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Background and Clinical Significance: Intracerebral hemorrhage (ICH) is a very rare complication following endovascular closure of direct carotid-cavernous fistulas (CCFs). When reported, ICH typically appears within the first 48 h after CCF closure. We performed an extensive literature review, starting from the case of a 48-year-old patient presenting with an intracerebral hemorrhage after CCF closure. Case Presentation: A 48-year-old woman with arterial hypertension developed an intracerebral hemorrhage in the right frontal lobe 12 days after successful closure of a traumatic CCF. The patient exhibited acute neurological deterioration in a previously hypoperfused territory. A narrative review identifies the classical molecular theory of hemodynamic dysregulation, known as Normal Perfusion Pressure Breakthrough (NPPB), as the principal pathophysiological mechanism. Other mechanisms such as oxidative stress, microglial activation, blood–brain barrier disruption, metalloproteinase expression, and possible genetic alterations such as ICA1L variants are also implicated. Conclusions: This case underscores the importance of considering molecular mechanisms in the pathophysiology of delayed post-endovascular treatment of ICH, as well as the need for hemodynamic monitoring and follow-up in patients with vascular comorbidities.

Acetylsalicylic acid (ASA) and statins have been identified as potentially reducing the risk of intracranial aneurysms (IA) rupture. We aim to determine the effect of this drugs on the risk of rupture of IA. We performed a retrospective cohort study from a prospective database of patients with IA treated in our institution between January 2013 and December 2018. Demographics, previous oral treatments, presence of multiple aneurysms, size of aneurysm, lobulation, location and morphology of the aneurysms were recorded. Patients were dichotomized as ruptured and unruptured IA. A total of 408 IA were treated, of which 283 (68.6%) were in women. The median age was 53, 194 (47.5%) were ruptured IA. 38 patients (9.3%) were receiving ASA and 84 (20.6%) were receiving statins at the moment of the IA diagnosis. In the multivariable regression analysis, ASA plus statin use and multiple aneurysms were independently associated with unruptured IA (OR 5.01, 95% CI, 1.37-18.33, P = 0.015 and OR 2.72, 95% CI 1.68-4.27, P<0.001, respectively). Whereas, lobulated wall aneurysm and PComA/AComA location were inversely and independently associated with unruptured IA condition (OR 0.34, 95% CI 0.21-0.55, P<0.001 and OR 0.37, 95% CI 0.23-0.60, P<0.001, respectively). However, ASA and statins in monotherapy were not independently associated with unruptured IA condition. In our study population ASA plus statins treatment is independently associated with unruptured IA. Larger and prospective studies are required to explore this potential protective effect against IA rupture.

The Frank's sign is a diagonal earlobe crease running from the tragus to the edge of the auricle at an angle of 45°. Many studies have associated this sign with coronary artery disease and some with cerebrovascular disease. The objective of this study was to analyse the prevalence of the Frank's sign in patients suffering from acute stroke with a particular focus on its prevalence in each of the five aetiopathogenic stroke subtypes. Special interest is given to embolic stroke of undetermined source (ESUS), correlating the sign with clinical and radiological markers that support an underlying causal profile in this subgroup. Cross-sectional descriptive study including 124 patients admitted consecutively to a stroke unit after suffering an acute stroke. The Frank's sign was evaluated by the same blinded member of the research team from photographs taken of the patients. The stroke subtype was classified following SSS-TOAST criteria and the aetiological study was performed following the ESO guidelines. The Frank's sign was present in 75 patients and was more prevalent in patients with an ischaemic stroke in comparison with haemorrhagic stroke (63.9 vs. 37.5, p<0.05). A similar prevalence was found in the different ischaemic stroke subtypes. The Frank's sign was significantly associated with age, particularly in patients older than 70 who had vascular risk factors. Atherosclerotic plaques found in carotid ultrasonography were significantly more frequent in patients with the Frank's sign (63.6%, p<0.05). Analysing the ESUS, we also found an association with age and a higher prevalence of the Frank's sign in patients with vascular risk factors and a tendency to a high prevalence of atherosclerosis markers. The Frank's sign is prevalent in all aetiopathogenic ischaemic stroke subtypes, including ESUS, where it could be helpful in suspecting the underlying cardioembolic or atherothrombotic origin and guiding the investigation of atherosclerosis in patients with ESUS and the Frank's sign.

Atheromatous disease is the first cause of death and dependency in developed countries and carotid artery atherosclerosis is one of the main causes of severe ischaemic strokes. Current management strategies are mainly based on the degree of stenosis and patient selection has limited accuracy. This information could be complemented by the identification of biomarkers of plaque vulnerability, which would permit patients at greater and lesser risk of stroke to be distinguished, thus enabling a better selection of patients for surgical or intensive medical treatment. Although several circulating protein-based biomarkers with significance for both the diagnosis of carotid artery disease and its prognosis have been identified, at present, none have been clinically implemented. This review focuses especially on the most relevant clinical parameters to take into account in routine clinical practice and summarises the most up-to-date data on epigenetic biomarkers of carotid atherosclerosis and plaque vulnerability.

Hematoma expansion (HE) occurs in 20% of patients with hemorrhagic stroke within 24 h of onset, and it is associated with a poorer patient outcome. From a clinical point of view, predicting HE from the initial patient computed tomography (CT) image is useful to improve therapeutic decisions and minimize prognosis errors. In this work, we propose an end-to-end deep learning framework for predicting the final hematoma expansion and its corresponding lesion mask. We also explore the problem of having limited data and propose to augment the available dataset with synthetic images. The obtained results show an improved HE prediction when incorporating the use of synthetic images into the model, with a mean Dice score of the HE growth area of 0.506 and an average prediction error in hematoma volume of −3.44 mL. The proposed approach achieved results in line with state-of-the-art methods with far fewer data by using synthetic image generation and without requiring the inclusion of patient clinical data.

The identification of large vessel occlusion with underlying intracranial atherosclerotic disease (ICAS-LVO) before endovascular treatment (EVT) continues to be a challenge. We aimed to analyze baseline clinical-radiological features associated with ICAS-LVO that could lead to a prompt identification. We performed a retrospective cross-sectional study of consecutive patients with stroke treated with EVT from January 2020 to April 2022. We included anterior LVO involving intracranial internal carotid artery and middle cerebral artery. We analyzed baseline clinical and radiological variables associated with ICAS-LVO and evaluated the diagnostic value of a multivariate logistic regression model to identify ICAS-LVO before EVT. ICAS-LVO was defined as presence of angiographic residual stenosis or a trend to re-occlusion during EVT procedure. A total of 338 patients were included in the study. Of them, 28 patients (8.3%) presented with ICAS-LVO. After adjusting for confounders, absence of atrial fibrillation (OR 9.33, 95% CI 1.11–78.42; p  = 0.040), lower hypoperfusion intensity ratio (HIR [Tmax > 10 s/Tmax > 6 s ratio], (OR 0.69, 95% CI 0.50–0.95; p  = 0.025), symptomatic intracranial artery calcification (IAC, OR .15, 95% CI 1.64–26.42, p  = 0.006), a more proximal occlusion (ICA, MCA-M1: OR 4.00, 95% CI 1.23–13.03; p  = 0.021), and smoking (OR 2.91, 95% CI 1.08–7.90; p  = 0.035) were associated with ICAS-LVO. The clinico-radiological model showed an overall well capability to identify ICAS-LVO (AUC = 0.88, 95% CI 0.83–0.94; p  < 0.001). In conclusion, a combination of clinical and radiological features available before EVT can help to identify an ICAS-LVO. This approach could be useful to perform a rapid assessment of underlying etiology and suggest specific pathophysiology-based measures. Prospective studies are needed to validate these findings in other populations.

RationaleThe potential value of rescue intra-arterial thrombolysis in patients with large vessel occlusion (LVO) stroke treated with mechanical thrombectomy (MT) remains to be validated in randomised trials.AimThe Chemical Optimization of Cerebral Embolectomy 2 (CHOICE 2) trial is designed to confirm whether adjunctive intra-arterial alteplase, administered after successful MT, improves clinical outcomes in patients with LVO stroke.Sample size estimatesA total of 440 patients (220 per group) randomised in a 1:1 ratio to receive intra-arterial thrombolysis or not intra-arterial thrombolysis provides 80% statistical power to detect a 14% absolute benefit in the primary endpoint (the proportion of patients achieving modified Rankin Scale (mRS) 0–1 at 90 days), assuming a rate of 40% in the control group, a 5% two-sided type I error. The sample size also provides >95% power for detecting an 18% absolute benefit in secondary imaging endpoints, assuming a 58% rate in the control group.Methods and designMulticentre, randomised, open, blinded end-point assessment phase III trial. Eligible patients are adults (≥18 years) with symptomatic LVO who undergo MT with successful or complete reperfusion at end of the procedure. Patients in the intervention group will receive a 15 min intra-arterial infusion of alteplase (1.0 mg/mL, maximum dose 20 mg).Study outcome(s)The primary outcome is the proportion of patients achieving excellent functional outcome (mRS 0–1) at 90 days. Key secondary outcomes are the presence of hypoperfusion on brain CT perfusion at 36±24 hours post randomisation, infarct expansion, Barthel Index and quality of life. Mortality and symptomatic intracerebral haemorrhage will also be evaluated.DiscussionThis trial will provide evidence whether rescue intra-arterial thrombolysis improves clinical outcome in patients with LVO stroke who achieve successful or complete angiographic reperfusion following MT.

Background: We aimed to study anxiety, depression and quality of life in smokers after stroke by sex. Methods: A longitudinal prospective study with a 24-month follow-up of acute stroke patients who were previously active smokers. Anxiety and depression were evaluated with the Hospital Anxiety and Depression scale, and quality of life was evaluated with the EQ-5D questionnaire. Results: One hundred and eighty patients participated (79.4% men); their mean age was 57.6 years. Anxiety was most prevalent at 3 months (18.9% in men and 40.5% in women) and depression at 12 months (17.9% in men and 27% in women). The worst perceived health occurred at 24 months (EQ-VAS 67.5 in men and 65.1 in women), which was associated with depression (p < 0.001) and Rankin Scale was worse in men (p < 0.001) and depression in women (p < 0.001). Continued tobacco use was associated with worse perceived health at 3 months in men (p = 0.034) and at 12 months in both sexes. Predictor variables of worse perceived health at 24 months remaining at 3 and 12 months were tobacco use in men and neurological damage in women. Conclusion: Differences by sex are observed in the prevalence of anxiety and depression and associated factors and in the predictive factors of perceived health.

Background Stent assisted coiling technique have shown to be an effective and safe endovascular strategy for wide neck bifurcation aneurysms in achieving greater packing, allowing the closure of the aneurysm and preserving the parent arteries, compared to simple coiling. Material and Methods We conducted a retrospective analysis of 79 patients with cerebral aneurysms treated using ‘Y’-configuration double Neuroform® stent-assisted coiling at our center from July 2009 to July 2022. Results Of the 79 patients, 76% (60/79) were incidental unruptured cerebral aneurysm and 24% were patients treated for aneurysm recanalization of a previous ruptured aneurysm (19/79). The most frequent locations were anterior communicating artery (AComA) 44.3% (35/79) and middle cerebral artery (MCA) 32.9% (26/79). We found a complete and almost complete aneurysm occlusion (Raymond-Roy occlusion classification (RROC) 1 and 2): in 100% (79/79) in the angiography after procedure, in 97.6% (42/43) at the first follow-up at 6–8 months and 100% (57/57) at the first 1–2 years of follow-up. No mortality related to treatment was detected. We registered 2.5% (2/79) major ipsilateral strokes, one due to acute in stent thrombosis (patient had a mRS: 0 in follow up at 90 days) and a spinal anterior artery occlusion (patient had a mRS: 3 in follow up at 90 days). Conclusion The ‘Y’ stent-assisted coiling technique with double Neuroform® is a safe and effective technique for the treatment of wide-neck bifurcation aneurysms, with high rates of complete occlusion, preserving the permeability of the afferent and efferent arteries and low rate of complications.

Rationale In-stent reocclusion after endovascular therapy has a negative impact on outcomes in acute ischemic stroke (AIS) due to tandem lesions (TL). Optimal antiplatelet therapy approach in these patients to avoid in-stent reocclusion is yet to be elucidated. Aims To assess efficacy and safety of intravenous tirofiban versus intravenous aspirin in patients undergoing MT plus carotid stenting in the setting of AIS due to TL. Sample size estimates Two hundred forty patients will be enrolled, 120 in every treatment arm. Methods and design A multicenter, prospective, randomized, controlled (aspirin group), assessor-blinded clinical trial will be conducted. Patients fulfilling the inclusion criteria will be randomized at MT onset to the experimental or control group (1:1). Intravenous aspirin will be administered at a 500-mg single dose and tirofiban at a 500-mcg bolus followed by a 200-mcg/h infusion during the first 24 h. All patients will be followed for up to 3 months. Study outcomes Primary efficacy outcome will be the proportion of patients with carotid in-stent thrombosis within the first 24 h after MT. Primary safety outcome will be the rate of symptomatic intracranial hemorrhage. Discussion This will be the first clinical trial to assess the best antiplatelet therapy to avoid in-stent thrombosis after MT in patients with TL. Trial registration The trial is registered as NCT05225961. February, 7th, 2022.