Identification of At-Risk Patients That Need More Intensive Treatment Following mTBI: Post-Hoc Insights From the UPFRONT-Study.

OBJECTIVE: To investigate which factors within an at-risk group make patients less likely to benefit from preventive treatment following mild traumatic brain injury (mTBI). SETTING: Inclusion in 3 level I trauma centers in the Netherlands. Data collection through surveys as outpatients. PARTICIPANTS: mTBI patients (18-66 years), reporting 3 or more complaints 2 weeks postinjury (at-risk status). Eighty-four patients included and randomized (39 patients cognitive behavioral therapy, 45 patients telephonic counseling). Eighty patients filled out the questionnaires 12 months postinjury. Post hoc analysis investigating 80 patients as 1 at-risk group receiving psychological treatment. DESIGN: Post hoc study of a randomized controlled trial (RCT). Binomial logistic regression performed determining which variables 2 weeks postinjury contributed strongly to unsuccessful return to work/study (RTW) and unfavorable outcome at 12 months. MAIN MEASURES: RTW and functional outcome as measured with the Glasgow Outcome Scale-Extended (GOSE) at 12 months postinjury. RESULTS: Out of 80 patients, 43 (53.8%) showed a favorable functional outcome at 12 months, and 56 (70%) patients had a full RTW. Patients with unfavorable outcome had a higher age and higher reports of anxiety, depression at 2 weeks and 12 months postinjury. Patients with an unsuccessful RTW had a higher age and higher reports of depression, and posttraumatic stress disorder at 2 weeks and 12 months postinjury. A logistic regression model for functional outcome (GOSE) was statistically significant (χ²7 = 40.30, P < .0001). Of 6 predictor variables, 3 were significant: anxiety, depression, and treatment condition. For RTW, logistic regression was also statistically significant (χ²7 = 19.15, P = .008), with only 1 out of 6 predictor variables (ie, age) being significant. CONCLUSION: Main findings comprise differences in demographic and psychological measures between patients with favorable and unfavorable outcomes and patients with RTW versus no RTW. Prediction models of outcome and RTW showed several psychological measures at 2 weeks greatly determining patients' likelihood benefitting from the preventive treatment. Results suggest that from the beginning there are some patients for whom a short preventive treatment is not sufficient. Selection and treatment of at-risk patients might be better based on psychological symptoms instead of posttraumatic complaints.

Trajectories of Fatigue, Psychological Distress, and Coping Styles After Mild Traumatic Brain Injury: A 6-Month Prospective Cohort Study.

OBJECTIVE: To analyze fatigue after mild traumatic brain injury (TBI) with latent class growth analysis (LCGA) to determine distinct recovery trajectories and investigate influencing factors, including emotional distress and coping styles. DESIGN: An observational cohort study design with validated questionnaires assessing fatigue, anxiety, depression, posttraumatic stress, and coping at 2 weeks and 3 and 6 months postinjury. SETTING: Three level 1 trauma centers. PARTICIPANTS: Patients with mild TBI (N=456). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Fatigue was measured with the fatigue severity subscale of the Checklist Individual Strength, including 8 items (sum score, 8-56). Subsequently, 3 clinical categories were created: high (score, 40-56), moderate (score, 26-38), and low (score, 8-25). RESULTS: From the entire mild TBI group, 4 patient clusters with distinct patterns for fatigue, emotional distress, and coping styles were found with LCGA. Clusters 1 and 2 showed favorable recovery from fatigue over time, with low emotional distress and the predominant use of active coping in cluster 1 (30%) and low emotional distress and decreasing passive coping in cluster 2 (25%). Clusters 3 and 4 showed unfavorable recovery, with persistent high fatigue and increasing passive coping together with low emotional distress in cluster 3 (27%) and high emotional distress in cluster 4 (18%). Patients with adverse trajectories were more often women and more often experiencing sleep disturbances and pain. CONCLUSIONS: The prognosis for recovery from posttraumatic fatigue is favorable for 55% of mild TBI patients. Patients at risk for chronic fatigue can be signaled in the acute phase postinjury based on the presence of high fatigue, high passive coping, and, for a subgroup of patients, high emotional distress. LCGA proved to be a highly valuable and multipurpose statistical method to map distinct courses of disease-related processes over time.

Coping with stress before and after mild traumatic brain injury: a pilot hair cortisol study.

Background: Cortisol is a crucial hormone for adaptation to challenging and stressful situations. Hair cortisol measurement is used to determine chronic stress; the growth rate of hair allows to determine averaged cortisol levels for a longer period. Objective: Pre- and post-injury measures of hair cortisol were compared in patients with mild traumatic brain injury (mTBI), and related to their coping styles.Methods: For 46 patients with mTBI, 3 cm scalp hair samples were collected 4-6 weeks post-injury, resulting in two 1 cm segments, pre- and post-injury. Hair samples were also collected for 11 healthy controls. Hair cortisol was quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Complaints, anxiety, depression and coping style were measured two weeks post-injury and long term (six-twelve months), added with measures for post-traumatic stress and functional outcome.Results: There were no differences between patients' pre- and post-injury cortisol levels, nor between cortisol levels of patients and controls. However, pre- and post-injury cortisol levels of patients were negatively correlated with both passive and an avoidant coping style.Conclusions: Our findings suggest that mTBI has no separate impact on chronic long-term cortisol levels, possibility indicating that variability in cortisol levels reflects individuals' premorbid characteristics determining coping with stress in general.

Early Predictors for Long-Term Functional Outcome After Mild Traumatic Brain Injury in Frail Elderly Patients.

OBJECTIVE: To identify the effect of frailty and early postinjury measures on the long-term outcome after mild traumatic brain injury in elderly patients. SETTING: Patients admitted to 3 Dutch hospitals designated as level 1 trauma centers. PARTICIPANTS: The elderly (≥60 years) with mild traumatic brain injury (N = 161). DESIGN: A prospective observational cohort study. MAIN MEASURES: Posttraumatic complaints and the Hospital Anxiety and Depression Scale determined 2 weeks postinjury; the Glasgow Outcome Scale Extended and Groningen frailty indicator determined 1 to 3 years postinjury. RESULTS: A total of 102 nonfrail (63%) and 59 frail elderly (37%) patients, mean age of 70.8 (6.3) years were included. Most patients (54%; 72% nonfrail and 24% frail) recovered completely 1 to 3 years postinjury. Two weeks postinjury, 81% had posttraumatic complaints (83% frail and 80% nonfrail elderly), and 30% showed emotional distress (50% frail and 20% nonfrail). Frailty (odds ratio, 2.1; 95% confidence interval, 1.59-2.77) and presence of early complaints (odds ratio, 1.13; 95% confidence interval, 1.01-1.27) (Nagelkerke R = 46%) were found to predict long-term outcome, whereas age was not a significant predictor. CONCLUSION: The frail elderly had worse long-term outcome, and early complaints were found to be a stronger predictor of unfavorable outcome than age. Understanding the implications of frailty on outcome could help clinicians recognize patients at risk of a poor outcome and allocate care more efficiently.

Description of an early cognitive behavioral intervention (UPFRONT-intervention) following mild traumatic brain injury to prevent persistent complaints and facilitate return to work.

PURPOSE: Many patients with mild traumatic brain injury do not fully return to work owing to persistent posttraumatic complaints. Research suggests that preventing chronic complaints might be prevented by giving cognitive behavioral therapy early after injury. Therefore, a new cognitive behavioral intervention (UPFRONT-intervention) was developed to not only prevent chronic complaints but to also establish a more successful return to work. The intervention is currently being evaluated in a multicenter randomized controlled trial design (trial number ISRCTN86191894) in mild traumatic brain injury patients who are at-risk of negative outcomes (patients with high numbers of early complaints). Two case examples are presented to demonstrate the application of the intervention. RATIONALE: Psychological factors, like cognitive appraisal and coping, play an important role in the persistence of posttraumatic complaints. Some patients are less able to adapt and thus to cope with the injury and its initial consequences than others. Dealing with the injury in a passive, avoidant way, focusing on negative feelings, will hamper recovery and is therefore a valuable target for an intervention. Theory into practice: The UPFRONT intervention is a short cognitive behavioral therapy intervention for patients that are at-risk of developing persistent posttraumatic complaints. Patients will undergo five sessions of cognitive behavioral therapy within 4-10 weeks after trauma. The intervention aims to enhance patients' feeling of competency of dealing with the consequences of mild traumatic brain injury by providing psycho-education, identifying and challenging unrealistic illness perceptions and improving coping style (decreasing maladaptive coping and enhancing adaptive coping).

Brain network dysregulation, emotion, and complaints after mild traumatic brain injury.

OBJECTIVES: To assess the role of brain networks in emotion regulation and post-traumatic complaints in the sub-acute phase after non-complicated mild traumatic brain injury (mTBI). EXPERIMENTAL DESIGN: Fifty-four patients with mTBI (34 with and 20 without complaints) and 20 healthy controls (group-matched for age, sex, education, and handedness) were included. Resting-state fMRI was performed at four weeks post-injury. Static and dynamic functional connectivity were studied within and between the default mode, executive (frontoparietal and bilateral frontal network), and salience network. The hospital anxiety and depression scale (HADS) was used to measure anxiety (HADS-A) and depression (HADS-D). PRINCIPAL OBSERVATIONS: Regarding within-network functional connectivity, none of the selected brain networks were different between groups. Regarding between-network interactions, patients with complaints exhibited lower functional connectivity between the bilateral frontal and salience network compared to patients without complaints. In the total patient group, higher HADS-D scores were related to lower functional connectivity between the bilateral frontal network and both the right frontoparietal and salience network, and to higher connectivity between the right frontoparietal and salience network. Furthermore, whereas higher HADS-D scores were associated with lower connectivity within the parietal midline areas of the bilateral frontal network, higher HADS-A scores were related to lower connectivity within medial prefrontal areas of the bilateral frontal network. CONCLUSIONS: Functional interactions of the executive and salience networks were related to emotion regulation and complaints after mTBI, with a key role for the bilateral frontal network. These findings may have implications for future studies on the effect of psychological interventions.

Dynamic phase-locking states and personality in sub-acute mild traumatic brain injury: An exploratory study.

Research has shown that maladaptive personality characteristics, such as Neuroticism, are associated with poor outcome after mild traumatic brain injury (mTBI). The current exploratory study investigated the neural underpinnings of this process using dynamic functional network connectivity (dFNC) analyses of resting-state (rs) fMRI, and diffusion MRI (dMRI). Twenty-seven mTBI patients and 21 healthy controls (HC) were included. After measuring the Big Five personality dimensions, principal component analysis (PCA) was used to obtain a superordinate factor representing emotional instability, consisting of high Neuroticism, moderate Openness, and low Extraversion, Agreeableness, and Conscientiousness. Persistent symptoms were measured using the head injury symptom checklist at six months post-injury; symptom severity (i.e., sum of all items) was used for further analyses. For patients, brain MRI was performed in the sub-acute phase (~1 month) post-injury. Following parcellation of rs-fMRI using independent component analysis, leading eigenvector dynamic analysis (LEiDA) was performed to compute dynamic phase-locking brain states. Main patterns of brain diffusion were computed using tract-based spatial statistics followed by PCA. No differences in phase-locking state measures were found between patients and HC. Regarding dMRI, a trend significant decrease in fractional anisotropy was found in patients relative to HC, particularly in the fornix, genu of the corpus callosum, anterior and posterior corona radiata. Visiting one specific phase-locking state was associated with lower symptom severity after mTBI. This state was characterized by two clearly delineated communities (each community consisting of areas with synchronized phases): one representing an executive/saliency system, with a strong contribution of the insulae and basal ganglia; the other representing the canonical default mode network. In patients who scored high on emotional instability, this relationship was even more pronounced. Dynamic phase-locking states were not related to findings on dMRI. Altogether, our results provide preliminary evidence for the coupling between personality and dFNC in the development of long-term symptoms after mTBI.

Executive functioning in relation to coping in mild versus moderate-severe traumatic brain injury.

OBJECTIVE: To examine associations between executive functioning (EF) and coping styles, separately for mild and moderate-severe traumatic brain injury (TBI) in the chronic phase postinjury. METHOD: Patients with mild (n = 47) and moderate-severe TBI (n = 59) were included, in addition to healthy controls (HCs; n = 51). Assessment consisted of EF tests (Trail Making Test, Zoo Map Test, Controlled Oral Word Association Test) and questionnaires examining EF (Dysexecutive Questionnaire) and coping styles (Utrecht Coping List). RESULTS: Moderate-severe TBI patients showed significant more EF deficits, lower active coping and higher passive coping than mild TBI patients and HCs, whereas mild TBI patients did not differ from HCs. In the moderate-severe TBI group, a higher number of self-reported EF problems was related to lower levels of active coping, r = -.43, p < .01 and higher levels of passive coping, r = .58, p < .001, with proxy-reports relating to lower levels of active coping, r = -.33, p < .05. For mild TBI, a higher amount of self-reported EF problems was related to lower levels of active coping, r = -.38, p < .05 and higher levels of passive coping, r = .55, p < .001, with proxy-reports relating to higher levels of passive coping, r = .39, p < .05. Except for mental flexibility, EF performances were not associated with coping. CONCLUSIONS: This study shows strong associations between reported EF problems in daily life and coping styles. For moderate-severe TBI, proxy-reports may reflect EF impairments that complicate active problem-solving. However, reported EF problems by mild and moderate-severe TBI patients are also likely to reflect a psychological distress related to the way patients are inclined to deal with stressing situations that put a demand on their executive abilities. (PsycINFO Database Record

Patients "At Risk" of Suffering from Persistent Complaints after Mild Traumatic Brain Injury: The Role of Coping, Mood Disorders, and Post-Traumatic Stress.

Although most patients recover fully following mild traumatic brain injury (mTBI), a minority (15-25%) of all patients develop persistent post-traumatic complaints (PTC) that interfere with the resumption of previous activities. An early identification of patients who are at risk for PTC is currently performed by measuring the number of complaints in the acute phase. However, only part of this group will actually develop persisting complaints, stressing the need for studies on additional risk factors. This study aimed to compare this group of patients with many complaints with patients with few and no complaints to identify potential additional discriminating characteristics and to evaluate which of these factors have the most predictive value for being at risk. We evaluated coping style, presence of psychiatric history, injury characteristics, mood-related symptoms, and post-traumatic stress. We included 820 patients (Glasgow Coma Scale [GCS] score 13-15) admitted to three level-1 trauma centers as part of the UPFRONT-study. At 2 weeks after injury, 60% reported three or more complaints (PTC-high), 25% reported few complaints (PTC-low), and 15% reported no complaints (PTC-zero). Results showed that PTC-high consisted of more females (78% vs. 73% and 52%, p < 0.001), were more likely to have a psychiatric history (7% vs. 2% and 5%), and had a higher number of reported depression (22% vs. 6% and 3%, p < 0.001), anxiety (25% vs. 7% and 5%), and post-traumatic stress (37% vs. 27% and 19%, p < 0.001) than the PTC-low and PTC-zero groups. We conclude that in addition to reported complaints, psychological factors such as coping style, depression, anxiety, and post-traumatic stress symptoms had the highest predictive value and should be taken into account in the identification of at-risk patients for future treatment studies.

Altered Wiring of the Human Structural Connectome in Adults with Mild Traumatic Brain Injury.

In this study, structural connectivity after mild traumatic brain injury (mTBI) was examined from a network perspective, with a particular focus on post-traumatic complaints. Fifty-three patients with and without self-reported complaints at 2 weeks after uncomplicated mTBI were included, in addition to 20 matched healthy controls. Diffusion weighted imaging was performed at 4 weeks post-injury, and neuropsychological tests measuring processing speed and verbal memory were administered at 3 months post-injury to determine cognitive outcome. Structural connectivity was investigated using whole brain tractography and subsequent graph theory analysis. In patients with mTBI, eigenvector centrality within the left temporal pole was lower than in healthy controls. In patients without complaints, global and mean local efficiency were lower than in patients with complaints, although no differences were found between either subgroup and the group of healthy controls. Neuropsychological test scores were similar for patients with mTBI and healthy controls. However, patients with complaints showed higher processing speed than patients without complaints. Within the total mTBI group, a trend was found toward a correlation between lower network clustering and higher processing speed. Additionally, significant correlations were found between higher betweenness centrality values of language areas and lower verbal memory scores in patients with mTBI. In conclusion, our findings may indicate that global graph measures of the structural connectome are associated with pre- and/or non-injury-related factors that determine the susceptibility to developing (persistent) complaints after mTBI. Further, correlations between graph measures and neuropsychological test scores could suggest early compensatory mechanisms to maintain adequate cognitive performance.

Non-Hospitalized Patients with Mild Traumatic Brain Injury: The Forgotten Minority.

Non-hospitalized mild traumatic brain injury (mTBI) patients comprise a substantial part of the trauma population. For these patients, guidelines recommend specialized follow-up only in the case of persistent complaints or problems in returning to previous activities. This study describes injury and outcome characteristics of non-hospitalized mTBI patients, and the possibility of predicting which of the non-hospitalized patients will return to the outpatient neurology clinic. Data from all non-hospitalized mTBI patients (Glasgow Coma Scale [GCS] score 13-15, n = 462) from a prospective follow-up study on mTBI (UPFRONT-study) conducted in three level 1 trauma centers were analyzed. At 2 weeks, and 3 and 6 months after injury, patients completed questionnaires on post-traumatic complaints, depression, anxiety, outpatient follow-up, and resumption of activities. Most patients were male (57%), with a mean age of 40 years (range 16-91 years). Injuries were most often caused by traffic accidents (32%) or falls (39%). Six months after injury, 36% showed incomplete recovery as defined by the Glasgow Outcome Scale - Extended (GOS-E). Twenty-five percent of the non-hospitalized patients returned to the outpatient neurology clinic within 6 months after injury, of which one third had not completely resumed pre-injury activities. Regression analyses showed an increased risk for outpatient follow-up for patients scoring above the cutoff value for anxiety (odds ratio [OR] = 3.0), depression (OR = 3.5), or both (OR = 3.7) 2 weeks after injury. Our findings underline that clinicians and researchers should be aware of recovery for all mTBI patients, preventing their transition into a forgotten minority.

Stability of coping and the role of self-efficacy in the first year following mild traumatic brain injury.

BACKGROUND AND AIMS: Coping, the psychological adaptation to stressors and serious life events, has been found to have a great influence on the development and persistence of posttraumatic complaints. Coping has received much attention for having been found to be modifiable in treatment following mild traumatic brain injury (mTBI) and for its potential to identify the Patients who are at risk of suffering from long-term complaints. Currently, coping styles are assumed to be stable over time. Although interventions to facilitate adaptive coping are given at different time intervals after the injury, little is known about spontaneous changes in preferred strategies over time following mTBI. This study aimed to investigate the stability of different coping styles over a one-year period following mTBI (at two weeks', six and twelve months' post-injury) and to investigate the relation between coping styles and feelings of self-efficacy. METHODS: We included 425 mTBI patients (Glasgow Coma Scale [GCS] score 13-15) admitted to three Level-1 trauma centers in the Netherlands as part of a prospective follow-up study. All participants filled out The Utrecht Coping List (UCL) to determine their position on seven coping subscales. RESULTS: Most coping styles showed a decrease over time, except for positive reframing, which showed a decrease and then increased. Interestingly, the passive coping style was found to stabilize over time within the year after injury. High feelings of self-efficacy were related to a high active coping style (r = 0.36), and low feelings of self-efficacy with passive coping (r = -0.32). CONCLUSIONS: These results hold important possibilities for the use of the passive coping strategy as an inclusion criterion for intervention studies and an entry point for treatment itself. Considering the intertwinement of coping with self-efficacy, improving feelings of self-efficacy could form an effective part of an intervention to improve outcome.

Prediction of work resumption and sustainability up to 1 year after mild traumatic brain injury.

OBJECTIVE: To study return to work (RTW) after mild traumatic brain injury (mTBI) at several intervals after injury and to predict RTW on the basis of occupational factors in addition to demographic, personality, and injury-related factors at 6 and 12 months after injury. METHODS: This was a prospective cohort study (UPFRONT study, n = 1,151) of patients with mTBI admitted to the emergency department. Patients received questionnaires at 2 weeks and 3, 6, and 12 months after injury. RTW was divided into 3 levels: complete (cRTW), partial (pRTW), and no RTW. RESULTS: Rates of cRTW increased from 34% at 2 weeks to 77% at 12 months after injury, pRTW varied from 8% to 16% throughout the year. Logistic regression (complete vs incomplete RTW) demonstrated that apart from previously identified predictors such as demographics (e.g., age and education) and injury characteristics (e.g., cause and severity of injury) and indicators of psychological distress, occupational factors were of influence on work resumption after 6 months (area under the curve [AUC] = 0.82), At 12 months, however, the model was based solely on the presence of extracranial injuries and indicators of maladaptation after injury (AUC = 0.81). CONCLUSIONS: RTW after mTBI is a gradual process, with varying levels of RTW throughout the first year after injury. Different predictors were relevant for short- vs long-term work resumption, with occupational factors influencing short-term RTW. However, for both short- and long-term RTW, posttraumatic complaints and signs of psychological distress early after injury were relevant predictors, allowing early identification of patients at risk for problematic work resumption.

The Default Mode Network as a Biomarker of Persistent Complaints after Mild Traumatic Brain Injury: A Longitudinal Functional Magnetic Resonance Imaging Study.

The objective of this study was to examine longitudinal functional connectivity of resting-state networks in patients with and without complaints after uncomplicated mild traumatic brain injury (mTBI). Second, we aimed to determine the value of network connectivity in predicting persistent complaints, anxiety, depression and long-term outcome. Thirty mTBI patients with three or more post-traumatic complaints at 2 weeks post-injury, 19 without complaints, and 20 matched healthy controls were selected for this study. Resting-state functional MRI (fMRI) was performed in patients at 1 month and 3 months post-injury, and once in healthy controls. Independent component analysis (ICA) was used to investigate the default mode, executive and salience networks. Persistent post-traumatic complaints, anxiety, and depression were measured at 3 months post-injury, and outcome was determined at 1 year post-injury. Within the group with complaints, higher functional connectivity between the anterior and posterior components of the default mode network at 1 month post-injury was associated with a greater number of complaints at 3 months post-injury (ρ = 0.59, p = 0.001). Minor longitudinal changes in functional connectivity were found for patients with and without complaints after mTBI, which were limited to connectivity within the precuneus component of the default mode network. No significant results were found for the executive and salience networks. Current results suggest that the default mode network may serve as a biomarker of persistent complaints in patients with uncomplicated mTBI.

Graph Analysis of Functional Brain Networks in Patients with Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) is one of the most common neurological disorders worldwide. Posttraumatic complaints are frequently reported, interfering with outcome. However, a consistent neural substrate has not yet been found. We used graph analysis to further unravel the complex interactions between functional brain networks, complaints, anxiety and depression in the sub-acute stage after mTBI. This study included 54 patients with uncomplicated mTBI and 20 matched healthy controls. Posttraumatic complaints, anxiety and depression were measured at two weeks post-injury. Patients were selected based on presence (n = 34) or absence (n = 20) of complaints. Resting-state fMRI scans were made approximately four weeks post-injury. High order independent component analysis resulted in 89 neural components that were included in subsequent graph analyses. No differences in graph measures were found between patients with mTBI and healthy controls. Regarding the two patient subgroups, degree, strength, local efficiency and eigenvector centrality of the bilateral posterior cingulate/precuneus and bilateral parahippocampal gyrus were higher, and eigenvector centrality of the frontal pole/ bilateral middle & superior frontal gyrus was lower in patients with complaints compared to patients without complaints. In patients with mTBI, higher degree, strength and eigenvector centrality of default mode network components were related to higher depression scores, and higher degree and eigenvector centrality of executive network components were related to lower depression scores. In patients without complaints, one extra module was found compared to patients with complaints and healthy controls, consisting of the cingulate areas. In conclusion, this research extends the knowledge of functional network connectivity after mTBI. Specifically, our results suggest that an imbalance in the function of the default mode- and executive network plays a central role in the interaction between emotion regulation and the persistence of posttraumatic complaints.

Early predictors of outcome after mild traumatic brain injury (UPFRONT): an observational cohort study.

BACKGROUND: Mild traumatic brain injury (mTBI) accounts for most cases of TBI, and many patients show incomplete long-term functional recovery. We aimed to create a prognostic model for functional outcome by combining demographics, injury severity, and psychological factors to identify patients at risk for incomplete recovery at 6 months. In particular, we investigated additional indicators of emotional distress and coping style at 2 weeks above early predictors measured at the emergency department. METHODS: The UPFRONT study was an observational cohort study done at the emergency departments of three level-1 trauma centres in the Netherlands, which included patients with mTBI, defined by a Glasgow Coma Scale score of 13-15 and either post-traumatic amnesia lasting less than 24 h or loss of consciousness for less than 30 min. Emergency department predictors were measured either on admission with mTBI-comprising injury severity (GCS score, post-traumatic amnesia, and CT abnormalities), demographics (age, gender, educational level, pre-injury mental health, and previous brain injury), and physical conditions (alcohol use on the day of injury, neck pain, headache, nausea, dizziness)-or at 2 weeks, when we obtained data on mood (Hospital Anxiety and Depression Scale), emotional distress (Impact of Event Scale), coping (Utrecht Coping List), and post-traumatic complaints. The functional outcome was recovery, assessed at 6 months after injury with the Glasgow Outcome Scale Extended (GOSE). We dichotomised recovery into complete (GOSE=8) and incomplete (GOSE≤7) recovery. We used logistic regression analyses to assess the predictive value of patient information collected at the time of admission to an emergency department (eg, demographics, injury severity) alone, and combined with predictors of outcome collected at 2 weeks after injury (eg, emotional distress and coping). FINDINGS: Between Jan 25, 2013, and Jan 6, 2015, data from 910 patients with mTBI were collected 2 weeks after injury; the final date for 6-month follow-up was July 6, 2015. Of these patients, 764 (84%) had post-traumatic complaints and 414 (45%) showed emotional distress. At 6 months after injury, outcome data were available for 671 patients; complete recovery (GOSE=8) was observed in 373 (56%) patients and incomplete recovery (GOSE ≤7) in 298 (44%) patients. Logistic regression analyses identified several predictors for 6-month outcome, including education and age, with a clear surplus value of indicators of emotional distress and coping obtained at 2 weeks (area under the curve [AUC]=0·79, optimism 0·02; Nagelkerke R2=0·32, optimism 0·05) than only emergency department predictors at the time of admission (AUC=0·72, optimism 0·03; Nagelkerke R2=0·19, optimism 0·05). INTERPRETATION: Psychological factors (ie, emotional distress and maladaptive coping experienced early after injury) in combination with pre-injury mental health problems, education, and age are important predictors for recovery at 6 months following mTBI. These findings provide targets for early interventions to improve outcome in a subgroup of patients at risk of incomplete recovery from mTBI, and warrant validation. FUNDING: Dutch Brain Foundation.

Cognitive Behavioral Intervention Compared to Telephone Counseling Early after Mild Traumatic Brain Injury: A Randomized Trial.

Many patients do not return to work (RTW) after mild traumatic brain injury (mTBI) because of persistent complaints that are often resistant to therapy in the chronic phase. Recent studies suggest that psychological interventions should be implemented early post-injury to prevent patients from developing chronic complaints. This study is a randomized, controlled trial that examines the effectiveness of a newly developed cognitive behavioral therapy (CBT) intervention (CBTi) compared to telephonic counseling (TC) in at-risk mTBI patients (patients with high reports of early complaints). Patients underwent either five sessions of CBT treatment or five phone conversations starting 4-6 weeks post-trauma. The main outcome measure was RTW 6 and 12 months post-trauma. Secondary measures comprised functional outcome at 6 and 12 months, and depression, anxiety, and reported post-traumatic complaints at 3, 6, and 12 months post-injury. After excluding dropouts, CBTi consisted of 39 patients and TC of 45 patients. No significant differences were found with regard to RTW, with 65% of CBTi patients and 67% of TC patients reporting a RTW at previous level. However, TC patients reported fewer complaints at 3 (8 vs. 6; p = 0.010) and 12 months post-injury (9 vs. 5; p = 0.006), and more patients in the TC group showed a full recovery 12 months post-injury compared to the CBTi group (62% vs. 39%). The results of this study suggest that early follow-up of at-risk patients can have a positive influence on patients' well-being, and that a low-intensive, low-cost telephonic intervention might be more effective than a CBT intervention at improving outcome in at-risk patients.

Acute Alcohol Intoxication in Patients with Mild Traumatic Brain Injury: Characteristics, Recovery, and Outcome.

A substantial number of patients (30% to 50%) sustains a mild traumatic brain injury (mTBI) while they are under the influence of alcohol. An acute alcohol intoxication (AAI) at the time of injury has been subject of research in severe TBI, but little is known about the relation between AAI and mTBI. This study aimed to describe the characteristics of this intoxicated subgroup and evaluate recovery and outcome in comparison to sober mTBI patients. We included 528 mTBI patients (Glasgow Coma Scale [GCS] score 13-15) admitted to two Level 1 trauma centers as part of a prospective follow-up study. We compared clinical characteristics, demographics, and injury mechanism between groups. Post-concussive complaints, mood disorders, and post-traumatic stress-related complaints were assessed at 2 weeks post-injury, and outcome at 6 months with the Glasgow Outcome Scale Extended (GOSE). Thirty-three percent of the mTBI patients were intoxicated. Results showed that the intoxicated group was younger (36 vs. 40 years; p = 0.001) and were more frequently of male gender (78% vs. 60%; p < .001). The groups also differed in injury related characteristics, with intoxicated patients more frequently sustaining falls or violence-related injuries. The intoxicated group was assessed with a lower GCS score and had a higher hospital admission rate. However, at 2 weeks post-injury, intoxicated patients reported less complaints than the non-alcohol group and showed a better recovery at 6 months (average GOSE scores 7 vs. 7.3; p = 0.030). We conclude that AAI in mTBI represents a characteristically different group, which has implications for prevention measures, as well as the course of recovery.

Post-concussive complaints after mild traumatic brain injury associated with altered brain networks during working memory performance.

The aim was to investigate brain network function during working memory (WM) task performance in patients with uncomplicated mild traumatic brain injury (mTBI) in the sub-acute phase post-injury. We were particularly interested in differences between patients with (PCC-present) and without post-concussive complaints (PCC-absent). Fifty-two patients and twenty healthy controls (HCs) (matched for age, sex, education and handedness) were included. Two patient groups were created based on reported post-concussive complaints at two weeks post-injury: PCC-present (n = 32) and PCC-absent (n = 20). Functional MRI scans were made at approximately four weeks post-injury. Participants performed an n-back task consisting of three conditions (0-, 1- and 2-back) with increasing difficulty. General linear model analysis was performed to investigate activation patterns. Independent component analysis was used to identify brain networks. The frontal executive network (FEN), frontoparietal network (FPN) and default mode network (DMN) were selected for further analyses based on their highest task-relatedness. Task accuracy and reaction times were similar for patients with mTBI and HCs. During high WM load (2-vs.0-back contrast), mTBI patients exhibited lower activation within the medial prefrontal cortex compared to HCs. No differences were found between PCC-present and PCC-absent patients. Regarding network function, PCC-absent patients showed stronger deactivation of the DMN compared to PCC-present patients and HCs, especially during difficult task conditions. Furthermore, functional connectivity between the DMN and FEN was lower in PCC-absent patients compared to PCC-present patients. Interestingly, network function did not differ between PCC-present patients and HCs, suggesting that non-injury related factors may underlie post-concussive complaints after mTBI.