Adaptation after mild traumatic brain injury:The role of structural and functional brain networks

Elk jaar lopen miljoenen mensen wereldwijd een licht traumatisch hersenletsel (LTH) op. Het is onduidelijk waarom sommige mensen heel snel weer hersteld zijn, terwijl anderen soms maanden of zelfs jaren na het ongeval nog klachten ervaren. Er wordt gedacht dat psychologische adaptatie, en dan vooral de capaciteit om negatieve emoties en stress te reguleren, belangrijk is voor het voorkomen van persisterende klachten en een goed herstel. In dit proefschrift is diffusie en functionele MRI gebruikt om de rol van de prefrontale cortex, wat een belangrijk gebied is voor cognitie en emotie regulatie, en de hersennetwerken waar dit gebied deel van uitmaakt, te onderzoeken in patiënten na een LTH

Drugs with anti-inflammatory effects to improve outcome of traumatic brain injury:a meta-analysis

Outcome after traumatic brain injury (TBI) varies largely and degree of immune activation is an important determinant factor. This meta-analysis evaluates the efficacy of drugs with anti-inflammatory properties in improving neurological and functional outcome. The systematic search following PRISMA guidelines resulted in 15 randomized placebo-controlled trials (3734 patients), evaluating progesterone, erythropoietin and cyclosporine. The meta-analysis (15 studies) showed that TBI patients receiving a drug with anti-inflammatory effects had a higher chance of a favorable outcome compared to those receiving placebo (RR = 1.15; 95% CI 1.01-1.32, p = 0.041). However, publication bias was indicated together with heterogeneity (I-2 = 76.59%). Stratified analysis showed that positive effects were mainly observed in patients receiving this treatment within 8 h after injury. Subanalyses by drug type showed efficacy for progesterone (8 studies, RR 1.22; 95% CI 1.01-1.47, p = 0.040), again heterogeneity was high (I-2 = 62.92%) and publication bias could not be ruled out. The positive effect of progesterone covaried with younger age and was mainly observed when administered intramuscularly and not intravenously. Erythropoietin (4 studies, RR 1.20; p = 0.110; I-2 = 76.59%) and cyclosporine (3 studies, RR 0.75; p = 0.189, I-2 = 0%) did not show favorable significant effects. While negative findings for erythropoietin may reflect insufficient power, cyclosporine did not show better outcome at all. Current results do not allow firm conclusions on the efficacy of drugs with anti-inflammatory properties in TBI patients. Included trials showed heterogeneity in methodological and sample parameters. At present, only progesterone showed positive results and early administration via intramuscular administration may be most effective, especially in young people. The anti-inflammatory component of progesterone is relatively weak and other mechanisms than mitigating overall immune response may be more important

Clinical relevance of microhemorrhagic lesions in subacute mild traumatic brain injury.

Magnetic resonance imaging (MRI) is often performed in patients with persistent complaints after mild traumatic brain injury (mTBI). However, the clinical relevance of detected microhemorrhagic lesions is still unclear. In the current study, 54 patients with uncomplicated mTBI and 20 matched healthy controls were included. Post-traumatic complaints were measured at two weeks post-injury. Susceptibility weighted imaging and T2*-gradient echo imaging (at 3 Tesla) were performed at four weeks post-injury. Microhemorrhagic lesions (1–10 mm) were subdivided based on depth (superficial or deep) and anatomical location (frontal, temporoparietal and other regions). Twenty-eight per cent of patients with mTBI had ≥1 lesions compared to 0 % of the healthy controls. Lesions in patients with mTBI were predominantly located within the superficial frontal areas. Number, depth and anatomical location of lesions did not differ between patients with and without post-traumatic complaints. Within the group of patients with complaints, number of complaints was not correlated with number of lesions. In summary, microhemorrhages were found in one out of four patients with uncomplicated mTBI during follow-up at four weeks post-injury, but they were not related to early complaints

Blood-based biomarkers of inflammation in mild traumatic brain injury:A systematic review

Inflammation is an important secondary physiological response to traumatic brain injury (TBI). Most of the current knowledge on this response is derived from research in moderate and severe TBI. In this systematic review we summarize the literature on clinical studies measuring blood based inflammatory markers following mild traumatic brain injury (mTBI) and identify the value of inflammatory markers as biomarkers. Twenty-three studies were included. This review suggests a distinct systemic inflammatory response following mTBI, quantifiable within 6 hours up to 12 months post-injury. Interleukin-6 is the most promising biomarker for the clinical diagnosis of brain injury while interleukin-10 is a potential candidate for triaging CT scans. The diagnostic and prognostic utility of inflammatory markers may be more fully appreciated as a component of a panel of biomarkers. However, discrepancies in study design, analysis and reporting make it difficult to draw any definite conclusions. For the same reasons, a meta-analysis was not possible. We provide recommendations to follow standardized methodologies to allow for reproducibility of results in future studies

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 =-032).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. (C) 2017 Elsevier Ltd. All rights reserved.</p

A Decentralized ComBat Algorithm and Applications to Functional Network Connectivity

Recent studies showed that working with neuroimage data collected from different research facilities or locations may incur additional source dependency, affecting the overall statistical power. This problem can be mitigated with data harmonization approaches. Recently, the ComBat method has become commonly adopted for various neuroimage modalities. While open neuroimaging datasets are becoming more common, a substantial amount of data is still unable to be shared for various reasons. In addition, current approaches require moving all the data to a central location, which requires additional resources and creates redundant copies of the same datasets. To address these issues, we propose a decentralized harmonization approach that does not create redundant copies of the original datasets and performs remote operations on the datasets separately without sharing any individual subject data, ensuring a certain level of privacy and reducing regulatory hurdles. We proposed a novel approach called “Decentralized ComBat” which can harmonize datasets separately without combining the datasets. We tested our model by harmonizing functional network connectivity datasets from two traumatic brain injury studies in a decentralized way. Also, we used simulations to analyze the performance and scalability of our model when the number of data collection sites increases. We compare the output with centralized ComBat and show that the proposed approach produces similar results, increasing the sensitivity of the functional network connectivity analysis and validating our approach. Simulations show that our model can be easily scaled to many more datasets based on the requirement. In sum, we believe this provides a powerful tool, further complementing open data and allowing for integrating public and private datasets

A Decentralized ComBat Algorithm and Applications to Functional Network Connectivity

Recent studies showed that working with neuroimage data collected from different research facilities or locations may incur additional source dependency, affecting the overall statistical power. This problem can be mitigated with data harmonization approaches. Recently, the ComBat method has become commonly adopted for various neuroimage modalities. While open neuroimaging datasets are becoming more common, a substantial amount of data is still unable to be shared for various reasons. In addition, current approaches require moving all the data to a central location, which requires additional resources and creates redundant copies of the same datasets. To address these issues, we propose a decentralized harmonization approach that does not create redundant copies of the original datasets and performs remote operations on the datasets separately without sharing any individual subject data, ensuring a certain level of privacy and reducing regulatory hurdles. We proposed a novel approach called "Decentralized ComBat " which can harmonize datasets separately without combining the datasets. We tested our model by harmonizing functional network connectivity datasets from two traumatic brain injury studies in a decentralized way. Also, we used simulations to analyze the performance and scalability of our model when the number of data collection sites increases. We compare the output with centralized ComBat and show that the proposed approach produces similar results, increasing the sensitivity of the functional network connectivity analysis and validating our approach. Simulations show that our model can be easily scaled to many more datasets based on the requirement. In sum, we believe this provides a powerful tool, further complementing open data and allowing for integrating public and private datasets.</p

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 (&lt; 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 &lt; 0.05), but not between TBI-A and TBI-S (p &lt; 0.05). The frequency of the posterior dominant rhythm was significantly slower in TBI-A (0.6 Hz, p &lt; 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.</p