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Background: Endovascular thrombectomy (EVT) has been proven effective in anterior circulation stroke due to large vessel occlusion (LVO). However, translation from randomized clinical trials (RCTs) with highly selected patients to real-world requires confirmation, particularly to identify associations outside of strict selection criteria., Aims: This study aims to compare functional outcomes after EVT in real-world with those reported in RCTs, and to identify associations with functional outcome after EVT outside RCT-criteria., Methods: This study analyzed longitudinal German real-world data from the Stroke Research Consortium in Northern Bavaria (STAMINA) cohort from January, 2015 to June, 2019. We conducted a trial emulation, comparing patients with anterior circulation stroke and LVO meeting selection criteria for RCTs investigating EVT (1) predominantly within 6 hours with those from HERMES meta-analysis, and (2) within 6-24 hours with those from AURORA meta-analysis. We (3) analyzed treatment effects of EVT and association with functional outcome in patients treated outside RCT criteria., Results: Of 598 patients, 281 (47.0%) met RCT-criteria for treatment within 6 hours (hereinafter STAMINA-HERMES), 74 (12.4%) met RCT-criteria for treatment within 6-24 hours (STAMINA-AURORA), and 277 (46.3%) patients received EVT outside RCT-criteria. We observed no difference in rates of functional independence or mortality, comparing STAMINA-HERMES with HERMES meta-analysis (mRS 0-1: n=120/281 [43%] vs. 291/633 [46%], p=0.36; mortality: n=34/281 [12%] vs. 97/633 [15%], p=0.20), and STAMINA-AURORA with AURORA meta-analysis (mRS 0-1: n=26/74 [35%] vs. 122/266 [46%], p=0.10, mortality: n=10/74 [14%] vs. 45/266 [17%], p=0.48). Patients treated outside RCT-criteria had worse outcome (mRS 0-1: n=38/277 [14%], mortality: n=90/277 [32%], both p<0.001); possibly driven by pre-existing functional dependence (n=172/277 [62%]). Compared to matched controls, EVT outside of RCT-criteria was associated with lower mortality (absolute treatment effect: -14%, 95% Confidence Interval [CI] -23 to -5, p<0.01), but not with recovery to functional independence or premorbid functional status (treatment effect: 4%, CI -4 to 11, p=0.34), which was associated with lower NIHSS (Odds ratio [OR] 0.86, CI 0.80-0.92, p<0.001) and age (OR 0.95, CI 0.93-0.98, p=0.002)., Conclusions: Translation of EVT outcomes reported in RCTs into real-world is possible, however, almost half of patients did not meet trial criteria. Identification of patients who functionally benefit from frequently performed EVT outside RCT-criteria requires further investigation., Trial Registration: Clinicaltrials.gov, NCT04357899., (© 2024. The Author(s).)

Background: Acute ischemic stroke with isolated posterior cerebral artery occlusion (iPCAO) lacks management evidence from randomized trials. We aimed to evaluate whether the association between endovascular treatment (EVT) and outcomes in iPCAO acute ischemic stroke is modified by initial stroke severity (baseline National Institutes of Health Stroke Scale [NIHSS]) and arterial occlusion site., Methods: Based on the multicenter, retrospective, case-control study of consecutive iPCAO acute ischemic stroke patients (PLATO study [Posterior Cerebral Artery Occlusion Stroke]), we assessed the heterogeneity of EVT outcomes compared with medical management (MM) for iPCAO, according to baseline NIHSS score (≤6 versus >6) and occlusion site (P1 versus P2), using multivariable regression modeling with interaction terms. The primary outcome was the favorable shift of 3-month modified Rankin Scale (mRS). Secondary outcomes included excellent outcome (mRS score 0-1), functional independence (mRS score 0-2), symptomatic intracranial hemorrhage, and mortality., Results: From 1344 patients assessed for eligibility, 1059 were included (median age, 74 years; 43.7% women; 41.3% had intravenous thrombolysis): 364 receiving EVT and 695 receiving MM. Baseline stroke severity did not modify the association of EVT with 3-month mRS distribution ( P interaction =0.312) but did with functional independence ( P interaction =0.010), with a similar trend on excellent outcome ( P interaction =0.069). EVT was associated with more favorable outcomes than MM in patients with baseline NIHSS score >6 (mRS score 0-1, 30.6% versus 17.7%; adjusted odds ratio [aOR], 2.01 [95% CI, 1.22-3.31]; mRS score 0 to 2, 46.1% versus 31.9%; aOR, 1.64 [95% CI, 1.08-2.51]) but not in those with NIHSS score ≤6 (mRS score 0-1, 43.8% versus 46.3%; aOR, 0.90 [95% CI, 0.49-1.64]; mRS score 0-2, 65.3% versus 74.3%; aOR, 0.55 [95% CI, 0.30-1.0]). EVT was associated with more symptomatic intracranial hemorrhage regardless of baseline NIHSS score ( P interaction =0.467), while the mortality increase was more pronounced in patients with NIHSS score ≤6 ( P interaction =0.044; NIHSS score ≤6: aOR, 7.95 [95% CI, 3.11-20.28]; NIHSS score >6: aOR, 1.98 [95% CI, 1.08-3.65]). Arterial occlusion site did not modify the association of EVT with outcomes compared with MM., Conclusions: Baseline clinical stroke severity, rather than the occlusion site, may be an important modifier of the association between EVT and outcomes in iPCAO. Only severely affected patients with iPCAO (NIHSS score >6) had more favorable disability outcomes with EVT than MM, despite increased mortality and symptomatic intracranial hemorrhage., Competing Interests: Disclosures Dr Dabus: consultancy for Cerenovus, Penumbra, Route 92, Medtronic, MicroVention, and Stryker; stock holdings in RIST and InNeuroCo. Dr Fifi: consultancy for Cerenovus, MicroVention, and Stryker; Data Safety Monitoring Board (DSMB) for MIVI; stock holdings in Imperative Care and Sim&Cure. Dr Fischer: research support from the Swiss National Science Foundation (SNF), Medtronic, Stryker, Rapid Medical, Penumbra, and Phenox; consultancies for Stryker and CSL Behring; is on the advisory board for Alexion/Portola, Boehringer Ingelheim, Biogen, and Acthera. Dr Haussen: consultancy for Vesalio, Cerenovus, Stryker, Brainomix, Poseydon Medical, and Chiesi USA; DSMB for Jacobs Institute; stock options in viz AI. Dr Herweh: consultancy for Brainomix; speaker with Stryker. Dr Jadhav: consulting with Basking Biosciences; stock options in Gravity Medical Technology; a patent for a novel stent retriever device licensed to Basking Biosciences; and Editor-in-Chief for the Stroke: Vascular and Interventional Neurology journal. Dr Kaesmacher: grants from the Swiss Academy of Medical Sciences/Bangerter Foundation, Swiss Stroke Society, and Clinical Trials Unit Bern. Dr Kaiser: grants from the Joachim Herz Foundation. Dr Kuramatsu: grants from Alexion Pharmaceuticals, Bayer Healthcare, Sanofi Pasteur, and Biogen Idec. Dr Marto: consulting and speaker fees from Amicus Therapeutics and Boehringer Ingelheim. Dr Michel: grants from the University of Lausanne and SNF. Dr Möhlenbruch: grants from Medtronic, Stryker, and MicroVention. Dr Mokin: stock holdings in BrainQ, Serenity Medical, Synchron, and Bendit Technology; consulting at MicroVention, Medtronic, and Johnson & Johnson. Dr Nagel: consultancy for Brainomix; speaker at Boehringer Ingelheim and Pfizer. Dr Nguyen: Associate Editor of Stroke, advisory board at Aruna Bio and Brainomix. Dr Nogueira: consultancy for Biogen, Brainomix, Corindus, Cerenovus, Stryker, Medtronic, Ceretrieve, Anaconda Biomed, Vesalio, Imperative Care, NeuroVasc Technologies, viz AI, Genentech, Prolong Pharmaceuticals, Perfuze, Phenox, and RapidPulse; stock options in viz AI, Vesalio, Perfuze, Corindus, Brainomix, and Ceretrieve; grants from Cerenovus and Stryker. Dr Nolte: research support and compensation from Novartis, AstraZeneca, Deutsches Zentrum für Herz-Kreislaufforschung, and Deutsches Zentrum für Neurodegenerative Erkrankungen; consultancy for Alexion, Daiichi Sankyo, Novartis, AstraZeneca, Bayer Healthcare, Pfizer, Alexion, and Bristol Myers Squibb. S. Poli: research grants from BMS/Pfizer, Boehringer Ingelheim, Daiichi Sankyo, German Federal Joint Committee Innovation Fund, and German Federal Ministry of Education and Research, Helena Laboratories and Werfen as well as speakers’ honoraria/consulting fees from Alexion, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb/Pfizer, Daiichi Sankyo, Portola, and Werfen (all outside of the submitted work). Dr Psychogios: grants from Penumbra, Rapid Medical, Medtronic, Phenox, Bangerter-Rhyner Stiftung, SNF, Siemens Healthineers, and Stryker Neurovascular; travel support from Medtronic, Siemens Healthineers, Phenox, Penumbra, and Stryker; consultancy for Siemens Healthineers. Dr Puetz: lecturer for Daiichi Sankyo. Dr Ribo: consultancy for Medtronic MiniMed, Cerenovus, AptaTargets, Stryker, and Philips; stock holdings in Methinks, Nora, and Anaconda Biomed. Dr Ringleb: travel support from Bayer and Bristol Myers Squibb; consultancy for Daiichi Sankyo Company and Boehringer Ingelheim. Dr Romoli: research grants from the Italian Stroke Association; consultancy for CSL Behring. Dr Sheth: consultancy for Imperative Care, viz AI, and Penumbra; compensation from Motif Neurosciences (other services); grants from the National Institutes of Health. Dr Siddiqui: ownership stake in Integra Lifesciences and Medtronic; consultancy for Cordis, Rapid Medical, MicroVention, Medtronic Vascular, Vassol, IRRAS USA, Boston Scientific, Amnis Therapeutics, Minnetronix Neuro, Canon Medical Systems USA, Cardinal Health 200, Johnson & Johnson–Latin America, Corindus, Penumbra, Apellis Pharmaceuticals, W.L. Gore & Associates, Stryker Corporation, and viz AI; stock holdings in E8, Spinnaker Medical, Endostream Medical, Cerebrotech Medical Systems, Adona Medical, Bend IT Technologies, Whisper Medical, Neurotechnology Investors, Collavidence, Instylla, Q’Appel Medical, Serenity Medical, Borvo Medical, NeuroRadial Technologies, Sense Diagnostics, Tulavi Therapeutics, Synchron, Neurolutions, Viseon, BlinkTBI, Radical Catheter Technologies, and Truvic Medical; stock options in viz AI, StimMed, Three Rivers Medical, Silk Road Medical, Imperative Care, CVAid Ltd, Cerevatech Medical, InspireMD, PerFlow Medical; security holdings in Vastrax, Launch NY, QAS.ai, VICIS, Inc, Neurovascular Diagnostics, Cognition Medical, and SongBird Therapy. Dr Strbian: Assistant Editor of Stroke, Editorial Board of European Stroke Journal, advisory board at Boehringer Ingelheim, Alexion/AstraZeneca, and Bristol Myers Squibb/Janssen; research support from Boehringer Ingelheim; consultancies for Orion, Herantis Pharma, and CSL Behring. The other authors report no conflicts.

Background and Purpose: Posterior cerebral artery occlusion (PCAo) can cause long-term disability, yet randomized controlled trials to guide optimal reperfusion strategy are lacking. We compared the outcomes of PCAo patients treated with endovascular thrombectomy (EVT) with or without intravenous thrombolysis (IVT) to patients treated with IVT alone., Methods: From the multicenter retrospective Posterior cerebraL ArTery Occlusion (PLATO) registry, we included patients with isolated PCAo treated with reperfusion therapy within 24 hours of onset between January 2015 and August 2022. The primary outcome was the distribution of the modified Rankin Scale (mRS) at 3 months. Other outcomes comprised 3-month excellent (mRS 0-1) and independent outcome (mRS 0-2), early neurological improvement (ENI), mortality, and symptomatic intracranial hemorrhage (sICH). The treatments were compared using inverse probability weighted regression adjustment., Results: Among 724 patients, 400 received EVT+/-IVT and 324 IVT alone (median age 74 years, 57.7% men). The median National Institutes of Health Stroke Scale score on admission was 7, and the occluded segment was P1 (43.9%), P2 (48.3%), P3-P4 (6.1%), bilateral (1.0%), or fetal posterior cerebral artery (0.7%). Compared to IVT alone, EVT+/-IVT was not associated with improved functional outcome (adjusted common odds ratio [OR] 1.07, 95% confidence interval [CI] 0.79-1.43). EVT increased the odds for ENI (adjusted OR [aOR] 1.49, 95% CI 1.05-2.12), sICH (aOR 2.87, 95% CI 1.23-6.72), and mortality (aOR 1.77, 95% CI 1.07-2.95)., Conclusion: Despite higher odds for early improvement, EVT+/-IVT did not affect functional outcome compared to IVT alone after PCAo. This may be driven by the increased risk of sICH and mortality after EVT.

Objective: Hematoma expansion (HE) is the most important therapeutic target during acute care of patients with intracerebral hemorrhage (ICH). Imaging biomarkers such as non-contrast CT (NCCT) markers have been associated with increasing risk for HE. The aim of the present study was to evaluate the influence of NCCT markers with functional long-term outcome and with HE in patients with deep (basal ganglia and thalamus) ICH who represent an important subgroup of patients at the highest risk for functional deterioration with HE due to the eloquence of the affected brain region., Methods: From our prospective institutional database, all patients maximally treated with deep ICH were included and retrospectively analyzed. NCCT markers were recorded at diagnostic imaging, ICH volume characteristics were volumetrically evaluated, and all patients received follow-up imaging within 0-48 h. We explored associations of NCCT makers with unfavorable functional outcome, defined as modified Rankin scale 4-6, after 12 months and with HE. Bias and confounding were addressed by multivariable regression modeling., Results: In 322 patients with deep ICH, NCCT markers were distributed as follows: irregular shape: 69.6%, heterogenous density: 55.9%, hypodensities: 52.5%, island sign: 19.3%, black hole sign: 11.5%, and blend sign: 4.7%. Upon multivariable regression analyses, independent associations were documented with the functional outcome for irregular shape (aOR: 2.73, 95%CI: 1.42-5.22, p  = 0.002), heterogenous density (aOR: 2.62, 95%CI: 1.40-4.90, p  = 0.003) and island sign (aOR: 2.54, 95%CI: 1.05-6.14, p  = 0.038), and with HE for heterogenous density (aOR: 5.01, 95%CI: 1.93-13.05, p  = 0.001) and hypodensities (aOR: 3.75, 95%CI: 1.63-8.62, p  = 0.002)., Conclusion: NCCT markers are frequent in deep ICH patients and provide important clinical implications. Specifically, markers defined by diverging intra-hematomal densities provided associations with a 5-times higher risk for HE and a 2.5-times higher likelihood for unfavorable functional long-term outcome. Hence, these markers allow the identification of patients with deep ICH at high risk for clinical deterioration due to HE., 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. JK declared that he was an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Kölbl, Hock, Xu, Sembill, Mrochen, Balk, Lang, Volbers, Engelhorn, Kallmünzer and Kuramatsu.)

Background: The avoidance of hematoma expansion is the most important therapeutic goal during acute care of patients with intracerebral hemorrhage. Hematoma expansion occurs in up to 20-40% of patients and leads to poorer patient outcome in one of the most severe sub-types of stroke., Main Text: At current, randomized controlled trials have failed to provide evidence for interventions that effectively improve functional outcome in patients with intracerebral hemorrhage. Hence, hematoma expansion may serve as important surrogate target that appears causally linked with a poorer prognosis. Therefore, reduction of hematoma expansion rates will eventually translate to improved patient outcome overall. Recent years have shed light on the importance of early and aggressive treatment in order to reduce the risk for hematoma expansion in these patients. Time measures and imaging markers have been identified that may allow patient selection at very high risk for hematoma expansion., Conclusions: Refinements in patient selection may increase chance for randomized trials to show true benefit. Therefore, this current review article will critically evaluate and discuss available evidence associated with hematoma expansion in patients with intracerebral hemorrhage., (© 2023. The Author(s).)

Background: The optimal management of patients with isolated posterior cerebral artery occlusion is uncertain. We compared clinical outcomes for endovascular therapy (EVT) versus medical management (MM) in patients with isolated posterior cerebral artery occlusion., Methods: This multinational case-control study conducted at 27 sites in Europe and North America included consecutive patients with isolated posterior cerebral artery occlusion presenting within 24 hours of time last well from January 2015 to August 2022. Patients treated with EVT or MM were compared with multivariable logistic regression and inverse probability of treatment weighting. The coprimary outcomes were the 90-day modified Rankin Scale ordinal shift and ≥2-point decrease in the National Institutes of Health Stroke Scale., Results: Of 1023 patients, 589 (57.6%) were male with median (interquartile range) age of 74 (64-82) years. The median (interquartile range) National Institutes of Health Stroke Scale was 6 (3-10). The occlusion segments were P1 (41.2%), P2 (49.2%), and P3 (7.1%). Overall, intravenous thrombolysis was administered in 43% and EVT in 37%. There was no difference between the EVT and MM groups in the 90-day modified Rankin Scale shift (aOR, 1.13 [95% CI, 0.85-1.50]; P =0.41). There were higher odds of a decrease in the National Institutes of Health Stroke Scale by ≥2 points with EVT (aOR, 1.84 [95% CI, 1.35-2.52]; P =0.0001). Compared with MM, EVT was associated with a higher likelihood of excellent outcome (aOR, 1.50 [95% CI, 1.07-2.09]; P =0.018), complete vision recovery, and similar rates of functional independence (modified Rankin Scale score, 0-2), despite a higher rate of SICH and mortality (symptomatic intracranial hemorrhage, 6.2% versus 1.7%; P =0.0001; mortality, 10.1% versus 5.0%; P =0.002)., Conclusions: In patients with isolated posterior cerebral artery occlusion, EVT was associated with similar odds of disability by ordinal modified Rankin Scale, higher odds of early National Institutes of Health stroke scale improvement, and complete vision recovery compared with MM. There was a higher likelihood of excellent outcome in the EVT group despite a higher rate of symptomatic intracranial hemorrhage and mortality. Continued enrollment into ongoing distal vessel occlusion randomized trials is warranted., Competing Interests: Disclosures Dr Asdaghi reported employment by the American Heart Association. Dr Dabus reported consultancy for Cerenovus, Penumbra, Route 92, Medtronic, MicroVention, and Stryker and stock holdings in RIST and InNeuroCo. Dr Fifi reported consultancy for Cerenovus, MicroVention, and Stryker; Data Safety Monitoring Board (DSMB) for MIVI; and stock holdings in Imperative Care and Sim&Cure. Dr Fischer reported research support from the Swiss National Science Foundation (SNF), Medtronic, Stryker, Rapid Medical, Penumbra, and Phenox; consultancies for Stryker and CSL Behring; and is on the advisory board for Alexion/Portola, Boehringer Ingelheim, Biogen, and Acthera. Dr Finitsis reports patent US11166738B2. Dr Haussen reported consultancy for Vesalio, Cerenovus, Stryker, Brainomix, Poseydon Medical, and Chiesi USA; DSMB from Jacobs Institute; and stock options in Viz AI. Dr Herweh reported consultancy for Brainomix and Speaker with Stryker. Dr Jadhav reports consulting with Basking Biosciences; stock options in Gravity Medical Technology; and a patent for a novel stent retriever device licensed to Basking Biosciences. Dr Kaesmacher reported grants from the Swiss Academy of Medical Sciences/Bangerter Foundation, Swiss Stroke Society, and Clinical Trials Unit Bern. Dr Kaiser reported grants from the Joachim Herz Foundation. Dr Kuramatsu reports grants from Alexion Pharmaceuticals, Bayer Healthcare, Sanofi Pasteur, and Biogen Idec. Dr Pedro Marto reported consulting from Amicus Therapeutics and Boehringer Ingelheim and Speaker with Boehringer Ingelheim. Dr Michel reported grants from the University of Lausanne and Swiss National Science Foundation (SNF). Dr Möhlenbruch reported grants from Medtronic, Stryker, and MicroVention. Dr Mokin reported stock holdings in BrainQ, Serenity Medical, Synchron, and Bendit Technology and consulting from MicroVention, Medtronic, and Johnson & Johnson. Dr Nagel reported consultancy for Brainomix and is a speaker with Boehringer Ingelheim and Pfizer. Dr Nguyen reported research support from Society of Vascular and Interventional Neurology (SVIN) and Medtronic and is on the advisory board with Idorsia. Dr Nogueira reported consultancy for Biogen, Brainomix, Corindus, Cerenovus, Stryker, Medtronic, Ceretrieve, Anaconda Biomed, Vesalio, Imperative Care, NeuroVasc Technologies, Viz AI, Genentech, Prolong Pharmaceuticals, Perfuze, Phenox, and RapidPulse; stock options in Viz AI, Vesalio, Perfuze, Corindus, Brainomix, and Ceretrieve; and grants from Cerenovus and Stryker. Dr Nolte reported compensation (other services) from Novartis, AstraZeneca, Deutsches Zentrum für Herz-Kreislaufforschung, and Deutsches Zentrum für Neurodegenerative Erkrankungen and consultancy for Daiichi Sankyo, Bayer Healthcare, Pfizer, Alexion, and Bristol Myers Squibb. Dr Psychogios reported grants from Penumbra, Rapid Medical, Medtronic, Phenox, Bangerter-Rhyner Stiftung, SNF, Siemens Healthineers, and Stryker Neurovascular; travel support from Medtronic, Siemens Healthineers, Phenox, Penumbra, and Stryker; and consultancy for Siemens Healthineers. Dr Puetz reported being a lecturer for Daiichi Sankyo. Dr Ribo reported consultancy for Medtronic MiniMed, Cerenovus, AptaTargets, Stryker, and Philips and stock holdings in Methinks, Nora, and Anaconda Biomed. Dr Ringleb reported travel support from Bayer and Bristol Myers Squibb and consultancy for Daiichi Sankyo Company and Boehringer Ingelheim. Dr Sheth reported consultancy for Imperative Care, Viz AI, and Penumbra; compensation from Motif Neurosciences (other services); and grants from the National Institutes of Health. Dr Siddiqui reported an ownership stake in Integra Lifesciences and Medtronic; consultancy for Cordis, Rapid Medical, MicroVention, Medtronic Vascular, Vassol, IRRAS USA, Boston Scientific, Amnis Therapeutics, Minnetronix Neuro, Canon Medical Systems USA, Cardinal Health 200, Johnson & Johnson–Latin America, Corindus, Penumbra, Apellis Pharmaceuticals, W.L. Gore & Associates, Stryker Corporation, and Viz AI; stock holdings in E8, Spinnaker Medical, Endostream Medical, Cerebrotech Medical Systems, Adona Medical, Bend IT Technologies, Whisper Medical, Neurotechnology Investors, Collavidence, Instylla, Q’Appel Medical, Serenity Medical, Borvo Medical, NeuroRadial Technologies, Sense Diagnostics, Tulavi Therapeutics, Synchron, Neurolutions, Viseon, BlinkTBI, Radical Catheter Technologies, and Truvic Medical; stock options in Viz AI, StimMed, Three Rivers Medical, Silk Road Medical, Imperative Care, CVAID, Cerevatech Medical, InspireMD, and PerFlow Medical; and security holdings in Vastrax, Launch NY, QAS.ai, VICIS, Neurovascular Diagnostics, Cognition Medical, and SongBird Therapy. The other authors report no conflicts.

Integrating cerebrospinal fluid-biomarkers into diagnostic workup of patients with sporadic cerebral amyloid angiopathy may support early and correct identification. We aimed to identify and validate clinical- and cerebrospinal fluid-biomarkers for in vivo diagnosis of cerebral amyloid angiopathy. This observational cohort study screened 2795 consecutive patients admitted for cognitive complaints to the academic departments of neurology and psychiatry over a 10-year period (2009-2018). We included 372 patients with available hemosiderin-sensitive MR imaging and cerebrospinal fluid-based neurochemical dementia diagnostics, i.e. Aβ40, Aβ42, t -tau, p -tau. We investigated the association of clinical- and cerebrospinal fluid-biomarkers with the MRI-based diagnosis of cerebral amyloid angiopathy, applying confounder-adjusted modelling, receiver operating characteristic and unsupervised cluster analyses. We identified 67 patients with cerebral amyloid angiopathy, 76 patients with Alzheimer's disease, 75 patients with mild cognitive impairment due to Alzheimer's disease, 76 patients with mild cognitive impairment with unlikely Alzheimer's disease and 78 healthy controls. Patients with cerebral amyloid angiopathy showed a specific cerebrospinal fluid pattern: average concentration of Aß40 [13 792 pg/ml (10 081-18 063)] was decreased compared to all controls ( P < 0.05); Aß42 [634 pg/ml (492-834)] was comparable to Alzheimer's disease and mild cognitive impairment due to Alzheimer's disease ( P = 0.10, P = 0.93) but decreased compared to mild cognitive impairment and healthy controls (both P < 0.001); p -tau [67.3 pg/ml (42.9-91.9)] and t -tau [468 pg/ml (275-698)] were decreased compared to Alzheimer's disease ( P < 0.001, P = 0.001) and mild cognitive impairment due to Alzheimer's disease ( P = 0.001, P = 0.07), but elevated compared to mild cognitive impairment and healthy controls (both P < 0.001). Multivariate modelling validated independent clinical association of cerebral amyloid angiopathy with older age [odds-ratio: 1.06, 95% confidence interval (1.02-1.10), P < 0.01], prior lobar intracerebral haemorrhage [14.00 (2.64-74.19), P < 0.01], prior ischaemic stroke [3.36 (1.58-7.11), P < 0.01], transient focal neurologic episodes (TFNEs) [4.19 (1.06-16.64), P = 0.04] and gait disturbance [2.82 (1.11-7.15), P = 0.03]. For cerebrospinal fluid-biomarkers per 1 pg/ml, both lower Aß40 [0.9999 (0.9998-1.0000), P < 0.01] and lower Aß42 levels [0.9989 (0.9980-0.9998), P = 0.01] provided an independent association with cerebral amyloid angiopathy controlled for all aforementioned clinical confounders. Both amyloid biomarkers showed good discrimination for diagnosis of cerebral amyloid angiopathy among adjusted receiver operating characteristic analyses (area under the receiver operating characteristic curves, Aß40: 0.80 (0.73-0.86), P < 0.001; Aß42: 0.81 (0.75-0.88), P < 0.001). Unsupervised Euclidian clustering of all cerebrospinal fluid-biomarker-profiles resulted in distinct segregation of cerebral amyloid angiopathy patients from all controls. Together, we demonstrate that a distinctive set of cerebrospinal fluid-biomarkers effectively differentiate cerebral amyloid angiopathy patients from patients with Alzheimer's disease, mild cognitive impairment with or without underlying Alzheimer's disease, and healthy controls. Integrating our findings into a multiparametric approach may facilitate diagnosing cerebral amyloid angiopathy, and may aid clinical decision-making, but warrants future prospective validation., Competing Interests: M.I.S. reports grants from the Interdisciplinary Center for Clinical Research and Marohn Foundation. P.L. received consultation and/or lecture honoraria from IBL International, Fujirebio Europe, AJ Roboscreen, Biogen, and Roche. J.B.K. received speaker honoraria from Sanofi, Biogen, Bayer, Alexion, Boston Scientific, and BI. The other authors report no conflicts of interest related to the contents of the manuscript., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Stent-assisted coiling is well-established for treatment of cerebral aneurysms. The technique enables treatment of wide-neck, bifurcation and recurrent aneurysms with high packing rates. While described in extenso for laser cut stents, the results of patients treated with the Leo+ Baby (Balt, Montmorency, France) braided microstent are presented., Material and Methods: Patients were included if treated with a Leo+ Baby and with digital subtraction angiography (DSA) follow-up available of at least 6 months. Data were evaluated for successful deployment, aneurysm occlusion according to the modified Raymond-Roy classification (MRRC), stent patency and procedure-related morbidity and mortality., Results: A total of 81 patients were included and Leo+ Baby deployment was successful in all cases. Coils were used in 80 cases. In 1 case 2 stents were used stent-in-stent without additional coiling. Initial aneurysm occlusion rates were MRRC i 1 51.9%, MRRC i 2 11.1%, MRRC i 3a 24.7% and MRRC i 3b 12.3%. Occlusion rates after 6 months were MRRC 6m 1 78.9%, MRRC 6m 2 3.9%, MRRC 6m 3a 6.6% and MRRC 6m 3b 10.5%. Procedure-related morbidity was 1 case of acute stent thrombosis successfully treated with tirofiban and 1 case with transient hemiparesis due to stent thrombosis after 4 months. There was 1 case of coil-associated subarachnoid hemorrhage (SAH) which caused prolonged hospitalization. No procedure-related mortality was observed., Conclusion: The results confirm that stent-assisted coiling with the Leo+ Baby stent is safe and efficient for treatment of wide neck or recurrent cerebral aneurysms. Spontaneous progressive aneurysm occlusion over 6 months supports the theory of considerable flow-modulating effects of Leo+ Baby.

Background and Purpose: The impact of platelets on hematoma enlargement (HE) of intracerebral hemorrhage (ICH) is not yet sufficiently elucidated. Especially the role of reduced platelet counts on HE and clinical outcomes is still poorly understood. This study investigated the influence of thrombocytopenia on HE, functional outcome, and mortality in patients with ICH with or without prior antiplatelet therapy (APT)., Methods: Individual participant data of multicenter cohort studies (multicenter RETRACE program [German-Wide Multicenter Analysis of Oral Anticoagulation-Associated Intracerebral Hemorrhage] and single-center UKER-ICH registry [Universitätsklinikum Erlangen Cohort of Patients With Spontaneous ICH]) were grouped into APT and non-APT ICH patients according to the platelet count, that is, with or without thrombocytopenia (cells <150×10 9 /L). Of all patients, 51.5% (1124 of 2183) were on vitamin K antagonist. Imbalances in baseline characteristics including proportions of vitamin K antagonist patients were addressed using propensity score matching. Outcome analyses included HE (>33%), as well as mortality and functional outcome, after 3 months using the modified Rankin Scale, dichotomized into favorable (modified Rankin Scale score, 0-3) and unfavorable (modified Rankin Scale score, 4-6)., Results: Of overall 2252 ICH patients, 11.4% (52 of 458) under APT and 14.0% (242 of 1725) without APT presented with thrombocytopenia on admission. The proportion of patients with HE was not significantly different between patients with or without thrombocytopenia among APT and non-APT ICH patients after propensity score matching (HE: APT patients: 9 of 40 [22.5%] thrombocytopenia versus 27 of 115 [23.5%] nonthrombocytopenia, P =0.89; non-APT patients: 54 of 174 [31.0%] thrombocytopenia versus 106 of 356 [29.8%] nonthrombocytopenia, P =0.77). In both (APT and non-APT) propensity score matching cohorts, there were no significant differences regarding functional outcome. Mortality after 3 months did not differ among non-APT patients, whereas the mortality rate was significantly higher for APT patients with thrombocytopenia versus APT patients with normal platelet count (APT: 29 of 46 [63.0%] thrombocytopenia versus 58 of 140 [41.4%] nonthrombocytopenia, P =0.01; non-APT: 95 of 227 [41.9%] thrombocytopenia versus 178 of 455 [39.1%] nonthrombocytopenia, P =0.49)., Conclusions: Our study implies that thrombocytopenia does not affect rates of HE and functional outcome among ICH patients, neither in patients with nor without APT. In light of increased mortality, the significance of platelet transfusions for ICH patients with thrombocytopenia and previous APT should be explored in future studies.

Purpose: New antiepileptic drugs (AEDs) are increasingly applied in second-line therapy of status epilepticus (SE). In our study, we analyzed the impact of the choice of second-line AEDs on the course and prognosis of SE., Methods: This retrospective single- center study used data of an 8 year cohort of SE in adults from 2007 to 2014. Based on the year of market introduction with a cutoff at 1990, we classified AEDs as traditional or new. Prescription pattern associated differences in prognosis were measured through univariate and multivariable analysis of 3 endpoints: occurrence of refractory SE (RSE), functional outcome in survivors to discharge (good: mRS at discharge <3 or identical to admission mRS; otherwise poor), and in-hospital mortality., Results: From 362 SE episodes during the study period, 222 episodes were included into the study, among those 150 episodes treated with new and 72 with traditional AEDs. Use of new AEDs increased during the study period. After adjustment for confounders, treatment with new AEDs was on the one hand associated with higher rate of RSE occurrence (OR 1.95, 95 % CI 1.05-3.62, p = 0.03), but, on the other hand, also with better functional outcome at discharge (OR 2.64, 95 % CI 1.16-6.00, p = 0.02), while it was not an independent predictor of in- hospital mortality (OR 0.88, 95 % CI 0.33-2.33, p = 0.80)., Conclusion: Our observation that new AEDs may be associated with a higher rate of RSE development and relatively better functional outcome when adjusted for the premorbid mRS needs confirmation in prospective studies., (Copyright © 2019 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: Stroke-associated immunosuppression and inflammation are increasingly recognized as factors triggering infections and thus potentially influencing outcome after stroke. Several studies have demonstrated that elevated neutrophil-to-lymphocyte ratio (NLR) is a significant predictor of adverse outcomes for patients with ischemic stroke or intracerebral hemorrhage. Thus far, in patients with subarachnoid hemorrhage the association between NLR and outcome is insufficiently established. The authors sought to investigate the association between NLR on admission and functional outcome in aneurysmal subarachnoid hemorrhage (aSAH)., Methods: This observational study included all consecutive aSAH patients admitted to a German tertiary center over a 5-year period (2008-2012). Data regarding patient demographics and clinical, laboratory, and in-hospital measures, as well as neuroradiological data, were retrieved from institutional databases. Functional outcome was assessed at 3 and 12 months using the modified Rankin Scale (mRS) score and categorized into favorable (mRS score 0-2) and unfavorable (mRS score 3-6). Patients' radiological and laboratory characteristics were compared between aSAH patients with favorable and those with unfavorable outcome at 3 months. In addition, multivariate analysis was conducted to investigate parameters independently associated with favorable outcome. Receiver operating characteristic (ROC) curve analysis was undertaken to identify the best cutoff for NLR to discriminate between favorable and unfavorable outcome in these patients. To account for imbalances in baseline characteristics, propensity score matching was carried out to assess the influence of NLR on outcome measures., Results: Overall, 319 patients with aSAH were included. Patients with unfavorable outcome at 3 months were older, had worse clinical status on admission (Glasgow Coma Scale score and Hunt and Hess grade), greater amount of subarachnoidal and intraventricular hemorrhage (modified Fisher Scale grade and Graeb score), and higher rates of infectious complications (pneumonia and sepsis). A significantly higher NLR on admission was observed in patients with unfavorable outcome according to mRS score (median [IQR] NLR 5.8 [3.0-10.0] for mRS score 0-2 vs NLR 8.3 [4.5-12.6] for mRS score 3-6; p < 0.001). After adjustments, NLR on admission remained a significant predictor for unfavorable outcome in SAH patients (OR [95% CI] 1.014 [1.001-1.027]; p = 0.028). In ROC analysis, an NLR of 7.05 was identified as the best cutoff value to discriminate between favorable and unfavorable outcome (area under the curve = 0.614, p < 0.001, Youden's index = 0.211; mRS score 3-6: 94/153 [61.4%] for NLR ≥ 7.05 vs 67/166 [40.4%] for NLR < 7.05; p < 0.001). Subanalysis of patients with NLR levels ≥ 7.05 vs < 7.05, performed using 2 propensity score-matched cohorts (n = 133 patients in each group), revealed an increased proportion of patients with unfavorable functional outcome at 3 months in patients with NLR ≥ 7.05 (mRS score 3-6 at 3 months: NLR ≥ 7.05 82/133 [61.7%] vs NLR < 7.05 62/133 [46.6%]; p = 0.014), yet without differences in mortality at 3 months (NLR ≥ 7.05 37/133 [27.8%] vs NLR < 7.05 27/133 [20.3%]; p = 0.131)., Conclusions: Among aSAH patients, NLR represents an independent parameter associated with unfavorable functional outcome. Whether the impact of NLR on functional outcome is related to preexisting comorbidities or represents independent causal relationships in the context of stroke-associated immunosuppression should be investigated in future studies.

Background: The influence of prior nicotine or alcohol use (legal drug use [LDU]) on outcome measures after intracerebral hemorrhage (ICH) is insufficiently established. We investigated drug-specific associations with (1) neuroradiologic and clinical parameters and (2) functional long-term outcome after ICH., Methods: This observational cohort study analyzed consecutive spontaneous patients with ICH (n = 554) from our prospective institutional registry over a 5-year study period (January 2010 to December 2014). We compared no-LDU patients with LDU patients, and patients using only nicotine, only alcohol, or both. To account for baseline imbalances, we reanalyzed cohorts after propensity score matching., Results: Prevalence of prior LDU was 197 of 554 (35.6%), comprising 94 of 554 (17.0%) with only nicotine use, 33 of 554 (6.0%) with only alcohol use, and 70 of 554 (12.6%) with alcohol and nicotine use. LDU patients were younger (65 [56-73] versus 75 [67-82], P <.01), less often female (n = 61 of 197 [31.0%] versus n = 188 of 357 [52.7%], P <.01), had more often prior myocardial infarction (n = 29 of 197 [14.7%] versus n = 24 of 357 [6.7%], P <.01), and in-hospital complications (sepsis or systemic inflammatory response syndrome: n = 95 of 197 [48.2%] versus n = 98 of 357 [27.5%], P <.01; pneumonia: n = 89 of 197 [45.2%] versus n = 110 of 357 [30.8%], P <.01). Except for an increased risk of pneumonia (odds ratio 2.22, confidence interval [1.04-4.75], P = .04) in patients using both nicotine and alcohol, we detected no significant differences upon reanalysis after propensity score matching of neuroradiologic or clinical parameters, complications, or long-term outcome between patients with and without LDU (mortality: n = 48 of 150 [32.0%] versus n = 45 of 150 [30.0%], P = .71; favorable outcome [modified Rankin Scale 0-3]: n = 56 of 150 [37.3%] versus n = 53 of 150 [35.3%], P = .72)., Conclusions: Prior nicotine use, alcohol use, and their combination were associated with significant differences in baseline characteristics. However, adjusting for unevenly balanced baseline parameters revealed no differences in functional long-term outcome after ICH., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)