AUTHOR=Shetty Teena , Nguyen Joseph T. , Cogsil Taylor , Tsiouris Apostolos John , Niogi Sumit N. , Kim Esther U. , Dalal Aashka , Halvorsen Kristin , Cummings Kelianne , Zhang Tianhao , Masdeu Joseph C. , Mukherjee Pratik , Marinelli Luca TITLE=Clinical Findings in a Multicenter MRI Study of Mild TBI JOURNAL=Frontiers in Neurology VOLUME=Volume 9 - 2018 YEAR=2018 URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2018.00836 DOI=10.3389/fneur.2018.00836 ISSN=1664-2295 ABSTRACT=Background: Uncertainty continues to surround mild traumatic brain injury (mTBI) diagnosis, symptoms, prognosis, and outcome due in part to a lack of objective biomarkers of injury and recovery. As mTBI gains recognition as a serious public health epidemic, there is need to identify risk factors, diagnostic tools, and imaging biomarkers to help guide diagnosis and management. Methods: 111 patients (15-50 years old) were enrolled acutely after mTBI and followed with up to 4 standardized serial assessments over 3 months. Each encounter included a clinical exam, neuropsychological assessment, and magnetic resonance imaging (MRI). Chi-square and linear mixed models were used to assess changes over time and determine potential biomarkers of mTBI severity and outcome. Results: The symptoms most frequently endorsed after mTBI were headache (91%), not feeling right (89%), fatigue (86%), and feeling slowed down (84%). Of the 104 mTBI patients with a processed MRI scan, 28 (27%) subjects had white matter changes which were deemed unrelated to age, and 26 of these findings were deemed unrelated to acute trauma. Of the neuropsychological assessments tested, 5- and 6-Digit Backward Recall, the modified Balance Error Scoring System (BESS), and Immediate 5-Word Recall significantly improved longitudinally in mTBI subjects and differentiated between mTBI subjects and controls. Female sex was found to increase symptom severity scores (SSS) at every time point. Age ≥ 25 years was correlated with increased SSS. Subjects aged ≥ 25 also did not improve longitudinally on 5-Digit Backward Recall, Immediate 5-Word Recall, or Single-Leg Stance of the BESS, whereas subjects < 25 years improved significantly. Patients who reported personal history of depression, anxiety, or other psychiatric disorder had higher SSS at each time point. Conclusions: The results of this study show that 5- and 6-Digit Backward Recall, the modified BESS, and Immediate 5-Word Recall should be considered useful in demonstrating cognitive and vestibular improvement during the mTBI recovery process. Clinicians should take female sex, older age, and history of psychiatric disorder into¬ account when managing mTBI patients. Further study is necessary to determine the true prevalence of white matter changes in people with mTBI.