Arterial Recanalization During Interhospital Transfer for Thrombectomy.

BACKGROUND: Patients with acute ischemic stroke harboring a large vessel occlusion admitted to nonendovascular-capable centers often require interhospital transfer for thrombectomy. We evaluated the incidence and predictors of arterial recanalization during transfer, as well as the relationship between interhospital recanalization and clinical outcomes. METHODS: We analyzed data from 2 cohorts of patients with an anterior circulation large vessel occlusion transferred for consideration of thrombectomy to a comprehensive center, with arterial imaging at the referring hospital and on comprehensive stroke center arrival. Interhospital recanalization was determined by comparison of the baseline and posttransfer arterial imaging and was defined as revised arterial occlusive lesion (rAOL) score 2b to 3. Pretransfer variables independently associated with interhospital recanalization were studied using multivariable logistic regression analysis. RESULTS: Of the 520 included patients (Montpellier, France, n=237; Stanford, United States, n=283), 111 (21%) experienced interhospital recanalization (partial [rAOL=2b] in 77% and complete [rAOL=3] in 23%). Pretransfer variables independently associated with recanalization were intravenous thrombolysis (adjusted odds ratio, 6.8 [95% CI, 4.0-11.6]), more distal occlusions (intracranial carotid occlusion as reference: adjusted odds ratio, 2.0 [95% CI, 0.9-4.5] for proximal first segment of the middle cerebral artery, 5.1 [95% CI, 2.3-11.5] for distal first segment of the middle cerebral artery, and 5.0 [95% CI, 2.1-11.8] for second segment of the middle cerebral artery), and smaller clot burden (clot burden score 0-4 as reference: adjusted odds ratio, 3.4 [95% CI, 1.5-7.6] for 5-7 and 5.6 [95% CI, 2.4-12.7] for 8-9). Recanalization on arrival at the comprehensive center was associated with less interhospital infarct growth (rAOL, 0-2a: 11.6 mL; rAOL, 2b: 2.2 mL; rAOL, 3: 0.6 mL; Ptrend<0.001) and greater interhospital National Institutes of Health Stroke Scale score improvement (0 versus -5 versus -6; Ptrend<0.001). Interhospital recanalization was associated with reduced 3-month disability (adjusted common odds ratio, 2.51 [95% CI, 1.68-3.77]) with greater benefit from complete than partial recanalization. CONCLUSIONS: Recanalization is frequently observed during interhospital transfer for thrombectomy and is strongly associated with favorable outcomes, even when partial. Broadening thrombolysis indications in primary centers, and developing therapies that increase recanalization during transfer, will likely improve clinical outcomes.

Inter-hospital transfer for thrombectomy: transfer time is brain.

BACKGROUND AND PURPOSE: Patients with acute ischaemic stroke and a large vessel occlusion who present to a non-endovascular-capable centre often require inter-hospital transfer for thrombectomy. Whether the inter-hospital transfer time is associated with 3-month functional outcome is poorly known. METHODS: Acute stroke patients enrolled between January 2015 and December 2022 in the prospective French multicentre Endovascular Treatment of Ischaemic Stroke registry were retrospectively analysed. Patients with an anterior circulation large vessel occlusion transferred from a non-endovascular to a comprehensive stroke centre for thrombectomy were eligible. Inter-hospital transfer time was defined as the time between imaging in the referring hospital and groin puncture for thrombectomy. The relationship between transfer time and favourable 3-month functional outcome (modified Rankin Scale 0-2) was assessed through a mixed logistic regression model adjusting for centre and symptom-onset-to-referring-hospital imaging time, age, sex, diabetes, referring hospital National Institutes of Health Stroke Scale score, Alberta Stroke Programme Early Computed Tomography Score, occlusion site and intravenous thrombolysis use. RESULTS: Overall, 3769 patients were included (median inter-hospital transfer time 161 min, interquartile range 128-195; 46% with favourable outcome). A longer transfer time was independently associated with lower rates of favourable outcome (p < 0.001). Compared to patients with transfer time below 120 min, there was a 15% reduction in the odds of achieving favourable outcome for transfer times between 120 and 180 min (adjusted odds ratio 0.85; 95% confidence interval 0.67-1.07), and a 36% reduction for transfer times beyond 180 min (adjusted odds ratio 0.64; 95% confidence interval 0.50-0.81). CONCLUSIONS: A shorter inter-hospital transfer time is strongly associated with favourable 3-month functional outcome. A speedier inter-hospital transfer is of critical importance to improve outcome.

Clinical and Imaging Features Associated With Fast Infarct Growth During Interhospital Transfers of Patients With Large Vessel Occlusions.

BACKGROUND AND OBJECTIVES: Acute ischemic stroke patients with a large vessel occlusion (LVO) who present to a primary stroke center (PSC) often require transfer to a comprehensive stroke center (CSC) for thrombectomy. Not much is known about specific characteristics at the PSC that are associated with infarct growth during transfer. Gaining more insight into these features could aid future trials with cytoprotective agents targeted at slowing infarct growth. We aimed to identify baseline clinical and imaging characteristics that are associated with fast infarct growth rate (IGR) during interhospital transfer. METHODS: We included patients from the CT Perfusion to Predict Response to Recanalization in Ischemic Stroke Project, a prospective multicenter study. Patients with an anterior circulation LVO who were transferred from a PSC to a CSC for consideration of thrombectomy were eligible if imaging criteria were fulfilled. A CT perfusion (CTP) needed to be obtained at the PSC followed by an MRI at the CSC, before consideration of thrombectomy. The interhospital IGR was defined as the difference between the infarct volumes on MRI and CTP, divided by the time between the scans. Multivariable logistic regression was used to determine characteristics associated with fast IGR (≥5 mL/h). RESULTS: A total of 183 patients with a median age of 74 years (interquartile range 61-82), of whom 99 (54%) were male and 82 (45%) were fast progressors, were included. At baseline, fast progressors had a higher NIH Stroke Scale score (median 16 vs 13), lower cerebral blood volume index (median 0.80 vs 0.89), more commonly poor collaterals on CT angiography (35% vs 13%), higher hypoperfusion intensity ratios (HIRs) (median 0.51 vs 0.34), and larger core volumes (median 11.80 mL vs 0.00 mL). In multivariable analysis, higher HIR (adjusted odds ratio [aOR] for every 0.10 increase 1.32 [95% CI 1.10-1.59]) and larger core volume (aOR for every 10 mL increase 1.54 [95% CI 1.20-2.11]) remained independently associated with fast IGR. DISCUSSION: Fast infarct growth during interhospital transfer of acute stroke patients is associated with imaging markers of poor collaterals on baseline imaging. These markers are promising targets for patient selection in cytoprotective trials aimed at reducing interhospital infarct growth.

Incidence and predictors of intracranial hemorrhage after intravenous thrombolysis with tenecteplase.

BACKGROUND: Despite its increasing use, there are limited data on the risk of intracranial hemorrhage (ICH) after intravenous thrombolysis with tenecteplase in the setting of acute ischemic stroke. Our aim was to investigate the incidence and predictors of ICH after tenecteplase administration. METHODS: We reviewed data from the prospective ongoing multicenter TETRIS (Tenecteplase Treatment in Ischemic Stroke) registry. Patients with available day-1 imaging were included in this study. Clinical, imaging and biological variables were collected. Follow-up imaging performed 24 h after IVT was locally reviewed by senior neuroradiologists and neurologists. The incidence of parenchymal hematoma (PH) and any ICH were investigated. Potential predictors of PH and any ICH were assessed in multivariable logistic regressions. Subgroup analyses focusing on patients intended for endovascular treatment were performed. RESULTS: PH and any ICH occurred in 126/1321 (incidence rate: 9.5%, 95% CI 8.1-11.2) and 521/1321 (39.4%, 95% CI 36.8-42.1) patients, respectively. Symptomatic ICH was observed in 77/1321 (5.8%; 95% CI 4.7-7.2). PH occurrence was significantly associated with poorer functional outcomes (p < 0.0001) and death (p < 0.0001) after 3 months. Older age (aOR = 1.03; 95% CI 1.01-1.05), male gender (aOR = 2.07; 95% CI 1.28-3.36), a history of hypertension (aOR = 2.08; 95% CI 1.19-3.62), a higher baseline NIHSS (aOR = 1.07; 95% CI 1.03-1.10) and higher admission blood glucose level (aOR = 1.12; 95% CI 1.05-1.19) were independently associated with PH occurrence. Similar associations were observed in the subgroup of patients intended for endovascular treatment. CONCLUSION: We quantified the incidence of ICH after IVT with tenecteplase in a real-life prospective registry and determined independent predictors of ICH. These findings allow to identify patients at high risk of ICH.

Dynamic Evolution of Infarct Volumes at MRI in Ischemic Stroke Due to Large Vessel Occlusion.

BACKGROUND AND OBJECTIVES: The typical infarct volume trajectories in stroke patients, categorized as slow or fast progressors, remain largely unknown. This study aimed to reveal the characteristic spatiotemporal evolutions of infarct volumes caused by large vessel occlusion (LVO) and show that such growth charts help anticipate clinical outcomes. METHODS: We conducted a secondary analysis from prospectively collected databases (FRAME, 2017-2019; ETIS, 2015-2022). We selected acute MRI data from anterior LVO stroke patients with witnessed onset, which were divided into training and independent validation datasets. In the training dataset, using Gaussian mixture analysis, we classified the patients into 3 growth groups based on their rate of infarct growth (diffusion volume/time-to-imaging). Subsequently, we extrapolated pseudo-longitudinal models of infarct growth for each group and generated sequential frequency maps to highlight the spatial distribution of infarct growth. We used these charts to attribute a growth group to the independent patients from the validation dataset. We compared their 3-month modified Rankin scale (mRS) with the predicted values based on a multivariable regression model from the training dataset that used growth group as an independent variable. RESULTS: We included 804 patients (median age 73.0 years [interquartile range 61.2-82.0 years]; 409 men). The training dataset revealed nonsupervised clustering into 11% (74/703) slow, 62% (437/703) intermediate, and 27% (192/703) fast progressors. Infarct volume evolutions were best fitted with a linear (r = 0.809; p < 0.001), cubic (r = 0.471; p < 0.001), and power (r = 0.63; p < 0.001) function for the slow, intermediate, and fast progressors, respectively. Notably, the deep nuclei and insular cortex were rapidly affected in the intermediate and fast groups with further cortical involvement in the fast group. The variable growth group significantly predicted the 3-month mRS (multivariate odds ratio 0.51; 95% CI 0.37-0.72, p < 0.0001) in the training dataset, yielding a mean area under the receiver operating characteristic curve of 0.78 (95% CI 0.66-0.88) in the independent validation dataset. DISCUSSION: We revealed spatiotemporal archetype dynamic evolutions following LVO stroke according to 3 growth phenotypes called slow, intermediate, and fast progressors, providing insight into anticipating clinical outcome. We expect this could help in designing neuroprotective trials aiming at modulating infarct growth before EVT.

Advancing diagnostic precision of delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage: The potential for a vasospasm index score on perfusion imaging to detect vasospasm.

BACKGROUND: The occurrence of delayed cerebral ischemia and vasospasm following aneurysmal subarachnoid hemorrhage (aSAH) results in high morbidity and mortality, but the diagnosis remains challenging. This study aimed to identify neuroimaging perfusion parameters indicative of delayed cerebral ischemia in patients with suspected vasospasm. METHODS: This is a case-control study. Cases were adult aSAH patients who underwent magnetic resonance perfusion or computed tomography perfusion (CTP) imaging ≤ 24 h before digital subtraction angiography performed for vasospasm diagnosis and treatment. Controls were patients without aSAH who underwent CTP. Quantitative perfusion parameters at different thresholds, including Tmax 4-6-8-10 s delay, cerebral blood flow and cerebral blood volume were measured and compared between cases and controls. The Vasospasm Index Score was calculated as the ratio of brain volume with time-to-max (Tmax) delay > 6 s over volume with Tmax > 4 s. RESULTS: 54 patients with aSAH and 119 controls without aSAH were included. Perfusion parameters with the strongest prediction of vasospasm on cerebral angiography were the combination of the Vasospasm Index Score (Tmax6/Tmax4) + CBV ≤ 48 % (area under the curve value of 0.85 [95 % CI 0.78-0.91]) with a sensitivity of 63 % and specificity of 95 %. CONCLUSION: The Vasospasm Index Score in combination with CBV ≤ 48 % on cerebral perfusion imaging reliably identified vasospasm as the cause of DCI on perfusion imaging.

Clinical change during inter-hospital transfer for thrombectomy: Incidence, associated factors, and relationship with outcome.

BACKGROUND: Patients with acute ischemic stroke with a large vessel occlusion (LVO) admitted to non endovascular-capable centers often require inter-hospital transfer for thrombectomy. We aimed to describe the incidence of substantial clinical change during transfer, the factors associated with clinical change, and its relationship with 3-month outcome. METHODS: We analyzed data from two cohorts of acute stroke patients transferred for thrombectomy to a comprehensive center (Stanford, USA, November 2019 to January 2023; Montpellier, France, January 2015 to January 2017), regardless of whether thrombectomy was eventually attempted. Patients were included if they had evidence of an LVO at the referring hospital and had a National Institute of Health Stroke Scale (NIHSS) score documented before and immediately after transfer. Inter-hospital clinical change was categorized as improvement (⩾4 points and ⩾25% decrease between the NIHSS score in the referring hospital and upon comprehensive center arrival), deterioration (⩾4 points and ⩾25% increase), or stability (neither improvement nor deterioration). The stable group was considered as the reference and was compared to the improvement or deterioration groups separately. RESULTS: A total of 504 patients were included, of whom 22% experienced inter-hospital improvement, 14% deterioration, and 64% were stable. Pre-transfer variables independently associated with clinical improvement were intravenous thrombolysis use, more distal occlusions, and lower serum glucose; variables associated with deterioration included more proximal occlusions and higher serum glucose. On post-transfer imaging, clinical improvement was associated with arterial recanalization and smaller infarct growth and deterioration with larger infarct growth. As compared to stable patients, those with clinical improvement had better 3-month functional outcome (adjusted common odds ratio (cOR) = 2.43; 95% confidence interval (CI) = 1.59-3.71; p < 0.001), while those with deterioration had worse outcome (adjusted cOR = 0.60; 95% CI = 0.37-0.98; p = 0.044). CONCLUSION: Substantial inter-hospital clinical changes are frequently observed in LVO-related ischemic strokes, with significant impact on functional outcome. There is a need to develop treatments that improves the clinical status during transfer. DATA ACCESS STATEMENT: The data that support the findings of this study are available upon reasonable request.

Cerebral microbleeds and risk of symptomatic hemorrhagic transformation following mechanical thrombectomy for large vessel ischemic stroke.

BACKGROUND AND PURPOSE: In patients with acute ischemic stroke (AIS) treated with endovascular therapy (EVT), the association of pre-existing cerebral small vessel disease (cSVD) with symptomatic intracerebral hemorrhage (sICH) remains controversial. We tested the hypothesis that the presence of cerebral microbleeds (CMBs) and their burden would be associated with sICH after EVT of AIS. METHODS: We conducted a retrospective study combining cohorts of patients that underwent EVT between January 1st 2015 and January 1st 2020. CMB presence, burden, and other cSVD markers were assessed on a pre-treatment MRI, evaluated independently by two observers. Primary outcome was the occurrence of sICH. RESULTS: 445 patients with pretreatment MRI were included, of which 70 (15.7%) demonstrated CMBs on baseline MRI. sICH occurred in 36 (7.6%) of all patients. Univariate analysis did not demonstrate an association between CMB and the occurrence of sICH (7.5% in CMB+ group vs 8.6% in CMB group, p = 0.805). In multivariable models, CMBs' presence was not significantly associated with increased odds for sICH (-aOR- 1.19; 95% CI [0.43-3.27], p = 0.73). Only ASPECTs (aOR 0.71 per point increase; 95% CI [0.60-0.85], p < 0.001) and collaterals status (aOR 0.22 for adequate versus poor collaterals; 95% CI [0.06-0.93], p 0.019) were independently associated with sICH. CONCLUSION: CMB presence and burden is not associated with increased occurrence of sICH after EVT. This result incites not to exclude patients with CMBs from EVT. The risk of sICH after EVT in patients with more than10 CMBs will require further investigation. REGISTRATION: Registration-URL: http://www. CLINICALTRIALS: gov ; Unique identifier: NCT01062698.

Functional Outcome and Hemorrhage Rates After Bridging Therapy With Tenecteplase or Alteplase in Patients With Large Ischemic Core.

BACKGROUND AND OBJECTIVES: IV tenecteplase is an alternative to alteplase before mechanical thrombectomy (MT) in patients with large-vessel occlusion (LVO) ischemic stroke. Little data are available on its use in patients with large ischemic core. We aimed to compare the efficacy and safety of both thrombolytics in this population. METHODS: We conducted a retrospective analysis of patients with anterior circulation LVO strokes and diffusion-weighed imaging Alberta Stroke Program Early CT Score (DWI-ASPECTS) ≤5 treated with tenecteplase or alteplase before MT from the TETRIS (tenecteplase) and ETIS (alteplase) French multicenter registries. Primary outcome was reduced disability at 3 months (ordinal analysis of the modified Rankin scale [mRS]). Safety outcomes were 3-month mortality, parenchymal hematoma (PH), and symptomatic intracranial hemorrhage (sICH). We used propensity score overlap weighting to reduce baseline differences between treatment groups. RESULTS: We analyzed 647 patients (tenecteplase: n = 194; alteplase: n = 453; inclusion period 2015-2022). Median (interquartile range) age was 71 (57-81) years, with NIH Stroke Scale score 19 (16-22), DWI-ASPECTS 4 (3-5), and last seen well-to-IV thrombolysis and puncture times 165 minutes (130-226) and 260 minutes (203-349), respectively. After MT, the successful reperfusion rate was 83.1%. After propensity score overlap weighting, all baseline variables were well balanced between both treatment groups. Compared with patients treated with alteplase, patients treated with tenecteplase had better 3-month mRS (common odds ratio [OR] for reduced disability: 1.37, 1.01-1.87, p = 0.046) and lower 3-month mortality (OR 0.52, 0.33-0.81, p < 0.01). There were no significant differences between thrombolytics for PH (OR 0.84, 0.55-1.30, p = 0.44) and sICH incidence (OR 0.70, 0.42-1.18, p = 0.18). DISCUSSION: Our data are encouraging regarding the efficacy and reassuring regarding the safety of tenecteplase compared with that of alteplase in bridging therapy for patients with LVO strokes and a large ischemic core in routine clinical care. These results support its consideration as an alternative to alteplase in bridging therapy for patients with large ischemic cores. TRIALS REGISTRATION INFORMATION: NCT03776877 (ETIS registry) and NCT05534360 (TETRIS registry). CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that patients with anterior circulation LVO stroke and DWI-ASPECTS ≤5 treated with tenecteplase vs alteplase before MT experienced better functional outcomes and lower mortality at 3 months.