Neuroanatomical Substrates and Symptoms Associated With Magnetic Resonance Imaging of Patients With Mild Traumatic Brain Injury

This multicenter cohort study assesses neuroanatomical substrates in patients with mild traumatic brain injury and the optimal timing for magnetic resonance imaging. Question What neuroanatomical changes are associated with symptoms after mild traumatic brain injury (mTBI), and when is the optimal time for acute imaging? Findings In this multicenter cohort study, 81 patients with mTBI underwent advanced magnetic resonance imaging within 72 hours and 2 to 3 weeks after injury. White matter volume and integrity evolved during that window in tandem with symptoms and were most closely associated with clinical recovery if imaging was performed within 72 hours. Meaning These findings suggest that white matter injury is associated with symptoms after mTBI and could, if detected early, help select patients at risk of poor outcome for clinical follow-up or interventional trials. 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 (MRI). Design, Setting, and Participants This prospective multicenter cohort study encompassed all eligible patients from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study (December 19, 2014, to December 17, 2017) and a local cohort (November 20, 2012, to December 19, 2013). Patients presented to the hospital within 24 hours of an mTBI (Glasgow Coma Score, 13-15), satisfied local criteria for computed tomographic scanning, and underwent MRI scanning less than 72 hours (MR1) and 2 to 3 weeks (MR2) after injury. In addition, 104 control participants were enrolled across all sites. Data were analyzed from January 1, 2019, to December 31, 2020. Exposure Mild TBI. Main Outcomes and Measures Volumes and diffusion parameters were extracted via automated bespoke pipelines. Symptoms were measured using the Rivermead Post Concussion Symptoms Questionnaire in the short term and the extended Glasgow Outcome Scale at 3 months. Results Among the 81 patients included in the analysis (73 CENTER-TBI and 8 local), the median age was 45 (interquartile range [IQR], 24-59; range, 14-85) years, and 57 (70.4%) were male. Structural sequences were available for all scans; diffusion data, for 73 MR1 and 79 MR2 scans. After adjustment for multiple comparisons between scans, visible lesions did not differ significantly, but cerebral white matter volume decreased (MR2:MR1 ratio, 0.98; 95% CI, 0.96-0.99) and ventricular volume increased (MR2:MR1 ratio, 1.06; 95% CI, 1.02-1.10). White matter volume was within reference limits on MR1 scans (patient to control ratio, 0.99; 95% CI, 0.97-1.01) and reduced on MR2 scans (patient to control ratio, 0.97; 95% CI, 0.95-0.99). Diffusion parameters changed significantly between scans in 13 tracts, following 1 of 3 trajectories. Symptoms measured by Rivermead Post Concussion Symptoms Questionnaire scores worsened in the progressive injury phenotype (median, +5.00; IQR, +2.00 to +5.00]), improved in the minimal change phenotype (median, -4.50; IQR, -9.25 to +1.75), and were variable in the pseudonormalization phenotype (median, 0.00; IQR, -6.25 to +9.00) (P = .02). Recovery was favorable for 33 of 65 patients (51%) and was more closely associated with MR1 than MR2 (area under the curve, 0.87 [95% CI, 0.78-0.96] vs 0.75 [95% CI, 0.62-0.87]; P = .009). Conclusions and Relevance These findings suggest that advanced MRI reveals potential neuroanatomical substrates of mTBI in white matter and is most strongly associated with odds of recovery if performed within 72 hours, although future validation is required.

Automated summary

The study found that white matter injury is associated with symptoms after mild traumatic brain injury (mTBI), and performing imaging within 72 hours of injury can better predict clinical recovery. This could help in identifying high-risk patients for clinical follow-up or interventional trials.