Thrombectomy in Patients With Ischemic Stroke Without Salvageable Tissue on CT Perfusion.

BACKGROUND: Computed tomography perfusion (CTP) imaging is regularly used to guide patient selection for mechanical thrombectomy (MT). However, the effect of MT in patients without salvageable tissue on CTP has not been investigated. The purpose of this study was to assess the effect of MT in patients with stroke without perfusion mismatch profiles. METHODS: This observational study analyzed patients with ischemic stroke consecutively treated between March 1, 2015, and January 31, 2022, triaged by multimodal-computed tomography undergoing MT. CTP lesion-core mismatch profiles were defined using a mismatch volume/ratio of ≥10 mL/1.2, respectively. The primary end point was the rate of functional independence at 90 days, defined as the modified Rankin Scale score of 0 to 2. Recanalization was evaluated with the modified Thrombolysis in Cerebral Infarction scale. The effect of baseline variables on functional outcome was assessed using multivariable logistic regression analysis. Outcomes of patients with and without CTP-mismatch profiles were compared using 1:1 propensity score matching. RESULTS: Of 724 patients who met the inclusion criteria of this retrospective observational study, 110 (15%) patients had no CTP mismatch and were analyzed. The median age was 74 (interquartile range, 62-80) years and 53% were women. Successful recanalization (modified Thrombolysis in Cerebral Infarction score, ≥2b) was achieved in 66% (73) and associated with functional independence at 90 days (adjusted odds ratio, 7.33 [95% CI, 1.22-43.70]; P=0.03). A significant interaction was observed between recanalization and age, as well as the extent of infarction, indicating MT to be most effective in patients <70 years and with a baseline Alberta Stroke Program Early Computed Tomography Score range between 3 and 7. These findings remained stable after propensity score matching, analyzing 152 matched pairs with similar rates of functional independence between patients with and without CTP-mismatch profiles (17% versus 23%; P=0.42). CONCLUSIONS: In patients without CTP-mismatch profiles defined according to the EXTEND (Extending the Time for Thrombolysis in Emergency Neurological Deficits) criteria, recanalization was associated with improved functional outcomes. This effect was associated with baseline Alberta Stroke Program Early Computed Tomography Score and age, but not with the time from onset to imaging.

Association of clinical outcome and imaging endpoints in extensive ischemic stroke-comparing measures of cerebral edema.

OBJECTIVES: Ischemic edema is associated with worse clinical outcomes, especially in large infarcts. Computed tomography (CT)-based densitometry allows direct quantification of absolute edema volume (EV), which challenges indirect biomarkers like midline shift (MLS). We compared EV and MLS as imaging biomarkers of ischemic edema and predictors of malignant infarction (MI) and very poor clinical outcome (VPCO) in early follow-up CT of patients with large infarcts. MATERIALS AND METHODS: Patients with anterior circulation stroke, large vessel occlusion, and Alberta Stroke Program Early CT Score (ASPECTS) ≤ 5 were included. VPCO was defined as modified Rankin scale (mRS) ≥ 5 at discharge. MLS and EV were quantified at admission and in follow-up CT 24 h after admission. Correlation was analyzed between MLS, EV, and total infarct volume (TIV). Multivariable logistic regression and receiver operating characteristics curve analyses were performed to compare MLS and EV as predictors of MI and VPCO. RESULTS: Seventy patients (median TIV 110 mL) were analyzed. EV showed strong correlation to TIV (r = 0.91, p < 0.001) and good diagnostic accuracy to classify MI (EV AUC 0.74 [95%CI 0.61-0.88] vs. MLS AUC 0.82 [95%CI 0.71-0.94]; p = 0.48) and VPCO (EV AUC 0.72 [95%CI 0.60-0.84] vs. MLS AUC 0.69 [95%CI 0.57-0.81]; p = 0.5) with no significant difference compared to MLS, which did not correlate with TIV < 110 mL (r = 0.17, p = 0.33). CONCLUSION: EV might serve as an imaging biomarker of ischemic edema in future studies, as it is applicable to infarcts of all volumes and predicts MI and VPCO in patients with large infarcts with the same accuracy as MLS. CLINICAL RELEVANCE STATEMENT: Utilization of edema volume instead of midline shift as an edema parameter would allow differentiation of patients with large and small infarcts based on the extent of edema, with possible advantages in the prediction of treatment effects, complications, and outcome. KEY POINTS: • CT densitometry-based absolute edema volume challenges midline shift as current gold standard measure of ischemic edema. • Edema volume predicts malignant infarction and poor clinical outcome in patients with large infarcts with similar accuracy compared to MLS irrespective of the lesion extent. • Edema volume might serve as a reliable quantitative imaging biomarker of ischemic edema in acute stroke triage independent of lesion size.

Follow-up infarct volume on fluid attenuated inversion recovery (FLAIR) imaging in distal medium vessel occlusions: the role of cerebral blood volume index.

BACKGROUND: Distal medium vessel occlusions (DMVOs) contribute substantially to the incidence of acute ischemic strokes (AIS) and pose distinct challenges in clinical management and prognosis. Neuroimaging techniques, such as Fluid Attenuation Inversion Recovery (FLAIR) imaging and cerebral blood volume (CBV) index derived from perfusion imaging, have significantly improved our ability to assess the impact of strokes and predict their outcomes. The primary objective of this study was to investigate relationship between follow-up infarct volume (FIV) as assessed by FLAIR imaging in patients with DMVOs. METHODS: This prospectively collected, retrospective reviewed cohort study included patients from two comprehensive stroke centers within the Johns Hopkins Medical Enterprise, spanning August 2018-October 2022. The cohort consisted of adults with AIS attributable to DMVO. Detailed imaging analyses were conducted, encompassing non-contrast CT, CT angiography (CTA), CT perfusion (CTP), and FLAIR imaging. Univariable and multivariable linear regression models were employed to assess the association between different factors and FIV. RESULTS: The study included 79 patients with DMVO stroke with a median age of 69 years (IQR, 62-77 years), and 57% (n = 45) were female. There was a negative correlation between the CBV index and FIV in a univariable linear regression analysis (Beta = - 16; 95% CI, - 23 to - 8.3; p < 0.001) and a multivariable linear regression model (Beta = - 9.1 per 0.1 change; 95% CI, - 15 to - 2.7; p = 0.006). Diabetes was independently associated with larger FIV (Beta = 46; 95% CI, 16 to 75; p = 0.003). Additionally, a higher baseline ASPECTS was associated with lower FIV (Beta = - 30; 95% CI, - 41 to - 20; p < 0.001). CONCLUSION: Our findings underscore the CBV index as an independent association with FIV in DMVOs, which highlights the critical role of collateral circulation in determining stroke outcomes in this patient population. In addition, our study confirms a negative association of ASPECTS with FLAIR FIV and identifies diabetes as independent factor associated with larger FIV. These insights pave the way for further large-scale, prospective studies to corroborate these findings, thereby refining the strategies for stroke prognostication and management.

Multisite Thrombosis in a Patient with Paroxysmal Nocturnal Hemoglobinuria.

CASE: Paroxysmal nocturnal hemoglobinuria (PNH) is an extremely rare bone marrow disorder caused by acquired mutations in the phosphatidylinositol glycan class A gene, which lead to a partial or total loss of the cellular complement regulators CD55 and CD59.1 In addition to complement-mediated hemolysis and cytopenia, venous and arterial thromboses at multiple and/or unusual sites are a common complication and occur in up to 44% of patients in historic PNH cohorts.1 2.

Association between occlusion location, net water uptake and ischemic lesion growth in large vessel anterior circulation strokes.

Ischemic lesion net water uptake (NWU) represents a quantitative imaging biomarker for cerebral edema in acute ischemic stroke. Data on NWU for distinct occlusion locations remain scarce, but might help to improve the prognostic value of NWU. In this retrospective multicenter cohort study, we compared NWU between patients with proximal large vessel occlusion (pLVO; ICA or proximal M1) and distal large vessel occlusion (dLVO; distal M1 or M2). NWU was quantified by densitometric measurements of the early ischemic region. Arterial collateral status was assessed using the Maas scale. Regression analysis was used to investigate the relationship between occlusion location, NWU and ischemic lesion growth. A total of 685 patients met inclusion criteria. Early ischemic lesion NWU was higher in patients with pLVO compared with dLVO (7.7% vs 3.9%, P < .001). The relationship between occlusion location and NWU was partially mediated by arterial collateral status. NWU was associated with absolute ischemic lesion growth between admission and follow-up imaging (ß estimate, 5.50, 95% CI, 3.81-7.19, P < .001). This study establishes a framework for the relationship between occlusion location, arterial collateral status, early ischemic lesion NWU and ischemic lesion growth. Future prognostic thresholds for NWU might be optimized by adjusting for the occlusion location.

CTA Supplemented by CTP Increases Interrater Reliability and Endovascular Treatment Use in Patients with Aneurysmal SAH.

BACKGROUND AND PURPOSE: Cerebral vasospasm is a common complication of aneurysmal SAH and remains a risk factor for delayed cerebral ischemia and poor outcome. The interrater reliability of CTA in combination with CTP has not been sufficiently studied. We aimed to investigate the reliability of CTA alone and in combination with CTP in the detection of cerebral vasospasm and the decision to initiate endovascular treatment. MATERIALS AND METHODS: This is a retrospective single-center study including patients treated for aneurysmal SAH. Inclusion criteria were a baseline CTA and follow-up imaging including CTP due to suspected vasospasm. Three neuroradiologists were asked to grade 15 intracranial arterial segments in 71 cases using a tripartite scale (no, mild <50%, or severe >50% vasospasm). Raters further evaluated whether endovascular treatment should be indicated. The ratings were performed in 2 stages with a minimum interval of 6 weeks. The first rating included only CTA images, whereas the second rating additionally encompassed CTP images. All raters were blinded to any clinical information of the patients. RESULTS: Interrater reliability for per-segment analysis of vessels was highly variable (κ = 0.16-0.61). We observed a tendency toward higher interrater reliability in proximal vessel segments, except for the ICA. CTP did not improve the reliability for the per-segment analysis. When focusing on senior raters, the addition of CTP images resulted in higher interrater reliability for severe vasospasm (κ = 0.28; 95% CI, 0.10-0.46 versus κ = 0.46; 95% CI, 0.26-0.66) and subsequently higher concordance (κ = 0.23; 95% CI, -0.01-0.46 versus κ = 0.73; 95% CI, 0.55-0.91) for the decision of whether endovascular treatment was indicated. CONCLUSIONS: CTA alone offers only low interrater reliability in the graduation of cerebral vasospasm. However, using CTA in combination with CTP might help, especially senior neuroradiologists, to increase the interrater reliability to identify severe vasospasm following aneurysmal SAH and to increase the reliability regarding endovascular treatment decisions.

Early and recurrent cerebral vasospasms after aneurysmal subarachnoid hemorrhage: The impact of age.

INTRODUCTION: Cerebral vasospasms remain a strong predictor of poor outcome after aneurysmal SAH. The aim of this study was to describe the time course of relevant vasospasms after aneurysmal SAH and to determine the variables associated with early-onset or prolonged and recurrent vasospasms. PATIENTS AND METHODS: We conducted a retrospective, single-center study of consecutive adult patients with aneurysmal SAH admitted between 2016 and 2022 at our tertiary stroke center. Relevant vasospasms, defined as vessel narrowing detected in DSA in combination with clinical deterioration or new perfusion deficit, were detected according to our in-house algorithm and eventually treated endovascularly. The primary endpoint was the diagnosis of relevant vasospasms. As secondary endpoints, the time from hemorrhage to the onset of vasospasms and the time from the first to the last endovascular intervention were measured. RESULTS: Of 368 patients with aneurysmal SAH, 135 (41.0%) developed relevant vasospasms. The median time between ictus and detection of vasospasms was 8 days (IQR: 6-10). Patients with early-onset vasospasms were significantly younger (mean 52.7 ± 11.2 years vs 58.7 ± 11.5 years, p = 0.003) and presented more frequently vasospasm-related infarctions at discharge (58.8% vs 38.7%, p = 0.03). In 74 patients (54.8%), recurrent relevant vasospasms were observed despite endovascular treatment. Younger age and early onset were significantly associated with longer duration of relevant vasospasms (both p < 0.05). DISCUSSION AND CONCLUSION: Younger age was associated with early-onset and longer duration of relevant vasospasms in this study. More frequent clinical and diagnostic follow-up should be considered in this subgroup of patients that are at risk for poor outcomes.

Early neurological deterioration in patients with acute ischemic stroke is linked to unfavorable cerebral venous outflow.

INTRODUCTION: Early neurological deterioration (END) is associated with poor outcomes in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). Causes of END after mechanical thrombectomy (MT) include unsuccessful recanalization and reperfusion hemorrhages. However, little is known about END excluding the aforementioned causes. We aimed to investigate factors associated with unexplained END (ENDunexplained) with regard to the cerebral collateral status. PATIENTS AND METHODS: Multicenter retrospective study of AIS-LVO patients with successful MT (mTICI 2b-3). On admission CT angiography (CTA), pial arterial collaterals and venous outflow (VO) were assessed using the modified Tan-Scale and the Cortical Vein Opacification Score (COVES), respectively. ENDunexplained was defined as an increase in NIHSS score of ⩾ 4 within the first 24 hours after MT without parenchymal hemorrhage on follow-up imaging. Multivariable regression analyses were performed to examine factors of ENDunexplained and unfavorable functional outcome (modified Rankin Scale score 3-6). RESULTS: A total of 620 patients met the inclusion criteria. ENDunexplained occurred in 10% of patients. While there was no significant difference in pial arterial collaterals, patients with ENDunexplained exhibited more often unfavorable VO (81% vs. 53%; P < 0.001). Unfavorable VO (aOR [95% CI]; 2.56 [1.02-6.40]; P = 0.045) was an independent predictor of ENDunexplained. ENDunexplained was independently associated with unfavorable functional outcomes at 90 days (aOR [95% CI]; 6.25 [2.06-18.94]; P = 0.001). DISCUSSION AND CONCLUSION: Unfavorable VO on admission CTA was associated with ENDunexplained. ENDunexplained was independently linked to unfavorable functional outcomes at 90 days. Identifying AIS-LVO patients at risk of ENDunexplained may help to select patients for intensified monitoring and guide to optimal treatment regimes.

Prognostic value of recanalization attempts in endovascular therapy for M2 segment middle cerebral artery occlusions.

BACKGROUND: There is growing evidence suggesting efficacy of endovascular therapy for M2 occlusions of the middle cerebral artery. More than one recanalization attempt is often required to achieve successful reperfusion in M2 occlusions, associated with general concerns about the safety of multiple maneuvers in these medium vessel occlusions. AIM: The aim of this study was to investigate the association between the number of recanalization attempts and functional outcomes in M2 occlusions in comparison with large vessel occlusions (LVO). METHODS: Retrospective multicenter cohort study of patients who underwent endovascular therapy for primary M2 occlusions. Patients were enrolled in the German Stroke Registry at 1 of 25 comprehensive stroke centers between 2015 and 2021. The study cohort was subdivided into patients with unsuccessful reperfusion (mTICI 0-2a) and successful reperfusion (mTICI 2b-3) at first, second, third, fourth, or ⩾fifth recanalization attempt. Primary outcome was 90-day functional independence defined as modified Rankin Scale score of 0-2. Safety outcome was the occurrence of symptomatic intracranial hemorrhage. Internal carotid artery or M1 occlusions were defined as LVO and served as comparison group. RESULTS: A total of 1078 patients with M2 occlusion were included. Successful reperfusion was observed in 87.1% and 90-day functional independence in 51.9%. The rate of functional independence decreased gradually with increasing number of recanalization attempts (p < 0.001). In both M2 occlusions and LVO, successful reperfusion within three attempts was associated with greater odds of functional independence, while success at ⩾fourth attempt was not. Patients with ⩾4 attempts exhibited higher rates of symptomatic intracranial hemorrhage in M2 occlusions (6.5% vs 2.7%, p = 0.02) and LVO (7.2% vs 3.5%, p < 0.001). CONCLUSION: This study suggests a clinical benefit of successful reperfusion within three recanalization attempts in endovascular therapy for M2 occlusions, which was similar in LVO. Our findings reduce concerns about the risk-benefit ratio of multiple attempts in M2 medium vessel occlusions. DATA ACCESS STATEMENT: The data that support the findings of this study are available on reasonable request after approval of the German Stroke Registry (GSR) steering committee. CLINICAL TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT03356392.

Brain edema growth after thrombectomy is associated with comprehensive collateral blood flow.

BACKGROUND: We determined whether a comprehensive assessment of cerebral collateral blood flow is associated with ischemic lesion edema growth in patients successfully treated by thrombectomy. METHODS: This was a multicenter retrospective study of ischemic stroke patients who underwent thrombectomy treatment of large vessel occlusions. Collateral status was determined using the cerebral collateral cascade (CCC) model, which comprises three components: arterial collaterals (Tan Scale) and venous outflow profiles (Cortical Vein Opacification Score) on CT angiography, and tissue-level collaterals (hypoperfusion intensity ratio) on CT perfusion. Quantitative ischemic lesion net water uptake (NWU) was used to determine edema growth between admission and follow-up non-contrast head CT (ΔNWU). Three groups were defined: CCC+ (good pial collaterals, tissue-level collaterals, and venous outflow), CCC- (poor pial collaterals, tissue-level collaterals, and venous outflow), and CCCmixed (remainder of patients). Primary outcome was ischemic lesion edema growth (ΔNWU). Multivariable regression models were used to assess the primary and secondary outcomes. RESULTS: 538 patients were included. 157 patients had CCC+, 274 patients CCCmixed, and 107 patients CCC- profiles. Multivariable regression analysis showed that compared with patients with CCC+ profiles, CCC- (ß 1.99, 95% CI 0.68 to 3.30, P=0.003) and CCC mixed (ß 1.65, 95% CI 0.75 to 2.56, P<0.001) profiles were associated with greater ischemic lesion edema growth (ΔNWU) after successful thrombectomy treatment. ΔNWU (OR 0.74, 95% CI 0.68 to 0.8, P<0.001) and CCC+ (OR 13.39, 95% CI 4.88 to 36.76, P<0.001) were independently associated with functional independence. CONCLUSION: A comprehensive assessment of cerebral collaterals using the CCC model is strongly associated with edema growth and functional independence in acute stroke patients successfully treated by endovascular thrombectomy.

Edema Reduction versus Penumbra Salvage: Investigating Treatment Effects of Mechanical Thrombectomy in Ischemic Stroke.

OBJECTIVE: Mechanical thrombectomy (MT) is of benefit to patients with ischemic stroke; however, the effect of recanalization on lesion pathophysiology is not yet well understood. The aim of this study was to quantitatively assess how the effect of vessel recanalization on clinical outcome is mediated by edema reduction versus penumbra salvage. METHODS: Consecutive analysis was made of anterior circulation ischemic stroke patients triaged by multimodal computed tomography (CT) undergoing MT. Edema reduction was defined using the difference of quantitative net water uptake (NWU) determined on baseline and follow-up CT (∆NWU). Penumbra salvage volume (PSV) was defined as the difference between admission penumbra and net infarct growth volumes to follow-up. Mediation analyses were performed with vessel recanalization as independent variable (modified Thrombolysis in Cerebral Infarction ≥ 2b) and ∆NWU/PSV as mediator variables. Modified Rankin Scale scores at 90 days served as endpoint. RESULTS: Of 422 included patients, 321 (76%) achieved successful recanalization. The median ∆NWU was 6.8% (interquartile range [IQR] = 3.9-10.4), and the median PSV was 66ml (IQR = 8-124). ∆NWU, PSV, and recanalization were significantly associated with functional outcome in logistic regression analysis. ∆NWU and PSV partially mediated the relationship between recanalization and outcome. Sixty-six percent of the relationship between recanalization and functional outcome could be explained by treatment-induced edema reduction, whereas 22% was mediated by PSV (p < 0.0001). INTERPRETATION: Compared to penumbra salvage, edema reduction was a stronger mediator of the effect of recanalization on functional outcome. Given the current trials on adjuvant neuroprotectants also targeting ischemic edema formation, combining reperfusion with antiedematous neuroprotectants may have synergistic effects resulting in better outcomes in patients with ischemic stroke. ANN NEUROL 2023.

Comparison of Thrombolysis In Cerebral Infarction (TICI) 2b and TICI 3 reperfusion in endovascular therapy for large ischemic anterior circulation strokes.

BACKGROUND: Landmark thrombectomy trials have provided evidence that selected patients with large ischemic stroke benefit from successful endovascular therapy, commonly defined as incomplete (modified Thrombolysis In Cerebral Infarction (mTICI) 2b) or complete reperfusion (mTICI 3). We aimed to investigate whether mTICI 3 improves functional outcomes compared with mTICI 2b in large ischemic strokes. METHODS: This retrospective multicenter cohort study was conducted to compare mTICI 2b versus mTICI 3 in large ischemic strokes in the anterior circulation. Patients enrolled in the German Stroke Registry between 2015-2021 were analyzed. Large ischemic stroke was defined as an Alberta Stroke Program Early CT Score (ASPECTS) of 3-5. Patients were matched by final mTICI grade using propensity score matching. Primary outcome was the 90-day modified Rankin Scale (mRS) score. RESULTS: After matching, 226 patients were included. Baseline and imaging characteristics were balanced between mTICI 2b and mTICI 3 patients. There was no shift on the mRS favoring mTICI 3 compared with mTICI 2b in large ischemic strokes (adjusted common odds ratio (acOR) 1.12, 95% confidence interval (95% CI) 0.64 to 1.94, P=0.70). The rate of symptomatic intracranial hemorrhage was higher in mTICI 2b than in mTICI 3 patients (12.6% vs 4.5%, P=0.03). Mortality at 90 days did not differ between mTICI 3 and mTICI 2b (33.6% vs 37.2%; adjusted OR 0.69, 95% CI 0.33 to 1.45, P=0.33). CONCLUSIONS: In endovascular therapy for large ischemic strokes, mTICI 3 was not associated with better 90-day functional outcomes compared with mTICI 2b. This study suggests that mTICI 2b might be warranted as the final angiographic result, questioning the benefit/risk ratio of additional maneuvers to seek for mTICI 3 in large ischemic strokes. TRIAL REGISTRATION NUMBER: NCT03356392.

CT perfusion to measure venous outflow in acute ischemic stroke in patients with a large vessel occlusion.

BACKGROUND: Robust venous outflow (VO) profiles, measured by degree of venous opacification on pre-thrombectomy CT angiography (CTA) studies, are strongly correlated with favorable outcomes in patients with large vessel occlusion acute ischemic stroke treated by thrombectomy. However, VO measurements are laborious and require neuroimaging expertise. OBJECTIVE: To develop a semi-automated method to measure VO using CTA and CT perfusion imaging studies. METHODS: We developed a graphical interface using The Visualization Toolkit, allowing for voxel selection at the confluence and bilateral internal cerebral veins on CTA along with arterial input functions (AIFs) from both internal carotid arteries. We extracted concentration-time curves from the CT perfusion study at the corresponding locations associated with AIF and venous output function (VOF). Outcome analyses were primarily conducted by the Mann-Whitney U and Jonckheere-Terpstra tests. RESULTS: Segmentation at the pre-selected AIF and VOF locations was performed on a sample of 97 patients. 65 patients had favorable VO (VO+) and 32 patients had unfavorable VO (VO-). VO+ patients were found to have a significantly shorter VOF time to peak (8.26; 95% CI 7.07 to 10.34) than VO- patients (9.44; 95% CI 8.61 to 10.91), P=0.007. No significant difference was found in VOF curve width and the difference in time between AIF and VOF peaks. CONCLUSIONS: Time to peak of VOF at the confluence of sinuses was significantly associated with manually scored venous outflow. Further studies should aim to understand better the association between arterial inflow and venous outflow, and capture quantitative metrics of venous outflow at other locations.

Association Between Recanalization Attempts and Functional Outcome After Thrombectomy for Large Ischemic Stroke.

BACKGROUND: Recently, 3 randomized controlled trials provided high-level evidence that patients with large ischemic stroke achieved better functional outcomes after endovascular therapy than with medical care alone. We aimed to investigate whether the clinical benefit of endovascular therapy is associated with the number of recanalization attempts in extensive baseline infarction. METHODS: This retrospective multicenter study enrolled patients from the German Stroke Registry who underwent endovascular therapy for anterior circulation large vessel occlusion between 2015 and 2021. Large ischemic stroke was defined as an Alberta Stroke Program Early Computed Tomography Score of 3 to 5. The study cohort was divided into patients with unsuccessful reperfusion (Thrombolysis in Cerebral Infarction score, 0-2a) and successful reperfusion (Thrombolysis in Cerebral Infarction score, 2b/3) at attempts 1, 2, 3, or ≥4. The primary outcome was favorable functional outcome defined as modified Rankin Scale score of 0 to 3 at 90 days. Safety outcomes were symptomatic intracranial hemorrhage after 24 hours and death within 90 days. Multivariable logistic regression was used to identify independent determinants of primary and secondary outcomes. RESULTS: A total of 348 patients met the inclusion criteria. Successful reperfusion was observed in 83.3% and favorable functional outcomes in 36.2%. Successful reperfusion at attempts 1 (adjusted odds ratio, 5.97 [95% CI, 1.71-24.43]; P=0.008) and 2 (adjusted odds ratio, 6.32 [95% CI, 1.73-26.92]; P=0.008) increased the odds of favorable functional outcome, whereas success at attempts 3 or ≥4 did not. Patients with >2 attempts showed higher rates of symptomatic intracranial hemorrhage (12.8% versus 6.5%; P=0.046). Successful reperfusion at any attempt lowered the odds of death compared with unsuccessful reperfusion. CONCLUSIONS: In patients with large vessel occlusion and Alberta Stroke Program Early Computed Tomography Score of 3 to 5, the clinical benefit of endovascular therapy was linked to the number of recanalization attempts required for successful reperfusion. Our findings encourage to perform at least 2 recanalization attempts to seek for successful reperfusion in large ischemic strokes, while >2 attempts should follow a careful risk-benefit assessment in these highly affected patients. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03356392.

Diagnosis and endovascular management of vasospasm after aneurysmal subarachnoid hemorrhage - survey of real-life practices.

BACKGROUND: Vasospasm and delayed cerebral ischemia (DCI) are the leading causes of morbidity and mortality after intracranial aneurysmal subarachnoid hemorrhage (aSAH). Vasospasm detection, prevention and management, especially endovascular management varies from center to center and lacks standardization. We aimed to evaluate this variability via an international survey of how neurointerventionalists approach vasospasm diagnosis and endovascular management. METHODS: We designed an anonymous online survey with 100 questions to evaluate practice patterns between December 2021 and September 2022. We contacted endovascular neurosurgeons, neuroradiologists and neurologists via email and via two professional societies - the Society of NeuroInterventional Surgery (SNIS) and the European Society of Minimally Invasive Neurological Therapy (ESMINT). We recorded the physicians' responses to the survey questions. RESULTS: A total of 201 physicians (25% [50/201] USA and 75% non-USA) completed the survey over 10 months, 42% had >7 years of experience, 92% were male, median age was 40 (IQR 35-46). Both high-volume and low-volume centers were represented. Daily transcranial Doppler was the most common screening method (75%) for vasospasm. In cases of symptomatic vasospasm despite optimal medical management, endovascular treatment was directly considered by 58% of physicians. The most common reason to initiate endovascular treatment was clinical deficits associated with proven vasospasm/DCI in 89%. The choice of endovascular treatment and its efficacy was highly variable. Nimodipine was the most common first-line intra-arterial therapy (40%). Mechanical angioplasty was considered the most effective endovascular treatment by 65% of neurointerventionalists. CONCLUSION: Our study highlights the considerable heterogeneity among the neurointerventional community regarding vasospasm diagnosis and endovascular management. Randomized trials and guidelines are needed to improve standard of care, determine optimal management approaches and track outcomes.

Association Between Intravenous Thrombolysis and Clinical Outcomes Among Patients With Ischemic Stroke and Unsuccessful Mechanical Reperfusion.

Importance: Clinical evidence of the potential treatment benefit of intravenous thrombolysis preceding unsuccessful mechanical thrombectomy (MT) is scarce. Objective: To determine whether intravenous thrombolysis (IVT) prior to unsuccessful MT improves functional outcomes in patients with acute ischemic stroke. Design, Setting, and Participants: Patients were enrolled in this retrospective cohort study from the prospective, observational, multicenter German Stroke Registry-Endovascular Treatment between May 1, 2015, and December 31, 2021. This study compared IVT plus MT vs MT alone in patients with acute ischemic stroke due to anterior circulation large-vessel occlusion in whom mechanical reperfusion was unsuccessful. Unsuccessful mechanical reperfusion was defined as failed (final modified Thrombolysis in Cerebral Infarction grade of 0 or 1) or partial (grade 2a). Patients meeting the inclusion criteria were matched by treatment group using 1:1 propensity score matching. Interventions: Mechanical thrombectomy with or without IVT. Main Outcomes and Measures: Primary outcome was functional independence at 90 days, defined as a modified Rankin Scale score of 0 to 2. Safety outcomes were the occurrence of symptomatic intracranial hemorrhage and death. Results: After matching, 746 patients were compared by treatment arms (median age, 78 [IQR, 68-84] years; 438 women [58.7%]). The proportion of patients who were functionally independent at 90 days was 68 of 373 (18.2%) in the IVT plus MT and 42 of 373 (11.3%) in the MT alone group (adjusted odds ratio [AOR], 2.63 [95% CI, 1.41-5.11]; P = .003). There was a shift toward better functional outcomes on the modified Rankin Scale favoring IVT plus MT (adjusted common OR, 1.98 [95% CI, 1.35-2.92]; P < .001). The treatment benefit of IVT was greater in patients with partial reperfusion compared with failed reperfusion. There was no difference in symptomatic intracranial hemorrhages between treatment groups (AOR, 0.71 [95% CI, 0.29-1.81]; P = .45), while the death rate was lower after IVT plus MT (AOR, 0.54 [95% CI, 0.34-0.86]; P = .01). Conclusions and Relevance: These findings suggest that prior IVT was safe and improved functional outcomes at 90 days. Partial reperfusion was associated with a greater treatment benefit of IVT, indicating a positive interaction between IVT and MT. These results support current guidelines that all eligible patients with stroke should receive IVT before MT and add a new perspective to the debate on noninferiority of combined stroke treatment.

The negative effect of aging on cerebral venous outflow in acute ischemic stroke.

Cortical venous outflow (VO) represents an imaging biomarker of increasing interest in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). We conducted a retrospective multicenter cohort study to investigate the effect of aging on VO. A total of 784 patients met the inclusion criteria. Cortical Vein Opacification Score (COVES) was used to assess VO profiles on admission CT angiography. Cerebral microperfusion was determined using the hypoperfusion intensity ratio (HIR) derived from perfusion imaging. Arterial collaterals were assessed using the Tan scale. Multivariable regression analysis was performed to identify independent determinants of VO, HIR and arterial collaterals. In multivariable regression, higher age correlated with worse VO (adjusted odds ratio [95% CI]; 0.83 [0.73-0.95]; P = 0.006) and poorer HIR (ß coefficient [95% CI], 0.014 [0.005-0.024]; P = 0.002). The negative effect of higher age on VO was mediated by the extent of HIR (17.3%). We conclude that higher age was associated with worse VO in AIS-LVO, partially explained by the extent of HIR reflecting cerebral microperfusion. Our study underlines the need to assess collateral blood flow beyond the arterial system and provides valuable insights into deteriorated cerebral blood supply in elderly AIS-LVO patients.

Unfavorable cerebral venous outflow is associated with futile recanalization in acute ischemic stroke patients.

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) has proven to be the standard of care for patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). However, high revascularization rates do not necessarily result in favorable functional outcomes. We aimed to investigate imaging biomarkers associated with futile recanalization, defined as unfavorable functional outcome despite successful recanalization in AIS-LVO patients. METHODS: A retrospective multicenter cohort study was made of AIS-LVO patients treated by MT. Successful recanalization was defined as modified Thrombolysis in Cerebral Infarction score of 2b-3. A modified Rankin Scale score of 3-6 at 90 days was defined as unfavorable functional outcome. Cortical Vein Opacification Score (COVES) was used to assess venous outflow (VO), and the Tan scale was utilized to determine pial arterial collaterals on admission computed tomography angiography (CTA). Unfavorable VO was defined as COVES ≤ 2. Multivariable regression analysis was performed to investigate vascular imaging factors associated with futile recanalization. RESULTS: Among 539 patients in whom successful recanalization was achieved, unfavorable functional outcome was observed in 59% of patients. Fifty-eight percent of patients had unfavorable VO, and 31% exhibited poor pial arterial collaterals. In multivariable regression, unfavorable VO was a strong predictor (adjusted odds ratio = 4.79, 95% confidence interval = 2.48-9.23) of unfavorable functional outcome despite successful recanalization. CONCLUSIONS: We observe that unfavorable VO on admission CTA is a strong predictor of unfavorable functional outcomes despite successful vessel recanalization in AIS-LVO patients. Assessment of VO profiles could help as a pretreatment imaging biomarker to determine patients at risk for futile recanalization.

Thrombectomy in M2 occlusion compared to M1 occlusion: treatment effects of Thrombolysis In Cerebral Infarction (TICI) 2b and TICI 3 recanalization on functional outcome.

BACKGROUND: Emerging data suggest that mechanical thrombectomy (MT) might also be safe and efficient for medium and distal occlusions. This study aims to compare average treatment effects on functional outcome of different degrees of recanalization after MT in patients with M2 occlusion and M1 occlusion. METHODS: All patients enrolled in the German Stroke Registry (GSR) between June 2015 and December 2021 were analyzed. Inclusion criteria were stroke with primary M1 occlusion or M2 occlusion, and availability of relevant clinical data. 4259 patients were included, thereof 1353 with M2 occlusion and 2906 with M1 occlusion. Treatment effects were analyzed using double-robust inverse-probability-weighted regression-adjustment (IPWRA) estimators to control for confounding covariates. Binarized endpoint metrics were defined as good outcome with modified Rankin Scale (mRS) ≤2 at 90 days, and linearized endpoint metrics were defined as mRS shift pre-stroke to 90 days. Effects were evaluated for near complete recanalization (Thrombolysis In Cerebral Infarction scale (TICI) 2b) and complete recanalization (TICI 3). RESULTS: Treatment effect estimation for TICI ≥2b versus TICI <2b in M2 occlusions showed an increase in the probability of a good outcome from 27% to 47% with a number-needed-to-treat (NNT) of 5. For M1 occlusions the probability of a good outcome increased from 16% to 38% with NNT 4.5. TICI 3 versus TICI 2b increased the probability of a good outcome by 7 percentage points in M1 occlusions; for M2 occlusions the beneficial effect was not significant. CONCLUSIONS: Results suggest that successful recanalization with TICI ≥2b versus TICI <2b after MT in M2 occlusions provides significant patient benefit with treatment effects comparable to M1 occlusions. The probability of functional independence increased by 20 percentage points (NNT 5) and stroke-related mRS increase was reduced by 0.9 mRS points. In contrast to M1 occlusions, complete recanalization TICI 3 versus TICI 2b had lower additional beneficial effect.