A fully automatic method for vascular tortuosity feature extraction in the supra-aortic region: unraveling possibilities in stroke treatment planning

Vascular tortuosity of supra-aortic vessels is widely considered one of the main reasons for failure and delays in endovascular treatment of large vessel occlusion in patients with acute ischemic stroke. Characterization of tortuosity is a challenging task due to the lack of objective, robust and effective analysis tools. We present a fully automatic method for arterial segmentation, vessel labelling and tortuosity feature extraction applied to the supra-aortic region. A sample of 566 computed tomography angiography scans from acute ischemic stroke patients (aged 74.8 ± 12.9, 51.0% females) were used for training, validation and testing of a segmentation module based on a U-Net architecture (162 cases) and a vessel labelling module powered by a graph U-Net (566 cases). Successively, 30 cases were processed for testing of a tortuosity feature extraction module. Measurements obtained through automatic processing were compared to manual annotations from two observers for a thorough validation of the method. The proposed feature extraction method presented similar performance to the inter-rater variability observed in the measurement of 33 geometrical and morphological features of the arterial anatomy in the supra-aortic region. This system will contribute to the development of more complex models to advance the treatment of stroke by adding immediate automation, objectivity, repeatability and robustness to the vascular tortuosity characterization of patients

Bridging intravenous thrombolysis in patients with atrial fibrillation.

Background and purpose 40% of acute ischemic stroke patients treated by mechanical thrombectomy (MT) have a clinical history of atrial fibrillation (AF). The safety of bridging intravenous thrombolysis (IVT) (MT + IVT) is currently being discussed. We aimed to analyze the interaction between oral anticoagulation (OAC) status or AF with bridging IVT, regarding the occurrence of symptomatic intracranial hemorrhage (sICH) and functional outcome. Materials and Methods Multicentric observational cohort study (BEYOND-SWIFT registry) of consecutive patients undergoing MT between 2010 and 2018 (n = 2,941). Multinomial regression models were adjusted for prespecified baseline and plausible pathophysiological covariates identified on a univariate analysis to assess the association of AF and OAC status with sICH and good outcomes (90-day modified Rankin Scale score 0-2). Results In the total cohort (median age 74, 50.6% women), 1,347 (45.8%) patients had AF. Higher admission National Institutes of Health Stroke Scale (NIHSS) score (aOR 1.04 [95% 1.02-1.06], per point of increase) and prior medication with Vitamin K antagonists (VKA) (aOR 2.19 [95% 1.27-3.66]) were associated with sICH. Neither AF itself (aOR 0.71 [95% 0.41-1.24]) nor bridging IVT (aOR 1.08 [0.67-1.75]) were significantly associated with increased sICH. Receiving bridging IVT (aOR 1.61 [95% 1.24-2.11]) was associated with good 90-day outcome, with no interaction between AF and IVT (p = 0.92). Conclusion Bridging IVT appears to be a reasonable clinical option in selected patients with AF. Given the increased sICH risk in patients with VKA, subgroup analysis of the randomized controlled trials should analyze whether patients with VKA might benefit from withholding bridging IVT. Registration clinicaltrials.gov; Unique identifier: NCT03496064

Headache : A striking prodromal and persistent symptom, predictive of COVID-19 clinical evolution

To define headache characteristics and evolution in relation to COVID-19 and its inflammatory response. This is a prospective study, comparing clinical data and inflammatory biomarkers of COVID-19 patients with and without headache, recruited at the Emergency Room. We compared baseline with 6-week follow-up to evaluate disease evolution. Of 130 patients, 74.6% (97/130) had headache. In all, 24.7% (24/97) of patients had severe pain with migraine-like features. Patients with headache had more anosmia/ageusia (54.6% vs. 18.2%; p < 0.0001). Clinical duration of COVID-19 was shorter in the headache group (23.9 ± 11.6 vs. 31.2 ± 12.0 days; p = 0.028). In the headache group, IL-6 levels were lower at the ER (22.9 (57.5) vs. 57.0 (78.6) pg/mL; p = 0.036) and more stable during hospitalisation. After 6 weeks, of 74 followed-up patients with headache, 37.8% (28/74) had ongoing headache. Of these, 50% (14/28) had no previous headache history. Headache was the prodromal symptom of COVID-19 in 21.4% (6/28) of patients with persistent headache (p = 0.010). Headache associated with COVID-19 is a frequent symptom, predictive of a shorter COVID-19 clinical course. Disabling headache can persist after COVID-19 resolution. Pathophysiologically, its migraine-like features may reflect an activation of the trigeminovascular system by inflammation or direct involvement of SARS-CoV-2, a hypothesis supported by concomitant anosmia

Granulocytes-Rich Thrombi in Cerebral Large Vessel Occlusion Are Associated with Increased Stiffness and Poorer Revascularization Outcomes

Altres ajuts: acords transformatius de la UABWe aim to identify a profile of intracranial thrombus resistant to recanalization by mechanical thrombectomy (MT) in acute stroke treatment. The first extracted clot of each MT was analyzed by flow cytometry obtaining the composition of the 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. To explore the relationship between stiffness of intracranial clots and cellular composition, unconfined compression tests were performed in other cohorts of cases. Thrombi obtained in 225 patients were analyzed. MTF were observed in 30 cases (13%). MTF was associated with atherosclerosis etiology (33.3% vs. 15.9%; p = 0.021) and higher number of passes (3 vs. 2; p < 0.001). Clot analysis of MTF showed higher percentage of granulocytes [82.46 vs. 68.90% p < 0.001] and lower percentage of monocytes [9.18% vs.17.34%, p < 0.001] in comparison to successful MT cases. The proportion of clot granulocytes (aOR 1.07; 95% CI 1.01-1.14) remained an independent marker of MTF. Among thirty-eight clots mechanically tested, there was a positive correlation between granulocyte proportion and thrombi stiffness (Pearson's r = 0.35, p = 0.032), with a median clot stiffness of 30.2 (IQR, 18.9-42.7) kPa. Granulocytes-rich thrombi are harder to capture by mechanical thrombectomy due to increased stiffness, so a proportion of intracranial granulocytes might be useful to guide personalized endovascular procedures in acute stroke treatment. Supplementary Information: The online version contains supplementary material available at 10.1007/s13311-023-01385-1

Functional Recovery and Serum Angiogenin Changes According to Intensity of Rehabilitation Therapy After Stroke

Rehabilitation is still the only treatment available to improve functional status after the acute phase of stroke. Most clinical guidelines highlight the need to design rehabilitation treatments considering starting time, intensity, and frequency, according to the tolerance of the patient. However, there are no homogeneous protocols and the biological effects are under investigation. To investigate the impact of rehabilitation intensity (hours) after stroke on functional improvement and serum angiogenin (ANG) in a 6-month follow-up study. A prospective, observational, longitudinal, and multicenter study with three cohorts: strokes in intensive rehabilitation therapy (IRT, minimum 15 h/week) vs. conventional therapy (NO-IRT, <15 h/week), and controls subjects (without known neurological, malignant, or inflammatory diseases). A total of seven centers participated, with functional evaluations and blood sampling during follow-up. The final cohort includes 62 strokes and 43 controls with demographic, clinical, blood samples, and exhaustive functional monitoring. The median (IQR) number of weekly hours of therapy was different: IRT 15 (15-16) vs. NO-IRT 7.5 (5-9), p < 0.01, with progressive and significant improvements in both groups. However, IRT patients showed earlier improvements (within 1 month) on several scales (CAHAI, FMA, and FAC; p < 0.001) and the earliest community ambulation achievements (0.89 m/s at 3 months). There was a significant difference in ANG temporal profile between the IRT and NO-IRT groups (p < 0.01). Additionally, ANG was elevated at 1 month only in the IRT group (p < 0.05) whereas it decreased in the NO-IRT group (p < 0.05). Our results suggest an association of rehabilitation intensity with early functional improvements, and connect the rehabilitation process with blood biomarkers

Endovascular Stroke Treatment and Risk of Intracranial Hemorrhage in Anticoagulated Patients.

Background and Purpose- We aimed to determine the safety and mortality after mechanical thrombectomy in patients taking vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs). Methods- In a multicenter observational cohort study, we used multiple logistic regression analysis to evaluate associations of symptomatic intracranial hemorrhage (sICH) with VKA or DOAC prescription before thrombectomy as compared with no anticoagulation. The primary outcomes were the rate of sICH and all-cause mortality at 90 days, incorporating sensitivity analysis regarding confirmed therapeutic anticoagulation. Additionally, we performed a systematic review and meta-analysis of literature on this topic. Results- Altogether, 1932 patients were included (VKA, n=222; DOAC, n=98; no anticoagulation, n=1612); median age, 74 years (interquartile range, 62-82); 49.6% women. VKA prescription was associated with increased odds for sICH and mortality (adjusted odds ratio [aOR], 2.55 [95% CI, 1.35-4.84] and 1.64 [95% CI, 1.09-2.47]) as compared with the control group, whereas no association with DOAC intake was observed (aOR, 0.98 [95% CI, 0.29-3.35] and 1.35 [95% CI, 0.72-2.53]). Sensitivity analyses considering only patients within the confirmed therapeutic anticoagulation range did not alter the findings. A study-level meta-analysis incorporating data from 7462 patients (855 VKAs, 318 DOACs, and 6289 controls) from 15 observational cohorts corroborated these observations, yielding an increased rate of sICH in VKA patients (aOR, 1.62 [95% CI, 1.22-2.17]) but not in DOAC patients (aOR, 1.03 [95% CI, 0.60-1.80]). Conclusions- Patients taking VKA have an increased risk of sICH and mortality after mechanical thrombectomy. The lower risk of sICH associated with DOAC may also be noticeable in the acute setting. Improved selection might be advisable in VKA-treated patients. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT03496064. Systematic Review and Meta-Analysis: CRD42019127464

Estratègies per a agilitzar la detecció d'oclusions vasculars en pacients amb ictus isquèmic agut

Introducció: El tractament endovascular ha esdevingut la teràpia estàndard en pacients amb ictus isquèmic amb oclusió de gran vas. Cada vegada hi ha més interès en estudiar l'eficàcia de la trombectomia mecànica en oclusions de vasos més distals, per això cal assegurar que aquestes oclusions s'identifiquen de forma precisa. Objectius: Analitzar la precisió en la detecció d'oclusions vasculars en les diferents modalitats d'imatge utilitzades de forma rutinària i analitzar si és possible la detecció d'oclusions vasculars en una tomografia computeritzada (TC) sense contrast a partir d'un algoritme d'intel·ligència artificial. Mètodes: Es va realitzar un anàlisi retrospectiu de pacients amb sospita d'ictus isquèmic valorats a centres terciaris, als que se'ls va realitzar un estudi basal d'imatge que constava de: TC sense contrast, angio-TC i, en alguns casos, TC de perfusió. Es va analitzar la sensibilitat de la lectura aïllada de l'angio-TC per part de dos neuroradiòlegs. En un segon lloc es va validar un algoritme d'intel·ligència artificial per a la detecció d'oclusions vasculars en la TC sense contrast. Resultats: La lectura aïllada de l'angio-TC per part dels radiòlegs va tenir una sensibilitat per a la detecció d'oclusions del 50.3% de forma global i del 69.9% entre els pacients que van rebre trombectomia mecànica. La sensibilitat va ser superior per oclusions més proximals (artèria caròtide interna: 91.7%, segment M1 d'artèria cerebral mitja: 84.4% i d'un 36.1% en la resta de localitzacions) i s'associava al volum d'hipoperfusió mesurat com a Tmax>6s (OR 1.03 (IC 95% 1.02-1.04, p6s (OR 1.03 (IC 95% 1.02-1.04, p6s hypoperfusion volume (OR 1.03 (CI 95% 1.02-1.04, p<0.001)). A deep learning algorithm showed a sensitivity at detecting proximal vessel occlusions of 83.2%. The accuracy of the algorithm at determining the presence of a large vessel occlusion was similar to a NIHSS cut-off point of ≥ 10 (area under the curve of 0.86 vs. 0.87 respectively). The combination of radiological and clinical data in the Machine learning algorithm obtained the best accuracy (area under the curve 0.91). Inter-rater agreement between radiologists ranged from 0.68 to 0.80. Conclusions: Assessment of vessel occlusions solely based on CTA may result in missing potential EVT candidates. The development of diagnostic aid tools based on machine learning algorithms might be a useful strategy to increase the detection of vessel occlusions without need of contrast enhanced imaging in suspected acute stroke patients

Abstract Number ‐ 241: Simultaneous IV tPA During Thrombectomy Reduces Post‐Procedure Hypoperfusion Volumes in Anterior LVO Patients

Introduction Simultaneous tPA administration during mechanical thrombectomy may induce synergistic benefits (1). We aimed to characterize the hypoperfusion status after thrombectomy according to the timing of tPA administration and the degree of final recanalization. Methods We studied consecutive anterior circulation large vessel occlusion (LVO) stroke patients treated with mechanical thrombectomy who received a CT perfusion (CTP) immediately after endovascular procedure (2). Patients were divided in three groups according to: no iv tPA treatment (non‐tPA), tPA administration before 120 minutes (tPA>120) or iv tPA administration within 120 min (tPA6s) and relative hypoperfusion reduction compared with admission CTP (volume post‐procedure – admission Tmax>6s/admission Tmax>6s) according to final TICI scores were compared between the three study groups. Results One hundred and sixty‐nine patients were included in the study, mean age 72 years and median baseline NIHSS of 15. Thirty (17.8%) patients received iv tPA more than 2h before groin puncture (tPA>120), 32(18.9%) within 2h of the puncture (tPA 120 groups. For each final TICI score the post‐procedure hypoperfusion tended to be lower in the tPA< 120‐group, with a stronger reduction in patients with lower degree of recanalization (Figure). Conclusions A reduction of post‐thrombectomy hypoperfusion volumes was detected in patients treated with iv tPA during or shortly before thrombectomy, which could be a surrogate marker of the beneficial effect of tPA on the microcirculation. The specific reperfusion synergistic effect of tPA and mechanical thrombectomy beyond LVO recanalization warrants future studies

BRIVA-LIFE-A multicenter retrospective study of the long-term use of brivaracetam in clinical practice.

Evaluate long-term effectiveness and tolerability of brivaracetam in clinical practice in patients with focal epilepsy. This was a multicenter retrospective study. Patients aged ≥16 years were started on brivaracetam from November 2016 to June 2017 and followed over 1 year. Data were obtained from medical records at 3, 6 and 12 months after treatment initiation for evaluation of safety- and seizure-related outcomes. A total of 575 patients were included in analyses; most had been treated with ≥4 lifetime antiepileptic drugs. Target dosage was achieved by 30.6% of patients on the first day. Analysis of primary variables at 12 months revealed that mean reduction in seizure frequency was 36.0%, 39.7% of patients were ≥50% responders and 17.5% were seizure-free. Seizure-freedom was achieved by 37.5% of patients aged ≥65 years. Incidence of adverse events (AEs) and psychiatric AEs (PAEs) was 39.8% and 14.3%, respectively, and discontinuation due to these was 8.9% and 3.7%, respectively. Somnolence, irritability, and dizziness were the most frequently reported AEs. At baseline, 228 (39.7%) patients were being treated with levetiracetam; most switched to brivaracetam (dose ratio 1:10-15). Among those who switched because of PAEs (n = 53), 9 (17%) reported PAEs on brivaracetam, and 3 (5.7%) discontinued because of PAEs. Tolerability was not highly affected among patients with learning disability or psychiatric comorbidity. In a large population of patients with predominantly drug-resistant epilepsy, brivaracetam was effective and well-tolerated; no unexpected AEs occurred over 1 year, and the incidence of PAEs was lower compared with levetiracetam

Association of initial imaging modality and futile recanalization after thrombectomy.

OBJECTIVE To test the hypothesis that selection by initial imaging modality (MRI vs CT) is associated with rate of futile recanalizations (FR) after mechanical thrombectomy (MT), we assessed this association in a multicenter, retrospective observational registry (BEYOND-SWIFT, NCT03496064). METHODS In 2011 patients (49.7% female, median age 73 [61-81]) included between 2009 and 2017, we performed univariate and multivariate analyses regarding the occurrence of FR. FR were defined as 90 days modified Rankin Scale (mRS) 4-6 despite successful recanalization in patients selected by MRI (N = 690) and CT (N = 1,321) with a sensitivity analysis considering only patients with mRS 5-6 as futile. RESULTS MRI as compared to CT resulted in similar rates of subsequent MT (aOR 1.048, 95% CI 0.677-1.624). Rates of FR were as follows: 571/1,489 (38%) FR mRS 4-6 including 393/1,489 (26%) FR mRS 5-6. CT based selection was associated with increased rates of futile recanalizations compared to MRI (44% [41%-47%] vs 29% [25%-32%], p < 0.001; aOR 1.77 [95%-CI: 1.25-2.51]). These findings were robust in sensitivity analysis. MRI-selected patients had a delay of approximately 30 minutes in workflow metrics in real-world university comprehensive stroke centers. However, functional outcome and mortality were more favorable in patients selected by MRI compared to patients selected with CT. CONCLUSIONS CT-selection for MT was associated with an increased risk of futile recanalizations as compared to MR-selection. Efforts are still needed to shorten workflow delays in MRI patients. Further research is needed to clarify the role of the initial imaging modality on FR occurrence and to develop a reliable FR prediction algorithm