In this paper we assessed how traumatic hemorrhagic lesions progressed following moderate-to-severe TBI, and how this progression is related to neurological outcome. Contusions were the most common lesion type, and progressed more, and for a longer period of time, than SDH, EDH and tSAH. Total LPV was also independently associated with 12-month GOS. To the best of our knowledge, this is the first study to arrive at these conclusions by combining volumetric lesion analysis with temporal data in TBI patients.
This study confirms previous observations that lesion progression is more common in contusions than EDH, SDH and tSAH [2, 4, 5, 20]. In addition, we found that the mean total LPV was 3.85 ml, with contusions expanding the most of any lesion type. Our mean contusion progression volume of 4.72 ml is comparable to the 6.0 ml seen in the control group of a recent CENTER-TBI study on the effects of antiplatelet therapy on contusion expansion . We also found that lesions stopped progressing within a median of 5.98 hours, with contusions progressing the longest of any lesion type. These findings shed light on a potential time-window for interventions that target hematoma expansion. The differences in LPV and LPT between contusions and extra-axial hematomas may be due to their underlying pathophysiology; while the growth of extra-axial hematomas can be credited to bleeding from damaged vessels, contusion progression has also been attributed to the effects of a traumatic penumbra surrounding the lesion, where molecular processes may lead to delayed microvessel structural failure and bleeding progression, even in regions that appear to be unaffected on the first CT scan . Our identification of a trend towards decreasing lesion volume change over time (Fig. 5), also indicates that treatment delay will reduce the potential for hemostatic agents to prevent intracranial bleeding. This is supported by results from the CRASH-3 trial of tranexamic acid in TBI , which found that early treatment conferred the greatest mortality benefit. However, while the CRASH-3 study employed a time window for eligibility of 3 hours, our finding that many lesions progress beyond this limit might enable future studies of other hemostatic agents to expand this window, especially in contusion subgroups, as long as the risk of progression outweighs that of thrombotic complications.
Although some studies have reported that lesion progression is associated with neurological outcome, this has not consistently been observed . Juratli and colleagues showed that patients with contusion progression were more likely to show a modified Rankin Scale score ≥ 4 at follow-up , and Cepeda et al found that both the presence and volume of progression were associated with 6-month unfavorable GOS . Similarly, Qureshi et al reported a higher proportion of patients with favorable 6-month Extended GOS (GOSE) in those without lesion progression . While these studies demonstrated univariate associations between lesion progression and neurological outcome, the associations did not remain significant in multivariate analyses, leading to a belief that lesion progression might represent severe TBI rather than have a direct impact on outcome . It is therefore interesting that total LPV was independently associated with 12-month GOS in our study, even after adjusting for other known TBI outcome predictors . This is consistent with a hypothesis that lesion expansion is a driver, and not simply a marker, of severe injury and poor outcome. Total LPV had an explanatory power (pseudo-R2) of 0.082 – lower than GCS (pseudo-R2 = 0.130), age (pseudo-R2 = 0.094) and bilateral dilated pupils (pseudo-R2 = 0.094), but higher than the explanatory power of EDH (pseudo-R2 = 0.057). It was also the only independent outcome predictor that is potentially preventable, highlighting its role as a potential therapeutic opportunity to improve outcome in TBI patients.
Our omission of non-operated lesions tended to exclude large extra-axial hematomas, as they were more likely to be surgically treated. For example, 40 % (185/458) of SDHs and 61 % (95/157) of EDHs were evacuated, as compared to 10 % of contusions (51/491), with evacuated lesions being significantly larger than those managed conservatively (Supplementary table 1). This likely contributed to the fact that contusions appeared to progress for longer periods of time and to a greater extent than EDH or SDH. Requiring at least 2 CT scans within 48 hours also excluded the most severely injured patients who passed away before a second CT scan could be performed, as well as the less injured patients who did not receive a second CT scan within this time frame. Highlighting this, out of the 21 patients excluded due to only 1 CT scan performed, 17 (81 %) passed away during hospitalization. LPT was also highly dependent on the timing of the second and third CT scans, and we can therefore only conclude that a lesion stopped progressing within a certain time frame, rather than at a certain time point. Lastly, we deliberately refrained from identifying predictors of lesion progression, as we considered it to be beyond the scope of this manuscript. Instead, we plan on doing so in a more detailed manner in future studies. Despite these limitations, our study draws strength from the large study population, volumetric calculation of lesion sizes, consideration of the time of injury, and continuous rather than binary measurement of lesion progression. For this reason, we believe that this study provides important information on the progression of traumatic intracranial lesions and how this may affect outcome.