Neurointervention.  2023 Jul;18(2):123-128. 10.5469/neuroint.2023.00052.

Intra-Arterial Thrombolysis to Improve Final Thrombolysis in Cerebral Infarction Score after Thrombectomy: A Case-Series Analysis

• Mase AD
• Candelaresi P
• Spina E
• Giordano F
• Barbato S
• Servillo G
• Prestipino E
• Fasolino A
• Guarnieri G
• Leone G
• Muto M
• Muto M
• Andreone V

• KMID: 2543367
• DOI: http://doi.org/10.5469/neuroint.2023.00052

Abstract

Endovascular thrombectomy is the standard treatment in selected patients with acute ischemic stroke and large vessel occlusion, but continuous improvement in angiographic and clinical outcome is still needed. Intra-arterial thrombolysis has been tested as a possible rescue tool in unsuccessful thrombectomy, or as an adjuvant therapy after the endovascular procedure, to pursue complete recanalization. Here we present a case series analysis of intra-arterial alteplase administration (5 mg bolus, repeated up to 15 mg if Thrombolysis in Cerebral Infarction (TICI) scale ≥2c is not achieved) in 15 consecutive anterior circulation stroke patients after unsuccessful thrombectomy, defined as TICI score ≤2b after at least 3 passes or if unsuitable for further endovascular attempts, with the aim of improving recanalization. An improvement of final TICI score was achieved in 10 of 15 patients (66.7%). TICI score ≥2c was achieved after 5 mg intra-arterial tissue plasminogen activator (iaTPA) in 4 patients, and after 10 mg iaTPA in 5 cases. Six of 15 patients received 15 mg iaTPA: 1 of 6 showed angiographical improvement. A major effect of intra-arterial alteplase was observed for distally migrated emboli. None of the patients experienced any symptomatic hemorrhagic transformation or other major bleeding. Our report shows, in a very small cohort, a high rate of final TICI score improvement, encouraging the development of randomized controlled trials of rescue intra-arterial thrombolysis in patients with suboptimal angiographic results after mechanical thrombectomy.

Keyword

Ischemic stroke; Acute stroke; Thrombectomy; Alteplase

Figure

• 

  Fig. 1. Internal carotid occlusion in supraclinoid segment (A); performing thrombectomy with Solumbra technique (B); distalized thrombus occluding distal M2/M3 segment (white arrow) showing a Thrombolysis in Cerebral Infarction (TICI) 2b (C); TICI 3 achievement after 3 boluses (15 mg) of intra-arterial tissue plasminogen activator (D).

Reference

1. Saver JL, Goyal M, Bonafe A, Diener HC, Levy EI, Pereira VM, SWIFT PRIME Investigators, et al. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med. 2015; 372:2285–2295.

2. Berkhemer OA, Fransen PS, Beumer D, van den Berg LA, Lingsma HF, Yoo AJ, MR CLEAN Investigators, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med 2015;372:11-20 Erratum in: N Engl J Med. 2015; 372:394.

3. Goyal M, Menon BK, van Zwam WH, Dippel DW, Mitchell PJ, Demchuk AM, HERMES Collaborators, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016; 387:1723–1731.

4. Fugate JE, Klunder AM, Kallmes DF. What is meant by “TICI”? AJNR Am J Neuroradiol. 2013; 34:1792–1797.

5. Dargazanli C, Consoli A, Barral M, Labreuche J, Redjem H, Ciccio G, et al. Impact of modified TICI 3 versus modified TICI 2b reperfusion score to predict good outcome following endovascular therapy. AJNR Am J Neuroradiol. 2017; 38:90–96.

6. Kleine JF, Wunderlich S, Zimmer C, Kaesmacher J. Time to redefine success? TICI 3 versus TICI 2b recanalization in middle cerebral artery occlusion treated with thrombectomy. J Neurointerv Surg. 2017; 9:117–121.

7. Tung EL, McTaggart RA, Baird GL, Yaghi S, Hemendinger M, Dibiasio EL, et al. Rethinking thrombolysis in cerebral infarction 2b: which thrombolysis in cerebral infarction scales best define near complete recanalization in the modern thrombectomy era? Stroke. 2017; 48:2488–2493.

8. Heiferman DM, Li DD, Pecoraro NC, Smolenski AM, Tsimpas A, Ashley WW Jr. Intra-arterial alteplase thrombolysis during mechanical thrombectomy for acute ischemic stroke. J Stroke Cerebrovasc Dis. 2017; 26:3004–3008.

9. Yi TY, Chen WH, Wu YM, Zhang MF, Lin DL, Lin XH. Adjuvant intra-arterial rt-PA injection at the initially deployed solitaire stent enhances the efficacy of mechanical thrombectomy in acute ischemic stroke. J Neurol Sci. 2018; 386:69–73.

10. Zaidi SF, Castonguay AC, Jumaa MA, Malisch TW, Linfante I, Marden FA, et al. Intraarterial thrombolysis as rescue therapy for large vessel occlusions. Stroke. 2019; 50:1003–1006.

11. Zaidi SF, Castonguay AC, Zaidat OO, Mueller-Kronast N, Liebeskind DS, Salahuddin H, et al. Intra-arterial thrombolysis after unsuccessful mechanical thrombectomy in the STRATIS registry. AJNR Am J Neuroradiol. 2021; 42:708–712.

12. Kaesmacher J, Abdullayev N, Maamari B, Dobrocky T, Vynckier J, Piechowiak EI, et al. Safety and angiographic efficacy of intra-arterial fibrinolytics as adjunct to mechanical thrombectomy: results from the INFINITY registry. J Stroke. 2021; 23:91–102.

13. Renú A, Millán M, San Román L, Blasco J, Martí-Fàbregas J, Terceño M, CHOICE Investigators, et al. Effect of intra-arterial alteplase vs placebo following successful thrombectomy on functional outcomes in patients with large vessel occlusion acute ischemic stroke: the CHOICE randomized clinical trial. JAMA. 2022; 327:826–835.

14. Turc G, Tsivgoulis G, Audebert HJ, Boogaarts H, Bhogal P, De Marchis GM, et al. European Stroke Organisation - European Society for Minimally Invasive Neurological Therapy expedited recommendation on indication for intravenous thrombolysis before mechanical thrombectomy in patients with acute ischaemic stroke and anterior circulation large vessel occlusion. Eur Stroke J. 2022; 7:I–XXVI.

15. Turc G, Bhogal P, Fischer U, Khatri P, Lobotesis K, Mazighi M, et al. European Stroke Organisation (ESO) - European Society for Minimally Invasive Neurological Therapy (ESMINT) guidelines on mechanical thrombectomy in acute ischaemic strokeendorsed by Stroke Alliance for Europe (SAFE). Eur Stroke J. 2019; 4:6–12.

16. Larrue V, von Kummer R R, Müller A, Bluhmki E. Risk factors for severe hemorrhagic transformation in ischemic stroke patients treated with recombinant tissue plasminogen activator: a secondary analysis of the European-Australasian Acute Stroke Study (ECASS II). Stroke. 2001; 32:438–441.

17. Demeestere J, Wouters A, Christensen S, Lemmens R, Lansberg MG. Review of perfusion imaging in acute ischemic stroke: from time to tissue. Stroke. 2020; 51:1017–1024.

18. Acheampong P, Ford GA. Pharmacokinetics of alteplase in the treatment of ischaemic stroke. Expert Opin Drug Metab Toxicol. 2012; 8:271–281.