Identification of the ischemic stroke etiology: A step-by-step algorithm. A review
- Authors: Kulesh A.A.1,2, Demin D.A.1,3, Mekhryakov S.A.1,2, Kayleva N.A.1,2
-
Affiliations:
- Vagner Perm State Medical University
- City Clinical Hospital №4, Perm
- Moscow Multidisciplinary Clinical Center "Kommunarka"
- Issue: Vol 27, No 11 (2025): Neurology and rheumatology
- Pages: 637-645
- Section: Articles
- URL: https://journal-vniispk.ru/2075-1753/article/view/365525
- DOI: https://doi.org/10.26442/20751753.2025.11.203418
- ID: 365525
Cite item
Full Text
Abstract
Identification of the ischemic stroke etiology is the most critical task of stroke departments, along with reperfusion therapy and medical rehabilitation. The earliest possible determination of the pathogenetic subtype of stroke facilitates effective secondary prevention, which reduces the risk of early neurological deterioration, relapse, and, in the long term, repeated stroke and other cardiovascular events. In this article, the diagnosis of the stroke cause is presented as a sequence of the following five steps: analysis of clinical clues, analysis of radiological clues, standard diagnostic search, symptom- and focus-oriented search, and exclusion of rare causes.
Keywords
About the authors
Aleksey A. Kulesh
Vagner Perm State Medical University; City Clinical Hospital №4, Perm
Author for correspondence.
Email: aleksey.kulesh@gmail.com
ORCID iD: 0000-0001-6061-8118
D. Sci. (Med.), Prof.
Russian Federation, Perm; PermDmitry A. Demin
Vagner Perm State Medical University; Moscow Multidisciplinary Clinical Center "Kommunarka"
Email: aleksey.kulesh@gmail.com
ORCID iD: 0000-0003-2670-4172
Cand. Sci. (Med.)
Russian Federation, Perm; MoscowSergey A. Mekhryakov
Vagner Perm State Medical University; City Clinical Hospital №4, Perm
Email: aleksey.kulesh@gmail.com
ORCID iD: 0000-0001-5679-4100
Cand. Sci. (Med.)
Russian Federation, Perm; PermNadezhda A. Kayleva
Vagner Perm State Medical University; City Clinical Hospital №4, Perm
Email: aleksey.kulesh@gmail.com
Cand. Sci. (Med.)
Russian Federation, Perm; PermReferences
- Шамалов Н., Кустова М. Криптогенный инсульт. Неврология, нейропсихиатрия, психосоматика. 2014;6(2S):42-9 [Shamalov N, Kustova M. Cryptogenic stroke. Neurology, Neuropsychiatry, Psychosomatics. 2014;6(2S):42-9 (in Russian)]. doi: 10.14412/2074-2711-2014-2s-42-49
- Кулеш А.А., Демин Д.А., Виноградов О.И. Патогенетические механизмы ишемического инсульта: от верификации до вторичной профилактики. Consilium Medicum. 2022;23(11): 792-9 [Kulesh AA, Demin DA, Vinogradov OI. Pathogenetic mechanisms of ischemic stroke: from verification to secondary prevention. Consilium Medicum. 2022;23(11):792-9 (in Russian)]. doi: 10.26442/20751753.2021.11.201153
- Демин Д.А., Кулеш А.А., Янишевский С.Н., и др. Криптогенный инсульт. Часть 3: предсердная кардиопатия и скрытая фибрилляция предсердий. Медицинский Совет. 2022;(21):8-18 [Demin DA, Kulesh AA, Yanishevskiy SN, et al. Cryptogenic stroke. Part 3: atrial cardiopathy and silent atrial fibrillation. Meditsinskiy sovet = Medical Council. 2022;(21):8-18 (in Russian)]. doi: 10.21518/2079-701x-2022-16-21-8-18
- Кулеш А.А., Демин Д.А., Белопасова А.В., и др. Криптогенный инсульт. Часть 2: парадоксальная эмболия. Медицинский Совет. 2021;(19):16-33 [Kulesh AA, Demin DA, Belopasova AV, et al. Cryptogenic stroke. Part 2: paradoxical embolism. Meditsinskiy sovet = Medical Council. 2021;(19):16-33 (in Russian)]. doi: 10.21518/2079-701x-2021-19-16-33
- Дрешина С.А., Янишевский С.Н. Редкие причины криптогенного инсульта: систематический обзор литературы. Российский журнал персонализированной медицины. 2024;4(2):170-7 [Dreshina SA, Yanishevskiy SN. Rare causes of cryptogenic stroke. Russian Journal for Personalized Medicine. 2024;4(2):170-7 (in Russian)]. doi: 10.18705/2782-3806-2024-4-2-170-179
- Кулеш А.А., Демин Д.А., Виноградов О.И. Криптогенный инсульт. Часть 1: аорто-артериальная эмболия. Медицинский Совет. 2021;(4):78-87 [Kulesh AA, Demin DA, Vinogradov OI. Cryptogenic stroke. Part 1: Aorto-arterial embolism. Meditsinskiy sovet = Medical Council. 2021;(4):78-87 (in Russian)]. doi: 10.21518/2079-701x-2021-4-78-87
- Кулеш А.А., Нуриева Ю.А., Сыромятникова Л.И. Причины ишемического инсульта у пациентов моложе 45 лет: анализ данных регионального сосудистого центра. Неврология, нейропсихиатрия, психосоматика. 2021;13(1):24-30 [Kulesh AA, Nurieva YA, Syromyatnikova LI. Causes of ischemic stroke in patients younger than 45 years: analysis of data from the regional vascular center. Neurology, Neuropsychiatry, Psychosomatics. 2021;13(1):24-30 (in Russian)]. doi: 10.14412/2074-2711-2021-1-24-30
- Ишемический инсульт и транзиторная ишемическая атака. Клинические рекомендации. 2024. Режим доступа: https://cr.minzdrav.gov.ru/view-cr/814_1. Ссылка активна на 31.08.2025 [Ishemicheskii insul't i tranzitornaia ishemicheskaia ataka. Klinicheskie rekomendatsii. 2024. Available at: https://cr.minzdrav.gov.ru/view-cr/814_1. Accessed: 31.08.2025 (in Russian)].
- Ay H, Benner T, Arsava EM, et al. A computerized algorithm for etiologic classification of ischemic stroke: the Causative Classification of Stroke System. Stroke. 2007;38(11):2979-84. doi: 10.1161/STROKEAHA.107.490896
- Babikian VL, Caplan LR. Brain embolism is a dynamic process with variable characteristics. Neurology. 2000;54(4):797-801. doi: 10.1212/wnl.54.4.797
- Caplan's stroke: a clinical approach. Edited by LR Caplan. Cambridge; New York: Cambridge University Press, 2016.
- Arboix A, Alio J. Acute cardioembolic cerebral infarction: answers to clinical questions. Curr Cardiol Rev. 2012;8(1):54-67. doi: 10.2174/157340312801215791
- Griñán K, Arboix A, Massons J, et al. Cardioembolic Stroke: Risk Factors, Clinical Features, and Early Outcome in 956 Consecutive Patients. Rev Invest Clin. 2020;73(1):023-30. doi: 10.24875/RIC.20000227
- Kimura K, Minematsu K, Yamaguchi T, Japan Multicenter Stroke Investigators' Collaboration (J-MUSIC). Atrial fibrillation as a predictive factor for severe stroke and early death in 15,831 patients with acute ischaemic stroke. J Neurol Neurosurg Psychiatry. 2005;76(5):679-83. doi: 10.1136/jnnp.2004.048827
- Johansen MC, Chen J, Schneider ALC, et al. Association Between Ischemic Stroke Subtype and Stroke Severity: The Atherosclerosis Risk in Communities Study. Neurology. 2023;101(9):e913-91. doi: 10.1212/WNL.0000000000207535
- Minematsu K, Yamaguchi T, Omae T. 'Spectacular shrinking deficit': rapid recovery from a major hemispheric syndrome by migration of an embolus. Neurology. 1992;42(1):157-62. doi: 10.1212/wnl.42.1.157
- Seners P, Baron JC. Revisiting 'progressive stroke': incidence, predictors, pathophysiology, and management of unexplained early neurological deterioration following acute ischemic stroke. J Neurol. 2018;265(1):216-25. doi: 10.1007/s00415-017-8490-3
- Hacke W, Schwab S, Horn M, et al. 'Malignant' middle cerebral artery territory infarction: clinical course and prognostic signs. Arch Neurol. 1996;53(4):309-15. doi: 10.1001/archneur.1996.00550040037012
- Barth A, Bogousslavsky J, Regli F. The clinical and topographic spectrum of cerebellar infarcts: a clinical-magnetic resonance imaging correlation study. Ann Neurol. 1993;33(5):451-6. doi: 10.1002/ana.410330507
- Amarenco P. Cerebellar infarctions and their mechanisms. Rev Neurol (Paris). 1993;149(11):728-48. (in French).
- Kumral E, Kisabay A, Ataç C. Lesion patterns and etiology of ischemia in superior cerebellar artery territory infarcts. Cerebrovasc Dis. 2005;19(5):283-90. doi: 10.1159/000084496
- Edlow JA, Newman-Toker DE, Savitz SI. Diagnosis and initial management of cerebellar infarction. Lancet Neurol. 2008;7(10):951-64. doi: 10.1016/S1474-4422(08)70216-3
- Knepper LE, Biller J, Tranel D, et al. Etiology of stroke in patients with Wernicke's aphasia. Stroke. 1989;20(12):1730-2. doi: 10.1161/01.str.20.12.1730
- Hoffmann M, Chen R. The spectrum of aphasia subtypes and etiology in subacute stroke. J Stroke Cerebrovasc Dis. 2013;22(8):1385-92. doi: 10.1016/j.jstrokecerebrovasdis.2013.04.017
- Caplan LR. "Top of the basilar" syndrome. Neurology. 1980;30(1):72-9. doi: 10.1212/wnl.30.1.72
- Schwarz S, Egelhof T, Schwab S, Hacke W. Basilar artery embolism. Clinical syndrome and neuroradiologic patterns in patients without permanent occlusion of the basilar artery. Neurology. 1997;49(5):1346-52. doi: 10.1212/wnl.49.5.1346
- Zhang Z, Sun X, Liu X, et al. Clinical features, etiology, and prognosis of hand knob stroke: a case series. BMC Neurol. 2022;22(1). doi: 10.1186/s12883-022-02858-0
- Rissardo JP, Byroju VV, Mukkamalla S, Caprara ALF. A Narrative Review of Stroke of Cortical Hand Knob Area. Medicina (Kaunas). 2024;60(2):318. doi: 10.3390/medicina60020318
- Kuschner SH, Berihun H. Robert Wartenberg Syndrome and Sign: A Review Article. TOORTHJ. 2021;15(1):13-6. doi: 10.2174/1874325002115010013
- Brigo F, Ragnedda G, Canu P, Nardone R. Synkinetic wrist extension in distinguishing cortical hand from radial nerve palsy. Pract Neurol. 2018;18(6):520-2. doi: 10.1136/practneurol-2018-001971
- Kang SY, Kim JS. Anterior cerebral artery infarction: stroke mechanism and clinical-imaging study in 100 patients. Neurology. 2008;70(24 Pt 2):2386-93. doi: 10.1212/01.wnl.0000314686.94007.d0
- Kim JS, Caplan LR. Clinical Stroke Syndromes. Front Neurol Neurosci. 2016;40:72-92. doi: 10.1159/000448303
- Virgo JD, Plant GT. Internuclear ophthalmoplegia. Pract Neurol. 2017;17(2):149-53. doi: 10.1136/practneurol-2016-001428
- Xia C, Chen HS, Wu SW, Xu WH. Etiology of isolated pontine infarctions: a study based on high-resolution MRI and brain small vessel disease scores. BMC Neurol. 2017;17(1):216:s12883-017-0999-7. doi: 10.1186/s12883-017-0999-7
- Kim JS. Pure lateral medullary infarction: clinical-radiological correlation of 130 acute, consecutive patients. Brain. 2003;126(Pt 8):1864-72. doi: 10.1093/brain/awg169
- Tao LS, Lin JJ, Zou M, et al. A comparative analysis of 375 patients with lateral and medial medullary infarction. Brain Behav. 2021;11(8):e2224:e2224. doi: 10.1002/brb3.2224
- Верещагин Н.В. Патология вертебрально-базилярной системы и нарушения мозгового кровообращения. М.: Медицина, 1980 [Vereshchagin N.V. Patologiia vertebral'no-baziliarnoi sistemy i narusheniia mozgovogo krovoobrashcheniia. Moscow: Meditsina, 1980 (in Russian)].
- Кулеш А.А., Дёмин Д.А. Синдром Валленберга–Захарченко в неотложной ангионеврологии. Consilium Medicum. 2024;26(11):711-1 [Kulesh AA, Demin DA. Wallenberg–Zakharchenko syndrome in vascular neurology emergency care: A review. Consilium Medicum. 2024;26(11):711-8 (in Russian)]. doi: 10.26442/20751753.2024.11.203020
- Шмидт Е.В. Стеноз и тромбоз сонных артерий и нарушения мозгового кровообращения. М.: Медгиз, 1963 [Shmidt E.V. Stenoz i tromboz sonnykh arterii i narusheniia mozgovogo krovoobrashcheniia. Moscow: Medgiz, 1963 (in Russian)].
- Callizo J, Feltgen N, Pantenburg S, et al. Cardiovascular Risk Factors in Central Retinal Artery Occlusion: Results of a Prospective and Standardized Medical Examination. Ophthalmology. 2015;122(9):1881-8. doi: 10.1016/j.ophtha.2015.05.044
- Mac Grory B, Schrag M, Biousse V, et al. Management of Central Retinal Artery Occlusion: A Scientific Statement From the American Heart Association. Stroke. 2021;52(6):e282-94. doi: 10.1161/STR.0000000000000366
- Ting RJE, Hui M, Thoo C, et al. Light-induced Amaurosis: A Rare Manifestation of Internal Carotid Artery Stenosis. Cureus. 2019;11(10):e5817. doi: 10.7759/cureus.5817
- Wong KS, Caplan LR, Kim JS. Stroke Mechanisms. Front Neurol Neurosci. 2016;40:58-71. doi: 10.1159/000448302
- Huang R, Zhang X, Chen W, et al. Stroke Subtypes and Topographic Locations Associated with Neurological Deterioration in Acute Isolated Pontine Infarction. J Stroke Cerebrovasc Dis. 2016;25(1):206-13. doi: 10.1016/j.jstrokecerebrovasdis.2015.09.019
- Romano JG, Gardener H, Smith EE, et al. Frequency and Prognostic Significance of Clinical Fluctuations Before Hospital Arrival in Stroke. Stroke. 2022;53(2):482-8. doi: 10.1161/STROKEAHA.121.034124
- Psychogios M, Brehm A, López-Cancio E, et al. European Stroke Organisation guidelines on treatment of patients with intracranial atherosclerotic disease. Eur Stroke J. 2022;7(3):III-IV. doi: 10.1177/23969873221099715
- Caplan LR. Lacunar infarction and small Vessel disease: pathology and pathophysiology. J Stroke. 2015;17(1):2-6. doi: 10.5853/jos.2015.17.1.2
- Regenhardt RW, Das AS, Lo EH, Caplan LR. Advances in Understanding the Pathophysiology of Lacunar Stroke: A Review. JAMA Neurol. 2018;75(10):1273-81. doi: 10.1001/jamaneurol.2018.1073
- Deguchi I, Takahashi S. Pathophysiology and Optimal Treatment of Intracranial Branch Atheromatous Disease. J Atheroscler Thromb. 2023;30(7):701-9. doi: 10.5551/jat.RV22003
- Arboix A, Martí-Vilalta JL. Lacunar stroke. Expert Rev Neurother. 2009;9(2):179-96. doi: 10.1586/14737175.9.2.179
- He L, Xu R, Wang J, et al. Capsular warning syndrome: clinical analysis and treatment. BMC Neurol. 2019;19(1):285. doi: 10.1186/s12883-019-1522-0
- Saposnik G, Noel de Tilly L, Caplan LR. Pontine warning syndrome. Arch Neurol. 2008;65(10):1375-7. doi: 10.1001/archneur.65.10.1375
- Stocker A, Struffert T, Engelhorn T, Huttner HB. Consecutive Lacunar Strokes Mimicking Brainstem Symptoms in a Patient With Pseudobulbar Palsy. Neurologist. 2015;20(1):16-7. doi: 10.1097/NRL.0000000000000038
- Кулеш А.А., Дёмин Д.А. Инсульт в бассейне артерии Першерона. Consilium Medicum. 2024;26(11):734-8 [Kulesh AA, Demin DA. Artery of Percheron stroke: A review. Consilium Medicum. 2024;26(11):734-8 (in Russian)]. doi: 10.26442/20751753.2024.11.203049
- Кулеш А.А., Мехряков С.А., Демин Д.А., и др. Роль очага инфаркта мозга в определении этиологии ишемического инсульта. Неврология и нейрохирургия. Восточная Европа. 2025;15(3):436-45 [Kulesh AA, Mekhriakov SA, Demin DA, et al. Rol' ochaga infarkta mozga v opredelenii etiologii ishemicheskogo insul'ta. Nevrologiia i neirokhirurgiia. Vostochnaia Evropa. 2025;15(3):436-45 (in Russian)].
- Танашян М.М., Кузнецова П.И., Лагода О.В., и др. Миелопролиферативные заболевания и ишемический инсульт. Анналы клинической и экспериментальной неврологии. 2014;8(2):41-5 [Tanashyan MM, Kuznetsova PI, Lagoda OV, et al. Myeloproliferative diseases and ischemic stroke. Annaly klinicheskoi i eksperimental'noi nevrologii. 2014;8(2):41-5 (in Russian)].
- Arboix A, Jiménez C, Massons J, et al. Hematological disorders: a commonly unrecognized cause of acute stroke. Expert Rev Hematol. 2016;9(9):891-901. doi: 10.1080/17474086.2016.1208555
- Дёмин Д.А., Кулеш А.А., Виноградов О.И., и др. Неврологические осложнения инфекционного эндокардита: 10 правил ведения пациента. Неврология, нейропсихиатрия, психосоматика. 2022;14(4):4-11 [Demin DA, Kulesh AA, Vinogradov OI, et al. Nevrologicheskie oslozhneniia infektsionnogo endokardita: 10 pravil vedeniia patsienta. Nevrologiia, neiropsikhiatriia, psikhosomatika. 2022;14(4):4-11 (in Russian)].
- Пизова Н.В. Первичные системные васкулиты и поражение центральной нервной системы. Журнал неврологии и психиатрии им. С.С. Корсакова. 2014;114(3):98-102 [Pizova NV. Primary systemic vasculitis and damages of the central nervous system. S.S. Korsakov Journal of Neurology and Psychiatry. 2014;114(3):98-102 (in Russian)].
- Hart RG, Diener HC, Coutts SB, et al. Embolic strokes of undetermined source: the case for a new clinical construct. Lancet Neurol. 2014;13(4):429-38. doi: 10.1016/S1474-4422(13)70310-7
- Yang D, Elkind MSV. Current perspectives on the clinical management of cryptogenic stroke. Expert Rev Neurother. 2023;23(3):213-26. doi: 10.1080/14737175.2023.2192403
- Caplan LR. Intracranial branch atheromatous disease: a neglected, understudied, and underused concept. Neurology. 1989;39(9):1246-50. doi: 10.1212/wnl.39.9.1246
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