Rivermead Post-Concussion Questionnaire Research Articles

Effectiveness of personalized rehabilitation in adults suffering from persistent concussion symptoms as compared to usual care: a randomized control trial protocol

BackgroundSymptoms reported by patients who sustain a concussion are non-specific. As such, clinicians are better able to manage patients when a standardized clinical exam is performed to sub-type the driver(s) of symptoms. Aerobic exercise and multimodal rehabilitation have consistently shown to be a possibly effective means to manage this population; however, the optimal training prescription is unclear. Thus, there is a need to further examine the effectiveness of personalized rehabilitative treatments. Our primary aim is to evaluate the response to personalized therapy on recovery, as measured by The Rivermead Post-concussion Symptoms Questionnaire (RPQ) when compared to an active control.MethodsWe will conduct a multi-center 12-week case-crossover randomized controlled trial. 50 participants will be recruited from out-patient University Health Network clinics and community-based clinical practices around the greater Toronto area. Participants will be randomized at baseline to Group A: a personalized care program followed by an active control or Group B: an active control followed by a personalized care program. Participants will be included should they be 21 years of age and older and have symptoms that have persisted beyond 4 weeks but less than 1 year. Participants will undergo 6-weeks of care in their respective streams. After 6-weeks, participants will undergo a re-examination. They will then crossover and undertake the alternative treatment for 6 weeks. At the end of 12 weeks, participants will undertake the endpoint examinations. The primary outcome will be the Rivermead Postconcussion Questionnaire (RPQ). The secondary outcomes will be changes in standardized clinical examination, Neck Disability Index (NDI), Patient Health Questionnaire (PHQ-9) and an electroencephalography (EEG) via NeuroCatch™. The statistical analysis to be performed is composed of an adjusted model using an analysis of variance, specifically using an unpaired t-test to test for associations between variables and outcomes.DiscussionGiven the recommendations from reviews on the topic of rehabilitation for adults with persistent concussion symptoms, we are undertaking a controlled trial. The documented high costs for patients seeking care for persistent symptoms necessitate the need to evaluate the effectiveness of a personalized rehabilitative program compared to the current standard of care.Trial registrationClinicalTrials.gov ID: NCT06069700.

Sub-concussive head impacts from heading footballs do not acutely alter brain excitability as compared to a control group.

Repeated sub-concussive head impacts are a growing brain health concern, but their possible biomarkers remain elusive. One impediment is the lack of a randomised controlled human experimental model to study their effects on the human brain. This work had two objectives. The first one was to provide a randomised controlled human experimental model to study the acute effects of head impacts on brain functions. To achieve this, this work's second objective was to investigate if head impacts from heading footballs acutely alter brain excitability by increasing corticospinal inhibition as compared to a control group. In practised and unpractised young healthy adults, transcranial magnetic stimulation was used to assess corticospinal silent period (CSP) duration and corticospinal excitability (CSE) before and immediately after performing headings by returning 20 hand-thrown balls directed to the head (Headings; n = 30) or the dominant foot (Control; n = 30). Moreover, the Rivermead Post-Concussion Questionnaire (RPQ) was used to assess the symptoms of head impacts. Head acceleration was also assessed in subgroups of participants. The intervention lengthened CSP duration in both the Headings (6.4 ± 7.5%) and Control groups (4.6 ± 2.6%), with no difference in lengthening between the two groups. Moreover, CSE was not altered by the intervention and did not differ between groups. However, performing headings increased headaches and dizziness symptoms and resulted in greater head acceleration upon each football throw (12.5 ± 1.9g) as compared to the control intervention (5.5 ± 1.3g). The results suggest that head impacts from football headings do not acutely alter brain excitability as compared to a control intervention. However, the results also suggest that the present protocol can be used as an experimental model to investigate the acute effects of head impacts on the human brain.

Investigating cognitive reserve, symptom resolution and brain connectivity in mild traumatic brain injury

BackgroundA proportion of patients with mild traumatic brain injury (mTBI) suffer long-term consequences, and the reasons behind this are still poorly understood. One factor that may affect outcomes is cognitive reserve, which is the brain's ability to maintain cognitive function despite injury. It is often assessed through educational level or premorbid IQ tests. This study aimed to explore whether there were differences in post-concussion symptoms and symptom resolution between patients with mTBI and minor orthopedic injuries one week and three months after injury. Additional aims were to explore the relationship between cognitive reserve and outcome, as well as functional connectivity according to resting state functional magnetic resonance imaging (rs-fMRI).MethodFifteen patients with mTBI and 15 controls with minor orthopedic injuries were recruited from the emergency department. Assessments, including Rivermead Post-Concussion Questionnaire (RPQ), neuropsychological testing, and rs-fMRI scans, were conducted on average 7 days (SD = 2) and 122 days (SD = 51) after injury.ResultsAt the first time point, significantly higher rates of post-concussion symptoms (U = 40.0, p = 0.003), state fatigue (U = 56.5, p = 0.014), and fatigability (U = 58.5, p = 0.025) were observed among the mTBI group than among the controls. However, after three months, only the difference in post-concussion symptoms remained significant (U = 27.0, p = 0.003). Improvement in post-concussion symptoms was found to be significantly correlated with cognitive reserve, but only in the mTBI group (Spearman’s rho = -0.579, p = .038). Differences in the trajectory of recovery were also observed for fatigability between the two groups (U = 36.5, p = 0.015). Moreover, functional connectivity differences in the frontoparietal network were observed between the groups, and for mTBI patients, functional connectivity differences in an executive control network were observed over time.ConclusionThe findings of this pilot study suggest that mTBI, compared to minor orthopedic trauma, is associated to both functional connectivity changes in the brain and concussion-related symptoms. While there is improvement in these symptoms over time, a small subgroup with lower cognitive reserve appears to experience more persistent and possibly worsening symptoms over time. This, however, needs to be validated in larger studies.Trial registrationNCT05593172. Retrospectively registered.

Prevalence of and Risk Factors for Post-traumatic Headache in Civilian Patients After Mild Traumatic Brain Injury: A TRACK-TBI Study

ObjectiveTo ascertain the prevalence of and risk factors for post-traumatic headache (PTH) attributed to mild traumatic brain injury (mTBI). Patients and MethodsA prospective, longitudinal, multicenter cohort study of patients with mTBI and orthopedic trauma controls who were enrolled from February 26, 2014, to August 8, 2018. The baseline assessment was conducted as soon as possible following evaluation at the emergency department. Follow-ups were scheduled at 2 weeks, 3 months, 6 months, and 12 months postinjury. Eligible patients with mTBI included those 18 years of age or older who presented to the emergency department within 24 hours of head injury warranting evaluation by noncontrast head computed tomography scan. Acute PTH was considered present when a patient reported a headache score of greater than or equal to 2 on the Rivermead Post-concussion Questionnaire at 2 weeks postinjury (ie, headache is at least a mild problem compared with pre-injury). Persistent PTH was defined when a patient with acute PTH reported a Rivermead Post-concussion Questionnaire headache score of greater than or equal to 2 at the scheduled follow-up examinations. ResultsAcute PTH was reported by 963 (60.4%) of 1594 patients with mTBI at 2 weeks postinjury. Among those with acute PTH, 439 (52.4%) of 837 patients reported persistent PTH at 3 months postinjury. This figure decreased over time and 278 (37.5%) of 742 patients continued to report persistent PTH at 6 months, whereas 187 (28.9%) of 646 patients did so as well at 12 months postinjury. Risk factors for acute PTH included younger age, female sex, fewer years of formal education, computed tomography–positive scans, alteration of consciousness, psychiatric history, and history of migraine. Risk factors for persistent PTH included female sex, fewer years of formal education, and history of migraine. ConclusionPost-traumatic headache is a prevalent sequela of mTBI that persists for at least 12 months in a considerable proportion of affected individuals. The attributable burden necessitates better patient follow-up, disease characterization, improved awareness of PTH in clinical practice, and identification of effective therapies.

Network analysis applied to post-concussion symptoms in two mild traumatic brain injury samples.

A latent disease explanation cannot exclusively explain post-concussion symptoms after mild traumatic brain injury (mTBI). Network analysis offers an alternative form of explanation for relationships between symptoms. The study aimed to apply network analysis to post-concussion symptoms in two different mTBI cohorts; an acute treatment-seeking sample and a sample 10 years post-mTBI. The treatment-seeking sample (n = 258) were on average 6 weeks post-injury; the 10 year post mTBI sample (n = 193) was derived from a population-based incidence and outcomes study (BIONIC). Network analysis was completed on post-concussion symptoms measured using the Rivermead Post-Concussion Questionnaire. In the treatment-seeking sample, frustration, blurred vision, and concentration difficulties were central to the network. These symptoms remained central in the 10 year post mTBI sample. A Network Comparison Test revealed evidence of a difference in network structure across the two samples (p = 0.045). However, the only symptoms that showed significant differences in strength centrality across samples were irritability and restlessness. The current findings suggest that frustration, blurred vision and concentration difficulties may have an influential role in the experience and maintenance of post-concussion symptoms. The impact of these symptoms may remain stable over time. Targeting and prioritising the management of these symptoms may be beneficial for mTBI rehabilitation.

Hyperbaric Oxygen Therapy versus placebo for post-concussion syndrome (HOT-POCS): A randomized, double-blinded controlled pilot study

Post-Concussion Syndrome (PCS) refers to the persistence of physical, cognitive, and emotional symptoms following mild traumatic brain injury (mTBI)/concussion, occurring in roughly 15–30% of individuals. Hyperbaric oxygen therapy (HBOT) has been suggested as a potential treatment for PCS; however, the evidence to date is mixed due to inconsistencies in the treatment protocol and focus on veterans with combat-related injuries, which may not be generalizable to the general population. The goal of Hyperbaric Oxygen Therapy for Post-Concussion Syndrome (HOT-POCS) is to assess the efficacy and safety of HBOT for the treatment of PCS in the civilian population. This randomized, controlled pilot study will be using a standardized HBOT protocol (20 sessions of 100% O2 at 2.0 atm absolute [ATA]) compared with a true placebo gas system that mimics the oxygen composition at room air (20 sessions of 10.5% O2 and 89.5% nitrogen at 2.0 ATA) in a cohort of 100 adults with persistent post-concussive symptoms 3–12 months following injury. Change in symptoms on the Rivermead Post-concussion Questionnaire (RPQ) will be the primary outcome of interest. Secondary outcomes include the rate of adverse events, change in the quality of life, and change in cognitive function. Exploratory outcome measures will include changes in physical function and changes in cerebral brain perfusion and oxygen metabolism on MRI brain imaging. Overall, the HOT-POCS study will compare the efficacy of a standardized HBOT treatment protocol against a true placebo gas for the treatment of PCS within 12 months after injury.

Agglomerative Hierarchical Clustering of Long-Lasting Post-Concussive Symptoms: Symptom-Centric Association with Functional Impairments (P8-1.001)

<h3>Objective:</h3> The aim of this study was to characterize the underlying clusters of prolonged post-concussive symptoms lasting more than 12 months, and to investigate their association with functional impairments. <h3>Background:</h3> Following a concussion, approximately 15% of individuals experience persistent symptoms that can lead to functional deficits. However, underlying symptom-clusters that persist beyond 12 months have not been adequately characterized, and their relevance to functional deficits are unclear. <h3>Design/Methods:</h3> Although hierarchical clustering is ideally suited in evaluating subjective symptom severities, it has not been applied to post-concussive symptoms or the Rivermead Post-Concussion Questionnaire (RPQ). The RPQ and functional impairments questions were administered via a smartphone application to 445 individuals who self-reported prolonged post-concussive symptoms. Symptom-clusters were obtained using agglomerative hierarchical clustering, and their association with functional deficits were investigated with sensitivity analyses, and corrected for multiple comparisons. <h3>Results:</h3> Five symptom-clusters were identified: headache-related, sensitivity to light and sound, cognitive, mood-related, and sleep-fatigue. Individuals with more severe RPQ symptoms were more likely to report functional deficits (p&lt;0.0001). Whereas the headache and sensitivity clusters were associated with at most one impairment, at-least-mild sleeping difficulties and fatigue were associated with four, and moderate-to-severe cognitive difficulties with five functional impairments (all p&lt;0.01). <h3>Conclusions:</h3> Symptom-clusters may be clinically useful for functional outcome stratification and for targeted rehabilitation therapies, for example directed towards mild trouble sleeping. Further studies are required to replicate these findings in other cohorts and questionnaires, and to ascertain the effects of symptomatic intervention on functional outcomes. <b>Disclosure:</b> Mr. Kuleindiren has nothing to disclose. Mr. Tiersen has received personal compensation for serving as an employee of Mindstep. Mr. Tiersen has stock in Mindstep. Mr. Tiersen has received research support from Imperial College London. Dr. Johal has nothing to disclose. Dr. Lin has nothing to disclose. Mr. Selim has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for Mindstep . Mr. Selim has stock in Mindstep. Dr. Rifkin-Zybutz has received personal compensation for serving as an employee of Mindset Technologies Ltd. Dr. Rifkin-Zybutz has received research support from National Institute for Health and Care Research. Mr. Mahmud has received personal compensation for serving as an employee of Mindset Technologies Ltd .

Impact of cognitive exertion on autonomic reactivity in individuals with persistent post-concussive symptoms (P7-1.010)

<h3>Objective:</h3> Examine the impact of cognitive exertion on autonomic reactivity in symptomatic and asymptomatic individuals with history of concussion and controls without history of concussion. <h3>Background:</h3> Following concussive head injuries, many individuals continue to experience physical, cognitive, and emotional symptoms that can persist for months or years. Recent studies suggest that concussive head injuries can also produce persistent dysfunction of the autonomic nervous system. However, it remains unclear if acute bouts of cognitive exertion moderate autonomic dysfunction in individuals with persistent post-concussion symptoms. <h3>Design/Methods:</h3> A cross-sectional design was used to investigate autonomic reactivity in 23 individuals without history of concussion (HC-) and 35 individuals with history of concussion, including 20 symptomatic (HCx-S) and 15 asymptomatic (HCx-A). Participants were classified based on clinical history and symptom reports obtained from a comprehensive questionnaire of their medical history and the Rivermead Post-Concussion Questionnaire (RPQ). Participants initially completed a seated, six-minute resting assessment with eyes open in the dimly lit room. They then completed a continuous reaching variant of the traditional Go/NoGo task. Continuous electrocardiography was recorded and utilized to compute time-domain metrics of heart rate variability (HRV) during the resting assessment and cognitive task. <h3>Results:</h3> HCx-S participants reported greater symptom burden on the RPQ and performed significantly worse on the Go/NoGo task compared to HC- and HCx-A participants. While HRV metrics failed to reveal any significant differences between HCx-S, HCx-A, and HC-participants during resting assessment (p’s &gt; 0.8), HCx-S participants exhibited significantly greater HRV than HCx-A and HC-participants during the Go/NoGo task (p’s &lt; 0.03). <h3>Conclusions:</h3> Increased HRV in HCx-S participants compared to HC- and HCx-A participants during the Go/NoGo task indicates that concussion may induce greater autonomic reactivity, characterized by higher levels of vagal/parasympathetic tone. This may reflect impairments in the capacity of the autonomic nervous system to efficiently adapt to situational demands. <b>Disclosure:</b> Dr. Moore has nothing to disclose. Taylor Marie Wynne has nothing to disclose. Dr. Broglio has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for MCW. Dr. Broglio has received personal compensation in the range of $0-$499 for serving as a Consultant for U Calgary. Dr. Broglio has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Montgomery McCracken Walker &amp; Rhoads LLP. The institution of Dr. Broglio has received research support from DoD. The institution of Dr. Broglio has received research support from NCAA. The institution of Dr. Herter has received research support from Woodcock Institute. The institution of Dr. Herter has received research support from National Institutes of Health. The institution of Dr. Herter has received research support from National Institutes of Health. The institution of an immediate family member of Dr. Herter has received research support from Centers for Disease Control and Prevention.

The incidence and severity of symptoms similiar to peristing concussion symptoms in neurologically healthy individuals in aotearoa New Zealand

The non-specificity of persisting concussion symptoms (PCS) following concussion can make treatment and rehabilitation a complex and challenging endeavour for clinicians. International studies have demonstrated that in neurologically healthy individuals similar symptoms also exist. This study aimed to examine the presence and frequency of symptoms similar to PCS in neurologically healthy adults in Aotearoa New Zealand and compare these to PCS following concussion. 252 neurologically healthy adults (34.22 years); completed the Rivermead Post-Concussion Questionnaire (RPQ). Scores on this measure were evaluated and compared with 146 individuals who were at least three months post-injury (34.62 years). 25.79% (n = 65) of the neurologically healthy individuals had scores on the RPQ of ≥16. Fatigue was the most commonly endorsed symptom (67.9%), followed by sleep disturbances (59.9%). Certain demographic factors (age, education history and gender) were associated with higher endorsement but only on specific symptoms. The concussion group had significantly higher scores on the RPQ and significantly more individuals with PCS. However, at the individual item level, just over half of PCS symptoms were significantly higher in the concussion group. These symptoms were predominately neurological, with only forgetfulness and irritability significantly different between the concussion and neurologically healthy groups. Symptoms similar to PCS are prevalent in neurologically healthy individuals in Aotearoa New Zealand. The implications of these findings on the rehabilitation and management of PCS are discussed.

Hierarchical clustering of prolonged post-concussive symptoms after 12 months: symptom-centric analysis and association with functional impairments

ABSTRACT Background Following a concussion, approximately 15% of individuals experience persistent symptoms that can lead to functional deficits. However, underlying symptom-clusters that persist beyond 12 months have not been adequately characterized, and their relevance to functional deficits are unclear. The aim of this study was to characterize the underlying clusters of prolonged post-concussive symptoms lasting more than 12 months, and to investigate their association with functional impairments. Methods Although hierarchical clustering is ideally suited in evaluating subjective symptom severities, it has not been applied to the Rivermead Post-Concussion Questionnaire (RPQ). The RPQ and functional impairments questions were administered via a smartphone application to 445 individuals who self-reported prolonged post-concussive symptoms. Symptom-clusters were obtained using agglomerative hierarchical clustering, and their association with functional deficits were investigated with sensitivity analyses, and corrected for multiple comparisons. Results Five symptom-clusters were identified: headache-related, sensitivity to light and sound, cognitive, mood-related, and sleep-fatigue. Individuals with more severe RPQ symptoms were more likely to report functional deficits (p < 0.0001). Whereas the headache and sensitivity clusters were associated with at most one impairment, at-least-mild sleeping difficulties and fatigue were associated with four, and moderate-to-severe cognitive difficulties with five (all p < 0.01). Conclusions Symptom-clusters may be clinically useful for functional outcome stratification for targeted rehabilitation therapies. Further studies are required to replicate these findings in other cohorts and questionnaires, and to ascertain the effects of symptomatic intervention on functional outcomes.

Post-concussion symptoms 1-year after traumatic brain injury: using the Rivermead Post-concussion Questionnaire to identify predictors of severity

ABSTRACT Background Patients who suffer traumatic brain injury (TBI) often experience a constellation of physical, cognitive, and emotional/behavioral symptoms called “post-concussion symptoms” and subsequent long-term disability. This study aimed to investigate the incidence of persistent post-concussion symptoms and possible predictors of long-term disability focusing on demographic, injury, and psychological factors. It was hoped to identify groups at high risk. Methods A prospective cohort of 1322 individuals admitted with TBI were assessed in a specialist neurorehabilitation clinic at 10 weeks and 1-year post injury between August 2011 and July 2015. The outcome (post-concussion symptoms) was measured using the Rivermead Post-concussion Questionnaire (RPQ) at 1-year post injury. Results At 1 yr, 1131 individuals were identified (>90% follow-up). Over 20% exhibited moderate or severe symptom levels on RPQ. A linear regression model showed that previous psychiatric history, lower Glasgow Coma Scale (GCS), severe CT abnormalities, injury caused by assault, pre-injury unemployment, and inability to return to work at 6 weeks post-injury were associated with worse symptoms at 1 yr. The adjusted R2 of the model was 25.1%. Conclusion These findings confirm the high incidence of post-concussion symptoms at 1 yr and identify certain associated features that increase risk. This may allow targeting of certain groups, e.g., return to work or victims of assault.

Post-Concussion Symptoms Rule: Derivation and Validation of a Clinical Decision Rule for Early Prediction of Persistent Symptoms after a Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) is a common problem. Depending on diagnostic criteria, 13 to 62% of those patients develop persistent post-concussion symptoms (PPCS). The main objective of this prospective multi-center study is to derive and validate a clinical decision rule (CDR) for the early prediction of PPCS. Patients aged ≥14 years were included if they presented to one of our seven participating emergency departments (EDs) within 24 h of an mTBI. Clinical data were collected in the ED, and symptom evolution was assessed at 7, 30 and 90 days post-injury using the Rivermead Post-Concussion Questionnaire (RPQ). The primary outcome was PPCS at 90 days after mTBI. A predictive model called the Post-Concussion Symptoms Rule (PoCS Rule) was developed using the methodological standards for CDR. Of the 1083 analyzed patients (471 and 612 for the derivation and validation cohorts, respectively), 15.6% had PPCS. The final model included the following factors assessed in the ED: age, sex, history of prior TBI or mental health disorder, headache in ED, cervical sprain and hemorrhage on computed tomography. The 7-day follow-up identified additional risk factors: headaches, sleep disturbance, fatigue, sensitivity to light, and RPQ ≥21. The PoCS Rule had a sensitivity of 91.4% and 89.6%, a specificity of 53.8% and 44.7% and a negative predictive value of 97.2% and 95.8% in the derivation and validation cohorts, respectively. The PoCS Rule will help emergency physicians quickly stratify the risk of PPCS in mTBI patients and better plan post-discharge resources.

Changes In Serum Neurofilament Light And Brain White Matter Microstructure In Female Football Players: A Pilot Study

Repeated mechanical loading of the head can cause axonal damage in a dose-dependent manner. The corpus callosum (CC), a thick commissural white matter tract, is believed to be particularly sensitive to this loading. Neurofilament light (NfL) has emerged as a blood-based biomarker that is sensitive to axonal damage and may be useful for monitoring athlete brain health. However, the source of circulating NfL in contact and collision sport athletes who may have sustained axonal damage due to mechanical loading of the head, but have not been diagnosed with a brain injury, is poorly understood. PURPOSE: To compare changes in serum NfL to changes in corpus callosum (CC) microstructure over a single season of competition. METHODS: Semi-professional female tackle football players (n = 5) had blood drawn (8.5 mL) and underwent diffusion MRI (64 directions, bval = 1300 s/mm2) and structural MRI (T1w, MPRAGE) before and after their season (4 games and 39 practices over 12 weeks). Despite that no participant reported a medical diagnosis of concussion during the season, participants were asked to report the presence and degree of concussion-related symptoms at each time point using the Rivermead Post-Concussion Questionnaire. Serum samples were assayed for (NfL) at pre and post season time points. The CC was reconstructed for each participant from preprocessed diffusion MRI data using automatic fiber tracking and atlas-guided tract recognition with bilateral cerebellar hemispheres as regions of avoidance (DSI Studio). Microstructural metrics were computed from these reconstructed tracts to represent CC integrity. RESULTS: Increases in NfL were associated with increases in CC radial diffusivity (r2 = .845) and decreases in CC quantitative anisotropy (r2 = .675) and fractional anisotropy (r2 = .967). Changes in NfL and CC integrity were moderately related to changes in concussive symptoms (r2 = .366-.772). CONCLUSIONS: The relationships observed in these preliminary data suggest that changes in serum NfL may be sufficiently sensitive to detect subclinical, ‘subconcussive’ axonal injuries in collision sport athletes.

A-169 Utilizing the Rivermead Post Concussion Questionnaire (RPQ) during Post-Covid-19 Patient Follow-up

Objective: To examine the utility of The Rivermead PCS Questionnaire (RPQ) for patients endorsing persistent cognitive and psychiatric symptoms after COVID infection. The RPQ is a self-report measure of persistent symptoms in those suffering a mild traumatic brain injury (mTBI) beyond the typical recovery period of 10-21 days. Like mTBI, a considerable percentage of patients who have had COVID-19 report persistent cognitive, somatic, and emotional symptoms after recovering from the disease.Data Selection: Literature reviewed included up to date peer-reviewed research examining the following key terms: prevalence of long-COVID, constellation of symptoms, overlap with Post-Concussion Syndrome (PCS), and assessment. Articles were excluded if they examined severe illnesses requiring mechanical ventilation, or if participants had comorbid neurocognitive and/or comorbid psychiatric conditions.Data Synthesis: The “other” category allows for assessment of additional COVID-19 symptoms such as anosmia. Factor analysis demonstrated the existence of cognitive, somatic, and emotional factors with a high degree of covariation. Post-COVID patients endorsed issues with word-finding, attention, fatigue, migraines, anxiety, and depression; symptoms which are also frequently noted in PCS. These symptoms were also commonly reported in the general population, orthopedic patients, and other medical populations, suggesting non-specificity.Conclusions: Given the similar symptom constellation between PCS and persistent-COVID, the RPQ may be an adequate tool for identifying patients suffering from actual or perceived symptoms. As many of these patients may benefit from treatment outside traditional medicine, including sleep hygiene training, stress management, behavior modification, and counseling, the RPQ could also be used for progress monitoring and/or identifying those requiring further cognitive assessment.

Elevations in Tumor Necrosis Factor Alpha and Interleukin 6 From Neuronal-Derived Extracellular Vesicles in Repeated Low-Level Blast Exposed Personnel.

ObjectiveThe purpose of this pilot study was to determine if military service members with histories of hundreds to thousands of low-level blast exposures (i. e., experienced breachers) had different levels of serum and neuronal-derived extracellular vesicle (EV) concentrations of interleukin (IL)-6, IL-10, and tumor necrosis factor alpha (TNFα), compared to matched controls, and if these biomarkers related to neurobehavioral symptoms.MethodsParticipants were experienced breachers (n = 20) and matched controls without blast exposures (n = 14). Neuronal-derived EVs were isolated from serum and identified with mouse anti-human CD171. Serum and neuronal-derived EVs were analyzed for IL-6, IL-10, and TNFα using an ultra-sensitive assay.ResultsSerum TNFα concentrations were decreased in breachers when compared to control concentrations (p < 0.01). There were no differences in serum concentrations of IL-6, IL-10, or the IL-6/IL-10 ratio between breachers and controls (p's > 0.01). In neuronal-derived EVs, TNFα and IL-6 levels were increased in breachers compared to controls (p's < 0.01), and IL-10 levels were decreased in the breacher group compared to controls (p < 0.01). In breachers the IL-6/IL-10 ratio in neuronal-derived EVs was higher compared to controls, which correlated with higher total Rivermead Post-concussion Questionnaire (RPQ) scores (p's < 0.05).ConclusionsThese findings suggest that exposure of personnel to high numbers of low-level blast over a career may result in enduring central inflammation that is associated with chronic neurological symptoms. The data also suggest that peripheral markers of inflammation are not necessarily adequate surrogates for central neuroinflammation.

Persistent post-concussive syndrome in children after mild traumatic brain injury is prevalent and vastly underdiagnosed

Data on epidemiology and prognosticators of persistent post-concussion syndrome (PPCS) after mild traumatic brain injury (mTBI) in the pediatric population is scarce. The aim of this study was to evaluate the prevalence of PPCS in children after mTBI and to identify clinical variables in children who are at high risk for developing PPCS. A multicenter, retrospective matched cohort in which PPCS symptoms were evaluated in children 8–15-year-old, 6–60 months after being admitted to the emergency department because of mTBI. The control group included children admitted to the emergency department because of uncomplicated distal radius fractures. The children's guardians were interviewed for the presence of PPCS symptoms using the "Rivermead Post-Concussion Questionnaire". A multivariable logistic regression model was used to identify predictors of PPCS. Two-hundred and five children were included in the mTBI group and 205 in the control. The median time from the injury was 33.5 months in the mTBI group and 33.8 in the control. The prevalence of PPCS in the mTBI group was 25.3% and PPCS like symptoms in the control was 2.4%, p < 0.001. Within the 6–60 months period, the PPCS prevalence was not influenced by the time that elapsed from the injury. In the mTBI group, motor vehicle accidents and adolescence were found to be risk factors for PPCS. PPCS is underdiagnosed in the pediatric population and 25% of children admitted to the ED due to mTBI may suffer from PPCS. Screening guidelines should be implemented to identify and properly treat these children.

326 Concussion Subtype Symptomatology in Complicated Mild Traumatic Brain Injury Patients

INTRODUCTION: Post-concussive symptom scales (PCSS) can help discern recently defined concussion subtypes such as cognitive, ocular-motor, headache/migraine, vestibular, and anxiety/mood with concussion-associated sleep disturbance and cervical strain. However, there is limited knowledge as to the utility of using subtype symptomatology in the assessment of complicated mild traumatic brain injury (TBI) patients. METHODS: We included mild TBI patients who presented to a neurosurgery TBI clinic and had completed a Rivermead Post Concussion Questionnaire (RPQ). Patient demographic factors such as age, sex, mechanism of injury, and arrival GCS were extracted from the medical record. Patients were characterized into groups based on imaging findings including epidural and subdural hematomas (extra-axial), or intraparenchymal, subarachnoid, or intraventricular blood (intra-axial) or both. We excluded patients with negative head CT results. We used the RPQ itemized questions to define symptom subtypes. Differences between groups were analyzed using an ANOVA and general linear model analysis in SPSS. RESULTS: We included a total of 163 patients, 52 showed intra-axial bleeds, 40 showed extra-axial bleeds, and 71 exhibited both intra- and extra-axial bleeds. ANOVA results show statistically significant differences in ocular-motor (p = 0.035), headache/migraine (p = 0.010), and vestibular (p = 0.032) subtype scores between groups. Specifically, multiple comparisons revealed the extra-axial means were lower in the ocular-motor (0.947 ± 0.235 SEM vs. 2.13 ± 0.312; p = 0.011), headache/migraine (1.50 ± 0.310 vs. 2.79 ± 0.258; p=0.003), and vestibular (1.18 ± 0.226 vs. 2.09 ± 0.198; p = 0.011) subtypes. Further analysis to determine the effects of several covariates found that age contributed significantly to the associated condition of sleep disturbance (p=0.049). CONCLUSION: Patients with complicated mild TBI have post-injury symptoms that can be classified into concussion subtypes. Patients with extra-axial bleeds exhibited consistently better subtype scores compared to those with intra-axial bleeds. Understanding subtype symptomatology may allow for subtype directed therapy to improve symptom recovery for mild TBI patients.

Examining the Association Between Childhood Trauma, Brain Injury, and Neurobehavioral Symptoms Among Survivors of Intimate Partner Violence: A Cross-Sectional Analysis.

Understanding factors contributing to neurobehavioral symptom burden among intimate partner violence (IPV) survivors has important implications for prevention, screening, and intervention in this vulnerable population. This study aimed to (1) identify the relationship between childhood trauma and neurobehavioral symptoms among a shelter- and community-based sample of IPV survivors, including investigating the mediating role of posttraumatic stress symptoms and alexithymia in this relationship; (2) assess the association between IPV-related brain injury (BI) severity and neurobehavioral symptoms; and (3) assesses whether physical, emotional, or cognitive domains of neurobehavioral symptom burden show differential associations with childhood trauma or IPV-related BI. Community sites serving women who had experienced IPV such as domestic violence shelters and transitional housing sites. Women survivors of IPV with and without BI (n = 99), aged 18 to 54 years. Retrospective, cross-sectional study design. The following self-reported questionnaires were used: Rivermead Post Concussion Questionnaire (RPQ); Childhood Trauma Questionnaire (CTQ); a modified version of the Conflict Tactics Scale; Brain Injury Severity Assessment (BISA); Clinician-Administered PTSD Scale for DSM IV; and Toronto Alexithymia Scale. The final multivariate regression model assessed the association between childhood abuse, BI severity, and neurobehavioral symptoms (as measured by the RPQ) adjusting for age, educational attainment, and abuse in the past year. We created separate models with total neurobehavioral symptom score as an outcome, as well as somatic, emotional, and cognitive symptom scores. We used structural equation modeling to assess whether posttraumatic stress and alexithymia mediated the effect of childhood trauma and neurobehavioral symptoms. Childhood trauma was associated with higher levels (P < .01) of overall neurobehavioral symptom burden in women independent of BI and specifically associated with RPQ Emotional and Somatic subscale symptoms (P ≤ .05). BI was positively associated with somatic symptoms in the full sample and cognitive neurobehavioral symptoms in the sample of women with IPV-related BI (P < .05) independent of childhood trauma. Posttraumatic stress symptoms, but not alexithymia, partially mediated the effect of childhood trauma effect on neurobehavioral symptoms. Childhood trauma and BI should not be overlooked as part of efforts to meet the needs of IPV survivors who may experience a range of emotional, somatic, and cognitive symptoms.

Cerebrovascular Responses to O2-CO2 Exchange Ratio under Brief Breath-Hold Challenge in Patients with Chronic Mild Traumatic Brain Injury.

Breath-by-breath oxygen-carbon dioxide (O2-CO2) exchange ratio (bER) is a respiratory gas exchange (RGE) metric, which is the ratio of the changes in the partial pressure of O2 (ΔPO2) to CO2 (ΔPCO2) between end-inspiration and end-expiration, has been demonstrated to characterize the cerebrovascular responses to breath-hold challenge in healthy individuals. We aimed to explore whether bER could characterize cerebrovascular responses in patients with chronic mild traumatic brain injury (mTBI) under breath-hold challenge. We also investigated the correlation between bER and the severity of post-concussion symptoms. Blood-oxygenation-level-dependent (BOLD) images were acquired using functional magnetic resonance imaging (fMRI) on 10 patients with chronic mTBI and 10 controls without brain injury history when performing a breath-hold task. Time series of RGE metrics of ΔPO2, ΔPCO2, and bER were computed, and their cross-correlation with regional change in BOLD (ΔBOLD) was calculated. Symptom burden was assessed using the Rivermead Post Concussion Questionnaire (RPQ), and its correlation with RGE changes was also measured. Compared with controls, a diffuse decrease in the correlation between regional ΔBOLD and bER was found in the brain of patients with mTBI (pfdr < 0.05). No significant difference was found between patients and controls for the correlation of regional ΔBOLD with ΔPO2 and ΔPCO2. Symptom severity indicated by RPQ scores increased with a decrease in the averaged changes of bER (ρ = 0.79, p = 0.01) and ΔPO2 (ρ = 0.70, p = 0.03) in breath-hold epochs. Our imaging and symptom severity findings suggest that bER can be used to characterize cerebrovascular responses to breath hold in patients with mTBI. The RGE may contribute to the post-concussive symptom severity.

Perceived Injustice After Mild Traumatic Brain Injury.

Objective:To examine perceived injustice and its associations with self-reported symptoms and return to work at 3 months after injury in a prospectively recruited sample of patients with mild traumatic brain injury (mTBI).Design:Observational study.Setting:TBI outpatient unit.Participants:Adult patients aged 18 to 68 years with mTBI (n = 100) or orthopedic injury ([OI]; n = 34).Main Measures:The Injustice Experience Questionnaire (IEQ) and its associations with the Rivermead Post Concussion Questionnaire (RPQ), Beck Depression Inventory–Second Edition (BDI-II), PTSD Checklist–Civilian Version (PCL-C), and Pain Visual Analog Scale (PVAS). Information on injury-related characteristics, compensation seeking and litigation, and return-to-work status was also collected.Results:Median IEQ total score was 3 (range, 0-23) in the mTBI group and 2.5 (range, 0-25) in the OI group. In the mTBI group, IEQ was significantly correlated with RPQ (rs = 0.638, P < .01), BDI-II (rs = 0.612, P < .01), PCL-C (rs = 0.679, P < .01), and PVAS (rs = 0.232, P < .05). The association between IEQ and PCL-C (rs =0.797, P < .01) and BDI-II (rs = 0.395, P < .05) was also found in the OI group. In both groups, patients who were still on sick leave at 3 months after injury tended to report higher perceived injustice (IEQ total score) than patients who had returned to work or studies. However, this difference did not reach statistical significance.Conclusions:Perceived injustice is associated with self-reported symptoms in patients with mTBI. Our results suggest that perceived injustice could be a relevant construct to consider in clinical management of patients with mTBI. Also, perceived injustice could be a potential target for psychological interventions promoting recovery after mTBI.