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1. Effect of the Factor XIa Inhibitor Asundexian According to Baseline Infarct Pattern and on MRI Covert Infarct Outcomes

Author

Smith, Eric E., Shoamanesh, Ashkan, Xu, Lizhen, Heenan, Laura, Saad, Feryal, Colorado, Pablo, Chen, Chih-Hao, Lemmens, Robin, De Marchis, Gian Marco, Caso, Valeria, Masjuan, Jaime, Hirano, Teruyuki, Milanov, Ivan, Campbell, Bruce C.V., Mas, Jean-Louis, Connolly, Stuart J., Mundl, Hardi, Hart, Robert G., Bailey, P., Campbell, B.C.V., Kleinig, T., Cordato, D., Choi, P., Garcia-Esperon, C., Chew, A., Cloud, G., Stanislaus, V., Krause, M., Priglinger, M., Grimley, R., Ghia, D., Sahathevan, R., Brown, H., Kwan, C., Devlin, M., Greisenegger, S., Bonelli-Nauer, S., Rath, J., Langer, A., Marko, M., Ferrari, J., Bernegger, A., Baumgartinger, M., Vigl, M., Krebs, S., Lang, W., Knoflach, M., Dejakum, B., Kiechl, S., Töll, T., Domig, L., Mutzenbach, J.S., Ganser, B., Hecker, C., Rösler, C., Bubel, N., Pikija, S., Zellner, T., Leitner, U., Berger, O., Surböck, B., Beirer, S., Staykov, D., Schrammel, D., Halilovic, A., Frattner, M., Barmherzigen, D., Lampl, C., Höfer, C., Nagl, S., Bocksrucker, C., Lemmens, R., Demeestere, J., Desfontaines, P., Ciobanu, C., De Pauw, A., Terwecoren, A., Hasenbroekx, M.C., Clement, F., De Klippel, N., Soors, P., Hermans, S., De Raedt, S., Vandervorst, F., Seynaeve, L., Fockaert, N., Smet, S., Rutgers, M., Del Gaudio, N., Paindeville, P., Staikov, I., Simeonova, A., Stoyanova, I., Cholakova, M., Mihnev, N., Petrova, T., Koralova, A., Dimov, D., Kuzev, Y., Danovska, M., Marinova, D., Marinova-Trifonova, D., Ovcharova, E., Mladenovski, I., Yanakieva, M., Stoev, P., Dimitrova, M., Todorova-Georgieva, S., Haralanov, L., Milkov, B., Solakov, D., Petkova, N., Ignatova-Valkova, V., Karabinov, V., Marinova, V., Miteva, Y., Andonova, V., Kasabova, D., Kostadinova, E., Shopova-Vrabcheva, Y., Gatev, D., Semova, D., Halil, E., Kaprelyan, A., Ivanov, B., Panov, G., Grudkova, M., Syuleyman, N., Kalpachki, R., Alexiev, F., Ivanova, I., Kancheva, K., Sakelarova, T., Maslarov, D., Drenska, D., Georgiev, V., Petrova, K., Petrova, N., Ivanova, I., Milanov, I., Semerdjieva, N., Zhelyazkov, P., Spasova-Markova, S., Dong, X., Wang, D., Wang, S., Huang, W., Zhao, H., Wang, C., Jie, L., Xinyang, Y., Ping, Z., Dong, Q., Wang, Y., Fuling, Y., Yue, W., Liu, R., Yang, Y., Stetkarova, I., Mikulenka, P., Vasko, P., Peisker, T., Bar, M., Roubec, M., Mikulik, R., Cabukova, M., Vinklarek, J., Kovar, M., Pansky, M., Mencl, P., Skoda, O., Carek, M., Pernicka, M., Skodova, M., Geier, P., Cepkova, J., Drlik, J., Prax, T., Herzig, R., Krajickova, D., Vitkova, E., Haluskova, S., Vaclavik, D., Martinkova, J., Blejcharova, K., Tkacova, M., Pavlik, O., Nevšímalová, M., Rosol, J., Nevsimalova, M., Hruby, R., Iversen, H., Andersen, A.V., Rahimi, D., Christensen, H., Grundtvig, J., Hjort, N., Andersen, G., Sandal, B., Stilund, M., Modrau, B., Strade, A., Porobic, M., Andersen, S.D., Kruuse, C., Ölmestig, J., Kolmos, M., Parvez, A., Christensen, T., Stokholm, J., Jensen, H.B., Putaala, J., Strbian, D., Sibolt, G., Tiainen, M., Martinez-Majander, N., Curtze, S., Raty, S., Kraemer, Y., Roine, R., Aivo, J., Ruuskanen, J., Ylikotila, P., Roine, S., Hallikainen, M., Jakala, P., Kurl, S., Julkunen, V., Sibon, I., Olindo, S., Richard, S., Larrue, V., Gollion, C., Catala, H., Henon, H., Lucie, D.S., Nelly, D., Mas, J.L., Calvet, D., Malbranque, A., Mazé, B., Barbieux-Ghitu, C., Pitie Salpetriere, G.H., Rosso, C., Samson, Y., Vannier, S., Moulin, T., Bonnet, L., Reiner, P., Buffon, F., Denier, C., Amri, K., Legris, N., Chassin, O., Selli, N., Mariana, S., Berrouschot, J., Stoll, A., Klunk, D., Keilitz, J., Neustadt, M., Zerrenner, S., Veltkamp, R., Hajjar, K., Heeger, A., Winezki, E., Apel, L., Pompsch, M., Mueller, P., Rappard, P., Auer, R., Ringleb, P.A., Berberich, A., Heyse, M., Mundiyanapurath, S., Reiff, T., Poli, S., Gomez-Exposito, A., Mengel, A., Tünnerhoff, J., Adeyemi, K., Poli, K., Kusch, V., Pelz, J., Michalski, D., Wartenberg, K., Althaus, K., Tavares, F., Mueller, S., Soda, H., Rascher, A., Hiermann, E., Weinhardt, R., Weissenborn, K., Leotescu, A., Grosse, G., Worthmann, H., Ernst, J., Gabriel, M., Schuppner, R., Schäfer, J.H., Charisse, D., Gruber, K., Kurka, N., Reitz, S.C., Pfeilschifter, W., Lee, J.I., Gliem, M., Moll, M., Steiner, T., Segura, L., Szegedi, N., Barandi, D., Uhrinakova, L., Czencz, M., Pasztor, M., Gyuker, N., Bartha, N.E., May, Z., Simony, Z., Szasz, G., Kakuk, I., Pető, N., Panczel, G.F., Olah, A., Racz, O., Balla, T., Horvath, B., Tuba, K., Czinderi, V., Klivenyi, P., Annus, A., Hertelendy, P., Szapary, L., Bosnyak, E., Kalmar, P., Karadi, Z., Cziba, L., Olah, L., Berki, A., Hudak, L., Kozák, M., Babel, S., Nemeth, L., Molnár, B., Simon, Z., Roveri, L., Cerri, F., Giacalone, G., Zini, A., Mauro, G., Asioli, G.M., Forlivesi, S., Arnone, G., Caso, V., Fiaccadori, A., Maria Fontana Francesca, E., Allegra, G., Mosconi, M.G., Longoni, M., Terlizzi, R., Paolucci, M., Tassi, R., Franci, B., Lucani, B., Domenichelli, C., Paoletti, D., Acampa, M., Zedde, M.L., Pezzella, F.R., Mangiardi, M., Galizia, P., Anticoli, S., Scalise, S., Lattanzi, S., Norata, D., Cannuccia, M., Cavallini, A., Federica, F., Denaro, M.F., Tosi, P., Sonoda, K., Kawajiri, M., Kusano, Y., Haraguchi, K., Kawano, H., Terasaki, T., Kaneko, C., Murase, S., Kumagai, M., Murai, N., Miyazaki, Y., Mori, T., Hatano, T., Kawanishi, M., Ochiai, J., Ishihara, S., Uehara, T., Yasaka, M., Nakagawa, H., Makino, M., Yonehara, T., Fukushima, Y., Hirotsune, N., Sakai, N., Yamasaki, M., Coutinho, J., Wouters, A., den Hertog, H., Zwartbol, R., Beumer, D., Kerklaan, J., Hilkens, P., Schreuder, T., Propper, D., Slowik, A., Wlodarczyk, E., Wrona, P., Pulyk, R., Lasek-Bal, A., Kosarz-Lanczek, K., Puz, P., Bilik, M., Magielska, A., Zamiela – Żółciak, A., Ochocinska, L., Bahdasaryan, S., Stępień, A., Dębiec, A., Joanna, K., Pawel, M., Jacek, S., Daniel, P., Marta, S., Rejdak, K., Wojczal, J., Luchowski, P., Fryze, W., Wisniewska, A., Krzyzanowska, M., Skowron, P., Wolosz, A., Galan, A., Grzymala, K., Krajewska, M., Nowak, R., Kłos, M., Cruz, V., Castro, P., Ferro, J., Canhão, P., Gouveia, R., Inácio, N., Rodrigues, M., Rachão, A., Ionel, C., Pereira, L., Viana-Baptista, M., Machado, C., Fernandes, C., Sargento, J., Inácio, N., Timchenko, L., Mironova, J., Zhadan, O., Torgashova, A., Bazhenova, O., Barashenkova, M., Kireeva, M., Romadina, N., Stepanova, I., Lenskaya, L., Lukinykh, L., Vorontsova, T., Agafina, A., Fedorova, A., Yashina, A., Alasheev, A., Smolkin, A., Prazdnichkova, E., Lutskovich, O., Gonysheva, Y., Mordvintseva, E., Nechaev, A., Martynova, E., Fedoraeva, N., Vishnyakova, T., Popov, D., Merzliakova, A., Margarita, K., Rechkalova, L., Ilyina, A., Kurenkova, N., Barbarash, O., Bazdyrev, E., Zvereva, T., Hromova, A., Morkvenas, A., Postnikova, E., Kovalenko, G., Taran, I., Pavlov, L., Ott, M., Chernitsova, N., Vodopyanova, N., Drozdova, E., Korebo, E., Lobanova, M., Lazareva, N., Snegova, N., Nikolaeva, O., Kolesnikov, Y., Kosheleva, Y., Krastev, G., Tomasova, K., Danis, M., Mako, M., Jankovicova, Z., Stevkova, Z., Kovacik, M., Kubikova, T., Jarosova, A., Serdahely, V., Cilingova, I., Pribulova, I., Sedlak, J., Slebodova, K., Paldaufova, M., Risnovsky, R., Berndtova, B., Urbanova, I., Junas, R., Karapetian, S., Gurcik, L., Vantrobova, A., Verbovsky, F., Vanacka, K., Ferenc, M., Galik, P., Bucakova, S., Ferencova, M., Kubalova, P., Boksanska, Z., Zacharova, E., Mahundi, E., Judita, H., Bachnak, M., Turcani, P., Kvasnicova Kamenska, A., Jurik, M., Vestenicka, V., Kycina, M., Sagatova, E., Dvorak, M., Hlubekova, A., Kucera, C., Gernath, L., Ferenc, M., Frimmelova, P., Slebodnikova, J., Aksteinerova, N., Horny, V., Gregova, Z., Segura, T., Romero, C., Ayo, O., Masjuan Vallejo, J., Cruz, A., . De felipe, A, Matute, M.C., Garcia, S., Tembl Ferrairo, J., Vielba, I., Morales Caba, L., Molina, C., Garcia-Tornel García-Camba, Á., Requena Ruiz, M., Noelia, R., Rodriguez-Yañez, M., Rodriguez Castro, E., Lopez, I., Santamaria, M., Arias, S., Purroy García, F., Vázquez Justes, D., Mauri Capdevila, G., Vicente Pascual, M., Martí Fabregas, J., Camps Renom, P., Rodríguez Campello, A., Giralt, E., Krupinski, J., Molina, J., Trillo Senin, C. Ramos Martin, S., De La Fuente Sanz, E., Moniche, F., Manuel, M.R., Pardo, B., Martínez, I., Hernández Pérez, M., Arenillas Lara, J.F., De Lera, M., Egido, J.A., Gomez Escalonilla, C., Guillan, M., Martinez, J., Lindgren, A., Andsberg, G., Wictor, L., Leonidou, M., Stenman, M., Dalberg, N., Laska, A.C., Grünfeldt, A., Lundström, A., Nadzjafov, E., Rooth, E., Dalenbring, I., Sandén, P., Johansson, E., Thomas, G., De Marchis, G.M., Zietz, A.V., Rudin, S., Dittrich, T.D., Lilian, K., Kägi, G., Vehoff, J., Arnold, M., Scutelnic, A., Clénin, L., Beyeler, M., Madlaine, M., Maamari, B., Siepen, B., Vynckier, J., Tarnutzer, A., Bertschi, D., Luciani, M., Cereda, C., Maulucci, F., Bianco, G., Shairin, S., Pihan, H.A., Salmen, S., Quinn, T., McAlpine, C., Wright, F., Kalladka, D., Taylor, E., Sohaa, J., Brown, Z., Dawson, J., Cameron, A., Muir, S., Dima, S., Khan, U., Zhang, L., Warburton, E., Chatterjee, K., Nallasivan, A., Curran, D., Haider, S., Ghani, U., Kenton, A., Dallol, B., Mirza, M., Menezes, B., Davies, R., Robinson, T.G., Manning, L., Sztriha, L., Phinney, T., Sethi, P., Altafullah, I., Sharaf, A., Ostrander, M., Renati, S., Burgin, W.S., Olds, K., Delio, P., Malek, A., Dissin, J., Khatri, P., Flaherty, M., Demel, S., and Dofitas, S.

Published
2024
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3. Establishing an online resource to facilitate global collaboration and inclusion of underrepresented populations: Experience from the MJFF Global Genetic Parkinson's Disease Project.

Author

Eva-Juliane Vollstedt, Harutyun Madoev, Anna Aasly, Azlina Ahmad-Annuar, Bashayer Al-Mubarak, Roy N Alcalay, Victoria Alvarez, Ignacio Amorin, Grazia Annesi, David Arkadir, Soraya Bardien, Roger A Barker, Melinda Barkhuizen, A Nazli Basak, Vincenzo Bonifati, Agnita Boon, Laura Brighina, Kathrin Brockmann, Andrea Carmine Belin, Jonathan Carr, Jordi Clarimon, Mario Cornejo-Olivas, Leonor Correia Guedes, Jean-Christophe Corvol, David Crosiers, Joana Damásio, Parimal Das, Patricia de Carvalho Aguiar, Anna De Rosa, Jolanta Dorszewska, Sibel Ertan, Rosangela Ferese, Joaquim Ferreira, Emilia Gatto, Gençer Genç, Nir Giladi, Pilar Gómez-Garre, Hasmet Hanagasi, Nobutaka Hattori, Faycal Hentati, Dorota Hoffman-Zacharska, Sergey N Illarioshkin, Joseph Jankovic, Silvia Jesús, Valtteri Kaasinen, Anneke Kievit, Peter Klivenyi, Vladimir Kostic, Dariusz Koziorowski, Andrea A Kühn, Anthony E Lang, Shen-Yang Lim, Chin-Hsien Lin, Katja Lohmann, Vladana Markovic, Mika Henrik Martikainen, George Mellick, Marcelo Merello, Lukasz Milanowski, Pablo Mir, Özgür Öztop-Çakmak, Márcia Mattos Gonçalves Pimentel, Teeratorn Pulkes, Andreas Puschmann, Ekaterina Rogaeva, Esther M Sammler, Maria Skaalum Petersen, Matej Skorvanek, Mariana Spitz, Oksana Suchowersky, Ai Huey Tan, Pichet Termsarasab, Avner Thaler, Vitor Tumas, Enza Maria Valente, Bart van de Warrenburg, Caroline H Williams-Gray, Ruey-Mei Wu, Baorong Zhang, Alexander Zimprich, Justin Solle, Shalini Padmanabhan, and Christine Klein

Subjects
Medicine, Science
Abstract

Parkinson's disease (PD) is the fastest-growing neurodegenerative disorder, currently affecting ~7 million people worldwide. PD is clinically and genetically heterogeneous, with at least 10% of all cases explained by a monogenic cause or strong genetic risk factor. However, the vast majority of our present data on monogenic PD is based on the investigation of patients of European White ancestry, leaving a large knowledge gap on monogenic PD in underrepresented populations. Gene-targeted therapies are being developed at a fast pace and have started entering clinical trials. In light of these developments, building a global network of centers working on monogenic PD, fostering collaborative research, and establishing a clinical trial-ready cohort is imperative. Based on a systematic review of the English literature on monogenic PD and a successful team science approach, we have built up a network of 59 sites worldwide and have collected information on the availability of data, biomaterials, and facilities. To enable access to this resource and to foster collaboration across centers, as well as between academia and industry, we have developed an interactive map and online tool allowing for a quick overview of available resources, along with an option to filter for specific items of interest. This initiative is currently being merged with the Global Parkinson's Genetics Program (GP2), which will attract additional centers with a focus on underrepresented sites. This growing resource and tool will facilitate collaborative research and impact the development and testing of new therapies for monogenic and potentially for idiopathic PD patients.

Published
2023
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6. Eye-tracking-aided characterization of saccades and antisaccades in SYNE1 ataxia patients: a pilot study

Author

Laszlo Szpisjak, Gabor Szaraz, Andras Salamon, Viola L. Nemeth, Noemi Szepfalusi, Gabor Veres, Balint Kincses, Zoltan Maroti, Tibor Kalmar, Malgorzata Rydzanicz, Rafal Ploski, Peter Klivenyi, and Denes Zadori

Subjects
SYNE1, Ataxia, Genetics, Eye movement, Eye tracking, Saccade, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurophysiology and neuropsychology, QP351-495
Abstract

Abstract Background SYNE1 ataxia is an autosomal recessive hereditary condition, the main characteristic features of which are gait and limb ataxia and cerebellar dysarthria. Reports have revealed that the clinical phenotype of SYNE1 ataxia is more complex than the first published cases with pure cerebellar signs indicated. The aim of this study was to characterize eye movement alterations in the first diagnosed Hungarian SYNE1 ataxia patients. Results Saccades and antisaccades were examined with an eye tracker device in 3 SYNE1 (one patient has two frameshift mutations [c.8515_8516insA, p.Met2839Asnfs*53 and c.11594_11595insG, p.Glu3866*] in a compound heterozygous state, whereas two subjects have a splicing variant [c.23146-2A > G] in a homozygous state), 6 Friedreich ataxia (FA) patients and 12 healthy controls. Besides that, detailed clinical phenotyping and comprehensive neuropsychological assessment were carried out in all patients with ataxia. In addition to the characteristic cerebellar alterations, pyramidal signs and polyneuropathy were observed at least in 2 SYNE1 ataxia patients, for which no other underlying reason was found. The eye tracking assessment revealed hypometric saccades in the longer amplitude (18.4°) saccadic paradigm in all SYNE1 patients, whereas 2 out of 3 SYNE1 subjects performed slow saccades as well. In the antisaccade task, higher incorrect ratios of antisaccades were demonstrated in SYNE1 patients compared to healthy controls, showing inverse correlation with working memory test results. The corresponding data of FA patients was dispersed over a wide range, partially overlapping with control data. Conclusions The current study draws attention to the presence of eye movement disorders in patients with SYNE1 ataxia and demonstrates that alterations in the antisaccade paradigm may be related to working memory deficits.

Published
2021
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7. A longitudinally extensive H3 K27M-mutant diffuse midline glioma in an elderly patient clinically mimicking central nervous system inflammation: a case report

Author

Kristof Babarczy, Zita Reisz, Elza Szabo, Cecilia Rajda, Laszlo Vecsei, Istvan Bodi, Peter Klivenyi, Tibor Hortobagyi, and Levente Szalardy

Subjects
diffuse intrinsic pontine glioma, diffuse midline glioma, elderly, histone, k27m., Medicine
Abstract

Diffuse midline gliomas, H3 K27M-mutant, World Health Organization (WHO) grade IV represent a distinct glioma entity with a predominantly paediatric presentation and remarkably poor prognosis. This report presents a case of a 73-year-old woman with a diffuse midline glioma, H3 K27M-mutant, WHO grade IV with a remarkable longitudinal extension, extending from the cervical myelon to the basal ganglia. On imaging, the lesion was predominantly suggestive of inflammatory oedema, and it was clinically associated with progressive hemi- and later tetraparesis with severe autonomic and bulbar symptoms. Laboratory examinations suggested a generalized inflammatory process; however, neither infectious nor autoimmune aetiology could be confirmed. Biopsy was deemed unfeasible given the critical localization. Presuming a seronegative autoimmune encephalomyelitis, high-dose corticosteroid therapy and plasma exchanges were conducted, resulting in a modest but transient relief. The patient passed away two months after hospitalization. Neuropathological examination of the lesion revealed a high-grade diffuse glioma with H3 K27M mutation (grade IV). Although originally considered as a paediatric entity, our case confirms reports from recent years that diffuse midline gliomas, H3 K27M-mutant, WHO grade IV can occur in adults, even among the elderly, and can mimic inflammatory alterations, posing diagnostic difficulty. Our case is one of the oldest patients reported with this pathology, the oldest with an extensive diffusely infiltrating growth pattern, and with the most extensive lesion reported in adulthood.

Published
2021
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12. The ARCA Registry: A Collaborative Global Platform for Advancing Trial Readiness in Autosomal Recessive Cerebellar Ataxias

Author

Andreas Traschütz, Selina Reich, Astrid D. Adarmes, Mathieu Anheim, Mahmoud Reza Ashrafi, Jonathan Baets, A. Nazli Basak, Enrico Bertini, Bernard Brais, Cynthia Gagnon, Janina Gburek-Augustat, Hasmet A. Hanagasi, Anna Heinzmann, Rita Horvath, Peter de Jonghe, Christoph Kamm, Peter Klivenyi, Thomas Klopstock, Martina Minnerop, Alexander Münchau, Mathilde Renaud, Richard H. Roxburgh, Filippo M. Santorelli, Tommaso Schirinzi, Deborah A. Sival, Dagmar Timmann, Stefan Vielhaber, Michael Wallner, Bart P. van de Warrenburg, Ginevra Zanni, Stephan Zuchner, Thomas Klockgether, Rebecca Schüle, Ludger Schöls, PREPARE Consortium, and Matthis Synofzik

Subjects
ataxia, registry, network, natural history, trial readiness, Neurology. Diseases of the nervous system, RC346-429
Abstract

Autosomal recessive cerebellar ataxias (ARCAs) form an ultrarare yet expanding group of neurodegenerative multisystemic diseases affecting the cerebellum and other neurological or non-neurological systems. With the advent of targeted therapies for ARCAs, disease registries have become a precious source of real-world quantitative and qualitative data complementing knowledge from preclinical studies and clinical trials. Here, we review the ARCA Registry, a global collaborative multicenter platform (>15 countries, >30 sites) with the overarching goal to advance trial readiness in ARCAs. It presents a good clinical practice (GCP)- and general data protection regulation (GDPR)-compliant professional-reported registry for multicenter web-based capture of cross-center standardized longitudinal data. Modular electronic case report forms (eCRFs) with core, extended, and optional datasets allow data capture tailored to the participating site's variable interests and resources. The eCRFs cover all key data elements required by regulatory authorities [European Medicines Agency (EMA)] and the European Rare Disease (ERD) platform. They capture genotype, phenotype, and progression and include demographic data, biomarkers, comorbidity, medication, magnetic resonance imaging (MRI), and longitudinal clinician- or patient-reported ratings of ataxia severity, non-ataxia features, disease stage, activities of daily living, and (mental) health status. Moreover, they are aligned to major autosomal-dominant spinocerebellar ataxia (SCA) and sporadic ataxia (SPORTAX) registries in the field, thus allowing for joint and comparative analyses not only across ARCAs but also with SCAs and sporadic ataxias. The registry is at the core of a systematic multi-component ARCA database cluster with a linked biobank and an evolving study database for digital outcome measures. Currently, the registry contains more than 800 patients with almost 1,500 visits representing all ages and disease stages; 65% of patients with established genetic diagnoses capture all the main ARCA genes, and 35% with unsolved diagnoses are targets for advanced next-generation sequencing. The ARCA Registry serves as the backbone of many major European and transatlantic consortia, such as PREPARE, PROSPAX, and the Ataxia Global Initiative, with additional data input from SPORTAX. It has thus become the largest global trial-readiness registry in the ARCA field.

Published
2021
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13. Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of undetermined source: a prespecified subgroup analysis from the NAVIGATE ESUS trial

Author

Abdelhamid, N, Abdul Rahman, D, Abdul-Saheb, M, Abreu, P, Abroskina, M, Abu Ahmad, F, Accassat, S, Acciaresi, M, Adami, A, Ahmad, N, Ahmed, F, Alberto Hawkes, M, Alemseged, F, Ali, A, Altavilla, R, Alwis, L, Amarenco, P, Amaro, S, Amaya Sanchez, LE, Amelia Pinto, A, Ameriso, SF, Amin, H, Amino, T, Amjad, AK, Anagnostou, E, Andersen, G, Anderson, C, Anderson, DC, Andrea Falco, M, Andres Mackinnon, F, Andreu, D, Androulakis, M, Angel Gamero, M, Angel Saredo, G, Angeles Diaz, R, Angels Font, M, Anticoli, S, Arauz, A, Arauz Gongora, AA, Araya, P, Arenillas Lara, JF, Arias Rivas, S, Arnold, M, Augustin, S, Avelar, W, Azevedo, E, Babikian, V, Bacellar, A, Badalyan, K, Bae, HJ, Baez Martinez, EM, Bagelmann, H, Bailey, P, Bak, Z, Baker, M, Balazs, A, Baldaranov, D, Balogun, I, Balueva, T, Bankuti, Z, Bar, M, Baranowska, A, Bardutzky, J, Barker Trejo, S, Barlinn, J, Baronnet, F, Barroso, C, Barteys, M, Bartolottiova, T, Barulin, A, Bas, M, Bashir, S, Basile, V, Bathe-Peters, R, Bathula, R, Batista, C, Batur Caglayan, H, Baumgartner, P, Bazan, R, Bazhenova, O, Beaudry, M, Beer, J, Behnam, Y, Beilei, C, Beinlich, A, Bejot, Y, Belkin, A, Benavente, OR, Benjamin, A, Berardi, V, Bereczki, D, Berkowitz, SD, Berlingieri, J, Berrios, W, Berrouschot, J, Bhandari, M, Bhargavah, M, Bicker, H, Bicsak, T, Bilik, M, Bindila, D, Birchenall, J, Birnbaum, L, Black, T, Blacker, D, Blacquiere, D, Blanc-Labarre, C, Blank, C, Blazejewska-Hyzorek, B, Bloch, S, Bodiguel, E, Bogdanov, E, Boos, L, Borcsik, L, Bornstein, N, Bouly, S, Braga, G, Bragado, I, Bravi, MC, Brokalaki, C, Brola, W, Brouns, R, Bruce, D, Brzoska-Mizgalska, J, Buck, B, Buksinska-Lisik, M, Burke, J, Burn, M, Bustamante, G, Cabrejo, L, Cai, K, Cajaraville, S, Calejo, M, Calvet, D, Campillo, J, Campos Costa, E, Camps, P, Can Alaydin, H, Candeloro, E, Canepa, C, Cantu Brito, CG, Cappellari, M, Carcel, C, Cardona Portela, P, Cardoso, F, Carek, M, Carletti, M, Carlos Portilla, J, Caruso, P, Casado-Naranjo, I, Castellini, P, 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Krassen, Perera, Kanjana, Santo, Gustavo, Olavarria, Veronica, Lindgren, Arne, Bangdiwala, Shrikant, Shoamanesh, Ashkan, Berkowitz, Scott D, Mundl, Hardi, Connolly, Stuart J, and Hart, Robert G

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2018
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15. Correction to: Eye-tracking-aided characterization of saccades and antisaccades in SYNE1 ataxia patients: a pilot study

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Laszlo Szpisjak, Gabor Szaraz, Andras Salamon, Viola L. Nemeth, Noemi Szepfalusi, Gabor Veres, Balint Kincses, Zoltan Maroti, Tibor Kalmar, Malgorzata Rydzanicz, Rafal Ploski, Peter Klivenyi, and Denes Zadori

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurophysiology and neuropsychology, QP351-495
Abstract

An amendment to this paper has been published and can be accessed via the original article.

Published
2021
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16. Responsiveness of the Scale for the Assessment and Rating of Ataxia and Natural History in 884 Recessive and Early Onset Ataxia Patients.

Author

Traschütz, A., Adarmes-Gómez, A.D., Anheim, M., Baets, J., Brais, B., Gagnon, C., Gburek-Augustat, J., Doss, S., Hanağası, H.A., Kamm, C., Klivenyi, P., Klockgether, T., Klopstock, T., Minnerop, M., Münchau, A., Renaud, M., Santorelli, F.M., Schöls, L., Thieme, A., Vielhaber, S., Warrenburg, B.P.C. van de, Zanni, G., Hilgers, R.D., Synofzik, M., Traschütz, A., Adarmes-Gómez, A.D., Anheim, M., Baets, J., Brais, B., Gagnon, C., Gburek-Augustat, J., Doss, S., Hanağası, H.A., Kamm, C., Klivenyi, P., Klockgether, T., Klopstock, T., Minnerop, M., Münchau, A., Renaud, M., Santorelli, F.M., Schöls, L., Thieme, A., Vielhaber, S., Warrenburg, B.P.C. van de, Zanni, G., Hilgers, R.D., and Synofzik, M.

Abstract

01 september 2023, Contains fulltext : 296141.pdf (Publisher’s version ) (Open Access), OBJECTIVE: The Scale for the Assessment and Rating of Ataxia (SARA) is the most widely applied clinical outcome assessment (COA) for genetic ataxias, but presents metrological and regulatory challenges. To facilitate trial planning, we characterize its responsiveness (including subitem-level relations to ataxia severity and patient-focused outcomes) across a large number of ataxias, and provide first natural history data for several of them. METHODS: Subitem-level correlation and distribution-based analysis of 1,637 SARA assessments in 884 patients with autosomal recessive/early onset ataxia (370 with 2-8 longitudinal assessments) were complemented by linear mixed effects modeling to estimate progression and sample sizes. RESULTS: Although SARA subitem responsiveness varied between ataxia severities, gait/stance showed a robust granular linear scaling across the broadest range (SARA < 25). Responsiveness was diminished by incomplete subscale use at intermediate or upper levels, nontransitions ("static periods"), and fluctuating decreases/increases. All subitems except nose-finger showed moderate-to-strong correlations to activities of daily living, indicating that metric properties-not content validity-limit SARA responsiveness. SARA captured mild-to-moderate progression in many genotypes (eg, SYNE1-ataxia: 0.55 points/yr, ataxia with oculomotor apraxia type 2: 1.14 points/yr, POLG-ataxia: 1.56 points/yr), but no change in others (autosomal recessive spastic ataxia of Charlevoix-Saguenay, COQ8A-ataxia). Whereas sensitivity to change was optimal in mild ataxia (SARA < 10), it substantially deteriorated in advanced ataxia (SARA > 25; 2.7-fold sample size). Use of a novel rank-optimized SARA without subitems finger-chase and nose-finger reduces sample sizes by 20 to 25%. INTERPRETATION: This study comprehensively characterizes COA properties and annualized changes of the SARA across and within a large number of ataxias. It suggests specific approaches for optimizing it

Published
2023

17. Autosomal Recessive Cerebellar Ataxias in Europe: Frequency, Onset, and Severity in 677 Patients.

Author

Traschütz, A., Adarmes-Gomez, A.D., Anheim, M., Baets, J., Falkenburger, B.H., Gburek-Augustat, J., Doss, S., Kamm, C., Klivenyi, P., Grobe-Einsler, M., Klopstock, T., Minnerop, M., Münchau, A., Pane, C., Renaud, M., Santorelli, F.M., Schöls, L., Timmann, D., Vielhaber, S., Haack, T.B., Warrenburg, B.P.C. van de, Zanni, G., Synofzik, M., Traschütz, A., Adarmes-Gomez, A.D., Anheim, M., Baets, J., Falkenburger, B.H., Gburek-Augustat, J., Doss, S., Kamm, C., Klivenyi, P., Grobe-Einsler, M., Klopstock, T., Minnerop, M., Münchau, A., Pane, C., Renaud, M., Santorelli, F.M., Schöls, L., Timmann, D., Vielhaber, S., Haack, T.B., Warrenburg, B.P.C. van de, Zanni, G., and Synofzik, M.

Abstract

01 juni 2023, Item does not contain fulltext

Published
2023

18. Establishing an online resource to facilitate global collaboration and inclusion of underrepresented populations: Experience from the MJFF Global Genetic Parkinson's Disease Project.

Author

Vollstedt, E.J., Madoev, H., Aasly, A., Ahmad-Annuar, A., Al-Mubarak, B., Alcalay, R.N., Alvarez, V., Amorin, I., Annesi, G., Arkadir, D., Bardien, S., Barker, R.A., Barkhuizen, M., Basak, A.N., Bonifati, V., Boon, A., Brighina, L., Brockmann, K., Carmine Belin, A., Carr, J., Clarimon, J., Cornejo-Olivas, M., Correia Guedes, L., Corvol, J.C., Crosiers, D., Damásio, J., Das, P., Carvalho Aguiar, P. de, Rosa, A. De, Dorszewska, J., Ertan, S., Ferese, R., Ferreira, J., Gatto, E., Genç, G., Giladi, N., Gómez-Garre, P., Hanagasi, H., Hattori, N., Hentati, F., Hoffman-Zacharska, D., Illarioshkin, S.N., Jankovic, J., Jesús, S., Kaasinen, V., Kievit, A., Klivenyi, P., Kostic, V., Koziorowski, D., Kühn, A.A., Lang, A.E., Lim, S.Y., Lin, Chih-Yu, Lohmann, K., Markovic, V., Martikainen, M.H., Mellick, G., Merello, M., Milanowski, L., Mir, P., Öztop-Çakmak, Ö., Pimentel, M.M.G., Pulkes, T., Puschmann, A., Rogaeva, E., Sammler, E.M., Skaalum Petersen, M., Skorvanek, M., Spitz, M., Suchowersky, O., Tan, A.H., Termsarasab, P., Thaler, Avner, Tumas, V., Valente, E.M., Warrenburg, B.P.C. van de, Williams-Gray, C.H., Wu, R.M., Zhang, B., Zimprich, A., Solle, J., Padmanabhan, S., Klein, Christine, Vollstedt, E.J., Madoev, H., Aasly, A., Ahmad-Annuar, A., Al-Mubarak, B., Alcalay, R.N., Alvarez, V., Amorin, I., Annesi, G., Arkadir, D., Bardien, S., Barker, R.A., Barkhuizen, M., Basak, A.N., Bonifati, V., Boon, A., Brighina, L., Brockmann, K., Carmine Belin, A., Carr, J., Clarimon, J., Cornejo-Olivas, M., Correia Guedes, L., Corvol, J.C., Crosiers, D., Damásio, J., Das, P., Carvalho Aguiar, P. de, Rosa, A. De, Dorszewska, J., Ertan, S., Ferese, R., Ferreira, J., Gatto, E., Genç, G., Giladi, N., Gómez-Garre, P., Hanagasi, H., Hattori, N., Hentati, F., Hoffman-Zacharska, D., Illarioshkin, S.N., Jankovic, J., Jesús, S., Kaasinen, V., Kievit, A., Klivenyi, P., Kostic, V., Koziorowski, D., Kühn, A.A., Lang, A.E., Lim, S.Y., Lin, Chih-Yu, Lohmann, K., Markovic, V., Martikainen, M.H., Mellick, G., Merello, M., Milanowski, L., Mir, P., Öztop-Çakmak, Ö., Pimentel, M.M.G., Pulkes, T., Puschmann, A., Rogaeva, E., Sammler, E.M., Skaalum Petersen, M., Skorvanek, M., Spitz, M., Suchowersky, O., Tan, A.H., Termsarasab, P., Thaler, Avner, Tumas, V., Valente, E.M., Warrenburg, B.P.C. van de, Williams-Gray, C.H., Wu, R.M., Zhang, B., Zimprich, A., Solle, J., Padmanabhan, S., and Klein, Christine

Abstract

Item does not contain fulltext, Parkinson's disease (PD) is the fastest-growing neurodegenerative disorder, currently affecting ~7 million people worldwide. PD is clinically and genetically heterogeneous, with at least 10% of all cases explained by a monogenic cause or strong genetic risk factor. However, the vast majority of our present data on monogenic PD is based on the investigation of patients of European White ancestry, leaving a large knowledge gap on monogenic PD in underrepresented populations. Gene-targeted therapies are being developed at a fast pace and have started entering clinical trials. In light of these developments, building a global network of centers working on monogenic PD, fostering collaborative research, and establishing a clinical trial-ready cohort is imperative. Based on a systematic review of the English literature on monogenic PD and a successful team science approach, we have built up a network of 59 sites worldwide and have collected information on the availability of data, biomaterials, and facilities. To enable access to this resource and to foster collaboration across centers, as well as between academia and industry, we have developed an interactive map and online tool allowing for a quick overview of available resources, along with an option to filter for specific items of interest. This initiative is currently being merged with the Global Parkinson's Genetics Program (GP2), which will attract additional centers with a focus on underrepresented sites. This growing resource and tool will facilitate collaborative research and impact the development and testing of new therapies for monogenic and potentially for idiopathic PD patients.

Published
2023

19. Histopathological comparison of Kearns-Sayre syndrome and PGC-1α-deficient mice suggests a novel concept for vacuole formation in mitochondrial encephalopathy

Author

Levente Szalardy, Mate Molnar, Rita Torok, Denes Zadori, Laszlo Vecsei, Peter Klivenyi, Paweł Piotr Liberski, and Gabor Geza Kovacs

Subjects
Kearns-Sayre syndrome, PGC-1α, mitochondrial encephalopathy, vacuole, myelin, oligodendrocyte, Medicine
Abstract

Despite the current hypotheses about myelinic and astrocytic ion-dyshomeostasis underlying white (WM) and grey matter (GM) vacuolation in mitochondrial encephalopathies, there is a paucity of data on the exact mechanism of vacuole formation. To revisit the concepts of vacuole formation associated with mitochondrial dysfunction, we performed a comparative neuropathological analysis in Kearns-Sayre syndrome (KSS) and full-length peroxisome proliferator-activated receptor-g coactivator-1a (FL-PGC-1a)-deficient mice, a recently proposed morphological model of mitochondrial encephalopathies. Brain tissues from an individual with genetically proven KSS (22-year-old man) and aged FL-PGC-1a-deficient and wild-type (male, 70-75-week-old) mice were analysed using ultrastructural and immunohistochemical methods, with a specific focus on myelin-related, oligodendroglial, axonal and astrocytic pathologies. Besides demonstrating remarkable similarities in the lesion profile of KSS and FL-PGC-1a-deficient mice, this study first provides morphological evidence for the identical origin of WM and GM vacuolation as well as for the presence of intracytoplasmic oligodendroglial vacuoles in mitochondriopathies. Based on these observations, the paper proposes a theoretical model for the development of focal myelin vacuolation as opposed to the original concepts of intramyelin oedema. Placing oligodendrocytes in the centre of tissue lesioning in conditions related to defects in mitochondria, our observations support the rationale for cytoprotective targeting of oligodendrocytes in mitochondrial encephalopathies, and may also have implications in brain aging and multiple sclerosis, as discussed.

Published
2016
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22. Non-motor Behavioral Alterations of PGC-1α-Deficient Mice – A Peculiar Phenotype With Slight Male Preponderance and No Apparent Progression

Author

Levente Szalardy, Mate F. Molnar, Denes Zadori, Edina K. Cseh, Gabor Veres, Gabor G. Kovacs, Laszlo Vecsei, and Peter Klivenyi

Subjects
anxiety, behavior, depression, memory, peroxisome proliferator-activated receptor gamma coactivator, PGC-1α, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Dysfunction of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1α) has been linked to various neurodegenerative and neuropsychiatric disorders; however, reports on psychic behavioral alterations on PGC-1α-deficient animals are sparse. The present study revisited prior observations of anxiety-related, depression-related, and hippocampal memory-related observations having been made on different PGC-1α-deficient murine strains, in a large-scale analysis on whole-body full-length (FL-)PGC-1α-deficient mice. The examinations were performed on animals covering a wide age range enrolled from both sexes, and included paradigms such as the open-field, elevated plus maze, light-dark box, tail suspension test, and spatial recognition two-trial Y-maze. The findings revealed no signs of previously reported anxiety-like behavior, but revealed an unexpected phenotype with decreased anxiety behavior consistent throughout different paradigms, with slight male preponderance. This was associated with despair-like anhedonic behavior, consistent with that reported previously, but did not associate with either peripheral or brain alterations in kynurenic acid synthesis, which was previously proposed. Though male FL-PGC-1α-deficient mice tended to perform poorer in the hippocampus-based spatial learning paradigm, the genotype overall was not associated with impairment in spatial memory, contradicting with prior observations. None of the observed alterations deteriorated with age, similarly to motor alterations as reported previously. The most likely contributors of this peculiar phenotype are discussed, with clinicopathological correlations drawn. Being the first to address these behavioral domains within the same PGC-1α-deficient strain, our findings extend the knowledge about the complex in vivo effect of PGC-1α dysfunction and add important notes to research in the field of PGC-1α in connection with neuropsychiatric disorders.

Published
2018
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23. Language Deficits in Pre-Symptomatic Huntington's Disease: Evidence from Hungarian

Author

Nemeth, Dezso, Dye, Cristina D., Sefcsik, Tamas, Janacsek, Karolina, Turi, Zsolt, Londe, Zsuzsa, Klivenyi, Peter, Kincses, Zsigmond Tamas, Szabo, Nikoletta, Vecsei, Laszlo, and Ullman, Michael T.

Abstract

A limited number of studies have investigated language in Huntington's disease (HD). These have generally reported abnormalities in rule-governed (grammatical) aspects of language, in both syntax and morphology. Several studies of verbal inflectional morphology in English and French have reported evidence of over-active rule processing, such as over-suffixation errors (e.g., walkeded) and over-regularizations (e.g., digged). Here we extend the investigation to noun inflection in Hungarian, a Finno-Ugric agglutinative language with complex morphology, and to genetically proven pre-symptomatic Huntington's disease (pre-HD). Although individuals with pre-HD have no clinical, motor or cognitive symptoms, the underlying pathology may already have begun, and thus sensitive behavioral measures might reveal already-present impairments. Indeed, in a Hungarian morphology production task, pre-HD patients made both over-suffixation and over-regularization errors. The findings suggest the generality of over-active rule processing in both HD and pre-HD, across languages from different families with different morphological systems, and for both verbal and noun inflection. Because the neuropathology in pre-HD appears to be largely restricted to the caudate nucleus and related structures, the findings further implicate these structures in language, and in rule-processing in particular. Finally, the need for effective treatments in HD, which will likely depend in part on the ability to sensitively measure early changes in the disease, suggests the possibility that inflectional morphology, and perhaps other language measures, may provide useful diagnostic, tracking, and therapeutic tools for assessing and treating early degeneration in pre-HD and HD. (Contains 2 tables and 1 figure.)

Published
2012
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26. Mice lacking alpha-synuclein are resistant to mitochondrial toxins

Author

Peter Klivenyi, Donald Siwek, Gabrielle Gardian, Lichuan Yang, Anatoly Starkov, Carine Cleren, Robert J. Ferrante, Neil W. Kowall, Asa Abeliovich, and M. Flint Beal

Subjects
MPTP, Paraquat, 3-Nitropropionic acid, Malonate, MPP+, MPP+ levels, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Abnormalities in the function of α-synuclein are implicated in the pathogenesis of Parkinson's disease (PD). We found that α-synuclein-deficient mice are resistant to MPTP-induced degeneration of dopaminergic neurons. There was dose-dependent protection against loss of both dopamine in the striatum and dopamine transporter (DAT) immunoreactive neurons in the substantia nigra. These effects were not due to alterations in MPTP processing. We found that α-synuclein-deficient mice are also resistant to both malonate and 3-nitropropionic acid (3-NP) neurotoxicity. There was reduced generation of reactive oxygen species in α-synuclein-deficient mice following administration of 3-NP. These findings implicate α-synuclein as a modulator of oxidative damage, which has been implicated in neuronal death produced by MPTP and other mitochondrial toxins.

Published
2006
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27. Using global team science to identify genetic parkinson's disease worldwide

Author

Vollstedt, E, Kasten, M, Klein, C, Aasly, J, Adler, C, Ahmad-Annuar, A, Albanese, A, Alcalay, R, Al-Mubarak, B, Alvarez, V, Andree-Munoz, B, Annesi, G, Appel-Cresswell, S, Arkadir, D, Armasu, S, Barber, T, Bardien, S, Barkhuizen, M, Barrett, M, Basak, A, Beach, T, Benitez, B, Berg, D, Bhatia, K, Binkofski, F, Blauwendraat, C, Bonifati, V, Borges, V, Bozi, M, Brice, A, Brighina, L, Brockmann, K, Brucke, T, Bruggemann, N, Camacho, M, Cardoso, F, Belin, A, Carr, J, Chan, P, Chang-Castello, J, Chase, B, Chen-Plotkin, A, Ju Chung, S, Cilia, R, Clarimon, J, Clark, L, Cornejo-Olivas, M, Corvol, J, Cosentino, C, Cras, P, Crosiers, D, Damasio, J, Das, P, de Carvalho Aguiar, P, De Michele, G, De Rosa, A, Dieguez, E, Dorszewska, J, Erer, S, Ertan, S, Farrer, M, Fedotova, E, Ferese, R, Ferrarese, C, Ferraz, H, Fiala, O, Foroud, T, Friedman, A, Frigerio, R, Funayama, M, Gambardella, S, Garraux, G, Gatto, E, Genc, G, Giladi, N, Goldwurm, S, Gomez-Esteban, J, Gomez-Garre, P, Gorostidi, A, Grosset, D, Hanagasi, H, Hardy, J, Hassan, A, Hattori, N, Hauser, R, Hedera, P, Hentati, F, Hertz, J, Holton, J, Houlden, H, Hutz, M, Ikeuchi, T, Illarioshkin, S, Inca-Martinez, M, Infante, J, Jankovic, J, Jeon, B, Jesus, S, Jimenez-Del-Rio, M, Kaasinen, V, Kataoka, H, Kawakami, H, Kim, Y, Klivenyi, P, Koks, S, Konig, I, Kostic, V, Koziorowski, D, Kruger, R, Krygowska-Wajs, A, Kulisevsky, J, Lai, D, Lang, A, Ledoux, M, Lesage, S, Lim, S, Lin, C, Lohmann, K, Lopera, F, Lopez, G, Lu, C, Lynch, T, Machaczka, M, Madoev, H, Magalhaes, M, Majamaa, K, Maraganore, D, Marder, K, Markopoulou, K, Martikainen, M, Mata, I, Mazzetti, P, Mellick, G, Menendez-Gonzalez, M, Micheli, F, Mirelman, A, Mir, P, Morino, H, Morris, H, Munhoz, R, Naito, A, Olszewska, D, Ozelius, L, Padmanabhan, S, Paisan-Ruiz, C, Payami, H, Peluso, S, Petkovic, S, Petrucci, S, Pezzoli, G, Pimentel, M, Pirker, W, Pramstaller, P, Pulkes, T, Puschmann, A, Quattrone, A, Raggio, V, Ransmayr, G, Rieder, C, Riess, O, Rodriguez-Porcel, F, Rogaeva, E, Ross, O, Ruiz-Martinez, J, Sammler, E, San Luciano, M, Satake, W, Saunders-Pullman, R, Sazci, A, Scherzer, C, Schrag, A, Schumacher-Schuh, A, Sharma, M, Sidransky, E, Singleton, A, Petersen, M, Smolders, S, Spitz, M, Stefanis, L, Struhal, W, Sue, C, Swan, M, Swanberg, M, Taba, P, Taipa, R, Tan, M, Tan, A, Tan, E, Tang, B, Tayebi, N, Thaler, A, Thomas, A, Toda, T, Toft, M, Torres, L, Tumas, V, Valente, E, Van Broeckhoven, C, Vecsei, L, Velez-Pardo, C, Vidailhet, M, Warner, T, Williams-Gray, C, Winkelmann, J, Woitalla, D, Wood, N, Wszolek, Z, Wu, R, Wu, Y, Xie, T, Yoshino, H, Zhang, B, Zimprich, A, Vollstedt E. -J., Kasten M., Klein C., Aasly J., Adler C., Ahmad-Annuar A., Albanese A., Alcalay R. N., Al-Mubarak B., Alvarez V., Andree-Munoz B., Annesi G., Appel-Cresswell S., Arkadir D., Armasu S., Barber T. R., Bardien S., Barkhuizen M., Barrett M. J., Basak A. N., Beach T., Benitez B. A., Berg D., Bhatia K., Binkofski F., Blauwendraat C., Bonifati V., Borges V., Bozi M., Brice A., Brighina L., Brockmann K., Brucke T., Bruggemann N., Camacho M., Cardoso F., Belin A. C., Carr J., Chan P., Chang-Castello J., Chase B., Chen-Plotkin A., Ju Chung S., Cilia R., Clarimon J., Clark L., Cornejo-Olivas M., Corvol J. -C., Cosentino C., Cras P., Crosiers D., Damasio J., Das P., de Carvalho Aguiar P., De Michele G., De Rosa A., Dieguez E., Dorszewska J., Erer S., Ertan S., Farrer M., Fedotova E., Ferese R., Ferrarese C., Ferraz H., Fiala O., Foroud T., Friedman A., Frigerio R., Funayama M., Gambardella S., Garraux G., Gatto E. M., Genc G., Giladi N., Goldwurm S., Gomez-Esteban J. C., Gomez-Garre P., Gorostidi A., Grosset D., Hanagasi H., Hardy J., Hassan A., Hattori N., Hauser R. A., Hedera P., Hentati F., Hertz J. M., Holton J. L., Houlden H., Hutz M. H., Ikeuchi T., Illarioshkin S., Inca-Martinez M., Infante J., Jankovic J., Jeon B. S., Jesus S., Jimenez-Del-Rio M., Kaasinen V., Kataoka H., Kawakami H., Kim Y. J., Klivenyi P., Koks S., Konig I. R., Kostic V., Koziorowski D., Kruger R., Krygowska-Wajs A., Kulisevsky J., Lai D., Lang A., LeDoux M., Lesage S., Lim S. -Y., Lin C. -H., Lohmann K., Lopera F., Lopez G., Lu C. -S., Lynch T., Machaczka M., Madoev H., Magalhaes M., Majamaa K., Maraganore D., Marder K., Markopoulou K., Martikainen M. H., Mata I., Mazzetti P., Mellick G., Menendez-Gonzalez M., Micheli F., Mirelman A., Mir P., Morino H., Morris H., Munhoz R. P., Naito A., Olszewska D. A., Ozelius L. J., Padmanabhan S., Paisan-Ruiz C., Payami H., Peluso S., Petkovic S., Petrucci S., Pezzoli G., Pimentel M., Pirker W., Pramstaller P. P., Pulkes T., Puschmann A., Quattrone A., Raggio V., Ransmayr G., Rieder C., Riess O., Rodriguez-Porcel F., Rogaeva E., Ross O. A., Ruiz-Martinez J., Sammler E., San Luciano M., Satake W., Saunders-Pullman R., Sazci A., Scherzer C., Schrag A., Schumacher-Schuh A., Sharma M., Sidransky E., Singleton A. B., Petersen M. S., Smolders S., Spitz M., Stefanis L., Struhal W., Sue C. M., Swan M., Swanberg M., Taba P., Taipa R., Tan M., Tan A. H., Tan E. -K., Tang B., Tayebi N., Thaler A., Thomas A., Toda T., Toft M., Torres L., Tumas V., Valente E. M., Van Broeckhoven C., Vecsei L., Velez-Pardo C., Vidailhet M., Warner T. T., Williams-Gray C. H., Winkelmann J., Woitalla D., Wood N. W., Wszolek Z. K., Wu R. -M., Wu Y. -R., Xie T., Yoshino H., Zhang B., Zimprich A., Vollstedt, E, Kasten, M, Klein, C, Aasly, J, Adler, C, Ahmad-Annuar, A, Albanese, A, Alcalay, R, Al-Mubarak, B, Alvarez, V, Andree-Munoz, B, Annesi, G, Appel-Cresswell, S, Arkadir, D, Armasu, S, Barber, T, Bardien, S, Barkhuizen, M, Barrett, M, Basak, A, Beach, T, Benitez, B, Berg, D, Bhatia, K, Binkofski, F, Blauwendraat, C, Bonifati, V, Borges, V, Bozi, M, Brice, A, Brighina, L, Brockmann, K, Brucke, T, Bruggemann, N, Camacho, M, Cardoso, F, Belin, A, Carr, J, Chan, P, Chang-Castello, J, Chase, B, Chen-Plotkin, A, Ju Chung, S, Cilia, R, Clarimon, J, Clark, L, Cornejo-Olivas, M, Corvol, J, Cosentino, C, Cras, P, Crosiers, D, Damasio, J, Das, P, de Carvalho Aguiar, P, De Michele, G, De Rosa, A, Dieguez, E, Dorszewska, J, Erer, S, Ertan, S, Farrer, M, Fedotova, E, Ferese, R, Ferrarese, C, Ferraz, H, Fiala, O, Foroud, T, Friedman, A, Frigerio, R, Funayama, M, Gambardella, S, Garraux, G, Gatto, E, Genc, G, Giladi, N, Goldwurm, S, Gomez-Esteban, J, Gomez-Garre, P, Gorostidi, A, Grosset, D, Hanagasi, H, Hardy, J, Hassan, A, Hattori, N, Hauser, R, Hedera, P, Hentati, F, Hertz, J, Holton, J, Houlden, H, Hutz, M, Ikeuchi, T, Illarioshkin, S, Inca-Martinez, M, Infante, J, Jankovic, J, Jeon, B, Jesus, S, Jimenez-Del-Rio, M, Kaasinen, V, Kataoka, H, Kawakami, H, Kim, Y, Klivenyi, P, Koks, S, Konig, I, Kostic, V, Koziorowski, D, Kruger, R, Krygowska-Wajs, A, Kulisevsky, J, Lai, D, Lang, A, Ledoux, M, Lesage, S, Lim, S, Lin, C, Lohmann, K, Lopera, F, Lopez, G, Lu, C, Lynch, T, Machaczka, M, Madoev, H, Magalhaes, M, Majamaa, K, Maraganore, D, Marder, K, Markopoulou, K, Martikainen, M, Mata, I, Mazzetti, P, Mellick, G, Menendez-Gonzalez, M, Micheli, F, Mirelman, A, Mir, P, Morino, H, Morris, H, Munhoz, R, Naito, A, Olszewska, D, Ozelius, L, Padmanabhan, S, Paisan-Ruiz, C, Payami, H, Peluso, S, Petkovic, S, Petrucci, S, Pezzoli, G, Pimentel, M, Pirker, W, Pramstaller, P, Pulkes, T, Puschmann, A, Quattrone, A, Raggio, V, Ransmayr, G, Rieder, C, Riess, O, Rodriguez-Porcel, F, Rogaeva, E, Ross, O, Ruiz-Martinez, J, Sammler, E, San Luciano, M, Satake, W, Saunders-Pullman, R, Sazci, A, Scherzer, C, Schrag, A, Schumacher-Schuh, A, Sharma, M, Sidransky, E, Singleton, A, Petersen, M, Smolders, S, Spitz, M, Stefanis, L, Struhal, W, Sue, C, Swan, M, Swanberg, M, Taba, P, Taipa, R, Tan, M, Tan, A, Tan, E, Tang, B, Tayebi, N, Thaler, A, Thomas, A, Toda, T, Toft, M, Torres, L, Tumas, V, Valente, E, Van Broeckhoven, C, Vecsei, L, Velez-Pardo, C, Vidailhet, M, Warner, T, Williams-Gray, C, Winkelmann, J, Woitalla, D, Wood, N, Wszolek, Z, Wu, R, Wu, Y, Xie, T, Yoshino, H, Zhang, B, Zimprich, A, Vollstedt E. -J., Kasten M., Klein C., Aasly J., Adler C., Ahmad-Annuar A., Albanese A., Alcalay R. N., Al-Mubarak B., Alvarez V., Andree-Munoz B., Annesi G., Appel-Cresswell S., Arkadir D., Armasu S., Barber T. R., Bardien S., Barkhuizen M., Barrett M. J., Basak A. N., Beach T., Benitez B. A., Berg D., Bhatia K., Binkofski F., Blauwendraat C., Bonifati V., Borges V., Bozi M., Brice A., Brighina L., Brockmann K., Brucke T., Bruggemann N., Camacho M., Cardoso F., Belin A. C., Carr J., Chan P., Chang-Castello J., Chase B., Chen-Plotkin A., Ju Chung S., Cilia R., Clarimon J., Clark L., Cornejo-Olivas M., Corvol J. -C., Cosentino C., Cras P., Crosiers D., Damasio J., Das P., de Carvalho Aguiar P., De Michele G., De Rosa A., Dieguez E., Dorszewska J., Erer S., Ertan S., Farrer M., Fedotova E., Ferese R., Ferrarese C., Ferraz H., Fiala O., Foroud T., Friedman A., Frigerio R., Funayama M., Gambardella S., Garraux G., Gatto E. M., Genc G., Giladi N., Goldwurm S., Gomez-Esteban J. C., Gomez-Garre P., Gorostidi A., Grosset D., Hanagasi H., Hardy J., Hassan A., Hattori N., Hauser R. A., Hedera P., Hentati F., Hertz J. M., Holton J. L., Houlden H., Hutz M. H., Ikeuchi T., Illarioshkin S., Inca-Martinez M., Infante J., Jankovic J., Jeon B. S., Jesus S., Jimenez-Del-Rio M., Kaasinen V., Kataoka H., Kawakami H., Kim Y. J., Klivenyi P., Koks S., Konig I. R., Kostic V., Koziorowski D., Kruger R., Krygowska-Wajs A., Kulisevsky J., Lai D., Lang A., LeDoux M., Lesage S., Lim S. -Y., Lin C. -H., Lohmann K., Lopera F., Lopez G., Lu C. -S., Lynch T., Machaczka M., Madoev H., Magalhaes M., Majamaa K., Maraganore D., Marder K., Markopoulou K., Martikainen M. H., Mata I., Mazzetti P., Mellick G., Menendez-Gonzalez M., Micheli F., Mirelman A., Mir P., Morino H., Morris H., Munhoz R. P., Naito A., Olszewska D. A., Ozelius L. J., Padmanabhan S., Paisan-Ruiz C., Payami H., Peluso S., Petkovic S., Petrucci S., Pezzoli G., Pimentel M., Pirker W., Pramstaller P. P., Pulkes T., Puschmann A., Quattrone A., Raggio V., Ransmayr G., Rieder C., Riess O., Rodriguez-Porcel F., Rogaeva E., Ross O. A., Ruiz-Martinez J., Sammler E., San Luciano M., Satake W., Saunders-Pullman R., Sazci A., Scherzer C., Schrag A., Schumacher-Schuh A., Sharma M., Sidransky E., Singleton A. B., Petersen M. S., Smolders S., Spitz M., Stefanis L., Struhal W., Sue C. M., Swan M., Swanberg M., Taba P., Taipa R., Tan M., Tan A. H., Tan E. -K., Tang B., Tayebi N., Thaler A., Thomas A., Toda T., Toft M., Torres L., Tumas V., Valente E. M., Van Broeckhoven C., Vecsei L., Velez-Pardo C., Vidailhet M., Warner T. T., Williams-Gray C. H., Winkelmann J., Woitalla D., Wood N. W., Wszolek Z. K., Wu R. -M., Wu Y. -R., Xie T., Yoshino H., Zhang B., and Zimprich A.

Published
2019

28. Neuroprotective mechanisms of creatine occur in the absence of mitochondrial creatine kinase

Author

Peter Klivenyi, Noel Y Calingasan, Anatoly Starkov, Irina G Stavrovskaya, Bruce S Kristal, Lichuan Yang, Bé Wieringa, and M.Flint Beal

Subjects
Creatine, Creatine kinase, MPTP, Phosphocreatine, Mitochondria, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

There is substantial evidence that creatine administration exerts neuroprotective effects both in vitro and in vivo. The precise mechanisms for these neuroprotective effects however are as yet unclear. We investigated whether creatine administration could exert neuroprotective effects in mice deficient in ubiquitous mitochondrial creatine kinase (UbMi-CK). UbMi-CK-deficient mice showed increased sensitivity to 1-methyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced dopamine depletion and loss of tyrosine hydroxylase (TH) stained neurons. Isolated mitochondria from these mice showed no alterations in calcium retention, oxygen utilization, membrane potential, or swelling in response to a calcium challenge. Creatine administration significantly increased brain concentrations of both creatine and PCr in the UbMi-CK knockout mice. Creatine administration to the UbMi-CK-deficient mice exerted significant neuroprotective effects against MPTP toxicity that were comparable in magnitude to those seen in wild-type mice. These results suggest that the neuroprotective effects of creatine are not mediated by an effect on UbMi-CK to inhibit the mitochondrial permeability transition, and are more likely to be mediated by maintenance of appropriate ATP/ADP and PCr/Cr levels.

Published
2004
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29. Global Impact of COVID-19 on Stroke Care and IV Thrombolysis

Author

Nogueira, R.G. Qureshi, M.M. Abdalkader, M. Martins, S.O. Yamagami, H. Qiu, Z. Mansour, O.Y. Sathya, A. Czlonkowska, A. Tsivgoulis, G. Aguiar de Sousa, D. Demeestere, J. Mikulik, R. Vanacker, P. Siegler, J.E. Kõrv, J. Biller, J. Liang, C.W. Sangha, N.S. Zha, A.M. Czap, A.L. Holmstedt, C.A. Turan, T.N. Ntaios, G. Malhotra, K. Tayal, A. Loochtan, A. Ranta, A. Mistry, E.A. Alexandrov, A.W. Huang, D.Y. Yaghi, S. Raz, E. Sheth, S.A. Mohammaden, M.H. Frankel, M. Bila Lamou, E.G. Aref, H.M. Elbassiouny, A. Hassan, F. Menecie, T. Mustafa, W. Shokri, H.M. Roushdy, T. Sarfo, F.S. Alabi, T.O. Arabambi, B. Nwazor, E.O. Sunmonu, T.A. Wahab, K. Yaria, J. Mohammed, H.H. Adebayo, P.B. Riahi, A.D. Sassi, S.B. Gwaunza, L. Ngwende, G.W. Sahakyan, D. Rahman, A. Ai, Z. Bai, F. Duan, Z. Hao, Y. Huang, W. Li, G. Li, W. Liu, G. Luo, J. Shang, X. Sui, Y. Tian, L. Wen, H. Wu, B. Yan, Y. Yuan, Z. Zhang, H. Zhang, J. Zhao, W. Zi, W. Leung, T.W. Chugh, C. Huded, V. Menon, B. Pandian, J.D. Sylaja, P.N. Usman, F.S. Farhoudi, M. Hokmabadi, E.S. Horev, A. Reznik, A. Sivan Hoffmann, R. Ohara, N. Sakai, N. Watanabe, D. Yamamoto, R. Doijiri, R. Tokuda, N. Yamada, T. Terasaki, T. Yazawa, Y. Uwatoko, T. Dembo, T. Shimizu, H. Sugiura, Y. Miyashita, F. Fukuda, H. Miyake, K. Shimbo, J. Sugimura, Y. Yagita, Y. Takenobu, Y. Matsumaru, Y. Yamada, S. Kono, R. Kanamaru, T. Yamazaki, H. Sakaguchi, M. Todo, K. Yamamoto, N. Sonoda, K. Yoshida, T. Hashimoto, H. Nakahara, I. Kondybayeva, A. Faizullina, K. Kamenova, S. Zhanuzakov, M. Baek, J.-H. Hwang, Y. Lee, J.S. Lee, S.B. Moon, J. Park, H. Seo, J.H. Seo, K.-D. Sohn, S.I. Young, C.J. Ahdab, R. Wan Zaidi, W.A. Aziz, Z.A. Basri, H.B. Chung, L.W. Ibrahim, A.B. Ibrahim, K.A. Looi, I. Tan, W.Y. Yahya, N.W. Groppa, S. Leahu, P. Al Hashmi, A.M. Imam, Y.Z. Akhtar, N. Pineda-Franks, M.C. Co, C.O. Kandyba, D. Alhazzani, A. Al-Jehani, H. Tham, C.H. Mamauag, M.J. Venketasubramanian, N. Chen, C.-H. Tang, S.-C. Churojana, A. Akil, E. Aykaç, Ö. Ozdemir, A.O. Giray, S. Hussain, S.I. John, S. Le Vu, H. Tran, A.D. Nguyen, H.H. Nhu Pham, T. Nguyen, T.H. Nguyen, T.Q. Gattringer, T. Enzinger, C. Killer-Oberpfalzer, M. Bellante, F. De Blauwe, S. Vanhooren, G. De Raedt, S. Dusart, A. Lemmens, R. Ligot, N. Pierre Rutgers, M. Yperzeele, L. Alexiev, F. Sakelarova, T. Bedeković, M.R. Budincevic, H. Cindric, I. Hucika, Z. Ozretic, D. Saric, M.S. Pfeifer, F. Karpowic, I. Cernik, D. Sramek, M. Skoda, M. Hlavacova, H. Klecka, L. Koutny, M. Vaclavik, D. Skoda, O. Fiksa, J. Hanelova, K. Nevsimalova, M. Rezek, R. Prochazka, P. Krejstova, G. Neumann, J. Vachova, M. Brzezanski, H. Hlinovsky, D. Tenora, D. Jura, R. Jurák, L. Novak, J. Novak, A. Topinka, Z. Fibrich, P. Sobolova, H. Volny, O. Krarup Christensen, H. Drenck, N. Klingenberg Iversen, H. Simonsen, C.Z. Truelsen, T.C. Wienecke, T. Vibo, R. Gross-Paju, K. Toomsoo, T. Antsov, K. Caparros, F. Cordonnier, C. Dan, M. Faucheux, J.-M. Mechtouff, L. Eker, O. Lesaine, E. Ondze, B. Peres, R. Pico, F. Piotin, M. Pop, R. Rouanet, F. Gubeladze, T. Khinikadze, M. Lobjanidze, N. Tsiskaridze, A. Nagel, S. Ringleb, P.A. Rosenkranz, M. Schmidt, H. Sedghi, A. Siepmann, T. Szabo, K. Thomalla, G. Palaiodimou, L. Sagris, D. Kargiotis, O. Klivenyi, P. Szapary, L. Tarkanyi, G. Adami, A. Bandini, F. Calabresi, P. Frisullo, G. Renieri, L. Sangalli, D. Pirson, A. Uyttenboogaart, M. van den Wijngaard, I. Kristoffersen, E.S. Brola, W. Fudala, M. Horoch-Lyszczarek, E. Karlinski, M. Kazmierski, R. Kram, P. Rogoziewicz, M. Kaczorowski, R. Luchowski, P. Sienkiewicz-Jarosz, H. Sobolewski, P. Fryze, W. Wisniewska, A. Wiszniewska, M. Ferreira, P. Ferreira, P. Fonseca, L. Marto, J.P. Pinho E Melo, T. Nunes, A.P. Rodrigues, M. Tedim Cruz, V. Falup-Pecurariu, C. Krastev, G. Mako, M. de Leciñana, M.A. Arenillas, J.F. Ayo-Martin, O. Cruz Culebras, A. Tejedor, E.D. Montaner, J. Pérez-Sánchez, S. Tola Arribas, M.A. Rodriguez Vasquez, A. Mayza, M. Bernava, G. Brehm, A. Machi, P. Fischer, U. Gralla, J. Michel, P.L. Psychogios, M.-N. Strambo, D. Banerjee, S. Krishnan, K. Kwan, J. Butt, A. Catanese, L. Demchuk, A.M. Field, T. Haynes, J. Hill, M.D. Khosravani, H. Mackey, A. Pikula, A. Saposnik, G. Scott, C.A. Shoamanesh, A. Shuaib, A. Yip, S. Barboza, M.A. Barrientos, J.D. Portillo Rivera, L.I. Gongora-Rivera, F. Novarro-Escudero, N. Blanco, A. Abraham, M. Alsbrook, D. Altschul, D. Alvarado-Ortiz, A.J. Bach, I. Badruddin, A. Barazangi, N. Brereton, C. Castonguay, A. Chaturvedi, S. Chaudry, S.A. Choe, H. Choi, J.H. Dharmadhikari, S. Desai, K. Devlin, T.G. Doss, V.T. Edgell, R. Etherton, M. Farooqui, M. Frei, D. Gandhi, D. Grigoryan, M. Gupta, R. Hassan, A.E. Helenius, J. Kaliaev, A. Kaushal, R. Khandelwal, P. Khawaja, A.M. Khoury, N.N. Kim, B.S. Kleindorfer, D.O. Koyfman, F. Lee, V.H. Leung, L.Y. Linares, G. Linfante, I. Lutsep, H.L. Macdougall, L. Male, S. Malik, A.M. Masoud, H. McDermott, M. Mehta, B.P. Min, J. Mittal, M. Morris, J.G. Multani, S.S. Nahab, F. Nalleballe, K. Nguyen, C.B. Novakovic-White, R. Ortega-Gutierrez, S. Rahangdale, R.H. Ramakrishnan, P. Romero, J.R. Rost, N. Rothstein, A. Ruland, S. Shah, R. Sharma, M. Silver, B. Simmons, M. Singh, A. Starosciak, A.K. Strasser, S.L. Szeder, V. Teleb, M. Tsai, J.P. Voetsch, B. Balaguera, O. Pujol Lereis, V.A. Luraschi, A. Almeida, M.S. Cardoso, F.B. Conforto, A. De Deus Silva, L. Varrone Giacomini, L. Oliveira Lima, F. Longo, A.L. Magalhães, P.S.C. Martins, R.T. Mont'alverne, F. Mora Cuervo, D.L. Costa Rebello, L. Valler, L. Zetola, V.F. Lavados, P.M. Navia, V. Olavarría, V.V. Almeida Toro, J.M. Amaya, P.F.R. Bayona, H. Corredor, A. Rivera Ordonez, C.E. Mantilla Barbosa, D.K. Lara, O. Patiño, M.R. Diaz Escobar, L.F. Dejesus Melgarejo Fariña, D.E. Cardozo Villamayor, A. Zelaya Zarza, A.J. Barrientos Iman, D.M. Rodriguez Kadota, L. Campbell, B. Hankey, G.J. Hair, C. Kleinig, T. Ma, A. Tomazini Martins, R. Sahathevan, R. Thijs, V. Salazar, D. Yuan-Hao Wu, T. Haussen, D.C. Liebeskind, D. Yavagal, D.R. Jovin, T.G. Zaidat, O.O. Nguyen, T.N. SVIN COVID-19 Global Stroke Registry SVIN COVID-19 Global Stroke Registry

Abstract

OBJECTIVE: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods. METHODS: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. RESULTS: There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95% confidence interval [CI] -11.7 to -11.3, p < 0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95% CI -13.8 to -12.7, p < 0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95% CI -13.7 to -10.3, p = 0.001). Recovery of stroke hospitalization volume (9.5%, 95% CI 9.2-9.8, p < 0.0001) was noted over the 2 later (May, June) vs the 2 earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was noted in 3.3% (1,722/52,026) of all stroke admissions. CONCLUSIONS: The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID-19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months. © 2021 American Academy of Neurology.

Published
2021

30. The ARCA Registry: A Collaborative Global Platform for Advancing Trial Readiness in Autosomal Recessive Cerebellar Ataxias

Author

Traschütz, A., Reich, S., Adarmes, A.D., Anheim, M., Ashrafi, M.R., Baets, J., Basak, A.N., Bertini, E., Brais, B., Gagnon, C., Gburek-Augustat, J., Hanagasi, H.A., Heinzmann, A., Horvath, R., Jonghe, P. De, Kamm, C., Klivenyi, P., Klopstock, T., Minnerop, M., Münchau, A., Renaud, M., Roxburgh, R.H., Santorelli, F.M., Schirinzi, T., Sival, D.A., Timmann, D., Vielhaber, S., Wallner, M., Warrenburg, B.P.C. van de, Zanni, G., Zuchner, S., Klockgether, T., Schüle, R., Schöls, L., Synofzik, M., Traschütz, A., Reich, S., Adarmes, A.D., Anheim, M., Ashrafi, M.R., Baets, J., Basak, A.N., Bertini, E., Brais, B., Gagnon, C., Gburek-Augustat, J., Hanagasi, H.A., Heinzmann, A., Horvath, R., Jonghe, P. De, Kamm, C., Klivenyi, P., Klopstock, T., Minnerop, M., Münchau, A., Renaud, M., Roxburgh, R.H., Santorelli, F.M., Schirinzi, T., Sival, D.A., Timmann, D., Vielhaber, S., Wallner, M., Warrenburg, B.P.C. van de, Zanni, G., Zuchner, S., Klockgether, T., Schüle, R., Schöls, L., and Synofzik, M.

Abstract

Contains fulltext : 238566.pdf (Publisher’s version ) (Open Access), Autosomal recessive cerebellar ataxias (ARCAs) form an ultrarare yet expanding group of neurodegenerative multisystemic diseases affecting the cerebellum and other neurological or non-neurological systems. With the advent of targeted therapies for ARCAs, disease registries have become a precious source of real-world quantitative and qualitative data complementing knowledge from preclinical studies and clinical trials. Here, we review the ARCA Registry, a global collaborative multicenter platform (>15 countries, >30 sites) with the overarching goal to advance trial readiness in ARCAs. It presents a good clinical practice (GCP)- and general data protection regulation (GDPR)-compliant professional-reported registry for multicenter web-based capture of cross-center standardized longitudinal data. Modular electronic case report forms (eCRFs) with core, extended, and optional datasets allow data capture tailored to the participating site's variable interests and resources. The eCRFs cover all key data elements required by regulatory authorities [European Medicines Agency (EMA)] and the European Rare Disease (ERD) platform. They capture genotype, phenotype, and progression and include demographic data, biomarkers, comorbidity, medication, magnetic resonance imaging (MRI), and longitudinal clinician- or patient-reported ratings of ataxia severity, non-ataxia features, disease stage, activities of daily living, and (mental) health status. Moreover, they are aligned to major autosomal-dominant spinocerebellar ataxia (SCA) and sporadic ataxia (SPORTAX) registries in the field, thus allowing for joint and comparative analyses not only across ARCAs but also with SCAs and sporadic ataxias. The registry is at the core of a systematic multi-component ARCA database cluster with a linked biobank and an evolving study database for digital outcome measures. Currently, the registry contains more than 800 patients with almost 1,500 visits representing all ages and disease stages; 65% of

Published
2021

31. Manganese Superoxide Dismutase Overexpression Attenuates MPTP Toxicity

Author

Peter Klivenyi, Daret St. Clair, Marike Wermer, Hsin-Chuan Yen, Terry Oberley, Lichuan Yang, and M.Flint Beal

Subjects
MPTP, Parkinson's disease, free radicals, oxidative damage, superoxide dismutase., Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

There is substantial evidence implicating mitochondrial dysfunction and free radical generation in the neurotoxicity of MPTP. Manganese superoxide dismutase (MnSOD) is the primary antioxidant enzyme protecting against superoxide radicals produced within mitochondria. Overexpression of human MnSOD in transgenic mice resulted in increased MnSOD localized to mitochondria in neurons and a 50% increase in total MnSOD activity in brain homogenates. We found that MPTP toxicity was significantly attenuated in the MnSOD transgenic mice which overexpress the human manganese superoxide dismutase gene, with these mice showing threefold greater dopamine levels than controls following MPTP. There were no alterations in MPP+levels, suggesting that the effects were not due to altered metabolism of MPTP. A significant increase in 3-nitrotyrosine levels was seen in littermate controls but not in transgenic mice overexpressing human MnSOD. These results provide further evidence implicating mitochondrial dysfunction and oxidative damage in the pathogenesis of MPTP neurotoxicity.

Published
1998
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37. Epidemiologic characteristics of a Hungarian subpopulation of Huntington’s Disease patients

Author

Jakab K, G Gardian, Kincses Tz, Despotov K, Gábor Veres, Dénes Zádori, Klivenyi P, Tóth E, Ajtay A, Bereczki D, and Vecsei L

Subjects
medicine.medical_specialty, Huntington's disease, business.industry, medicine, medicine.disease, Psychiatry, business
Abstract

Background: recent advances in the therapeutic options may prevent deterioration related to Huntington’s disease (HD) even at the presymptomatic stage. However, a well-characterized patient population is essential for screening and outcome monitoring as well. Accordingly, the aim of this study was to describe the characteristics of a Hungarian subpopulation of HD patients and mutation carriers diagnosed at the University of Szeged.Methods: we conducted a search for International Classification of Diseases (ICD) code G10H0 in the local medical database for the period between 1 January 1998 and 31 December 2018.Results: we identified 90 HD cases (male: 45, female: 45) and 34 asymptomatic carriers (male: 15, female: 19). The median age of onset was 45 years (range: 16-79). There were 3 cases of juvenile (3.3%), and 7 of late disease onset (7.8%). The median repeat length was 43 (range: 36-70) for the pathological and 19 for the non-pathological alleles (range: 9-35). 17.5% of the pathological alleles was in the decreased penetrance range, while 7% of non-pathological alleles was intermediate.Conclusions: the genetic and clinical features of the population examined in present study was in line with the previous Hungarian study as well as with international literature, the exceptions being the higher ratio of reduced penetrance and intermediate alleles.

Published
2020

41. cNEUPRO: Novel Biomarkers for Neurodegenerative Diseases

Author

Philipp Spitzer, Hans Wolfgang Klafki, Kaj Blennow, Luc Buée, Hermann Esselmann, Sanna-Kaisa Herruka, Connie Jimenez, Peter Klivenyi, Piotr Lewczuk, Juan Manuel Maler, Katrin Markus, Helmut E. Meyer, Chris Morris, Thorsten Müller, Markus Otto, Lucilla Parnetti, Hilkka Soininen, Susanna Schraen, Charlotte Teunissen, Laszlo Vecsei, Henrik Zetterberg, and Jens Wiltfang

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Geriatrics, RC952-954.6
Abstract

“clinical NEUroPROteomics of neurodegenerative diseases” (cNEUPRO) is a Specific Targeted Research Project (STREP) within the sixth framework program of the European Commission dedicated to the search for novel biomarker candidates for Alzheimer's disease and other neurodegenerative diseases. The ultimate goal of cNEUPRO is to identify one or more valid biomarker(s) in blood and CSF applicable to support the early and differential diagnosis of dementia disorders. The consortium covers all steps required for the discovery of novel biomarker candidates such as acquisition of high quality CSF and blood samples from relevant patient groups and controls, analysis of body fluids by various methods, and finally assay development and assay validation. Here we report the standardized procedures for diagnosis and preanalytical sample-handling within the project, as well as the status of the ongoing research activities and some first results.

Published
2010
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43. SAT 1-1

Author

Aquilonius, S.-M., Klivenyi, P., Odin, P., and Antonini, A.

Published
2011
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46. Using global team science to identify genetic parkinson's disease worldwide

Author

Vollstedt, E. -J., Kasten, M., Klein, C., Aasly, J., Adler, C., Ahmad-Annuar, A., Albanese, Alberto, Alcalay, R. N., Al-Mubarak, B., Alvarez, V., Andree-Munoz, B., Annesi, G., Appel-Cresswell, S., Arkadir, D., Armasu, S., Barber, T. R., Bardien, S., Barkhuizen, M., Barrett, M. J., Basak, A. N., Beach, T., Benitez, B. A., Berg, D., Bhatia, K., Binkofski, F., Blauwendraat, C., Bonifati, V., Borges, V., Bozi, M., Brice, A., Brighina, L., Brockmann, K., Brucke, T., Bruggemann, N., Camacho, M., Cardoso, F., Belin, A. C., Carr, J., Chan, P., Chang-Castello, J., Chase, B., Chen-Plotkin, A., Ju Chung, S., Cilia, R., Clarimon, J., Clark, L., Cornejo-Olivas, M., Corvol, J. -C., Cosentino, C., Cras, P., Crosiers, D., Damasio, J., Das, P., de Carvalho Aguiar, P., De Michele, G., De Rosa, A., Dieguez, E., Dorszewska, J., Erer, S., Ertan, S., Farrer, M., Fedotova, E., Ferese, R., Ferrarese, C., Ferraz, H., Fiala, O., Foroud, T., Friedman, A., Frigerio, R., Funayama, M., Gambardella, S., Garraux, G., Gatto, E. M., Genc, G., Giladi, N., Goldwurm, S., Gomez-Esteban, J. C., Gomez-Garre, P., Gorostidi, A., Grosset, D., Hanagasi, H., Hardy, J., Hassan, A., Hattori, N., Hauser, R. A., Hedera, P., Hentati, F., Hertz, J. M., Holton, J. L., Houlden, H., Hutz, M. H., Ikeuchi, T., Illarioshkin, S., Inca-Martinez, M., Infante, J., Jankovic, J., Jeon, B. S., Jesus, S., Jimenez-Del-Rio, M., Kaasinen, V., Kataoka, H., Kawakami, H., Kim, Y. J., Klivenyi, P., Koks, S., Konig, I. R., Kostic, V., Koziorowski, D., Kruger, R., Krygowska-Wajs, A., Kulisevsky, J., Lai, D., Lang, A., Ledoux, M., Lesage, S., Lim, S. -Y., Lin, C. -H., Lohmann, K., Lopera, F., Lopez, G., Lu, C. -S., Lynch, T., Machaczka, M., Madoev, H., Magalhaes, M., Majamaa, K., Maraganore, D., Marder, K., Markopoulou, K., Martikainen, M. H., Mata, I., Mazzetti, P., Mellick, G., Menendez-Gonzalez, M., Micheli, F., Mirelman, A., Mir, P., Morino, H., Morris, H., Munhoz, R. P., Naito, A., Olszewska, D. A., Ozelius, L. J., Padmanabhan, S., Paisan-Ruiz, C., Payami, H., Peluso, S., Petkovic, S., Petrucci, S., Pezzoli, G., Pimentel, M., Pirker, W., Pramstaller, P. P., Pulkes, T., Puschmann, A., Quattrone, A., Raggio, V., Ransmayr, G., Rieder, C., Riess, O., Rodriguez-Porcel, F., Rogaeva, E., Ross, O. A., Ruiz-Martinez, J., Sammler, E., San Luciano, M., Satake, W., Saunders-Pullman, R., Sazci, A., Scherzer, C., Schrag, A., Schumacher-Schuh, A., Sharma, M., Sidransky, E., Singleton, A. B., Petersen, M. S., Smolders, S., Spitz, M., Stefanis, L., Struhal, W., Sue, C. M., Swan, M., Swanberg, M., Taba, P., Taipa, R., Tan, M., Tan, A. H., Tan, E. -K., Tang, B., Tayebi, N., Thaler, A., Thomas, A., Toda, T., Toft, M., Torres, L., Tumas, V., Valente, E. M., Van Broeckhoven, C., Vecsei, L., Velez-Pardo, C., Vidailhet, M., Warner, T. T., Williams-Gray, C. H., Winkelmann, J., Woitalla, D., Wood, N. W., Wszolek, Z. K., Wu, R. -M., Wu, Y. -R., Xie, T., Yoshino, H., Zhang, B., Zimprich, A., Albanese A. (ORCID:0000-0002-5864-0006), Vollstedt, E. -J., Kasten, M., Klein, C., Aasly, J., Adler, C., Ahmad-Annuar, A., Albanese, Alberto, Alcalay, R. N., Al-Mubarak, B., Alvarez, V., Andree-Munoz, B., Annesi, G., Appel-Cresswell, S., Arkadir, D., Armasu, S., Barber, T. R., Bardien, S., Barkhuizen, M., Barrett, M. J., Basak, A. N., Beach, T., Benitez, B. A., Berg, D., Bhatia, K., Binkofski, F., Blauwendraat, C., Bonifati, V., Borges, V., Bozi, M., Brice, A., Brighina, L., Brockmann, K., Brucke, T., Bruggemann, N., Camacho, M., Cardoso, F., Belin, A. C., Carr, J., Chan, P., Chang-Castello, J., Chase, B., Chen-Plotkin, A., Ju Chung, S., Cilia, R., Clarimon, J., Clark, L., Cornejo-Olivas, M., Corvol, J. -C., Cosentino, C., Cras, P., Crosiers, D., Damasio, J., Das, P., de Carvalho Aguiar, P., De Michele, G., De Rosa, A., Dieguez, E., Dorszewska, J., Erer, S., Ertan, S., Farrer, M., Fedotova, E., Ferese, R., Ferrarese, C., Ferraz, H., Fiala, O., Foroud, T., Friedman, A., Frigerio, R., Funayama, M., Gambardella, S., Garraux, G., Gatto, E. M., Genc, G., Giladi, N., Goldwurm, S., Gomez-Esteban, J. C., Gomez-Garre, P., Gorostidi, A., Grosset, D., Hanagasi, H., Hardy, J., Hassan, A., Hattori, N., Hauser, R. A., Hedera, P., Hentati, F., Hertz, J. M., Holton, J. L., Houlden, H., Hutz, M. H., Ikeuchi, T., Illarioshkin, S., Inca-Martinez, M., Infante, J., Jankovic, J., Jeon, B. S., Jesus, S., Jimenez-Del-Rio, M., Kaasinen, V., Kataoka, H., Kawakami, H., Kim, Y. J., Klivenyi, P., Koks, S., Konig, I. R., Kostic, V., Koziorowski, D., Kruger, R., Krygowska-Wajs, A., Kulisevsky, J., Lai, D., Lang, A., Ledoux, M., Lesage, S., Lim, S. -Y., Lin, C. -H., Lohmann, K., Lopera, F., Lopez, G., Lu, C. -S., Lynch, T., Machaczka, M., Madoev, H., Magalhaes, M., Majamaa, K., Maraganore, D., Marder, K., Markopoulou, K., Martikainen, M. H., Mata, I., Mazzetti, P., Mellick, G., Menendez-Gonzalez, M., Micheli, F., Mirelman, A., Mir, P., Morino, H., Morris, H., Munhoz, R. P., Naito, A., Olszewska, D. A., Ozelius, L. J., Padmanabhan, S., Paisan-Ruiz, C., Payami, H., Peluso, S., Petkovic, S., Petrucci, S., Pezzoli, G., Pimentel, M., Pirker, W., Pramstaller, P. P., Pulkes, T., Puschmann, A., Quattrone, A., Raggio, V., Ransmayr, G., Rieder, C., Riess, O., Rodriguez-Porcel, F., Rogaeva, E., Ross, O. A., Ruiz-Martinez, J., Sammler, E., San Luciano, M., Satake, W., Saunders-Pullman, R., Sazci, A., Scherzer, C., Schrag, A., Schumacher-Schuh, A., Sharma, M., Sidransky, E., Singleton, A. B., Petersen, M. S., Smolders, S., Spitz, M., Stefanis, L., Struhal, W., Sue, C. M., Swan, M., Swanberg, M., Taba, P., Taipa, R., Tan, M., Tan, A. H., Tan, E. -K., Tang, B., Tayebi, N., Thaler, A., Thomas, A., Toda, T., Toft, M., Torres, L., Tumas, V., Valente, E. M., Van Broeckhoven, C., Vecsei, L., Velez-Pardo, C., Vidailhet, M., Warner, T. T., Williams-Gray, C. H., Winkelmann, J., Woitalla, D., Wood, N. W., Wszolek, Z. K., Wu, R. -M., Wu, Y. -R., Xie, T., Yoshino, H., Zhang, B., Zimprich, A., and Albanese A. (ORCID:0000-0002-5864-0006)

Abstract

Talks on rare diseases in the field of neurology often start with a statement like this: “About 80% of all rare diseases have a neurologic manifestation and about 80% of those are genetic in origin.” Although these numbers probably represent more of an estimate than well-documented evidence, rapidly advancing and cost-effective sequencing technologies have led to the quickly growing identification of patients with hereditary neurological diseases. Although the importance of genetics for diagnosis and genetic counseling is undisputed, the recent development of first genetargeted therapies entering clinical trial1,2 is adding an important new layer to the (re-)consideration of genetic testing in neurology. However, establishing accurate genotype– phenotype and genotype–treatment relationships requires large sample sizes. Systematic reviews can serve as instruments to combine information from several small samples, but unfortunately, this is often complicated by inconsistent and incomplete reporting of clinical and genetic data across studies. Thus, large multicenter approaches are necessary to systematically and uniformly characterize patients with genetic neurologic conditions and to eventually establish sizable clinical trial-ready cohorts.

Published
2019

49. Rivaroxaban for stroke prevention after embolic stroke of undetermined source

Author

Hart, Robert G, Sharma, Mukul, Mundl, Hardi, Kasner, Scott E, Bangdiwala, Shrikant I, Berkowitz, Scott D, Swaminathan, Balakumar, Lavados, Pablo, Wang, Yongjun, Wang, Yilong, Davalos, Antonio, Shamalov, Nikolay, Mikulik, Robert, Cunha, Luis, Lindgren, Arne, Arauz, Antonio, Lang, Wilfried, Czlonkowska, Anna, Eckstein, Jens, Gagliardi, Rubens J, Amarenco, Pierre, Ameriso, Sebastian F, Tatlisumak, Turgut, Veltkamp, Roland, Hankey, Graeme J, Toni, Danilo, Bereczki, Daniel, Uchiyama, Shinichiro, Ntaios, George, Yoon, Byung-Woo, Brouns, Raf, Endres, Matthias, Muir, Keith W, Bornstein, Natan, Ozturk, Serefnur, O'Donnell, Martin J, De Vries Basson, Matthys M, Pare, Guillaume, Pater, Calin, Kirsch, Bodo, Sheridan, Patrick, Peters, Gary, Weitz, Jeffrey I, Peacock, W Frank, Shoamanesh, Ashkan, Benavente, Oscar R, Joyner, Campbell, Themeles, Ellison, Connolly, Anderson DC, Stuart J., Demets, Dl, Kaste, M, Norrving, B, Wyse, Dg, Alet, M, Allende, G, Beinlich, A, Berrios, W, Bruera, G, Castro, D, Chialvo, L, Claverie, S, Contardo, L, Couto, J, Deganutto, R, Diaz, R, Dossi, D, Esnaola, M, Falco, M, Fernandez Pirrone, P, Ferrari, J, Firstenfeld, A, Galli Giqueauk, E, Gilli, M, Gonzalez, L, Gonzalez Toledo, M, Grecco, M, Halac, B, Hawkes, M, Ioli, P, Jure, L, Klein, F, Lepera, S, Lujan, S, Mackinnon, F, Marroquin, M, Martin, J, Parisi, V, Perez Leguizamon, P, Persi, G, Povedano, P, Povedano, G, Pujol Lereis, V, Radrizzani, L, Reich, E, Repetto, M, Rodriguez Lucci, F, Romano, M, Saredo, G, Schneider, M, Simonsini, C, Sumay, G, Thomson, A, Toledo, W, Torres, C, Vila, A, Abdul Rasheed, N, Anderson, C, Bailey, P, Blacker, D, Carcel, C, Clissold, B, Delcourt, C, Field, D, Gangadharan, S, Ghia, D, Kleinig, T, Leyden, J, Ly, J, Ma, H, Mackey, E, Mishra, S, Moey, A, Musuka, T, Pepper, E, Phan, T, Sabet, A, Saw, J, Singh, B, Tryambake, D, Tu, H, Wijeratne, T, Wong, A, Augustin, S, Esterbauer, M, Garnauf, M, Gasiorek, K, Gasser, S, Gaugg, M, Greisenegger, S, Harrasser, M, Heine, M, Huber, B, Joachim, B, Kapeller, P, Krebs, S, Kreuzpointer, R, Kunzmann, J, Lechner, H, Lohninger, B, Luschin, G, Macher, S, Marko, M, Matosevic, B, Mayr, A, Mismas, A, Mitrovic, N, Mutzenbach, J, Oberndorfer, S, Obmann, S, Raffelsberger, T, Roesler, C, Salletmayr, T, Serles, W, Stadler, K, Tinchon, A, Tolino, M, Verocai, V, Vigl, M, Voglsperger, B, Weber, J, Werner, P, Windt, J, Winkler, A, Wurzinger, H, Zelenka, I, Cras, P, Crols, R, De Keyser, J, De Klippel, N, De Pauw, A, De Smedt, A, Dhollander, I, Hermans, S, Ligot, N, Maqueda, V, Maqueda Maqueda, V, Naeije, G, Seynaeve, L, Soors, P, Van Daele, W, Vanacker, P, Vanderschueren, G, Willems, C, Yperzeele, L, Avelar, W, Bacellar, A, Batista, C, Bazan, R, Braga, G, Cardoso, F, Dagnino, M, Fabio, S, Ferreira Junior, G, Freitas, G, Friedrich, M, Gomes Neto, A, Guarda, S, Katsurayama, M, Machado, M, Martins, S, Meira, F, Minelli, C, Morais, R, Moro, C, Neto, O, Polin, M, Silva, D, Weiss, G, Basile, V, Beaudry, M, Berlingieri, J, Blacquiere, D, Buck, B, Chan, R, Coutts, S, Das, S, Desai, J, Ehrensperger, E, Field, T, Gladstone, D, Hachinski, V, Hassan, A, Hegedus, J, Hill, M, Jin, A, Khaw, A, Mackey, A, Maclean, G, Mandzia, J, Mann, S, Mehdiratta, M, Murphy, C, Ng, K, Oczkowski, W, Penn, A, Perera, K, Perez, Y, Pesant, Y, Phillips, S, Poppe, A, Sahlas, J, Shuaib, A, Spence, D, Sposato, L, Stotts, G, Tamayo, A, Teal, P, Wilson, L, Winder, T, Yegappan, C, Yip, S, Andreu, D, Araya, P, Bustamante, G, Figueroa, C, Gasic, K, Herrero, D, Matamala, G, Munoz, S, Olavarria, V, Pasten, J, Polanco, J, Reyes, P, Roldan, A, Salamanca, P, Silva, P, Toloza, C, Verdugo, M, Cai, K, Che, C, Chen, J, Chen, Z, Chen, T, Chen, H, Chen, X, Chen, B, Chen, G, Chen, L, Chu, F, Cui, L, Dai, C, Ding, N, Ding, J, Du, P, Du, J, Fang, L, Feng, J, Gao, Y, Geng, J, Guan, J, Hao, L, Huang, D, Huang, H, Jin, X, Jing, P, Ke, K, Li, G, Li, M, Li, S, Li, J, Liang, Z, Lin, H, Liu, K, Liu, X, Lu, Z, Ma, C, Pei, H, Qiu, J, Qu, X, Shen, W, Sun, X, Tian, J, Tong, L, Tong, Z, Wang, J, Wang, L, Wang, X, Wang, W, Wang, N, Wang, D, Wang, H, Wen, G, Weng, G, Wu, W, Wu, S, Xiao, B, Xiaopeng, W, Xiong, L, Xiong, Y, Xu, Y, Xu, J, Xu, Z, Yang, L, Yang, Y, Yang, X, Yang, J, Yang, Q, Yang, B, Zhang, C, Zhang, B, Zhang, Y, Zhang, S, Zhang, M, Zhang, X, Zhang, J, Zhao, L, Zhou, L, Bar, M, Barteys, M, Bartolottiova, T, Carek, M, Ferencova, K, Fiksa, J, Gallo, J, Goldemund, D, Hanouskova, L, Herzig, R, Hon, P, Jankovych, J, Jura, R, Kadlcikova, J, Kemlink, D, Kopecky, S, Krajickova, D, Kral, M, Krejci, V, Pavlik, O, Peisker, T, Pernicka, M, Peska, S, Rapantova, P, Reif, M, Rekova, P, Sanak, D, Sebejova, M, Skoda, O, Slonkova, J, Stetkarova, I, Tenora, D, Tumova, R, Vaclavik, D, Vasko, P, Veverka, T, Vitkova, E, Volna, J, Andersen, G, Christensen, H, Christensen, T, Damgaard, D, Iversen, H, Krarup Hansen, C, Kruuse, C, Martinussen, M, Modrau, B, Murtuzova, A, Ovesen, C, Papina, M, Svaneborg, N, Von Weitzel-Mudersbach, P, Curtze, S, Fanta, S, Huhtakangas, J, Keskinarkaus, I, Kivioja, R, Koivu, M, Korpela, J, Larjo, T, Linna, M, Marinkovic, I, Martinez-Majander, N, Nieminen, T, Nikkanen, M, Numminen, H, Ortiz, R, Österlund-Tauriala, E, Roine, R, Roine, S, Ruuskanen, J, Saarinen, J, Shulga, A, Sibolt, G, Tapanainen, A, Tapiola, T, Tiainen, M, Tomppo, L, Tumpula, O, Tuomainen, P, Tynkkynen, J, Vainikka, S, Valpas, J, Virta, J, Ylikallio, E, Ylikotila, P, Accassat, S, Aniculaesei, A, Baronnet, F, Bejot, Y, Bindila, D, Birchenall, J, Blanc-Labarre, C, Bodiguel, E, Bouly, S, Cabrejo, L, Calvet, D, Corlobe, A, Crozier, S, Delpont, B, Deltour, S, Diaconu, M, Domigo, V, Epinat, M, Ferreira, A, Fisselier, M, Garnier, P, Gimenez, L, Gueguen, A, Guidoux, C, Guillon, B, Guiraudg, V, Hervieu-Begue, M, Hobeanu, M, Khoumri, C, Lamy, C, Lauer, V, Le Bouc, R, Lecouturier, K, Leder, S, Leger, A, Macian-Montoro, F, Meseguer, E, Morar-Precup, D, Morvan, T, Morvan, E, Obadia, M, Osseby, G, Philippi, S, Pico, F, Quenardelle, V, Reiner, P, Rigual, R, Rosso, C, Sabben, C, Samson, Y, Sevin, M, Sibon, I, Thouvenot, E, Timsit, S, Touze, E, Turc, G, Vahedi, K, Varvat, J, Wacongne, A, Wolff, V, Yalo, B, Zinchenko, I, Bagelmann, H, Bardutzky, J, Barlinn, J, Bathe-Peters, R, Berrouschot, J, Dietzel, J, Ehrlich, S, Fatar, M, Filipov, A, Fluri, F, Gabriel, M, Geran, R, Gliem, M, Graf, S, Griebe, M, Grosse, G, Haeusler, K, Harmel, P, Held, V, Hellwig, S, Henkner, J, Hieber, M, Hoyer, C, Jander, S, Keilitz, J, Kellner, J, Knecht, S, Koch, M, Koehler, L, Kucken, D, Kusnick, G, Lambeck, J, Lee, J, Leisse, I, Lubke-Detring, S, Machetanz, J, Mensch, A, Meyer, N, Molis, A, Mueller, T, Muhl, C, Nave, A, Radtke, A, Roth, Y, Roukens, R, Schlachetzki, F, Schneider, I, Schuppner, R, Schurig, J, Schwarzbach, C, Seidel, G, Sonntag, N, Steinert, S, Stoll, A, Stumpp, A, Taggeselle, J, Trommer, A, Tuetuencue, S, Wartenberg, K, Weissenborn, K, Wittayer, M, Wolf, M, Wolter, C, Worthmann, H, Wunderlich, S, Zitzmann, A, Anagnostou, E, Brokalaki, C, Hatzitolios, A, Kakaletsis, N, Kanellos, I, Kei, A, Korompoki, E, Koutroubi, A, Liamis, G, Makaritsis, K, Manios, E, Michas, F, Milionis, H, Papadopoulos, G, Papadopoulou, E, Papagiannis, A, Polychronopoulou, E, Sagris, D, Satsoglou, S, Savopoulos, C, Solganov, I, Spengos, K, Stamatelopoulos, K, Terentiou, A, Tountopoulou, A, Vassilopoulou, S, Amjad, A, Balazs, A, Bankuti, Z, Bicsak, T, Borcsik, L, Csanyi, A, Csiba, L, Csontos, K, Csuha, R, Czurko, M, Danku, V, Dioszeghy, P, Faust, K, Fazekas, F, Gerocs, Z, Gottschal, M, Gyuker, N, Hajas, A, Horvath, L, Horvath, M, Iljicsov, A, Jakab, K, Javor, L, Kakuk, I, Karasz, O, Kasa, K, Kasza, J, Kerekgyarto, M, Klivenyi, P, Kovacs, K, Kovacs, T, Kovacs, H, Lajos, B, Lovasz, R, Magyar, T, Matoltsy, A, May, Z, Molnar, S, Monosi, C, Motko, T, Nemeth, R, Nemeth, L, Nikl, J, Olah, L, Orosz, V, Panczel, G, Pentek, S, Prendl, B, Rozsa, C, Rum, G, Sas, K, Sas, A, Semjen, J, Simony, Z, Sipos, I, Szabo, K, Szasz, G, Szegedi, N, Szekely, A, Szilagyi, G, Szoboszlai, K, Szpisjak, L, Toth, G, Uhrinyakova, L, Valikovics, A, Varga, Z, Vass, L, Vastagh, I, Vecsei, L, Zboznovits, D, Coveney, S, Horgan, G, Kelly, P, Murphy, S, Smyth, A, Waters, R, Abu Ahmad, F, Bloch, S, Dorodnicov, E, Hallevi, H, Haratz, S, Horev, A, Kolianov, V, Leker, R, Mahagney, A, Marzelik, O, Rephaeli, G, Tanne, D, Weller, B, Acciarresi, M, Adami, A, Agostoni, E, Alemseged, F, Altavilla, R, Angelocola, S, Anticoli, S, Berardi, V, Bravi, M, Candeloro, E, Cappellari, M, Carletti, M, Caruso, P, Castellini, P, Cavallini, A, Cenciarelli, S, Cerrone, P, Condurso, R, Consoli, D, Danese, A, Della Marca, G, Denaro, M, Di Mascio, M, Diomedi, M, Distefano, M, Frisullo, G, Furlanis, G, Galati, F, Gallina, A, Gallinella, E, Giannandrea, D, Giatsidis, F, Greco, L, Impellizzeri, M, Landolfi, A, Lanfranconi, S, Latte, L, Lembo, G, Longoni, M, Marando, C, Marini, C, Marsili, E, Mastrocola, S, Mazzoli, T, Melis, M, Micheletti, N, Moller, J, Monzani, V, Naccarato, M, Paciaroni, M, Padiglioni, C, Persico, A, Pezzella, F, Pieroni, A, Piras, V, Postorino, P, Pozzerese, C, Profice, P, Ricci, S, Rinaldi, C, Rizzato, B, Rocco, A, Roveri, L, Santalucia, P, Semerano, A, Sicilia, I, Silvestrini, M, Sucapane, P, Tomelleri, G, Tropepi, D, Venti, M, Amino, T, Chin, M, Deguchi, I, Fujigasaki, H, Fukuyama, K, Haraguchi, K, Hasegawa, Y, Hattori, M, Hayashi, T, Hirose, M, Honma, Y, Igarashi, S, Irie, S, Itabashi, R, Ito, Y, Kamata, T, Kaneko, C, Kawanishi, M, Kimura, R, Kitagawa, K, Kobayashi, Y, Kondo, T, Kuwashiro, T, Matsumoto, S, Miyake, H, Nagakane, Y, Nishino, S, Nishiyama, Y, Nogawa, S, Ochiai, J, Ohira, M, Okamoto, Y, Okubo, S, Okuda, S, Ooyama, K, Sakai, N, Suenaga, T, Suzuki, H, Takamatsu, K, Takao, M, Taki, W, Takizawa, S, Tokunaga, K, Toyoda, K, Urui, S, Yamada, T, Yamasaki, M, Yoshida, Y, Yuasa, H, Bae, H, Cha, J, Chang, D, Chung, C, Heo, J, Hong, K, Kim, J, Lee, B, Nah, H, Oh, K, Park, M, Park, J, Rha, J, Sohn, S, Amaya Sanchez, L, Arauz Gongora, A, Cantu Brito, C, Chiquete 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Skowronska, M, Sliwinska, B, Sobolewski, P, Sobota, A, Stoiński, J, Szczuchniak, W, Szczyrba, S, Szewczyk, Z, Szlufik, S, Tarasiuk, J, Tutaj, A, Uchwat, U, Wach-Klink, A, Winska-Tereszkiewicz, A, Wisniewska, A, Włodek, A, Wojnarowska-Arendt, A, Zalewska, J, Zielinska-Turek, J, Ziomek, M, Zwiernik, J, Abreu, P, E Silva A, Amaral, Azevedo, E, Barroso, C, Calejo, M, Campillo, J, Campos Costa, E, Coelho, J, Correia, M, Correia, C, Gregorio, T, Lopes, D, Machado, C, Mendonca, T, Pereira, L, Pidal, A, Pineiro, S, Pinto, A, Ribeiro, J, Rodrigues, M, Salgado, P, Salgado, A, Santo, G, Sargento, J, Varela, R, Abroskina, M, Badalyan, K, Balueva, T, Barulin, A, Bazhenova, O, Belkin, A, Bogdanov, E, Daineko, A, Druzenko, I, Fedin, A, Fidler, M, Gogoleva, E, Golikov, K, Gonysheva, Y, Greshnova, I, Guryanova, N, Gusev, V, Kashaeva, E, Kaygorodtseva, S, Khairutdinova, D, Kholopov, M, Kirpicheva, S, Koltsov, I, Konkov, I, Kurenkova, N, Kurtenkova, N, Kurushina, O, Kustova, M, Lagutenko, M, Lenskaya, L, 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Clavijo, M, Gil Nunez, A, Giralt, E, Gomez-Choco, M, Gomis, M, Gutiérrez, R, Iglesias Mohedano, A, Lago, A, Lara Lezama, L, Lara Rodriguez, B, Llull, L, Lopez Fernandez, M, Lorenzo, A, Maestre-Moreno, J, Marta Moreno, J, Marti-Fabregas, J, Martínez Sánchez, P, Mauri Cabdevila, G, Mengual Chirifie, J, Molina, C, Molina, J, Moniche, F, Morales, L, Morales, A, Nombela, F, Núñez, F, Pagola, J, Perez, S, Portilla, J, Prats, L, Purroy, F, Quesada Garcia, H, Ramirez Moreno, J, Redondo Robles, L, Renu, A, Riveira Rodriguez, C, Roa, A, Rodriguez Campello, A, Rodriguez Pardo De Donlebun, J, Rodriguez Yanez, M, Rudilosso, S, Ruiz Ares, G, Sànchez Cerón, M, Santamaria Cadavid, M, Sanz Cuesta, B, Serena, J, Silva, Y, Soriano Soriano, C, Tejada Garcia, J, Tejada Meza, H, Tembl, J, Terceno, M, Trillo, S, Urra, X, Usero Ruiz, M, Vazquez, P, Vilar, C, Villanueva Osorio, J, Ximenez-Carrillo, A, Zapata, E, Esbjornsson, M, Karlsson, J, Kremer, C, Kuris, A, Staaf, G, Stiehm, M, Timberg, I, Tossavainen, C, Wester, P, Arnold, M, Baumgartner, P, Beer, J, Bicker, H, Boos, L, Cereda, C, Chaloulos-Iakovidis, P, Christian, L, Engelter, S, Fisch, L, Fischer, U, Frey, S, Frick, M, Hauk, M, Hoffmann, M, Kahles, T, Manno, C, Medlin, F, Mircea, D, Nedeltchev, K, Panos, L, Polymeris, A, Schillinger, N, Stocker, R, Sztajzel, R, Alaydin, H, Batur Caglayan, H, Colakoglu, S, Demirci, N, Duman, T, Eren, F, Gokce, M, Inanc, Y, Nazliel, B, Ongun, G, Ozcekic Demirhan, S, Ozyurt, E, Selcuk, D, Sorgun, M, Tezcan, S, Togay Isikay, C, Tokgoz, O, Ulku Acar, R, Uluduz Ugurlu, D, Abdul-Saheb, M, Ahmad, N, Ali, A, Alwis, L, Balogun, I, Bathula, R, Behnam, Y, Bhandari, M, Bhargavah, M, Black, T, Blank, C, Bruce, D, Burn, M, Canepa, C, Chakrabarti, A, Chandrasena, D, Chembala, J, Cheripelli, B, Clarke, R, Cohen, D, Collas, D, Constantin, C, Dani, K, Del Giudice, A, Dennis, M, Devine, J, Dima, S, Doubal, F, Duodu, Y, Dutta, D, El Ta Wil, S, Elyas, S, Evans, N, Eveson, D, Fotherby, K, France, E, Furnace, J, Grabowski, S, Gunathilagan, G, Gutierrez, R, Guyler, P, Hargroves, D, Harkness, K, Harvey, M, Hayhoe, H, Hicken, L, Hussain, M, Kelly, S, Lam, M, Lindert, R, Louw, S, Luder, R, Macleod, M, Majid, A, Mangion, D, Markova, S, Markus, H, Marsh, R, Mcarthur, K, Menon, N, Metcalf, K, Minhas, J, Minns, M, Mistri, A, Moreton, F, Mpelembue, M, Muddegowda, G, Mudhar, O, Musarrat, K, Myint, M, Natarajan, I, Naylor, D, Ngeh, J, Papavasileiou, V, Perry, R, Piechowski-Jozwiak, B, Pradhan, M, Rani, A, Rashed, K, Robinson, T, Roffe, C, Saksena, R, Sattar, N, Sekaran, L, Selvarajah, J, Shah, S, Sinha, D, Sivakumar, R, Sztriha, L, Walters, D, Webb, T, Werring, D, Whiteley, W, Whiting, R, Abdelhamid, N, Abdul Rahman, D, Amin, H, Androulakis, M, Babikian, V, Baker, M, Barker Trejo, S, Benjamin, A, Birnbaum, L, Burke, J, Chen, S, Clark, W, Coull, B, De Havenon, A, Dearborn, J, Degeorgia, M, Essa, B, Fares, M, Favate, A, Furlan, A, Gebreyohanns, M, Goddeau, R, Green, D, Greer, D, Haralur Sreekantaiah, Y, Hasan, R, Hedna, V, Henninger, N, Holmstedt, C, Ishida, K, Jagolino, A, Johnson, M, Jun-Oconnell, A, Kaur, S, Khanna, A, Kirshner, H, Kittner, S, Kleindorfer, D, Leira, E, Loomis, C, Lord, A, Lowenkopf, T, Lutsep, H, Magadan, A, Majjhoo, A, Maud, A, Mayasi, Y, Mccullough, L, Mckinney, J, Mehta, S, Mehta, D, Mehta, B, Messe, S, Miller, B, Milling, T, Moonis, M, Navaratnam, D, Okpala, M, Patel, N, Pettigrew, L, Phinney, T, Ramos-Estebanez, C, Rasmussen, J, Rodriguez, G, Rybinnik, I, Santiago, P, Sarraj, A, Savitz, S, Sawyer, R, Scandura, T, Schindler, J, Sen, S, Shang, T, Sharrief, A, Sila, C, Simpkins, A, Sundararajan, S, Talahma, M, Tayal, A, Thaler, D, Tirschwell, D, Torres, J, Vora, N, Warnack, W, Waters, M, Wilson, C, Xiong, W, Zweifler, R, Zanferrari, C., St Marys Development Trust, Servicio de Neurologia (SANTIAGO - Neurologie), Universidad del Desarrollo, Department of Neurology (Dep Neuro - BEIJING), Tiantan Hospital, Neurology department, Universidade de Coimbra [Coimbra], Department of Internal Medicine, University Hospital Basel [Basel], 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), Department of Neurological Sciences, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Department of Neurology, Seoul National University Hospital, Institute of Neurosciences and Psychology [Glasgow], University of Glasgow, Neurology Department, Ichilov Medical Center, CIC Brest, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Cavale Blanche, Yperzeele, Laetitia, NAVIGATE ESUS Investigators, and Selçuk Üniversitesi

Subjects
Stroke/etiology, Male, [SDV]Life Sciences [q-bio], Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Brain Ischemia, Brain ischemia, 0302 clinical medicine, DESIGN, Rivaroxaban, Hemorrhage/chemically induced, Secondary Prevention, Medicine, Factor Xa Inhibitors/adverse effects, Stroke, Rivaroxaban/adverse effects, ComputingMilieux_MISCELLANEOUS, 11 Medical and Health Sciences, Aspirin, Atrial fibrillation, General Medicine, FORAMEN OVALE CLOSURE, Middle Aged, TRIALS, Intracranial Embolism, SAFETY, Aged, Factor Xa Inhibitors, Female, Hemorrhage, Humans, Platelet Aggregation Inhibitors, Medicine (all), Cardiology, Foramen ovale closure, Platelet aggregation inhibitor, Settore MED/26 - Neurologia, Life Sciences & Biomedicine, medicine.drug, medicine.medical_specialty, Platelet Aggregation Inhibitors/adverse effects, ANTITHROMBOTIC THERAPY, Aspirin/adverse effects, WARFARIN, 03 medical and health sciences, Secondary Prevention/methods, Medicine, General & Internal, Internal medicine, Intracranial Embolism/drug therapy, General & Internal Medicine, NAVIGATE ESUS Investigators, METAANALYSIS, Science & Technology, CRYPTOGENIC STROKE, business.industry, Warfarin, medicine.disease, EFFICACY, ATRIAL-FIBRILLATION, Human medicine, business, Brain Ischemia/prevention & control, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

WOS: 000434263000007, PubMed: 29766772, BACKGROUND Embolic strokes of undetermined source represent 20% of ischemic strokes and are associated with a high rate of recurrence. Anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, may result in a lower risk of recurrent stroke than aspirin. METHODS We compared the efficacy and safety of rivaroxaban (at a daily dose of 15 mg) with aspirin (at a daily dose of 100 mg) for the prevention of recurrent stroke in patients with recent ischemic stroke that was presumed to be from cerebral embolism but without arterial stenosis, lacune, or an identified cardioembolic source. The primary efficacy outcome was the first recurrence of ischemic or hemorrhagic stroke or systemic embolism in a time-to-event analysis; the primary safety outcome was the rate of major bleeding. RESULTS A total of 7213 participants were enrolled at 459 sites; 3609 patients were randomly assigned to receive rivaroxaban and 3604 to receive aspirin. Patients had been followed for a median of 11 months when the trial was terminated early because of a lack of benefit with regard to stroke risk and because of bleeding associated with rivaroxaban. The primary efficacy outcome occurred in 172 patients in the rivaroxaban group (annualized rate, 5.1%) and in 160 in the aspirin group (annualized rate, 4.8%) (hazard ratio, 1.07; 95% confidence interval [CI], 0.87 to 1.33; P=0.52). Recurrent ischemic stroke occurred in 158 patients in the rivaroxaban group (annualized rate, 4.7%) and in 156 in the aspirin group (annualized rate, 4.7%). Major bleeding occurred in 62 patients in the rivaroxaban group (annualized rate, 1.8%) and in 23 in the aspirin group (annualized rate, 0.7%) (hazard ratio, 2.72; 95% CI, 1.68 to 4.39; P, BayerBayer AG; Janssen Research and Development, Supported by Bayer and Janssen Research and Development.

Published
2018

50. Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of undetermined source: a prespecified subgroup analysis from the NAVIGATE ESUS trial

Author

Kasner, Scott E, primary, Swaminathan, Balakumar, additional, Lavados, Pablo, additional, Sharma, Mukul, additional, Muir, Keith, additional, Veltkamp, Roland, additional, Ameriso, Sebastian F, additional, Endres, Matthias, additional, Lutsep, Helmi, additional, Messé, Steven R, additional, Spence, J David, additional, Nedeltechev, Krassen, additional, Perera, Kanjana, additional, Santo, Gustavo, additional, Olavarria, Veronica, additional, Lindgren, Arne, additional, Bangdiwala, Shrikant, additional, Shoamanesh, Ashkan, additional, Berkowitz, Scott D, additional, Mundl, Hardi, additional, Connolly, Stuart J, additional, Hart, Robert G, additional, Abdelhamid, N, additional, Abdul Rahman, D, additional, Abdul-Saheb, M, additional, Abreu, P, additional, Abroskina, M, additional, Abu Ahmad, F, additional, Accassat, S, additional, Acciaresi, M, additional, Adami, A, additional, Ahmad, N, additional, Ahmed, F, additional, Alberto Hawkes, M, additional, Alemseged, F, additional, Ali, A, additional, Altavilla, R, additional, Alwis, L, additional, Amarenco, P, additional, Amaro, S, additional, Amaya Sanchez, LE, additional, Amelia Pinto, A, additional, Ameriso, SF, additional, Amin, H, additional, Amino, T, additional, Amjad, AK, additional, Anagnostou, E, additional, Andersen, G, additional, Anderson, C, additional, Anderson, DC, additional, Andrea Falco, M, additional, Andres Mackinnon, F, additional, Andreu, D, additional, Androulakis, M, additional, Angel Gamero, M, additional, Angel Saredo, G, additional, Angeles Diaz, R, additional, Angels Font, M, additional, Anticoli, S, additional, Arauz, A, additional, Arauz Gongora, AA, additional, Araya, P, additional, Arenillas Lara, JF, additional, Arias Rivas, S, additional, Arnold, M, additional, Augustin, S, additional, Avelar, W, additional, Azevedo, E, additional, Babikian, V, additional, Bacellar, A, additional, Badalyan, K, additional, Bae, HJ, additional, Baez Martinez, EM, additional, Bagelmann, H, additional, Bailey, P, additional, Bak, Z, additional, Baker, M, additional, Balazs, A, additional, Baldaranov, D, additional, Balogun, I, additional, Balueva, T, additional, Bankuti, Z, additional, Bar, M, additional, Baranowska, A, additional, Bardutzky, J, additional, Barker Trejo, S, additional, Barlinn, J, additional, Baronnet, F, additional, Barroso, C, additional, Barteys, M, additional, Bartolottiova, T, additional, Barulin, A, additional, Bas, M, additional, Bashir, S, additional, Basile, V, additional, Bathe-Peters, R, additional, Bathula, R, additional, Batista, C, additional, Batur Caglayan, H, additional, Baumgartner, P, additional, Bazan, R, additional, Bazhenova, O, additional, Beaudry, M, additional, Beer, J, additional, Behnam, Y, additional, Beilei, C, additional, Beinlich, A, additional, Bejot, Y, additional, Belkin, A, additional, Benavente, OR, additional, Benjamin, A, additional, Berardi, V, additional, Bereczki, D, additional, Berkowitz, SD, additional, Berlingieri, J, additional, Berrios, W, additional, Berrouschot, J, additional, Bhandari, M, additional, Bhargavah, M, additional, Bicker, H, additional, Bicsak, T, additional, Bilik, M, additional, Bindila, D, additional, Birchenall, J, additional, Birnbaum, L, additional, Black, T, additional, Blacker, D, additional, Blacquiere, D, additional, Blanc-Labarre, C, additional, Blank, C, additional, Blazejewska-Hyzorek, B, additional, Bloch, S, additional, Bodiguel, E, additional, Bogdanov, E, additional, Boos, L, additional, Borcsik, L, additional, Bornstein, N, additional, Bouly, S, additional, Braga, G, additional, Bragado, I, additional, Bravi, MC, additional, Brokalaki, C, additional, Brola, W, additional, Brouns, R, additional, Bruce, D, additional, Brzoska-Mizgalska, J, additional, Buck, B, additional, Buksinska-Lisik, M, additional, Burke, J, additional, Burn, M, additional, Bustamante, G, additional, Cabrejo, L, additional, Cai, K, additional, Cajaraville, S, additional, Calejo, M, additional, Calvet, D, additional, Campillo, J, additional, Campos Costa, E, additional, Camps, P, additional, Can Alaydin, H, additional, Candeloro, E, additional, Canepa, C, additional, Cantu Brito, CG, additional, Cappellari, M, additional, Carcel, C, additional, Cardona Portela, P, additional, Cardoso, F, additional, Carek, M, additional, Carletti, M, additional, Carlos Portilla, J, additional, Caruso, P, additional, Casado-Naranjo, I, additional, Castellini, P, additional, Castro, D, additional, Castro Meira, F, additional, Cavallini, A, additional, Cayuela Caudevilla, N, additional, Cenciarelli, S, additional, Cereda, C, additional, Cerrone, P, additional, Chakrabarti, A, additional, Chaloulos-Iakovidis, P, additional, Chamorro, A, additional, Chandrasena, D, additional, Chang, DI, additional, Che, C, additional, Chembala, J, additional, Chen, J, additional, Chen, Z, additional, Chen, T, additional, Chen, H, additional, Chen, X, additional, Chen, G, additional, Chen, L, additional, Chen, S, additional, Cheripelli, B, additional, Chin, M, additional, Chiquete Anaya, E, additional, Chorazy, M, additional, Christensen, H, additional, Christensen, T, additional, Christian, L, additional, Chu, F, additional, Chung, CS, additional, Clark, W, additional, Clarke, R, additional, Claverie, S, additional, Clemente Agostoni, E, additional, Clissold, B, additional, Coelho, J, additional, Cohen, D, additional, Colakoglu, S, additional, Collas, D, additional, Condurso, R, additional, Connolly, SJ, additional, Consoli, D, additional, Constantin, C, additional, Constantino Silva, AB, additional, Contardo, L, additional, Corlobe, A, additional, Correia, M, additional, Correia, C, additional, Cortijo Garcia, E, additional, Coull, B, additional, Coutts, S, additional, Coveney, S, additional, Cras, P, additional, Crols, R, additional, Crozier, S, additional, Csanyi, A, additional, Csiba, L, additional, Csontos, K, additional, Csuha, R, additional, Cui, L, additional, Cunha, L, additional, 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2018
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