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Background: Cognitive improvement after endovascular embolization of an intracranial dural arteriovenous fistula (dAVF) remains unexplored. We aim to investigate cognitive changes following endovascular embolization of dAVFs., Methods: Neuropsychology in dural ArterIal Fistula (NAIF) was a prospective multicentric study including patients with an angiographic diagnosis of dAVF who underwent endovascular embolization over the course of 4 years. A complete neuropsychological evaluation comprising five cognitive domains (attention and executive functions, memory, language, praxis, gnosis) was performed at baseline and 3 months follow-up. Mean Z scores for cognitive tests were compared pre- and post-treatment using paired sample t-tests, where higher Z scores indicate better cognition. Effect sizes were computed as Cohen's d., Results: A total of 32 patients (mean age 61.1±15.4 years, 10 (31.3%) females) were included. Patients exhibited improved performance in attention and executive functions: executive functions-attention (+0.282, P=0.009, d=0.29), executive functions-fluencies (+0.283, P=0.029, d=0.4), and executive functions-processing speed (+0.471, P=0.039, d=0.41). There was an increase in memory: verbal learning and verbal delayed recall scores (+0.513, P<0.001, d=0.55, and +0.385, P=0.001, d=0.41, respectively), while verbal recognition parameters (+0.839, P=0.086, d=0.37) and visual memory (delayed recall) (+0.430, P=0.060, d=0.35) displayed trends toward improved performance. Regarding language, there was significant overall improvement (+0.300, P=0.014, d=0.24), but neither praxis nor gnosis changed significantly. These cognitive outcomes were independent of the severity (measured as Cognard classification), and no patient experienced cognitive worsening., Conclusion: This study suggests that endovascular embolization confers cognitive benefits on dAVF patients undergoing endovascular embolization and may be beneficial even for patients with a low risk of hemorrhage., Competing Interests: Competing interests: This study was supported by Medtronic. The supporter had no role in the design, conduct, collection, management, analysis, and interpretation of the data, preparation and approval of the manuscript. Dr Gramegna had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Dr Tomasello has received personal fees from Anaconda Biomed, Balt, Medtronic, Perflow, and Stryker outside the submitted work. No other disclosures were reported., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The aim of this is to explore the histological basis of vessel wall enhancement (WE) on magnetic resonance imaging (MRI), which is a strong radiological biomarker of aneurysmal prone to rupture compared to other classical risk predictors (e.g., PHASES score, size, morphology)., Methods: A prospective observational study was performed including all consecutive patients presenting with a saccular intracranial aneurysm at Vall d'Hebron University Hospital between October 2017 and May 2019. The patients underwent high-resolution 3 T MRI, and their aneurysms were classified into asymptomatic, symptomatic, and ruptured. A histological and immunohistochemical study was performed in a subgroup of patients (n = 20, of which 15 presented with WE). Multiple regression analyses were performed to identify predictors of rupture and aneurysm symptoms., Results: A total of 132 patients were enrolled in the study. WE was present in 36.5% of aneurysms: 22.9% asymptomatic, 76.9% symptomatic, and 100% ruptured. Immunohistochemical markers associated with WE were CD3 T cell receptor (p = 0.05) and CD45 leukocyte common antigen (p = 0.05). Moreover, WE is an independent predictor of symptomatic and ruptured aneurysms (p < 0.001)., Conclusions: Aneurysms with WE present multiple histopathological changes that may contribute to wall disruption and represent the pathophysiological basis of radiological WE. Moreover, WE is an independent diagnostic predictor of aneurysm symptoms and rupture., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Objective: The goal of this study was to evaluate the effectiveness and safety of a new noncompletely occlusive net-assisted remodeling technique in which the Cascade net device is used for temporary bridging of intracranial aneurysms., Methods: Between July 2018 and May 2019, patients underwent coil embolization with the Cascade net device within 4 centers in Europe. Analysis of angiographic (modified Raymond-Roy classification [MRRC]) and clinical outcomes data was conducted immediately following treatment and at the 6-month follow-up., Results: Fifteen patients were included in the study (mean age 58 ± 13 years, 11/15 [73.3%] female). Ten patients had unruptured aneurysms, and 5 presented with ruptured aneurysms with acute subarachnoid hemorrhage. The mean aneurysm dome length was 6.27 ± 2.33 mm and the mean neck width was 3.64 ± 1.19 mm. Immediately postprocedure, MRRC type I (complete obliteration) was achieved in 11 patients (73.3%), whereas a type II (residual neck) was achieved in 4 patients (26.7%). Follow-up examination was performed in 7/15 patients and showed stabilization of aneurysm closure with no thromboembolic complications and only 1 patient with an increased MRRC score (from I to II) due to coil compression., Conclusions: Initial experience shows that the use of a new noncompletely occlusive net-assisted remodeling technique with the Cascade net device may be safe and effective for endovascular coil embolization of intracranial aneurysms.

Background: First-pass recanalization via mechanical thrombectomy (MT) has been associated with improved clinical outcome in patients with acute ischaemic stroke. The optimal approach to achieve first-pass effect (FPE) remains unclear. No study has evaluated angiographic features associated with the achievement of FPE. We aimed to determine the procedural approaches and angiographic signs that may predict FPE., Methods: We performed a prospective, multi-centre, observational study of FPE in patients with anterior circulation stroke treated with MT between February and June 2017. MTs were performed using different devices, deployment manoeuvres (standard versus 'Push and Fluff' technique), proximal balloon guide catheter (PBGC), distal aspiration catheter (DAC) or both. The angiographic clot protrusion sign (ACPS) was recorded. Completed FPE (cFPE) was defined as a modified thrombolysis in cerebral infarction score of 2c-3. Associations were sought between cFPE and procedural approaches and angiographic signs., Results: A total of 193 patients were included. cFPE was achieved in 74 (38.3%) patients. The use of the push and fluff technique (odds ratio (OR) 3.45, 95% confidence interval (CI): 1.28-9.29, p  = 0.010), PBGC (OR 3.81, 95% CI: 1.41-10.22, p  = 0.008) and ACPS (OR 4.71, 95% CI: 1.78-12.44, p  = 0.002) were independently associated with cFPE. Concurrence of these three variables led to cFPE in 82 vs 35% of the remaining cases ( p  = 0.002)., Conclusions: The concurrence of the PBGC, the push and fluff technique, and the ACPS was associated with the highest rates of cFPE. Appropriate selection of the thrombectomy device and deployment technique may lead to better procedural outcomes. ACPS could be used to assess clot integration strategies in future trials.

Background: Endovascular treatment is considered a reasonable approach for patients with acute posterior circulation stroke, but it remains uncertain which patients will benefit the most from it., Objective: To find independent clinical and angiographic predictors of outcome after endovascular treatment for posterior circulation stroke., Methods: We evaluated consecutive patients with acute posterior circulation stroke who underwent endovascular treatment in our comprehensive stroke center from January 2015 to December 2017. Good outcome was defined as a modified Rankin score of 0-3 at 90 days. Intracranial atheromatous disease was established on focal stenosis recorded during endovascular treatment. Associations were sought between a good outcome and clinical and angiographic factors. Adjusted logistic regression models were used to define independent outcome predictors., Results: Forty-seven consecutive patients were included: mean age 70.9 ± 12.1 years, median admission NIHSS score, 16 (IQR: 8-30). On univariate analysis, age (p = 0.01), smoking (p = 0.04), hypertension (p = 0.03), successful reperfusion (p = 0.04), presence of extracranial atherosclerosis (p = 0.02), and absence of atherosclerosis (p = 0.03) were significantly associated with a good outcome. On multivariate analysis, age <70 years (odds ratio = 6.20, 95%CI 1.52-25.47, p = 0.01) and absence of intracranial atherosclerosis (odds ratio = 6.45, 95% CI 1.09-38.24, p = 0.04) were independently associated with a good outcome., Conclusions: Pretreatment determination of the presence or absence of intracranial atherosclerosis can aid management of posterior circulation stroke patients. The absence of intracranial atherosclerosis may have value as a positive selection criterion for endovascular treatment in future trials. The presence of intracranial atherosclerosis could be used as a selection tool in future studies investigating new treatment protocols for this population., (Copyright © 2019. Published by Elsevier B.V.)

In this pilot study, we have evaluated bedside diffuse optical monitoring combining diffuse correlation spectroscopy and near-infrared diffuse optical spectroscopy to assess the effect of thrombolysis with an intravenous recombinant tissue plasminogen activator (rtPA) on cerebral hemodynamics in an acute ischemic stroke. Frontal lobes of five patients with an acute middle cerebral artery occlusion were measured bilaterally during rtPA treatment. Both ipsilesional and contralesional hemispheres showed significant increases in cerebral blood flow, total hemoglobin concentration and oxy-hemoglobin concentration during the first 2.5 hours after rtPA bolus. The increases were faster and higher in the ipsilesional hemisphere. The results show that bedside optical monitoring can detect the effect of reperfusion therapy for ischemic stroke in real-time., Competing Interests: We disclose that ICFO has equity ownership in the spin-off company HemoPhotonics S.L. in a related technology. Potential financial conflicts of interest and objectivity of research have been monitored by ICFO’s Knowledge & Technology Transfer Department and none was identified.

Background and Purpose: It has been proposed that the deposition of the β-amyloid peptide (Aβ) in the brain parenchyma and brain blood vessels has deleterious effects. We tested the hypothesis that the levels of plasma Aβ are related to the outcome in patients with intracerebral hemorrhage., Methods: In a multicenter study, we prospectively included patients with spontaneous intracerebral hemorrhage within the first 24 hours after onset. At admission, we measured plasma Aβ40 and Aβ42 levels using ELISA techniques. Also, we recorded age, sex, vascular risk factors, National Institutes of Health Stroke Scale score, presence of intraventricular hemorrhage, localization, cause, and volume of the hematoma. We obtained the modified Rankin scale and defined a unfavorable outcome as modified Rankin scale >2 at 3 months. Bivariate and multivariate regression analyses were performed., Results: We studied 160 patients (mean age, 73.8±11.3 years; 59.4% of them were men). A favorable outcome was observed in 64 (40%) of the patients. In the bivariate analyses, unfavorable outcome was associated with high age, female sex, diabetes mellitus, presence of intraventricular hemorrhage, high blood glucose, high National Institutes of Health Stroke Scale score, high volume, and high plasma levels of Aβ42 and Aβ40. The multivariate analysis showed that increased age (odds ratio, 1.07; 95% confidence interval, 1.035-1.21; P<0.0001), high admission National Institutes of Health Stroke Scale score (odds ratio, 1.29, 95% confidence interval, 1.17-1.42; P<0.0001), presence of diabetes mellitus (odds ratio, 4.15; 95% confidence interval, 1.21-14.1; P=0.02), and Aβ42 levels >9.7 pg/mL (odds ratio, 4.11; 95% confidence interval, 1.65-10.1; P=0.02) were independently associated with an increased likelihood of an unfavorable outcome., Conclusions: High levels of plasma Aβ42 in patients with acute intracerebral hemorrhage are associated with a poor functional prognosis.

Rationale and Objectives: In patients with severe internal carotid artery steno-occlusive lesions (ISOL), impaired cerebrovascular reactivity (CVR) is predictive of future ischemic stroke (IS) or transient ischemic attack (TIA). Therefore, the evaluation of CVR in ISOL patients may be a means to evaluate the risk for IS/TIA and decide on an intervention. Our aim was (1) to explore the feasibility of concurrent near-infrared spectroscopy (NIRS-DOS), diffuse correlation spectroscopy, and transcranial Doppler for CVR assessment in ISOL patients, and (2) to compare macrovascular and microvascular CVR in ISOL patients and explore its potential for IS/TIA risk stratification., Materials and Methods: Twenty-seven ISOL patients were recruited. The changes in continuous microvascular and macrovascular hemodynamics upon acetazolamide injection were used to determine CVR., Results: Oxyhemoglobin (HbO2, by near-infrared spectroscopy), microvascular cerebral blood flow (CBF, by diffuse correlation spectroscopy) and CBF velocity (by transcranial Doppler) showed significant increases upon acetazolamide injection in all subjects (P < .03). Only macrovascular CVR (P = .024) and none of the microvascular measures were significantly dependent on the presence of ISOL. In addition, while CBF was significantly correlated with HbO2, neither of these microvascular measures correlated with macrovascular CBF velocity., Conclusions: We demonstrated the simultaneous, continuous, and noninvasive evaluation of CVR at both the microvasculature and macrovasculature. We found that macrovascular CVR response depends on the presence of ISOL, whereas the microvascular CVR did not significantly depend on the ISOL presence, possibly due to the role of collaterals other than those of the circle of Willis. The concurrent microvascular and macrovascular CVR measurement in the ISOL patients might improve future IS/TIA risk assessment., (Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.)

The ultimate goal of therapeutic strategies for ischemic stroke is to reestablish the blood flow to the ischemic region of the brain. However, currently, the local cerebral hemodynamics (microvascular) is almost entirely inaccessible for stroke clinicians at the patient bed-side, and the recanalization of the major cerebral arteries (macrovascular) is the only available measure to evaluate the therapy, which does not always reflect the local conditions. Here we report the case of an ischemic stroke patient whose microvascular cerebral blood flow and oxygenation were monitored by a compact hybrid diffuse optical monitor during thrombolytic therapy. This monitor combined diffuse correlation spectroscopy and near-infrared spectroscopy. The reperfusion assessed by hybrid diffuse optics temporally correlated with the recanalization of the middle cerebral artery (assessed by transcranial-Doppler) and was in agreement with the patient outcome. This study suggests that upon further investigation, diffuse optics might have a potential for bed-side acute stroke monitoring and therapy guidance by providing hemodynamics information at the microvascular level.

Objectives: The levels of circulating endothelial progenitor cells (EPCs) in ischemic stroke have not been studied extensively and reported results are inconsistent. We aimed to investigate the time course, the prognostic relevance, and the variables associated with EPC counts in patients with ischemic stroke at different time points., Material and Methods: We studied prospectively 146 consecutive patients with ischemic stroke within the first 48 h from the onset of symptoms (baseline). We evaluated demographic data, classical vascular risk factors, treatment with thrombolysis and statins, stroke etiology, National Institute of Health and Stroke Scale score and outcome (favorable when Rankin scale score 0-2). Blood samples were collected at baseline, at day 7 after stroke (n = 121) and at 3 months (n = 92). The EPC were measured by flow cytometry., Results: We included 146 patients with a mean age of 70.8 ± 12.2 years. The circulating EPC levels were higher on day 7 than at baseline or at 3 months (P = 0.045). Pretreatment with statins (odds ratio [OR] 3.11, P = 0.008) and stroke etiology (P = 0.032) were predictive of EPC counts in the baseline sample. EPC counts were not associated with stroke severity or functional outcome in all the patients. However, using multivariate analyses, a better functional outcome was found in patients with higher EPC counts in large-artery atherosclerosis and small-vessel disease etiologic subtypes., Conclusions: After acute ischemic stroke, circulating EPC counts peaked at day 7. Pretreatment with statins increased the levels of EPC. In patients with large-artery atherosclerosis and small-vessel disease subtypes, higher counts were related to better outcome at 3 months.

Background: Intracranial amyloid and hypertensive angiopathy have been related to impaired blood vessel function and the etiology of intracerebral hemorrhage (ICH). Microbleeds (MBs) are surrogate radiological markers that are associated with these underlying angiopathies. We assessed the hypothesis that MBs are associated with hematoma expansion (HE) in patients with hyperacute ICH., Methods: We studied patients with spontaneous supratentorial ICH within the first 6 h after onset. HE was defined as an increase≥33% in the volume of hematoma on the follow-up CT in comparison with the admission CT. The volume was calculated using the ABC/2 formula. MBs were detected by specific magnetic resonance sequences (gradient-echo). The presence, number and distribution of MBs were analyzed., Results: Our study included 44 patients. Their mean age was 68.9±11.1 years, and 70.5% of them were men. HE was observed in 14 of the patients (31.8%). HE was more prevalent in patients with more than 10 MBs compared with patients with 1-10 MBs (60 vs 12.5%; p=0.03)., Conclusion: A high burden of MBs is associated with an increased risk of HE in patients with ICH. This is probably a marker of a more severe underlying angiopathy., (Copyright © 2013 S. Karger AG, Basel.)

Objective: To prospectively evaluate longitudinal changes in white matter lesions (WMLs) in migraineurs with aura, by magnetic resonance imaging (MRI), and to correlate WMLs modifications with patients' clinical characteristics., Methods: Forty-one consecutive migraineurs with aura were followed for a mean time of 33.2 months. Patients underwent MRI at baseline and follow-up and were evaluated for cerebrovascular risk factors. Presence of WMLs on MRI was assessed by two neuroradiologists., Results: WMLs were present in 26 subjects (63.4%) at baseline MRI. At follow-up a total of 8 patients had new WMLs (19.5%). There was a significant correlation between aura duration and number of new WMLs, and between the number of migraine attacks with aura and new WMLs., Conclusions: Our study demonstrates that in migraine with aura WMLs number can progress over time and suggests an association between aura features and WMLs progression. Studies with a higher number of patients are required to confirm these findings., (Copyright © 2012 by the American Society of Neuroimaging.)

Background: Sonothrombolysis is a promising but unproven tool for treating acute ischaemic stroke. There is an ongoing debate about the efficacy, safety, technical aspects of ultrasound administration and the possible potentiating effect of microbubbles., Objectives: To assess the effectiveness and safety of sonothrombolysis in patients with acute ischaemic stroke., Search Methods: We searched the Cochrane Stroke Group Trials Register (last searched in November 2011), the Cochrane Controlled Trials Register (The Cochrane Library 2011, Issue 12), MEDLINE (1950 to November 2011), EMBASE (1980 to November 2011), Database of Abstract and Review of Effects (DARE) (The Cochrane Library 2011, Issue 11), Stroke Trials Registry, Clinicaltrials.gov and Current Controlled Trials. We also searched the reference lists from relevant articles and reviews, and contacted colleagues, authors and researchers active in the field. Searching was completed in November 2011., Selection Criteria: Randomised trials of sonothrombolysis (any duration, any frequency of ultrasound, with or without microbubbles administration) started within 12 hours of symptom onset compared with intravenous tissue plasminogen activator (tPA) or conventional treatment. , Data Collection and Analysis: Two review authors selected trials for inclusion, assessed trial quality and extracted the data independently. We contacted study authors for missing data., Main Results: We identified five eligible studies (233 patients). For the primary outcome (death or dependency at three months), five studies with a total number of 206 patients were available (four defined independence as a modified Rankin score of 0 to 2 and one used 0 to 1). Patients treated with sonothrombolysis were less likely to be dead or disabled at three months (odds ratio (OR) 0.50, 95% confidence interval (CI) 0.27 to 0.91). For the secondary outcomes, failure to recanalise was lower in the sonothrombolysis group (230 patients) (OR 0.28, 95% CI 0.16 to 0.50), no significant difference was found in mortality (206 patients) and in cerebral haemorrhage (233 patients)., Authors' Conclusions: Sonothrombolysis appears to reduce death or dependency at three months (although CIs are quite wide), and increases recanalisation without clear hazard. A larger clinical trial is warranted.

Background: Acute ischemic stroke treatment is meant to induce early reperfusion before ischemic lesion becomes definitive; unfortunately, in many cases, recanalization occurs too late. We present a case in which oxygenated blood was perfused through the occluding clot during intra-arterial (IA) thrombolysis to anticipate reperfusion., Summary: A 63-year-old woman was admitted 1 hour after acute left-sided hemiplegia National Institutes of Health Stroke Scale (NIHSS 18). Transcranial Doppler (TCD) showed proximal right middle cerebral artery (MCA) occlusion. Systemic thrombolysis failed to recanalize MCA, so IA rescue was initiated. During the procedure, TCD recorded flow in MCA. A microcatheter was passed through the clot and 20 mL of oxygenated blood was injected over 2 minutes beyond occlusion. During blood perfusion, TCD detected nonpulsating flow in distal M2 branches. Then, tissue plasminogen activator (t-PA) was injected directly intrathrombus; mechanic fragmentation was also attempted. No recanalization was observed, however, neurological status partially improved. The process was repeated until 6 hours after symptom onset. Only partial Thrombolysis in Cerebral Ischemia (TICI-2a) recanalization was achieved, but physical examination revealed substantial improvement: NIHSS score of 11. Repeated TCD showed partial recanalization (9 hours) and complete recanalization (12 hours). At 24 hours, NIHSS score was 1., Conclusion: Momentary reperfusion of ischemic penumbra with oxygenated blood is feasible and may allow to "buy time" until definitive reperfusion is achieved.

The relationship between migraine with aura and patent foramen ovale (PFO) is still debatable. We report 2 cases of migraine with aura attacks after diagnostic microbubble injection for contrast transcranial Doppler (cTCD), in subjects with large PFO. In one case MR images, including diffusion weighted imaging and apparent diffusion coefficient, performed during aura did not show any signal abnormality. Patients with migraine with aura may have an attack during cTCD, probably by a "non-ischemic" mechanism.

Background and Purpose: Right-to-left shunt (RLS) due to patent foramen ovale is a well-established risk factor for cryptogenic stroke and is highly prevalent in cases of migraine, cluster headache, and obstructive apnea. It can be diagnosed by gaseous-contrast transcranial Doppler, yet in a small percentage of cases it cannot be done owing to an insufficient temporal window. The aim of the study was to compare transtemporal with transoccipital approaches for gaseous-contrast transcranial Doppler for RLS diagnosis., Methods: We evaluated 183 subjects with a standard protocol for RLS diagnosis by simultaneously monitoring the right middle cerebral and vertebrobasilar circulations., Results: Vertebrobasilar recording reached high specificity (100%) and good sensitivity (83.72%) for the diagnosis of RLS after the Valsalva maneuver. For only medium and large shunts, both sensitivity and specificity reached 100%. Time to bubble appearance after injection was higher in the vertebrobasilar circulation (4.36+/-1.7 vs 6.77+/-2.5 seconds; P<0.001). There was a positive correlation between the number of bubbles in the right middle cerebral and vertebrobasilar circulation (kappa=0.97)., Conclusions: Transcranial Doppler with vertebrobasilar monitoring is highly sensitive and specific in detecting RLS, particularly when medium or large. It can be proposed for subjects with an insufficient temporal bone window.