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Introduction: After positive findings in clinical trials the time window for endovascular thrombectomy (EVT) for patients with an acute ischemic stroke has been expanded up to 24 h from symptom onset or last seen well (LSW). We aimed to compare EVT patients' characteristics and outcomes in the early versus extended time window and to compare outcomes with the DAWN and DEFUSE 3 trial results., Patients and Methods: Consecutive EVT patients from 16 mostly European comprehensive stroke centers from the EVA-TRISP cohort were included. We compared rates of 90-day good functional outcomes (Modified Rankin Scale 0-2), symptomatic intracranial hemorrhage (sICH), and 90-day mortality between patients treated in the early (<6 h after onset or LSW) versus extended (6-24 h after onset or LSW) time windows., Results: We included 9313 patients, of which 6876 were treated in the early and 2437 in the extended time window. National Institutes of Health Stroke Scale (NIHSS) score at presentation was lower in patients treated in the extended time window (median 13 [IQR 7-18] vs 15 [IQR 9-19], p  < 0.001). The percentage of patients with good functional outcome was slightly lower in the extended time window (37.4% vs 42.2%, p  < 0.001). However, rates of successful recanalization, sICH, and mortality were similar. Good functional outcome rates after EVT were slightly lower for patients in the extended window in the EVA-TRISP cohort as compared to DAWN and DEFUSE 3., Discussion and Conclusion: According to this large multicenter cohort study reflecting daily clinical practice, EVT use in the extended time window appears safe and effective., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Ivana Berisavac: speaker honoraria from Medtronic. Visnja Padjen: speaker honoraria from Medtronic and Boehringer Ingelheim. Ronen R. Leker: received speaker honoraria from IscemaView, Boehringer Ingelheim, Pfizer, Jansen, Biogen, Medtronic and Abott and advisory board honoraria from Jansen and Filterlex. Andrea Zini: has received funding for speaker honoraria and consulting fees from Boehringer Ingelheim, Astra Zeneca, Daiichi Sankyo, CSL Behring, for scientific advisory board from Bayer, Astra Zeneca. Mirjam R. Heldner: reports grants from Swiss National Science Foundation, SITEM Research Support Funds and Swiss Heart Foundation, not directly related to this manuscript. Christian H Nolte: has received honoraria for lectures or speaker’s bureau from Alexion, AstraZeneca, BMS, Novartis and Pfizer. The other authors report nothing to disclose.

Functional Neurological Disorders (FNDs) are characterized by the symptoms experienced by the individuals but also by how they express personal experiences and concerns related to the clinical condition. Access to care programs for functional neurological symptoms appears challenging and may entail circular, self-perpetuating healthcare pathways. Given the challenging and misleading interpretations around FND, in advocating for care pathways beyond medical therapies, we designed a scoping review to map recently suggested practices and interventions. We identified 31 relevant papers published between January 2018 and December 2022. Most of the literature was gathered from the US and UK healthcare experiences, with documented interventions provided by multi-professional teams or stand-alone psychotherapists. We found different care pathways addressing either motor or non-motor manifestations. Persons with Functional Motor Disorder are more likely to be referred to physical therapy first, while Persons suffering from Non-Epileptic Seizures are to mental health services. A narrow focus was given to minor components of multimodal approaches (e.g. social workers, and occupational therapists). High heterogeneity was found between assessment instruments as well, reflecting different perspectives in selecting treatment outcomes (e.g., reduction of non-epileptic events, psychological functioning, motor symptoms). Among healthcare professionals, neurologists and (neuro)psychiatrists are typically engaged in formulating and delivering diagnoses, while treatment is often administered by physiotherapists and/or psychologists. In the context of FNDs, the complex etiopathological nature of the condition, including comorbidities, suggests the recommendation of multidisciplinary treatments adopting a stepped care model progressing from standard to higher level individualized modules may better suit individual complexities., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: The routinely used computed tomography (CT)-based workup in the setting of acute ischemic stroke (AIS) includes non-contrast brain CT, CT angiography (CTA), and CT perfusion. Several CT, CTA, CTP-based radiological biomarkers of hemorrhagic transformation (HT) were reported., Aim of the Study: To assess the predictive value of the combined multimodal CT parameters for HT after AIS and proposal of predictive scoring scale., Methods: The source images of the NCCT, CTA and CTP of 282 AIS patients involving the anterior circulation (HT = 91, non-HT = 191) were retrospectively reviewed and the following biomarkers were recorded and analyzed: Early subtle ischemic signs, hyperdense middle cerebral artery sign (HMCAS) and Alberta Stroke Program Early CT Score (ASPECTS) < 7 in NCCT, large-vessel occlusion (LVO), clot burden score (CBS) < 6, large-vessel occlusion, poor collateral score (CS) and Tmax > 6 s ≥ 56.5 ml. A scoring system to predict HT based on these biomarkers was developed. Each biomarker counts for a single point with the total score ranging from 0 to 7., Results: All the aforementioned multimodal CT biomarkers and the selected cut offs were significantly associated with higher HT risk. The calculated scores were statistically significant different between the HT and the non-HT groups with AUC 0.761 (95% CI 0.703-0.819, P < 0.0000001). Rates of HT were approximately five times higher in patients with score ≥ 3., Conclusion: Multimodal CT-based scoring system may provide highly reliable predictive model of hemorrhagic transformation in acute ischemic stroke., (© 2023. The Author(s) under exclusive licence to Belgian Neurological Society.)

Introduction: The role of computed tomography perfusion (CTP) in prediction of hemorrhagic transformation (HT) has been evolving. We aimed to study the role of automated perfusion post-processing software in prediction of HT using the commercially available RAPID software., Methods: Two hundred eighty-two patients with anterior circulation ischemic stroke, who underwent CTP with RAPID automated post-processing, were retrospectively enrolled and divided into HT ( n = 91) and non-HT groups ( n = 191). The automated RAPID-generated perfusion maps were reviewed. Mismatch volume and ratio, time to maximum (Tmax) > 4-10s volumes, hypoperfusion index, cerebral blood flow (CBF) < 20-38% volumes, cerebral blood volume (CBV) < 34%-42% volumes, and CBV index were recorded and analyzed., Results: The volumes of brain tissues suffering from reduction of cerebral blood flow (CBF < 20%-38%), reduction in cerebral blood volumes (CBV < 34-42%), and delayed contrast arrival times (Tmax > 4-10s) were significantly higher in the HT group. The mismatch volumes were also higher in the HT group ( p = .001). Among these parameters, the Tmax > 6s volume was the most reliable and sensitive predictor of HT ( p = .001, AUC = 0.667). However, the combination of the perfusion parameters can slightly improve the diagnostic efficiency (AUC = 0.703). There was no statistically significant difference between the non-HT group and either the parenchymal or the symptomatic subtypes., Conclusion: The RAPID automated CTP parameters can provide a reliable predictor of HT overall but not the parenchymal or the symptomatic subtypes. The infarct area involving the penumbra and core represented by the Tmax > 6s threshold is the most sensitive predictor; however, the combination of the perfusion parameters can slightly improve the diagnostic efficiency.

Background: Symptomatic intracerebral hemorrhage (sICH) and major bleeding can be fatal complications of intravenous thrombolysis (IVT) for acute ischemic stroke. We investigated the impact of early fibrinogen depletion after IVT on major bleeding events., Methods: This multicenter observational prospective cohort study enrolled 1678 consecutive patients receiving IVT for acute ischemic stroke at 6 Italian centers, undergoing fibrinogen concentration assessment at baseline, 2 hours and 6 hours after IVT. Fibrinogen depletion was defined as a reduction below 200 mg/dL after 2 hours from IVT, or as a reduction below 50% of baseline fibrinogen levels after 2 hours from IVT. Main outcomes were (1) sICH (National Institute of Neurological Disorders and Stroke criteria) and (2) major bleeding defined as fatal bleeding, decrease in the hemoglobin level>2 g/dL/>1 unit transfusion, or bleeding at critical site. Additional outcomes were (1) any ICH, (2) any bleeding, (3) fatal ICH, and (4) sICH according to ECASSII definition. Good functional recovery was defined as modified Rankin Scale score 0 to 2 at 3 months., Results: Overall, 1678 patients were included (mean age 72 years, 46% female). sICH (n=116) and major bleeding (n=297) were associated with lower rate of good functional recovery ( P <0.001). Despite similar fibrinogen levels at admission, fibrinogen depletion after 2 hours from IVT was more common in people with sICH, major bleeding and all additional bleeding outcomes. In the backward stepwise multivariable logistic regression model, fibrinogen depletion remained a significant predictor of sICH (OR, 1.55 [95% CI, 1.04-2.32]) and major bleeding (OR, 1.36 [95% CI, 1.03-1.8]). Thirty-one percent of sICH could be attributable to fibrinogen depletion. The association between fibrinogen depletion and worse clinical outcome at 3 months after stroke ( P =0.012) was attributable to the higher risk of major bleeding/sICH., Conclusions: Fibrinogen depletion significantly increases the risk of sICH and major bleeding after IVT for acute ischemic stroke. Fibrinogen depletion represents an independent risk factor for bleeding, and routine assessment could be considered to stratify the risk of ICH. Trials on early fibrinogen repletion are needed to investigate mitigation of bleeding risk.

Background: Ischemic stroke is a known complication of COVID-19. It may have a different pathogenesis and worse outcome compared to stroke in patients without COVID-19. Furthermore, patients with COVID-19 and out-of-hospital stroke onset might have different characteristics compared to patients with COVID-19 and in-hospital stroke onset. The aim of our study was to analyze the characteristics of patients with stroke with and without COVID-19 and of patients with COVID-19 with in-hospital and out-of-hospital stroke., Methods: We performed a retrospective study of all consecutive patients admitted to our hospital with ischemic stroke between October 2020 and February 2021. We compared functional outcome, lab test, demographic, and clinical characteristics between patients with or without COVID-19. We performed a sub-analysis comparing patients with COVID-19 and in-hospital and out-of-hospital stroke onset., Results: We included in the final analysis 137 patients of whom 26 with COVID-19. Half (13) had out-of-hospital stroke and half in-hospital stroke onset. Overall, patients with COVID-19 had higher mortality compared to the control group (27% vs 9%, p: 0.02), and non-significantly lower rate of good functional outcome (50% vs 63%, p: 0.22). Patients with COVID-19 and out-of-hospital stroke had higher rate of good functional outcome (69% vs 39%, p: 0.05), higher lymphocyte count, and lower D-dimer compared with patients with in-hospital stroke onset., Conclusions: Patients with stroke and COVID-19 had higher mortality compared to patients without COVID-19. Among patients with COVID-19 those with out-of-hospital stroke had better outcome and fewer blood test abnormalities compared to patients with in-hospital stroke., (© 2021. Fondazione Società Italiana di Neurologia.)

Objectives: the efficacy of delayed intravenous tissue plasminogen activator (tPA), beyond the 4.5 h window, is evolving. Advanced age and high admission National Institutes of Health Stroke Scale (NIHSS) score are proposed to adversely affect the outcome of delayed thrombolysis and limit the inclusion criteria. The summation of patient age and admission NIHSS score was introduced as the SPAN-100 index as a tool of prediction of the clinical outcome after acute ischemic stroke (AIS). We aimed to assess the SPAN-100 index in AIS thrombolysed patients after 4.5 h., Materials and Methods: The SPAN-100 index was applied to AIS patients receiving delayed IV thrombolysis (IVT) after 4.5 h. Patients demographics, risk factors, clinical, laboratory and radiological data, mismatch evidence, treatment onset and modality, NIHSS score at baseline and at discharge, and 3 months follow-up modified Rankin Scale (mRS) were reviewed. SPAN-100 score ≥ 100 is classified as SPAN-100 positive while score < 100 is SPAN-100 negative. Clinical outcomes, death and intracerebral hemorrhage (ICH) incidences were compared between SPAN-100 positive and negative groups., Results: SPAN-100-positive delayed IVT-patients (11/136) had a 6-fold increased risk for unfavorable outcome compared to SPAN-negative patients (OR 6.34; 95% CI 1.59-25.24 p=0.004), however there was no relation between the SPAN-100 positivity and mortality or ICH., Conclusion: SPAN-100-positive patients are more likely to achieve non-favorable outcome with delayed IVT in comparison to the SPAN-100-negative patients. SPAN-100 index may influence the eligibility criteria of delayed thrombolysis., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Evidence of the intravenous tissue plasminogen activator (tPA) efficacy beyond the 4.5hours window is emerging. We aim to study the factors affecting the outcome of delayed thrombolysis in patients of clear onset acute ischemic stroke (AIS)., Methods: Data of patients with AIS who received intravenous thrombolytic after 4.5hours were reviewed including: demographics, risk factors, clinical, laboratory, investigational and radiological data, evidence of mismatch, treatment type and onset, National Institutes of Health Stroke Scale (NIHSS) score at baseline, 24hours, 7days after thrombolysis and before discharge, and 3 months follow-up modified Rankin Scale (mRS)., Results: We report 136 patients treated by intravenous tPA between 4.53 and 19.75hours with average duration of 5.7h. The ASPECT score of our patients was≥7. Sixty-four cases showed intracranial arterial occlusion. Perfusion mismatch was detected in 117 (84.6%) patients, while clinical imaging mismatch was detected in 19 (15.4%). Early neurological improvement after 24hours occurred in 114 (83.8%) patients. At 90days, 91 patients (67%) achieved good outcome (mRS 0-2), while 45 (33%) had bad outcome (mRS 3-6). Age, endovascular treatment, NIHSS, AF, and HT were significantly higher in the bad outcome group. Age (P=0.001, OR: 1.099, 95% CI: 1.042-1.160) and baseline NIHSS were predictive of the poor outcome (P=0.002, OR: 1.151, 95% CI: 1.055-1.256). The best cutoff value of age was 72.5 with AUC of 0.76, sensitivity 73.3% and specificity 60.4%. While for NIHSS at admission, the cutoff value of 7 showed the best results with AUC of 0.73, sensitivity 71.1% and specificity 63.7%. Combination of age and admission NIHSS raised the sensitivity and specificity to 84.4% and 63.7%, respectively., Conclusion: Increased age and admission NIHSS may adversely affect the outcome of delayed thrombolysis and narrow the eligibility criteria. Age and baseline NIHSS based stratification of the patients may provide further evidence as regards the efficacy of the delayed thrombolysis., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Cancer-related coagulopathy is a known cause of stroke and can lead to formation of thrombi with a unique composition. The effectiveness of mechanical thrombectomy in cancer patients is still unknown. The aim of the study was to evaluate the rate of successful reperfusion and the clinical outcome in cancer patients with stroke treated with endovascular therapies, compared to patients without cancer. We performed a retrospective analysis of consecutive patients with ischemic stroke treated with endovascular therapies at our hospital between January 2008 and January 2016. A sub-group analysis was performed including only patients with cryptogenic stroke. We included in the final analysis 14 patients with active cancer and 267 patients without cancer. Successful reperfusion was achieved in 79% of patients without cancer, and 71% of patients with active cancer (P = 0.68). Patients with cryptogenic stroke and active cancer had a lower reperfusion rate compared to patients with cryptogenic stroke without active cancer, although not significantly so (2/4 cancer patients, 50% vs 37/50, 74%, p: 0.31). Mortality rate was higher among cancer patients. Hemorrhagic transformation occurred in similar proportions in the two groups. Endovascular treatment in cancer patients seems, thus, effective., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: Many studies showed that platelet reactivity testing can predict ischemic events after carotid stenting or ischemic stroke. The aim of our study was to assess the role of early platelet function monitoring in predicting 90-days functional outcome, stent thrombosis and hemorrhagic transformation in patients with ischemic stroke treated with endovascular procedures requiring emergent extracranial stenting., Materials and Methods: We performed a retrospective study on consecutive patients with acute anterior circulation stroke admitted to our hospital between January 2015 and March 2020, in whom platelet reactivity testing was performed within 10 days from stenting. Patients were divided according to validated cutoffs in acetylsalicylic acid and Clopidogrel responders and not responders. Group comparison and regression analyses were performed to identify differences between groups and outcome predictors., Results: We included in the final analysis 54 patients. Acetylsalicylic acid resistance was an independent predictor of poor 90 days outcome (OR for modified Rankin scale (mRS) ≤ 2: 0.10 95% CI: 0.02 - 0.69) whereas Clopidogrel resistance was an independent predictor of good outcome (OR for mRS ≤ 2: 7.09 95%CI: 1.33 - 37.72). Acetylsalicylic acid resistance was also associated with increased 90-days mortality (OR: 18.42; 95% CI: 1.67 - 203.14)., Conclusion: We found a significant association between resistance to acetylsalicylic acid and poor 90-days functional outcome and between resistance to Clopidogrel and good 90-days functional outcome. If confirmed, our results might improve pharmacological management after acute carotid stenting., Competing Interests: Declaration of Competing Interest Andrea Zini has received consultancy and speaker fees from Boehringer-Ingelheim, Medtronic, Stryker, Daiichi Sankyo, Johnson&Johnson. The other authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Olfactory and taste disorders were reported in up to 30%-80% of COVID-19 patients. The purpose of our study was to objectively assess smell impairment in COVID-19 patients and to correlate olfactory function with viral recovery., Methods: Between 15 and 30 April 2020, hospitalized patients with confirmed SARS-CoV-2 infection underwent an objective assessment of olfactory function with the Smell Identification subtest of the Sniffin' Sticks Test (SI-SST). Association between viral recovery and SI-SST performance was evaluated., Results: 51 patients were enrolled (49% males, mean age 66.2 ± 14.6 years). At the time of test administration, 45% were clinically recovered and 39% were virus-free. Objective hyposmia/anosmia was found in 45% of the patients. Subjective olfactory disorders showed no association with the clinical or viral recovery status of the patients. On the contrary, none of the patients with anosmia and the 5% of hyposmic patients at test had viral recovery. The relative risk for hyposmic patients to be still positive at swab test was 10.323 (95% CI 1.483-71.869, p < .0001). Logistic regression analysis showed an independent and significant correlation between viral clearance and SI-SST scores (OR = 2.242; 95% CI 1.322-3.802, p < .003). ROC curve analysis confirmed that a SI-SST > 10.5 predicts viral clearance with 79% sensitivity and 87% specificity (AUC = 0.883)., Conclusion: Hyposmia is part of COVID-19 symptoms; however, only objectively assessed olfactory function is associated with viral recovery. SI-SST is an easy and safe instrument, and further large multicentric studies should assess its value to predict infection and recovery., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Purpose: To compare the diagnostic accuracy (ACC) in the detection of acute posterior circulation strokes between qualitative evaluation of software-generated colour maps and automatic assessment of CT perfusion (CTP) parameters., Methods: Were retrospectively collected 50 patients suspected of acute posterior circulation stroke who underwent to CTP (GE "Lightspeed", 64 slices) within 24 h after symptom onset between January 2016 and December 2018. The Posterior circulation-Acute Stroke Prognosis Early CT Score (pc-ASPECTS) was used for quantifying the extent of ischaemic areas on non-contrast (NC)CT and colour-coded maps generated by CTP4 (GE) and RAPID (iSchemia View) software. Final pc-ASPECTS was calculated on follow-up NCCT and/or MRI (Philips Intera 3.0 T or Philips Achieva Ingenia 1.5 T). RAPID software also elaborated automatic quantitative mismatch maps., Results: By qualitative evaluation of colour-coded maps, MTT-CTP4D and Tmax-RAPID showed the highest sensitivity (SE) (88.6% and 90.9%, respectively) and ACC (84% and 88%, respectively) compared with the other perfusion parameters (CBV, CBF). Baseline NCCT and CBF provided by RAPID quantitative perfusion mismatch maps had the lowest SE (29.6% and 6.8%, respectively) and ACC (38% and 18%, respectively). CBF and Tmax assessment provided by quantitative RAPID perfusion mismatch maps showed significant lower SE and ACC than qualitative evaluation. No significant differences were found between the pc-ASPECTSs assessed on colour-coded MTT and Tmax maps neither between the scores assessed on colour-coded CBV-CTP4D and CBF-RAPID maps., Conclusion: Qualitative analysis of colour-coded maps resulted more sensitive and accurate in the detection of ischaemic changes than automatic quantitative analysis.

We present a clinical case of a patient with SARS-CoV-2 infection and respiratory symptoms, complicated with a pro-thrombotic state involving multiple vascular territories and concomitant interleukin-6 increase. This case underlines the possibility to develop a COVID-19-related coagulopathy.

Background and Purpose: The trajectory of cardiogenic emboli could be affected by anatomical and flow characteristics of the aortic arch. We aimed to study the relation between the different aortic arch patterns and the laterality of cardiogenic emboli., Methods: 192 cardioembolic strokes were classified into 3 groups according to the type of the aortic arch; type 1 (n = 69), type 2 (n = 49), type 3 (n = 74). The side and site of the cerebral vessels occlusion were divided into anterior and posterior circulation strokes, and anterior strokes were further subdivided into right or left internal carotid, middle or anterior cerebral arteries occlusion., Results: Overall, the anterior circulation embolic occlusions were more common than the posterior, and middle cerebral artery more commonly affected than internal carotid artery. The left side propensity was higher either in the total patients' pool or after segregation into atrial fibrillation (AF) and non AF cardio-embolic cases in all types of aortic arch except for type 1 aortic arch in the non AF cases. This propensity tended to get higher with advancement of the aortic arch types but failed to show statistically significant difference between the 3 arch types, however combination of type 2 and 3 arches into a single group showed statistically significant rise in the left side propensity in the total cardioembolic cases (P = 0.039) and in the non AF cardioembolic cases (P = 0.029). The bovine arch also showed increased left side propensity., Conclusion: Cardioemboli tends to have left anterior cerebrovascular predilection especially with AF. Different geometrical patterns of aortic arch branching seem to affect the laterality of cardioemboli and increase its left side predilection., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder due to heterozygous pathogenic variants in transforming growth factor beta (TGFβ) signaling-related genes. LDS types 1-6 are distinguished depending on the involved gene. LDS is characterized by multiple arterial aneurysms and dissections in addition to variable neurological and systemic manifestations. Patient 1: a 68-year-old man was admitted due to an aphasic transient ischemic attack (TIA). Brain CT-scan and CT angiography revealed a chronic and asymptomatic right vertebral artery dissection. Stroke diagnostic panel was unremarkable. His history showed mild stroke familiarity. At age of 49, he was treated for dissecting-aneurysm of the ascending aorta and started anticoagulation therapy. Seven years later, he underwent surgery for dissecting aneurysm involving aortic arch, descending-thoracic aorta, left subclavian artery, and both iliac arteries. Patient 2: a 47-year-old man presented a left hemiparesis due to right middle cerebral artery (MCA) and anterior cerebral artery (ACA) occlusion caused by right internal carotid artery (ICA) dissection after sport activity. Despite i.v. thrombolysis and mechanical thrombectomy, he developed malignant cerebral infarction and underwent decompressive hemicraniectomy. Digital subtraction angiography showed bilateral carotid and vertebral kinking, aneurysmatic dilatation on both common iliac arteries and proximal ectasia of the descending aorta. His father and his uncle died because of an ischemic stroke and a cerebral aneurysm rupture with a subarachnoid hemorrhage (SAH), respectively., Discussion: in both cases, considering the family history and the multiple dissections and aneurysms, LDS molecular analysis was performed. In patient 1, the novel NM&#95;005902.3 (SMAD3): c.840T > G; p.(Asn280Lys) likely pathogenic variant was identified, thus leading to a diagnosis of LDS type 3. In patient 2, the novel NM&#95;004612.2 (TGFBR1): c.1225T > G; p.(Trp409Gly) likely pathogenic variant was found, allowing for a diagnosis of LDS type 1., Conclusion: LDS is characterized by genetic and clinical variability. Our report suggests that this genetically-determined connective tissue disorder is probably underestimated, as it might firstly show up with cerebrovascular events, although mild systemic manifestations. These findings could lead to identify people at risk of severe vascular complications (i.e., through genetic consult on asymptomatic relatives), in order to perform adequate vascular assessments and follow-up to prevent complications such as stroke., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: Post-thrombotic intracerebral hemorrhage (ICH) is experienced by 6-8% of stroke patients and is associated with multiple factors, including acquired coagulopathy induced by the thrombolytic drug., Objectives: The objective of this study was to assess the outcome of the intravenous (IV) administration of fibrinogen concentrate in a series of acute stroke patients who developed iatrogenic fibrinogen critical depletion after IV thrombolysis., Material and Methods: Of the 39 ischemic stroke patients treated with IV thrombolysis with a severe hypofibrinogenemia requiring infusion with IV fibrinogen concentrate, 30 patients were treated with 2 g of IV recombinant tissue plasminogen activator (rt-PA), followed by further doses until the fibrinogen level reached 200 mg/dL in hemorrhagic patients or 100 mg/dL in non-hemorrhagic patients, and 9 were treated with IV rt-PA followed by endovascular thrombectomy., Results: Preand post-thrombolysis National Institutes of Health Stroke Scale (NIHSS) scores were statistically different for the Cochran-Mantel-Haenszel test overall (p = 0.0002), at 24-hour evaluation (p = 0.0455) and at 7-day assessment (p = 0.0006). Within the first 7 days post-thrombolysis, the brain computed tomography (CT) scans showed that 20/39 (51.28%) patients had ICH. Of the whole sample, 25.6% of the ICH patients had symptomatic intracerebral hemorrhage (SICH), according to National Institute of Neurological Disorders and Stroke (NINDS) classification. After rt-PA treatment, the median pre-thrombolysis fibrinogenemia of 332 mg/dL significantly dropped to 133 mg/dL (p < 0.0001). After the fibrinogen concentrate infusion, the median level of fibrinogenemia rose to 160 mg/dL, which was significantly higher than the median postthrombolysis levels (p < 0.0001). Recanalization was observed in 25/28 patients (89.29%): complete in 18 and partial in 7 patients. After fibrinogen IV infusion, no thrombotic complications were seen in 37 out of 39 patients (94.77%); 2/39 (0.05%) patients experienced a pulmonary embolism, 1 of them a segmental one., Conclusions: This study showed the clinical safety of administering IV fibrinogen concentrate in order to increase plasma fibrinogen levels in a series of acute stroke patients with iatrogenic fibrinogen depletion after IV thrombolysis.

Background: The measurement of platelet reactivity in patients with stroke undergoing antiplatelet therapies is not commonly performed in clinical practice. We assessed the prevalence of therapy responsiveness in patients with stroke and further investigated differences between patients on prevention therapy at stroke onset and patients naive to antiplatelet medications. We also sought differences in responsiveness between etiological subtypes and correlations between Clopidogrel responsiveness and genetic polymorphisms., Methods: A total of 624 stroke patients on antiplatelet therapy were included. Two different groups were identified: "non-naive patients", and "naive patients". Platelet function was measured with multiple electrode aggregometry, and genotyping assays were used to determine CYP2C19 polymorphisms., Results: Aspirin (ASA) responsiveness was significantly more frequent in naive patients compared with non-naive patients (94.9% versus 82.6%, P < .0010). A better responsiveness to ASA compared with Clopidogrel or combination therapy was found in the entire population (P < .0010), in non-naive patients (P < .0253), and in naive patients (P < .0010). Multivariate analysis revealed a strong effect of Clopidogrel as a possible "risk factor" for unresponsiveness (odds ratio 3.652, P < .0001). No difference between etiological subgroups and no correlations between responsiveness and CYP2C19 polymorphisms were found., Conclusion: In our opinion, platelet function testing could be potentially useful in monitoring the biological effect of antiplatelet agents. A substantial proportion of patients with stroke on ASA were "resistant", and the treatment with Clopidogrel was accompanied by even higher rates of unresponsiveness. Longitudinal studies are needed to assess whether aggregometry might supply individualized prognostic information and whether it can be considered a valid tool for future prevention strategies., (Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Rotation thromboelastometry is a viscoelastometric method that provides a rapid assessment of a patient's hemostatic processes in emergency settings, allowing prompt identification of specific coagulation abnormalities. Its results thus might guide targeted replacement therapy in hemorrhagic conditions, in case of platelet or coagulation factor deficiency, or hyperfibrinolysis, which is difficult to identify otherwise. Although currently used in emergency and traumatic surgery, there are limited data about thromboelastometry in ischemic stroke, particularly in monitoring the coagulative response to recombinant tissue plasminogen activator after intravenous thrombolysis (IVT). Here we report a case of ischemic stroke complicated by a remote asymptomatic intracranial hemorrhage after IVT and additional endovascular therapy that has been successfully treated with intravenous infusion of tranexamic acid after the detection of the status of hyperfibrinolysis provided by thromboelastometry. Further studies are needed to provide the potential usefulness of thromboelastometry and tranexamic acid in ischemic stroke complicated by intracranial bleeding., (Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Internal carotid artery occlusion (ICAO) is defined as "untouchable" by all specialists; no treatment is indicated because intervention risks (carotid endarterectomy (CEA) or endovascular treatment) are usually much more than benefits.(1,2) We report the case of a patient admitted to our hospital with an atherothrombotic ischemic stroke due to symptomatic acute ICAO, who developed a recurrent stroke with hemispheric hypoperfusion and was treated in the emergency department with ICAO revascularization after 60 days of occlusion finding., Case Description: D.G., a 62-year-old man, came to our attention for a transient episode of left weakness and hypoesthesia. The electrocardiogram revealed a new diagnosis of atrial fibrillation. CT angiography showed right ICAO; computed tomography and magnetic resonance imaging studies with perfusion imaging revealed a severe hemispheric hypoperfusion. Full anticoagulation therapy was started, and antihypertensive therapy was reduced to help collateral circulation. Some weeks later, the patient was readmitted to the stroke unit for 2 episodes of left-hand weakness. Cerebral angiography confirmed right ICAO from the proximal tract to the siphon. After some days, the patient suffered a femoral hemorrhagic lesion, with active bleeding, and was treated with surgical intervention. On the following day, the patient presented with left hemiplegia with hemianesthesia (National Institutes of Health Stroke Scale score = 14). The patient was treated in the emergency department with a complex endovascular treatment with complete recanalization of ICAO by positioning 3 stents through the intravenous infusion of abciximab. After intensive rehabilitation, at the 3- and 6-month follow-up evaluations, the patient regained autonomy., Conclusion: In literature, treatment of chronic ICAO is not indicated. Endovascular recanalization may be beneficial to patients with chronic cerebral hypoperfusion due to ICAO, when all conservative medical therapies have failed., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

The role of interleukin-6 (IL-6) as a risk factor for developing depressive symptoms, neuropsychological impairment, and related functional and neurological symptom severity during the acute phase of ischemic stroke is still underexplored. Here, the authors assessed this issue, in 48 patients without significant clinical history for major medical illnesses or other factors that promote inflammation, 72 hours after a first-ever acute ischemic stroke. In the acute phase of ischemic stroke, increased IL-6 plays a key role in the onset of depressive disorders, apathy/amotivation, somatic symptoms of depression, and neurological/functional symptoms, resulting in higher disability and poor outcome of stroke patients.

Background. Endarterectomy (CEA) or stenting (CAS) of a stenotic carotid artery is currently undertaken to reduce stroke risk. In addition removal of the arterial narrowing has been hypothesized to improve cerebral hemodynamics and provide benefits in cognitive functions, by supposedly resolving a "hypoperfusion" condition. Methods. In this study we sought to test whether resolution of a carotid stenosis is followed by measurable changes in cognitive functions in 22 subjects with "asymptomatic" stenosis. Results. A main finding of the study was the statistically significant pre-post difference observed in the performance of phonological verbal fluency and Rey's 15-word immediate recall. Remarkably, there was a significant interaction between phonological verbal fluency performance and side of the carotid intervention, as the improvement in the verbal performance, a typical "lateralized" skill, was associated with resolution of the left carotid stenosis. Conclusion. The results reflect a substantial equivalence of the overall performance at the before- and after- CEA or CAS tests. In two domains, however, the postintervention performance resulted improved. The findings support the hypothesis that recanalization of a stenotic carotid could improve brain functions by resolving hypothetical "hypoperfusion" states, associated with the narrowing of the vessels.

Stroke has been shown to lead to depressive disorders, anxiety disorders and other emotional consequences. Although the cause of these disorders is a subject of debate, stroke has clearly been shown to lead to the production of pro-inflammatory cytokines, which we hypothesized to play a role in the production of post-stroke emotional disorders. Thus we investigated here whether acute stroke might be associated with changes in the normal serum levels of IL-18 and if these changes were related to stroke severity, as well as to the presence and severity of alexithymia and depression. Thirty patients with a first-ever symptomatic ischemic stroke were included. Alexithymia (Toronto Alexithymia Scale; TAS-20), depression (Hamilton Depression Rating Scale; HDRS-17) and serum IL-18 were assessed. Stroke patients showed serum levels of IL-18 significantly related to stroke severity. Furthermore, a strong positive correlation was observed between IL-18 levels and severity of alexithymia, particularly among patients with right-hemisphere lesions. Specifically, circulating concentrations of IL-18 were significantly increased in patients with categorical alexithymia (TAS-20 score 61), as compared with both non alexithymic patients and control subjects. In addition, stroke was more severe in alexithymic patients, as compared to non alexithymic patients. Following multivariate regression, serum IL-18 levels appeared to be specifically associated with alexithymia rather than with stroke severity in patients with right-hemisphere lesions only. These results suggest that IL-18 might be specifically implicated in the pathogenesis of post-stroke alexithymia, ultimately contributing to impaired recovery from stroke.