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Importance: The best reperfusion strategy in patients with acute minor stroke and large vessel occlusion (LVO) is unknown. Accurately predicting early neurological deterioration of presumed ischemic origin (ENDi) following intravenous thrombolysis (IVT) in this population may help to select candidates for immediate transfer for additional thrombectomy., Objective: To develop and validate an easily applicable predictive score of ENDi following IVT in patients with minor stroke and LVO., Design, Setting, and Participants: This multicentric retrospective cohort included 729 consecutive patients with minor stroke (National Institutes of Health Stroke Scale [NIHSS] score of 5 or less) and LVO (basilar artery, internal carotid artery, first [M1] or second [M2] segment of middle cerebral artery) intended for IVT alone in 45 French stroke centers, ie, including those who eventually received rescue thrombectomy because of ENDi. For external validation, another cohort of 347 patients with similar inclusion criteria was collected from 9 additional centers. Data were collected from January 2018 to September 2019., Main Outcomes and Measures: ENDi, defined as 4 or more points' deterioration on NIHSS score within the first 24 hours without parenchymal hemorrhage on follow-up imaging or another identified cause., Results: Of the 729 patients in the derivation cohort, 335 (46.0%) were male, and the mean (SD) age was 70 (15) years; of the 347 patients in the validation cohort, 190 (54.8%) were male, and the mean (SD) age was 69 (15) years. In the derivation cohort, the median (interquartile range) NIHSS score was 3 (1-4), and the occlusion site was the internal carotid artery in 97 patients (13.3%), M1 in 207 (28.4%), M2 in 395 (54.2%), and basilar artery in 30 (4.1%). ENDi occurred in 88 patients (12.1%; 95% CI, 9.7-14.4) and was strongly associated with poorer 3-month outcomes, even in patients who underwent rescue thrombectomy. In multivariable analysis, a more proximal occlusion site and a longer thrombus were independently associated with ENDi. A 4-point score derived from these variables-1 point for thrombus length and 3 points for occlusion site-showed good discriminative power for ENDi (C statistic = 0.76; 95% CI, 0.70-0.82) and was successfully validated in the validation cohort (ENDi rate, 11.0% [38 of 347]; C statistic = 0.78; 95% CI, 0.70-0.86). In both cohorts, ENDi probability was approximately 3%, 7%, 20%, and 35% for scores of 0, 1, 2 and 3 to 4, respectively., Conclusions and Relevance: The substantial ENDi rates observed in these cohorts highlights the current debate regarding whether to directly transfer patients with IVT-treated minor stroke and LVO for additional thrombectomy. Based on the strong associations observed, an easily applicable score for ENDi risk prediction that may assist decision-making was derived and externally validated.

Background and Purpose: Whether bridging therapy (intravenous thrombolysis [IVT] followed by mechanical thrombectomy) is superior to IVT alone in minor stroke with basilar artery occlusion remains uncertain., Methods: Multicentric retrospective observational study of consecutive minor stroke patients (National Institutes of Health Stroke Scale score ≤5) with basilar artery occlusion intended for IVT alone or bridging therapy. Propensity-score weighting was used to reduce baseline between-groups differences, and residual imbalance was addressed through adjusted logistic regression, with excellent outcome (3-month modified Rankin Scale score 0-1) as the dependent variable., Results: Fifty-seven patients were included (28 and 29 in the bridging therapy and IVT alone groups, respectively). Following propensity-score weighting, the distribution of baseline clinical and radiological variables was similar across the 2 patient groups, except age, posterior circulation Alberta Stroke Program Early CT Score, history of hypertension and smoking, and onset-to-IVT time. Compared with IVT alone, bridging therapy was associated with excellent outcome (adjusted odds ratio=3.37 [95% CI, 1.13-10.03]; P =0.03). No patient experienced symptomatic intracranial hemorrhage., Conclusions: Our results suggest that bridging therapy may be superior to IVT alone in minor stroke with basilar artery occlusion.

Objective: Whether bridging therapy (intravenous thrombolysis [IVT] followed by endovascular treatment) is superior to IVT alone in minor stroke with large vessel occlusion (LVO) is unknown., Methods: Multicentric retrospective observational study including, in intention-to-treat, consecutive IVT-treated minor strokes (National Institutes of Health Stroke Scale [NIHSS] ≤ 5) with LVO, with or without additional mechanical thrombectomy. Propensity-score (inverse probability of treatment weighting) was used to reduce baseline between-groups differences. The primary outcome was excellent outcome, that is, modified Rankin score 0 to 1 at 3 months follow-up., Results: Overall, 598 patients were included (214 and 384 in the bridging therapy and IVT groups, respectively). Following propensity-score weighting, the distribution of baseline clinical and radiological variables was similar across the two patient groups. Compared with IVT alone, bridging therapy was not associated with excellent outcome (odds ratio [OR] = 0.96; 95% confidence interval [CI] = 0.75-1.24; p = 0.76), but was associated with symptomatic intracranial hemorrhage (OR = 3.01; 95% CI = 1.77-5.11; p < 0.0001). Occlusion site was a strong modifier of the effect of bridging therapy on outcome (p interaction < 0.0001), with bridging therapy associated with higher odds of excellent outcome in proximal M1 (OR = 3.26; 95% CI = 1.67-6.35; p = 0.0006) and distal M1 (OR = 1.69; 95% CI = 1.01-2.82; p = 0.04) occlusions, but with lower odds of excellent outcome for M2 (OR = 0.53; 95% CI = 0.38-0.75; p = 0.0003) occlusions. Bridging therapy was associated with higher rates of symptomatic intracranial hemorrhage in M2 occlusions only (OR = 4.40; 95% CI = 2.20-8.83; p < 0.0001)., Interpretation: Although overall outcomes were similar in intended bridging therapy as compared to intended IVT alone in minor strokes with LVO, our results suggest that intended bridging therapy may be beneficial in M1 occlusions, whereas the benefit-risk profile may favor IVT alone in M2 occlusions. ANN NEUROL 2020 ANN NEUROL 2020;88:160-169., (© 2020 American Neurological Association.)

Background and Purpose- In acute stroke patients with large vessel occlusion, the goal of intravenous thrombolysis (IVT) is to achieve early recanalization (ER). Apart from occlusion site and thrombus length, predictors of early post-IVT recanalization are poorly known. Better collaterals might also facilitate ER, for instance, by improving delivery of the thrombolytic agent to both ends of the thrombus. In this proof-of-concept study, we tested the hypothesis that good collaterals independently predict post-IVT recanalization before thrombectomy. Methods- Patients from the registries of 6 French stroke centers with the following criteria were included: (1) acute stroke with large vessel occlusion treated with IVT and referred for thrombectomy between May 2015 and March 2017; (2) pre-IVT brain magnetic resonance imaging, including diffusion-weighted imaging, T2*, MR angiography, and dynamic susceptibility contrast perfusion-weighted imaging; and (3) ER evaluated ≤3 hours from IVT start on either first angiographic run or noninvasive imaging. A collateral flow map derived from perfusion-weighted imaging source data was automatically generated, replicating a previously validated method. Thrombus length was measured on T2*-based susceptibility vessel sign. Results- Of 224 eligible patients, 37 (16%) experienced ER. ER occurred in 10 of 83 (12%), 17 of 116 (15%), and 10 of 25 (40%) patients with poor/moderate, good, and excellent collaterals, respectively. In multivariable analysis, better collaterals were independently associated with ER ( P=0.029), together with shorter thrombus ( P<0.001) and more distal occlusion site ( P=0.010). Conclusions- In our sample of patients with stroke imaged with perfusion-weighted imaging before IVT and intended for thrombectomy, better collaterals were independently associated with post-IVT recanalization, supporting our hypothesis. These findings strengthen the idea that advanced imaging may play a key role for personalized medicine in identifying patients with large vessel occlusion most likely to benefit from IVT in the thrombectomy era.

Background and Purpose- Whether bridging therapy, that is, intravenous thrombolysis [IVT] followed by mechanical thrombectomy, is beneficial as compared with IVT alone in minor stroke (National Institutes of Health Stroke Scale ≤5) with large vessel occlusion is unknown and should be tested in randomized trials. To help select the most appropriate candidates for such trials, we aimed to identify strong predictors of lack of post-IVT early recanalization (ER)-a surrogate marker of poor outcome. Methods- From a large multicenter French registry of patients with large vessel occlusion referred for thrombectomy immediately after IVT start between 2015 and 2017, we extracted 97 minor strokes with ER evaluated on first angiographic run or noninvasive imaging ≤3 hours from IVT start. Thrombus length was measured using the susceptibility vessel sign on T2* imaging. Results- Median National Institutes of Health Stroke Scale was 3 (interquartile range, 2-4), and occlusion sites were proximal (intracranial carotid or M1) and distal (M2) in 50% and 50% of patients, respectively. On pre-IVT MRI, median length of susceptibility vessel sign (visible in 90%) was 9.2 mm (interquartile range, 7.4-13.3). ER was present in 34% of patients, and susceptibility vessel sign length was the only clinical or radiological variable associated with no-ER after stepwise variable selection into a multivariable model (odds ratio, 1.53 per 1-mm increase; 95% CI, 1.21-1.92; P<0.001). The C statistic of susceptibility vessel sign length for no-ER prediction was 0.82 (95% CI, 0.73-0.92), and the optimal cutoff (Youden) was 9 mm. Sensitivity and specificity of this cutoff for no-ER were 67.8% (95% CI, 55.9-79.7) and 84.6% (95% CI, 70.7-98.5), respectively. Conclusions- ER was frequent in this cohort of IVT-treated minor stroke patients with large vessel occlusion considered for thrombectomy, and thrombus length was a powerful independent predictor of no-ER. These findings may help design randomized trials aiming to test bridging therapy versus IVT alone in this population.

Background and Purpose—Whether all acute stroke patients with large vessel occlusion need to undergo intravenous thrombolysis before mechanical thrombectomy (MT) is debated as (1) the incidence of post-thrombolysis early recanalization (ER) is still unclear; (2) thrombolysis may be harmful in patients unlikely to recanalize; and, conversely, (3) transfer for MT may be unnecessary in patients highly likely to recanalize. Here, we determined the incidence and predictors of post-thrombolysis ER in patients referred for MT and derive ER prediction scores for trial design. Methods—Registries from 4 MT-capable centers gathering patients referred for MT and thrombolyzed either on site (mothership) or in a non MT-capable center (drip-and-ship) after magnetic resonance– or computed tomography–based imaging between 2015 and 2017. ER was identified on either first angiographic run or noninvasive imaging. In the magnetic resonance imaging subsample, thrombus length was determined on T2*-based susceptibility vessel sign. Independent predictors of no- ER were identified using multivariable logistic regression models, and scores were developed according to the magnitude of regression coefficients. Similar registries from 4 additional MT-capable centers were used as validation cohort. Results—In the derivation cohort (N=633), ER incidence was ≈20%. In patients with susceptibility vessel sign (n=498), no-ER was independently predicted by long thrombus, proximal occlusion, and mothership paradigm. A 6-point score derived from these variables showed strong discriminative power for no-ER (C statistic, 0.854) and was replicated in the validation cohort (n=353; C statistic, 0.888). A second score derived from the whole sample (including negative T2* or computed tomography–based imaging) also showed good discriminative power and was similarly validated. Highest grades on both scores predicted no-ER with >90% specificity, whereas low grades did not reliably predict ER. Conclusions—The substantial ER rate underlines the benefits derived from thrombolysis in bridging populations. Both prediction scores afforded high specificity for no-ER, but not for ER, which has implications for trial design.

Background and Purpose: Early neurological deterioration (END) after anterior circulation stroke is strongly associated with poor outcome. Apart from straightforward causes, such as intracerebral hemorrhage and malignant edema, the mechanism of END occurring after intravenous thrombolysis remains unclear in most instances. We tested the hypothesis that unexplained END is associated with thrombus extension., Methods: From our database of consecutively thrombolysed patients, we identified anterior circulation stroke patients who had both admission and 24-hour T2* magnetic resonance imaging, visible occlusion on admission magnetic resonance angiography and no recanalization on 24-hour magnetic resonance angiography. END was defined as ≥4 National Institutes of Health Stroke Scale-point deterioration on 24-hour clinical assessment and unexplained END as END without clear cause. The incidence of susceptibility vessel sign extension on T2* imaging, defined as any new occurrence or extension of susceptibility vessel sign from admission to 24-hour follow-up magnetic resonance, was compared between patients with unexplained END and those without END., Results: Of 120 eligible patients for the present study, 22 experienced unexplained END. Susceptibility vessel sign extension was present in 41 (34%) patients and was significantly more frequent in the unexplained END than in the no-END group (59% versus 29%, respectively; adjusted odds ratio=3.96; 95% confidence interval, 1.25-12.53; P=0.02)., Conclusions: In this study, unexplained END occurring after thrombolysis was independently associated with susceptibility vessel sign extension, suggesting in situ thrombus extension or re-embolization. These findings strengthen the need to further investigate early post-thrombolysis administration of antithrombotics to reduce the risk of this ominous clinical event., (© 2016 American Heart Association, Inc.)

Background and Purpose: After the demonstration of efficacy of bridging therapy, reliably predicting early recanalization (ER; ≤3 hours after start of intravenous thrombolysis) would be essential to limit futile, resource-consuming, interhospital transfers. We present the first systematic review on the incidence and predictors of ER after intravenous thrombolysis alone., Methods: We systematically searched for studies including patients solely treated by intravenous thrombolysis that reported incidence of ER and its association with baseline variables. Using meta-analyses, we estimated pooled incidence of ER, including according to occlusion site, and summarized the available evidence regarding predictors of no-ER., Results: We identified 26 studies that together included 2063 patients. The overall incidence of partial or complete ER was 33% (95% confidence interval, 27-40). It varied according to occlusion site: 52% (39-64) for distal middle cerebral artery, 35% (28-42) for proximal middle cerebral artery, 13% (6-22) for intracranial carotid artery, and 13% (0-35) for basilar occlusion. Corresponding rates for complete ER were 38% (22-54), 21% (15-29), 4% (1-8), and 4% (0-22), respectively. Proximal occlusion and higher National Institute of Health Stroke Scale were the most consistent no-ER predictors. Other factors, such as long or totally occlusive thrombus and poor collateral circulation, emerged as potential predictors but will need confirmation., Conclusion: The overall incidence of ER after intravenous thrombolysis is substantial, highlighting the importance of reliably predicting ER to limit futile, interhospital transfers. Incidence of no-ER is particularly high for proximal occlusion and severe strokes. Given the scarcity of published data, further studies are needed to improve no-ER prediction accuracy., (© 2016 American Heart Association, Inc.)

Background and Purpose: Whether to withhold recanalization treatment when the diffusion-weighted imaging (DWI) lesion exceeds a given volume is unsettled. Our aim was to assess the impact of recanalization on outcome in patients with baseline DWI lesion ≥70 mL (DWI≥70 mL) treated ≤4.5 hours from onset. We hypothesized that recanalization is beneficial in a sizeable fraction of these patients and that this is associated with a larger DWI lesion reversal., Methods: We analyzed 267 consecutive patients treated with intravenous recombinant tissue-type plasminogen activator for middle cerebral artery territory stroke in whom an occlusion was present on magnetic resonance angiography and 24-hour recanalization and 90-day clinical outcome could be assessed. After stratification relative to the 70-mL DWI lesion cut point, we calculated the odds ratio for recanalization of the primary arterial occlusive lesion (AOL score ≥2) to predict favorable outcome (modified Rankin scale score ≤2). DWI lesion reversal was compared between recanalizers with DWI≥70 mL with favorable and unfavorable outcomes., Results: Median (interquartile range) DWI lesion volume was 22 mL (10-60), and median onset time to imaging was 116 minutes (86-151). Twelve (22%) of the 54 patients with DWI≥70 mL experienced favorable outcome, of which 9 had recanalized. In patients with DWI≥70 mL, recanalization was significantly associated with favorable outcome after adjustment for age and National Institutes of Health Stroke Scale (odds ratio =4.72 [1.09-20.32]; P=0.0375). Among recanalizers with DWI≥70 mL, absolute and relative DWI reversal volumes were larger in those with favorable as compared with unfavorable outcome (18.8 mL [12.2-47.6] versus 8.5 mL [4.3-31.1]; P=0.17; and 19.6% [10.9-62.8] versus 8.7% [3.9-16.5], respectively; P=0.049)., Conclusions: Patients with DWI lesion volume ≥70 mL can benefit from recanalization after intravenous recombinant tissue-type plasminogen activator. This may partly reflect a larger amount of DWI lesion reversal., (© 2016 American Heart Association, Inc.)

Background and Purpose: Early neurological deterioration (END) after anterior circulation stroke is a serious clinical event strongly associated with poor outcome. Regarding specifically END occurring within 24 hours of intravenous recombinant tissue-type plasminogen activator, apart from definite causes such as symptomatic intracranial hemorrhage and malignant edema whose incidence, predictors, and clinical management are well established, little is known about END without clear mechanism (ENDunexplained)., Methods: We analyzed 309 consecutive patients thrombolysed intravenously ≤4.5 hours from onset of anterior circulation stroke. ENDunexplained was defined as a ≥4-point deterioration on 24-hour National Institutes of Health Stroke Scale, without definite mechanism on concomitant imaging. ENDunexplained and no-END patients were compared for pretreatment clinical and imaging (including magnetic resonance diffusion and diffusion/perfusion mismatch volumes) data and 24-hour post-treatment clinical (including blood pressure and glycemic changes) and imaging (24-hour recanalization) data, using univariate logistic regression. Exploratory multivariate analysis was also performed after variable reduction, with bootstrap analysis for internal validation., Results: Among 33 END patients, 23 (7% of whole sample) had ENDunexplained. ENDunexplained was associated with poor 3-month outcome (P<0.01). In univariate analysis, admission predictors of ENDunexplained included no prior use of antiplatelets (P=0.02), lower National Institutes of Health Stroke Scale score (P<0.01), higher glycemia (P=0.03), larger mismatch volume (P=0.03), and proximal occlusion (P=0.01), with consistent results from the multivariate analysis. Among factors recorded during the first 24 hours, only no recanalization was associated with ENDunexplained in multivariate analysis (P=0.02)., Conclusions: ENDunexplained affected 7% of patients and accounted for most cases of END. Several predictors and associated factors were identified, with important implications regarding underlying mechanisms and potential prevention of this ominous event., (© 2014 American Heart Association, Inc.)

Background and Purpose: In acute ischemic stroke, white matter (WM) is considered more resistant to infarction than gray matter (GM). To test this hypothesis, we compared the fate of WM and GM voxels belonging to the acute diffusion-weighted imaging (DWI) lesion, expecting WM voxels to be more prone to reversal after thrombolysis., Methods: Reversible acute DWI (RAD) lesion was defined voxel-wise as an acute lesion on initial DWI (DWI1) with no visible lesion on 24-hour DWI (DWI2). Only patients with RAD lesions >10 mL and >10% of DWI1 from our previously reported cohort were eligible. The core was defined as voxels hyperintense on DWI1 and DWI2. Semiautomated segmentation of DWI1, core, and RAD lesions, normalization into standard space, and WM/GM segmentation allowed calculations of WM/GM proportions in each region of interest using a voxel-counting algorithm., Results: Thirty patients were eligible (RAD lesion median volume [interquartile range], 23.3 mL [19.1-35.0 mL]; onset-to-treatment time, 134 minutes [105-185 minutes]). WM voxels fraction was greater in RAD lesions than in the core (59.4% [52.8%-68.9%] versus 49.6% [43.0%-57.5%]; P=0.011). The proportion of reversibility was greater for WM than for GM voxels (60.8% [25.5%-88.7%] versus 53.5% [21.1%-77.3%]; P=0.02). The percentage of RAD lesions increased with the proportion of WM present in the acute DWI lesion (P<0.0001; R=0.67)., Conclusions: Acute DWI lesions predominantly involving WM may be more prone to reversal and, hence, to respond to therapy than their GM counterparts.

Background Intravenous thrombolysis (IVT) for patients treated with mechanical thrombectomy (MT) for proximal occlusions has recently been questioned through randomized trials. However, few patients with M2 occlusions were included. We investigated the influence of prior IVT for patients presenting M2 occlusions treated with MT in comparison with MT alone. Methods We conducted a retrospective analysis of the Endovascular Treatment in Ischemic Stroke (ETIS) registry, a multicenter observational study. Data from consecutive patients treated with MT for M2 occlusions between January 2015 and January 2022 at 26 comprehensive stroke centers were analyzed. The primary endpoint was 90-day modified Rankin Scale score of 0-2. Outcomes were compared using propensity score approaches. We also performed sensitivity analysis in relevant subgroups of patients. Results Among 1132 patients with M2 occlusions treated with MT, 570 received prior IVT. The two groups were comparable after propensity analysis. The rate of favorable functional outcome was significantly higher in the IVT+MT group compared with the MT alone group (59.8% vs 44.7%; adjusted OR 1.38, 95% CI 1.10 to 1.75, P=0.008). Hemorrhagic and procedural complications were similar in both groups. In sensitivity analysis excluding patients with anticoagulation treatment, favorable recanalization was more frequent in the IVT+MT group (OR 1.37, 95% CI 1.11 to 1.70, P=0.004). Conclusions In cases of M2 occlusions, prior IVT combined with MT resulted in better functional outcome than MT alone, without increasing the rate of hemorrhagic or procedural complications. These [ABSTRACT FROM AUTHOR]

Background The number of mechanical thrombectomy (MT) passes is strongly associated with angiographic reperfusion as well as clinical outcomes in patients with anterior circulation ischemic stroke. However, these associations have not been analyzed in patients with basilar artery occlusion (BAO). We investigated the influence of the number of MT passes on the degree of reperfusion and clinical outcomes, and compared outcome after ≤3 passes versus >3 passes. Methods We used data from the prospective multicentric Endovascular Treatment in Ischemic Stroke (ETIS) Registry at 18 sites in France. Patients with BAO treated with MT were included. The primary outcome was a favorable outcome, defined as a modified Rankin Scale score of 0-3 at 90 days. We fit mixed multiple regression models, with center as a random effect. Results We included 275 patients. Successful recanalization (modified Thrombolysis In Cerebral Infarction (mTICI) 2b-3) was achieved in 88.4%, and 41.8% had a favorable outcome. The odds ratio for favorable outcome with each pass above 1 was 0.41 (95% CI 0.23 to 0.73) and for recanalization (mTICI 2b-3) it was 0.70 (95% CI 0.57 to 0.87). In patients with ≤3 passes, the rate of favorable outcome in recanalized versus non-recanalized patients was 50.5% versus 10.0% (p=0.001), while in those with >3 passes it was 16.7% versus 15.2% (p=0.901). Conclusions We found that BAO patients had a significant relationship between the number of MT passes and both recanalization and favorable functional outcome. We further found that the benefit of recanalization in BAO patients was significant only when recanalization was achieved within three passes, encouraging at least three passes before stopping the procedure. [ABSTRACT FROM AUTHOR]

Objective: Mechanical thrombectomy (MT) is not recommended for acute stroke with large vessel occlusion (LVO) and a large volume of irreversibly injured tissue ("core"). Perfusion imaging may identify a subset of patients with large core who benefit from MT. Methods: We compared two cohorts of LVO‐related patients with large core (>50 ml on diffusion‐weighted‐imaging or CT‐perfusion using RAPID), available perfusion imaging, and treated within 6 hours from onset by either MT + Best Medical Management (BMM) in one prospective study, or BMM alone in the pre‐MT era from a prospective registry. Primary outcome was 90‐day modified Rankin Scale ≤2. We searched for an interaction between treatment group and amount of penumbra as estimated by the mismatch ratio (MMRatio = critical hypoperfusion/core volume). Results: Overall, 107 patients were included (56 MT + BMM and 51 BMM): Mean age was 68 ± 15 years, median core volume 99 ml (IQR: 72–131) and MMRatio 1.4 (IQR: 1.0–1.9). Baseline clinical and radiological variables were similar between the two groups, except for a higher intravenous thrombolysis rate in the BMM group. The MMRatio strongly modified the clinical outcome following MT (pinteraction < 0.001 for continuous MMRatio); MT was associated with a higher rate of good outcome in patients with, but not in those without, MMRatio>1.2 (adjusted OR [95% CI] = 6.8 [1.7–27.0] vs 0.7 [0.1–6.2], respectively). Similar findings were present for MMRatio ≥1.8 in the subgroup with core ≥70 ml. Parenchymal hemorrhage on follow‐up imaging was more frequent in the MT + BMM group regardless of the MMRatio. Interpretation: Perfusion imaging may help select which patients with large core should be considered for MT. Randomized studies are warranted. ANN NEUROL 2021;90:417–427 [ABSTRACT FROM AUTHOR]

Background: Infarct growth (IG) is used as surrogate end-point in therapeutic trials. For practical reasons, infarct growth is commonly assessed using simple subtraction of acute from follow-up diffusion-weighted imaging (DWI) lesion volumes. However, the volume subtraction method will underestimate true infarct growth in case of diffusion-weighted imaging lesion reversal. Aim: To measure the size of the difference between true infarct growth on voxel-based coregistration and infarct growth approximated with simple volume subtraction. Methods: We retrospectively analyzed 322 consecutive stroke patients (median (IQR) age: 70 years (57-80), National Institute of Health Stroke Score at admission 14 (8-19)), who underwent a magnetic resonance imaging before (DWI1) and ~24 h (DWI2) after IV-thrombolysis. IGvoxel-based was defined as the volume of signal changes on DWI2 that did not overlap with that on coregistered DWI1. This was compared with simply subtracting DWI1 from DWI2 lesion volume (IGsubtracted). We also compared these two metrics for the prediction of three-month unfavorable outcome (mRS ≥ 2) using c-statistics of multivariable models, adjusted for age, and National Institute of Health Stroke Score. Results: Infarct growth volume metrics were strongly correlated (r = 0.94), but IGsubtracted substantially underestimated IGvoxel-based (median (IQR): 9.52 (0.23-38.9) vs. 16.98 (4.4-45.4) mL). Of the 75 patients with shrinking or stable diffusion-weighted imaging lesion using volume subtraction, IGvoxel-based was 2:5 mL in 20 (27% of the subset, 6.2% of the whole population). Moreover, IGvoxel-based better predicted unfavorable outcome than IGsubtracted (c-statistics = 0.86 (95% CI, 0.82-0.90) vs. 0.82 (0.78-0.87), P = 0.003). Conclusion: At early post-thrombolysis time points, the simple subtraction of lesion volumes masked substantial diffusion-weighted imaging lesion growth in 6.2% of patients. Although more time-consuming, the voxel-based method may impact results of trials that use infarct growth attenuation as an end-point. [ABSTRACT FROM AUTHOR]