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1. Pragmatic solutions to reduce the global burden of stroke: a World Stroke Organization–Lancet Neurology Commission

Author

Feigin, V, Owolabi, M, Abd-Allah, F, Akinyemi, R, Bhattacharjee, N, Brainin, M, Cao, J, Caso, V, Dalton, B, Davis, A, Dempsey, R, Duprey, J, Feng, W, Ford, G, Gall, S, Gandhi, D, Good, D, Hachinski, V, Hacke, W, Hankey, G, Ishida, M, Johnson, W, Kim, J, Lavados, P, Lindsay, P, Mahal, A, Martins, S, Murray, C, Nguyen, T, Norrving, B, Olaiya, M, Olalusi, O, Pandian, J, Phan, H, Platz, T, Ranta, A, Rehman, S, Roth, G, Sebastian, I, Smith, A, Suwanwela, N, Sylaja, P, Thapa, R, Thrift, A, Uvere, E, Vollset, S, Yavagal, D, Yaria, J, Abera, S, Ibrahim, N, Liu, L, Ovbiagele, B, Piradov, M, Abanto, C, Addissie, A, Adeleye, A, Adilbekov, Y, Adilbekova, B, Adoukonou, T, Aguiar de Sousa, D, Akhmetzhanova, Z, Akpalu, A, El Alaoui-Faris, M, Ameriso, S, Andonova, S, Arsovska, A, Awoniyi, F, Bakhiet, M, Barboza, M, Basri, H, Bath, P, Bereczki, D, Beretta, S, Berkowitz, A, Bernhardt, J, Berzina, G, Bhavsar, B, Bisharyan, M, Bohara, M, Bovet, P, Budincevic, H, Cadilhac, D, Cerimagic, D, Charway-Felli, A, Chen, C, Chin, J, Christensen, H, Chwojnicki, K, Conforto, A, Correia, M, Mora Cuervo, D, Czlonkowska, A, D'Amelio, M, Danielyan, K, Davis, S, Demarin, V, Demchuk, A, Dichgans, M, Dokova, K, Donnan, G, Duran, J, Ekeng, G, Elkind, M, Endres, M, Fischer, U, Flomin, Y, Gankpe, F, Gavidia, M, Gaye Saavedra, A, Gebreyohanns, M, George, M, Gierlotka, M, Giroud, M, Gnedovskaya, E, Goncalves, I, Gongora-Rivera, F, Gunaratne, P, Hamadeh, R, Hamzat, T, Heldner, M, Ibrahim, E, Ihle-Hansen, H, Jee, S, Jiann-Shing, J, Johnston, S, Jovanovic, D, Jurjans, K, Kalani, R, Kalkonde, Y, Kamenova, S, Karaszewski, B, Kelly, P, Kiechl, S, Kondybayeva, A, Korv, J, Kozera, G, Kravchenko, M, Krespi, Y, Krishnamurthi, R, Kruja, J, Kutluk, K, Langhorne, P, Law, Z, Lebedynets, D, Lee, T, Leung, T, Liebeskind, D, Lopez-Jaramillo, P, Lotufo, P, Machline-Carrion, M, Maia, L, Malojcic, B, Markus, H, Marquez-Romero, J, Medina, M, Medukhanova, S, Mehndiratta, M, Miglane, E, Mihejeva, I, Mikulik, R, Mirrakhimov, E, Mohl, S, Munakomi, S, Murphy, S, Musa, K, Nasreldein, A, Nogueira, R, Nolte, C, Noubiap, J, Novarro-Escudero, N, Ocampo, C, O'Donnell, M, Ogun, Y, Ogunniyi, A, Oraby, M, Orken, D, Ozdemir, A, Ozturk, S, Paccot, M, Pereira, T, Peeters, A, Potpara, T, Proios, H, Rathore, F, Sacco, R, Sahathevan, R, Sandset, E, Renato Santos, I, Saposnik, G, Sarfo, F, Sargento-Freitas, J, Sharma, M, Shaw, L, Sheth, K, Shin, Y, Shobhana, A, Silva, S, Tedim Cruz, V, Thakur, K, Thapa, L, Toni, D, Topcuoglu, M, Torales, J, Towfighi, A, Truelsen, T, Tsiskaridze, A, Tulloch-Reid, M, Useche, J, Vanacker, P, Vassilopoulou, S, Vukorepa, G, Vuletic, V, Wahab, K, Wang, W, Wijeratne, T, Wojtyniak, B, Wolfe, C, Yacouba, M, Yang, J, Yifru, Y, Yock-Corrales, A, Yonemoto, N, Yperzeele, L, Zagozdzon, P, Feigin V. L., Owolabi M. O., Abd-Allah F., Akinyemi R. O., Bhattacharjee N. V., Brainin M., Cao J., Caso V., Dalton B., Davis A., Dempsey R., Duprey J., Feng W., Ford G. A., Gall S., Gandhi D., Good D. C., Hachinski V., Hacke W., Hankey G. J., Ishida M., Johnson W., Kim J., Lavados P., Lindsay P., Mahal A., Martins S., Murray C., Nguyen T. P., Norrving B., Olaiya M. T., Olalusi O. V., Pandian J., Phan H., Platz T., Ranta A., Rehman S., Roth G., Sebastian I. A., Smith A. E., Suwanwela N. C., Sylaja P. N., Thapa R., Thrift A. G., Uvere E., Vollset S. E., Yavagal D., Yaria J., Abera S. F., Akinyemi R., Dempsey R. J., Ibrahim N. M., Liu L., Ovbiagele B., Piradov M., Suwanwela N., Abanto C., Addissie A., Adeleye A. O., Adilbekov Y., Adilbekova B., Adoukonou T. A., Aguiar de Sousa D., Akhmetzhanova Z., Akpalu A., El Alaoui-Faris M., Ameriso S. F., Andonova S., Arsovska A., Awoniyi F. E., Bakhiet M., Barboza M. A., Basri H., Bath P. M., Bereczki D., Beretta S., Berkowitz A. L., Bernhardt J., Berzina G., Bhavsar B., Bisharyan M. S., Bohara M., Bovet P., Budincevic H., Cadilhac D. A., Cerimagic D., Charway-Felli A., Chen C., Chin J. H., Christensen H., Chwojnicki K., Conforto A. B., Correia M., Mora Cuervo D. L., Czlonkowska A., D'Amelio M., Danielyan K. E., Davis S., Demarin V., Demchuk A. M., Dichgans M., Dokova K., Donnan G., Duran J. C., Ekeng G., Elkind M. S., Endres M., Fischer U., Flomin Y., Gankpe F., Gavidia M., Gaye Saavedra A., Gebreyohanns M., George M., Gierlotka M., Giroud M., Gnedovskaya E. V., Goncalves I. P., Gongora-Rivera F., Gunaratne P. S., Hamadeh R. R., Hamzat T. -H. K., Heldner M. R., Ibrahim E., Ihle-Hansen H., Jee S., Jiann-Shing J., Johnston S. C., Jovanovic D., Jurjans K., Kalani R., Kalkonde Y., Kamenova S., Karaszewski B., Kelly P., Kiechl S., Kondybayeva A., Korv J., Kozera G., Kravchenko M., Krespi Y., Krishnamurthi R., Kruja J., Kutluk K., Langhorne P., Law Z. K., Lebedynets D., Lee T. -H., Leung T. W., Liebeskind D. S., Lopez-Jaramillo P., Lotufo P. A., Machline-Carrion M. J., Maia L. F., Malojcic B., Markus H. S., Marquez-Romero J. M., Medina M. T., Medukhanova S., Mehndiratta M. M., Miglane E., Mihejeva I., Mikulik R., Mirrakhimov E., Mohl S., Munakomi S., Murphy S., Musa K. I., Nasreldein A., Nogueira R. G., Nolte C. H., Noubiap J. J., Novarro-Escudero N., Ocampo C., O'Donnell M., Ogun Y., Ogunniyi A., Oraby M. I., Orken D. N., Ozdemir A. O., Ozturk S., Paccot M., Pereira T., Peeters A., Potpara T., Proios H., Rathore F. A., Sacco R. L., Sahathevan R., Sandset E. S., Renato Santos I., Saposnik G., Sarfo F. S., Sargento-Freitas J., Sharma M., Shaw L., Sheth K. N., Shin Y. -I., Shobhana A., Silva S. N., Tedim Cruz V., Thakur K., Thapa L. J., Toni D., Topcuoglu M. A., Torales J., Towfighi A., Truelsen T., Tsiskaridze A., Tulloch-Reid M., Useche J. N., Vanacker P., Vassilopoulou S., Vukorepa G., Vuletic V., Wahab K. W., Wang W., Wijeratne T., Wojtyniak B., Wolfe C., Yacouba M. N., Yang J., Yifru Y. M., Yock-Corrales A., Yonemoto N., Yperzeele L., Zagozdzon P., Feigin, V, Owolabi, M, Abd-Allah, F, Akinyemi, R, Bhattacharjee, N, Brainin, M, Cao, J, Caso, V, Dalton, B, Davis, A, Dempsey, R, Duprey, J, Feng, W, Ford, G, Gall, S, Gandhi, D, Good, D, Hachinski, V, Hacke, W, Hankey, G, Ishida, M, Johnson, W, Kim, J, Lavados, P, Lindsay, P, Mahal, A, Martins, S, Murray, C, Nguyen, T, Norrving, B, Olaiya, M, Olalusi, O, Pandian, J, Phan, H, Platz, T, Ranta, A, Rehman, S, Roth, G, Sebastian, I, Smith, A, Suwanwela, N, Sylaja, P, Thapa, R, Thrift, A, Uvere, E, Vollset, S, Yavagal, D, Yaria, J, Abera, S, Ibrahim, N, Liu, L, Ovbiagele, B, Piradov, M, Abanto, C, Addissie, A, Adeleye, A, Adilbekov, Y, Adilbekova, B, Adoukonou, T, Aguiar de Sousa, D, Akhmetzhanova, Z, Akpalu, A, El Alaoui-Faris, M, Ameriso, S, Andonova, S, Arsovska, A, Awoniyi, F, Bakhiet, M, Barboza, M, Basri, H, Bath, P, Bereczki, D, Beretta, S, Berkowitz, A, Bernhardt, J, Berzina, G, Bhavsar, B, Bisharyan, M, Bohara, M, Bovet, P, Budincevic, H, Cadilhac, D, Cerimagic, D, Charway-Felli, A, Chen, C, Chin, J, Christensen, H, Chwojnicki, K, Conforto, A, Correia, M, Mora Cuervo, D, Czlonkowska, A, D'Amelio, M, Danielyan, K, Davis, S, Demarin, V, Demchuk, A, Dichgans, M, Dokova, K, Donnan, G, Duran, J, Ekeng, G, Elkind, M, Endres, M, Fischer, U, Flomin, Y, Gankpe, F, Gavidia, M, Gaye Saavedra, A, Gebreyohanns, M, George, M, Gierlotka, M, Giroud, M, Gnedovskaya, E, Goncalves, I, Gongora-Rivera, F, Gunaratne, P, Hamadeh, R, Hamzat, T, Heldner, M, Ibrahim, E, Ihle-Hansen, H, Jee, S, Jiann-Shing, J, Johnston, S, Jovanovic, D, Jurjans, K, Kalani, R, Kalkonde, Y, Kamenova, S, Karaszewski, B, Kelly, P, Kiechl, S, Kondybayeva, A, Korv, J, Kozera, G, Kravchenko, M, Krespi, Y, Krishnamurthi, R, Kruja, J, Kutluk, K, Langhorne, P, Law, Z, Lebedynets, D, Lee, T, Leung, T, Liebeskind, D, Lopez-Jaramillo, P, Lotufo, P, Machline-Carrion, M, Maia, L, Malojcic, B, Markus, H, Marquez-Romero, J, Medina, M, Medukhanova, S, Mehndiratta, M, Miglane, E, Mihejeva, I, Mikulik, R, Mirrakhimov, E, Mohl, S, Munakomi, S, Murphy, S, Musa, K, Nasreldein, A, Nogueira, R, Nolte, C, Noubiap, J, Novarro-Escudero, N, Ocampo, C, O'Donnell, M, Ogun, Y, Ogunniyi, A, Oraby, M, Orken, D, Ozdemir, A, Ozturk, S, Paccot, M, Pereira, T, Peeters, A, Potpara, T, Proios, H, Rathore, F, Sacco, R, Sahathevan, R, Sandset, E, Renato Santos, I, Saposnik, G, Sarfo, F, Sargento-Freitas, J, Sharma, M, Shaw, L, Sheth, K, Shin, Y, Shobhana, A, Silva, S, Tedim Cruz, V, Thakur, K, Thapa, L, Toni, D, Topcuoglu, M, Torales, J, Towfighi, A, Truelsen, T, Tsiskaridze, A, Tulloch-Reid, M, Useche, J, Vanacker, P, Vassilopoulou, S, Vukorepa, G, Vuletic, V, Wahab, K, Wang, W, Wijeratne, T, Wojtyniak, B, Wolfe, C, Yacouba, M, Yang, J, Yifru, Y, Yock-Corrales, A, Yonemoto, N, Yperzeele, L, Zagozdzon, P, Feigin V. L., Owolabi M. O., Abd-Allah F., Akinyemi R. O., Bhattacharjee N. V., Brainin M., Cao J., Caso V., Dalton B., Davis A., Dempsey R., Duprey J., Feng W., Ford G. A., Gall S., Gandhi D., Good D. C., Hachinski V., Hacke W., Hankey G. J., Ishida M., Johnson W., Kim J., Lavados P., Lindsay P., Mahal A., Martins S., Murray C., Nguyen T. P., Norrving B., Olaiya M. T., Olalusi O. V., Pandian J., Phan H., Platz T., Ranta A., Rehman S., Roth G., Sebastian I. A., Smith A. E., Suwanwela N. C., Sylaja P. N., Thapa R., Thrift A. G., Uvere E., Vollset S. E., Yavagal D., Yaria J., Abera S. F., Akinyemi R., Dempsey R. J., Ibrahim N. M., Liu L., Ovbiagele B., Piradov M., Suwanwela N., Abanto C., Addissie A., Adeleye A. O., Adilbekov Y., Adilbekova B., Adoukonou T. A., Aguiar de Sousa D., Akhmetzhanova Z., Akpalu A., El Alaoui-Faris M., Ameriso S. F., Andonova S., Arsovska A., Awoniyi F. E., Bakhiet M., Barboza M. A., Basri H., Bath P. M., Bereczki D., Beretta S., Berkowitz A. L., Bernhardt J., Berzina G., Bhavsar B., Bisharyan M. S., Bohara M., Bovet P., Budincevic H., Cadilhac D. A., Cerimagic D., Charway-Felli A., Chen C., Chin J. H., Christensen H., Chwojnicki K., Conforto A. B., Correia M., Mora Cuervo D. L., Czlonkowska A., D'Amelio M., Danielyan K. E., Davis S., Demarin V., Demchuk A. M., Dichgans M., Dokova K., Donnan G., Duran J. C., Ekeng G., Elkind M. S., Endres M., Fischer U., Flomin Y., Gankpe F., Gavidia M., Gaye Saavedra A., Gebreyohanns M., George M., Gierlotka M., Giroud M., Gnedovskaya E. V., Goncalves I. P., Gongora-Rivera F., Gunaratne P. S., Hamadeh R. R., Hamzat T. -H. K., Heldner M. R., Ibrahim E., Ihle-Hansen H., Jee S., Jiann-Shing J., Johnston S. C., Jovanovic D., Jurjans K., Kalani R., Kalkonde Y., Kamenova S., Karaszewski B., Kelly P., Kiechl S., Kondybayeva A., Korv J., Kozera G., Kravchenko M., Krespi Y., Krishnamurthi R., Kruja J., Kutluk K., Langhorne P., Law Z. K., Lebedynets D., Lee T. -H., Leung T. W., Liebeskind D. S., Lopez-Jaramillo P., Lotufo P. A., Machline-Carrion M. J., Maia L. F., Malojcic B., Markus H. S., Marquez-Romero J. M., Medina M. T., Medukhanova S., Mehndiratta M. M., Miglane E., Mihejeva I., Mikulik R., Mirrakhimov E., Mohl S., Munakomi S., Murphy S., Musa K. I., Nasreldein A., Nogueira R. G., Nolte C. H., Noubiap J. J., Novarro-Escudero N., Ocampo C., O'Donnell M., Ogun Y., Ogunniyi A., Oraby M. I., Orken D. N., Ozdemir A. O., Ozturk S., Paccot M., Pereira T., Peeters A., Potpara T., Proios H., Rathore F. A., Sacco R. L., Sahathevan R., Sandset E. S., Renato Santos I., Saposnik G., Sarfo F. S., Sargento-Freitas J., Sharma M., Shaw L., Sheth K. N., Shin Y. -I., Shobhana A., Silva S. N., Tedim Cruz V., Thakur K., Thapa L. J., Toni D., Topcuoglu M. A., Torales J., Towfighi A., Truelsen T., Tsiskaridze A., Tulloch-Reid M., Useche J. N., Vanacker P., Vassilopoulou S., Vukorepa G., Vuletic V., Wahab K. W., Wang W., Wijeratne T., Wojtyniak B., Wolfe C., Yacouba M. N., Yang J., Yifru Y. M., Yock-Corrales A., Yonemoto N., Yperzeele L., and Zagozdzon P.

Published
2023

2. Primary stroke prevention worldwide: translating evidence into action

Author

Owolabi, M, Thrift, A, Mahal, A, Ishida, M, Martins, S, Johnson, W, Pandian, J, Abd-Allah, F, Yaria, J, Phan, H, Roth, G, Gall, S, Beare, R, Phan, T, Mikulik, R, Akinyemi, R, Norrving, B, Brainin, M, Feigin, V, Abanto, C, Abera, S, Addissie, A, Adebayo, O, Adeleye, A, Adilbekov, Y, Adilbekova, B, Adoukonou, T, Aguiar de Sousa, D, Ajagbe, T, Akhmetzhanova, Z, Akpalu, A, Alvarez Ahlgren, J, Ameriso, S, Andonova, S, Awoniyi, F, Bakhiet, M, Barboza, M, Basri, H, Bath, P, Bello, O, Bereczki, D, Beretta, S, Berkowitz, A, Bernabe-Ortiz, A, Bernhardt, J, Berzina, G, Bisharyan, M, Bovet, P, Budincevic, H, Cadilhac, D, Caso, V, Chen, C, Chin, J, Chwojnicki, K, Conforto, A, Cruz, V, D'Amelio, M, Danielyan, K, Davis, S, Demarin, V, Dempsey, R, Dichgans, M, Dokova, K, Donnan, G, Elkind, M, Endres, M, Fischer, U, Gankpe, F, Gaye Saavedra, A, Gil, A, Giroud, M, Gnedovskaya, E, Hachinski, V, Hafdi, M, Hamadeh, R, Hamzat, T, Hankey, G, Heldner, M, Ibrahim, E, Ibrahim, N, Inoue, M, Jee, S, Jeng, J, Kalkonde, Y, Kamenova, S, Karaszewski, B, Kelly, P, Khan, T, Kiechl, S, Kondybayeva, A, Korv, J, Kravchenko, M, Krishnamurthi, R, Kruja, J, Lakkhanaloet, M, Langhorne, P, Lavados, P, Law, Z, Lawal, A, Lazo-Porras, M, Lebedynets, D, Lee, T, Leung, T, Liebeskind, D, Lindsay, P, Lopez-Jaramillo, P, Lotufo, P, Machline-Carrion, J, Makanjuola, A, Markus, H, Marquez-Romero, J, Medina, M, Medukhanova, S, Mehndiratta, M, Merkin, A, Mirrakhimov, E, Mohl, S, Moscoso-Porras, M, Muller-Stierlin, A, Murphy, S, Musa, K, Nasreldein, A, Nogueira, R, Nolte, C, Noubiap, J, Novarro-Escudero, N, Ogun, Y, Oguntoye, R, Oraby, M, Osundina, M, Ovbiagele, B, Orken, D, Ozdemir, A, Ozturk, S, Paccot, M, Phromjai, J, Piradov, P, Platz, T, Potpara, T, Ranta, A, Rathore, F, Richard, E, Sacco, R, Sahathevan, R, Santos Carquin, I, Saposnik, G, Sarfo, F, Sharma, M, Sheth, K, Shobhana, A, Suwanwela, N, Svyato, I, Sylaja, P, Tao, X, Thakur, K, Toni, D, Topcuoglu, M, Torales, J, Towfighi, A, Truelsen, T, Tsiskaridze, A, Tulloch-Reid, M, Useche, N, Vanacker, P, Vassilopoulou, S, Vukorepa, G, Vuletic, V, Wahab, K, Wang, W, Wijeratne, T, Wolfe, C, Yifru, Y, Yock-Corrales, A, Yonemoto, N, Yperzeele, L, Zhang, P, Owolabi M. O., Thrift A. G., Mahal A., Ishida M., Martins S., Johnson W. D., Pandian J., Abd-Allah F., Yaria J., Phan H. T., Roth G., Gall S. L., Beare R., Phan T. G., Mikulik R., Akinyemi R. O., Norrving B., Brainin M., Feigin V. L., Abanto C., Abera S. F., Addissie A., Adebayo O., Adeleye A. O., Adilbekov Y., Adilbekova B., Adoukonou T. A., Aguiar de Sousa D., Ajagbe T., Akhmetzhanova Z., Akpalu A., Alvarez Ahlgren J., Ameriso S., Andonova S., Awoniyi F. E., Bakhiet M., Barboza M., Basri H., Bath P., Bello O., Bereczki D., Beretta S., Berkowitz A., Bernabe-Ortiz A., Bernhardt J., Berzina G., Bisharyan M., Bovet P., Budincevic H., Cadilhac D., Caso V., Chen C., Chin J., Chwojnicki K., Conforto A., Cruz V. T., D'Amelio M., Danielyan K., Davis S., Demarin V., Dempsey R., Dichgans M., Dokova K., Donnan G., Elkind M. S., Endres M., Fischer U., Gankpe F., Gaye Saavedra A., Gil A., Giroud M., Gnedovskaya E., Hachinski V., Hafdi M., Hamadeh R., Hamzat T. K., Hankey G., Heldner M., Ibrahim E. A., Ibrahim N. M., Inoue M., Jee S., Jeng J. -S., Kalkonde Y., Kamenova S., Karaszewski B., Kelly P., Khan T., Kiechl S., Kondybayeva A., Korv J., Kravchenko M., Krishnamurthi R. V., Kruja J., Lakkhanaloet M., Langhorne P., Lavados P. M., Law Z. K., Lawal A., Lazo-Porras M., Lebedynets D., Lee T. -H., Leung T., Liebeskind D. S., Lindsay P., Lopez-Jaramillo P., Lotufo P. A., Machline-Carrion J., Makanjuola A., Markus H. S., Marquez-Romero J. M., Medina M., Medukhanova S., Mehndiratta M. M., Merkin A., Mirrakhimov E., Mohl S., Moscoso-Porras M., Muller-Stierlin A., Murphy S., Musa K. I., Nasreldein A., Nogueira R. G., Nolte C., Noubiap J. J., Novarro-Escudero N., Ogun Y., Oguntoye R. A., Oraby M. I., Osundina M., Ovbiagele B., Orken D. N., Ozdemir A. O., Ozturk S., Paccot M., Phromjai J., Piradov P., Platz T., Potpara T., Ranta A., Rathore F., Richard E., Sacco R. L., Sahathevan R., Santos Carquin I., Saposnik G., Sarfo F. S., Sharma M., Sheth K., Shobhana A., Suwanwela N., Svyato I., Sylaja P. N., Tao X., Thakur K. T., Toni D., Topcuoglu M. A., Torales J., Towfighi A., Truelsen T. C., Tsiskaridze A., Tulloch-Reid M., Useche N., Vanacker P., Vassilopoulou S., Vukorepa G., Vuletic V., Wahab K. W., Wang W., Wijeratne T., Wolfe C., Yifru Y. M., Yock-Corrales A., Yonemoto N., Yperzeele L., Zhang P., Owolabi, M, Thrift, A, Mahal, A, Ishida, M, Martins, S, Johnson, W, Pandian, J, Abd-Allah, F, Yaria, J, Phan, H, Roth, G, Gall, S, Beare, R, Phan, T, Mikulik, R, Akinyemi, R, Norrving, B, Brainin, M, Feigin, V, Abanto, C, Abera, S, Addissie, A, Adebayo, O, Adeleye, A, Adilbekov, Y, Adilbekova, B, Adoukonou, T, Aguiar de Sousa, D, Ajagbe, T, Akhmetzhanova, Z, Akpalu, A, Alvarez Ahlgren, J, Ameriso, S, Andonova, S, Awoniyi, F, Bakhiet, M, Barboza, M, Basri, H, Bath, P, Bello, O, Bereczki, D, Beretta, S, Berkowitz, A, Bernabe-Ortiz, A, Bernhardt, J, Berzina, G, Bisharyan, M, Bovet, P, Budincevic, H, Cadilhac, D, Caso, V, Chen, C, Chin, J, Chwojnicki, K, Conforto, A, Cruz, V, D'Amelio, M, Danielyan, K, Davis, S, Demarin, V, Dempsey, R, Dichgans, M, Dokova, K, Donnan, G, Elkind, M, Endres, M, Fischer, U, Gankpe, F, Gaye Saavedra, A, Gil, A, Giroud, M, Gnedovskaya, E, Hachinski, V, Hafdi, M, Hamadeh, R, Hamzat, T, Hankey, G, Heldner, M, Ibrahim, E, Ibrahim, N, Inoue, M, Jee, S, Jeng, J, Kalkonde, Y, Kamenova, S, Karaszewski, B, Kelly, P, Khan, T, Kiechl, S, Kondybayeva, A, Korv, J, Kravchenko, M, Krishnamurthi, R, Kruja, J, Lakkhanaloet, M, Langhorne, P, Lavados, P, Law, Z, Lawal, A, Lazo-Porras, M, Lebedynets, D, Lee, T, Leung, T, Liebeskind, D, Lindsay, P, Lopez-Jaramillo, P, Lotufo, P, Machline-Carrion, J, Makanjuola, A, Markus, H, Marquez-Romero, J, Medina, M, Medukhanova, S, Mehndiratta, M, Merkin, A, Mirrakhimov, E, Mohl, S, Moscoso-Porras, M, Muller-Stierlin, A, Murphy, S, Musa, K, Nasreldein, A, Nogueira, R, Nolte, C, Noubiap, J, Novarro-Escudero, N, Ogun, Y, Oguntoye, R, Oraby, M, Osundina, M, Ovbiagele, B, Orken, D, Ozdemir, A, Ozturk, S, Paccot, M, Phromjai, J, Piradov, P, Platz, T, Potpara, T, Ranta, A, Rathore, F, Richard, E, Sacco, R, Sahathevan, R, Santos Carquin, I, Saposnik, G, Sarfo, F, Sharma, M, Sheth, K, Shobhana, A, Suwanwela, N, Svyato, I, Sylaja, P, Tao, X, Thakur, K, Toni, D, Topcuoglu, M, Torales, J, Towfighi, A, Truelsen, T, Tsiskaridze, A, Tulloch-Reid, M, Useche, N, Vanacker, P, Vassilopoulou, S, Vukorepa, G, Vuletic, V, Wahab, K, Wang, W, Wijeratne, T, Wolfe, C, Yifru, Y, Yock-Corrales, A, Yonemoto, N, Yperzeele, L, Zhang, P, Owolabi M. O., Thrift A. G., Mahal A., Ishida M., Martins S., Johnson W. D., Pandian J., Abd-Allah F., Yaria J., Phan H. T., Roth G., Gall S. L., Beare R., Phan T. G., Mikulik R., Akinyemi R. O., Norrving B., Brainin M., Feigin V. L., Abanto C., Abera S. F., Addissie A., Adebayo O., Adeleye A. O., Adilbekov Y., Adilbekova B., Adoukonou T. A., Aguiar de Sousa D., Ajagbe T., Akhmetzhanova Z., Akpalu A., Alvarez Ahlgren J., Ameriso S., Andonova S., Awoniyi F. E., Bakhiet M., Barboza M., Basri H., Bath P., Bello O., Bereczki D., Beretta S., Berkowitz A., Bernabe-Ortiz A., Bernhardt J., Berzina G., Bisharyan M., Bovet P., Budincevic H., Cadilhac D., Caso V., Chen C., Chin J., Chwojnicki K., Conforto A., Cruz V. T., D'Amelio M., Danielyan K., Davis S., Demarin V., Dempsey R., Dichgans M., Dokova K., Donnan G., Elkind M. S., Endres M., Fischer U., Gankpe F., Gaye Saavedra A., Gil A., Giroud M., Gnedovskaya E., Hachinski V., Hafdi M., Hamadeh R., Hamzat T. K., Hankey G., Heldner M., Ibrahim E. A., Ibrahim N. M., Inoue M., Jee S., Jeng J. -S., Kalkonde Y., Kamenova S., Karaszewski B., Kelly P., Khan T., Kiechl S., Kondybayeva A., Korv J., Kravchenko M., Krishnamurthi R. V., Kruja J., Lakkhanaloet M., Langhorne P., Lavados P. M., Law Z. K., Lawal A., Lazo-Porras M., Lebedynets D., Lee T. -H., Leung T., Liebeskind D. S., Lindsay P., Lopez-Jaramillo P., Lotufo P. A., Machline-Carrion J., Makanjuola A., Markus H. S., Marquez-Romero J. M., Medina M., Medukhanova S., Mehndiratta M. M., Merkin A., Mirrakhimov E., Mohl S., Moscoso-Porras M., Muller-Stierlin A., Murphy S., Musa K. I., Nasreldein A., Nogueira R. G., Nolte C., Noubiap J. J., Novarro-Escudero N., Ogun Y., Oguntoye R. A., Oraby M. I., Osundina M., Ovbiagele B., Orken D. N., Ozdemir A. O., Ozturk S., Paccot M., Phromjai J., Piradov P., Platz T., Potpara T., Ranta A., Rathore F., Richard E., Sacco R. L., Sahathevan R., Santos Carquin I., Saposnik G., Sarfo F. S., Sharma M., Sheth K., Shobhana A., Suwanwela N., Svyato I., Sylaja P. N., Tao X., Thakur K. T., Toni D., Topcuoglu M. A., Torales J., Towfighi A., Truelsen T. C., Tsiskaridze A., Tulloch-Reid M., Useche N., Vanacker P., Vassilopoulou S., Vukorepa G., Vuletic V., Wahab K. W., Wang W., Wijeratne T., Wolfe C., Yifru Y. M., Yock-Corrales A., Yonemoto N., Yperzeele L., and Zhang P.

Abstract

Stroke is the second leading cause of death and the third leading cause of disability worldwide and its burden is increasing rapidly in low-income and middle-income countries, many of which are unable to face the challenges it imposes. In this Health Policy paper on primary stroke prevention, we provide an overview of the current situation regarding primary prevention services, estimate the cost of stroke and stroke prevention, and identify deficiencies in existing guidelines and gaps in primary prevention. We also offer a set of pragmatic solutions for implementation of primary stroke prevention, with an emphasis on the role of governments and population-wide strategies, including task-shifting and sharing and health system re-engineering. Implementation of primary stroke prevention involves patients, health professionals, funders, policy makers, implementation partners, and the entire population along the life course.

Published
2022

6. Primary stroke prevention worldwide: translating evidence into action.

Author

Owolabi M.O., Thrift A.G., Mahal A., Ishida M., Martins S., Johnson W.D., Pandian J., Abd-Allah F., Yaria J., Phan H.T., Roth G., Gall S.L., Beare R., Phan T.G., Mikulik R., Akinyemi R.O., Norrving B., Brainin M., Feigin V.L., Abanto C., Abera S.F., Addissie A., Adebayo O., Adeleye A.O., Adilbekov Y., Adilbekova B., Adoukonou T.A., Aguiar de Sousa D., Ajagbe T., Akhmetzhanova Z., Akpalu A., Alvarez Ahlgren J., Ameriso S., Andonova S., Awoniyi F.E., Bakhiet M., Barboza M., Basri H., Bath P., Bello O., Bereczki D., Beretta S., Berkowitz A., Bernabe-Ortiz A., Bernhardt J., Berzina G., Bisharyan M., Bovet P., Budincevic H., Cadilhac D., Caso V., Chen C., Chin J., Chwojnicki K., Conforto A., Cruz V.T., D'Amelio M., Danielyan K., Davis S., Demarin V., Dempsey R., Dichgans M., Dokova K., Donnan G., Elkind M.S., Endres M., Fischer U., Gankpe F., Gaye Saavedra A., Gil A., Giroud M., Gnedovskaya E., Hachinski V., Hafdi M., Hamadeh R., Hamzat T.K., Hankey G., Heldner M., Ibrahim E.A., Ibrahim N.M., Inoue M., Jee S., Jeng J.-S., Kalkonde Y., Kamenova S., Karaszewski B., Kelly P., Khan T., Kiechl S., Kondybayeva A., Korv J., Kravchenko M., Krishnamurthi R.V., Kruja J., Lakkhanaloet M., Langhorne P., Lavados P.M., Law Z.K., Lawal A., Lazo-Porras M., Lebedynets D., Lee T.-H., Leung T., Liebeskind D.S., Lindsay P., Lopez-Jaramillo P., Lotufo P.A., Machline-Carrion J., Makanjuola A., Markus H.S., Marquez-Romero J.M., Medina M., Medukhanova S., Mehndiratta M.M., Merkin A., Mirrakhimov E., Mohl S., Moscoso-Porras M., Muller-Stierlin A., Murphy S., Musa K.I., Nasreldein A., Nogueira R.G., Nolte C., Noubiap J.J., Novarro-Escudero N., Ogun Y., Oguntoye R.A., Oraby M.I., Osundina M., Ovbiagele B., Orken D.N., Ozdemir A.O., Ozturk S., Paccot M., Phromjai J., Piradov P., Platz T., Potpara T., Ranta A., Rathore F., Richard E., Sacco R.L., Sahathevan R., Santos Carquin I., Saposnik G., Sarfo F.S., Sharma M., Sheth K., Shobhana A., Suwanwela N., Svyato I., Sylaja P.N., Tao X., Thakur K.T., Toni D., Topcuoglu M.A., Torales J., Towfighi A., Truelsen T.C., Tsiskaridze A., Tulloch-Reid M., Useche N., Vanacker P., Vassilopoulou S., Vukorepa G., Vuletic V., Wahab K.W., Wang W., Wijeratne T., Wolfe C., Yifru Y.M., Yock-Corrales A., Yonemoto N., Yperzeele L., Zhang P., Owolabi M.O., Thrift A.G., Mahal A., Ishida M., Martins S., Johnson W.D., Pandian J., Abd-Allah F., Yaria J., Phan H.T., Roth G., Gall S.L., Beare R., Phan T.G., Mikulik R., Akinyemi R.O., Norrving B., Brainin M., Feigin V.L., Abanto C., Abera S.F., Addissie A., Adebayo O., Adeleye A.O., Adilbekov Y., Adilbekova B., Adoukonou T.A., Aguiar de Sousa D., Ajagbe T., Akhmetzhanova Z., Akpalu A., Alvarez Ahlgren J., Ameriso S., Andonova S., Awoniyi F.E., Bakhiet M., Barboza M., Basri H., Bath P., Bello O., Bereczki D., Beretta S., Berkowitz A., Bernabe-Ortiz A., Bernhardt J., Berzina G., Bisharyan M., Bovet P., Budincevic H., Cadilhac D., Caso V., Chen C., Chin J., Chwojnicki K., Conforto A., Cruz V.T., D'Amelio M., Danielyan K., Davis S., Demarin V., Dempsey R., Dichgans M., Dokova K., Donnan G., Elkind M.S., Endres M., Fischer U., Gankpe F., Gaye Saavedra A., Gil A., Giroud M., Gnedovskaya E., Hachinski V., Hafdi M., Hamadeh R., Hamzat T.K., Hankey G., Heldner M., Ibrahim E.A., Ibrahim N.M., Inoue M., Jee S., Jeng J.-S., Kalkonde Y., Kamenova S., Karaszewski B., Kelly P., Khan T., Kiechl S., Kondybayeva A., Korv J., Kravchenko M., Krishnamurthi R.V., Kruja J., Lakkhanaloet M., Langhorne P., Lavados P.M., Law Z.K., Lawal A., Lazo-Porras M., Lebedynets D., Lee T.-H., Leung T., Liebeskind D.S., Lindsay P., Lopez-Jaramillo P., Lotufo P.A., Machline-Carrion J., Makanjuola A., Markus H.S., Marquez-Romero J.M., Medina M., Medukhanova S., Mehndiratta M.M., Merkin A., Mirrakhimov E., Mohl S., Moscoso-Porras M., Muller-Stierlin A., Murphy S., Musa K.I., Nasreldein A., Nogueira R.G., Nolte C., Noubiap J.J., Novarro-Escudero N., Ogun Y., Oguntoye R.A., Oraby M.I., Osundina M., Ovbiagele B., Orken D.N., Ozdemir A.O., Ozturk S., Paccot M., Phromjai J., Piradov P., Platz T., Potpara T., Ranta A., Rathore F., Richard E., Sacco R.L., Sahathevan R., Santos Carquin I., Saposnik G., Sarfo F.S., Sharma M., Sheth K., Shobhana A., Suwanwela N., Svyato I., Sylaja P.N., Tao X., Thakur K.T., Toni D., Topcuoglu M.A., Torales J., Towfighi A., Truelsen T.C., Tsiskaridze A., Tulloch-Reid M., Useche N., Vanacker P., Vassilopoulou S., Vukorepa G., Vuletic V., Wahab K.W., Wang W., Wijeratne T., Wolfe C., Yifru Y.M., Yock-Corrales A., Yonemoto N., Yperzeele L., and Zhang P.

Abstract

Stroke is the second leading cause of death and the third leading cause of disability worldwide and its burden is increasing rapidly in low-income and middle-income countries, many of which are unable to face the challenges it imposes. In this Health Policy paper on primary stroke prevention, we provide an overview of the current situation regarding primary prevention services, estimate the cost of stroke and stroke prevention, and identify deficiencies in existing guidelines and gaps in primary prevention. We also offer a set of pragmatic solutions for implementation of primary stroke prevention, with an emphasis on the role of governments and population-wide strategies, including task-shifting and sharing and health system re-engineering. Implementation of primary stroke prevention involves patients, health professionals, funders, policy makers, implementation partners, and the entire population along the life course.Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

Published
2022

12. Association of Apolipoprotein E With Intracerebral Hemorrhage Risk by Race/Ethnicity A Meta-analysis

Author

Marini, S, Crawford, K, Morotti, A, Lee, MJ, Pezzini, A, Moomaw, CJ, Flaherty, ML, Montaner, J, Roquer, J, Jimenez-Conde, J, Giralt-Steinhauer, E, Elosua, R, Cuadrado-Godia, E, Soriano-Tarraga, C, Slowik, A, Jagiella, JM, Pera, J, Urbanik, A, Pichler, A, Hansen, BM, McCauley, JL, Tirschwell, DL, Selim, M, Brown, DL, Silliman, SL, Worrall, BB, Meschia, JF, Kidwell, CS, Testai, FD, Kittner, SJ, Schmidt, H, Enzinger, C, Deary, LJ, Rannikmae, K, Samarasekera, N, Salman, RA-S, Sudlow, CL, Klijn, CJM, van Nieuwenhuizen, KM, Fernandez-Cadenas, I, Delgado, P, Nonving, B, Lindgren, A, Goldstein, JN, Viswanathan, A, Greenberg, SM, Falcone, GJ, Biffi, A, Langefeld, CD, Woo, D, Rosand, J, Anderson, CD, Smoller, S, Sorkin, J, Wang, X, Pikula, A, Wolf, P, Debette, S, Seshadri, S, de Bakker, P, Chasman, D, Rexrode, K, Chen, I, Rotter, J, Luke, M, Sale, M, Lee, T-H, Chang, K-C, Elkind, M, Goldstein, L, James, ML, Breteler, M, O'Donnell, C, Leys, D, Carty, C, Kidwell, C, Olesen, J, Sharma, P, Rich, S, Tatlisumak, T, Happola, O, Bijlenga, P, Soriano, C, Giralt, E, Cotlarcius, L, Hardy, J, Korostynski, M, Boncoraglio, G, Ballabio, E, Parati, E, Mateusz, A, Dziedzic, T, Jagiella, J, Gasowski, J, Wnuk, M, Olszanecki, R, Juchniewicz, KJ, Levi, C, Nyquist, P, Cendes, I, Cabral, N, Franca, P, Goncalves, A, Keller, L, Crisby, M, Kostulas, K, Lennnnens, R, Ahmadi, K, Opherk, C, Duering, M, Dichgans, M, Malik, R, Gonik, M, Staals, J, Melander, O, Burri, P, Sadr-Nabavi, A, Romero, J, Anderson, C, Falcone, G, Brouwers, B, Rost, N, Du, R, Kourkoulis, C, Battey, T, Lubitz, S, Mueller-Myhsok, B, Meschia, J, Brott, T, Pare, G, Schmidt, R, Seiler, S, Blanton, S, Yamada, Y, Bersano, A, Rundek, T, Sacco, R, Chan, Y-FY, Gschwendtner, A, Deng, Z, Barr, T, Gwinn, K, Corriveau, R, Singleton, A, Waddy, S, Launer, L, Chen, C, Le, KE, Lee, WL, Tan, EK, Olugbodi, A, Rothwell, P, Schilling, S, Mok, V, Lebedeva, E, Jem, C, Jood, K, Olsson, S, Kim, H, Lee, C, Kilarski, L, Markus, H, Peycke, J, Bevan, S, Sheu, W, Chiou, HY, Chern, J, Giraldo, E, Taqi, M, Jain, V, Lam, O, Howard, G, Kittner, S, Mitchell, B, Cole, J, O'Connell, J, Milewicz, D, Illoh, K, Worrall, B, Stine, C, Karaszewski, B, Werring, D, Sofat, R, Smalley, J, Hansen, B, Norrving, B, Smith, G, Martin, JJ, Thijs, V, Klijn, K, van't Hof, F, Algra, A, Macleod, M, Perry, R, Arnett, D, Padovani, A, Cramer, S, Fisher, M, Saleheen, D, Broderick, J, Kissela, B, Doney, A, Sudlow, C, Silliman, S, McDonough, C, Walters, M, Pedersen, A, Nakagawa, K, Chang, C, Dobbins, M, McArdle, P, Chang, Y-C, Brown, R, Brown, D, Holliday, E, Kalaria, R, Maguire, J, Hunter, J, Attia, J, Farrall, M, Giese, A-K, Fomage, M, Majersik, J, Cushman, M, Keene, K, Bennett, S, Tirschwell, D, Psaty, B, Reiner, A, Longstreth, W, Spence, D, Langefeld, C, Bushnell, C, Heitsch, L, Lee, J-M, Sheth, K, Marini, S, Crawford, K, Morotti, A, Lee, MJ, Pezzini, A, Moomaw, CJ, Flaherty, ML, Montaner, J, Roquer, J, Jimenez-Conde, J, Giralt-Steinhauer, E, Elosua, R, Cuadrado-Godia, E, Soriano-Tarraga, C, Slowik, A, Jagiella, JM, Pera, J, Urbanik, A, Pichler, A, Hansen, BM, McCauley, JL, Tirschwell, DL, Selim, M, Brown, DL, Silliman, SL, Worrall, BB, Meschia, JF, Kidwell, CS, Testai, FD, Kittner, SJ, Schmidt, H, Enzinger, C, Deary, LJ, Rannikmae, K, Samarasekera, N, Salman, RA-S, Sudlow, CL, Klijn, CJM, van Nieuwenhuizen, KM, Fernandez-Cadenas, I, Delgado, P, Nonving, B, Lindgren, A, Goldstein, JN, Viswanathan, A, Greenberg, SM, Falcone, GJ, Biffi, A, Langefeld, CD, Woo, D, Rosand, J, Anderson, CD, Smoller, S, Sorkin, J, Wang, X, Pikula, A, Wolf, P, Debette, S, Seshadri, S, de Bakker, P, Chasman, D, Rexrode, K, Chen, I, Rotter, J, Luke, M, Sale, M, Lee, T-H, Chang, K-C, Elkind, M, Goldstein, L, James, ML, Breteler, M, O'Donnell, C, Leys, D, Carty, C, Kidwell, C, Olesen, J, Sharma, P, Rich, S, Tatlisumak, T, Happola, O, Bijlenga, P, Soriano, C, Giralt, E, Cotlarcius, L, Hardy, J, Korostynski, M, Boncoraglio, G, Ballabio, E, Parati, E, Mateusz, A, Dziedzic, T, Jagiella, J, Gasowski, J, Wnuk, M, Olszanecki, R, Juchniewicz, KJ, Levi, C, Nyquist, P, Cendes, I, Cabral, N, Franca, P, Goncalves, A, Keller, L, Crisby, M, Kostulas, K, Lennnnens, R, Ahmadi, K, Opherk, C, Duering, M, Dichgans, M, Malik, R, Gonik, M, Staals, J, Melander, O, Burri, P, Sadr-Nabavi, A, Romero, J, Anderson, C, Falcone, G, Brouwers, B, Rost, N, Du, R, Kourkoulis, C, Battey, T, Lubitz, S, Mueller-Myhsok, B, Meschia, J, Brott, T, Pare, G, Schmidt, R, Seiler, S, Blanton, S, Yamada, Y, Bersano, A, Rundek, T, Sacco, R, Chan, Y-FY, Gschwendtner, A, Deng, Z, Barr, T, Gwinn, K, Corriveau, R, Singleton, A, Waddy, S, Launer, L, Chen, C, Le, KE, Lee, WL, Tan, EK, Olugbodi, A, Rothwell, P, Schilling, S, Mok, V, Lebedeva, E, Jem, C, Jood, K, Olsson, S, Kim, H, Lee, C, Kilarski, L, Markus, H, Peycke, J, Bevan, S, Sheu, W, Chiou, HY, Chern, J, Giraldo, E, Taqi, M, Jain, V, Lam, O, Howard, G, Kittner, S, Mitchell, B, Cole, J, O'Connell, J, Milewicz, D, Illoh, K, Worrall, B, Stine, C, Karaszewski, B, Werring, D, Sofat, R, Smalley, J, Hansen, B, Norrving, B, Smith, G, Martin, JJ, Thijs, V, Klijn, K, van't Hof, F, Algra, A, Macleod, M, Perry, R, Arnett, D, Padovani, A, Cramer, S, Fisher, M, Saleheen, D, Broderick, J, Kissela, B, Doney, A, Sudlow, C, Silliman, S, McDonough, C, Walters, M, Pedersen, A, Nakagawa, K, Chang, C, Dobbins, M, McArdle, P, Chang, Y-C, Brown, R, Brown, D, Holliday, E, Kalaria, R, Maguire, J, Hunter, J, Attia, J, Farrall, M, Giese, A-K, Fomage, M, Majersik, J, Cushman, M, Keene, K, Bennett, S, Tirschwell, D, Psaty, B, Reiner, A, Longstreth, W, Spence, D, Langefeld, C, Bushnell, C, Heitsch, L, Lee, J-M, and Sheth, K

Published
2019

13. Blood pressure in acute ischemic stroke: Challenges in trial interpretation and clinical management: Position of the ESH Working Group on Hypertension and the Brain

Author

Gasecki, D. Coca, A. Cunha, P. Hering, D. Manios, E. Lovic, D. Zaninelli, A. Sierra, C. Kwarciany, M. Narkiewicz, K. Karaszewski, B.

Abstract

Altered blood pressure (BP) is a common phenomenon in acute ischemic stroke (AIS), with high BP being the most frequent scenario. The pathophysiology of BP changes in AIS is complex and only partially understood. The available evidence indicates that extremely high BP during AIS is associated with a poor outcome. Importantly, the observed relationship between BP and stroke outcome may or may not be causally related. Higher baseline BPs in focal cerebral ischemia may indicate preexisting hypertension, but may also be an effect of both nonspecific and stroke-related factors. Although antihypertensive therapy effectively reduces BP in AIS, studies on early BP lowering in AIS produce conflicting results in terms of functional outcome and mortality. Systematic reviews on BP management in AIS did not result in clinically applicable conclusions in general. However, the investigation on the effect of BP and its alterations in AIS are hampered by various important methodological issues. This position statement was prepared by a group of experts from the European Society of Hypertension and invited neurologists to discuss the main reasons for the discrepancies in the current evidence on the prognosis and treatment of altered BP in AIS which should be taken into account in future studies. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

Published
2018

14. Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes

Author

Pulit, SL, Weng, L-C, McArdle, PF, Trinquart, L, Choi, SH, Mitchell, BD, Rosand, J, de Bakker, PIW, Benjamin, EJ, Ellinor, PT, Kittner, SJ, Lubitz, SA, Anderson, CD, Christophersen, IE, Rienstra, M, Roselli, C, Yin, X, Geelhoed, B, Barnard, J, Lin, H, Arking, DE, Smith, A, Albert, CM, Chaffin, M, Tucker, NR, Li, M, Klarin, D, Bihlmeyer, NA, Low, S-K, Weeke, PE, Mueller-Nurasyid, M, Smith, JG, Brody, JA, Niemeijer, MN, Doerr, M, Trompet, S, Huffman, J, Gustafsson, S, Schurmann, C, Kleber, ME, Lyytikainen, L-P, Seppala, I, Malik, R, Horimoto, ARVR, Perez, M, Sinisalo, J, Aeschbacher, S, Theriault, S, Yao, J, Radmanesh, F, Weiss, S, Teumer, A, Clauss, S, Deo, R, Rader, DJ, Shah, S, Sun, A, Hopewell, JC, Debette, S, Chauhan, G, Yang, Q, Worrall, BB, Pare, G, Kamatani, Y, Hagemeijer, YP, Verweij, N, Siland, JE, Kubo, M, Smith, JD, Van Wagoner, DR, Bis, JC, Perz, S, Psaty, BM, Ridker, PM, Magnani, JW, Harris, TB, Launer, LJ, Shoemaker, MB, Padmanabhan, S, Haessler, J, Bartz, TM, Waldenberger, M, Lichtner, P, Arendt, M, Krieger, JE, Kahonen, M, Risch, L, Mansur, AJ, Peters, A, Smith, BH, Lind, L, Scott, SA, Lu, Y, Bottinger, EB, Hernesniemi, J, Lindgren, CM, Wong, JA, Huang, J, Eskola, M, Morris, AP, Ford, I, Reiner, AP, Delgado, G, Chen, LY, Chen, Y-DI, Sandhu, RK, Boerwinkle, E, Eisele, L, Lannfelt, L, Rost, N, Taylor, KD, Campbell, A, Magnusson, PK, Porteous, D, Hocking, LJ, Vlachopoulou, E, Pedersen, NL, Nikus, K, Orho-Melander, M, Hamsten, A, Heeringa, J, Denny, JC, Kriebel, J, Darbar, D, Newton-Cheh, C, Shaffer, C, Macfarlane, PW, Heilmann, S, Almgren, P, Huang, PL, Sotoodehnia, N, Soliman, EZ, Uitterlinden, AG, Hofman, A, Franco, OH, Voelker, U, Joeckel, K-H, Sinner, MF, Lin, HJ, Guo, X, Dichgans, M, Ingelsson, E, Kooperberg, C, Melander, O, Loos, RJF, Laurikka, J, Conen, D, van der Harst, P, Lokki, M-L, Kathiresan, S, Pereira, A, Jukema, JW, Hayward, C, Rotter, J, Maerz, W, Lehtimaki, T, Stricker, BH, Chung, MK, Felix, SB, Gudnason, V, Alonso, A, Roden, DM, Kaeaeb, S, Chasman, D, Heckbert, SR, Tanaka, T, Lunetta, KL, Smoller, S, Sorkin, J, Wang, X, Selim, M, Pikula, A, Wolf, P, Seshadri, S, de Bakker, P, Rexrode, K, Chen, I, Luke, M, Sale, M, Lee, T-H, Chang, K-C, Elkind, M, Goldstein, L, James, ML, Breteler, M, O'Donnell, C, Leys, D, Carty, C, Kidwell, C, Olesen, J, Sharma, P, Rich, S, Tatlisumak, T, Happola, O, Bijlenga, P, Soriano, C, Giralt, E, Roquer, J, Jimenez-Conde, J, Cotlarcius, I, Hardy, J, Korostynski, M, Boncoraglio, G, Ballabio, E, Parati, E, Mateusz, A, Urbanik, A, Dziedzic, T, Jagiella, J, Gasowski, J, Wnuk, M, Olszanecki, R, Pera, J, Slowik, A, Juchniewicz, KJ, Levi, C, Nyquist, P, Cendes, I, Cabral, N, Franca, P, Goncalves, A, Keller, L, Crisby, M, Kostulas, K, Lemmens, R, Ahmadi, K, Opherk, C, Duering, M, Gonik, M, Staals, J, Burri, P, Sadr-Nabavi, A, Romero, J, Biffi, A, Anderson, C, Falcone, G, Brouwers, B, Du, R, Kourkoulis, C, Battey, T, Lubitz, S, Mueller-Myhsok, B, Meschia, J, Brott, T, Pichler, A, Enzinger, C, Schmidt, H, Schmidt, R, Seiler, S, Blanton, S, Yamada, Y, Bersano, A, Rundek, T, Sacco, R, Chan, Y-FY, Gschwendtner, A, Deng, Z, Barr, T, Gwinn, K, Corriveau, R, Singleton, A, Waddy, S, Launer, L, Chen, C, Le, KE, Lee, WL, Tan, EK, Olugbodi, A, Rothwell, P, Schilling, S, Mok, V, Lebedeva, E, Jern, C, Jood, K, Olsson, S, Kim, H, Lee, C, Kilarski, L, Markus, H, Peycke, J, Bevan, S, Sheu, W, Chiou, HY, Chern, J, Giraldo, E, Taqi, M, Jain, V, Lam, O, Howard, G, Woo, D, Kittner, S, Mitchell, B, Cole, J, O'Connell, J, Milewicz, D, Illoh, K, Worrall, B, Stine, C, Karaszewski, B, Werring, D, Sofat, R, Smalley, J, Lindgren, A, Hansen, B, Norrving, B, Smith, G, Jose Martin, J, Thijs, V, Klijn, K, van't Hof, F, Algra, A, Macleod, M, Perry, R, Arnett, D, Pezzini, A, Padovani, A, Cramer, S, Fisher, M, Saleheen, D, Broderick, J, Kissela, B, Doney, A, Sudlow, C, Rannikmae, K, Silliman, S, McDonough, C, Walters, M, Pedersen, A, Nakagawa, K, Chang, C, Dobbins, M, McArdle, P, Chang, Y-C, Brown, R, Brown, D, Holliday, E, Kalaria, R, Maguire, J, Attia, J, Farrall, M, Giese, A-K, Fornage, M, Majersik, J, Cushman, M, Keene, K, Bennett, S, Tirschwell, D, Psaty, B, Reiner, A, Longstreth, W, Spence, D, Montaner, J, Fernandez-Cadenas, I, Langefeld, C, Bushnell, C, Heitsch, L, Lee, J-M, Sheth, K, Pulit, SL, Weng, L-C, McArdle, PF, Trinquart, L, Choi, SH, Mitchell, BD, Rosand, J, de Bakker, PIW, Benjamin, EJ, Ellinor, PT, Kittner, SJ, Lubitz, SA, Anderson, CD, Christophersen, IE, Rienstra, M, Roselli, C, Yin, X, Geelhoed, B, Barnard, J, Lin, H, Arking, DE, Smith, A, Albert, CM, Chaffin, M, Tucker, NR, Li, M, Klarin, D, Bihlmeyer, NA, Low, S-K, Weeke, PE, Mueller-Nurasyid, M, Smith, JG, Brody, JA, Niemeijer, MN, Doerr, M, Trompet, S, Huffman, J, Gustafsson, S, Schurmann, C, Kleber, ME, Lyytikainen, L-P, Seppala, I, Malik, R, Horimoto, ARVR, Perez, M, Sinisalo, J, Aeschbacher, S, Theriault, S, Yao, J, Radmanesh, F, Weiss, S, Teumer, A, Clauss, S, Deo, R, Rader, DJ, Shah, S, Sun, A, Hopewell, JC, Debette, S, Chauhan, G, Yang, Q, Worrall, BB, Pare, G, Kamatani, Y, Hagemeijer, YP, Verweij, N, Siland, JE, Kubo, M, Smith, JD, Van Wagoner, DR, Bis, JC, Perz, S, Psaty, BM, Ridker, PM, Magnani, JW, Harris, TB, Launer, LJ, Shoemaker, MB, Padmanabhan, S, Haessler, J, Bartz, TM, Waldenberger, M, Lichtner, P, Arendt, M, Krieger, JE, Kahonen, M, Risch, L, Mansur, AJ, Peters, A, Smith, BH, Lind, L, Scott, SA, Lu, Y, Bottinger, EB, Hernesniemi, J, Lindgren, CM, Wong, JA, Huang, J, Eskola, M, Morris, AP, Ford, I, Reiner, AP, Delgado, G, Chen, LY, Chen, Y-DI, Sandhu, RK, Boerwinkle, E, Eisele, L, Lannfelt, L, Rost, N, Taylor, KD, Campbell, A, Magnusson, PK, Porteous, D, Hocking, LJ, Vlachopoulou, E, Pedersen, NL, Nikus, K, Orho-Melander, M, Hamsten, A, Heeringa, J, Denny, JC, Kriebel, J, Darbar, D, Newton-Cheh, C, Shaffer, C, Macfarlane, PW, Heilmann, S, Almgren, P, Huang, PL, Sotoodehnia, N, Soliman, EZ, Uitterlinden, AG, Hofman, A, Franco, OH, Voelker, U, Joeckel, K-H, Sinner, MF, Lin, HJ, Guo, X, Dichgans, M, Ingelsson, E, Kooperberg, C, Melander, O, Loos, RJF, Laurikka, J, Conen, D, van der Harst, P, Lokki, M-L, Kathiresan, S, Pereira, A, Jukema, JW, Hayward, C, Rotter, J, Maerz, W, Lehtimaki, T, Stricker, BH, Chung, MK, Felix, SB, Gudnason, V, Alonso, A, Roden, DM, Kaeaeb, S, Chasman, D, Heckbert, SR, Tanaka, T, Lunetta, KL, Smoller, S, Sorkin, J, Wang, X, Selim, M, Pikula, A, Wolf, P, Seshadri, S, de Bakker, P, Rexrode, K, Chen, I, Luke, M, Sale, M, Lee, T-H, Chang, K-C, Elkind, M, Goldstein, L, James, ML, Breteler, M, O'Donnell, C, Leys, D, Carty, C, Kidwell, C, Olesen, J, Sharma, P, Rich, S, Tatlisumak, T, Happola, O, Bijlenga, P, Soriano, C, Giralt, E, Roquer, J, Jimenez-Conde, J, Cotlarcius, I, Hardy, J, Korostynski, M, Boncoraglio, G, Ballabio, E, Parati, E, Mateusz, A, Urbanik, A, Dziedzic, T, Jagiella, J, Gasowski, J, Wnuk, M, Olszanecki, R, Pera, J, Slowik, A, Juchniewicz, KJ, Levi, C, Nyquist, P, Cendes, I, Cabral, N, Franca, P, Goncalves, A, Keller, L, Crisby, M, Kostulas, K, Lemmens, R, Ahmadi, K, Opherk, C, Duering, M, Gonik, M, Staals, J, Burri, P, Sadr-Nabavi, A, Romero, J, Biffi, A, Anderson, C, Falcone, G, Brouwers, B, Du, R, Kourkoulis, C, Battey, T, Lubitz, S, Mueller-Myhsok, B, Meschia, J, Brott, T, Pichler, A, Enzinger, C, Schmidt, H, Schmidt, R, Seiler, S, Blanton, S, Yamada, Y, Bersano, A, Rundek, T, Sacco, R, Chan, Y-FY, Gschwendtner, A, Deng, Z, Barr, T, Gwinn, K, Corriveau, R, Singleton, A, Waddy, S, Launer, L, Chen, C, Le, KE, Lee, WL, Tan, EK, Olugbodi, A, Rothwell, P, Schilling, S, Mok, V, Lebedeva, E, Jern, C, Jood, K, Olsson, S, Kim, H, Lee, C, Kilarski, L, Markus, H, Peycke, J, Bevan, S, Sheu, W, Chiou, HY, Chern, J, Giraldo, E, Taqi, M, Jain, V, Lam, O, Howard, G, Woo, D, Kittner, S, Mitchell, B, Cole, J, O'Connell, J, Milewicz, D, Illoh, K, Worrall, B, Stine, C, Karaszewski, B, Werring, D, Sofat, R, Smalley, J, Lindgren, A, Hansen, B, Norrving, B, Smith, G, Jose Martin, J, Thijs, V, Klijn, K, van't Hof, F, Algra, A, Macleod, M, Perry, R, Arnett, D, Pezzini, A, Padovani, A, Cramer, S, Fisher, M, Saleheen, D, Broderick, J, Kissela, B, Doney, A, Sudlow, C, Rannikmae, K, Silliman, S, McDonough, C, Walters, M, Pedersen, A, Nakagawa, K, Chang, C, Dobbins, M, McArdle, P, Chang, Y-C, Brown, R, Brown, D, Holliday, E, Kalaria, R, Maguire, J, Attia, J, Farrall, M, Giese, A-K, Fornage, M, Majersik, J, Cushman, M, Keene, K, Bennett, S, Tirschwell, D, Psaty, B, Reiner, A, Longstreth, W, Spence, D, Montaner, J, Fernandez-Cadenas, I, Langefeld, C, Bushnell, C, Heitsch, L, Lee, J-M, and Sheth, K

Abstract

OBJECTIVE: We sought to assess whether genetic risk factors for atrial fibrillation (AF) can explain cardioembolic stroke risk. METHODS: We evaluated genetic correlations between a previous genetic study of AF and AF in the presence of cardioembolic stroke using genome-wide genotypes from the Stroke Genetics Network (N = 3,190 AF cases, 3,000 cardioembolic stroke cases, and 28,026 referents). We tested whether a previously validated AF polygenic risk score (PRS) associated with cardioembolic and other stroke subtypes after accounting for AF clinical risk factors. RESULTS: We observed a strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearson r = 0.77 and 0.76, respectively, across SNPs with p < 4.4 × 10-4 in the previous AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio [OR] per SD = 1.40, p = 1.45 × 10-48), explaining ∼20% of the heritable component of cardioembolic stroke risk. The AF PRS was also associated with stroke of undetermined cause (OR per SD = 1.07, p = 0.004), but no other primary stroke subtypes (all p > 0.1). CONCLUSIONS: Genetic risk of AF is associated with cardioembolic stroke, independent of clinical risk factors. Studies are warranted to determine whether AF genetic risk can serve as a biomarker for strokes caused by AF.

Published
2018

16. Genome-wide meta-analysis of cerebral white matter hyperintensities in patients with stroke

Author

Traylor, M, Zhang, Cr, Adib Samii, P, Devan, Wj, Parsons, Oe, Lanfranconi, S, Gregory, S, Cloonan, L, Falcone, Gj, Radmanesh, F, Fitzpatrick, K, Kanakis, A, Barrick, Tr, Moynihan, B, Lewis, Cm, Boncoraglio, Gb, Lemmens, R, Thijs, V, Sudlow, C, Wardlaw, J, Rothwell, Pm, Meschia, Jf, Worrall, Bb, Levi, C, Bevan, S, Furie, Kl, Dichgans, M, Rosand, J, Markus, Hs, Rost, N, Smoller, S, Sorkin, J, Wang, X, Selim, M, Pikula, A, Wolf, P, Debette, S, Seshadri, S, de Bakker, P, Chasman, D, Rexrode, K, Chen, I, Rotter, J, Luke, M, Sale, M, Lee, Th, Chang, Kc, Elkind, M, Goldstein, L, James, Ml, Breteler, M, O'Donnell, C, Leys, D, Carty, C, Kidwell, C, Olesen, J, Sharma, P, Rich, S, Tatlisumak, T, Happola, O, Bijlenga, P, Soriano, C, Giralt, E, Roquer, J, Jimenez Conde, J, Cotlarcius, I, Hardy, J, Korostynski, M, Boncoraglio, G, Ballabio, E, Parati, E, Mateusz, A, Urbanik, A, Dziedzic, T, Jagiella, J, Gasowski, J, Wnuk, M, Olszanecki, R, Pera, J, Slowik, A, Juchniewicz, Kj, Nyquist, P, Cendes, I, Cabral, N, Franca, P, Goncalves, A, Keller, L, Crisby, M, Kostulas, K, Ahmadi, K, Opherk, C, Duering, M, Malik, R, Gonik, M, Staals, J, Melander, O, Burri, P, Sadr Nabavi, A, Romero, J, Biffi, A, Anderson, C, Falcone, G, Brouwers, B, Du, R, Kourkoulis, C, Battey, T, Lubitz, S, Mueller Myhsok, B, Meschia, J, Brott, T, Pare, G, Pichler, A, Enzinger, C, Schmidt, H, Schmidt, R, Seiler, S, Blanton, S, Yamada, Y, Bersano, A, Rundek, T, Sacco, R, Yvonne Chan, Yf, Gschwendtner, A, Deng, Z, Barr, T, Gwinn, K, Corriveau, R, Singleton, A, Waddy, S, Launer, L, Chen, C, Ke, Le, Lee, Wl, Tan, Ek, Olugbodi, A, Rothwell, P, Schilling, S, Mok, V, Lebedeva, E, Jern, C, Jood, K, Olsson, S, Kim, H, Lee, C, Kilarski, L, Markus, H, Peycke, J, Sheu, W, Chiou, Hy, Chern, J, Giraldo, E, Taqi, M, Jain, V, Lam, O, Howard, G, Woo, D, Kittner, S, Mitchell, B, Cole, J, O'Connell, J, Milewicz, D, Illoh, K, Worrall, B, Stine, C, Karaszewski, B, Werring, D, Sofat, R, Smalley, J, Lindgren, A, Hansen, B, Norrving, B, Smith, G, Martín, Jj, Klijn, K, Van't Hof, F, Algra, A, Macleod, M, Perry, R, Arnett, D, Pezzini, Alessandro, Padovani, Alessandro, Cramer, S, Fisher, M, Saleheen, D, Broderick, J, Kissela, B, Doney, A, Rannikmae, K, Silliman, S, Mcdonough, C, Walters, M, Pedersen, A, Nakagawa, K, Chang, C, Dobbins, M, Mcardle, P, Chang, Yc, Brown, R, Brown, D, Holliday, E, Kalaria, R, Maguire, J, Attia, J, Farrall, M, Giese, Ak, Fornage, M, Majersik, J, Cushman, M, Keene, K, Bennett, S, Tirschwell, D, Psaty, B, Reiner, A, Longstreth, W, Spence, D, Montaner, J, Fernandez Cadenas, I, Langefeld, C, Bushnell, C, Heitsch, L, Lee, Jm, and Sheth, K.

Subjects
Cerebral Small Vessel Diseases, Genetic Predisposition to Disease, Genetic Testing, Humans, Polymorphism, Single Nucleotide, Risk Factors, Stroke, White Matter, Genome-Wide Association Study, Neurology (clinical), Single Nucleotide, C420 Human Genetics, Article, C431 Medical Genetics, C400 Genetics, Polymorphism, C440 Molecular Genetics
Abstract

Objective: For 3,670 stroke patients from the United Kingdom, United States, Australia, Belgium, and Italy, we performed a genome-wide meta-analysis of white matter hyperintensity volumes (WMHV) on data imputed to the 1000 Genomes reference dataset to provide insights into disease mechanisms. Methods: We first sought to identify genetic associations with white matter hyperintensities in a stroke population, and then examined whether genetic loci previously linked to WMHV in community populations are also associated in stroke patients. Having established that genetic associations are shared between the 2 populations, we performed a meta-analysis testing which associations with WMHV in stroke-free populations are associated overall when combined with stroke populations. Results: There were no associations at genome-wide significance with WMHV in stroke patients. All previously reported genome-wide significant associations with WMHV in community populations shared direction of effect in stroke patients. In a meta-analysis of the genome-wide significant and suggestive loci (p Conclusions: Genetic associations with WMHV are shared in otherwise healthy individuals and patients with stroke, indicating common genetic susceptibility in cerebral small vessel disease.

Published
2016
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20. PP.34.20

Author

Gasecki, D., primary, Kowalczyk, K., additional, Kwarciany, M., additional, Nowicki, T., additional, Szurowska, E., additional, Karaszewski, B., additional, and Narkiewicz, K., additional

Published
2015
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31. Brain choline concentration

Author

Karaszewski, B., Thomas, R.G.R., Chappell, F.M., Armitage, P.A., Carpenter, T.K., Lymer, G.K.S., Dennis, M.S., Marshall, I., and Wardlaw, J.M.

Abstract

Better prediction of tissue prognosis in acute stroke might improve treatment decisions. We hypothesized that there are metabolic ischemic disturbances measurable noninvasively by proton magnetic resonance spectroscopy (1H MRS) that occur earlier than any structural changes visible on diffusion-tensor imaging (DTI), which may therefore serve for territorial identification of tissue at risk.

Published
2010
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32. Primary stroke prevention worldwide:translating evidence into action

Author

Owolabi, Mayowa O., Thrift, Amanda G., Mahal, Ajay, Ishida, Marie, Martins, Sheila, Johnson, Walter D., Pandian, Jeyaraj, Abd-Allah, Foad, Yaria, Joseph, Phan, Hoang T., Roth, Greg, Gall, Seana L., Beare, Richard, Phan, Thanh G., Mikulik, Robert, Akinyemi, Rufus O., Norrving, Bo, Brainin, Michael, Feigin, Valery L., Abanto, Carlos, Abera, Semaw Ferede, Addissie, Adamu, Adebayo, Oluwadamilola, Adeleye, Amos Olufemi, Adilbekov, Yerzhan, Adilbekova, Bibigul, Adoukonou, Thierry Armel, Aguiar de Sousa, Diana, Ajagbe, Temitope, Akhmetzhanova, Zauresh, Akpalu, Albert, Álvarez Ahlgren, Jhon, Ameriso, Sebastián, Andonova, Silva, Awoniyi, Foloruso Emmanuel, Bakhiet, Moiz, Barboza, Miguel, Basri, Hamidon, Bath, Philip, Bello, Olamide, Bereczki, Dániel, Beretta, Simone, Berkowitz, Aaron, Bernabé-Ortiz, Antonio, Bernhardt, Julie, Berzina, Guna, Bisharyan, Mher, Bovet, Pascal, Budincevic, Hrvoje, Cadilhac, Dominique, Caso, Valeria, Chen, Christopher, Chin, Jerome, Chwojnicki, Kamil, Conforto, Adriana, Cruz, Vitor Tedim, D'Amelio, Marco, Danielyan, Kristine, Davis, Stephen, Demarin, Vida, Dempsey, Robert, Dichgans, Martin, Dokova, Klara, Donnan, Geoffrey, Elkind, Mitchell S., Endres, Matthias, Fischer, Urs, Gankpé, Fortuné, Gaye Saavedra, Andrés, Gil, Artyom, Giroud, Maurice, Gnedovskaya, Elena, Hachinski, Vladimir, Hafdi, Melanie, Hamadeh, Randah, Hamzat, T. Kolapo, Hankey, Graeme, Heldner, Mirjam, Ibrahim, Etedal Ahmed, Ibrahim, Norlinah Mohamed, Inoue, Manabu, Jee, Sungju, Jeng, Jiann-Shing, Kalkonde, Yogesh, Kamenova, Saltanat, Karaszewski, Bartosz, Kelly, Peter, Khan, Taskeen, Kiechl, Stefan, Kondybayeva, Aida, Kõrv, Janika, Kravchenko, Michael, Krishnamurthi, Rita V., Kruja, Jera, Lakkhanaloet, Mongkol, Langhorne, Peter, Lavados, Pablo M., Law, Zhe Kang, Lawal, Abisola, Lazo-Porras, Maria, Lebedynets, Dmytro, Lee, Tsong-Hai, Leung, Thomas, Liebeskind, David S., Lindsay, Patrice, López-Jaramillo, Patricio, Lotufo, Paulo Andrade, Machline-Carrion, Julia, Makanjuola, Akintomiwa, Markus, Hugh Stephen, Marquez-Romero, Juan Manuel, Medina, Marco, Medukhanova, Sabina, Mehndiratta, Man Mohan, Merkin, Alexandr, Mirrakhimov, Erkin, Mohl, Stephanie, Moscoso-Porras, Miguel, Müller-Stierlin, Annabel, Murphy, Sean, Musa, Kamarul Imran, Nasreldein, Ahmed, Nogueira, Raul Gomes, Nolte, Christian, Noubiap, Jean Jacques, Novarro-Escudero, Nelson, Ogun, Yomi, Oguntoye, Richard Ayobami, Oraby, Mohammed Ibrahim, Osundina, Morenike, Ovbiagele, Bruce, Orken, Dilek Necioglu, Ozdemir, Atilla Özcan, Ozturk, Serefnur, Paccot, Melanie, Phromjai, Jurairat, Piradov, Piradov, Platz, Thomas, Potpara, Tatjana, Ranta, Annemarei, Rathore, Farooq, Richard, Edo, Sacco, Ralph L., Sahathevan, Ramesh, Santos Carquín, Irving, Saposnik, Gustavo, Sarfo, Fred Stephen, Sharma, Mike, Sheth, Kevin, Shobhana, A., Suwanwela, Nijasri, Svyato, Irina, Sylaja, P.N., Tao, Xuanchen, Thakur, Kiran T., Toni, Danilo, Topcuoglu, Mehmet Akif, Torales, Julio, Towfighi, Amytis, Truelsen, Thomas Clement, Tsiskaridze, Alexander, Tulloch-Reid, Marshall, Useche, Nicolás, Vanacker, Peter, Vassilopoulou, Sophia, Vukorepa, Gorana, Vuletic, Vladimira, Wahab, Kolawole W., Wang, Wenzhi, Wijeratne, Tissa, Wolfe, Charles, Yifru, Yared Mamushet, Yock-Corrales, Adriana, Yonemoto, Naohiro, Yperzeele, Laetitia, Zhang, Puhong, Oguntoye, Stroke Experts Collaboration Group, Owolabi M.O., Thrift A.G., Mahal A., Ishida M., Martins S., Johnson W.D., Pandian J., Abd-Allah F., Yaria J., Phan H.T., Roth G., Gall S.L., Beare R., Phan T.G., Mikulik R., Akinyemi R.O., Norrving B., Brainin M., Feigin V.L., Abanto C., Abera S.F., Addissie A., Adebayo O., Adeleye A.O., Adilbekov Y., Adilbekova B., Adoukonou T.A., Aguiar de Sousa D., Ajagbe T., Akhmetzhanova Z., Akpalu A., Alvarez Ahlgren J., Ameriso S., Andonova S., Awoniyi F.E., Bakhiet M., Barboza M., Basri H., Bath P., Bello O., Bereczki D., Beretta S., Berkowitz A., Bernabe-Ortiz A., Bernhardt J., Berzina G., Bisharyan M., Bovet P., Budincevic H., Cadilhac D., Caso V., Chen C., Chin J., Chwojnicki K., Conforto A., Cruz V.T., D'Amelio M., Danielyan K., Davis S., Demarin V., Dempsey R., Dichgans M., Dokova K., Donnan G., Elkind M.S., Endres M., Fischer U., Gankpe F., Gaye Saavedra A., Gil A., Giroud M., Gnedovskaya E., Hachinski V., Hafdi M., Hamadeh R., Hamzat T.K., Hankey G., Heldner M., Ibrahim E.A., Ibrahim N.M., Inoue M., Jee S., Jeng J.-S., Kalkonde Y., Kamenova S., Karaszewski B., Kelly P., Khan T., Kiechl S., Kondybayeva A., Korv J., Kravchenko M., Krishnamurthi R.V., Kruja J., Lakkhanaloet M., Langhorne P., Lavados P.M., Law Z.K., Lawal A., Lazo-Porras M., Lebedynets D., Lee T.-H., Leung T., Liebeskind D.S., Lindsay P., Lopez-Jaramillo P., Lotufo P.A., Machline-Carrion J., Makanjuola A., Markus H.S., Marquez-Romero J.M., Medina M., Medukhanova S., Mehndiratta M.M., Merkin A., Mirrakhimov E., Mohl S., Moscoso-Porras M., Muller-Stierlin A., Murphy S., Musa K.I., Nasreldein A., Nogueira R.G., Nolte C., Noubiap J.J., Novarro-Escudero N., Ogun Y., Oguntoye R.A., Oraby M.I., Osundina M., Ovbiagele B., Orken D.N., Ozdemir A.O., Ozturk S., Paccot M., Phromjai J., Piradov P., Platz T., Potpara T., Ranta A., Rathore F., Richard E., Sacco R.L., Sahathevan R., Santos Carquin I., Saposnik G., Sarfo F.S., Sharma M., Sheth K., Shobhana A., Suwanwela N., Svyato I., Sylaja P.N., Tao X., Thakur K.T., Toni D., Topcuoglu M.A., Torales J., Towfighi A., Truelsen T.C., Tsiskaridze A., Tulloch-Reid M., Useche N., Vanacker P., Vassilopoulou S., Vukorepa G., Vuletic V., Wahab K.W., Wang W., Wijeratne T., Wolfe C., Yifru Y.M., Yock-Corrales A., Yonemoto N., Yperzeele L., and Zhang P.

Subjects
Global Burden of Disease, 03 medical and health sciences, 0302 clinical medicine, Nursing, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Neurology, Medicine, 030212 general & internal medicine, Stroke, Health policy, Cause of death, Entire population, Health professionals, business.industry, Health Policy, Public Health, Environmental and Occupational Health, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Neurologija, medicine.disease, 3. Good health, Action (philosophy), Stroke prevention, Occlusive Cerebrovascular Disease, Life course approach, Human medicine, business, 030217 neurology & neurosurgery
Abstract

Stroke is the second leading cause of death and the third leading cause of disability worldwide and its burden is increasing rapidly in low-income and middle-income countries, many of which are unable to face the challenges it imposes. In this Health Policy paper on primary stroke prevention, we provide an overview of the current situation regarding primary prevention services, estimate the cost of stroke and stroke prevention, and identify deficiencies in existing guidelines and gaps in primary prevention. We also offer a set of pragmatic solutions for implementation of primary stroke prevention, with an emphasis on the role of governments and population-wide strategies, including task-shifting and sharing and health system re-engineering. Implementation of primary stroke prevention involves patients, health professionals, funders, policy makers, implementation partners, and the entire population along the life course.

Published
2022
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33. Accelerated remyelination and immune modulation by the EBI2 agonist 7α,25-dihydroxycholesterol analogue in the cuprizone model.

Author

Konieczna-Wolska K, Caratis F, Opiełka M, Biernacki K, Urbanowicz K, Klimaszewska J, Pobiarzyn P, Krajewski O, Demkowicz S, Smoleński RT, Karaszewski B, Seuwen K, and Rutkowska A

Subjects
Animals, Mice, Receptors, G-Protein-Coupled metabolism, Receptors, G-Protein-Coupled agonists, Corpus Callosum drug effects, Corpus Callosum metabolism, Corpus Callosum pathology, Myelin Sheath drug effects, Myelin Sheath metabolism, Male, Brain drug effects, Brain metabolism, Brain pathology, Cuprizone, Remyelination drug effects, Disease Models, Animal, Mice, Inbred C57BL, Demyelinating Diseases chemically induced, Demyelinating Diseases drug therapy, Hydroxycholesterols pharmacology
Abstract

Research indicates a role for EBI2 receptor in remyelination, demonstrating that its deficiency or antagonism inhibits this process. However, activation of EBI2 with its endogenous ligand, oxysterol 7α,25-dihydroxycholesterol (7α,25OHC), does not enhance remyelination beyond the levels observed in spontaneously remyelinating tissue. We hypothesized that the short half-life of the natural ligand might explain this lack of beneficial effects and tested a synthetic analogue, CF 3 -7α,25OHC, in the cuprizone model. The data showed that extending the bioavailability of 7α,25OHC is sufficient to accelerate remyelination in vivo. Moreover, the analogue, in contrast to the endogenous ligand, upregulated brain expression of Ebi2 and the synthesis of 15 lipids in the mouse corpus callosum. Mechanistically, the increased concentration of oxysterol likely disrupted its gradient in demyelinated areas of the brain, leading to the dispersion of infiltrating EBI2-expressing immune cells rather than their accumulation in demyelinated regions. Remarkably, the analogue CF 3 -7α,25OHC markedly decreased the lymphocyte and monocyte counts mimicking the key mechanism of action of some of the most effective disease-modifying therapies for multiple sclerosis. Furthermore, the Cd4+ transcripts in the cerebellum and CD4+ cell number in the corpus callosum were reduced compared to vehicle-treated mice. These findings suggest a mechanism by which EBI2/7α,25OHC signalling modulates the immune response and accelerates remyelination in vivo., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Aleksandra Rutkowska has patent #EP24191137.9 pending to n/a. Bartosz Karaszewski has patent #EP24191137.9 pending to n/a. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Published
2024
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34. Baseline characteristics, reperfusion treatment secondary prevention and outcome after acute ischemic stroke in three different socioeconomic environments in Europe.

Author

Berger C, Hammer H, Costa M, Lowiec P, Yagensky A, Scutelnic A, Antonenko K, Biletska O, Karaszewski B, Sarikaya H, Zdrojewski T, Klymiuk A, Bassetti C, Yashchuk N, Chwojnicki K, Arnold M, Saner H, and Heldner MR

Subjects
Humans, Female, Male, Aged, Middle Aged, Europe epidemiology, Socioeconomic Factors, Treatment Outcome, Risk Factors, Aged, 80 and over, Reperfusion methods, Cohort Studies, Hypertension complications, Hypertension therapy, Hypertension epidemiology, Ischemic Stroke therapy, Ischemic Stroke mortality, Ischemic Stroke prevention & control, Ischemic Stroke epidemiology, Secondary Prevention methods
Abstract

Introduction: The differences in vascular risk factors' and stroke burden across Europe are notable, however there is limited understanding of the influence of socioeconomic environment on the quality of secondary prevention and outcome after acute ischemic stroke., Patients and Methods: In this observational multicenter cohort study, we analyzed baseline characteristics, reperfusion treatment, outcome and secondary prevention in patients with acute ischemic stroke from three tertiary-care teaching hospitals with similar service population size in different socioeconomic environments: Bern/CH/ n  = 293 (high-income), Gdansk/PL/ n  = 140 (high-income), and Lutsk/UA/ n  = 188 (lower-middle-income)., Results: We analyzed 621 patients (43.2% women, median age = 71.4 years), admitted between 07 and 12/2019. Significant differences were observed in median BMI (CH = 26/PL = 27.7/UA = 27.8), stroke severity [(median NIHSS CH = 4(0-40)/PL = 11(0-33)/UA = 7(1-30)], initial neuroimaging (CT:CH = 21.6%/PL = 50.7%/UA = 71.3%), conservative treatment (CH = 34.1%/PL = 38.6%/UA = 95.2%) (each p  < 0.001), in arterial hypertension (CH = 63.8%/PL = 72.6%/UA = 87.2%), atrial fibrillation (CH = 28.3%/PL = 41.4%/UA = 39.4%), hyperlipidemia (CH = 84.9%/PL = 76.4%/UA = 17%) (each p  < 0.001) and active smoking (CH = 32.2%/PL = 27.3%/UA = 10.2%) ( p  < 0.007). Three-months favorable outcome (mRS = 0-2) was seen in CH = 63.1%/PL = 50%/UA = 59% (unadjusted- p  = 0.01/adjusted- p CH-PL/CH-UA = 0.601/0.981), excellent outcome (mRS = 0-1) in CH = 48.5%/PL = 32.1%/UA = 27% (unadjusted- p  < 0.001/adjusted- p CH-PL/CH-UA = 0.201/0.08 and adjusted-OR CH-UA = 2.09). Three-months mortality was similar between groups (CH = 17.2%/PL = 15.7%/UA = 4.8%) (unadjusted- p  = 0.71/adjusted- p CH-PL/CH-UA = 0.087/0.24). Three-months recurrent stroke/TIA occurred in CH = 3.1%/PL = 10.7%/UA = 3.1%, adjusted- p /OR CH-PL = 0.04/0.32). Three-months follow-up medication intake rates were the same for antihypertensives. Statin/OAC intake was lowest in UA = 67.1%/25.5% (CH = 87.3%/39.2%/unadjusted- p  < 0.001/adjusted- p CH-UA = 0.02/0.012/adjusted-OR CH-UA = 2.33/2.18). Oral intake of antidiabetics was lowest in CH = 10.8% (PL = 15.7%/UA = 16.1%/unadjusted- p  = 0.245/adjusted- p CH-PL/CH-UA = 0.061/0.002/adjusted-OR CH-UA = 0.25). Smoking rates decreased in all groups during follow-up., Discussion and Conclusion: Substantial differences in presentation, treatment and secondary prevention measures, are linked to a twofold difference in adjusted 3-months excellent outcome between Switzerland and Ukraine. This underscores the importance of socioeconomic factors that influence stroke outcomes, emphasizing the necessity for targeted interventions to address disparities in treatment and secondary prevention strategies., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MRH reports grants from SITEM Research Funds and the. Swiss Heart Foundation, outside the sumbitted work and grants from the Swiss National Science Foundation partly related to the submitted work. KA reports grants from the Swiss National Science Foundation, partly related to the submitted work. All other co-authors report no disclosures directly related to this manuscript.

Published
2024
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36. Circulating miRNA profiles and the risk of hemorrhagic transformation after thrombolytic treatment of acute ischemic stroke: a pilot study.

Author

Stańczak M, Wyszomirski A, Słonimska P, Kołodziej B, Jabłoński B, Stanisławska-Sachadyn A, and Karaszewski B

Abstract

Background: Hemorrhagic transformation (HT) in acute ischemic stroke is likely to occur in patients treated with intravenous thrombolysis (IVT) and may lead to neurological deterioration and symptomatic intracranial hemorrhage (sICH). Despite the complex inclusion and exclusion criteria for IVT and some useful tools to stratify HT risk, sICH still occurs in approximately 6% of patients because some of the risk factors for this complication remain unknown., Objective: This study aimed to explore whether there are any differences in circulating microRNA (miRNA) profiles between patients who develop HT after thrombolysis and those who do not., Methods: Using qPCR, we quantified the expression of 84 miRNAs in plasma samples collected prior to thrombolytic treatment from 10 individuals who eventually developed HT and 10 patients who did not. For miRNAs that were downregulated (fold change (FC) <0.67) or upregulated (FC >1.5) with p < 0.10, we investigated the tissue specificity and performed KEGG pathway annotation using bioinformatics tools. Owing to the small patient sample size, instead of multivariate analysis with all major known HT risk factors, we matched the results with the admission NIHSS scores only., Results: We observed trends towards downregulation of miR-1-3p, miR-133a-3p, miR-133b and miR-376c-3p, and upregulation of miR-7-5p, miR-17-3p, and miR-296-5p. Previously, the upregulated miR-7-5p was found to be highly expressed in the brain, whereas miR-1, miR-133a-3p and miR-133b appeared to be specific to the muscles and myocardium., Conclusion: miRNA profiles tend to differ between patients who develop HT and those who do not, suggesting that miRNA profiling, likely in association with other omics approaches, may increase the current power of tools predicting thrombolysis-associated sICH in acute ischemic stroke patients. This study represents a free hypothesis-approach pilot study as a continuation from our previous work. Herein, we showed that applying mathematical analyses to extract information from raw big data may result in the identification of new pathophysiological pathways and may complete standard design works., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Stańczak, Wyszomirski, Słonimska, Kołodziej, Jabłoński, Stanisławska-Sachadyn and Karaszewski.)

Published
2024
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37. The proton-sensing receptors TDAG8 and GPR4 are differentially expressed in human and mouse oligodendrocytes: Exploring their role in neuroinflammation and multiple sclerosis.

Author

Caratis F, Opiełka M, Hausmann M, Velasco-Estevez M, Rojek B, de Vallière C, Seuwen K, Rogler G, Karaszewski B, and Rutkowska A

Subjects
Animals, Humans, Mice, Genome-Wide Association Study, Hydrogen-Ion Concentration, Neuroinflammatory Diseases, Protons, Multiple Sclerosis genetics, Receptors, G-Protein-Coupled metabolism, Oligodendroglia metabolism
Abstract

Acidosis is one of the hallmarks of demyelinating central nervous system (CNS) lesions in multiple sclerosis (MS). The response to acidic pH is primarily mediated by a family of G protein-coupled proton-sensing receptors: OGR1, GPR4 and TDAG8. These receptors are inactive at alkaline pH, reaching maximal activation at acidic pH. Genome-wide association studies have identified a locus within the TDAG8 gene associated with several autoimmune diseases, including MS. Accordingly, we here found that expression of TDAG8, as opposed to GPR4 or OGR1, is upregulated in MS plaques. This led us to investigate the expression of TDAG8 in oligodendrocytes using mouse and human in vitro and in vivo models. We observed significant upregulation of TDAG8 in human MO3.13 oligodendrocytes during maturation and in response to acidic conditions. However, its deficiency did not impact normal myelination in the mouse CNS, and its expression remained unaltered under demyelinating conditions in mouse organotypic cerebellar slices. Notably, our data revealed no expression of TDAG8 in primary mouse oligodendrocyte progenitor cells (OPCs), in contrast to its expression in primary human OPCs. Our investigations have revealed substantial species differences in the expression of proton-sensing receptors in oligodendrocytes, highlighting the limitations of the employed experimental models in fully elucidating the role of TDAG8 in myelination and oligodendrocyte biology. Consequently, the study does not furnish robust evidence for the role of TDAG8 in such processes. Nonetheless, our findings tentatively point towards a potential association between TDAG8 and myelination processes in humans, hinting at a potential link between TDAG8 and the pathophysiology of MS and warrants further research., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Caratis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Published
2024
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38. The use of andexanet alpha in the Polish setting: An interdisciplinary protocol. Expert consensus statement of the Polish Cardiac Society.

Author

Kazimierczyk E, Dąbrowska M, Gierlotka M, Kapica-Topczewska K, Karaszewski B, Kobayashi A, Krasiński Z, Kubica J, Kułakowska A, Kurek K, Ładny R, Pleban E, Rejdak K, Rydzewska G, Słowik A, Szopiński P, Woźniak A, and Tycińska A

Subjects
Humans, Poland, Factor Xa Inhibitors therapeutic use, Hemorrhage chemically induced, Hemorrhage drug therapy, Recombinant Proteins therapeutic use, Anticoagulants therapeutic use, Rivaroxaban therapeutic use, Factor Xa therapeutic use
Abstract

Andexanet alfa (AA) is a recombinant inactive analog of human activated factor X (FXa), effectively reversing the effects of its inhibitors - rivaroxaban and apixaban, which are available in Poland. The drug was approved for clinical use registration after the publication of the results of the ANNEXA-4 trial (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXa Inhibitors 4), in which its efficacy in restoring hemostasis in life-threatening hemorrhages in patients receiving using the aforementioned anticoagulants was demonstrated. Hence, AA is now recommended for patients on apixaban or rivaroxaban therapy with massive and uncontrollable hemorrhages, including hemorrhagic strokes (HS) and gastrointestinal bleeding. Drug-specific chromogenic anti-Xa assays are generally best suited for estimating rivaroxaban and apixaban plasma levels, aside from direct assessment of their concentrations. The absence of anti-Xa activity, determined using these assays, allows us to rule out the presence of clinically relevant plasma concentrations of any FXa inhibitor. On the other hand, the dose of AA should not be modified based on the results of coagulation tests, as it depends solely on the time that elapsed since the last dose of FXa inhibitor and oon the dose and type of FXa inhibitor. AA is administered as an intravenous (i.v.) bolus, followed by an i.v. infusion of the drug. The maximum reversal of anti-Xa activity occurs within two minutes of the end of the bolus treatment, with the continuation of the continuous i.v. infusion allowing the effect to be maintained for up to two hours afterwards. Because anticoagulant activity can reappear after the infusion is completed, it is currently unclear at what point after AA administration FXa inhibitors or heparin should be re-administered. In Poland AA is starting to become available and its urgent need to administer it to patients with severe bleeding on apixaban or rivaroxaban.

Published
2024
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39. Case report: First treatment of acute ischaemic stroke in a patient on active rivaroxaban therapy using andexanet alfa and rtPA combined with early complete recovery.

Author

Karaszewski B, Szczyrba S, Jabłoński B, Gąsecki D, Kraszewski P, Wyszomirski A, Kowalski R, Kaliszan W, and Dąbrowska M

Abstract

Patients with non-large vessel occlusion acute ischemic stroke (NL-AIS) on oral anticoagulants (OAC) constitute the biggest portion among those who cannot receive any potential-reperfusion treatment even if they appear early in the hospital. We present the first case of therapy for NL-AIS in a patient with active anti-Xa anticoagulation, combining andexanet alfa and rtPA, who was recruited for STRoke On AntiCoagulants for Thrombolysis (acronym: STROACT), an ongoing therapeutic trial for non-LVO ischemic stroke on a DOAC. This is also the first report of the use of andexanet alfa-rtPA for AIS in a patient on rivaroxaban, which is the most frequently used non-vitamin K antagonist oral anticoagulant. The patient received the intravenous bolus of 800 mg of andexanet (contralateral arm), followed by a bolus of rtPA (10% of the calculated dose; ipsilateral arm), then a continuous infusion of andexanet at 8 mg/min for 120 min (contralateral arm), and rtPA (90% of the calculated dose; ipsilateral arm)-both stopped after completion of 38.9 and 74% of infusion dose, respectively, due to the severe adverse event related to the administration of rtPA. In this schema, both infusions are ongoing concurrently for approximately 60 min, and then andexanet is administered alone until the completion of the dose (altogether lasting approximately 3 h). The therapy was spectacularly effective, with early and complete improvement in NIHSS from 8 to 0 points in 70 min from the initiation of the therapy; mRS = 0. Obviously, a single case cannot drive any standard therapeutic decisions, but the experience we share in this article may help manage selected special clinical problems, especially when a patient's expected outcome is poor and there is no other way to help than experimentally. Additionally, it seems a valuable addition to recent meta-data on thrombolysis in anticoagulated patients., Trial Registration: https://www.clinicaltrialsregister.eu. Identifier: 2020-004898-41. Date of registration: March 31, 2021., Competing Interests: BK has been a member of an AstraZeneca Advisory Board in regard to unrelated usage of andexanet alfa. The membership followed the STROACT study initiation. AstraZeneca had no involvement with the STROACT study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Karaszewski, Szczyrba, Jabłoński, Gąsecki, Kraszewski, Wyszomirski, Kowalski, Kaliszan and Dąbrowska.)

Published
2023
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40. The association between white matter tract structural connectivity and information processing speed in relapsing-remitting multiple sclerosis.

Author

Chylińska M, Karaszewski B, Komendziński J, Wyszomirski A, Hałas M, Szurowska E, and Sabisz A

Subjects
Humans, Diffusion Tensor Imaging methods, Processing Speed, Quality of Life, Brain diagnostic imaging, White Matter diagnostic imaging, Multiple Sclerosis, Relapsing-Remitting diagnostic imaging, Multiple Sclerosis, Relapsing-Remitting complications, Multiple Sclerosis complications
Abstract

Background: Information processing speed (IPS) deterioration is common in relapsing-remitting multiple sclerosis (RRMS) patients [1] and might severely affect quality of life and occupational activity. However, understanding of its neural substrate is not fully elucidated. We aimed to investigate the associations between MRI-derived metrics of neuroanatomical structures, including the tracts, and IPS., Methods: Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), and Color Trails Test (CTT) were used to evaluate IPS in 73 RRMS consecutive patients, all undergoing only interferon beta (IFN-β) therapy during the study. At the same time, 1.5T MRI including diffusion tensor imaging (DTI) data was acquired for each recruited subject. We analyzed volumetric and diffusion MRI measures (FreeSurfer 6.0) including normalized brain volume (NBV), cortical thickness (thk), white matter hypointensities (WMH), volume (vol), diffusion parameters: mean (MD), radial (RD), axial (AD) diffusivities, and fractional anisotropy (FA) of 18 major white-matter (WM) tracts. Multiple linear regression model with interaction resulted in distinguishing the neural substrate of IPS deficit in the IPS impaired subgroup of patients., Results: The most significant tract abnormalities contributing to IPS deficit were right inferior longitudinal fasciculus (R ILF) FA, forceps major (FMAJ) FA, forceps minor (FMIN) FA, R uncinate fasciculus (UNC) AD, R corticospinal tract (CST) FA, and left superior longitudinal fasciculus FA (L SLFT). Among volumetric MRI metrics, IPS deficit was associated with L and R thalamic vol. and cortical thickness of insular regions., Conclusion: In this study, we showed that disconnection of the selected WM tracts, in addition to cortical and deep gray matter (GM) atrophy, might underlie IPS deficit in RRMS patients but more extensive studies are needed for precise associations., (© 2023. The Author(s).)

Published
2023
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41. Brain Atrophy as an Outcome of Disease-Modifying Therapy for Remitting-Relapsing Multiple Sclerosis.

Author

Chylińska M, Komendziński J, Wyszomirski A, and Karaszewski B

Abstract

Introduction: Currently, clinical trials of DMTs strive to determine their effect on neuroinflammation and neurodegeneration. We aimed to determine the impact of currently used DMTs on brain atrophy and disability in RRMS. The main goal of this review is to evaluate the neuroprotective potential of MS therapy and assess its impact on disability., Methods: We performed a systematic analysis of clinical trials that used brain atrophy as an outcome or performed post hoc analysis of volumetric MRI parameters to assess the neuroprotective potential of applied therapies. Trials between 2008 and 2019 that included published results of brain parenchymal fraction (BPF) change and brain volume loss (BVL) in the period from baseline to week 96 or longer were considered., Results: Twelve from 146 clinical trials met the inclusion criteria and were incorporated into the analysis. DMTs that presented a large reduction in BVL also exhibited robust effects on clinical disability worsening, e.g., alemtuzumab with a 42% risk reduction in 6-month confirmed disability accumulation ( p = 0.0084), ocrelizumab with a 40% risk reduction in 6-month confirmed disability progression ( p = 0.003), and other DMTs (cladribine and teriflunomide) with moderate influence on brain atrophy were also associated with a marked impact on disability worsening. Dimethyl fumarate (DEFINE) and fingolimod (FREEDOMS I) initially exhibited significant effect on BVL; however, this effect was not confirmed in further clinical trials: CONFIRM and FREEDOMS II, respectively. Peg-IFN- β 1a shows a modest effect on BVL and disability worsening., Conclusion: Our results show that BVL in one of the components of clinical disability worsening, together with other variables (lesion volume and annualized relapse rate). Standardization of atrophy measurement technique as well as harmonization of disability worsening and progression criteria in further clinical trials are of utmost importance as they enable a reliable comparison of neuroprotective potential of DMTs., Competing Interests: BK received independent (investigator initiated, project leader) grants from Siemens and Nutricia; is a member of an Astra Zeneca advisory board working on standard use of a new therapy for anticoagulant associated intracranial haemorrhage; provided content-independent lectures funded by Astra Zeneca, Biogen, Novartis, Medtronic, Boehringer Ingelheim, Servier, Angels Initiative; and was/is an investigator in clinical trials founded by Baxalta, Roche, Novartis, Astra Zeneca. MC was an investigator in clinical trials founded by Novartis, Teva, Biogen, Sanofi, and Serono. The authors JK and AW declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Magdalena Chylińska et al.)

Published
2023
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43. Supine blood pressure normalised by daytime series values is independently associated with ischaemic wake-up stroke.

Author

Kowalczyk K, Kwarciany M, Narkiewicz K, Karaszewski B, and Gąsecki D

Subjects
Male, Humans, Female, Blood Pressure physiology, Blood Pressure Monitoring, Ambulatory, Brain Ischemia diagnosis, Brain Ischemia complications, Stroke etiology, Hypertension, Ischemic Stroke diagnosis
Abstract

Purpose: Wake-up stroke constitutes up to 1/4 of all ischaemic strokes; however, its pathomechanisms remain largely unknown. Although low nocturnal blood flow may be the underlying cause, little is known about blood pressure (BP) characteristic of wake-up stroke patients. The aim of our study was to look for differences in BP variables between wake-up stroke and known-onset stroke patients and to seek BP indices which could distinguish wake-up stroke patients from other stroke patients., Materials and Methods: In the study, we included ischaemic stroke patients in whom office BP measurement and Ambulatory BP monitoring (ABPM) were recorded at day 7, after acute hypertensive response. The daytime period was defined as the interval from 6 a.m. to 10 p.m. From ABPM, we obtained parameters of BP variability. Additionally, we calculated the BP percentage differences defined as (supine office BP-average daytime BP)/average daytime BP for systolic, diastolic, and mean blood pressure. We calculated analogous indices for night-time. The univariate and multivariate relationships between BP variables and wake-up stroke were analysed., Results: Among the recruited 120 patients (aged 61.6 ± 12.3; 88 [73%] males; the baseline National Institutes of Health stroke scale score 4 [3-8]), 36 (30%) had wake-up stroke. In a univariate analysis, the systolic and mean daytime and night-time BP differences were significantly lower in patients with wake-up stroke [(-1.92 (-11.55 to 3.95) vs 4.12 (-2.48 to 11.31), p  = 0.006 and -6.20 (-12.32 to 7.42) vs 2.00 (-6.86 to 11.65), p  = 0.029 for daytime, respectively; 0.00 (-9.79 to 11.82) vs 9.84 (0.00 to 18.25), p  = 0.003 and 0.51 (-8.49 to 12.08) vs 7.82 (-2.47 to 20.39), p  = 0.026, for night-time, respectively]. After adjustment for possible confounders, the systolic BP difference remained significantly associated with wake-up stroke (odds ratio = 0.96, 95% confidence interval = 0.92-1.00, p  = 0.039)., Conclusion: The subacute office-ambulatory BP difference including the dynamic (systolic BP), but not static BP component was independently associated with wake-up stroke.

Published
2022
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44. The impaired distribution of adenosine deaminase isoenzymes in multiple sclerosis plasma and cerebrospinal fluid.

Author

Kutryb-Zajac B, Kawecka A, Caratis F, Urbanowicz K, Braczko A, Furihata T, Karaszewski B, Smolenski RT, and Rutkowska A

Abstract

Background: Adenosine deaminase (ADA) via two isoenzymes, ADA1 and ADA2, regulates intra- and extracellular adenosine concentrations by converting it to inosine. In the central nervous system (CNS), adenosine modulates the processes of neuroinflammation and demyelination that together play a critical role in the pathophysiology of multiple sclerosis (MS). Except for their catalytic activities, ADA isoenzymes display extra-enzymatic properties acting as an adhesion molecule or a growth factor., Aims: This study aimed to explore the distribution and activity of ADA1 and ADA2 in the plasma and the CSF of MS patients as well as in the human brain microvascular endothelial cells (HBMEC), human brain vascular pericytes and human astrocytes., Methods and Results: The enzyme assay following reverse phase-high performance liquid chromatography (HPLC) analysis was used to detect the ADA1 and ADA2 activities and revealed an increased ratio of ADA1 to ADA2 in both the plasma and the CSF of MS patients. Plasma ADA1 activity was significantly induced in MS, while ADA2 was decreased in the CSF, but significance was not reached. The brain astrocytes, pericytes and endothelial cells revealed on their surface the activity of ADA1, with its basal level being five times higher in the endothelial cells than in the astrocytes or the pericytes. In turn, ADA2 activity was only observed in pericytes and endothelial cells. Stimulation of the cells with pro-inflammatory cytokines TNFα/IL17 for 18 h decreased intracellular nucleotide levels measured by HPLC only in pericytes. The treatment with TNFα/IL17 did not modulate cell-surface ATP and AMP hydrolysis nor adenosine deamination in pericytes or astrocytes. Whereas in endothelial cells it downregulated AMP hydrolysis and ADA2 activity and upregulated the ADA1, which reflects the ADA isoenzyme pattern observed here in the CSF of MS patients., Conclusion: In this study, we determined the impaired distribution of both ADA isoenzymes in the plasma and the CSF of patients with MS. The increased ADA1 to ADA2 ratio in the CSF and plasma may translate to unfavorable phenotype that triggers ADA1-mediated pro-inflammatory mechanisms and decreases ADA2-dependent neuroprotective and growth-promoting effects in MS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kutryb-Zajac, Kawecka, Caratis, Urbanowicz, Braczko, Furihata, Karaszewski, Smolenski and Rutkowska.)

Published
2022
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45. Skeletonized mean diffusivity and neuropsychological performance in relapsing-remitting multiple sclerosis.

Author

Chylińska M, Karaszewski B, Komendziński J, Wyszomirski A, Sabisz A, Halas M, and Szurowska E

Subjects
Biomarkers, Cross-Sectional Studies, Diffusion Tensor Imaging methods, Humans, Magnetic Resonance Imaging methods, Neuropsychological Tests, Multiple Sclerosis complications, Multiple Sclerosis, Relapsing-Remitting pathology, White Matter diagnostic imaging, White Matter pathology
Abstract

Background: Peak width of Skeletonized Mean Diffusivity (PSMD), as a novel marker of white matter (WM) microstructure damage, is associated with cognitive decline in several WM pathologies (i.e., small vessel disorders). We hypothesized that markers combining alterations in whole WM could be associated with cognitive dysfunction in relapsing-remitting multiple sclerosis (RRMS) patients., Methods: We used PSMD based on tract-based spatial statistics (TBSS) of diffusion tensor imaging (DTI) magnetic resonance (MR) scans. We investigated RRMS patients (n = 73) undergoing interferon beta (IFN-β) therapy. In this cross-sectional study, we investigated the association between neuropsychological data and clinical and MRI variables: PSMD, WM hypointensities, and normalized brain volume (NBV)., Results: In our cohort, 37 (50.7%) patients were recognized as cognitively impaired (CI) and 36 (49.3%) patients were cognitively normal (CN). In regression analysis, PSMD was a statistically significant contributor in the California Verbal Learning Test (CVLT) list A (p = 0.04) and semantic fluency (p = 0.036). PSMD (p < 0.001, r 2  = 0.35), NBV (p = 0.002, r 2  = 2.6) and WM hypointensities (p < 0.001, r 2  = 0.40) were major contributors to upper extremity disability (9HPT) in the CN subgroup. A significant contributor in the majority of neuropsychological measures was education attainment., Conclusion: We investigated PSMD as a new parameter of WM microstructure damage that is a contributor in complex cognitive tasks, CVLT performance, and semantic fluency. PSMD was a statistically significant contributor to upper extremity disability (9HPT) together with WM hypointensities and NBV. Education attainment proved to be relevant in the majority of cognitive domains. Further studies are needed to estimate PSMD relevance as a marker of CI in MS., (© 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Published
2022
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47. New Remote Cerebral Microbleeds on T2 * -Weighted Echo Planar MRI After Intravenous Thrombolysis for Acute Ischemic Stroke.

Author

Jabłoński B, Gójska-Grymajło A, Ossowska D, Szurowska E, Wyszomirski A, Rojek B, and Karaszewski B

Abstract

Background: The main and well-defined complication of intravenous administration of recombinant tissue plasminogen activator (tPA) in patients with acute ischemic stroke (AIS) is symptomatic intracranial hemorrhage (sICH). However, rtPA might also be connected with the formation of cerebral microbleeds (CMBs), located remotely from the ischemic lesions, that may remain clinically silent. This association might be important because the load of CMBs has been associated with cognitive impairment. We investigated whether administration of rtPA in AIS results in the appearance of new CMBs and if the initial load of CMBs is associated with hemorrhagic transformation., Methods: A total of fifty-nine consecutive patients with AIS treated with rtPA underwent MRI including T2 * -weighted Echo Planar Imaging (T2 * -EPI) shortly before and 7-9 days after rtPA administration. We calculated the load of new CMBs located outside the MR diffusion restriction area in the follow-up imaging and assessed hemorrhagic transformation with ECASS-II scoring., Results: A total of forty-nine patients were included for the final analysis. On initial T2 * -EPI-GRE, 37 baseline microbleeds (CMBs) were observed in 14 patients (28.6%). On follow-up T2 * -EPI-GRE amount of CMBs increased to a total number of 103. New CMBs were found in 5 (14.3%) of 35 patients without and in 9 (64.3%) of 14 with any baseline CMBs. Multiple logistic regression analysis indicated that presence of baseline CMBs (risk ratio [RR] 5.95, 95% CI 2.69-13.20, p < 0.001) and lower platelets level (risk ratio [RR] 0.992, 95% CI 0.986-0.998, p = 0.007) were independently associated with new CMBs. The baseline load of CMBs was not associated with the risk of hemorrhagic transformation., Conclusion: In this study, new CMBs were found in nearly 30% of patients with AIS on the 7-9 days after rtPA treatment. Baseline CMBs correlated with a higher risk of new CMBs appearing after the rtPA treatment, independently of other factors. At the same time, in our sample, baseline CMBs did not correlate with an increased risk of hemorrhagic transformation. Since the associations between the CMBs load and cognitive impairment have already been proved, further studies are warranted to investigate possible associations between the thrombolytic treatment of patients with AIS, mainly those with baseline CMBs, and the risk of earlier cognitive decline., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jabłoński, Gójska-Grymajło, Ossowska, Szurowska, Wyszomirski, Rojek and Karaszewski.)

Published
2022
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48. Effect of Glucocorticoid Administration in Intravenous Pulses on Selected Parameters of the Coagulation System.

Author

Kłosowski P, Świątkowska-Stodulska R, Stodulski D, Kaszubowski M, Karaszewski B, and Sworczak K

Subjects
Blood Coagulation Factors metabolism, Blood Coagulation Tests, Humans, Methylprednisolone therapeutic use, Glucocorticoids, Thromboplastin
Abstract

Background: Changes of the coagulation system are promoted by serious infectious or noninfectious diseases, surgical procedures, and exogenous substances, including drugs. This study aimed to assess the effect of methylprednisolone pulses on selected parameters of the coagulation system., Methods: The study group consisted of patients suffering from multiple sclerosis, thyroid orbitopathy, or sudden sensorineural hearing loss. 48 patients and 20 healthy volunteers were examined. The hemostatic parameters: activity of coagulation factors (VIII, IX, and XI), antithrombin activity, protein C and S activity, and concentration of soluble tissue factor were analyzed at baseline and after 3 g and 5 g of methylprednisolone administration., Results: A statistically significant increase was noted in the activity of all the studied plasma coagulation factors, plasma coagulation inhibitors (except protein S activity), and the concentration of soluble tissue factor after methylprednisolone administration., Conclusion: The glucocorticoids administered in the intravenous pulses of methylprednisolone shift the balance toward thromboembolic complications., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Przemysław Kłosowski et al.)

Published
2022
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49. Trends of stroke hospitalisation and fatality rates in young vs. elderly people in Poland during 2010-2019 decade.

Author

Jermakow N, Maluchnik M, Sienkiewicz-Jarosz H, Karaszewski B, Wierzchowska-Cioch E, and Ryglewicz D

Subjects
Aged, Young Adult, Humans, Poland, Hospitalization, Registries, Stroke epidemiology, Brain Ischemia epidemiology
Abstract

Introduction: Since the turn of the century, epidemiological studies have shown an increase in stroke hospitalisation rates among young adults in contrast to a decline in rates seen among the older population. The aim of the present study was to investigate the trends of stroke hospitalisation rates and case fatality ratios (CFR) over the decade starting in 2010 in different age groups of the Polish population., Material and Methods: The patients were identified on the basis of the Polish National Health Fund that gathers all the data of the Hospital Discharge Registry as well as the National Cause of Death Registry of patients with stroke who were hospitalised between 2010 and 2019 and who were diagnosed according to the International Classification of Diseases - Tenth Revision (ICD-10) with haemorrhagic stroke (HS; codes I61* and I62*) and ischaemic stroke (IS; codes I63*)., Results: From a total nationwide cohort of 799,132 stroke patients (86.2% with IS and 13.8% with HS) treated between 2010 and 2019, a group of 22,329 patients (2.79%) aged 18-44 years was selected, among whom 69.6% had IS and 30.4% had HS. We documented a statistically significant increase in the IS hospitalisation rate in young adults alongside a decrease of this rate in those aged > 64. Among young adults with IS, the highest increase (p = 0.001) was observed for those aged 35-44 in 2019 (up to 39.2), and was significant each year starting from 2017 (2017-2019: p < 0.01). In the case of HS, the annual number of patients did not change significantly. In 2019 (compared to 2010), a decrease in 30-day, 90-day and 1-year CFR was noted in all age groups of patients with IS and HS. Stroke aetiology of IS was diagnosed in 60% of patients. More than 40% of patients with IS were discharged with the diagnosis of stroke of unspecified cause., Conclusions: In the case of IS, opposite trends of hospitalisation rates in younger and older age groups were documented, with the highest increase of IS in patients aged 35-44. A decline in CFR was observed for both IS and HS in all age groups.

Published
2022
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50. Retinal nerve fiber and ganglion cell complex layer thicknesses mirror brain atrophy in patients with relapsing-remitting multiple sclerosis.

Author

Glasner P, Sabisz A, Chylińska M, Komendziński J, Wyszomirski A, and Karaszewski B

Subjects
Atrophy, Brain, Humans, Nerve Fibers pathology, Retina diagnostic imaging, Retrospective Studies, Tomography, Optical Coherence methods, Central Nervous System Diseases pathology, Multiple Sclerosis complications, Multiple Sclerosis, Relapsing-Remitting complications, Multiple Sclerosis, Relapsing-Remitting diagnostic imaging, Multiple Sclerosis, Relapsing-Remitting pathology, Neurodegenerative Diseases
Abstract

Background: Multiple sclerosis (MS) is associated with progressive brain atrophy, which in turn correlates with disability, depression, and cognitive impairment. Relapsing-remitting multiple sclerosis (RRMS) is a type of MS in which relapses of the disease are followed by remission periods. This is the most common type of the disease. There is a significant need for easy and low-cost methods to these cerebral changes. Changes in retinal layer thickness may reflect alterations in brain white and gray matter volumes. Therefore, this paper aims to determine whether retinal layer thickness, measured using optical coherence tomography (OCT), correlates with volumetric brain assessments obtained by magnetic resonance imaging (MRI)., Methods: This retrospective cohort study recruited 53 patients with relapsing-remitting MS who underwent MRI and OCT examinations for evaluation of brain compartment volumes and thickness of retinal layers, respectively. OCT parameters, including central retinal thickness; retinal nerve fiber layer thickness (RNFL, peripapillary thickness); ganglion cell complex thickness (GCC, macular thickness); and Expanded Disability Status Scale (EDSS) results were compared with MRI parameters (cerebral cortex; cerebral cortex and basal ganglia combined; brain hemispheres without the ventricular system; and white matter plaques). We also checked whether there is a correlation between the number of RRMS and OCT parameters., Objective: Our primary objective was to identify whether these patients had retinal thickness changes, and our secondary objective was to check if those changes correlated with the MRI brain anatomical changes., Results: RNFL and GCC thicknesses were strongly (p-value < 0.05) associated with (i) cerebral cortex volume, (ii) combination of brain cortex and basal ganglia volumes, and (iii) the hemispheres but without the ventricular system. White matter plaques (combined) showed only weak or no correlation with RNFL and GCC. There was no correlation between central retinal thickness and brain compartment volumes, and there were weak or no correlations between the summary EDSS scores and OCT results., Conclusions: Retinal layer thickness measured by OCT correlates with select volumetric brain assessments on MRI. During the course of RRMS, the anatomo-pathological structure of the retina might serve as a surrogate marker of brain atrophy and clinical progression within selected domains.

Published
2022
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