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Background: Several lines of evidence support the involvement of the lectin pathway of complement (LP) in the pathogenesis of acute ischemic stroke. The aim of this multicenter observational study was to assess the prognostic value of different circulating LP initiators in acute stroke.Methods: Plasma levels of the LP initiators ficolin-1, -2, and -3 and mannose-binding lectin (MBL) were measured in 80 stroke patients at 6 h only and in 85 patients at 48 h and later. Sixty-one age- and sex-matched healthy individuals served as controls. Stroke severity was measured on admission using the National Institutes of Health Stroke Scale (NIHSS). The outcome was measured at 90 days by the modified Rankin Scale (mRS).Results: Ficolin-1 was decreased in patients compared with controls measured at 6 h (median 0.13 vs 0.33 μg/ml, respectively, p < 0.0001). At 48 h, ficolin-1 was significantly higher (0.45 μg/ml, p < 0.0001) compared to the 6 h samples and to controls. Likewise, ficolin-2 was decreased at 6 h (2.70 vs 4.40 μg/ml, p < 0.0001) but not at 48 h. Ficolin-3 was decreased both at 6 and 48 h (17.3 and 18.23 vs 21.5 μg/ml, p < 0.001 and <0.05, respectively). For MBL no difference was detected between patients and controls or within patients at the different time points. In multivariate analysis, early ficolin-1 was independently associated with unfavorable mRS outcome (adjusted odds ratio (OR): 2.21, confidence interval (CI) 95 % 1.11-4.39, p = 0.023). Early ficolin-1 improved the discriminating ability of an outcome model including NIHSS and age (area under the curve (AUC) 0.95, CI 95 % 0.90-0.99, p = 0.0001).Conclusions: The ficolins are consumed within 6 h after stroke implicating activation of the LP. Early ficolin-1 is selectively related to 3-month unfavorable outcome. [ABSTRACT FROM AUTHOR]

Background and Purpose: Guidelines help physicians to provide optimal care for stroke patients, but implementation is challenging due to the quantity of recommendations. Therefore a practical overview related to applicability of recommendations can be of assistance., Methods: A systematic review was performed on ischaemic stroke guidelines published in scientific journals, covering the whole acute care process for patients with ischaemic stroke. After data extraction, experts rated the recommendations on dimensions of applicability, that is, actionability, feasibility and validity, on a 9-point Likert scale. Agreement was defined as a score of ≥8 by ≥80% of the experts., Results: Eighteen articles were identified and 48 recommendations were ultimately extracted. Papers were included only if they described the whole acute care process for patients with ischaemic stroke. Data extraction and analysis revealed variation in terms of both content and comprehensiveness of this description. Experts reached agreement on 34 of 48 (70.8%) recommendations in the dimension actionability, for 16 (33.3%) in feasibility and for 15 (31.3%) in validity. Agreement on all three dimensions was reached for seven (14.6%) recommendations: use of a stroke unit, exclusion of intracerebral haemorrhage as differential diagnosis, administration of intravenous thrombolysis, performance of electrocardiography/cardiac evaluation, non-invasive vascular examination, deep venous thrombosis prophylaxis and administration of statins if needed., Discussion and Conclusion: Substantial variation in agreement was revealed on the three dimensions of the applicability of recommendations. This overview can guide stroke physicians in improving the care process and removing barriers where implementation may be hampered by validity and feasibility., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Objective: Stroke is the leading cause of death and disability. Timely differentiation between ischemic stroke, hemorrhagic stroke, and stroke mimics is critical for tailored treatment and triage. To accelerate the identification of stroke's subtype, we propose to use the levels of circulating tPA as a biomarker., Methods: Biostroke is an observational study performed at the Caen Hospital. We quantified tPA levels in 110 patients with ischemic strokes, 30 patients with hemorrhagic strokes, and 67 stroke mimic patients upon their arrival at the emergency. Two logistic regression models were formulated: one with parameters measurable in an ambulance (Model A) and one with parameters measurable at the hospital (Model H). These models were both tested with or without plasma tPA measurements. Our initial assessment involved evaluating the effectiveness of both models in distinguishing between hemorrhagic strokes, ischemic strokes, and stroke mimics within our study cohort., Results: Plasmatic tPA levels exhibit significant distinctions between hemorrhagic, ischemic, and mimic stroke patients (1.8; 2.5; 2.4 ng/mL, respectively). The inclusion of tPA in model A significantly enhances the classification accuracy of hemorrhagic patients only, increasing identification from 0.67 (95% CI, 0.59 to 0.75) to 0.78 (95% CI, 0.7 to 0.85) (p = 0.0098). Similarly, in model H, classification accuracy of hemorrhagic patients significantly increased with the addition of tPA, rising from 0.75 (95% CI, 0.67 to 0.83) without tPA to 0.86 (95% CI, 0.81 to 0.91) with tPA (p = 0.024)., Interpretations: Our findings underscore the valuable role of tPA levels in distinguishing between stroke subtypes., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background and Purpose: Decompressive hemicraniectomy (DH) improves survival and functional outcome in large middle cerebral artery (MCA) infarcts. However, long-term cognitive outcomes after DH remain underexplored. In a cohort of patients with large right-hemisphere MCA infarction undergoing DH, we assessed the rates of long-term cognitive impairment over 3-year follow-up., Methods: We prospectively evaluated consecutive patients included in the Lille Decompressive Surgery Database (May 2005-April 2022) undergoing DH according to existing guidelines for large hemisphere MCA infarction. We included patients with right-sided stroke and screened with the Mini-Mental State Examination (MMSE) in at least one of the prespecified follow-ups (3-month, 1-year, 3-year). Cognitive impairment was defined as an MMSE score < 24. We included only right-hemisphere strokes to avoid testing biases related to severe aphasia. We compared clinical and neuroimaging data in patients with and without cognitive impairment., Results: Three hundred four patients underwent DH during the study period. Among 3-month survivors, 95 had a right-hemisphere stroke and underwent at least one cognitive screening (median age = 51 years, 56.8% men). Forty-four patients (46.3%) exhibited cognitive impairment at least once during the 3-year follow-up. Baseline characteristics did not significantly differ between patients with and without cognitive impairment. Regarding long-term temporal trends, cognitive impairment was observed in 23 of 76 (30.3%), 25 of 80 (31.3%), and 19 of 66 (28.8%) patients at 3-month, 1-year, and 3-year follow-up, respectively, and it was associated with higher rates of functional disability (all p < 0.05)., Conclusions: The persistently high rates of cognitive impairment after DH highlight the importance of cognitive monitoring to improve the long-term management of survivors., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Introduction: Depressive symptoms are commonly reported after spontaneous intracerebral haemorrhage (ICH) and frequently associated with cognitive decline. Using hierarchical clustering analysis (HCA), we aimed to identify different post-ICH depressive symptoms profiles and to evaluate their association with dementia risk., Methods: We included consecutive patients from the prospective Prognosis of Intracerebral Haemorrhage (PITCH) study who survived 6 months after the ICH. We performed HCA using depressive symptoms severity (assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS)), along with the presence of apathy and anxiety (screened using Neuropsychiatric Inventory questionnaire). Baseline clinical/neuroimaging characteristics and risk of incident dementia were compared between different profiles using univariate and multivariable models., Results: Of 265 six-month ICH survivors, 221 (83%) underwent neuropsychiatric screening (mean age 65.5 years; 57% male). Using HCA, 3 profiles were identified: (1) without significant depressive symptoms ( n  = 152; median MADRS score = 2 [IQR 0-4]); (2) depressive symptoms with predominant apathy ( n  = 41; median MADRS score = 15 [IQR 5-20], 68% with apathy); (3) depressive symptoms profile with predominant anxiety ( n  = 28; median MADRS score = 17 [IQR 9-25]; 100% with anxiety). Compared to patients without depressive symptoms, patients with depressive symptoms and predominant apathy (but not those with predominant anxiety) were more likely to have cerebral atrophy (OR = 2.4, 95% CI = 1.4-4.2) and had significantly higher long-term new-onset dementia risk (adjusted hazard ratio = 2.2, 95% CI = 1.3-3.8)., Conclusion: Screening for apathy and anxiety on top of depressive symptoms might help identifying patients at risk for dementia. Future studies on treatment should account for different post-ICH depressive symptoms profiles that may impact on cognitive function., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Objectives: Cerebral amyloid angiopathy-related inflammation (CAA-RI) and biopsy-positive primary angiitis of the CNS (BP-PACNS) have overlapping clinicoradiologic presentations. It is unknown whether clinical and radiologic features can differentiate CAA-RI from BP-PACNS and whether both diseases have different relapse rates. The objectives of this study were to compare clinicoradiologic presentations and relapse rates in patients with CAA-RI vs BP-PACNS., Methods: Patients with CAA-RI and BP-PACNS were enrolled from 2 retrospective multicenter cohorts. Patients with CAA-RI were biopsy-positive or met probable clinicoradiologic criteria. Patients with BP-PACNS had histopathologic confirmation of CNS angiitis, with no secondary etiology. A neuroradiologist read brain MRIs, blinded to the diagnosis of CAA-RI or BP-PACNS. Clinicoradiologic features were compared using univariable logistic regression models. Relapse rates were compared using a univariable Fine-Gray subdistribution hazard model, with death as a competing risk., Results: This study enrolled 104 patients with CAA-RI (mean age 73 years, 48% female sex) and 52 patients with BP-PACNS (mean age 45 years, 48% female sex). Patients with CAA-RI more often had white matter hyperintense lesions meeting the probable CAA-RI criteria (93% vs 51%, p < 0.001), acute subarachnoid hemorrhage (15% vs 2%, p = 0.02), cortical superficial siderosis (27% vs 4%, p < 0.001), ≥1 lobar microbleed (94% vs 26%, p < 0.001), past intracerebral hemorrhage (17% vs 4%, p = 0.04), ≥21 visible centrum semiovale perivascular spaces (34% vs 4%, p < 0.01), and leptomeningeal enhancement (70% vs 27%, p < 0.001). Patients with BP-PACNS more often had headaches (56% vs 31%, p < 0.01), motor deficits (56% vs 36%, p = 0.02), and nonischemic parenchymal gadolinium enhancement (82% vs 16%, p < 0.001). The prevalence of acute ischemic lesions was 18% in CAA-RI and 22% in BP-PACNS ( p = 0.57). The features with the highest specificity for CAA-RI were acute subarachnoid hemorrhage (98%), cortical superficial siderosis (96%), past intracerebral hemorrhage (96%), and ≥21 visible centrum semiovale perivascular spaces (96%). The probable CAA-RI criteria had a 71% sensitivity (95% CI 44%-90%) and 91% specificity (95% CI 79%-98%) in differentiating biopsy-positive CAA-RI from BP-PACNS. The rate of relapse in the first 2 years after remission was lower in CAA-RI than in BP-PACNS (hazard ratio 0.46, 95% CI 0.22-0.96, p = 0.04)., Conclusion: Clinicoradiologic features differed between patients with CAA-RI and those with BP-PACNS. Specific markers for CAA-RI were hemorrhagic signs of subarachnoid involvement, past intracerebral hemorrhage, ≥21 visible centrum semiovale perivascular spaces, and the probable CAA-RI criteria. A biopsy remains necessary for diagnosis in some cases of CAA-RI. The rate of relapse in the first 2 years after disease remission was lower in CAA-RI than in BP-PACNS.

Background: The dramatic clinical improvement offered by mechanical thrombectomy raised questions about the relevance of prior intravenous thrombolysis in large-vessel occlusion strokes. Hence, studying intravenous thrombolysis susceptibility and its dependence on thrombus composition is crucial. We used an observational proteomic study of whole thrombi retrieved by mechanical thrombectomy to identify factors associated with fibrin content and fibrinolytic activity (FA)., Methods: In 104 stroke patients, the thrombi proteome was established by mass spectrometry coupled to liquid chromatography. FA was estimated in clots both outside (FA out ) by measuring D-dimer levels at the blood-thrombus interface and inside (FA in ) by evaluating the ratio of fibrinogen α to its plasmin-cleaved forms using proteomics coupled with protein electrophoresis. The factors associated with fibrin content, FA in , and FA out were determined by intravenous thrombolysis-adjusted linear regression., Results: FA out ( P <0.0001) and FA in ( P =0.0147) were driven by recombinant tissue-type plasminogen activator (r-tPA) administration (47/104) and thrombus composition. Indeed, FA out was greater with fibrin-rich than erythrocyte-rich thrombi, presumably because of more (r)tPA substrates. Thus, FA out was increased with cardioembolic thrombi (72/104), which are rich in fibrin ( P =0.0300). Opposite results were found inside the thrombus, suggesting that (r)tPA penetrability was hampered by the density of the fibrinous cap. Moreover, blood cells had a strong impact on thrombus structure and susceptibility to (r)tPA. Indeed, fibrin content was negatively associated with erythrocyte-specific proteins in the thrombus, admission hematocrit ( P =0.0139), and hemoglobin level ( P =0.0080), which underlines the key role of erythrocytes in thrombus composition. Also, an increased number of neutrophils impaired FA out ( P =0.0225), which suggests that their aggregation around the thrombus prevented the (r)tPA attack. Only FA out was significantly associated with reduced thrombus weight ( P =0.0310), increased recanalization rate ( P =0.0150), good clinical outcome ( P =0.0480), and reduced mortality ( P =0.0080)., Conclusions: Proteomics can offer new insights into the close relationship between thrombus composition and susceptibility to fibrinolysis, paving the way for new adjuvant therapies., Competing Interests: Disclosures None.

Stroke affects up to one in five people during their lifetime in some high-income countries, and up to almost one in two in low-income countries. Globally, it is the second leading cause of death. Clinically, the disease is characterised by sudden neurological deficits. Vascular aetiologies contribute to the most common causes of ischaemic stroke, including large artery disease, cardioembolism, and small vessel disease. Small vessel disease is also the most frequent cause of intracerebral haemorrhage, followed by macrovascular causes. For acute ischaemic stroke, multimodal CT or MRI reveal infarct core, ischaemic penumbra, and site of vascular occlusion. For intracerebral haemorrhage, neuroimaging identifies early radiological markers of haematoma expansion and probable underlying cause. For intravenous thrombolysis in ischaemic stroke, tenecteplase is now a safe and effective alternative to alteplase. In patients with strokes caused by large vessel occlusion, the indications for endovascular thrombectomy have been extended to include larger core infarcts and basilar artery occlusion, and the treatment time window has increased to up to 24 h from stroke onset. Regarding intracerebral haemorrhage, prompt delivery of bundled care consisting of immediate anticoagulation reversal, simultaneous blood pressure lowering, and prespecified stroke unit protocols can improve clinical outcomes. Guided by underlying stroke mechanisms, secondary prevention encompasses pharmacological, vascular, or endovascular interventions and lifestyle modifications., Competing Interests: Declaration of interests NAH receives research support from the Dutch Heart Foundation (03–005–2022–0031). BC has received research grants from Regional GIRCI Méditerranée, Nice University Hospital, Acticor Biotech, and Bayer; support for attending meetings from the European Stroke Organisation, French Neurovascular Society, Belgium Stroke Council, and French Neurology Society; and is an editorial board member of the European Stroke Journal, chair of the European Stroke Organisation (ESO) Simulation Committee, and chair of the Education and Communication committee within StrokeLink (all unpaid). TWL has received support for the present manuscript from the Kwok Tak Seng Centre for Stroke Research and Intervention and the SHKP Kwok Brain Health Research Centre; an educational grant from Boehringer Ingelheim; consulting fees from Shionogi & Co and Janssen Research & Development; honoraria from Daiichi-Sankyo and Argenica Therapeutics; payment for expert testimony; travel expenses from Pfizer, Daiichi-Sankyo, and Boehringer Ingelheim; was a member of the data safety monitoring board for the ENCHANTED2/MT study at The George Institute for Global Health; and is chairman of the exemptions sub-committee, and member of the licentiate committee for The Medical Council of Hong Kong, co-chair of the co-chairs committee for Mission Thrombectomy 2020+ as part of The Society of Vascular Interventional Neurology, associate editor for the International Journal of Stroke, assistant editor for the journal Stroke, and board member of the specialty board in neurology at Hong Kong College of Physicians (all unpaid). F-EdL received funding from the Dutch Heart Foundation, Abbott, and ZonMW; serves as a member of the scientific advisory board of the Dutch Heart Foundation and is associate editor for the International Journal of Stroke (unpaid); and has received registration fees from ESO for the ESO Conference. None of these parties or funders had any influence in any part of the preparation of this Seminar., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Aims: To assess the efficacy and safety of a standardised hyperbaric oxygen therapy protocol (HBOT) monitored by fluorescein angiography (FA) in patients with retinal artery occlusion (RAO)., Methods: It is a prospective, non-comparative, monocentric study conducted between July 2016 and March 2022. All consecutive patients diagnosed with RAO within 7 days underwent visual acuity measurement, FA, macular optical coherence tomography (OCT) and OCT-angiography. They received two daily HBOT sessions (2.5 atmosphere absolute, 90 min) until revascularisation assessed by FA. Complete ophthalmic follow-up was scheduled at day 14, day 21 and at 1 month. The main outcome measure was a best-corrected visual acuity (BCVA) improvement defined as a decrease ≥0.3 logMAR at 1 month., Results: Thirty-one patients were included and received a mean number of 33.9 (13-56) HBOT sessions. Retinal revascularisation was observed in 48.4% and 87.1% of patients at days 14 and 21, respectively. The mean BCVA on referral and at 1 month was 1.51 logMAR and 1.10 logMAR, respectively. Fifteen (48.4%) patients achieved the main outcome measure. Six (19.4%) patients experienced minor barotrauma that did not require HBOT discontinuation. The univariate analysis showed that antiplatelet-treated patients (p=0.044) and patients with a poor initial BCVA (p=0.008) were more likely to achieve a BCVA improvement. OCT-angiography was not sensitive enough to diagnose RAO or assess revascularisation., Conclusion: In RAO patients monitored by FA until spontaneous revascularisation of the central retinal artery, HBOT was effective and safe., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: We evaluated the clinical and safety outcomes of emergent carotid artery stenting (eCAS) plus endovascular thrombectomy (EVT) among patients with anterior tandem lesion (TL) and large ischemic core (LIC)., Methods: This retrospective study included consecutive stroke patients enrolled in the Endovascular Treatment in Ischemic Stroke Registry in France between January 2015 and June 2023. We compared the outcomes of carotid stenting vs no stenting in tandem lesion with pre-treatment LIC (Alberta Stroke Program Early CT Score (ASPECTS) 3-5) and stenting in tandem lesion vs thrombectomy alone for isolated intracranial occlusions with pre-treatment LIC. Primary outcome was a score of 0 to 3 on the modified Rankin scale (mRS) at 90 days. Multivariable mixed-effects logistic regression was performed., Results: Among 218 tandem patients with LIC, 55 were treated with eCAS plus EVT. The eCAS group had higher odds of 90-day mRS 0-3 (adjusted Odds Ratio (aOR) 2.40, 95% confidence interval (CI) 1.10 to 5.21; p=0.027). There were no differences in the risk of any intracerebral hemorrhage (OR 1.41, 95% CI 0.69 to 2.86; p=0.346), parenchymal hematoma (aOR 1.216, 95% CI 0.49 to 3.02; p=0.675), symptomatic intracerebral hemorrhage (aOR 1.45, 95% CI 0.60 to 3.48; p=0.409), or 90-day mortality (aOR 0.74, 95% CI 0.33 to 1.68; p=0.472). eCAS was associated with a higher rate of carotid patency at day 1 (aOR 3.54, 95% CI 1.14 to 11.01; p=0.028). Safety outcomes were similar between EVT+eCAS group in TL-LIC and EVT alone group in isolated intracranial occlusions with LIC., Conclusion: eCAS appears to be a safe and effective strategy in patients with TL and LIC volume., Competing Interests: Competing interests: Dr. Marnat reports consulting fees from Microvention and Stryker outside the submitted work. Dr. Soize reports personal fees from Balt and Microvention outside the submitted work. Dr. Richard reports consulting fees from Stryker and Microvention outside the submitted work. Dr. Bourcier reports consulting fees from ACTICOR and payments for lectures from ACTICOR, BMS, Pfizer, and Bayer outside the submitted work. Dr. Casolla reports consulting fees from ACTICOR and payments for lectures from ACTICOR, BMS, Pfizer, and Bayer outside the submitted work. The other authors report no conflicts., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Fatigue is a major complaint in stroke survivors, but data focusing on intracerebral haemorrhage (ICH) survivors are scarce. In a cohort of spontaneous ICH survivors, we assessed the long-term prevalence of fatigue and its associated factors., Methods: We included consecutive 1-year ICH survivors from the prospective, observational, single-centre Prognosis of Intracerebral Haemorrhage (PITCH) study. We evaluated fatigue (defined as a score ≥ 4 in Chalder Fatigue Scale); the severity of neurological, depressive, and anxiety symptoms; and functional disability 1, 3, and 6 years after ICH. We performed univariable and multivariable models to evaluate clinical factors and brain magnetic resonance imaging (MRI) small vessel disease (SVD) markers associated with fatigue., Results: Of 255 1-year ICH survivors, 153 (60%) underwent fatigue screening and were included in this study. Seventy-eight patients (51%) reported fatigue at 1-year, 56/110 (51%) at 3-year, and 27/67 (40%) at 6-year follow-up. Patients with fatigue exhibited more severe concomitant depressive/anxiety symptoms, but the severity of depressive symptoms was the only clinical factor significantly associated with 1-year fatigue in multivariable analysis (adjusted odds ratio 1.4 for one-point increase; 95% confidence interval 1.2-1.6). Patients with severe cortical atrophy at baseline had increased risk of fatigue at 1-year follow-up compared to patients with mild/no cortical atrophy (adjusted odds ratio 2.5; 95% confidence interval 1.1-5.8)., Conclusions: Fatigue after ICH is frequent and long-lasting, and it is associated with cortical atrophy (but not with other MRI markers of cerebral SVD). The link between fatigue and depressive symptoms may represent a potential therapeutic target., (© 2023. Fondazione Società Italiana di Neurologia.)

Introduction: Antiphospholipid syndrome (APS) is an autoimmune thrombotic disease with various systemic presentations. This study aimed to identify homogeneous groups of patients based on a non-supervised hierarchical cluster analysis and assess the rate of relapse associated with antinuclear antibodies (ANA)., Methods: This retrospective observational study enrolled patients, over a 90-month period, who had APS as defined by the 2006 Sydney classification criteria, and for whom ANA workup was performed. Agglomerative unsupervised hierarchical clustering was conducted to classify patients into subgroups using 24 variables reflecting a range of clinical and biological baseline features associated with APS., Results: Hundred and seventy-four patients were included and were categorized into four phenotypes. Cluster 1 (n=73) associated mostly middle-aged men with risk factors for cardiovascular disease. Obstetrical APS with low-risk thrombosis made up cluster 2 (n=25). Patients with venous thromboembolism (VTE), microvascular findings and double/triple positive APL antibodies (50%) were represented in cluster 3 (n=33). Whereas cluster 4 (n=43) characterized a predominantly female subpopulation with positive ANA and systemic lupus (n=23) that exhibited a high thrombotic risk and more frequent relapses (n=38) (p<0.001)., Conclusions: This study identified four homogenous groups of patients with APS listed as: i) cardiovascular and arterial risk, ii) obstetrical, iii) VTE and microvascular, and iv) ANA-positive APS. We found that ANA-positivity was associated with higher rates of relapse. Applying ANA status to classification criteria could constitute a novel approach to tailoring management for APS, based on phenotypic patterns and risk assessment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ottavi, Toulon, Casolla and Martis.)

Introduction: Patients with chronic kidney disease (CKD) have an increased risk of stroke, and CKD seems associated with worse outcome after a stroke. The main objective of our study RISOTTO was to evaluate the influence of CKD and acute kidney injury (AKI) on the clinical outcome and mortality of ischemic stroke patients after thrombolysis and/or thrombectomy., Methods: This multicenter cohort study included patients in the acute phase of ischemic stroke due to large artery occlusion managed by thrombectomy. Functional outcome at 3 months was assessed by the modified Rankin Scale (mRS)., Results: 280 patients were included in the analysis. Fifty-nine patients (22.6%) had CKD. At 3 months, CKD was associated with similar functional prognosis (mRS 3-6: 50.0% vs. 41.7%, p = 0.262) but higher mortality (24.2% versus 9.5%, p = 0.004). In univariate analysis, patients with CKD had a higher burden of white matter hyperintensities (Fazekas score: 1.7 ± 0.8 vs. 1.0 ± 0.8, p = 0.002), lower initial infarct volume with equivalent severity, and lower recanalization success (86.4% vs. 97.0%, p = 0.008) compared to non-CKD patients. Forty-seven patients (20.0%) developed AKI. AKI was associated with poorer 3-month functional outcome (mRS 3-6: 63.8% vs. 49.0%, p = 0.002) and mortality (23.4% versus 7.7%, p = 0.002). In multivariate analysis, AKI appeared as an independent risk factor for poor functional outcome (mRS 3-6: adjOR 2.79 [1.11-7.02], p = 0.029) and mortality (adjOR 2.52 [1.03-6.18], p = 0.043) at 3 months, while CKD was not independently associated with 3-month mortality and poor neurological outcome., Conclusions: AKI is independently associated with poorer functional outcome and increased mortality at 3 months. CKD was not an independent risk factor for 3-month mortality or poor functional prognosis., (© 2024 S. Karger AG, Basel.)

Background and Purpose: This study aimed to investigate the effect of endovascular treatment (EVT, with or without intravenous thrombolysis [IVT]) versus IVT alone on outcomes in patients with acute ischemic stroke (AIS) and intracranial large vessel occlusion (LVO) attributable to cervical artery dissection (CeAD)., Methods: This multinational cohort study was conducted based on prospectively collected data from the EVA-TRISP (EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients) collaboration. Consecutive patients (2015-2019) with AIS-LVO attributable to CeAD treated with EVT and/or IVT were included. Primary outcome measures were (1) favorable 3-month outcome (modified Rankin Scale score 0-2) and (2) complete recanalization (thrombolysis in cerebral infarction scale 2b/3). Odds ratios with 95% confidence intervals (OR [95% CI]) from logistic regression models were calculated (unadjusted, adjusted). Secondary analyses were performed in the patients with LVO in the anterior circulation (LVOant) including propensity score matching., Results: Among 290 patients, 222 (76.6%) had EVT and 68 (23.4%) IVT alone. EVT-treated patients had more severe strokes (National Institutes of Health Stroke Scale score, median [interquartile range]: 14 [10-19] vs. 4 [2-7], P<0.001). The frequency of favorable 3-month outcome did not differ significantly between both groups (EVT: 64.0% vs. IVT: 86.8%; ORadjusted 0.56 [0.24-1.32]). EVT was associated with higher rates of recanalization (80.5% vs. 40.7%; ORadjusted 8.85 [4.28-18.29]) compared to IVT. All secondary analyses showed higher recanalization rates in the EVT-group, which however never translated into better functional outcome rates compared to the IVT-group., Conclusion: We observed no signal of superiority of EVT over IVT regarding functional outcome in CeAD-patients with AIS and LVO despite higher rates of complete recanalization with EVT. Whether pathophysiological CeAD-characteristics or their younger age might explain this observation deserves further research.

Introduction: Internal carotid artery dissection (ICAD) is a rare cause of acute ischemic stroke with large vessel occlusion (AIS-LVO). We aimed investigating the impact on outcome of internal carotid artery (ICA) patency after mechanical thrombectomy (MT) for AIS-LVO due to occlusive ICAD., Patients and Methods: We included consecutive patients with AIS-LVO due to occlusive ICAD treated with MT from January 2015 to December 2020 in three European stroke centers. We excluded patients with unsuccessful intracranial reperfusion after MT (modified Thrombolysis in Cerebral Infarction (mTICI) score < 2b). We compared 3-month favorable clinical outcome rate, defined as a modified Rankin scale (mRS) score ⩽2, according to ICA status (patency vs occlusion) at the end of MT and at 24-h follow-up imaging, using univariate and multivariable models., Results: Among 70 included patients, ICA was patent in 54/70 (77%) at the end of MT, and in 36/66 (54.5%) patients with 24-h follow-up imaging. Among patients with ICA patency at the end of MT, 32% presented ICA occlusion at 24-h control imaging. Favorable 3-month outcome occurred in 41/54 (76%) patients with ICA patency post-MT and in 9/16 (56%) patients with occluded ICA post-MT ( p  = 0.21). Rates of favorable outcome were significantly higher in patients with 24-h ICA patency compared to patients with 24-h ICA occlusion (32/36 [89%] vs 15/30 [50%]), with an adjusted odds ratio of 4.67 (95% CI: 1.26-17.25)., Discussion and Conclusion: Obtaining sustained (24-h) ICA patency after MT could be a therapeutic target for improving functional outcome in patients with AIS-LVO due to ICAD., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© European Stroke Organisation 2022.)

Background: Although anxiety is common in several neurological conditions, it has been poorly investigated after spontaneous intracerebral hemorrhage (ICH)., Aims: In consecutive ICH survivors, we assessed the long-term prevalence of anxiety and its clinical and radiological determinants., Methods: Using the Hospital Anxiety and Depression Scale (HADS), we evaluated ICH survivors enrolled in the prospective, single-center Prognosis of Intracerebral Hemorrhage (PITCH) study. The prevalence of anxiety (defined as a HADS-anxiety subscale score >7) was evaluated at three time points (1-2, 3-5, and 6-8 years after ICH), along with neurological symptoms severity, functional disability, and cognitive impairment scores. Clinical and radiological characteristics associated with anxiety were evaluated in univariate and multivariable models., Results: Of 560 patients with spontaneous ICH, 255 were alive 1 year later, 179 of whom completed the HADS questionnaire and were included in the study. Thirty-one patients (17%; 95% confidence interval (CI) = 12-23) had anxiety 1-2 years, 38 (27%; 95% CI = 19-34) 3-5 years, and 18 (21%; 95% CI = 12-30) 6-8 years after ICH. In patients with anxiety, the prevalence of associated depressive symptoms was 48% 1-2 years, 61% 3-5 years, and 56% 6-8 years after ICH. Among clinical and radiological baseline characteristics, only lobar ICH location was significantly associated with anxiety 1-2 years after ICH (odds ratio = 2.8; 95% CI = 1.2-6.5). Anxiety was not associated with concomitant neurological symptoms severity, functional disability, or cognitive impairment., Conclusion: Anxiety is frequent in ICH survivors, often in association with depressive symptoms, even many years after the index event.

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: Cerebral amyloid angiopathy (CAA) is an age-related small vessel disease, characterised pathologically by progressive deposition of amyloid β in the cerebrovascular wall. The Boston criteria are used worldwide for the in-vivo diagnosis of CAA but have not been updated since 2010, before the emergence of additional MRI markers. We report an international collaborative study aiming to update and externally validate the Boston diagnostic criteria across the full spectrum of clinical CAA presentations., Methods: In this multicentre, hospital-based, retrospective, MRI and neuropathology diagnostic accuracy study, we did a retrospective analysis of clinical, radiological, and histopathological data available to sites participating in the International CAA Association to formulate updated Boston criteria and establish their diagnostic accuracy across different populations and clinical presentations. Ten North American and European academic medical centres identified patients aged 50 years and older with potential CAA-related clinical presentations (ie, spontaneous intracerebral haemorrhage, cognitive impairment, or transient focal neurological episodes), available brain MRI, and histopathological assessment for CAA diagnosis. MRI scans were centrally rated at Massachusetts General Hospital (Boston, MA, USA) for haemorrhagic and non-haemorrhagic CAA markers, and brain tissue samples were rated by neuropathologists at the contributing sites. We derived the Boston criteria version 2.0 (v2.0) by selecting MRI features to optimise diagnostic specificity and sensitivity in a prespecified derivation cohort (Boston cases 1994-2012, n=159), then externally validated the criteria in a prespecified temporal validation cohort (Boston cases 2012-18, n=59) and a geographical validation cohort (non-Boston cases 2004-18; n=123), comparing accuracy of the new criteria to the currently used modified Boston criteria with histopathological assessment of CAA as the diagnostic standard. We also assessed performance of the v2.0 criteria in patients across all cohorts who had the diagnostic gold standard of brain autopsy., Findings: The study protocol was finalised on Jan 15, 2017, patient identification was completed on Dec 31, 2018, and imaging analyses were completed on Sept 30, 2019. Of 401 potentially eligible patients presenting to Massachusetts General Hospital, 218 were eligible to be included in the analysis; of 160 patient datasets from other centres, 123 were included. Using the derivation cohort, we derived provisional criteria for probable CAA requiring the presence of at least two strictly lobar haemorrhagic lesions (ie, intracerebral haemorrhages, cerebral microbleeds, or foci of cortical superficial siderosis) or at least one strictly lobar haemorrhagic lesion and at least one white matter characteristic (ie, severe visible perivascular spaces in centrum semiovale or white matter hyperintensities in a multispot pattern). The sensitivity and specificity of these criteria were 74·8% (95% CI 65·4-82·7) and 84·6% (71·9-93·1) in the derivation cohort, 92·5% (79·6-98·4) and 89·5% (66·9-98·7) in the temporal validation cohort, 80·2% (70·8-87·6) and 81·5% (61·9-93·7) in the geographical validation cohort, and 74·5% (65·4-82·4) and 95·0% (83·1-99·4) in all patients who had autopsy as the diagnostic standard. The area under the receiver operating characteristic curve (AUC) was 0·797 (0·732-0·861) in the derivation cohort, 0·910 (0·828-0·992) in the temporal validation cohort, 0·808 (0·724-0·893) in the geographical validation cohort, and 0·848 (0·794-0·901) in patients who had autopsy as the diagnostic standard. The v2.0 Boston criteria for probable CAA had superior accuracy to the current Boston criteria (sensitivity 64·5% [54·9-73·4]; specificity 95·0% [83·1-99·4]; AUC 0·798 [0·741-0854]; p=0·0005 for comparison of AUC) across all individuals who had autopsy as the diagnostic standard., Interpretation: The Boston criteria v2.0 incorporate emerging MRI markers of CAA to enhance sensitivity without compromising their specificity in our cohorts of patients aged 50 years and older presenting with spontaneous intracerebral haemorrhage, cognitive impairment, or transient focal neurological episodes. Future studies will be needed to determine generalisability of the v.2.0 criteria across the full range of patients and clinical presentations., Funding: US National Institutes of Health (R01 AG26484)., Competing Interests: Declaration of interests AC reports receiving funding from the Bodossaki Foundation and the Frechette Family Foundation and consulting fees from Imperative Care. MPF reports receiving funding from Biogen and Voyager Therapeutics. Gba reports receiving funding from the Rosetrees Trust, Alzheimer's Research UK, NIHR, and the Stroke Association. CC reports receiving funding from the French Ministry of Health and honoraria from Amgen, and participating in data safety monitoring, advisory, or steering committees for the University of Glasgow, University of Caen, Op2Lysis, AstraZeneca, Bristol Myers Squibb, and Biogen. MD reports receiving funding from Deutsche Forschungsgemeinschaft under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology and the Vascular Dementia Research Foundation. JH reports receiving funding from the German Research Foundation and German Center for Neurodegenerative Diseases and tissue from Neurobiobank Munich. JL reports serving on a serving on an advisory board for Biogen and Mediaire. LP reports receiving honoraria from Daiichi Sankyo Ireland. FP reports receiving funding from the Alzheimer's Association (AARG-18-561699), participation on an Advisory Board for Roche, and leadership of the CAA Study Group of the Italia Society of Neurology-Dementia and the iCAB International Network. SR reports receiving funding from the German Research Foundation and brain tissue from Neurobiobank Munich. MAR reports receiving funding from the Wellcome Trust. JAS reports receiving funding from the US National Institutes of Health, consulting fees from Alnylam Pharmaceuticals, Apellis Pharmaceuticals, and Avid Radiopharmaceuticals, honoraria from Weil Cornell University, payment for expert testimony from the National Hockey League, support for travel from the US National Institutes for Health, serving on safety monitoring or advisory boards for the Framingham Heart Study, DISCOVERY, University of Kansas, Boston University, and University of California Irvine, and serving in leadership positions for the Alzheimer's Association and Foundation Alzheimer France. CSm reports receiving funding from the Medical Research Council UK. LS reports receiving funding from the Hungarian Academy of Sciences and Ministry for Innovation and Technology of Hungary from the source of the National Research. JMW reports receiving funding from the UK Dementia Research Institute funded by the UK Medical Research Council, Alzheimer's Society, and Alzheimer's Research UK, and a leadership role for the European Stroke Organization SVD Guidelines. FAW reports receiving honoraria from Alexion Pharm. MEG reports receiving funding from Avid Radiopharmaceuticals, Pfizer, and Boston Scientific. AV reports receiving funding from the US National Institutes of Health and consulting fees from Alnylam Pharmaceuticals and Biogen Pharmaceuticals. RA-SS reports receiving funding from the UK Medical Research Council and the Stroke Association. EES reports receiving funding from the Canadian Institutes of Health Research, Brain Canada, and Biogen, and consulting fees from Biogen and Eli Lily. DJW reports receiving consulting fees from Alnylam and Novo Nordisk, honoraria from Bayer and Alexion, participation on a safety monitoring board for the OXHARP study, and serving in leadership for the British Association of Stroke Physicians. SMG reports receiving funding from the US National Institutes of Health, royalties from Up-To-Date, consulting fees from Eli Lily, and serving on data safety monitoring committees for Washington University, Bayer, Biogen, and Roche. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Patients with anterior circulation ischemic strokes due to large vessel occlusion (AIS-LVO) and very severe neurological deficits (National Institutes of Health Stroke Scale (NIHSS) score > 25) were under-represented in clinical trials on endovascular treatment (EVT). We aimed to evaluate safety and outcomes of EVT in patients with very severe vs. severe (NIHSS score 15-25) neurological deficits., Methods: We included consecutive patients undergoing EVT for AIS-LVO between January 2015 and December 2019 at Lille University Hospital. We compared rates of parenchymal hemorrhage (PH), symptomatic intracranial hemorrhage (SICH), procedural complications, and 90-day mortality between patients with very severe vs. severe neurological deficit using univariable and multivariable logistic regression analyses. Functional outcome (90-days modified Rankin Scale) was compared between groups using ordinal logistic regression analysis., Results: Among 1484 patients treated with EVT, 108 (7%) had pre-treatment NIHSS scores > 25, 873 (59%) with NIHSS scores 15-25 and 503 (34%) with NIHSS scores < 15. Rates of PH, SICH, successful recanalization, and procedural complications were similar in patients with NIHSS scores > 25 and NIHSS 15-25. Patients with NIHSS > 25 had a lower likelihood of improved functional outcome ( adj common OR 0.31[95% CI 0.21-0.47]) and higher odds of mortality at 90 days ( adj OR 2.3 [95% CI 1.5-3.7]) compared to patients with NIHSS 15-25. Successful recanalization was associated with better functional outcome ( adj common OR 3.8 [95% CI 1.4-10.4]), and lower odds of mortality ( adj OR 0.3 [95% CI 0.1-0.9]) in patients with very severe stroke. The therapeutic effect of recanalization on functional outcome and mortality was similar in both groups., Conclusions: In patients with very severe neurological deficit, EVT was safe and successful recanalization was strongly associated with better functional outcome at 90 days., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: I ntracranial vertebral dissections have polymorphs clinical presentations and can lead to haemorrhagic complications if they are intracranial. We here describe a case of a thrombosed dissecting aneurysm of postero-inferior cerebellar artery (PICA) revealed by a Wallenberg syndrome preceded by headaches., Case: A 23-year-old patient, without neurological or vascular past medical history, was admitted for dizziness preceded by headache. The clinical examination on admission revealed an incomplete Wallenberg syndrome, associating hemiface sensitive deficit, Horner's syndrome, dysmetria and nystagmus. The brain MRI showed a latero-medullary infarct with a homolateral PICA thrombosed dissecting aneurysm., Conclusion: The diagnosis of intracranial dissecting aneurysms needs particular caution because aneurysm sac thrombosis can give false reassurance on angiographic MR sequences. Moreover, the anatomic features of intracranial artery walls make them prone to sub-adventitial dissection and subsequent subarachnoid haemorrhages. Therefore, antithrombotic therapy should be used with caution, due to the risk of bleeding in these intracranial dissections., (© 2022. Fondazione Società Italiana di Neurologia.)

Background: Distal medium vessel occlusions (DMVOs) are increasingly recognized as a next target for endovascular thrombectomy (EVT). Our objective was to investigate safety and clinical outcomes of EVT for DMVO of the middle cerebral artery (MCA)., Methods: We analyzed data of the Lille Reperfusion Registry from January 2017 to September 2020. Patients with a primary or secondary DMVO of the MCA seen on pretreatment angiogram were included. Only patients with a eTICI score 2b50-2b67 on initial angiogram were considered. Baseline characteristics, angiographic clinical, and safety outcomes were compared between patients treated with EVT or standard medical treatment (no-EVT)., Results: Of the 171 patients included, 96 received EVT (46.9% male, 68.7 ± 15.8 years) and 75 received standard medical treatment (44% male, 73.9 ± 13.1 years). EVT patients had a better improvement of the NIHSS score at discharge (adjusted mean difference: 3.71; 95% CI: 1.18-6.24). In the distal M2 occlusions subgroup, EVT was significantly associated with a higher rate of early neurologic improvement (adjusted OR: 3.62 95% CI: 1.31-10.03), NIHSS improvement at discharge (adjusted mean difference: 5.23; 95% CI: 2.18-8.29), and improved modified Rankin Scale score at 3 months (adjusted common OR for 1 point improvement: 3.06; 95% CI: 1.30 to 7.23). Symptomatic intracranial hemorrhage occurred in 3.1% in the EVT group and in 9.5% in the no-EVT group., Conclusions: EVT for DMVO of the MCA appears to be safe and may lead to improved clinical outcomes. This effect was especially pronounced in patients with distal M2 occlusions, warranting randomized trials to validate this result., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: Neuropsychiatric (NP) symptoms are prominent features of cognitive decline, but they have been understudied in patients with spontaneous intracerebral haemorrhage (ICH). In ICH survivors, we aimed at assessing NP symptoms prevalence and profiles, and their influence on long-term outcomes., Methods: We analysed data from consecutive 6-month ICH survivors enrolled in the Prognosis of Intracerebral Haemorrhage study. We performed NP evaluation using the Neuropsychiatric Inventory Questionnaire. Patients underwent long-term clinical follow-up after ICH (median follow-up time 7.2 years, IQR 4.8-8.2)., Results: Out of 560 patients with ICH, 265 survived at 6 months. NP evaluation 6 months after ICH was feasible in 202 patients. NP symptoms were present in 112 patients (55%), and in 36 out of 48 patients (75%) with post-ICH dementia. Affective symptoms were present in 77 patients (38%), followed by vegetative symptoms (52 patients, 26%) and hyperactivity (47 patients, 23%). Apathy and hyperactivity were associated with post-ICH dementia and cerebral amyloid angiopathy MRI profile (all p<0.05). Apathy and hyperactivity prevailing over affective symptoms at 6-month follow-up were associated with higher risks of developing new-onset dementia (HR 5.40; 95% CI 2.27 to 12.84), while presence or severity of NP symptoms were not., Conclusion: NP symptoms were present in more than half of 6-month ICH survivors, with higher prevalence and severity in patients with post-ICH dementia. Distinctive NP profile might be associated to cognitive status and inform on long-term dementia risk., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Thrombosis with thrombocytopenia syndrome (TTS) has been reported after vaccination with the SARS-CoV-2 vaccines ChAdOx1 nCov-19 (Oxford-AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson)., Objective: To describe the clinical characteristics and outcome of patients with cerebral venous sinus thrombosis (CVST) after SARS-CoV-2 vaccination with and without TTS., Design, Setting, and Participants: This cohort study used data from an international registry of consecutive patients with CVST within 28 days of SARS-CoV-2 vaccination included between March 29 and June 18, 2021, from 81 hospitals in 19 countries. For reference, data from patients with CVST between 2015 and 2018 were derived from an existing international registry. Clinical characteristics and mortality rate were described for adults with (1) CVST in the setting of SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia, (2) CVST after SARS-CoV-2 vaccination not fulling criteria for TTS, and (3) CVST unrelated to SARS-CoV-2 vaccination., Exposures: Patients were classified as having TTS if they had new-onset thrombocytopenia without recent exposure to heparin, in accordance with the Brighton Collaboration interim criteria., Main Outcomes and Measures: Clinical characteristics and mortality rate., Results: Of 116 patients with postvaccination CVST, 78 (67.2%) had TTS, of whom 76 had been vaccinated with ChAdOx1 nCov-19; 38 (32.8%) had no indication of TTS. The control group included 207 patients with CVST before the COVID-19 pandemic. A total of 63 of 78 (81%), 30 of 38 (79%), and 145 of 207 (70.0%) patients, respectively, were female, and the mean (SD) age was 45 (14), 55 (20), and 42 (16) years, respectively. Concomitant thromboembolism occurred in 25 of 70 patients (36%) in the TTS group, 2 of 35 (6%) in the no TTS group, and 10 of 206 (4.9%) in the control group, and in-hospital mortality rates were 47% (36 of 76; 95% CI, 37-58), 5% (2 of 37; 95% CI, 1-18), and 3.9% (8 of 207; 95% CI, 2.0-7.4), respectively. The mortality rate was 61% (14 of 23) among patients in the TTS group diagnosed before the condition garnered attention in the scientific community and 42% (22 of 53) among patients diagnosed later., Conclusions and Relevance: In this cohort study of patients with CVST, a distinct clinical profile and high mortality rate was observed in patients meeting criteria for TTS after SARS-CoV-2 vaccination.

Background and Purpose: Decompressive hemicraniectomy (DH) reduces mortality of large middle cerebral artery (MCA) territory infarcts. Survivors are at high risk of poststroke seizures (PSSs). This study aims to describe the incidence of PSSs, to identify associated factors, and to assess their impact on long-term outcomes., Methods: We included consecutive patients who underwent DH for large MCA infarcts from May 2005 to December 2019 at Lille University Hospital. Patients were followed up at 3 months, 1 year, and 3 years. We analysed (i) the incidence and associated factors of early onset PSSs (EPSSs) with logistic regression models; (ii) the incidence and associated factors of late onset PSSs (LPSSs) in survivors at 7 days with a univariate Cox proportional hazard regression model for interval-censored data; and (iii) the impact of PSSs (EPSSs and LPSSs) on mortality with univariate and multivariate Cox proportional hazard regression models and modified Rankin Scale at 1 and 3 years, with univariate and adjusted multivariate ordinal logistic regression analyses., Results: Of 248 patients (150 men, 60.5%; mean age = 50.4 ± 9.6 years), 106 (42.7%) presented PSSs (six inaugural seizures, 22 EPSSs, 78 LPSSs) during follow-up. The PSS cumulative incidence was 12.3% at 7 days, 24.9% at 3 months, 49.8% at 1 years, and 54.8% at 3 years. No predictor was significantly associated with either EPSSs or LPSSs. PSSs did not significantly impact mortality and long-term functional outcome., Conclusions: The incidence of PSSs after DH is high, reaching more than 50% 3 years after stroke, but PSSs did not influence long-term mortality or functional outcome., (© 2021 European Academy of Neurology.)

Introduction: Intracerebral haemorrhage (ICH) in young adults is rare but has devastating consequences. We investigated long-term mortality rates, causes of death and predictors of long-term mortality in young spontaneous ICH survivors., Patients and Methods: We included consecutive patients aged 18-55 years from the Prognosis of Intracerebral Haemorrhage cohort (PITCH), a prospective observational cohort of patients admitted to Lille University Hospital (2004-2009), who survived at least 30 days after spontaneous ICH. We studied long-term mortality with Kaplan-Meier analyses, collected causes of death, performed uni-/multivariable Cox-regression analyses for the association of baseline characteristics with long-term mortality., Results: Of 560 patients enrolled in the PITCH, 75 patients (75% men) met our inclusion criteria (median age 50 years, interquartile range [IQR] 44-53 years). During a median follow-up of 8.2 years (IQR 5.0-10.1), 26 patients died (35%), with a standardized mortality ratio of 13.0 (95% confidence interval [95% CI] 8.5-18.0) compared to peers from the general population. Causes of death were vascular in 7 (27%) patients, non-vascular in 13 (50%) and unknown in 6 (23%). Global cerebral atrophy (hazard ratio [HR] 3.0, 95% CI 1.1-8.6), modified Rankin Score >2 before ICH (HR 3.4, 95% CI 1.0-11.0), and excessive alcohol consumption (HR 3.3, 95% CI 1.1-10.2) were independently associated with long-term mortality., Discussion: We found a 13-fold higher mortality risk for young ICH survivors compared to the general French population. Predictors of long-term mortality were pre-existing conditions, not ICH-characteristics., Conclusion: Young ICH survivors remain at increased mortality risk of vascular and non-vascular death for years after ICH., Competing Interests: Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: FEL serves as associate editor for the International Journal of Stroke. CJMK serves as vice editor for the European Stroke Journal. DL reports participation in symposia organized by Boehringer Ingelheim, Bayer, BMS, and Pfizer (honoraria paid to Adrinord); he was (until December 31, 2019) vice-editor of the European Stroke Journal (honoraria paid by the European Stroke Organisation to Adrinord); he is (since January 1, 2020) editor in chief of the European Journal of Neurology (honoraria paid by John Wiley and Sons to Adrinord), vice president of the scientific committee of the Fondation de Recherche sur les AVC (unpaid); is member of the scientific committee of the Servier Institute (unpaid); and was member of DSMBs for institutional trials (unpaid) (INCH, Germany; TARDIS, United Kingdom; and TO-ACT, the Netherlands). CC served for trial steering committee for Biogen, other for Boehringer Ingelheim and Pfizer, and serves as Associate Editor of the Stroke journal. The other authors report no relevant disclosures or conflicts of interest., (© European Stroke Organisation 2021.)

Background: Factors associated with long-term mortality after spontaneous intracerebral hemorrhage (ICH) have been poorly investigated., Aim: Our objective was to identify variables associated with long-term mortality in a prospective cohort of 30-day ICH survivors., Methods: We prospectively included consecutive 30-day spontaneous ICH survivors. We evaluated baseline and follow-up clinical characteristics and magnetic resonance imaging (MRI) markers of chronic brain injury as variables associated with long-term mortality using univariate and multivariable Cox proportional hazard regression models., Results: Of 560 patients with spontaneous ICH, 304 (54.2%) survived more than 30 days and consented for follow-up. During a median follow-up of 10 years (interquartile range: 8.0-10.5), 176 patients died. The cumulative survival rate at 10 years was 38%. In multivariable analysis, variables independently associated with long-term mortality were age (hazard ratio (HR) per 10-year increase: 1.68, 95% confidence interval (CI): 1.45-1.95), male gender (HR: 1.41, CI: 1.02-1.95), prestroke dependency (HR: 1.66, CI: 1.15-2.39), National Institutes of Health Stroke Scale score (HR per 1-point increase: 1.03, CI: 1.01-1.04), occurrence of any stroke (HR: 2.24, CI: 1.39-3.60), and dementia (HR: 1.51, CI: 1.06-2.16) during follow-up. Among MRI markers, only cerebral atrophy (HR per 1-point increase: 1.50, CI: 1.13-2.00) was independently associated with long-term mortality., Conclusions: Preexisting comorbidities, clinical severity at presentation, and significant clinical event during follow-up are associated with long-term mortality. Among MRI markers of chronic brain injury, only cerebral atrophy is associated with long-term mortality.

Immune dysregulation is a hallmark of patients infected by SARS-CoV2 and the balance between immune reactivity and tolerance is a key determinant of all stages of infection, including the excessive inflammatory state causing the acute respiratory distress syndrome. The kynurenine pathway (KP) of tryptophan (Trp) metabolism is activated by pro-inflammatory cytokines and drives mechanisms of immune tolerance. We examined the state of activation of the KP by measuring the Kyn:Trp ratio in the serum of healthy subjects (n = 239), and SARS-CoV2-negative (n = 305) and -positive patients (n = 89). Patients were recruited at the Emergency Room of St. Andrea Hospital (Rome, Italy). Kyn and Trp serum levels were assessed by HPLC/MS-MS. Compared to healthy controls, both SARS-CoV2-negative and -positive patients showed an increase in the Kyn:Trp ratio. The increase was larger in SARS-CoV2-positive patients, with a significant difference between SARS-CoV2-positive and -negative patients. In addition, the increase was more prominent in males, and positively correlated with age and severity of SARS-CoV2 infection, categorized as follows: 1 = no need for intensive care unit (ICU); 2 ≤ 3 weeks spent in ICU; 3 ≥ 3 weeks spent in ICU; and 4 = death. The highest Kyn:Trp values were found in SARS-CoV2-positive patients with severe lymphopenia. These findings suggest that the Kyn:Trp ratio reflects the level of inflammation associated with SARS-CoV2 infection, and, therefore, might represent a valuable biomarker for therapeutic intervention., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To identify in patients who survived 6 months after a spontaneous intracerebral haemorrhage (ICH) baseline characteristics and new clinical events associated with functional decline., Methods: In a single-centre study, we prospectively included 6-month survivors with a modified Rankin Scale (mRS) score 0-3. We defined functional decline by a transition to mRS 4-5. We evaluated associations of baseline characteristics and new clinical events with functional decline, using univariate and multivariable models., Results: Of 560 patients, 174 (31%) had an mRS score 0-3 at 6 months. During a median follow-up of 9 years (IQR 8.1-9.5), 40 (23%) converted to mRS 4-5. Age, diabetes mellitus, ICH volume and higher mRS scores at 6 months were independently associated with functional decline. Among baseline MRI markers, presence of strictly lobar cerebral microbleeds (CMBs), and mixed lobar and deep CMBs were independently associated with functional decline. When new clinical events occurring during follow-up were added in multivariable models, age (cause-specific HR (CSHR): 1.07; 95% CI: 1.03 to 1.11), ICH volume (CSHR: 1.03; 95% CI: 1.01 to 1.06), mRS score at 6 months (CSHR per 1 point increase 1.61, 95% CI 1.07 to 2.43), occurrence of dementia (CSHR: 3.81, 95% CI: 1.78 to 8.16) and occurrence of any stroke (CSHR: 4.29, 95% CI: 1.80 to 10.22) remained independently associated with transition to mRS 4-5., Interpretation: Almost one-fourth of patients with spontaneous ICH developed a functional decline over time. Age, ICH volume, higher mRS score at 6 months and new clinical events after ICH are the major determinants., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)