Subclinical brain manifestations of repeated mild traumatic brain injury are changed by chronic exposure to sleep loss, caffeine, and sleep aids.

INTRODUCTION: After mild traumatic brain injury (mTBI), the brain is labile for weeks and months and vulnerable to repeated concussions. During this time, patients are exposed to everyday circumstances that, in themselves, affect brain metabolism and blood flow and neural processing. How commonplace activities interact with the injured brain is unknown. The present study in an animal model investigated the extent to which three commonly experienced exposures-daily caffeine usage, chronic sleep loss, and chronic sleep aid medication-affect the injured brain in the chronic phase. METHODS: Subclinical trauma by repeated mTBIs was produced by our head rotational acceleration injury model, which causes brain injury consistent with the mechanism of concussion in humans. Forty-eight hours after a third mTBI, chronic administrations of caffeine, sleep restriction, or zolpidem (sedative hypnotic) began and were continued for 70 days. On Days 30 and 60 post injury, resting state functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) were performed. RESULTS: Chronic caffeine, sleep restriction, and zolpidem each changed the subclinical brain characteristics of mTBI at both 30 and 60 days post injury, detected by different MRI modalities. Each treatment caused microstructural alterations in DTI metrics in the insular cortex and retrosplenial cortex compared with mTBI, but also uniquely affected other gray and white matter regions. Zolpidem administration affected the largest number of individual structures in mTBI at both 30 and 60 days, and not necessarily toward normalization (sham treatment). Chronic sleep restriction changed local functional connectivity at 30 days in diametrical opposition to chronic caffeine ingestion, and both treatment outcomes were different from sham, mTBI-only and zolpidem comparisons. The results indicate that commonly encountered exposures modify subclinical brain activity and structure long after healing is expected to be complete. CONCLUSIONS: Changes in activity and structure detected by fMRI are widely understood to reflect changes in the functions of the affected region which conceivably underlie mTBI neuropathology and symptomatology in the chronic phase after injury.

mTBI Biological Biomarkers as Predictors of Postconcussion Syndrome-Review.

Postconcussion syndrome (PCS) is one of the leading complications that may appear in patients after mild head trauma. Every day, thousands of people, regardless of age, gender, and race, are diagnosed in emergency departments due to head injuries. Traumatic Brain Injury (TBI) is a significant public health problem, impacting an estimated 1.5 million people in the United States and up to 69 million people worldwide each year, with 80% of these cases being mild. An analysis of the available research and a systematic review were conducted to search for a solution to predicting the occurrence of postconcussion syndrome. Particular biomarkers that can be examined upon admission to the emergency department after head injury were found as possible predictive factors of PCS development. Setting one unequivocal definition of PCS is still a challenge that causes inconsistent results. Neuron Specific Enolase (NSE), Glial Fibrillary Acidic Protein (GFAP), Ubiquitin C-terminal Hydrolase-L1 (UCH-L1), Serum Protein 100 B (s100B), and tau protein are found to be the best predictors of PCS development. The presence of all mentioned biomarkers is confirmed in severe TBI. All mentioned biomarkers are used as predictors of PCS. A combined examination of NSE, GFAP, UCH-1, S100B, and tau protein should be performed to detect mTBI and predict the development of PCS.

The Postconcussion Syndrome and Posttraumatic Headaches in Civilians, Soldiers, and Athletes.

Posttraumatic headaches are one of the most common and controversial secondary headache types. After a mild traumatic brain, an estimated 11% to 82% of people develop a postconcussion syndrome, which has been controversial for more than 160 years. Headache is estimated as present in 30% to 90% of patients after a mild head injury. Most headaches are tension-type-like or migraine-like. Headaches in civilians, soldiers, athletes, and postcraniotomy are reviewed. The treatments are the same as for the primary headaches. Persistent posttraumatic headaches can continue for many years.

Multidisciplinary interventions increase weekly working hours and quality of life in persons with post-concussion syndrome.

OBJECTIVES: To improve labor market attachment, general health and quality of life in persons suffering from post-concussion syndrome. Labor market attachment often changes after mTBI, and especially in persons suffering from post-concussion syndrome, and constitutes a huge societal burden. METHODS: Eighty-two adults with persistent post-concussion syndrome participated in this single-center and uncontrolled interventional efficacy open-label investigation. The primary endpoint was to increase weekly working hours. Outcome measures ranged from self-reported cognitive symptoms to objective performance testing. Multidisciplinary interventions were used to reduce symptoms of fatigue, stress, pain, oculomotor malfunction, and sensitivity to both sound and light. RESULTS: Workhours improved from median 0 to 6 hours (p = 0.00002). Several significant improvements were observed in quality of life measured by the SF-36. General fatigue measured by the MFI-20 was reduced (p < 0.0001), and symptoms of depression were reduced (p < 0.0001). The COPM results were improved for task completion satisfaction and for ability to perform a task (p < 0.0001). Reading speed, and performances in the Groffman Visual Tracing Test and the King-Devick Test, all improved (p < 0.01). The intervention did not reduce perception of pain intensity (p = 0.11). CONCLUSION: After the intervention, participants increased weekly workhours and improved in many aspects of life - including quality of life, performance in everyday activities, fatigue and depression. Perception of pain intensity was not improved.

The impact of the war in Ukraine on the reproductive health of female military personnel.

OBJECTIVE: To explore the link between mental health, physical well-being, and reproductive system pathology in females who suffered war-related concussions. METHODS: A study was conducted at the Kyiv Center of Reproductive and Perinatal Medicine with 715 participants. The group included 457 female military personnel with concussions (211 with post-concussive syndrome (PCS), 246 without), 208 women from occupied/deoccupied areas (103 with PCS, 105 without), and 50 civilians from safe zones. Average deployment time (mean ± standard deviation) was 60.26 ± 42.21 months, and trauma occurred 18.81 ± 9.221 months ago. Medical history and physical examinations were performed. RESULTS: Female soldiers with PCS had a 1.3 times higher likelihood (P < 0.015) of experiencing longer menstrual periods. Painful menstruation was 1.47 times more frequent (P < 0.001), and heavy periods were 1.64 times more common (P < 0.003). Infertility duration in concussed women was 5.36 ± 0.13 years, whereas those with PCS experienced 1.29 times longer duration (6.02 ± 0.21 years) (P < 0.001) compared with women without PCS (4.69 ± 0.13 years). Among concussed soldiers, 69.27% had endometrial structural pathology, with PCS occurring 1.64 times more often (P < 0.001). CONCLUSIONS: The health decline in female veterans and active-duty personnel extends beyond medical implications and has social significance. The well-being of these Ukrainian women affects the country's defense, demographic patterns, socio-political landscape, and social stability.

Investigation of long-term symptoms and influencing factors in patients with mild traumatic brain injury: A cross-sectional study.

BACKGROUND: Traumatic brain injury is the leading cause of death and disability in individuals under the age of 45, which places a heavy disease burden on patients and society. However, the prevalence of long-term symptoms in individuals who suffered from mild traumatic brain injury and how psychosocial factors affect their long-term symptoms remain unclear. OBJECTIVE: To determine howpsychosocial factors influence long-term symptomsin individuals who suffered from mild traumatic brain injury as well as the prevalence of long-term symptoms. METHODS: A demographic characteristics questionnaire, adapted self-report questionnaire of family relationship quality, revised Chinese version of the disease perception questionnaire, Rivermead postconcussion syndrome symptom questionnaire, Glasgow Outcome Scale-Extended, and Brief Symptoms Inventory 18 were used to collect data anonymously. Psychosocial factors associated with long-term symptoms in individuals who suffered from mild traumatic brain injury weremeasuredusingmultiple linear regression. RESULTS: More than half of individuals who suffered from mild traumatic brain injury showed at least 1 long-term symptom after injury. Our results indicated that family relationship quality, disease perception, and demographic characteristics were related to the long-term symptoms of individuals who suffered from mild traumatic brain injury. CONCLUSIONS: Our study shows that theprevalence of long-term symptomsfollowingmild traumatic brain injuryishigh. Psychosocial factors are related to patients' long-term symptoms. The findings indicate that healthcare administrators ought to adopt a robust health promotion strategy that prioritizes familial support and health education of diseases to ameliorate long-term symptoms in individuals who suffered from mild traumatic brain injury.

Hyperbaric Oxygen Therapy for the Management of Mild and Moderate Traumatic Brain Injury: A Single-Center Experience.

BACKGROUND: Hyperbaric oxygen therapy (HBOT) has been shown to be an effective modality in the management of a variety of conditions. However, its role in the treatment of traumatic brain injury (TBI) remains an area of controversy. This study aims to evaluate the safety and outcomes of HBOT in managing the long-term sequelae of TBI. METHODS: The records of TBI patients who underwent increments of 40 sessions of HBOT at 1.5 atmosphere absolute at a single medical center were reviewed. The outcome measures included physical, cognitive (i.e., Trail Making Test, parts A and B; U.S. Department of Veterans Affairs' Evaluation of Cognitive Impairment and Subjective Symptoms tool), and single-photon emission computed tomography findings. The complications and withdrawals were recorded. RESULTS: During the study period, 17 patients underwent HBOT to manage the long-term sequelae of their TBI. Of the 17 patients, 12 (70.6%) completed 120 HBOT sessions and were evaluated 3 months after treatment. All 12 patients had statistically significant improvements in their Trail Making Test, parts A and B, and U.S. Department of Veterans Affairs' Evaluation of Cognitive Impairment and Subjective Symptoms scores (P < 0.05). Additionally, single-photon emission computed tomography depicted increased cerebral blood flow and oxygen metabolism among studied subjects compared with the baseline values. A total of 5 patients withdrew from the study, which was related to new-onset headaches associated with HBOT for 1 patient. CONCLUSIONS: HBOT using 1.5 atmosphere absolute in increments of 40 sessions was found to be a safe and effective modality in the management of the long-term sequelae of TBI. HBOT should be considered in the management of this patient population.

Missed Emergency Department Diagnosis of Mild Traumatic Brain Injury in Patients with Chronic Pain After Motor Vehicle Collision.

BACKGROUND: Mild traumatic brain injury (mTBI), or concussion, is the most common presentation of TBI in the emergency department (ED), but a diagnosis of mTBI may be missed in patients presenting with other acute injuries after a motor vehicle collision (MVC). OBJECTIVE: To estimate the frequency of missed diagnoses of mTBI in patients seen in the ED after MVC who later developed chronic pain syndromes. STUDY DESIGN: Retrospective cohort study. SETTING: An interventional pain management clinic. METHODS: Data were drawn from information collected during standardized intake assessments completed by 33 patients involved in an MVC referred to a community-based clinic for chronic pain management. The prevalence of missed mTBI and postconcussion syndrome (PCS) were estimated based on the clinical diagnosis, which included reviewing acute care medical records, the Rivermead Post-Concussion Symptoms Questionnaire (RPQ) scores, and patient-reported injury history. RESULTS: There was a high prevalence of presumed mTBI in this sample (69.7%) of patients involved in an MVC, but an acute care diagnosis was made in only 39.1% of cases. Patients diagnosed with mTBI at acute care had significantly lower PCS symptom scores than patients whose diagnosis was missed (P < 0.05). Diagnostic brain imaging (magnetic resonance imaging [MRI] or computed tomography [CT]) was more frequently ordered (P < 0.05) in patients diagnosed with mTBI. Using a modified RPQ developed for use with chronic pain patients, 54.5% of the sample met criteria for PCS. Loss of consciousness, meeting established criteria for mTBI, postinjury headache, and meeting criteria for posttraumatic stress disorder were significantly correlated with the development of PCS. LIMITATIONS: Data may be subject to recall and selection bias. Additional research with a larger study sample is needed to investigate correlations between individual symptoms and the development of PCS following an MVC. CONCLUSION: Patients presenting to the ED following an MVC have a high prevalence of mTBI. Patients whose diagnosis of mTBI is missed end up with significantly more severe postconcussion symptoms. While all patients included in this study were either referred or being treated for chronic pain after an MVC, they all also went on to develop PCS and disability following their accident, suggesting that better screening for mTBI after an MVC might identify those who may require more follow-up or rehabilitation therapy. In particular, those presenting with loss of consciousness, an altered mental state, posttraumatic amnesia, or postinjury headache are at increased risk of PCS.

Relationship between psychosocial and psychiatric risk factors and poor long-term outcome following mild traumatic brain injury: A systematic review.

BACKGROUND AND PURPOSE: Mild traumatic brain injury (mTBI) has an estimated worldwide incidence of >60 million per year, and long-term persistent postconcussion symptoms (PPCS) are increasingly recognized as being predicted by psychosocial variables. Patients at risk for PPCS may be amenable to closer follow-up to treat modifiable symptoms and prevent chronicity. In this regard, similarities seem to exist with psychosocial risk factors for chronicity in other health-related conditions. However, as opposed to other conditions, no screening instruments exist for mTBI. METHODS: A systematic search of the literature on psychological and psychiatric predictors of long-term symptoms in mTBI was performed by two independent reviewers using PubMed, Embase, and Web of Science. RESULTS: Fifty papers were included in the systematic analysis. Anxiety, depressive symptoms, and emotional distress early after injury predict PPCS burden and functional outcome up to 1 year after injury. In addition, coping styles and preinjury psychiatric disorders and mental health also correlate with PPCS burden and functional outcome. Associations between PPCS and personality and beliefs were reported, but either these effects were small or evidence was limited. CONCLUSIONS: Early psychological and psychiatric factors may negatively interact with recovery potential to increase the risk of chronicity of PPCS burden after mTBI. This opens opportunities for research on screening tools and early intervention in patients at risk.

Attachment and Clinical Outcomes Among Treatment-Seeking Adults With Persistent Symptoms After Mild Traumatic Brain Injury.

OBJECTIVE: Interpersonal attachment influences the development and course of disease. Overreliance on insecure attachment strategies may increase risk for poor disease outcomes. This study aimed to investigate largely unexplored relationships between attachment strategies and clinical outcomes among adults with persistent symptoms after mild traumatic brain injury (mTBI). METHODS: Participants with persistent symptoms after mTBI (N=83) completed measures assessing dimensions of insecure attachment (Relationship Scales Questionnaire [RSQ]), persistent symptoms (Rivermead Post-Concussion Symptoms Questionnaire), depression (Patient Health Questionnaire-9), anxiety (Generalized Anxiety Disorder-7), and health-related quality of life (HRQOL) (Quality of Life After Brain Injury-Overall Scale). Questionnaires were administered at clinic intake (mean=18.1 weeks postinjury) and again 3-4 months later (mean=32.2 weeks postinjury), except the RSQ, which was administered only in the follow-up assessment. Treatment response for each outcome was calculated as the difference between scores at clinic intake and follow-up. Generalized linear models were fitted for each clinical outcome, with RSQ variables as predictors. RESULTS: Higher attachment anxiety was associated with greater persistent symptom severity, greater depression and anxiety symptoms, and worse HRQOL at follow-up. Higher attachment anxiety was also associated with less improvement in depression and HRQOL over time. In contrast, attachment avoidance was unrelated to any of the clinical outcomes. CONCLUSIONS: Attachment anxiety, the fear that a significant other will not be available in stressful circumstances, may be a particularly important social factor associated with health among adults with persistent symptoms after mTBI. Greater consideration of the attachment system is warranted in mTBI care and research.

Use of Novel Concussion Protocol With Infralow Frequency Neuromodulation Demonstrates Significant Treatment Response in Patients With Persistent Postconcussion Symptoms, a Retrospective Study.

Introduction: Concussion is a growing public health concern. No uniformly established therapy exists; neurofeedback studies report treatment value. We use infralow frequency neuromodulation (ILF) to remediate disabling neurological symptoms caused by traumatic brain injury (TBI) and noted improved outcomes with a novel concussion protocol. Postconcussion symptoms (PCS) and persistent postconcussion symptoms (PPCS; >3 months post head injury) are designated timelines for protracted neurological complaints following TBI. We performed a retrospective study to explore effectiveness of ILF in PCS/PPCS and investigated the value of using this concussion protocol. Method: Patients with PCS/PPCS seen for their first neurology office visit or received their first neurofeedback session between 1 August 2018 and 31 January 2021 were entered. Outcomes were compared following treatment as usual (TAU) vs. TAU with ILF neurotherapy (TAU+ILF). The study cohort was limited to PPCS patients; the TAU+ILF group was restricted further to PPCS patients receiving at least 10 neurotherapy sessions. Within the TAU+ILF group, comparisons were made between those who trained at least 10 sessions using concussion protocol (TAU+ILF+CP) and those who trained for at least 10 sessions of ILF regardless of protocol (TAU+ILF-CP). Results: Among our resultant PPCS cohort (n = 59) leading persistent neurological complaints were headache (67.8%), memory impairment (57.6%), and brain fog (50.8%). PPCS patients in TAU+ILF+CP (n = 25) demonstrated greater net (p = 0.004) and percent (p = 0.026) improvement of symptoms compared to PPCS subjects in TAU (n = 26). PPCS patients in TAU+ILF-CP (n = 8) trended toward significant symptom improvements compared to TAU, and TAU+ILF+CP trended toward greater efficacy than TAU+ILF-CP. Conclusion: PPCS patients who received TAU+ILF+CP demonstrated significantly greater improvement as a group when compared to TAU. When used as an integrative modality to treatment as usual in managing patients with PPCS, ILF neuromodulation with use of concussion protocol provided significant symptom improvements.

Systematic Review and Dosage Analysis: Hyperbaric Oxygen Therapy Efficacy in Mild Traumatic Brain Injury Persistent Postconcussion Syndrome.

Background: Mild traumatic brain injury results in over 15% of patients progressing to Persistent Postconcussion Syndrome, a condition with significant consequences and limited treatment options. Hyperbaric oxygen therapy has been applied to Persistent Postconcussion Syndrome with conflicting results based on its historical understanding/definition as a disease-specific therapy. This is a systematic review of the evidence for hyperbaric oxygen therapy (HBOT) in Persistent Postconcussion Syndrome using a dose-analysis that is based on the scientific definition of hyperbaric oxygen therapy as a dual-component drug composed of increased barometric pressure and hyperoxia. Methods: In this review, PubMed, CINAHL, and the Cochrane Systematic Review Database were searched from August 8-22, 2021 for all adult clinical studies published in English on hyperbaric oxygen therapy in mild traumatic brain injury Persistent Postconcussion Syndrome (symptoms present at least 3 months). Randomized trials and studies with symptomatic and/or cognitive outcomes were selected for final analysis. Randomized trials included those with no-treatment control groups or control groups defined by either the historical or scientific definition. Studies were analyzed according to the dose of oxygen and barometric pressure and classified as Levels 1-5 based on significant immediate post-treatment symptoms or cognitive outcomes compared to control groups. Levels of evidence classifications were made according to the Centre for Evidence-Based Medicine and a practice recommendation according to the American Society of Plastic Surgeons. Methodologic quality and bias were assessed according to the PEDro Scale. Results: Eleven studies were included: six randomized trials, one case-controlled study, one case series, and three case reports. Whether analyzed by oxygen, pressure, or composite oxygen and pressure dose of hyperbaric therapy statistically significant symptomatic and cognitive improvements or cognitive improvements alone were achieved for patients treated with 40 HBOTS at 1.5 atmospheres absolute (ATA) (four randomized trials). Symptoms were also improved with 30 treatments at 1.3 ATA air (one study), positive and negative results were obtained at 1.2 ATA air (one positive and one negative study), and negative results in one study at 2.4 ATA oxygen. All studies involved <75 subjects/study. Minimal bias was present in four randomized trials and greater bias in 2. Conclusion: In multiple randomized and randomized controlled studies HBOT at 1.5 ATA oxygen demonstrated statistically significant symptomatic and cognitive or cognitive improvements alone in patients with mild traumatic brain injury Persistent Postconcussion Syndrome. Positive and negative results occurred at lower and higher doses of oxygen and pressure. Increased pressure within a narrow range appears to be the more important effect than increased oxygen which is effective over a broad range. Improvements were greater when patients had comorbid Post Traumatic Stress Disorder. Despite small sample sizes, the 1.5 ATA HBOT studies meet the Centre for Evidence-Based Medicine Level 1 criteria and an American Society of Plastic Surgeons Class A Recommendation for HBOT treatment of mild traumatic brain injury persistent postconcussion syndrome.

Post-concussion Syndrome Light Sensitivity: A Case Report and Review of the Literature.

Photophobia is considered the second most common symptom of both concussion and post-concussion syndrome. Soldiers on duty experience photophobia after blast-related concussions or mild traumatic brain injury in 60-75% of instances. In addition, soldiers report other symptoms, such as asthenopia, squinting, dry eyes and headaches, for which they are considered to be at high risk. According to the International Brain Injury Association, some concussed patients report indirect symptoms such as multi-tasking difficulties, dizziness, vertigo, and fatigue. Moreover, some concussed individuals experience photophobia for approximately 6 months or indefinitely. We present the case of a 23-year-old soldier who presented with severe photophobia after a mild traumatic head injury. His photophobia was alleviated after the administration of topical anaesthetic drops in the eyes in the absence of any ocular surface pathology. He was diagnosed with post-concussion syndrome light sensitivity and was managed successfully with rose-coloured special photophobia glasses tinted with FL-41. Photophobia is a common neurological symptom in military personnel that needs more attention as it affects body and mind. We have reported an uncommon pathway of photophobia, which may unveil an unrecognised mechanism that may play a role in post-concussion photophobia.

Treatment of Persistent Postconcussion Syndrome With Repetitive Transcranial Magnetic Stimulation Using Functional Near-Infrared Spectroscopy as a Biomarker of Response: Protocol for a Randomized Controlled Clinical Trial.

BACKGROUND: Approximately one-third of all concussions lead to persistent postconcussion syndrome (PPCS). Repetitive transcranial magnetic stimulation (rTMS) is a form of noninvasive brain stimulation that has been extensively used to treat refractory major depressive disorder and has a strong potential to be used as a treatment for patients with PPCS. Functional near-infrared spectroscopy (fNIRS) has already been used as a tool to assess patients with PPCS and may provide insight into the pathophysiology of rTMS treatment in patients with PPCS. OBJECTIVE: The primary objective of this research is to determine whether rTMS treatment improves symptom burden in patients with PPCS compared to sham treatment using the Rivermead postconcussion symptom questionnaire. The secondary objective is to explore the neuropathophysiological changes that occur following rTMS in participants with PPCS using fNIRS. Exploratory objectives include determining whether rTMS treatment in participants with PPCS will also improve quality of life, anxiety, depressive symptoms, cognition, posttraumatic stress, and function secondary to headaches. METHODS: A total of 44 adults (18-65 years old) with PPCS (>3 months to 5 years) will participate in a double-blind, sham-controlled, concealed allocation, randomized clinical trial. The participants will engage in either a 4-week rTMS treatment protocol or sham rTMS protocol (20 treatments). The left dorsolateral prefrontal cortex will be located through Montreal Neurologic Institute coordinates. The intensity of the rTMS treatment over the left dorsolateral prefrontal cortex will be 120% of resting motor threshold, with a frequency of 10 Hz, 10 trains of 60 pulses per train (total of 600 pulses), and intertrain interval of 45 seconds. Prior to starting the rTMS treatment, participant and injury characteristics, questionnaires (symptom burden, quality of life, depression, anxiety, cognition, and headache), and fNIRS assessment will be collected. Repeat questionnaires and fNIRS will occur immediately after rTMS treatment and at 1 month and 3 months post rTMS. Outcome parameters will be analyzed by a 2-way (treatment × time) mixed analysis of variance. RESULTS: As of May 6, 2021, 5 participants have been recruited for the study, and 3 have completed the rTMS protocol. The estimated completion date of the trial is May 2022. CONCLUSIONS: This trial will expand our knowledge of how rTMS can be used as a treatment option of PPCS and will explore the neuropathophysiological response of rTMS through fNIRS analysis. TRIAL REGISTRATION: ClinicalTrials.gov NCT04568369; https://clinicaltrials.gov/ct2/show/NCT04568369. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/31308.

Brain Connectivity Changes in Postconcussion Syndrome as the Neural Substrate of a Heterogeneous Syndrome.

Background: Postconcussion syndrome (PCS) or persistent symptoms of concussion refers to a constellation of symptoms that persist for weeks and months after a concussion. To better capture the heterogeneity of the symptoms of patients with PCS, we aimed to separate patients into clinical subtypes based on brain connectivity changes. Methods: Subject-specific structural and functional connectomes were created based on diffusion weighted and resting state functional magnetic resonance imaging, respectively. Following an informed dimensionality reduction, a Gaussian mixture model was used on patient-specific structural and functional connectivity matrices to find potential patient clusters. For validation, the resulting patient subtypes were compared in terms of cognitive, neuropsychiatric, and postconcussive symptom differences. Results: Multimodal analyses of brain connectivity were predictive of behavioral outcomes. Our modeling revealed two patient subtypes: mild and severe. The severe subgroup showed significantly higher levels of depression, anxiety, aggression, and a greater number of symptoms than the mild patient subgroup. Conclusion: This study suggests that structural and functional connectivity changes together can help us better understand the symptom severity and neuropsychiatric profiles of patients with PCS. This work allows us to move toward precision medicine in concussions and provides a novel machine learning approach that can be applicable to other heterogeneous conditions.

Sex-based differences in outcomes for adult patients presenting to the emergency department with a concussion.

OBJECTIVE: Patients with concussion frequently present to the emergency department (ED). Studies of athletes and children indicate that concussion symptoms are often more severe and prolonged in females compared with males. Given infrequent study of concussion symptoms in the general adult population, the authors conducted a sex-based comparison of patients with concussion. METHODS: Adults (≥ 17 years of age) presenting with concussion to one of three urban Canadian EDs were recruited. Discharged patients were contacted by telephone 30 and 90 days later to capture the extent of persistent postconcussion symptoms using the Rivermead Post Concussion Symptoms Questionnaire (RPQ). A multivariate logistic regression model for persistent symptoms that included biological sex was developed. RESULTS: Overall, 250 patients were included; 131 (52%) were women, and the median age of women was significantly higher than that of men (40 vs 32 years). Women had higher RPQ scores at baseline (p < 0.001) and the 30-day follow-up (p = 0.001); this difference resolved by 90 days. The multivariate logistic regression identified that women, patients having a history of sleep disorder, and those presenting to the ED with concussions after a motor vehicle collision were more likely to experience persistent symptoms. CONCLUSIONS: In a community concussion sample, inconsequential demographic differences existed between adult women and men on ED presentation. Based on self-reported and objective outcomes, work and daily activities may be more affected by concussion and persistent postconcussion symptoms for women than men. Further analysis of these differences is required to identify different treatment options and ensure adequate care and management of injury.

Emotion Dysregulation Following Trauma: Shared Neurocircuitry of Traumatic Brain Injury and Trauma-Related Psychiatric Disorders.

The psychological trauma associated with events resulting in traumatic brain injury (TBI) is an important and frequently overlooked factor that may impede brain recovery and worsen mental health following TBI. Indeed, individuals with comorbid posttraumatic stress disorder (PTSD) and TBI have significantly poorer clinical outcomes than individuals with a sole diagnosis. Emotion dysregulation is a common factor leading to poor cognitive and affective outcomes following TBI. Here, we synthesize how acute postinjury molecular processes stemming from either physical or emotional trauma may adversely impact circuitry subserving emotion regulation and ultimately yield long-term system-level functional and structural changes that are common to TBI and PTSD. In the immediate aftermath of traumatic injury, glucocorticoids stimulate excess glutamatergic activity, particularly in prefrontal cortex-subcortical circuitry implicated in emotion regulation. In human neuroimaging work, assessing this same circuitry well after the acute injury, TBI and PTSD show similar impacts on prefrontal and subcortical connectivity and activation. These neural profiles indicate that emotion regulation may be a useful target for treatment and early intervention to prevent the adverse sequelae of TBI. Ultimately, the success of future TBI and PTSD early interventions depends on the fields' ability to address both the physical and emotional impact of physical injury.

Quick cell-free DNA testing for the prediction of postconcussion syndrome: a single-center prospective pilot trial.

OBJECTIVE: Mild traumatic brain injury (mTBI) is a major cause of emergency room (ER) admission. Thirty percent of mTBI patients have postconcussion syndrome (PCS), and 15% have symptoms for over a year. This population is underdiagnosed and does not receive appropriate care. The authors proposed a fast and inexpensive fluorometric measurement of circulating cell-free DNA (cfDNA) as a biomarker for PCS. cfDNA is a proven, useful marker of a variety of acute pathological conditions such as trauma and acute illness. METHODS: Thirty mTBI patients were recruited for this prospective single-center trial. At admission, patients completed questionnaires and blood was drawn to obtain cfDNA. At 3-4 months after injury, 18 patients returned for cognitive assessments with questionnaires and the Color Trails Test (CTT). The fast SYBR Gold assay was used to measure cfDNA. RESULTS: Seventeen men and 13 women participated in this trial. The mean ± SD age was 50.9 ± 13.9 years. Of the 18 patients who returned for cognitive assessment, one-third reported working fewer hours, 4 (22.2%) changed their driving patterns, and 5 (27.7%) reduced or stopped performing physical activity. The median cfDNA level of the mTBI group was greater than that of the matched healthy control group (730.5 vs 521.5 ng/ml, p = 0.0395). Admission cfDNA concentration was negatively correlated with performance on the CTT1 and CTT2 standardized tests (r = -0.559 and -0.599), meaning that greater cfDNA level was correlated with decreased cognitive performance status. The performance of the patients with normal cfDNA level included in the mTBI group was similar to that of the healthy participants. In contrast, the increased cfDNA group (> 800 ng/ml) had lower scores on the CTT tests than the normal cfDNA group (p < 0.001). Furthermore, patients with moderate/severe cognitive impairment according to CTT1 results had a greater median cfDNA level than the patients with scores indicating mild impairment or normal function (1186 vs 473.5 ng/ml, p = 0.0441, area under the receiver operating characteristic curve = 0.8393). CONCLUSIONS: The data from this pilot study show the potential to use cfDNA, as measured with a fast test, as a biomarker to screen for PCS in the ER. A large-scale study is required to establish the value of cfDNA as an early predictor of PCS.

Perceptual-Motor Efficiency and Concussion History Are Prospectively Associated With Injury Occurrences Among High School and Collegiate American Football Players.

BACKGROUND: After a sport-related concussion (SRC), the risk for lower extremity injury is approximately 2 times greater, and the risk for another SRC may be as much as 3 to 5 times greater. PURPOSE: To assess the predictive validity of screening methods for identification of individual athletes who possess an elevated risk of SRC. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Metrics derived from a smartphone flanker test software application and self-ratings of both musculoskeletal function and overall wellness were acquired from American high school and college football players before study participation. Occurrences of core or lower extremity injury (CLEI) and SRC were documented for all practice sessions and games for 1 season. Receiver operating characteristic and logistic regression analyses were used to identify variables that provided the greatest predictive accuracy for CLEI or SRC occurrence. RESULTS: Overall, there were 87 high school and 74 American college football players included in this study. At least 1 CLEI was sustained by 45% (39/87) of high school players and 55% (41/74) of college players. Predictors of CLEI included the flanker test conflict effect ≥69 milliseconds (odds ratio [OR], 2.12; 90% CI, 1.24-3.62) and a self-reported lifetime history of SRC (OR, 1.70; 90% CI, 0.90-3.23). Of players with neither risk factor, only 38% (29/77) sustained CLEI compared with 61% (51/84) of players with 1 or both of the risk factors (OR, 2.56; 90% CI, 1.50-4.36). SRC was sustained by 7 high school players and 3 college players. Predictors of SRC included the Overall Wellness Index score ≤78 (OR, 9.83; 90% CI, 3.17-30.50), number of postconcussion symptoms ≥4 (OR, 8.35; 90% CI, 2.71-25.72), the Sport Fitness Index score ≤78 (OR, 5.16; 90% CI, 1.70-15.65), history of SRC (OR, 4.03; 90% CI, 1.35-12.03), and the flanker test inverse efficiency ratio ≥1.7 (OR, 3.19; 90% CI, 1.08-9.47). CONCLUSION: Survey responses and smartphone flanker test metrics predicted greater injury incidence among individual football players classified as high-risk compared with that for players with a low-risk profile.

Osteopathic manipulative medicine in the management of headaches associated with postconcussion syndrome.

CONTEXT: Previous studies have demonstrated the effectiveness of osteopathic manipulative treatment (OMT) for various headache types, with limited evidence of its use for headaches related to mild traumatic brain injury (MTBI). No studies prior studies were found regarding OMT for headaches in patients with postconcussion syndrome (PCS), defined as symptom persistence for longer than 3 months after MTBI. OBJECTIVES: To evaluate OMT for headaches in patients with PCS. METHODS: A controlled pilot study was conducted of patients with PCS who presented to an outpatient interdisciplinary rehabilitation clinic; patients with symptoms lasting longer than 3 months were enrolled and randomly assigned to an OMT treatment group or a control group. Primary outcome measures were immediate change in headache scores according to a Visual Analog Scale (VAS) and change in the six item Headache Impact Test (HIT-6) between baseline and follow up visits. The participants in the control group completed the HIT-6 between baseline and follow up visits but did not receive OMT and did not complete the VAS. Mean immediate VAS score change for the treatment group and mean improvement in HIT-6 scores for both groups between baseline and follow up were analyzed for statistical significance. RESULTS: A total of 26 patients were included in this study: 13 (50%) in the treatment group and 13 (50%) in the control group. Six patients (23.1%), three from each group, did not complete the study, so 10 subjects in each group were included in the final analysis. Statistically significant improvement in VAS scores was seen immediately after OMT in the treatment group (mean change, 2.1;p=0.002). Mean HIT-6 scores showed improvement in the treatment group compared with the control group, although the change was not statistically significant (p=0.15) from baseline to follow up visit. No adverse effects from treatments were noted. CONCLUSIONS: Patients with headaches secondary to PCS showed immediate benefit in headache pain intensity after OMT. However, no sustained benefit was found on the follow up visit compared with the control group.