIs is limited.ObjectiveTo 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 participantsThis 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.ExposuresPostindex TBI(s).Main outcomes and measuresDemographic 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.ResultsOf 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 relevanceIn 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.
| S-EPMC10523170 | biostudies-literature
Project description:The chronic consequences of traumatic brain injury (TBI) may contribute to the increased risk for early cognitive decline and dementia, primarily due to diffusion axonal injury. Previous studies in mild TBI (mTBI) have been controversial in describing the white matter tract integrity changes occurring at acute and subacute post-injury. In this prospective longitudinal study, we aim to investigate the longitudinal changes of white matter (WM) using diffusion tensor imaging (DTI) and their correlations with neuropsychological tests. Thirty-three patients with subacute mTBI and 31 matched healthy controls were studied with an extensive imaging and clinical battery. Neuroimaging was obtained within 7 days post-injury for acute scans and repeated at 1 and 3 months post-injury. Using a region-of-interest-based approach, tract-based spatial statistics was used to conduct voxel-wise analysis on diffusion changes in mTBI and was compared to those of healthy matched controls, scanned during the same time period and rescanned with an interval similar to that of patients. We found decreased fractional anisotropy (FA) values in the left anterior limb of internal capsule (ALIC) and right inferior fronto-occipital fasciculus (IFOF) during the 7 days post-injury, which showed longitudinal evidence of recovery following 1 month post-injury. Increased FA values in these two tracts at 1 month post-injury were positively associated with better performance on cognitive information processing speed at initial assessment. By contrast, there were also some tracts (right anterior corona radiata, forceps major, and body of corpus callosum) exhibiting the continuing loss of integrity sustaining even beyond 3 months, which can predict the persisting post-concussion syndromes. Continuing loss of structural integrity in some tracts may contribute to the persistent post-concussion syndromes in mTBI patients, suggesting certain tracts providing an objective biomarker for tracking the pathological recovery process following mTBI.
| S-EPMC6514143 | biostudies-literature
Project description:ImportancePediatric mild traumatic brain injury (TBI) and concussion are a public health challenge with up to 30% of patients experiencing prolonged recovery. Pediatric patients presenting to concussion clinics often have ongoing impairments and may be at increased risk for persistent symptoms. Understanding this population is critical for improved prognostic estimates and optimal treatment.ObjectiveTo describe pediatric patients presenting to concussion clinics and characterize factors associated with their recovery.Design, setting, and participantsThis prospective cohort study included patients enrolled at multicenter concussion specialty clinics from the Four Corners Youth Consortium from December 2017 to July 2019, with up to 12-month follow-up. Patients were eligible if they were aged 5 to 18.99 years with a diagnosis of mild TBI or concussion presenting to participating clinics within 8 weeks of injury. Patients were excluded if the patient or their parents were unable to read or sign the consent document, or if the patient had a Glasgow Coma Scale score less than 13 or a penetrating injury. Data were analyzed from February 2019 to April 2020.ExposuresDiagnosis of mild TBI or concussion.Main outcomes and measuresThis study used National Institute of Neurological Disorders and Stroke common data elements, including data on demographic characteristics, injury details, history, neurological and neuropsychological assessments, and treatment.ResultsA total of 600 patients were consecutively enrolled, among whom 324 (54.0%) were female and 435 (72.5%) were adolescents (ie, aged 13-18 years). A higher proportion of girls and women (248 patients [76.5%]) were adolescents compared with boys and men (187 patients [67.8%]) (P = .02), and girls and women reported significantly more preexisting anxiety compared with boys and men (80 patients [26.7%] vs 46 patients [18.7%]; P = .03). Significantly more adolescents reported preexisting migraines compared with preadolescents (82 patients [20.9%] vs 15 patients [10.9%]; P = .01). Girls and women recovered more slowly than boys and men (persistent symptoms after injury: week 4, 217 patients [81.6%] vs 156 patients [71.2%]; week 8, 146 patients [58.9%] vs 89 patients [44.3%]; week 12, 103 patients [42.6%] vs 58 patients [30.2%]; P = .01). Patients with history of migraine or anxiety or depression recovered more slowly than those without, regardless of sex.Conclusions and relevanceThese findings suggest that identification of subgroups of pediatric patients with mild TBI or concussion at risk for prolonged recovery could aid in better prognostic estimates and more targeted treatment interventions.
| S-EPMC7670312 | biostudies-literature
Project description:After mild traumatic brain injury (mTBI), a substantial proportion of individuals do not fully recover on the Glasgow Outcome Scale Extended (GOSE) or experience persistent post-concussion symptoms (PPCS). We aimed to develop prognostic models for the GOSE and PPCS at 6 months after mTBI and to assess the prognostic value of different categories of predictors (clinical variables; questionnaires; computed tomography [CT]; blood biomarkers). From the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, we included participants aged 16 or older with Glasgow Coma Score (GCS) 13-15. We used ordinal logistic regression to model the relationship between predictors and the GOSE, and linear regression to model the relationship between predictors and the Rivermead Post-concussion Symptoms Questionnaire (RPQ) total score. First, we studied a pre-specified Core model. Next, we extended the Core model with other clinical and sociodemographic variables available at presentation (Clinical model). The Clinical model was then extended with variables assessed before discharge from hospital: early post-concussion symptoms, CT variables, biomarkers, or all three categories (extended models). In a subset of patients mostly discharged home from the emergency department, the Clinical model was extended with 2-3-week post-concussion and mental health symptoms. Predictors were selected based on Akaike's Information Criterion. Performance of ordinal models was expressed as a concordance index (C) and performance of linear models as proportion of variance explained (R2). Bootstrap validation was used to correct for optimism. We included 2376 mTBI patients with 6-month GOSE and 1605 patients with 6-month RPQ. The Core and Clinical models for GOSE showed moderate discrimination (C = 0.68 95% confidence interval 0.68 to 0.70 and C = 0.70[0.69 to 0.71], respectively) and injury severity was the strongest predictor. The extended models had better discriminative ability (C = 0.71[0.69 to 0.72] with early symptoms; 0.71[0.70 to 0.72] with CT variables or with blood biomarkers; 0.72[0.71 to 0.73] with all three categories). The performance of models for RPQ was modest (R2 = 4% Core; R2 = 9% Clinical), and extensions with early symptoms increased the R2 to 12%. The 2-3-week models had better performance for both outcomes in the subset of participants with these symptoms measured (C = 0.74 [0.71 to 0.78] vs. C = 0.63[0.61 to 0.67] for GOSE; R2 = 37% vs. 6% for RPQ). In conclusion, the models based on variables available before discharge have moderate performance for the prediction of GOSE and poor performance for the prediction of PPCS. Symptoms assessed at 2-3 weeks are required for better predictive ability of both outcomes. The performance of the proposed models should be examined in independent cohorts.
| S-EPMC10458380 | biostudies-literature
Project description:Post-concussion syndrome has been related to axonal damage in patients with mild traumatic brain injury, but little is known about the consequences of injury on brain networks. In the present study, our aim was to characterize changes in functional brain networks following mild traumatic brain injury in patients with post-concussion syndrome using resting-state functional magnetic resonance imaging data. We investigated 17 injured patients with persistent post-concussion syndrome (under the DSM-IV criteria) at 6 months post-injury compared with 38 mild traumatic brain injury patients with no post-concussion syndrome and 34 healthy controls. All patients underwent magnetic resonance imaging examinations at the subacute (1-3 weeks) and late (6 months) phases after injury. Group-wise differences in functional brain networks were analyzed using graph theory measures. Patterns of long-range functional networks alterations were found in all mild traumatic brain injury patients. Mild traumatic brain injury patients with post-concussion syndrome had greater alterations than patients without post-concussion syndrome. In patients with post-concussion syndrome, changes specifically affected temporal and thalamic regions predominantly at the subacute stage and frontal regions at the late phase. Our results suggest that the post-concussion syndrome is associated with specific abnormalities in functional brain network that may contribute to explain deficits typically observed in PCS patients.
| S-EPMC3675039 | biostudies-literature
Project description:Sports-related concussions or mild traumatic brain injuries (mTBIs) are becoming increasingly recognized as a major public health concern; however, no effective therapy for these injuries is currently available. ω-3 (n-3) fatty acids, such as docosahexaenoic acid (DHA), have important structural and functional roles in the brain, with established clinical benefits for supporting brain development and cognitive function throughout life. Consistent with these critical roles of DHA in the brain, accumulating evidence suggests that DHA may act as a promising recovery aid, or possibly as a prophylactic nutritional measure, for mTBI. Preclinical investigations demonstrate that dietary consumption of DHA provided either before or after mTBI improves functional outcomes, such as spatial learning and memory. Mechanistic investigations suggest that DHA influences multiple aspects of the pathologic molecular signaling cascade that occurs after mTBI. This review examines the evidence of interactions between DHA and concussion and discusses potential mechanisms by which DHA helps the brain to recover from injury. Additional clinical research in humans is needed to confirm the promising results reported in the preclinical literature.
| S-EPMC4013179 | biostudies-literature
Project description:Objectives: The objective of this study was to assess if injury-related alterations in the Sport Concussion Assessment Tool-5 (SCAT5) are matched by changes in transcranial magnetic stimulation-derived intracortical inhibition. We hypothesised that neurophysiological measures would take longer to return to normal than recovery assessed by the SCAT5 following sport related concussion (SRC). Methods: Thirteen male contact sport athletes (20.5 ± 4.5 years), who reported a concussion were recruited from local Rugby and American football clubs. Participants were tested at 4 timepoints throughout the concussion recovery period: within 24 h of concussion (day 0), and at 7, 9, and 11 days after concussion. All participants completed the SCAT5 and underwent TMS to assess cortical silent period duration (CSp), a measure of intracortical inhibition. Results: After concussion CSp significantly declined from day 0 (122 ± 28 ms) to day 11 (106 ± 15 ms) [F (3, 33) = 7.80, p < 0.001]. SCAT5 measures of symptom number and severity were significantly decreased [symptom number: χ(3)2 = 30.44, p < 0.01; symptom severity: χ(3)2 = 25.75, p < 0.001] between the day 0 timepoint and each of the other timepoints. SCAT5 balance errors (mBESS) decreased significantly [F (3, 33) = 19.55, p < 0.001] between the day 0 timepoint and each of the other timepoints. CSp and SCAT5 recovery patterns were different. SCAT5 domains recovered faster showing no further significant changes after day 7, whilst CSp was still decreasing between days 7 and 9. Due to the small sample size we also used a Bayesian linear model to investigate the recovery of CSp and mBESS. The posterior distribution of our Bayesian model provided evidence that CSp decreased at day 7 and it continued to decrease at day 9, unlike mBESS which decreased at day 7 and then reached a plateau. Conclusion: There are clinically important discrepancies between clinical and neurophysiological measures of concussion recovery. This finding has important implications for return to play (RTP) protocols and the prevention of complications after sport concussion.
| S-EPMC8695881 | biostudies-literature
Project description:In this prospective cohort study, we investigated associations between acute diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) metrics and persistent post-concussion symptoms (PPCS) 3 months after mild traumatic brain injury (mTBI). Adult patients with mTBI (n = 176) and community controls (n = 78) underwent 3 Tesla magnetic resonance imaging (MRI) within 72 h post-injury, estimation of cognitive reserve at 2 weeks, and PPCS assessment at 3 months. Eight DTI and DKI metrics were examined with Tract-Based Spatial Statistics. Analyses were performed in the total sample in uncomplicated mTBI only (i.e., without lesions on clinical MRI), and with cognitive reserve both controlled for and not. Patients with PPCS (n = 35) had lower fractional anisotropy (in 2.7% of all voxels) and kurtosis fractional anisotropy (in 6.9% of all voxels), and higher radial diffusivity (in 0.3% of all voxels), than patients without PPCS (n = 141). In uncomplicated mTBI, only fractional anisotropy was significantly lower in patients with PPCS. Compared with controls, patients with PPCS had widespread deviations in all diffusion metrics. When including cognitive reserve as a covariate, no significant differences in diffusion metrics between patients with and without PPCS were present, but patients with PPCS still had significantly higher mean, radial, and axial diffusivity than controls. In conclusion, patients who developed PPCS had poorer white matter microstructural integrity acutely after the injury, compared with patients who recovered and healthy controls. Differences became less pronounced when cognitive reserve was controlled for, suggesting that pre-existing individual differences in axonal integrity accounted for some of the observed differences.
| S-EPMC8403189 | biostudies-literature
Project description:Mild traumatic brain injury (mTBI) is a common diagnosis and approximately one third of mTBI patients experience a variety of cognitive, emotional, psychosocial, and behavioral post-concussion symptoms. When a cluster of these symptoms persists for more than 3 months they are often classified as post-concussion syndrome (PCS). The objective of this study was to determine prevalence rates, risk factors, and functional outcome associated with PCS 6 months after mTBI, applying divergent classification methods. Follow-up questionnaires at 6 months after mTBI included the Rivermead Post-Concussion Symptoms Questionnaire (RPQ) and the Glasgow Outcome Scale Extended (GOSE). The RPQ was analyzed according to different classification methods: the mapped International Classification of Diseases, 10th revision (ICD-10)/Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), the RPQ total score, the RPQ3 and the three-factor model using two different cutoff points (mild or worse and moderate or worse). Our results from a sample of 731 mTBI patients showed that prevalence rates of PCS ranged from 11.4% to 38.7% using divergent classification methods. According to all eight methods, 6.3% (n = 46) of mTBI patients experienced PCS. Applying the divergent classification methods resulted in a different set of predictors being statistically significantly associated with PCS, and a different percentage of overlap with functional impairment, measured with the GOSE. In conclusion, depending on the classification method and rating score used, prevalence rates of PCS deviated considerably. For future research, consensus regarding the diagnostic criteria for PCS and the analysis of the RPQ should be reached, to enhance comparability of studies regarding PCS after mTBI.
| S-EPMC6909759 | biostudies-literature
Project description:Ionic imbalances and sodium channel dysfunction, well-known sequelae of traumatic brain injury (TBI), promote functional impairment in affected subjects. Therefore, non-invasive measurement of sodium concentrations using 23Na MRI has the potential to detect clinically relevant injury and predict persistent symptoms. Recently, we reported diffusely lower apparent total sodium concentrations (aTSC) in mild TBI patients compared to controls, as well as correlations between lower aTSC and worse clinical outcomes. The main goal of this study was to determine whether these aTSC findings, and their changes over time, predict outcomes at 3- and 12-month from injury. Twenty-seven patients previously studied with 23Na MRI and outcome measures at 22 ± 10 days (average ± standard deviation) after injury (visit-1, v1) were contacted at 3- (visit-2, v2) and 12-month after injury (visit-3, v3) to complete the Rivermead post-concussion symptoms questionnaire (RPQ), the extended Glasgow outcome scale (GOSE), and the brief test of adult cognition by telephone (BTACT). Follow-up 1H and 23Na MRI were additionally scheduled at v2. Linear regression was used to calculate aTSC in global grey and white matters. Six hypotheses were tested in relation to the serial changes in outcome measures and in aTSC, and in relation to the cross-sectional and serial relationships between aTSC and outcome. Twenty patients contributed data at v2 and fifteen at v3. Total RPQ and composite BTACT z-scores differed significantly for v2 and v3 in comparison to v1 (each P < 0.01), reflecting longitudinally reduced symptomatology and improved performance on cognitive testing. No associations between aTSC and outcome were observed at v2. Previously lower grey and white matter aTSC normalized at v2 in comparison to controls, in line with a statistically detectable longitudinal increase in grey matter aTSC between v1 and v2 (P = 0.0004). aTSC values at v1 predicted a subset of future BTACT subtest scores, but not future RPQ scores nor GOSE-defined recovery status. Similarly, aTSC rates of change correlated with BTACT rates of change, but not with those of RPQ. Tissue aTSC, previously shown to be diffusely decreased compared to controls at v1, was no longer reduced by v2, suggesting normalization of the sodium ionic equilibrium. These changes were accompanied by marked improvement in outcome. The results support the notion that early aTSC from 23Na MRI predicts future BTACT, but not RPQ scores, nor future GOSE status.
| S-EPMC11258572 | biostudies-literature