Persistent, long-term cerebral white matter changes after sports-related repetitive head impacts.

Repetitive head impacts (RHI) sustained in contact sports are thought to be necessary for the long-term development of chronic traumatic encephalopathy (CTE). Our objectives were to: 1) characterize the magnitude and persistence of RHI-induced white matter (WM) changes; 2) determine their relationship to kinematic measures of RHI; and 3) explore their clinical relevance.Prospective, observational study of 10 Division III college football players and 5 non-athlete controls during the 2011-12 season. All subjects underwent diffusion tensor imaging (DTI), physiologic, cognitive, and balance testing at pre-season (Time 1), post-season (Time 2), and after 6-months of no-contact rest (Time 3). Head impact measures were recorded using helmet-mounted accelerometers. The percentage of whole-brain WM voxels with significant changes in fractional anisotropy (FA) and mean diffusivity (MD) from Time 1 to 2, and Time 1 to 3 was determined for each subject and correlated to head impacts and clinical measures.Total head impacts for the season ranged from 431-1,850. No athlete suffered a clinically evident concussion. Compared to controls, athletes experienced greater changes in FA and MD from Time 1 to 2 as well as Time 1 to 3; most differences at Time 2 persisted to Time 3. Among athletes, the percentage of voxels with decreased FA from Time 1 to 2 was positively correlated with several helmet impact measures. The persistence of WM changes from Time 1 to 3 was also associated with changes in serum ApoA1 and S100B autoantibodies. WM changes were not consistently associated with cognition or balance.A single football season of RHIs without clinically-evident concussion resulted in WM changes that correlated with multiple helmet impact measures and persisted following 6 months of no-contact rest. This lack of WM recovery could potentially contribute to cumulative WM changes with subsequent RHI exposures

Trajectory of Subject-specific DTI Changes and Comparison by Subject Group.

<p>Line graphs show the percentage of WM voxels in each athlete (solid lines) and each control (hatched line) with significantly decreased (A and C) and increased (B and D) FA (A and B) and MD (C and D) from Time 1 to Time 2, and from Time 1 to Time 3. Box-and-whisker plots show the maximum and minimum (whiskers), inter quartile range (box) and median (line within box) values for the percentage of WM voxels in athletes (clear) and controls (black) with significantly decreased (A and C) and increased (B and D) FA (A and B) and MD (C and D) from baseline (Time 1) to 6 months of rest (Time 3).</p

Heat map display of correlations between helmet impact measures and DTI changes between pre- and post-season (T1 to T2), and pre- and 6 months post-season (T1 to T3).

<p>Color and shading reflect direction and strength of correlation, as indicated by the figure key. Correlations with p-values>0.10 are not reported. All DTI metrics refer to the proportion of white matter with the FA or MD change indicated.</p

Baseline comparison of athlete (n = 10) and control (n = 5) subjects.

<p>Baseline comparison of athlete (n = 10) and control (n = 5) subjects.</p

Physiologic and clinical correlations of DTI changes among athletes.

<p>Color and shading reflect direction and strength of correlation, as indicated by the figure key. Correlations with p-values>0.10 are not reported. All DTI metrics refer to the proportion of white matter with the FA or MD change indicated.</p

Subject-Specific DTI Changes.

<p>Subject-specific changes in FA (A and B) and MD (C and D) from Time 1 to Time 2 (A and C) and from Time 1 to Time 3 (B and D). Bars in each graph represent the percentage of white matter voxels in each individual subject with significantly decreased (black) and increased (grey) FA and MD over the specified time interval.</p

Helmet impact measures among athlete subjects (n = 10).

<p>Helmet impact measures among athlete subjects (n = 10).</p

Spatial Distribution of WM Voxels with Decreased FA and Increased MD.

<p>WM structures (left), and significant DTI changes from Time 1 to Time 2 (right) in a football player (A) and a control subject (B). Columns 2 and 4 depict voxels with significant ↓FA (blue), significant ↑MD (red) and both ↓FA and ↑MD (green). ALIC: anterior limb of internal capsule; BCC: body of corpus callosum; CP: cerebral peduncle; GCC: genu of corpus callosum; PLIC: posterior limb of internal capsule; PTR: posterior thalamic radiation; SCC: splenium of corpus callosum; SS: sagittal stratum (includes inferior longitudinal fasciculus and inferior fronto-occipital fasciculus).</p