Interaction of obesity and proteins associated with the NLRP3 inflammasome following mild traumatic brain injury.

The NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome has been associated with worse outcomes from severe traumatic brain injury (TBI). The NLRP3 inflammasome is also strongly associated with other pro-inflammatory conditions, such as obesity. Little is known about the potential effect of mild TBI (mTBI) on the NLRP3 inflammasome and the extent to which modifying factors, such as obesity, may augment the inflammatory response to mTBI. The purpose of this study was to evaluate the association of NLRP3 inflammasome proteins with obese body mass index (BMI ≥ 30) within 24 h of mTBI after presenting to a level 1 trauma center emergency department. This is a secondary analysis of prospectively enrolled patients with mTBI who presented to the emergency department of one U.S. Level 1 trauma center from 2013 to 2018 (n = 243). A series of regression models were built to evaluate the association of NLRP3 proteins obtained from blood plasma within 24 h of injury and BMI as well as the potential interaction effect of higher BMI with NLRP3 proteins (n = 243). A logistic regression model revealed a significant association between IL-18 (p < 0.001) in mTBI patients with obese BMI compared to mTBI patients with non-obese BMI (< 30). Moderation analyses revealed statistically significant interaction effects between apoptotic speck-like protein (ASC), caspase-1, IL-18, IL-1ß and obese BMI which worsened symptom burden, quality of life, and physical function at 2 weeks and 6 months post-injury. Higher acute concentrations of IL-1ß in the overall cohort predicted higher symptoms at 6-months and worse physical function at 2-weeks and 6-months. Higher acute concentrations of IL-18 in the overall cohort predicted worse physical function at 6-months. In this single center mTBI cohort, obese BMI interacted with higher acute concentrations of NLRP3 inflammasome proteins and worsened short- and long-term clinical outcomes.

Evidence for a multidomain clinical assessment of mild traumatic brain injury in older adults.

BACKGROUND: There are few guidelines on the appropriate clinical tools to evaluate mTBI in older adults. OBJECTIVE: We aimed to investigate the utility of a multidomain assessment to differentiate older adults with mTBI from controls. METHODS: Participants included 68 older adults (37% male) aged 60-76 (M = 66.24, SD = 4.50) years. Thirty-four patients were diagnosed with a mTBI at a specialty mTBI clinic within 90 days of injury, and age- and sex-matched to 34 community controls. Participants completed the following assessments: Post-Concussion Symptom Scale (PCSS), Short Fall Efficacy Scale-International (Short FES-I), Generalized Anxiety Disorder-7 Item Scale (GAD-7), Geriatric Depression Scale-5 Item (GDS-5), Wide Range Achievement Test-Fourth Edition (WRAT-4) reading subtest, subtests of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), clock drawing, and Vestibular/Ocular Motor Screening for Concussion (VOMS). Independent-samples t-tests or chi-squared analyses were used to compare assessment results between groups. A logistic regression (LR) was conducted to determine which combination of assessments best identified the mTBI group from controls. RESULTS: The mTBI group endorsed significantly more symptoms of concussion (p < .001), balance concerns (p < .001), anxiety (p < .001), and depression (p = 0.04), and performed worse on cognitive (p < .001), vestibular (p < .001), and oculomotor (p = .004) screening relative to controls. The LR (p < .001; r2 = 0.90) correctly identified 98.5% of older adults and retained concussion (p = .01) and depression (p = .02) symptoms, and cognitive (p = .03) and vestibular (p = .04) screening in the final model. DISCUSSION: The current findings support a multidomain assessment model of care for evaluating mTBI in older adults.

Predictors of poor reading performance in student-athletes following sport-related concussion.

The goal of the current study was to determine which sport/recreation-related concussion (SRC) assessments predict academic reading performance following SRC. The study included 70 concussed students aged 14-22 years (M = 16.21, SD = 1.90) evaluated 2-30 days (M = 8.41, SD = 5.88) post-injury. SRC assessments included: Post-Concussion Symptom Scale, Immediate Post-Concussion Assessment and Cognitive Testing, Vestibular/Ocular Motor Screening, and King-Devick test. The Nelson-Denny Reading Test (NDRT) comprehension subtest measured academic reading accuracy and rate. Pearson correlations examined relationships among SRC assessments and reading accuracy/rate; those assessments that significantly correlated with the NDRT were included in multiple regressions (MRs) predicting reading accuracy and reading rate. Results supported positive correlations between visual motor speed and reading accuracy (r = .31, p = .01), and near point of convergence (NPC) and reading rate (r = .30, p = .01). The MRs for reading accuracy (F = 4.61, p = .01) and reading rate (F = 4.61, p = .01) were significant, and predicted approximately 40% of the variance, with visual motor speed and NPC as the only significant predictors in both models. Symptoms were not predictive of reading accuracy or rate. The present study indicates that visual motor speed and NPC are predictive of academic reading performance after SRC, suggesting clinicians should consider these clinical outcomes to better inform academic accommodations.

Performance Validity Testing in Patients Presenting to a Specialty Clinic With a Mild Traumatic Brain Injury.

OBJECTIVE: To evaluate predictors of performance validity testing (PVT) and clinical outcome in patients presenting to a specialty clinic with a mild traumatic brain injury (mTBI). SETTING: An outpatient mTBI specialty clinic. PARTICIPANTS: Seventy-six (47% female) patients aged 16 to 66 (mean = 40.58, SD = 14.18) years within 3 to 433 days (mean = 30.63, SD = 54.88, median = 17.00) of a suspected mTBI between 2018 and 2019. DESIGN: A cross-sectional, observational study comparing patients who passed PVT (n = 43) with those who failed (n = 33). A logistic regression (LR) was conducted to evaluate factors that predicted failed PVT. Independent-samples t tests and general linear model were used to evaluate PVT groups on clinical outcomes. The LR with a receiver operating characteristic (ROC) curve was conducted to evaluate embedded validity indicators. MAIN MEASURES: Performance validity testing, computerized neurocognitive testing, vestibular/oculomotor screening, symptom reports. RESULTS: At their initial clinic visit 43% of patients failed PVT. PVT failure was predicted by presence of secondary gain (odds ratio [OR] = 8.11, P = .02), while a history of mental health predicted passing of PVT (OR = 0.29, P = .08). Those who failed PVT performed significantly worse on computerized neurocognitive testing (P < .05) and took an average of 33 days longer to return to work (P = .02). There was no significant difference (P = .20) in recovery time between failed/passed PVT groups when covarying for those who sustained a work injury. Word memory learning percentage less than 69% and design memory learning percentage less than 50% accurately classified patients who failed PVT (area under the ROC curve = 0.74; P < .001). CONCLUSION: Secondary gain was the best predictor of failed PVT. Patients presenting for mTBI evaluation and rehabilitation who fail PVT demonstrate worse performance on cognitive testing and take longer to return to work post-injury, but recover in a similar time frame compared with those who pass PVT. Clinicians should be cautious in discounting patients who yield invalid test results, as these patients appear to be able to achieve recovery in a treatment setting.

Multimodal Assessment of Sport-Related Concussion.

OBJECTIVE: The purpose of this study was to determine which assessments best identify athletes with sport-related concussion (SRC) from healthy controls in the acute/early subacute phase (within 10 days of SRC) of injury. DESIGN: Prospective, cohort study. SETTING: Specialty concussion clinic. PARTICIPANTS: Sixty-four athletes with SRC (52% male) and 59 matched (age and sex), healthy controls (56% male) aged 12 to 20 years (Mean [M] = 15.07, Standard Deviation [SD] = 2.23). ASSESSMENT: Participants completed symptom, cognitive, vestibular/oculomotor, near point of convergence (NPC), and balance assessments. MAIN OUTCOME MEASURES: Univariate analyses were conducted to compare athletes with SRC to healthy controls across all assessments. Assessments that significantly differed between the SRC group and healthy controls were used as predictors in an enter method logistic regression (LR) model and subsequent forward stepwise LR. RESULTS: Results of LR analyses indicated that symptom inventory and symptom provocation on vestibular/oculomotor assessments significantly predicted athletes with SRC versus controls. The forward stepwise LR accurately classified 84.6% of the overall sample (78.3% of athletes with SRC and 91.2% of controls were accurately predicted) and accounted for 60.5% of the variance in predicting athletes with SRC versus controls. Total symptom inventory score (P = 0.003) and vestibular/oculomotor symptom provocation (P < 0.01) were the most sensitive and specific measures in a comprehensive, multimodal assessment for distinguishing athletes with SRC from healthy controls within 10 days of injury. CONCLUSIONS: Elements within a multimodal evaluation that are the most robust at discriminating athletes with SRC from healthy controls in the acute/early subacute phase of injury include symptom report and provocation of symptoms on vestibular/oculomotor assessment. These assessments should be considered in conjunction with other objective assessments (ie, NPC measurement and cognitive testing) as part of a comprehensive evaluation of SRC.

Concussion Clinical Profiles Screening (CP Screen) Tool: Preliminary Evidence to Inform a Multidisciplinary Approach.

BACKGROUND: Current concussion symptom inventories emphasize total number or symptoms and severity and overlap with other conditions, such as mental health disorders, which may limit their specificity and clinical utility. OBJECTIVE: To develop and test the reliability and validity of a new Concussion Clinical Profiles Screening tool (CP Screen) in both healthy controls and concussed. METHODS: CP Screen is a 29-item self-report, clinical profile-based symptom inventory that measures the following 5 concussion clinical profiles: 1) anxiety/mood, 2) cognitive/fatigue, 3) migraine, 4) ocular, and 5) vestibular; and the following 2 modifying factors: 1) sleep and 2) neck. Post-Concussion Symptom Scale (PCSS), vestibular/ocular motor screening (VOMS) tool, and Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) were conducted. CP Screen was administered in community a concussion surveillance program and 2 sports medicine concussion clinics. Responses include 248 athletes, 121 concussed, and 127 controls, enrolled between 2018 and 2019. RESULTS: Internal consistency of the CP Screen in the control (Cronbach's alpha = .87) and concussed (Cronbach's alpha = .93) samples was high. Moderate to high correlations among the CP Screen factors and PCSS factors and VOMS items, supporting concurrent validity. ROC curve analysis for identifying concussed from controls was significant (P < .001) for all CP Screen factor and modifier scores with excellent AUCs for migraine (.93), ocular (.88), vestibular (.85), and cognitive (.81) factors, demonstrating predictive validity. CONCLUSION: The CP Screen demonstrated strong reliability, concurrent validity with commonly used concussion assessment (ie, PCSS, VOMS, and ImPACT), and predictive validity for identifying concussion. The CP Screen extends current symptom inventories by evaluating more specific symptoms that may reflect clinical profiles and inform better clinical care.

The utility of the Convergence Insufficiency Symptom Survey (CISS) post-concussion.

Background: The Convergence Insufficiency Symptom Survey (CISS) is being utilized as an assessment measure following concussion despite minimal research. This study explored the sensitivity and specificity of the CISS in identifying receded near point of convergence (NPC) post-concussion. Methods: Prospective study of 130 patients post-concussion aged 11-25, classified into normal NPC (n = 94) and CI (n = 36) groups (i.e., NPC >5 cm), completed the CISS, VOMS, and PCSS. Sensitivity and specificity identifying receded NPC were explored with published CISS cutoff score (>16). ROC with AUC analysis was conducted to determine an alternate CISS cutoff score to yield optimal sensitivity and specificity in patients with concussion. Results: Utilizing the published cutoff score, the CISS demonstrated adequate sensitivity (.78 [95% CI = .60-.89]) but poor specificity (.35 [95%CI = .26-.46]). ROC curve demonstrated that CISS score was significant (P = .01) in predicting a positive test result (i.e., NPC >5) with AUC of .65 (95%CI .54-.76). An alternative cutoff score (CISS>23) maximized sensitivity (.70) and specificity (.53) for identifying receded NPC. Conclusions: Both the previously published CISS cutoff and our sample-based cutoff score yielded a high rate of false positives for receded NPC. CISS scores post-concussion may help the clinician understand difficulties with visual tasks but is not a suitable diagnostic tool in this patient population.