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

Introduction: The 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. Methods: 216 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. Results: A 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). Conclusion: These 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.

Feasibility and preliminary efficacy for morning bright light therapy to improve sleep and plasma biomarkers in US Veterans with TBI. A prospective, open-label, single-arm trial.

Mild traumatic brain injury (TBI) is associated with persistent sleep-wake dysfunction, including insomnia and circadian rhythm disruption, which can exacerbate functional outcomes including mood, pain, and quality of life. Present therapies to treat sleep-wake disturbances in those with TBI (e.g., cognitive behavioral therapy for insomnia) are limited by marginal efficacy, poor patient acceptability, and/or high patient/provider burden. Thus, this study aimed to assess the feasibility and preliminary efficacy of morning bright light therapy, to improve sleep in Veterans with TBI (NCT03578003). Thirty-three Veterans with history of TBI were prospectively enrolled in a single-arm, open-label intervention using a lightbox (~10,000 lux at the eye) for 60-minutes every morning for 4-weeks. Pre- and post-intervention outcomes included questionnaires related to sleep, mood, TBI, post-traumatic stress disorder (PTSD), and pain; wrist actigraphy as a proxy for objective sleep; and blood-based biomarkers related to TBI/sleep. The protocol was rated favorably by ~75% of participants, with adherence to the lightbox and actigraphy being ~87% and 97%, respectively. Post-intervention improvements were observed in self-reported symptoms related to insomnia, mood, and pain; actigraphy-derived measures of sleep; and blood-based biomarkers related to peripheral inflammatory balance. The severity of comorbid PTSD was a significant positive predictor of response to treatment. Morning bright light therapy is a feasible and acceptable intervention that shows preliminary efficacy to treat disrupted sleep in Veterans with TBI. A full-scale randomized, placebo-controlled study with longitudinal follow-up is warranted to assess the efficacy of morning bright light therapy to improve sleep, biomarkers, and other TBI related symptoms.

Photosensitivity Is Associated with Chronic Pain following Traumatic Brain Injury.

Individuals with a history of traumatic brain injury (TBI) report increased rates of chronic pain. Photosensitivity is also a common chronic symptom following TBI and is prevalent among other types of chronic pain. The aim of this study was to better understand the relationship between chronic pain, pain-related disability, and photosensitivity in a TBI population. We quantified participants' visual photosensitivity thresholds (VPT) using an Ocular Photosensitivity Analyzer and measured pressure-pain sensitivity using pressure algometry. Participants also completed a battery of self-report measures related to chronic pain, TBI history, and mental health. A total of 395 participants completed testing, with 233 reporting a history of TBI. The TBI group was divided into 120 symptomatic TBI participants (s-TBI), and 113 asymptomatic TBI participants (a-TBI) based on their Neurobehavioral Symptom Inventory (NSI) scores. Participants in the s-TBI group scored significantly higher on self-reported chronic pain measures compared with a-TBI and no-TBI participants, including the Symptom Impact Questionnaire Revised (SIQR; p < 0.001) and the Michigan Body Map (MBM; p < 0.001). Despite differences in chronic pain complaints, groups displayed similar pressure-pain thresholds (p = 0.270). Additionally, s-TBI participants were more sensitive to light (lower VPT, p < 0.001), and VPT was correlated with SIQR scores across all participants (R = -0.452, p < 0.001). These data demonstrate that photosensitivity is associated with self-reported chronic pain and disability in individuals with chronic TBI symptomatology. Photosensitivity could therefore serve as a simple, more highly quantitative marker of high-impact chronic pain after TBI.

Different Methods for Traumatic Brain Injury Diagnosis Influence Presence and Symptoms of Post-Concussive Syndrome in United States Veterans.

Common methods for evaluating history of traumatic brain injury (TBI) include self-report, electronic medical record review (EMR), and structured interviews such as the Head Trauma Events Characteristics (HTEC). Each has strengths and weaknesses, but little is known regarding how TBI diagnostic rates or the associated symptom profile differ among them. This study examined 200 Veterans recruited within the VA Portland Health Care System, each evaluated for TBI using self-report, EMR, and HTEC. Participants also completed validated questionnaires assessing chronic symptom severity in broad health-related domains (pain, sleep, quality of life, post-concussive symptoms). The HTEC was more sensitive (80% of participants in our cohort) than either self-report or EMR alone (40%). As expected from the high sensitivity, participants screening positive for TBI through the HTEC included many people with mild or no post-concussive symptoms. Participants were grouped according to degree of concordance across these diagnostic methods: no TBI, n = 43; or TBI-positive in any one method (TBI-1dx, n = 53), positive in any two (TBI-2dx, n = 45), or positive in all three (TBI-3dx, n = 59). The symptom profile of the TBI-1dx group was indistinguishable from the no TBI group. The TBI-3dx group had the most severe symptom profile. Our results show that understanding the exact methods used to ascertain TBI is essential when interpreting results from other studies, given that results and conclusions may differ dramatically depending on the method. This issue will become even more critical when interpreting data merged from multiple sources within newer, centralized repositories (e.g., Federal Interagency Traumatic Brain Injury Research [FITBIR]).

Trauma-Associated Sleep Disturbances: a Distinct Sleep Disorder?

PURPOSE OF REVIEW: This paper describes a newly proposed sleep disorder, trauma-associated sleep disorder (TSD). Whether or not this represents a truly unique condition is controversial. In this paper, we describe the overlapping features and differences between TSD, post-traumatic stress disorder (PTSD) and Rapid Eye Movement (REM) sleep behavior disorder (RBD). RECENT FINDINGS: While REM sleep without atonia (RWA) and dream enactment are part of the diagnostic criteria for both RBD and TSD, only TSD features nightmares that occur both in non-REM and REM. A key difference between TSD and PTSD is the presence of symptoms during wakefulness in the latter, though the relationship between the two disorders is, as of yet, unclear. It is unknown whether or not a relationship exists between TSD and neurodegeneration, thus this needs to be explored further. SUMMARY: Additional research, such as application of TSD diagnostic criteria to more diverse population, would help to determine whether or not TSD is a distinct clinical entity, its relationships to PTSD, as well as the association of this condition with the development of neurodegeneration.

Increased Sleep Disturbances and Pain in Veterans With Comorbid Traumatic Brain Injury and Posttraumatic Stress Disorder.

STUDY OBJECTIVES: Veterans are at an increased risk for traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD), both of which are associated with sleep disturbances and increased pain. Furthermore, sleep disturbances and pain are reciprocally related such that each can exacerbate the other. Although both TBI and PTSD are independently linked to sleep disturbances and pain, it remains unclear whether Veterans with comorbid TBI+PTSD show worse sleep disturbances and pain compared to those with only TBI or PTSD. We hypothesized that sleep and pain would be worse in Veterans with comorbid TBI+PTSD compared to Veterans with only TBI or PTSD. METHODS: Veterans (n = 639) from the VA Portland Health Care System completed overnight polysomnography and self-report questionnaires. Primary outcome variables were self-reported sleep disturbances and current pain intensity. Participants were categorized into four trauma-exposure groups: (1) neither: without TBI or PTSD (n = 383); (2) TBI: only TBI (n = 67); (3) PTSD: only PTSD (n = 126); and (4) TBI+PTSD: TBI and PTSD (n = 63). RESULTS: The PTSD and TBI+PTSD groups reported worse sleep compared to the TBI and neither groups. The TBI+PTSD group reported the greatest pain intensity compared to the other groups. CONCLUSIONS: These data suggest sleep and pain are worst in Veterans with TBI and PTSD, and that sleep is similarly impaired in Veterans with PTSD despite not having as much pain. Thus, although this is a complex relationship, these data suggest PTSD may be driving sleep disturbances, and the added effect of TBI in the comorbid group may be driving pain in this population.