Christopher Wilkins, MD
Endovascular therapy has become an invaluable tool in the treatment of acute ischemic stroke as it can provide significant improvement in the functional outcome of selected patients. Since its reception, studies have broadened the time window for endovascular therapy by using perfusion imaging during acute ischemic strokes to determine how much cerebral tissue is, or close to be, infarcted (i.e., the core) and comparing it to tissue which has reduced blood flow but is likely salvageable with reperfusion (i.e., the penumbra). The volume of the core, as well as ratio between core and penumbra, ultimately determines which patients are appropriate for endovascular therapy. Studies have shown that cerebral collateral circulation can be a major determinant of final infarct volume and can thus impact who would be deemed appropriate for thrombectomy. However, data on whether the status of collateral circulation impacts final clinical outcome in those undergoing thrombectomy remains discrepant.
In this retrospective study, Al-Dasuqi et al. investigated how collateral status impacts final infarct size, as well as functional outcomes, in those with successful and unsuccessful recanalization following endovascular therapy with either mechanical thrombectomy or intra-arterial thrombolytic drug delivery. The authors selected patients who: had evidence of large vessel occlusion on CTA in the ICA or MCA at the M1 or proximal M2 segment; underwent mechanical thrombectomy or intraarterial thrombolysis, with or without IV-tPA before intervention; had follow up MRI obtained within 24 hours to 7 days post endovascular treatment. The collateral status of patients was defined using a grading system designed by Miteff et al.1 There are 3 grades which include: “good,” where the entire MCA distal to the occluded segment reconstitutes with contrast; “moderate,” where some MCA branches distal to the occluded segment reconstituted in the sylvian fissure; and “poor,” where only distal superficial MCA branches reconstituted distal to the occlusion. Though many different grading systems for collateralization have been created, Al-Dasuqi et al. used the grading system by Miteff et al. because this grading system showed to be reliable in predicting favorable and poor outcomes in patients treated with IV-tPA while other collateral grading systems were of limited value. Successful recanalization was defined by mTICI score of 2b-3. A summation map of all infarct lesions detected on MRI was created to identify regions of infarct associated with mTICI scores and collateral grading. Early functional outcome was measured using the modified Rankin Scale (mRS) at discharge with a favorable outcome defined as mRS score of 0 to 2.
Of the 283 patients included in the study, 129 (45%) had good collateral status while 97 (34%) had moderate and 57 (20%) had poor collateral status. Successful reperfusion was attained in 206 (73%) patients. The summation mapping of infarcts showed that poor collateral status was associated with infarction of the ACA-MCA and MCA-PCA watershed zones, whereas unsuccessful reperfusion was associated with infarction of the deep white matter tracts and the posterior limb of the internal capsule. Summation mapping also showed that infarcts in the left precentral gyrus, left insula, and right caudate nucleus were associated with worse early functional outcome. Both mTICI score (p<0.001) and collateral status (p<0.001) were independent predictors of final infarct volume, but only mTICI score (p<0.001) was associated with favorable early functional outcome. There was no significant correlation between collateral status and symptomatic hemorrhage (p=0.604). Though there appeared to be a higher likelihood of hemorrhagic transformation in those with worse collateral status and higher likelihood of disability in those with hemorrhagic transformation, these associations are not statistically significant after application of the Bonferroni correction which set statistical significance at a p-value <0.001.
The findings of this study suggest that collateral status have an impact on the final volume of infarction. However, the brain areas that may be preserved due to collateral status are less critical to overall neurological function compared to the deep structures persevered by successful reperfusion. This is attributed to successful endovascular therapy preserving areas of the brain, namely the precentral gyrus and posterior internal capsule, that contain the corticospinal tract and impact motor function. This study also suggests that collateral status does not impact the likelihood of having a symptomatic hemorrhage.
The study is limited by the lack of post discharge follow up. There is heterogeneity in the cohort due to some patients undergoing intraarterial thrombolysis while others underwent mechanical thrombectomy, and some patients receiving IV-tPA while others did not. There may have been undersampling of those with poor collateral status as these patients tend to have faster infarct evolution, thus were more likely to be excluded from endovascular therapy.
There continues to be discrepancy in studies investigating the effect of collateral status on functional outcome. For example, this study and another found that collateral status did not have a significant correlation with functional outcome or symptomatic hemorrhage.2 However, other studies have shown that poor collateral status is associated with higher risk of symptomatic hemorrhage and/or worse functional outcome.3,4 Of course, comparing these studies is cumbersome as they use different grading systems to determine collateral status.
Overall, the results of this study emphasize that location of the infarct can be more influential on functional outcome than total infarct volume. However, given the discrepancy between studies, more cohort studies are necessary to investigate the effect of collateral status on functional outcomes in patients undergoing thrombectomy. These future studies should evaluate post-discharge follow-up of patients undergoing thrombectomy to determine if collateral status impacts long-term functional outcomes. Such studies could eventually pave the way for prospective trials that investigate whether location of an infarct and its anticipated functional outcome would be a more accurate determinant of which patients are appropriate for thrombectomy.
References:
- Ferdinand Miteff, Christopher R. Levi, Grant A. Bateman, Neil Spratt, Patrick McElduff, Mark W. Parsons, The independent predictive utility of computed tomography angiographic collateral status in acute ischaemic stroke, Brain, Volume 132, Issue 8, August 2009, Pages 2231–2238, https://doi.org/10.1093/brain/awp155
- Shah VS, Eaton RG, Cua S, et al. Scoring of Middle Cerebral Artery Collaterals Predicts RAPID CT-Perfusion Analysis and Short-Term Outcomes in Acute Ischemic Stroke Patients Undergoing Thrombectomy. World Neurosurg. 2020;135:e494-e499. doi:10.1016/j.wneu.2019.12.033
- Hao Z, Yang C, Xiang L, Wu B, Liu M. Risk factors for intracranial hemorrhage after mechanical thrombectomy: a systematic review and meta-analysis. Expert Rev Neurother. 2019;19(10):927-935. doi:10.1080/14737175.2019.1632191
- Qian J, Fan L, Zhang W, Wang J, Qiu J, Wang Y. A meta-analysis of collateral status and outcomes of mechanical thrombectomy. Acta Neurol Scand. 2020;142(3):191-199. doi:10.1111/ane.13255
