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Decision

What is the last known well time?

Background

When evaluating a patient with AIS, the initial history, physical examination, laboratory testing, and imaging should be focused on rapidly determining candidacy for treatment. Eligibility for both IV tPA and mechanical thrombectomy is time dependent; therefore, one of the most important questions to answer is the patient’s last known well time. Often, the patient is unable to provide this history, and collateral information will have to be obtained from family or other witnesses. An important distinction must be made between a patient’s last known well time and when symptoms were first noticed in the patient. For instance, in patients who wake up with symptoms of an acute stroke, it is not the time they were first noticed to have these symptoms, but rather the time they were last known to be normal (often the night before when they went to bed) that is used to determine eligibility for treatment. The importance of precisely establishing the last known well time cannot be overstated.

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References

Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, random-ized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study is included in bold type following the ref-erence, where available. In addition, the most informative references cited in this paper, as determined by the authors, are noted by an asterisk (*) next to the number of the reference.

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  2. Carandang R, Seshadri S, Beiser A, et al. Trends in incidence, lifetime risk, severity, and 30-day mortality of stroke over the past 50 years. JAMA. 2006;296(24):2939-2946. (Prospective study; 9152 patients)
  3. Ovbiagele B, Goldstein LB, Higashida RT, et al. Forecasting the future of stroke in the United States: a policy statement from the American Heart Association and American Stroke Association. Stroke. 2013;44(8):2361-2375. (Cost-projection assessment)
  4. National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995;333(24):1581-1587. (Randomized double-blind trial; 624 patients) DOI: 10.1056/NEJM199512143332401
  5. Berkhemer OA, Fransen PS, Beumer D, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015;372(1):11-20. (Randomized trial; 500 patients) DOI: 10.1056/NEJMoa1411587
  6. Saver JL, Goyal M, Bonafe A, et al. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med. 2015;372(24):2285-2295. (Randomized controlled trial; 196 patients)
  7. Campbell BC, Mitchell PJ, Kleinig TJ, et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015;372(11):1009-1018. (Randomized controlled trial; 70 patients)
  8. Goyal M, Demchuk AM, Menon BK, et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015;372(11):1019-1030. (Randomized controlled trial; 238 patients)
  9. Bracard S, Ducrocq X, Mas JL, et al. Mechanical thrombectomy after intravenous alteplase versus alteplase alone after stroke (THRACE): a randomised controlled trial. Lancet Neurol. 2016;15(11):1138-1147. (Randomized controlled trial; 414 patients)
  10. Albers GW, Marks MP, Kemp S, et al. Thrombectomy for stroke at 6 to 16 hours with selec-tion by perfusion imaging. N Engl J Med. 2018;378(8):708-718. (Multicenter, randomized, open-label trial, with blinded outcome assessment; 182 patients, 92 to the endovascular-therapy group and 90 to the medical-therapy group).) DOI: 10.1056/NEJMoa1713973
  11. Nogueira RG, Jadhav AP, Haussen DC, et al. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. N Engl J Med. 2018;378(1):11-21. (Randomized controlled trial; 206 patients) DOI: 10.1056/NEJMoa1706442
  12. Emberson J, Lees KR, Lyden P, et al. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet. 2014;384(9958):1929-1935. (Review)
  13. Saver JL, Goyal M, van der Lugt A, et al. Time to treatment with endovascular thrombectomy and outcomes from ischemic stroke: a meta-analysis. JAMA. 2016;316(12):1279-1288. (Meta-analysis; 5 trials, 1287 patients)
  14. Powers WJ, Rabinstein AA, Ackerson T, 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-e110. (Guidelines)
  15. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2019;50(12):e344-e418. (Guidelines) DOI: 10.1161/STR.0000000000000211
  16. Demaerschalk BM, Kleindorfer DO, Adeoye OM, et al. Scientific Rationale for the Inclusion and Exclusion Criteria for Intravenous Alteplase in Acute Ischemic Stroke: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2016;47(2):581-641. (Review)
  17. Schaefer PW, Roccatagliata L, Ledezma C, et al. First-pass quantitative CT perfusion identifies thresholds for salvageable penumbra in acute stroke patients treated with intra-arterial therapy. AJNR Am J Neuroradiol. 2006;27(1):20-25. (Prospective study; 14 patients)
  18. Campbell BC, Christensen S, Levi CR, et al. Cerebral blood flow is the optimal CT perfusion parameter for assessing infarct core. Stroke. 2011;42(12):3435-3440. (Retrospective analysis; 54 patients)
  19. Olivot JM, Mlynash M, Thijs VN, et al. Optimal Tmax threshold for predicting penumbral tissue in acute stroke. Stroke. 2009;40(2):469-475. (Multicenter study; 33 patients)
  20. Broderick JP, Adeoye O, Elm J. Evolution of the modified Rankin Scale and its use in future stroke trials. Stroke. 2017;48(7):2007-2012. (Review)
  21. Hacke W, Donnan G, Fieschi C, et al. Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet. 2004;363(9411):768-774. (Meta-analysis; 6 randomized placebo-controlled trials)
  22. Wardlaw JM, Murray V, Berge E, et al. Recombinant tissue plasminogen activator for acute ischaemic stroke: an updated systematic review and meta-analysis. Lancet. 2012;379(9834):2364-2372. (Systematic review and meta-analysis; 12 trials)
  23. Wardlaw JM, Murray V, Berge E, et al. Thrombolysis for acute ischaemic stroke. Cochrane Database Syst Rev. 2014(7):CD000213. (Systematic review)
  24. Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008;359(13):1317-1329. (Randomized double-blind trial; 821 patients) DOI: 10.1056/NEJMoa0804656
  25. Thomalla G, Simonsen CZ, Boutitie F, et al. MRI-guided thrombolysis for stroke with unknown time of onset. N Engl J Med. 2018;379(7):611-622. (Multicenter randomized controlled trial; 503 patients) DOI: 10.1056/NEJMoa1804355
  26. Lin CB, Peterson ED, Smith EE, et al. Emergency medical service hospital prenotification is associated with improved evaluation and treatment of acute ischemic stroke. Circ Cardiovasc Qual Outcomes. 2012;5(4):514-522. (Multivariate analysis; 371,988 patients)
  27. Roffe C, Nevatte T, Sim J, et al. Effect of routine low-dose oxygen supplementation on death and disability in adults with acute stroke: the stroke oxygen study randomized clinical trial. JAMA. 2017;318(12):1125-1135. (Single-blind randomized clinical trial; 8003 patients)
  28. Josephson SA, Hills NK, Johnston SC. NIH Stroke Scale reliability in ratings from a large sample of clinicians. Cerebrovasc Dis. 2006;22(5-6):389-395. (Comparative study; 11 patients)
  29. Lyden P, Raman R, Liu L, et al. National Institutes of Health Stroke Scale certification is reliable across multiple venues. Stroke. 2009;40(7):2507-2511. (Inter-rater reliability assessment)
  30. Mazya M, Egido JA, Ford GA, et al. Predicting the risk of symptomatic intracerebral hemorrhage in ischemic stroke treated with intravenous alteplase: safe Implementation of Treatments in Stroke (SITS) symptomatic intracerebral hemorrhage risk score. Stroke. 2012;43(6):1524-1531. (Registry analysis; 31,627 patients)
  31. Butcher K, Christensen S, Parsons M, et al. Postthrombolysis blood pressure elevation is associated with hemorrhagic transformation. Stroke. 2010;41(1):72-77. (Randomized controlled trial; 97 patients)
  32. Stead LG, Gilmore RM, Decker WW, et al. Initial emergency department blood pressure as predictor of survival after acute ischemic stroke. Neurology. 2005;65(8):1179-1183. (Observational study; 357 patients)
  33. Alper BS, Foster G, Thabane L, et al. Thrombolysis with alteplase 3 – 4.5 hours after acute ischemic stroke: trial reanalysis adjusted for baseline imbalances. BMJ Evid Based Med. 2020;25(5):168-171. (Reanalysis of randomized placebo-controlled trial; 821 patients)
  34. Cronin CA, Sheth KN, Zhao X, et al. Adherence to Third European Cooperative Acute Stroke Study 3- to 4.5-hour exclusions and association with outcome: data from Get with the Guidelines-Stroke. Stroke. 2014;45(9):2745-2749. (Data analysis; 32,019 patients)
  35. Kidwell CS, Chalela JA, Saver JL, et al. Comparison of MRI and CT for detection of acute intracerebral hemorrhage. JAMA. 2004;292(15):1823-1830. (Prospective multicenter study; 200 patients)
  36. Fiebach JB, Schellinger PD, Gass A, et al. Stroke magnetic resonance imaging is accurate in hyperacute intracerebral hemorrhage: a multicenter study on the validity of stroke imaging. Stroke. 2004;35(2):502-506. (Prospective multicenter trial; 124 patients)
  37. The NINDS t-PA Stroke Study Group. Intracerebral hemorrhage after intravenous t-PA therapy for ischemic stroke. Stroke. 1997;28(11):2109-2118. (Subgroup analyses of data from a randomized double-blind placebo-controlled trial; 312 patients)
  38. Patel SC, Levine SR, Tilley BC, et al. Lack of clinical significance of early ischemic changes on computed tomography in acute stroke. JAMA. 2001;286(22):2830-2838. (Re-evaluation of randomized controlled trial; 624 patients)
  39. Turk AS 3rd, Siddiqui A, Fifi JT, et al. Aspiration thrombectomy versus stent retriever thrombectomy as first-line approach for large vessel occlusion (COMPASS): a multicentre, randomised, open label, blinded outcome, non-inferiority trial. Lancet. 2019;393(10175):998-1008. (Multicenter randomized open-label blinded outcome noninferiority trial; 15 sites, 270 patients)
  40. Lapergue B, Blanc R, Gory B, et al. Effect of endovascular contact aspiration vs stent retriever on revascularization in patients with acute ischemic stroke and large vessel occlusion: the ASTER randomized clinical trial. JAMA. 2017;318(5):443-452. (Randomized controlled open-label blinded end-point trial; 381 patients )
  41. Goyal M, Menon BK, van Zwam WH, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016;387(10029):1723-1731. (Meta-analysis; 5 trials, 1287 patients)
  42. Rimmele DL, Thomalla G. Wake-up stroke: clinical characteristics, imaging findings, and treatment option - an update. Front Neurol. 2014;5:35. (Review)
  43. Thomalla G, Rossbach P, Rosenkranz M, et al. Negative fluid-attenuated inversion recovery imaging identifies acute ischemic stroke at 3 hours or less. Ann Neurol. 2009;65(6):724-732. (Comparative study; 120 patients)
  44. Thomalla G, Cheng B, Ebinger M, et al. DWI-FLAIR mismatch for the identification of patients with acute ischaemic stroke within 4.5 h of symptom onset (PRE-FLAIR): a multicentre observational study. Lancet Neurol. 2011;10(11):978-986. (Multicenter observational study; 543 patients)
  45. Aoki J, Kimura K, Iguchi Y, et al. FLAIR can estimate the onset time in acute ischemic stroke patients. J Neurol Sci. 2010;293(1-2):39-44. (Retrospective study; 333 patients, 389 MRI studies)

0-4.5 Hours
0-4.5 Hours
4.5-6 hours
4.5-6 hours
6-24 hours
6-24 hours
Unknown, but >4.5 hours
Unknown, but >4.5 hours

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