Neuroanatomical substrates and symptoms associated with magnetic resonance imaging of patients with mild traumatic brain injury: a CENTER-TBI study

Abstract

Importance: Persistent symptoms after mild traumatic brain injury (mTBI) represent a major public health problem. Objective: To identify neuroanatomical substrates of mTBI and the optimal timing for magnetic resonance imaging (<72h or 2-3 weeks post-injury). Design: Prospective multi-center cohort encompassing all eligible patients from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study (2014–2017) and a local cohort (2012–2013), analysed 2019-2020. Setting: Multi-center European-based Participants: Patients presented to hospital within 24h of a mTBI (Glasgow Coma Score 13–15), satisfied local criteria for computed tomography scanning and received two magnetic resonance scans: <72h (MR1) and 2-3 weeks post-injury (MR2). Additionally, 104 controls were enrolled across all sites. Exposures: mild traumatic brain injury Main outcomes and measures: Volumes and diffusion parameters were extracted via automated bespoke pipelines. Symptoms were measured using the Rivermead post-concussion symptoms questionnaire acutely and the Glasgow Outcome Scale Extended at three months. Results: In this cohort study of 81 patients (73 CENTER-TBI, 8 local), with a median age of 45 years (range 14–85), 57 (70%) were men. Structural sequences were available for all scans, diffusion data for 73 MR1s and 79 MR2s. After adjustment for multiple comparisons between timepoints, visible lesions did not differ significantly, but cerebral white matter volume decreased (MR1/MR2 [95% CI]: 0.98 [0.96-0.99]) and ventricular volume increased (MR1/MR2 [95% CI]: 1.06 [1.02-1.10]). White matter volume was normal on MR1 (patient/control [95% CI]: 0.99 [0.97-1.01]) and reduced on MR2 (patient/control [95% CI]: 0.97 [0.95-0.99]). Diffusion parameters changed significantly between scans in 13 tracts, following one of three trajectories: progressive injury, minimal change, or pseudonormalisation. Symptoms worsened, improved or were variable in the three groups, respectively (median [Q1–Q3]: +5.00 [+2.00–+5.00], -4.5 [-9.25–+1.75], 0.00 [-6.25–+9.00], p=0.02). Recovery was favorable for 33/65 (51%) patients and was more closely associated with MR1 than MR2 (area under the curve [95% CI]: 0.87 [0.78–0.96] vs. 0.75 [0.62–0.87], p = 0.009). Conclusions and Relevance: Advanced MRI reveals potential neuroanatomical substrates of mTBI in white matter and correlates best with odds of recovery if done <72h, although future validation is required.