Contusion Volume is a Cross-cohort Predictor of Delayed Seizures after Traumatic Brain Injury
Discuss this preprint
Start a discussion What are Sciety discussions?Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Objective
Predicting specific cognitive, psychiatric, and health-related sequelae in patients after acute traumatic brain injury (TBI) remains an important but challenging clinical problem. Acute phase computed tomography (CT) scans acquired show hemorrhagic contusions, a common type of traumatic pathology. However, whether CT-measured contusions predict long-term sequelae is uncertain.
Methods
We established a Screening Cohort of patients with acute TBI who received care at a single TBI Model Systems (TBIMS) inpatient rehabilitation facility. Regions of hemorrhagic contusion and edema were labeled on acute brain CT scans using the fully-automated Brain Lesion Analysis and Segmentation Tool (BLAST-CT). We screened 198 outcome variables at 1-year post-injury for association with acute hemorrhagic contusion volume using the Harrell’s Concordance index (C-index), controlling for multiple comparisons using 5,000 outcome permutations. Finally, we tested whether the significant associations in the TBIMS database replicated in acute (Transforming Research and Clinical Knowledge in TBI [TRACK-TBI]) and chronic (Vietnam Head Injury Study [VHIS]) external validation cohorts.
Results
The TBIMS Screening Cohort included 345 participants (mean ± SD age: 55.7 ± 21.5 years) with median [IQR] contusion volume 2.3 cc [0.1, 14.6]. Among 198 candidate outcome variables, only delayed seizures were significantly associated with acute hemorrhagic contusion volume (C-index = 0.81; P FWE = 0.007). Contusion volume was not significantly associated with commonly-used measures of global functioning like the Glasgow Outcome Scale Extended, (C-index = 0.55; P FWE = 1). Within the screening cohort, 30 ccs was the optimal volume threshold for discriminating patients with versus without delayed seizures (OR 12.6, 95% CI: [4.6, 34.3]). Contusions larger than 30 cc remained significantly associated with delayed seizures in two external cohorts: (TRACK-TBI OR 4.1 [1.5, 11.2]; VHIS OR 3.2 [1.7, 6.2]).
Interpretation
Across three cohorts of patients with TBI, CT-derived contusion volume is robustly associated with the development of delayed seizures, in contrast to commonly-used outcomes measuring global functioning. A 30-cc volume threshold can be used to improve epilepsy prediction models and enrich populations for clinical trials.
