Approximately one-third of military personnel who deploy for combat operations sustain 1 or more traumatic brain injuries (TBIs), which increases the risk for chronic symptoms of postconcussive ...disorder, posttraumatic stress disorder, and depression and for the development of chronic traumatic encephalopathy. Elevated concentrations of tau are observed in blood shortly following a TBI, but, to our knowledge, the role of tau elevations in blood in the onset and maintenance of chronic symptoms after TBI has not been investigated.
To assess peripheral tau levels in military personnel exposed to TBI and to examine the relationship between chronic neurological symptoms and tau elevations.
Observational assessment from September 2012 to August 2014 of US military personnel at the Madigan Army Medical Center who had been deployed within the previous 18 months. Plasma total tau concentrations were measured using a novel ultrasensitive single-molecule enzyme-linked immunosorbent assay. Classification of participants with and without self-reported TBI was made using the Warrior Administered Retrospective Casualty Assessment Tool. Self-reported symptoms of postconcussive disorder, posttraumatic stress disorder, and depression were determined by the Neurobehavioral Symptom Inventory, the Posttraumatic Stress Disorder Checklist Military Version, and the Quick Inventory of Depressive Symptomatology, respectively. Group differences in tau concentrations were determined through analysis of variance models, and area under the receiver operating characteristic curve determined the sensitivity and specificity of tau concentrations in predicting TBI and chronic symptoms. Seventy participants with self-reported TBI on the Warrior Administered Retrospective Casualty Assessment Tool and 28 control participants with no TBI exposure were included.
Concentration of total tau in peripheral blood.
Concentrations of plasma tau were significantly elevated in the 70 participants with self-reported TBI compared with the 28 controls (mean SD, 1.13 0.78 vs 0.63 0.48 pg/mL, respectively; F1,97 = 4.97; P = .03). Within the self-reported TBI cases, plasma total tau concentrations were significantly associated with having a medical record of TBI compared with self-reported TBI only (mean SD, 1.57 0.92 vs 0.85 0.52 pg/mL, respectively; F1,69 = 6.15; P = .02) as well as reporting the occurrence of 3 of more TBIs during deployment compared with fewer than 3 TBIs (mean SD, 1.52 0.82 vs 0.82 0.60 pg/mL, respectively; F1,69 = 8.57; P = .008). The severity of total postconcussive symptoms correlated with total tau concentrations in the self-reported TBI group (r = 0.37; P = .003).
Military personnel who report multiple TBIs have long-term elevations in total tau concentration. The total tau concentration relates to symptoms of postconcussive disorder.
Concurrent posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) is common in military populations. The purpose of this study was to examine long‐term neurobehavioral outcomes in ...service members and veterans (SMVs) with versus without PTSD symptoms following TBI of all severities. Participants were 536 SMVs prospectively enrolled from three military medical treatment facilities who were recruited into three experimental groups: TBI, injured controls (IC), and noninjured controls (NIC). Participants completed the PTSD Checklist, Neurobehavioral Symptom Inventory, and the TBI–Quality of Life (TBI‐QOL) and were divided into six subgroups based on the three experimental categories, two PTSD categories (i.e., present vs. absent), and two broad TBI severity categories (unMTBI, which included uncomplicated mild TBI; and smcTBI, which included severe TBI, moderate TBI, and complicated mild TBI): (a) NIC/PTSD‐absent, (b) IC/PTSD‐absent, (c) unMTBI/PTSD‐absent, (d) unMTBI/PTSD‐present, (e) smcTBI/PTSD‐absent, and (f) smcTBI/PTSD‐present. There were significant main effects across the six groups for all TBI‐QOL measures, ps < .001. Select pairwise comparisons revealed significantly lower scores, p < .001, on all TBI‐QOL measures in the PTSD‐present groups when compared to the PTSD‐absent groups within the same TBI severity classification, ds = 0.90–2.11. In contrast, when controlling for PTSD, there were no significant differences among the TBI severity groups for any TBI‐QOL measures. These results provide support for the strong influence of PTSD but not TBI severity on neurobehavioral outcomes following TBI. Concurrent PTSD and TBI of all severities should be considered a risk factor for poor long‐term neurobehavioral outcomes that require ongoing monitoring.
Purpose
To examine change in health-related quality of life (HRQOL) during the COVID-19 pandemic in caregivers of service members/veterans (SMVs) with traumatic brain injury (TBI), by comparing HRQOL ...during the first year of the pandemic to HRQOL 12 months pre-pandemic.
Methods
Caregivers (
N
= 246) were classified into three COVID-19 Pandemic Impact groups based on impact ratings of the pandemic on HRQOL: No Impact (
n
= 50), Mild Impact (
n
= 117), and Moderate-Severe Impact (
n
= 79). Caregivers completed 19 measures across physical, social, caregiving, and economic HRQOL domains, and a measure of SMV Adjustment. T-scores were used to determine individual symptom trajectories for each measure as follows: Asymptomatic (pre + during < 60 T); Developed (pre < 60 + during ≥ 60 T); Improved (pre ≥ 60 T + during < 60 T); and Persistent (pre + during ≥ 60 T).
Results
Using ANOVA, during the pandemic, the Moderate-Severe Impact group reported worse scores on 19 measures (
d
= 0.41–0.89) compared to the No Impact group and 18 measures (
d
= 0.31–0.62) compared to the Mild Impact group (
d
= 0.31–0.38). The Mild Impact group reported worse scores on two measures compared to the No Impact group (
d
= 0.42–0.43). Using the entire sample, the majority of HRQOL measures were classified as Asymptomatic (47.2–94.7%), followed by Persistent (2.4–27.2%). Few were classified as Developed (0.4–12.6%) or Improved (2.4–13.8%). Using repeated measures ANOVA, no meaningful effects sizes were found for mean scores on all measures completed pre-pandemic compared to during the pandemic (
d
≤ 0.17).
Conclusion
The vast majority of caregivers reported stability in HRQOL pre-pandemic compared to during the pandemic. The COVID-19 pandemic was not associated with a high prevalence of decline in caregiver HRQOL.
To examine the relationship between service member/veteran (SM/V) traumatic brain injury (TBI) severity with caregiver health-related quality of life (HRQOL).
Military treatment facility.
Caregivers ...( N = 316) of SM/Vs following a TBI divided into 2 groups based on SM/V TBI severity: (1) caregivers of SM/Vs following an uncomplicated mild TBI (UnMTBI Caregiver group, n = 246), and (2) caregivers of SM//Vs following a complicated mild, moderate, severe, or penetrating TBI (STBI Caregiver group, n = 70). The STBI Caregiver group was further divided into 2 subgroups: Parent ( n = 21) versus Intimate Partner ( n = 49). The UnMTBI Caregiver group consisted of intimate partners.
Prospective cohort.
Caregivers completed 15 HRQOL measures.
Using analysis of variance and chi-square analysis, the UnMTBI Caregiver group reported worse scores on 12 HRQOL measures and more clinically elevated scores for 6 of 15 comparisons than the STBI Caregiver group. The UnMTBI Caregiver group also reported worse scores on 10 HRQOL measures than intimate partners in the STBI Caregiver group and 5 measures than parents in the STBI Caregiver group. Parents reported worse scores on 3 measures than intimate partners in the STBI Caregiver group. The UnMTBI Caregiver group reported more clinically elevated scores for 7 of 15 comparisons than intimate partners in the STBI Caregiver group.
Intimate partner caregivers of an SM/V following a remote uncomplicated MTBI reported worse HRQOL than intimate partners and parent caregivers of an SM/V following a more severe TBI, mostly likely due to SM/V physical and mental health comorbidities. Interventions that focus on the SM/V's TBI and other comorbidities, the caregiver's behavioral health problems, and the relationship and family factors that interact with each other will likely have the most success in improving individual and family outcomes for military families.
Traumatic brain injury, especially mild traumatic brain injury, is a common consequence of modern warfare. In the current conflicts in Iraq and Afghanistan, much attention has been devoted to blast ...as a "new" mechanism of brain injury. While the evidence for primary blast effects upon the central nervous system is limited and controversial, there are a number of aspects of blast-induced brain injury that may be different. These include high rates of sensory impairment, pain issues, and polytrauma. In addition, the emotional context in which the injury occurred must also be considered in understanding the clinical presentation of these patients. Successful treatment of these individuals must use a multidisciplinary approach focused on the varied conditions that occur in those injured.
Sub-concussive injuries have emerged as an important factor in the long-term brain health of athletes and military personnel. The objective of this study was to explore the relationship between ...service member and veterans (SMVs) lifetime blast exposure and recovery from a traumatic brain injury (TBI). A total of 558 SMVs with a history of TBI were examined. Lifetime blast exposure (LBE) was based on self-report (M = 79.4, standard deviation = 392.6; range = 0-7500) categorized into three groups: Blast Naive (
= 121), Low LBE (
= 223; LBE range 1-9), and High LBE (
= 214; LBE >10). Dependent variables were the Neurobehavioral Symptom Inventory (NSI) and Post-traumatic Stress Disorder Checklist-Civilian (PCL-C) and the Traumatic Brain Injury Quality of Life (TBI-QOL). Analyses controlled for demographic factors (age, gender, and race) as well as TBI factors (months since index TBI, index TBI severity, and total number lifetime TBIs). The Blast Naive group had significantly lower NSI and PCL-C scores compared with the Low LBE group and High LBE group, with small to medium effect sizes. On the TBI-QOL, the Blast Naïve group had better quality life on 10 of the 14 scales examined. The Low LBE did not differ from the High LBE group on the PCL-C, NSI, or TBI-QOL. Blast exposure over an SMV's career was associated with increased neurobehavioral and post-traumatic stress symptoms following a TBI. The influence of psychological trauma associated with blasts may be an important factor influencing symptoms as well as the accuracy of self-reported estimates of LBE.
The purpose of this study was to examine the association of serum tau, neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), and ubiquitin carboxy-terminal hydrolase L1 (UCHL-1) ...concentrations evaluated within the first 12 months after a military-related TBI, with longitudinal changes in neurobehavioral functioning extending two or more years post-injury. Participants were 84 United States service members and veterans (SMVs) prospectively enrolled in the Defense and Veterans Brain Injury Center of Excellence/Traumatic Brain Injury Center 15-Year Longitudinal TBI Study, separated into three discreet groups: (a) uncomplicated mild TBI (MTBI;
= 28), (b) complicated mild, moderate, severe, and penetrating TBI combined (STBI;
= 29, and (c) non-injured controls (NIC,
= 27). Participants completed a battery of self-report neurobehavioral symptom measures (e.g., depression, post-traumatic stress disorder PTSD, post-concussion, anxiety, somatic, cognitive, and neurological symptoms) within 12 months of injury (baseline), and then again at two or more years post-injury (follow-up). At baseline, participants also completed a blood draw to determine serum concentrations of tau, NFL, GFAP, and UCHL-1 using an ultra-sensitivity assay method. In the MTBI and STBI groups (using hierarchical regression analyses), (1) baseline tau concentrations predicted the deterioration of neurobehavioral symptoms from baseline to follow-up on measures of anxiety, PTSD, depression, post-concussion, somatic, and neurological symptoms (accounting for 10-28% of the variance); (2) NFL predicted the deterioration of depression, post-concussion, somatic, cognitive, and neurological symptoms (10-32% variance); (3) GFAP predicted the deterioration of post-concussion, PTSD, depression, anxiety, somatic, neurological, and cognitive symptoms (11-43% variance); and (4) UCHL-1 predicted the deterioration of anxiety, somatic, and neurological symptoms (10-16% variance). In the NIC group, no meaningful associations were found between baseline biomarker concentrations and the deterioration of neurobehavioral symptoms on the majority of measures. This study reports that elevated tau, NFL, GFAP, and UCHL-1 concentrations within the first 12 months of injury are associated with the deterioration of neurobehavioral symptoms that extends to the chronic phase of recovery after a TBI. These findings suggest that a blood-based panel including these biomarkers could be a useful prognostic tool to identifying those individuals at risk of poor future outcome after TBI.
Exposure to explosive armaments during Operation Iraqi Freedom and Operation Enduring Freedom contributed to approximately 14% of the 352612 traumatic brain injury (TBI) diagnoses in the US military ...between 2000 and 2016. The US Department of Defense issued guidelines in 2009 to (1) standardize TBI diagnostic criteria; (2) classify TBI according to mechanism and severity; (3) categorize TBI symptoms as somatic, psychological, or cognitive; and (4) systematize types of care given during the acute and rehabilitation stages of TBI treatment. Polytrauma and associated psychological and neurologic conditions may create barriers to optimal rehabilitation from TBI. Given the completion of recent combat operations and the transition of TBI patients into long-term care within the US Department of Veterans Affairs system, a review of the literature concerning TBI is timely. Long-term follow-up care for patients who have sustained TBI will remain a critical issue for the US military.
Purpose
To examine (1) the relationship between caregiver pain interference with caregiver health-related quality of life (HRQOL), caregiver age, and service member/veteran (SMV) functional ability, ...and (2) change in caregiver pain interference longitudinally over 5 years.
Method
Participants were 347 caregivers of SMVs diagnosed with traumatic brain injury (TBI). Caregivers completed the SF-12v2 Health Survey Bodily Pain scale at an initial baseline evaluation and up to four annual follow-up evaluations. Caregivers were divided into three pain interference groups: High Pain Interference (
n
= 104), Neutral Pain Interference (
n
= 117), and Low Pain Interference (
n
= 126). Caregivers also completed 15 HRQOL measures and a measure of SMV functional ability.
Results
The High Pain Interference group reported more clinically elevated scores on 13 measures compared to the Low Pain Interference group, and seven measures compared to the Neutral Pain Interference group. The Neutral Pain Interference group had more clinically elevated scores on three measures compared to the Low Pain Interference group. The High and Neutral Pain Interference groups were older than the Low Pain Interference group. Parent caregivers were older than intimate partner/sibling caregivers, but did not report worse pain interference. Caregiver age, and measures of Fatigue, Strain, Perceived Rejection, and Economic QOL were the strongest predictors of pain interference (
p
< .001), accounting for 28.2% of the variance. There was minimal change in Bodily Pain scores over five years. The interaction of time and age was not significant (
X
2
= 2.7,
p
= .61).
Conclusion
It is important to examine pain in the context of HRQOL in caregivers, regardless of age.
There is a paucity of human data on exposure to blast traumatic brain injury (bTBI) and the corresponding systemic cytokine immune response at later time points (i.e., months, years) post-injury.
We ...conducted a repeated measures, case-control study, examining associations of serum levels of pro- and anti-inflammatory cytokines, measured both pre- and post-deployment with having mild and moderate/severe bTBI. Utilizing serum from the Department of Defense Serum Repository cytokines were measured via an ELISA-based array for 15 cytokines. We compared pre- vs. post-levels among mild cases, moderate/severe cases, and controls and carried out case-control comparisons, using paired t- tests and generalized linear models.
The average time between bTBI and post-deployment/bTBI serum among cases was 315.8 days. From pre- to post-deployment/bTBI, levels of interleukin 8 (IL-8) were decreased among both mild cases (μ = - 83.43 pg/ml; s.e. = 21.66) and moderate/severe cases (μ = - 107.67 pg/ml; s.e. = 28.74 pg/ml), while levels increased among controls (μ = 32.86 pg/ml; s.e. = 30.29). The same pattern occurred for matrix metallopeptidase 3 (MMP3), with levels decreasing for moderate/severe cases (μ = - 3369.24 pg/ml; s.e. = 1701.68) and increasing for controls (μ = 1859.60 pg/ml; s.e. = 1737.51) from pre- to post-deployment/bTBI. Evidence was also suggestive of case-control differences, from pre- to post-deployment/bTBI for interleukin 1 alpha (IL-1α), interleukin 4 (IL-4), and interleukin 6 (IL-6) among moderate/severe cases.
The findings of this longitudinal study indicate that in the chronic phase of bTBI, levels of IL-8 and MMP3 may be substantially lower than pre-injury. These results need confirmation in other studies, potentially those that account for treatment differences, which was not possible in our study.
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