Melinda B. Roaldsen

 

Author and affiliations: Dr. Melinda B. Roaldsen UiT, The Arctic University of Norway, Department of Clinical Medicine and The Neurological Department at the University Hospital of North Norway, Tromsø, Norway

 

Approximately 1 in 5 acute ischaemic strokes occur during sleep.1-3 We know that clotbusting treatment with alteplase given within 4,5 hours of symptom onset improves clinical outcome4,5. However, patients who wakeup with their symptoms are not candidates for this treatment because we don’t know time of stroke onset,. There are studies that show that the time of stroke onset is often close to awakening,6,7. The finding that wake-up stroke patients share clinical and radiological findings with patients with a stroke duration under 4,5 hours also supports this.8-11 It is therefore possible that also wake-up stroke patients might benefit from clotbusting treatment.

Today we unfortunately do not have any data from larger randomised controlled trials regarding the effect of clotbusting treatment in wake-up stroke patients. But there are several randomised controlled trials that are on-going or have not yet published their results: WAKE-UP12, WASSABI13, EXTEND14, THAWS15 and TWIST16.

Positive results for endovascular thrombectomy treatment of wake-up stroke patients with effect up to 24 hours were presented at the 3rd ESOC 2017 in Prague from the DAWN trial17. It is important that patients are aware of the fact that it is common to get a stroke while sleeping, and for emergency services to consider to routinely transport patients to specialised health care centres and hospitals with neurological expertise so that patients with wake-up stroke may receive the best possible treatment.

Health care workers and the public at large have to be aware of this exciting current development; both the possibility of endovascular treatment for wake-up stroke and also that there are several on-going trials testing thrombolytic treatment in patients with wake-up strokes which they may be included in and benefit from.

When the results from these trials are presented hopefully we might be able to answer the question of which treatments are safe and effective for wake-up stroke patients. We also might be able to say more about which patients should be treated with each of the different treatment modalities that exist for a best possible clinical outcome. We encourage patients that wake up with newly acquired stroke symptoms to call their local emergency services so that they can be advised and guided regarding the local existing treatment options in their area.

If presented with the choice to become a part of a clinical trial please be advised that this is always a highly personal decision. Please make sure to talk it thoroughly through with your doctor, family and friends if possible before making your final decision. 18

References:

  1. Bassetti C, Aldrich M. Night time versus daytime transient ischaemic attack and ischaemic stroke: A prospective study of 110 patients. J Neurol Neurosurg Psychiatry. 1999;67:463-467.
  2. Moradiya Y, Janjua N. Presentation and outcomes of “wake-up strokes” in a large randomized stroke trial: Analysis of data from the international stroke trial. J Stroke Cerebrovasc Dis. 2013;22:e286-292.
  3. Wroe SJ, Sandercock P, Bamford J, Dennis M, Slattery J, Warlow C. Diurnal variation in incidence of stroke: Oxfordshire community stroke project. BMJ. 1992;304:155-157.¨
  4. IST-3 Collaborative Group. The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the Third International Stroke Trial [IST-3]): a randomised controlled trial. Lancet 2012;379:2352-63. [Erratum, Lancet 2012:380:730.]
  5. Emberson J, Lees KR, Lyden P, Blackwell L, Albers G, Bluhmki E, 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;384:1929-1935.
  6. Marsh EE 3rd, Biller J, Adams HP Jr, Marler JR, Hulbert JR, Love BB, et al. Circadian variation in onset of acute ischemic stroke. Arch Neurol. 1990;47:1178-1180.
  7. Marler JR, Price TR, Clark GL, Muller JE, Robertson T, Mohr JP, et al. Morning increase in onset of ischemic stroke. Stroke. 1989;20:473-476.
  8. Silva GS, Lima FO, Camargo EC, Smith WS, Singhal AB, Greer DM, et al. Wake-up stroke: clinical and neuroimaging characteristics. Cerebrovasc Dis. 2010;29:336-342.
  9. Roveri L, La Gioia S, Ghidinelli C, Anzalone N, De Filippis C, Comi G. Wake-up stroke within 3 hours of symptom awareness: Imaging and clinical features compared to standard recombinant tissue plasminogen activator treated stroke. J Stroke Cerebrovasc Dis. 2011.
  10. Fink JN, Kumar S, Horkan C, Linfante I, Selim MH, Caplan LR, et al. The stroke patient who woke up: clinical and radiological features, including diffusion and perfusion mri. Stroke. 2002;33:988-993.
  11. Mackey J, Kleindorfer D, Sucharew H, Moomaw CJ, Kissela BM, Alwell K, et al. Population-based study of wake-up strokes. Neurology. 2011;76:1662-1667.
  12. Thomalla G, Fiebach JB, Ostergaard L, Pedraza S, Thijs V, Nighoghossian N, et al. A multicenter, randomized, double-blind, placebo-controlled trial to test efficacy and safety of magnetic resonance imaging-based thrombolysis in wake-up stroke (wake-up). Int J Stroke. 2014;9:829-836.
  13. Wake up Symptomatic Stroke – Benefit of Intravenous Clot Busters or Endovascular Intervention (WASSABI). ClinicalTrials.gov Identifier: NCT01455935
  14. Ma H, Parsons MW, Christensen S, et al. A multicentre, randomized, double-blinded, placebo-controlled Phase III study to investigate EXtending the time for Thrombolysis in Emergency Neurological Deficits (EXTEND). Int J Stroke. 2012;7:74-80.
  15. Koga M, Toyoda K, Kimura K, Yamamoto H, Sasaki M, Hamasaki T, et al. THrombolysis for Acute Wake-up and unclear-onset Strokes with alteplase at 06 mg/kg (THAWS) Trial. Int J Stroke. 2014;9:1117-1124.
  16. Tenecteplase in Wake-up Ischaemic Stroke Trial (TWIST) ClinicalTrials.gov Identifier: NCT03181360
  17. Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention With Trevo (DAWN) gov Identifier: NCT02142283
  18. Information from the National Library of Medicine. ClinicalTrials.gov

 

Disclosure: The author is the International Trial Manager for the TWIST (Tenecteplase in Wake-up Ischaemic Stroke) Trial.