Overall, 353 patients underwent endovascular thrombectomy in the anterior circulation for LVO at both participating centers, and 346 fulfilled all criteria for inclusion in this study. The median age was 76 years (IQR 64–83 years), and the proportion of women was 58%. The median NIHSS at admission was 16 (IQR 12–19), and the proportion of wake-up stroke was 20%. A known history of previous stroke or TIA was present in 37 patients (11%). Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) (IVT) was administered in 187 (54%) patients. Median time from end of EVT and first control CT imaging was 1 day (IQR 1–1 day). Detailed demographic characteristics are listed in Table 1 and information about missing data is given in supplemental Table 1.

The median DT was 9mm (IQR 6–14mm) and was progressively smaller across larger ILV, except for the largest ILV, where no difference between other ILV groups was found (Fig. 2). A larger DT was associated with smaller ILV (ln-transformed), although the effect was small, r (344) = −0.15, p = 0.005 (Supplemental Fig. 1). Additionally, after splitting DT into three equal groups (range of values in mm: 0–7, > 7–12, > 12–28 for proximal, middle, and distal groups, respectively), the association with continuous ILV was significant at p = 0.003. Similarly, continuous DT was significantly associated with the ILV groups 0–15 ml vs. 70.1–200 ml and 15.1–70 ml vs. 70.1–200 ml, at p = 0.047. The measurements made by the two raters, who both have over 5 years of experience in the neurovascular field, demonstrated a high level of agreement in determining the DT on CT/MR images with an intraclass correlation coefficient of 0.87 (95% CI 0.69–0.95) for DT on CTA/MRA images.

Ischemic lesion volume (in ml) in relation to distance to thrombus (in mm) after mechanical thrombectomy in 346 patients with middle cerebral artery M1 occlusion treated during three year period 2018-2020 at two centers

The median ILV was 13.9 ml (IQR 2.2–53.1 ml). Age was significantly, albeit complexly, associated with ILV. The group with the largest ILV was the youngest; generally, the age had a negative correlation with ILV, r (345) = −0.13, p = 0.013. Patients waking up with stroke symptoms had significantly larger ILV (40.8 ml vs. 11.1 ml, p < 0.001). A lower ASPECTS score was predictive of a larger ILV (51.0 ml vs. 11.0 ml, p < 0.001). Good LC was protective for larger ILV (equal group having 5.8 ml vs. absent group having 17.3 ml, p = 0.021). Procedure time was the shortest in the smallest ILV group (35 min vs. 67 min. for 0–15 ml vs. 70.1–200 ml group, respectively, p < 0.001). Both devices used were associated with the largest ILV (13.9 ml vs. 8.7 ml for aspiration + stent retriever vs. aspiration only, p = 0.021). Total EVT passes performed were also positively correlated with ILV, 3 (IQR 2-4) steps in the largest ILV group, p < 0.001. Unsuccessful EVT measured by mTICI was associated with larger ILV (96.2 ml vs. 11.5 ml for 0–2a vs. 2b–3 mTICI outcome, respectively, p < 0.001) (Table 2). With an intraclass correlation coefficient 0.78 (CI 0.54–0.91) for ischemic infarct volume, good agreement in determining the ischemic lesion volume was also shown.

There were 64 (18%) missing mRS data. Therefore, the logistic regression analysis was performed on 282 patients. Good outcome (0–2 at 3 months) was recorded in 139 (49%) patients. Age (71 vs. 79 years, OR 0.96, CI 0.96–0.98, p < 0.001), not taking vitamin K oral anticoagulant (OAC) (1% vs. 7%, OR 0.20, CI 0.03–0.77, p = 0.038), thrombolysis (61% vs. 47%, OR 1.68, CI 1.05–2.70, p = 0.030), ASPECTS > 6 (93% vs. 83%, OR 2.58, CI 1.22–5.87, p = 0.017), less total thrombectomy steps performed (1 vs. 2, OR 0.82, 0.70–0.95, p = 0.009), successful first pass (59% vs. 52%, OR 2.44, CI 1.50–3.98, p < 0.001), 2b and 3 vs. 0–2a TICI outcome (94% vs. 86%, OR 0.34, CI 0.14–0.77, p = 0.013), lower ln-ILV (3.9 vs. 35.9, OR 0.61, CI 0.52–0.71, p < 0.001) were all associated with good outcome (Supplemental Table 2). The above predictors entered multivariate logistic regression analysis.

After adjusting for variables listed in the methods, R2 showed that our model only modestly explains (~27%) the variance in the ordinal dependent variable ILV. The best predictive value was observed for ILV 0–15ml and 15.1–70ml at p = 0.001. The most significant effect on ILV was for unsuccessful EVT measured by mTICI, raising the odds for larger ILV with an OR of 7.17 (CI 3.64–14.29). Stent retriever device usage (alone or with aspiration device) heightened odds for larger ILV, with an OR of 1.55 (CI 1.01–2.40), as was ASPECTS > 6 with an OR of 0.27 (CI 0.15–0.51). Finally, the DT per mm increase lowered the odds for larger ILV, with an OR of 0.96 (CI 0.92–0.99), p = 0.048 (Table 3).

After adjusting for variables showing p < 0.1 on univariate analysis (e.g., age, NIHSS at admission, vitamin K OAC, known time of symptom onset, systemic thrombolysis, ASPECTS > 6, good or equal LC, ipsilateral ICA diameter, total thrombectomy steps performed, successful first pass, TICI 0–2a, vessel perforation, hemorrhagic transformation type, ln-transformed ILV), the following variables showed a significant and negative association with good clinical outcome at 3 months: age (OR 0.94, 95% CI 0.91–0.96, p < 0.001), NIHSS at admission (OR 0.87, 95% CI 0.81–0.93, p < 0.001), class 3a–d hemorrhagic transformation vs. class I (OR 0.16, 95% CI 0.03–0.83, p = 0.03), ln-transfomed ILV (OR 0.52, 95% CI 0.40–0.67, p < 0.001) (Supplemental Table 3).

The mediation model in which DT was considered as a predictor, ILV a mediator, and good clinical outcome at 3 months as an outcome, indicated that the effect of distance to a thrombus (i.e., longer DT) on the clinical outcome at 3 months (mRS 0–2 vs. 3–6) was fully mediated via the ln-transformed infarct volume. The indirect effect of distance to thrombus in the mediation model was small: 0.005; however, it was statistically significant (p = 0.018). After adjusting for age, thrombectomy outcome, and ASPECTS (> 6 vs. ≤ 6), the mediation stayed statistically significant (p = 0.016); however, the effect was small at 0.004.