Plasma neurofilament light admission levels and development of axonal pathology in mild traumatic brain injury.

BACKGROUND: It is known that blood levels of neurofilament light (NF-L) and diffusion-weighted magnetic resonance imaging (DW-MRI) are both associated with outcome of patients with mild traumatic brain injury (mTBI). Here, we sought to examine the association between admission levels of plasma NF-L and white matter (WM) integrity in post-acute stage DW-MRI in patients with mTBI. METHODS: Ninety-three patients with mTBI (GCS ≥ 13), blood sample for NF-L within 24 h of admission, and DW-MRI ≥ 90 days post-injury (median = 229) were included. Mean fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated from the skeletonized WM tracts of the whole brain. Outcome was assessed using the Extended Glasgow Outcome Scale (GOSE) at the time of imaging. Patients were divided into CT-positive and -negative, and complete (GOSE = 8) and incomplete recovery (GOSE < 8) groups. RESULTS: The levels of NF-L and FA correlated negatively in the whole cohort (p = 0.002), in CT-positive patients (p = 0.016), and in those with incomplete recovery (p = 0.005). The same groups showed a positive correlation with mean MD, AD, and RD (p < 0.001-p = 0.011). In CT-negative patients or in patients with full recovery, significant correlations were not found. CONCLUSION: In patients with mTBI, the significant correlation between NF-L levels at admission and diffusion tensor imaging (DTI) measurements of diffuse axonal injury (DAI) over more than 3 months suggests that the early levels of plasma NF-L may associate with the presence of DAI at a later phase of TBI.

Post-acute blood biomarkers and disease progression in traumatic brain injury.

There is substantial interest in the potential for traumatic brain injury to result in progressive neurological deterioration. While blood biomarkers such as glial fibrillary acid protein (GFAP) and neurofilament light have been widely explored in characterizing acute traumatic brain injury (TBI), their use in the chronic phase is limited. Given increasing evidence that these proteins may be markers of ongoing neurodegeneration in a range of diseases, we examined their relationship to imaging changes and functional outcome in the months to years following TBI. Two-hundred and three patients were recruited in two separate cohorts; 6 months post-injury (n = 165); and >5 years post-injury (n = 38; 12 of whom also provided data ∼8 months post-TBI). Subjects underwent blood biomarker sampling (n = 199) and MRI (n = 172; including diffusion tensor imaging). Data from patient cohorts were compared to 59 healthy volunteers and 21 non-brain injury trauma controls. Mean diffusivity and fractional anisotropy were calculated in cortical grey matter, deep grey matter and whole brain white matter. Accelerated brain ageing was calculated at a whole brain level as the predicted age difference defined using T1-weighted images, and at a voxel-based level as the annualized Jacobian determinants in white matter and grey matter, referenced to a population of 652 healthy control subjects. Serum neurofilament light concentrations were elevated in the early chronic phase. While GFAP values were within the normal range at ∼8 months, many patients showed a secondary and temporally distinct elevations up to >5 years after injury. Biomarker elevation at 6 months was significantly related to metrics of microstructural injury on diffusion tensor imaging. Biomarker levels at ∼8 months predicted white matter volume loss at >5 years, and annualized brain volume loss between ∼8 months and 5 years. Patients who worsened functionally between ∼8 months and >5 years showed higher than predicted brain age and elevated neurofilament light levels. GFAP and neurofilament light levels can remain elevated months to years after TBI, and show distinct temporal profiles. These elevations correlate closely with microstructural injury in both grey and white matter on contemporaneous quantitative diffusion tensor imaging. Neurofilament light elevations at ∼8 months may predict ongoing white matter and brain volume loss over >5 years of follow-up. If confirmed, these findings suggest that blood biomarker levels at late time points could be used to identify TBI survivors who are at high risk of progressive neurological damage.

Cognitive functions and symptoms predicting later use of psychiatric services following mild traumatic brain injury in school-age.

OBJECTIVE: To investigate whether neuropsychological test performance or presence of some specific injury symptoms at 1-3 months following pediatric mild traumatic brain injury (mTBI) can help to identify the children at risk for developing post-traumatic psychiatric symptoms. METHODS: Data from 120 children and adolescents aged 7-15 years, treated at Turku University Hospital between 2010 and 2016 due to mTBI, and who had undergone neuropsychological evaluation at 1-3 months following injury, were enrolled from the hospital records. Neuropsychological test performancesand injury symptom reports were retrospectively retrieved from the patient files. RESULTS: Slow information processing speed (p = 0.044), emotion regulation deficit (p = 0.014), impulsivity (p = 0.013), verbal processing difficulties (p = 0.042) and headache (p = 0.026) were independent predictors for having later contact in psychiatric care. CONCLUSIONS: Neuropsychological examination containing measure of information processing speed, injury symptom interview, and parental questionnaires on behavioural issues of the child at 1-3 months following mTBI seems to be useful in detecting children with risk for post traumatic psychiatric symptoms. Targeted support and guidance for this group of children and adolescents and their families are recommended to prevent the development of an unfavorable psychosocial outcome.

Blood-based biomarkers and traumatic brain injury-A clinical perspective.

Blood-based biomarkers are promising tools to complement clinical variables and imaging findings in the diagnosis, monitoring and outcome prediction of traumatic brain injury (TBI). Several promising biomarker candidates have been found for various clinical questions, but the translation of TBI biomarkers into clinical applications has been negligible. Measured biomarker levels are influenced by patient-related variables such as age, blood-brain barrier integrity and renal and liver function. It is not yet fully understood how biomarkers enter the bloodstream from the interstitial fluid of the brain. In addition, the diagnostic performance of TBI biomarkers is affected by sampling timing and analytical methods. In this focused review, the clinical aspects of glial fibrillary acidic protein, neurofilament light, S100 calcium-binding protein B, tau and ubiquitin C-terminal hydrolase-L1 are examined. Current findings and clinical caveats are addressed.

Rehabilitation and outcomes after complicated vs uncomplicated mild TBI: results from the CENTER-TBI study.

BACKGROUND: Despite existing guidelines for managing mild traumatic brain injury (mTBI), evidence-based treatments are still scarce and large-scale studies on the provision and impact of specific rehabilitation services are needed. This study aimed to describe the provision of rehabilitation to patients after complicated and uncomplicated mTBI and investigate factors associated with functional outcome, symptom burden, and TBI-specific health-related quality of life (HRQOL) up to six months after injury. METHODS: Patients (n = 1379) with mTBI from the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study who reported whether they received rehabilitation services during the first six months post-injury and who participated in outcome assessments were included. Functional outcome was measured with the Glasgow Outcome Scale - Extended (GOSE), symptom burden with the Rivermead Post Concussion Symptoms Questionnaire (RPQ), and HRQOL with the Quality of Life after Brain Injury - Overall Scale (QOLIBRI-OS). We examined whether transition of care (TOC) pathways, receiving rehabilitation services, sociodemographic (incl. geographic), premorbid, and injury-related factors were associated with outcomes using regression models. For easy comparison, we estimated ordinal regression models for all outcomes where the scores were classified based on quantiles. RESULTS: Overall, 43% of patients with complicated and 20% with uncomplicated mTBI reported receiving rehabilitation services, primarily in physical and cognitive domains. Patients with complicated mTBI had lower functional level, higher symptom burden, and lower HRQOL compared to uncomplicated mTBI. Rehabilitation services at three or six months and a higher number of TOC were associated with unfavorable outcomes in all models, in addition to pre-morbid psychiatric problems. Being male and having more than 13 years of education was associated with more favorable outcomes. Sustaining major trauma was associated with unfavorable GOSE outcome, whereas living in Southern and Eastern European regions was associated with lower HRQOL. CONCLUSIONS: Patients with complicated mTBI reported more unfavorable outcomes and received rehabilitation services more frequently. Receiving rehabilitation services and higher number of care transitions were indicators of injury severity and associated with unfavorable outcomes. The findings should be interpreted carefully and validated in future studies as we applied a novel analytic approach. TRIAL REGISTRATION: ClinicalTrials.gov NCT02210221.

Potential of heart fatty-acid binding protein, neurofilament light, interleukin-10 and S100 calcium-binding protein B in the acute diagnostics and severity assessment of traumatic brain injury.

BACKGROUND: There is substantial interest in blood biomarkers as fast and objective diagnostic tools for traumatic brain injury (TBI) in the acute setting. METHODS: Adult patients (≥18) with TBI of any severity and indications for CT scanning and orthopaedic injury controls were prospectively recruited during 2011-2013 at Turku University Hospital, Finland. The severity of TBI was classified with GCS: GCS 13-15 was classified as mild (mTBI); GCS 9-12 as moderate (moTBI) and GCS 3-8 as severe (sTBI). Serum samples were collected within 24 hours of admission and biomarker levels analysed with high-performance kits. The ability of biomarkers to distinguish between severity of TBI and CT-positive and CT-negative patients was assessed. RESULTS: Among 189 patients recruited, neurofilament light (NF-L) was obtained from 175 patients with TBI and 40 controls. S100 calcium-binding protein B (S100B), heart fatty-acid binding protein (H-FABP) and interleukin-10 (IL-10) were analysed for 184 patients with TBI and 39 controls. There were statistically significant differences between levels of all biomarkers between the severity classes, but none of the biomarkers distinguished patients with moTBI from patients with sTBI. Patients with mTBI discharged from the ED had lower levels of IL-10 (0.26, IQR=0.21, 0.39 pg/mL), H-FABP (4.15, IQR=2.72, 5.83 ng/mL) and NF-L (8.6, IQR=6.35, 15.98 pg/mL) compared with those admitted to the neurosurgical ward, IL-10 (0.55, IQR=0.31, 1.42 pg/mL), H-FABP (6.022, IQR=4.19, 20.72 ng/mL) and NF-L (13.95, IQR=8.33, 19.93 pg/mL). We observed higher levels of H-FABP and NF-L in older patients with mTBI. None of the biomarkers or their combinations was able to distinguish CT-positive (n=36) or CT-negative (n=58) patients with mTBI from controls. CONCLUSIONS: S100B, H-FABP, NF-L and IL-10 levels in patients with mTBI were significantly lower than in patients with moTBI and sTBI but alone or in combination, were unable to distinguish patients with mTBI from orthopaedic controls. This suggests these biomarkers cannot be used alone to diagnose mTBI in trauma patients in the acute setting.

"Omics" in traumatic brain injury: novel approaches to a complex disease.

BACKGROUND: To date, there is neither any pharmacological treatment with efficacy in traumatic brain injury (TBI) nor any method to halt the disease progress. This is due to an incomplete understanding of the vast complexity of the biological cascades and failure to appreciate the diversity of secondary injury mechanisms in TBI. In recent years, techniques for high-throughput characterization and quantification of biological molecules that include genomics, proteomics, and metabolomics have evolved and referred to as omics. METHODS: In this narrative review, we highlight how omics technology can be applied to potentiate diagnostics and prognostication as well as to advance our understanding of injury mechanisms in TBI. RESULTS: The omics platforms provide possibilities to study function, dynamics, and alterations of molecular pathways of normal and TBI disease states. Through advanced bioinformatics, large datasets of molecular information from small biological samples can be analyzed in detail and provide valuable knowledge of pathophysiological mechanisms, to include in prognostic modeling when connected to clinically relevant data. In such a complex disease as TBI, omics enables broad categories of studies from gene compositions associated with susceptibility to secondary injury or poor outcome, to potential alterations in metabolites following TBI. CONCLUSION: The field of omics in TBI research is rapidly evolving. The recent data and novel methods reviewed herein may form the basis for improved precision medicine approaches, development of pharmacological approaches, and individualization of therapeutic efforts by implementing mathematical "big data" predictive modeling in the near future.

Cognitive-Linguistic outcome in moderate to severe diffuse axonal injury and association with fatigue.

PURPOSE: Individuals with traumatic brain injury (TBI) often have persistent cognitive-linguistic deficits that negatively influence their life. Our objective was to examine the cognitive-linguistic outcome in individuals with moderate to severe diffuse axonal injury (DAI) with a novel test battery. As fatigue is a common symptom affecting the lives of individuals with DAI, we also wanted to assess whether the self-reported fatigue was associated with cognitive-linguistic abilities. METHODS: Selected cognitive-linguistic subtests of the Finnish KAT test and The Mental Fatigue Scale (MFS) were applied to 48 adults with moderate to severe DAI and 27 healthy controls. The majority of the participants with DAI were in the chronic stage. The groups were compared using ANCOVA. Linear regressions were used to analyze the association between MFS and cognitive-linguistic outcomes. RESULTS: The participants with DAI had significantly poorer scores than the controls in most cognitive-linguistic variables and reported significantly more fatigue. Two of the four cognitive-linguistic composite variables were associated with the degree of self-reported fatigue. CONCLUSIONS: Cognitive-linguistic deficits are common in individuals with moderate to severe DAI, and The Finnish KAT test is a valuable tool to detect those. Fatigue was associated with linguistic working memory and language production.

Influence of Concomitant Extracranial Injury on Functional and Cognitive Recovery From Mild Versus Moderateto Severe Traumatic Brain Injury.

OBJECTIVE: To determine the effect of extracranial injury (ECI) on 6-month outcome in patients with mild traumatic brain injury (TBI) versus moderate-to-severe TBI. PARTICIPANTS/SETTING: Patients with TBI (n = 135) or isolated orthopedic injury (n = 25) admitted to a UK major trauma center and healthy volunteers (n = 99). DESIGN: Case-control observational study. MAIN MEASURES: Primary outcomes: (a) Glasgow Outcome Scale Extended (GOSE), (b) depression, (c) quality of life (QOL), and (d) cognitive impairment including verbal fluency, episodic memory, short-term recognition memory, working memory, sustained attention, and attentional flexibility. RESULTS: Outcome was influenced by both TBI severity and concomitant ECI. The influence of ECI was restricted to mild TBI; GOSE, QOL, and depression outcomes were significantly poorer following moderate-to-severe TBI than after isolated mild TBI (but not relative to mild TBI plus ECI). Cognitive impairment was driven solely by TBI severity. General health, bodily pain, semantic verbal fluency, spatial recognition memory, working memory span, and attentional flexibility were unaffected by TBI severity and additional ECI. CONCLUSION: The presence of concomitant ECI ought to be considered alongside brain injury severity when characterizing the functional and neurocognitive effects of TBI, with each presenting challenges to recovery.

Integrative Analysis of Circulating Metabolite Profiles and Magnetic Resonance Imaging Metrics in Patients with Traumatic Brain Injury.

Recent evidence suggests that patients with traumatic brain injuries (TBIs) have a distinct circulating metabolic profile. However, it is unclear if this metabolomic profile corresponds to changes in brain morphology as observed by magnetic resonance imaging (MRI). The aim of this study was to explore how circulating serum metabolites, following TBI, relate to structural MRI (sMRI) findings. Serum samples were collected upon admission to the emergency department from patients suffering from acute TBI and metabolites were measured using mass spectrometry-based metabolomics. Most of these patients sustained a mild TBI. In the same patients, sMRIs were taken and volumetric data were extracted (138 metrics). From a pool of 203 eligible screened patients, 96 met the inclusion criteria for this study. Metabolites were summarized as eight clusters and sMRI data were reduced to 15 independent components (ICs). Partial correlation analysis showed that four metabolite clusters had significant associations with specific ICs, reflecting both the grey and white matter brain injury. Multiple machine learning approaches were then applied in order to investigate if circulating metabolites could distinguish between positive and negative sMRI findings. A logistic regression model was developed, comprised of two metabolic predictors (erythronic acid and myo-inositol), which, together with neurofilament light polypeptide (NF-L), discriminated positive and negative sMRI findings with an area under the curve of the receiver-operating characteristic of 0.85 (specificity = 0.89, sensitivity = 0.65). The results of this study show that metabolomic analysis of blood samples upon admission, either alone or in combination with protein biomarkers, can provide valuable information about the impact of TBI on brain structural changes.

Association between parent mental health and paediatric TBI: epidemiological observations from the 1987 Finnish Birth Cohort.

BACKGROUND: This study examined whether parental mental illness has implications for child risk for traumatic brain injuries (TBI). METHOD: Data on 60 069 Finnish children born in 1987 and their parents were examined for demographic and mental health-related variables in relationship with paediatric TBI. Altogether, 15 variables were derived from the cohort data with ICD-10 F-codes being available for mental health diagnoses for all parents. Bivariate and multivariate analyses were carried out using inpatient and outpatient diagnoses of child TBI. RESULTS: Paternal disorders due to psychoactive substance use (F10-F19) was associated with an increased inpatient TBI (OR=1.51; CI=1.07 to 2.14). Mood disorders (F30-F39) were associated with higher rates of outpatient TBI (OR=1.42; CI=1.06 to 1.90). Paternal personality and behavioural disorders (F60-F69) were linked with a twofold increase in risk across both categories of child TBI (OR=2.35; CI=1.41 to 3.90) and (OR=2.29; CI=1.45 to 3.61), respectively. Among the maternal mental health factors associated with child TBI, schizophrenia and other non-mood psychotic disorders (F20-F29) were associated with an increase in inpatient traumatic brain injuries (iTBI) (OR=1.78; 1.22 to 2.59). Mothers having mood disorders (F30-F39) were more likely to have had a child who experienced an iTBI (OR=1.64; CI=1.20 to 2.22). Mothers with personality and behavioural disorders (F60-F69) were also found to have had children with an increased risk for iTBI (OR=2.30; CI=1.14 to 3.65). CONCLUSION: Taken together, these data should call attention to methods and strategies designed to augment and support caregiving environments with modalities that can foster mutually supportive households in cooperation with parents who have been diagnosed with a mental disorder.

Practitioners' opinions on traumatic brain injury care pathways in Finland and France: different organizations, common issues.

OBJECTIVE: In traumatic brain injury (TBI), differences in health-care contexts have profound effects on care pathways. Objectives were to compare TBI pathways of care and practitioners' views on quality of care issues in two large European areas: Varsinais-Suomi, Finland and Ile-de-France, France. METHODS: Thematic analysis of semi-structured interviews was conducted with TBI practitioners (n = 10) from all stages of TBI care. Interviews addressed organization and financing of care, decision-making on care transitions, and perceived issues. The structure-process-outcome model of Donabedian was used to classify findings related to quality of care issues. RESULTS: Main differences in organization of care pathways for people with TBI were related to financing modalities, number of pathway alternatives, inpatient versus outpatient rehabilitation, and indirect versus direct referrals to rehabilitation. Similar categories of issues were raised in the two settings. Issues in structures involved availability of services, financial access, and heterogeneity of expertise. Issues in processes involved diagnosis and follow-up, training regarding cognitive impairments, decision-making for referrals, transition delays, and care pathways of very severely affected patients. CONCLUSIONS: These findings provide clues to address care pathways in further comparative studies. Determinants of care pathway quality could be classified as direct or indirect, binding or adaptive organizational factors.

Brain Cholinergic Function and Response to Rivastigmine in Patients With Chronic Sequels of Traumatic Brain Injury: A PET Study.

OBJECTIVE: To investigate quantitative positron emission tomography (PET) findings and to study whether the cholinergic function differs between respondents to cholinergic medication versus nonrespondents. SETTING: Outpatient clinic and university PET imaging center. PARTICIPANTS: We studied 17 subjects for more than 1 year after at least moderate traumatic brain injury. Ten of the subjects were respondents and 7 nonrespondents to cholinergic medication. DESIGN: Cholinergic function was assessed with [methyl-C] N-methylpiperidyl-4-acetate-PET (C-MP4A-PET), which reflects the activity of the acetylcholinesterase (AChE) enzyme. The subjects were PET scanned twice: without medication and after a 4-week treatment with rivastigmine 1.5 mg twice a day. MEASURES: Regional cerebral AChE activity was measured with PET. RESULTS: At baseline Statistical Parametric Mapping analyses showed significantly lower AChE activity in respondents bilaterally in the frontal cortex as compared with nonrespondents. Region of interest (ROI) analysis revealed that the difference was most pronounced in the lateral frontal cortex (-9.4%, P = .034) and anterior cingulate (-6.0%, P = .049). After rivastigmine treatment, AChE activity was notably lower throughout the cortex in both respondents and nonrespondents, without significant differences between them. CONCLUSION: Our study suggests that frontal cholinergic dysfunction is associated with the clinical response to cholinergic stimulation in patients with traumatic brain injury.

Comparing disability between traumatic brain injury and spinal cord injury using the 12-item WHODAS 2.0 and the WHO minimal generic data set covering functioning and health.

OBJECTIVE:: To compare disability between two patient groups using short validated tools based on International Classification of Functioning, Disability and Health (ICF). DESIGN:: Cross-sectional study. SETTING:: University hospital specialist outpatient clinic. SUBJECTS:: A total of 94 patients with traumatic brain injury and 59 with spinal cord injury. MAIN MEASURES:: Disability evaluated using self-reported and proxy 12-item WHODAS 2.0 (World Health Organization Disability Assessment Schedule), and physician-rated WHO minimal generic data set covering functioning and health. RESULTS:: The two measures used showed severe but very different disabilities in these patient groups. Disability was assessed worse by physicians in the spinal cord injury population (sum 15.8 vs. 12.7, P = 0.0001), whereas disability assessed by the patients did not differ significantly between the two groups (sum 18.4 vs. 21.2). Further analysis revealed that in patients with "high disability" (the minimal generic data set score ⩾15), self-reported functioning was more severely impaired in the traumatic brain injury group compared to the spinal cord injury group (29.7 vs. 21.4, P < 0.0001), with no difference between these two diagnostic groups in patients with "low disability" (the minimal generic data set below 15). Patients with traumatic brain injury perceived more difficulties in cognition, getting along and participation, patients with spinal cord injury in mobility and self-care. CONCLUSION:: Both generic measures were able to detect severe disability but also to detect differences between two patient populations with different underlying diagnoses.

Digital Gaming for Improving the Functioning of People With Traumatic Brain Injury: Randomized Clinical Feasibility Study.

BACKGROUND: Traumatic brain injury (TBI) is a major health problem that often requires intensive and long-term rehabilitation. OBJECTIVE: The aim of this study was to determine whether rehabilitative digital gaming facilitates cognitive functioning and general well-being in people with TBI. METHODS: A total of 90 Finnish-speaking adults with TBI (18-65 years) were recruited from an outpatient neuroscience clinic. The participants were randomly allocated to one of the three groups: a rehabilitation gaming group (n=29, intervention), an entertainment gaming group (n=29, active control), or a passive control group (n=32). The gaming groups were instructed to engage in gaming for a minimum of 30 min per day for 8 weeks. Primary and secondary outcomes were measured at three time points: before the intervention, after the intervention, and 3 months following the intervention. The primary outcome was cognitive status measured by processing speed and visuomotor tasks (The Trail Making Test; Wechsler Adult Intelligence Scale-Fourth Edition, WAIS-IV, symbol search, coding, and cancellation tasks). Secondary outcomes were attention and executive functions (Simon task), working memory (WAIS-IV digit span and Paced Auditory Serial Addition Test, PASAT), depression (Patient Health Questionnaire-9), self-efficacy (General Self-efficacy Scale), and executive functions (Behavior Rating Inventory of Executive Function-Adult Version). Feasibility information was assessed (acceptability, measurement instruments filled, dropouts, adherence, usability, satisfaction, and possible future use). Cognitive measurements were conducted in face-to-face interviews by trained psychologists, and questionnaires were self-administered. RESULTS: The effects of rehabilitation gaming did not significantly differ from the effects of entertainment gaming or being in a passive control group. For primary outcomes and PASAT tests, the participants in all three groups showed overall improvement in test scores across the three measurement points. However, depression scores increased significantly between baseline and after 8 weeks and between baseline and after 3 months in the rehabilitative gaming group. No differences were found in patients' self-efficacy between the three measuring points in any of the groups. Participants did use the games (rehabilitation group: 93%, 27/29; entertainment group 100%, 29/29). Games were seen as a usable intervention (rehabilitation group: 70%, 14/29; entertainment group: 83%, 20/29). The rehabilitation group was less satisfied with the gaming intervention (68%, 13/29 vs 83%, 20/29), but they were more willing to use the game after the intervention period (76%, 16/29 vs 63%, 15/29). Total time spent on gaming during the intervention period was low (15.22 hour rehabilitation gaming group, 19.22 hour entertainment gaming group). CONCLUSIONS: We did not find differences between the groups in improvement in the outcome measures. The improvements in test performance by all three groups may reflect rehearsal effects. Entertainment gaming had elements that could be considered when rehabilitative games are designed for, implemented in, and assessed in larger clinical trials for persons with TBI. TRIAL REGISTRATION: ClinicalTrials.gov NCT02425527; https://clinicaltrials.gov/ct2/show/NCT02425527 (Archived by WebCite at http://www.webcitation.org/6esKI1uDH).

Injury profiles, demography and representativeness of patients with TBI attending a regional emergency department.

OBJECTIVES: The aim of this study was to describe the demography and epidemiology of Finnish patients with TBI and to analyse the representativeness of a study sample. MATERIALS AND METHODS: This prospective multi-centre study was conducted as part of an international collaboration within the EU-funded TBIcare project. The study group was recruited from patients attending the regional emergency department (ED) of the Turku University Hospital, Finland. Pre-defined exclusion criteria included age < 18 years, more than 2 weeks from the injury and uncertain diagnosis of TBI. To be included, a need for an acute head CT (NICE-criteria) was required. RESULTS: Of the 620 patients with TBI or suspected TBI, 203 patients were recruited to the study. Falls were the most common injury mechanism. The study group included more males than the total eligible population (p = 0.011), but no other statistical differences were found. The most common cause for being excluded was lack of information available to the research group before discharge (34%). CONCLUSION: This study supports previous findings that falls are the most common injury mechanism in the Western countries. Uncertainty about the diagnosis of TBI, lack of representativeness without continuous recruitment and poor information transfer about the ED attendees are major challenges for prospective TBI studies.

Outcomes from mild and moderate traumatic brain injuries among children and adolescents: A systematic review of studies from 2008-2013.

AIM: To systematically review existing empirical evidence concerning neuropsychological, psychosocial and academic outcomes following mild and moderate TBI during childhood and adolescence. METHOD: The studies reviewed include data on 8553 children and adolescents from ages 0-18 that experienced mild and moderate TBIs. A literature search using MeSH terms for 'children' cross-referenced with terms associated with 'head injuries' and 'cognition' was conducted using Pubmed, CINAHL Plus and Scopus databases as well as other data sources to retrieve grey literature results. Articles published between 1 January 2008 and 22 April 2013 were included. RESULTS: Fifty-five studies were included in the review, with multiple studies including information on both mild and moderate TBI; 46 studies focused on mild TBI outcomes and 22 studies focused on moderate TBI outcomes. The majority of outcomes were described as psychosocial (50%) or neuropsychological (40%); 51% of studies presented adverse outcomes. CONCLUSIONS: The results suggest that not all children with mild or moderate TBI recover without long-term problems. Few studies followed children and adolescents with mild TBIs for extended periods of time, although it is clinically important to monitor patients over time.

Clinical correlates of retrograde amnesia in mild traumatic brain injury.

PRIMARY OBJECTIVE: The purpose of this study was to examine the clinical significance of retrograde amnesia (RA) in patients with acute mild traumatic brain injuries (MTBI). METHODS AND PROCEDURES: An emergency department sample of patients (n = 75), aged 18-60 years, with no pre-morbid medical or psychiatric conditions, who met the WHO criteria for MTBI were enrolled in this prospective, descriptive, follow-up study. This study examined the presence and duration of RA in relation to socio-demographics, MTBI severity markers including neuroimaging (CT, MRI) and clinical outcomes (Rivermead post-concussion symptoms questionnaire, post-concussion syndrome (PCS) diagnosis and return to work (RTW) status) at 2 weeks, 1 month and 6 months post-injury. MAIN OUTCOMES AND RESULTS: GCS scores and duration of post-traumatic amnesia (PTA) were related to RA. Those with GCS scores of 14 vs. 15 were more likely to have RA (χ(2)(1) = 13.70, p < 0.0001) and a longer duration (Mann-Whitney U = 56.0, p < 0.0001, d = 1.15) of RA. The duration of RA and PTA correlated positively (Spearman ρ(75) = 0.42, p < 0.0001) and those with RA had longer durations of PTA (Mann-Whitney U = 228.5, p = 0.001, d = 1.21). During the follow-up, the presence and duration of RA were not significantly associated with PCS diagnosis or time to RTW. CONCLUSIONS: In this study, the presence and duration of RA was not associated with outcome.

Diffusion tensor tractography-based analysis of the cingulum: clinical utility and findings in traumatic brain injury with chronic sequels.

INTRODUCTION: To evaluate the clinical utility of quantitative diffusion tensor tractography (DTT) and tractography-based core analysis (TBCA) of the cingulum by defining the reproducibility, normal values, and findings in traumatic brain injury (TBI). METHODS: Eighty patients with TBI and normal routine MRI and 78 controls underwent MRI at 3T. To determine reproducibility, 12 subjects were scanned twice. Superior (SC) and inferior (IC) cingulum were analyzed separately by DTT (fractional anisotropy (FA) thresholds 0.15 and 0.30). TBCA was performed from volumes defined by tractography with gradually changed FA thresholds. FA values were correlated with clinical and neuropsychological data. RESULTS: The lowest coefficient of variation was obtained at DTT threshold 0.30 (2.0 and 2.4 % for SC and IC, respectively), but in proportion to standard deviations of normal controls, the reproducibility of TBCA was better in SC and similar to that of DTT in IC. In patients with TBI, volume reduction with loss of peripheral fibers was relatively common; mean FA was mostly normal in these tractograms. The frequency of FA reductions (>2 SD) was in DTT smaller than in TBCA, in which FA decrease was present in 42 (13.1 %) of the 320 measurements. Central FA values in SC predicted visuoperceptual ability, and those in left IC predicted cognitive speed, language, and communication ability (p < 0.05). CONCLUSION: Tractography-based measurements have sufficient reproducibility for demonstration of severe abnormalities of the cingulum. TBCA is preferential for clinical FA analysis, because it measures corresponding areas in patients and controls without inaccuracies due to trauma-induced structural changes.