. 2023 Mar 21;100(12):e1267-e1281.

doi: 10.1212/WNL.0000000000201723. Epub 2022 Dec 19.

Stroke Risk and Antithrombotic Treatment During Follow-up of Patients With Ischemic Stroke and Cortical Superficial Siderosis

Joan Martí-Fàbregas¹, Pol Camps-Renom², Jonathan G Best², Anna Ramos-Pachon², Marina Guasch-Jiménez², Alejandro Martinez-Domeño², Daniel Guisado-Alonso², Beatriz M Gómez-Ansón², Gareth Ambler², Duncan Wilson², Keon-Joo Lee², Jae-Sung Lim², Hee-Joon Bae², Masayuki Shiozawa², Masatoshi Koga², Kazunori Toyoda², Michael G Hennerici², Hugues Chabriat², Eric Jouvent², Debbie Yuen Kwun Wong², Henry Mak², Kui Kai Lau², Young Dae Kim², Tae-Jin Song², Ji-Hoe Heo², Sebastian Eppinger², Thomas Gattringer², Ender Uysal², Derya Selçuk Demirelli², Natan Bornstein², Einor Ben Assayag², Hen Hallevi², Jeremy A Molad², Masashi Nishihara², Jun Tanaka², Hideo Hara², Yusuke Yakushiji², Shelagh B Coutts², Eric Smith², Alexandros A Polymeris², Benjamin Wagner², David Seiffge², Philippe A Lyrer², Nils Peters², Stefan T Engelter², Rustam Al-Shahi Salman², Hans Rudolf Jäger², Gregory Y H Lip², Martina Goeldlin², Leonidas Panos², Christopher Charles Karayiannis², Thanh G Phan², Velandai K Srikanth², Nicolas Christ², Sarah Gunkel², Felix Fluri², Thomas W Leung², Yannie O Y Soo², Winnie Chu², Jill Abrigo², Carmen Barbato², Simone Browning², Robert Simister², Anne-Marie Mendyk², Régis Bordet², Saima Hilal², Bibek Gyanwali², Christopher Chen², Simon Jung², Dilek Necioglu Orken², David Werring², Luis Prats-Sanchez²; Microbleeds International Collaborative Network (MICON)

Affiliations

¹ From the Department of Neurology (J.M-F., P.C-R., A.R-P., M.G-J., A.M-D., D.G-A., L.P-S., L.P-S.), Neuroradiology Unit (B.M.G-A.), Department of Radiology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Barcelona, Spain; Department of Brain Repair and Rehabilitation (J.G.B., D.W., C.B., S.B., R.S., D.W.), UCL Stroke Research Centre, University College London Queen Square, Institute of Neurology, UK; Department of Statistical Science (G.A.), University College London, UK; Seoul National University College of Medicine Cerebrovascular Disease Center (K-J.L., H-J.B.); Department of Neurology (J-S.L.), Asan Medical Center University of Ulsan College of Medicine, South Korea; Department of Cerebrovascular Medicine (M.S., M.K., K.T.), National Cerebral and Cardiovascular Centre, Japan; Federation Universitätsmedizin Mannheim (M.G.H.), University of Heidelberg, Germany; Department of Neurology (H.C., E.J.), Translational Neurovascular Centre, Assistance Publique Hôpitaux de Paris, Lariboisière Hospital, France; Division of Neurology, Department of Medicine and Department of Diagnostic Radiology (D.Y.K.W., H.M., K.K.L.), The University of Hong Kong; Department of Neurology (Y.D.K., T-J.S., J-H.H.), Yonsei University College of Medicine, Seoul, South Korea; Department of Neurology (S.E., T.G.), Medical University of Graz, Austria; Department of Neurology (E.U., D.S.D.), Saglık Bilimleri University, Hamidiye Etfal Education and Research Hospital, Istanbul, Turkey; Department of Neurology (N.B., E.B.A., H.H., J.A.M.), Tel-Aviv Sourasky Medical Center, Israel; Department of Radiology and Division of Neurology, Department of Internal Medicine (M.N., J.T., H.H., Y.Y.), Saga University Faculty of Medicine, Japan; Calgary Stroke Program, Department of Clinical Neurosciences, Radiology and Community Health Sciences (S.B.C., E.S.), Hotchkiss Brain Institute, University of Calgary, Canada; Department of Neurology and Stroke Centre (A.A.P., B.W., D.S., P.A.L., N.P., S.T.E.), University Hospital Basel and University of Basel, Switzerland; Centre for Clinical Brain Sciences (R.A-S.S.), School of Clinical Sciences, University of Edinburgh; Lysholm Department of Neuroradiology and the Neuroradiological Academic Unit, Department of Brain Repair and Rehabilitation (H.R.J.), University College London Institute of Neurology and the National Hospital for Neurology and Neurosurgery; Liverpool Centre for Cardiovascular Science (G.Y.H.L.), University of Liverpool, UK; Department of Neurology (M.G., L.P., S.J.), Inselspital, Bern University Hospital and University of Bern, Switzerland; Peninsula Clinical School (C.C.K., T.G.P., V.K.S.), Peninsula Health and Stroke and Ageing Research Group, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia; Department of Neurology (N.C., S.G., F.F.), University Hospital of Würzburg, Germany; Department of Medicine and Therapeutics (T.W.L., Y.O.Y.S., W.C., J.A.), Prince of Wales Hospital, The Chinese University of Hong Kong; Univ Lille (A-M.M., R.B.), Inserm, CHU de Lille. Lille Neuroscience & Cognition, Paris, France; Memory Aging & Cognition Centre (S.H., B.G., C.C.), Yong Loo Lin School of Medicine, National University of Singapore; Department of Neurology (D.N.O.), Istanbul Arel University, Turkey. jmarti@santpau.cat.
² From the Department of Neurology (J.M-F., P.C-R., A.R-P., M.G-J., A.M-D., D.G-A., L.P-S., L.P-S.), Neuroradiology Unit (B.M.G-A.), Department of Radiology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Barcelona, Spain; Department of Brain Repair and Rehabilitation (J.G.B., D.W., C.B., S.B., R.S., D.W.), UCL Stroke Research Centre, University College London Queen Square, Institute of Neurology, UK; Department of Statistical Science (G.A.), University College London, UK; Seoul National University College of Medicine Cerebrovascular Disease Center (K-J.L., H-J.B.); Department of Neurology (J-S.L.), Asan Medical Center University of Ulsan College of Medicine, South Korea; Department of Cerebrovascular Medicine (M.S., M.K., K.T.), National Cerebral and Cardiovascular Centre, Japan; Federation Universitätsmedizin Mannheim (M.G.H.), University of Heidelberg, Germany; Department of Neurology (H.C., E.J.), Translational Neurovascular Centre, Assistance Publique Hôpitaux de Paris, Lariboisière Hospital, France; Division of Neurology, Department of Medicine and Department of Diagnostic Radiology (D.Y.K.W., H.M., K.K.L.), The University of Hong Kong; Department of Neurology (Y.D.K., T-J.S., J-H.H.), Yonsei University College of Medicine, Seoul, South Korea; Department of Neurology (S.E., T.G.), Medical University of Graz, Austria; Department of Neurology (E.U., D.S.D.), Saglık Bilimleri University, Hamidiye Etfal Education and Research Hospital, Istanbul, Turkey; Department of Neurology (N.B., E.B.A., H.H., J.A.M.), Tel-Aviv Sourasky Medical Center, Israel; Department of Radiology and Division of Neurology, Department of Internal Medicine (M.N., J.T., H.H., Y.Y.), Saga University Faculty of Medicine, Japan; Calgary Stroke Program, Department of Clinical Neurosciences, Radiology and Community Health Sciences (S.B.C., E.S.), Hotchkiss Brain Institute, University of Calgary, Canada; Department of Neurology and Stroke Centre (A.A.P., B.W., D.S., P.A.L., N.P., S.T.E.), University Hospital Basel and University of Basel, Switzerland; Centre for Clinical Brain Sciences (R.A-S.S.), School of Clinical Sciences, University of Edinburgh; Lysholm Department of Neuroradiology and the Neuroradiological Academic Unit, Department of Brain Repair and Rehabilitation (H.R.J.), University College London Institute of Neurology and the National Hospital for Neurology and Neurosurgery; Liverpool Centre for Cardiovascular Science (G.Y.H.L.), University of Liverpool, UK; Department of Neurology (M.G., L.P., S.J.), Inselspital, Bern University Hospital and University of Bern, Switzerland; Peninsula Clinical School (C.C.K., T.G.P., V.K.S.), Peninsula Health and Stroke and Ageing Research Group, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia; Department of Neurology (N.C., S.G., F.F.), University Hospital of Würzburg, Germany; Department of Medicine and Therapeutics (T.W.L., Y.O.Y.S., W.C., J.A.), Prince of Wales Hospital, The Chinese University of Hong Kong; Univ Lille (A-M.M., R.B.), Inserm, CHU de Lille. Lille Neuroscience & Cognition, Paris, France; Memory Aging & Cognition Centre (S.H., B.G., C.C.), Yong Loo Lin School of Medicine, National University of Singapore; Department of Neurology (D.N.O.), Istanbul Arel University, Turkey.

PMID: 36535778
PMCID: PMC10033167
DOI: 10.1212/WNL.0000000000201723

Stroke Risk and Antithrombotic Treatment During Follow-up of Patients With Ischemic Stroke and Cortical Superficial Siderosis

Joan Martí-Fàbregas et al. Neurology. 2023.

. 2023 Mar 21;100(12):e1267-e1281.

doi: 10.1212/WNL.0000000000201723. Epub 2022 Dec 19.

Authors

Affiliations

¹ From the Department of Neurology (J.M-F., P.C-R., A.R-P., M.G-J., A.M-D., D.G-A., L.P-S., L.P-S.), Neuroradiology Unit (B.M.G-A.), Department of Radiology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Barcelona, Spain; Department of Brain Repair and Rehabilitation (J.G.B., D.W., C.B., S.B., R.S., D.W.), UCL Stroke Research Centre, University College London Queen Square, Institute of Neurology, UK; Department of Statistical Science (G.A.), University College London, UK; Seoul National University College of Medicine Cerebrovascular Disease Center (K-J.L., H-J.B.); Department of Neurology (J-S.L.), Asan Medical Center University of Ulsan College of Medicine, South Korea; Department of Cerebrovascular Medicine (M.S., M.K., K.T.), National Cerebral and Cardiovascular Centre, Japan; Federation Universitätsmedizin Mannheim (M.G.H.), University of Heidelberg, Germany; Department of Neurology (H.C., E.J.), Translational Neurovascular Centre, Assistance Publique Hôpitaux de Paris, Lariboisière Hospital, France; Division of Neurology, Department of Medicine and Department of Diagnostic Radiology (D.Y.K.W., H.M., K.K.L.), The University of Hong Kong; Department of Neurology (Y.D.K., T-J.S., J-H.H.), Yonsei University College of Medicine, Seoul, South Korea; Department of Neurology (S.E., T.G.), Medical University of Graz, Austria; Department of Neurology (E.U., D.S.D.), Saglık Bilimleri University, Hamidiye Etfal Education and Research Hospital, Istanbul, Turkey; Department of Neurology (N.B., E.B.A., H.H., J.A.M.), Tel-Aviv Sourasky Medical Center, Israel; Department of Radiology and Division of Neurology, Department of Internal Medicine (M.N., J.T., H.H., Y.Y.), Saga University Faculty of Medicine, Japan; Calgary Stroke Program, Department of Clinical Neurosciences, Radiology and Community Health Sciences (S.B.C., E.S.), Hotchkiss Brain Institute, University of Calgary, Canada; Department of Neurology and Stroke Centre (A.A.P., B.W., D.S., P.A.L., N.P., S.T.E.), University Hospital Basel and University of Basel, Switzerland; Centre for Clinical Brain Sciences (R.A-S.S.), School of Clinical Sciences, University of Edinburgh; Lysholm Department of Neuroradiology and the Neuroradiological Academic Unit, Department of Brain Repair and Rehabilitation (H.R.J.), University College London Institute of Neurology and the National Hospital for Neurology and Neurosurgery; Liverpool Centre for Cardiovascular Science (G.Y.H.L.), University of Liverpool, UK; Department of Neurology (M.G., L.P., S.J.), Inselspital, Bern University Hospital and University of Bern, Switzerland; Peninsula Clinical School (C.C.K., T.G.P., V.K.S.), Peninsula Health and Stroke and Ageing Research Group, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia; Department of Neurology (N.C., S.G., F.F.), University Hospital of Würzburg, Germany; Department of Medicine and Therapeutics (T.W.L., Y.O.Y.S., W.C., J.A.), Prince of Wales Hospital, The Chinese University of Hong Kong; Univ Lille (A-M.M., R.B.), Inserm, CHU de Lille. Lille Neuroscience & Cognition, Paris, France; Memory Aging & Cognition Centre (S.H., B.G., C.C.), Yong Loo Lin School of Medicine, National University of Singapore; Department of Neurology (D.N.O.), Istanbul Arel University, Turkey. jmarti@santpau.cat.
² From the Department of Neurology (J.M-F., P.C-R., A.R-P., M.G-J., A.M-D., D.G-A., L.P-S., L.P-S.), Neuroradiology Unit (B.M.G-A.), Department of Radiology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Barcelona, Spain; Department of Brain Repair and Rehabilitation (J.G.B., D.W., C.B., S.B., R.S., D.W.), UCL Stroke Research Centre, University College London Queen Square, Institute of Neurology, UK; Department of Statistical Science (G.A.), University College London, UK; Seoul National University College of Medicine Cerebrovascular Disease Center (K-J.L., H-J.B.); Department of Neurology (J-S.L.), Asan Medical Center University of Ulsan College of Medicine, South Korea; Department of Cerebrovascular Medicine (M.S., M.K., K.T.), National Cerebral and Cardiovascular Centre, Japan; Federation Universitätsmedizin Mannheim (M.G.H.), University of Heidelberg, Germany; Department of Neurology (H.C., E.J.), Translational Neurovascular Centre, Assistance Publique Hôpitaux de Paris, Lariboisière Hospital, France; Division of Neurology, Department of Medicine and Department of Diagnostic Radiology (D.Y.K.W., H.M., K.K.L.), The University of Hong Kong; Department of Neurology (Y.D.K., T-J.S., J-H.H.), Yonsei University College of Medicine, Seoul, South Korea; Department of Neurology (S.E., T.G.), Medical University of Graz, Austria; Department of Neurology (E.U., D.S.D.), Saglık Bilimleri University, Hamidiye Etfal Education and Research Hospital, Istanbul, Turkey; Department of Neurology (N.B., E.B.A., H.H., J.A.M.), Tel-Aviv Sourasky Medical Center, Israel; Department of Radiology and Division of Neurology, Department of Internal Medicine (M.N., J.T., H.H., Y.Y.), Saga University Faculty of Medicine, Japan; Calgary Stroke Program, Department of Clinical Neurosciences, Radiology and Community Health Sciences (S.B.C., E.S.), Hotchkiss Brain Institute, University of Calgary, Canada; Department of Neurology and Stroke Centre (A.A.P., B.W., D.S., P.A.L., N.P., S.T.E.), University Hospital Basel and University of Basel, Switzerland; Centre for Clinical Brain Sciences (R.A-S.S.), School of Clinical Sciences, University of Edinburgh; Lysholm Department of Neuroradiology and the Neuroradiological Academic Unit, Department of Brain Repair and Rehabilitation (H.R.J.), University College London Institute of Neurology and the National Hospital for Neurology and Neurosurgery; Liverpool Centre for Cardiovascular Science (G.Y.H.L.), University of Liverpool, UK; Department of Neurology (M.G., L.P., S.J.), Inselspital, Bern University Hospital and University of Bern, Switzerland; Peninsula Clinical School (C.C.K., T.G.P., V.K.S.), Peninsula Health and Stroke and Ageing Research Group, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia; Department of Neurology (N.C., S.G., F.F.), University Hospital of Würzburg, Germany; Department of Medicine and Therapeutics (T.W.L., Y.O.Y.S., W.C., J.A.), Prince of Wales Hospital, The Chinese University of Hong Kong; Univ Lille (A-M.M., R.B.), Inserm, CHU de Lille. Lille Neuroscience & Cognition, Paris, France; Memory Aging & Cognition Centre (S.H., B.G., C.C.), Yong Loo Lin School of Medicine, National University of Singapore; Department of Neurology (D.N.O.), Istanbul Arel University, Turkey.

PMID: 36535778
PMCID: PMC10033167
DOI: 10.1212/WNL.0000000000201723

Abstract

Background and objectives: In patients with ischemic stroke (IS) or transient ischemic attack (TIA) and cortical superficial siderosis (cSS), there are few data regarding the risk of future cerebrovascular events and also about the benefits and safety of antithrombotic drugs for secondary prevention. We investigated the associations of cSS and stroke risk in patients with recent IS or TIA.

Methods: We retrospectively analyzed the Microbleeds International Collaborative Network (MICON) database. We selected patients with IS or TIA from cohorts who had MRI-assessed cSS, available data on antithrombotic treatments, recurrent cerebrovascular events (intracranial hemorrhage [ICrH], IS, or any stroke [ICrH or IS]), and mortality. We calculated incidence rates (IRs) and performed univariable and multivariable Cox regression analyses.

Results: Of 12,669 patients (mean age 70.4 ± 12.3 years, 57.3% men), cSS was detected in 273 (2.2%) patients. During a mean follow-up of 24 ± 17 months, IS was more frequent than ICrH in both cSS (IR 57.1 vs 14.6 per 1,000 patient-years) and non-cSS (33.7 vs 6.3 per 1,000 patient-years) groups. Compared with the non-cSS group, cSS was associated with any stroke on multivariable analysis {IR 83 vs 42 per 1,000 patient-years, adjusted hazard ratio [HR] for cSS 1.62 (95% CI: 1.14-2.28; p = 0.006)}. This association was not significant in subgroups of patients treated with antiplatelet drugs (n = 6,554) or with anticoagulants (n = 4,044). Patients with cSS who were treated with both antiplatelet drugs and anticoagulants (n = 1,569) had a higher incidence of ICrH (IR 107.5 vs 4.9 per 1,000 patient-years, adjusted HR 13.26; 95% CI: 2.90-60.63; p = 0.001) and of any stroke (IR 198.8 vs 34.7 per 1,000 patient-years, adjusted HR 5.03; 95% CI: 2.03-12.44; p < 0.001) compared with the non-cSS group.

Discussion: Patients with IS or TIA with cSS are at increased risk of stroke (ICrH or IS) during follow-up; the risk of IS exceeds that of ICrH for patients receiving antiplatelet or anticoagulant treatment alone, but the risk of ICrH exceeds that of IS in patients receiving both treatments. The findings suggest that either antiplatelet or anticoagulant treatment alone should not be avoided in patients with cSS, but combined antithrombotic therapy might be hazardous. Our findings need to be confirmed by randomized clinical trials.

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Conflict of interest statement

The authors report no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures.

Figures

**Figure 1. Incidence Rate per 1,000 Patient-Years, Stratified by cSS and by Antithrombotic Treatment**
cSS = cortical superficial siderosis.

**Figure 2. Results of the Univariable and Multivariable Cox Regression Analyses Comparing cSS vs Non-cSS Groups**
cSS = cortical superficial siderosis.

**Figure 3. Kaplan-Meier Survival Curves for IS**
(A), ICrH (B), Any Stroke (C) and Death (D) Comparing the cSS and Non-cSS Groups. cSS = cortical superficial siderosis; ICrH = intracranial hemorrhage.

See this image and copyright information in PMC

Comment in

Antithrombotic Therapy in Patients With Cerebral Microbleeds or Cortical Siderosis: Is This Contraindicated?
Schneck MJ, Biller J. Schneck MJ, et al. Neurology. 2023 Mar 21;100(12):551-552. doi: 10.1212/WNL.0000000000206818. Epub 2022 Dec 19. Neurology. 2023. PMID: 36535776 No abstract available.

References

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Stroke Risk and Antithrombotic Treatment During Follow-up of Patients With Ischemic Stroke and Cortical Superficial Siderosis

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Stroke Risk and Antithrombotic Treatment During Follow-up of Patients With Ischemic Stroke and Cortical Superficial Siderosis

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