Alessandro Biffi1,2,3,4, Sebastian Urday1, Patryk Kubiszewski2, Lee Gilkerson5, Padmini Sekar5, Axana Rodriguez-Torres1,3, Margaret Bettin6, Andreas Charidimou1,3, Marco Pasi1,3, Christina Kourkoulis1,2,3,4, Kristin Schwab3, Zora DiPucchio1,3, Tyler Behymer5, Jennifer Osborne5, Misty Morgan5, Charles J Moomaw5, Michael L James7, Steven M Greenberg1,3, Anand Viswanathan1,3, M Edip Gurol1,3, Bradford B Worrall6, Fernando D Testai8, Jacob L McCauley9, Guido J Falcone10, Carl D Langefeld11, Christopher D Anderson1,2,3,4,12, Hooman Kamel13, Daniel Woo5, Kevin N Sheth, Jonathan Rosand1,2,3,4,12. 1. Department of Neurology (A.B., S.U., A.R.-T., A.C., M.P., C.K., K.S., Z.D., S.M.G., A.V., M.E.G., C.D.A., J.R.), Massachusetts General Hospital, Boston. 2. Center for Genomic Medicine (A.B., P.K., C.K., C.D.A., J.R.), Massachusetts General Hospital, Boston. 3. Hemorrhagic Stroke Research Program (A.B., A.R.-T., A.C., M.P., C.K., K.S., Z.D., S.M.G., A.V., M.E.G., C.D.A, J.R.), Massachusetts General Hospital, Boston. 4. Henry and Allison McCance Center for Brain Health (A.B., C.K., C.D.A., J.R.), Massachusetts General Hospital, Boston. 5. Department of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, OH (L.G., P.S., T.B., J.O., M.M., C.J.M., D.W.). 6. Department of Neurology, University of Virginia Health System, Charlottesville (M.B., B.B.W.). 7. Department of Anesthesiology, Duke University, Durham, NC (M.L.J.). 8. Department of Neurology and Rehabilitation, University of Illinois at Chicago College of Medicine, Chicago (F.D.T.). 9. Center for Genome Technology and Biorepository Facility, University of Miami, Miller School of Medicine, FL (J.L.M.). 10. Department of Neurology, Yale University School of Medicine, New Haven, CT (G.J.F.). 11. Department of Biostatistics and Data Sciences, Wake Forest University, Winston-Salem, NC (C.D.L.). 12. Program in Medical and Population Genetics, Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge (C.D.A., J.R.). 13. Department of Neurology, Weill Cornell School of Medicine, New York, NY (H.K.).
Abstract
BACKGROUND AND PURPOSE: For survivors of oral anticoagulation therapy (OAT)-associated intracerebral hemorrhage (OAT-ICH) who are at high risk for thromboembolism, the benefits of OAT resumption must be weighed against increased risk of recurrent hemorrhagic stroke. The ε2/ε4 alleles of the apolipoprotein E (APOE) gene, MRI-defined cortical superficial siderosis, and cerebral microbleeds are the most potent risk factors for recurrent ICH. We sought to determine whether combining MRI markers and APOE genotype could have clinical impact by identifying ICH survivors in whom the risks of OAT resumption are highest. METHODS: Joint analysis of data from 2 longitudinal cohort studies of OAT-ICH survivors: (1) MGH-ICH study (Massachusetts General Hospital ICH) and (2) longitudinal component of the ERICH study (Ethnic/Racial Variations of Intracerebral Hemorrhage). We evaluated whether MRI markers and APOE genotype predict ICH recurrence. We then developed and validated a combined APOE-MRI classification scheme to predict ICH recurrence, using Classification and Regression Tree analysis. RESULTS: Cortical superficial siderosis, cerebral microbleed, and APOE ε2/ε4 variants were independently associated with ICH recurrence after OAT-ICH (all P<0.05). Combining APOE genotype and MRI data resulted in improved prediction of ICH recurrence (Harrell C: 0.79 versus 0.55 for clinical data alone, P=0.033). In the MGH (training) data set, CSS, cerebral microbleed, and APOE ε2/ε4 stratified likelihood of ICH recurrence into high-, medium-, and low-risk categories. In the ERICH (validation) data set, yearly ICH recurrence rates for high-, medium-, and low-risk individuals were 6.6%, 2.5%, and 0.9%, respectively, with overall area under the curve of 0.91 for prediction of recurrent ICH. CONCLUSIONS: Combining MRI and APOE genotype stratifies likelihood of ICH recurrence into high, medium, and low risk. If confirmed in prospective studies, this combined APOE-MRI classification scheme may prove useful for selecting individuals for OAT resumption after ICH.
BACKGROUND AND PURPOSE: For survivors of oral anticoagulation therapy (OAT)-associated intracerebral hemorrhage (OAT-ICH) who are at high risk for thromboembolism, the benefits of OAT resumption must be weighed against increased risk of recurrent hemorrhagic stroke. The ε2/ε4 alleles of the apolipoprotein E (APOE) gene, MRI-defined cortical superficial siderosis, and cerebral microbleeds are the most potent risk factors for recurrent ICH. We sought to determine whether combining MRI markers and APOE genotype could have clinical impact by identifying ICH survivors in whom the risks of OAT resumption are highest. METHODS: Joint analysis of data from 2 longitudinal cohort studies of OAT-ICH survivors: (1) MGH-ICH study (Massachusetts General Hospital ICH) and (2) longitudinal component of the ERICH study (Ethnic/Racial Variations of Intracerebral Hemorrhage). We evaluated whether MRI markers and APOE genotype predict ICH recurrence. We then developed and validated a combined APOE-MRI classification scheme to predict ICH recurrence, using Classification and Regression Tree analysis. RESULTS: Cortical superficial siderosis, cerebral microbleed, and APOE ε2/ε4 variants were independently associated with ICH recurrence after OAT-ICH (all P<0.05). Combining APOE genotype and MRI data resulted in improved prediction of ICH recurrence (Harrell C: 0.79 versus 0.55 for clinical data alone, P=0.033). In the MGH (training) data set, CSS, cerebral microbleed, and APOE ε2/ε4 stratified likelihood of ICH recurrence into high-, medium-, and low-risk categories. In the ERICH (validation) data set, yearly ICH recurrence rates for high-, medium-, and low-risk individuals were 6.6%, 2.5%, and 0.9%, respectively, with overall area under the curve of 0.91 for prediction of recurrent ICH. CONCLUSIONS: Combining MRI and APOE genotype stratifies likelihood of ICH recurrence into high, medium, and low risk. If confirmed in prospective studies, this combined APOE-MRI classification scheme may prove useful for selecting individuals for OAT resumption after ICH.
Authors: Daniel Woo; Jonathan Rosand; Chelsea Kidwell; Jacob L McCauley; Jennifer Osborne; Mark W Brown; Sandra E West; Eric W Rademacher; Salina Waddy; Jamie N Roberts; Sebastian Koch; Nicole R Gonzales; Gene Sung; Steven J Kittner; Lee Birnbaum; Michael Frankel; Fernando Daniel Testai; Christiana E Hall; Mitchell S V Elkind; Matthew Flaherty; Bruce Coull; Ji Y Chong; Tanya Warwick; Marc Malkoff; Michael L James; Latisha K Ali; Bradford B Worrall; Floyd Jones; Tiffany Watson; Anne Leonard; Rebecca Martinez; Ralph I Sacco; Carl D Langefeld Journal: Stroke Date: 2013-09-10 Impact factor: 7.914
Authors: Sergi Martinez-Ramirez; Jose-Rafael Romero; Ashkan Shoamanesh; Ann C McKee; Ellis Van Etten; Octavio Pontes-Neto; Eric A Macklin; Alison Ayres; Eitan Auriel; Jayandra J Himali; Alexa S Beiser; Charles DeCarli; Thor D Stein; Victor E Alvarez; Matthew P Frosch; Jonathan Rosand; Steven M Greenberg; M Edip Gurol; Sudha Seshadri; Anand Viswanathan Journal: Alzheimers Dement Date: 2015-06-13 Impact factor: 21.566
Authors: Andreas Charidimou; Sergi Martinez-Ramirez; Ashkan Shoamanesh; Jamary Oliveira-Filho; Matthew Frosch; Anastasia Vashkevich; Alison Ayres; Jonathan Rosand; Mahmut Edip Gurol; Steven M Greenberg; Anand Viswanathan Journal: Neurology Date: 2015-02-25 Impact factor: 9.910
Authors: Daniel M Witt; Thomas Delate; Elaine M Hylek; Nathan P Clark; Mark A Crowther; Francesco Dentali; Walter Ageno; Kerri D Martinez; David A Garcia Journal: Thromb Res Date: 2013-10-17 Impact factor: 3.944
Authors: Alessandro Biffi; Christopher D Anderson; Thomas W K Battey; Alison M Ayres; Steven M Greenberg; Anand Viswanathan; Jonathan Rosand Journal: JAMA Date: 2015-09-01 Impact factor: 56.272
Authors: Alessandro Biffi; Joji B Kuramatsu; Audrey Leasure; Hooman Kamel; Christina Kourkoulis; Kristin Schwab; Alison M Ayres; Jordan Elm; M Edip Gurol; Steven M Greenberg; Anand Viswanathan; Christopher D Anderson; Stefan Schwab; Jonathan Rosand; Fernando D Testai; Daniel Woo; Hagen B Huttner; Kevin N Sheth Journal: Ann Neurol Date: 2017-10-31 Impact factor: 10.422
Authors: Joanna M Wardlaw; Eric E Smith; Geert J Biessels; Charlotte Cordonnier; Franz Fazekas; Richard Frayne; Richard I Lindley; John T O'Brien; Frederik Barkhof; Oscar R Benavente; Sandra E Black; Carol Brayne; Monique Breteler; Hugues Chabriat; Charles Decarli; Frank-Erik de Leeuw; Fergus Doubal; Marco Duering; Nick C Fox; Steven Greenberg; Vladimir Hachinski; Ingo Kilimann; Vincent Mok; Robert van Oostenbrugge; Leonardo Pantoni; Oliver Speck; Blossom C M Stephan; Stefan Teipel; Anand Viswanathan; David Werring; Christopher Chen; Colin Smith; Mark van Buchem; Bo Norrving; Philip B Gorelick; Martin Dichgans Journal: Lancet Neurol Date: 2013-08 Impact factor: 44.182
Authors: Jessica R Abramson; Juan Pablo Castello; Sophia Keins; Christina Kourkoulis; Axana Rodriguez-Torres; Evangelos Pavlos Myserlis; Haitham Alabsi; Andrew D Warren; Jonathan Q A Henry; M Edip Gurol; Anand Viswanathan; Steven M Greenberg; Amytis Towfighi; Lesli Skolarus; Christopher D Anderson; Jonathan Rosand; Alessandro Biffi Journal: Neurology Date: 2022-02-07 Impact factor: 11.800