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Background: CT perfusion (CTP) is used in patients with anterior circulation acute ischemic stroke (AIS) for predicting the final infarct volume (FIV). Tandem occlusion (TO), involving both intracranial large vessels and the ipsilateral cervical internal carotid artery could generate hemodynamic changes altering perfusion parameters. Our aim is to evaluate the accuracy of CTP in the prediction of the FIV in TOs., Methods: consecutive patients with AIS due to middle cerebral artery occlusion, referred to a tertiary stroke center between March 2019 and January 2021, with an automated CTP and successful recanalization (mTICI = 2b - 3) after endovascular treatment were retrospectively included in the tandem group (TG) or in the control group (CG). Patients with parenchymal hematoma type 2, according to ECASS II classification of hemorrhagic transformations, were excluded in a secondary analysis. Demographic, clinical, radiological, time intervals, safety, and outcome measures were collected., Results: among 319 patients analyzed, a comparison between the TG (N = 22) and CG (n = 37) revealed similar cerebral blood flow (CBF) > 30% (29.50 ± 32.33 vs. 15.76 ± 20.93 p = 0.18) and FIV (54.67 ± 65.73 vs. 55.14 ± 64.64 p = 0.875). Predicted ischemic core (PIC) and FIV correlated in both TG (tau = 0.761, p < 0.001) and CG (tau = 0.315, p = 0.029). The Bland-Altmann plot showed agreement between PIC and FIV for both groups, mainly in the secondary analysis., Conclusion: automated CTP could represent a good predictor of FIV in patients with AIS due to TO.

Background: The optimal management of patients with acute ischemic stroke (AIS) due to tandem occlusion (TO) and underlying carotid dissection (CD) remains unclear., Objective: We present our multicenter-experience of endovascular treatment (EVT) approach used and outcomes for AIS patients with CD-related TO (CD-TO)., Methods: Consecutive AIS patients underwent EVT for CD-TO at five Italian Neuro-interventional Tertiary Stroke Centers were retrospectively identified. TO from atherosclerosis and other causes of, were excluded from the final analysis. Primary outcome was successful (mTICI 2b-3) and complete reperfusion (mTICI 3); secondary outcome was patients' 3-months functional independence (mRS≤2)., Results: Among 214 AIS patients with TO, 45 presented CD-TO. Median age was 54 years (range 29-86), 82.2% were male. Age <65 years ( p < 0.0001), lower baseline NIHSS score ( p = 0.0002), and complete circle of Willis ( p = 0.0422) were associated with mRS ≤ 2 at the multivariate analysis. Comparisons between antegrade and retrograde approaches resulted in differences for baseline NIHSS scores ( p = 0.001) and number of EVT attempts per-procedure ( p = 0.001). No differences in terms of recanalization rates were observed between antegrade and retrograde EVT approaches ( p = 0.811) but higher rates of mTICI3 revascularization was observed with the retrograde compared to the antegrade approach (78.6% vs 73.3%), anyway not statistically significant. CD management technique (angioplasty vs aspiration vs emergent stenting) did not correlate with 3-months mRS≤2., Conclusion: AIS patients with CD-TO were mostly treated with the retrograde approach with lower number of attempts per-procedure but it offered similar recanalization rates compared with the antegrade approach. Emergent carotid artery stenting (CAS) proved to be safe for CD management but it does not influence 3-months patients' clinical outcomes.

Objective: This study aimed at identifying the incidence, predictors, and impact on long-term mortality and dementia of early-onset delirium in a cohort of patients with spontaneous intracerebral hemorrhage., Methods: We prospectively recruited consecutive patients in the Prognosis of InTra-Cerebral Hemorrhage (PITCH) cohort and analyzed incidence rate of early-onset delirium (i.e. during the first seven days after intracerebral hemorrhage onset) with a competing risk model. We used a multivariable Fine-Gray model to identify baseline predictors, a Cox regression model to study its impact on the long-term mortality risk, and a Fine-Gray model adjusted for pre-specified confounders to analyze its impact on new-onset dementia., Results: The study population consisted of 248 patients (mean age 70 years, 54% males). Early-onset delirium incidence rate was 29.8% (95% confidence interval (CI) 24.3-35.6). Multivariate analysis showed that pre-existing dementia (subhazard ratio (SHR) 2.08, 95%CI 1.32-3.32, p = 0.002), heavy alcohol intake (SHR 1.79, 95%CI 1.13-2.82, p = 0.013), and intracerebral hemorrhage lobar location (SHR 1.56, 95%CI 1.01-2.42, p = 0.049) independently predicted early-onset delirium. Median follow-up was 9.5 years. Early-onset delirium was associated with higher mortality rates during the first five years of follow-up (HR 1.52, 95%CI 1.00-2.31, p = 0.049), but did not predict new-onset dementia (SHR 1.31, 95%CI 0.60-2.87)., Conclusion: Early-onset delirium is a frequent complication after intracerebral hemorrhage; it is associated with markers of pre-existing brain vulnerability and with higher mortality risk, but not with higher dementia rates during long-term follow-up.

Background: This guideline (GL) on carotid surgery as updating of "Stroke: Italian guidelines for Prevention and Treatment" of the ISO-SPREAD Italian Stroke Organization-Group, has recently been published in the National Guideline System and shared with the Italian Society of Vascular and Endovascular Surgery (SICVE) and other Scientific Societies and Patient's Association., Methods: GRADE-SIGN version, AGREE quality of reporting checklist. Clinical questions formulated according to the PICO model. Recommendations developed based on clinical questions by a multidisciplinary experts' panel and patients' representatives. Systematic reviews performed for each PICO question. Considered judgements filled by assessing the evidence level, direction, and strength of the recommendations., Results: The panel provided indications and recommendations for appropriate, comprehensive, and individualized management of patients with carotid stenosis. Diagnostic and therapeutic processes of the best medical therapy, carotid endarterectomy (CEA), carotid stenting (CAS) according to the evidences and the judged opinions were included. Symptomatic carotid stenosis in elective and emergency, asymptomatic carotid stenosis, association with ischemic heart disease, preoperative diagnostics, types of anesthesia, monitoring in case of CEA, CEA techniques, comparison between CEA and CAS, post-surgical carotid restenosis, and medical therapy are the main topics, even with analysis of uncertainty areas for risk-benefit assessments in the individual patient (personalized medicine [PM])., Conclusions: This GL updates on the main recommendations for the most appropriate diagnostic and medical-surgical management of patients with atherosclerotic carotid artery stenosis to prevent ischemic stroke. This GL also provides useful elements for the application of PM in good clinical practice.

Background: In patients with atrial fibrillation who suffered an ischemic stroke while on treatment with nonvitamin K antagonist oral anticoagulants, rates and determinants of recurrent ischemic events and major bleedings remain uncertain., Methods: This prospective multicenter observational study aimed to estimate the rates of ischemic and bleeding events and their determinants in the follow-up of consecutive patients with atrial fibrillation who suffered an acute cerebrovascular ischemic event while on nonvitamin K antagonist oral anticoagulant treatment. Afterwards, we compared the estimated risks of ischemic and bleeding events between the patients in whom anticoagulant therapy was changed to those who continued the original treatment., Results: After a mean follow-up time of 15.0±10.9 months, 192 out of 1240 patients (15.5%) had 207 ischemic or bleeding events corresponding to an annual rate of 13.4%. Among the events, 111 were ischemic strokes, 15 systemic embolisms, 24 intracranial bleedings, and 57 major extracranial bleedings. Predictive factors of recurrent ischemic events (strokes and systemic embolisms) included CHA 2 DS 2 -VASc score after the index event (odds ratio [OR], 1.2 [95% CI, 1.0-1.3] for each point increase; P =0.05) and hypertension (OR, 2.3 [95% CI, 1.0-5.1]; P =0.04). Predictive factors of bleeding events (intracranial and major extracranial bleedings) included age (OR, 1.1 [95% CI, 1.0-1.2] for each year increase; P =0.002), history of major bleeding (OR, 6.9 [95% CI, 3.4-14.2]; P =0.0001) and the concomitant administration of an antiplatelet agent (OR, 2.8 [95% CI, 1.4-5.5]; P =0.003). Rates of ischemic and bleeding events were no different in patients who changed or not changed the original nonvitamin K antagonist oral anticoagulants treatment (OR, 1.2 [95% CI, 0.8-1.7])., Conclusions: Patients suffering a stroke despite being on nonvitamin K antagonist oral anticoagulant therapy are at high risk of recurrent ischemic stroke and bleeding. In these patients, further research is needed to improve secondary prevention by investigating the mechanisms of recurrent ischemic stroke and bleeding.

Background and Aims: In order to systematically review the latest evidence on anesthesia, intraoperative neurologic monitoring, postoperative heparin reversal, and postoperative blood pressure management for carotid endarterectomy. The present review is based on a single chapter of the Italian Health Institute Guidelines for diagnosis and treatment of extracranial carotid stenosis and stroke prevention., Methods and Results: A systematic article review focused on the previously cited topics published between January 2016 and October 2020 has been performed; we looked for both primary and secondary studies in the extensive archive of Medline/PubMed and Cochrane library databases. We selected 14 systematic reviews and meta-analyses, 13 randomized controlled trials, 8 observational studies, and 1 narrative review. Based on this analysis, syntheses of the available evidence were shared and recommendations were indicated complying with the GRADE-SIGN version methodology., Conclusions: From this up-to-date analysis, it has emerged that any type of anesthesia and neurological monitoring method is related to a better outcome after carotid endarterectomy. In addition, insufficient evidence was found to justify reversal or no-reversal of heparin at the end of surgery. Furthermore, despite a low evidence level, a suggestion for blood pressure monitoring in the postoperative period was formulated., (© 2022. The Author(s).)

Background and Purpose: The National Institutes of Health Stroke Scale (NIHSS) underestimates clinical severity in posterior circulation stroke and patients presenting with low NIHSS may be considered ineligible for reperfusion therapies. This study aimed to develop a modified version of the NIHSS, the Posterior NIHSS (POST-NIHSS), to improve NIHSS prognostic accuracy for posterior circulation stroke patients with mild-moderate symptoms., Methods: Clinical data of consecutive posterior circulation stroke patients with mild-moderate symptoms (NIHSS <10), who were conservatively managed, were retrospectively analyzed from the Basilar Artery Treatment and Management registry. Clinical features were assessed within 24 hours of symptom onset; dysphagia was assessed by a speech therapist within 48 hours of symptom onset. Random forest classification algorithm and constrained optimization were used to develop the POST-NIHSS in the derivation cohort. The POST-NIHSS was then validated in a prospective cohort. Poor outcome was defined as modified Rankin Scale score ≥3 at 3 months., Results: We included 202 patients (mean [SD] age 63 [14] years, median NIHSS 3 [interquartile range, 1-5]) in the derivation cohort and 65 patients (mean [SD] age 63 [16] years, median NIHSS 2 [interquartile range, 1-4]) in the validation cohort. In the derivation cohort, age, NIHSS, abnormal cough, dysphagia and gait/truncal ataxia were ranked as the most important predictors of functional outcome. POST-NIHSS was calculated by adding 5 points for abnormal cough, 4 points for dysphagia, and 3 points for gait/truncal ataxia to the baseline NIHSS. In receiver operating characteristic analysis adjusted for age, POST-NIHSS area under receiver operating characteristic curve was 0.80 (95% CI, 0.73-0.87) versus NIHSS area under receiver operating characteristic curve, 0.73 (95% CI, 0.64-0.83), P =0.03. In the validation cohort, POST-NIHSS area under receiver operating characteristic curve was 0.82 (95% CI, 0.69-0.94) versus NIHSS area under receiver operating characteristic curve 0.73 (95% CI, 0.58-0.87), P =0.04., Conclusions: POST-NIHSS showed higher prognostic accuracy than NIHSS and may be useful to identify posterior circulation stroke patients with NIHSS <10 at higher risk of poor outcome.

Background: TIA and stroke, both ischemic and hemorrhagic, may complicate Fabry disease at young-adult age and be the first manifestation that comes to the clinician's attention. No definite indications have yet been elaborated to guide neurologists in Fabry disease diagnostics. In current practice, it is usually sought in case of cryptogenic strokes (while Fabry-related strokes can also occur by classical pathogenic mechanisms) or through screening programs in young cerebrovascular populations. Data on recurrence and secondary prevention of Fabry's stroke are scanty., Methods: The study had a prospective observational design involving 33 Italian neurological Stroke Units. Considering the incidence of TIA/stroke in the European population aged < 60 years and the frequency of Fabry disease in this category (as foreseen by a pilot study held at the Careggi University-Hospital, Florence), we planned to screen for Fabry disease a total of 1740 < 60-year-old individuals hospitalized for TIA, ischemic, or hemorrhagic stroke. We investigated TIA and stroke pathogenesis through internationally validated scales and we gathered information on possible early signs of Fabry disease among all cerebrovascular patients. Every patient was tested for Fabry disease through dried blood spot analysis. Patients who received Fabry disease diagnosis underwent a 12-month follow-up to monitor stroke recurrence and multi-system progression after the cerebrovascular event., Discussion: The potential implications of this study are as follows: (i) to add information about the yield of systematic screening for Fabry disease in a prospective large cohort of acute cerebrovascular patients; (ii) to deepen knowledge of clinical, pathophysiological, and prognostic characteristics of Fabry-related stroke., (© 2021. The Author(s).)

Objective: Different etiologies of extracranial internal carotid artery steno-occlusive lesions (ECLs) in patients with acute ischemic stroke (AIS) and tandem occlusion (TO) have been pooled together in randomized trials. However, carotid atherosclerosis (CA) and carotid dissection (CD), the two most common ECL etiologies, are distinct nosological entities. The authors aimed to determine if ECL etiology has impacts on the endovascular management and outcome of patients with TO., Methods: A multicenter, retrospective study of prospectively collected data was conducted. AIS patients were included who had TO due to internal CA or CD and ipsilateral M1 middle cerebral artery occlusion and underwent endovascular treatment (EVT). Comparative analyses including demographic data, safety, successful recanalization rates, and clinical outcome were performed according to EVT and ECL etiology., Results: In total, 214 AIS patients with TOs were included (77.6% CA related, 22.4% CD related). Patients treated with a retrograde approach were more often functionally independent at 3 months than patients treated with an antegrade approach (OR 0.6, 95% CI 0.4-0.9). Patients with CD-related TOs achieved 90-day clinical independence more often than patients with CA-related TOs (OR 1.4, 95% CI 1.1-2.0). Emergency stenting use was associated with good 3-month clinical outcome only in patients with CA-related TOs (OR 1.4, 95% CI 1.1-2.1). Symptomatic intracranial hemorrhage (sICH) occurred in 10.7% of patients, without differences associated with ECL etiology., Conclusions: ECL etiology impacts both EVT approach and clinical outcome in patients with TOs. Patients with CD-related TO achieved higher 3-month functional independence rates than patients with CA-related TOs. A retrograde approach can be desirable for both CA- and CD-related TOs, and emergency stenting is likely better justified in CA-related TOs.

Background and Purpose: Alzheimer's disease (AD) is considered a clinical and biological continuum identified via cerebrospinal fluid (CSF) or imaging biomarkers. Chronic hypoperfusion is held as one of the main features of Alzheimer's disease, as part of the processes causing neuronal degeneration. The mechanism responsible for such condition is still debated, although recently a direct connection with amyloid peptides has been shown. Here the aim was to investigate whether measures of hypoperfusion change along the AD continuum., Methods: Seventy patients with mild AD were recruited and stratified according to their CSF biomarker profile-as indicated by the National Institute on Aging and Alzheimer's Association research framework-into patients with either isolated amyloid pathology (A+T-) or full-blown AD (A+T+), and further layered according to apolipoprotein E genotype. After evaluation of vascular risk factors, a transcranial Doppler was performed on each patient, to evaluate mean flow velocity and pulsatility index in the middle cerebral artery, and to calculate the breath-holding index. Patients were compared to a cohort of 17 healthy controls., Results: The breath-holding index was reduced in the AD continuum and was inversely correlated to CSF amyloid β42 levels. Such correlation was stronger in the A+T+ than in the A+T- group, and unexpectedly reached statistical significance only in the E3 and not in the E4 genotype carriers., Conclusions: These results suggest a tight and effective relationship between amyloid β42, vascular hypoperfusion, cerebrovascular reactivity and epsilon genotype., (© 2021 European Academy of Neurology.)

[Figure: see text].

Objective: To investigate the efficacy of tenecteplase (TNK), a genetically modified variant of alteplase with greater fibrin specificity and longer half-life than alteplase, prior to endovascular thrombectomy (EVT) in patients with basilar artery occlusion (BAO)., Methods: To determine whether TNK is associated with better reperfusion rates than alteplase prior to EVT in BAO, clinical and procedural data of consecutive patients with BAO from the Basilar Artery Treatment and Management (BATMAN) registry and the Tenecteplase vs Alteplase before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK) trial were retrospectively analyzed. Reperfusion >50% or absence of retrievable thrombus at the time of the initial angiogram was evaluated., Results: We included 110 patients with BAO treated with IV thrombolysis prior to EVT (mean age 69 [SD 14] years; median NIH Stroke Scale score 16 [interquartile range (IQR) 7-32]). Nineteen patients were thrombolysed with TNK (0.25 mg/kg or 0.40 mg/kg) and 91 with alteplase (0.9 mg/kg). Reperfusion >50% occurred in 26% (n = 5/19) of patients thrombolysed with TNK vs 7% (n = 6/91) thrombolysed with alteplase (risk ratio 4.0, 95% confidence interval 1.3-12; p = 0.02), despite shorter thrombolysis to arterial puncture time in the TNK-treated patients (48 [IQR 40-71] minutes) vs alteplase-treated patients (110 [IQR 51-185] minutes; p = 0.004). No difference in symptomatic intracranial hemorrhage was observed (0/19 [0%] TNK, 1/91 [1%] alteplase; p = 0.9)., Conclusions: TNK may be associated with an increased rate of reperfusion in comparison with alteplase before EVT in BAO. Randomized controlled trials to compare TNK with alteplase in patients with BAO are warranted., Clinicaltrialsgov Identifiers: NCT02388061 and NCT03340493., Classification of Evidence: This study provides Class III evidence that TNK leads to higher reperfusion rates in comparison with alteplase prior to EVT in patients with BAO., (© 2021 American Academy of Neurology.)

Purpose: Intracranial carotid artery occlusion represents an underinvestigated cause of acute ischemic stroke as well as an indication for mechanical thrombectomy. We investigated baseline and procedural characteristics, outcomes and predictors of outcome in patients with acute ischemic stroke secondary to intracranial carotid artery occlusion., Methods: A retrospective analysis of the Italian Registry of Endovascular Treatment in Acute Stroke was performed. Patients with intracranial carotid artery occlusion (infraclinoid and supraclinoid) with or without cervical artery occlusion but with patent intracranial arteries were included. The 3‑month functional independence, mortality, successful reperfusion and symptomatic intracranial hemorrhage were evaluated., Results: Intracranial carotid artery occlusion with patent intracranial arteries was diagnosed in 387 out of 4940 (7.8%) patients. The median age was 74 years and median baseline National Institute of Health Stroke Scale (NIHSS) was 18. Functional independence was achieved in 130 (34%) patients, successful reperfusion in 289 (75%) and symptomatic intracranial hemorrhage in 33 (9%), whereas mortality occurred in 111 (29%) patients. In univariate analysis functional independence was associated with lower age, lower NIHSS at presentation, higher rate of successful reperfusion and lower rate of symptomatic intracranial hemorrhage. Multivariable regression analysis found age (odds ratio, OR:1.03; P = 0.006), NIHSS at presentation (OR: 1.07; P < 0.001), diabetes (OR: 2.60; P = 0.002), successful reperfusion (OR:0.20; P < 0.001) and symptomatic intracranial hemorrhage (OR: 4.17; P < 0.001) as the best independent predictors of outcome., Conclusion: Our study showed a not negligible rate of intracranial carotid artery occlusion with patent intracranial arteries, presenting mostly as severe stroke, with an acceptable rate of 3‑month functional independence. Age, NIHSS at presentation and successful reperfusion were the best independent predictors of outcome.

Objective: Some antiepileptic drugs (AEDs), like sodium channel blockers are significantly associated with autonomic dysfunction in patients with epilepsy. Unlike other sodium-blockers AEDs, lacosamide (LCM) is a third generation AEDs which enhances the slow inactivation of voltage-gated sodium channels. So far, data about LCM on autonomic nervous system are still unknown. This study was designed to investigate cardiovascular autonomic and sudomotor function in patients affected by focal epilepsy on LCM monotherapy, compared to patients treated with carbamazepine (CBZ) monotherapy and healthy subjects., Methods: Patients on LCM underwent autonomic function tests including head up tilt test (HUTT), Valsalva maneuver, deep breathing, hand grip, and cold face. Heart rate variability (HRV) analysis was performed in rest condition and during HUTT. Sudomotor function was assessed through Sudoscan. All results were compared with patients on carbamazepine (CBZ) monotherapy and with healthy subjects., Results: Fourteen patients on LCM monotherapy, 12 patients on CBZ monotherapy and 16 healthy controls were studied. At cardiovascular function tests, delta systolic blood pressure (∆SBP) at 3 min of HUTT and ∆SBP early phase II-late phase II at Valsalva maneuver were significantly lower in CBZ group compared to LCM patients. Spectral analysis of HRV showed no significant differences among LCM, CBZ and control groups. No difference in sudomotor function was found in all three groups., Conclusions: In conclusion, our findings suggest that LCM and CBZ on monotherapy do not affect autonomic cardiovascular and sudomotor functions compared to controls. Nevertheless, patients on CBZ showed a lower sympathetic reactivity with respect to LCM., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background and Purpose: There is no consensus on the optimal antithrombotic medication for patients with acute ischemic stroke with anterior circulation tandem occlusions treated with emergent carotid stent placement and mechanical thrombectomy. The identification of factors influencing hemorrhagic risks can assist in creating appropriate therapeutic algorithms for such patients. This study aimed to investigate the impact of medical therapy on functional and safety outcomes in patients treated with carotid stent placement and mechanical thrombectomy for tandem occlusions., Materials and Methods: A multicenter retrospective study on prospectively collected data was conducted. Only patients treated with carotid stent placement and mechanical thrombectomy for tandem occlusions of the anterior circulation were included. Univariate and multivariate analyses were performed on preprocedural, procedural, and postprocedural variables to assess factors influencing clinical outcome, symptomatic intracranial hemorrhage, stent patency, and successful intracranial vessel recanalization., Results: Ninety-five patients with acute ischemic stroke and tandem occlusions were included. Good clinical outcome (mRS ≤ 2) at 3 months was reached by 33 (39.3%) patients and was associated with baseline ASPECTS ≥ 8 (OR = 1.53; 95% CI, 1.16-2.00), ≤2 mechanical thrombectomy attempts (OR = 0.71; 95% CI, 0.55-0.99), and the absence of symptomatic intracranial hemorrhage (OR = 0.13; 95% CI , 0.03-0.51). Symptomatic intracranial hemorrhage was associated with a higher amount of intraprocedural heparin, ASPECTS ≤ 7, and ≥3 mechanical thrombectomy attempts. No relationships among types of acute antiplatelet regimen, intravenous thrombolysis, and symptomatic intracranial hemorrhage were observed. Patients receiving dual-antiplatelet therapy after hemorrhagic transformation had been ruled out on 24-hour CT were more likely to achieve functional independence and had a lower risk of symptomatic intracranial hemorrhage., Conclusions: During carotid stent placement and mechanical thrombectomy for tandem occlusion treatment, higher intraprocedural heparin dosage (≥3000 IU) increased symptomatic intracranial hemorrhage risk when the initial ASPECTS was ≤7, and mechanical thrombectomy needs more than one passage for complete recanalization. Antiplatelets antiplatelets use were safe, and dual-antiaggregation therapy was related to better functional outcomes., (© 2020 by American Journal of Neuroradiology.)

First-line therapy of acute ischemic stroke is intravenous thrombolysis (IVT) irrespective of etiology. We report on a patient with acute ischemic stroke secondary to carotid plaque rupture who experienced plaque thrombosis and marked clinical worsening despite IVT. While the latter is the gold standard therapy optimal platelets inhibition should be guaranteed to allow a safe as possible carotid intervention. Hereby we discuss all available strategies to be considered in order to better individualized treatment decision-making.

Background: The use of mechanical thrombectomy (MT) for acute ischemic stroke (AIS) patients has increased with a parallel burden in procedural costs. We tested whether a new prognostic score could identify patients who are unlikely to benefit from MT., Methods: Patients from our endovascular stroke registry were assessed for imaging and clinical outcome measures and randomly divided into two subsets for derivation and validation. We created a new prognostic score based on clinical and radiological prognostic factors of poor outcome (mRS score ≥ 3) from the derivation cohort. Receiver operating characteristics curve analysis was used to assess the discrimination ability of the score. The score was then validated and compared to the MR PREDICTS score., Results: The derivation/validation included 270/116 patients, respectively. After multivariate logistic regression analysis, pre stroke mRS, age, admission glycaemia, admission NIHSS, collateral flow, Clot Burden Score, Alberta Stroke Program Early CT score were used to create a new prognostic scoring system called Tor Vergata Stroke Score (TVSS). TVSS revealed a good prognostic accuracy with an AUC of 0.825 [95% CI 0.77-0.88] in the derivation cohort and an AUC of 0.820 [95% CI 0.74-0.90] in the validation cohort. When compared to the MR PREDICTS in the validation cohort, TVSS demonstrated higher prediction ability which was, however, not statistically significant (0.80 vs 0.78; P = 0.26)., Conclusions: TVSS is a reliable tool for selection of AIS candidates for MT and optimization of transfer to comprehensive stroke centers.

Background and Purpose: the effect of intravenous heparin during mechanical thrombectomy for acute ischemic stroke is not clear. We aimed to study efficacy and safety of heparin use during endovascular stroke treatment in a real-world setting., Materials and Methods: patients with anterior circulation stroke were divided, based on the use of intraprocedural heparin, in those treated and those untreated. Main outcomes were successful reperfusion defined as a TICI Score ≥ 2b, 3-month functional independence defined as a modified Rankin Scale ≤ 2, symptomatic intracranial hemorrhage (sICH) and mortality., Results: 361 patients were eligible for analysis; 200 were (H+) and 161 (H-). The (H-) group showed higher age and ASPECTS (74 ± 14 vs. 68.9 ± 12.2; P = 0.001; 8 ± 1.6 vs. 7.4 ± 2.1; P = 0.009) without differences in vascular risk factors. Heparin untreated patients showed a shorter onset-to-reperfusion time (271 ± 57.6 min vs. 309 ± 102.2 min; P < 0.001). No differences were found in 3-month functional independence, sICH and mortality whereas the rate of successful reperfusion was higher in the (H-) group. After logistic regression analysis successful reperfusion was independently associated with CT ASPECTS (OR: 1.16; 95%CI 1.01-1.35; P = 0.040) but inversely associated with the use of heparin (OR: 0.48; 95% CI 0.24-0.98; P = 0.045)., Conclusions: Heparin use during mechanical thrombectomy for anterior circulation acute ischemic stroke in a real world setting is safe., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background and Purpose: Epidemiological correlations between active malignancy (AM) and acute ischemic stroke (AIS) are well-established. However, the effect of reperfusion strategies, particularly mechanical thrombectomy (MT), has been barely investigated in patients with AIS and AM. We aim to evaluate safety and efficacy of reperfusion strategies in such patients., Materials and Methods: We performed a case-control analysis comparing patients with AM and AIS (AM group) to a group of cancer-free patients with AIS (control group). All enrolled patients underwent reperfusion therapies (i.e. intravenous thrombolysis, MT, intravenous thrombolysis plus MT). Main outcomes were 3-month functional independence, successful reperfusion, 3-month mortality, symptomatic intracranial hemorrhage., Results: Total 24 patients with AM and AIS (mean age: 69 ± 10.1) were individually matched to 24 control patients (mean age: 70.7 ± 9.3). In both groups 50% were treated with MT, 46% with intravenous thrombolysis and 4% with intravenous thrombolysis plus MT. No difference were found in successful reperfusion, 3-month functional independence, symptomatic intracranial hemorrhage, and mortality. However an overall mortality of 33% in the AM group was reported., Conclusions: Reperfusion strategies for AIS patients with AM seem to be safe and effective. However an individualized approach to understand cancer stage and life-expectation is warranted., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and Purpose- Despite treatment with oral anticoagulants, patients with nonvalvular atrial fibrillation (AF) may experience ischemic cerebrovascular events. The aims of this case-control study in patients with AF were to identify the pathogenesis of and the risk factors for cerebrovascular ischemic events occurring during non-vitamin K antagonist oral anticoagulants (NOACs) therapy for stroke prevention. Methods- Cases were consecutive patients with AF who had acute cerebrovascular ischemic events during NOAC treatment. Controls were consecutive patients with AF who did not have cerebrovascular events during NOACs treatment. Results- Overall, 713 cases (641 ischemic strokes and 72 transient ischemic attacks; median age, 80.0 years; interquartile range, 12; median National Institutes of Health Stroke Scale on admission, 6.0; interquartile range, 10) and 700 controls (median age, 72.0 years; interquartile range, 8) were included in the study. Recurrent stroke was classified as cardioembolic in 455 cases (63.9%) according to the A-S-C-O-D (A, atherosclerosis; S, small vessel disease; C, cardiac pathology; O, other causes; D, dissection) classification. On multivariable analysis, off-label low dose of NOACs (odds ratio [OR], 3.18; 95% CI, 1.95-5.85), atrial enlargement (OR, 6.64; 95% CI, 4.63-9.52), hyperlipidemia (OR, 2.40; 95% CI, 1.83-3.16), and CHA 2 DS 2 -VASc score (OR, 1.72 for each point increase; 95% CI, 1.58-1.88) were associated with ischemic events. Among the CHA 2 DS 2 -VASc components, age was older and presence of diabetes mellitus, congestive heart failure, and history of stroke or transient ischemic attack more common in patients who had acute cerebrovascular ischemic events. Paroxysmal AF was inversely associated with ischemic events (OR, 0.45; 95% CI, 0.33-0.61). Conclusions- In patients with AF treated with NOACs who had a cerebrovascular event, mostly but not exclusively of cardioembolic pathogenesis, off-label low dose, atrial enlargement, hyperlipidemia, and high CHA 2 DS 2 -VASc score were associated with increased risk of cerebrovascular events.

Background: CT perfusion may improve diagnostic accuracy in posterior circulation stroke. The posterior circulation Acute Stroke Prognosis Early CT score (pc-ASPECTS) on Computed Tomography Angiography source images (CTA-SI) predicts functional outcome in patients with basilar artery occlusion., Aims: We assessed the prognostic value of pc-ASPECTS on CT perfusion in patients with vertebral and basilar artery occlusion (VBAO) in comparison with CTA-SI., Methods: Whole-brain CT perfusion from consecutive stroke patients with VBAO at four stroke centers was retrospectively analyzed. pc-ASPECTS - a 10-point score assessing hypoattenuation on CTA-SI - was calculated from CT perfusion parameters as focally reduced cerebral blood flow or cerebral blood volume, focally increased time to peak of the deconvolved tissue residue function (Tmax) or mean transit time. Two investigators independently reviewed the images. Reliability was assessed with intraclass correlation coefficient. Good outcome was defined as modified Rankin scale ≤3 at three months., Results: We included 60 patients with VBAO. After assessment of four CT perfusion maps simultaneously, area-under-ROC curve (AROC) was 0.83 (95%CI 0.72-0.93) for cerebral blood volume, 0.76 (95%CI 0.64-0.89) for cerebral blood flow, 0.77 (95%CI 0.64-0.89) for Tmax, 0.70 (95%CI 0.56-0.84) for mean transit time versus area-under-ROC curve 0.64 (95%CI 0.50-0.79) for CTA-SI. Cerebral blood volume had greater accuracy compared with CTA-SI for poor outcome (p = 0.04). In logistic regression analysis, cerebral blood volume pc-ASPECTS≤8 was independently associated with poor outcome (OR 9.3 95%CI 2.2-41; p = 0.003, adjusted for age and clinical severity). Inter-rater agreement was substantial for cerebral blood volume pc-ASPECTS (intraclass correlation coefficient 0.82 95%CI 0.71-0.90 versus 0.67 for CTA-SI 95%CI 0.43-0.81)., Conclusions: Cerebral blood volume pc-ASPECTS may identify VBAO patients at higher risk of disability.

Background and Purpose: To compare outcomes of minor stroke patients with intracranial vessel occlusions (IVO) underwent mechanical thrombectomy (MT) versus those treated with intravenous thrombolysis alone (IVT)., Methods: We retrospectively reviewed two large prospective stroke databases from two European centers searching for patients admitted with minor stroke (i.e. NIHSS Score░≤░5), baseline mRS░=░0 and occlusion of the M1-M2 segment of the middle cerebral artery (MCA). Groups receiving (A) IVT alone and (B) MT+/-IVT were compared. Primary outcome measures were MT safety, successful recanalization rate (mTICI 2b-3) and NIHSS shift (discharge NIHSS minus admission NIHSS); secondary outcomes included discharge rates and excellent outcome (mRS 0-1) at 3 months. Univariate and multivariate analyses were performed., Results: Thirty-two patients were enrolled in Group B (19░MT alone; 13 MT░+░IVT) and 24 in Group A. Successful recanalization (mTICI 2b-3) was obtained in 100% of cases in Group B vs 38% in Group A. Symptomatic hemorrhagic transformation rate did not differ between the two groups. Multivariate analysis reported MT as the only predictor of early (<░12░h) favorable NIHSS shift and lower NIHSS at discharge. Moreover, discharge at home and excellent outcome at 3-month follow-up were statistically associated with MT., Conclusions: MT in patients with minor strokes and intracranial vessel occlusion (IVO) is safe and can determine a rapid improvement of NIHSS Score. MT seems also associated with a higher rate of patients discharged at home after hospitalization and better clinical outcome at 3-month follow-up. Larger randomized trials are warranted to confirm these results., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background and Purpose- The benefit of endovascular therapy in extended time windows has been demonstrated in patients with anterior circulation large vessel occlusion ischemic stroke and favorable imaging profile. We evaluated whether collaterals and thrombus burden influence the associations between revascularization, time-to-treatment, and outcome in endovascular therapy-treated patients with basilar artery occlusion. Methods- We retrospectively analyzed clinical and imaging data of consecutive endovascular therapy-treated patients with basilar artery occlusion included in the multicenter Basilar Artery Treatment and Management Collaboration. The BATMAN (Basilar Artery on Computed Tomography Angiography score, which evaluates thrombus burden and collaterals) and the PC-CS (Posterior Circulation Collateral score, which evaluates collaterals) were assessed on computed tomography angiography, blinded to clinical outcome. Good outcome was defined as modified Rankin Scale score of ≤3 within 3 months; revascularization (successful reperfusion) as modified Thrombolysis in Cerebral Infarction 2b-3 (or TIMI [Thrombolysis in Myocardial Infarction] 2-3 in the BASICS [Basilar Artery International Cooperation Study] registry). Results- We included 172 patients with basilar artery occlusion treated with endovascular therapy (124 with mechanical thrombectomy): mean (SD) age 65 (13) years, median National Institutes of Health Stroke Scale 22 (interquartile range 12-30), 64 (37%) treated >6 hours. Revascularization (achieved in 79% of patients) was associated with good outcome ( P =0.003). The use of new generation thrombectomy devices was associated with good outcome ( P =0.03). In patients who achieved revascularization, 29/46 (63%) of patients with a favorable BATMAN score and 26/51 (51%) with favorable PC-CS had good outcomes. In logistic regression analysis (adjusted for age, National Institutes of Health Stroke Scale, and time-to-treatment ≤6/>6 hours), revascularization was associated with good outcome in patients with favorable BATMAN score (odds ratio, 15.8; 95% CI, 1.4-175; P =0.02) or PC-CS (odds ratio, 9.4; 95% CI, 1.4-64; P =0.02). In patients who achieved revascularization, early (time-to-treatment ≤6 hours) but not late treatment was associated with improved outcome in patients with unfavorable BATMAN score (18/52 [35%]; odds ratio, 15; 95% CI, 1.9-124; P =0.01) or PC-CS (16/44 [36%]; odds ratio, 5.5; 95% CI, 1.4-21; P =0.01). Conclusions- Revascularization is associated with good outcome in patients with basilar artery occlusion with good collaterals and less extensive occlusion, even >6 hours after onset.

Background and Purpose: Computed tomography perfusion (CTP) and multiphase CT angiography (mCTA) help selection for endovascular treatment (EVT) in anterior ischemic stroke (AIS). Our aim was to investigate the ability of perfusion maps and collateral score to predict functional outcome after EVT., Patients and Methods: Patients with M1-middle cerebral artery occlusion, evaluated by mCTA and CTP and treated with EVT within six hours of onset, were enrolled. Perfusion parametric maps of cerebral blood flow (CBF), cerebral blood volume (CBV) and time to maximum of tissue residue function ( T max ) were generated; areas of altered perfusion were manually outlined to obtain volumes CBF v , CBV v , T max , v 16 - 25 s and T max , v 9 . 5 - 25 s . Diffusion-weighted imaging (DWI) at 24-36 hours was used to manually outline the ischemic core (volume: DWI v ). Collateral vessels were assessed on mCTA considering extent and delay of maximal enhancement (six-point scale). Functional outcome was evaluated by modified Rankin Scale score at three months. Volumes in good and poor outcome groups were compared by Wilcoxon rank-sum test t, and their discriminative ability for outcome was determined by receiver operating characteristic analysis. A logistic regression model, including T max , CBF and collaterals, was used to differentiate good and poor outcome., Results: Seventy-one patients (mean age 75 ± 11 years, range 45-99 years) were included. T max , v 16 - 25 s , T max , v 9 . 5 - 25 s , CBV v , CBF v and DWI v were statistically different between the two groups. CBF had the best discriminative value for good and poor outcome (area under the curve (AUC) 0.73; 64.5% sensitivity; 74.4% specificity); the logistic regression model might be promising (AUC 0.79, 64.5% sensitivity, 82.1% specificity)., Conclusions: In patients with AIS, the combined use of CTP and mCTA predicts functional outcome of EVT and might allow better selection.

Ojective: To investigate cardiovascular and sudomotor autonomic functions in patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) during wakefulness compared to patients with Parkinson's disease (PD) and healthy subjects., Methods: Drug-naïve iRBD patients, PD patients and healthy controls underwent cardiovascular function tests including head-up tilt test (HUTT), Valsalva maneuver, deep breathing, hand grip, and cold face. Heart rate variability (HRV) analysis was performed in the frequency domain using an autoregressive algorithm in the rest supine condition and during HUTT. Sudomotor function was assessed through Sudoscan., Results: Fourteen iRBD patients, 17 PD patients and 12 healthy controls were included in the study. In the supine resting condition, the baseline values of systolic and diastolic blood pressure and heart rate were comparable in all groups. At Valsalva maneuver, iRBD patients and PD patients showed an overshoot which was significantly lower than controls. In addition, iRBD patients showed a significant reduction of sinus arrhythmia at deep breathing compared to controls. Cardiovascular responses to cold face were similar in the three groups while isometric handgrip was significantly reduced in PD patients with respect to healthy subjects. Spectral analysis of HRV showed no significant differences among iRBD, PD patients and controls in the supine resting condition; whereas during HUTT the low-frequency (LF) component of HRV was significantly higher in controls with respect to iRBD and the high-frequency (HF) component was significantly higher in iRBD patients compared to controls. In addition, a significant increase in the LF/HF ratio in healthy subjects was detected compared to iRBD. Finally, four out of 14 iRBD patients (29%) and nine of 17 PD patients (53%) had a sudomotor dysfunction., Conclusions: Our findings obtained in de novo iRBD and PD patients indicate that some alterations of the autonomic nervous system are shared by both groups of patients, reinforcing the close link between the two pathologies, and show an autonomic fragility during wakefulness in iRBD that mainly arises under stress conditions., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective and Design: Whether combining intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) is superior to mechanical thrombectomy alone for large vessel occlusion acute ischemic stroke is still uncertain. Our aim was to compare the safety and the efficacy of these two therapeutic strategies., Materials: Patients with acute ischemic stroke secondary to anterior circulation large vessel occlusion., Methods: A retrospective analysis was conducted. IVT was performed with full dose recombinant tissue plasminogen activator. MT alone was performed only if intravenous thrombolysis was contraindicated. Primary outcomes were successful reperfusion, 3-month functional independence, symptomatic intracranial hemorrhage (sICH), and 3-month mortality., Results: 325 patients were analyzed: 193 treated with combined IVT and MT, 132 with MT alone. The combined treatment group showed higher systolic blood pressure (140 [80-230] vs 150 [90-220]; p = 0.036), rate of good collaterals (55.9% vs 67%; p = 0.03), use of aspiration devices (68.2% vs 79.3%; p = 0.003) and shorter onset-to-reperfusion time (300 [90-845] vs 288 [141-435]; p = 0.008). No differences were found in the efficacy and safety outcomes except for mortality which was lower in the combined treatment group (36.4% vs 25.4%; p = 0.02). However, after multivariable analysis combined treatment was not associated with lower mortality (OR 1.47; 95% CI 0.73-2.96; p = 0.3)., Conclusions: Our study suggests that mechanical thrombectomy alone is effective and safe in patients with contraindications to intravenous thrombolysis. Preceding use of IVT in eligible patients was not associated with increased harm or benefit. Randomized controlled trials are needed to clarify whether intravenous thrombolysis before mechanical thrombectomy is associated with additional benefit.

Background and Purpose: To report clinical and procedural outcomes of acute ischemic stroke patients after endovascular treatment with the new thromboaspiration catheter AXS Catalyst 6., Methods: Patients with anterior and posterior circulation stroke were selected. Successful reperfusion defined as a Thrombolysis in Cerebral Infarction (TICI) score ≥2 b and 3-month functional independence defined as a modified Rankin Scale (mRS) ≤2 were the main efficacy outcomes. Symptomatic intracranial hemorrhage and mortality were the main safety outcomes., Results: 107 patients were suitable for analysis. Mean age was 73.18±12.62 year and median baseline NIHSS was 17 (range: 3-32). The most frequent site of occlusion was the middle cerebral artery (MCA) (60.7%). 76.6% of patients were treated with AXS Catalyst 6 alone without the need for rescue devices or thromboaspiration catheters. Successful reperfusion was achieved in 84.1%, functional independence in 47.6%, symptomatic intracranial hemorrhage occurred in 3.7%, and mortality in 21.4%., Conclusions: Endovascular treatment with AXS Catalyst 6 proved to be safe, technically feasible, and effective. Comparison analyses with other devices for mechanical thrombectomy are needed., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: To compare feasibility, 12-month outcome, and periprocedural and postprocedural risks between carotid artery stent (CAS) placement and carotid endarterectomy (CEA) performed within 1 week after transient ischemic attack (TIA) or mild to severe stroke onset in a single comprehensive stroke center., Materials and Methods: Retrospective analysis of prospective data collected from 1,148 patients with ischemic stroke admitted to a single stroke unit between January 2013 and July 2015 was conducted. Among 130 consecutive patients with symptomatic carotid stenosis, 110 (10 with TIA, 100 with stroke) with a National Institutes of Health Stroke Scale (NIHSS) score < 20 and a prestroke modified Rankin Scale (mRS) score < 2 were eligible for CAS placement or CEA and treated according to the preference of the patient or a surrogate. Periprocedural (< 48 h) and postprocedural complications, functional outcome, stroke, and death rate up to 12 months were analyzed., Results: Sixty-two patients were treated with CAS placement and 48 were treated with CEA. Several patients presented with moderate or major stroke (45.8% CEA, 64.5% CAS). NIHSS scores indicated slightly greater severity at onset in patients treated with a CAS vs CEA (6.6 ± 5.7 vs 4.2 ± 3.4; P = .08). Complication rates were similar between groups. mRS scores showed a significant improvement over time and a significant interaction with age in both groups. Similar incidences of death or stroke were shown on survival analysis. A subanalysis in patients with NIHSS scores ≥ 4 showed no differences in complication rate and outcome., Conclusions: CAS placement and CEA seem to offer early safe and feasible secondary stroke prevention treatments in experienced centers, even after major atherosclerotic stroke., (Copyright © 2018 SIR. Published by Elsevier Inc. All rights reserved.)

Background: Few data exist on malignant middle cerebral artery infarction (MMI) among patients with acute ischemic stroke (AIS) after endovascular treatment (ET). Numerous predictors of MMI evolution have been proposed, but a comprehensive research of patients undergoing ET has never been performed. Our purpose was to find a practical model to determine robust predictors of MMI in patients undergoing ET., Methods: Patients from a prospective single-center database with AIS secondary to large intracranial vessel occlusion of the anterior circulation, treated with ET, were retrospectively analyzed. We investigated demographic, clinical, and radiological data. Multivariate regression analysis was used to identify clinical and imaging predictors of MMI., Results: 98 patients were included in the analysis, 35 of whom developed MMI (35.7%). No differences in the rate of successful reperfusion and time from stroke onset to reperfusion were found between the MMI and non-MMI groups. The following parameters were identified as independent predictors of MMI: systolic blood pressure (SBP) on admission (p=0.008), blood glucose (BG) on admission (p=0.024), and the CTangiography (CTA) Alberta Stroke Program Early CT Score (ASPECTS) (p=0.001). A scoreof ≤5 in CTA ASPECTS was the best cut-off to predict MMI evolution (sensitivity 46%; specificity 97%; positive predictive value 78%; negative predictive value 65%)., Conclusions: in our study a clinical and radiological features-based model was strongly predictive of MMI evolution in AIS. High SBP and BG on admission and, especially, a CTA ASPECTS ≤5 may help to make decisions quickly, regardless of time to treatment and successful reperfusion., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Collateral flow (CF) is an effective predictor of outcome in acute ischemic stroke (AIS) with potential to sustain the ischemic penumbra. However, the clinical prognostic value of CF in patients with AIS undergoing mechanical thrombectomy has not been clearly established. We evaluated the relationship of CF with clinical outcomes in patients with large artery anterior circulation AIS treated with mechanical thrombectomy., Methods: Baseline collaterals of patients with AIS (n=135) undergoing mechanical thrombectomy were independently evaluated by CT angiography (CTA) and conventional angiography and dichotomized into poor and good CF. Multivariable analyses were performed to evaluate the predictive effect of CF on outcome and the effect of time to reperfusion on outcome based on adequacy of the collaterals., Results: Evaluation of CF was consistent by both CTA and conventional angiography (p<0.0001). A higher rate of patients with good collaterals had good functional outcome at 3-month follow-up compared with those with poor collaterals (modified Rankin Scale (mRS) 0-2: 60% vs 10%, p=0.0001). Patients with poor collaterals had a significantly higher mortality rate (mRS 6: 45% vs 8%, p=0.0001). Multivariable analyses showed that CF was the strongest predictor of outcome. Time to reperfusion had a clear effect on favorable outcome (mRS ≤2) in patients with good collaterals; in patients with poor collaterals this effect was only seen when mRS ≤3 was considered an acceptable outcome., Conclusions: CTA is a valid tool for assessing the ability of CF to predict clinical outcome in patients with AIS treated with mechanical thrombectomy. Limiting time to reperfusion is of definite value in patients with good collaterals and also to some extent in those with poor collaterals., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background Sickle cell disease (SCD) is one of the most common causes of stroke in children worldwide. Based on the results of the Stroke Prevention Trial in Sickle Cell Anemia (STOP), annual transcranial Doppler ultrasound (TCD) screening for affected children is standard practice. However, the need for TCD surveillance programs could override the accuracy of the screening, affecting the correct stratification of stroke risk and subsequent clinical management of the target population. Aims To shed light on this issue, a systematic review of the literature on TCD screening for children and adolescents with SCD was carried out (CRD42016050549), according to a list of clinically relevant questions, with a particular focus on screening practices in European countries. Quality of the evidence was rated using the grading of recommendations assessment, development and evaluation. Summary of review Thirty-three studies published in English or French were included (5 randomized controlled trials, 8 experimental non-randomized, and 20 observational studies). The quality of the retrieved evidence ranged between low and high, but was rated as moderate or high most of the times. TCD is effective as a screening tool for the primary prevention of stroke in SCD children. There is no high-quality evidence on the effectiveness of alternative screening methods, such as imaging-TCD with or without angle correction or magnetic resonance angiography. No evidence was found on effectiveness of the screening on children on hydroxyurea and with genotypes other than HbSS and HbS/β0. No European data were found on screening rates or adherence of screening practices to the STOP protocol. Conclusions High-quality studies on alternative screening methods that are currently used in real-world practice, and on screening applicability to specific subgroups of patients are urgently needed. Considering the low awareness of the disease in European countries and the lack of data on screening practices and adherence, clinicians need up-to-date guidelines for more uniform and evidence-based surveillance of children with SCD.

Background and Purpose: Noncontrast CT ASPECTS has been investigated as a predictor of outcome in patients with acute ischemic stroke. Our purpose was to investigate whether CTA source images are a better predictor of clinical and radiologic outcomes than NCCT ASPECTS in candidates for endovascular stroke therapy., Materials and Methods: CT scans of patients ( n = 124) were independently evaluated by 2 readers for baseline NCCT and CTA source image ASPECTS and for follow-up ASPECTS. An mRS of ≤2 at 3 months was considered a favorable outcome. Receiver operating characteristic curve analysis was used to assess the ability of NCCT and CTA source image ASPECTS to identify patients with favorable outcomes. A stepwise multiple regression analysis was performed to find independent predictors of outcome., Results: Baseline CTA source image ASPECTS correlated better than NCCT ASPECTS with follow-up ASPECTS ( r = 0.76 versus r = 0.51; P for comparison of the 2 coefficients < .001). Receiver operating characteristic curve analysis showed that baseline CTA source image ASPECTS compared with NCCT ASPECTS can better identify patients with favorable outcome (CTA source image area under the curve = 0.83; 95% CI, 0.76-0.91; NCCT area under the curve = 0.67; 95% CI, 0.58-0.77; P < .001). Finally, the stepwise regression analysis showed that lower age, good recanalization, lower time to recanalization, and good baseline CTA source image ASPECTS, not NCCT ASPECTS, were independent predictors of favorable outcome., Conclusions: CTA source image ASPECTS predicts outcome better than NCCT ASPECTS; this finding suggests CTA rather than NCCT as a main step in the decision-making process for patients with acute ischemic stroke., (© 2017 by American Journal of Neuroradiology.)

Objectives: To evaluate the safety and efficacy of endovascular therapy in elderly adults treated for acute ischemic stroke., Design: Retrospective cohort study., Setting: Comprehensive Stroke Center, University of Tor Vergata, Rome, Italy., Participants: Elderly adults treated for acute ischemic stroke (N = 219)., Measurements: Participants were divided into two groups based on their age (n = 62, ≥80; n = 157, <80). Baseline and procedural characteristics, safety outcomes such as intracranial hemorrhage (ICH) and mortality and efficacy outcomes such as successful reperfusion and 3-month good clinical outcome of the two groups were compared. Mutivariable analysis was performed to identify predictors of clinical outcome., Results: Intravenous thrombolysis was more frequent (67.7% vs 52.8%, P = .04), and onset to reperfusion time was shorter (318.7 ± 128.7 vs 282 ± 53.5, P = .02) in participants aged 80 and older, but no between-group differences were found in terms of successful reperfusion (69% vs 63%, P = .4), good clinical outcome (30.6% vs 34.3%, P = .6), any (37% vs 37.5%, P > .99) or symptomatic (11% vs 14%, P = .6) ICH, or mortality (40.3% vs 29.2%, P = .14). Multivariable analysis revealed that, in the older group, onset National Institute of Health Stroke Scale (NIHSS) score (odds ratio (OR) = 0.65, 95% confidence interval (CI) = 0.44-0.96, P = .03) and 24-hour clinical improvement (OR = 141.13, 95% CI = 2.96-6,720.7, P = .01) were independent predictors of 3-month functional independence., Conclusion: These findings suggest that endovascular treatment for stroke in selected elderly adults could be safe and effective. Major determinants of outcome in this subgroup of elderly patients are presentation NIHSS score and 24-hour clinical improvement., (© 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.)

Stroke patients should be dispatched at the highest level of care available in the shortest time. In this context, a transportable system in specialized ambulances, able to evaluate the presence of an acute brain lesion in a short time interval (i.e., few minutes), could shorten delay of treatment. UWB radar imaging is an emerging diagnostic branch that has great potential for the implementation of a transportable and low-cost device. Transportability, low cost and short response time pose challenges to the signal processing algorithms of the backscattered signals as they should guarantee good performance with a reasonably low number of antennas and low computational complexity, tightly related to the response time of the device. The paper shows that a PCA-based preprocessing algorithm can: (1) achieve good performance already with a computationally simple beamforming algorithm; (2) outperform state-of-the-art preprocessing algorithms; (3) enable a further improvement in the performance (and/or decrease in the number of antennas) by using a multistatic approach with just a modest increase in computational complexity. This is an important result toward the implementation of such a diagnostic device that could play an important role in emergency scenario.

Purpose: To evaluate outcomes and prognostic factors in patients with acute ischemic stroke caused by tandem internal carotid artery/middle cerebral artery occlusion undergoing endovascular treatment., Materials and Methods: Characteristics of consecutive patients with tandem occlusion (TO) were extracted from a prospective registry. Collateral vessel quality on pretreatment computed tomographic (CT) angiography was evaluated on a 4-point grading scale, and patients were dichotomized as having poor or good collateral flow. Outcome measures included successful reperfusion according to Thrombolysis In Cerebral Infarction score, good outcome at 3 months defined as a modified Rankin scale score ≤ 2, symptomatic intracranial hemorrhage (ICH; sICH), and mortality., Results: A total of 72 patients with TO (mean age, 65.6 y ± 12.8) were treated. Intravenous thrombolysis was performed in 54.1% of patients, and a carotid stent was inserted in 48.6%. Successful reperfusion was achieved in 64% of patients, and a good outcome was achieved in 32%. sICH occurred in 12.5% of patients, and the overall mortality rate was 32%. Univariate analysis demonstrated that good outcome was associated with good collateral flow (P = .0001), successful reperfusion (P = .001), and lower rate of any ICH (P = .02) and sICH (P = .04). On multivariate analysis, good collateral flow (odds ratio [OR], 0.18; 95% confidence interval [CI], 0.04-0.75; P = .01) and age (OR, 1.08; 95% CI, 1.01-1.15; P = .01) were the only predictors of good outcome. The use of more than one device for thrombectomy was the only predictor of sICH (OR, 10.74; 95% CI, 1.37-84.13; P = .02)., Conclusions: Endovascular treatment for TO resulted in good outcomes. Collateral flow and age were independent predictors of good clinical outcomes at 3 months., (Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Basilar artery occlusion is associated with high risk of disability and mortality. This study aimed to assess the prognostic value of a new radiological score: the Basilar Artery on Computed Tomography Angiography (BATMAN) score., Methods: A retrospective analysis of consecutive stroke patients with basilar artery occlusion diagnosed on computed tomographic angiography was performed. BATMAN score is a 10-point computed tomographic angiography-based grading system which incorporates thrombus burden and the presence of collaterals. Reliability was assessed with intraclass coefficient correlation. Good outcome was defined as modified Rankin Scale score of ≤3 at 3 months and successful reperfusion as thrombolysis in cerebral infarction 2b-3. BATMAN score was externally validated and compared with the Posterior Circulation Collateral score., Results: The derivation cohort included 83 patients with 41 in the validation cohort. In receiver operating characteristic (ROC) analysis, BATMAN score had an area under receiver operating characteristic curve of 0.81 (95% confidence interval [CI], 0.7-0.9) in derivation cohort and an area under receiver operating characteristic curve of 0.74 (95% CI, 0.6-0.9) in validation cohort. In logistic regression adjusted for age and clinical severity, BATMAN score of <7 was associated with poor outcome in derivation cohort (odds ratio, 5.5; 95% CI, 1.4-21; P =0.01), in validation cohort (odds ratio, 6.9; 95% CI, 1.4-33; P =0.01), and in endovascular patients, after adjustment for recanalization and time to treatment (odds ratio, 4.8; 95% CI, 1.2-18; P =0.01). BATMAN score of <7 was not associated with recanalization. Interrater agreement was substantial (intraclass coefficient correlation, 0.85; 95% CI, 0.8-0.9). BATMAN score had greater accuracy compared with Posterior Circulation Collateral score ( P =0.04)., Conclusions: The addition of collateral quality to clot burden in BATMAN score seems to improve prognostic accuracy in basilar artery occlusion patients., (© 2017 American Heart Association, Inc.)

Background: The vascular contributions to neurodegeneration and neuroinflammation may be assessed by magnetic resonance imaging (MRI) and ultrasonography (US). This review summarises the methodology for these widely available, safe and relatively low cost tools and analyses recent work highlighting their potential utility as biomarkers for differentiating subtypes of cognitive impairment and dementia, tracking disease progression and evaluating response to treatment in various neurocognitive disorders., Methods: At the 9th International Congress on Vascular Dementia (Ljubljana, Slovenia, October 2015) a writing group of experts was formed to review the evidence on the utility of US and arterial spin labelling (ASL) as neurophysiological markers of normal ageing, vascular cognitive impairment (VCI) and Alzheimer's disease (AD). Original articles, systematic literature reviews, guidelines and expert opinions published until September 2016 were critically analysed to summarise existing evidence, indicate gaps in current knowledge and, when appropriate, suggest standards of use for the most widely used US and ASL applications., Results: Cerebral hypoperfusion has been linked to cognitive decline either as a risk or an aggravating factor. Hypoperfusion as a consequence of microangiopathy, macroangiopathy or cardiac dysfunction can promote or accelerate neurodegeneration, blood-brain barrier disruption and neuroinflammation. US can evaluate the cerebrovascular tree for pathological structure and functional changes contributing to cerebral hypoperfusion. Microvascular pathology and hypoperfusion at the level of capillaries and small arterioles can also be assessed by ASL, an MRI signal. Despite increasing evidence supporting the utility of these methods in detection of microvascular pathology, cerebral hypoperfusion, neurovascular unit dysfunction and, most importantly, disease progression, incomplete standardisation and missing validated cut-off values limit their use in daily routine., Conclusions: US and ASL are promising tools with excellent temporal resolution, which will have a significant impact on our understanding of the vascular contributions to VCI and AD and may also be relevant for assessing future prevention and therapeutic strategies for these conditions. Our work provides recommendations regarding the use of non-invasive imaging techniques to investigate the functional consequences of vascular burden in dementia.

Glucose transporter 1 (GLUT1) deficiency syndrome (GLUT1DS) was initially described in the early 90s as a sporadic clinical condition, characterized by seizures, motor and intellectual impairment with variable clinical presentation, and without a known genetic cause. Although causative mutations in SLC2A1 were later identified and much more is known about the disease, it still remains largely underdiagnosed. In the current study, a previously described Italian family was re-analyzed using whole exome sequencing and clinically re-evaluated. Affected individuals presented with spastic paraplegia as a predominant symptom, with epilepsy and intellectual disability, inherited as an autosomal dominant trait with variable clinical presentation. While a novel variant of hereditary spastic paraplegia (HSP) was initially hypothesized in this family, previous linkage studies of known HSP genes did not identify the genetic cause. Exome-sequencing study identified a p.Arg126Cys mutation in the SLC2A1 gene, encoding GLUT1, which segregated with the affected members of the family. The diagnosis of GLUT1DS was further confirmed by cerebrospinal fluid analysis, and treatment was started with good initial response. The description of this large family provides further clinical information on this rare disease. It also offers an example of how GLUT1DS can be challenging to diagnose, and emphasizes the importance of lumbar puncture in the workflow of similar syndromes. Finally, it suggests that analysis of SLC2A1 should be considered in the diagnostic work up of HSP, especially if it is associated with epilepsy., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

There are currently no data available on the prevalence of symptomatic intracranial atherosclerosis (ICAS) in Italy. The aim of this prospective, multicenter, hospital-based, transcranial ultrasound study was to establish the prevalence of ICAS among patients hospitalized with acute ischemic stroke. At 11 stroke centers across Italy, patients consecutively admitted for their first ever acute ischemic stroke were assessed prospectively over a 24-month period either with transcranial color-coded Doppler sonography (TCCS) or transcranial Doppler (TCD) according to validated criteria. ICAS was diagnosed when there was an evidence of a cerebral infarction in the territory of a ≥50 % stenosis detected by TCCS/TCD and confirmed by magnetic resonance angiography or computed tomography angiography. A total of 1134 patients were enrolled, 665 of them (58.6 %) men, with a mean age of 71.2 ± 13.3 years. ICAS was recorded in 99 patients (8.7 % of the whole sample, 8.9 % among Caucasians), most commonly located in the anterior circulation (63 of 99, 5.5 %). After adjusting for potential confounders, multivariate analysis identified carotid/vertebral ≥50 % stenosis [odds ratio (OR) 2.59, 95 % (confidence interval) CI 1.77-6.33; P = 0.02] and hypercholesterolemia (OR 1.38, 95 % CI 1.02-1.89; P = 0.02) as being independently associated with ICAS. ICAS is a surprisingly relevant cause of ischemic stroke in Italy, identified in almost 9 % of first-ever stroke patients. It is more prevalent in the anterior circulation and independently associated with hemodynamically significant cervical vessel atherosclerosis and hypercholesterolemia. These findings support the systematic use of transcranial ultrasound to identify ICAS in patients presenting with acute ischemic stroke and in cases with ≥50 % cervical vessel stenoses.

Background: Anderson-Fabry disease (AFD) is a rare X-linked lysosomal storage disease, caused by defects of the alpha-galactosidase A (GLA) gene. AFD can affect the heart, brain, kidney, eye, skin, peripheral nerves, and gastrointestinal tract. Cardiology (hypertrophic cardiomyopathy), neurology (cryptogenic stroke), and nephrology (end-stage renal failure) screening studies suggest the prevalence of GLA variants is 0.62%, with diagnosis confirmation in 0.12%., Objectives: This study sought to expand screening from these settings to include ophthalmology, dermatology, gastroenterology, internal medicine, pediatrics, and medical genetics to increase diagnostic yield and comprehensively evaluate organ involvement in AFD patients., Methods: In a 10-year prospective multidisciplinary, multicenter study, we expanded clinical, genetic, and biochemical screening to consecutive patients enrolled from all aforementioned clinical settings. We tested the GLA gene and α-galactosidase A activity in plasma and leukocytes. Inclusion criteria comprised phenotypical traits and absence of male-to-male transmission. Screening was extended to relatives of probands harboring GLA mutations., Results: Of 2,034 probands fulfilling inclusion criteria, 37 (1.8%) were carriers of GLA mutations. Cascade family screening identified 60 affected relatives; clinical data were available for 4 affected obligate carriers. Activity of α-galactosidase A in plasma and leukocytes was diagnostic in male subjects, but not in female subjects. Of the 101 family members harboring mutations, 86 were affected, 10 were young healthy carriers, and 5 refused clinical evaluation. In the 86 patients, involved organs or organ systems included the heart (69%), peripheral nerves (46%), kidney (45%), eye (37%), brain (34%), skin (32%), gastrointestinal tract (31%), and auditory system (19%). Globotriaosylceramide accumulated in organ-specific and non-organ-specific cells in atypical and classic variants, respectively., Conclusions: Screening probands with clinically suspected AFD significantly increased diagnostic yield. The heart was the organ most commonly involved, independent of the clinical setting in which the patient was first evaluated., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of this study is to investigate the role of a computed tomography angiography (CTA)-based approach in patients undergoing mechanical thrombectomy for vertebrobasilar stroke treatment., Methods: A CTA and digital subtraction angiography (DSA) retrospective analysis of patients with acute vertebrobasilar stroke treated with thrombectomy was performed. A modified Rankin Scale score of 3 or lower at 3 months was considered as favorable outcome. The posterior circulation ASPECTS (pc-ASPECTS) was evaluated on CTA and vertebrobasilar segments involved in the occlusion were assessed using a 6-point posterior circulation computed tomography angiography (pc-CTA) vascular score aimed at evaluating the posterior circulation vascular pattern including collaterals. The primary end point was the correlation between pc-CTA and outcome; secondary end points included the concordance between CTA-DSA images and the correlation between pc-ASPECTS and outcome., Results: Fifteen patients with vertebrobasilar stroke were retrospectively analyzed. All patients in coma showed a bad outcome (P = .01) and all patients with an alert state showed a good outcome (P = .004). An excellent interobserver agreement for pc-CTA (P = .001) was observed with poor interobserver agreement for pc-ASPECTS (P = .21). No significant correlations between pc-ASPECTS and clinical outcome were observed. Patients with good outcome had a lower pc-CTA (P = .02). The patency of the distal third of the basilar artery and both posterior cerebral arteries was related with good outcome., Conclusion: The pc-CTA seems to have prognostic value in patients with vertebrobasilar stroke undergoing mechanical thrombectomy. It may be used as an additional prognostic triage technique in this subgroup of stroke patients., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Although several authors have studied the association between patent foramen ovale (PFO) and ischaemic stroke, the matter is still controversial; few have suggested an association between cryptogenetic stroke and PFO, while others have denied this association. The aim of this study was to evaluate PFO prevalence in the whole ischaemic stroke population, independently from age and stroke subtypes and to identify the characteristics associated with the presence of PFO., Methods: SISIFO study was a multicenter, prospective, single-wave, cross-sectional survey conducted on consecutive patients with acute ischemic stroke admitted to selected clinical centres. Data regarding vascular risk factors were registered for each patient; all patients underwent computed tomography scan and/or magnetic resonance imaging of the brain; an electrocardiogram and standard laboratory blood tests were performed. A Doppler ultrasound study of extra-cranial arteries was performed too. The cases were classified according to TOAST and OCSP criteria. Each patient underwent transcranial Doppler or transcranial color-coded duplex sonography with bubble test as diagnostic tool for right-to-left-shunt. Where right-to-left shunt was detected, PFO presence was confirmed by echocardiography., Findings: 1,130 consecutive patients were included. We found a PFO in 247 (21.9%; 95% CI, 19.5-24.3%) patients; PFO was present in 23.5% of patients with cryptogenic stroke and in 21.3% of patients with stroke of known causes; this difference was not statistically significant. At the univariate analysis, decreasing age, hypertension, diabetes mellitus, and atrial fibrillation, and stroke characteristics such as NIHSS, OCSP and TOAST were predictors of PFO presence. At the multivariate analysis, we found a significant interaction between age and OCSP syndrome. Being LACI the reference category, the prevalence of PFO in PACI and POCI decreased significantly along with age, whereas there was no change in TACI., Conclusion: If any relationship exists between stroke and PFO, this is more likely in PACI and POCI at a younger age. Our results are consistent with recent findings that underline PFO alone must not be considered a significant independent predictor for stroke; so the presence of PFO alone doesn't permit rushed causal correlations or 'therapeutic aggressiveness'., (© 2015 S. Karger AG, Basel.)

Background and Purposes: This study aimed to identify clinical and ultrasound imaging predictors of progression of carotid luminal narrowing in subjects with asymptomatic moderate internal carotid artery (ICA) stenosis., Methods: A total of 571 subjects with asymptomatic moderate (50-69%) ICA stenoses were enrolled. They underwent ultrasound examination at baseline and after 12 months. Demographics, vascular risk factors, medications, plaque characteristics (surface and echogenicity) and common carotid intima-media thickness (IMT) were collected. At the follow-up examination, any change of ICA stenosis was graded in three categories (i) ≥70% to near occlusion, (ii) near occlusion, and (iii) occlusion. Progression of stenosis was defined as an increase in the stenosis degree by at least one category from baseline to follow-up., Results: At 12 months, progression occurred in 142 subjects (prevalence rate 25%). At the multivariable logistic model, pathological IMT values (considered as binary variable: normal: ≤1 mm vs. pathologic: >1 mm) significantly predicted the risk for plaque progression after adjusting the model for possible confounders (OR 2.28, 95% CI 1.18-4.43, P = .014, multivariable logistic model)., Conclusions: Our results confirm the role of carotid wall thickening as a marker of atherosclerosis. Carotid IMT measurement should be considered to implement risk stratification in patients with asymptomatic carotid disease.

Patent foramen ovale (PFO) is a common congenital anatomical defect in the general population with a mean prevalence of 20 %. Transcranial Doppler sonography and echocardiography, both with infusion of agitated saline as an echo contrast, have been introduced for the diagnosis of PFO. Transesophageal echocardiography is considered the gold standard. Several studies have suggested an association between cryptogenetic stroke and PFO, but the role of this condition as a risk factor for stroke is still debated. The aims of this prospective multicentre study are the evaluation of PFO prevalence in the whole ischemic stroke population and the identification of a stroke recurrence profile risk in patients with PFO. All consecutive patients admitted for acute ischemic stroke and with a confirmed diagnosis at discharge are eligible cases for the study. Demographic and vascular risk factors are registered. Clinical severity is summarized by the National Institute of Health stroke scale. Echocardiographic and transcranial studies are performed in each patient to detect the presence of PFO. Prevalence of PFO will be calculated with 95 % CIs. Univariate analysis will be performed to detect the correlation of PFO with different registered factors and multivariable analysis with PFO as independent variable. The present study should contribute to better identify the role of PFO in ischemic stroke risk and recurrence-related events. Qualifying findings of the study are represented by the high number of enrolled patients, the prospective methodology of the study and the presence of secondary instrumental endpoints.