Treatment of chronic symptoms following mild traumatic brain injury with transcranial LED: a sham run-in pilot study of photobiomodulation therapy.

PRIMARY OBJECTIVE: We evaluated whether photobiomodulation with red/near infrared light applied transcranially via light emitting diodes (LED) was associated with reduced symptoms and improved cognitive functioning in patients with chronic symptoms following mild traumatic brain injury. RESEARCH DESIGN: Participants (3 men, 6 women; 22-61 years-old) underwent a 6-week intervention involving 18 40-minute transcranial LED treatment sessions. METHODS AND PROCEDURES: Reliable change indices were calculated for 10 neuropsychological test scores and 3 self-report questionnaires of subjective cognition, post-concussion symptoms, and depression at baseline and following treatment. Questionnaires were also administered after 2-week sham and at 1-month and 2-month follow-ups. MAIN OUTCOME AND RESULTS: Only 2 participants improved on neuropsychological testing. On questionnaires, 4 reported improved cognition, 5 reported improved post-concussion symptoms, and 3 reported improved depression. Significant improvement in 2 or more domains was reported by 4 participants and mostly maintained at both follow-ups. CONCLUSIONS: Most participants did not improve on neuropsychological testing. A minority self-reported improvement in symptoms, potentially explained by the intervention, psychiatric medication changes, placebo effects, or other factors. Selecting participants with different clinical characteristics, and dosing and delivery system changes, may produce different results. A study design accounting for placebo effects appears warranted in future trials.

A Framework for Understanding the Contribution of Psychosocial Factors in Biopsychosocial Explanatory Models of Persistent Postconcussion Symptoms.

Biopsychosocial models are currently used to explain the development of persistent postconcussion symptoms (PPCS) following concussion. These models support a holistic multidisciplinary management of postconcussion symptoms. One catalyst for the development of these models is the consistently strong evidence pertaining to the role of psychological factors in the development of PPCS. However, when applying biopsychosocial models in clinical practice, understanding and addressing the influence of psychological factors in PPCS can be challenging for clinicians. Accordingly, the objective of this article is to support clinicians in this process. In this Perspective article, we discuss current understandings of the main psychological factors involved in PPCS in adults and summarize these into 5 interrelated tenets: preinjury psychosocial vulnerabilities, psychological distress following concussion, environment and contextual factors, transdiagnostic processes, and the role of learning principles. With these tenets in mind, an explanation of how PPCS develop in one person but not in another is proposed. The application of these tenets in clinical practice is then outlined. Guidance is provided on how these tenets can be used to identify psychosocial risk factors, derive predictions, and mitigate the development of PPCS after concussion from a psychological perspective within biopsychosocial conceptualizations. IMPACT: This Perspective helps clinicians apply biopsychosocial explanatory models to the clinical management of concussion, providing summary tenets that can guide hypothesis testing, assessment, and treatment.

Neurorehabilitation of Persistent Sport-Related Post-Concussion Syndrome.

BACKGROUND: Persistent Sport-Related Post-Concussion Syndrome is often diagnosed with any type of prolonged PCS symptoms. However, there are not specific diagnostic criteria for PPCS such that misdiagnosis often occurs. Further, the signs and symptoms of PCS overlap with other common illnesses such as depression, anxiety, migraines, ADHD and others. Misdiagnosis may lead to less than efficacious treatment, resulting in prolonged symptoms. OBJECTIVE: This article will review relevant evidence-based literature on PCS, pointing out the lack of a systemic diagnostic framework. It will also provide evidence that highlights the multiple conflicting findings in the literature. This article will posit the BioPsychoSocial framework as the best diagnostic framework for understanding the impact of concussions on the person and to generate individualized and personal interventions. METHODS: A narrative review of sport concussion-related articles was conducted, after extensive searches of relevant and non-relevant literature by each author, as well as articles recommended by colleagues. Articles varied from American Academy of Neurology Class I to IV for evaluation and critique. Class IV articles were reviewed, as there is much public misconception regarding sport and other concussion treatment that needed identification and discussion. RESULTS: Articles reviewed varied by quality of research design and methodology. Multiple symptoms, recovery patterns and rehabilitation treatment approaches are purported in the sport-related concussion literature. Current consensus data as well as the mixed and contradictory findings were explored. CONCLUSIONS: Persistent Sport-Related Post-Concussion Syndrome is a topic of great interest to both professionals and the general public. There is much misunderstanding about the etiology, causation, diagnostic formulations, symptom presentation, prolonging factors and treatment involved in this syndrome. This article posits an individualized multi-system diagnostic formulation, examining all relevant factors, as generating the best interventions for neurorehabilitation of Persistent Sport-Related Post-Concussion Syndrome.

Behavioral Therapies and Mind-Body Interventions for Posttraumatic Headache and Post-Concussive Symptoms: A Systematic Review.

BACKGROUND: There are no clear guidelines on how to treat posttraumatic headache (PTH) or post-concussive symptoms (PCS). However, behavioral interventions such as cognitive behavioral therapy, biofeedback, and relaxation are Level-A evidence-based treatments for headache prevention. To understand how to develop and study further mind-body interventions (MBIs) and behavioral therapies for PTH and PCS, we developed the following question using the PICO framework: Are behavioral therapies and MBIs effective for treating PTH and PCS? METHODS: We conducted a systematic search of 3 databases (Medline, PsycINFO, and EMBASE) for behavioral interventions and MBIs with the subject headings and keywords for PTH, concussion, and traumatic brain injury (TBI). Inclusion criteria were (1) randomized controlled trials, (2) the majority of the intervention had to be behavioral or mind-body therapy focused, (3) the majority of the participants (>50%) had to have had a mild TBI (not a moderate or severe TBI), (4) published in a peer-reviewed publication, and (5) meeting pre-specified primary and/or secondary outcomes. Primary outcome(s): whether there was a significant change in concussion symptom severity (yes/no) based on the symptom severity checklist/scale used, whether there was a 50% reduction in headache days and/or disability; secondary outcome(s): sleep variables, cognitive complaints, depression, and anxiety. The search identified 917 individual studies. Two independent reviewers screened citations and full-text articles independently. Nineteen articles were pulled for full article review. Seven articles met the final inclusion criteria. The systematic review was registered in Prospero (CRD42017070072). RESULTS: Overall, there was vast heterogeneity across the studies, making it difficult to fully assess efficacy. The heterogeneity ranged from differences in patient populations, the timing of when the interventions were initiated, the types of intervention implemented, and the measures used to assess outcomes. Seven studies were identified as meeting final inclusion criteria, resulting in a total of 1108 adult participants ranging from 18 to 80. Sixty-nine percent were male. Of the 7 studies, 3 were focused on military staff (retired and active). Time post-injury for inclusion into the studies varied from 48 hours post-injury to more than 2 years post-injury. One of the 7 studies did not include time post-TBI in the inclusion criteria. Two studies recruited patients who had visited their emergency departments, 4 of the studies recruited subjects through outpatient referrals, and 1 study recruited patients who had been in a prior traffic accident with resulting chronic PTH directly from a headache center. Group cognitive behavioral therapy (CBT) sessions and telephonic counseling or communication were common intervention methods used in the studies, with group CBT being used in 2 of the studies and telephonic counseling being used in 3. Other intervention methods used included individual CBT, cognitive training, psychoeducation, and computer-based and/or therapist-directed cognitive rehabilitation. CONCLUSIONS: Many of the interventions offered vastly different methods of delivery of intervention and doses of intervention. Many of the negative studies were done after an extended duration post-injury (>1-year posttraumatic brain injury [TBI]). In addition, the participants were lumped together regardless of their pre-concussion comorbidities, their mechanism of injury, their symptoms, and the duration from injury to the start of the intervention. The mass heterogeneity found between the studies led to inconclusive findings. Thus, there are various considerations for the design of the intervention for future behavioral/MBI studies for PTH and concussion that must be addressed before the leading question of this review may be effectively answered.

Prevention of post-concussion-like symptoms in patients presenting at the emergency room, early single eye movement desensitization, and reprocessing intervention versus usual care: study protocol for a two-center randomized controlled trial.

BACKGROUND: Recent data suggest that 10-20% of injury patients will suffer for several months after the event from diverse symptoms, generally referred to as post-concussion-like symptoms (PCLS), which will lead to a decline in quality of life. A preliminary randomized control trial suggested that this condition may be induced by the stress experienced during the event or emergency room (ER) stay and can be prevented in up to 75% of patients with a single, early, short eye movement desensitization and reprocessing (EMDR) psychotherapeutic session delivered in the ER. The protocol of the SOFTER 3 study was designed to compare the impact on 3-month PCLS of early EMDR intervention and usual care in patients presenting at the ER. Secondary outcomes included 3-month post-traumatic stress disorder, 12-month PCLS, self-reported stress at the ER, self-assessed recovery expectation at discharge and 3 months, and self-reported chronic pain at discharge and 3 months. METHODS: This is a two-group, open-label, multicenter, comparative, randomized controlled trial with 3- and 12-month phone follow-up for reports of persisting symptoms (PCLS and post-traumatic stress disorder). Those eligible for inclusion were adults (≥18 years old) presenting at the ER departments of the University Hospital of Bordeaux and University Hospital of Lyon, assessed as being at high risk of PCLS using a three-item scoring rule. The intervention groups were a (1) EMDR Recent Traumatic Episode Protocol intervention performed by a trained psychologist during ER stay or (2) usual care. The number of patients to be enrolled in each group was 223 to evidence a 15% decrease in PCLS prevalence in the EMDR group. DISCUSSION: In 2012, the year of the last national survey in France, 10.6 million people attended the ER, some of whom did so several times since 18 million visits were recorded in the same year. The SOFTER 3 study therefore addresses a major public health challenge. TRIAL REGISTRATION: Clinical Trials. NCT03400813 . Registered 17 January 2018 - retrospectively registered.

Hyperbaric oxygen may induce angiogenesis in patients suffering from prolonged post-concussion syndrome due to traumatic brain injury.

PURPOSE: Recent clinical studies present convincing evidence that hyperbaric oxygen therapy (HBOT) may be the coveted neurotherapeutic method for brain repair. One of the most interesting ways in which HBOT can induce neuroplasticity is angiogenesis. The objective in this study was to assess the neurotherapeutic effect of HBOT in post TBI patients using brain perfusion imaging and clinical cognitive functions. METHODS: Retrospective analysis of patients suffering from chronic neuro-cognitive impairment from TBI treated with HBOT. The HBOT protocol included 60 daily HBOT sessions, 5 days per week. All patients had pre and post HBOT objective computerized cognitive tests (NeuroTrax) and brain perfusion MRI. RESULTS: Ten post-TBI patients were treated with HBOT with mean of 10.3±3.2 years after their injury. After HBOT, whole-brain perfusion analysis showed significantly increased cerebral blood flow and cerebral blood volume. Clinically, HBOT induced significant improvement in the global cognitive scores (p = 0.007). The most prominent improvements were seen in information processing speed, visual spatial processing and motor skills indices. CONCLUSION: HBOT may induce cerebral angiogenesis, which improves perfusion to the chronic damage brain tissue even months to years after the injury.

Neuropsychological and psychological rehabilitation interventions in refractory sport-related post-concussive syndrome.

BACKGROUND: The neuropsychological, physical, vestibular and oculomotor sequelae of sports-related concussion are extremely well documented. However, there is a paucity of interventions for these symptoms in refractory sports-related concussions. AIM: The intent of this article is to review the known and emerging neuropsychological and psychological rehabilitation interventions for reducing morbidity in refractory sports-related concussions (SRCs). METHODS: The authors openly acknowledge the limited amount of empirical data available for review, as did the Zurich consensus papers, but posit a mindful and ethical approach towards rehabilitation interventions in the absence of evidence-based guidelines. Further, rehabilitation interventions proven useful with similar injuries or illnesses, particularly non-sports-related mild TBI, will be reviewed for applicability. Such interventions include Cognitive-Behavioural psychotherapy, biofeedback, cranial electrical stimulation, neurofeedback and cognitive rehabilitation. RESULTS AND CONCLUSIONS: Modified approaches for rehabilitation with young children within family and school systems are provided. Recommendations for further research are offered.

EEG Neurofeedback therapy: Can it attenuate brain changes in TBI?

BACKGROUND: Electroencephalogram Neurofeedback therapy (EEG-NFT) has several potential beneficial effects in terms of improving cognition and electrophysiological regulation among patients with brain injury. However, in vivo structural and functional changes remain less explored. OBJECTIVE: The aim of the present study is to explore EEG-NFT induced in vivo changes in traumatic brain injury (TBI) patients. METHOD: Two patients with mean age of 15 years with moderate head injury who had more than seven post concussion symptoms and poor cognitive performances (<5 percentile) were subjected to 20 sessions of EEG-NFT. The neuropsychological test scores, post concussion symptoms and MRI scan of the brain were recorded pre-post to EEG-NFT. RESULTS: During EEG-NFT the cognitive scores and concussion symptoms improved significantly (p < 0.05). The EEG-NFT has shown significant increase in cortical grey matter (GM) volumes (p < 0.0001) and fractional anisotropy (FA) of cortical white matter (WM) tracts (p < 0.0001, voxel max 60 and above). There was a significant decrease in global, local efficiency, cost and clustering coefficient of functional connectivity (Wilcoxon Sign Rank Test p < 0.05). Interestingly there was a significant increase in thalamo-cortical connection (increase FA value) after EEG-NFT. CONCLUSION: The EEG-NFT therapy has shown significant changes in structural and functional connectivity among young moderately injured TBI patients.

Longitudinal and prognostic evaluation of mild traumatic brain injury: A 1H-magnetic resonance spectroscopy study.

In the majority of patients with mild traumatic brain injury (mTBI), brain tissue impairment is undetectable by computed tomography and/or structural magnetic resonance imaging. Even in confirmed cases of head injury, conventional neuroimaging methods lack sensitivity in predicting neuropsychological outcomes of patients. The objectives of this study were to (1) cross-sectionally determine deviations in the neurometabolic profile of patients with mTBI from healthy controls at different stages of mTBI using tightly controlled examination windows, and (2) determine associations between acute neurometabolic markers of mTBI and chronic neurocognitive performance. Patients were examined at the early subacute (n=43; 5.44 ± 3.15 days post-injury (DPI)), late subacute (n=33; 37.00 ± 12.26 DPI) and chronic (n=27; 195.30 ± 19.60 DPI) stages of mTBI. Twenty-one neurologically intact subjects were used as controls. Proton magnetic resonance spectroscopy imaging ((1)H-MRSI) was used to obtain metabolic measurements from different brain regions. The Automated Neuropsychological Assessment Metrics (ANAM) was used for cognitive evaluation of patients at the chronic stage of mTBI. Measurements in the thalamus and centrum semiovale (CSV) emerged as the most indicative of injury and were used to predict neurocognitive outcome. The major findings of this study are (1) decreases in Cho/Cre (choline-to-creatine ratio) measured in the thalamus (p=0.042) and CSV (p=0.017) at the late subacute stage of mTBI; (2) positive associations of early subacute Cre measurements in the CSV with chronic ANAM scores measuring performance in delayed (r=0.497, p=0.019) and immediate (r=0.391, p=0.072) code substitution. These findings show that metabolic measurements in the thalamus and CSV can potentially serve as diagnostic and prognostic markers of mTBI.

Randomized, Sham-Controlled, Feasibility Trial of Hyperbaric Oxygen for Service Members With Postconcussion Syndrome: Cognitive and Psychomotor Outcomes 1 Week Postintervention.

Background Mild traumatic brain injury (mTBI) and residual postconcussion syndrome (PCS) are common among combatants of the recent military conflicts in Iraq and Afghanistan. Hyperbaric oxygen (HBO2) is a proposed treatment but has not been rigorously studied for this condition. Objectives In a secondary analysis, examine for possible effects on psychomotor (balance and fine motor) and cognitive performance 1 week after an HBO2 intervention in service members with PCS after mTBI. Methods A randomized, double-blind, sham control, feasibility trial comparing pretreatment and posttreatment was conducted in 60 male active-duty marines with combat-related mTBI and PCS persisting for 3 to 36 months. Participants were randomized to 1 of 3 preassigned oxygen fractions (10.5%, 75%, or 100%) at 2.0 atmospheres absolute (ATA), resulting in respective groups with an oxygen exposure equivalent to (1) breathing surface air (Sham Air), (2) 100% oxygen at 1.5 ATA (1.5 ATAO2), and (3) 100% oxygen at 2.0 ATA (2.0 ATAO2). Over a 10-week period, participants received 40 hyperbaric chamber sessions of 60 minutes each. Outcome measures, including computerized posturography (balance), grooved pegboard (fine motor speed/dexterity), and multiple neuropsychological tests of cognitive performance, were collected preintervention and 1-week postintervention. Results Despite the multiple sensitive cognitive and psychomotor measures analyzed at an unadjusted 5% significance level, this study demonstrated no immediate postintervention beneficial effect of exposure to either 1.5 ATAO2 or 2.0 ATAO2 compared with the Sham Air intervention. Conclusions These results do not support the use of HBO2 to treat cognitive, balance, or fine motor deficits associated with mTBI and PCS.

The effect of hyperbaric oxygen on persistent postconcussion symptoms.

BACKGROUND: The high incidence of persistent postconcussion symptoms in service members with combat-related mild traumatic brain injury has prompted research in the use of hyperbaric oxygen (HBO2) for management. OBJECTIVE: The effects of HBO2 on persistent postconcussion symptoms in 60 military service members with at least 1 combat-related mild traumatic brain injury were examined in a single-center, double-blind, randomized, sham-controlled, prospective trial at the Naval Medicine Operational Training Center at Naval Air Station Pensacola. METHODS: Over a 10-week period, subjects received a series of 40, once-daily, hyperbaric chamber compressions at 2.0 atmospheres absolute (ATA). During each session, subjects breathed 1 of 3 preassigned oxygen fractions (10.5%, 75%, or 100%) for 60 minutes, resulting in an oxygen exposure equivalent to breathing surface air, 100% oxygen at 1.5 ATA, or 100% oxygen at 2.0 ATA, respectively. Individual, subscale and total item responses on the Rivermead Postconcussion Symptom Questionnaire and individual and total Posttraumatic Disorder Checklist-Military Version were measured just prior to intervention and immediately postintervention. RESULTS: Between-group testing of pre- and postintervention means revealed no significant differences on individual or total scores on the Posttraumatic Disorder Checklist-Military Version or Rivermead Postconcussion Symptom Questionnaire, demonstrating a successful randomization and no significant main effect for HBO2 at 1.5 or 2.0 ATA equivalent compared with the sham compression. Within-group testing of pre- and postintervention means revealed significant differences on several individual items for each group and difference in the Posttraumatic Disorder Checklist-Military Version total score for the 2.0 ATA HBO2 group. DISCUSSION: The primary analyses of between group differences found no evidence of efficacy for HBO2. The scattered within group differences are threatened by Type 2 errors and could be explained by nonspecific effects. CONCLUSION: This study demonstrated that HBO2 at either 1.5 or 2.0 ATA equivalent had no effect on postconcussion symptoms after mild traumatic brain injury when compared with sham compression.

Enzogenol for cognitive functioning in traumatic brain injury: a pilot placebo-controlled RCT.

BACKGROUND AND PURPOSE: Enzogenol, a flavonoid-rich extract from Pinus radiata bark with antioxidant and anti-inflammatory properties has been shown to improve working memory in healthy adults. In traumatic brain injury (TBI), oxidation and inflammation have been linked to poorer cognitive outcomes. Hence, this phase II, randomized controlled trial investigated safety, compliance and efficacy of Enzogenol for improving cognitive functioning in people following mild TBI. METHODS: Sixty adults, who sustained a mild TBI, 3-12 months prior to recruitment, and who were experiencing persistent cognitive difficulties [Cognitive Failures Questionnaire (CFQ) score > 38], were randomized to receive Enzogenol (1000 mg/day) or matching placebo for 6 weeks. Subsequently, all participants received Enzogenol for a further 6 weeks, followed by placebo for 4 weeks. Compliance, side-effects, cognitive failures, working and episodic memory, post-concussive symptoms and mood were assessed at baseline, 6, 12 and 16 weeks. Simultaneous estimation of treatment effect and breakpoint was effected, with confidence intervals (CIs) obtained through a treatment-placebo balance-preserving bootstrap procedure. RESULTS: Enzogenol was found to be safe and well tolerated. Trend and breakpoint analyses showed a significant reduction in cognitive failures after 6 weeks [mean CFQ score, 95% CI, Enzogenol versus placebo -6.9 (-10.8 to -4.1)]. Improvements in the frequency of self-reported cognitive failures were estimated to continue until week 11 before stabilizing. Other outcome measures showed some positive trends but no significant treatment effects. CONCLUSIONS: Enzogenol supplementation is safe and well tolerated in people after mild TBI, and may improve cognitive functioning in this patient population. This study provides Class IIB evidence that Enzogenol is well tolerated and may reduce self-perceived cognitive failures in patients 3-12 months post-mild TBI.

A pilot study examining the effect of mindfulness-based stress reduction on symptoms of chronic mild traumatic brain injury/postconcussive syndrome.

OBJECTIVE: To evaluate the effectiveness of the mindfulness-based stress reduction (MBSR) program tailored to individuals with mild traumatic brain injury (mTBI). DESIGN: A convenience sample recruited from clinical referrals over a 2-year period completed outcome measures pre- and posttreatment intervention. SETTING: Post-acute brain injury rehabilitation center within a suburban medical facility. PARTICIPANTS: Twenty-two individuals with mTBI and a time postinjury more than 7 months. Eleven participants were men and 11 were women, ranging in age from 18 to 62 years. INTERVENTION: A 10-week group (with weekly 2-hour sessions) modeled after the MBSR program of Kabat-Zinn, but with modifications designed to facilitate implementation in a population of individuals with brain injury. (The treatment involved enhancement of attentional skills, in addition to increased awareness of internal and external experiences associated with the perspective change of acceptance and nonjudgmental attitude regarding those experiences). MAIN OUTCOME MEASURES: Perceived Quality of Life Scale, Perceived Self-Efficacy Scale, and the Neurobehavioral Symptom Inventory. Secondary measures included neuropsychological tests, a self-report problem-solving inventory, and a self-report measure of mindfulness. RESULTS: Clinically meaningful improvements were noted on measures of quality of life (Cohen d = 0.43) and perceived self-efficacy (Cohen d = 0.50) with smaller but still significant effects on measures of central executive aspects of working memory and regulation of attention. CONCLUSION: The MBSR program can be adapted for participants with mTBI. Improved performance on measures associated with improved quality of life and self-efficacy may be related to treatment directed at improving awareness and acceptance, thereby minimizing the catastrophic assessment of symptoms associated with mTBI and chronic disability. Additional research on the comparative effectiveness of the MBSR program for people with mTBI is warranted.

Hyperbaric side effects in a traumatic brain injury randomized clinical trial.

OBJECTIVE: To catalog the side effects of 2.4 atmospheres absolute (atm abs) hyperbaric oxygen (HBO2) vs. sham on post-concussion symptoms in military service members with combat-related, mild traumatic brain injury (TBI). METHODS: Fifty subjects diagnosed with TBI were randomized to either a sham (1.3 atm abs breathing air) or treatment (2.4 atm abs breathing 100% oxygen) hyperbaric profile. Forty-eight subjects completed 30 exposures. Medical events during hyperbaric exposures were separately annotated by medical staff and chamber operators. After the blind was broken, events were segregated into the exposure groups. RESULTS: These side effects were observed as rate (sham/treatment): ear block (ear barotrauma) 5.51% (1.09%/5.91%), sinus squeeze 0.14% (0.0%/0.27%), and confinement anxiety 0.27% (0.27%/0.27%). Other conditions that occurred included: headache 0.61% (0.68%/0.54%); nausea 0.2% (0.14%/0.27%); numbness 0.07% (0%/0.13%); heartburn 0.07% (0.14%/0%); musculoskeletal chest pain 0.07% (0%/0.13%); latex allergy 0.07% (0.14%/0%); and hypertension 0.07% (0.14%/0%). CONCLUSION: This study demonstrated no major adverse events, such as pulmonary barotraumas, pulmonary edema or seizure. Given the infrequent, mild side effect profile, the authors feel the study demonstrated that hyperbaric oxygen therapy (HBO2T) was safe at a relatively high treatment pressure in TBI subjects, and these data can be used to evaluate the risk/ benefit calculation when deciding to utilize HBO2T for treatment of various diseases in the TBI population.

Symptoms of post-concussional syndrome are non-specifically related to mild traumatic brain injury in UK Armed Forces personnel on return from deployment in Iraq: an analysis of self-reported data.

BACKGROUND: Mild traumatic brain injury (mTBI) is being claimed as the 'signature' injury of the Iraq war, and is believed to be the cause of long-term symptomatic ill health (post-concussional syndrome; PCS) in an unknown proportion of military personnel. METHOD: We analysed cross-sectional data from a large, randomly selected cohort of UK military personnel deployed to Iraq (n=5869). Two markers of PCS were generated: 'PCS symptoms' (indicating the presence of mTBI-related symptoms: none, 1-2, 3+) and 'PCS symptom severity' (indicating the presence of mTBI-related symptoms at either a moderate or severe level of severity: none, 1-2, 3+). RESULTS: PCS symptoms and PCS symptom severity were associated with self-reported exposure to blast whilst in a combat zone. However, the same symptoms were also associated with other in-theatre exposures such as potential exposure to depleted uranium and aiding the wounded. Strong associations were apparent between having PCS symptoms and other health outcomes, in particular being a post-traumatic stress disorder or General Health Questionnaire case. CONCLUSIONS: PCS symptoms are common and some are related to exposures such as blast injury. However, this association is not specific, and the same symptom complex is also related to numerous other risk factors and exposures. Post-deployment screening for PCS and/or mTBI in the absence of contemporaneous recording of exposure is likely to be fraught with hazards.