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1. Carbonated Beverage, Fruit Drink, and Water Consumption and Risk of Acute Stroke: the INTERSTROKE Case-Control Study

Author: Andrew Smyth, Graeme J. Hankey, Albertino Damasceno, Helle Klingenberg Iversen, Shahram Oveisgharan, Fawaz Alhussain, Peter Langhorne, Dennis Xavier, Patricio Lopez Jaramillo, Aytekin Oguz, Clodagh McDermott, Anna Czlonkowska, Fernando Lanas, Danuta Ryglewicz, Catriona Reddin, Xingyu Wang, Annika Rosengren, Salim Yusuf, and Martin O’Donnell
Subjects: stroke, carbonated beverages, fruit juice, water, diet, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background and Purpose Cold beverage intake (carbonated drinks, fruit juice/drinks, and water) may be important population-level exposures relevant to stroke risk and prevention. We sought to explore the association between intake of these beverages and stroke. Methods INTERSTROKE is an international matched case-control study of first stroke. Participants reported beverage intake using food frequency questionnaires or were asked “How many cups do you drink each day of water?” Multivariable conditional logistic regression estimated odds ratios (OR) and 95% confidence intervals (CI) for associations with stroke. Results We include 13,462 cases and 13,488 controls; mean age was 61.7±13.4 years and 59.6% (n=16,010) were male. After multivariable adjustment, carbonated beverages were linearly associated with ischemic stroke (OR 2.39 [95% CI 1.64–3.49]); only consumption once/day was associated with intracerebral hemorrhage (ICH) (OR 1.58 [95% CI 1.23–2.03]). There was no association between fruit juice/drinks and ischemic stroke, but increased odds of ICH for once/day (OR 1.37 [95% CI 1.08–1.75)] or twice/day (OR 3.18 [95% CI 1.69–5.97]). High water intake (>7 cups/day) was associated ischemic stroke (OR 0.82 [95% CI 0.68–0.99]) but not ICH. Associations differed by Eugeographical region—increased odds for carbonated beverages in some regions only; opposing directions of association of fruit juices/drinks with stroke in selected regions. Conclusion Carbonated beverages were associated with increased odds of ischemic stroke and ICH, fruit juice/drinks were associated with increased odds of ICH, and high water consumption was associated with reduced odds of ischemic stroke, with important regional differences. Our findings suggest optimizing water intake, minimizing fruit juice/drinks, and avoiding carbonated beverages.
Published: 2024
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2. Non-ceruloplasmin copper and urinary copper in clinically stable Wilson disease: Alignment with recommended targets

Author: Peter Ott, Thomas Sandahl, Aftab Ala, David Cassiman, Eduardo Couchonnal-Bedoya, Rubens Gisbert Cury, Anna Czlonkowska, Gerald Denk, Renata D’Inca, Francisco de Assis Aquino Gondim, Joanna Moore, Aurelia Poujois, Carlos Alexandre Twardowschy, Karl Heinz Weiss, Massimo Zuin, C.Omar F. Kamlin, and Michael L. Schilsky
Subjects: Exchangeable copper, bioavailable copper, free serum copper, protein speciation, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Background & Aims: Wilson disease (WD) is caused by accumulation of copper primarily in the liver and brain. During maintenance therapy of WD with D-penicillamine, current guidelines recommend on-treatment ranges of urinary copper excretion (UCE) of 200-500 μg/24 h and serum non-ceruloplasmin-bound copper (NCC) of 50-150 μg/L. We compared NCC (measured by two novel assays) and UCE from patients with clinically stable WD on D-penicillamine therapy with these recommendations. Methods: This is a secondary analysis of data from the Chelate trial (NCT03539952) that enrolled physician-selected patients with clinically stable WD on D-penicillamine maintenance therapy (at an unaltered dose for at least 4 months). We analyzed laboratory samples from the first screening visit, prior to interventions. NCC was measured by either protein speciation (NCC-Sp) using anion exchange high-performance liquid chromatography protein speciation followed by copper determination with inductively coupled plasma mass spectroscopy or as exchangeable copper (NCC-Ex). NCC-Sp was also analyzed in healthy controls (n = 75). Results: In 76 patients with WD with 21.3±14.3 average treatment-years, NCC-Sp (mean±SD: 56.6±26.2 μg/L) and NCC-Ex (mean±SD: 57.9±24.7 μg/L) were within the 50-150 μg/L target in 61% and 54% of patients, respectively. In addition, 36% and 31%, respectively, were even below the normal ranges (NCC-Sp: 46-213 μg/L, NCC-Ex: 41-71 μg/L). NCC-Ex positively correlated with NCC-Sp (r2 = 0.66, p
Published: 2024
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3. Diagnóstico de la enfermedad de Wilson y sus fenotipos usando inteligencia artificial

Author: Valentina Medici, Anna Czlonkowska, Tomasz Litwin, and Cecilia Giulivi
Subjects: Ciclo de Krebs, ciclo de la urea, cobre, hígado, metabolismo intermediario, mitocondria, Medicine, Biology (General), QH301-705.5
Abstract: La EW es causada por las variantes de ATP7B que alteran el eflujo de cobre y provocan una acumulación excesiva de cobre, principalmente en el hígado y el cerebro. El diagnóstico de la EW se ve dificultado por su evolución clínica variable, su aparición, su morbilidad y el tipo de variante ATP7B. Actualmente se diagnostica mediante una combinación de síntomas/signos clínicos, parámetros aberrantes del metabolismo del cobre (por ejemplo, niveles séricos bajos de ceruloplasmina y concentraciones elevadas de cobre urinario y hepático) y cuando están disponibles, a través de pruebas genéticas de mutaciones ATP7B. Dado que el diagnóstico y el tratamiento precoces son clave para obtener resultados favorables, es fundamental identificar a los sujetos antes de la aparición de manifestaciones clínicas manifiestamente perjudiciales. Con este fin, tratamos de mejorar el diagnóstico de la EW mediante algoritmos de redes neuronales artificiales (parte de la inteligencia artificial) integrando los parámetros clínicos y moleculares disponibles. Sorprendentemente, el diagnóstico de la EW se basó en los niveles plasmáticos de glutamato, asparagina, taurina y el cociente de Fischer. Dado que estos aminoácidos están relacionados con los ciclos urea-Krebs, nuestro estudio no sólo subraya el papel central de las mitocondrias hepáticas en la patología de la EW, sino también que la mayoría de los pacientes con EW presentan una disfunción hepática subyacente. Nuestro estudio aporta pruebas novedosas de que la inteligencia artificial utilizada para el análisis integrado de la EW puede dar lugar a un diagnóstico más precoz y a tratamientos mecánicamente relevantes para los pacientes con EW.
Published: 2023
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4. Global Impact of the COVID-19 Pandemic on Cerebral Venous Thrombosis and Mortality

Author: Thanh N. Nguyen, Muhammad M. Qureshi, Piers Klein, Hiroshi Yamagami, Mohamad Abdalkader, Robert Mikulik, Anvitha Sathya, Ossama Yassin Mansour, Anna Czlonkowska, Hannah Lo, Thalia S. Field, Andreas Charidimou, Soma Banerjee, Shadi Yaghi, James E. Siegler, Petra Sedova, Joseph Kwan, Diana Aguiar de Sousa, Jelle Demeestere, Violiza Inoa, Setareh Salehi Omran, Liqun Zhang, Patrik Michel, Davide Strambo, João Pedro Marto, Raul G. Nogueira, and SVIN COVID-19 Global COVID Stroke Registry
Subjects: Diseases of the circulatory (Cardiovascular) system, RC666-701
Published: 2024
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5. Global Impact of the COVID-19 Pandemic on Cerebral Venous Thrombosis and Mortality

Author: Thanh N. Nguyen, Muhammad M. Qureshi, Piers Klein, Hiroshi Yamagami, Mohamad Abdalkader, Robert Mikulik, Anvitha Sathya, Ossama Yassin Mansour, Anna Czlonkowska, Hannah Lo, Thalia S. Field, Andreas Charidimou, Soma Banerjee, Shadi Yaghi, James E. Siegler, Petra Sedova, Joseph Kwan, Diana Aguiar de Sousa, Jelle Demeestere, Violiza Inoa, Setareh Salehi Omran, Liqun Zhang, Patrik Michel, Davide Strambo, João Pedro Marto, and Raul G. Nogueira
Subjects: covid-19, cerebral venous thrombosis, vaccine-induced immune thrombotic thrombocytopenia, mortality, sars-cov-2, stroke, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background and Purpose Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. Methods We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). Results There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P
Published: 2022
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6. Association of Lipids, Lipoproteins, and Apolipoproteins with Stroke Subtypes in an International Case Control Study (INTERSTROKE)

Author: Martin J. O’Donnell, Matthew McQueen, Allan Sniderman, Guillaume Pare, Xingyu Wang, Graeme J. Hankey, Sumathy Rangarajan, Siu Lim Chin, Purnima Rao-Melacini, John Ferguson, Denis Xavier, Liu Lisheng, Hongye Zhang, Prem Pais, Patricio Lopez-Jaramillo, Albertino Damasceno, Peter Langhorne, Annika Rosengren, Antonio L. Dans, Ahmed Elsayed, Alvaro Avezum, Charles Mondo, Conor Judge, Hans-Christoph Diener, Danuta Ryglewicz, Anna Czlonkowska, Nana Pogosova, Christian Weimar, Romana Iqbal, Rafael Diaz, Khalid Yusoff, Afzalhussein Yusufali, Aytekin Oguz, Ernesto Penaherrera, Fernando Lanas, Okechukwu S. Ogah, Adesola Ogunniyi, Helle K. Iversen, German Malaga, Zvonko Rumboldt, Shahram Oveisgharan, Fawaz Al Hussain, Yongchai Nilanont, and Salim Yusuf
Subjects: stroke, risk factor, dyslipidemia, lipoproteins, apolipoproteins, case-control, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background and Purpose The association of dyslipidemia with stroke has been inconsistent, which may be due to differing associations within etiological stroke subtypes. We sought to determine the association of lipoproteins and apolipoproteins within stroke subtypes. Methods Standardized incident case-control STROKE study in 32 countries. Cases were patients with acute hospitalized first stroke, and matched by age, sex and site to controls. Concentrations of total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (apoA1), and apoB were measured. Non-HDL-C was calculated. We estimated multivariable odds ratio (OR) and population attributable risk percentage (PAR%). Outcome measures were all stroke, ischemic stroke (and subtypes), and intracerebral hemorrhage (ICH). Results Our analysis included 11,898 matched case-control pairs; 77.3% with ischemic stroke and 22.7% with ICH. Increasing apoB (OR, 1.10; 95% confidence interval [CI], 1.06 to 1.14 per standard deviation [SD]) and LDL-C (OR, 1.06; 95% CI, 1.02 to 1.10 per SD) were associated with an increase in risk of ischemic stroke, but a reduced risk of ICH. Increased apoB was significantly associated with large vessel stroke (PAR 13.4%; 95% CI, 5.6 to 28.4) and stroke of undetermined cause. Higher HDL-C (OR, 0.75; 95% CI, 0.72 to 0.78 per SD) and apoA1 (OR, 0.63; 95% CI, 0.61 to 0.66 per SD) were associated with ischemic stroke (and subtypes). While increasing HDL-C was associated with an increased risk of ICH (OR, 1.20; 95% CI, 1.14 to 1.27 per SD), apoA1 was associated with a reduced risk (OR, 0.80; 95% CI, 0.75 to 0.85 per SD). ApoB/A1 (OR, 1.38; 95% CI, 1.32 to 1.44 per SD) had a stronger magnitude of association than the ratio of LDL-C/HDL-C (OR, 1.26; 95% CI, 1.21 to 1.31 per SD) with ischemic stroke (P
Published: 2022
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7. Antiplatelet drugs and liver fibrosis

Author: Pamela Czajka, Adam Przybyłkowski, Anna Nowak, Marek Postula, Marta Wolska, Dagmara Mirowska-Guzel, Anna Czlonkowska, and Ceren Eyileten
Subjects: acetylsalicylic acid, antiplatelet treatment, hepatocellular carcinoma, liver fibrosis, p2y12 inhibitors, platelets, Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Liver fibrosis results from an imbalance between extracellular matrix formation and degradation. The background of liver fibrosis is chronic inflammation and subsequent microcirculation disturbance including microthrombosis. Platelets actively participate in liver fibrosis not only as a part of the clotting system but also by releasing granules containing important mediators. In fact, platelets may play a dual role in the pathophysiology of liver fibrosis as they are able to stimulate regeneration as well as aggravate the destruction of the liver. Recent studies revealed that antiplatelet therapy correlates with inhibition of liver fibrosis. However, liver impairment is associated with extensive coagulation disorders thus the safety of antiplatelet therapy is an area for detailed exploration. In this review, the role of platelets in liver fibrosis and accompanying hemostatic disorders are discussed. Additionally, results of animal and human studies on antiplatelet drugs in liver disorders and their potential therapeutic utility are presented.
Published: 2022
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8. Effect of continuing versus stopping pre-stroke antihypertensive agents within 12 h on outcome after stroke: A subgroup analysis of the efficacy of nitric oxide in stroke (ENOS) trial

Author: Lisa J. Woodhouse, Jason P. Appleton, Polly Scutt, Lisa Everton, Gwenllian Wilkinson, Valeria Caso, Anna Czlonkowska, John Gommans, Kailash Krishnan, Ann C. Laska, George Ntaios, Serefnur Ozturk, Stephen Phillips, Stuart Pocock, Kameshwar Prasad, Szabolcs Szatmari, Joanna M. Wardlaw, Nikola Sprigg, and Philip M. Bath
Subjects: Medicine (General), R5-920
Abstract: Summary: Background: It is not known whether to continue or temporarily stop existing antihypertensive drugs in patients with acute stroke. Methods: We performed a prospective subgroup analysis of patients enrolled into the Efficacy of Nitric Oxide in Stroke (ENOS) trial who were randomised to continue vs stop prior antihypertensive therapy within 12 h of stroke onset. The primary outcome was functional outcome, assessed with the modified Rankin Scale at 90 days by observers blinded to treatment assignment, and analysed with ordinal logistic regression. Findings: Of 4011 patients recruited into ENOS from 2001 to 2014, 2097 patients were randomised to continue vs stop prior antihypertensive treatment, and 384 (18.3%, continue 185, stop 199) were enrolled within 12 h of ictus: mean (SD) age 71.8 (11.8) years, female 193 (50.3%), ischaemic stroke 342 (89.1%) and total anterior circulation syndrome 114 (29.7%). As compared with stopping, continuing treatment within 12 h of onset lowered blood pressure by 15.5/9.6 mmHg (p
Published: 2022
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9. A Century of Progress on Wilson Disease and the Enduring Challenges of Genetics, Diagnosis, and Treatment

Author: Louis C. Penning, Marina Berenguer, Anna Czlonkowska, Kay L. Double, Petr Dusek, Carmen Espinós, Svetlana Lutsenko, Valentina Medici, Wiebke Papenthin, Wolfgang Stremmel, Jose Willemse, and Ralf Weiskirchen
Subjects: Wilson disease, copper accumulation, hepatic disfunction, neurological disfunction, psychiatric disorders, patients’ involvement, Biology (General), QH301-705.5
Abstract: Wilson disease (WD) is a rare, inherited metabolic disorder manifested with varying clinical presentations including hepatic, neurological, psychiatric, and ophthalmological features, often in combination. Causative mutations in the ATP7B gene result in copper accumulation in hepatocytes and/or neurons, but clinical diagnosis remains challenging. Diagnosis is complicated by mild, non-specific presentations, mutations exerting no clear effect on protein function, and inconclusive laboratory tests, particularly regarding serum ceruloplasmin levels. As early diagnosis and effective treatment are crucial to prevent progressive damage, we report here on the establishment of a global collaboration of researchers, clinicians, and patient advocacy groups to identify and address the outstanding challenges posed by WD.
Published: 2023
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10. Social and demographic characteristics of a Polish cohort with Wilson disease and the impact of treatment persistence

Author: Wojciech Maselbas, Tomasz Litwin, and Anna Czlonkowska
Subjects: Wilson disease, Neurological manifestations, Treatment persistence, Medicine
Abstract: Abstract Background Wilson disease (WD) is a genetic disorder involving impaired copper metabolism, which presents with hepatic, neurological, and/or psychiatric manifestations. WD requires lifelong pharmacotherapy and treatment persistence may be problematic. We studied social characteristics, education, and work-related activities and how they are affected by WD symptoms and treatment persistence. Methods In a cross-sectional study, data on demographic characteristics, achieved education level, household and marital status, plus a primary source of income were collected from 202 Polish subjects (mean ± standard deviation age of 36.4 ± 9.9 years at assessment) with WD. Results Overall, WD appeared to have a negative impact on achieved level of education and influenced the ability to work as compared with the general Polish population. Patients with neurological manifestations less often achieved upper-secondary/post-secondary or higher education compared with those with hepatic manifestations (65.5% vs. 83.6%; p = 0.003). They also significantly less frequently stated salary (19.6% vs. 56.2%; p
Published: 2019
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11. Diagnostic Performance of Circulating miRNAs and Extracellular Vesicles in Acute Ischemic Stroke

Author: Ceren Eyileten, Daniel Jakubik, Andleeb Shahzadi, Aleksandra Gasecka, Edwin van der Pol, Salvatore De Rosa, Dominika Siwik, Magdalena Gajewska, Dagmara Mirowska-Guzel, Iwona Kurkowska-Jastrzebska, Anna Czlonkowska, and Marek Postula
Subjects: miR-19a, miR-186, let-7f, platelet extracellular vesicles, leukocyte extracellular vesicles, platelet reactivity, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: Background: Increased inflammation activates blood coagulation system, higher platelet activation plays a key role in the pathophysiology of ischemic stroke (IS). During platelet activation and aggregation process, platelets may cause increased release of several proinflammatory, and prothrombotic mediators, including microRNAs (miRNAs) and extracellular vesicles (EVs). In the current study we aimed to assess circulating miRNAs profile related to platelet function and inflammation and circulating EVs from platelets, leukocytes, and endothelial cells to analyse their diagnostic and predictive utility in patients with acute IS. Methods: The study population consisted of 28 patients with the diagnosis of the acute IS. The control group consisted of 35 age- and gender-matched patients on acetylsalicylic acid (ASA) therapy without history of stroke and/or TIA with established stable coronary artery disease (CAD) and concomitant cardiovascular risk factors. Venous blood samples were collected from the control group and patients with IS on ASA therapy (a) 24 h after onset of acute IS, (b) 7-days following index hospitalization. Flow cytometry was used to determine the concentration of circulating EVs subtypes (from platelets, leukocytes, and endothelial cells) in platelet-depleted plasma and qRT-PCR was used to determine several circulating plasma miRNAs (miR-19a-3p, miR-186-5p and let-7f). Results: Patients with high platelet reactivity (HPR, based on arachidonic acid-induced platelet aggregometry) had significantly elevated platelet-EVs (CD62+) and leukocyte-EVs (CD45+) concentration compared to patients with normal platelet reactivity at the day of 1 acute-stroke (p = 0.012, p = 0.002, respectively). Diagnostic values of baseline miRNAs and EVs were evaluated with receiver operating characteristic (ROC) curve analysis. The area under the ROC curve for miR-19a-3p was 0.755 (95% CI, 0.63–0.88) p = 0.004, for let-7f, it was 0.874 (95% CI, 0.76–0.99) p = 0.0001; platelet-EVs was 0.776 (95% CI, 0.65–0.90) p = 0.001, whereas for leukocyte-EVs, it was 0.715 (95% CI, 0.57–0.87) p = 0.008. ROC curve showed that pooling the miR-19a-3p expressions, platelet-EVs, and leukocyte-EVs concentration yielded a higher AUC than the value of each individual biomarker as AUC was 0.893 (95% CI, 0.79–0.99). Patients with moderate stroke had significantly elevated miR-19a-3p expression levels compared to patients with minor stroke at the first day of IS. (AUC: 0.867, (95% CI, 0.74–0.10) p = 0.001). Conclusion: Combining different biomarkers of processes underlying IS pathophysiology might be beneficial for early diagnosis of ischemic events. Thus, we believe that in the future circulating biomarkers might be used in the prehospital phase of IS. In particular, circulating plasma EVs and non-coding RNAs including miRNAs are interesting candidates as bearers of circulating biomarkers due to their high stability in the blood and making them highly relevant biomarkers for IS diagnostics.
Published: 2022
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12. Diagnosis of Wilson Disease and Its Phenotypes by Using Artificial Intelligence

Author: Valentina Medici, Anna Czlonkowska, Tomasz Litwin, and Cecilia Giulivi
Subjects: Wilson disease, copper, mitochondria, liver, intermediary metabolism, urea cycle, Microbiology, QR1-502
Abstract: WD is caused by ATP7B variants disrupting copper efflux resulting in excessive copper accumulation mainly in liver and brain. The diagnosis of WD is challenged by its variable clinical course, onset, morbidity, and ATP7B variant type. Currently it is diagnosed by a combination of clinical symptoms/signs, aberrant copper metabolism parameters (e.g., low ceruloplasmin serum levels and high urinary and hepatic copper concentrations), and genetic evidence of ATP7B mutations when available. As early diagnosis and treatment are key to favorable outcomes, it is critical to identify subjects before the onset of overtly detrimental clinical manifestations. To this end, we sought to improve WD diagnosis using artificial neural network algorithms (part of artificial intelligence) by integrating available clinical and molecular parameters. Surprisingly, WD diagnosis was based on plasma levels of glutamate, asparagine, taurine, and Fischer’s ratio. As these amino acids are linked to the urea–Krebs’ cycles, our study not only underscores the central role of hepatic mitochondria in WD pathology but also that most WD patients have underlying hepatic dysfunction. Our study provides novel evidence that artificial intelligence utilized for integrated analysis for WD may result in earlier diagnosis and mechanistically relevant treatments for patients with WD.
Published: 2021
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13. The Clinical Development of Cerebrolysin: New Approaches in Stroke Studies: A Commentary to The Cars Study

Author: Anna Czlonkowska
Subjects: Neurorecovery, thrombolysis, neurotrophic factors, Cerebrolysin®, multimodal medication, neuroplasticity, neurorehabilitation, clinical development., Neurology. Diseases of the nervous system, RC346-429
Abstract: Additional efficacious treatment options for stroke are urgently needed as thrombolysis and endovascular thrombectomy are too rarely utilised due to the narrow time window. This article reviews the clinical profile of Cerebrolysin® (EVER Pharma, Austria), a well-documented compound indicated for the treatment of acute stroke, which has also shown promising results in neurorecovery. Well-conducted clinical trials have shown strong and encouraging treatment signals, either as a single therapy or in combination with recombinant tissue plasminogen activator. This review focusses on the latest research results, especially on the randomised, controlled CARS study, which combined pharmacological and rehabilitation therapy. Furthermore, this study reached the primary endpoint at Day 90 in the Action Research Arm Test and showed significant improvements in modified Rankin Scale (mRS) at Day 90. The same applies to important secondary endpoints such as the National Institutes of Health Stroke Scale (NIHSS) at Day 21 (early benefit). CARS is a rehabilitation study with a larger sample size and gives neurologists as well as rehabilitation specialists renewed confidence in this class of neuroprotective/ neurorecovery-enhancing compounds. Furthermore, ongoing research projects like CREGS-S are discussed, a large-scale prospective registry that adds valuable real-world data to the existing portfolio of Cerebrolysin studies.
Published: 2017

14. MicroRNAs as Diagnostic and Prognostic Biomarkers in Ischemic Stroke—A Comprehensive Review and Bioinformatic Analysis

Author: Ceren Eyileten, Zofia Wicik, Salvatore De Rosa, Dagmara Mirowska-Guzel, Aleksandra Soplinska, Ciro Indolfi, Iwona Jastrzebska-Kurkowska, Anna Czlonkowska, and Marek Postula
Subjects: miRNA, bioinformatic analysis, ischemic stroke, miRNA-gene target interaction, network, biomarker, diagnosis, prognosis, Cytology, QH573-671
Abstract: Stroke is the second-most common cause of death worldwide. The pathophysiology of ischemic stroke (IS) is related to inflammation, atherosclerosis, blood coagulation, and platelet activation. MicroRNAs (miRNAs) play important roles in physiological and pathological processes of neurodegenerative diseases and progression of certain neurological diseases, such as IS. Several different miRNAs, and their target genes, are recognized to be involved in the pathophysiology of IS. The capacity of miRNAs to simultaneously regulate several target genes underlies their unique value as diagnostic and prognostic markers in IS. In this review, we focus on the role of miRNAs as diagnostic and prognostic biomarkers in IS. We discuss the most common and reliable detection methods available and promising tests currently under development. We also present original results from bioinformatic analyses of published results, identifying the ten most significant genes (HMGB1, YWHAZ, PIK3R1, STAT3, MAPK1, CBX5, CAPZB, THBS1, TNFRSF10B, RCOR1) associated with inflammation, blood coagulation, and platelet activation and targeted by miRNAs in IS. Additionally, we created miRNA-gene target interaction networks based on Gene Ontology (GO) information derived from publicly available databases. Among our most interesting findings, miR-19a-3p is the most widely modulated miRNA across all selected ontologies and might be proposed as novel biomarker in IS to be tested in future studies.
Published: 2018
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15. Population-Specific Associations of Deleterious Rare Variants in Coding Region of P2RY1–P2RY12 Purinergic Receptor Genes in Large-Vessel Ischemic Stroke Patients

Author: Piotr K. Janicki, Ceren Eyileten, Victor Ruiz-Velasco, Khaled Anwar Sedeek, Justyna Pordzik, Anna Czlonkowska, Iwona Kurkowska-Jastrzebska, Shigekazu Sugino, Yuka Imamura-Kawasawa, Dagmara Mirowska-Guzel, and Marek Postula
Subjects: DNA sequencing, platelets, genetic polymorphism, cerebrovascular stroke, purinergic receptors, large-vessel ischemic stroke, Polish population, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: The contribution of low-frequency and damaging genetic variants associated with platelet function to ischemic stroke (IS) susceptibility remains unknown. We employed a deep re-sequencing approach in Polish patients in order to investigate the contribution of rare variants (minor allele frequency, MAF < 1%) to the IS genetic susceptibility in this population. The genes selected for re-sequencing consisted of 26 genes coding for proteins associated with the surface membrane of platelets. Targeted pooled re-sequencing (Illumina HiSeq 2500) was performed on genomic DNA of 500 cases (patients with history of clinically proven diagnosis of large-vessel IS) and 500 controls. After quality control and prioritization based on allele frequency and damaging probability, follow-up individual genotyping of deleterious rare variants was performed in patients from the original cohort. Gene-based analyses identified an association between IS and 6 rare functional and damaging variants in the purinergic genes (P2RY1 and P2RY12 locus). The predicted properties of the most damaging rare variants in P2RY1 and P2RY12 were confirmed by using mouse fibroblast cell cultures transfected with plasmid constructs containing cDNA of mutated variants (FLIPR on FlexStation3). This study identified a putative role for rare variants in P2RY1 and P2RY12 genes involved in platelet reactivity on large-vessel IS susceptibility in a Polish population.
Published: 2017
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16. Infections and Ischemic Stroke Outcome

Author: Katarzyna Grabska, Grazyna Gromadzka, and Anna Czlonkowska
Subjects: Neurology. Diseases of the nervous system, RC346-429
Abstract: Background. Infections increase the risk of ischemic stroke (IS) and may worsen IS prognosis. Adverse effects of in-hospital infections on stroke outcome were also reported. We aimed to study the prevalence of pre- and poststroke infections and their impact on IS outcome. Methods. We analysed clinical data of 2066 IS patients to assess the effect of pre-stroke and post-stroke infections on IS severity, as well as short-term (up to 30 days) and long-term (90 days) outcome. The independent impact of infections on poor outcome (death, death/dependency) was investigated by use of logistic regression analysis. The effect of antibiotic therapy during hospitalization on the outcome was also assessed. Results. Pre-stroke infections independently predicted worse short-term outcome. In-hospital infections were associated with worse short-term and long-term IS prognosis. Antibacterial treatment during hospitalization did not improve patients' outcome. Conclusions. Prevention of infections may improve IS prognosis. The role of antibiotic therapy after IS requires further investigations.
Published: 2011
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17. Delivery of acute ischaemic stroke treatments in the European region in 2019 and 2020

Author: Aguiar de Sousa, Diana, primary, Wilkie, Arlene, additional, Norrving, Bo, additional, Macey, Chris, additional, Bassetti, Claudio, additional, Tiu, Cristina, additional, Roth, Greg, additional, Lunde, Grethe, additional, Christensen, Hanne, additional, Fiehler, Jens, additional, Pezzella, Francesca Romana, additional, Dichgans, Martin, additional, Roaldsen, Melinda B, additional, Kelly, Peter, additional, Mikulik, Robert, additional, Sacco, Simona, additional, Caso, Valeria, additional, Fischer, Urs, additional, Basha, Entela, additional, Yeghiazaryan, Nune, additional, Kiechl, Stefan, additional, Shiraliyeva, Rana, additional, Vanacker, Peter, additional, Bender, Marija, additional, Emilov Tsalta-Mladenov, Mihael, additional, Budincevic, Hrvoje, additional, Tomek, Ales, additional, Kaponides, Georgios, additional, Klingenberg Iversen, Helle, additional, Faiss, Jürgen, additional, Kõrv, Janika, additional, Sairanen, Tiina, additional, Igor, Sibon, additional, Tsiskaridze, Alexander, additional, Ntaios, George, additional, Tsivgoulis, Georgios, additional, Szapary, Laszlo, additional, Logi Thorarinsson, Bjorn, additional, Harbison, Joe, additional, Bornstein, Natan M., additional, Toni, Danilo, additional, Fisnik, Jashari, additional, Karbozova, Kunduz, additional, Miglane, Evija, additional, Dalius, Jatužis, additional, Droste, Dirk, additional, Mallia, Maria, additional, Jevto, Erakovic, additional, Arsovska, Anita, additional, Fromm, Annette, additional, Kobayashi, Adam, additional, Azevedo, Elsa, additional, Groppa, Stanislav, additional, Cristina, Tiu, additional, Guekht, Alla, additional, Zivanovic, Zeljko, additional, Nosal, Vladimir, additional, Zvan, Bojana, additional, López-Cancio, Elena, additional, Pérez de la Ossa, Natàlia, additional, Nedeltchev, Krassen, additional, Vrijhoef, Bert, additional, Akif Topcuoglu, Mehmet, additional, Flomin, Yuriy, additional, Ahmed, Rubina, additional, Shelesko, Andrey, additional, Petrela, Mentor, additional, Zubalova, Lina, additional, Hasanov, Rovshan, additional, Raedt, Sylvie De, additional, Nevena, Mahmutbegović, additional, Peteva Andonova, Silva, additional, Poljakovic, Zdravka, additional, Skoda, Ondrej, additional, Søren Paaske, Johnsen, additional, med. Helmuth Steinmetz, Prof. Dr., additional, Denis, Sablot, additional, Lobjanidze, Nino, additional, Milionis, Haralambos, additional, Mitsias, Panagiotis, additional, Tarkanyi MD, Gabor, additional, Elisabeth Klinke, Marianne, additional, Tanne, David, additional, Luca, Petraglia, additional, Dren, Boshnjaku, additional, Turgumbaev, Dzhamal, additional, Guntis, Karelis, additional, Mladen, Debeljevic, additional, Kurz, Martin, additional, Anna, Czlonkowska, additional, Eremei, Zota, additional, Elena Oana, Terecoasa, additional, Martinov, Mikhail, additional, Jovanović, Dejana, additional, Gdovinova, Zuzana, additional, Camps Renom, Pol, additional, Kwa, Vincent, additional, Murat Arsava, Ethem, additional, Gulyayeva, Maryna, additional, Dharmasiri, Michelle, additional, Korompoki, Eleni, additional, Vadikolias, Konstantinos, additional, Bereczki MD, Daniel, additional, Bryndis Einarsdottir, Anna, additional, Afrim, Blyta, additional, Mamytova, Elmira, additional, Kristaps, Jurjans, additional, Daiva, Rastenytė, additional, Costache, Oana, additional, Milovan, Roganovic, additional, Michal, Karlinski, additional, Alexandru, Gasnas, additional, Sorin, Tuta, additional, Fidler, Mikhail, additional, Raičević, Ranko, additional, Zaletel, Marjan, additional, Castellanos, Mar, additional, Gómez-Choco, Manuel, additional, Sirin, Hadiye, additional, Lebedynets, Dmytro, additional, Khaira, Jattinder, additional, Enesi, Eugen, additional, Sahakyan, David, additional, Mammadbayli, Ayten, additional, Lemmens, Robin, additional, Dževdet, Smajlović, additional, Sramek, Martin, additional, Nabavi, med. Darius, additional, Vibo, Riina, additional, Strbian, Daniel, additional, Aliyev, Rahim, additional, Ozretic, David, additional, Rocek, Miloslav, additional, Trine, Stavngaard, additional, med. Claus Zimmer, Prof. Dr., additional, Malikov, Vladislav, additional, Lappalainen, Kimmo, additional, Jerome, Berge, additional, Khinikadze, Mirza, additional, Brountzos, Elias, additional, Vilmarsson, Vilhjalmur, additional, Karlis, Kupcs, additional, Marius, Kurminas, additional, Hoffmann, Michel, additional, Grech, Reuben, additional, Marija, Mitric, additional, Kjellevold Wathle, Gaute, additional, Wojciech, Poncyljusz, additional, Igor, Crivorucica, additional, Bogdan, Dorobat, additional, Till, Viktor, additional, Klepanec, Andrej, additional, Milosevic, Zoran, additional, Macho, Juan, additional, Ozdemir, Ozcan, additional, Shchehlov, Dmytro, additional, Dorte, Damgaard, additional, Hermanek, Peter, additional, Sturua, Lela, additional, Siskou, Olga, additional, Libruder, Carmit, additional, Indredavik, Bent, additional, Elena, Manole, additional, Mijajlović, Milija, additional, Turcani, Peter, additional, Bonati, Leo, additional, Nederkoorn, Paul, additional, Ertuğrul Eğin, Muhammed, additional, Samofalov, Dmytro, additional, Diana, Ose, additional, and Rita, Gaidelytė, additional
Published: 2023
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18. Diagnostic and predictive value of circulating microRNAs and their regulation of BDNF signaling pathway in stroke patients

Author: Mikolaj Marszalek, Disha Keshwani, Ceren Eyileten, Zofia Wicik, Anna Nowak, Salvatore de. Rosa, Dagmara Mirowska-Guzel, Anna Czlonkowska, Guillaume Paré, and Marek Postula
Published: 2023

19. Association of Psychosocial Stress With Risk of Acute Stroke

Author: Catriona, Reddin, Robert, Murphy, Graeme J, Hankey, Conor, Judge, Denis, Xavier, Annika, Rosengren, John, Ferguson, Alberto, Alvarez-Iglesias, Shahram, Oveisgharan, Helle K, Iversen, Fernando, Lanas, Fawaz, Al-Hussein, Anna, Czlonkowska, Aytekin, Oguz, Clodagh, McDermott, Nana, Pogosova, German, Málaga, Peter, Langhorne, Xingyu, Wang, Mohammad, Wasay, Salim, Yusuf, Martin, O'Donnell, and Alfzalhussein, Yusufali
Subjects: Risk, Psychosocial Stress, Acute Stroke, General Medicine
Abstract: ImportancePsychosocial stress is considered a modifiable risk factor for stroke. Given the prevalence of chronic and acute exposure to stress, it represents a potentially attractive target for population-health interventions.ObjectivesTo determine the association of psychosocial stress with the risk of acute stroke and explore factors that might modify the association of stress with risk of acute stroke in a large international population.Design, Setting, and ParticipantsINTERSTROKE is an international retrospective case-control study of risk factors for first acute stroke in 32 countries in Asia, North and South America, Europe, Australia, the Middle East, and Africa. A total of 13 462 patients with stroke and 13 488 matched controls were recruited between January 11, 2007, and August 8, 2015. The present analyses were performed from June 1 to 30, 2021, and included 13 350 cases and 13 462 controls with available data on psychosocial stress.ExposuresPsychosocial stress and occurrence of stressful life events within the preceding year were measured using a standardized questionnaire of self-reported stress at home and work.Main Outcomes and MeasuresThe association of stress with acute stroke and its subtypes was examined using multivariable conditional logistic regression and factors that might modify the association, particularly self-reported locus of control.ResultsAmong 26 812 participants included in the analysis, the mean (SD) age of cases was 62.2 (13.6) years; that of controls, 61.3 (13.3) years; 7960 cases (59.6%) and 8017 controls (59.6%) were men. Several periods of stress and permanent stress were reported for 2745 cases (20.5%) and 1933 controls (14.4%), with marked regional variation in prevalence, with the lowest in China (201 of 3981 [5.0%] among controls and 364 of 3980 [9.1%] among cases) and highest in South East Asia (233 of 855 [26.1%] among controls and 241 of 782 [30.8%] among cases). Increased stress at home (odds ratio [OR], 1.95 [95% CI, 1.77-2.15]) and at work (OR, 2.70 [95% CI, 2.25-3.23]) and recent stressful life events (OR, 1.31 [95% CI, 1.19-1.43]) were associated with an increased risk of acute stroke on multivariable analyses (vs no self-reported stress). Higher locus of control at home was associated with a reduced odds of all stroke (OR, 0.73 [95% CI, 0.68-0.79]), and higher locus of control both at work and at home were associated with a lower odds of acute stroke and significantly diminished the association with stress at work (OR, 2.20 [95% CI, 1.88-2.58]; P = .008 for interaction) and home (OR, 1.69 [95% CI, 1.44-1.98]; P < .001 for interaction) for acute stroke.Conclusions and RelevancePsychosocial stress is a common risk factor for acute stroke. The findings of this case-control study suggest that higher locus of control is associated with lower risk of stroke and may be an important effect modifier of the risk associated with psychosocial stress.
Published: 2022

20. Trientine tetrahydrochloride versus penicillamine for maintenance therapy in Wilson disease (CHELATE):a randomised, open-label, non-inferiority, phase 3 trial

Author: Michael L Schilsky, Anna Czlonkowska, Massimo Zuin, David Cassiman, Carlos Twardowschy, Aurelia Poujois, Francisco de Assis A Gondim, Gerald Denk, Rubens G Cury, Peter Ott, Joanna Moore, Aftab Ala, Renata D'Inca, Eduardo Couchonnal-Bedoya, Koenraad D'Hollander, Nicolas Dubois, C Omar F Kamlin, Karl Heinz Weiss, Uyen To, Amar Patel, Daksshi Hettiarachchi, Alessia Giorgini, Sara Monico, Tomasz Litwin, Agnieszka Piechal, Marta Skowronska, Alain Lachaux, Abdelouahed Belmalih, Alexandra Boogers, Isabelle Mohr, Andrea Langel, Christian Freitas, Egberto Reis Barbosa, Thomas D Sandahl, Lisbet Gerdes, Alexandre Obadia, Djamila Rahli, and Jeremy Cosgrove
Subjects: Adult, Hepatology, Hepatolenticular Degeneration, Penicillamine, Gastroenterology, Humans, Trientine, Copper, Chelating Agents
Abstract: Background: Wilson disease is an inherited disorder of copper transport. Whereas penicillamine is used therapeutically to re-establish copper balance, trientine is indicated for patients with penicillamine intolerance. We aimed to compare penicillamine with trientine tetrahydrochloride (TETA4) for maintenance therapy in patients with Wilson disease. Methods: We conducted a randomised, open-label, non-inferiority, phase 3 trial at 15 health-care centres across nine countries (patients were recruited from 13 of these health-care centres across Brazil, Europe, and the USA). We enrolled patients aged 18–75 years with stable Wilson disease who were treated for at least 1 year with penicillamine. Patients entered a 12-week period to determine stability through clinical assessment by site investigators and predefined thresholds for serum non-caeruloplasmin-bound copper (NCC; by an exchangeable copper assay; 25–150 μg/L), 24 h urinary copper excretion (100–900 μg/24 h), and alanine aminotransferase (ALT
Published: 2022

21. O01 Efficacy and safety of ALXN1840 versus standard of care in Wilson disease: primary results from an ongoing phase 3, randomized, controlled, rater-blinded trial

Author: Karl Heinz Weiss, Michael Schilsky, Anna Czlonkowska, Frederick Askari, Aftab Ala, Peter Ferenci, Peter Ott, Dzhamal Abdurakhmanov, Ferenc Szalay, Piotr Socha, Norikazu Shimizu, Jeff Bronstein, Danny Bega, Sihoun Hahn, Eugene Scott Swenson, Yi Chen, and Aurelia Poujois
Published: 2022

22. Résultats à un an de l’étude chelate : comparaison de la trientine tétrahydrochloride à la D-Pénicillamine chez des patients stables atteints de la maladie de Wilson

Author: Poujois, Aurélia, primary, Giovanni, Zuin Massimo, additional, Anna, Czlonkowska, additional, Obadia, Mickael Alexandre, additional, Henry, Audrey, additional, Weiss, Karl Heinz, additional, and Schilsky, Michael, additional
Published: 2022
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23. Effect of continuing versus stopping pre-stroke antihypertensive agents within 12 h on outcome after stroke:A subgroup analysis of the efficacy of nitric oxide in stroke (ENOS) trial

Author: Lisa J. Woodhouse, Jason P. Appleton, Polly Scutt, Lisa Everton, Gwenllian Wilkinson, Valeria Caso, Anna Czlonkowska, John Gommans, Kailash Krishnan, Ann C. Laska, George Ntaios, Serefnur Ozturk, Stephen Phillips, Stuart Pocock, Kameshwar Prasad, Szabolcs Szatmari, Joanna M. Wardlaw, Nikola Sprigg, and Philip M. Bath
Subjects: Medicine (General), R5-920, General Medicine, Articles
Abstract: Background: It is not known whether to continue or temporarily stop existing antihypertensive drugs in patients with acute stroke. Methods: We performed a prospective subgroup analysis of patients enrolled into the Efficacy of Nitric Oxide in Stroke (ENOS) trial who were randomised to continue vs stop prior antihypertensive therapy within 12 h of stroke onset. The primary outcome was functional outcome, assessed with the modified Rankin Scale at 90 days by observers blinded to treatment assignment, and analysed with ordinal logistic regression. Findings: Of 4011 patients recruited into ENOS from 2001 to 2014, 2097 patients were randomised to continue vs stop prior antihypertensive treatment, and 384 (18.3%, continue 185, stop 199) were enrolled within 12 h of ictus: mean (SD) age 71.8 (11.8) years, female 193 (50.3%), ischaemic stroke 342 (89.1%) and total anterior circulation syndrome 114 (29.7%). As compared with stopping, continuing treatment within 12 h of onset lowered blood pressure by 15.5/9.6 mmHg (p
Published: 2022

24. The role of non-coding RNAs in neuroinflammatory process in multiple sclerosis

Author: Anna Nowak, Zofia Wicik, Marta Wolska, Andleeb Shahzadi, Piotr Szwed, Joanna Jarosz-Popek, Jeffrey Palatini, Marek Postula, Anna Czlonkowska, Dagmara Mirowska-Guzel, and Ceren Eyileten
Subjects: Cellular and Molecular Neuroscience, MicroRNAs, Multiple Sclerosis, RNA, Untranslated, Neurology, Neuroscience (miscellaneous), Humans, RNA, Long Noncoding, Biomarkers
Abstract: Multiple sclerosis (MS) is a central nervous system chronic neuroinflammatory disease followed by neurodegeneration. The diagnosis is based on clinical presentation, cerebrospinal fluid testing and magnetic resonance imagining. There is still a lack of a diagnostic blood-based biomarker for MS. Due to the cost and difficulty of diagnosis, new and more easily accessible methods are being sought. New biomarkers should also allow for early diagnosis. Additionally, the treatment of MS should lead to the personalization of the therapy. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) as well as their target genes participate in pathophysiology processes in MS. Although the detailed mechanism of action of non-coding RNAs (ncRNAs, including miRNAs and lncRNAs) on neuroinflammation in MS has not been fully explained, several studies were conducted aiming to analyse their impact in MS. In this article, we review up-to-date knowledge on the latest research concerning the ncRNAs in MS and evaluate their role in neuroinflammation. We also point out the most promising ncRNAs which may be promising in MS as diagnostic and prognostic biomarkers.
Published: 2022

25. Rationale and design of the AXIOMATIC-SSP phase II trial : Antithrombotic treatment with factor XIa inhibition to Optimize Management of Acute Thromboembolic events for Secondary Stroke Prevention

Author: Mukul Sharma, Carlos A. Molina, Kazunori Toyoda, Daniel Bereczki, Scott E. Kasner, Helmi L. Lutsep, Georgios Tsivgoulis, George Ntaios, Anna Czlonkowska, Ashfaq Shuaib, Pierre Amarenco, Matthias Endres, Hans Christoph Diener, David Gailani, Anja Kahl, Mark Donovan, Vidya Perera, Danshi Li, Graeme J. Hankey, Institut Català de la Salut, [Sharma M] Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada. [Molina CA] Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Toyoda K] National Cerebral and Cardiovascular Center, Osaka, Japan. [Bereczki D] Semmelweis University, Budapest, Hungary. [Kasner SE] Hospital of the University of Pennsylvania, Philadelphia, PA, USA. [Lutsep HL] Oregon Health and Science University, Portland, OR, USA, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Malalties cerebrovasculars - Prevenció, Otros calificadores::Otros calificadores::/prevención & control [Otros calificadores], Cardiovascular Diseases::Vascular Diseases::Embolism and Thrombosis::Thromboembolism [DISEASES], Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Hematologic Agents::Anticoagulants [CHEMICALS AND DRUGS], Medizin, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Hemorrhage, enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::trastornos cerebrovasculares::accidente cerebrovascular [ENFERMEDADES], Other subheadings::Other subheadings::/drug therapy [Other subheadings], Factor XIa, Article, Other subheadings::Other subheadings::/prevention & control [Other subheadings], Double-Blind Method, Fibrinolytic Agents, Anticoagulants (Medicina) - Ús terapèutic, Thromboembolism, Tromboembolisme - Tractament, Secondary Prevention, Humans, Ischemic Stroke, Aspirin, Rehabilitation, enfermedades cardiovasculares::enfermedades vasculares::embolia y trombosis::tromboembolia [ENFERMEDADES], acciones y usos químicos::acciones farmacológicas::usos terapéuticos::fármacos hematológicos::anticoagulantes [COMPUESTOS QUÍMICOS Y DROGAS], Clopidogrel, Stroke, Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Cerebrovascular Disorders::Stroke [DISEASES], Treatment Outcome, Ischemic Attack, Transient, Surgery, Drug Therapy, Combination, Neurology (clinical), Cardiology and Cardiovascular Medicine, Platelet Aggregation Inhibitors
Abstract: MRI; Milvexian; Stroke prevention Resonancia magnética; Milvexian; Prevención de ictus Ressonància magnètica; Milvexian; Prevenció d'ictus Background Individuals with ischemic stroke or transient ischemic attack (TIA) have a high early risk of ischemic stroke despite dual antiplatelet therapy. The risk of ischemic stroke, and associated disability, represents a significant unmet clinical need. Genetic variants resulting in reduced factor XI levels are associated with reduced risk for ischemic stroke but are not associated with increased intracranial bleeding. Milvexian is an oral small-molecule inhibitor of FXIa that binds activated factor XI with high affinity and selectivity and may reduce the risk of stroke when added to antiplatelet drugs without significant bleeding. We aimed to evaluate the dose-response relationship of milvexian in participants treated with dual antiplatelets. Methods We began a phase II, double-blinded, randomized, placebo-controlled trial at 367 sites in 2019. Participants (N = 2366) with ischemic stroke (National Institutes of Health Stroke Scale score ≤7) or high-risk TIA (ABCD2 score ≥6) were randomized to 1 of 5 doses of milvexian or placebo for 90 days. Participants also received clopidogrel 75 mg daily for the first 21 days and aspirin 100 mg for 90 days. The efficacy endpoint was the composite of ischemic stroke or incident infarct on magnetic resonance imaging. Major bleeding, defined as type 3 or 5 bleeding according to the Bleeding Academic Research Consortium, was the safety endpoint. Participant follow-up will end in 2022. Conclusion The AXIOMATIC-SSP trial will evaluate the dose-response of milvexian for ischemic stroke occurrence in participants with ischemic stroke or TIA. This study is sponsored by Bristol Myers Squibb and Janssen Research & Development, LLC.
Published: 2022

26. Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events

Author: Thanh N Nguyen, Muhammad M Qureshi, Piers Klein, Hiroshi Yamagami, Robert Mikulik, Anna Czlonkowska, Mohamad Abdalkader, Petra Sedova, Anvitha Sathya, Hannah C Lo, Mahmoud H Mohammaden, Diogo C Haussen, Espen Saxhaug Kristoffersen, Virginia Pujol Lereis, Sergio Daniel Scollo, Bruce CV Campbell, Alice Ma, James Orton Thomas, Mark W Parsons, Shaloo Singhal, Lee-Anne Slater, Rodrigo Tomazini Martins, Chris Enzinger, Thomas Gattringer, Aminur Rahman, Thomas Bonnet, Noemie Ligot, Sylvie De Raedt, Robin Lemmens, Peter Vanacker, Fenne Vandervorst, Adriana Bastos Conforto, Raquel CT Hidalgo, Luciana de Oliveira Neves, Rodrigo Targa Martins, Daissy Liliana Mora Cuervo, Leticia C Rebello, Igor Bessa Santiago, Isabelle Lameirinhas da Silva, Teodora Sakelarova, Rosen Kalpachki, Filip Alexiev, Luciana Catanese, Elena Adela Cora, Mayank Goyal, Michael D Hill, Michael E Kelly, Houman Khosravani, Pascale Lavoie, Lissa Peeling, Aleksandra Pikula, Rodrigo Rivera, Hui-Sheng Chen, Yimin Chen, Xiaochuan Huo, Zhongrong Miao, Shuiquan Yang, Marina Roje Bedekovic, Marina Bralic, Hrvoje Budincevic, Angel Basilio Corredor- Quintero, Osvaldo E Lara-Sarabia, Martin Cabal, Dusan Tenora, Petr Fibrich, Roman Herzig, Helena Hlaváčová, Emanuela Hrabanovska, David Hlinovsky, Lubomir Jurak, Raul G. Nogueira, and the SVIN COVID-19 Global Stroke Registry
Subjects: Stroke, IV thrombolysis, COVID-19 pandemic
Abstract: Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).
Published: 2022

27. Clinical utility of non-ceruloplasmin copper determined by copper speciation for monitoring Wilson disease therapy: comparative data analysis with 24-hour urinary copper excretion from the CHELATE trial

Author: Michael Schilsky, Aurelia Poujois, Massimo Giovanni Zuin, Peter Ott, Karl Heinz Weiss, David Cassiman, Aftab Ala, Anna Czlonkowska, Nicolas Dubois, Naseem Amin, and C.Oma Kamlin
Subjects: Hepatology
Published: 2022

28. Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Author: Alison Halliday, Richard Bulbulia, Leo H Bonati, Johanna Chester, Andrea Cradduck-Bamford, Richard Peto, Hongchao Pan, John Potter, Hans Henning Eckstein, Barbara Farrell, Marcus Flather, Averil Mansfield, Boby Mihaylova, Kazim Rahimi, David Simpson, Dafydd Thomas, Peter Sandercock, Richard Gray, Andrew Molyneux, Cliff P Shearman, Peter Rothwell, Anna Belli, Will Herrington, Parminder Judge, Peter Leopold, Marion Mafham, Michael Gough, Piergiorgio Cao, Sumaira MacDonald, Vasha Bari, Clive Berry, S Bradshaw, Wojciech Brudlo, Alison Clarke, Robin Cox, Susan Fathers, Kamran Gaba, Mo Gray, Elizabeth Hayter, Constance Holliday, Rijo Kurien, Michael Lay, Steffi le Conte, Jessica McManus, Zahra Madgwick, Dylan Morris, Andrew Munday, Sandra Pickworth, Wiktor Ostasz, Michiel Poorthuis, Sue Richards, Louisa Teixeira, Sergey Tochlin, Lynda Tully, Carol Wallis, Monique Willet, Alan Young, Renato Casana, Chiara Malloggi, Andrea Odero Jr, Vincenzo Silani, Gianfranco Parati, Giuseppe Malchiodi, Giovanni Malferrari, Francesco Strozzi, Nicola Tusini, Enrico Vecchiati, Gioacchino Coppi, Antonio Lauricella, Roberto Moratto, Roberto Silingardi, Jessica Veronesi, Andrea Zini, Emanuele Ferrero, Michelangelo Ferri, Andrea Gaggiano, Carmelo Labate, Franco Nessi, Daniele Psacharopulo, Andrea Viazzo, Giovanni Malacrida, Daniela Mazzaccaro, Giovanni Meola, Alfredo Modafferi, Giovanni Nano, Maria Teresa Occhiuto, Paolo Righini, Silvia Stegher, Stefano Chiarandini, Filippo Griselli, Sandro Lepidi, Fabio Pozzi Mucelli, Marcello Naccarato, Mario D'Oria, Barbara Ziani, Andrea Stella, Mortalla Dieng, Gianluca Faggioli, Mauro Gargiulo, Sergio Palermo, Rodolfo Pini, Giovanni Maria Puddu, Andrea Vacirca, Domenico Angiletta, Claudio Desantis, Davide Marinazzo, Giovanni Mastrangelo, Guido Regina, Raffaele Pulli, Paolo Bianchi, Lea Cireni, Elisabetta Coppi, Rocco Pizzirusso, Filippo Scalise, Giovanni Sorropago, Valerio Tolva, Valeria Caso, Enrico Cieri, Paola DeRango, Luca Farchioni, Giacomo Isernia, Massimo Lenti, Gian Battista Parlani, Guglielmo Pupo, Grazia Pula, Gioele Simonte, Fabio Verzini, Federico Carimati, Maria Luisa Delodovici, Federico Fontana, Gabriele Piffaretti, Matteo Tozzi, Efrem Civilini, Giorgio Poletto, Bernhard Reimers, Barbara Praquin, Sonia Ronchey, Laura Capoccia, Wassim Mansour, Enrico Sbarigia, Francesco Speziale, Pasqualino Sirignano, Danilo Toni, Roberto Galeotti, Vincenzo Gasbarro, Francesco Mascoli, Tiberio Rocca, Elpiniki Tsolaki, Giulia Bernardini, Ester DeMarco, Alessia Giaquinta, Francesco Patti, Massimiliano Veroux, Pierfrancesco Veroux, Carla Virgilio, Nicola Mangialardi, Matteo Orrico, Vincenzo Di Lazzaro, Nunzio Montelione, Francesco Spinelli, Francesco Stilo, Carlo Cernetti, Sandro Irsara, Giuseppe Maccarrone, Diego Tonello, Adriana Visonà, Beniamino Zalunardo, Emiliano Chisci, Stefano Michelagnoli, Nicola Troisi, Maela Masato, Massimo Dei Negri, Andrea Pacchioni, Salvatore Saccà, Giovanni Amatucci, Alfredo Cannizzaro, Federico Accrocca, Cesare Ambrogi, Renzo Barbazza, Giustino Marcucci, Andrea Siani, Guido Bajardi, Giovanni Savettieri, Angelo Argentieri, Riccardo Corbetta, Attilio Odero, Pietro Quaretti, Federico Z Thyrion, Alessandro Cappelli, Domenico Benevento, Gianmarco De Donato, Maria Agnese Mele, Giancarlo Palasciano, Daniela Pieragalli, Alessandro Rossi, Carlo Setacci, Francesco Setacci, Domenico Palombo, Maria Cecilia Perfumo, Edoardo Martelli, Aldo Paolucci, Santi Trimarchi, Viviana Grassi, Luigi Grimaldi, Giuliana La Rosa, Domenico Mirabella, Matteo Scialabba, Leonildo Sichel, Costantino L D'Angelo, Gian Franco Fadda, Holta Kasemi, Mario Marino, Francesco Burzotta, Francesco Alberto Codispoti, Angela Ferrante, Giovanni Tinelli, Yamume Tshomba, Claudio Vincenzoni, Deborah Amis, Dawn Anderson, Martin Catterson, Mike Clarke, Michelle Davis, Anand Dixit, Alexander Dyker, Gary Ford, Ralph Jackson, Sreevalsan Kappadath, David Lambert, Tim Lees, Stephen Louw, James McCaslin, Noala Parr, Rebecca Robson, Gerard Stansby, Lucy Wales, Vera Wealleans, Lesley Wilson, Michael Wyatt, Hardeep Baht, Ibrahim Balogun, Ilse Burger, Tracy Cosier, Linda Cowie, Gunaratnam Gunathilagan, David Hargroves, Robert Insall, Sally Jones, Hannah Rudenko, Natasha Schumacher, Jawaharlal Senaratne, George Thomas, Audrey Thomson, Tom Webb, Ellen Brown, Bernard Esisi, Ali Mehrzad, Shane MacSweeney, Norman McConachie, Alison Southam, Wayne Sunman, Ahmed Abdul-Hamiq, Jenny Bryce, Ian Chetter, Duncan Ettles, Raghuram Lakshminarayan, Kim Mitchelson, Christopher Rhymes, Graham Robinson, Paul Scott, Alison Vickers, Ray Ashleigh, Stephen Butterfield, Ed Gamble, Jonathan Ghosh, Charles N McCollum, Mark Welch, Sarah Welsh, Leszek Wolowczyk, Mary Donnelly, Stephen D'Souza, Anselm A Egun, Bindu Gregary, Thomas Joseph, Christine Kelly, Shuja Punekar, M Asad Rahi, Sonia Raj, Dare Seriki, George Thomson, James Brown, Ragunath Durairajan, Iris Grunwald, Paul Guyler, Paula Harman, Matthew Jakeways, Christopher Khuoge, 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Parry, Gavin Young, Simon Ashley, James Barwell, Francis Dix, Azlisham M Nor, Chris Parry, Angela Birt, Paul Davies, Jim George, Anne Graham, Leon Jonker, Nicci Kelsall, Caroline Potts, Toni Wilson, Jamie Crinnion, Larissa Cuenoud, Nikola Aleksic, Srdan Babic, Nenad Ilijevski, Đorde Radak, Dragan Sagic, Slobodan Tanaskovic, Momcilo Colic, Vladimir Cvetic, Lazar Davidovic, Dejana R Jovanovic, Igor Koncar, Perica Mutavdžic, Miloš Sladojevic, Ivan Tomic, Eike S Debus, Ulrich Grzyska, Dagmar Otto, Götz Thomalla, Jessica Barlinn, Johannes Gerber, Kathrin Haase, Christian Hartmann, Stefan Ludwig, Volker Pütz, Christian Reeps, Christine Schmidt, Norbert Weiss, Sebastian Werth, Simon Winzer, Janine Gemper, Albrecht Günther, Bianka Heiling, Elisabeth Jochmann, Panagiota Karvouniari, Carsten Klingner, Thomas Mayer, Julia Schubert, Friederike Schulze-Hartung, Jürgen Zanow, Yvonne Bausback, Franka Borger, Spiridon Botsios, Daniela Branzan, Sven Bräunlich, Henryk Hölzer, Janin Lenzer, Christopher 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Tusini N., Vecchiati E., Coppi G., Lauricella A., Moratto R., Silingardi R., Veronesi J., Zini A., Ferrero E., Ferri M., Gaggiano A., Labate C., Nessi F., Psacharopulo D., Viazzo A., Malacrida G., Mazzaccaro D., Meola G., Modafferi A., Nano G., Occhiuto M.T., Righini P., Stegher S., Chiarandini S., Griselli F., Lepidi S., Pozzi Mucelli F., Naccarato M., D'Oria M., Ziani B., Stella A., Dieng M., Faggioli G., Gargiulo M., Palermo S., Pini R., Puddu G.M., Vacirca A., Angiletta D., Desantis C., Marinazzo D., Mastrangelo G., Regina G., Pulli R., Bianchi P., Cireni L., Coppi E., Pizzirusso R., Scalise F., Sorropago G., Tolva V., Caso V., Cieri E., DeRango P., Farchioni L., Isernia G., Lenti M., Parlani G.B., Pupo G., Pula G., Simonte G., Verzini F., Carimati F., Delodovici M.L., Fontana F., Piffaretti G., Tozzi M., Civilini E., Poletto G., Reimers B., Praquin B., Ronchey S., Capoccia L., Mansour W., Sbarigia E., Speziale F., Sirignano P., Toni D., Galeotti R., Gasbarro V., Mascoli F., Rocca 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M., Szostek M., Andziak P., Dratwicki M., Gil R., Nowicki M., Pniewski J., Rzezak J., Seweryniak P., Dabek P., Juszynski M., Madycki G., Pacewski B., Raciborski W., Slowinski P., Staszkiewicz W., Bombic M., Chlouba V., Fiedler J., Hes K., Kostal P., Sova J., Kriz Z., Privara M., Reif M., Staffa R., Vlachovsky R., Vojtisek B., Hrbac T., Kuliha M., Prochazka V., Roubec M., Skoloudik D., Netuka D., Steklacova A., Benes III V., Buchvald P., Endrych L., Sercl M., Campos W., Casella I.B., de Luccia N., Estenssoro A.E.V., Presti C., Puech-Leao P., Neves C.R.B., da Silva E.S., Sitrangulo C.J., Monteiro J.A.T., Tinone G., Bellini Dalio M., Joviliano E.E., Pontes Neto O.M., Serra Ribeiro M., Cras P., Hendriks J.M.H., Hoppenbrouwers M., Lauwers P., Loos C., Yperzeele L., Geenens M., Hemelsoet D., van Herzeele I., Vermassen F., Astarci P., Hammer F., Lacroix V., Peeters A., Verhelst R., Cirelli S., Dormal P., Grimonprez A., Lambrecht B., Lerut P., Thues E., De Koster G., Desiron Q., Maertens de Noordhout A., Malmendier D., Massoz M., Saad G., Bosiers M., Callaert J., Deloose K., Blanco Canibano E., Garcia Fresnillo B., Guerra Requena M., Morata Barrado P.C., Muela Mendez M., Yusta Izquierdo A., Aparici Robles F., Blanes Orti P., Garcia Dominguez L., Martinez Lopez R., Miralles Hernandez M., Tembl Ferrairo J.I., Chamorro A., Macho J., Obach V., Riambau V., San Roman L., Ahlhelm F.J., Blackham K., Engelter S., Eugster T., Gensicke H., Gurke L., Lyrer P., Mariani L., Maurer M., Mujagic E., Muller M., Psychogios M., Stierli P., Stippich C., Traenka C., Wolff T., Wagner B., Wiegert M.M., Clarke S., Diepers M., Grochenig E., Gruber P., Isaak A., Kahles T., Marti R., Nedeltchev K., Remonda L., Tissira N., Valenca Falcao M., de Borst G.J., Lo R.H., Moll F.L., Toorop R., van der Worp B.H., Vonken E.J., Kappelle J.L., Jahrome O., Vos F., Schuiling W., van Overhagen H., Keunen R.W.M., Knippenberg B., Wever J.J., Lardenoije J.W., Reijnen M., Smeets L., van Sterkenburg S., Fraedrich G., Gizewski E., Gruber I., Knoflach M., Kiechl S., Rantner B., Abdulamit T., Bergeron P., Padovani R., Trastour J.-C., Cardon J.-M., Le Gallou-Wittenberg A., Allaire E., Becquemin J.-P., Cochennec-Paliwoda F., Desgranges P., Hosseini H., Kobeiter H., Marzelle J., Almekhlafi M.A., Bal S., Barber P.A., Coutts S.B., Demchuk A.M., Eesa M., Gillies M., Goyal M., Hill M.D., Hudon M.E., Jambula A., Kenney C., Klein G., McClelland M., Mitha A., Menon B.K., Morrish W.F., Peters S., Ryckborst K.J., Samis G., Save S., Smith E.E., Stys P., Subramaniam S., Sutherland G.R., Watson T., Wong J.H., Zimmel L., Flis V., Matela J., Miksic K., Milotic F., Mrdja B., Stirn B., Tetickovic E., Gasparini M., Grad A., Kompara I., Milosevic Z., Palmiste V., Toomsoo T., Aidashova B., Kospanov N., Lyssenko R., Mussagaliev D., Beyar R., Hoffman A., Karram T., Kerner A., Nikolsky E., Nitecki S., Andonova S., Bachvarov C., Petrov V., Cvjetko I., Vidjak V., Haluzan D., Petrunic M., Liu B., Liu C.-W., Bartko D., Beno P., Rusnak F., Zelenak K., Ezura M., Inoue T., Kimura N., Kondo R., Matsumoto Y., Shimizu H., Endo H., Furui E., Bakke S., Krohg-Sorensen K., Nome T., Skjelland M., Tennoe B., Albuquerque e Castro J., Alves G., Bastos Goncalves F., de Aragao Morais J., Garcia A.C., Valentim H., Vasconcelos L., Belcastro F., Cura F., Zaefferer P., Abd-Allah F., Eldessoki M.H., Heshmat Kassem H., Soliman Gharieb H., Colgan M.P., Haider S.N., Harbison J., Madhavan P., Moore D., Shanik G., Kazan V., Nazzal M., Ramsey-Williams V., and Gargiulo M
Subjects: Male, medicine.medical_specialty, Time Factors, Time Factor, medicine.medical_treatment, Carotid Stenosi, MEDLINE, Carotid endarterectomy, Rate ratio, Risk Assessment, Asymptomatic, law.invention, Randomized controlled trial, law, Risk Factors, carotid artery stenting (CAS), carotid endarterectomy (CEA), Stent, medicine, Humans, Carotid Stenosis, Stroke, Endarterectomy, Aged, Endarterectomy, Carotid, business.industry, carotid artery, Risk Factor, Articles, General Medicine, trial, medicine.disease, Settore MED/22 - CHIRURGIA VASCOLARE, Surgery, Stenosis, Treatment Outcome, Settore MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, Female, Stents, Human medicine, medicine.symptom, business, Human
Abstract: Summary Background Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding UK Medical Research Council and Health Technology Assessment Programme.
Published: 2021

29. Sphenopalatine Ganglion Stimulation to Augment Cerebral Blood Flow

Author: Natan M. Bornstein, Jeffrey L. Saver, Hans-Christoph Diener, Philip B. Gorelick, Ashfaq Shuaib, Yoram Solberg, Thomas Devlin, Thomas Leung, Carlos A. Molina, David Skoloudik, Jan Fiksa, Derk Krieger, Grethe Andersen, Joerg Berrouschot, Carsten Hobohm, Dietmar Schneider, Bernd Griewing, Matthias Endres, Karl-Georg Hausler, Hubert Kimmig, Peter Ringleb, Christian Weimar, Matthias Schilling, Martin Kohrmann, Andreas Hetzel, Manfred Kaps, Raymond Cheung, Piotr Sobolewski, Walenty Nyke, Anna Czlonkowska, Adam Stepien, Brola Waldemar, Agnieszka Słowik, Stelmasiakiem Zbigniewem, Ignacy Lubiński, Pedro Portela, Tomas Segure, Joan Marti-Fabregas, Maria Alonso, Antonio Nunez, Miguel Blanco Miguel, Anna Campello, Joaquin Arenillas, Nash Marshall, David Chiu, Harish Shownkeen, Marilyn Rymer, Souvik Sen, Martin Roubec, Martin Kuliha, Ctirad Lakomý, David Tyl, David Kemlink, Ondřej Doležal, Petra Rekova, Veronika Krejčí, Anders Christensen, Bo Belhage, Christian Maschmann, Christian Kruse Larsen, Frank Pott, Hanne Christensen, Jakob Marstrand, Jens Kjellberg Nielsen, Per Meden, Svend Prytz, Sverre Rosenbaum, Jens Christian Hedemann Sorensen, Kaare Stenhoj Meier, Kare Schmift Ettrup, Kristina Dupont Hougaard, Paul Von Wietzel, Anett Stoll, Hans Schwetlick, Hendirk Pradel, Alexander Hemprich, Andreas Schulz, Bernhard Frerich, Christopher Weise, Dominik Michalski, Felix Schaller, Franziska Schiefke, Jens Helmrich, Johann Pelz, Martin Schnieder, Martin Schneider, Peter Matzen, Rudiger Langos, Stephan Müller-Duerwald, Sven Lukhaup, Ute Bauer, Wolfgang Kloppig, Erich Hiermann, Gregor Mucha, Hassan Soda, Renate Weinhardt, Teresa Mucha, Volker Ziegler, Alexander Abbushi, Benjamin Hotter, Benjamin Winter, Birgit Anthofer, Cornelia Noack, Dinah Laubisch, Gerd Heldge Schneider, Gerhard Jan Jungehulsing, Heiko Mueller, Jens Dreier, Jochen Fiebach, Julia Flechsenhar, Kersten Villringer, Martin Ebinger, Michael Rozanski, Peter Vajkoczy, Randolf Klingebiel, Robert Steinicke, Sandra Pittl, Sarah Hoffmann, Stephan Maul, Thomas Krause, Thomas Liman, Thomas Plath, Tim Nowe, Wolf Schmidt, Carsten Fritzsch, Christopher Haas, Hans-Gerd Will, Katja Haußmann-Betz, Mohsen Bayat, Tomazs Pordzik, Andreas Hug, Christian Jürgen Staff, Christoph Lichy, Georg Eggers, Manja Kloss, Martin Bendszus, Oliver Herrmann, Robin Seeberger, Soenke Schwarting, Stefan Rhode, Timolaos Rizos, Werner Hacke, Benedikt Frank, Bessi Bozkurt, Dagny Holle, Daniel Mueller, Dirk Koch, Hind Shanib, Joachim Sudendey, Johannes Brenck, Kolja Busch, Kristina Gartzen, Thomas Gasser, Tim Hagenacker, Boris Buerke, Gudrun Prigge, Jens Minnerup, Johannes Albers, Kai Wermker, Wolfram Schwindt, Ringlestein, Bernd Kallmünzer, Eva Hauer, Lorenz Breuer, Peter Schellinger, Rainer Kollmar, Roland Sauer, Stefan Schwab, Tobias Struffert, Anette Funfack, Anne Stechmann, Axel Schlaeger, Claus Laeppchen, Florian Schuchardt, Jan-Helge Klingler, Janine Reis, Johann Lambeck, Mirko Friedrich, Mona Laible, Philip Wellermeyer, Sandra Beck, Sebastian Rutsch, Wolf-Dirk Niesen, Christian Tanislav, Heidrun Schaaf, Heiko Kerkmann, Ingo Schirotzek, Jens Allendörfer, Stephanie Wolff, Alexander Yuk-Lun Lau, Anne Yin Yan Chan, Deyond Siu, Edward HC Wong, George Kwok Chu Wong, Howan Leung, Lawrence K.S. Wong, Xian Lun Zhu, Yannie Oi Yan Soo, Alan Choi Ting Tse, Gilberto Ka Kit Leung, Kar Ming Leung, Kwan Ngai Hung, May Wai Mei Kwan, Mona Man Yu Tse, Philip Tse, Ping Hon Chan, Raymand Lee, Richard Shek Kwan Chang, Shirley Yin Yu Pang, Sonny Fong Kwong Hon, Tat Sun Cheng, Wai Man Lui, Windsor Wai Wo Mak, Anna Sobota, Baeta Wiater, Barbara Loch, Genowefa Wolak, Irena Łabudzka, Jan Dabal, Marcin Grzesik, Monika Sledzinska, Renata Hatalska-Żerebiec, Wiktor Szczuchniak, Anna Gójska, Dariusz Nałęcz, Dariusz Gasecki, Grzegorz Kozera, Łukasz Dylewicz, Marcin Niekra, Mariusz Kwarciany, Piotr Chomik, Piotr Skowron, Adam Kobayashi, Grzegorz Chabik, Grzegorz Makowicz, Jan Bembenek, Julia Jędrzejewska, Michal Karlinski, Wojciech Czepiel, Bogdan Brodacki, Jacek Staszewski, Jarosław Kosek, Marcin Jadczak, Marta Durka-Kęsy, Krzysztof Kaluzny, Małgorzata Ziomek, Małgorzata Fudala, Zbigniew Sosnowski, Antoni Ferens, Elżbieta Szczygieł, Krzysztof Banaszkiewicz, Maciej Ziomek, Marcin Wnuk, Anna Szczepańska-Szerej, Ewa Jach, Grazyna Elzbieta Maslanko, Joanna Wojczal, Piotr Luchowski, Andrzej Kowalczyk, Jerzy Jakubiak, Joanna Kopcewicz, Maciej Gajda, Malgorzata Wichlinska-Lubinska, David Rodriguez, Estevo Santamarin, Jorge Pagola, Juan Lorente Guerrero, Marc Ribo, Marta Rubiera, Olga Maisterra, Soccoro Pinero, Valera Catalina Iglesias, Gerard Plans, Helena Quesada, Marco Alberto Aparicio Caballero, Pedro Cardona Portela, Antonio Belinchon De Diego, David Sopelana Garay, Máximo Rafael García Rodriguez, Oscar Ayo Martin, Silvia Crusat Braña, Jorge Garcia, Fernando Munoz Hernandez, Ignasi Catala, Josep Lluis Marti-Vilalta, Rachel Delgado Mederos, Schmid Cristian de Quintana, Sergi Martinez-Ramirez, Jaime Valcarcel Gonzalez, Jaime Masjuan Vallejo, Jorge Diamantopoulus, Marta Del Alamo, Pedro Domingo Poveda, Andres Garcia Pastor, Calros Fernandez Carballal, Fernando Diaz, Roberto Garcia Leal, Ruiz Juretschke, Eduardo Arán Echabe, Jose Castillo Sanchez, Manuel Rodriguez Yanez, Ramon Serramito Garcia, Rogelio Leira Muino, Susana Arias Rivas, Demian Manzano Lopez Gonzalez, Elisa Cuadrado, Eva Giralt, Gloria Villalba, Jaime Roquer, Ois Angel, Maria Jimenez, René Robles Cedeño, Ruy Salinas, Saioa Lejarreta, Yolanda Silva, Adela Fraile, Ana Calleja, Guillermo Arturo Cepeda Landínez, Nieves Tellez, Pablo Garcia Bermejo, Pérez Jaime Santos, Rosa Fernandez Herranz, Peter Hunt, Donald Browning, Michael Violette, Robert Hoddeson, James Rose, Jonathan Zhang, Avi Mazumdar, Henri Echiverri, James Chow, Darren Lovick, Martin Coleman, Naveed Akhtar, Rebecca Sugg, Adam Zanation, Anand Germanwala, Brent Senior, David Huang, Natalie Aucutt-Walter, Scott Kasner, Peter LeRoux, Rüdiger von Kummer, and Yuko Palesch
Subjects: Advanced and Specialized Nursing, medicine.medical_specialty, business.industry, medicine.medical_treatment, Medizin, Vasodilation, Stimulation, Thrombolysis, Blood–brain barrier, Collateral circulation, Ganglion, medicine.anatomical_structure, Cerebral blood flow, Internal medicine, medicine, Cardiology, Neurology (clinical), Augment, Cardiology and Cardiovascular Medicine, business
Abstract: Background and Purpose— Many patients with acute ischemic stroke are not eligible for thrombolysis or mechanical reperfusion therapies due to contraindications, inaccessible vascular occlusions, late presentation, or large infarct core. Sphenopalatine ganglion (SPG) stimulation to enhance collateral flow and stabilize the blood-brain barrier offers an alternative, potentially more widely deliverable, therapy. Methods— In a randomized, sham-controlled, double-masked trial at 41 centers in 7 countries, patients with anterior circulation ischemic stroke not treated with reperfusion therapies within 24 hours of onset were randomly allocated to active SPG stimulation or sham control. The primary efficacy outcome was improvement beyond expectations on the modified Rankin Scale of global disability at 90 days (sliding dichotomy), assessed in the modified intention-to-treat population. The initial planned sample size was 660 patients, but the trial was stopped early when technical improvements in device placement occurred, so that analysis of accumulated experience could be conducted to inform a successor trial. Results— Among 303 enrolled patients, 253 received at least one active SPG or sham stimulation, constituting the modified intention-to-treat population (153 SPG stimulation and 100 sham control). Age was median 73 years (interquartile range, 64–79), 52.6% were female, deficit severity on the National Institutes of Health Stroke Scale was median 11 (interquartile range, 9–15), and time from last known well median 18.6 hours (interquartile range, 14.5–22.5). For the primary outcome, improved 3-month disability beyond expectations, rates in the SPG versus sham treatment groups were 49.7% versus 40.0%; odds ratio, 1.48 (95% CI, 0.89–2.47); P =0.13. A significant treatment interaction with stroke location (cortical versus noncortical) was noted, P =0.04. In the 87 patients with confirmed cortical involvement, rates of improvement beyond expectations were 50.0% versus 27.0%; odds ratio, 2.70 (95% CI, 1.08–6.73); P =0.03. Similar response patterns were observed for all prespecified secondary efficacy outcomes. No differences in mortality or serious adverse event safety end points were observed. Conclusions— SPG stimulation within 24 hours of onset is safe in acute ischemic stroke. SPG stimulation was not shown to statistically significantly improve 3-month disability above expectations, though favorable outcomes were nominally higher with SPG stimulation. Beneficial effects may distinctively be conferred in patients with confirmed cortical involvement. The results of this study need to be confirmed in a larger pivotal study. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT03767192.
Published: 2019

30. Efficacy and safety of ALXN1840 versus standard of care in Wilson disease: primary results from an ongoing phase 3, randomized, controlled, rater-blinded trial

Author: Karl Heinz Weiss, Michael Schilsky, Anna Czlonkowska, Fred Askari, Aftab Ala, Peter Ferenci, Peter Ott, Dzhamal Abdurakhmanov, Ferenc Szalay, Piotr Socha, Norikazu Shimizu, Jeff Bronstein, Danny Bega, Sihoun Hahn, Eugene Swenson, Yi Chen, and Aurelia Poujois
Subjects: Hepatology
Published: 2022

31. 163 Long-term safety of adjunctive cenobamate in patients with uncontrolled focal seizures

Author: Irene Garcia Morales, Martin J Brodie, Ivan Milanov, Anna Czlonkowska, Christian Brandt, Lee Fin- lan, Elena Alvarez-Baron, and Bernhard J Steinhoff
Subjects: Psychiatry and Mental health, Surgery, Neurology (clinical)
Abstract: PurposeResults from two double-blind, placebo-controlled studies demonstrated that adjunctive ceno- bamate significantly reduced the frequency of seizures vs placebo. Cenobamate 200mg/day achieved seizure freedom in 28.3% vs 8.8% placebo (PMethodsAdults with uncontrolled FOS were enrolled in two double-blind, placebo-controlled studies. Patients completing both double-blinded phases were invited to participate in OLE studies (n=504).ResultsAs of July 2019, 58.3% of the patients who entered the OLEs, continued; at baseline, median age was 38 years, and 86.5% were taking ≥2 concomitant AEDs. Median (range) length of exposure was 237 weeks (1–407). The most frequent TEAEs (≥10%) were dizziness (33.9%), somnolence (23.6%), headache (18.7%), fatigue (14.3%), diplopia (12.9%) and upper respiratory tract infections (12.3%). Most TEAEs were mild or moderate (78%). 22% experienced SAEs of which only seizure exceeded 1% (n=11). Discontinu- ations were due to TEAE (8%), withdrawal by patient (12%), lack of efficacy (12%), other (4%). No cases of DRESS were reported.ConclusionsLong-term adjunctive cenobamate treatment (up to 94 months) is generally well tolerated. Most TEAEs were CNS-related and consistent with those shown in the two double-blind studies.lee.finlan@arvelletx.com
Published: 2022

32. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study

Author: Ludwig Kappos, Amit Bar-Or, Bruce A C Cree, Robert J Fox, Gavin Giovannoni, Ralf Gold, Patrick Vermersch, Douglas L Arnold, Sophie Arnould, Tatiana Scherz, Christian Wolf, Erik Wallström, Frank Dahlke, Anat Achiron, Lutz Achtnichts, Kadriye Agan, Gulsen Akman-Demir, Alison B Allen, Jack P Antel, Alfredo Rodriguez Antiguedad, Michelle Apperson, Angela M Applebee, Guillermo Izquierdo Ayuso, Masayuki Baba, Ovidiu Bajenaru, Rodica Balasa, Belgin Petek Balci, Michael Barnett, Ann Bass, Veit U Becker, Mihaela Bejinariu, Florian Then Bergh, Arnfin Bergmann, Evanthia Bernitsas, Achim Berthele, Virender Bhan, Felix Bischof, Randall John Bjork, Gregg Blevins, Matthias Boehringer, Thomas Boerner, Robert Bonek, James D Bowen, Allen Bowling, Alexey N Boyko, Cavit Boz, Vera Bracknies, Stefan Braune, Vincenzo Brescia Morra, Bruno Brochet, Waldemar Brola, Paul Kenneth Brownstone, Miroslav Brozman, Donald Brunet, Ioan Buraga, Margaret Burnett, Mathias Buttmann, Helmut Butzkueven, Jonathan Cahill, Jonathan C Calkwood, William Camu, Mark Cascione, Giovani Castelnovo, Diego Centonze, Joao Cerqueira, Andrew Chan, Andrea Cimprichova, Stanley Cohan, Giancarlo Comi, Jill Conway, Joanna A Cooper, John Corboy, Jorge Correale, Brian Costell, David A Cottrell, Patricia K Coyle, Matthew Craner, Liying Cui, Luis Cunha, Anna Czlonkowska, Ana Martins da Silva, Joao de Sa, Jérôme de Seze, Marc Debouverie, Jan Debruyne, Danny Decoo, Gilles Defer, Tobias Derfuss, Norma H Deri, Bhupesh Dihenia, Peter Dioszeghy, Vladimir Donath, Benedicte Dubois, Martin Duddy, Pierre Duquette, Gilles Edan, Husnu Efendi, Stanton Elias, Peter J Emrich, Bonaventura Casanova Estruch, Evgeniy P Evdoshenko, Juergen Faiss, Alexander S Fedyanin, Wolfgang Feneberg, Jiske Fermont, Oscar Fernandez Fernandez, Francisco Coret Ferrer, Katharina Fink, Helen Ford, Corey Ford, Ada Francia, Mark Freedman, Benjamin Frishberg, Simonetta Galgani, George P Garmany, Klaus Gehring, Jeffrey Gitt, Claudio Gobbi, Lawrence P Goldstick, Rafael Arroyo Gonzalez, Francois Grandmaison, Nikolaos Grigoriadis, Olga Grigorova, Luigi Maria Edoardo Grimaldi, Jeffrey Gross, Katrin Gross-Paju, Mark Gudesblatt, Daniel Guillaume, Judith Haas, Viera Hancinova, Anca Hancu, Orla Hardiman, Arndt Harmjanz, Fedor R Heidenreich, G J D Hengstman, Joseph Herbert, Mark Herring, Suzanne Hodgkinson, Olaf M Hoffmann, Werner E Hofmann, William D Honeycutt, Le Hanh Hua, Dehui Huang, Yining Huang, DeRen Huang, Raymond Hupperts, Piroska Imre, Alan Keith Jacobs, Gabor Jakab, Elzbieta Jasinska, Kenichi Kaida, Jolanta Kalnina, Ara Kaprelyan, Guntis Karelis, Dimitrios Karussis, Amos Katz, Farit A Khabirov, Bhupendra Khatri, Takashi Kimura, Ilya Kister, Rasa Kizlaitiene, Eleonora Klimova, Juergen Koehler, Aparna Komatineni, Anselm Kornhuber, Krisztina Kovacs, Agnes Koves, Wojciech Kozubski, Georgi Krastev, Lauren B Krupp, Egon Kurca, Christoph Lassek, Guy Laureys, Liesly Lee, Eckart Lensch, Fritz Leutmezer, Hongzeng Li, Ralf A Linker, Michael Linnebank, Petra Liskova, Cristina Llanera, Jiahong Lu, Andreas Lutterotti, Jan Lycke, Richard Macdonell, Maciej Maciejowski, Mathias Maeurer, Rim V Magzhanov, Eva-Maria Maida, Lina Malciene, Yang Mao-Draayer, Girolama Alessandra Marfia, Clyde Markowitz, Vasileios Mastorodimos, Klotild Matyas, Jose Meca-Lallana, Juan Antonio Garcia Merino, Ioan Gheorghe Mihetiu, Ivan Milanov, Aaron E Miller, Andrejs Millers, Massimiliano Mirabella, Masanori Mizuno, Xavier Montalban, Lilina Montoya, Masahiro Mori, Stefanie Mueller, Jin Nakahara, Yuji Nakatsuji, Scott Newsome, Richard Nicholas, A Scott Nielsen, Esmaeil Nikfekr, Ugo Nocentini, Chiyoko Nohara, Kyoichi Nomura, Miroslav M Odinak, Tomas Olsson, B W van Oosten, Celia Oreja-Guevara, Patrick Oschmann, James Overell, Andrew Pachner, Gyula Panczel, Massimo Pandolfo, Caroline Papeix, Liliana Patrucco, Jean Pelletier, Raul Piedrabuena, Misha Pless, Udo Polzer, Krisztian Pozsegovits, Daiva Rastenyte, Sebastian Rauer, Gerd Reifschneider, Roberto Rey, Syed A Rizvi, Derrick Robertson, Jose Martinez Rodriguez, David Rog, Homayoun Roshanisefat, Vernon Rowe, Csilla Rozsa, Susan Rubin, Stanislaw Rusek, Francesco Saccà, Takahiko Saida, Antonio Vasco Salgado, Victoria Eugenia Fernandez Sanchez, Kalina Sanders, Maria Satori, Denis V Sazonov, Elio Angelo Scarpini, Eugen Schlegel, Myriam Schluep, Stephan Schmidt, Erich Scholz, H M Schrijver, Matthias Schwab, Raymond Schwartz, James Scott, Krzysztof Selmaj, Stuart Shafer, Basil Sharrack, Ivan A Shchukin, Yuko Shimizu, Penko Shotekov, Arno Siever, Karl-Otto Sigel, Scott Silliman, Magdolna Simo, Mihaela Simu, Vladimiro Sinay, Antonio Escartin Siquier, Aksel Siva, Ondrej Skoda, Andrew Solomon, Martin Stangel, Dusan Stefoski, Brian Steingo, Igor D Stolyarov, Pavel Stourac, Katrin Strassburger-Krogias, Erik Strauss, Olaf Stuve, Ivaylo Tarnev, Antonios Tavernarakis, Cristina Ramo Tello, Murat Terzi, Veronika Ticha, Marina Ticmeanu, Klaus Tiel-Wilck, Toomas Toomsoo, Niall Tubridy, Mark J Tullman, Hayrettin Tumani, Peter Turcani, Ben Turner, Antonio Uccelli, Francisco Javier Olascoaga Urtaza, Marta Vachova, Attila Valikovics, Silke Walter, Bart Van Wijmeersch, Ludo Vanopdenbosch, Joerg R Weber, Sara Weiss, Robert Weissert, Timothy West, Heinz Wiendl, Sandrine Wiertlewski, Brigitte Wildemann, Barbara Willekens, L H Visser, Galina Vorobeychik, Xianhao Xu, Takashi Yamamura, Yi N Yang, Sergio Martinez Yelamos, Michael Yeung, Alan Zacharias, Marvin Zelkowitz, Uwe Zettl, Meini Zhang, Hongyu Zhou, Ulf Zieman, Tjalf Ziemssen, Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, Biomedicine, and Biomedical Engineering, University Hospital, University of Basel, Basel, Center for Neuroinflammation and Neurotherapeutics, and Multiple Sclerosis Division, Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, Neuroimmunology Unit, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, UCSF Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, Mellen Centre for Multiple Sclerosis Treatment and Research, Neurological Institute, Cleveland Clinic, Cleveland, OH, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, Department of Neurology St. Josef-Hospital, Ruhr University Bochum, Germany, Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Montreal Neurological Institute, McGill University, Montreal, QC, Canada, NeuroRx Research, Montreal, QC, Novartis Pharma AG, Lycalis, Brussels, AP-HM, CHU Timone, Pole de Neurosciences Cliniques, Department of Neurology, Marseille, France., Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM] (CEMEREM), Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Kappos, Ludwig, Bar-Or, Amit, Cree, Bruce A C, Fox, Robert J, Giovannoni, Gavin, Gold, Ralf, Vermersch, Patrick, Arnold, Douglas L, Arnould, Sophie, Scherz, Tatiana, Wolf, Christian, Wallström, Erik, Dahlke, Frank, Achiron, Anat, Achtnichts, Lutz, Agan, Kadriye, Akman-Demir, Gulsen, Allen, Alison B, Antel, Jack P, Antiguedad, Alfredo Rodriguez, Apperson, Michelle, Applebee, Angela M, Ayuso, Guillermo Izquierdo, Baba, Masayuki, Bajenaru, Ovidiu, Balasa, Rodica, Balci, Belgin Petek, Barnett, Michael, Bass, Ann, Becker, Veit U, Bejinariu, Mihaela, Bergh, Florian Then, Bergmann, Arnfin, Bernitsas, Evanthia, Berthele, Achim, Bhan, Virender, Bischof, Felix, Bjork, Randall John, Blevins, Gregg, Boehringer, Matthia, Boerner, Thoma, Bonek, Robert, Bowen, James D, Bowling, Allen, Boyko, Alexey N, Boz, Cavit, Bracknies, Vera, Braune, Stefan, Brescia Morra, Vincenzo, Brochet, Bruno, Brola, Waldemar, Brownstone, Paul Kenneth, Brozman, Miroslav, Brunet, Donald, Buraga, Ioan, Burnett, Margaret, Buttmann, Mathia, Butzkueven, Helmut, Cahill, Jonathan, Calkwood, Jonathan C, Camu, William, Cascione, Mark, Castelnovo, Giovani, Centonze, Diego, Cerqueira, Joao, Chan, Andrew, Cimprichova, Andrea, Cohan, Stanley, Comi, Giancarlo, Conway, Jill, Cooper, Joanna A, Corboy, John, Correale, Jorge, Costell, Brian, Cottrell, David A, Coyle, Patricia K, Craner, Matthew, Cui, Liying, Cunha, Lui, Czlonkowska, Anna, da Silva, Ana Martin, de Sa, Joao, de Seze, Jérôme, Debouverie, Marc, Debruyne, Jan, Decoo, Danny, Defer, Gille, Derfuss, Tobia, Deri, Norma H, Dihenia, Bhupesh, Dioszeghy, Peter, Donath, Vladimir, Dubois, Benedicte, Duddy, Martin, Duquette, Pierre, Edan, Gille, Efendi, Husnu, Elias, Stanton, Emrich, Peter J, Estruch, Bonaventura Casanova, Evdoshenko, Evgeniy P, Faiss, Juergen, Fedyanin, Alexander S, Feneberg, Wolfgang, Fermont, Jiske, Fernandez, Oscar Fernandez, Ferrer, Francisco Coret, Fink, Katharina, Ford, Helen, Ford, Corey, Francia, Ada, Freedman, Mark, Frishberg, Benjamin, Galgani, Simonetta, Garmany, George P, Gehring, Klau, Gitt, Jeffrey, Gobbi, Claudio, Goldstick, Lawrence P, Gonzalez, Rafael Arroyo, Grandmaison, Francoi, Grigoriadis, Nikolao, Grigorova, Olga, Grimaldi, Luigi Maria Edoardo, Gross, Jeffrey, Gross-Paju, Katrin, Gudesblatt, Mark, Guillaume, Daniel, Haas, Judith, Hancinova, Viera, Hancu, Anca, Hardiman, Orla, Harmjanz, Arndt, Heidenreich, Fedor R, Hengstman, G J D, Herbert, Joseph, Herring, Mark, Hodgkinson, Suzanne, Hoffmann, Olaf M, Hofmann, Werner E, Honeycutt, William D, Hua, Le Hanh, Huang, Dehui, Huang, Yining, Huang, Deren, Hupperts, Raymond, Imre, Piroska, Jacobs, Alan Keith, Jakab, Gabor, Jasinska, Elzbieta, Kaida, Kenichi, Kalnina, Jolanta, Kaprelyan, Ara, Karelis, Gunti, Karussis, Dimitrio, Katz, Amo, Khabirov, Farit A, Khatri, Bhupendra, Kimura, Takashi, Kister, Ilya, Kizlaitiene, Rasa, Klimova, Eleonora, Koehler, Juergen, Komatineni, Aparna, Kornhuber, Anselm, Kovacs, Krisztina, Koves, Agne, Kozubski, Wojciech, Krastev, Georgi, Krupp, Lauren B, Kurca, Egon, Lassek, Christoph, Laureys, Guy, Lee, Liesly, Lensch, Eckart, Leutmezer, Fritz, Li, Hongzeng, Linker, Ralf A, Linnebank, Michael, Liskova, Petra, Llanera, Cristina, Lu, Jiahong, Lutterotti, Andrea, Lycke, Jan, Macdonell, Richard, Maciejowski, Maciej, Maeurer, Mathia, Magzhanov, Rim V, Maida, Eva-Maria, Malciene, Lina, Mao-Draayer, Yang, Marfia, Girolama Alessandra, Markowitz, Clyde, Mastorodimos, Vasileio, Matyas, Klotild, Meca-Lallana, Jose, Merino, Juan Antonio Garcia, Mihetiu, Ioan Gheorghe, Milanov, Ivan, Miller, Aaron E, Millers, Andrej, Mirabella, Massimiliano, Mizuno, Masanori, Montalban, Xavier, Montoya, Lilina, Mori, Masahiro, Mueller, Stefanie, Nakahara, Jin, Nakatsuji, Yuji, Newsome, Scott, Nicholas, Richard, Nielsen, A Scott, Nikfekr, Esmaeil, Nocentini, Ugo, Nohara, Chiyoko, Nomura, Kyoichi, Odinak, Miroslav M, Olsson, Toma, van Oosten, B W, Oreja-Guevara, Celia, Oschmann, Patrick, Overell, Jame, Pachner, Andrew, Panczel, Gyula, Pandolfo, Massimo, Papeix, Caroline, Patrucco, Liliana, Pelletier, Jean, Piedrabuena, Raul, Pless, Misha, Polzer, Udo, Pozsegovits, Krisztian, Rastenyte, Daiva, Rauer, Sebastian, Reifschneider, Gerd, Rey, Roberto, Rizvi, Syed A, Robertson, Derrick, Rodriguez, Jose Martinez, Rog, David, Roshanisefat, Homayoun, Rowe, Vernon, Rozsa, Csilla, Rubin, Susan, Rusek, Stanislaw, Saccà, Francesco, Saida, Takahiko, Salgado, Antonio Vasco, Sanchez, Victoria Eugenia Fernandez, Sanders, Kalina, Satori, Maria, Sazonov, Denis V, Scarpini, Elio Angelo, Schlegel, Eugen, Schluep, Myriam, Schmidt, Stephan, Scholz, Erich, Schrijver, H M, Schwab, Matthia, Schwartz, Raymond, Scott, Jame, Selmaj, Krzysztof, Shafer, Stuart, Sharrack, Basil, Shchukin, Ivan A, Shimizu, Yuko, Shotekov, Penko, Siever, Arno, Sigel, Karl-Otto, Silliman, Scott, Simo, Magdolna, Simu, Mihaela, Sinay, Vladimiro, Siquier, Antonio Escartin, Siva, Aksel, Skoda, Ondrej, Solomon, Andrew, Stangel, Martin, Stefoski, Dusan, Steingo, Brian, Stolyarov, Igor D, Stourac, Pavel, Strassburger-Krogias, Katrin, Strauss, Erik, Stuve, Olaf, Tarnev, Ivaylo, Tavernarakis, Antonio, Tello, Cristina Ramo, Terzi, Murat, Ticha, Veronika, Ticmeanu, Marina, Tiel-Wilck, Klau, Toomsoo, Tooma, Tubridy, Niall, Tullman, Mark J, Tumani, Hayrettin, Turcani, Peter, Turner, Ben, Uccelli, Antonio, Urtaza, Francisco Javier Olascoaga, Vachova, Marta, Valikovics, Attila, Walter, Silke, Van Wijmeersch, Bart, Vanopdenbosch, Ludo, Weber, Joerg R, Weiss, Sara, Weissert, Robert, West, Timothy, Wiendl, Heinz, Wiertlewski, Sandrine, Wildemann, Brigitte, Willekens, Barbara, Visser, L H, Vorobeychik, Galina, Xu, Xianhao, Yamamura, Takashi, Yang, Yi N, Yelamos, Sergio Martinez, Yeung, Michael, Zacharias, Alan, Zelkowitz, Marvin, Zettl, Uwe, Zhang, Meini, Zhou, Hongyu, Zieman, Ulf, Ziemssen, Tjalf, and EXPAND Clinical Investigators
Subjects: Adult, Male, 0301 basic medicine, Relative risk reduction, medicine.medical_specialty, Adolescent, Placebo, law.invention, Cohort Studies, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, Multiple Sclerosis, Chronic Progressive / drug therapy, 0302 clinical medicine, Double-Blind Method, Randomized controlled trial, law, Internal medicine, Benzyl Compounds, Clinical endpoint, Humans, Medicine, ComputingMilieux_MISCELLANEOUS, Settore MED/36 - DIAGNOSTICA PER IMMAGINI E RADIOTERAPIA, Expanded Disability Status Scale, Dose-Response Relationship, Drug, business.industry, Hazard ratio, General Medicine, Middle Aged, Multiple Sclerosis, Chronic Progressive, Fingolimod, Treatment Outcome, Settore M-EDF/01 - METODI E DIDATTICHE DELLE ATTIVITÀ MOTORIE, 030104 developmental biology, Siponimod, chemistry, Disease Progression, Azetidines, Female, Settore MED/26 - Neurologia, Human medicine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery, medicine.drug
Abstract: Summary Background No treatment has consistently shown efficacy in slowing disability progression in patients with secondary progressive multiple sclerosis (SPMS). We assessed the effect of siponimod, a selective sphingosine 1-phosphate (S1P) receptor 1,5 modulator, on disability progression in patients with SPMS. Methods This event-driven and exposure-driven, double-blind, phase 3 trial was done at 292 hospital clinics and specialised multiple sclerosis centres in 31 countries. Using interactive response technology to assign numbers linked to treatment arms, patients (age 18–60 years) with SPMS and an Expanded Disability Status Scale score of 3·0–6·5 were randomly assigned (2:1) to once daily oral siponimod 2 mg or placebo for up to 3 years or until the occurrence of a prespecified number of confirmed disability progression (CDP) events. The primary endpoint was time to 3-month CDP. Efficacy was assessed for the full analysis set (ie, all randomly assigned and treated patients); safety was assessed for the safety set. This trial is registered with ClinicalTrials.gov, number NCT01665144. Findings 1651 patients were randomly assigned between Feb 5, 2013, and June 2, 2015 (1105 to the siponimod group, and 546 to the placebo group). One patient did not sign the consent form, and five patients did not receive study drug, all of whom were in the siponimod group. 1645 patients were included in the analyses (1099 in the siponimod group and 546 in the placebo). At baseline, the mean time since first multiple sclerosis symptoms was 16·8 years (SD 8·3), and the mean time since conversion to SPMS was 3·8 years (SD 3·5); 1055 (64%) patients had not relapsed in the previous 2 years, and 918 (56%) of 1651 needed walking assistance. 903 (82%) patients receiving siponimod and 424 (78%) patients receiving placebo completed the study. 288 (26%) of 1096 patients receiving siponimod and 173 (32%) of 545 patients receiving placebo had 3-month CDP (hazard ratio 0·79, 95% CI 0·65–0·95; relative risk reduction 21%; p=0·013). Adverse events occurred in 975 (89%) of 1099 patients receiving siponimod versus 445 (82%) of 546 patients receiving placebo; serious adverse events were reported for 197 (18%) patients in the siponimod group versus 83 (15%) patients in the placebo group. Lymphopenia, increased liver transaminase concentration, bradycardia and bradyarrhythmia at treatment initiation, macular oedema, hypertension, varicella zoster reactivation, and convulsions occurred more frequently with siponimod than with placebo. Initial dose titration mitigated cardiac first-dose effects. Frequencies of infections, malignancies, and fatalities did not differ between groups. Interpretation Siponimod reduced the risk of disability progression with a safety profile similar to that of other S1P modulators and is likely to be a useful treatment for SPMS. Funding Novartis Pharma AG.
Published: 2018

33. An injectable implant to stimulate the sphenopalatine ganglion for treatment of acute ischaemic stroke up to 24 h from onset (ImpACT-24B): an international, randomised, double-blind, sham-controlled, pivotal trial

Author: Natan M Bornstein, Jeffrey L Saver, Hans Christoph Diener, Philip B Gorelick, Ashfaq Shuaib, Yoram Solberg, Lisa Thackeray, Milan Savic, Tamar Janelidze, Natia Zarqua, David Yarnitsky, Carlos A Molina, Michael Hill, Daniel Vaclavik, David Skoloudik, Jan Fiksa, Grethe Andersen, Pekka Jakala, Turgut Tatlisumak, Igor Kuzmanovski, Benoit Guillon, Hugues Chabriat, Marie Helene Mahagne, Serge Timsit, Thomas Ronziere, Gocha Ingorokva, Maya Beridze, Mzia Beridze, Nino Kharaishvili, Nodar Kakabadze, Bernd Griewing, Carsten Hobohm, Dietmar Schneider, Christian Weimar, Holger Poppert, Hubert Kimmig, Joerg Berrouschot, Peter Ringleb, Stefan Schwab, Martin Kohrmann, Bernd Kallmunzer, Rainer Kollmar, Matthias Endres, Karl-Georg Hausler, Raymond Cheung, Thomas Wai Hong Leung, Elena Dorodnicov, Hen Halevi, Eitan Auriel, Jonathan Streifler, Ronen Leker, Yvonne Schwammenthal, Danilo Toni, Giancarlo Agnelli, Valeria Caso, Agnieszka Słowik, Anna Czlonkowska, Ignacy Lubinski, Jan Kochanowicz, Piotr Sobolewski, Waldemar Brola, Antonio Vasco Salgado, Carlos Correia, Elsa Azevedo, Jose Roriz, Marija Zarkov, Zarko Petrovic, Georgi Krastev, Miloslav Dvorak, Ana Rodriguez Campello, Antonio Gil Nunez, Carlos Molina, Francisco Purroy, Joan Marti-Fabregas, Juan Arenillas, Maria Alonso, Pedro Cardona, Miguel Blanco Gonzalez, Silvia Tur, Tomas Segura Martin, Payenok Anzhelika, Harish Shownkeen, Mauricio Concha, Pramod Sethi, Souvik Sen, Syed Zaidi, and Thomas Devlin
Subjects: Adult, Male, Population, Medizin, Stimulation, Electric Stimulation Therapy, 030204 cardiovascular system & hematology, law.invention, Brain Ischemia, 03 medical and health sciences, 0302 clinical medicine, Reperfusion therapy, Randomized controlled trial, Quality of life, Double-Blind Method, law, medicine, Humans, 030212 general & internal medicine, education, Aged, Aged, 80 and over, education.field_of_study, business.industry, Ganglia, Parasympathetic, General Medicine, Odds ratio, Middle Aged, Ganglion, Stroke, medicine.anatomical_structure, Implantable Neurostimulators, Treatment Outcome, Anesthesia, Quality of Life, Female, Implant, business, Tomography, X-Ray Computed
Abstract: Sphenopalatine ganglion stimulation increased cerebral collateral blood flow, stabilised the blood-brain barrier, and reduced infarct size, in preclinical models of acute ischaemic stroke, and showed potential benefit in a pilot randomised trial in humans. The pivotal ImpACT-24B trial aimed to determine whether sphenopalatine ganglion stimulation 8-24 h after acute ischaemic stroke improved functional outcome.ImpACT-24B is a randomised, double-blind, sham-controlled, pivotal trial done at 73 centres in 18 countries. It included patients (men aged 40-80 years and women aged 40-85 years) with anterior-circulation acute ischaemic stroke, not undergoing reperfusion therapy. Enrolled patients were randomly assigned via web-based randomisation to receive active sphenopalatine ganglion stimulation (intervention group) or sham stimulation (sham-control group) 8-24 h after stroke onset. Patients, clinical care providers, and all outcome assessors were masked to treatment allocation. The primary efficacy endpoint was the difference between active and sham groups in the proportion of patients whose 3-month level of disability improved above expectations. This endpoint was evaluated in the modified intention-to-treat (mITT) population (defined as all patients who received one active or sham treatment session) and the population with confirmed cortical involvement (CCI) and was analysed using the Hochberg multi-step procedure (significance in both populations if p0·05 in both, and in one population if p0·025 in that one). Safety endpoints at 3 months were all serious adverse events (SAEs), SAEs related to implant placement or removal, SAEs related to stimulation, neurological deterioration, and mortality. All patients who underwent an attempted sphenopalatine ganglion stimulator or sham stimulator placement procedure were included in the safety analysis. This trial is registered with ClinicalTrials.gov, number NCT00826059.Between June 10, 2011, and March 7, 2018, 1078 patients were enrolled and randomly assigned to either the intervention or the sham-control group. 1000 patients received at least one session of sphenopalatine ganglion stimulation or sham stimulation and entered the mITT population (481 [48%] received sphenopalatine ganglion stimulation, 519 [52%] were sham controls), among whom 520 (52%) patients had CCI on imaging. The proportion of patients in the mITT population whose 3-month disability level was better than expected was 49% (234/481) in the intervention group versus 45% (236/519) in the sham-control group (odds ratio 1·14, 95% CI 0·89-1·46; p=0·31). In the CCI population, the proportion was 50% (121/244) in the intervention group versus 40% (110/276) in the sham-control group (1·48, 1·05-2·10; p=0·0258). There was an inverse U-shaped dose-response relationship between attained sphenopalatine ganglion stimulation intensity and the primary outcome in the CCI population: the proportion with favourable outcome increased from 40% to 70% at low-midrange intensity and decreased back to 40% at high intensity stimulation (p=0·0034). There were no differences in mortality or SAEs between the intervention group (n=536) and the sham-control group (n=519) in the safety population.Sphenopalatine ganglion stimulation is safe for patients with acute ischaemic stroke 8-24 h after onset, who are ineligible for thrombolytic therapy. Although not reaching significance, the trial's results support that, among patients with imaging evidence of cortical involvement at presentation, sphenopalatine ganglion stimulation is likely to improve functional outcome.BrainsGate Ltd.
Published: 2019

34. Recurrent Stroke With Rivaroxaban Compared With Aspirin According to Predictors of Atrial Fibrillation

Author: Jeff S. Healey, David J. Gladstone, Balakumar Swaminathan, Jens Eckstein, Hardi Mundl, Andrew E. Epstein, Karl Georg Haeusler, Robert Mikulik, Scott E. Kasner, Danilo Toni, Antonio Arauz, George Ntaios, Graeme J. Hankey, Kanjana Perera, Jorge Pagola, Ashfaq Shuaib, Helmi Lutsep, Xiaomeng Yang, Shinichiro Uchiyama, Matthias Endres, Shelagh B. Coutts, Michal Karlinski, Anna Czlonkowska, Carlos A. Mo
Published: 2019
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35. Brain Magnetic Resonance Imaging in Wilson’s Disease—Significance and Practical Aspects—A Narrative Review

Author: Tomasz Litwin, Barbara Rędzia-Ogrodnik, Agnieszka Antos, Adam Przybyłkowski, Anna Członkowska, and Jan Paweł Bembenek
Subjects: Wilson’s disease, copper, magnetic resonance imaging, brain, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Wilson’s disease (WD) is a genetic disorder of copper metabolism with pathological copper accumulation in many organs, resulting in clinical symptoms, mostly hepatic and neuropsychiatric. As copper accumulates in the brain during WD, and almost 50% of WD patients at diagnosis present with neurological symptoms, neuroimaging studies (especially brain magnetic resonance imaging (MRI)) are part of WD diagnosis. The classical sequences (T1, T2, and fluid-attenuated inversion recovery) were used to describe brain MRI; however, with the development of neuroradiology, several papers proposed the use of new MRI sequences and techniques like susceptibility-weighted images, T2*, diffusion MRI, tractography, volumetric assessment and post-processing brain MRI analysis of paramagnetic accumulation—quantitative susceptibility mapping. Based on these neuroradiological data in WD, currently, brain MRI semiquantitative scale and the pathognomonic neuroradiological brain MRI signs in WD were proposed. Further, the volumetric studies and brain iron accumulation MRI analysis suggested brain atrophy and iron accumulation as biomarkers of neurological WD disease severity. All these results highlight the significance of brain MRI examinations in WD. Due to the extreme progress of these studies, based on the available literature, the authors present the current state of knowledge about the significance, practical aspects, and future directions of brain MRI in WD.
Published: 2024
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36. Ultraearly hematoma growth in active intracerebral hemorrhage

Author: David, Rodriguez-Luna, Pilar, Coscojuela, Marta, Rubiera, Michael D, Hill, Dar, Dowlatshahi, Richard I, Aviv, Yolanda, Silva, Imanuel, Dzialowski, Cheemun, Lum, Anna, Czlonkowska, Jean-Martin, Boulanger, Carlos S, Kase, Gord, Gubitz, Rohit, Bhatia, Vasantha, Padma, Jayanta, Roy, Alejandro, Tomasello, Andrew M, Demchuk, Carlos A, Molina, and Hirak, Roychowdhury
Subjects: Adult, Male, medicine.medical_specialty, Computed Tomography Angiography, 030204 cardiovascular system & hematology, Article, 03 medical and health sciences, 0302 clinical medicine, Hematoma, Predictive Value of Tests, Internal medicine, medicine, Humans, Prospective Studies, cardiovascular diseases, Prospective cohort study, Aged, Cerebral Hemorrhage, Aged, 80 and over, Intracerebral hemorrhage, medicine.diagnostic_test, business.industry, Odds ratio, Middle Aged, medicine.disease, Confidence interval, Cerebral Angiography, Surgery, Treatment Outcome, Predictive value of tests, Angiography, Disease Progression, Cardiology, Female, Neurology (clinical), Nervous System Diseases, business, 030217 neurology & neurosurgery, Cerebral angiography
Abstract: Objective: To determine the association of ultraearly hematoma growth (uHG) with the CT angiography (CTA) spot sign, hematoma expansion, and clinical outcomes in patients with acute intracerebral hemorrhage (ICH). Methods: We analyzed data from 231 patients enrolled in the multicenter Predicting Haematoma Growth and Outcome in Intracerebral Haemorrhage Using Contrast Bolus CT study. uHG was defined as baseline ICH volume/onset-to-CT time (mL/h). The spot sign was used as marker of active hemorrhage. Outcome parameters included significant hematoma expansion (>33% or >6 mL, primary outcome), rate of hematoma expansion, early neurologic deterioration, 90-day mortality, and poor outcome. Results: uHG was higher in spot sign patients ( p p 4.7 mL/h ( p = 0.002) and the CTA spot sign ( p = 0.030) showed effects on rate of hematoma expansion but not its interaction (2-way analysis of variance, p = 0.477). uHG >4.7 mL/h improved the sensitivity of the spot sign in the prediction of significant hematoma expansion (73.9% vs 46.4%), early neurologic deterioration (67.6% vs 35.3%), 90-day mortality (81.6% vs 44.9%), and poor outcome (72.8% vs 29.8%), respectively. uHG was independently related to significant hematoma expansion (odds ratio 1.06, 95% confidence interval 1.03–1.10) and clinical outcomes. Conclusions: uHG is a useful predictor of hematoma expansion and poor clinical outcomes in patients with acute ICH. The combination of high uHG and the spot sign is associated with a higher rate of hematoma expansion, highlighting the need for very fast treatment in ICH patients.
Published: 2016

37. Practice patterns and outcomes after stroke across countries at different economic levels (INTERSTROKE): An international observational study

Author: Peter Langhorne, Martin J O'Donnell, Siu Lim Chin, Hongye Zhang, Denis Xavier, Alvaro Avezum, Nandini Mathur, Melanie Turner, Mary Joan MacLeod, Patricio Lopez-Jaramillo, Albertino Damasceno, Graeme J Hankey, Antonio L Dans, Ahmed Elsayed, Charles Mondo, Mohammad Wasay, Anna Czlonkowska, Christian Weimar, Afzal Hussein Yusufali, Fawaz Al Hussain, Liu Lisheng, Hans-Christoph Diener, Danuta Ryglewicz, Nana Pogosova, Romana Iqbal, Rafael Diaz, Khalid Yusoff, Aytekin Oguz, Xingyu Wang, Ernesto Penaherrera, Fernando Lanas, Okechukwu S Ogah, Adesola Ogunniyi, Helle K Iversen, German Malaga, Zvonko Rumboldt, Daliwonga Magazi, Yongchai Nilanont, Annika Rosengren, Shahram Oveisgharan, Salim Yusuf, M. O'Donnell, S. Yusuf, S. Rangarajan, P. Rao-Melacini, X. Michelle Zhang, S. Islam, C. Kabali, A. Casanova, S.L. Chin, J. DeJesus, M. Dehghan, S. Agapay, M. McQueen, K. Hall, J. Keys, X. Wang, A. Devanath, R. Gupta, D. Prabhakaran, R. Diaz, P. Schygiel, M. Garrote, M.A. Rodriguez, A. Caccavo, R.G. Duran, L. Sposato, J. Molinos, P. Valdez, C.M. Cedrolla, P.G. Nofal, M.F. Huerta, P.M. Desmery, M.C. Zurru, B. Della Vedova, J. Varigos, G. Hankey, T. Kraemer, P. Gates, C. Bladin, G. Herkes, A. Avezum, M.P. Pereira, L. Minuzzo, L. Oliveira, M. Teixeira, H. Reis, A. Carvalho, S. Ouriques Martins, J.J. Carvalho, O. Gebara, C. Minelli, D.C. Oliveira, A.C. Sobral Sousa, A.C. Ferraz de Almeida, M.E. Hernandez, M. Friedrich, D.M. Mota, L.E. Ritt, D. Correa Vila Nova, P. Teal, D. Gladstone, A. Shuaib, F. Silver, D. Dowlatshahi, F. Lanas, D. Carcamo, C. Santibañez, E. Garces, L.S. Liu, H.Y. Zhang, H.P. Fang, M.F. Lian, F. Shen, F.X. Luo, X.X. Wen, Z.Q. Xu, Z.Z. Liu, W. Yan, J.F. Yu, W.K. Wang, L.H. Liu, Y.H. Sun, L.C. Zhou, Z.F. Zhang, J. LV, C.S. Zhang, G. Chen, H.L. Wang, Y. Chen, H. Zheng, J.J. Huang, W.Z. Li, L.J. Wang, J.X. Shi, C.Y. Hu, H.F. Song, R.Y. Ji, D.L. Wang, L.H. Meng, Q.W. Meng, L.J. Duan, H.F. Liu, Y.C. Luo, Q.Y. Zhang, Y.B. Wu, C.R. Wang, J.G. Zhao, S.G. Liu, C.L. Shi, X.Y. Wang, P. Lopez-Jaramillo, A. Martinez, G. Sanchez-Vallejo, D.I. Molina, T. Espinosa, H. Garcia Lozada, D. Gomez-Arbelaez, P.A. Camacho, Z. Rumboldt, I. Lusic, H.K. Iversen, T. Truelsen, C. Back, M.M. Pedersen, E. Peñaherrera, Y.C. Duarte, S. Cevallos, D. Tettamanti, S. Caceres, H.C. Diener, C. Weimar, A. Grau, J. Rother, M. Ritter, T. Back, Y. Winter, P. Pais, D. Xavier, A. Sigamani, N. Mathur, P. Rahul, A. Murali, A.K. Roy, G.R.K. Sarma, T. Matthew, G. Kusumkar, K.A. Salam, U. Karadan, L. Achambat, Y. Singh, J.D. Pandian, R. Verma, V. Atam, A. Agarwal, N. Chidambaram, R. Umarani, S. Ghanta, G.K. Babu, G. Sathyanarayana, G. Sarada, S. Navya Vani, R. Sundararajan, S.S. Sivakumar, R.S. Wadia, S. Bandishti, R.R. Agarwal, I. Mohan, S. Joshi, S. Kulkarni, S. Partha Saradhi, P. Joshi, M. Pandharipande, N. Badnerkar, R. Joshi, S.P. Kalantri, S. Somkumar, S. Chauhan, H. Singh, S. Varma, G.K. Sidhu, R. Singh, K.L. Bansal, A. Bharani, S. Pagare, A. Chouhan, B.N. Mahanta, T.G. Mahanta, G. Rajkonwar, S.K. Diwan, S.N. Mahajan, P. Shaikh, H.R. Devendrappa, B.K. Agrawal, A. Agrawal, D. Khurana, S. Thakur, V. Jain, S. Oveisgharan, A. Bahonar, R. Kelishadi, A. Hossienzadeh, M. Raeisidehkordi, H. Akhavan, T. Walsh, O. Albaker, K. Yusoff, A. Chandramouli, S. Shahadan, Z. Ibrahim, A. Husin, A. Damasceno, V. Lobo, S. Loureiro, V.A. Govo, O.S. Ogah, A. Ogunniyi, R.O. Akinyemi, M.O. Owolabi, M.U. Sani, L.F. Owolabi, R. Iqbal, M. Wasay, A. Raza, G.G. Malaga, M. Lazo-Porras, J.D. Loza-Herrera, A. Acuña-Villaorduña, D. Cardenas-Montero, A. Dans, E. Collantes, D. Morales, A. Roxas, M.V.C. Villarruz-Sulit, A. Czlonkowska, D. Ryglewicz, M. Skowronska, M. Restel, A. Bochynska, K. Chwojnicki, M. Kubach, A. Stowik, M. Wnuk, N. Pogosova, A. Ausheva, A. Karpova, V. Pshenichnikova, A. Vertkin, A. Kursakov, S. Boytsov, F. Al-Hussain, L. DeVilliers, D. Magazi, B. Mayosi, A.S.A. Elsayed, A. Bikhari, Z. Sawaraldahab, H. Hamad, M. ElTaher, A. Abdelhameed, M. Alawad, D. Alkabashi, H. Alsir, A. Rosengren, M. Andreasson, J. Kembro Johansson, B. Cederin, C. Schander, A.C. Elgasen, E. Bertholds, K. Boström Bengtsson, Y. Nilanont, S. Nidhinandana, P. Tatsanavivat, N. Paryoonwiwat, N. Poungvarin, N.C. Suwanwela, S. Tiamkao, R. Tulyapornchote, S. Boonyakarnkul, S. Hanchaiphiboolkul, S. Muengtaweepongsa, K. Watcharasaksilp, P. Sathirapanya, P. Pleumpanupat, A. Oguz, A.A. Akalin, O.T. Caklili, N. Isik, B. Caliskan, B. Sanlisoy, E. Balkuv, H. Tireli, V. Yayla, M. Cabalar, A. Culha, S. Senadim, B. Arpaci, C. Dayan, T. Argun, S. Yilmaz, S. Celiker, A. Kocer, T. Asil, G. Eryigit, C. Mondo, J. Kayima, M. Nakisige, S. Kitoleeko, A.M. Yusufali, B.J. Zuberi, H.Z. Mirza, A.A. Saleh, J.M. BinAdi, F. Hussain, P. Langhorne, K. Muir, M. Walters, C. McAlpine, S. Ghosh, A. Doney, S. Johnston, P. Mudd, T. Black, P. Murphy, D. Jenkinson, D. Kelly, R. Whiting, D. Dutta, L. Shaw, C. Mcfarlane, E. Ronald, and K. McBurnie
Subjects: Male, medicine.medical_specialty, MEDLINE, Medizin, Developing country, 030204 cardiovascular system & hematology, Health Services Accessibility, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, medicine, Humans, Practice Patterns, Physicians', Stroke, Developing Countries, Poverty, Aged, Evidence-Based Medicine, business.industry, Developed Countries, Case-control study, General Medicine, Evidence-based medicine, Middle Aged, medicine.disease, Survival Analysis, purl.org/pe-repo/ocde/ford#3.02.00 [https], Patient Outcome Assessment, Treatment Outcome, Family medicine, Case-Control Studies, Observational study, Female, Interstroke, business, Developed country, 030217 neurology & neurosurgery
Abstract: 9 p., Background: Stroke disproportionately affects people in low-income and middle-income countries. Although improvements in stroke care and outcomes have been reported in high-income countries, little is known about practice and outcomes in low and middle-income countries. We aimed to compare patterns of care available and their association with patient outcomes across countries at different economic levels. Methods: We studied the patterns and effect of practice variations (ie, treatments used and access to services) among participants in the INTERSTROKE study, an international observational study that enrolled 13 447 stroke patients from 142 clinical sites in 32 countries between Jan 11, 2007, and Aug 8, 2015. We supplemented patient data with a questionnaire about health-care and stroke service facilities at all participating hospitals. Using univariate and multivariate regression analyses to account for patient casemix and service clustering, we estimated the association between services available, treatments given, and patient outcomes (death or dependency) at 1 month. Findings: We obtained full information for 12 342 (92%) of 13 447 INTERSTROKE patients, from 108 hospitals in 28 countries; 2576 from 38 hospitals in ten high-income countries and 9766 from 70 hospitals in 18 low and middle-income countries. Patients in low-income and middle-income countries more often had severe strokes, intracerebral haemorrhage, poorer access to services, and used fewer investigations and treatments (p
Published: 2018

38. Long-term adjunctive lacosamide treatment in patients with partial-onset seizures

Author: David Reutens, László Vécsei, Alla Guekht, Anna Czlonkowska, Samuel Berkovic, Anatoly Fedin, Ernest Somerville, Maria Mazurkiewicz-Bełdzińska, Petr Marusic, Terence O'Brien, Michal Bar, Antonio Gil-Nagel MD PhD, and Vladimir Karlov
Subjects: Diplopia, Lacosamide, business.industry, General Medicine, 03 medical and health sciences, 0302 clinical medicine, Neurology, Tolerability, Anesthesia, Concomitant, Adjunctive treatment, Cohort, Medicine, In patient, 030212 general & internal medicine, Neurology (clinical), medicine.symptom, business, Adverse effect, 030217 neurology & neurosurgery, medicine.drug
Abstract: Objective To evaluate long-term (up to 5.5 years) safety, seizure reduction, and maintenance of efficacy of the antiepileptic drug (AED) lacosamide as adjunctive treatment in an open-label extension trial (SP774; ClinicalTrials.gov: NCT00515619). Methods Three hundred and seventy-six adults with partial-onset seizures taking 1–3 AEDs enrolled following completion of a double-blind trial of adjunctive lacosamide. During open-label treatment, dosage of lacosamide (100–800 mg/day) and/or concomitant AEDs could be adjusted to optimize tolerability and seizure control. Results Kaplan–Meier estimates of patient retention were 74.5% at 12 months, 52.9% at 36 months, and 40.6% at 60 months; median open-label treatment duration was 1183 days (~3.2 years). The most frequently reported treatment-emergent adverse events were dizziness (24.2%), headache (14.4%), diplopia (13.8%), and nasopharyngitis (13.8%); 9.0% of patients discontinued due to adverse events, most commonly dizziness (1.3%). Median percent reduction in 28-day seizure frequency from baseline of the double-blind trial was 49.9% overall, 55.4% for 1-year completers, and 62.3% for 3-year completers. Overall, 50.0% of patients were considered ≥50% responders (achieved ≥50% reduction in 28-day seizure frequency); 55.9% of 1-year completers and 63.0% of 3-year completers were ≥50% responders. Conclusion In eligible patients who entered the open-label extension trial, lacosamide was generally well tolerated. For most patients within each yearly completer cohort, seizure reduction was maintained over time.
Published: 2015

39. NeuroAiDTM (MLC601, MLC901): A New Bench-to-Bedside Approach to the Treatment of Ischemic Brain Injury

Author: Michel Dib, Hossein Pakdaman, Yomi Ogun, Hovhannes Manvelyan, Anna Czlonkowska, Ivan Milanov, Aurelio Mendez, Anatoly Fedin, Dodik Tugasworo, Siwaporn Chankrachang, and Ihsan Zahra
Subjects: Clinical trial, medicine.medical_specialty, business.industry, Internal medicine, Ischemia, medicine, Cardiology, Ischemic brain injury, Pharmacology, medicine.disease, business, Stroke, Bench to bedside
Published: 2015

40. Wilson Disease

Author: Anna Czlonkowska, Michael Schilsky, Anna Czlonkowska, and Michael Schilsky
Subjects: Hepatolenticular degeneration
Abstract: Wilson Disease provides a comprehensive guide on this inherited genetic disorder that has devastating consequences for both the liver and neurologic/psychiatric health. This disease is of increasing interest to neurologists, hepatologists, and geneticists, but when the disease is diagnosed early, it is treatable, with patients living normal lives. This volume describes the molecular pathophysiology of WD and the clinical and pathological effects of copper. Separate sections address both diagnosis and medical and surgical approaches to treatment. Both adult and pediatric perspectives on diagnosis and treatment are addressed, and a section on genetics highlights advances in molecular diagnostics. Patient support groups that can aid in coping with this disease are also discussed, as are animal models for those interested in basic research on cell biology, pathophysiology, and treatment. - Addresses the molecular pathophysiology of WD and the clinical and pathological effects of copper - Offers coverage of both diagnosis and medical and surgical approaches to treatment - Includes perspectives on both adult and pediatric diagnosis and treatment - Edited work with chapters authored by leaders in the field from around the globe—the broadest, most expert coverage available
Published: 2017

41. Changes in the profile of patients with multiple sclerosis over the last 30 years due to evolution of diagnostic criteria

Author: Anna Czlonkowska
Published: 2017

42. Risk for Major Bleeding in Patients Receiving Ticagrelor Compared With Aspirin After Transient Ischemic Attack or Acute Ischemic Stroke in the SOCRATES Study (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes)

Author: J. Donald Easton, Maria Aunes, Gregory W. Albers, Pierre Amarenco, Sara Bokelund-Singh, Hans Denison, Scott R. Evans, Peter Held, Marianne Jahreskog, Jenny Jonasson, Kazuo Minematsu, Carlos A. Molina, Yongjun Wang, K.S. Lawrence Wong, S. Claiborne Johnston, Sebastiá F. Ameriso, Geoffrey Donnan, Robin Lemmens, Ayrton Massaro, Ekaterina Titianova, Michael D. Hill, Pablo Lavados, David Skoloudik, Joachim Röther, Szegedi Norbert, Giancarlo Agnelli, Natan Bornstein, Norio Tanahashi, Angel Arauz Góngora, Edwin Pretell, Maria Cristina Z. San Jose, Anna Czlonkowska, Ovidiu Bajenaru, Ludmila Stakhovskaya, Miroslav Brozman, Jong-Sung Kim, Nils Wahlgren, Patrik Michel, Tsong Hai Lee, Nijasri Charnnarong Suwanwela, Kursad Kutluk, Sergii Moskovko, Scott Kasner, Daniel Laskowitz, Wayne Clark, Huy Thang Nguyen, Sebastian Ameriso, Sandra Lepera, Marina Romano, David Paulon, Pablo Ioli, Cristina Zurru, Guadalupe Bruera, Lorena Jure, Francisco Klein, Guillermo Povedano, Christopher Levi, Thanh Phan, Romesh Markus, Craig Anderson, Arman Sabet, Stephen Davis, Andrew Lee, Timothy Kleinig, Andrew Wong, Martin Krause, Jim Jannes, Tissa Wijeratne, Dimitri Hemelsoet, André Peeters, Philippe Tack, Peter Vanacker, Patrice Laloux, William Van Landegem, Geert Vanhooren, Philippe Desfontaines, Marc Van Orshoven, Fabio Oliveira, Mauricio Friedrich, Rosane Brondani, Rubens Gagliardi, Soraia Fabio, Marianna Dracoulakis, Rodrigo Bazan, Luiz Marrone, Octavio Pontes Neto, Gisele Silva, Pedro Kowacs, Paraskeva Stamenova, Marin Daskalov, Ivan Staikov, Dimo Baldaranov, Dimitar Maslarov, Hristo Lilovski, Plamen Petkov, Neli Petrova, Radoslav Mavrov, Veska Markova, Valeria Petrova, Tanya Beleva, Borislav Kralev, Nikolay Sotirov, Veska Lekova, Dimcho Hristov, Vera Ermenkova, Lyudmil Mateev, Rumeliya Mitkova, Liybomir Haralanov, Rosen Ikonomov, Margarita Mihailova, Ivan Georgiev, Ashfaq Shuaib, Vladimir Hachinski, Jean-Martin Boulanger, Sharan Mann, Ayman Hassan, Ariane Mackey, Bijoy Menon, Jeffrey Minuk, Muzaffar Siddiqui, Marsha Eustace, Lucia Vieira, Daniel Selchen, Michel Beaudry, Grant Stotts, Angel Castro, Kristo Gasic, Rodrigo Rivas, Pablo Sanchez, Andres Roldan, Ingrid Grossmann, Christian Figueroa, Jimei Li, Xiaolin Xu, Huisheng Chen, Xiaohong Li, Yi Yang, Chunsheng Zhang, Baojun Wang, Guanglai Li, Dong Wang, Hong Lin, Yamei Tang, Anding Xu, Yanjiang Wang, Wenke Hong, Zhi Song, Xu Zhang, Xiaoping Jin, Yun Xu, Fuling Yan, Weihong Zheng, Xiaoping Wang, Qiang Dong, Zhongxin Zhao, Baorong Zhang, Wangtao Zhong, Guoqiang Wen, Jun Xu, Guozhong Li, Xueshuang Dong, Xiangyang Tian, Zhaohui Zhang, En Xu, Kaixiang Liu, Jun Chen, Ondrej Skoda, Edvard Ehler, Daniel Vaclavik, Daniel Sanak, Sylva Klimosova, Eva Vitkova, Jan Fiksa, Robert Mikulik, Jiri Neumann, Richard Plny, Didier Leys, Igor Sibon, Jean-Louis Mas, Sonia Alamowitch, Fernando Pico, Hassan Hosseini, Marie-Hélène Mahagne, Emmanuel Touze, Wilfried Vadot, Stéphane Vannier, Norbert Nighoghossian, Yves Samson, Pierre Garnier, Emmanuel Ellie, Benoît Guillon, Serge Timsit, Maurice Giroud, Frédéric Philippeau, Aude Bagan-Triquenot, Valérie Wolff, Nicolas Raposo, Michel Obadia, Severine Debiais, Jérôme Grimaud, Stéphane Illouz, Didier Smadja, Cédric Urbanczyk, Jörg Berrouschot, Christian Weimar, Georg Gahn, Hassan Soda, Sven Klimpe, Darius Nabavi, Jörg Glahn, Martin Köhrmann, Lars Krause, Christoph Terborg, Peter Urban, Thorsten Steiner, Andreas Ferbert, Rainer Dziewas, Günter Seidel, Götz Thomalla, Richard Li, Wing Chi Fong, Raymond Cheung, Norbert Szegedi, Krisztián Pozsegovits, Attila Valikovics, Gyula Pánczél, Csilla Rózsa, László Németh, Péter Diószeghy, Csaba Óváry, Attila Csányi, Levente Kerényi, Valéria Nagy, Sámuel Komoly, Dániel Bereczki, Sándor Molnár, István Kondákor, David Tanne, Guy Raphaeli, Gregory Telman, Ronen Leker, Yair Lampl, Francesco Corea, Stefano Ricci, Donata Guidetti, Giovanni Malferrari, Simona Marcheselli, Giuseppe Micieli, Andrea Zini, Vincenzo Di Lazzaro, Carlo Gandolfo, Andrea Salmaggi, Rossana Tassi, Maurizia Rasura, Giovanni Orlandi, Giancarlo Comi, Michelangelo Mancuso, Marialuisa Delodovici, Paolo Bovi, Domenico Consoli, Kimiaki Utsugisawa, Tsuneo Fujita, Hideyuki Kurihara, Chikashi Maruki, Takeshi Hayashi, Tsuneaki Ogiichi, Morio Kumagai, Katsunobu Takenaka, Kazunori Toyoda, Kazuhiro Takamatsu, Ryo Ogami, Shigenari Kin, Takeshi Aoki, Katsumi Takizawa, Shigehiro Omori, Takehiko Umezawa, Yasuyuki Toba, Yutaka Nonoyama, Hidemitsu Nakagawa, Takashi Naka, Masanori Morimoto, Shuichi Matsumoto, Tsutomu Hitotsumatsu, Tatsuya Shingaki, Satoshi Okuda, Mamoru Ota, Nobuyuki Sakai, Takeshi Yamada, Jun Niwa, Hitoshi Fujita, Akihito Moriki, Kimihiro Yoshino, Yoshihisa Fukushima, Takahisa Mori, Atsushi Sato, Yoshikazu Kusano, Michiya Kubo, Masashi Yamazaki, Takao Ooasa, Takafumi Nishizaki, Naoki Kitagawa, Masahiro Yasaka, Yasuhiro Manabe, Akira Yoshioka, Masayuki Ishihara, Takato Kagawa, Toshikazu Ichihashi, Hideki Matsuoka, Yasuhiro Ito, Masahiro Yamasaki, Hitonori Takaba, Hisatoshi Saito, Masahiro Sato, Kazumasa Fukuda, Sumio Endo, Minoru Kidooka, Toshitaka Umemura, Yuriko Kikkawa, Shuta Toru, Kentaro Yamada, Hideki Sakai, Jun Asari, Masayuki Ezura, Hisashi Nitta, Keiko Nagano, Jun Ochiai, Keiichi Sakai, Yasutaka Kobayashi, Yasuhiro Yoshii, Hirotomo Miake, Tomohiro Takita, Hidekazu Taniguchi, Kazuhiko Kuroki, Takamitsu Mizota, Kenichi Yamamoto, Hiroshi Nakane, Takeshi Iwanaga, Kei Chiba, Tetsuyuki Yoshimoto, Tsuyoshi Torii, Takeo Kitagawa, Hiroshi Takashima, Naoki Shirasaki, Makoto Dehara, Naomichi Wada, Kensuke Hamada, Noriyuki Kato, Yoshinori Go, Ichiro Izumi, Hirotomo Ninomiya, Junichiro Kumai, Yoshikazu Nakajima, Yasuhiko Kaku, Yukihiro Isayama, Masahiro Kawanishi, Shinya Noda, Kazuhide Yamamoto, Takanori Hazama, Hiroshi Takahashi, Yohei Tanaka, Takashi Hata, Kiyoshi Kazekawa, Eisuke Furui, Hideki Hondo, Nobuyuki Sato, Katsusuke Kusunoki, Kazunori Nanri, Satoshi Abe, Noboru Sasaoka, Takayuki Kuroyanagi, Hisahiko Suzuki, Kouzou Fukuyama, Kimihiro Nakahara, Fernando Gongora, Carlos Cantú Brito, Jorge Villarreal Careaga, Rosalia Vazquez Alfaro, Geronimo Aguayo Leytte, Percy Berrospi, Carlos Chavez, Liliana Rodriguez, Nilton Custodio, Cesar Castañeda, Julio Perez, Maria Cristina San Jose, Alejandro Baroque, Epifania Collantes, Abdias Aquino, Alejandro Díaz, Artemio Roxas, Johnny Lokin, Joel Advincula, Emerito Calderon, Jose Navarro, John Hiyadan, Arturo Surdilla, Danuta Ryglewicz, Grzegorz Krychowiak, Waldemar Fryze, Piotr Sobolewski, Ryszard Nowak, Urszula Fiszer, Beata Papierowska, Justyna Zielińska-Turek, Anetta Lasek-Bal, Ewa Kołodziejska, Anna Kamińska, Bożena Adamkiewicz, Andrzej Tutaj, Dorota Szkopek, Krzysztof Musiatowicz, Zbigniew Bąk, Sławomir Brzozowski, Waldemar Brola, Antoni Ferens, Marek Zalisz, Konrad Rejdak, Monika Rudzińska, Cristina Panea, Mihaela Simu, Rodica Balasa, Iulian Cuciureanu, Bogdan Popescu, Monica Sabau, Corina Roman-Filip, Leonid Pimenov, Alla Gekht, Anna Milto, Ivan Shchukin, Vladimir Parfenov, Liudmila Stakhovskaya, Mikhail Arkhipov, Nadezhda Sokolova, Enver Bogdanov, Radiy Esin, Dina Khasanova, Konstantin Golikov, Elena Melnikova, Leonid Zaslavskiy, Igor Voznyuk, Alexander Nazarov, Leila Akhmadeeva, Aida Iakupova, Nikolay Shamalov, Galina Belskaya, Svetlana Chuprina, Olga Denisova, Ekaterina Drozdova, Yuliya Karakulova, Ilya Sholomov, Nikolay Spirin, Elena Vostrikova, Elena Mordvintseva, Vera Grigoryeva, Dmitry Zateyshchikov, Vladimir Gorbachev, Zhanna Chefranova, Mikhail Dudarev, Rostislav Nilk, Alexey Rozhdestvenskiy, Ladislav Gurcik, Miloslav Dvorak, Georgi Krastev, Egon Kurca, Juraj Vyletelka, Jong Sung Kim, Hee-Joon Bae, Yong-Won Kim, Joon-Tae Kim, Jae-Kwan Cha, Hyo Suk Nam, Dae-Il Chang, Yong-Seok Lee, Kyungmi Oh, Sung-Wook Yu, Sung-Il Sohn, Jun Lee, Han Jin Cho, Eung-Gyu Kim, Joung-Ho Rha, Seo Hyun Kim, Carlos Molina Cateriano, Joaquín Serena Leal, José Vivancos Mora, Manuel Rodríguez Yañez, Jaume Roquer González, Francisco Purroy García, Meritxell Gomis Cortina, Jaime Masjuan Vallejo, Juan Arenillas Lara, Tomás Segura Martín, José Antonio Egido Herrero, Jose Ignacio Tembl Ferrairó, Jaime Gállego Culleré, Francisco Moniche Álvarez, Anna Steinberg, Margarita Callander, Ann Charlotte Laska, Lena Bokemark, Thomas Mooe, Tor-Björn Käll, Lennart Welin, Lars Sjöblom, Joakim Hambraeus, Jörg Teichert, Hans Wannberg, Johan Sanner, Bo Ramströmer, Bo Ziedén, Stefan Olsson Hau, Claes Gustafsson, Timo Kahles, Philippe Lyrer, Marcel Arnold, Martin Liesch, Friedrich Medlin, Carlo Cereda, Georg Kägi, Andreas Luft, Emmanuel Carrera, Tsong-Hai Lee, Helen L. Po, Chang-Ming Chern, Li-Ming Lien, Lung Chan, Chung-Hsiang Liu, Shey-Lin Wu, Jiann-Der Lee, Chih-Hung Chen, Huey-Juan Lin, Ruey-Tay Lin, Wei-Hsi Chen, Yu Sun, Tasanee Tantirittisak, Sombat Muengtaweepongsa, Yongchai Nilanont, Somsak Tiamkao, Chesda Udommongkol, Kanokwan Watcharasaksilp, Witoon Jantararotai, Hadiye Sirin, Birsen Ince, Talip Asil, Murat Arsava, Tulay Kurt Incesu, Hulya Tireli, Hayriye Kucukoglu, Fikri Ak, Ali Unal, Serefnur Ozturk, Nevzat Uzuner, Galyna Chmyr, Volodymyr Lebedynets, Vadym Nikonov, Lyudmyla Shulga, Volodymyr Smolanka, Marta Khavunka, Valentyna Yavorska, Nataliya Tomakh, Olexandr Kozyolkin, Galyna Litovaltseva, Maarten Lansberg, Richard Bernstein, David Brown, Jonathan Dissin, Carmelo Graffagnino, Jonathan Harris, William Hicks, Irene Katzan, Jeffrey Kramer, Joshua Willey, Scott Silliman, Sidney Starkman, David Thaler, Margaret Tremwel, Mauricio Concha, Kumar Rajamani, Bhuvaneswari Dandapani, Brian Silver, Nathan Deal, Ira Chang, Ameer Hassan, Steven Rudolph, Kenneth Fischer, Howard Kirshner, William Logan, Sidney Mallenbaum, Hebah Hefzy, Julius Latorre, Steven Levine, Anthony Ciabarra, Rima Dafer, Benjamin Anyanwu, Laurel Cherian, Spozhmy Panezai, Anna Khanna, Jodi Dodds, Michel Torbey, James Gebel, Henry Woo, David Chiu, Xiao Androulakis, William Burgin, Maria Pineda, Engin Yilmaz, Irfan Altafullah, Christine Boutwell, Salvador Cruz-Flores, Biggya Sapkota, Pierre Fayad, Michael Jacoby, Shahid Rafiq, Efrain Salgado, Eugene Lafranchise, Warren Felton, Ramesh Madhavan, Osama Zaidat, Connie Pieper, Ralph Riviello, Aaron Burnett, Michelle Fischer, Nina Gentile, Christopher Calder, Dennis Dietrich, Jonathan Cross, Larry Blankenship, Liliana Montoya, Wendell Grogan, Mark Young, Farrukh Khan, Duane Campbell, Nizar Daboul, Andrey Espinoza, Paul Cullis, Gilberto Concepcion, John Wulff, Haider Afzal, Naseem Jaffrani, William Reiter, Tamjeed Arshad, Timothy Lukovits, James Welker, Fen Lei Chang, Aamir Badruddin, Viken Babikian, Ravi Menon, James Sander, Mellanie Springer, Ashish Nanda, Luis Mas, Raj Rajan, Bruce Silverman, David Huang, David Carpenter, Joni Clark, Marilou Ching, Sunitha Santhakumar, Jeffrey Gould, Vibhav Bansal, Gabriel Vidal, Timothy Mikesell, John Brick, William French, Qaisar Shah, Christine Holmstedt, Nadir Ishag-Osman, John Kostis, Abbas Shehadeh, Pramodkumak Sethi, Asher Imam, Carl Mccomas, Duc Tran, Mehari Gebreyohanns, Brian Wiseman, Maheen Malik, Aron Schwarcz, Dorothea Altschul, John Castaldo, Amer Alshekhlee, Stephen Gancher, Nagesh Krish, Mai Nguyen-Huynh, Margaret Tremwell, Jitendra Sharma, Lance Lee, William Neil, Fazeel Siddiqui, Ali Malek, Charles Romero, Thang Nguyen Huy, Hoa Hoang, Thang Nguyen, Anh Nguyen, Hung Nguyen, Laboratoire de Recherche Vasculaire Translationnelle ( LVTS ), Université Paris 13 ( UP13 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), AstraZeneca, National Cerebral and Cardiovascular Center ( NCCC - OSAKA ), Osaka University [Osaka], Department of Neurology ( Dep Neuro - BEIJING ), Tiantan Hospital, University of Melbourne, Faculty of Mathematics and Statistics, Ton Duc Thang University, Ho Chi Minh City, Heidelberg University, Centre hospitalier de Namur, IBM Thomas J. Watson Research Center, IBM, Bulgarian Academy of Sciences, Department of Clinical Neurological Sciences [London, Canada], University of Western Ontario ( UWO ), Servicio de Neurologia ( SANTIAGO - Neurologie ), Universidad de Santiago de Chile [Santiago] ( USACH ) -Universidad del Desarrollo, Institut de Chimie de Clermont-Ferrand - Clermont Auvergne ( ICCF ), Sigma CLERMONT ( Sigma CLERMONT ) -Université Clermont Auvergne ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Universidad de Talca, Shanghai Second Polytechnic University, Northwest Normal University [Lanzhou], Zhongda Hospital, Southeast University [Jiangsu], Cryogenics Laboratory ( CRYOGENICS LABORATORY ), Huazhong University of Science and Technology [Wuhan] ( HUST ) -Wuhan University [China], Centre for Synthetic and Systems Biology, University of Edinburgh-School of Biological Sciences, Duke university [Durham], Fiber Glass, Glass Business and Discovery Center, PPG Industries, National University of Defense Technology [Changsha], School of Oceanography [Seattle], University of Washington [Seattle], Key Laboratory of New Processing Technology for Nonferrous Metals and Materials, Guilin University of Technologie, Laboratoire de Génie Electrique et Ferroélectricité ( LGEF ), Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Université de Lyon-Institut National des Sciences Appliquées ( INSA ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Université de Bordeaux ( UB ), Service de Pédiatrie, Centre Hospitalier Universitaire de Nice ( CHU Nice ) -Hôpital l'Archet, Université Pierre et Marie Curie - Paris 6 ( UPMC ), Centre Hospitalier de Versailles ( CHV ), Service de neurologie, Hôpital Sainte-Anne, Functional Exploration of Nervous, CHU Grenoble, Service de Neurologie [Rennes], Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière ( NEMESIS-CRICM ), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière ( CRICM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Français de Mécanique Avancée ( IFMA ), Neurologie - Côte Basque ( NEUROLOGIE ), Hopital, Laboratoire d'Intégration des Systèmes et des Technologies ( LIST ), Université Paris-Saclay-Direction de Recherche Technologique (CEA) ( DRT (CEA) ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) ( GGB ), Institut Brestois Santé Agro Matière ( IBSAM ), Université de Brest ( UBO ) -Université de Brest ( UBO ) -EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ), CIC Brest, Université de Brest ( UBO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital de la Cavale Blanche, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), CHU Strasbourg, Imagerie cérébrale et handicaps neurologiques, Institut des sciences du cerveau de Toulouse. ( ISCT ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès ( UT2J ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès ( UT2J ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Department of Neurology, Asklepios Klinik Altona, Department of Neurology and Stroke Center, Universität Duisburg-Essen [Essen], Department of Neurology, University of Mainz, Vivantes Klinikum Neukölln, University of Erlangen, University Hospital Münster, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] ( UKE ), PROTOMED, Neurology Department, Ichilov Medical Center, Internal and Cardiovascular Medicine - Stroke Unit ( PERUGIA - ICM-SU ), Università degli Studi di Perugia ( UNIPG ), University Hospital San Raffaele Milan, Scientific Institute and University Ospedale San Raffaele, Dipartimento di Scienze Fisiche, della Terra e dell'Ambiente., Università degli Studi di Siena ( UNISI ), Department of Education, Yamagata University, Nippon Medical School, Catalan Institute of Ornithology (ICO), Museu de Ciències Naturals (Zoologia), Wroclaw University of Science and Technology, Department of neurology, Jagiellonian University [Krakow] ( UJ ), LInguistique et DIdactique des Langues Étrangères et Maternelles ( LIDILEM ), Université Stendhal - Grenoble 3-Université Grenoble Alpes ( UGA ), Metacohorts Consortium, GenXpro GmBH, Lausanne University Hospital, Lausanne university hospital, Northeastern University [Boston], Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), National Cerebral and Cardiovascular Center (NCCC - OSAKA), Department of Neurology (Dep Neuro - BEIJING), Bulgarian Academy of Sciences (BAS), University of Western Ontario (UWO), Servicio de Neurologia (SANTIAGO - Neurologie), Universidad del Desarrollo, Institut de Chimie de Clermont-Ferrand (ICCF), SIGMA Clermont (SIGMA Clermont)-Institut de Chimie du CNRS (INC)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Shanghai Polytechnic University (SSPU), Cryogenics Laboratory (CRYOGENICS LABORATORY), Huazhong University of Science and Technology [Wuhan] (HUST)-Wuhan University [China], Centre for Synthetic and Systems Biology (Ssynthsys), University of Edinburgh, Duke University [Durham], National University of Defense Technology [China], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Bordeaux (UB), Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital l'Archet, Université Pierre et Marie Curie - Paris 6 (UPMC), Centre Hospitalier de Versailles André Mignot (CHV), Service de Neurologie [Rennes] = Neurology [Rennes], CHU Pontchaillou [Rennes], Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière (NEMESIS-CRICM), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut Français de Mécanique Avancée (IFMA), Neurologie - Côte Basque (NEUROLOGIE), Centre hospitalier universitaire de Nantes (CHU Nantes), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Cavale Blanche, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Internal and Cardiovascular Medicine - Stroke Unit (PERUGIA - ICM-SU), Università degli Studi di Perugia (UNIPG), Università degli Studi di Siena = University of Siena (UNISI), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neurologie - Côte Basque, Centre Hospitalier de la Côte Basque (CHCB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Università degli Studi di Perugia = University of Perugia (UNIPG), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-SIGMA Clermont (SIGMA Clermont), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Jagiellonian University [Krakow] (UJ), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Institut National de la Santé et de la Recherche Médicale (INSERM), Weimar, Christian (Beitragende*r), and Calvez, Ghislaine
Subjects: Male, Risk, Ticagrelor, Adenosine, [SDV]Life Sciences [q-bio], Population, Medizin, Hemorrhage, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Platelet aggregation inhibitors, Physiology (medical), [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, medicine, Humans, Myocardial infarction, education, Stroke, ComputingMilieux_MISCELLANEOUS, Aged, Aspirin, Ischemic attack, Transient, Female, Ischemic Attack, Transient, Purinergic P2Y Receptor Antagonists, Treatment Outcome, Cardiology and Cardiovascular Medicine, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [ SDV ] Life Sciences [q-bio], Ischemic Attack, business.industry, medicine.disease, Clopidogrel, [SDV] Life Sciences [q-bio], Anesthesia, Platelet aggregation inhibitor, business, 030217 neurology & neurosurgery, TIMI, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: Background: Patients with minor acute ischemic stroke or transient ischemic attack are at high risk for subsequent stroke, and more potent antiplatelet therapy in the acute setting is needed. However, the potential benefit of more intense antiplatelet therapy must be assessed in relation to the risk for major bleeding. The SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) was the first trial with ticagrelor in patients with acute ischemic stroke or transient ischemic attack in which the efficacy and safety of ticagrelor were compared with those of aspirin. The main safety objective was assessment of PLATO (Platelet Inhibition and Patient Outcomes)–defined major bleeds on treatment, with special focus on intracranial hemorrhage (ICrH). Methods: An independent adjudication committee blinded to study treatment classified bleeds according to the PLATO, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definitions. The definitions of ICrH and major bleeding excluded cerebral microbleeds and asymptomatic hemorrhagic transformations of cerebral infarctions so that the definitions better discriminated important events in the acute stroke population. Results: A total of 13 130 of 13 199 randomized patients received at least 1 dose of study drug and were included in the safety analysis set. PLATO major bleeds occurred in 31 patients (0.5%) on ticagrelor and 38 patients (0.6%) on aspirin (hazard ratio, 0.83; 95% confidence interval, 0.52–1.34). The most common locations of major bleeds were intracranial and gastrointestinal. ICrH was reported in 12 patients (0.2%) on ticagrelor and 18 patients (0.3%) on aspirin. Thirteen of all 30 ICrHs (4 on ticagrelor and 9 on aspirin) were hemorrhagic strokes, and 4 (2 in each group) were symptomatic hemorrhagic transformations of brain infarctions. The ICrHs were spontaneous in 6 and 13, traumatic in 3 and 3, and procedural in 3 and 2 patients on ticagrelor and aspirin, respectively. In total, 9 fatal bleeds occurred on ticagrelor and 4 on aspirin. The composite of ICrH or fatal bleeding included 15 patients on ticagrelor and 18 on aspirin. Independently of bleeding classification, PLATO, TIMI, or GUSTO, the relative difference between treatments for major/severe bleeds was similar. Nonmajor bleeds were more common on ticagrelor. Conclusions: Antiplatelet therapy with ticagrelor in patients with acute ischemic stroke or transient ischemic attack showed a bleeding profile similar to that of aspirin for major bleeds. There were few ICrHs. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01994720.
Published: 2017

43. Abstract 184: Intravenous Thrombolysis for Acute Ischemic Stroke in the 'Golden Hour': a Propensity-matched Analysis of SITS-EAST Registry

Author: Georgios Tsivgoulis, Aristeidis H Katsanos, Pavla Kadlecova, Anna Czlonkowska, Adam Kobayashi, Miroslav Brozman, Viktor Švigelj, Laszlo Csiba, Klara Fekete, Janika Kõrv, Vida Demarin, Aleksandras Vilionskis, Dalius Jatuzis, Yakup Krespi, Chrissoula Liantinioti, Sotirios Giannopoulos, and Robert Mikulik
Subjects: Advanced and Specialized Nursing, Scarce data, medicine.medical_specialty, business.industry, medicine.medical_treatment, Thrombolysis, 030204 cardiovascular system & hematology, medicine.disease, Surgery, 03 medical and health sciences, 0302 clinical medicine, Emergency medicine, Propensity score matching, medicine, Golden hour (medicine), Neurology (clinical), Symptom onset, Cardiology and Cardiovascular Medicine, business, Stroke, Acute ischemic stroke, 030217 neurology & neurosurgery
Abstract: Background & Purpose: There are scarce data regarding outcomes of AIS patients treated with IVT within 60 min from symptom onset (“golden hour”). We sought to compare outcomes between AIS patients treated within (OTT≤60 min) and outside (OTT: 61-270min) the “golden hour” [GH(+) & GH (-)] using a propensity score matching approach. Methods: Patients were evaluated during a 12-year period in a large, international, prospective registry of IVT (SITS-EAST). They underwent serial NIHSS-score assessments at baseline, 2 hrs and 24 hrs following tPA-bolus. Clinical recovery (CR) at 2 and 24 hrs was defined as a reduction of ≥10 points in NIHSS-score compared with baseline, or a NIHSS-score of ≤3 at 2 and 24 hrs respectively. A relative reduction in NIHSS-score of ≥40% at 2 hrs was predictive of complete recanalization (CREC). sICH was defined using SITS-MOST criteria; 3-month favourable functional outcome (FFO) was defined as a mRS-score of 0-1. The two groups were matched for demographics, risk factors, baseline NIHSS, admission blood pressure and serum glucose. Results: Out of 19.077 tPA-treated AIS patients, 71 patients in GH(+) group [mean age 67±13 years; median NIHSS-score 12 points (IQR 10); median onset to treatment time (OTT) 55min, (IQR 10)] were matched to 6882 patients in GH(-) group (mean age 67±12 years; median NIHSS-score 11 points (IQR 9); median OTT 155min (IQR 55)]. The two groups did not differ in any of the matched characteristics (p>0.1). GH(+) had significantly (p0.2) in the two groups. GH(+) was independently (p Conclusions: AIS patients treated with IVT within the GH have substantially higher odds of early CR and FFO. These findings highlight the potential of mobile stroke units to further improve AIS outcomes by increasing the rates of tPA delivery within the GH.
Published: 2017

44. Efficacy and safety of extended‐release oxcarbazepine (Oxtellar XR™) as adjunctive therapy in patients with refractory partial‐onset seizures: a randomized controlled trial

Author: E.I. Bogdanov, Waldemar Brola, Anna Czlonkowska, Vitalii Laskov, Anamarija Mrdjen, Urszula Fiszer, Maria Mazurkiewicz-Bełdzińska, Jacqueline French, David Burdette, Ildefonso Rodriguez-Leyva, and Hrvoje Hecimovic
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, adjunctive therapy, International Cooperation, Population, Oxcarbazepine, Phases of clinical research, partial-onset seizures, Placebo, Statistics, Nonparametric, law.invention, Young Adult, Drug Delivery Systems, Double-Blind Method, Randomized controlled trial, law, Internal medicine, medicine, Humans, education, Adverse effect, Aged, Retrospective Studies, education.field_of_study, Dose-Response Relationship, Drug, business.industry, Original Articles, refractory epilepsy, General Medicine, Middle Aged, extended-release oxcarbazepine, Carbamazepine, Neurology, Tolerability, Concomitant, Anesthesia, Anticonvulsants, Female, Epilepsies, Partial, Neurology (clinical), business, Follow-Up Studies, medicine.drug
Abstract: TM ) as adjunctive therapy in patients with refractory partial-onset seizures: a randomized controlled trial. Acta Neurol Scand 2014: 129: 143‐153. © 2013 The Authors. Acta Neurologica Scandinavica published by John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Objective – To evaluate the efficacy, tolerability, and safety of oncedaily 1200 mg and 2400 mg SPN-804 (Oxtellar XR TM , Supernus Pharmaceuticals), an extended-release tablet formulation of oxcarbazepine (OXC), added to 1-3 concomitant antiepileptic drugs (AEDs) in adults with refractory partial-onset seizures, with or without secondary generalization. Methods – The Prospective, Randomized Study of OXC XR in Subjects with Partial Epilepsy Refractory (PROSPER) study was a multinational, randomized, double-blind, parallel-group Phase 3 study. The primary efficacy endpoint was median percent reduction from baseline in monthly (28-day) seizure frequency for the 16-week double-blind treatment period in the intentto-treat (ITT) population with analyzable seizure data. Other efficacy analyses included proportion of patients with ≥ 50% seizure reduction, proportion of patients seizure free, and the relationship between clinical response and plasma concentration. Results – Median percent reduction was -28.7% for placebo, 38.2% (P = 0.08 vs placebo) for once-daily SPN-804 1200 mg, and 42.9% (P = 0.003) for SPN-804 2400 mg. Responder rates were 28.1%, 36.1% (P = 0.08), and 40.7% (P = 0.02); 16-week seizure-free rates in a pragmatic ITT analysis were 3.3%, 4.9% (P = 0.59), and 11.4% (P = 0.008), respectively. When data were analyzed separately for study site clusters, a post hoc analysis demonstrated that both SPN-804 dosages were significantly superior to placebo in median percent seizure reduction (placebo: 13.3%; 1200 mg: 34.5%, P = 0.02; 2400 mg: 52.7%, P = 0.006) in the North American study site cluster. A concentration–response analysis also supported a clinically meaningful effect for 1200 mg. Adverse event types reflected the drug’s established profile. Adverse event frequency was consistent with a pharmacokinetic profile in which SPN-804 produces lower peak plasma concentrations vs immediate-release OXC. Once-daily dosing was not associated with any new safety signals. Conclusions – Adjunctive once-daily SPN-804 improved seizure control in patients with inadequately controlled partial-onset seizures. Adverse event occurrence and discontinuations due to adverse events suggest improved tolerability vs previously published data with immediaterelease OXC.
Published: 2013

45. Autoantibodies in Wilson disease: Impact on clinical course

Author: Magdalena Antczak‐Kowalska, Anna Członkowska, Ceren Eyileten, Anna Palejko, Agnieszka Cudna, Marta Wolska, Agnieszka Piechal, and Tomasz Litwin
Subjects: antineuronal antibodies, anti‐neutrophil cytoplasmic antibodies, antinuclear antibodies, autoantibodies, drug‐induced antibodies, Wilson disease, Diseases of the endocrine glands. Clinical endocrinology, RC648-665, Genetics, QH426-470
Abstract: Abstract Symptoms of Wilson disease (WD) vary and additional factors such as autoimmunity may play an important role in WD pathogenesis. The presence of antinuclear antibodies (ANA), anti‐neutrophil cytoplasmic antibodies, neuronal surface antibodies, and onconeural antibodies in WD was investigated using standardized indirect immunofluorescence assays and Western Blot analysis. The presence of all studied autoantibodies was higher in WD patients in comparison to healthy subjects, but there was no statistically significant difference in autoantibodies frequency according to disease manifestation. D‐penicillamine treatment was associated with a higher presence of ANA than zinc sulfate but without an increase in autoimmune diseases rate.
Published: 2022
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46. Oxfordshire community stroke project clinical stroke syndrome and appearances of tissue and vascular lesions on pretreatment ct in hyperacute ischemic stroke among the first 510 patients in the Third International Stroke Trial (IST-3)

Author: Steff Lewis, Anna Czlonkowska, Christian Lueck, Richard Lindley, Andrea Zini, Joanna Wardlaw, and Peter Sandercock
Subjects: medicine.medical_specialty, Brain Ischemia, law.invention, Lesion, Brain ischemia, Plasminogen Activators, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Randomized controlled trial, law, Internal medicine, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Infarction, Anterior Cerebral Artery, Stroke, Advanced and Specialized Nursing, Cerebral infarction, Vascular disease, business.industry, Ischemic Change, Australia, Brain, medicine.disease, Magnetic Resonance Imaging, Recombinant Proteins, 3. Good health, Surgery, Tissue Plasminogen Activator, Acute Disease, Cardiology, Neurology (clinical), medicine.symptom, Tomography, X-Ray Computed, Cardiology and Cardiovascular Medicine, business, Algorithms, 030217 neurology & neurosurgery
Abstract: Background and Purpose— The Oxfordshire Community Stroke Project (OCSP) clinical stroke syndrome classification correlates well with the stroke lesion in established ischemic stroke, but there are few data in patients with hyperacute stroke. We wished to assess whether the OCSP correlated with the site and size of the ischemic lesion and location of cerebral vessel lesion on computed tomography (CT) in hyperacute stroke. Methods— Prospective study of ischemic stroke patients presenting within 6 hours of onset in the Third International Stroke Trial (IST-3), a randomized, controlled trial of rt-PA. OCSP syndrome was assigned by a computer-based algorithm. The CT assessment was made by a neuroradiologist blinded to clinical details. Results— We assessed baseline data and CT findings for the first 510 patients; early tissue ischemic changes were present in 329/510 (65%) total anterior circulation syndrome (TACS) - 79%; partial anterior circulation syndrome (PACS) - 57%, lacunar syndrome (LACS) - 40%; posterior circulation syndrome (POCS) - 33%. The site and size of ischemic change on CT was compatible with the clinical syndrome in 79%, 37%, 2%, and 14%, respectively. Assuming that all patients with a normal CT scan will develop an incompatible lesion these numbers reflected the “worst possible scenario.” For the “best possible scenario” we presumed that those with a normal CT will develop concordant ischemic change and the proportions were 100%, 80%, 62% and 81%, respectively. The hyperattenuated artery sign was seen in 206/510 (40%); (TACS 54%; PACS 35%, LACS 5%, and POCS 19%). Conclusions— Within 6 hours of stroke, in patients with a nonlacunar syndrome, the OCSP syndrome correlated well with the pattern of ischemic change on CT. For clinicians who wish to restrict the use of thrombolytic therapy to large-artery ischemic stroke, concordance of clinical and CT appearances may give greater confidence in making therapeutic decisions in hyperacute stroke. In centers where immediate access to MR is limited, use of the classification may help focus use of MR on patients with suspected LACS and POCS. The utility of the classification may further increase if IST-3 establishes that the OCSP syndrome significantly modifies response to thrombolytic therapy.
Published: 2009
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47. Abstract 93: Do Intracerebral Hemorrhage 'Non-Expanders' Actually Expand into the Ventricular Space?

Author: Anirudda Deshpande, Andrew M Demchuk, David R Luna, Richard I Aviv, Carlos A Molina, Yolanda S Blas, Imanuel Dzialowski, Cheemun Lum, Anna Czlonkowska, Jean M Boulanger, Carlos S Kase, Gord Gubitz, Rohit Bhatia, Vasantha Padma, Jayanta Roy, Michael D Hill, and Dar Dowlatshahi
Subjects: Advanced and Specialized Nursing, Neurology (clinical), Cardiology and Cardiovascular Medicine
Abstract: Background: The CT-angiography spot sign as a predictor of hematoma expansion (HE) is limited by its modest sensitivity and PPV. Spot sign studies restrict HE definitions to the parenchymal component of ICH and do not consistently evaluate intraventricular hemorrhage (IVH) expansion. Decompression of ICH into the ventricular space can lead to underestimation of HE and overestimation of false-positive spot signs. We hypothesized that a proportion of ICH “non-expanders” expand into the ventricular space and including IVH expansion in HE definitions will improve the predictive performance of the spot sign. Our objectives were: 1) determine the proportion of ICH “non-expanders” who have IVH expansion, 2) determine the proportion of “false-positive” spot signs that have IVH expansion, 3) compare the known predictive performance of the spot sign to its performance when using an HE definition incorporating IVH expansion, and 4) explore the predictors of IVH expansion. Methods: We analyzed patients from the multicenter PREDICT ICH spot sign study. We defined HE as ≥6mL or ≥33% ICH expansion or >2ml IVH expansion, and compared the performance of this new definition with the conventional 6mL/33% parenchymal definition using ROC analysis. We used regression analysis to determine the predictors of IVH expansion. Results: Of 315 patients with complete imaging, 215 did not meet the 6mL/33% expansion definition ("non-expanders"). Only 14/215 (6.5%) of “non-expanders” had ≥2mL IVH expansion. Of the “false positive” spot signs, 4/39 (10.3%) had >2mL ventricular expansion. The AUC for spot sign to predict significant ICH expansion was 0.65 [95% CI 0.58-0.72], which was no different then when IVH expansion was added to the HE definition: AUC 0.64 [95% CI 0.58-0.71]. Predictors for IVH expansion included IVH at baseline (aOR 2.5, p=0.013), elevated INR (aOR 2.5, p=0.011), and spot sign (aOR 5.9, p Conclusions: IVH expansion occurs in a small minority of “non-expanders”, and only 10% of “false positive” post signs actually expended in the ventricular space. Furthermore, revising HE definitions to include IVH expansion did not alter the predictive performance of the spot sign.
Published: 2015

48. Successful treatment with intravenous recombinant tissue plasminogen activator in an acute stroke patient presenting with hemiballism

Author: Anna Czlonkowska and Jan Bembenek
Subjects: General Neuroscience, Neurology (clinical), General Medicine
Published: 2015

49. Abstract 30: Association of Fluid Levels, Density Heterogeneity and Irregular Margins on Baseline Non-Contrast Computerized Tomography With Significant Hematoma Expansion in Intracerebral Hemorrhage

Author: Dylan Blacquiere, Andrew Demchuk, Mohammed al-Hazzaa, Cheemun Lum, David Rodriguez-Luna, Carlos Molina, Yolanda Silva Blas, Immanuel Dzialowski, Anna Czlonkowska, Jean-Martin Boulanger, Gord Gubitz, Vasantha Padma, Rohit Bhatia, Jayanta Roy, Carlos Kase, Michael Hill, Richard Aviv, and Dar Dowlatshahi
Subjects: Advanced and Specialized Nursing, Neurology (clinical), Cardiology and Cardiovascular Medicine
Abstract: Introduction: The PREDICT study confirmed that the spot sign was a valid predictor of expansion in intracerebral hemorrhage (ICH) at 24h, with a positive predictive value (PPV) of 61%. This technique requires access to computed tomography angiography (CTA). Other markers may enhance the ability to predict expansion in ICH, or be useful in cases where multimodal imaging is not available. Previous studies have suggested that markers on non-contrast computed tomography (NCCT) such as density heterogeneity within the hematoma, irregularity of external margins, or internal fluid levels are associated with hematoma expansion (HE). Methods: Baseline NCCT scans of patients enrolled in PREDICT were examined for the presence of internal fluid levels (defined as a change within the hematoma resulting in a linear interface between two discrete fluid densities) and for the presence of hematoma density heterogeneity and margin irregularity (using an ordinal scale of 1-5 defined, published and validated previously). The association of each marker with median 24h absolute growth and with significant HE (defined as an increase in hematoma size of 6 mL or 33% measured 24h from baseline) were determined. Results: Fluid levels were present in 29 (8.3%) of 351 eligible patients. The presence of fluid levels were associated with significant HE at 24h (χ2 =7.64, df=1, p Conclusions: Density heterogeneity and fluid levels are associated with significant HE at 24h, and margin irregularity is associated with increased median hematoma size. These markers may be useful for predicting significant HE in ICH in cases where CTA is unavailable to identify the presence of a spot sign. They may also provide additional variables to incorporate into risk scores for hematoma expansion.
Published: 2014

50. Abstract 75: Safety of Statin Pretreatment in Intravenous Thrombolysis (IVT) for Acute Ischemic Stroke (AIS)

Author: Georgios Tsivgoulis, Pavla Kadlecová, Anna Czlonkowska, Miroslav Brozman, Victor Švigelj, Laszlo Csiba, Janika Kõrv, Vanja Bašic Kes, Dalius Jatuzis, Jobst Rudolf, Ekaterini-Christina Tampaki, Yakup Krespi, and Robert Mikulik
Subjects: Advanced and Specialized Nursing, Neurology (clinical), Cardiology and Cardiovascular Medicine
Abstract: Background&Purpose: A recent meta-analysis investigating the association between statin pretreatment and early outcomes in patients with AIS indicated that pre-stroke statin treatment was associated with increased risk of 90-day mortality and symptomatic intracranial hemorrhage (sICH). We sought to investigate the potential association of statin pretreatment with early outcomes in a large, international registry of AIS patients treated with IVT. Subjects&Methods: We analyzed prospectively collected data from the Safe Implementation of Treatments in Stroke-East registry (SITS-EAST) on consecutive AIS patients treated with IVT during a seven-year period. We used three widely accepted definitions for sICH from NINDS-rtPA-Stroke Study, ECASS II trial and SITS registry. Dramatic clinical recovery (DCR) within 24 hours was defined as reduction in the baseline NIHSS-score of ≥10 points. Favorable functional outcome (FFO) at three months was defined as modified Rankin Scale score of 0-1. Results: We analyzed a total of 1660 AIS patients (mean age 67±13 years, median baseline NIHSS-score 11 points, interquartile range 5-16). Patients with statin pretreatment (n=373, 23%) had higher (p=0.019) baseline stroke severity compared to cases who had not received any statin at symptom onset. After adjusting for demographics, baseline stroke severity, onset-to-treatment time, history of previous stroke, risk factors, and admission blood pressure levels, statin pretreatment was not associated with a higher likelihood of sICH defined by the NINDS (OR: 1.41; 95%CI: 0.83-2.39; p=0.201), ECASS II (OR: 1.13; 95%CI: 0.60-2.14; p=0.712) or SITS (OR: 1.89; 95%CI: 0.75-4.77; p=0.178) criteria. Statin pretreatment was not related to three-month all-cause mortality (OR: 0.92; 95%CI: 0.57-1.49; p=0.741) or three-month FFO (OR: 0.81; 95%CI: 0.52-1.27; p=0.364). Statin pretreatment was independently associated with a higher odds of DCR (OR: 1.91; 95%CI: 1.25-2.92; p=0.003). Conclusions: Our findings indicate that statin therapy at symptom onset is not associated with adverse outcomes in AIS patients treated with IVT, while statin pretreatment almost doubles the likelihood of DCR during the first hours following tPA-infusion.
Published: 2014

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