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Introduction:After achieving successful reperfusion some acute stroke patients still exhibit persistent perfusion deficits. These deficits have been defined in a heterogeneous manner by using CBF, CBV or Tmax maps as a perfusion deficit in the previous ischemic penumbra (impaired microcirculation perfusion-IMP) or inside the infarcted tissue (no reflow-NR). The significance, frequency and pathophysiology of this phenomenon are so far unknown.Methods:Prospective cohort of patients with isolated anterior intracranial occlusion undergoing endovascular treatment (EVT) and achieving complete recanalization (final mTICI≥2B). Brain MRI was performed on arrival (pre-EVT) and &lt2h after EVT (post-EVT). Infarcted tissue was segmented on DWI pre-EVT. Pre and post-EVT perfusion maps were obtained with Olea software. NR was defined in the post-EVT perfusion maps as the region inside the infarcted tissue which showed a CBV&lt15% compared to the contralateral side, while IMP was the equivalent area inside the previous tissue in penumbra. We evaluated the association between both NR and IMP and NIHSS at 24h, NIHSS at discharge and modified Rankin score (mRS) at three months adjusting by baseline NIHSS and final mTICI.Results:Thirty-five patients were included. All of them had IMP areas and 25 (71%) had NR areas. The median volume of NR and IMP was 3.43ml [IQR 1.43-8.81], corresponding to 17.9% of the infarcted tissue [IQR 4.2-50.3] and 33.9ml [IQR 14.0-69.3] (27.7% [IQR 8.2-51.2] of the penumbra) respectively. Patients with NR areas had higher NIHSS at 24 h and at discharge and higher mRS at 3 months. Volume of NR was independently associated with higher NIHSS at 24 h and at discharge. No independent association was found with IMP volume. Neither NR nor IMP were associated with hemorrhagic transformation. Patients receiving rTPA previous to EVT showed higher perfusion values inside the infarct than patients with primary EVT (2.31 mL/100g [1.48-2.43] vs 0.92 [0.7-1.47] p=0.02), although NR areas appeared in the same proportion in both groups.Conclusions:No reflow phenomenon can be a marker of poor outcome in the early evaluation of successfully recanalized stroke patients especially when the persistent perfusion deficit is located inside the infarcted tissue.

Introduction:We aimed to evaluate venous delay before and after treatment as a marker of radiological and clinical outcome in stroke patients receiving endovascular treatment (EVT).Methods:Prospective cohort of patients with anterior intracranial occlusion undergoing EVT. Brain MRI was performed on arrival (pre-EVT), <2h after EVT (post-EVT), and 5 days after stroke. Final infarct volume was segmented on DWI at 5 days. We evaluated the veins of Labbé, Trolard and the superficial middle cerebral vein at both hemispheres on the dynamic MR angiography (dmRA) pre-EVT and post-EVT. For each vein we calculated a standardized venous delay measure:[(time to maximum venous contrast filling in the healthy hemisphere-time to maximum venous contrast filling in the affected hemisphere)/time to maximum venous contrast filling in the healthy hemisphere]x100. We defined venous delay as the value of the most delayed vein in each patient. We assessed the association between venous delay pre-EVT and post-EVT and final infarct volume and modified Rankin Scale (mRS) at 90 days, using multivariable regressions adjusted by successful reperfusion (mTICI≥2b) and other relevant variables.Results:From 98 included patients (median NIHSS 17, final mTICI≥2b 86%), 89 pre-EVT dMRIs and 88 post-EVT dMRIs were evaluable. The median venous delay pre-EVT and post-EVT were -31.9[-58.1;-16.7]% and -13.5[-34.5;-7.5]%, respectively. Venous delay pre-EVT was not related to infarct volume or clinical outcome. When final mTICI≥2B, venous asymmetry decreased but still persisted. For each 10% of increment in venous delay post-EVT, there was an adjusted increase of 0.12[0.05-0.19]ml in the final infarct volume. Venous delay post-EVT was independently associated with mRS at 90 days (cOR 1.013 [95%CI 1.001-1.0256]).Conclusion:Cortical vein delay assessed after but not before EVT, is associated with a larger final infarct volume and with a worse clinical outcome.

Hypothesis:We aim to identify a profile of intracranial thrombus resistant to recanalization by standard mechanical thrombectomy (MT) in acute stroke treatment.Methods:First extracted clot of each MT were analyzed by Flow Cytometry obtaining composition of main leukocyte populations: granulocytes, monocytes and lymphocytes. Demographics, reperfusion treatment and grade of recanalization were registered. MT Failure ( MTF) was defined as final Thrombolysis in Cerebral Infarction score IIa or lower and/ or need of permanent intracranial stenting as a rescue therapy after standard MT. In other cohort of cases, unconfined compression tests were performed to explore stiffness of retrieved clots . We looked for correlation between mechanical characterization tests and clot composition.Results:Among 225 patients, there were 13 % of MTF that were significantly associated to atherosclerosis etiology ( 33.3% vs. 15.9% ; p 0.021) , more passes ( 3 vs. 2; p <0.001), higher proportion of clot granulocytes ( 82.46% vs. 68.90% ; p <0.001) and lower proportion of clot monocytes ( 9.18% vs.17.34% ; p<0.001). The proportion of clot granulocytes (aOR 1.07; 95% CI 1.01-1.14) remained as an independent marker of MTF. Among Thirty eight clots tested by unconfined compression median clot stiffness was 30.2 (IQR, 18.9-42.7) kPa. There was a positive correlation between granulocyte proportion and thrombi stiffness (Pearson’s r=0.35, p=0.032).Conclusions:There is a positive correlation between granulocyte proportion and thrombi stiffness that may explain endovascular resistance to recanalization. Influence of granulocytes within thrombus may be a target for future reperfusion treatments.

Introduction:Our objective is to identify thrombus composition associated with first pass recanalization (FPR) in mechanical thrombectomy (MT).Methods:Intracranial thrombi obtained in MT were divided in two equal parts. One part was analyzed with anatomopathological studies to quantify fibrin, red-blood cell( Hematoxilin & Eosin) and platelets( cd61 Immunohistochemical staining) , the other part was analyzed by flow cytometry to quantify leukocyte populations (granulocytes, lymphocytes and monocytes) and their relative proportions . FPR were defined as ≥ mTICI 2b after first pass in MT. Thrombi composition, baseline variables (demographics, previos use of antiplatelets or anticoagulants, blood pressure and blood glucose at hospital arrival ) etiology, intravenous fibrinolysis, ASPECTS score and first attempt thrombectomy devices: direct aspiration, stent retriever or combinations were compared between FPR and Non-FPR groups.Results:Fifty percent (38/76) of the cases analyzed obtained FPR. There were no differences in baseline variables , etiology, Aspects score, previous use of fibrinolysis or type of device used for MT. The thrombi obtained with FPR presented higher proportion of red blood cells (33.64% vs 18.16% p = 0.048) and lymphocytes (10.07% vs 4.43% p = 0.042) and lower proportion of platelets (61, 48% vs 67.26% p = 0.042) in comparison to non-FPR group. The proportion of platelets was an independent marker of FPR (OR 0.97; CI 0.95-0.99). There was an inverse correlation between the proportion of platelets and lymphocytes (rho -0.44, p <0.001).Conclusion:Platelets proportion in intracranial thrombus is an independent marker of first pass recanalization. Inverse relationship between lymphocytes and platelets may be a target for future reperfusion treatments

Hypothesis:Somatosensory evoked potentials (SEPs), as surrogate of cerebral blood flow, may give substantial additional predictive value to that provided by clinical and imaging factors and optimize the selection of patients benefiting from mechanical thrombectomy (MT)Methods:Bilateral median nerve SEPs were recorded before and continuously during MT in consecutive patients with AIS and anterior LVO. N20 response ipsilateral to the ischemic hemisphere was measured. The adjusted predictive value of the N20 on functional Independence (modified Rankin Scale score ≤2) after MT was analyzed by binary logistic regression and its predictive value on the full range of disability by ordinal logistic regression. We constructed different regression models with other clinical and imaging predictors at the pre- and in- hospital setting to determine the independent predictive power of N20 for a potential treatment decision-makingResults:A total of 223 patients were recruited. A blinded reading of SEPs recordings identified presence of N20 in 110 (49.3%), absence in 58 (26%) and not assessable in 55 patients due to radiofrequency interferences. Prior to MT, N20 had positive predictive value (PPV) of 93% (95%CI, 0.8 to 0.98) and increased 10 fold the likelihood of good functional outcome at 7 days (adjusted OR, 9.9; 95%CI, 3.1-44.6). Receiver operating curves showed that N20 had a higher capacity to predict good functional outcome (AUC 0.82) than models constructed with pre-hospital (age, sex, serum glucose, median blood pressure, NIHSS; AUC 0.75) or in-hospital (NIHSS, ASPECTS; AUC 0.72) factors. During MT, N20 had PPV of 100% (95% CI, 0.85-1) and was the unique independent factor associated with functional independence (adjusted OR, 2.74; 95%CI, 1.90-4.29). Perfusion CT or MR was available in a subgroup of 116 patients. Baseline N20 showed a higher capacity to predict good functional outcome (n=168, AUC 0.71) compared with ischemic core (n=127, AUC 0.66), ischemic penumbra (Tmax>6) (n=116, AUC 0.54) and collateral status (n=191, AUC 0.61)Conclusions:SEPs monitoring is a fast and bedside technique that could complement current clinical factors in terms of increasing the eligibility of AIS patients for MT and improving prognosis.

Aim:We performed a histological and immune analysis of the clot in acute stroke patients to detect surrogates of stroke etiology.Methods:We conducted a prospective observational study of consecutive patients with acute stroke who underwent thrombectomy that obtained extracted thrombus (ITACAT study). Several staining were performed to evaluate red blood cells/fibrin (hematoxylin/eosin), platelets (CD61) and leucocytes (CD4, CD8 and CD20). All patients received CT angio to detect extra/intracranial vascular stenosis and 30-day cardiac monitoring to diagnose AF. According to TOAST classification the thrombi were classified in cardioembolic etiology CE (T-CE), due to symptomatic atherosclerosis (T-AT) and without any cause (T-CRYP). We excluded strokes due to double cause or incomplete workup.Results:Of the 117 patients: 30 were T-AT, 55 were T-CE and 32 were T-CRYP. T-AT patients were younger: T-AT 68 years (60-77) Vs. T-CE 75 years (68-80) Vs. T-CRYP 72 years (55-81) (p=0.034). T-AT group had higher percentage of CD4: T-AT 6.52% (4-13) Vs. T-CE (3.31% (12.9) Vs .T-CRYP 3.72% (1.5-12) (p=0.015) and lower percentage of CD61: T-AT 51.18% (34-68) Vs. CE 64.70% (19.56) Vs. CRYP 70.3% (19) (p=0.001). There were no correlation between CD4 and platelets. Both CD4 OR 1.05 (1-1.10) (p=0.020) and CD61 (OR 0.96 (0.94-0.98) (p=0.01) independently predicted T-AT from the age. Final analysis (n=400 cases) will be ended in September 2021.Conclusions:Patients with high percentage of CD4 and low percentage of CD61 are related to atherosclerosis etiology.