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14. Development of imaging-based risk scores for prediction of intracranial haemorrhage and ischaemic stroke in patients taking antithrombotic therapy after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies.

Author

Best J.G., Ambler G., Wilson D., Lee K.-J., Lim J.-S., Shiozawa M., Koga M., Li L., Lovelock C., Chabriat H., Hennerici M., Wong Y.K., Mak H.K.F., Prats-Sanchez L., Martinez-Domeno A., Inamura S., Yoshifuji K., Arsava E.M., Horstmann S., Purrucker J., Lam B.Y.K., Wong A., Kim Y.D., Song T.-J., Lemmens R., Eppinger S., Gattringer T., Uysal E., Tanriverdi Z., Bornstein N.M., Ben Assayag E., Hallevi H., Molad J., Nishihara M., Tanaka J., Coutts S.B., Polymeris A., Wagner B., Seiffge D.J., Lyrer P., Algra A., Kappelle L.J., Al-Shahi Salman R., Jager H.R., Lip G.Y.H., Fischer U., El-Koussy M., Mas J.-L., Legrand L., Karayiannis C., Phan T., Gunkel S., Christ N., Abrigo J., Leung T., Chu W., Chappell F., Makin S., Hayden D., Williams D.J., Mess W.H., Nederkoorn P.J., Barbato C., Browning S., Wiegertjes K., Tuladhar A.M., Maaijwee N., Guevarra A.C., Yatawara C., Mendyk A.-M., Delmaire C., Kohler S., van Oostenbrugge R., Zhou Y., Xu C., Hilal S., Gyanwali B., Chen C., Lou M., Staals J., Bordet R., Kandiah N., de Leeuw F.-E., Simister R., Hendrikse J., Kelly P.J., Wardlaw J., Soo Y., Fluri F., Srikanth V., Calvet D., Jung S., Kwa V.I.H., Engelter S.T., Peters N., Smith E.E., Hara H., Yakushiji Y., Orken D.N., Fazekas F., Thijs V., Heo J.H., Mok V., Veltkamp R., Ay H., Imaizumi T., Gomez-Anson B., Lau K.K., Jouvent E., Rothwell P.M., Toyoda K., Bae H.-J., Marti-Fabregas J., Werring D.J., Harkness K., Shaw L., Sword J., Mohd Nor A., Sharma P., Kelly D., Harrington F., Randall M., Smith M., Mahawish K., Elmarim A., Esisi B., Cullen C., Nallasivam A., Price C., Barry A., Roffe C., Coyle J., Hassan A., Birns J., Cohen D., Sekaran L., Parry-Jones A., Parry A., Hargroves D., Proschel H., Datta P., Darawil K., Manoj A., Burn M., Patterson C., Giallombardo E., Smyth N., Mansoor S., Anwar I., Marsh R., Ispoglou S., Chadha D., Prabhakaran M., Meenakishundaram S., O'Connell J., Scott J., Krishnamurthy V., Aghoram P., McCormick M., Sprigg N., O'Mahony P., Cooper M., Choy L., Wilkinson P., Leach S., Caine S., Burger I., Gunathilagan G., Guyler P., Emsley H., Davis M., Manawadu D., Pasco K., Mamun M., Luder R., Sajid M., Okwera J., Warburton E., Saastamoinen K., England T., Putterill J., Flossman E., Power M., Dani K., Mangion D., Suman A., Corrigan J., Lawrence E., Vahidassr D., Shakeshaft C., Brown M., Charidimou A., Cohen H., Banerjee G., Houlden H., White M., Yousry T., Flossmann E., Muir K., Gratz P., Mattle H., Panos L., Korczyn A., Kliper E., Maeder P., Gass A., Pachai C., Bracoub L., Douste-Blazy M.-Y., Fratacci M.D., Vicaut E., Sato S., Miwa K., Fujita K., Ide T., Ma H., Ly J., Singhal S., Chandra R., Slater L.-A., Soufan C., Moran C., Traenka C., Thilemann S., Fladt J., Gensicke H., Bonati L., Kim B.J., Han M.-K., Kang J., Ko E., Yang M.H., Jang M.S., Murphy S., Carty F., Akijian L., Thornton J., Schembri M., Douven E., Delgado-Mederos R., Marin R., Camps-Renom P., Guisado-Alonso D., Nunez F., Medrano-Martorell S., Merino E., Iida K., Ikeda S., Irie H., Demirelli D.S., Medanta J.M., Zerna C., Hernandez M.V., Armitage P., Heye A., Munoz-Maniega S., Sakka E., Thrippleton M., Dennis M., Beigneux Y., Silva M., Venketasubramanian N., Ho S.L., Cheung R.T.F., Chan K.H., Teo K.C., Hui E., Kwan J.S.K., Chang R., Tse M.Y., Hoi C.P., Chan C.Y., Chan O.L., Cheung R.H.K., Wong E.K.M., Leung K.T., Tsang S.F., Ip H.L., Ma S.H., Ma K., Fong W.C., Li S.H., Li R., Ng P.W., Wong K.K., Liu W., Wong L., Ramos L., De Schryver E., Jobsis J., van der Sande J., Brouwers P., Roos Y., Stam J., Bakker S., Verbiest H., Schoonewille W., Linn C., Hertzberger L., van Gemert M., Berntsen P., Van Dam-Nolen D., Kooi M.E., Van der Lugt A., Koudstaal P., Leff A., Ward N., Nachev P., Perry R., Ozkan H., Mitchell J., Best J.G., Ambler G., Wilson D., Lee K.-J., Lim J.-S., Shiozawa M., Koga M., Li L., Lovelock C., Chabriat H., Hennerici M., Wong Y.K., Mak H.K.F., Prats-Sanchez L., Martinez-Domeno A., Inamura S., Yoshifuji K., Arsava E.M., Horstmann S., Purrucker J., Lam B.Y.K., Wong A., Kim Y.D., Song T.-J., Lemmens R., Eppinger S., Gattringer T., Uysal E., Tanriverdi Z., Bornstein N.M., Ben Assayag E., Hallevi H., Molad J., Nishihara M., Tanaka J., Coutts S.B., Polymeris A., Wagner B., Seiffge D.J., Lyrer P., Algra A., Kappelle L.J., Al-Shahi Salman R., Jager H.R., Lip G.Y.H., Fischer U., El-Koussy M., Mas J.-L., Legrand L., Karayiannis C., Phan T., Gunkel S., Christ N., Abrigo J., Leung T., Chu W., Chappell F., Makin S., Hayden D., Williams D.J., Mess W.H., Nederkoorn P.J., Barbato C., Browning S., Wiegertjes K., Tuladhar A.M., Maaijwee N., Guevarra A.C., Yatawara C., Mendyk A.-M., Delmaire C., Kohler S., van Oostenbrugge R., Zhou Y., Xu C., Hilal S., Gyanwali B., Chen C., Lou M., Staals J., Bordet R., Kandiah N., de Leeuw F.-E., Simister R., Hendrikse J., Kelly P.J., Wardlaw J., Soo Y., Fluri F., Srikanth V., Calvet D., Jung S., Kwa V.I.H., Engelter S.T., Peters N., Smith E.E., Hara H., Yakushiji Y., Orken D.N., Fazekas F., Thijs V., Heo J.H., Mok V., Veltkamp R., Ay H., Imaizumi T., Gomez-Anson B., Lau K.K., Jouvent E., Rothwell P.M., Toyoda K., Bae H.-J., Marti-Fabregas J., Werring D.J., Harkness K., Shaw L., Sword J., Mohd Nor A., Sharma P., Kelly D., Harrington F., Randall M., Smith M., Mahawish K., Elmarim A., Esisi B., Cullen C., Nallasivam A., Price C., Barry A., Roffe C., Coyle J., Hassan A., Birns J., Cohen D., Sekaran L., Parry-Jones A., Parry A., Hargroves D., Proschel H., Datta P., Darawil K., Manoj A., Burn M., Patterson C., Giallombardo E., Smyth N., Mansoor S., Anwar I., Marsh R., Ispoglou S., Chadha D., Prabhakaran M., Meenakishundaram S., O'Connell J., Scott J., Krishnamurthy V., Aghoram P., McCormick M., Sprigg N., O'Mahony P., Cooper M., Choy L., Wilkinson P., Leach S., Caine S., Burger I., Gunathilagan G., Guyler P., Emsley H., Davis M., Manawadu D., Pasco K., Mamun M., Luder R., Sajid M., Okwera J., Warburton E., Saastamoinen K., England T., Putterill J., Flossman E., Power M., Dani K., Mangion D., Suman A., Corrigan J., Lawrence E., Vahidassr D., Shakeshaft C., Brown M., Charidimou A., Cohen H., Banerjee G., Houlden H., White M., Yousry T., Flossmann E., Muir K., Gratz P., Mattle H., Panos L., Korczyn A., Kliper E., Maeder P., Gass A., Pachai C., Bracoub L., Douste-Blazy M.-Y., Fratacci M.D., Vicaut E., Sato S., Miwa K., Fujita K., Ide T., Ma H., Ly J., Singhal S., Chandra R., Slater L.-A., Soufan C., Moran C., Traenka C., Thilemann S., Fladt J., Gensicke H., Bonati L., Kim B.J., Han M.-K., Kang J., Ko E., Yang M.H., Jang M.S., Murphy S., Carty F., Akijian L., Thornton J., Schembri M., Douven E., Delgado-Mederos R., Marin R., Camps-Renom P., Guisado-Alonso D., Nunez F., Medrano-Martorell S., Merino E., Iida K., Ikeda S., Irie H., Demirelli D.S., Medanta J.M., Zerna C., Hernandez M.V., Armitage P., Heye A., Munoz-Maniega S., Sakka E., Thrippleton M., Dennis M., Beigneux Y., Silva M., Venketasubramanian N., Ho S.L., Cheung R.T.F., Chan K.H., Teo K.C., Hui E., Kwan J.S.K., Chang R., Tse M.Y., Hoi C.P., Chan C.Y., Chan O.L., Cheung R.H.K., Wong E.K.M., Leung K.T., Tsang S.F., Ip H.L., Ma S.H., Ma K., Fong W.C., Li S.H., Li R., Ng P.W., Wong K.K., Liu W., Wong L., Ramos L., De Schryver E., Jobsis J., van der Sande J., Brouwers P., Roos Y., Stam J., Bakker S., Verbiest H., Schoonewille W., Linn C., Hertzberger L., van Gemert M., Berntsen P., Van Dam-Nolen D., Kooi M.E., Van der Lugt A., Koudstaal P., Leff A., Ward N., Nachev P., Perry R., Ozkan H., and Mitchell J.

Abstract

Background: Balancing the risks of recurrent ischaemic stroke and intracranial haemorrhage is important for patients treated with antithrombotic therapy after ischaemic stroke or transient ischaemic attack. However, existing predictive models offer insufficient performance, particularly for assessing the risk of intracranial haemorrhage. We aimed to develop new risk scores incorporating clinical variables and cerebral microbleeds, an MRI biomarker of intracranial haemorrhage and ischaemic stroke risk. Method(s): We did a pooled analysis of individual-patient data from the Microbleeds International Collaborative Network (MICON), which includes 38 hospital-based prospective cohort studies from 18 countries. All studies recruited participants with previous ischaemic stroke or transient ischaemic attack, acquired baseline MRI allowing quantification of cerebral microbleeds, and followed-up participants for ischaemic stroke and intracranial haemorrhage. Participants not taking antithrombotic drugs were excluded. We developed Cox regression models to predict the 5-year risks of intracranial haemorrhage and ischaemic stroke, selecting candidate predictors on biological relevance and simplifying models using backward elimination. We derived integer risk scores for clinical use. We assessed model performance in internal validation, adjusted for optimism using bootstrapping. The study is registered on PROSPERO, CRD42016036602. Finding(s): The included studies recruited participants between Aug 28, 2001, and Feb 4, 2018. 15 766 participants had follow-up for intracranial haemorrhage, and 15 784 for ischaemic stroke. Over a median follow-up of 2 years, 184 intracranial haemorrhages and 1048 ischaemic strokes were reported. The risk models we developed included cerebral microbleed burden and simple clinical variables. Optimism-adjusted c indices were 0.73 (95% CI 0.69-0.77) with a calibration slope of 0.94 (0.81-1.06) for the intracranial haemorrhage model and 0.63 (0.62-0.65) w

Published
2021

17. Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies.

Author

Jung S., van Dam-Nolen D.H.K., Douven E., Delgado-Mederos, R., Marin R., Camps-Renom P., Guisado-Alonso D., Nunez F., Medrano-Martorell S., Merino E., Iida K., Ikeda S., Nishihara M., Irie H., Demirelli D.S., Medanta J.M., Zerna C., Hernandez M.V., Armitage P., Heye A., Munoz-Maniega S., Sakka E., Thrippleton M., Dennis M., Beigneux Y., Silva M., Venketasubramanian N., Ho S.L., Cheung R.T.F., Chan K.H., Teo K.C., Hui E., Kwan J.S.K., Chang R., Tse M.Y., Hoi C.P., Chan C.Y., Chan O.L., Cheung R.H.K., Wong E.K.M., Leung K.T., Tsang S.F., Ip H.L., Ma S.H., Ma K., Fong W.C., Li S.H., Li R., Ng P.W., Wong K.K., Liu W., Wong L., Ramos L., De Schryver E., Jobsis J., van der Sande J., Brouwers P., Roos Y., Stam J., Bakker S., Verbiest H., Schoonewille W., Linn C., Hertzberger L., van Gemert M., Berntsen P., Hendrikse J., Nederkoorn P., Mess W., Koudstaal P., Leff A., Ward N., Nachev P., Perry R., Ozkan H., Mitchell J., Wilson D., Ambler G., Lee K.-J., Lim J.-S., Shiozawa M., Koga M., Li L., Lovelock C., Chabriat H., Hennerici M., Wong Y.K., Mak H.K.F., Prats-Sanchez L., Martinez-Domeno A., Inamura S., Yoshifuji K., Arsava E.M., Horstmann S., Purrucker J., Lam B.Y.K., Wong A., Kim Y.D., Song T.-J., Schrooten M., Lemmens R., Eppinger S., Gattringer T., Uysal E., Tanriverdi Z., Bornstein N.M., Assayag E.B., Hallevi H., Tanaka J., Hara H., Coutts S.B., Hert L., Polymeris A., Seiffge D.J., Lyrer P., Algra A., Kappelle J., Al-Shahi Salman R., Jager H.R., Lip G.Y.H., Mattle H.P., Panos L.D., Mas J.-L., Legrand L., Karayiannis C., Phan T., Gunkel S., Christ N., Abrigo J., Leung T., Chu W., Chappell F., Makin S., Hayden D., Williams D.J., Kooi M.E., Barbato C., Browning S., Wiegertjes K., Tuladhar A.M., Maaijwee N., Guevarra C., Yatawara C., Mendyk A.-M., Delmaire C., Kohler S., van Oostenbrugge R., Zhou Y., Xu C., Hilal S., Gyanwali B., Chen C., Lou M., Staals J., Bordet R., Kandiah N., de Leeuw F.-E., Simister R., van der Lugt A., Kelly P.J., Wardlaw J.M., Soo Y., Fluri F., Srikanth V., Calvet D., Kwa V.I.H., Engelter S.T., Peters N., Smith E.E., Yakushiji Y., Orken D.N., Fazekas F., Thijs V., Heo J.H., Mok V., Veltkamp R., Ay H., Imaizumi T., Gomez-Anson B., Lau K.K., Jouvent E., Rothwell P.M., Toyoda K., Bae H.-J., Marti-Fabregas J., Werring D.J., Harkness K., Shaw L., Sword J., Mohd Nor A., Sharma P., Kelly D., Harrington F., Randall M., Smith M., Mahawish K., Elmarim A., Esisi B., Cullen C., Nallasivam A., Price C., Barry A., Roffe C., Coyle J., Hassan A., Birns J., Cohen D., Sekaran L., Parry-Jones A., Parry A., Hargroves D., Proschel H., Datta P., Darawil K., Manoj A., Burn M., Patterson C., Giallombardo E., Smyth N., Mansoor S., Anwar I., Marsh R., Ispoglou S., Chadha D., Prabhakaran M., Meenakishundaram S., O'Connell J., Scott J., Krishnamurthy V., Aghoram P., McCormick M., Sprigg N., O'Mahony P., Cooper M., Choy L., Wilkinson P., Leach S., Caine S., Burger I., Gunathilagan G., Guyler P., Emsley H., Davis M., Manawadu D., Pasco K., Mamun M., Luder R., Sajid M., Okwera J., Warburton E., Saastamoinen K., England T., Putterill J., Flossman E., Power M., Dani K., Mangion D., Suman A., Corrigan J., Lawrence E., Vahidassr D., Shakeshaft C., Brown M., Charidimou A., Cohen H., Banerjee G., Houlden H., White M., Yousry T., Flossmann E., Muir K., El-Koussy M., Gratz P., Molad J., Korczyn A., Kliper E., Maeder P., Gass A., Pachai C., Bracoub L., Douste-Blazy M.-Y., Fratacci M.D., Vicaut E., Sato S., Miwa K., Fujita K., Ide T., Ma H., Ly J., Singhal S., Chandra R., Slater L.-A., Soufan C., Moran C., Traenka C., Thilemann S., Fladt J., Gensicke H., Bonati L., Kim B.J., Han M.-K., Kang J., Ko E., Yang M.H., Jang M.S., Murphy S., Carty F., Akijian L., Thornton J., Schembri M., Jung S., van Dam-Nolen D.H.K., Douven E., Delgado-Mederos, R., Marin R., Camps-Renom P., Guisado-Alonso D., Nunez F., Medrano-Martorell S., Merino E., Iida K., Ikeda S., Nishihara M., Irie H., Demirelli D.S., Medanta J.M., Zerna C., Hernandez M.V., Armitage P., Heye A., Munoz-Maniega S., Sakka E., Thrippleton M., Dennis M., Beigneux Y., Silva M., Venketasubramanian N., Ho S.L., Cheung R.T.F., Chan K.H., Teo K.C., Hui E., Kwan J.S.K., Chang R., Tse M.Y., Hoi C.P., Chan C.Y., Chan O.L., Cheung R.H.K., Wong E.K.M., Leung K.T., Tsang S.F., Ip H.L., Ma S.H., Ma K., Fong W.C., Li S.H., Li R., Ng P.W., Wong K.K., Liu W., Wong L., Ramos L., De Schryver E., Jobsis J., van der Sande J., Brouwers P., Roos Y., Stam J., Bakker S., Verbiest H., Schoonewille W., Linn C., Hertzberger L., van Gemert M., Berntsen P., Hendrikse J., Nederkoorn P., Mess W., Koudstaal P., Leff A., Ward N., Nachev P., Perry R., Ozkan H., Mitchell J., Wilson D., Ambler G., Lee K.-J., Lim J.-S., Shiozawa M., Koga M., Li L., Lovelock C., Chabriat H., Hennerici M., Wong Y.K., Mak H.K.F., Prats-Sanchez L., Martinez-Domeno A., Inamura S., Yoshifuji K., Arsava E.M., Horstmann S., Purrucker J., Lam B.Y.K., Wong A., Kim Y.D., Song T.-J., Schrooten M., Lemmens R., Eppinger S., Gattringer T., Uysal E., Tanriverdi Z., Bornstein N.M., Assayag E.B., Hallevi H., Tanaka J., Hara H., Coutts S.B., Hert L., Polymeris A., Seiffge D.J., Lyrer P., Algra A., Kappelle J., Al-Shahi Salman R., Jager H.R., Lip G.Y.H., Mattle H.P., Panos L.D., Mas J.-L., Legrand L., Karayiannis C., Phan T., Gunkel S., Christ N., Abrigo J., Leung T., Chu W., Chappell F., Makin S., Hayden D., Williams D.J., Kooi M.E., Barbato C., Browning S., Wiegertjes K., Tuladhar A.M., Maaijwee N., Guevarra C., Yatawara C., Mendyk A.-M., Delmaire C., Kohler S., van Oostenbrugge R., Zhou Y., Xu C., Hilal S., Gyanwali B., Chen C., Lou M., Staals J., Bordet R., Kandiah N., de Leeuw F.-E., Simister R., van der Lugt A., Kelly P.J., Wardlaw J.M., Soo Y., Fluri F., Srikanth V., Calvet D., Kwa V.I.H., Engelter S.T., Peters N., Smith E.E., Yakushiji Y., Orken D.N., Fazekas F., Thijs V., Heo J.H., Mok V., Veltkamp R., Ay H., Imaizumi T., Gomez-Anson B., Lau K.K., Jouvent E., Rothwell P.M., Toyoda K., Bae H.-J., Marti-Fabregas J., Werring D.J., Harkness K., Shaw L., Sword J., Mohd Nor A., Sharma P., Kelly D., Harrington F., Randall M., Smith M., Mahawish K., Elmarim A., Esisi B., Cullen C., Nallasivam A., Price C., Barry A., Roffe C., Coyle J., Hassan A., Birns J., Cohen D., Sekaran L., Parry-Jones A., Parry A., Hargroves D., Proschel H., Datta P., Darawil K., Manoj A., Burn M., Patterson C., Giallombardo E., Smyth N., Mansoor S., Anwar I., Marsh R., Ispoglou S., Chadha D., Prabhakaran M., Meenakishundaram S., O'Connell J., Scott J., Krishnamurthy V., Aghoram P., McCormick M., Sprigg N., O'Mahony P., Cooper M., Choy L., Wilkinson P., Leach S., Caine S., Burger I., Gunathilagan G., Guyler P., Emsley H., Davis M., Manawadu D., Pasco K., Mamun M., Luder R., Sajid M., Okwera J., Warburton E., Saastamoinen K., England T., Putterill J., Flossman E., Power M., Dani K., Mangion D., Suman A., Corrigan J., Lawrence E., Vahidassr D., Shakeshaft C., Brown M., Charidimou A., Cohen H., Banerjee G., Houlden H., White M., Yousry T., Flossmann E., Muir K., El-Koussy M., Gratz P., Molad J., Korczyn A., Kliper E., Maeder P., Gass A., Pachai C., Bracoub L., Douste-Blazy M.-Y., Fratacci M.D., Vicaut E., Sato S., Miwa K., Fujita K., Ide T., Ma H., Ly J., Singhal S., Chandra R., Slater L.-A., Soufan C., Moran C., Traenka C., Thilemann S., Fladt J., Gensicke H., Bonati L., Kim B.J., Han M.-K., Kang J., Ko E., Yang M.H., Jang M.S., Murphy S., Carty F., Akijian L., Thornton J., and Schembri M.

Abstract

Background: Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. Method(s): We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602. Finding(s): Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1.34 years [IQR 0.19-2.44]) were included in our analyses. The adjusted hazard ratio [aHR] comparing patients with cerebral microbleeds to those without was 1.35 (95% CI 1.20-1.50) for the composite outcome of

Published
2019

18. Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies

Author

Wilson, D. (Duncan), Ambler, G. (Gareth), Lee, K.-J. (Keon-Joo), Lim, J.-S. (Jae-Sung), Shiozawa, M. (Masayuki), Koga, M. (Masatoshi), Li, L. (Linxin), Lovelock, C. (Caroline), Chabriat, H. (Hugues), Hennerici, M.G. (Michael), Wong, Y.K. (Yuen Kwun), Mak, H.K.F. (Henry Ka Fung), Prats-Sánchez, L. (Luis), Martínez-Domeño, A. (Alejandro), Inamura, S. (Shigeru), Yoshifuji, K. (Kazuhisa), Arsava, E.M. (Ethem Murat), Horstmann, S. (Solveig), Purrucker, J. (Jan), Lam, B.Y.K. (Bonnie Yin Ka), Wong, A. (Adrian), Kim, Y.D. (Young Dae), Song, T.-J. (Tae-Jin), Schrooten, M. (Maarten), Lemmens, R. (Robin), Eppinger, S. (Sebastian), Gattringer, T. (Thomas), Uysal, E. (Ender), Tanriverdi, Z. (Zeynep), Bornstein, S.R. (Stefan), Assayag, E.B. (Einor Ben), Hallevi, H. (Hen), Tanaka, J. (Jun), Hara, H. (Hideo), Coutts, S.B. (Shelagh B), Hert, L. (Lisa), Polymeris, A. (Alexandros), Seiffge, D.J. (David J), Lyrer, P.A. (Philippe), Algra, A. (Ale), Kappelle, L.J. (Jaap), Al-Shahi Salman, R. (Rustam), Jäger, H.R. (Rolf), Lip, G.Y.H. (Gregory Y H), Mattle, H., Panos, L.D. (Leonidas D), Mas, J.L. (J.), Legrand, L. (Laurence), Karayiannis, C. (Christopher), Phan, T.G. (Thanh), Gunkel, S. (Sarah), Christ, N. (Nicolas), Abrigo, J. (Jill), Leung, T. (Thomas), Chu, W. (Winnie), Chappell, F. (Francesca), Makin, S. (Stephen), Hayden, D. (Derek), Williams, D.J. (David J), Kooi, M.E. (M. Eline), van Dam-Nolen, D.H.K. (Dianne H K), Barbato, C. (Carmen), Browning, S. (Simone), Wiegertjes, K. (Kim), Tuladhar, A.M. (Anil M.), Maaijwee, N. (Noortje), Guevarra, C. (Christine), Yatawara, C. (Chathuri), Mendyk, A.-M. (Anne-Marie), Delmaire, C. (Christine), Köhler, S. (Sebastian), Oostenbrugge, R.J. (Robert) van, Zhou, Y. (Ying), Xu, C. (Chao), Hilal, S. (Saima), Gyanwali, B. (Bibek), Chen, C. (Christopher), Lou, M. (Min), Staals, J. (Julie), Bordet, R. (Régis), Kandiah, N. (Nagaendran), Leeuw, H.F. (Frank) de, Simister, R. (Robert), Lugt, A. (Aad) van der, Kelly, P.J. (Peter J), Wardlaw, J.M. (J.), Soo, Y. (Yannie), Fluri, F. (Felix), Srikanth, V. (Velandai), Calvet, D. (David), Jung, S. (Simon), Kwa, V.I.H., Engelter, S.T. (Stefan), Peters, N. (Nils), Smith, E.E. (Eric), Yakushiji, Y. (Yusuke), Orken, D.N. (Dilek Necioglu), Fazekas, F. (Franz), Thijs, V. (Vincent), Heo, J.H. (Ji Hoe), Mok, V. (Vincent), Veltkamp, R. (Roland), Ay, H. (Hakan), Imaizumi, T. (Toshio), Gomez-Anson, B. (Beatriz), Lau, K.K. (Kui Kai), Jouvent, E. (Eric), Rothwell, P.M. (Peter), Toyoda, K. (Kazunori), Bae, H.-J. (Hee-Joon), Marti-Fabregas, J. (Joan), Werring, D.J. (David), Harkness, K. (Kirsty), Shaw, L. (Louise), Sword, J. (Jane), Mohd Nor, A. (Azlisham), Sharma, P. (Pankaj), Kelly, D. (Deborah), Harrington, F. (Frances), Randall, M. (Marc), Smith, M. (Matthew), Mahawish, K. (Karim), Elmarim, A. (Abduelbaset), Esisi, B. (Bernard), Cullen, C. (Claire), Nallasivam, A. (Arumug), Price, C. (Christopher), Barry, A. (Adrian), Roffe, C. (Christine), Coyle, J. (John), Hassan, A. (Ahamad), Birns, J. (Jonathan), Cohen, D. (David), Sekaran, L. (Lakshmanan), Parry-Jones, A. (Adrian), Parry, A. (Anthea), Hargroves, D. (David), Proschel, H. (Harald), Datta, P. (Prabel), Darawil, K. (Khaled), Manoj, A. (Aravindakshan), Burn, M. (Mathew), Patterson, C. (Chris), Giallombardo, E. (Elio), Smyth, N. (Nigel), Mansoor, S. (Syed), Anwar, I. (Ijaz), Marsh, R. (Rachel), Ispoglou, S. (Sissi), Chadha, D. (Dinesh), Prabhakaran, M. (Mathuri), Meenakishundaram, S. (Sanjeevikumar), O'Connell, J. (Janice), Scott, J. (Jon), Krishnamurthy, V. (Vinodh), Aghoram, P. (Prasanna), McCormick, M. (Michael), Sprigg, N. (Nikola), O'Mahony, P. (Paul), Cooper, M. (Martin), Choy, L. (Lillian), Wilkinson, P. (Peter), Leach, S. (Simon), Caine, S. (Sarah), Burger, I. (Ilse), Gunathilagan, G. (Gunaratam), Guyler, P. (Paul), Emsley, H. (Hedley), Davis, M. (Michelle), Manawadu, D. (Dulka), Pasco, K. (Kath), Mamun, M. (Maam), Luder, R. (Robert), Sajid, M. (Mahmud), Okwera, J. (James), Warburton, E. (Elizabeth), Saastamoinen, K. (Kari), England, T. (Timothy), Putterill, J. (Janet), Flossman, E. (Enrico), Power, M. (Michael), Dani, K. (Krishna), Mangion, D. (David), Suman, A. (Appu), Corrigan, J. (John), Lawrence, E. (Enas), Vahidassr, D. (Djamil), Shakeshaft, C. (Clare), Brown, M. (Martin), Charidimou, A. (Andreas), Cohen, H. (Hannah), Banerjee, G. (Gargi), Houlden, H. (Henry), White, M. (Mark), Yousry, T. (Tarek), Flossmann, E. (Enrico), Muir, K. (Keith), El-Koussy, M. (Marwan), Gratz, P. (Pascal), Molad, J. (Jeremy), Korczyn, A.D. (A.), Kliper, E. (Efrat), Maeder, P. (Philippe), Gass, A. (Achim), Pachai, C. (Chahin), Bracoub, L. (Luc), Douste-Blazy, M.-Y. (Marie-Yvonne), Fratacci, M.D. (Marie Dominique), Vicaut, E. (Eric), Sato, S. (Shoichiro), Miwa, K. (Kaori), Fujita, K. (Kyohei), Ide, T. (Toshihiro), Ma, H. (Henry), Ly, J. (John), Singhal, S. (Shahoo), Chandra, R. (Ronil), Slater, L.-A. (Lee-Anne), Soufan, C. (Cathy), Moran, C. (Christopher), Traenka, C. (Christopher), Thilemann, S. (Sebastian), Fladt, J. (Joachim), Gensicke, H. (Henrik), Bonati, L. (Leo), Kim, B.J. (Beom Joon), Han, M.-K. (Moon-Ku), Kang, J. (Jihoon), Ko, E. (Eunbin), Yang, M.H. (Mi Hwa), Jang, M.S. (Myung Suk), Murphy, S. (Sean), Carty, F. (Fiona), Akijian, L. (Layan), Thornton, J. (John), Schembri, M. (Mark), Douven, E. (Elles), Delgado-Mederos;, R. (Raquel), Marín, R. (Rebeca), Camps-Renom, P. (Pol), Guisado-Alonso, D. (Daniel), Nuñez, F. (Fidel), Medrano-Martorell, S. (Santiago), Merino, E. (Elisa), Iida, K. (Kotaro), Ikeda, S. (Syuhei), Nishihara, M. (Masashi), Irie, H. (Hiroyuki), Demirelli, D.S. (Derya Selcuk), Medanta, J.M. (Jayesh Modi), Zerna, C. (Charlotte), Hernández, M.V. (Maria Valdés), Armitage, P. (Paul), Heye, A. (Anna), Muñoz Maniega, S. (Susana), Sakka, E. (Eleni), Thrippleton, M. (Michael), Dennis, M.S. (M.), Beigneux, Y. (Ysoline), Silva, M. (Mauro), Venketasubramanian, N. (Narayanaswamy), Ho, S.L. (Shu Leung), Cheung, R.T.F. (Raymond Tak Fai), Chan, K.H. (Koon Ho), Teo, K.C. (Kay Cheong), Hui, E. (Edward), Kwan, J.S.K. (Joseph Shiu Kwong), Chang, R. (Richard), Tse, M.Y. (Man Yu), Hoi, C.P. (Chu Peng), Chan, C.Y. (Chung Yan), Chan, O.L. (Oi Ling), Cheung, R.H.K. (Ryan Hoi Kit), Wong, E.K.M. (Edmund Ka Ming), Leung, K.T. (Kam Tat), Tsang, S.F. (Suk Fung), Ip, H.L. (Hing Lung), Ma, S.H. (Sze Ho), Ma, K. (Karen), Fong, W.C. (Wing Chi), Li, S.H. (Siu Hung), Li, R. (Richard), Ng, P.W. (Ping Wing), Wong, K.K. (Kwok Kui), Liu, W. (Wenyan), Wong, L. (Lawrence), Ramos, L. (Lino), Schryver, E.L.L.M. (Els) de, Jöbsis, J. (Joost), van der Sande, J. (Jaap), Brouwers, P.J. (Paul), Roos, Y.B.W.E.M. (Yvo), Stam, J. (Jan), Bakker, S.L.M. (Stef), Verbiest, H. (Henk), Schoonewille, W. (Wouter), Linn, C. (Cisca), Hertzberger, L., Gemert, M. (Maarten) van, Berntsen, P. (Paul), Hendrikse, J. (Jeroen), Nederkoorn, P.J. (Paul), Mess, W.H. (Werner), Koudstaal, P.J. (Peter), Leff, A. (Alexander), Ward, N. (Nicholas), Nachev, P. (Parashkev), Perry, R. (Richard), Ozkan, H. (Hatice), Mitchell, J. (John), Wilson, D. (Duncan), Ambler, G. (Gareth), Lee, K.-J. (Keon-Joo), Lim, J.-S. (Jae-Sung), Shiozawa, M. (Masayuki), Koga, M. (Masatoshi), Li, L. (Linxin), Lovelock, C. (Caroline), Chabriat, H. (Hugues), Hennerici, M.G. (Michael), Wong, Y.K. (Yuen Kwun), Mak, H.K.F. (Henry Ka Fung), Prats-Sánchez, L. (Luis), Martínez-Domeño, A. (Alejandro), Inamura, S. (Shigeru), Yoshifuji, K. (Kazuhisa), Arsava, E.M. (Ethem Murat), Horstmann, S. (Solveig), Purrucker, J. (Jan), Lam, B.Y.K. (Bonnie Yin Ka), Wong, A. (Adrian), Kim, Y.D. (Young Dae), Song, T.-J. (Tae-Jin), Schrooten, M. (Maarten), Lemmens, R. (Robin), Eppinger, S. (Sebastian), Gattringer, T. (Thomas), Uysal, E. (Ender), Tanriverdi, Z. (Zeynep), Bornstein, S.R. (Stefan), Assayag, E.B. (Einor Ben), Hallevi, H. (Hen), Tanaka, J. (Jun), Hara, H. (Hideo), Coutts, S.B. (Shelagh B), Hert, L. (Lisa), Polymeris, A. (Alexandros), Seiffge, D.J. (David J), Lyrer, P.A. (Philippe), Algra, A. (Ale), Kappelle, L.J. (Jaap), Al-Shahi Salman, R. (Rustam), Jäger, H.R. (Rolf), Lip, G.Y.H. (Gregory Y H), Mattle, H., Panos, L.D. (Leonidas D), Mas, J.L. (J.), Legrand, L. (Laurence), Karayiannis, C. (Christopher), Phan, T.G. (Thanh), Gunkel, S. (Sarah), Christ, N. (Nicolas), Abrigo, J. (Jill), Leung, T. (Thomas), Chu, W. (Winnie), Chappell, F. (Francesca), Makin, S. (Stephen), Hayden, D. (Derek), Williams, D.J. (David J), Kooi, M.E. (M. Eline), van Dam-Nolen, D.H.K. (Dianne H K), Barbato, C. (Carmen), Browning, S. (Simone), Wiegertjes, K. (Kim), Tuladhar, A.M. (Anil M.), Maaijwee, N. (Noortje), Guevarra, C. (Christine), Yatawara, C. (Chathuri), Mendyk, A.-M. (Anne-Marie), Delmaire, C. (Christine), Köhler, S. (Sebastian), Oostenbrugge, R.J. (Robert) van, Zhou, Y. (Ying), Xu, C. (Chao), Hilal, S. (Saima), Gyanwali, B. (Bibek), Chen, C. (Christopher), Lou, M. (Min), Staals, J. (Julie), Bordet, R. (Régis), Kandiah, N. (Nagaendran), Leeuw, H.F. (Frank) de, Simister, R. (Robert), Lugt, A. (Aad) van der, Kelly, P.J. (Peter J), Wardlaw, J.M. (J.), Soo, Y. (Yannie), Fluri, F. (Felix), Srikanth, V. (Velandai), Calvet, D. (David), Jung, S. (Simon), Kwa, V.I.H., Engelter, S.T. (Stefan), Peters, N. (Nils), Smith, E.E. (Eric), Yakushiji, Y. (Yusuke), Orken, D.N. (Dilek Necioglu), Fazekas, F. (Franz), Thijs, V. (Vincent), Heo, J.H. (Ji Hoe), Mok, V. (Vincent), Veltkamp, R. (Roland), Ay, H. (Hakan), Imaizumi, T. (Toshio), Gomez-Anson, B. (Beatriz), Lau, K.K. (Kui Kai), Jouvent, E. (Eric), Rothwell, P.M. (Peter), Toyoda, K. (Kazunori), Bae, H.-J. (Hee-Joon), Marti-Fabregas, J. (Joan), Werring, D.J. (David), Harkness, K. (Kirsty), Shaw, L. (Louise), Sword, J. (Jane), Mohd Nor, A. (Azlisham), Sharma, P. (Pankaj), Kelly, D. (Deborah), Harrington, F. (Frances), Randall, M. (Marc), Smith, M. (Matthew), Mahawish, K. (Karim), Elmarim, A. (Abduelbaset), Esisi, B. (Bernard), Cullen, C. (Claire), Nallasivam, A. (Arumug), Price, C. (Christopher), Barry, A. (Adrian), Roffe, C. (Christine), Coyle, J. (John), Hassan, A. (Ahamad), Birns, J. (Jonathan), Cohen, D. (David), Sekaran, L. (Lakshmanan), Parry-Jones, A. (Adrian), Parry, A. (Anthea), Hargroves, D. (David), Proschel, H. (Harald), Datta, P. (Prabel), Darawil, K. (Khaled), Manoj, A. (Aravindakshan), Burn, M. (Mathew), Patterson, C. (Chris), Giallombardo, E. (Elio), Smyth, N. (Nigel), Mansoor, S. (Syed), Anwar, I. (Ijaz), Marsh, R. (Rachel), Ispoglou, S. (Sissi), Chadha, D. (Dinesh), Prabhakaran, M. (Mathuri), Meenakishundaram, S. (Sanjeevikumar), O'Connell, J. (Janice), Scott, J. (Jon), Krishnamurthy, V. (Vinodh), Aghoram, P. (Prasanna), McCormick, M. (Michael), Sprigg, N. (Nikola), O'Mahony, P. (Paul), Cooper, M. (Martin), Choy, L. (Lillian), Wilkinson, P. (Peter), Leach, S. (Simon), Caine, S. (Sarah), Burger, I. (Ilse), Gunathilagan, G. (Gunaratam), Guyler, P. (Paul), Emsley, H. (Hedley), Davis, M. (Michelle), Manawadu, D. (Dulka), Pasco, K. (Kath), Mamun, M. (Maam), Luder, R. (Robert), Sajid, M. (Mahmud), Okwera, J. (James), Warburton, E. (Elizabeth), Saastamoinen, K. (Kari), England, T. (Timothy), Putterill, J. (Janet), Flossman, E. (Enrico), Power, M. (Michael), Dani, K. (Krishna), Mangion, D. (David), Suman, A. (Appu), Corrigan, J. (John), Lawrence, E. (Enas), Vahidassr, D. (Djamil), Shakeshaft, C. (Clare), Brown, M. (Martin), Charidimou, A. (Andreas), Cohen, H. (Hannah), Banerjee, G. (Gargi), Houlden, H. (Henry), White, M. (Mark), Yousry, T. (Tarek), Flossmann, E. (Enrico), Muir, K. (Keith), El-Koussy, M. (Marwan), Gratz, P. (Pascal), Molad, J. (Jeremy), Korczyn, A.D. (A.), Kliper, E. (Efrat), Maeder, P. (Philippe), Gass, A. (Achim), Pachai, C. (Chahin), Bracoub, L. (Luc), Douste-Blazy, M.-Y. (Marie-Yvonne), Fratacci, M.D. (Marie Dominique), Vicaut, E. (Eric), Sato, S. (Shoichiro), Miwa, K. (Kaori), Fujita, K. (Kyohei), Ide, T. (Toshihiro), Ma, H. (Henry), Ly, J. (John), Singhal, S. (Shahoo), Chandra, R. (Ronil), Slater, L.-A. (Lee-Anne), Soufan, C. (Cathy), Moran, C. (Christopher), Traenka, C. (Christopher), Thilemann, S. (Sebastian), Fladt, J. (Joachim), Gensicke, H. (Henrik), Bonati, L. (Leo), Kim, B.J. (Beom Joon), Han, M.-K. (Moon-Ku), Kang, J. (Jihoon), Ko, E. (Eunbin), Yang, M.H. (Mi Hwa), Jang, M.S. (Myung Suk), Murphy, S. (Sean), Carty, F. (Fiona), Akijian, L. (Layan), Thornton, J. (John), Schembri, M. (Mark), Douven, E. (Elles), Delgado-Mederos;, R. (Raquel), Marín, R. (Rebeca), Camps-Renom, P. (Pol), Guisado-Alonso, D. (Daniel), Nuñez, F. (Fidel), Medrano-Martorell, S. (Santiago), Merino, E. (Elisa), Iida, K. (Kotaro), Ikeda, S. (Syuhei), Nishihara, M. (Masashi), Irie, H. (Hiroyuki), Demirelli, D.S. (Derya Selcuk), Medanta, J.M. (Jayesh Modi), Zerna, C. (Charlotte), Hernández, M.V. (Maria Valdés), Armitage, P. (Paul), Heye, A. (Anna), Muñoz Maniega, S. (Susana), Sakka, E. (Eleni), Thrippleton, M. (Michael), Dennis, M.S. (M.), Beigneux, Y. (Ysoline), Silva, M. (Mauro), Venketasubramanian, N. (Narayanaswamy), Ho, S.L. (Shu Leung), Cheung, R.T.F. (Raymond Tak Fai), Chan, K.H. (Koon Ho), Teo, K.C. (Kay Cheong), Hui, E. (Edward), Kwan, J.S.K. (Joseph Shiu Kwong), Chang, R. (Richard), Tse, M.Y. (Man Yu), Hoi, C.P. (Chu Peng), Chan, C.Y. (Chung Yan), Chan, O.L. (Oi Ling), Cheung, R.H.K. (Ryan Hoi Kit), Wong, E.K.M. (Edmund Ka Ming), Leung, K.T. (Kam Tat), Tsang, S.F. (Suk Fung), Ip, H.L. (Hing Lung), Ma, S.H. (Sze Ho), Ma, K. (Karen), Fong, W.C. (Wing Chi), Li, S.H. (Siu Hung), Li, R. (Richard), Ng, P.W. (Ping Wing), Wong, K.K. (Kwok Kui), Liu, W. (Wenyan), Wong, L. (Lawrence), Ramos, L. (Lino), Schryver, E.L.L.M. (Els) de, Jöbsis, J. (Joost), van der Sande, J. (Jaap), Brouwers, P.J. (Paul), Roos, Y.B.W.E.M. (Yvo), Stam, J. (Jan), Bakker, S.L.M. (Stef), Verbiest, H. (Henk), Schoonewille, W. (Wouter), Linn, C. (Cisca), Hertzberger, L., Gemert, M. (Maarten) van, Berntsen, P. (Paul), Hendrikse, J. (Jeroen), Nederkoorn, P.J. (Paul), Mess, W.H. (Werner), Koudstaal, P.J. (Peter), Leff, A. (Alexander), Ward, N. (Nicholas), Nachev, P. (Parashkev), Perry, R. (Richard), Ozkan, H. (Hatice), and Mitchell, J. (John)

Abstract

Background: Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. Methods: We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or

Published
2019
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34. Genetic and environmental risk factors for Parkinson's disease in a Chinese population

Author

Hung, W.T., Chan, D.K.Y., Hui, E., Woo, J., Orr, K., Kwok, T., Kay, R., Ho, S.C., Pang, C.P., Law, L.K., Ng, P.W., and Leung, M.F.

Abstract

An epidemiological study of the environmental and genetic factors as well as the possible interplay between them was conducted among 215 patients with Parkinson's disease and 313 controls in a Chinese population in Hong Kong. In univariate analysis, a regular tea drinking habit was found to be a protective factor, which had not been reported before. Smoking (a protective factor), family history, duration of pesticide exposure (in years) in farming and pesticide exposure during farming in women (both risk factors) have been reported previously. In multivariate analysis, current smoking reached borderline significance at the 5% level and the variables, years exposed to pesticides and family history were significant at the 10% level. By contrast with the common occurrence of polymorphism of the CYP2D6 gene (a gene involved with xenobiotic metabolism) in white people, it is very rare in China and is not thought to be a significant factor contributing to Parkinson's disease in Chinese people.

Published
1998

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