There may be hope for stroke patients presenting late, but remember: time is brain!
Author: Dr Salvatore Rudilosso, Functional Unit of Cerebrovascular Diseases, Hospital Clínic, Barcelona, Spain
The aphorism “time is brain” is common among health professionals involved in stroke care. We can even give detailed estimations of the loss of brain tissue due to stroke over time: in a standard stroke, every minute of ischemia corresponds to a loss of approximately 2 million neurons and 14 km of nerve fibers (Saver JL. 2006). These numbers reflect the urgency to restore the brain perfusion as fast as possible. Data from randomized trials of intravenous thrombolysis confirmed that the functional outcome is inversely related with the delay to treatment, losing its effectiveness after 4.5h from stroke onset (Emberson J et al. 2014). This means that at 90 minutes from stroke onset only 4 or 5 patients need to be treated for one of them to achieve a good functional outcome at 3 months, but this number increases to 14 patients at 4.5 hours from stroke onset. The new endovascular therapies for acute stroke were initially used mostly as rescue therapies when intravenous therapy was not successful or could not be given due to late presentation. However, a meta-analysis from five positive trials comparing mechanical thrombectomy to medical care alone showed that the time-dependency of endovascular therapy was even greater than that of intravenous thrombolysis, with the benefit losing significance after 7.3 h (Saver JL et al. 2016).
However, we also know that the brain lesion does not develop at the same pace in all stroke patients, the ones at the beginning of the post are just average numbers. Individual differences in the brain viability after a vascular occlusion occur due to several factors, the best known being the quality of collateral blood supply. Thus, under certain conditions, the brain parenchyma can be viable although the reperfusion exceeds the traditional time windows. In this sense, hopeful news arrived at the last 2017 ESOC conference in Prague: the DAWN trial investigators announced the yet unpublished positive results of the trial showing that mechanical thrombectomy is effective beyond 6 h of time last seen well and up to 24 h, as long as a large core stroke was not identified in advanced imaging (Jovin TG et al. ESOC 2017). The DEFUSE 3 study that investigated the benefit of thrombectomy in patients treated between 6 and 16 hours has also been terminated due to high likelihood of benefit in the endovascular group.
These encouraging results must not be misleading. Although these trials suggest that some patients presenting late (wake-up strokes, patients with unknown time from last seen well) may be successful treated, the likelihood of having a small established brain lesion and therefore benefiting from revascularization is much lower in late time windows. Many healthcare providers are responsible for shortening the time to treatment: those involved in the transportation of patients, those making the diagnostic assessment and the teams that deliver the revascularization therapy. But even in the best organized healthcare systems, the recognition of the symptoms by patients or nearby people and a prompt call to the emergency services is first needed. There are several simple ways to recognize stroke symptoms, for example the instructions of the “FAST” acronym: face looks uneven, arm is weak, speech is strange and time to call. The diffusion of these tools through social networks, informative sessions in public places and media talks may be helpful, although the long-term effectiveness of these educational measures has not always been demonstrated. Anyway, we are happily observing an increasing number of patients with acute stroke that arrive at the emergency services in the first few hours. We think that this is partly explained by the greater awareness of much of the population regarding stroke symptoms, even regarding the great importance of time to treatment in this condition. We hope this post may be helpful for those who were not aware of that!
Saver JL. Time Is Brain—Quantified. Stroke 2006;37:263-266.
Emberson J 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.
Saver JL et al. Time to Treatment With Endovascular Thrombectomy and Outcomes From Ischemic Stroke: A Meta-analysis. Jama Neurology 2016;316:1279-1289.
Jovin TG et al. DAWN in full daylight (DWI or CTP assessment with clinical mismatch in the triage of wake up and late presenting strokes undergoing neurointervention). ESO Conference, Prague 2017.