Clinical and imaging assessment of acute combat mild traumatic brain injury in Afghanistan

Abstract

Objective: To evaluate whether diffusion tensor imaging (DTI) will noninvasively reveal white matter changes not present on conventional MRI in acute blast-related mild traumatic brain injury (mTBI) and to determine correlations with clinical measures and recovery.

Methods: Prospective observational study of 95 US military service members with mTBI enrolled within 7 days from injury in Afghanistan and 101 healthy controls. Assessments included Rivermead Post-Concussion Symptoms Questionnaire (RPCSQ), Post-Traumatic Stress Disorder Checklist Military (PCLM), Beck Depression Inventory (BDI), Balance Error Scoring System (BESS), Automated Neuropsychological Assessment Metrics (ANAM), conventional MRI, and DTI.

Results: Significantly greater impairment was observed in participants with mTBI vs controls: RPCSQ (19.7 ± 12.9 vs 3.6 ± 7.1, p < 0.001), PCLM (32 ± 13.2 vs 20.9 ± 7.1, p < 0.001), BDI (7.4 ± 6.8 vs 2.5 ± 4.9, p < 0.001), and BESS (18.2 ± 8.4 vs 15.1 ± 8.3, p = 0.01). The largest effect size in ANAM performance decline was in simple reaction time (mTBI 74.5 ± 148.4 vs control -11 ± 46.6 milliseconds, p < 0.001). Fractional anisotropy was significantly reduced in mTBI compared with controls in the right superior longitudinal fasciculus (0.393 ± 0.022 vs 0.405 ± 0.023, p < 0.001). No abnormalities were detected with conventional MRI. Time to return to duty correlated with RPCSQ (r = 0.53, p < 0.001), ANAM simple reaction time decline (r = 0.49, p < 0.0001), PCLM (r = 0.47, p < 0.0001), and BDI (r = 0.36 p = 0.0005).

Conclusions: Somatic, behavioral, and cognitive symptoms and performance deficits are substantially elevated in acute blast-related mTBI. Postconcussive symptoms and performance on measures of posttraumatic stress disorder, depression, and neurocognitive performance at initial presentation correlate with return-to-duty time. Although changes in fractional anisotropy are uncommon and subtle, DTI is more sensitive than conventional MRI in imaging white matter integrity in blast-related mTBI acutely.

Figure 1. Participant screening and enrollment

A total of 230 US military service members were screened from March through September 2012 at 2 sites in Afghanistan; 212 participated, and complete data were obtained from 196 service members. CTL = controls; TBI = traumatic brain injury; TOMM = Test of Memory Malingering.

Figure 2. More-severe concussive symptoms, depression, posttraumatic stress disorder, impaired balance, and cognitive dysfunction in participants with mTBI

(A) RPCSQ (n = 101 CTL, 95 mTBI, Mann–Whitney U). (B) BESS (n = 99 CTL, 89 mTBI: 2 CTL and 6 mTBI participants did not complete BESS because of musculoskeletal injuries, Student t test). (C) BDI (n = 101 CTL, 95 mTBI, Mann–Whitney U). (D) PCLM (n = 101 CTL, 95 mTBI, Mann–Whitney U). (E–L) Change in ANAM measures, where deltas are defined as study ANAM scores minus baseline ANAM scores (n = 87 CTL, 84 mTBI). (E) Sleep index; (F) SRT; (G) 2SRT; (H) processing speed, assessed with PRT; (I) associative learning assessed by CSL; (J) delayed memory assessed by CSD; (K) working memory assessed by MTP; (L) visual-spatial memory assessed by MTS. All were significant after Bonferroni correction for multiple comparisons. Dashed lines represent maximum scores. For box plot displays, boxes indicate first, second, and third quartiles, plus (+) symbols indicate means, bars indicate 5–95 percentiles, and values outside of 5–95 percentiles are shown as discrete symbols. ANAM = Automated Neuropsychological Assessment Metrics; BDI = Beck Depression Inventory; BESS = Balance Error Scoring System; CSD = Code Substitution Delayed; CSL = Code Substitution Learning; CTL = controls; mTBI = mild traumatic brain injury; MTP = mathematical processing; MTS = Matching to Sample; PCLM = Post-Traumatic Stress Disorder Checklist Military; PRT = Procedural Reaction Time; RPCSQ = Rivermead Post-Concussion Symptoms Questionnaire; SRT = simple reaction time; 2SRT = repeat SRT.

Figure 3. Reduced fractional anisotropy on diffusion tensor imaging in the right superior longitudinal fasciculus in participants with mTBI

(A) Scatterplot of fractional anisotropy values for each participant. Solid horizontal lines represent the means and the SDs. The dotted horizontal line marks 2 SDs below the mean for CTL. Solid symbol points (triangles for mTBI, squares for CTL) represent participants below this level. (B) Diffusion tensor fractional anisotropy images displaying signal loss in the right superior longitudinal fasciculus in a participant with mTBI compared with a CTL (arrows). Images are displayed in anatomical convention. CTL = controls; mTBI = mild traumatic brain injury.

Figure 4. Correlates of time to return to duty

(A) LOC. (B) Total postconcussive symptom severity scored with the RPCSQ. (C) Change from baseline in simple reaction time on ANAM testing. (D) PTSD symptom severity scored using the PCLM. (E) Depression symptom severity scored using the BDI. (F) Overall prediction of return-to-duty time using a multivariate linear model including LOC, RPCSQ, ANAM, PCLM, and BDI. ANAM = Automated Neuropsychological Assessment Metrics; BDI = Beck Depression Inventory; LOC = loss of consciousness; PCLM = Post-Traumatic Stress Disorder Checklist Military; PTSD = posttraumatic stress disorder; RPCSQ = Rivermead Post-Concussion Symptoms Questionnaire.