Dexamethasone versus Surgery for Chronic Subdural Hematoma.

BACKGROUND: The role of glucocorticoids without surgical evacuation in the treatment of chronic subdural hematoma is unclear. METHODS: In this multicenter, open-label, controlled, noninferiority trial, we randomly assigned symptomatic patients with chronic subdural hematoma in a 1:1 ratio to a 19-day tapering course of dexamethasone or to burr-hole drainage. The primary end point was the functional outcome at 3 months after randomization, as assessed by the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]). Noninferiority was defined by a lower limit of the 95% confidence interval of the odds ratio for a better functional outcome with dexamethasone than with surgery of 0.9 or more. Secondary end points included scores on the Markwalder Grading Scale of symptom severity and on the Extended Glasgow Outcome Scale. RESULTS: From September 2016 through February 2021, we enrolled 252 patients of a planned sample size of 420; 127 were assigned to the dexamethasone group and 125 to the surgery group. The mean age of the patients was 74 years, and 77% were men. The trial was terminated early by the data and safety monitoring board owing to safety and outcome concerns in the dexamethasone group. The adjusted common odds ratio for a lower (better) score on the modified Rankin scale at 3 months with dexamethasone than with surgery was 0.55 (95% confidence interval, 0.34 to 0.90), which failed to show noninferiority of dexamethasone. The scores on the Markwalder Grading Scale and Extended Glasgow Outcome Scale were generally supportive of the results of the primary analysis. Complications occurred in 59% of the patients in the dexamethasone group and 32% of those in the surgery group, and additional surgery was performed in 55% and 6%, respectively. CONCLUSIONS: In a trial that involved patients with chronic subdural hematoma and that was stopped early, dexamethasone treatment was not found to be noninferior to burr-hole drainage with respect to functional outcomes and was associated with more complications and a greater likelihood of later surgery. (Funded by the Netherlands Organization for Health Research and Development and others; DECSA EudraCT number, 2015-001563-39.).

Exploring the kynurenine pathway in mild traumatic brain injury: A longitudinal study.

A potential source of novel biomarkers for mTBI is the kynurenine pathway (KP), a metabolic pathway of tryptophan (Trp), that is up-regulated by neuroinflammation and stress. Considering that metabolites of the KP (kynurenines) are implicated in various neuropsychiatric diseases, exploration of this pathway could potentially bridge the gap between physiological and psychological factors in the recovery process after mTBI. This study, therefore, set out to characterize the KP after mTBI and to examine associations with long-term outcome. Patients were prospectively recruited at the emergency department (ED), and blood samples were obtained in the acute phase (<24 h; N = 256) and at 1-month follow-up (N = 146). A comparison group of healthy controls (HC; N = 32) was studied at both timepoints. Trp, kynurenines, and interleukin (IL)-6 and IL-10 were quantified in plasma. Clinical outcome was measured at six months post-injury. Trp, xanthurenic acid (XA), and picolinic acid (PA) were significantly reduced in patients with mTBI relative to HC, corrected for age and sex. For Trp (d = -0.57 vs. d = -0.29) and XA (d = -0.98 vs. d = -0.32), larger effects sizes were observed during the acute phase compared to one-month follow-up, while for PA (d = -0.49 vs. d = -0.52) effect sizes remained consistent. Findings for other kynurenines (e.g., kynurenine, kynurenic acid, and quinolinic acid) were non-significant after correction for multiple testing. Within the mTBI group, lower acute Trp levels were significantly related to incomplete functional recovery and higher depression scores at 6 months post-injury. No significant relationships were found for Trp, XA, and PA with IL-6 or IL-10 concentrations. In conclusion, our findings indicate that perturbations of the plasma KP in the hyperacute phase of mTBI and 1 month later are limited to the precursor Trp, and glutamate system modulating kynurenines XA and PA. Correlations between acute reductions of Trp and unfavorable outcomes may suggest a potential substrate for pharmacological intervention.

Etomidate versus Ketamine as Prehospital Induction Agent in Patients with Suspected Severe Traumatic Brain Injury.

BACKGROUND: Severe traumatic brain injury is a leading cause of morbidity and mortality among young people around the world. Prehospital care focuses on the prevention and treatment of secondary brain injury and commonly includes tracheal intubation after induction of general anesthesia. The choice of induction agent in this setting is controversial. This study therefore investigated the association between the chosen induction medication etomidate versus S(+)-ketamine and the 30-day mortality in patients with severe traumatic brain injury who received prehospital airway management in the Netherlands. METHODS: This study is a retrospective analysis of the prospectively collected observational data of the Brain Injury: Prehospital Registry of Outcomes, Treatments and Epidemiology of Cerebral Trauma (BRAIN-PROTECT) cohort study. Patients with suspected severe traumatic brain injury who were transported to a participating trauma center and who received etomidate or S(+)-ketamine for prehospital induction of anesthesia for advanced airway management were included. Statistical analyses were performed with multivariable logistic regression and inverse probability of treatment weighting analysis. RESULTS: In total, 1,457 patients were eligible for analysis. No significant association between the administered induction medication and 30-day mortality was observed in unadjusted analyses (32.9% mortality for etomidate versus 33.8% mortality for S(+)-ketamine; P = 0.716; odds ratio, 1.04; 95% CI, 0.83 to 1.32; P = 0.711), as well as after adjustment for potential confounders (odds ratio, 1.08; 95% CI, 0.67 to 1.73; P = 0.765; and risk difference 0.017; 95% CI, -0.051 to 0.084; P = 0.686). Likewise, in planned subgroup analyses for patients with confirmed traumatic brain injury and patients with isolated traumatic brain injury, no significant differences were found. Consistent results were found after multiple imputations of missing data. CONCLUSIONS: The analysis found no evidence for an association between the use of etomidate or S(+)-ketamine as an anesthetic agent for intubation in patients with traumatic brain injury and mortality after 30 days in the prehospital setting, suggesting that the choice of induction agent may not influence the patient mortality rate in this population.

Neurophysiological signatures of mild traumatic brain injury in the acute and subacute phase.

BACKGROUND: Mild traumatic brain injury (mTBI) affects 48 million people annually, with up to 30% experiencing long-term complaints such as fatigue, blurred vision, and poor concentration. Assessing neurophysiological features related to visual attention and outcome measures aids in understanding clinical symptoms and prognostication. METHODS: We recorded EEG and eye movements in mTBI patients during a computerized task performed in the acute (< 24 h, TBI-A) and subacute phase (4-6 weeks thereafter). We estimated the posterior dominant rhythm, reaction times (RTs), fixation duration, and event-related potentials (ERPs). Clinical outcome measures were assessed using the Head Injury Symptom Checklist (HISC) and the Extended Glasgow Outcome Scale (GOSE) at 6 months post-injury. Similar analyses were performed in an age-matched control group (measured once). Linear mixed effect modeling was used to examine group differences and temporal changes within the mTBI group. RESULTS: Twenty-nine patients were included in the acute phase, 30 in the subacute phase, and 19 controls. RTs and fixation duration were longer in mTBI patients compared to controls (p < 0.05), but not between TBI-A and TBI-S (p < 0.05). The frequency of the posterior dominant rhythm was significantly slower in TBI-A (0.6 Hz, p < 0.05) than TBI-S. ERP mean amplitude was significantly lower in mTBI patients than in controls. Neurophysiological features did not significantly relate to clinical outcome measures. CONCLUSION: mTBI patients demonstrate impaired processing speed and stimulus evaluation compared to controls, persisting up to 6 weeks after injury. Neurophysiological features in mTBI can assist in determining the extent and temporal progression of recovery.

Efficacy of an Intensive Exposure Intervention for Individuals With Persistent Concussion Symptoms Following Concussion: A Concurrent Multiple Baseline Single-Case Experimental Design (SCED) Study.

OBJECTIVE: After a concussion, 1 in 3 patients report persistent symptoms and experience long-term consequences interfering with daily functioning, known as persistent concussion symptoms (PCS). Evidence suggests PCS is (partly) maintained by anxious thoughts about brain functioning, recovery, and experienced symptoms, leading to avoidance behaviors, which may prevent patients from meeting life demands. We aimed to investigate the efficacy of a newly developed intensive exposure intervention for individuals with PCS after concussion aimed to tackle avoidance behavior. SETTING: Participants took part in the intervention at the Maastricht University faculty. PARTICIPANTS: Four participants who experienced PCS after concussion partook in the exploratory study. Participants' age ranged between 20 and 32 (mean = 26.5, SD = 5.9) years, with an average length of time after the concussion of 9.8 months. DESIGN: A concurrent multiple-baseline single-case design was conducted. The baseline period (A phase) length was randomly determined across participants (3, 4, 5, or 6 weeks). The exposure intervention (B phase) was conducted by psychologists over a 4-week period and consisted of 3 stages: exploration (2 sessions), active exposure (12 sessions conducted over 1 week), and 2 booster sessions. MAIN MEASURES: Participants answered daily questions on a visual analog scale related to symptom experience, satisfaction with daily functioning, and degree of avoidance of feared activities. Additional outcomes included symptom severity, catastrophizing, fear of mental activity, anxiety, depression, and societal participation. RESULTS: Tau-U yielded significant effects (P < .05) for all participants on all measures when comparing baseline and intervention phases. The pooled standardized mean difference was high for all measures (symptom experience = 0.93, satisfaction of daily functioning = 1.86, and activity avoidance = -2.05). CONCLUSIONS: The results show efficacy of the newly developed intensive exposure treatment for PCS after concussion, which is based on the fear avoidance model. Replication in a larger heterogeneous sample is warranted and needed.

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.

Frequency and predictors of headache in the first 12 months after traumatic brain injury: results from CENTER-TBI.

BACKGROUND: Headache is a prevalent and debilitating symptom following traumatic brain injury (TBI). Large-scale, prospective cohort studies are needed to establish long-term headache prevalence and associated factors after TBI. This study aimed to assess the frequency and severity of headache after TBI and determine whether sociodemographic factors, injury severity characteristics, and pre- and post-injury comorbidities predicted changes in headache frequency and severity during the first 12 months after injury. METHODS: A large patient sample from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study was used. Patients were stratified based on their clinical care pathway: admitted to an emergency room (ER), a ward (ADM) or an intensive care unit (ICU) in the acute phase. Headache was assessed using a single item from the Rivermead Post-Concussion Symptoms Questionnaire measured at baseline, 3, 6 and 12 months after injury. Mixed-effect logistic regression analyses were applied to investigate changes in headache frequency and associated predictors. RESULTS: A total of 2,291 patients responded to the headache item at baseline. At study enrolment, 59.3% of patients reported acute headache, with similar frequencies across all strata. Female patients and those aged up to 40 years reported a higher frequency of headache at baseline compared to males and older adults. The frequency of severe headache was highest in patients admitted to the ICU. The frequency of headache in the ER stratum decreased substantially from baseline to 3 months and remained from 3 to 6 months. Similar trajectory trends were observed in the ICU and ADM strata across 12 months. Younger age, more severe TBI, fatigue, neck pain and vision problems were among the predictors of more severe headache over time. More than 25% of patients experienced headache at 12 months after injury. CONCLUSIONS: Headache is a common symptom after TBI, especially in female and younger patients. It typically decreases in the first 3 months before stabilising. However, more than a quarter of patients still experienced headache at 12 months after injury. Translational research is needed to advance the clinical decision-making process and improve targeted medical treatment for headache. TRIAL REGISTRATION: ClinicalTrials.gov NCT02210221.

The American Congress of Rehabilitation Medicine Diagnostic Criteria for Mild Traumatic Brain Injury.

OBJECTIVE: To develop new diagnostic criteria for mild traumatic brain injury (TBI) that are appropriate for use across the lifespan and in sports, civilian trauma, and military settings. DESIGN: Rapid evidence reviews on 12 clinical questions and Delphi method for expert consensus. PARTICIPANTS: The Mild Traumatic Brain Injury Task Force of the American Congress of Rehabilitation Medicine Brain Injury Special Interest Group convened a Working Group of 17 members and an external interdisciplinary expert panel of 32 clinician-scientists. Public stakeholder feedback was analyzed from 68 individuals and 23 organizations. RESULTS: The first 2 Delphi votes asked the expert panel to rate their agreement with both the diagnostic criteria for mild TBI and the supporting evidence statements. In the first round, 10 of 12 evidence statements reached consensus agreement. Revised evidence statements underwent a second round of expert panel voting, where consensus was achieved for all. For the diagnostic criteria, the final agreement rate, after the third vote, was 90.7%. Public stakeholder feedback was incorporated into the diagnostic criteria revision prior to the third expert panel vote. A terminology question was added to the third round of Delphi voting, where 30 of 32 (93.8%) expert panel members agreed that 'the diagnostic label 'concussion' may be used interchangeably with 'mild TBI' when neuroimaging is normal or not clinically indicated.' CONCLUSIONS: New diagnostic criteria for mild TBI were developed through an evidence review and expert consensus process. Having unified diagnostic criteria for mild TBI can improve the quality and consistency of mild TBI research and clinical care.

The Cognitive Profile of Elderly Patients With Mild Traumatic Brain Injury: A Role for Cognitive Reserve?

OBJECTIVE: To assess cognitive status in elderly patients with mild traumatic brain injury (mTBI) in the subacute phase, examine the role of cognitive reserve, and investigate associations with cognitive complaints, mental distress, and functional outcomes. SETTING: A level 1 trauma center in the Netherlands. PARTICIPANTS: A total of 52 individuals with mTBI and 42 healthy controls. DESIGN: A prospective observational cohort study. MAIN MEASURES: Neuropsychological assessment in the subacute phase (2 weeks to 6 months post-injury) to objectively measure the cognitive functioning, the Head Injury Symptom Checklist for subjective cognitive complaints, the Hospital Anxiety and Depression Scale for anxiety and depression, the Cognitive Reserve Index questionnaire for cognitive reserve, the Community Integration Questionnaire for community integration, and the Glasgow Outcome Scale Extended for functional outcome. RESULTS: Cognitive impairments were observed in memory (P < .001) and attention, processing speed and executive control (P < .001). Cognitive reserve was not associated with neuropsychological test performance, except for one test measuring working memory. The relationship between injury severity and cognitive outcome was not moderated by cognitive reserve. Elderly patients reported significantly more complains than healthy controls regarding forgetfulness, concentration problems, and slowness. Complaints of concentration were associated with cognitive impairment. All cognitive complaints were significantly correlated with mental distress. CONCLUSIONS: Cognitive impairments may be present in elderly patients in the subacute phase after mTBI, and these impairments were not significantly associated with cognitive reserve. This suggests that cognitive reserve might not serve as a protective factor against the effects of mTBI in the elderly. Concentration complaints may serve as a specific indicator for cognitive impairment, while complaints of memory and mental slowness may represent more generic indicators of mental distress. These findings highlight the importance of careful screening in older adults with mTBI, guiding clinicians toward specific treatment targets encompassing cognitive impairment, diminished mental well-being, or both.

The cognitive status of chronic subdural hematoma patients after treatment: an exploratory study.

OBJECTIVE: Chronic subdural hematoma (CSDH) is a common neurological condition, often affecting the elderly. Cognitive impairment is frequently observed at presentation. However, the course and longer term aspects of the cognitive status of CSDH patients are unknown. In this study, we aim to explore the cognitive status of CSDH patients after treatment. METHODS: An exploratory study in which CSDH patients were assessed 3 months after treatment and compared to healthy controls. A total of 56 CSDH patients (age 72.1 SD ± 10.8 years with 43 [77%] males) and 60 healthy controls were included (age 67.5 ± SD 4.8 with 34 [57%] males). Cognitive testing was performed using the Telephonic Interview of Cognitive Status-modified (TICS-m), a 12-item questionnaire in which a total of 50 points can be obtained on several cognitive domains. RESULTS: Median time between treatment and cognitive testing was 93 days (range 76-139). TICS-m scores of CSDH patients were significantly lower than healthy controls, after adjusting for age and sex: mean score 34.6 (95% CI: 33.6-35.9) vs. 39.6 (95% CI: 38.5-40.7), p value < 0.001. More than half (54%) of CSDH patients have cognitive scores at follow-up that correspond with cognitive impairment. CONCLUSION: A large number of CSDH patients show significantly worse cognitive status 3 months after treatment compared to healthy controls. This finding underlines the importance of increased awareness for impaired cognition after CSDH. Further research on this topic is warranted.

Imaging of neuroinflammation due to repetitive head injury in currently active kickboxers.

PURPOSE: Chronic traumatic encephalopathy refers to a neurodegenerative disease resulting from repetitive head injury of participants in contact sports. Similar to other neurodegenerative diseases, neuroinflammation is thought to play a role in the onset and progression of the disease. Limited knowledge is available regarding the neuroinflammatory consequences of repetitive head injury in currently active contact sports athletes. PET imaging of the 18-kDa translocator protein (TSPO) allows quantification of microglial activation in vivo, a marker of neuroinflammation. METHODS: Eleven rank A kickboxers and 11 age-matched controls underwent TSPO PET using [11C]-PK11195, anatomical MRI, diffusion tensor imaging, and neuropsychological testing. Relevant imaging parameters were derived and correlated with the outcomes of the neuropsychological testing. RESULTS: On a group level, no statistically significant differences were detected in non-displaceable binding potential (BPND) using PET. Individually, 3 kickboxers showed increased BPNDs in widespread regions of the brain without a correlation with other modalities. Increased FA was observed in the superior corona radiata bilaterally. DTI parameters in other regions did not differ between groups. CONCLUSION: Despite negative results on a group level, individual results suggest that neuroinflammation may be present as a consequence of repetitive head injury in active kickboxers. Future studies using a longitudinal design may determine whether the observed TSPO upregulation is related to the future development of neuropsychiatric symptoms.

Presenting symptoms and functional outcome of chronic subdural hematoma patients.

BACKGROUND: Patients with chronic subdural hematoma (CSDH) can present with a variety of signs and symptoms. The relationship of these signs and symptoms with functional outcome is unknown. Knowledge of these associations might aid clinicians in the choice to initiate treatment and may allow them to better inform patients on expected outcomes. OBJECTIVE: To investigate if presenting signs and symptoms influence functional outcome in patients with CSDH. METHODS: We conducted a retrospective analysis of consecutive CSDH patients in three hospitals. Glasgow Outcome Scale Extended (GOS-E) scores were obtained from the first follow-up visit after treatment. An ordinal multivariable regression analysis was performed, to assess the relationship between the different signs and symptoms on the one hand and functional outcome on the other adjusted for potential confounders. RESULTS: We included 1,307 patients, of whom 958 (73%) were male and mean age was 74 (SD ± 11) years. Cognitive complaints were associated with lower GOS-E scores at follow-up (aOR 0.7, 95% CI: 0.5 - 0.8) Headache and higher Glasgow Coma Scale (GCS) scores were associated with higher GOS-E scores. (aOR 1.9, 95% CI: 1.5-2.3 and aOR 1.3, 95% CI: 1.2-1.4). CONCLUSION: Cognitive complaints are independently associated with worse functional outcome, whereas headache and higher GCS scores are associated with better outcome. The increased probability of unfavorable outcome in patients with CSDH who present with cognitive complaints favors a more prominent place of assessing cognitive status at diagnosis.

Pathophysiology of transient neurological deficit in patients with chronic subdural hematoma: A systematic review.

Patients with chronic subdural hematoma (CSDH) can have transient neurological deficits deficit (TND) mimicking transient ischemic attacks. The prevalence of TNDs in CSDH varies between 1%-24%, depending on TND definition. Despite this high prevalence the pathophysiology of TND in CSDH is not clear in many cases. In this systematic review, we aim to unravel the responsible mechanism. Pubmed and Embase were searched for all articles concerning the pathophysiology of TND as a presenting symptom in patients with CSDH. There were no publication date restrictions for the articles in the search. Two reviewers independently selected studies for inclusion and subsequently extracted the necessary data. Out of 316 identified references, 15 met the inclusion criteria. Several articles mentioned multiple pathophysiological mechanisms. One of the proposed etiologies of TND was epileptic activity, stated by three articles. In contrast, three different studies stated that seizures are unlikely to cause TND. Five papers suggested that obstruction of blood flow, caused by the hematoma or subsequent swelling, might be the cause. Six articles made no definite statement on the responsible pathophysiological mechanism of TND. Different mechanisms have been proposed to be the cause of TNDs in patients with CSDH. Based on this review, the exact pathophysiology of TND remains unclear. We suggest that future studies on this topic should incorporate MRI of the brain (with diffusion-weighted imaging) and EEG, to provide better insight into TND pathophysiology. The knowledge resulting from future studies might contribute to better understanding of TND and optimal treatment in CSDH.

Development of prognostic models for Health-Related Quality of Life following traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of impairments affecting Health-Related Quality of Life (HRQoL). We aimed to identify predictors of and develop prognostic models for HRQoL following TBI. METHODS: We used data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Core study, including patients with a clinical diagnosis of TBI and an indication for computed tomography presenting within 24 h of injury. The primary outcome measures were the SF-36v2 physical (PCS) and mental (MCS) health component summary scores and the Quality of Life after Traumatic Brain Injury (QOLIBRI) total score 6 months post injury. We considered 16 patient and injury characteristics in linear regression analyses. Model performance was expressed as proportion of variance explained (R2) and corrected for optimism with bootstrap procedures. RESULTS: 2666 Adult patients completed the HRQoL questionnaires. Most were mild TBI patients (74%). The strongest predictors for PCS were Glasgow Coma Scale, major extracranial injury, and pre-injury health status, while MCS and QOLIBRI were mainly related to pre-injury mental health problems, level of education, and type of employment. R2 of the full models was 19% for PCS, 9% for MCS, and 13% for the QOLIBRI. In a subset of patients following predominantly mild TBI (N = 436), including 2 week HRQoL assessment improved model performance substantially (R2 PCS 15% to 37%, MCS 12% to 36%, and QOLIBRI 10% to 48%). CONCLUSION: Medical and injury-related characteristics are of greatest importance for the prediction of PCS, whereas patient-related characteristics are more important for the prediction of MCS and the QOLIBRI following TBI.

Mortality after chronic subdural hematoma is associated with frailty.

PURPOSE: Chronic subdural hematoma (CSDH) is a common neurological disease often affecting the elderly. Long-term excess mortality for patients after CSDH has been suggested but causes of death are unknown. We hypothesize that excess mortality of CSDH patients is related to frailty. In this article, we describe mortality rates and causes of death of CSDH patients compared with the general population and assess the association of frailty with mortality. METHODS: A cohort study in which consecutive CSDH patients were compared to the general population regarding mortality rates. Furthermore, the association of six frailty indicators (cognitive problems, frequent falling, unable to live independently, unable to perform daily self-care, use of benzodiazepines or psychotropic drugs, and number of medications) with mortality was assessed. RESULTS: A total of 1307 CSDH patients were included, with a mean age of 73.7 (SD ± 11.4) years and 958 (73%) were male. Median follow-up was 56 months (range: 0-213). Compared with controls CSDH patients had a hazard ratio for mortality of 1.34 (95% CI: 1.2-1.5). CSDH patients more often died from cardiovascular diseases (37% vs. 30%) and falls (7.2% vs. 3.7%). Among CSDH patients frequent falling (HR 1.3; 95% CI: 1.0-1.7), inability to live independently (HR 1.4, 95% CI: 1.1-1.8), inability to perform daily self-care (HR 1.5; 95% CI: 1.1-1.9), and number of medications used (HR 1.0; 95% CI: 1.0-1.1) were independently associated with mortality. CONCLUSIONS: CSDH patients have higher mortality rates than the general population. Frailty in CSDH patients is associated with higher mortality risk. More attention for the frailty of CSDH patients is warranted.

External validation of prognostic models predicting outcome after chronic subdural hematoma.

BACKGROUND: Several prognostic models for outcomes after chronic subdural hematoma (CSDH) treatment have been published in recent years. However, these models are not sufficiently validated for use in daily clinical practice. We aimed to assess the performance of existing prediction models for outcomes in patients diagnosed with CSDH. METHODS: We systematically searched relevant literature databases up to February 2021 to identify prognostic models for outcome prediction in patients diagnosed with CSDH. For the external validation of prognostic models, we used a retrospective database, containing data of 2384 patients from three Dutch regions. Prognostic models were included if they predicted either mortality, hematoma recurrence, functional outcome, or quality of life. Models were excluded when predictors were absent in our database or available for < 150 patients in our database. We assessed calibration, and discrimination (quantified by the concordance index C) of the included prognostic models in our retrospective database. RESULTS: We identified 1680 original publications of which 1656 were excluded based on title or abstract, mostly because they did not concern CSDH or did not define a prognostic model. Out of 18 identified models, three could be externally validated in our retrospective database: a model for 30-day mortality in 1656 patients, a model for 2 months, and another for 3-month hematoma recurrence both in 1733 patients. The models overestimated the proportion of patients with these outcomes by 11% (15% predicted vs. 4% observed), 1% (10% vs. 9%), and 2% (11% vs. 9%), respectively. Their discriminative ability was poor to modest (C of 0.70 [0.63-0.77]; 0.46 [0.35-0.56]; 0.59 [0.51-0.66], respectively). CONCLUSIONS: None of the examined models showed good predictive performance for outcomes after CSDH treatment in our dataset. This study confirms the difficulty in predicting outcomes after CSDH and emphasizes the heterogeneity of CSDH patients. The importance of developing high-quality models by using unified predictors and relevant outcome measures and appropriate modeling strategies is warranted.

Highlights mild traumatic brain injury 2021.

PURPOSE: Mild traumatic brain injury (TBI) is one of the most common causes of morbidity worldwide. Patients at risk of unfavourable outcome may benefit from additional attention and help but identification of these patients necessitates the development of diagnostic methods to assess indices of brain injury at an early stage. The aim of this overview is to highlight studies that reflect the growing scientific attention to the early diagnosis and prognostication of mild TBI. RECENT FINDINGS: The value of serum biomarkers for the diagnosis of TBI severity has been acknowledged in recent studies. The diagnostic and prognostic utility of several biomarkers of brain injury, such as glial fibrillary acidic protein, and of inflammation, such as interleukin (IL)-6 and IL-10, holds promise for application in daily clinical practice in a point-of-care platform. Besides head CT imaging, early advanced MRI brain imaging has been reported as a tool for assessment of injury severity and prognostication. The introduction of direct oral anticoagulants (DOACs) has raised new challenges for the treatment of intracranial traumatic haemorrhage at the Emergency Department. SUMMARY: Promising findings of new diagnostic markers of brain injury severity highlight the potential prognostic value of serum biomarkers and early MRI imaging. The accurate assessment of patients at risk of incomplete recovery after mTBI will enhance more timely and individualized treatment.

White matter microstructure of the neural emotion regulation circuitry in mild traumatic brain injury.

Emotion regulation is related to recovery after mild traumatic brain injury (mTBI). This longitudinal tractography study examined white matter tracts subserving emotion regulation across the spectrum of mTBI, with a focus on persistent symptoms. Four groups were examined: (a) symptomatic (n = 33) and (b) asymptomatic (n = 20) patients with uncomplicated mTBI (i.e., no lesions on computed tomography [CT]), (c) patients with CT-lesions in the frontal areas (n = 14), and (d) healthy controls (HC) (n = 20). Diffusion and conventional MRI were performed approximately 1- and 3-months post-injury. Whole-brain deterministic tractography followed by region of interest analyses was used to identify forceps minor (FM), uncinate fasciculus (UF), and cingulum bundle as tracts of interest. An adjusted version of the ExploreDTI Atlas Based Tractography method was used to obtain reliable tracts for every subject. Mean fractional anisotropy (FA), mean, radial and axial diffusivity (MD, RD, AD), and number of streamlines were studied per tract. Linear mixed models showed lower FA, and higher MD, and RD of the right UF in asymptomatic patients with uncomplicated mTBI relative to symptomatic patients and HC. Diffusion alterations were most pronounced in the group with frontal lesions on CT, particularly in the FM and UF; these effects increased over time. Within the group of patients with uncomplicated mTBI, there were no associations of diffusion measures with the number of symptoms nor with lesions on conventional MRI. In conclusion, mTBI can cause microstructural changes in emotion regulation tracts, however, no explanation was found for the presence of symptoms.

Behaviors of Concern after Acquired Brain Injury: The Role of Negative Emotion Recognition and Anger Misattribution.

OBJECTIVE: Behavioral changes are common after acquired brain injury (ABI) and may be caused by social cognition impairments. We investigated whether impaired emotion recognition, specifically Negative Emotion Recognition (NER) and Anger Misattribution (AM), after ABI was related to behavioral problems, so-called Behaviors of Concern (BoC). METHOD: The study included 139 participants with ABI and 129 healthy controls. BoC was measured using four scales of the Brock Adaptive Functioning Questionnaire (BAFQ): Impulsivity, Aggression, Social Monitoring, and Empathy. Both self-ratings and informant ratings of BoC were obtained. Emotion recognition was measured with the Ekman 60 Faces Test (FEEST). A NER score was composed of the summed scores on Anger, Disgust, Fear, and Sadness. An AM score was composed of the number of facial expressions wrongly recognized as Anger. RESULTS: Total FEEST scores in ABI participants were significantly worse than in healthy controls. The effect size is moderate. Informants rated significantly more problems in Social Monitoring and Empathy than participants. Effect sizes were small. Scores on FEEST total, NER, and AM were significantly correlated to informant ratings of Social Monitoring. Correlations were weak to moderate. CONCLUSIONS: Worse NER and more profound AM were related to more informant-rated problems in social monitoring. In addition, informants rated more problems in social monitoring and empathy than participants. This strongly suggests problems in self-awareness in ABI participants. Consequently, social cognition tests and informant ratings should be used in clinical practice to improve the detection and treatment of BoC after ABI.

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.