Discussion
edema, thrombus, no-reflow, neurotoxic, excitotoxicity
LYSING, EDEMA, THROMBUS, LEAKAGE
In this study where patients were randomized to receive or not receive IVT before EVT, we showed no significant association between treatment with IVT before EVT with the occurrence or extent of late lesion growth in the post-treatment subacute period (between 24 hours and 1 week). The lesion continues to evolve after treatment, which is line with previous studies from our research group. Furthermore, we showed that late lesion growth is associated with worse functional outcome and that IVT does not influence this association between late lesion growth and worse functional outcome.There are no previous studies assessing the influence of IVT on late lesion growth after treatment. There is little consensus on the influence of IVT on lesion growth in the pre- and post-treatment time window. In two previous studies, lesion growth in the pre- and 24-hour post-treatment window was also comparable between patients that did and did not receive IVT.In our study, we did not find the significant differences in lesion volume and late lesion growth in patients that did and did not receive tPA. Alteplase is a fibrin specific activator that helps in the conversion of plasminogen to plasmin, thereby softening the occluding thrombus. This may facilitate easier thrombectomy or even lysing the residual and/or distal thrombus fragments that can be formed during the intervention, thereby reducing late lesion growth. On the other hand, tPA may also be neurotoxic, especially when the blood flow has not been restored to the downstream territory. In such scenarios, the pressure inside the vessels increases, opening tight junctions within the endothelium allowing the leakage of tPA across the blood-brain barrier and injuring both the neurovascular unit and the brain parenchyma. This may lead to increase in excitotoxicity, more blood-brain barrier injury, and edema.Similar to the findings in our population, several studies have shown that patients with successful treatment have lower lesion volumes at 24 hours and 1 week.In this study we showed that despite accounting for treatment success and the 24-hour lesion volume, the late, post-treatment lesion growth is still associated with worse clinical outcome. This finding is in line with previous studies from our group.Our study has some limitations. By only including the patients that received NCCT at 24-hours and 1-week, we included less than a third of the trial population. This has led to reduction of statistical power, to assess the effect of thrombus fragmentation and no-reflow phenomenon (especially in the direct IAT treatment arm) on lesion volumes and growth, and validating our group’s previous findings that post-treatment lesion growth is independently associated with an unfavorable functional outcome (mRS ≤ 2).