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Introduction Cryptogenic stroke (CS) represents one-third of ischemic strokes. Atrial fibrillation (AF) can be detected in up to 30% of CS. Therefore, there is a clinical need for predicting AF to guide the optimal secondary prevention strategy. The evidence about the role of advanced echocardiography, including left atrial 3D index volume and left atrial strain (LAS) techniques, to predict underlying AF in this setting is lacking. Methods From April 2019 to November 2021 seventy-eight consecutive patients with ischemic stroke or transient ischemic attack with ABCD2 scale ≥4 of unknown etiology were prospectively recruited. Echocardiography was performed during admission. All patients underwent 15 days wearable Holter monitoring. The primary outcome measure was AF detection during follow-up. Results Twenty -two patients (28%) developed AF. Patients in the AF group were older (81±6.3 vs 76.5±7.8 years; p=0.012). Left atrial (LA) diastolic indexed volume was higher in AF group (37.2±12.8 vs 29.7±11 ml/m2 p=0.01). 3D LA indexed volume were also higher in patients with AF (41.4±14 vs 32.2±10 ml/m2 p=0.009). LAS reservoir, LAS conduct and LAS contraction (LASct) were significantly lower in patients with AF (19±5.6 vs 32±10.3%; 9±4.5 vs 15±7.6; 10±5.3 vs 17±6.4, respectively, all p44.5 ml/m2 were independent predictors of AF (OR 10.9 [95% CI 1.09–108.2], p=0.042) (Table 1, Figure 1) Conclusion LASct 44.5 ml/m2 are independent predictors of underlying AF in patients with CS. Our results demonstrate the usefulness of advanced echocardiography in this challenging clinical setting. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Spanish Society of Cardiology

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Spanish Society of Cardiology Introduction CHA2DS2-VASc Score is widely used to predict thromboembolic risk in patients with Atrial Fibrillation (AF). However the role of CHA2DS2-VASC score for predicting AF in patients with cryptogenic stroke (CS) remains unknown. Methods Sixty-three consecutive patients with ischemic stroke or transient ischemic attack with ABCD2 scale≥4 of unknown etiology, were prospectively recruited. They were classified according to CHA2DS2-VASc Score: group 1 (score ≤ 5), and group 2 (score >5). The primary outcome measure was the occurrence of AF during clinical follow-up. Results Twenty-six (41%) patients had a CHA2DS2VASC score > 5 (group 2). Patients in this group were older (81 ± 5.5 vs 75 ± 8 years; p 5 was an independent predictor of AF in patients with CS (HR 7.3 [95% CI 1.2-45.6] p = 0.032) Conclusion A CHA2DS2VASC score >5 is an independent predictor of AF in patients with CS. This score provides a new clinical tool to inform clinicians with regards to the optimal treatment of these challenging patients

BACKGROUND AND PURPOSE: The treatment of symptomatic carotid near-occlusion is controversial. Our aim was to analyze the results of carotid endarterectomy and carotid artery stent placement in patients with symptomatic carotid near-occlusion and to identify factors related to technical failure, periprocedural complications, and restenosis. MATERIALS AND METHODS: We conducted a multicenter, prospective nonrandomized study. Patients with angiography-confirmed carotid near-occlusion were included. We assessed the revascularization rate and periprocedural stroke or death. Twenty-four-month clinical and carotid imaging follow-up was performed, and rates of carotid restenosis or occlusion, ipsilateral stroke, and mortality were analyzed. Carotid artery stent placement, carotid endarterectomy, and medical treatment were compared. RESULTS: One hundred forty-one patients were included. Forty-four carotid artery stent placement and 23 carotid endarterectomy procedures were performed within 6 months after the event. Complete revascularization was achieved in 83.6%, 81.8% in the carotid artery stent placement group and 87% with carotid endarterectomy (P = .360). Periprocedural stroke or death occurred in 6% (carotid artery stent placement = 2.3%; carotid endarterectomy = 13%; P = .077) and was not related to revascularization failure. The carotid restenosis or occlusion rate was 8.3% (5% restenosis, 3.3% occlusion); with carotid artery stent placement it was 10.5%; and with carotid endarterectomy it was 4.5% (P = .419). The 24-month cumulative rate of ipsilateral stroke was 4.8% in the carotid artery stent placement group, 17.4% for carotid endarterectomy, and 13.1% for medical treatment (P = .223). Mortality was 12%, 4.5%, and 5.6%, respectively (P = .422). Revascularization failure and restenosis occurred more frequently in patients with full collapse compared with patients without full collapse (33.3% versus 5.6%, P = .009; 21.4% versus 2.9%, P = .032, respectively). CONCLUSIONS: Carotid artery stent placement and carotid endarterectomy are associated with high rates of failure and periprocedural stroke. Carotid near-occlusion with full collapse appears to be associated with an increased risk of technical failure and restenosis. Carotid near-occlusion revascularization does not seem to reduce the risk of stroke at follow-up compared with medical treatment.

Funding Acknowledgements Type of funding sources: None. onbehalf DECRYPTORING study Introduction Cryptogenic stroke (CS) represents up to 30% of all stroke types. In one third of CS, atrial fibrillation (AF) is identified as the underlying cause. Predictors of AF in the setting of CS have been described, however these findings were based on retrospective studies and with maximum ECG monitoring of 72 hours. To overcome these limitations, we designed the prospective Decryptoring study whose objective is to create a comprehensive predictive model for AF in patients with CS. Methods From April 2019, 41 consecutive patients with a CS and age > 60 years were included. On admission, a transthoracic echocardiogram with 3D volume and left atrial (LA) strain was performed. All patients were monitored with a 15-day ECG-Holter after discharge. Patients were classified according to AF detection. Results AF was detected in 9 patients (22%). Patients with AF were older (75.9 ± 8 vs. 81.9 ± 4.3 years, p = 0.041). There was no difference in T-troponin levels. NTproBNP was higher in the group with AF (350 ± 586 pg / ml vs. 1084 ± 1416 pg / ml, p = 0.018). Regarding LA strain, patients with AF presented reservoir LA strain (25.5 ± 8.2% vs 17.4 ± 4.3%; p = 0.006) and conduct LA strain (12 ± 5.2% vs 7.2 ± 1.5%; p = 0.01) lower than patients without AF. There were no differences in contraction LA strain or other echocardiographic variables. The risk of developing AF was higher in patients with NTproBNP> 165 pg / ml (OR 11.3 [95% CI 1.2-102.9] p = 0.031), LA reservoir strain Conclusions This prospective study, demonstrates that high NTproBNP, low reservoir LA strain and low conduct LA strain are associated with underlying AF in patients with cryptogenic stroke. No AF (n = 32) AF (n = 9) P value Age (years) 75.9 ± 8 81.9 ± 4.3 p = 0.041 NTPROBNP (pg/ml) 350 ± 586 1084 ± 1416 P = 0.018 LA indexed diastolic volume (ml/m2) 30 ± 11.8 33.8 ± 9.8 P = 0.35 LA EF (%) 45 ± 16.7 45 ± 12.8 P = 1 Reservoir LA strain (%) 25.5± 8.2 17.4± 4.3 P = 0.006 Conduct LA strain (%) 12 ± 5.2 7.2 ± 1.5 P = 0.01 Contraction LA strain (%) 13.5 ±5.3 10.2± 3.9 P = 0.10 NTPROBNP > 165 pg/ml 12 (41%) 8 (89%) OR 11.3 [IC 95% 1.2-102.9]; p = 0.031 Reservoir LA strain

Background: Intracerebral hemorrhage (ICH) is 7- to 10-fold higher in anticoagulated patients. Given the more extended use of oral anticoagulants, an increase in the prevalence of ICH associated with oral anticoagulation (ICH-OAC) could be expected. However, there is no previous study that assesses the time trends of ICH-OAC in Spain. Methods: We conducted a combined data analysis after creating a joint database of the 3 most important epidemiological studies on ICH-OAC of our country: the EPICES study (2008-2009), the TAC Registry (TR) study (2012-2013) and the TAC Registry 2 (TR2) study (2015). We finally included 65, 235, and 366 patients from the EPICES, TR, and TR2 studies, respectively. Results: We have observed a 3.73-fold increase in the crude annual incidence of ICH-OAC throughout the period of study, with proportion of ICH-OAC out of total ICH increasing from 8.4% in 2008 to 18.2% in 2015. Age, dyslipidemia, and prior antiplatelet treatment increased during the study, but we found no statistically significant differences in other risk factors for ICH-OAC. Conclusions: The incidence of ICH-OAC is increasing in our country. It might at least be partly explained by aging of the population, with mean age at presentation being higher in the last years.

Objective To assess the risk of recurrent ipsilateral ischemic stroke in patients with symptomatic near-occlusion with and without full collapse. Methods Included were consecutive patients eligible for revascularization, grouped into symptomatic conventional ≥ 50% carotid stenosis (n = 266), near-occlusion without full collapse (n = 57) and near-occlusion with full collapse (n = 42). The risk of preoperative recurrent ipsilateral ischemic stroke was analyzed, or, for cases not revascularized within 90 days, 90-day risk was analyzed. Results The risk of a preoperative recurrent ipsilateral ischemic stroke or ipsilateral retinal artery occlusion was 15% (95% CI 9–20%) for conventional ≥ 50% stenosis, 22% (95% CI 6–38%) among near-occlusion without full collapse and 30% (95% CI 16–44%) among near-occlusion with full collapse (p = 0.01, log rank test). In multivariate analysis, near-occlusion with full collapse had a higher risk of recurrent ipsilateral ischemic stroke (adjusted HR 2.6, 95% CI 1.3–5.3) and near-occlusion without full collapse tended to have a higher risk (adjusted HR 2.0, 95% CI 0.9–4.5) than conventional ≥ 50% stenosis. Only 24% of near-occlusion with full collapse underwent revascularization, common causes for abstaining were misdiagnosis as occlusion (31%), deemed surgically unfeasible (21%) and low perceived benefit (10%). Conclusions Symptomatic carotid near-occlusion has a high short-term risk of recurrent ipsilateral ischemic stroke, especially near-occlusion with full collapse.

S44819, a selective GABARESTORE BRAIN was an international, randomised, double-blind, parallel-group, placebo-controlled, multicentre phase 2 trial that evaluated the safety and efficacy of oral S44189 in patients with recent ischaemic stroke. The study was done in specialised stroke units in 92 actively recruiting centres in 14 countries: ten were European countries (Belgium, Czech Republic, France, Germany, Hungary, Italy, Netherlands, Poland, Spain, and the UK) and four were non-European countries (Australia, Brazil, Canada, and South Korea). Patients aged 18-85 years with acute ischaemic stroke involving cerebral cortex (National Institute of Health Stroke Scale [NIHSS] score 7-20) without previous disability were eligible for inclusion. Participants were randomly assigned to receive 150 mg S44819 twice a day, 300 mg S44819 twice a day, or placebo twice a day by a balanced, non-adaptive randomisation method with a 1:1:1 ratio. Treatment randomisation and allocation were centralised via the interactive web response system using computer-generated random sequences with a block size of 3. Blinding of treatment was achieved by identical appearance and taste of all sachets. Patients, investigators and individuals involved in the analysis of the trial were masked to group assignment. The primary endpoint was the modified Rankin Scale (mRS) score 90 days from onset of treatment, evaluated by shift analysis (predefined main analysis) or by dichotomised analyses using 0-1 versus 2-6 and 0-2 versus 3-6 cutoffs (predefined secondary analysis). Secondary endpoints were the effects of S44819 on the NIHSS and Montreal Cognitive Assessment (MoCA) scores, time needed to complete parts A and B of the Trail Making Test, and the Barthel index. Efficacy analyses were done on all patients who received at least one dose of treatment and had at least one mRS score taken after day 5 (specifically, on or after day 30). Safety was compared across treatment groups for all patients who received at least one dose of treatment. The study was registered at ClinicalTrials.gov, NCT02877615.Between Dec 19, 2016, and Nov 16, 2018, 585 patients were enrolled in the study. Of these, 197 (34%) were randomly assigned to receive 150 mg S44819 twice a day, 195 (33%) to receive 300 mg S44819 twice a day, and 193 (33%) to receive placebo twice a day. 189 (96%) of 197 patients in the 150 mg S44819 group, 188 (96%) of 195 patients in the 300 mg S44819 group, and 191 (99%) patients in the placebo group received at least one dose of treatment and had at least one mRS score taken after day 5, and were included in efficacy analyses. 195 (99%) of 197 patients in the 150 mg S44819 group, 194 (99%) of 195 patients in the 300 mg S44819 group, and 193 (100%) patients in the placebo group received at least one dose of treatment, and were included in safety analyses. The primary endpoint of mRS at day 90 did not differ between each of the two S44819 groups and the placebo group (OR 0·91 [95% CI 0·64-1·31]; p=0·80 for 150 mg S44819 compared with placebo and OR 1·17 [95% CI 0·81-1·67]; p=0·80 for 300 mg S44819 compared with placebo). Likewise, dichotomised mRS scores at day 90 (mRS 0-2 vs 3-6 or mRS 0-1 vs 2-6) did not differ between groups. Secondary endpoints did not reveal any significant group differences. The median NIHSS score at day 90 did not differ between groups (4 [IQR 2-8] in 150 mg S44819 group, 4 [2-7] in 300 mg S44819 group, and 4 [2-6] in placebo group), nor did the number of patients at day 90 with an NIHSS score of up to 5 (95 [61%] of 156 in 150 mg S44819 group, 106 [66%] of 161 in 300 mg S44819 group, and 104 [66%] of 157 in placebo group) versus more than 5 (61 [39%] in 150 mg S44819 group, 55 [34%] in 300 mg S44819 group, and 53 [34%] in placebo group). Likewise, the median MoCA score (22·0 [IQR 17·0-26·0] in 150 mg S44819 group, 23·0 [19·0-26·5] in 300 mg S44819 group, and 22·0 [17·0-26·0] in placebo group), time needed to complete parts A (50 s [IQR 42-68] in 150 mg S44819 group, 49 s [36-63] in 300 mg S44819 group, and 50 s [38-68] in placebo group) and B (107 s [81-144] in 150 mg S44819 group, 121 s [76-159] in 300 mg S44819 group, and 130 s [86-175] in placebo group) of the Trail Making Test, and the Barthel index (90 [IQR 60-100] in 150 mg S44819 group, 90 [70-100] in 300 mg S44819 group, and 90 [70-100] in placebo group) were similar in all groups. Number and type of adverse events were similar between the three groups. There were no drug-related adverse events and no drug-related deaths.There was no evidence that S44819 improved clinical outcome in patients after ischaemic stroke, and thus S44819 cannot be recommended for stroke therapy. The concept of tonic inhibition after stroke should be re-evaluated in humans.Servier.

The risk of recurrent stroke amongst patients with symptomatic carotid near-occlusion (SCNO) has not been clearly established, and its management remains controversial. The aim was to define the 24-month risk of recurrent stroke and to analyse the effect of the different treatment modalities (medical treatment and revascularization) in a population of patients with SCNO.

Background: \ud Patent foramen ovale (PFO) is a contributor to embolic stroke of undetermined source (ESUS). Subgroup analyses from previous studies suggest that anticoagulation could reduce recurrent stroke compared with antiplatelet therapy. We hypothesised that anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, would reduce the risk of recurrent ischaemic stroke compared with aspirin among patients with PFO enrolled in the NAVIGATE ESUS trial.\ud \ud Methods: \ud NAVIGATE ESUS was a double-blinded, randomised, phase 3 trial done at 459 centres in 31 countries that assessed the efficacy and safety of rivaroxaban versus aspirin for secondary stroke prevention in patients with ESUS. For this prespecified subgroup analysis, cohorts with and without PFO were defined on the basis of transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE). The primary efficacy outcome was time to recurrent ischaemic stroke between treatment groups. The primary safety outcome was major bleeding, according to the criteria of the International Society of Thrombosis and Haemostasis. The primary analyses were based on the intention-to-treat population. Additionally, we did a systematic review and random-effects meta-analysis of studies in which patients with cryptogenic stroke and PFO were randomly assigned to receive anticoagulant or antiplatelet therapy.\ud \ud Findings: \ud Between Dec 23, 2014, and Sept 20, 2017, 7213 participants were enrolled and assigned to receive rivaroxaban (n=3609) or aspirin (n=3604). Patients were followed up for a mean of 11 months because of early trial termination. PFO was reported as present in 534 (7·4%) patients on the basis of either TTE or TOE. Patients with PFO assigned to receive aspirin had a recurrent ischaemic stroke rate of 4·8 events per 100 person-years compared with 2·6 events per 100 person-years in those treated with rivaroxaban. Among patients with known PFO, there was insufficient evidence to support a difference in risk of recurrent ischaemic stroke between rivaroxaban and aspirin (hazard ratio [HR] 0·54; 95% CI 0·22–1·36), and the risk was similar for those without known PFO (1·06; 0·84–1·33; pinteraction=0·18). The risks of major bleeding with rivaroxaban versus aspirin were similar in patients with PFO detected (HR 2·05; 95% CI 0·51–8·18) and in those without PFO detected (HR 2·82; 95% CI 1·69–4·70; pinteraction=0·68). The random-effects meta-analysis combined data from NAVIGATE ESUS with data from two previous trials (PICSS and CLOSE) and yielded a summary odds ratio of 0·48 (95% CI 0·24–0·96; p=0·04) for ischaemic stroke in favour of anticoagulation, without evidence of heterogeneity.\ud \ud Interpretation: \ud Among patients with ESUS who have PFO, anticoagulation might reduce the risk of recurrent stroke by about half, although substantial imprecision remains. Dedicated trials of anticoagulation versus antiplatelet therapy or PFO closure, or both, are warranted.\ud \ud Funding: \ud Bayer and Janssen.

Background The risk of recurrent stroke among patients with symptomatic carotid near-occlusion is not well established, and management of the condition remains controversial. Symptomatic carotid near-occlusion with full collapse has been identified as a strong predictor of early recurrence. We aimed to analyze the 90-day risk of recurrent ipsilateral ischemic stroke in medically treated patients with symptomatic carotid near-occlusion. Methods We performed a multicenter, nationwide, prospective study from January 2010 to May 2016. Patients with angiography-confirmed symptomatic carotid near-occlusion were included. The primary endpoint was ipsilateral ischemic stroke or transient ischemic attack (TIA) within 90 days after the presenting event. For this analysis, patients who underwent revascularization within 90 days after stroke were excluded. Results The study population comprised 141 patients from 17 Spanish centers; 83 patients were treated medically. Primary endpoint occurred in eight patients, resulting in a cumulative rate of 10.6% (95% CI, 3.7-17.5). Previous history of stroke or transient ischemic attack was identified as an independent predictor for recurrence in the multivariate Cox regression analysis (HR, 4.37 [95% CI, 1.05-18.18]; p=0.043), while the presence of full collapse was not associated with an increased risk (HR, 0.81 [95% CI, 0.17-3.92]; p=0.793). The risk of recurrence was also not affected by the presence of significant stenosis or occlusion of the contralateral carotid artery, or by the collateral circulation. Conclusions Patients with symptomatic carotid near-occlusion seem to have an increased risk of early ipsilateral recurrent stroke. Our results contrast with the low risk of symptomatic carotid near-occlusion reported to date. Full collapse did not increase the risk of recurrent stroke in our study.

Objective: To update the Spanish Society of Neurology's guidelines for subarachnoid haemorrhage diagnosis and treatment. Material and methods: A review and analysis of the existing literature. Recommendations are given based on the level of evidence for each study reviewed. Results: The most common cause of spontaneous subarachnoid haemorrhage (SAN) is cerebral aneurysm rupture. Its estimated incidence in Spain is 9/100 000 inhabitants/year with a relative frequency of approximately 5% of all strokes. Hypertension and smoking are the main risk factors. Stroke patients require treatment in a specialised centre. Admission to a stroke unit should be considered for SAH patients whose initial clinical condition is good (Grades I or II on the Hunt and Hess scale). We recommend early exclusion of aneurysms from the circulation. The diagnostic study of choice for SAH is brain CT (computed tomography) without contrast. If the test is negative and SAH is still suspected, a lumbar puncture should then be performed. The diagnostic tests recommended in order to determine the source of the haemorrhage are MRI (magnetic resonance imaging) and angiography. Doppler ultrasonography studies are very useful for diagnosing and monitoring vasospasm. Nimodipine is recommended for preventing delayed cerebral ischaemia. Blood pressure treatment and neurovascular intervention may be considered in treating refractory vasospasm. Conclusions: SAH is a severe and complex disease which must be managed in specialised centres by professionals with ample experience in relevant diagnostic and therapeutic processes. (C) 2012 Sociedad Espanola de Neurologia. Published by Elsevier Espana, S.L. All rights reserved.