HEMORRHAGIC TRANSFORMATION OF ISCHEMIC STROKE: RISK FACTORS, EARLY OUTCOMES AND REHABILITION OF MOTOR DISORDERS
Keywords:
ischemic stroke, hemorrhagic transformation, clinical risk factors, pathophysiology, biomarkers, clinicopathological studies, antithrombotic treatmentAbstract
Objective: Hemorrhagic transformation (HT) after reperfusion therapy for acute ischemic stroke often predicts a poor prognosis. This systematic review and meta-analysis aimed to identify risk factors for HT and how they are modified by hyperacute treatment [intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT)].
Research Methods: PubMed and EMBASE electronic databases were used to search for relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated.
Results : A total of 120 studies were included. Atrial fibrillation and NIHSS scores were overall predictors of any intracerebral hemorrhage (ICH) after reperfusion therapy (IVT and EVT), hyperdense artery sign (OR = 2.605, 95% CI 1.212-5.599, I %) and number 2 = 0.000. Thrombectomy (OR = 1.151, 95% CI 1.041-1.272, I 2 = 54.3% were predictors of any ICH after IVT and EVT, respectively. The common predictors for symptomatic ICH (sICH) after reperfusion therapy were age and serum glucose level. Atrial fibrillation (OR = 3.867, 95% CI 1.970-7.591, I 2 = 29.1%), NIHSS score (OR = 1.082, 95% CI 1.060-1.105, I 2 = 54.5%), and time to onset (OR-TO) = 1.003, 95% CI 1.001-1.005, I 2 = 0.0%) were predictors of sICH after IVT. Alberta Stroke Program Early CT Score (ASPECTS) (OR = 0.686, 95% CI 0.565-0.833, I 2 = 77.6%) and number of thrombectomy passes (OR = 1.374, 95% CI 1.012-1.012-1.6 % ) = 1.866, I 2 = 1.866. were predictors of sICH after EVT.
Conclusion : Several predictors of ICH have been identified, which differ depending on the type of treatment. Studies based on larger and multicenter data sets should be prioritized to confirm the results.
Ischemic stroke, which results from a lack of blood supply to the brain, is one of the leading causes of death and disability worldwide. Hemorrhagic transformation (HT), a potentially serious complication of the disease itself or its treatment aimed at restoring optimal blood flow, increases morbidity and mortality. Detailed conclusions can be found in the literature on the pathophysiological background of hemorrhagic transformation, potential clinical risk factors that increase its likelihood, and various biomarkers that are expected to help predict it and contribute to clinical outcome. Clinicopathological studies also contribute to improving our knowledge of hemorrhagic transformation. We summarized the clinical risk factors for hemorrhagic transformation of ischemic stroke in terms of risk reduction and collected the most promising biomarkers in the field. Also, adjuvant treatment options in reperfusion therapy were reviewed and summarized. We emphasized the importance of the optimal timing of revascularization treatment for carefully selected patients and the individual treatment of underlying diseases and comorbidities. Another important conclusion is that more intensive clinical follow-up, including serial cranial CT, may be recommended for selected patients, as clinicopathological examinations indicated that HT was more common than clinically suspected.
References
Sanna T, Diener HC., Passman RS, et al.: Cryptogenic stroke and essential atrial fibrillation. N Engl J Med 370: 2478–2486, 2014. doi: 10.1056/NEJMoa1313600
Ospel JM, Kappelhof M, Ganesh A, et al.: Symptomatic nonstenotic carotid artery disease: current challenges and opportunities for diagnosis and treatment. J Neurointerv Surg jnis-2022-020005, 2023.. doi: 10.1136/jnis-2022-020005 online ahead of print.
Caprio FZ, Sorond FA: Cerebrovascular disease: Primary and secondary stroke prevention. Med Clin North Am 103(2):295–308, 2019. doi:10.1016/j.mcna.2018.10.001 Epub 2018 Nov 28.
Lodder J, Krijne-Kubat B, Broekman J. Cerebral hemorrhagic infarction at autopsy; The cause of cardiac embolism and its relationship to cause of death. Stroke. (1986) 17:626–9. 10.1161/01.STR.17.4.626 [ DOI ] [ PubMed ] [ Google Scholar ]
Okada Y, Yamaguchi T, Minematsu K, Miyashita T, Sawada T, Sadoshima S, et al. Hemorrhagic transformation in cerebral embolism. Vascul. (1989) 20:598–603. 10.1161/01.STR.20.5.598 [ DOI ] [ PubMed ] [ Google Scholar ]
England TJ, Bath PM, Sare GM, Geeganage C, Moulin T, O'Neill D, et al. Asymptomatic hemorrhagic transformation of infarct and its association with functional outcome and stroke subtype: Evaluation from the Tinzaparin in Acute Ischemic Stroke Trial. Stroke. (2010) 41:2834–9. 10.1161/STROKEAHA.109.573063 [ DOI ] [ PubMed ] [ Google Scholar ]
Lee JH. Hemorrhagic transformation after acute ischemic stroke; factors and mechanisms predicting its occurrence. J Neurocrit Care. (2013) 6:59–66. [Google Scholar]
www.Med1.uz
van Kranendonk KR, Treurniet KM, Boers AMM, Berkhemer OA, Coutinho JM, Lingsma HF, et al. Additional prognostic value of quantifying hemorrhagic transformation in patients with acute ischemic stroke. Front Neurol. (2020) 11:582767. 10.3389/fneur.2020.582767 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
Fiorelli MBS, von Kummer R, del Zoppo GJ, Larrue V, Lesaffre E, Ringleb AP, et al. Hemorrhagic changes within 36 hours after cerebral infarction are associated with early clinical deterioration and 3-month outcomes in the European Collaborative Acute Stroke Study I (ECASS I) cohort. Stroke. (1999) 30:2280–4. 10.1161/01.STR.30.11.2280 [ DOI ] [ PubMed ] [ Google Scholar ]
Valentino F, Gentile L, Terruso V, Mastrilli S, Aridon P, Ragonese P, et al. Frequency and determinants of hemorrhagic transformation of posterior cerebral stroke: posterior ischemic stroke and hemorrhagic transformation. BMC Res Notes. (2017) 10:592. 10.1186/s13104-017-2889-x [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
Marcell László J, Hortobágyi T. Hemorrhagic transformation of ischemic stroke. Vasc Dis Therap. (2017) 2:1–25. 10.15761/VDT.1000130 [ DOI ] [ Google Scholar ]
Berge E, Whiteley W, Audebert H, De Marchis GM, Fonseca AC, Padiglioni C, et al. European Stroke Organization (ESO) guidelines for intravenous thrombolysis for acute ischemic stroke. Eur Stroke J. (2021) 6:I-LXII. 10.1177/2396987321989865 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
Settecase F. Endovascular therapy for acute ischemic stroke. Handb Clin Neurol. (2021) 176:199–227. 10.1016/B978-0-444-64034-5.00008-0 [ DOI ] [ PubMed ] [ Google Scholar ]
Bhaskar S, Stanwell P, Cordato D, Attia J, Levi C. Reperfusion therapy in acute ischemic stroke: dawn of a new era? BMC Neurol. (2018) 18:8. 10.1186/s12883-017-1007-y [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
Maier B, Desilles JP, Mazighi M. Intracranial hemorrhage after reperfusion therapy in patients with acute ischemic stroke. Front Neurol. (2020) 11:599908. 10.3389/fneur.2020.599908 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
van Kranendonk KR, Treurniet KM, Boers AMM, Berkhemer OA, van den Berg LA, Chalos V, et al. Hemorrhagic transformation is associated with poor functional outcome in patients with acute ischemic stroke due to large vessel occlusion. J Neurointerv Surg. (2019) 11:464–8. 10.1136/neurintsurg-2018-014141 [ DOI ] [ PubMed ] [ Google Scholar ]
Chiu D, Peterson L, Elkind MSV, Rosand J, Gerber LM, Silverstein MD, et al. Comparison of outcomes after intracerebral hemorrhage and ischemic stroke. J Stroke Cerebrovasc Dis. (2010) 19:225–9. 10.1016/j.jstrokecerebrovasdis.2009.06.002 [ DOI ] [ PubMed ] [ Google Scholar ]
An SJ, Kim TJ, Yoon BW. Epidemiology, risk factors, and clinical features of intracerebral hemorrhage: an update. J Stroke. (2017) 19:3–10. 10.5853/jos.2016.00864 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
Charbonnier G, Bonnet L, Biondi A, Moulin T. Intracranial hemorrhage after reperfusion therapy in acute ischemic stroke. Front Neurol. (2020) 11:629920. 10.3389/fneur.2020.629920 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
Paciaroni M, Agnelli G, Corea F, Ageno V, Alberti A, Lanari A, et al. Early hemorrhagic transformation of cerebral infarction: incidence, predictive factors, and impact on clinical outcome: results of a prospective multicenter study. Stroke. (2008) 39:2249–56.
1161/STROKEAHA.107.510321 [ DOI ] [ PubMed ] [ Google Scholar ]
Lee JH, Park KY, Shin JH, Cha JK, Kim HY, Kwon JH, et al. Symptomatic hemorrhagic transformation in acute ischemic stroke with atrial fibrillation and its prognosis. Eur Neurol. (2010) 64:193–200. 10.1159/000319048 [ DOI ] [ PubMed ] [ Google Scholar ]
Stone JA, Willey JZ, Keyrouz S, Butera J, McTaggart RA, Cutting S, et al. Treatment options for hemorrhagic transformation in acute ischemic stroke. Curr Treat Options Neurol. (2017) 19:1. 10.1007/s11940-017-0438-5 [ DOI ] [ PubMed ] [ Google Scholar ]
Elsaid N, Mustafa V, Saied A. Radiological indicators of hemorrhagic transformation after acute ischemic stroke: an evidence-based analysis. Neuroradiol J. (2020) 33:118–33. 10.1177/1971400919900275 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
