Acute Endovascular Treatment of Patients With Ischemic Stroke From Intracranial Large Vessel Occlusion and Extracranial Carotid Dissection

Introduction: Carotid artery dissection (CAD) and atherosclerotic carotid artery occlusion (ACAO) are major causes of a tandem occlusion in patients with intracranial large vessel occlusion (LVO). Presence of tandem occlusions may hamper intracranial access and potentially increases the risk of procedural complications of endovascular treatment (EVT). Our aim was to assess neurological, functional and technical outcome and complications of EVT for intracranial LVO in patients with CAD in comparison to patients with ACAO and to patients without CAD or ACAO.Methods: We analyzed data of the MR CLEAN trial intervention arm and MR CLEAN Registry, acquired in 16 Dutch EVT-centers. Primary outcome was the change in stroke severity by comparing the National Institute of Health Stroke Scale (NIHSS) score at 24–48 h after treatment vs. baseline. Secondary outcomes included reperfusion rate and symptomatic intracranial hemorrhage (sICH). We compared outcomes and complications between patients with CAD vs. patients with ACAO and patients without CAD or ACAO.Results: In total, we identified 74 (4.7%) patients with CAD, 92 (5.9%) patients with ACAO and 1398 (89.4%) patients without CAD or ACAO. Neurological improvement at short-term after EVT in patients with CAD was significantly better compared to ACAO (resp. mean −5 vs. mean −1 NIHSS point; p = 0.03) and did not differ compared to patients without CAD or ACAO (−4 NIHSS points; p = 0.62). Rates of successful reperfusion in patients with CAD (47%) was comparable to patients with ACAO (47%; p = 1.00), but was less often achieved compared to patients without CAD or ACAO (58%; p = 0.08). Occurrence of sICH did not differ significantly between CAD patients (5%) and ACAO (11%; p = 0.33) or without CAD/ACAO (6%; p = 1.00).Conclusion: EVT in patients with intracranial LVO due to CAD results in neurological improvement comparable to patients without tandem occlusions. Therefore, carotid artery dissection by itself should not be a contraindication for endovascular treatment in stroke patients with intracranial large vessel occlusion. Although more challenging endovascular procedures are to be suspected in both patients with CAD or ACAO, accurate distinction between CAD and ACAO might influence clinical decision making as better clinical outcome can be expected in patients with CAD

Influence of Onset to Imaging Time on Radiological Thrombus Characteristics in Acute Ischemic Stroke

Introduction: Radiological thrombus characteristics are associated with patient outcomes and treatment success after acute ischemic stroke. These characteristics could be expected to undergo time-dependent changes due to factors influencing thrombus architecture like blood stasis, clot contraction, and natural thrombolysis. We investigated whether stroke onset-to-imaging time was associated with thrombus length, perviousness, and density in the MR CLEAN Registry population.Methods: We included 245 patients with M1-segment occlusions and thin-slice baseline CT imaging from the MR CLEAN Registry, a nation-wide multicenter registry of patients who underwent endovascular treatment for acute ischemic stroke within 6.5 h of onset in the Netherlands. We used multivariable linear regression to investigate the effect of stroke onset-to-imaging time (per 5 min) on thrombus length (in mm), perviousness and density (both in Hounsfield Units). In the first model, we adjusted for age, sex, intravenous thrombolysis, antiplatelet use, and history of atrial fibrillation. In a second model, we additionally adjusted for observed vs. non-observed stroke onset, CT-angiography collateral score, direct presentation at a thrombectomy-capable center vs. transfer, and stroke etiology. We performed exploratory subgroup analyses for intravenous thrombolysis administration, observed vs. non-observed stroke onset, direct presentation vs. transfer, and stroke etiology.Results: Median stroke onset-to-imaging time was 83 (interquartile range 53–141) min. Onset to imaging time was not associated with thrombus length nor perviousness (β 0.002; 95% CI −0.004 to 0.007 and β −0.002; 95% CI −0.015 to 0.011 per 5 min, respectively) and was weakly associated with thrombus density in the fully adjusted model (adjusted β 0.100; 95% CI 0.005–0.196 HU per 5 min). The subgroup analyses showed no heterogeneity of these findings in any of the subgroups, except for a significantly positive relation between onset-to-imaging time and thrombus density in patients transferred from a primary stroke center (adjusted β 0.18; 95% CI 0.022–0.35).Conclusion: In our population of acute ischemic stroke patients, we found no clear association between onset-to-imaging time and radiological thrombus characteristics. This suggests that elapsed time from stroke onset plays a limited role in the interpretation of radiological thrombus characteristics and their effect on treatment results, at least in the early time window

Informal modernism - spontaneous building in Mexico City

Die überall aufragenden Betonstützen der unfertigen Selbstbau-Häuser sind in Mexiko-Stadt zum Symbol des spontanen Bauens geworden. Gleichzeitig haben die chaotischen Hüttensiedlungen längst einem routinierten Selbsthilfe-Städtebau Platz gemacht, der das Wohnungsproblem informell, aber gut organisiert und im großen Stil angeht. So kann man auch von einer improvisierten oder "informellen Moderne" sprechen, die sich die Menschen überall dort geschaffen haben, wo die formelle Stadtplanung und Wohnungsversorgung versagt oder auf halbem Wege stecken geblieben ist.The looming concrete columns of unfinished self-help-houses in Mexico City have become a symbol of spontaneous building worldwide. At the same time, the chaotic clusters of miserable huts have long since made way for a routinized self help urbanism, which approaches the housing problem informally, yet well organized and on a large scale. Thus one may speak of an improvised or "informal modernism" that people have created everywhere, where formal city planning and housing has either failed or gotten stuck midway

Advancements in diagnostic and interventional radiology for stroke treatment: the path from trial to bedside through the pre-MR CLEAN, MR CLEAN, and MR CLEAN II eras

Abstract The stroke field is inevitably connected with imaging in which radiologists fulfill a central role. Our landmark MR CLEAN trial led to the implementation of baseline computed tomography angiography or magnetic resonance angiography in the acute stroke workup and subsequent endovascular treatment (EVT) for ischemic stroke patients with a large vessel occlusion in the anterior circulation, resulting in numerous patients worldwide currently being treated often successfully. A reversal of the pathophysiologic process behind an acute cerebrovascular event was made possible. Subsequently, in the MR CLEAN II trials, the clinical impact of both diagnostic and interventional radiologists remained a cornerstone of our research, which means value-based radiology. Within these MR CLEAN II trials, we proved that aspirin and heparin during EVT should be avoided due to increased symptomatic intracranial hemorrhage risk (MR CLEAN-MED). We concluded there is additional benefit of EVT in the 6-to-24-h window after stroke in the presence of good collaterals on baseline CTA (MR CLEAN-LATE). The impactful success of our stroke trials that changed many guidelines was mainly attributable to (1) the societal burden of the disease, with two thirds of patients dying or being independent at 3 months; (2) the fact that stroke is a common disease, (3) the relatively simple and pragmatic approach of the trials resembling real-world setting; (4) the acceleration of implementation in clinical practice facilitated by a structured approach to guideline development and conditional funding; and foremost (5) the excellent collaboration on a professional level between-disciplines, i.e., diagnostic radiologists, interventionalists, and neurologists. Critical relevance statement The MR CLEAN and MR CLEAN II trials have had tremendous impact on clinical practice, directly by more patients being treated with an effective intervention and indirectly through adoption of evidence-based guidelines. It is in this setting of stroke treatment that diagnostic and interventional radiologists have played a crucial role and created clinical impact

Sensitivity of prehospital stroke scales for different intracranial large vessel occlusion locations

Introduction: Prehospital stroke scales have been proposed to identify stroke patients with a large vessel occlusion to allow direct transport to an intervention centre capable of endovascular treatment (EVT). It is unclear whether these scales are able to detect not only proximal, but also more distal treatable occlusions. Our aim was to assess the sensitivity of prehospital stroke scales for different EVT-eligible occlusion locations in the anterior circulation. Patients and methods: The MR CLEAN Registry is a prospective, observational study in all centres that perform EVT in the Netherlands. We included adult patients with an anterior circulation stroke treated between March 2014 and November 2017. We used National Institutes of Health Stroke Scale scores at admission to reconstruct previously published prehospital stroke scales. We compared the sensitivity of each scale for different occlusion locations. Occlusions were assessed with CT angiography by an imaging core laboratory blinded to clinical findings. Results: We included 3021 patients for the analysis of 14 scales. All scales had the highest sensitivity to detect internal carotid artery terminus occlusions (ranging from 0.21 to 0.97) and lowest for occlusions of the M2 segment (0.08 to 0.84, p-values &lt; 0.001). Discussion and conclusion: Although prehospital stroke scales are generally sensitive for proximal large vessel occlusions, they are less sensitive to detect more distal occlusions.</p

The Role of Edema in Subacute Lesion Progression After Treatment of Acute Ischemic Stroke

Background: Ischemic lesions commonly continue to progress even days after treatment, and this lesion growth is associated with unfavorable functional outcome in acute ischemic stroke patients. The aim of this study is to elucidate the role of edema in subacute lesion progression and its influence on unfavorable functional outcome by quantifying net water uptake. Methods: We included all 187 patients from the MR CLEAN trial who had high quality follow-up non-contrast CT at 24 h and 1 week. Using a CT densitometry-based method to calculate the net water uptake, we differentiated total ischemic lesion volume (TILV) into edema volume (EV) and edema-corrected infarct volume (ecIV). We calculated these volumes at 24 h and 1 week after stroke and determined their progression in the subacute period. We assessed the effect of 24-h lesion characteristics on EV and ecIV progression. We evaluated the influence of edema and edema-corrected infarct progression on favorable functional outcome after 90 days (modified Rankin Scale: 0–2) after correcting for potential confounders. Lastly, we compared these volumes between subgroups of patients with and without successful recanalization using the Mann–Whitney U-test. Results: Median TILV increased from 37 (IQR: 18–81) ml to 68 (IQR: 30–130) ml between 24 h and 1 week after stroke, while the net water uptake increased from 22 (IQR: 16–26)% to 27 (IQR: 22–32)%. The TILV progression of 20 (8.8–40) ml was mostly caused by ecIV with a median increase of 12 (2.4–21) ml vs. 6.5 (2.7–15) ml of EV progression. Larger TILV, EV, and ecIV volumes at 24 h were all associated with more edema and lesion progression. Edema progression was associated with unfavorable functional outcome [aOR: 0.53 (0.28–0.94) per 10 ml; p-value: 0.05], while edema-corrected infarct progression showed a similar, non-significant association [aOR: 0.80 (0.62–0.99); p-value: 0.06]. Lastly, edema progression was larger in patients without successful recanalization, whereas ecIV progression was comparable between the subgroups. Conclusion: EV increases in evolving ischemic lesions in the period between 1 day and 1 week after acute ischemic stroke. This progression is larger in patients without successful recanalization and is associated with unfavorable functional outcome. However, the extent of edema cannot explain the total expansion of ischemic lesions since edema-corrected infarct progression is larger than the edema progression.</p

Value of CT Perfusion for Collateral Status Assessment in Patients with Acute Ischemic Stroke

Good collateral status in acute ischemic stroke patients is an important indicator for good outcomes. Perfusion imaging potentially allows for the simultaneous assessment of local perfusion and collateral status. We combined multiple CTP parameters to evaluate a CTP-based collateral score. We included 85 patients with a baseline CTP and single-phase CTA images from the MR CLEAN Registry. We evaluated patients' CTP parameters, including relative CBVs and tissue volumes with several time-to-maximum ranges, to be candidates for a CTP-based collateral score. The score candidate with the strongest association with CTA-based collateral score and a 90-day mRS was included for further analyses. We assessed the association of the CTP-based collateral score with the functional outcome (mRS 0-2) by analyzing three regression models: baseline prognostic factors (model 1), model 1 including the CTA-based collateral score (model 2), and model 1 including the CTP-based collateral score (model 3). The model performance was evaluated using C-statistic. Among the CTP-based collateral score candidates, relative CBVs with a time-to-maximum of 6-10 s showed a significant association with CTA-based collateral scores (p = 0.02) and mRS (p = 0.05) and was therefore selected for further analysis. Model 3 most accurately predicted favorable outcomes (C-statistic = 0.86, 95% CI: 0.77-0.94) although differences between regression models were not statistically significant. We introduced a CTP-based collateral score, which is significantly associated with functional outcome and may serve as an alternative collateral measure in settings where MR imaging is not feasible

Supplementary Material for: Is Intra-Arterial Treatment for Acute Ischemic Stroke Less Effective in Women than in Men?

<i>Introduction:</i> Stroke etiology and outcome after ischemic stroke differ between men and women. We examined if sex modifies the effect of intra-arterial treatment (IAT) in a randomized clinical trial of IAT for acute ischemic stroke in the Netherlands (MR CLEAN). <i>Patients and Methods:</i> The primary outcome was the score on the modified Rankin scale at 90 days. We tested for interaction between sex and treatment and estimated the treatment effect by sex with multiple ordinal logistic regression with adjustment for prognostic factors. <i>Results:</i> All 500 patients were included in the analysis; 292 (58.4%) were men. The treatment effect (adjusted common odds ratio) was 2.39 [95% confidence interval (CI) 1.55-3.68] in men and 0.99 (95% CI 0.60-1.66) in women (pinteraction = 0.016). In women, mortality was higher in the intervention group than in the control group (24 vs. 15%, p = 0.07). Serious adverse events occurred more often in women than in men undergoing intervention. There were no differences in neuro-imaging outcomes. <i>Discussion and Conclusion:</i> Contrary to other studies, we found a significant interaction between sex and treatment effect in the MR CLEAN trial. Pooled analyses of all published thrombectomy trials did not confirm this finding. In MR CLEAN, women seem to have a slightly more unfavorable profile, causing higher mortality and more serious adverse events, but insufficient to explain the absence of an overall effect. This suggests a play of chance and makes it clear that IAT should not be withheld in women

Outcome prediction based on automatically extracted infarct core image features in patients with acute ischemic stroke

Infarct volume (FIV) on follow-up diffusion-weighted imaging (FU-DWI) is only moderately associated with functional outcome in acute ischemic stroke patients. However, FU-DWI may contain other imaging biomarkers that could aid in improving outcome prediction models for acute ischemic stroke. We included FU-DWI data from the HERMES, ISLES, and MR CLEAN-NO IV databases. Lesions were segmented using a deep learning model trained on the HERMES and ISLES datasets. We assessed the performance of three classifiers in predicting functional independence for the MR CLEAN-NO IV trial cohort based on: (1) FIV alone, (2) the most important features obtained from a trained convolutional autoencoder (CAE), and (3) radiomics. Furthermore, we investigated feature importance in the radiomic-feature-based model. For outcome prediction, we included 206 patients: 144 scans were included in the training set, 21 in the validation set, and 41 in the test set. The classifiers that included the CAE and the radiomic features showed AUC values of 0.88 and 0.81, respectively, while the model based on FIV had an AUC of 0.79. This difference was not found to be statistically significant. Feature importance results showed that lesion intensity heterogeneity received more weight than lesion volume in outcome prediction. This study suggests that predictions of functional outcome should not be based on FIV alone and that FU-DWI images capture additional prognostic information