Volume 33, Issue 156 (January & February 2025)                   J Adv Med Biomed Res 2025, 33(156): 28-38 | Back to browse issues page

Ethics code: IR.ZUMS.REC.1398.291

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Ghoreishi A, Nasiri H, Karami Zarandi F, Hadiloo K. Thrombolysis Treatment in Patients Who Are Awake and Have an Unknown Duration of Stroke Receiving Effective and Safe Treatment or Who Are Futile and At Risk: A Study-Based SITS. J Adv Med Biomed Res 2025; 33 (156) :28-38
URL: http://journal.zums.ac.ir/article-1-7430-en.html
Thrombolysis Treatment in Patients Who Are Awake and Have an Unknown Duration of Stroke Receiving Effective and Safe Treatment or Who Are Futile and At Risk: A Study-Based SITS
Abdoreza Ghoreishi1 , Hamideh Nasiri2 , Fatemeh Karami Zarandi3 , Kaveh Hadiloo *4
1- Stroke Research Group, Head of Stroke Care Unit, Department of Neurology, Vali-e-Asr Hospital, School of Medicine, Zanjan University of Medical Science, Zanjan, Iran
2- Student Research Committee, Department of Neurology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
3- School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
4- Student Research Committee, Department of Neurology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran , kaveh.hadiloo@gmail.com
Abstract:   (128 Views)

Background: Stroke is a leading cause of death worldwide, with approximately 800,000 new cases and 140,000 deaths annually in the United States. Intravenous tissue plasminogen activator (IV tPA) is the standard treatment for acute ischemic stroke (AIS) within a 4.5-hour window. Wake-up stroke (WUS), where the exact onset time is unknown, poses challenges for tPA treatment because of its uncertain timing. This study evaluated the efficacy and safety of IV tPA in WUS patients, with a focus on clinical outcomes and adverse effects.
Methods: This single-center, open-label clinical trial was conducted at the Vali-e-Asr Hospital Stroke Care Unit, Zanjan, Iran. A total of 107 patients with WUS were enrolled and divided into two groups: 53 who received IV tPA and 54 who did not receive thrombolysis. The inclusion criteria included acute neurological symptoms consistent with stroke upon waking and presentation within four hours of symptom onset. The exclusion criteria included various factors, such as intracranial hemorrhage, contraindications to MRI, severe comorbidities, and recent use of anticoagulants. Patient evaluations included NIHSS scores at admission and also at discharge, mRS scores at discharge and three months after stroke, and imaging with MRI and CT. Descriptive statistics, nonparametric tests, and regression analyses were used for data analysis.
Results: The tPA group had significantly lower discharge NIHSS scores (4.51 vs. 6.98, p=0.006) and lower in-hospital mortality rates (3.8% vs. 22.2%, p=0.008). At three months, the tPA group had a greater proportion of favorable mRS scores (mRS 0–1: 60.4% vs. 11.1%, p<0.001) and lower total mortality (6 vs. 17 deaths, p=0.011). No significant differences in adverse effects were observed for patients over 80 years old.
Conclusions: Compared with no treatment, IV tPA treatment in WUS patients was associated with improved clinical outcomes and reduced mortality without an increased risk of adverse effects. These findings support the consideration of tPA for WUS within the specified treatment window.

Keywords: Ischemic Stroke, Wake-up Strokes, Tissue Plasminogen Activator, Treatment Outcome, Safety
     
Type of Study: Original Research Article | Subject: Clinical Medicine
Received: 2024/10/22 | Accepted: 2025/02/11 | Published: 2025/03/13
References
1. Feigin VL, Brainin M, Norrving B, Martins S, Sacco RL, Hacke W, et al. World Stroke Organization (WSO): global stroke fact sheet 2022. Int J Stroke. 2022;17(1):18-29. [DOI:10.1177/17474930211065917] [PMID]
2. Robbins BT, Howington GT, Swafford K, Zummer J, Woolum JA. Advancements in the management of acute ischemic stroke: A narrative review. J Am Coll Emerg Physicians Open. 2023;4(1):e12896. [DOI:10.1002/emp2.12896] [PMID] [PMCID]
3. Elfil M, Eldokmak M, Baratloo A, Ahmed N, Amin HP, Koo BB. Pathophysiologic mechanisms, neuroimaging and treatment in wake-up stroke. CNS Spectra. 2020;25(4):460-7. [DOI:10.1017/S1092852919001354] [PMID]
4. Maïer B, Desilles JP, Mazighi M. Intracranial hemorrhage after reperfusion therapies in acute ischemic stroke patients. Front Neurol. 2020;11:599908. [DOI:10.3389/fneur.2020.599908] [PMID] [PMCID]
5. Siddiqi AZ, Wadhwa A. Treatment of acute stroke: current practices and future horizons. Cardiovasc Revascularization Med. 2023;49:56-65. [DOI:10.1016/j.carrev.2022.11.012] [PMID]
6. Hacke W, Kaste M, Bluhmki E, Brozman M, Dávalos A, Guidetti D, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. New Eng J Med. 2008;359(13):1317-29. [DOI:10.1056/NEJMoa0804656] [PMID]
7. Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. 2018 guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018;49(3):e46-e99. [DOI:10.1161/STR.0000000000000158] [PMID]
8. Mackey J, Kleindorfer D, Sucharew H, Moomaw C, Kissela B, Alwell K, et al. Population-based study of wake-up strokes. Neurology. 2011;76(19):1662-7. [DOI:10.1212/WNL.0b013e318219fb30] [PMID] [PMCID]
9. Macha K, Hoelter P, Siedler G, Knott M, Schwab S, Doerfler A, et al. Multimodal CT or MRI for IV thrombolysis in ischemic stroke with unknown time of onset. Neurology. 2020;95(22):e2954-e64. [DOI:10.1212/WNL.0000000000011059] [PMID]
10. Broocks G, Leischner H, Hanning U, Flottmann F, Faizy TD, Schön G, et al. Lesion age imaging in acute stroke: water uptake in CT versus DWI‐FLAIR mismatch. Ann Neurol. 2020;88(6):1144-52. [DOI:10.1002/ana.25903] [PMID]
11. Jakubicek S, Krebs S, Posekany A, Ferrari J, Szabo J, Siarnik P, et al. Modified DWI-FLAIR mismatch guided thrombolysis in unknown onset stroke. J Thromb Thrombolysis. 2019;47:167-73. [DOI:10.1007/s11239-018-1766-3] [PMID]
12. Aoki J, Kimura K, Iguchi Y, Shibazaki K, Sakai K, Iwanaga T. FLAIR can estimate the onset time in acute ischemic stroke patients. J Neurol Sci. 2010;293(1-2):39-44. [DOI:10.1016/j.jns.2010.03.011] [PMID]
13. Ebinger M, Ostwaldt A-C, Galinovic I, Rozanski M, Brunecker P, Nolte CH, et al. Clinical and radiological courses do not differ between fluid-attenuated inversion recovery-positive and negative patients with stroke after thrombolysis. Stroke. 2010;41(8):1823-5. [DOI:10.1161/STROKEAHA.110.583971] [PMID]
14. Emeriau S, Serre I, Toubas O, Pombourcq F, Oppenheim C, Pierot L. Can diffusion-weighted imaging-fluid-attenuated inversion recovery mismatch (positive diffusion-weighted imaging/negative fluid-attenuated inversion recovery) at 3 Tesla identify patients with stroke at< 4.5 Hours?. Stroke. 2013;44(6):1647-51. [DOI:10.1161/STROKEAHA.113.001001] [PMID]
15. Huisa BN, Liebeskind DS, Raman R, Hao Q, Meyer BC, Meyer DM, et al. Diffusion-weighted imaging-fluid attenuated inversion recovery mismatch in nocturnal stroke patients with unknown time of onset. J Stroke Cerebrovasc Dis. 2013;22(7):972-7. [DOI:10.1016/j.jstrokecerebrovasdis.2012.01.004] [PMID] [PMCID]
16. Wiśniewski A. Safety and efficacy of intravenous thrombolytic treatment in wake‐up stroke: Experiences from a single center. Brain Behav. 2021;11(6):e02152. [DOI:10.1002/brb3.2152] [PMID] [PMCID]
17. Nagai K, Aoki J, Sakamoto Y, Kimura K. Approximately 30% of wake-up stroke patients may be candidate for the tPA therapy using negative-FLAIR as a "tissue clock". J Neurol Sci. 2017;382:101-4. [DOI:10.1016/j.jns.2017.09.042] [PMID]
18. Mac Grory B, Saldanha IJ, Mistry EA, Stretz C, Poli S, Sykora M, et al. Thrombolytic therapy for wake‐up stroke: A systematic review and meta‐analysis. Eur J Neurol. 2021;28(6):2006-16. [DOI:10.1111/ene.14839] [PMID]
19. Krebs S, Posekany A, Ferrari J, Lang W, Sommer P, Gattringer T, et al. Intravenous thrombolysis in wake‐up stroke: real‐world data from the Austrian Stroke Unit Registry. Eur J Neurol. 2019;26(5):754-9. [DOI:10.1111/ene.13884] [PMID]
20. Campbell BC, Ma H, Parsons MW, Churilov L, Yassi N, Kleinig TJ, et al. Association of reperfusion after thrombolysis with clinical outcome across the 4.5-to 9-Hours and wake-up stroke time window: a meta-analysis of the extend and epithet randomized clinical trials. JAMA Neurol. 2021;78(2):236-40. [DOI:10.1001/jamaneurol.2020.4123] [PMID] [PMCID]
21. Liu M, Kobeissi H, Ghozy S, Kallmes DF. Outcomes of wake-up stroke undergoing mechanical thrombectomy: A systematic review and meta-analysis. Interv Neuroradiol. 2022:15910199221133167. [DOI:10.1177/15910199221133167] [PMID]
22. Roaldsen MB, Lindekleiv H, Mathiesen EB. Intravenous thrombolytic treatment and endovascular thrombectomy for ischemic wake‐up stroke. Cochrane Database Syst Rev. 2021;2021(12):CD01099 [DOI:10.1002/14651858.CD010995.pub3] [PMID] [PMCID]
23. Biag E, Solis K, Abd Elazim A, Hussein O. COVID-19 Associated Wake-Up Stroke Treated With DWI/FLAIR Mismatch Guided Intravenous Alteplase: A Case Report. Neurologist. 2021;26(6):271. [DOI:10.1097/NRL.0000000000000355] [PMID] [PMCID]
24. Roaldsen MB, Eltoft A, Wilsgaard T, Christensen H, Engelter ST, Indredavik B, et al. Safety and efficacy of tenecteplase in patients with wake-up stroke assessed by noncontrast CT (TWIST): a multicenter, open-label, randomized controlled trial. Lancet Neurol. 2023;22(2):117-26. [DOI:10.1016/S1474-4422(22)00484-7] [PMID]
25. Ahmed HK, Logallo N, Thomassen L, Novotny V, Mathisen SM, Kurz MW. Clinical outcomes and safety profile of Tenecteplase in wake‐up stroke. Acta Neurol Scand. 2020;142(5):475-9. [DOI:10.1111/ane.13296] [PMID]
26. Bhandari S, Baral MR, Espana Schmidt C. Thrombolytic Therapy in the Oldest Old: Successful Alteplase Administration in a 105-Year-Old Female With Ischemic Stroke. Cureus. 2021;13(11):e19346. [DOI:10.7759/cureus.19346]
27. Bluhmki E, Danays T, Biegert G, Hacke W, Lees KR. Alteplase for acute ischemic stroke in patients aged> 80 years: pooled analyses of individual patient data. Stroke. 2020;51(8):2322-31. [DOI:10.1161/STROKEAHA.119.028396] [PMID] [PMCID]
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