r-n-jРоссийский неврологический журналRussian neurological journal2658-79472686-7192МИА10.30629/2658-7947-2019-24-6-29-38r-n-j-44Research ArticleКЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯ И НАБЛЮДЕНИЯCLINICAL RESEARCH AND SURVEILLANCEАмилоидный ангиит и прогрессирующий корковый поверхностный сидероз как агрессивные фенотипы церебральной амилоидной ангиопатии: принципы рационального ведения пациентовAmyloid angiitis and progressive cortical superficial siderosis as aggressive phenotypes of cerebral amyloid angiopathy: principles of rational managementhttps://orcid.org/0000-0001-6061-8118КулешА. А.KuleshA. A.

Кулеш Алексей Александрович.

Пермь.

Kulesh Alexey A.

Perm.

aleksey.kulesh@gmail.comhttps://orcid.org/0000-0001-8922-5764ГорстН. Х.GorstN. Kh.

Пермь.

Perm.

GorstHope@gmail.comКузинаЕ. В.KuzinaN. V.

Пермь.

Perm.

evgenij.83kuzin@gmail.comhttps://orcid.org/0000-0001-8523-2692ДробахаВ. Е.DrobakhaV. E.

Пермь.

Perm.

drobakha.v@gmail.comhttps://orcid.org/0000-0002-6310-9316ШестаковВ. В.ShestakovV. V.

Пермь.

Perm.

shvnerv@mail.ruhttps://orcid.org/0000-0002-7536-2060КаракуловаЮ. B.KarakulovaYu. V.

Пермь.

Perm.

julia.karakulova@mail.ruПермский государственный медицинский университет им. академика Е.А. Вагнера Минздрава России; Городская клиническая больница №4РоссияE.A. Vagner Perm State Medical University; City Clinical Hospital №4Russian FederationПермский государственный медицинский университет им. академика Е.А. Вагнера Минздрава РоссииРоссияE.A. Vagner Perm State Medical UniversityRussian FederationПермская центральная районная больницаРоссияPerm central district hospitalRussian Federation2019280120202462938Copyright © Кулеш А.А., Горст Н.Х., Кузина Е.В., Дробаха В.Е., Шестаков В.В., Каракулова Ю.B., 20202020Кулеш А.А., Горст Н.Х., Кузина Е.В., Дробаха В.Е., Шестаков В.В., Каракулова Ю.B.Kulesh A.A., Gorst N.K., Kuzina N.V., Drobakha V.E., Shestakov V.V., Karakulova Y.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.r-n-j.com/jour/article/view/44

Церебральная  амилоидная  ангиопатия  (ЦАА) — распространенное  в старшей возрастной  группе заболевание, обладающее высокой клинической и визуализационной  гетерогенностью.  Представлены обзор литературы и два клинических случая, отражающих различные фенотипы ЦАА, — амилоидный ангиит (ЦАА, ассоциированная  с воспалением)  и «геморрагический  фенотип» (ЦАА, ассоциированная  с внутримозговым кровоизлиянием и прогрессирующим корковым поверхностным сидерозом). В каждом случае применительно к клинико-нейровизуализационной  картине рассмотрены направления спорных векторов вторичной профилактики и терапии ЦАА: антитромботической, антигипертензивной и гиполипидемической. Обсуждаются вопросы эпидемиологии, патогенеза, диагностики и лечения ЦАА.

Cerebral amyloid angiopathy (CAA) is a common disease in the older age group with high clinical and neurovisual heterogeneity. A literature review and two clinical cases reflecting different phenotypes of CAA are presented — amyloid angiitis (CAA-related inflammation) and “hemorrhagic phenotype” (CAA associated with intracerebral hemorrhage and progressive cortical superficial siderosis). In each case, in relation to the clinical and neuroimaging picture, the directions of the disputed vectors of secondary prevention and therapy of CAA are considered: antithrombotic, antihypertensive and lipid-lowering therapy. The issues of epidemiology, pathogenesis, diagnosis and treatment of CAA are discussed.

церебральная амилоидная ангиопатияассоциированная с воспалениемцеребральные микрокровоизлияниякорковый поверхностный сидерозантитромботическая терапиягиполипидемическая терапияантигипертензивная терапияcerebral amyloid angiopathy-related inflammationcerebral microbleedscortical superficial siderosisantithrombotic therapylipid-lowering therapyantihypertensive therapyReferencesAttems J, Lauda F, Jellinger KA. Unexpectedly low prevalence of intracerebral hemorrhages in sporadic cerebral amyloid angiopathy: an autopsy study. J Neurol. 2008;255:70–76.Attems J, Lauda F, Jellinger KA. Unexpectedly low prevalence of intracerebral hemorrhages in sporadic cerebral amyloid angiopathy: an autopsy study. J Neurol. 2008;255:70–76.Charidimou A, Boulouis G, Gurol ME et al. Emerging concepts in sporadic cerebral amyloid angiopathy. Brain. 2017;140(7):1829–1850.Charidimou A, Boulouis G, Gurol ME et al. Emerging concepts in sporadic cerebral amyloid angiopathy. Brain. 2017;140(7):1829–1850.Keable A, Fenna K, Yuen HM, Johnston DA, Smyth NR, Smith C. et al. Deposition of amyloid beta in the walls of human leptomen-ingeal arteries in relation to perivascular drainage pathways in cere-bral amyloid angiopathy. Biochim Biophys Acta. 2016;1862:1037–464.Keable A, Fenna K, Yuen HM, Johnston DA, Smyth NR, Smith C. et al. Deposition of amyloid beta in the walls of human leptomen-ingeal arteries in relation to perivascular drainage pathways in cere-bral amyloid angiopathy. Biochim Biophys Acta. 2016;1862:1037–464.Greenberg SM, Rebeck GW, Vonsattel JP, Gomez-Isla T, Hyman BT. Apolipoprotein E epsilon 4 and cerebral hemorrhage associated with amyloid angiopathy. Ann Neurol. 1995;38:254–259. doi: 10.1002/ana.410380219Greenberg SM, Rebeck GW, Vonsattel JP, Gomez-Isla T, Hyman BT. Apolipoprotein E epsilon 4 and cerebral hemorrhage associated with amyloid angiopathy. Ann Neurol. 1995;38:254–259. doi: 10.1002/ana.410380219Knudsen K, Rosand J, Karluk D, Greenberg SM. Clinical diagnosis of cerebral amyloid angiopathy: validation of the Boston criteria. Neurology. 2001Feb;27;56(4):537–9. doi: 10.1212/wnl.56.4.537Knudsen K, Rosand J, Karluk D, Greenberg SM. Clinical diagnosis of cerebral amyloid angiopathy: validation of the Boston criteria. Neurology. 2001Feb;27;56(4):537–9. doi: 10.1212/wnl.56.4.537Greenberg SM, Charidimou A. Diagnosis of Cerebral Amyloid Angiopathy: Evolution of the Boston Criteria. Stroke. 2018;49(2):491–497.Greenberg SM, Charidimou A. Diagnosis of Cerebral Amyloid Angiopathy: Evolution of the Boston Criteria. Stroke. 2018;49(2):491–497.Кулеш А.А., Дробаха В.Е., Шестаков В.В. Геморрагические проявления церебральной амилоидной ангиопатии — от патогенеза к клиническому значению. Неврология, нейропсихиатрия, психосоматика. 2018;10(3):4–11.Kulesh AA, Drobakha VE, Shestakov VV. Hemorrhagic manifestations of cerebral amyloid angiopathy: from pathogenesis to clinical significance. Neurology, neuropsychiatry, psychosomatics. 2018;10(3):4–11.Greenberg SM, Salman RA, Biessels GJ et al. Outcome markers for clinical trials in cerebral amyloid angiopathy. Lancet Neurol. 2014;13:419–28.Greenberg SM, Salman RA, Biessels GJ et al. Outcome markers for clinical trials in cerebral amyloid angiopathy. Lancet Neurol. 2014;13:419–28.Corovic A, Kelly S, Markus HS. Cerebral amyloid angiopathy associated with inflammation: A systematic review of clinical and imaging features and outcome. Int J Stroke. 2018Apr;13(3):257–267. doi: 10.1177/1747493017741569Corovic A, Kelly S, Markus HS. Cerebral amyloid angiopathy associated with inflammation: A systematic review of clinical and imaging features and outcome. Int J Stroke. 2018Apr;13(3):257–267. doi: 10.1177/1747493017741569Chung KK, Anderson NE, Hutchinson D, Synek B, Barber PA. Cerebral amyloid angiopathy related inflammation: three case reports and a review. J Neurol Neurosurg Psychiatry. 2011Jan;82(1):20–6. doi: 10.1136/jnnp.2009.204180Chung KK, Anderson NE, Hutchinson D, Synek B, Barber PA. Cerebral amyloid angiopathy related inflammation: three case reports and a review. J Neurol Neurosurg Psychiatry. 2011Jan;82(1):20–6. doi: 10.1136/jnnp.2009.204180Wardlaw JM, Smith EE, Biessels GJ. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 2013Aug;12(8):822–38. doi: 10.1016/S1474-4422(13)70124–8.Wardlaw JM, Smith EE, Biessels GJ. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 2013Aug;12(8):822–38. doi: 10.1016/S1474-4422(13)70124–8.Renard D, Tatu L, Collombier L, Wacongne A, Ayrignac X, Charif M, et al. Cerebral Amyloid Angiopathy and Cerebral Amyloid Angiopathy-Related Inflammation: Comparison of Hemorrhagic and DWI MRI Features. J Alzheimers Dis. 2018;64(4):1113–1121. doi: 10.3233/JAD-180269Renard D, Tatu L, Collombier L, Wacongne A, Ayrignac X, Charif M, et al. Cerebral Amyloid Angiopathy and Cerebral Amyloid Angiopathy-Related Inflammation: Comparison of Hemorrhagic and DWI MRI Features. J Alzheimers Dis. 2018;64(4):1113–1121. doi: 10.3233/JAD-180269Auriel E, Charidimou A, Gurol ME, Ni J, Van Etten ES, Martinez-Ramirez S, et al. . Validation of Clinicoradiological Criteria for the Diagnosis of Cerebral Amyloid Angiopathy–Related Inflammation. JAMA Neurol. 2016 Feb;73(2):197–202. doi: 10.1001/jamaneurol.2015.4078Auriel E, Charidimou A, Gurol ME, Ni J, Van Etten ES, Martinez-Ramirez S, et al. . Validation of Clinicoradiological Criteria for the Diagnosis of Cerebral Amyloid Angiopathy–Related Inflammation. JAMA Neurol. 2016 Feb;73(2):197–202. doi: 10.1001/jamaneurol.2015.4078Kirshner HS, Bradshaw M. The Inflammatory Form of Cerebral Amyloid Angiopathy or BCerebral Amyloid Angiopathy–Related Inflammation (CAARI). Curr Neurol Neurosci Rep. 2015 Aug;15(8):54. doi: 10.1007/s11910-015-0572-yKirshner HS, Bradshaw M. The Inflammatory Form of Cerebral Amyloid Angiopathy or BCerebral Amyloid Angiopathy–Related Inflammation (CAARI). Curr Neurol Neurosci Rep. 2015 Aug;15(8):54. doi: 10.1007/s11910-015-0572-yCharidimou A, Martinez-Ramirez S, Shoamanesh A et al. Cerebral amyloid angiopathy with and without hemorrhage: evidence for different disease phenotypes. Neurology. 2015;84:1206–12.Charidimou A, Martinez-Ramirez S, Shoamanesh A et al. Cerebral amyloid angiopathy with and without hemorrhage: evidence for different disease phenotypes. Neurology. 2015;84:1206–12.JH, Yu JT, Tan L. The role of cholesterol metabolism in Alzheimer’s disease. SunMol Neurobiol. 2015;51(3):947–65. doi: 10.1007/s12035-014-8749-y.JH, Yu JT, Tan L. The role of cholesterol metabolism in Alzheimer’s disease. SunMol Neurobiol. 2015;51(3):947–65. doi: 10.1007/s12035-014-8749-y.Pezzini A, Grassi M, Iacoviello L, et al. Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy) Investigators. Serum cholesterol levels, HMG-CoA reductase inhibitors and the risk of intracerebral haemorrhage. The Multicenter Study on cerebral haemorrhage in Italy (MUCH-Italy). J Neurol Neurosurg Psychiatry. 2016;87:924–9.10. 1136/jnnp-2015-312736Pezzini A, Grassi M, Iacoviello L, et al. Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy) Investigators. Serum cholesterol levels, HMG-CoA reductase inhibitors and the risk of intracerebral haemorrhage. The Multicenter Study on cerebral haemorrhage in Italy (MUCH-Italy). J Neurol Neurosurg Psychiatry. 2016;87:924–9.10. 1136/jnnp-2015-312736Bonetti PO, Lerman LO, Napoli C, et al. Statin effects beyond lipid lowering — are they clinically relevant? Eur Heart J. 2003;24:225–48.Bonetti PO, Lerman LO, Napoli C, et al. Statin effects beyond lipid lowering — are they clinically relevant? Eur Heart J. 2003;24:225–48.Chan DK, O’Rourke F, Shen Q, Mak JC, Hung WT. Meta-analysis of the cardiovascular benefits of intensive lipid lowering with statins. Acta Neurol Scand. 2011;124:188–195.Chan DK, O’Rourke F, Shen Q, Mak JC, Hung WT. Meta-analysis of the cardiovascular benefits of intensive lipid lowering with statins. Acta Neurol Scand. 2011;124:188–195.Hackam DG, Hegele RA.Cholesterol Lowering and Prevention of Stroke An Overview. Stroke. 2019;50:00–00. DOI: 10.1161/STROKEAHA.118.023167Hackam DG, Hegele RA.Cholesterol Lowering and Prevention of Stroke An Overview. Stroke. 2019;50:00–00. DOI: 10.1161/STROKEAHA.118.023167Pezzini A, Del Zotto E, Volonghi I, et al. New insights into the pleiotropic effects of statins for stroke prevention. Mini Rev Med Chem. 2009;9:794–804.Pezzini A, Del Zotto E, Volonghi I, et al. New insights into the pleiotropic effects of statins for stroke prevention. Mini Rev Med Chem. 2009;9:794–804.Bifulco M, Malfitano AM. Regulation of platelet function by statins. J Blood Disord. 2014;1:1–2.Bifulco M, Malfitano AM. Regulation of platelet function by statins. J Blood Disord. 2014;1:1–2.Goldstein LB, Amarenco P, Szarek M, Callahan A III, Hennerici M, Sillesen H, et al; SPARCL Investigators. Hemorrhagic stroke in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels study. Neurology. 2008;70(24 pt 2):2364–2370. doi: 10.1212/01.wnl.0000296277.63350.77Goldstein LB, Amarenco P, Szarek M, Callahan A III, Hennerici M, Sillesen H, et al; SPARCL Investigators. Hemorrhagic stroke in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels study. Neurology. 2008;70(24 pt 2):2364–2370. doi: 10.1212/01.wnl.0000296277.63350.77Romero JR, Preis SR, Beiser A, et al. Risk factors, stroke prevention treatments, and prevalence of cerebral microbleeds in the Framingham Heart Study. Stroke. 2014;45:1492–4. 10.1161/STROKEAHA.114.004130Romero JR, Preis SR, Beiser A, et al. Risk factors, stroke prevention treatments, and prevalence of cerebral microbleeds in the Framingham Heart Study. Stroke. 2014;45:1492–4. 10.1161/STROKEAHA.114.004130Woo D, Deka R, Falcone GJ, et al. Apolipoprotein E, statins, and risk of intracerebral hemorrhage. Stroke. 2013;44:3013–7.Woo D, Deka R, Falcone GJ, et al. Apolipoprotein E, statins, and risk of intracerebral hemorrhage. Stroke. 2013;44:3013–7.Martí-Fàbregas J, Medrano-Martorell S, Merino E et al. Statins do not increase Markers of Cerebral Angiopathies in patients with Cardioembolic Stroke. Sci Rep. 2018Jan 24;8(1):1492. doi: 10.1038/s41598-018-20055-3.Martí-Fàbregas J, Medrano-Martorell S, Merino E et al. Statins do not increase Markers of Cerebral Angiopathies in patients with Cardioembolic Stroke. Sci Rep. 2018Jan 24;8(1):1492. doi: 10.1038/s41598-018-20055-3.Ziff OJ, Banerjee G, Ambler G, Werring DJ. Statins and the risk of intracerebral haemorrhage in patients with stroke: systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2019Jan;90(1):75–83. doi: 10.1136/jnnp-2018-318483Ziff OJ, Banerjee G, Ambler G, Werring DJ. Statins and the risk of intracerebral haemorrhage in patients with stroke: systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2019Jan;90(1):75–83. doi: 10.1136/jnnp-2018-318483Phuah CL, Raffeld MR, Ayres AM, Viswanathan A, Greenberg SM, Biffi A, et al. Subacute decline in serum lipids precedes the occurrence of primary intracerebral hemorrhage. Neurology. 2016;86:2034–2041. doi: 10.1212/WNL.0000000000002716Phuah CL, Raffeld MR, Ayres AM, Viswanathan A, Greenberg SM, Biffi A, et al. Subacute decline in serum lipids precedes the occurrence of primary intracerebral hemorrhage. Neurology. 2016;86:2034–2041. doi: 10.1212/WNL.0000000000002716Lin HW, Ho YF, Lin FJ. Statin use associated with lower risk of epilepsy after intracranial haemorrhage: A population-based cohort study. Br J Clin Pharmacol. 2018Sep;84(9):1970–1979. doi: 10.1111/bcp.13626. Epub 2018 Jun 15.Lin HW, Ho YF, Lin FJ. Statin use associated with lower risk of epilepsy after intracranial haemorrhage: A population-based cohort study. Br J Clin Pharmacol. 2018Sep;84(9):1970–1979. doi: 10.1111/bcp.13626. Epub 2018 Jun 15.Endres M, Nolte CH, Scheitz JF.Statin Treatment in Patients With Intracerebral Hemorrhage. Stroke. 2018 Jan;49(1):240–246. doi: 10.1161/STROKEAHA.117.019322Endres M, Nolte CH, Scheitz JF.Statin Treatment in Patients With Intracerebral Hemorrhage. Stroke. 2018 Jan;49(1):240–246. doi: 10.1161/STROKEAHA.117.019322Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, et al; FOURIER Steering Committee and Investigators. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376:1713–1722. doi: 10.1056/NEJMoa1615664Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, et al; FOURIER Steering Committee and Investigators. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376:1713–1722. doi: 10.1056/NEJMoa1615664Charidimou A, Boulouis G, Xiong L. et al. Cortical superficial siderosis and first-ever cerebral hemorrhage in cerebral amyloid angiopathy. Neurology. 2017 Apr 25;88(17):1607–1614. doi: 10.1212/WNL.0000000000003866.Charidimou A, Boulouis G, Xiong L. et al. Cortical superficial siderosis and first-ever cerebral hemorrhage in cerebral amyloid angiopathy. Neurology. 2017 Apr 25;88(17):1607–1614. doi: 10.1212/WNL.0000000000003866.Charidimou A, Zonneveld HI, Shams S, Kantarci K, et al. APOE and cortical superficial siderosis in CAA: Meta-analysis and potential mechanisms. Neurology. 2019Jul;23;93(4):e358–e371. doi: 10.1212/WNL.0000000000007818.Charidimou A, Zonneveld HI, Shams S, Kantarci K, et al. APOE and cortical superficial siderosis in CAA: Meta-analysis and potential mechanisms. Neurology. 2019Jul;23;93(4):e358–e371. doi: 10.1212/WNL.0000000000007818.Charidimou A, Linn J, Vernooij MW et al. Cortical superficial siderosis: detection and clinical significance in cerebral amyloid angiopathy and related conditions. Brain. 2015;138(Pt 8):2126–39.Charidimou A, Linn J, Vernooij MW et al. Cortical superficial siderosis: detection and clinical significance in cerebral amyloid angiopathy and related conditions. Brain. 2015;138(Pt 8):2126–39.Linn J, Halpin A, Demaerel P et al. Prevalence of superficial siderosis in patients with cerebral amyloid angiopathy. Neurology. 2010; 74:1346-50.Linn J, Halpin A, Demaerel P et al. Prevalence of superficial siderosis in patients with cerebral amyloid angiopathy. Neurology. 2010; 74:1346-50.Khurram A, Kleinig T, Leyden J. Clinical associations and causes of convexity subarachnoid hemorrhage. Stroke. 2014;45:1151–3.Khurram A, Kleinig T, Leyden J. Clinical associations and causes of convexity subarachnoid hemorrhage. Stroke. 2014;45:1151–3.Charidimou A, Peeters AP, Jager R et al. Cortical superficial siderosis and intracerebral hemorrhage risk in cerebral amyloid angiopathy. Neurology. 2013;81:1666–73.Charidimou A, Peeters AP, Jager R et al. Cortical superficial siderosis and intracerebral hemorrhage risk in cerebral amyloid angiopathy. Neurology. 2013;81:1666–73.Charidimou A, Boulouis G, Xiong L, Pasi M, Roongpiboonsopit D, Ayres A, Schwab KM, Rosand J, Gurol ME, Viswanathan A, Greenberg SM. Cortical Superficial Siderosis Evolution. Stroke. 2019Apr;50(4):954–962. doi: 10.1161/STROKEAHA.118.023368Charidimou A, Boulouis G, Xiong L, Pasi M, Roongpiboonsopit D, Ayres A, Schwab KM, Rosand J, Gurol ME, Viswanathan A, Greenberg SM. Cortical Superficial Siderosis Evolution. Stroke. 2019Apr;50(4):954–962. doi: 10.1161/STROKEAHA.118.023368Wollenweber F, Opherk C, Zedde M, Catak C, Malik R, Duering M et al. Prognostic relevance of cortical superficial siderosis in cerebral amyloid angiopathy. Neurology. 2019Feb;19;92(8):e792–e801. doi: 10.1212/WNL.0000000000006956Wollenweber F, Opherk C, Zedde M, Catak C, Malik R, Duering M et al. Prognostic relevance of cortical superficial siderosis in cerebral amyloid angiopathy. Neurology. 2019Feb;19;92(8):e792–e801. doi: 10.1212/WNL.0000000000006956Al-Shahi Salman R, Dennis MS. Antiplatelet therapy may be continued after intracerebral hemorrhage. Stroke. 2014;45:3149–50.Al-Shahi Salman R, Dennis MS. Antiplatelet therapy may be continued after intracerebral hemorrhage. Stroke. 2014;45:3149–50.Falcone GJ, Rosand J. Aspirin should be discontinued after lobar intracerebral hemorrhage. Stroke. 2014;45:3151–2.Falcone GJ, Rosand J. Aspirin should be discontinued after lobar intracerebral hemorrhage. Stroke. 2014;45:3151–2.Biffi A, Halpin A, Towfighi A, Gilson A, Busl K, Rost N, Smith EE, Greenberg MS, Rosand J, Viswanathan A. Aspirin and recurrent intracerebral hemorrhage in cerebral amyloid angiopathy. Neurology. 2010Aug;24;75(8):693–8. doi: 10.1212/WNL.0b013e3181eee40fBiffi A, Halpin A, Towfighi A, Gilson A, Busl K, Rost N, Smith EE, Greenberg MS, Rosand J, Viswanathan A. Aspirin and recurrent intracerebral hemorrhage in cerebral amyloid angiopathy. Neurology. 2010Aug;24;75(8):693–8. doi: 10.1212/WNL.0b013e3181eee40fRESTARTCollaboration.Effectsofantiplatelet therapyafterstroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial. Lancet. 2019Jun;29;393(10191):2613–2623. doi: 10.1016/S0140-6736(19)30840RESTARTCollaboration.Effectsofantiplatelet therapyafterstroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial. Lancet. 2019Jun;29;393(10191):2613–2623. doi: 10.1016/S0140-6736(19)30840RESTART Collaboration. Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial. Lancet Neurol. 2019Jul;18(7):643–652. doi: 10.1016/S1474-4422(19)30184-XRESTART Collaboration. Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial. Lancet Neurol. 2019Jul;18(7):643–652. doi: 10.1016/S1474-4422(19)30184-XWilson D, Ambler G et al. Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies. Lancet Neurol. 2019Jul;18(7):653–665. doi: 10.1016/S1474-4422(19)30197-8Wilson D, Ambler G et al. Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies. Lancet Neurol. 2019Jul;18(7):653–665. doi: 10.1016/S1474-4422(19)30197-8Janaway BM, Simpson JE, Hoggard N, et al, and the MRC Cognitive Function and Ageing Neuropathology Study. Brain haemosiderin in older people: pathological evidence for an ischaemic origin of magnetic resonance imaging (MRI) microbleeds. Neuropathol Appl Neurobiol. 2014;40:258–69.Janaway BM, Simpson JE, Hoggard N, et al, and the MRC Cognitive Function and Ageing Neuropathology Study. Brain haemosiderin in older people: pathological evidence for an ischaemic origin of magnetic resonance imaging (MRI) microbleeds. Neuropathol Appl Neurobiol. 2014;40:258–69.Grutzendler J, Murikinati S, Hiner B, et al. Angiophagy prevents early embolus washout but recanalizes microvessels through embolus extravasation. Sci Transl Med. 2014;6:226ra31.Grutzendler J, Murikinati S, Hiner B, et al. Angiophagy prevents early embolus washout but recanalizes microvessels through embolus extravasation. Sci Transl Med. 2014;6:226ra31.Ito AO, Shindo A, Ii Y, et al. Small cortical infarcts transformed to lobar cerebral microbleeds: A Case Series. J Stroke Cerebrovasc Dis. 2019;28:e30–32.Ito AO, Shindo A, Ii Y, et al. Small cortical infarcts transformed to lobar cerebral microbleeds: A Case Series. J Stroke Cerebrovasc Dis. 2019;28:e30–32.Wardlaw JM, Smith C, Dichgans M. Small vessel disease: mechanisms and clinical implications. Lancet Neurol. 2019Jul;18(7):684–696. doi: 10.1016/S1474-4422(19)30079-1Wardlaw JM, Smith C, Dichgans M. Small vessel disease: mechanisms and clinical implications. Lancet Neurol. 2019Jul;18(7):684–696. doi: 10.1016/S1474-4422(19)30079-1Liu W, Liu R, Sun W, Peng Q, Zhang W, Xu E, et al. CASISP Study Group. Different impacts of blood pressure variability on the progression of cerebral microbleeds and white matter lesions. Stroke. 2012Nov;43(11):2916–22. doi: 10.1161/STROKEAHA.112.658369Liu W, Liu R, Sun W, Peng Q, Zhang W, Xu E, et al. CASISP Study Group. Different impacts of blood pressure variability on the progression of cerebral microbleeds and white matter lesions. Stroke. 2012Nov;43(11):2916–22. doi: 10.1161/STROKEAHA.112.658369Association Between Blood Pressure Control and Risk of Recurrent Intracerebral Hemorrhage. Biffi A, Anderson CD, Battey TW, Ayres AM, Greenberg SM, Viswanathan A, Rosand J. JAMA. 2015Sep;1;314(9):904–12. doi: 10.1001/jama.2015.10082Association Between Blood Pressure Control and Risk of Recurrent Intracerebral Hemorrhage. Biffi A, Anderson CD, Battey TW, Ayres AM, Greenberg SM, Viswanathan A, Rosand J. JAMA. 2015Sep;1;314(9):904–12. doi: 10.1001/jama.2015.10082Arima H, Tzourio C, Anderson C, Woodward M, Bousser MG, MacMahon S, et al. PROGRESS Collaborative Group. Effects of perindopril-based lowering of blood pressure on intracerebral hemorrhage related to amyloid angiopathy: the PROGRESS trial. Stroke. 2010Feb;41(2):394–6. doi: 10.1161/STROKEAHA.109.563932Arima H, Tzourio C, Anderson C, Woodward M, Bousser MG, MacMahon S, et al. PROGRESS Collaborative Group. Effects of perindopril-based lowering of blood pressure on intracerebral hemorrhage related to amyloid angiopathy: the PROGRESS trial. Stroke. 2010Feb;41(2):394–6. doi: 10.1161/STROKEAHA.109.563932

The authors declare that there are no conflicts of interest present.