Chronic Traumatic Encephalopathy in Soccer Players: Review of 14 Cases.

OBJECTIVE: Exposure to repetitive sports-related concussions or (sub)concussive head trauma may lead to chronic traumatic encephalopathy (CTE). Which impact (heading or concussion) poses the greatest risk of CTE development in soccer players? DESIGN: Narrative review. SETTING: Teaching hospital and University of Applied sciences. PATIENTS: A literature search (PubMed) was conducted for neuropathologic studies in the period 2005-December 2022, investigating soccer players with dementia and a CTE diagnosis, limited to English language publications. 210 papers were selected for final inclusion, of which 7 papers described 14 soccer players. ASSESSMENT: Magnetic resonance imaging studies in soccer players show that lifetime estimates of heading numbers are inversely correlated with cortical thickness, grey matter volume, and density of the anterior temporal cortex. Using diffusion tensor imaging-magnetic resonance imaging, higher frequency of headings-particularly with rotational accelerations-are associated with impaired white matter integrity. Serum neurofilament light protein is elevated after heading. MAIN OUTCOME MEASURES: Chronic traumatic encephalopathy pathology, history of concussion, heading frequency. RESULTS: In 10 of 14 soccer players, CTE was the primary diagnosis. In 4 cases, other dementia types formed the primary diagnosis and CTE pathology was a concomitant finding. Remarkably, 6 of the 14 cases had no history of concussion, suggesting that frequent heading may be a risk for CTE in patients without symptomatic concussion. Rule changes in heading duels, management of concussion during the game, and limiting the number of high force headers during training are discussed. CONCLUSIONS: Data suggest that heading frequency and concussions are associated with higher risk of developing CTE in (retired) soccer players. However based on this review of only 14 players, questions persist as to whether or not heading is a risk factor for CTE or long-term cognitive decline.

Health consequences of exposure to aircraft contaminated air and fume events: a narrative review and medical protocol for the investigation of exposed aircrew and passengers.

Thermally degraded engine oil and hydraulic fluid fumes contaminating aircraft cabin air conditioning systems have been well documented since the 1950s. Whilst organophosphates have been the main subject of interest, oil and hydraulic fumes in the air supply also contain ultrafine particles, numerous volatile organic hydrocarbons and thermally degraded products. We review the literature on the effects of fume events on aircrew health. Inhalation of these potentially toxic fumes is increasingly recognised to cause acute and long-term neurological, respiratory, cardiological and other symptoms. Cumulative exposure to regular small doses of toxic fumes is potentially damaging to health and may be exacerbated by a single higher-level exposure. Assessment is complex because of the limitations of considering the toxicity of individual substances in complex heated mixtures.There is a need for a systematic and consistent approach to diagnosis and treatment of persons who have been exposed to toxic fumes in aircraft cabins. The medical protocol presented in this paper has been written by internationally recognised experts and presents a consensus approach to the recognition, investigation and management of persons suffering from the toxic effects of inhaling thermally degraded engine oil and other fluids contaminating the air conditioning systems in aircraft, and includes actions and investigations for in-flight, immediately post-flight and late subsequent follow up.

A Child Presenting with a Glasgow Coma Scale Score of 13: Mild or Moderate Traumatic Brain Injury? A Narrative Review.

OBJECTIVE: The objective of this article was to compare children with traumatic brain injury (TBI) and Glasgow Coma Scale score (GCS) 13 with children presenting with GCS 14 and 15 and GCS 9 to 12. DATA SOURCE: We searched PubMed for clinical studies of children of 0 to 18 years of age with mild TBI (mTBI) and moderate TBI, published in English language in the period of 2000 to 2020. STUDY SELECTION: We selected studies sub-classifying children with GCS 13 in comparison with GCS 14 and 15 and 9 to 12. We excluded reviews, meta-analyses, non-U.S./European population studies, studies of abusive head trauma, and severe TBI. DATA SYNTHESIS: Most children (>85%) with an mTBI present at the emergency department with an initial GCS 15. A minority of only 5% present with GCS 13, 40% of which sustain a high-energy trauma. Compared with GCS 15, they present with a longer duration of unconsciousness and of post-traumatic amnesia. More often head computerized tomography scans show abnormalities (in 9-16%), leading to neurosurgical intervention in 3 to 8%. Also, higher rates of severe extracranial injury are reported. Admission is indicated in more than 90%, with a median length of hospitalization of more than 4 days and 28% requiring intensive care unit level care. These data are more consistent with children with GCS 9 to 12. In children with GCS 15, all these numbers are much lower. CONCLUSION: We advocate classifying children with GCS 13 as moderate TBI and treat them accordingly.

Susceptibility-Weighted MRI and Microbleeds in Mild Traumatic Brain Injury: Prediction of Posttraumatic Complaints?

BACKGROUND: Only in 7-15% of patients with mild traumatic brain injury (mTBI), traumatic CT-abnormalities are found. Nevertheless, 40% of mTBI patients suffer from posttraumatic complaints not resolving after 6 months. We discuss the ability of susceptibility-weighted imaging (SWI), sensitive for microbleeds, to detect more subtle brain abnormalities. SUMMARY: After a search on PubMed, we selected 15 studies on SWI in adult mTBI patients; 11 studies on 3T MRI, and 4 studies on 1.5T MRI. All 1.5T studies showed that, compared to T2, gradient echo, diffusion-weighted imaging, or fluid-attenuated inversion recovery sequences, SWI is more sensitive for microbleeds. Only two 1.5T studies described the association between SWI findings and outcome. In 3 of the 4 studies, no control group was present. The mean number of microbleeds varied from 3.2 to 6.4 per patient. In the 3T studies, the percentage of patients with traumatic microbleeds varied from 5.7 to 28.8%, compared to 0-13.3% in normal controls. Microbleeds were particularly located subcortical or juxtacortical. The number of microbleeds in mTBI varied from 1 to 10 per patient. mTBI patients with microbleeds appeared to have higher symptom severity at 12 months and perform worse on tests of psychomotor speed and speed of information processing after 3 and 12 months, compared to mTBI patients without microbleeds. KEY MESSAGES: There is some evidence that traumatic microbleeds predict cognitive outcome and persistent posttraumatic complaints in patients with mTBI.

Patients with mild traumatic brain injury and acute neck pain at the emergency department are a distinct category within the mTBI spectrum: a prospective multicentre cohort study.

BACKGROUND: Acute neck pain (ANP) has recently been demonstrated to be a predictor of persistent posttraumatic complaints after mild traumatic brain injury (mTBI). The aim of this study was to determine specific characteristics of patients with ANP following mTBI, their posttraumatic complaints and relationship with functional outcome. METHODS: Data from a prospective follow-up study of 922 mTBI patients admitted to the emergency department (ED) in three level-one trauma centres were analysed. Patients were divided into two groups: 156 ANP patients and 766 no acute neck pain (nANP) patients. Posttraumatic complaints were evaluated 2 weeks and 6 months post-injury using standardized questionnaires and functional outcome was evaluated at 6 months with the Glasgow Outcome Scale Extended (GOSE). RESULTS: ANP patients were more often female (p < 0.01), younger (38 vs. 47 years, p < 0.01) with more associated acute symptoms at the ED (p < 0.05) compared to nANP patients. More motor vehicle accidents (12% vs. 6%, p = 0.01) and less head wounds (58% vs. 73%, p < 0.01) in ANP patients indicated 'high-energy low-impact' trauma mechanisms. ANP patients showed more posttraumatic complaints 2 weeks and 6 months post-injury (p < 0.05) and more often incomplete recovery (GOSE < 8) was present after 6 months (56% vs. 40%, p = 0.01). CONCLUSIONS: MTBI patients with acute neck pain at the ED constitute a distinct group within the mTBI spectrum with specific injury and demographic characteristics. Early identification of this at risk group already at the ED might allow specific and timely treatment to avoid development of incomplete recovery.

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.

Chronic solvent-induced encephalopathy: course and prognostic factors of neuropsychological functioning.

PURPOSE: Working in conditions with daily exposure to organic solvents for many years can result in a disease known as chronic solvent-induced encephalopathy (CSE). The aims for this study were to describe the neuropsychological course of CSE after first diagnosis and to detect prognostic factors for neuropsychological impairment after diagnosis. METHODS: This prospective study follows a Dutch cohort of CSE patients who were first diagnosed between 2001 and 2011 and underwent a second neuropsychological assessment 1.5-2 years later. Cognitive subdomains were assessed and an overall cognitive impairment score was calculated. Paired t tests and multivariate linear regression analyses were performed to describe the neuropsychological course and to obtain prognostic factors for the neuropsychological functioning at follow-up. RESULTS: There was a significant improvement on neuropsychological subdomains at follow-up, with effect sizes between small and medium (Cohen's d 0.27-0.54) and a significant overall improvement of neuropsychological impairment with a medium effect size (Cohen's d 0.56). Prognostic variables for more neuropsychological impairment at follow-up were a higher level of neuropsychological impairment at diagnosis and having a comorbid diagnosis of a psychiatric disorder at diagnosis. CONCLUSIONS: Results are in line with previous research on the course of CSE, stating that CSE is a non-progressive disease after cessation of exposure. However, during follow-up the percentage patients with permanent work disability pension increased from 14 to 37%. Preventive action is needed in countries where exposure to organic solvents is still high to prevent new cases of CSE.

Risk factors and outcomes associated with post-traumatic headache after mild traumatic brain injury.

OBJECTIVES: To determine the prevalence and potential risk factors of acute and chronic post-traumatic headache (PTH) in patients with mild to moderate traumatic brain injury (TBI) in a prospective longitudinal observational multicentre study. Acute PTH (aPTH) is defined by new or worsening of pre-existing headache occurring within 7 days after trauma, whereas chronic PTH (cPTH) is defined as persisting aPTH >3 months after trauma. An additional goal was to study the impact of aPTH and cPTH in terms of return to work (RTW), anxiety and depression. METHODS: This was a prospective observational study conducted between January 2013 and February 2014 in three trauma centres in the Netherlands. Patients aged 16 years and older with a GCS score of 9-15 on admission to the ED, with loss of consciousness and/or amnesia were prospectively enrolled. Follow-up questionnaires were completed at 2 weeks and 3 months after injury with the Head Injury Symptom Checklist, the Hospital Anxiety and Depression Scale and RTW scale. RESULTS: In total, 628 patients were enrolled in the study, 469 completed the 2-week questionnaire (75%) at 2 weeks and 409 (65%) at 3 months. At 2 weeks, 238 (51%) had developed aPTH and at 3 months 95 (23%) had developed cPTH. Female gender, younger age, headache immediately at the ED and CT scan abnormalities increased the risk for aPTH. Risk factors for cPTH were female gender and headache at the ED. Patients with cPTH were less likely to have returned to work than those without cPTH (35% vs 14%, P=0.001). Patients with aPTH and cPTH more often report anxiety (20% and 28%, P=0.001) and depression (19% and 28%, P=0.001) after trauma in comparison with the group without PTH (10% anxiety and 8% depression). CONCLUSIONS: PTH is an important health problem with a significant impact on long-term outcome of TBI patients. Several risk factors were identified, which can aid in early identification of subjects at risk for PTH.

The juvenile head trauma syndrome: a trauma triggered migraine?

BACKGROUND: The underlying mechanism of the juvenile head trauma syndrome (JHTS) is still uncertain, but it has been suggested that there is a role in cortical spreading depression, a phenomenon that is assumed to be a part of the pathophysiology of migraine. HYPOTHESIS: We postulate that children affected by the JHTS are more susceptible to cortical spreading depression, caused by a genetic etiology similar to genetic factors in migraine. METHODS: Children with the JHTS were selected and evaluated retrospectively in an observational case-control study in two Dutch trauma centers in the period between January 2008 and July 2012. RESULTS: We included 33 patients with the JHTS, who were accounted for approximately 2.5% of the total number (1,342) of children seen at the emergency department with a mild head trauma. The prevalence of migraine in cases compared with controls did not differ. The proportion of patients with a first-degree relative with migraine was significantly higher in cases compared with controls (odds ratio, 2.69; 95% confidence interval, 1.16-6.22; p = 0.010). CONCLUSION: The JHTS is a relatively rare phenomenon, seen in approximately 2.5% of all children seen at the emergency department with mild brain injury. This study demonstrates a significant relationship between the JHTS and a positive history of migraine in first-degree relatives.

Mutations in potassium channel kcnd3 cause spinocerebellar ataxia type 19.

OBJECTIVE: To identify the causative gene for the neurodegenerative disorder spinocerebellar ataxia type 19 (SCA19) located on chromosomal region 1p21-q21. METHODS: Exome sequencing was used to identify the causal mutation in a large SCA19 family. We then screened 230 ataxia families for mutations located in the same gene (KCND3, also known as Kv4.3) using high-resolution melting. SCA19 brain autopsy material was evaluated, and in vitro experiments using ectopic expression of wild-type and mutant Kv4.3 were used to study protein localization, stability, and channel activity by patch-clamping. RESULTS: We detected a T352P mutation in the third extracellular loop of the voltage-gated potassium channel KCND3 that cosegregated with the disease phenotype in our original family. We identified 2 more novel missense mutations in the channel pore (M373I) and the S6 transmembrane domain (S390N) in 2 other ataxia families. T352P cerebellar autopsy material showed severe Purkinje cell degeneration, with abnormal intracellular accumulation and reduced protein levels of Kv4.3 in their soma. Ectopic expression of all mutant proteins in HeLa cells revealed retention in the endoplasmic reticulum and enhanced protein instability, in contrast to wild-type Kv4.3 that was localized on the plasma membrane. The regulatory ß subunit Kv channel interacting protein 2 was able to rescue the membrane localization and the stability of 2 of the 3 mutant Kv4.3 complexes. However, this either did not restore the channel function of the membrane-located mutant Kv4.3 complexes or restored it only partially. INTERPRETATION: KCND3 mutations cause SCA19 by impaired protein maturation and/or reduced channel function.

[Flying and COVID-19: options to reduce the risk of transmission]. / Vliegverkeer en covid-19.

With air travel continuing after the SARS-CoV-2 pandemic as before, is there a risk of in-flight-transmission? We found 18 papers describing a total number of 306 index patients on 150 flights, 79 infected passengers and four infected cabin crew. Infection transmission within the aircraft cabin depends on flight occupancy, proximity to the index patient, duration of flight and the prevailing virus variant. A negative PCR-test has a sensitivity of 95 %, around 5 % of travelers will get a false negative result. Airborne transmission of virus-containing saliva droplets (aerosols) is considered the most important infection mechanism; infection via contaminated surfaces is less common. Strict distancing, with an empty middle seat, is essential. The risk of in-flight transmission can be further minimized by mandatory masking, restricting passenger movements, restricting meals and beverages, frequent hand sanitizing and complying to rules while boarding or at disembarkation.

A Pyramidal Cause of a Cerebellar Ataxia: HSP-7.

A 43-year-old man presented with a slowly progressive fatigue and coordination problems, coupled with a radiological appearance of diffuse atrophy, especially in the cerebellar hemispheres. The diagnostic process was challenging because initially the additional investigations were focused on a cerebellar ataxia. In the following months, his ataxic gait developed in a more spastic pattern and whole exome sequencing revealed mutations in the SPG7 gene, confirming a diagnosis of hereditary spastic paraplegia. Therefore, the authors call for an extension of genetic panels in ataxia patients.

Aerotoxic syndrome, discussion of possible diagnostic criteria.

Introduction: The term aerotoxic syndrome (ATS) was proposed 20 years ago to describe a constellation of symptoms reported by pilots and cabin crew following exposure to hydraulic fluids, engine oil, and pyrolysis products during flight. Hydraulic fluids and engine oil contain a large number of potentially toxic chemicals, including various organophosphate compounds (OPCs). However, ATS is not yet recognised as a valid diagnosis in aviation or general medicine, because the incidence and aetiology continues to be debated.Discussion: Early studies report findings from symptom surveys or cognitive assessments of small samples of self-selected aircrew, but objective measures of exposure were lacking. Over the last decade, researchers have used more sophisticated techniques to measure exposure, such as on board monitoring studies and biomarkers of exposure (e.g., reduced levels of serum butyrylcholinesterases [BChE]) and more sophisticated techniques to detect nervous system injuries such as fMRI and autoantibody testing. Consideration has also been given to inter-individual differences in the ability to metabolise certain chemical compounds as a result of genetic polymorphisms and exclusion of other potential causes of ill health.Conclusions: We discuss factors which suggest a diagnosis of probable ATS; recommend an assessment protocol which incorporates the aforementioned techniques; and propose diagnostic criteria for probable ATS, based on our previously reported findings in aircrew and the results of recent studies.

[An abnormal CT scan following a mild traumatic brain injury; what then?] / Een afwijkende CT-scan bij licht traumatisch hoofdletsel, en dan?

CT scan reveals traumatic intracranial abnormalities in fewer than 10% of patients following mild traumatic brain injury (mTBI). Management policy in these patients is not clear. Clinical or radiological deterioration occurs in 10-20% of this risk group, usually within 24 hours and often without neurosurgical consequences. Patients with mTBI and subarachnoid blood or small foci of contusion do not need to be admitted to medium/high care or to the ICU. This is warranted in patients fulfilling the following criteria: age > 65 years; a Glasgow Coma Scale (GCS) score < 15; anticoagulant use; or multiple trauma. It is also warranted by fulfilment of one or more of the following CT-criteria: shift of the midline; subdural or epidural haematoma; a temporal or subfrontal focus of contusion; or intraparenchymatous bleeding > 10 ml. Repeated CT-scan is only indicated in case of clinical deterioration. Transfer to a neurosurgical centre is not necessary in the majority of patients with mTBI and CT abnormalities.

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.

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.

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.

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.