Longitudinal assessment of white matter abnormalities following sports-related concussion

Abstract

There is great interest in developing physiological-based biomarkers such as diffusion tensor imaging to aid in the management of concussion, which is currently entirely dependent on clinical judgment. However, the time course for recovery of white matter abnormalities following sports-related concussion (SRC) is unknown. We collected diffusion tensor imaging and behavioral data in forty concussed collegiate athletes on average 1.64 days (T1; n = 33), 8.33 days (T2; n = 30), and 32.15 days post-concussion (T3; n = 26), with healthy collegiate contact-sport athletes (HA) serving as controls (n = 46). We hypothesized that fractional anisotropy (FA) would be increased acutely and partially recovered by one month post-concussion. Mood symptoms were assessed using structured interviews. FA differences were assessed using both traditional and subject-specific analyses. An exploratory analysis of tau plasma levels was conducted in a subset of participants. Results indicated that mood symptoms improved over time post-concussion, but remained elevated at T3 relative to HA. Across both group and subject-specific analyses, concussed athletes exhibited increased FA in several white matter tracts at each visit post-concussion with no longitudinal evidence of recovery. Increased FA at T1 and T3 was significantly associated with an independent, real-world outcome measure for return-to-play. Finally, we observed a nonsignificant trend for reduced tau in plasma of concussed athletes at T1 relative to HA, with tau significantly increasing by T2. These results suggest white matter abnormalities following SRC may persist beyond one month and have potential as an objective biomarker for concussion outcome. Hum Brain Mapp 37:833-845, 2016. © 2015 Wiley Periodicals, Inc.

Keywords: diffusion tensor imaging; fractional anisotropy; mTBI; tau.

Figure 1

Primary and secondary behavioral measures: Shown are scores from structured interviews for anxiety (HAM‐A) and depression (HAM‐D) and the average scores from the cognitive battery and frequency of self‐reported symptoms in concussed athletes (CA) at one day (T1), one week (T2), and one month (T3) post‐concussion, as well as in healthy athletes (HA). Notches indicate 95% confidence interval of the median and whiskers represent data within 1.5 interquartile range.

Figure 2

ROI analyses: Shown is the average fractional anisotropy in a priori ROI, including the uncinate fasciculus (UF), anterior corona radiata (ACR), superior corona radiata (SCR), superior longitudinal fasciculus (SLF), cerebellar peduncles (CP), corpus callosum (CC), and the internal capsule (IC). * Indicates significant difference between healthy athletes (HA) and concussed athletes at one day (T1), one week (T2), and one month (T3) post‐concussion at p < 0.05. Notches indicate 95% confidence interval of the median and whiskers represent data within 1.5 interquartile range.

Figure 3

Cross‐sectional voxel‐wise differences: Regions where concussed athletes had significantly increased fractional anisotropy relative to healthy athletes are shown in red. The number represents the slice coordinate in the Z direction, L = left, R = right.

Figure 4

Subject‐specific abnormalities: (A) Shown is the square‐root transformed volume and number of clusters with increased or decreased fractional anisotropy at the subject‐level for healthy athletes (HA) and concussed athletes at one day (T1), one week (T2), and one month (T3) post‐concussion. * Indicates significant difference relative to HA at p<0.05, ^indicates non‐significant trend at p<0.10. Notches indicate 95% confidence interval of the median and whiskers represent data within 1.5 interquartile range. (B) Shown are anatomical regions in which at least three HA or three concussed athletes (CA) had subject‐specific clusters with increased FA. The number represents the slice coordinate in the Z direction, L = left; R = right.

Figure 5

Plasma tau levels: Shown are levels of tau in plasma of concussed athletes (CA) at one day (T1), one week (T2), and one month (T3) post‐concussion, as well as in healthy athletes (HA). Notches indicate 95% confidence interval of the median and whiskers represent data within 1.5 interquartile range.