Self-Reported Fatigue After Mild Traumatic Brain Injury Is Not Associated With Performance Fatigability During a Sustained Maximal Contraction

Patients with mild traumatic brain injury (mTBI) are frequently affected by fatigue. However, hardly any data is available on the fatigability of the motor system. We evaluated fatigue using the Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS) questionnaires in 20 participants with mTBI (>3 months post injury; 8 females) and 20 age- and sex matched controls. Furthermore, index finger abduction force and electromyography of the first dorsal interosseous muscle of the right hand were measured during brief and sustained maximal voluntary contractions (MVC). Double pulse stimulation (100 Hz) was applied to the ulnar nerve to evoke doublet-forces before and after the sustained contraction. Seven superimposed twitches were evoked during the sustained MVC to quantify voluntary muscle activation. mTBI participants reported higher FSS scores (mTBI: 5.2 +/- 0.8 SD vs. control: 2.8 +/- 0.8 SD; P <0.01). During the sustained MVC, force declined to similar levels in mTBI (30.0 +/- 9.9% MVC) and control participants (32.7 +/- 9.8% MVC, P = 0.37). The decline in doublet-forces after the sustained MVC (mTBI: to 37.2 +/- 12.1 vs. control: to 41.4 +/- 14.0% reference doublet, P = 0.32) and the superimposed twitches evoked during the sustained MVC (mTBI: median 9.3, range: 2.2-32.9 vs. control: median 10.3, range: 1.9-31.0% doublet(pre), P = 0.34) also did not differ between groups. Force decline was associated with decline in doublet-force (R-2 = 0.50, P <0.01) for both groups. Including a measure of voluntary muscle activation resulted in more explained variance for mTBI participants only. No associations between self-reported fatigue and force decline or voluntary muscle activation were found in mTBI participants. However, the physical subdomain of the MFIS was associated with the decline in doublet-force after the sustained MVC (R-2 = 0.23, P = 0.04). These results indicate that after mTBI, increased levels of self-reported physical fatigue reflected increased fatigability due to changes in peripheral muscle properties, but not force decline or muscle activation. Additionally, muscle activation was more important to explain the decline in voluntary force (performance fatigability) after mTBI than in control participants

The role of mood, post-traumatic stress, post-concussive symptoms and coping on outcome after MTBI in elderly patients

Elderly patients are at increased risk for persistent complaints after mild traumatic brain injury (MTBI). This study aimed to investigate the role of post-concussive symptoms, mood, post-traumatic stress, and coping on functional outcome in elderly with MTBI. Information on mood, post-concussive symptoms, post-traumatic stress, and coping was collected 2?weeks post-injury. Six months post-injury functional outcome was assessed with the Glasgow Outcome Scale Extended. One hundred and sixty-two patients aged ? 60 years were included, 55% male, mean age?=?71 (?6.2) years. The most frequent cause of injury was falls from standing height (75%). Two weeks post-injury anxiety, depression, and post-traumatic stress were present in 15%, 12%, and 38% of patients, respectively, with 73% reporting post-concussive symptoms. Avoidant coping was the most frequently used coping style. Six months post-injury, 44% showed incomplete recovery. Higher depression scores (OR?=?0.87, p?=?0.005) and number of post-concussive symptoms (OR?=?0.91, p?=?0.03) were associated with incomplete recovery. Half of the elderly showed incomplete recovery 6?months after MTBI, with early depression or post-concussive symptoms as important factors. Coping style was not related to outcome. These results underline the need for a different approach in elderly patients, focusing on other predicting factors and fall prevention strategies

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

Self-Reported Complaints as Prognostic Markers for Outcome After Mild Traumatic Brain Injury in Elderly:A Machine Learning Approach

Self-reported complaints are common after mild traumatic brain injury (mTBI). Particularly in the elderly with mTBI, the pre-injury status might play a relevant role in the recovery process. In most mTBI studies, however, pre-injury complaints are neither analyzed nor are the elderly included. Here, we aimed to identify which individual pre- and post-injury complaints are potential prognostic markers for incomplete recovery (IR) in elderly patients who sustained an mTBI. Since patients report many complaints across several domains that are strongly related, we used an interpretable machine learning (ML) approach to robustly deal with correlated predictors and boost classification performance. Pre- and post-injury levels of 20 individual complaints, as self-reported in the acute phase, were analyzed. We used data from two independent studies separately: UPFRONT study was used for training and validation and ReCONNECT study for independent testing. Functional outcome was assessed with the Glasgow Outcome Scale Extended (GOSE). We dichotomized functional outcome into complete recovery (CR; GOSE = 8) and IR (GOSE ≤ 7). In total 148 elderly with mTBI (median age: 67 years, interquartile range [IQR]: 9 years; UPFRONT: N = 115; ReCONNECT: N = 33) were included in this study. IR was observed in 74 (50%) patients. The classification model (IR vs. CR) achieved a good performance (the area under the receiver operating characteristic curve [ROC-AUC] = 0.80; 95% CI: 0.74–0.86) based on a subset of only 8 out of 40 pre- and post-injury complaints. We identified increased neck pain (p = 0.001) from pre- to post-injury as the strongest predictor of IR, followed by increased irritability (p = 0.011) and increased forgetfulness (p = 0.035) from pre- to post-injury. Our findings indicate that a subset of pre- and post-injury physical, emotional, and cognitive complaints has predictive value for determining long-term functional outcomes in elderly patients with mTBI. Particularly, post-injury neck pain, irritability, and forgetfulness scores were associated with IR and should be assessed early. The application of an ML approach holds promise for application in self-reported questionnaires to predict outcomes after mTBI

The Spectrum of Long-Term Behavioral Disturbances and Provided Care After Traumatic Brain Injury

Introduction: Behavioral disturbances are found in 50-60% of traumatic brain injury (TBI) survivors with an enormous impact on daily functioning and level of recovery. However, whether typical profiles can be distinguished and how these relate to provided care is unclear. The purpose of this study is to specify the characteristics of behavioral disturbances in patients with various severity of TBI and the impact on functional outcome. Furthermore, the pathways of care after hospital discharge for patients and their care givers are analyzed. Methods: We performed a retrospective cohort study comprising 226 patients with mild TBI (mTBI; n = 107) and moderate-to-severe TBI (mod/sevTBI; n = 119) treated at the outpatient clinic and/or rehabilitation center of our university hospital between 2010 and 2015. Inclusion criteria were: behavioral disturbances as determined with the Differential Outcome Scale and age >= 16 years. Functional outcome was determined by the Glasgow Outcome Scale Extended and return to work (RTW) at six months to one year post-injury. Behavioral impairments and pathway of care were derived from medical files and scored according to predefined criteria. Results: Overall 24% of patients showed serious behavioral disturbances; three times higher in mod/sevTBI (35%) compared to mTBI (13%). mTBI patients mostly showed irritation (82%) and anger (49%), while mod/sevTBI patients mostly showed irritation (65%) and disinhibition (55%). Most (92%) patients returned home, half of the patients did not RTW. Deficits in judgment and decision-making increased risk of no RTW 10-fold. One in ten patients was (temporarily) admitted to a nursing home or psychiatric institution. 13% Of caregivers received support for dealing with impairments of patients and 13% of the mTBI and 17% of the mod/sevTBI patients experienced relational problems. Conclusions: The spectrum of behavioral disturbances differs between TBI severity categories and serious behavioral disturbances are present in a quarter of patients. Only half of the patients resumed work regardless of severity of injury suggesting that particularly the presence and not the severity of long-term behavioral disturbances interferes with RTW. Most patients returned home despite these behavioral disturbances. These findings underline the importance of early identification and appropriate treatment of behavioral disturbances in TBI patients

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

Participation after traumatic brain injury:the surplus value of social cognition tests beyond measures for executive functioning and dysexecutive behavior in a statistical prediction model

Objective: This study evaluates the contribution of measures for social cognition (SC), executive functioning (EF) and dysexecutive behavior to the statistical prediction of social and vocational participation in patients with traumatic brain injury (TBI), taking into account age and injury severity. Method: A total of 63 patients with moderate to severe TBI participated. They were administered a semi-structured Role Resumption List for social (RRL-SR) and vocational participation (RRL-RTW). EF was measured with planning- and switching tasks. Assessment of SC included tests for facial affect recognition and Theory of Mind (ToM). Dysexecutive behavior was proxy-rated with a questionnaire. Additionally, healthy controls were assessed with the same protocol. Results: Patients with TBI performed significantly worse on tests and had significantly more behavioral problems compared to healthy controls. Hierarchical multiple regression analyses for the TBI group revealed that SC accounted for 22% extra variance in RRL-RTW and 10% extra variance in RRL-SR, which was significant over and above the amounts of variance explained by EF, dysexecutive behavior, age and injury severity. Conclusions: Our findings underline the added value of measures of SC and dysexecutive behavior in the prediction of social and vocational participation post-TBI. In particular, impairments in ToM, and dysexecutive behavior were related to a lower participation making them important targets for rehabilitation