Baseline executive functioning moderates treatment-related changes in quality of life in veterans with posttraumatic stress disorder and comorbid traumatic brain injury.

Posttraumatic stress disorder (PTSD) treatment has been associated with improvement in quality of life (QOL); however, little is known about factors that moderate treatment-related changes in QOL, particularly cognitive factors. Executive functioning (EF) is important for success across all aspects of everyday life and predicts better psychological and physical health. EF is important to QOL, but more work is needed to better understand the association between EF and QOL improvements following interventions. We hypothesized that poorer baseline EF would be associated with less improvement in overall life satisfaction and satisfaction with health following PTSD treatment. U.S. veterans who served after the September 11, 2001 terrorist attacks (post 9-11; N = 80) with PTSD and a history of mild-to-moderate traumatic brain injury were randomized to standard cognitive processing therapy (CPT) or CPT combined with cognitive rehabilitation (SMART-CPT). Multilevel modeling was used to examine whether baseline EF performance was associated with changes in QOL scores from pretreatment to follow-up across both groups. Results indicated that poorer baseline performance on EF tests of working memory and inhibition were associated with less treatment-related improvements in general life satisfaction and satisfaction with health, rs = .26-.36. Treatment condition did not moderate any results. Future research should examine whether implementing EF-focused techniques before and/or concurrently with CPT for individuals with poorer baseline working memory and inhibition enhances QOL treatment gains, particularly in terms of general life and health-related satisfaction.

Factors Influencing Clinical Correlates of Chronic Traumatic Encephalopathy (CTE): a Review.

Chronic traumatic encephalopathy (CTE) is a neuropathologically defined disease reportedly linked to a history of repetitive brain trauma. As such, retired collision sport athletes are likely at heightened risk for developing CTE. Researchers have described distinct pathological features of CTE as well a wide range of clinical symptom presentations, recently termed traumatic encephalopathy syndrome (TES). These clinical symptoms are highly variable, non-specific to individuals described as having CTE pathology in case reports, and are often associated with many other factors. This review describes the cognitive, emotional, and behavioral changes associated with 1) developmental and demographic factors, 2) neurodevelopmental disorders, 3) normal aging, 4) adjusting to retirement, 5) drug and alcohol abuse, 6) surgeries and anesthesia, and 7) sleep difficulties, as well as the relationship between these factors and risk for developing dementia-related neurodegenerative disease. We discuss why some professional athletes may be particularly susceptible to many of these effects and the importance of choosing appropriate controls groups when designing research protocols. We conclude that these factors should be considered as modifiers predominantly of the clinical outcomes associated with repetitive brain trauma within a broader biopsychosocial framework when interpreting and attributing symptom development, though also note potential effects on neuropathological outcomes. Importantly, this could have significant treatment implications for improving quality of life.

Study protocol: Identifying transcriptional regulatory alterations of chronic effects of blast and disturbed sleep in United States Veterans.

Injury related to blast exposure dramatically rose during post-911 era military conflicts in Iraq and Afghanistan. Mild traumatic brain injury (mTBI) is among the most common injuries following blast, an exposure that may not result in a definitive physiologic marker (e.g., loss of consciousness). Recent research suggests that exposure to low level blasts and, more specifically repetitive blast exposure (RBE), which may be subconcussive in nature, may also impact long term physiologic and psychological outcomes, though findings have been mixed. For military personnel, blast-related injuries often occur in chaotic settings (e.g., combat), which create challenges in the immediate assessment of related-injuries, as well as acute and post-acute sequelae. As such, alternate means of identifying blast-related injuries are needed. Results from previous work suggest that epigenetic markers, such as DNA methylation, may provide a potential stable biomarker of cumulative blast exposure that can persist over time. However, more research regarding blast exposure and associations with short- and long-term sequelae is needed. Here we present the protocol for an observational study that will be completed in two phases: Phase 1 will address blast exposure among Active Duty Personnel and Phase 2 will focus on long term sequelae and biological signatures among Veterans who served in the recent conflicts and were exposed to repeated blast events as part of their military occupation. Phase 2 will be the focus of this paper. We hypothesize that Veterans will exhibit similar differentially methylated regions (DMRs) associated with changes in sleep and other psychological and physical metrics, as observed with Active Duty Personnel. Additional analyses will be conducted to compare DMRs between Phase 1 and 2 cohorts, as well as self-reported psychological and physical symptoms. This comparison between Service Members and Veterans will allow for exploration regarding the natural history of blast exposure in a quasi-longitudinal manner. Findings from this study are expected to provide additional evidence for repetitive blast-related physiologic changes associated with long-term neurobehavioral symptoms. It is expected that findings will provide foundational data for the development of effective interventions following RBE that could lead to improved long-term physical and psychological health.

A randomized clinical trial for a self-guided sleep intervention following moderate-severe traumatic brain injury: Study protocol.

BACKGROUND: Individuals with a history of moderate-severe traumatic brain injury (TBI) experience a significantly higher prevalence of insomnia compared to the general population. While individuals living with TBI have been shown to benefit from traditional insomnia interventions (e.g., face-to-face [F2F]), such as Cognitive Behavioral Therapy for Insomnia (CBTI), many barriers exist that limit access to F2F evidence-based treatments. Although computerized CBT-I (CCBT-I) is efficacious in terms of reducing insomnia symptoms, individuals with moderate-severe TBI may require support to engage in such treatment. Here we describe the rationale, design, and methods of a randomized controlled trial (RCT) assessing the efficacy of a guided CCBT-I program for reducing insomnia symptoms for participants with a history of moderate-severe TBI. METHODS: This is an RCT of a guided CCBT-I intervention for individuals with a history of moderate-severe TBI and insomnia. The primary outcome is self-reported insomnia severity, pre- to post-intervention. Exploratory outcomes include changes in sleep misperception following CCBT-I and describing the nature of guidance needed by the Study Clinician during the intervention. CONCLUSION: This study represents an innovative approach to facilitating broader engagement with an evidence-based online treatment for insomnia among those with a history of moderate-severe TBI. Findings will provide evidence for the level and nature of support needed to implement guided CCBT-I. Should findings be positive, this study would provide support for a strategy by which to deliver guided CCBT-I to individuals with a history of moderate-severe TBI.

Sleep deprivation and compensatory cognitive effort on a visual information processing task.

STUDY OBJECTIVES: Total sleep deprivation (TSD) is often associated with worse performance on tasks of attention and working memory, but some studies show no performance changes. One possibility is that greater compensatory cognitive effort is put forth to achieve similar results after TSD. We aimed to better understand the relationship between TSD, cognitive engagement, and performance outcomes following TSD. METHODS: Twenty healthy adults completed cognitive testing following a night of normal sleep and again after ~55 hours of TSD. Participants detected target letters in low (3-item) and high (10-item) load visual letter displays on the span of apprehension task with concurrent pupillometry, a measure of cognitive effort. RESULTS: We found significantly poorer detection accuracy and marginally longer response times following TSD across both arrays. In both arrays, significantly greater preparatory pupillary responses were found just prior to array onset. There was also a significant session by array interaction for pupillary responses, such that significantly greater dilation was found for the 3-letter array after TSD, while a nonsignificant decline in dilation was found following the 10-letter array after TSD. CONCLUSIONS: These results suggest a complex relationship between attentional control and cognitive resource allocation following TSD. Sleep-deprived individuals may allocate more compensatory cognitive effort to easier tasks but choose to disengage from more challenging cognitive tasks that have little perceived reward or probability of success to preserve diminishing cognitive resources. More work is needed to better delineate the underlying neurological systems involved in these processing load-dependent attentional control mechanisms after TSD.

Impact of a Sleep Enhancement Protocol on Nighttime Room Entries in an Inpatient Rehabilitation Facility.

PURPOSE: This study examined whether a sleep enhancement protocol (SEP) could reduce nighttime room entries (NREs) for patients with orthopedic injury (OI) or acquired brain injury (ABI) in an inpatient rehabilitation facility. DESIGN: A two-wave prospective study assessing standard of care (SOC) versus SEP. METHODS: Sixty-five participants completed baseline and follow-up questionnaires and wore an actigraph for approximately 7 days. In the SEP, nighttime care was "bundled." FINDINGS: In SOC, NREs were associated with less efficient sleep and greater daytime fatigue. Nighttime room entries were approximately 50% lower in the SEP than SOC. Participants in the OI SOC had more room entries than any other group. There were no significant changes in room entries in the ABI SEP group. CONCLUSIONS: There was a relationship between NREs and sleep. The SEP was effective at reducing NREs for patients with OI, but not ABI. CLINICAL RELEVANCE: Sleep enhancement protocols in inpatient rehabilitation facilities may be effective at improving sleep. Future research may focus on developing individualized protocols to improve sleep across patients with a variety of presenting diagnoses.

Baseline sleep quality moderates symptom improvement in veterans with comorbid PTSD and TBI receiving trauma-focused treatment.

Poor sleep quality is common among Veterans with posttraumatic stress disorder (PTSD) and history of traumatic brain injury (TBI). However, the relationship between sleep quality and treatment outcomes following trauma-focused interventions is less well-understood in this population. We sought to better understand whether 1) sleep quality changed as a result of trauma-focused treatment and 2) if baseline sleep quality moderated psychological and neurobehavioral treatment outcomes. Our sample consisted of 100 Iraq/Afghanistan era Veterans with PTSD and history of mild to moderate TBI who were randomized to one of two trauma-focused treatments: 1) Cognitive Processing Therapy (CPT) or 2) combined CPT and Cognitive Symptom Management and Rehabilitation Therapy (SMART-CPT). Self-reported sleep quality, psychiatric symptoms (PTSD and depression), and neurobehavioral concerns were assessed at multiple timepoints throughout the study. Multilevel modeling showed sleep quality did not improve, regardless of treatment condition. However, worse baseline sleep quality was associated with less improvement in PTSD symptoms and cognitive complaints. There was no effect of baseline sleep quality on change in depression symptoms. These findings suggest that more targeted treatments to address sleep quality either prior to or in conjunction with trauma-focused therapy may help to improve treatment outcomes for Veterans with comorbid PTSD and TBI history.

Post-concussive symptom endorsement and symptom attribution following remote mild traumatic brain injury in combat-exposed Veterans: An exploratory study.

The purpose of this study was to examine rates of and relationships between "post-concussive" symptom endorsement and symptom attribution in Veterans with a history of mild traumatic brain injury (mTBI). This cross-sectional, exploratory study included 48 combat-exposed Iraq/Afghanistan Veterans with remote history of mTBI. All Veterans completed clinical interviews and self-report questionnaires assessing sociodemographic factors, injury and combat-related variables, psychiatric distress, self-efficacy, and coping style. To assess symptom endorsement and symptom attribution, a modified version of the Neurobehavioral Symptom Inventory was administered. Results showed that the most commonly endorsed "post-concussive" symptoms were several non-specific symptoms, while the symptoms most frequently attributed to mTBI included forgetfulness, poor concentration, and headaches. Furthermore, although there were some overlapping correlates of both symptom endorsement and symptom attribution, unique variables were associated with each domain. Specifically, symptom endorsement was uniquely associated with measures of psychiatric distress, while symptom attribution was uniquely associated with having a history of loss of consciousness and a greater degree of combat exposure. Taken together, results suggest that endorsement of symptoms may be significantly impacted by the presence of mental health comorbidities, but that perceptions or beliefs as to why symptoms are occurring are related more to mTBI and combat-related characteristics. Findings offer potential avenues for therapeutic intervention, emphasize the importance of psychoeducation, and highlight the need to consider using alternate terminology for these symptoms that promotes recovery and minimizes misattribution of symptoms.

Associations Between Multiple Remote Mild TBIs and Objective Neuropsychological Functioning and Subjective Symptoms in Combat-Exposed Veterans.

OBJECTIVE: The purpose of this study was to evaluate relationships between multiple mild traumatic brain injuries (mTBIs) and objective and subjective clinical outcomes in a sample of combat-exposed Veterans, adjusting for psychiatric distress and combat exposure. METHOD: In this cross-sectional study, 73 combat-exposed Iraq/Afghanistan Veterans were divided into three groups based on mTBI history: 0 mTBIs (n = 31), 1-2 mTBIs (n = 21), and 3+ mTBIs (n = 21). Veterans with mTBI were assessed, on average, 7.78 years following their most recent mTBI. Participants underwent neuropsychological testing and completed self-report measures assessing neurobehavioral, sleep, and pain symptoms. RESULTS: MANCOVAs adjusting for psychiatric distress and combat exposure showed no group differences on objective measures of attention/working memory, executive functioning, memory, and processing speed (all p's > .05; ηp2 = .00-.06). In contrast, there were significant group differences on neurobehavioral symptoms (p's = < .001-.036; ηp2 = .09-.43), sleep difficulties (p = .037; ηp2 = .09), and pain symptoms (p < .001; ηp2 = .21). Pairwise comparisons generally showed that the 3+ mTBI group self-reported the most severe symptoms, followed by comparable symptom reporting between the 0 and 1-2 mTBI groups. CONCLUSIONS: History of multiple, remote mTBIs is associated with elevated subjective symptoms but not objective neuropsychological functioning in combat-exposed Veterans. These results advance understanding of the long-term consequences of repetitive mTBI in this population and suggest that Veterans with 3+ mTBIs may especially benefit from tailored treatments aimed at ameliorating specific neurobehavioral, sleep, and pain symptoms.

Glymphatic system disruption as a mediator of brain trauma and chronic traumatic encephalopathy.

Traumatic brain injury (TBI) is an increasingly important issue among veterans, athletes and the general public. Difficulties with sleep onset and maintenance are among the most commonly reported symptoms following injury, and sleep debt is associated with increased accumulation of beta amyloid (Aß) and phosphorylated tau (p-tau) in the interstitial space. Recent research into the glymphatic system, a lymphatic-like metabolic clearance mechanism in the central nervous system (CNS) which relies on cerebrospinal fluid (CSF), interstitial fluid (ISF), and astrocytic processes, shows that clearance is potentiated during sleep. This system is damaged in the acute phase following mTBI, in part due to re-localization of aquaporin-4 channels away from astrocytic end feet, resulting in reduced potential for waste removal. Long-term consequences of chronic dysfunction within this system in the context of repetitive brain trauma and insomnia have not been established, but potentially provide one link in the explanatory chain connecting repetitive TBI with later neurodegeneration. Current research has shown p-tau deposition in perivascular spaces and along interstitial pathways in chronic traumatic encephalopathy (CTE), pathways related to glymphatic flow; these are the main channels by which metabolic waste is cleared. This review addresses possible links between mTBI-related damage to glymphatic functioning and physiological changes found in CTE, and proposes a model for the mediating role of sleep disruption in increasing the risk for developing CTE-related pathology and subsequent clinical symptoms following repetitive brain trauma.

Concussion-Like Symptom Reporting in Non-Concussed Collegiate Athletes.

OBJECTIVE: Non-concussed individuals may report a variety of concussion-like symptoms even in the absence of a diagnosed brain injury. Previous studies described concussion-like symptom reporting in adolescent athletes. This study provides complementary data on concussion-like symptoms in collegiate athletes. METHODS: We analyzed baseline symptom scales from 738 collegiate athletes (452 men and 286 women) who completed either the Sport Concussion Assessment Tool, 3 Symptom Evaluation (S3SE; n = 377) or the Post-Concussion Scale (PCS; n = 361) and determined if subjects met criteria for diagnosis of International Classification of Diseases 10th Revision (ICD-10) postconcussional syndrome. Symptoms were grouped as somatic, cognitive, emotional, or sleep-related. We analyzed associations with medical history factors using chi-square analyses, and examined recovery time of a subset of concussed athletes based on baseline symptomatology (n = 117) with independent samples t-test. RESULTS: Across all athletes, 120 (16.3%) reported baseline symptoms meeting criteria for ICD-10 postconcussional syndrome. Women were 1.7 times more likely to meet these criteria (21.7% vs. 12.8%, p = .002). Athletes completing the S3SE were 1.5 times more likely to meet criteria than those completing the PCS (p = .011). Previously diagnosed psychiatric disorder was significantly associated with emotional domain symptom reporting, and attention deficit-hyperactivity disorder diagnosis was associated with cognitive domain symptom reporting. On average, athletes meeting ICD-10 postconcussional syndrome criteria at baseline experienced longer recovery from concussion (t[115] = 2.35, p = .020). CONCLUSIONS: Non-concussed collegiate athletes report concussion-like symptoms at a clinically significant rate. Pre-injury medical history and reporting rates of concussion-like symptoms may explain variance in post-concussion symptom expression. Measured incidence of baseline postconcussional syndrome may, in part, depend on the symptom report measure that is used.

Research Gaps and Controversies in Chronic Traumatic Encephalopathy: A Review.

Importance: Scientific and lay interest in negative outcomes associated with exposure to repetitive brain trauma (RBT) continues to strengthen. Concerns about the association between RBT and dementia began more than a century ago, but have resurfaced in the last decade with the more recently described chronic traumatic encephalopathy (CTE). Chronic traumatic encephalopathy is a tauopathy associated with RBT that has become inextricably linked to conversations about sport-related concussion and mild traumatic brain injury. Accordingly, specific populations such as collision sport athletes and certain military personnel are of particular interest owing to their unique exposure to RBT. The gaps and controversies in our understanding of the epidemiologic factors, mechanism, and clinicopathological correlates of CTE reflect the current reliance on postmortem case series investigations. This review discusses the state of the science of CTE and raises considerations for researching and interpreting cognitive changes in members of at-risk populations. Observations: The recent development of pathological diagnostic criteria for CTE represented an important step for differentiating CTE from other neurodegenerative diseases. By comparison, defining the clinical syndrome(s) associated with CTE and the necessary and sufficient symptoms needed for its diagnosis lags behind. The absence of validated in vivo biomarkers of pathological characteristics of CTE and longitudinal tracking with neuropsychological evaluation remains a significant hurdle. Attribution of candidate symptoms in retired athletes to CTE is complicated by the presence of multiple premorbid and comorbid factors affecting cognitive reserve that influence normal or expected cognitive functioning. This is a critical issue in appropriately defining reference groups for normative comparisons. Conclusions and Relevance: Available data, while limited and complicated by selection bias, indicate that exposure to RBT represents the greatest risk factor for CTE pathological features, although clinicopathological correlates and the nature of onset and progression of symptoms are largely unknown. Considering aspects of cognitive reserve is likely essential for both interpreting cognitive outcomes associated with CTE and for developing preventive treatment programs. Research on CTE would benefit greatly from incorporating principles established within other areas of neurodegenerative disease and the nuances of clinicopathological considerations.

Clinical and surgical management of a congenital Type II split cord malformation presenting with progressive cranial neuropathies: case report.

Split cord malformation (SCM) is a rare abnormality of notochord development. The majority of cases occur in the thoracolumbar region, with more than 30 cases of cervical SCM reported. The clinical impact of SCMs involving the cervical cord is therefore largely unknown. In addition, the concomitant finding of brainstem involvement is presumably incompatible with life in the majority of patients, resulting in a paucity of data regarding this clinical scenario. In this paper the authors present the first case, to their knowledge, of an incomplete cervical SCM involving the brainstem and discuss its clinical impact, diagnosis, and management.

Risk factors and analysis of long-term headache in sporadic vestibular schwannoma: a multicenter cross-sectional study.

OBJECT: The primary goals of this study were: 1) to examine the influence of disease and treatment on headache in patients with sporadic vestibular schwannoma (VS); and 2) to identify clinical predictors of long-term headache disability. METHODS: This was a cross-sectional observational study with international multicenter enrollment. Patients included those with primary sporadic <3-cm VS and a separate group of general population control subjects without tumors. Interventions included a postal survey incorporating the Headache Disability Inventory (HDI), the Hospital Anxiety and Depression Scale, and a VS symptom questionnaire. The main outcome measures were univariate and multivariable associations with HDI total score. RESULTS: The overall survey response rate was 79%. Data from 538 patients with VS were analyzed. The mean age at time of survey was 64 years, 56% of patients were female, and the average duration between treatment and survey was 7.7 years. Twenty-seven percent of patients received microsurgery, 46% stereotactic radiosurgery, and 28% observation. Patients with VS who were managed with observation were more than twice as likely to have severe headache disability compared with 103 control subjects without VS. When accounting for baseline differences, there was no statistically significant difference in HDI outcome between treatment modalities at time of survey. Similarly, among the microsurgery cohort, the long-term risk of severe headache disability was not different between surgical approaches. Multivariable regression demonstrated that younger age, greater anxiety and depression, and a preexisting diagnosis of headache were the primary predictors of severe long-term headache disability, while tumor size and treatment modality had little influence. CONCLUSIONS: At a mean of almost 8 years following treatment, approximately half of patients with VS experience headaches of varying frequency and severity. Patient-driven factors including age, sex, mental health, and preexisting headache syndrome are the strongest predictors of long-term severe headache disability. Tumor size and treatment modality have less impact. These data may assist with patient counseling regarding long-term expectations following diagnosis and treatment.

Satisfaction with Cognitive Rehabilitation Delivered via the Internet in Persons with Acquired Brain Injury.

We examined the level of satisfaction with cognitive rehabilitation delivered via the Internet in persons with moderate to severe acquired brain injury (ABI). Fifteen adults with moderate to severe ABI were randomized to 30 days of Internet-based active treatment (AT) or to a wait list (WL) group, and crossed over to the opposite condition after 30 sessions. Both caregivers and participants were assessed at three time points during the study. This study focused on participant satisfaction with receiving treatment in this manner. Though the results of this study showed no significant treatment effect, the vast majority of participants (>87%) were satisfied with treatment. Treatment satisfaction accounted for 25% of additional variance in predicting lower family ratings of mood difficulties after final assessment (p<.03). Greater satisfaction with treatment was positively correlated with greater employment rate after treatment (r=.63, p=.02), as well as lower family ratings of memory and mood difficulties after final assessment (r=-.59, p=.03; r=-.58, p=.03,). Results suggest that treatment satisfaction in persons with ABI is related to less activity limitations, and maintaining employment after cognitive rehabilitation delivered via the Internet.