Chronic Traumatic Brain Injury Research Articles

Chronic traumatic encephalopathy and traumatic brain injury

Your understanding of these conditions will help you support patients and their families.

Pineal gland cyst-to fight or not to fight?

Since professional boxing is associated with substantial risk of both acute and chronic traumatic brain injury, many athletic (boxing) commissions in the United States and abroad request a neuroimaging study of the brain to determine brain fitness to fight. Either magnetic resonance imaging (MRI) brain or computed tomography (CT) head is needed to obtain a license to compete in professional combat sports and periodically thereafter. The neuroimaging study helps to identify and/or exclude structural brain lesions that may pose a risk of rupture or bleeding from head impact exposures (HIEs) sustained during the course of the bout. Identification of structural brain lesions such as large tumors, vascular malformations such as aneurysms, arteriovenous malformations, and large cavernous malformations results in a denial of licensure to fight. Pineal gland cysts (PC) are usually benign cysts discovered on occasions incidentally in MRI scans of boxers. A 25-year-old asymptomatic boxer was found to have a 2 cm PC with intracystic hemorrhage on MRI scan done for licensure. The medical literature was reviewed to determine whether boxers with PC can safety compete in combat sports.

Functional connectivity-hemodynamic (un)coupling changes in chronic mild brain injury are associated with mental health and neurocognitive indices: a resting state fMRI study.

To examine hemodynamic and functional connectivity alterations and their association with neurocognitive and mental health indices in patients with chronic mild traumatic brain injury (mTBI). Resting-state functional MRI (rs-fMRI) and neuropsychological assessment of 37 patients with chronic mTBI were performed. Intrinsic connectivity contrast (ICC) and time-shift analysis (TSA) of the rs-fMRI data allowed the assessment of regional hemodynamic and functional connectivity disturbances and their coupling (or uncoupling). Thirty-nine healthy age- and gender-matched participants were also examined. Patients with chronic mTBI displayed hypoconnectivity in bilateral hippocampi and parahippocampal gyri and increased connectivity in parietal areas (right angular gyrus and left superior parietal lobule (SPL)). Slower perfusion (hemodynamic lag) in the left anterior hippocampus was associated with higher self-reported symptoms of depression (r = - 0.53, p = .0006) and anxiety (r = - 0.484, p = .002), while faster perfusion (hemodynamic lead) in the left SPL was associated with lower semantic fluency (r = - 0.474, p = .002). Finally, functional coupling (high connectivity and hemodynamic lead) in the right anterior cingulate cortex (ACC)) was associated with lower performance on attention and visuomotor coordination (r = - 0.50, p = .001), while dysfunctional coupling (low connectivity and hemodynamic lag) in the left ventral posterior cingulate cortex (PCC) and right SPL was associated with lower scores on immediate passage memory (r = - 0.52, p = .001; r = - 0.53, p = .0006, respectively). Uncoupling in the right extrastriate visual cortex and posterior middle temporal gyrus was negatively associated with cognitive flexibility (r = - 0.50, p = .001). Hemodynamic and functional connectivity differences, indicating neurovascular (un)coupling, may be linked to mental health and neurocognitive indices in patients with chronic mTBI.

Neurobehavioral Symptom Profiles for the Behavioral Assessment Screening Tool in Chronic Traumatic Brain Injury.

To identify neurobehavioral symptom profiles among persons with chronic traumatic brain injury (TBI) using the Behavioral Assessment Screening Tool (BAST) and to consider participant characteristics that differ between profile groups. Community. Participants (n=615) were English-speaking adults (≥18) and had a self-reported history of at least one TBI of any severity. Secondary analysis of cross-sectional data. The BAST measures neurobehavioral symptoms in the domains of Negative Affect, Fatigue, Executive Dysfunction, Impulsivity, and Substance Misuse. Using latent profile analysis (LPA), we identified 3 different neurobehavioral profiles. Overall symptom frequency and differences in the pattern of symptom frequency across domains differentiated the profile groups. Average domain scores differed significantly across the profiles (P <.001) for all domains except Fatigue (P =.076). Those in profile 3 (High-Risk group) reported the most frequent symptoms across all domains (similar Negative Affect frequency as profile 1). Substance Misuse was especially high in this group. Compared to profile 2 (High Negative Affect group), participants in profile 1 (Moderate-Risk group) endorsed significantly more frequent (and more variable) symptoms across all BAST domains, particularly Impulsivity and Substance Misuse. Participants in profile 2 endorsed the least frequent symptoms across all domains. Demographic comparison showed that groups differed based on gender, age, and injury severity (mild vs moderate-severe), with profile 3 composed of the most men and the most persons in early adulthood, and profile 2 composed of the most women and those with mild TBI. We differentiated 3 neurobehavioral symptom profiles among persons with chronic TBI and determined differences in sociodemographic factors between the groups. Future research should focus on validating these profiles in another sample of individuals with chronic TBI. Characterizing persons according to multidimensional symptom profiles could allow for more tailored approaches to predict and prevent long-term negative outcomes.

Variability of the Behavioral Assessment Screening Tool for Mobile Health (BASTmHealth) for ecological momentary assessment in chronic traumatic brain injury

Variability of the Behavioral Assessment Screening Tool for Mobile Health (BASTmHealth) for ecological momentary assessment in chronic traumatic brain injury

Exploring Self-Reported Recent Greatest Problems among Individuals With and Without Chronic Traumatic Brain Injury via Open-Text Survey Responses

Exploring Self-Reported Recent Greatest Problems among Individuals With and Without Chronic Traumatic Brain Injury via Open-Text Survey Responses

Changes in Cortical Grey Matter Volumes After Plasticity-based Auditory Information Processing Remediation Training in Adults with a Chronic Traumatic Brain Injury: A Pilot Study

Changes in Cortical Grey Matter Volumes After Plasticity-based Auditory Information Processing Remediation Training in Adults with a Chronic Traumatic Brain Injury: A Pilot Study

Depression, Anxiety, and Suicidality in Individuals with Chronic Traumatic Brain Injury before and During the COVID-19 Pandemic: A NIDILRR TBIMS Study

Depression, Anxiety, and Suicidality in Individuals with Chronic Traumatic Brain Injury before and During the COVID-19 Pandemic: A NIDILRR TBIMS Study

Applying the Consensus Criteria for Traumatic Encephalopathy Syndrome Retrospectively to Case Studies of Boxers from the 20th Century.

There are no validated diagnostic criteria for traumatic encephalopathy syndrome (TES). During the early and middle 20th century, TES was described as a clinical condition that was experienced by some high-exposure boxers-and it was believed to reflect chronic traumatic brain injury. Consensus criteria for the diagnosis of TES were published in 2021. We applied the consensus criteria for TES retrospectively to cases of chronic brain damage in boxers described in articles published in the 20th century that were obtained from narrative and systematic reviews. The sample included 157 boxers identified in 21 articles published between 1929 and 1999. Two authors reviewed each case description and coded the criteria for TES. For the core clinical features, cognitive impairment was noted in 63.1%, and in 28.7% of cases the person's cognitive functioning appeared to be broadly normal. Neurobehavioral dysregulation was present in 25.5%. One third (34.4%) were identified as progressive, 30.6% were not progressive, and the course could not be clearly determined in 35.0%. In total, 29.9% met the TES consensus criteria, 28.0% did not, and 42.0% had insufficient information to make a diagnostic determination. TES, in the 20th century, was described as a neurological condition, not a psychiatric disorder-and this supports the decision of the 2021 consensus group to remove primary and secondary psychiatric diagnoses from being a core diagnostic feature. Future research is needed to determine whether, or the extent to which, cognitive impairment or neurobehavioral dysregulation described as characterizing TES are associated with chronic traumatic encephalopathy neuropathological change.

Relationship between Timed Up and Go performance and quantitative biomechanical measures of balance.

Traumatic brain injury (TBI) impairs sensory-motor functions, with debilitating consequences on postural control and balance, which persist during the chronic stages of recovery. The Timed Up and Go (TUG) test is a reliable, safe, time-efficient, and one of the most widely used clinical measures to assess gait, balance, and fall risk in TBI patients and is extensively used in inpatient and outpatient settings. Although the TUG test has been used extensively due to its ease of performance and excellent reliability, limited research has been published that investigates the relationship between TUG performance and quantitative biomechanical measures of balance. The objective of this paper was to quantify the relationship between biomechanical variables of balance and the TUG scores in individuals with chronic TBI. Regression models were constructed using six biomechanical variables to predict TUG scores. The model that conservatively removed gait speed (i.e., TUG-1/GS) gave the best results, achieving a root-mean-square error of ∼±2 s and explaining over 69% of the variability.

Transcranial Photobiomodulation and Chronic Traumatic Brain Injury

Traumatic brain injury (TBI) is a common cause of neurologic morbidity for which few effective therapies exist, especially during the chronic stage. A potential therapy for chronic TBI is transcranial photobiomodulation (tPBM). tPBM is a noninvasive neuromodulation technique that uses light to stimulate the cortex and increase blood flow and metabolism while also enhancing cognition and improving affect. There has been much work focusing on the efficacy of tPBM in acute TBI in small animals, but much less work has focused on chronic TBI. Patients with chronic TBI manifest microvascular injury, which may serve as a modifiable treatment target for tPBM. There is a need to study and improve tPBM, as the currently implemented protocols targeting microvascular injury have been relatively unsuccessful. This review includes 16 studies, which concluded that after tPBM application, there were improvements in neuropsychological outcomes in addition to increases in cerebral blood flow. However, these conclusions are confounded by differing tPBM parameters, small sample sizes, and heterogenous TBI populations. While these results are encouraging, there is a need to further understand the therapeutic potential of tPBM in chronic TBI.

Emotional, Behavioral, and Cognitive Symptom Associations With Community Participation in Chronic Traumatic Brain Injury.

To determine the association between self-reported emotional and cognitive symptoms and participation outcomes in chronic traumatic brain injury (TBI) and to explore the relative contribution of self-reported versus performance-based cognition to participation outcomes. Community. Community-dwelling adults ( n = 135) with a lifetime history of mild to severe TBI. Secondary analysis of a cross-sectional study on neurobehavioral symptoms in chronic TBI. Behavioral Assessment Screening Tool (BAST) (Negative Affect, Fatigue, Executive Dysfunction, Impulsivity, Substance Abuse subscales) measured self-reported neurobehavioral symptoms; Participation Assessment with Recombined Tools (Productivity, Social Relations, and Out and About) measured self-reported participation outcomes; and Brief Test of Adult Cognition by Telephone (BTACT) measured performance-based cognition (Episodic Memory and Executive Function summary scores) in a subsample ( n = 40). The BAST Executive Dysfunction was significantly associated with less frequent participation and had the strongest effect on participation in all participation domains. No other BAST subscales were associated with participation, after adjusting for all subscale scores and age, with the exception of BAST Impulsivity, which was associated with more frequent Social Relationships. Exploratory analysis in the sample including the BTACT revealed that, after accounting for subjective Executive Dysfunction using the BAST, performance-based Executive Function was associated with Productivity and Working Memory was associated with Social Relations, but neither was associated with being Out and About; the BAST Executive Dysfunction remained significant in all models even after including BTACT scores. Self-reported Executive Dysfunction contributed to participation outcomes after mild to severe TBI in community-dwelling adults, whereas self-reported emotional and fatigue symptoms did not. Performance-based cognition measures may capture different variability in participation after injury.

The safety and feasibility of transcranial direct current stimulation for patients with chronic severe traumatic brain injury in Japan, a phase I study

BackgroundDespite evidence regarding the benefits of transcranial direct current stimulation (tDCS) in patients with severe traumatic brain injury, few trials have examined the treatment safety. Therefore, we created a phase I trial in Japan to investigate the safety of tDCS after severe brain injury. MethodsWe verified the safety of tDCS through constant left frontal anodal stimulation at 2 mA for 20 min for 5 consecutive days. Additionally, we added a variable stimuli period to explore the effects of stimulus intensity, location, and duration. We adapted a traditional 3 + 3 study design. We assessed the rate of adverse effects, including skin burns and clinical seizure. Changes in neurological symptoms were evaluated using the Glasgow Coma Scale, Coma Recovery Scale-Revised, and 4 states of consciousness (coma, unresponsive wakefulness syndrome, minimally conscious state, and severe disability). ResultsSix patients completed the study. No obvious adverse events were observed during the constant stimulation period or the variable stimulation period (right frontal anodal stimulation, stimulation frequency 2–4 mA, 1 or 5 times per week for a period of 4 weeks). Regarding the Coma Recovery Scale-Revised, patients in 4 out of 6 instances (66.7 %) improved by more than 1 point. ConclusionOur phase I safety study indicated that a single course of tDCS was safe in patients with severe traumatic brain injury. The next step is a phase II trial to investigate the preliminary efficacy and safety of tDCS at 2 mA (in comparison with sham stimulation).

Methylphenidate Ameliorates Behavioural and Neurobiological Deficits in Executive Function for Patients with Chronic Traumatic Brain Injury

Methylphenidate Ameliorates Behavioural and Neurobiological Deficits in Executive Function for Patients with Chronic Traumatic Brain Injury

Long Noncoding RNA VLDLR-AS1 Levels in Serum Correlate with Combat-Related Chronic Mild Traumatic Brain Injury and Depression Symptoms in US Veterans.

More than 75% of traumatic brain injuries (TBIs) are mild (mTBI) and military service members often experience repeated combat-related mTBI. The chronic comorbidities concomitant with repetitive mTBI (rmTBI) include depression, post-traumatic stress disorder or neurological dysfunction. This study sought to determine a long noncoding RNA (lncRNA) expression signature in serum samples that correlated with rmTBI years after the incidences. Serum samples were obtained from Long-Term Impact of Military-Relevant Brain-Injury Consortium Chronic Effects of Neurotrauma Consortium (LIMBIC CENC) repository, from participants unexposed to TBI or who had rmTBI. Four lncRNAs were identified as consistently present in all samples, as detected via droplet digital PCR and packaged in exosomes enriched for CNS origin. The results, using qPCR, demonstrated that the lncRNA VLDLR-AS1 levels were significantly lower among individuals with rmTBI compared to those with no lifetime TBI. ROC analysis determined an AUC of 0.74 (95% CI: 0.6124 to 0.8741; p = 0.0012). The optimal cutoff for VLDLR-AS1 was ≤153.8 ng. A secondary analysis of clinical data from LIMBIC CENC was conducted to evaluate the psychological symptom burden, and the results show that lncRNAs VLDLR-AS1 and MALAT1 are correlated with symptoms of depression. In conclusion, lncRNA VLDLR-AS1 may serve as a blood biomarker for identifying chronic rmTBI and depression in patients.

Deep learning-based multimodality classification of chronic mild traumatic brain injury using resting-state functional MRI and PET imaging.

Mild traumatic brain injury (mTBI) is a public health concern. The present study aimed to develop an automatic classifier to distinguish between patients with chronic mTBI (n = 83) and healthy controls (HCs) (n = 40). Resting-state functional MRI (rs-fMRI) and positron emission tomography (PET) imaging were acquired from the subjects. We proposed a novel deep-learning-based framework, including an autoencoder (AE), to extract high-level latent and rectified linear unit (ReLU) and sigmoid activation functions. Single and multimodality algorithms integrating multiple rs-fMRI metrics and PET data were developed. We hypothesized that combining different imaging modalities provides complementary information and improves classification performance. Additionally, a novel data interpretation approach was utilized to identify top-performing features learned by the AEs. Our method delivered a classification accuracy within the range of 79-91.67% for single neuroimaging modalities. However, the performance of classification improved to 95.83%, thereby employing the multimodality model. The models have identified several brain regions located in the default mode network, sensorimotor network, visual cortex, cerebellum, and limbic system as the most discriminative features. We suggest that this approach could be extended to the objective biomarkers predicting mTBI in clinical settings.

Treatment effects of N-acetyl cysteine on resting-state functional MRI and cognitive performance in patients with chronic mild traumatic brain injury: a longitudinal study.

Mild traumatic brain injury (mTBI) is a significant public health concern, specially characterized by a complex pattern of abnormal neural activity and functional connectivity. It is often associated with a broad spectrum of short-term and long-term cognitive and behavioral symptoms including memory dysfunction, headache, and balance difficulties. Furthermore, there is evidence that oxidative stress significantly contributes to these symptoms and neurophysiological changes. The purpose of this study was to assess the effect of N-acetylcysteine (NAC) on brain function and chronic symptoms in mTBI patients. Fifty patients diagnosed with chronic mTBI participated in this study. They were categorized into two groups including controls (CN, n = 25), and patients receiving treatment with N-acetyl cysteine (NAC, n = 25). NAC group received 50 mg/kg intravenous (IV) medication once a day per week. In the rest of the week, they took one 500 mg NAC tablet twice per day. Each patient underwent rs-fMRI scanning at two timepoints including the baseline and 3 months later at follow-up, while the NAC group received a combination of oral and IV NAC over that time. Three rs-fMRI metrics were measured including fractional amplitude of low frequency fluctuations (fALFF), degree centrality (DC), and functional connectivity strength (FCS). Neuropsychological tests were also assessed at the same day of scanning for each patient. The alteration of rs-fMRI metrics and cognitive scores were measured over 3 months treatment with NAC. Then, the correlation analysis was executed to estimate the association of rs-fMRI measurements and cognitive performance over 3 months (p < 0.05). Two significant group-by-time effects demonstrated the changes of rs-fMRI metrics particularly in the regions located in the default mode network (DMN), sensorimotor network, and emotional circuits that were significantly correlated with cognitive function recovery over 3 months treatment with NAC (p < 0.05). NAC appears to modulate neural activity and functional connectivity in specific brain networks, and these changes could account for clinical improvement. This study confirmed the short-term therapeutic efficacy of NAC in chronic mTBI patients that may contribute to understanding of neurophysiological effects of NAC in mTBI. These findings encourage further research on long-term neurobehavioral assessment of NAC assisting development of therapeutic plans in mTBI.

The potential role of chronic pain and the polytrauma clinical triad in predicting prodromal PD: A cross-sectional study of U.S. Veterans

IntroductionThe research criteria for prodromal Parkinson disease (pPD) depends on prospectively validated clinical inputs with large effect sizes and/or high prevalence. Neither traumatic brain injury (TBI), post-traumatic stress disorder (PTSD), nor chronic pain are currently included in the calculator, despite recent evidence of association with pPD. These conditions are widely prevalent, co-occurring, and already known to confer risk of REM behavior disorder (RBD) and PD. Few studies have examined PD risk in the context of TBI and PTSD; none have examined chronic pain. This study aimed to measure the risk of pPD caused by TBI, PTSD, and chronic pain. Methods216 US Veterans were enrolled who had self-reported recurrent or persistent pain for at least three months. Of these, 44 met criteria for PTSD, 39 for TBI, and 41 for all three conditions. Several pain, sleep, affective, and trauma questionnaires were administered. Participants’ history of RBD was determined via self-report, with a subset undergoing confirmatory video polysomnography. ResultsA greater proportion of Veterans with chronic pain met criteria for RBD (36 % vs. 10 %) and pPD (18.0 % vs. 8.3 %) compared to controls. Proportions were increased in RBD (70 %) and pPD (27 %) when chronic pain co-occurred with TBI and PTSD. Partial effects were seen with just TBI or PTSD alone. When analyzed as continuous variables, polytrauma symptom severity correlated with pPD probability (r = 0.28, P = 0.03). ConclusionThese data demonstrate the potential utility of chronic pain, TBI, and PTSD in the prediction of pPD, and the importance of trauma-related factors in the pathogenesis of PD.

Broadening horizons: ferroptosis as a new target for traumatic brain injury.

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide, with ~50 million people experiencing TBI each year. Ferroptosis, a form of regulated cell death triggered by iron ion-catalyzed and reactive oxygen species-induced lipid peroxidation, has been identified as a potential contributor to traumatic central nervous system conditions, suggesting its involvement in the pathogenesis of TBI. Alterations in iron metabolism play a crucial role in secondary injury following TBI. This study aimed to explore the role of ferroptosis in TBI, focusing on iron metabolism disorders, lipid metabolism disorders and the regulatory axis of system Xc-/glutathione/glutathione peroxidase 4 in TBI. Additionally, we examined the involvement of ferroptosis in the chronic TBI stage. Based on these findings, we discuss potential therapeutic interventions targeting ferroptosis after TBI. In conclusion, this review provides novel insights into the pathology of TBI and proposes potential therapeutic targets.

Identifying a high-risk fighter in boxing

Boxing is one of the most popular of combat sports. The goal in boxing is to win by causing a knockout (KO). Every punch thrown at the opponent’s head is thrown with this intention. As a result boxers experience numerous head impact exposures (HIE) both in and out of competition. The sport carries a high incidence of acute and chronic traumatic brain injury (TBI) as well as occasional disabling orthopedic and ophthalmological injury. While no fighter (combatant) is immune to these injuries, there are fighters who for various reasons are more susceptible to these injuries or in whom these injuries carry high morbidity and mortality. These fighters are colloquially referred to as “high-risk fighters”. A high-risk fighter needs closer medical supervision before, during and after a bout. In this commentary an attempt is made to identify these high risk fighters.