Mild traumatic brain injury: longitudinal regional brain volume changes

Abstract

Purpose: To investigate longitudinal changes in global and regional brain volume in patients 1 year after mild traumatic brain injury (MTBI) and to correlate such changes with clinical and neurocognitive metrics.

Materials and methods: This institutional review board-approved study was HIPAA compliant. Twenty-eight patients with MTBI (with 19 followed up at 1 year) with posttraumatic symptoms after injury and 22 matched control subjects (with 12 followed up at 1 year) were enrolled. Automated segmentation of brain regions to compute regional gray matter (GM) and white matter (WM) volumes was performed by using three-dimensional T1-weighted 3.0-T magnetic resonance imaging, and results were correlated with clinical metrics. Pearson and Spearman rank correlation coefficients were computed between longitudinal brain volume and neurocognitive scores, as well as clinical metrics, over the course of the follow-up period.

Results: One year after MTBI, there was measurable global brain atrophy, larger than that in control subjects. The anterior cingulate WM bilaterally and the left cingulate gyrus isthmus WM, as well as the right precuneal GM, showed significant decreases in regional volume in patients with MTBI over the 1st year after injury (corrected P < .05); this was confirmed by means of cross-sectional comparison with data in control subjects (corrected P < .05). Left and right rostral anterior cingulum WM volume loss correlated with changes in neurocognitive measures of memory (r = 0.65, P = .005) and attention (r = 0.60, P = .01). At 1-year follow-up, WM volume in the left cingulate gyrus isthmus correlated with clinical scores of anxiety (Spearman rank correlation r = -0.68, P = .007) and postconcussive symptoms (Spearman rank correlation r = -0.65, P = .01).

Conclusion: These observations demonstrate structural changes to the brain 1 year after injury after a single concussive episode. Regional brain atrophy is not exclusive to moderate and severe traumatic brain injury but may be seen after mild injury. In particular, the anterior part of the cingulum and the cingulate gyrus isthmus, as well as the precuneal GM, may be distinctively vulnerable 1 year after MTBI.

Figures

Figure 1:

Coregistered data (from 28 patients with MTBI) projected onto right cerebral hemisphere template show areas of significant volume loss (Bonferroni-corrected P < .05) at 1-year follow-up according to both the one-sample t test for within-group longtitudinal comparision (patients at 1-year follow-up compared with patients at initial visit) and the two-sample t test for across-group comparision (patients at 1-year follow-up compared with control subjects) based on Freesurfer regional volumetry. A, and, B, show medial and lateral views, respectively.

Figure 2:

Coregistered data (from 22 control subjects) projected onto right cerebral hemisphere template show minor areas of volume loss in the occipital lobe (Bonferroni-corrected P < .05); atrophy was significant in no region after false-discovery-rate correction. A, and, B, show medial and lateral views, respectively.

Figure 3:

Areas of significant difference (threshold-free cluster enhancement; Bonferroni-corrected P < .05) using VBM (shown here overlaid on two-dimensional axial view of standard Montreal Neurological Institute 2-mm template on which across-group brain normalization morphometry was performed) highlight differences between patients with MTBI at 1-year follow-up and control subjects that confirm a pattern of differences in regional volume similar to that observed by using Freesurfer (ie, in the anterior cingulum, cingulate gyrus isthmus, right precuneus and cuneus, and scattered frontal areas).

Figure 4:

A, Bar graph shows that patients with MTBI showed significantly (P < .01) elevated scores on clinical symptom scales of depression, anxiety, and PCS compared with control subjects at both initial and 1-year follow-up visits. Higher scores on clinical symptom scales = more severe symptoms; error bars = standard errors of the mean. Average scores were also higher at 1-year follow-up than at the initial visit in patients with MTBI. B, Bar graph created after ANOVA with Friedman test after accounting for six confounding factors (age, sex, injury site, mechanism of injury, loss of consciousness duration, and time between injury and initial imaging) shows significantly elevated depression scores with least-square estimates in patients at follow-up compared with the initial visit (P = .001).

Figure 5:

A, Graph shows significant Pearson correlation (r = 0.65, P = .005) between longitudinal changes in left rAC WM volume after 1 year and changes in CVLT memory encoding z score during the same period in patients with MTBI. B, Graph shows additional correlation, which reached statistical significance (r = 0.60, P = .01), between longitudinal changes in right rAC WM volume after 1 year and changes in PASAT attention z score during the same period. Upper and lower lines = upper and lower 95% confidence intervals of linear fitting of data.

Figure 6:

Graphs show the significant Spearman rank correlations found between regional brain volume and clinical symptoms in patients with MTBI. A, Correlation of left cingulate gyrus isthmus WM volume and anxiety score at 1-year follow-up (r = −0.68, P = .007). B, Correlation of left cingulate gyrus isthmus WM volume and PCS score at 1-year follow-up (r = −0.65, P = .01).