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1. Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity

Author

Mark K. Bakker, Jos P. Kanning, Gad Abraham, Amy E. Martinsen, Bendik S. Winsvold, John-Anker Zwart, Romain Bourcier, Tomonobu Sawada, Masaru Koido, Yoichiro Kamatani, Sandrine Morel, Philippe Amouyel, Stéphanie Debette, Philippe Bijlenga, Takiy Berrandou, Santhi K. Ganesh, Nabila Bouatia-Naji, Gregory Jones, Matthew Bown, Gabriel J.E. Rinkel, Jan H. Veldink, Ynte M. Ruigrok, Anne Hege Aamodt, Anne Heidi Skogholt, Ben M Brumpton, Cristen J Willer, Else C Sandset, Espen S Kristoffersen, Hanne Ellekjær, Ingrid Heuch, Jonas B Nielsen, Knut Hagen, Kristian Hveem, Lars G Fritsche, Laurent F Thomas, Linda M Pedersen, Maiken E Gabrielsen, Oddgeir L Holmen, Sigrid Børte, Wei Zhou, Shérine Abboud, Massimo Pandolfo, Vincent Thijs, Didier Leys, Marie Bodenant, Fabien Louillet, Emmanuel Touzé, Jean-Louis Mas, Yves Samson, Sara Leder, Anne Léger, Sandrine Deltour, Sophie Crozier, Isabelle Méresse, Sandrine Canaple, Olivier Godefroy, Maurice Giroud, Yannick Béjot, Pierre Decavel, Elizabeth Medeiros, Paola Montiel, Thierry Moulin, Fabrice Vuillier, Jean Dallongeville, Antti J Metso, Tiina Metso, Turgut Tatlisumak, Caspar Grond-Ginsbach, Christoph Lichy, Manja Kloss, Inge Werner, Marie-Luise Arnold, Michael Dos Santos, Armin Grau, Martin Dichgans, Constanze Thomas-Feles, Ralf Weber, Tobias Brandt, Alessandro Pezzini, Valeria De Giuli, Filomena Caria, Loris Poli, Alessandro Padovani, Anna Bersano, Silvia Lanfranconi, Simone Beretta, Carlo Ferrarese, Giacomo Giacolone, Stefano Paolucci, Philippe Lyrer, Stefan Engelter, Felix Fluri, Florian Hatz, Dominique Gisler, Leo Bonati, Henrik Gensicke, Margareth Amort, Hugh Markus, Jennifer Majersik, Bradford Worrall, Andrew Southerland, John Cole, Steven Kittner, Evangelos Evangelou, Helen R Warren, He Gao, Georgios Ntritsos, Niki Dimou, Tonu Esko, Reedik Mägi, Lili Milani, Peter Almgren, Thibaud Boutin, Jun Ding, Franco Giulianini, Elizabeth G Holliday, Anne U Jackson, Ruifang Li-Gao, Wei-Yu Lin, Jian’an Luan, Massimo Mangino, Christopher Oldmeadow, Bram Peter Prins, Yong Qian, Muralidharan Sargurupremraj, Nabi Shah, Praveen Surendran, Sébastien Thériault, Niek Verweij, Sara M Willems, Jing-Hua Zhao, John Connell, Renée de Mutsert, Alex SF Doney, Martin Farrall, Cristina Menni, Andrew D Morris, Raymond Noordam, Guillaume Paré, Neil R Poulter, Denis C Shields, Alice Stanton, Simon Thom, Gonçalo Abecasis, Najaf Amin, Dan E Arking, Kristin L Ayers, Caterina M Barbieri, Chiara Batini, Joshua C Bis, Tineka Blake, Murielle Bochud, Michael Boehnke, Eric Boerwinkle, Dorret I Boomsma, Erwin P Bottinger, Peter S Braund, Marco Brumat, Archie Campbell, Harry Campbell, Aravinda Chakravarti, John C Chambers, Ganesh Chauhan, Marina Ciullo, Massimiliano Cocca, Francis Collins, Heather J Cordell, Gail Davies, Martin H de Borst, Eco J de Geus, Ian J Deary, Joris Deelen, Fabiola Del Greco M, Cumhur Yusuf Demirkale, Marcus Dörr, Georg B Ehret, Roberto Elosua, Stefan Enroth, A Mesut Erzurumluoglu, Teresa Ferreira, Mattias Frånberg, Oscar H Franco, Ilaria Gandin, Paolo Gasparini, Vilmantas Giedraitis, Christian Gieger, Giorgia Girotto, Anuj Goel, Alan J Gow, Vilmundur Gudnason, Xiuqing Guo, Ulf Gyllensten, Anders Hamsten, Tamara B Harris, Sarah E Harris, Catharina A Hartman, Aki S Havulinna, Andrew A Hicks, Edith Hofer, Albert Hofman, Jouke-Jan Hottenga, Jennifer E Huffman, Shih-Jen Hwang, Erik Ingelsson, Alan James, Rick Jansen, Marjo-Riitta Jarvelin, Roby Joehanes, Åsa Johansson, Andrew D Johnson, Peter K Joshi, Pekka Jousilahti, J Wouter Jukema, Antti Jula, Mika Kähönen, Sekar Kathiresan, Bernard D Keavney, Kay-Tee Khaw, Paul Knekt, Joanne Knight, Ivana Kolcic, Jaspal S Kooner, Seppo Koskinen, Kati Kristiansson, Zoltan Kutalik, Maris Laan, Marty Larson, Lenore J Launer, Benjamin Lehne, Terho Lehtimäki, David CM Liewald, Li Lin, Lars Lind, Cecilia M Lindgren, YongMei Liu, Ruth JF Loos, Lorna M Lopez, Yingchang Lu, Leo-Pekka Lyytikäinen, Anubha Mahajan, Chrysovalanto Mamasoula, Jaume Marrugat, Jonathan Marten, Yuri Milaneschi, Anna Morgan, Andrew P Morris, Alanna C Morrison, Peter J Munson, Mike A Nalls, Priyanka Nandakumar, Christopher P Nelson, Teemu Niiranen, Ilja M Nolte, Teresa Nutile, Albertine J Oldehinkel, Ben A Oostra, Paul F O’Reilly, Elin Org, Sandosh Padmanabhan, Walter Palmas, Aarno Palotie, Alison Pattie, Brenda WJH Penninx, Markus Perola, Annette Peters, Ozren Polasek, Peter P Pramstaller, Quang Tri Nguyen, Olli T Raitakari, Rainer Rettig, Kenneth Rice, Paul M Ridker, Janina S Ried, Harriëtte Riese, Samuli Ripatti, Antonietta Robino, Lynda M Rose, Jerome I Rotter, Igor Rudan, Daniela Ruggiero, Yasaman Saba, Cinzia F Sala, Veikko Salomaa, Nilesh J Samani, Antti-Pekka Sarin, Reinhold Schmidt, Helena Schmidt, Nick Shrine, David Siscovick, Albert V Smith, Harold Snieder, Siim Sõber, Rossella Sorice, John M Starr, David J Stott, David P Strachan, Rona J Strawbridge, Johan Sundström, Morris A Swertz, Kent D Taylor, Alexander Teumer, Martin D Tobin, Maciej Tomaszewski, Daniela Toniolo, Michela Traglia, Stella Trompet, Jaakko Tuomilehto, Christophe Tzourio, André G Uitterlinden, Ahmad Vaez, Peter J van der Most, Cornelia M van Duijn, Germaine C Verwoert, Veronique Vitart, Uwe Völker, Peter Vollenweider, Dragana Vuckovic, Hugh Watkins, Sarah H Wild, Gonneke Willemsen, James F Wilson, Alan F Wright, Jie Yao, Tatijana Zemunik, Weihua Zhang, John R Attia, Adam S Butterworth, Daniel I Chasman, David Conen, Francesco Cucca, John Danesh, Caroline Hayward, Joanna MM Howson, Markku Laakso, Edward G Lakatta, Claudia Langenberg, Olle Melander, Dennis O Mook-Kanamori, Colin NA Palmer, Lorenz Risch, Robert A Scott, Rodney J Scott, Peter Sever, Tim D Spector, Pim van der Harst, Nicholas J Wareham, Eleftheria Zeggini, Daniel Levy, Patricia B Munroe, Christopher Newton-Cheh, Morris J Brown, Andres Metspalu, Bruce M. Psaty, Louise V Wain, Paul Elliott, Mark J Caulfield, Padhraig Gormley, Verneri Anttila, Priit Palta, Tune H Pers, Kai-How Farh, Ester Cuenca-Leon, Mikko Muona, Nicholas A Furlotte, Tobias Kurth, Andres Ingason, George McMahon, Lannie Ligthart, Gisela M Terwindt, Mikko Kallela, Tobias M Freilinger, Caroline Ran, Scott G Gordon, Anine H Stam, Stacy Steinberg, Guntram Borck, Markku Koiranen, Lydia Quaye, Hieab H H Adams, Juho Wedenoja, David A Hinds, Julie E Buring, Markus Schürks, Maria Gudlaug Hrafnsdottir, Hreinn Stefansson, Susan M Ring, Brenda W J H Penninx, Markus Färkkilä, Ville Artto, Mari Kaunisto, Salli Vepsäläinen, Rainer Malik, Andrew C Heath, Pamela A F Madden, Nicholas G Martin, Grant W Montgomery, Mitja I Kurki, Mart Kals, Kalle Pärn, Eija Hämäläinen, Hailiang Huang, Andrea E Byrnes, Lude Franke, Jie Huang, Evie Stergiakouli, Phil H Lee, Cynthia Sandor, Caleb Webber, Zameel Cader, Bertram Muller-Myhsok, Stefan Schreiber, Thomas Meitinger, Johan G Eriksson, Kauko Heikkilä, Elizabeth Loehrer, Andre G Uitterlinden, Lynn Cherkas, Audun Stubhaug, Christopher S Nielsen, Minna Männikkö, Evelin Mihailov, Hartmut Göbel, Ann-Louise Esserlind, Anne Francke Christensen, Thomas Folkmann Hansen, Thomas Werge, Jaakko Kaprio, Arpo J Aromaa, Olli Raitakari, M Arfan Ikram, Tim Spector, Marjo-Riitta Järvelin, Christian Kubisch, Michel D Ferrari, Andrea C Belin, Maija Wessman, Arn M J M van den Maagdenberg, George Davey Smith, Kari Stefansson, Nicholas Eriksson, Mark J Daly, Benjamin M Neale, Jes Olesen, Dale R Nyholt, Masato Akiyama, Varinder S. Alg, Joseph P. Broderick, Ben M. Brumpton, Jérôme Dauvillier, Hubert Desal, Christian Dina, Christoph M. Friedrich, Emília I. Gaál-Paavola, Jean-Christophe Gentric, Sven Hirsch, Isabel C. Hostettler, Henry Houlden, Juha E. Jääskeläinen, Marianne Bakke Johnsen, Liming Li, Kuang Lin, Antti Lindgren, Olivier Martin, Koichi Matsuda, Iona Y. Millwood, Olivier Naggara, Mika Niemelä, Joanna Pera, Richard Redon, Guy A. Rouleau, Marie Søfteland Sandvei, Sabine Schilling, Eimad Shotar, Agnieszka Slowik, Chikashi Terao, W. M. Monique Verschuren, Robin G. Walters, David J. Werring, Cristen J. Willer, Daniel Woo, Bradford B. Worrall, Sirui Zhou, Biological Psychology, Amsterdam Reproduction & Development, APH - Mental Health, APH - Methodology, AMS - Sports, AMS - Ageing & Vitality, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Systems Ecology, Sociology and Social Gerontology, Bakker, Mark K., Kanning, Jos P., Abraham, Gad, Martinsen, Amy E., Winsvold, Bendik S., Zwart, John-Anker, Bourcier, Romain, Sawada, Tomonobu, Koido, Masaru, Kamatani, Yoichiro, Morel, Sandrine, Amouyel, Philippe, Debette, Stéphanie, Bijlenga, Philippe, Berrandou, Takiy, Ganesh, Santhi K., Bouatia-Naji, Nabila, Jones, Gregory, Bown, Matthew, Rinkel, Gabriel J. E., Veldink, Jan H., Ruigrok, Ynte M., Girotto, G., All-In Stroke, Hunt, Group, Cadisp, Consortium for Blood Pressure, International, Headache Genetics Consortium, International, Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group, International, Utrecht University [Utrecht], Baker Heart and Diabetes Institute (AUSTRALIA), University of Melbourne, University of Oslo (UiO), Norwegian University of Science and Technology (NTNU), Oslo University Hospital [Oslo], Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), The University of Tokyo (UTokyo), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Hôpital Universitaire de Genève = University Hospitals of Geneva (HUG), Université de Genève = University of Geneva (UNIGE), Excellence Laboratory LabEx DISTALZ, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), University of Michigan Medical School [Ann Arbor], University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, University of Otago [Dunedin, Nouvelle-Zélande], University of Leicester, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), CHU Amiens-Picardie, HUNT All-In Stroke, CADISP group, International Consortium for Blood Pressure, International Headache Genetics Consortium, International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group: Anne Hege Aamodt, Anne Heidi Skogholt, Ben M Brumpton, Cristen J Willer, Else C Sandset, Espen S Kristoffersen, Hanne Ellekjær, Ingrid Heuch, Jonas B Nielsen, Knut Hagen, Kristian Hveem, Lars G Fritsche, Laurent F Thomas, Linda M Pedersen, Maiken E Gabrielsen, Oddgeir L Holmen, Sigrid Børte, Wei Zhou, Shérine Abboud, Massimo Pandolfo, Vincent Thijs, Didier Leys, Marie Bodenant, Fabien Louillet, Emmanuel Touzé, Jean-Louis Mas, Yves Samson, Sara Leder, Anne Léger, Sandrine Deltour, Sophie Crozier, Isabelle Méresse, Sandrine Canaple, Olivier Godefroy, Maurice Giroud, Yannick Béjot, Pierre Decavel, Elizabeth Medeiros, Paola Montiel, Thierry Moulin, Fabrice Vuillier, Jean Dallongeville, Antti J Metso, Tiina Metso, Turgut Tatlisumak, Caspar Grond-Ginsbach, Christoph Lichy, Manja Kloss, Inge Werner, Marie-Luise Arnold, Michael Dos Santos, Armin Grau, Martin Dichgans, Constanze Thomas-Feles, Ralf Weber, Tobias Brandt, Alessandro Pezzini, Valeria De Giuli, Filomena Caria, Loris Poli, Alessandro Padovani, Anna Bersano, Silvia Lanfranconi, Simone Beretta, Carlo Ferrarese, Giacomo Giacolone, Stefano Paolucci, Philippe Lyrer, Stefan Engelter, Felix Fluri, Florian Hatz, Dominique Gisler, Leo Bonati, Henrik Gensicke, Margareth Amort, Hugh Markus, Jennifer Majersik, Bradford Worrall, Andrew Southerland, John Cole, Steven Kittner, Evangelos Evangelou, Helen R Warren, He Gao, Georgios Ntritsos, Niki Dimou, Tonu Esko, Reedik Mägi, Lili Milani, Peter Almgren, Thibaud Boutin, Jun Ding, Franco Giulianini, Elizabeth G Holliday, Anne U Jackson, Ruifang Li-Gao, Wei-Yu Lin, Jian'an Luan, Massimo Mangino, Christopher Oldmeadow, Bram Peter Prins, Yong Qian, Muralidharan Sargurupremraj, Nabi Shah, Praveen Surendran, Sébastien Thériault, Niek Verweij, Sara M Willems, Jing-Hua Zhao, John Connell, Renée de Mutsert, Alex Sf Doney, Martin Farrall, Cristina Menni, Andrew D Morris, Raymond Noordam, Guillaume Paré, Neil R Poulter, Denis C Shields, Alice Stanton, Simon Thom, Gonçalo Abecasis, Najaf Amin, Dan E Arking, Kristin L Ayers, Caterina M Barbieri, Chiara Batini, Joshua C Bis, Tineka Blake, Murielle Bochud, Michael Boehnke, Eric Boerwinkle, Dorret I Boomsma, Erwin P Bottinger, Peter S Braund, Marco Brumat, Archie Campbell, Harry Campbell, Aravinda Chakravarti, John C Chambers, Ganesh Chauhan, Marina Ciullo, Massimiliano Cocca, Francis Collins, Heather J Cordell, Gail Davies, Martin H de Borst, Eco J de Geus, Ian J Deary, Joris Deelen, Fabiola Del Greco M, Cumhur Yusuf Demirkale, Marcus Dörr, Georg B Ehret, Roberto Elosua, Stefan Enroth, A Mesut Erzurumluoglu, Teresa Ferreira, Mattias Frånberg, Oscar H Franco, Ilaria Gandin, Paolo Gasparini, Vilmantas Giedraitis, Christian Gieger, Giorgia Girotto, Anuj Goel, Alan J Gow, Vilmundur Gudnason, Xiuqing Guo, Ulf Gyllensten, Anders Hamsten, Tamara B Harris, Sarah E Harris, Catharina A Hartman, Aki S Havulinna, Andrew A Hicks, Edith Hofer, Albert Hofman, Jouke-Jan Hottenga, Jennifer E Huffman, Shih-Jen Hwang, Erik Ingelsson, Alan James, Rick Jansen, Marjo-Riitta Jarvelin, Roby Joehanes, Åsa Johansson, Andrew D Johnson, Peter K Joshi, Pekka Jousilahti, J Wouter Jukema, Antti Jula, Mika Kähönen, Sekar Kathiresan, Bernard D Keavney, Kay-Tee Khaw, Paul Knekt, Joanne Knight, Ivana Kolcic, Jaspal S Kooner, Seppo Koskinen, Kati Kristiansson, Zoltan Kutalik, Maris Laan, Marty Larson, Lenore J Launer, Benjamin Lehne, Terho Lehtimäki, David Cm Liewald, Li Lin, Lars Lind, Cecilia M Lindgren, YongMei Liu, Ruth Jf Loos, Lorna M Lopez, Yingchang Lu, Leo-Pekka Lyytikäinen, Anubha Mahajan, Chrysovalanto Mamasoula, Jaume Marrugat, Jonathan Marten, Yuri Milaneschi, Anna Morgan, Andrew P Morris, Alanna C Morrison, Peter J Munson, Mike A Nalls, Priyanka Nandakumar, Christopher P Nelson, Teemu Niiranen, Ilja M Nolte, Teresa Nutile, Albertine J Oldehinkel, Ben A Oostra, Paul F O'Reilly, Elin Org, Sandosh Padmanabhan, Walter Palmas, Aarno Palotie, Alison Pattie, Brenda Wjh Penninx, Markus Perola, Annette Peters, Ozren Polasek, Peter P Pramstaller, Quang Tri Nguyen, Olli T Raitakari, Rainer Rettig, Kenneth Rice, Paul M Ridker, Janina S Ried, Harriëtte Riese, Samuli Ripatti, Antonietta Robino, Lynda M Rose, Jerome I Rotter, Igor Rudan, Daniela Ruggiero, Yasaman Saba, Cinzia F Sala, Veikko Salomaa, Nilesh J Samani, Antti-Pekka Sarin, Reinhold Schmidt, Helena Schmidt, Nick Shrine, David Siscovick, Albert V Smith, Harold Snieder, Siim Sõber, Rossella Sorice, John M Starr, David J Stott, David P Strachan, Rona J Strawbridge, Johan Sundström, Morris A Swertz, Kent D Taylor, Alexander Teumer, Martin D Tobin, Maciej Tomaszewski, Daniela Toniolo, Michela Traglia, Stella Trompet, Jaakko Tuomilehto, Christophe Tzourio, André G Uitterlinden, Ahmad Vaez, Peter J van der Most, Cornelia M van Duijn, Germaine C Verwoert, Veronique Vitart, Uwe Völker, Peter Vollenweider, Dragana Vuckovic, Hugh Watkins, Sarah H Wild, Gonneke Willemsen, James F Wilson, Alan F Wright, Jie Yao, Tatijana Zemunik, Weihua Zhang, John R Attia, Adam S Butterworth, Daniel I Chasman, David Conen, Francesco Cucca, John Danesh, Caroline Hayward, Joanna Mm Howson, Markku Laakso, Edward G Lakatta, Claudia Langenberg, Olle Melander, Dennis O Mook-Kanamori, Colin Na Palmer, Lorenz Risch, Robert A Scott, Rodney J Scott, Peter Sever, Tim D Spector, Pim van der Harst, Nicholas J Wareham, Eleftheria Zeggini, Daniel Levy, Patricia B Munroe, Christopher Newton-Cheh, Morris J Brown, Andres Metspalu, Bruce M Psaty, Louise V Wain, Paul Elliott, Mark J Caulfield, Padhraig Gormley, Verneri Anttila, Priit Palta, Tonu Esko, Tune H Pers, Kai-How Farh, Ester Cuenca-Leon, Mikko Muona, Nicholas A Furlotte, Tobias Kurth, Andres Ingason, George McMahon, Lannie Ligthart, Gisela M Terwindt, Mikko Kallela, Tobias M Freilinger, Caroline Ran, Scott G Gordon, Anine H Stam, Stacy Steinberg, Guntram Borck, Markku Koiranen, Lydia Quaye, Hieab H H Adams, Terho Lehtimäki, Antti-Pekka Sarin, Juho Wedenoja, David A Hinds, Julie E Buring, Markus Schürks, Paul M Ridker, Maria Gudlaug Hrafnsdottir, Hreinn Stefansson, Susan M Ring, Jouke-Jan Hottenga, Brenda W J H Penninx, Markus Färkkilä, Ville Artto, Mari Kaunisto, Salli Vepsäläinen, Rainer Malik, Andrew C Heath, Pamela A F Madden, Nicholas G Martin, Grant W Montgomery, Mitja I Kurki, Mart Kals, Reedik Mägi, Kalle Pärn, Eija Hämäläinen, Hailiang Huang, Andrea E Byrnes, Lude Franke, Jie Huang, Evie Stergiakouli, Phil H Lee, Cynthia Sandor, Caleb Webber, Zameel Cader, Bertram Muller-Myhsok, Stefan Schreiber, Thomas Meitinger, Johan G Eriksson, Veikko Salomaa, Kauko Heikkilä, Elizabeth Loehrer, Andre G Uitterlinden, Albert Hofman, Cornelia M van Duijn, Lynn Cherkas, Linda M Pedersen, Audun Stubhaug, Christopher S Nielsen, Minna Männikkö, Evelin Mihailov, Lili Milani, Hartmut Göbel, Ann-Louise Esserlind, Anne Francke Christensen, Thomas Folkmann Hansen, Thomas Werge, Jaakko Kaprio, Arpo J Aromaa, Olli Raitakari, M Arfan Ikram, Tim Spector, Marjo-Riitta Järvelin, Andres Metspalu, Christian Kubisch, David P Strachan, Michel D Ferrari, Andrea C Belin, Martin Dichgans, Maija Wessman, Arn M J M van den Maagdenberg, Dorret I Boomsma, George Davey Smith, Kari Stefansson, Nicholas Eriksson, Mark J Daly, Benjamin M Neale, Jes Olesen, Daniel I Chasman, Dale R Nyholt, Aarno Palotie, Masato Akiyama, Varinder S Alg, Sigrid Børte, Joseph P Broderick, Ben M Brumpton, Jérôme Dauvillier, Hubert Desal, Christian Dina, Christoph M Friedrich, Emília I Gaál-Paavola, Jean-Christophe Gentric, Sven Hirsch, Isabel C Hostettler, Henry Houlden, Kristian Hveem, Juha E Jääskeläinen, Marianne Bakke Johnsen, Liming Li, Kuang Lin, Antti Lindgren, Olivier Martin, Koichi Matsuda, Iona Y Millwood, Olivier Naggara, Mika Niemelä, Joanna Pera, Richard Redon, Guy A Rouleau, Marie Søfteland Sandvei, Sabine Schilling, Eimad Shotar, Agnieszka Slowik, Chikashi Terao, W M Monique Verschuren, Robin G Walters, David J Werring, Cristen J Willer, Daniel Woo, Bradford B Worrall, Sirui Zhou, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, and Admin, Oskar

Subjects
Advanced and Specialized Nursing, Incidence, risk assessment, Smoking/epidemiology, intracranial aneurysm, genetic heterogeneity, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Risk Factors, Intracranial Aneurysm/epidemiology, Humans, Subarachnoid Hemorrhage/epidemiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, genetics, Neurology (clinical), aneurysmal subarachnoid hemorrhage, genetic, Cardiology and Cardiovascular Medicine
Abstract

Background: Recently, common genetic risk factors for intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (ASAH) were found to explain a large amount of disease heritability and therefore have potential to be used for genetic risk prediction. We constructed a genetic risk score to (1) predict ASAH incidence and IA presence (combined set of unruptured IA and ASAH) and (2) assess its association with patient characteristics. Methods: A genetic risk score incorporating genetic association data for IA and 17 traits related to IA (so-called metaGRS) was created using 1161 IA cases and 407 392 controls from the UK Biobank population study. The metaGRS was validated in combination with risk factors blood pressure, sex, and smoking in 828 IA cases and 68 568 controls from the Nordic HUNT population study. Furthermore, we assessed association between the metaGRS and patient characteristics in a cohort of 5560 IA patients. Results: Per SD increase of metaGRS, the hazard ratio for ASAH incidence was 1.34 (95% CI, 1.20–1.51) and the odds ratio for IA presence 1.09 (95% CI, 1.01–1.18). Upon including the metaGRS on top of clinical risk factors, the concordance index to predict ASAH hazard increased from 0.63 (95% CI, 0.59–0.67) to 0.65 (95% CI, 0.62–0.69), while prediction of IA presence did not improve. The metaGRS was statistically significantly associated with age at ASAH (β=−4.82×10 −3 per year [95% CI, −6.49×10 −3 to −3.14×10 −3 ]; P =1.82×10 −8 ), and location of IA at the internal carotid artery (odds ratio=0.92 [95% CI, 0.86–0.98]; P =0.0041). Conclusions: The metaGRS was predictive of ASAH incidence, although with limited added value over clinical risk factors. The metaGRS was not predictive of IA presence. Therefore, we do not recommend using this metaGRS in daily clinical care. Genetic risk does partly explain the clinical heterogeneity of IA warranting prioritization of clinical heterogeneity in future genetic prediction studies of IA and ASAH.

Published
2023

2. Stroke

Author

Christina Jern, Martin Stenman, Tobias Brandt, Sandra Freitag-Wolf, Braxton D. Mitchell, Manja Kloss, Didier Leys, Jonathan Rosand, Stefan T. Engelter, Michael Krawczak, Steven J. Kittner, Vincent Thijs, Giacomo Giacalone, Daniel Woo, J.J. Martin, Jordi Jimenez-Conde, Philip Ginsbach, Emmanuel Touzé, Armin J. Grau, Elisabetta Del Zotto, Tiina M. Metso, Philipp Erhart, Eyad Hayani, Dorothea Pfeiffer, Christoph Lichy, I. Werner, Valeria Caso, Bowang Chen, Antti J. Metso, Caspar Grond-Ginsbach, Arne Lindgren, Shérine Abboud, Anna Bersano, Natalia S. Rost, Kristina Schlicht, Jane Maguire, John W. Cole, Robin Lemmens, Alessandro Pezzini, Jin-Moo Lee, Philippe Lyrer, Steve Bevan, Christopher Traenka, Stéphanie Debette, Turgut Tatlisumak, Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
DNA copy number variations, Neurology, Gene Dosage, Logistic regression, Severity of Illness Index, Brain Ischemia, 0302 clinical medicine, Modified Rankin Scale, Gene Duplication, Chromosomes, Human, genetics, Stroke, RISK, 0303 health sciences, Middle Aged, stroke, VINTAGE, Medical genetics, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, Adult, medicine.medical_specialty, Genotype, Clinical Neurology, Subgroup analysis, COPY-NUMBER VARIATION, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Genetic imbalance, Internal medicine, OHNOLOGS, medicine, Humans, Aged, 030304 developmental biology, Advanced and Specialized Nursing, Science & Technology, Neurology & Neurosurgery, business.industry, GENOME-WIDE, Recovery of Function, Odds ratio, medicine.disease, Peripheral Vascular Disease, Cardiovascular System & Cardiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurosciences & Neurology, prognosis, Neurology (clinical), business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract

Background and Purpose— We sought to explore the effect of genetic imbalance on functional outcome after ischemic stroke (IS). Methods— Copy number variation was identified in high-density single-nucleotide polymorphism microarray data of IS patients from the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) and SiGN (Stroke Genetics Network)/GISCOME (Genetics of Ischaemic Stroke Functional Outcome) networks. Genetic imbalance, defined as total number of protein-coding genes affected by copy number variations in an individual, was compared between patients with favorable (modified Rankin Scale score of 0–2) and unfavorable (modified Rankin Scale score of ≥3) outcome after 3 months. Subgroup analyses were confined to patients with imbalance affecting ohnologs—a class of dose-sensitive genes, or to those with imbalance not affecting ohnologs. The association of imbalance with outcome was analyzed by logistic regression analysis, adjusted for age, sex, stroke subtype, stroke severity, and ancestry. Results— The study sample comprised 816 CADISP patients (age 44.2±10.3 years) and 2498 SiGN/GISCOME patients (age 67.7±14.2 years). Outcome was unfavorable in 122 CADISP and 889 SiGN/GISCOME patients. Multivariate logistic regression analysis revealed that increased genetic imbalance was associated with less favorable outcome in both samples (CADISP: P =0.0007; odds ratio=0.89; 95% CI, 0.82–0.95 and SiGN/GISCOME: P =0.0036; odds ratio=0.94; 95% CI, 0.91–0.98). The association was independent of age, sex, stroke severity on admission, stroke subtype, and ancestry. On subgroup analysis, imbalance affecting ohnologs was associated with outcome (CADISP: odds ratio=0.88; 95% CI, 0.80–0.95 and SiGN/GISCOME: odds ratio=0.93; 95% CI, 0.89–0.98) whereas imbalance without ohnologs lacked such an association. Conclusions— Increased genetic imbalance was associated with poorer functional outcome after IS in both study populations. Subgroup analysis revealed that this association was driven by presence of ohnologs in the respective copy number variations, suggesting a causal role of the deleterious effects of genetic imbalance.

Published
2019

3. Cervical artery dissection goes frequently undiagnosed

Author

Christoph Lichy, Maani Hakimi, Alessandro Pezzini, Turgut Tatlisumak, Armin J. Grau, Tiina M. Metso, Caspar Grond-Ginsbach, Manja Kloss, and Antti J. Metso

Subjects
Pediatrics, medicine.medical_specialty, Cervical Artery, Models, Biological, Asymptomatic, Stroke risk, Risk Factors, medicine, Humans, cervical artery dissection, Age of Onset, Stroke, business.industry, Incidence (epidemiology), Disease progression, Arteries, General Medicine, medicine.disease, Magnetic Resonance Imaging, Surgery, Aortic Dissection, Dissection, Disease Progression, medicine.symptom, Age of onset, business, Neck
Abstract

Cervical artery dissection (CeAD) is a frequent cause of stroke among young patients. It is unclear how many CeADs occur asymptomatically or cause subtle and unspecific clinical symptoms. We hypothesize that CeAD remains often unrecognized. Accordingly, the incidence of CeAD might be higher and the stroke risk lower than generally assumed. Lack of CeAD-indicating clinical symptoms is regarded as the main cause of missed diagnoses. We further hypothesize that underrepresentation of asymptomatic and oligosymptomatic patients in CeAD studies may have biased the association between ischemia and local symptoms in CeAD patients as well as the associations of CeAD with risk factors or co-morbidities. We finally hypothesize that symptomatic CeAD may be preceded by an initial asymptomatic phase. According to this final hypothesis, the time of onset of CeAD should be considered uncertain. The issue of unrecognized CeAD is relevant, as it may affect the associations between CeAD and putative risk factors. Furthermore, the existence of clinically silent CeADs may explain why recurrent and familial CeAD have been rarely observed.

Published
2013

4. Recurrent ischemic events in young adults after first-ever ischemic stroke

Author

Ville Artto, Tiina M. Metso, Jukka Putaala, Antti J. Metso, Elena Haapaniemi, Turgut Tatlisumak, and Markku Kaste

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Revascularization, Brain Ischemia, Recurrence, Risk Factors, Internal medicine, medicine, Humans, Myocardial infarction, Young adult, Stroke, Finland, Vascular disease, business.industry, Cerebral infarction, Hazard ratio, Age Factors, Middle Aged, Prognosis, medicine.disease, Confidence interval, Surgery, Neurology, Cardiovascular Diseases, Cardiology, Female, Neurology (clinical), business, Follow-Up Studies
Abstract

Objective:: Data on recurrence of vascular events and their prognostic factors in young (

Published
2010

5. Migraine with Aura Is a Risk Factor for Cervical Artery Dissection: A Case-Control Study

Author

Maija Wessman, Ville Artto, Elena Haapaniemi, T. M. Metso, Jukka Putaala, Mikko Kallela, Turgut Tatlisumak, Antti J. Metso, and Markus Färkkilä

Subjects
Adult, Male, medicine.medical_specialty, Time Factors, Aura, Migraine with Aura, 030204 cardiovascular system & hematology, Risk Assessment, Brain Ischemia, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Odds Ratio, Prevalence, medicine, Humans, cardiovascular diseases, Risk factor, Stroke, Finland, Aged, Chi-Square Distribution, business.industry, Case-control study, Odds ratio, Middle Aged, medicine.disease, Migraine with aura, 3. Good health, Surgery, Aortic Dissection, Logistic Models, Phenotype, Neurology, Migraine, Case-Control Studies, Cervical Vertebrae, Etiology, Female, Neurology (clinical), medicine.symptom, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery
Abstract

Background: Cervical artery dissection (CAD) is the most common single etiology for stroke in young adults. Migraine, especially with aura (MA), is a known risk factor for ischemic stroke. The association between CAD and migraine was suggested based on a few small studies, but there are no large-scale case-control data, and the mechanisms are not yet clear. Methods: We compared the lifetime prevalence of migraine and migraine characteristics in 313 CAD patients with 313 healthy age- and sex-matched controls. We also analyzed clinical and radiological characteristics of CAD with respect to migraine subtypes to investigate whether clear phenotypical associations can be found that might help in the search for a possible shared genetic background for migraine and CAD. Results: Migraine was clearly more common in CAD patients than in controls (36 vs. 23%; OR 2.15; 95% CI 1.48–3.14), and the association was also highly significant for MA (23 vs. 12%; OR 2.41; 95% CI 1.53–3.80). Percentages of reported migraine history and MA of CAD patients vs. controls compared separately for both sexes were as follows: for women, migraine 54 vs. 35% (OR 2.30; 95% CI 1.28–4.13), MA 35 vs. 18% (OR 2.79; 95% CI 1.40–5.59); for men, migraine 27 vs. 16% (OR 2.02; 95% CI 1.23–3.31), MA 16 vs. 10% (OR 2.21; 95% CI 1.19–4.11). Over 60% of the CAD patients with still active migraine at the time of dissection reported later alleviation of migraine activity. Conclusion: Our observations suggest that patients with CAD are a significant link between ischemic stroke and migraine. This connection may represent a common pathophysiological or genetic background, or both. Migraine activity appears to be alleviated by CAD.

Published
2010

6. Prognosis and Safety of Anticoagulation in Intracranial Artery Dissections in Adults

Author

Matti Porras, Johanna Helenius, Elena Haapaniemi, Juha Hernesniemi, Antti J. Metso, Tiina M. Metso, Oili Salonen, Turgut Tatlisumak, and Markku Kaste

Subjects
Adult, Male, medicine.medical_specialty, Subarachnoid hemorrhage, Adolescent, medicine.drug_class, Aneurysm, Modified Rankin Scale, medicine, Humans, cardiovascular diseases, Stroke, Aged, Retrospective Studies, Advanced and Specialized Nursing, business.industry, Vascular disease, Anticoagulant, Warfarin, Anticoagulants, Intracranial Aneurysm, Intracranial Artery, Middle Aged, Prognosis, medicine.disease, nervous system diseases, Surgery, Aortic Dissection, Female, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, medicine.drug
Abstract

Background and Purpose— To characterize different forms of intracranial artery dissections (IADs), and to test the assumption that IADs are frequently associated with subarachnoid hemorrhage (SAH) and poor outcome, and that anticoagulant therapy is contraindicated in these patients. Methods— We studied 81 consecutive non-SAH IAD patients and 22 IAD patients with SAH, diagnosed between 1994 and 2004 and 1998 and 2004, respectively, and treated the former patients immediately with heparin, followed with at least 3 months of warfarin. Outcomes were recorded at 3 months. Results— Approximately one-third of all cervicocephalic artery dissections were identifiably either completely located intracranially or extended into the intracranial space. At 3 months, 64 of the 81 non-SAH patients (79%) had a favorable outcome (modified Rankin Scale, 0 to 2); 1 patient died of brain infarction in the acute stage. Only 1 aneurysm developed during follow-up in the non-SAH group, and no intracranial bleeding was observed during anticoagulant treatment. Those presenting with SAH formed ≈25% of all IADs, and 21 cases out of 22 (95%) were associated with ruptured fusiform dissecting aneurysm. This latter group displayed significantly worse outcomes: 7 died, and only 7 had modified Rankin Scale 0 to 2 at 3 months. Conclusions— Our results provide important information for clinical practice. IADs appear to polarize into 2 groups: (1) nonaneurysmatic IADs presenting without SAH that are associated with favorable outcomes and safe anticoagulant therapy; and (2) aneurysmatic IADs, characterized by SAH and poorer prognosis. Literature on IADs may have been biased toward group 2.

Published
2007

7. Predictors of delayed stroke in patients with cervical artery dissection

Author

Turgut Tatlisumak, C. Lamy, Emmanuel Touzé, Valeria Caso, Stefan T. Engelter, Tobias Brandt, Vincent Thijs, Maria Sessa, Anna Bersano, Yves Samson, Alessandro Pezzini, Elisabeth De Bustos Medeiros, Christoph Lichy, Philippe Lyrer, Sherine Abboud, Antti J. Metso, Stéphanie Debette, Armin J. Grau, Tiina M. Metso, Simone Beretta, Manja Kloss, Didier Leys, Caspar Grond-Ginsbach, INSERM U897, University of Bordeaux, France, Department of Medical Neurobiology [Jérusalem], The Hebrew University of Jerusalem (HUJ), Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière (NEMESIS-CRICM), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Laboratory of Experimental Stroke Research, Department of Surgery and Translational Medicine, University of Milano Bicocca, Neuromi, Milan Center for Neuroscience, Centre d'Etudes Supérieures de Civilisation médiévale (CESCM), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Écophysiologie des Plantes sous Stress environnementaux (LEPSE), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Dipartimento di Medicina e Chirurgia = School of Medicine and Surgery [Monza], Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB)-Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), CHU Amiens-Picardie, Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Università degli Studi di Milano-Bicocca [Milano] (UNIMIB)-Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro), and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)

Subjects
Adult, Male, medicine.medical_specialty, Databases, Factual, Cervical Artery, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Vertebral artery dissection, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Ischemia, Horner syndrome, Dissection (medical), Carotid artery dissection, Predictive Value of Tests, Risk Factors, Internal medicine, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, cardiovascular diseases, Stroke, Vertebral Artery Dissection, 2. Zero hunger, business.industry, [INFO.INFO-CV]Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], Middle Aged, medicine.disease, 3. Good health, Surgery, Neurology, Migraine, Ischemic Attack, Transient, [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], Cardiology, Female, business, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing
Abstract

Background Stroke in patients with acute cervical artery dissection may be anticipated by initial transient ischemic or nonischemic symptoms. Aim Identifying risk factors for delayed stroke upon cervical artery dissection. Methods Cervical artery dissection patients from the multicenter Cervical Artery Dissection and Ischemic Stroke Patients study were classified as patients without stroke ( n = 339), with stroke preceded by nonstroke symptoms (delayed stroke, n = 244), and with stroke at onset ( n = 382). Demographics, clinical, and vascular findings were compared between the three groups. Results Patients with delayed stroke were more likely to present with occlusive cervical artery dissection ( P < 0·001), multiple cervical artery dissection ( P = 0·031), and vertebral artery dissection ( P < 0·001) than patients without stroke. No differences were observed in age, smoking, arterial hypertension, hypercholesterolemia, migraine, body mass index, infections during the last week, and trauma during the last month, but patients with delayed stroke had less often transient ischemic attack ( P < 0·001) and local signs (Horner syndrome and cranial nerve palsy; P < 0·001). Conclusions Occlusive cervical artery dissection, multiple cervical artery dissection, and vertebral artery dissection were associated with an increased risk for delayed stroke. No other risk factors for delayed stroke were identified. Immediate cervical imaging of cervical artery dissection patients without ischemic stroke is needed to identify patients at increased risk for delayed ischemia.

Published
2015

8. Characterization of the main transition of dinervonoylphosphocholine liposomes by fluorescence spectroscopy

Author

Antti J. Metso, Paavo K.J. Kinnunen, and Juha-Pekka Mattila

Subjects
Phase transition, Phosphorylcholine, Biophysics, Analytical chemistry, Fluorescence Polarization, Biochemistry, Phase Transition, Fluorescence spectroscopy, 03 medical and health sciences, Differential scanning calorimetry, Phase (matter), Transition Temperature, Fluorescent Dyes, 030304 developmental biology, 0303 health sciences, Pyrenes, Calorimetry, Differential Scanning, Chemistry, Pyrene, Vesicle, 030302 biochemistry & molecular biology, Cell Biology, Fluorescence, Liposome, Kinetics, Spectrometry, Fluorescence, Liposomes, Phosphatidylcholines, Thermodynamics, Steady state (chemistry), Fluorescence anisotropy
Abstract

The structural dynamics of the main phase transition of large unilamellar dinervonoylphosphocholine (DNPC) vesicles was investigated by steady state and time-resolved fluorescence spectroscopy of the membrane incorporated fluorescent lipid analog, 1-palmitoyl-2[10-(pyren-1-yl)]decanoyl-sn-glycero-3-phosphocholine (PPDPC). These data were supplemented by differential scanning calorimetry (DSC) and fluorescence anisotropy measured for 1-palmitoyl-2-(3-(diphenylhexatrienyl) propanoyl)-sn-glycero-3-phosphocholine (DPHPC). The collected data displayed several discontinuities in the course of the main transition and the pretransition. The discontinuities seen in the fluorescence properties may require modification of the existing models for phospholipid main transition as a first order process. From our previous study on dipalmitoylphosphocholine (DPPC), we concluded the transition to involve a first-order process resulting in the formation of an intermediate phase, which then converts into the liquid crystalline state by a second order process. Changes in the physical properties of the DNPC matrix influencing probe behavior were similar to those reported previously for PPDPC in DPPC. In gel state DNPC [(T-T(m))-10] the high values for excimer/monomer emission ratio (I(e)/I(m)) suggest enrichment of the probe in clusters. In this temperature range, excimer fluorescence for PPDPC (mole fraction X(PPDPC)=0.02) is described by two formation times up to (T-T(m)) approximately -10, with a gradual disappearance of the fractional intensity (I(R1)) of the shorter formation time (tau(R1)) with increasing temperature up to (T-T(m)) approximately -10. This would be consistent with the initiation of the bilayer melting at the PPDPC clusters and the subsequent dispersion of the one population of PPDPC domains. A pronounced decrement in I(e) starts at (T-T(m))=-10, continuing until T(m) is reached. No decrease was observed in fluorescence quantum yield in contrast to our previous study on DPPC/PPDPC large unilamellar vesicles (LUVs) [J. Phys. Chem., B 107 (2003) 1251], suggesting that a lack of proper hydrophobic mismatch may prevent the formation of the previously reported PPDPC superlattice. With further increase in temperature and starting at (T-T(m)) approximately -1, I(e), tau(R2), and excimer decay times (tau(D)) reach plateaus while increment in trans--gauche isomerization continues. This behavior is in keeping with an intermediate phase existing in the temperature range -1(T-T(m))4 and transforming into the liquid disordered phase as a second order process, the latter being completed when (T-T(m))--4 and corresponding to approximately 50% of the total transition enthalpy.

Published
2004

9. Evidence for the Lack of a Specific Interaction between Cholesterol and Sphingomyelin

Author

Juha M. Holopainen, Arimatti Jutila, Paavo K.J. Kinnunen, Antti J. Metso, and Juha-Pekka Mattila

Subjects
Macromolecular Substances, Lipid Bilayers, 030303 biophysics, Phospholipid, Biophysics, 7. Clean energy, Phase Transition, 03 medical and health sciences, chemistry.chemical_compound, Hydrophobic mismatch, Lipid bilayer, 030304 developmental biology, 0303 health sciences, Liposome, Membranes, Chromatography, Chemistry, Cholesterol, Vesicle, Temperature, Colocalization, Sphingomyelins, Liposomes, Phosphatidylcholines, Dimyristoylphosphatidylcholine, Sphingomyelin
Abstract

The putative specific interaction and complex formation by sphingomyelin and cholesterol was investigated. Accordingly, low contents (1 mol % each) of fluorescently labeled derivatives of these lipids, namely 1-palmitoyl-2[10-(pyren-1-yl)]decanoyl-sn-glycero-3-phosphocholine (PyrPC), n-[10-(1-pyrenyl)decanoyl]sphingomyelin (PyrSM), and increasing concentrations of cholesterol (up to 5 mol %), were included in large unilamellar vesicles composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) or 1,2-dinervonoyl-sn-glycero-3-phosphocholine (DNPC), and the excimer/monomer fluorescence emission ratio (I(e)/I(m)) was measured. In DNPC below the main phase transition, the addition of up to 5 mol % cholesterol reduced I(e)/I(m) significantly. Except for this, cholesterol had only a negligible effect in both matrices and for both probes. We then compared the efficiency of resonance energy transfer from PyrPC and PyrSM to 22-(n-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3beta-ol (NBDchol). An augmenting colocalization of the latter resonance energy transfer pair with temperature was observed in a DMPC matrix below the main phase transition. In contrast, compared to PyrSM the colocalization of PyrPC with NBDchol was more efficient in the longer DNPC matrix. These results could be confirmed using 5,6-dibromo-cholestan-3beta-ol as a collisional quencher for the pyrene-labeled lipids. The results indicate lack of a specific interaction between sphingomyelin and cholesterol, and further imply that hydrophobic mismatch between the lipid constituents could provide the driving force for the cosegregation of sphingomyelin and cholesterol in fluid phospholipid bilayers of thicknesses comparable to those found for biomembranes.

Published
2004
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10. Nature of the Main Transition of Dipalmitoylphosphocholine Bilayers Inferred from Fluorescence Spectroscopy

Author

Antti J. Metso, Juha-Pekka Mattila, Juha M. Holopainen, Arimatti Jutila, and Paavo K.J. Kinnunen

Subjects
0303 health sciences, Phase transition, Chemistry, Vesicle, Analytical chemistry, 010402 general chemistry, Mole fraction, Excimer, 01 natural sciences, Fluorescence, Fluorescence spectroscopy, 0104 chemical sciences, Surfaces, Coatings and Films, 03 medical and health sciences, Differential scanning calorimetry, Materials Chemistry, Physical and Theoretical Chemistry, Dispersion (chemistry), 030304 developmental biology
Abstract

The structural dynamics of the main phase transition of large unilamellar dipalmitoylphosphocholine (DPPC) vesicles were studied using differential scanning calorimetry (DSC) as well as steady-state and time-resolved fluorescence spectroscopy. Two membrane-incorporated fluorescent lipid analogues, 1-palmitoyl-2-[10-(pyren-1-yl)]decanoyl-sn-glycero-3-phosphocholine (PPDPC) and 1-palmitoyl-2-(3-(diphenylhexatrienyl) propanoyl)-sn-glycero-3-phosphocholine (DPHPC), were employed. In gel-state DPPC, the excimer formation times (τR) for PPDPC (mole fraction XPPDPC < 0.02) decrease with increasing temperature up to (T − Tm) ≈ −10 and together with high values for the excimer/monomer emission ratio (Ie/Im) suggest an enrichment of this probe in the clusters. A pronounced prolongation of τR observed with further increases in temperature and starting at (T − Tm) ≈ −10 is accompanied by only a modest decrement in Ie. This behavior is interpreted as with the dispersion of the clusters and the enrichment of PPDPC into...

Published
2003

11. Familial occurrence and heritable connective tissue disorders in cervical artery dissection

Author

Ayse Altintas, Didier Leys, Paolo Costa, Ralf W. Baumgartner, Christian Stapf, Stefano Paolucci, Valeria Caso, Anna Bersano, Yves Samson, Yannick Béjot, Barbara Goeggel Simonetti, Sabrina Schilling, Emmanuel Touzé, Caspar Grond-Ginsbach, Philippe Lyrer, Urs Fischer, C. Lamy, Tobias Brandt, Antti J. Metso, Stefan T. Engelter, Juan Jose Martin, Jean Dallongeville, Hugues Chabriat, Michael Frank, Manja Kloss, Elisabeth Tournier-Lasserve, Vincent Thijs, Maria Sessa, Ingrid Hausser, Christoph Lichy, Marcel Arnold, Dominique P. Germain, Stéphanie Debette, Alessandro Pezzini, Simon Jung, Turgut Tatlisumak, Marie-Germaine Bousser, Armin J. Grau, Tiina M. Metso, Dominique Hervé, Hakan Sarikaya, INSERM U897, University of Bordeaux, France, Department for Internal Medicine, Staedtische Kliniken Moenchengladbach, DAM Île-de-France (DAM/DIF), Direction des Applications Militaires (DAM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Universität Heidelberg [Heidelberg], Fondazione Santa Lucia [IRCCS], Clinical and Behavioral Neurology [IRCCS Santa Lucia], Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière (NEMESIS-CRICM), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire de physique des interfaces et des couches minces [Palaiseau] (LPICM), Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X), Institute for Infectiology (IMED), Friedrich-Loeffler-Institut (FLI), Centre d'Etudes Supérieures de Civilisation médiévale (CESCM), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Écophysiologie des Plantes sous Stress environnementaux (LEPSE), Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Deparment of Neurology (LARIBOISIERE - Neurologie), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), AP-HP Hôpital Raymond Poincaré [Garches], GEOMAR - Helmholtz Centre for Ocean Research [Kiel] (GEOMAR), Université Paris Diderot - Paris 7 (UPD7), U 744, Laboratoire d’Epidémiologie et de Santé Publique, Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (Inserm)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre européen de recherche et d'enseignement des géosciences de l'environnement (CEREGE), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Collège de France (CdF)-Institut national des sciences de l'Univers (INSU - CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), Universität Heidelberg [Heidelberg] = Heidelberg University, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Hôpital Raymond Poincaré [AP-HP], Helmholtz Centre for Ocean Research [Kiel] (GEOMAR), Université Lille Nord de France (COMUE)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (Inserm), Institut de Recherche pour le Développement (IRD)-Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers, Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro), Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Collège de France (CdF (institution))-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), DAM Île-de-France ( DAM/DIF ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière ( NEMESIS-CRICM ), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière ( CRICM ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Laboratoire de physique des interfaces et des couches minces [Palaiseau] ( LPICM ), École polytechnique ( X ) -Centre National de la Recherche Scientifique ( CNRS ), Institute for Infectiology ( IMED ), Friedrich-Loeffler-Institut ( FLI ), Centre d'Etudes Supérieures de Civilisation médiévale ( CESCM ), Université de Poitiers-Centre National de la Recherche Scientifique ( CNRS ), Écophysiologie des Plantes sous Stress environnementaux ( LEPSE ), Institut National de la Recherche Agronomique ( INRA ) -Centre international d'études supérieures en sciences agronomiques ( Montpellier SupAgro ) -Institut national d’études supérieures agronomiques de Montpellier ( Montpellier SupAgro ), Deparment of Neurology ( LARIBOISIERE - Neurologie ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ), GEOMAR - Helmholtz Centre for Ocean Research [Kiel] ( GEOMAR ), Université Paris Diderot - Paris 7 ( UPD7 ), Université Lille Nord de France-Institut National de la Santé et de la Recherche Médicale ( Inserm ) -Institut Pasteur de Lille, Centre européen de recherche et d'enseignement de géosciences de l'environnement ( CEREGE ), and Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ) -Collège de France ( CdF ) -Institut National de la Recherche Agronomique ( INRA ) -Institut national des sciences de l'Univers ( INSU - CNRS )

Subjects
Marfan syndrome, Male, Pathology, Internationality, Cervical Artery, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Vertebral artery dissection, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [ SPI.SIGNAL ] Engineering Sciences [physics]/Signal and Image processing, 030204 cardiovascular system & hematology, [ INFO.INFO-CV ] Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], Cohort Studies, 0302 clinical medicine, [ INFO.INFO-TI ] Computer Science [cs]/Image Processing, MESH : Female, 030212 general & internal medicine, Family history, Connective Tissue Diseases, MESH: Cohort Studies, [ SDV.IB.IMA ] Life Sciences [q-bio]/Bioengineering/Imaging, Vertebral Artery Dissection, MESH: Middle Aged, [ INFO.INFO-IM ] Computer Science [cs]/Medical Imaging, MESH : Adult, Middle Aged, 3. Good health, Dissection, medicine.anatomical_structure, Osteogenesis imperfecta, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], MESH : Connective Tissue Diseases, Female, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Cohort study, Adult, medicine.medical_specialty, MESH : Male, MESH : Cohort Studies, Connective tissue, MESH: Vertebral Artery Dissection, Dissection (medical), Article, 03 medical and health sciences, MESH : Internationality, Internal medicine, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, MESH : Middle Aged, MESH: Connective Tissue Diseases, MESH: Humans, MESH : Vertebral Artery Dissection, business.industry, MESH : Humans, Correction, [INFO.INFO-CV]Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], MESH: Adult, medicine.disease, MESH: Male, Surgery, Ehlers–Danlos syndrome, MESH: Internationality, Neurology (clinical), business, MESH: Female, 030217 neurology & neurosurgery
Abstract

Erratum in: Familial occurrence and heritable connective tissue disorders in cervical artery dissection. [Neurology. 2016]; International audience; In a large series of patients with cervical artery dissection (CeAD), a major cause of ischemic stroke in young and middle-aged adults, we aimed to examine frequencies and correlates of family history of CeAD and of inherited connective tissue disorders. We combined data from 2 large international multicenter cohorts of consecutive patients with CeAD in 23 neurologic departments participating in the CADISP-plus consortium, following a standardized protocol. Frequency of reported family history of CeAD and of inherited connective tissue disorders was assessed. Putative risk factors, baseline features, and 3-month outcome were compared between groups. Among 1,934 consecutive patients with CeAD, 20 patients (1.0%, 95% confidence interval: 0.6%-1.5%) from 17 families (0.9%, 0.5%-1.3%) had a family history of CeAD. Family history of CeAD was significantly more frequent in patients with carotid location of the dissection and elevated cholesterol levels. Two patients without a family history of CeAD had vascular Ehlers-Danlos syndrome with a mutation in COL3A1. This diagnosis was suspected in 2 additional patients, but COL3A1 sequencing was negative. Two patients were diagnosed with classic and hypermobile Ehlers-Danlos syndrome, one patient with Marfan syndrome, and one with osteogenesis imperfecta, based on clinical criteria only. In this largest series of patients with CeAD to date, family history of symptomatic CeAD was rare and inherited connective tissue disorders seemed exceptional. This finding supports the notion that CeAD is a multifactorial disease in the vast majority of cases.

Published
2014

12. Clinical import of Horner syndrome in internal carotid and vertebral artery dissection

Author

Vincent Thijs, Stéphanie Debette, Stefan T. Engelter, Didier Leys, Alessandro Pezzini, Christoph Lichy, Emmanuel Touzé, Caspar Grond-Ginsbach, Tobias Brandt, Valeria Caso, Antti J. Metso, Turgut Tatlisumak, Juan Jose Martin, Leo H. Bonati, Henrik Gensicke, Manja Kloss, Philippe Lyrer, Anna Bersano, and Tiina M. Metso

Subjects
Adult, Male, medicine.medical_specialty, Horner Syndrome, Databases, Factual, Vertebral artery dissection, ICAD, Horner syndrome, Observation, Carotid Artery, Internal, Dissection, 030204 cardiovascular system & hematology, Statistics, Nonparametric, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Outcome Assessment, Health Care, medicine, Humans, Prospective Studies, Prospective cohort study, Retrospective Studies, Vertebral Artery Dissection, Internal carotid artery dissection, business.industry, Retrospective cohort study, Odds ratio, Middle Aged, medicine.disease, 3. Good health, Surgery, Dissection, Cardiology, Female, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

To study the prognostic importance of Horner syndrome (HS) in patients with internal carotid artery dissection (ICAD) or vertebral artery dissection (VAD).In this observational study, characteristics and outcome of patients with ICAD or VAD from the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) database were analyzed. The presence of HS was systematically assessed using a standardized questionnaire. Patients with HS (HS+) were compared with HS- patients. Crude odds ratios (ORs) with 95% confidence intervals and ORs adjusted for age, sex, center, arterial occlusion, bilateral dissection, stroke severity, and type of antithrombotic treatment were calculated.We analyzed 765 patients (n = 496 with ICAD, n = 269 with VAD, n = 303 prospective, n = 462 retrospective). HS was present in 191 (38.5%) of the patients with ICAD and 36 (13.4%) of the patients with VAD (p0.001). HS+ ICAD patients presented less often with stroke or TIA (p0.001), less often had bilateral (p = 0.019) or occlusive (p = 0.001) dissections, and had fewer severe strokes (p = 0.041) than HS- ICAD patients. HS+ ICAD patients had a better functional 3-month outcome than those without HS (ORcrude = 4.0 [2.4-6.7]), and also after adjustment for outcome-relevant covariates (ORadjusted = 2.0 [1.1-4.0]). HS+ ICAD patients were less likely to have new strokes than HS- ICAD patients (p = 0.039). HS+ VAD patients more often had vessel occlusion (p = 0.014) than HS- patients but did not differ in any of the other aforementioned variables.In patients with ICAD, HS is an easily assessable marker that might indicate a more benign clinical course. HS had no prognostic meaning in patients with VAD.

Published
2014

13. Sphingomyelinase Activity Associated with Human Plasma Low Density Lipoprotein

Author

Juha M. Holopainen, Paavo K.J. Kinnunen, Antti J. Metso, and Oula Penate Medina

Subjects
Very low-density lipoprotein, Ceramide, Molecular Sequence Data, Endocytosis, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, High-density lipoprotein, Humans, Amino Acid Sequence, Molecular Biology, Apolipoproteins B, 030304 developmental biology, 0303 health sciences, Liposome, Sequence Homology, Amino Acid, Hydrolysis, Vesicle, 030302 biochemistry & molecular biology, technology, industry, and agriculture, Cell Biology, Sphingomyelins, Lipoproteins, LDL, Kinetics, Sphingomyelin Phosphodiesterase, chemistry, Low-density lipoprotein, Apolipoprotein B-100, Phosphatidylcholines, lipids (amino acids, peptides, and proteins), Sphingomyelin, Oxidation-Reduction
Abstract

Isolated human plasma low density lipoprotein (LDL) was observed to possess sphingomyelinase activity. Accordingly, the formation of ceramide was catalyzed by LDL at 37 degrees C using tertiary liposomes composed of sphingomyelin (mole fraction (x) = 0.2), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (x = 0.7), 1, 2-dimyristoyl-sn-glycero-3-phospho-rac-glycerol (x = 0.1), and either the fluorescent sphingomyelin analog Bodipy-sphingomyelin or [(14)C]sphingomyelin as substrates. However, this activity was not present in either very low density lipoprotein or the high density lipoprotein subfractions HDL(2) and HDL(3). Oxidation of LDL abrogated its sphingomyelinase activity. Aggregation of the liposomes upon incubation with LDL was evident from the light scattering measurements. Microinjection of LDL to the surface of giant liposomes composed of 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC), N-palmitoyl-d-sphingomyelin (C16:0-sphingomyelin), and Bodipy-sphingomyelin as a fluorescent tracer (0.75:- 0.20:0.05, respectively) revealed the induction of vectorial budding of vesicles, resembling endocytosis.

Published
2000

14. Abstract 3854: Family History Of Cervical Artery Dissection In A Large Multicenter Cohort: The CADISP Study

Author

C. Lamy, Alessandro Pezzini, Jean Dallongeville, Manja Kloss, Stefano Paolucci, Yves Samson, Stefan T. Engelter, Caspar Grond-Ginsbach, Armin J. Grau, Emmanuel Touzé, Tiina M. Metso, Yannick Béjot, Christoph Lichy, Antti J. Metso, Stéphanie Debette, Valeria Caso, Juan Jose Martin, Anna Bersano, Turgut Tatlisumak, Didier Leys, Philippe Lyrer, Vincent Thijs, and Ayse Altintas

Subjects
Advanced and Specialized Nursing, medicine.medical_specialty, Pediatrics, business.industry, Cervical Artery, Carotid arteries, Dissection (medical), 030204 cardiovascular system & hematology, medicine.disease, 3. Good health, Surgery, 03 medical and health sciences, 0302 clinical medicine, Cohort, Ischemic stroke, Medicine, Neurology (clinical), Young adult, Family history, Cardiology and Cardiovascular Medicine, business, Stroke, 030217 neurology & neurosurgery
Abstract

Background: Little data is available on familial occurrence of cervical artery dissection (CEAD), a major cause of ischemic stroke in young adults. We aimed to examine the prevalence of family history of CEAD in a large multicenter cohort of CEAD patients and compare characteristics of CEAD patients with and without such a family history. Methods: Across 18 neurological departments in 8 countries, consecutive patients with a diagnosis of CEAD were included in the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) cohort study following a standardized protocol and using the same questionnaire. Results: Among 921 consecutive CEAD patients, 11 patients (1.2%, 95%CI:0.5-1.9%) from 9 families (1.0%, 0.3-1.6%) had a family history of CEAD, mostly in a first degree relative (64%). One patient without family history of CEAD had biologically confirmed vascular Ehlers-Danlos syndrome, while none of the patients with a family history of CEAD had a diagnosis of known inherited connective tissue disorder. Risk factors, baseline features, and 3-month outcome did not differ significantly between CEAD patients with and without a family history of CEAD. Conclusion: In the largest series of CEAD patients to date, family history of CEAD was very rare, although slightly higher than expected by chance given the low disease incidence.

Published
2012

15. Age-dependent differences in cervical artery dissection

Author

Tobias Brandt, Stéphanie Debette, Caspar Grond-Ginsbach, Tiina M. Metso, Didier Leys, Manja Kloss, Anna Bersano, Turgut Tatlisumak, Alessandro Pezzini, Antti J. Metso, Stefan T. Engelter, Philippe Lyrer, and Vincent Thijs

Subjects
Adult, Male, medicine.medical_specialty, Cervical Artery, Vertebral artery dissection, Population, Dissection (medical), Age Distribution, Modified Rankin Scale, Internal medicine, medicine, Humans, Risk factor, education, Stroke, education.field_of_study, Internal carotid artery dissection, business.industry, Middle Aged, medicine.disease, Surgery, Aortic Dissection, Neurology, Female, Intracranial Arterial Diseases, Neurology (clinical), business
Abstract

The goal of this work was to explore age-dependent differences in cervical artery dissection (CeAD). This study is based on the Cervical Artery Dissection and Ischemic Stroke Patients population comprising 983 consecutive CeAD patients and 658 control patients with a non-CeAD ischemic stroke (IS), frequency-matched for age and gender. Patients were divided into three age categories: ≤33 (for CeAD, n = 150), 34-54 (n = 688), and ≥55 (n = 145) years, and the youngest and oldest groups were compared. The youngest patients were mostly women and the oldest men. The frequency of internal carotid artery dissection (ICAD) versus vertebral artery dissection (VAD) increased with age from 44 to 75 %. This age-related shift remained significant after adjustment for sex. The frequency of a transient ischemic event as the CeAD symptom declined from 33 % in the youngest age group, to 19 % in the oldest. Vascular risk factors increased in frequency with advancing age in both groups, but for hypertension the increase was steeper for non-CeAD IS patients. For CeAD patients, but not for patients with non-CeAD IS, preceding infection was more common in the oldest group. The youngest non-CeAD IS patients had better functional outcome (modified Rankin Scale 0-1) than the oldest, while the similar trend was not statistically significant among CeAD patients. Younger age seems to be associated with VAD and female gender, and older age with ICAD and male gender. Age-related changes in the frequencies of hypertension and recent infection were different between the CeAD and non-CeAD IS groups. Age does not seem to be an important outcome predictor in CeAD strokes.

Published
2012

16. Differential features of carotid and vertebral artery dissections: the CADISP study

Author

Stefan T. Engelter, Manja Kloss, Didier Leys, Emmanuel Touzé, E. Del Zotto, S. Canaple, Sherine Abboud, Jean Dallongeville, Giacomo Giacalone, Maurice Giroud, J.J. Martin, Philippe Lyrer, Tiina M. Metso, Yves Samson, Alessandro Pezzini, Turgut Tatlisumak, Caspar Grond-Ginsbach, Valeria Caso, Antti J. Metso, Stéphanie Debette, Tobias Brandt, and Marie Bodenant

Subjects
Adult, Male, medicine.medical_specialty, Cervical Artery, Vertebral artery, Vertebral artery dissection, ICAD, Carotid Artery, Internal, Dissection, Sex Factors, Modified Rankin Scale, medicine.artery, medicine, Humans, Prospective Studies, cardiovascular diseases, Risk factor, Retrospective Studies, Vertebral Artery Dissection, Internal carotid artery dissection, business.industry, Age Factors, Middle Aged, medicine.disease, Surgery, Dissection, Female, Neurology (clinical), business, Follow-Up Studies
Abstract

Objective: To examine whether risk factor profile, baseline features, and outcome of cervical artery dissection (CEAD) differ according to the dissection site. Methods: We analyzed 982 consecutive patients with CEAD included in the Cervical Artery Dissection and Ischemic Stroke Patients observational study (n = 619 with internal carotid artery dissection [ICAD], n = 327 with vertebral artery dissection [VAD], n = 36 with ICAD and VAD). Results: Patients with ICAD were older ( p p = 0.006), more frequently had a recent infection (odds ratio [OR] = 1.59 [95% confidence interval (CI) 1.09–2.31]), and tended to report less often a minor neck trauma in the previous month (OR = 0.75 [0.56–1.007]) compared to patients with VAD. Clinically, patients with ICAD more often presented with headache at admission (OR = 1.36 [1.01–1.84]) but less frequently complained of cervical pain (OR = 0.36 [0.27–0.48]) or had cerebral ischemia (OR = 0.32 [0.21–0.49]) than patients with VAD. Among patients with CEAD who sustained an ischemic stroke, the NIH Stroke Scale (NIHSS) score at admission was higher in patients with ICAD than patients with VAD (OR = 1.17 [1.12–1.22]). Aneurysmal dilatation was more common (OR = 1.80 [1.13–2.87]) and bilateral dissection less frequent (OR = 0.63 [0.42–0.95]) in patients with ICAD. Multiple concomitant dissections tended to cluster on the same artery type rather than involving both a vertebral and carotid artery. Patients with ICAD had a less favorable 3-month functional outcome (modified Rankin Scale score >2, OR = 3.99 [2.32–6.88]), but this was no longer significant after adjusting for baseline NIHSS score. Conclusion: In the largest published series of patients with CEAD, we observed significant differences between VAD and ICAD in terms of risk factors, baseline features, and functional outcome.

Published
2011

17. Thrombolysis in young adults with ischemic stroke

Author

Turgut Tatlisumak, Tiina M. Metso, Markku Kaste, Antti J. Metso, Elina Mäkelä, Jukka Putaala, Oili Salonen, and Elena Haapaniemi

Subjects
Adult, Male, medicine.medical_specialty, Aging, Adolescent, medicine.medical_treatment, Brain Ischemia, Brain ischemia, Young Adult, Fibrinolytic Agents, Modified Rankin Scale, Risk Factors, medicine, Humans, Glasgow Coma Scale, Thrombolytic Therapy, Young adult, Stroke, Aged, Advanced and Specialized Nursing, Intracerebral hemorrhage, business.industry, Cerebral infarction, Thrombolysis, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Treatment Outcome, Tissue Plasminogen Activator, Emergency medicine, Physical therapy, Female, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, Tomography, X-Ray Computed, Magnetic Resonance Angiography
Abstract

Background and Purpose— No exclusive systematic data exist on the safety and outcomes of thrombolytic treatment in young patients with ischemic stroke. Methods— We evaluated all 48 patients aged 16 to 49 years with hemispheric ischemic stroke treated with intravenous alteplase in Helsinki University Central Hospital from 1994 to 2007. For comparison of outcome, we selected, blinded to outcome data, 96 control subjects (1:2) with ischemic stroke not treated with alteplase matched by age, gender, and admission stroke severity (National Institutes of Health Stroke Scale). We selected similarly 96 older alteplase-treated gender and arrival National Institutes of Health Stroke Scale score-matched patients (aged, 50 to 79 years) for comparison of outcome and hemorrhage rate. A 3-month favorable outcome was defined as modified Rankin Scale score of 0 to 1. Symptomatic intracerebral hemorrhage was defined according to the Safe Implementation of Thrombolysis in Stroke Monitor Study. Results— Young alteplase-treated patients (67% males; mean age, 38.8±9.1 years) more often recovered completely (27% versus 10%, P =0.010) and achieved a favorable outcome (40% versus 22%, P =0.025) compared with their age-matched control subjects not treated with alteplase. In alteplase-treated patients, unfavorable outcome was more frequent in males and in those with carotid artery dissection. We observed no difference in outcome between cases and older control subjects treated with alteplase. However, none of the cases had symptomatic intracerebral hemorrhage versus 3 (3%) in the older control group ( P =0.551). Mortality rate was 2% ( P =0.552) in age-matched control subjects and 7% ( P =0.095) among older control subjects, whereas none of the case patients died during the 3-month follow-up. Conclusions— Young adults with acute hemispheric ischemic stroke benefited from intravenous thrombolysis with good safety.

Published
2009

18. Analysis of 1008 consecutive patients aged 15 to 49 with first-ever ischemic stroke: the Helsinki young stroke registry

Author

Jukka Putaala, Turgut Tatlisumak, Elena Haapaniemi, Markku Kaste, Antti J. Metso, Tiina M. Metso, Yvonn Kraemer, and Nina Konkola

Subjects
Adult, Male, medicine.medical_specialty, Pediatrics, Adolescent, Brain Ischemia, Brain ischemia, Young Adult, Age Distribution, Risk Factors, medicine, Humans, Registries, Young adult, Risk factor, Age of Onset, Sex Distribution, Stroke, Finland, Retrospective Studies, Advanced and Specialized Nursing, Cerebral infarction, business.industry, Retrospective cohort study, Middle Aged, medicine.disease, Physical therapy, Etiology, Female, Neurology (clinical), Age of onset, Cardiology and Cardiovascular Medicine, business
Abstract

Background and Purpose— To analyze trends in occurrence, risk factors, etiology, and neuroimaging features of ischemic stroke in young adults in a large cohort. Methods— We evaluated all 1008 consecutive ischemic stroke patients aged 15 to 49 admitted to Helsinki University Central Hospital, 1994 to 2007. Etiology was classified by Trial of Org 10172 in Acute Stroke Treatment criteria. Comparisons were done between groups stratified by gender and age. Results— Estimated annual occurrence was 10.8/100 000 (range 8.4 to 13.0), increasing exponentially with aging. Of our 628 male and 380 female (ratio 1.7:1) patients, females were preponderant among those 44 clearly had more risk factors. Cardioembolism (20%) and cervicocerebral artery dissection (15%) were the most frequent etiologic subgroups. Proportions of large-artery atherosclerosis (8%) and small-vessel disease (14%) began to enlarge at age 35, whereas frequency of undetermined etiology (33%) decreased along aging. Posterior circulation infarcts were more common among patients Conclusions— The frequency of ischemic stroke increases sharply at age 40. Etiology and risk factors start resembling those seen in the elderly in early midlife but causes defined in younger patients still are frequent in those aged 45 to 49. Subclinical infarcts were surprisingly common in the young.

Published
2009

19. Response to Letter by Arnold et al

Author

Antti J. Metso, Tiina M. Metso, Oili Salonen, and Turgut Tatlisumak

Subjects
Advanced and Specialized Nursing, medicine.medical_specialty, medicine.diagnostic_test, Lumbar puncture, Mri negative, business.industry, Intracranial Artery, Dissection (medical), medicine.disease, Anticoagulation Treatment, Surgery, Stenosis, Cerebrospinal fluid, Pathognomonic, medicine, cardiovascular diseases, Neurology (clinical), Cardiology and Cardiovascular Medicine, business
Abstract

Response: We thank Dr Arnold et al for their interest in our recent article.1 In their Letter,2 Arnold et al suggest that (1) the present data are not sufficient to conclude the safety of anticoagulation in intracranial artery dissection (IAD) patients presenting without subarachnoidal hemorrhage (SAH), and a routine lumbar puncture (LP) is necessary to exclude CT or MRI negative SAH, and (2) a filiform stenosis is not a reliable marker of dissection and more strict diagnostic criteria, ie, pathognomonic signs only, should be used for reliable diagnosis of IAD. Apparently, Arnold and his coauthors themselves2 use anticoagulation treatment in (some) IAD patients after routinely performing a LP to exclude SAH, as some patients may have a normal CT but blood in cerebrospinal fluid. In contrast to their …

Published
2007

20. Observation of the main phase transition of dinervonoylphosphocholine giant liposomes by fluorescence microscopy

Author

Hongxia Zhao, Ilkka Tuunainen, Paavo K.J. Kinnunen, and Antti J. Metso

Subjects
Phase transition, Hot Temperature, 1,2-Dipalmitoylphosphatidylcholine, Phosphorylcholine, Lipid Bilayers, Analytical chemistry, Biophysics, 02 engineering and technology, Calorimetry, Biochemistry, Giant liposome, Fluorescence spectroscopy, Biophysical Phenomena, 03 medical and health sciences, Differential scanning calorimetry, Phase (matter), Fluorescence microscope, Lipid bilayer, 030304 developmental biology, 0303 health sciences, Microscopy, Confocal, Calorimetry, Differential Scanning, Chemistry, Vesicle, technology, industry, and agriculture, Temperature, Stereoisomerism, Cell Biology, 021001 nanoscience & nanotechnology, Crystallography, Spectrometry, Fluorescence, Microscopy, Fluorescence, Liposomes, Phosphatidylcholines, lipids (amino acids, peptides, and proteins), 0210 nano-technology, Dimyristoylphosphatidylcholine
Abstract

The phase heterogeneity of giant unilamellar dinervonoylphosphocholine (DNPC) vesicles in the course of the main phase transition was investigated by confocal fluorescence microscopy observing the fluorescence from the membrane incorporated lipid analog, 1-palmitoyl-2-(N-4-nitrobenz-2-oxa-1,3-diazol)aminocaproyl-sn-glycero-3-phosphocholine (NBDPC). These data were supplemented by differential scanning calorimetry (DSC) of DNPC large unilamellar vesicles (LUV, diameter approximately 0.1 and 0.2 microm) and multilamellar vesicles (MLV). The present data collected upon cooling reveal a lack of micron-scale gel and fluid phase coexistence in DNPC GUVs above the temperature of 20.5 degrees C, this temperature corresponding closely to the heat capacity maxima (T(em)) of DNPC MLVs and LUVs (T(em) approximately 21 degrees C), measured upon DSC cooling scans. This is in keeping with the model for phospholipid main transition inferred from our previous fluorescence spectroscopy data for DMPC, DPPC, and DNPC LUVs. More specifically, the current experiments provide further support for the phospholipid main transition involving a first-order process, with the characteristic two-phase coexistence converting into an intermediate phase in the proximity of T(em). This at least macroscopically homogenous intermediate phase would then transform into the liquid crystalline state by a second-order process, with further increase in acyl chain trans-->gauche isomerization.

Published
2004

21. Antiplatelets versus Anticoagulants for the Treatment of Cervical Artery Dissection: Bayesian Meta-Analysis

Author

Ralf W. Baumgartner, Antti J. Metso, Bruno R. da Costa, Kathleen Duclos, Emmanuel Touzé, Marcel Arnold, Jean M. de Bray, Marcel Zwahlen, Peter Jüni, Antonio Arauz, Tiina M. Metso, Hakan Sarikaya, Clinicum, and Neurologian yksikkö

Subjects
Cervical Artery, lcsh:Medicine, Carotid Artery, Internal, Dissection, 3124 Neurology and psychiatry, law.invention, 0302 clinical medicine, Randomized controlled trial, law, YOUNG-ADULTS, Odds Ratio, ACUTE ISCHEMIC-STROKE, 030212 general & internal medicine, lcsh:Science, Stroke, Vertebral Artery Dissection, Multidisciplinary, RANDOMIZED CONTROLLED-TRIAL, 3. Good health, Treatment Outcome, Data extraction, Meta-analysis, INTERNAL CAROTID-ARTERY, Research Article, medicine.medical_specialty, education, 610 Medicine & health, 03 medical and health sciences, 360 Social problems & social services, Internal medicine, MANAGEMENT, medicine, Humans, TERM-FOLLOW-UP, business.industry, lcsh:R, Anticoagulants, Bayes Theorem, Odds ratio, medicine.disease, Surgery, ASPIRIN, MYOCARDIAL-INFARCTION, VERTEBRAL ARTERIES, Relative risk, ATRIAL-FIBRILLATION, lcsh:Q, Observational study, business, Platelet Aggregation Inhibitors, 030217 neurology & neurosurgery
Abstract

OBJECTIVE To compare the effects of antiplatelets and anticoagulants on stroke and death in patients with acute cervical artery dissection. DESIGN Systematic review with Bayesian meta-analysis. DATA SOURCES The reviewers searched MEDLINE and EMBASE from inception to November 2012, checked reference lists, and contacted authors. STUDY SELECTION Studies were eligible if they were randomised, quasi-randomised or observational comparisons of antiplatelets and anticoagulants in patients with cervical artery dissection. DATA EXTRACTION Data were extracted by one reviewer and checked by another. Bayesian techniques were used to appropriately account for studies with scarce event data and imbalances in the size of comparison groups. DATA SYNTHESIS Thirty-seven studies (1991 patients) were included. We found no randomised trial. The primary analysis revealed a large treatment effect in favour of antiplatelets for preventing the primary composite outcome of ischaemic stroke, intracranial haemorrhage or death within the first 3 months after treatment initiation (relative risk 0.32, 95% credibility interval 0.12 to 0.63), while the degree of between-study heterogeneity was moderate (τ(2) = 0.18). In an analysis restricted to studies of higher methodological quality, the possible advantage of antiplatelets over anticoagulants was less obvious than in the main analysis (relative risk 0.73, 95% credibility interval 0.17 to 2.30). CONCLUSION In view of these results and the safety advantages, easier usage and lower cost of antiplatelets, we conclude that antiplatelets should be given precedence over anticoagulants as a first line treatment in patients with cervical artery dissection unless results of an adequately powered randomised trial suggest the opposite.

Published
2013

22. Stroke in young adults: every saga has a beginning

Author

Jukka Putaala, Turgut Tatlisumak, Antti J. Metso, and T. M. Metso

Subjects
Pediatrics, medicine.medical_specialty, Neurology, Stroke etiology, business.industry, medicine, MEDLINE, Neurology (clinical), Young adult, Stroke mortality, medicine.disease, business, Stroke
Published
2010

23. Cervical artery dissections: multiple dissections and morphometric data

Author

Turgut Tatlisumak and Antti J. Metso

Subjects
medicine.medical_specialty, business.industry, Cervical Artery, medicine.disease, Annual incidence, Psychiatry and Mental health, Dissection, Cervicocerebral artery, Medicine, Surgery, cardiovascular diseases, Neurology (clinical), Radiology, business, Pathological, Stroke, Ischaemic strokes, Rare disease
Abstract

Cervicocerebral artery dissection (CAD) is “a common rare disease,” with an annual incidence of 2.6 to 2.9 patients per 100 000 people. In adults younger than 50 years of age, ∼15% of all ischaemic strokes are caused by CAD, while cardioembolism, representing a wider spectrum of pathological conditions, explain ∼20% of cases. Arnold et al 1 report the results of two studies, contributing to our understanding of the characteristics of CAD (see page 171) . They …

Published
2009

24. Hyperglycaemia and the outcome of stroke

Author

Kari Murros and Antti J. Metso

Subjects
endocrine system, medicine.medical_specialty, Lacunar stroke, endocrine system diseases, business.industry, digestive, oral, and skin physiology, nutritional and metabolic diseases, medicine.disease, Neuroprotection, Surgery, Internal medicine, Ischaemic stroke, medicine, Cardiology, cardiovascular diseases, Neurology (clinical), Serum glucose level, business, Stroke
Abstract

We read with great interest the article by Uyttenboogaart and co-workers on the association of serum glucose level with outcome in acute ischaemic stroke. In their multivariate analysis hyperglycaemia (glucose >8 mmol/l) was associated with worse functional outcome in a concentration-dependent manner in non-lacunar stroke, whereas in lacunar stroke hyperglycaemia was associated with favourable outcome, this beneficial effect diminishing with more severe hyperglycaemia (>12 mmol/l). Although Uyttenboogart and colleagues creditably discuss the potential neuroprotective effect of lactate produced by astrocytes, they fail in their conclusions stating that ‘hyperglycaemia has a detrimental effect in non-lacunar stroke, but moderate hyperglycaemia …

Published
2007

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