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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.

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., This diffusion MRI study examined frontal tracts supporting emotion regulation in patients with mild traumatic brain injury (mTBI). Asymptomatic patients with uncomplicated (i.e., no lesions on computed tomography [CT]) mTBI showed changes in the microstructure of the right uncinate fasciculus (UF), whereas symptomatic patients did not. Microstructural changes were most pronounced in patients with frontal lesions on CT, particularly in the forceps minor and UF. In uncomplicated mTBI, tract microstructure was not related to the number of symptoms or lesions on conventional MRI.

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.

Background: Impaired cognition can be a late effect after treatment in long-term testicular cancer (TC) survivors, negatively affecting their daily life. However, little data is available beyond 20 years post-treatment. We assessed cognitive impairment in very long-term TC survivors after CT or RT and compared the results with stage I TC survivors and controls. Methods: In this cross-sectional multicenter cohort study, we enrolled TC survivors (treated with orchiectomy followed by CT or RT or orchiectomy only)—with a follow-up duration ≥ 20 years—and age-matched healthy controls. Cognitive testing included the Auditory Verbal Learning Test, Letter Fluency Test, Category Fluency Test, and Trail Making Test. We used fasting blood samples to assess the presence of hypogonadism and measured cardiovascular aging parameters, including carotid pulse wave velocity (c-PWV) and advanced glycation end products (AGEs). Results: We included 184 TC survivors (66 CT patients, 53 RT patients, and 65 orchiectomy-only patients) and 70 healthy controls. The median follow-up was 26 years (range: 20–42). TC survivors had a lower combined score of the cognitive tests (mean cumulative Z-score −0.85, 95% CI −1.39 to −0.33) compared to controls (mean 0.67, 95% CI −0.21 to 1.57, p &lt, 0.01). In univariate analysis, the presence of hypogonadism (β −1.50, p &lt, 0.01), high c-PWV (β −0.35, p = 0.09), and high AGEs (β −1.27, p = 0.02) were associated with lower cognitive scores, while only AGEs (β −1.17, p = 0.03) remained a significant predictor in multivariate analysis (Model R2 0.31, p &lt, 0.01). Conclusions: Long-term TC survivors performed worse on cognitive tests compared to controls. Physicians and patients should be informed about timely cardiovascular risk management and testosterone supplementation therapy during follow-up to reduce the risk of cognitive impairment. Trial Registration: NCT02572934.

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.

BackgroundFunctional near-infrared spectroscopy (fNIRS) enables assessment of prefrontal hemodynamic response. This study explored the feasibility of fNIRS in determining hemodynamic changes related to cognitive task performance in pediatric traumatic brain injury (TBI) in order to assess its potential as a diagnostic tool.MethodsWe measured changes in oxygenated hemoglobin [O2Hb] during a verbal fluency task (VFT), which activates frontal brain regions involved in working memory, in 15 TBI patients and 21 healthy controls using a 3-channel fNIRS system. Baseline and absolute changes in [O2Hb] during the VFT were compared to the rest condition to obtain effect-scores. Patients were tested in the acute phase and six weeks after injury. Task-related fNIRS responses were categorized into positive, negative, and no response.ResultsFor patients and controls, a positive response was observed in 61% (n = 22), a negative response in 19% (n = 7), and no response in 19% (n = 7). Patients showed a mean [O2Hb] effect-score of 2.18 compared to 2.52 in the control group (p = 0.743) in the acute phase after injury. Follow-up effect-scores did not differ significantly (p = 0.721). Decreased task performance was associated with a higher effect-score in controls compared to decreased task performance with lower effect-score in the patient group.DiscussionOur study shows that it is feasible to assess hemodynamic response with fNIRS in pediatric TBI patients. A trend of reduced prefrontal hemodynamic response in patients in the acute phase after injury was found suggesting impairment in cognitive performance that warrants further study.

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

BACKGROUND Radiotherapy is a well-known risk factor for neurocognitive decline in glioma patients. Advanced radiotherapy techniques enable more selective brain irradiation. However, limited data exists on which brain regions are most relevant to avoid. The aim of this study was to explore the dose-effect relationship between brain subvolumes and neurocognitive performance. METHODS In this cross-sectional study, patients with grade II or III glioma treated with radiotherapy who were free of progression for at least one year were eligible. Patients underwent a neurocognitive test battery, including Rey Auditory Verbal Learning Test; (RAVLT), Trail Making Test (TMT), Copy of Rey’s Complex Figure Test (RCFT), Single Digit Modalities Test (SDMT) and Verbal Fluency tests (letters and categories). Test scores were correlated to radiation dose distributions in brain subvolumes using non-parametric tests. RESULTS The study was composed of 17 right-handed patients with grade II (n= 14) and grade III (n= 3) gliomas. The mean follow up after radiotherapy was 42 months, and the mean age 47 years. Performance on all tests was significantly worse for patients compared to healthy matched controls. Correlations were found between: 1) dose to the left hippocampus and performance on the RAVLT (Delayed Recall) (r= -0.60; p= 0.011); 2) dose to the supratentorial brain and performance on the TMT-A (r= 0.54; p= 0.025) and 3) dose to the left hemisphere and SDMT (r= -0.64; p= 0.006) and verbal fluency tests (for letters score: r= -0.73; p= 0.001). CONCLUSIONS We found significant correlations between radiation dose to the left hippocampus and hemisphere and neurocognitive performance. In this small sample we could not account for the effect of tumor location as a confounder. Reducing radiation dose to the left hippocampus and hemisphere by using advanced radiotherapy techniques may give superior neurocognitive outcomes.

Facial expressions have a communicatory function and the ability to read them is a prerequisite for understanding feelings and thoughts of other individuals. Impairments in recognition of facial emotional expressions are frequently found in patients with neurological conditions (e.g. stroke, traumatic brain injury, frontotemporal dementia). Hence, a standard neuropsychological assessment should include measurement of emotion recognition. However, there is debate regarding which tests are most suitable. The current study evaluates and compares three different emotion recognition tests. 84 healthy participants were included and assessed with three tests, in varying order: a. Ekman 60 Faces Test (FEEST) b. Emotion Recognition Task (ERT) c. Emotion Evaluation Test (EET). The tests differ in type of stimuli from static photographs (FEEST) to more dynamic stimuli in the form of morphed photographs (ERT) to videos (EET). Comparing performances on the three tests, the lowest total scores (67.3% correct answers) were found for the ERT. Significant, but moderate correlations were found between the total scores of the three tests, but nearly all correlations between the same emotions across different tests were not significant. Furthermore, we found cross-over effects of the FEEST and EET to the ERT; participants attained higher total scores on the ERT when another emotion recognition test had been administered beforehand. Moreover, the ERT proved to be sensitive to the effects of age and education. The present findings indicate that despite some overlap, each emotion recognition test measures a unique part of the construct. The ERT seemed to be the most difficult test: performances were lowest and influenced by differences in age and education and it was the only test that showed a learning effect after practice with other tests. This highlights the importance of appropriate norms.