Ayush Agarwal, MD, DM, DNB
The management of acute ischemic stroke continues to progress, and there is a shift towards ‘tissue window’ from the traditional ‘time window.’ Recent trials have demonstrated that thrombolysis can safely be done out of the traditional time window based on careful patient selection using advanced imaging techniques including brain MRI and CT-perfusion (1,2). Although, traditionally, alteplase has been the mainstay of treatment, tenecteplase usage is rapidly gaining ground based on ease of administration and higher fibrin specificity. It has not only been proven non-inferior, but also better at lysing large vessel clots (when compared to alteplase) (3). The advent of mobile stroke units with CT scanners and point-of-care laboratory support has further reduced door-to-needle times and led to even better stroke outcomes (4,5).
Endovascular thrombectomy (EVT) can also now be performed up to 24 hours after symptom onset in a select patient population (6,7). The AURORA meta-analysis showed that the treatment effect of endovascular thrombectomy was stronger for patients randomized between 12-24 hours compared to those randomized between 6-12 hours. There was no significant difference in clinical outcomes between patients undergoing EVT based on the use of general anesthesia or conscious sedation.
No definitive answers could be provided on skipping intravenous thrombolysis and doing direct EVT in patients with large vessel occlusions (LVO) (8–10). Therefore, the current evidence does not support skipping thrombolysis as bridging therapy prior to EVT.
Cytoprotection therapy may actually have a role to play as opposed to ‘neuroprotection’, as neurons are not the only injured neurological cell type during ischemia. Cytoprotection entails targeting multiple aspects of the ischemic cascade and prescription when documented salvageable penumbra is present. Numerous trials are underway based on this understanding.
1. Thomalla G, Simonsen CZ, Boutitie F, Andersen G, Berthezene Y, Cheng B, et al. MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset. N Engl J Med. 2018;379:611–22.
2. Ma H, Campbell BCV, Parsons MW, Churilov L, Levi CR, Hsu C, et al. Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke. N Engl J Med. 2019;380:1795–803.
3. Campbell BCV, Mitchell PJ, Churilov L, Yassi N, Kleinig TJ, Dowling RJ, et al. Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke. N Engl J Med. 2018;378:1573–82.
4. Ebinger M, Siegerink B, Kunz A, Wendt M, Weber JE, Schwabauer E, et al. Association Between Dispatch of Mobile Stroke Units and Functional Outcomes Among Patients With Acute Ischemic Stroke in Berlin. JAMA. 2021;325:454–66.
5. Grotta JC, Yamal JM, Parker SA, Rajan SS, Gonzales NR, Jones WJ, et al. Prospective, Multicenter, Controlled Trial of Mobile Stroke Units. N Engl J Med. 2021;385:971–81.
6. Nogueira RG, Jadhav AP, Haussen DC, Bonafe A, Budzik RF, Bhuva P, et al. Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct. N Engl J Med. 2018;378:11–21.
7. Albers GW, Marks MP, Kemp S, Christensen S, Tsai JP, Ortega-Gutierrez S, et al. Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. N Engl J Med. 2018;378:708–18.
8. LeCouffe NE, Kappelhof M, Treurniet KM, Rinkel LA, Bruggeman AE, Berkhemer OA, et al. A Randomized Trial of Intravenous Alteplase before Endovascular Treatment for Stroke. N Engl J Med. 2021;385:1833–44.
9. Yang P, Zhang Y, Zhang L, Zhang Y, Treurniet KM, Chen W, et al. Endovascular Thrombectomy with or without Intravenous Alteplase in Acute Stroke. N Engl J Med. 2020;382:1981–93.
10. Suzuki K, Matsumaru Y, Takeuchi M, Morimoto M, Kanazawa R, Takayama Y, et al. Effect of Mechanical Thrombectomy Without vs With Intravenous Thrombolysis on Functional Outcome Among Patients With Acute Ischemic Stroke: The SKIP Randomized Clinical Trial. JAMA. 2021;325:244–53.