Pathogenic Ischemic Stroke Phenotypes in the NINDS-Stroke Genetics Network

被引：45

作者：

Ay, Hakan ^{[1
,2
]}

Arsava, Ethem Murat ^{[1
]}

Andsberg, Gunnar ^{[4
]}

Benner, Thomas ^{[1
]}

Brown, Robert D., Jr. ^{[5
]}

Chapman, Sherita N. ^{[6
]}

Cole, John W. ^{[9
]}

Delavaran, Hossein ^{[4
]}

Dichgans, Martin ^{[11
]}

Engstroem, Gunnar ^{[12
]}

Giralt-Steinhauer, Eva ^{[13
]}

Grewal, Raji P. ^{[14
]}

Gwinn, Katrina ^{[15
]}

Jern, Christina ^{[16
]}

Jimenez-Conde, Jordi ^{[13
]}

Jood, Katarina ^{[17
]}

Katsnelson, Michael ^{[18
]}

Kissela, Brett ^{[19
]}

Kittner, Steven J. ^{[9
]}

Kleindorfer, Dawn O. ^{[19
]}

Labovitz, Daniel L. ^{[20
]}

Lanfranconi, Silvia ^{[21
]}

Lee, Jin-Moo ^{[22
]}

Lehm, Manuel ^{[11
]}

Lemmens, Robin ^{[23
]}

Levi, Chris ^{[24
]}

Li, Linxin ^{[25
]}

Lindgren, Arne ^{[4
]}

Markus, Hugh S. ^{[26
]}

McArdle, Patrick F. ^{[10
]}

Melander, Olle ^{[4
]}

Norrving, Bo ^{[4
,12
]}

Peddareddygari, Leema Reddy ^{[14
]}

Pedersen, Annie ^{[16
]}

Pera, Joanna ^{[27
]}

Rannikmaee, Kristiina ^{[28
]}

Rexrode, Kathryn M. ^{[29
]}

Rhodes, David ^{[30
]}

Rich, Stephen S. ^{[7
]}

Roquer, Jaume ^{[2
,3
]}

Rosand, Jonathan ^{[13
]}

Rothwell, Peter M. ^{[25
]}

Rundek, Tatjana ^{[18
]}

Sacco, Ralph L. ^{[18
]}

Schmidt, Reinhold ^{[31
]}

Schuerks, Markus ^{[32
]}

Seiler, Stephan ^{[31
]}

Sharma, Pankaj ^{[33
]}

Slowik, Agnieszka ^{[27
]}

Sudlow, Cathie ^{[28
]}

机构：

[1] Harvard Univ, AA Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Dept Radiol,Med Sch, Charlestown, MA 02129 USA

[2] Harvard Univ, Stroke Serv, Massachusetts Gen Hosp, Dept Neurol,Med Sch, Charlestown, MA 02129 USA

[3] Harvard Univ, Ctr Human Genet Res, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA

[4] Skane Univ Hosp, Dept Neurol & Rehabil Med, Lund, Sweden

[5] Mayo Clin, Dept Neurol, Rochester, MN USA

[6] Univ Virginia, Dept Neurol, Charlottesville, VA USA

[7] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA

[8] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA

[9] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA

[10] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD 21201 USA

[11] Univ Munich, Inst Stroke & Dementia Res, Klinikum Univ Munchen, Munich, Germany

[12] Lund Univ, Dept Clin Sci, Malmo, Sweden

[13] Univ Pompeu Fabra, Dept Neurol, Neurovasc Res Grp, IMIM,Hosp del Mar,Univ Autonoma Barcelona,DCEXS, Barcelona, Spain

[14] St Francis Med Ctr, Neurosci Inst, Trenton, NJ USA

[15] NINDS, NIH, Bethesda, MD 20892 USA

[16] Univ Gothenburg, Inst Biomed, Sahlgrenska Acad, Gothenburg, Sweden

[17] Univ Gothenburg, Inst Neurosci & Physiol, Sahlgrenska Acad, Gothenburg, Sweden

[18] Univ Miami, Dept Neurol, Miller Sch Med, Coral Gables, FL 33124 USA

[19] Univ Cincinnati, Dept Neurol, Coll Med, Cincinnati, OH 45221 USA

[20] Albert Einstein Coll Med, Stern Stroke Ctr, Dept Neurol, Bronx, NY 10467 USA

[21] Policlin Hosp Fdn IRCCS Ca Granda, Dept Neurosci & Sensory Organs, Milan, Italy

[22] Washington Univ, Dept Neurol, St Louis, MO USA

[23] Univ Hosp Leuven, Dept Neurol, Louvain, Belgium

[24] Univ Newcastle, John Hunter Hosp, Dept Neurol, Callaghan, NSW 2308, Australia

[25] Univ Oxford, Nuffield Dept Clin Neurosci, Oxford OX1 2JD, England

[26] Univ Cambridge, Dept Clin Neurosci, Cambridge CB2 1TN, England

[27] Jagiellonian Univ, Dept Neurol, Coll Med, Krakow, Poland

[28] Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh EH8 9YL, Midlothian, Scotland

[29] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA

[30] Univ Alabama Birmingham, Sch Publ Hlth, Birmingham, AL USA

[31] Med Univ Graz, Dept Neurol, Graz, Austria

[32] Univ Hosp Essen, Dept Neurol, Essen, Germany

[33] Imperial Coll London, Dept Med, Cerebrovasc Res Unit, London, England

[34] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA

来源：

STROKE | 2014年 / 45卷 / 12期

基金：

奥地利科学基金会; 英国惠康基金;

关键词：

classification; pathogenesis; phenotype; CAUSATIVE CLASSIFICATION; RELIABILITY; AGREEMENT; VARIANTS; SYSTEM; RISK;

D O I：

10.1161/STROKEAHA.114.007362

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background and Purpose-NINDS (National Institute of Neurological Disorders and Stroke)-SiGN (Stroke Genetics Network) is an international consortium of ischemic stroke studies that aims to generate high-quality phenotype data to identify the genetic basis of pathogenic stroke subtypes. This analysis characterizes the etiopathogenetic basis of ischemic stroke and reliability of stroke classification in the consortium. Methods-Fifty-two trained and certified adjudicators determined both phenotypic (abnormal test findings categorized in major pathogenic groups without weighting toward the most likely cause) and causative ischemic stroke subtypes in 16 954 subjects with imaging-confirmed ischemic stroke from 12 US studies and 11 studies from 8 European countries using the web-based Causative Classification of Stroke System. Classification reliability was assessed with blinded readjudication of 1509 randomly selected cases. Results-The distribution of pathogenic categories varied by study, age, sex, and race (P<0.001 for each). Overall, only 40% to 54% of cases with a given major ischemic stroke pathogenesis (phenotypic subtype) were classified into the same final causative category with high confidence. There was good agreement for both causative (kappa 0.72; 95% confidence interval, 0.69-0.75) and phenotypic classifications (kappa 0.73; 95% confidence interval, 0.70-0.75). Conclusions-This study demonstrates that pathogenic subtypes can be determined with good reliability in studies that include investigators with different expertise and background, institutions with different stroke evaluation protocols and geographic location, and patient populations with different epidemiological characteristics. The discordance between phenotypic and causative stroke subtypes highlights the fact that the presence of an abnormality in a patient with stroke does not necessarily mean that it is the cause of stroke.

引用

页码：3589 / +

页数：14

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