White Matter Hyperintensities on High-Resolution 3-T MRI: Frequency in Mild Traumatic Brain Injury and Associations with Clinical Markers-A Prospective Controlled Multicenter Study.

Abstract

Background: A challenge in management of patients with mild traumatic brain injury (mTBI) is the lack of objective biomarkers to guide diagnosis, classification, and prognostication. White matter hyperintensities (WMHs) on T2-weighted MRI sequences have been identified as a potential marker for this purpose. Objective: To compare WMHs on high-resolution 3-T MRI between individuals with and without mTBI and to assess associations of WMHs with clinical markers in mTBI. Methods: This prospective study recruited individuals with acute mTBI and a matched control group of individuals without mTBI from seven U.S. centers from November 2015 to January 2018. Participants underwent up to four clinical encounters (baseline through approximately 3 months after enrollment). At each encounter, clinical markers of head injury were tested, including the Rivermead Post-Concussion Symptoms Qustionnaire-3 (RPQ-3), assessing early postconcussive symptoms (physical symptoms), Rivermead Post-Concussion Symptoms Questionnaire-13 (RPQ-13), assessing late postconcussive symptoms (psychosocial functioning and lifestyle), and Balance Error Scoring System (BESS) test, assessing postural stability. Participants also underwent at each encounter 3-T MRI including a high-resolution isotropic 3D T2-weighted FLAIR sequence. Two neuroradiologists independently reviewed FLAIR sequences from baseline encounters for presence of at least one WMH and of abnormal WMHs (defined as ≥5 punctate foci, at least one focus measuring >3 mm, or at least one focus in an atypical location); discrepancies were resolved by a consensus process involving possible review by a group of four neuroradiologists. Results: The mTBI group included 303 participants (mean age, 21.6±8.2 years; 162 male, 141 female); the control group included 148 participants (mean age, 21.8±8.3 years; 71 male, 77 female). At least one WMH was present in 102 (34%) participants in the mTBI group, of which 40% (41) had abnormal WMHs, and 52 (35%) participants in the control group (p=.76), of which 35% (18) had abnormal WMHs (p=.50). Neither WMHs nor abnormal WMHs were associated with RPQ3-, RPQ-13, or BESS total score at any time point (p>.05). Conclusion: WMHs did not show significant differences between mTBI and control groups, nor significant associations with clinical markers in the mTBI group. Clinical Impact: The findings do not support WMHs as a marker of mTBI.