The Exact Science of Stroke Thrombolysis and the Quiet Art of Patient Selection

Joyce S. Balami; Gina Hadley; Brad A. Sutherland; Hasneen Karbalai; Alastair M. Buchan


Brain. 2013;136(12):3528-3553. 

In This Article

Abstract and Introduction


The science of metric-based patient stratification for intravenous thrombolysis, revolutionized by the landmark National Institute of Neurological Disorders and Stroke trial, has transformed acute ischaemic stroke therapy. Recanalization of an occluded artery produces tissue reperfusion that unequivocally improves outcome and function in patients with acute ischaemic stroke. Recanalization can be achieved mainly through intravenous thrombolysis, but other methods such as intra-arterial thrombolysis or mechanical thrombectomy can also be employed. Strict guidelines preclude many patients from being treated by intravenous thrombolysis due to the associated risks. The quiet art of informed patient selection by careful assessment of patient baseline factors and brain imaging could increase the number of eligible patients receiving intravenous thrombolysis. Outside of the existing eligibility criteria, patients may fall into therapeutic 'grey areas' and should be evaluated on a case by case basis. Important factors to consider include time of onset, age, and baseline blood glucose, blood pressure, stroke severity (as measured by National Institutes of Health Stroke Scale) and computer tomography changes (as measured by Alberta Stroke Programme Early Computed Tomography Score). Patients with traditional contraindications such as wake-up stroke, malignancy or dementia may have the potential to receive benefit from intravenous thrombolysis if they have favourable predictors of outcome from both clinical and imaging criteria. A proportion of patients experience complications or do not respond to intravenous thrombolysis. In these patients, other endovascular therapies or a combination of both may be used to provide benefit. Although an evidence-based approach to intravenous thrombolysis for acute ischaemic stroke is pivotal, it is imperative to examine those who might benefit outside of protocol-driven practice.


' If you cannot measure it, you cannot improve it.' Sir William Thomson, 1st Baron Kelvin

Despite initial scepticism about stroke care, the landmark National Institute of Neurological Disorders and Stroke (NINDS) trial (NINDS, 1995) not only revolutionized acute ischaemic stroke treatment, but also reinvigorated enthusiasm in acute ischaemic stroke care and further research. Similarly, recent acute ischaemic stroke trials have shed further rays of hope, past therapeutic nihilism to a point where acute ischaemic stroke is now a treatable medical emergency. The recent third International Stroke Trial (IST-3) (Sandercock et al., 2012) has reignited the debate surrounding the potential benefits of thrombolysis for acute ischaemic stroke patients presenting outside current parameters, specifically the thrombolysis time window and the maximum age of treatable patients.

Acute ischaemic stroke is a heterogeneous disorder with multiple causes and complex mechanisms. However, the major trials have confirmed that regardless of the cause, be it cardioembolic, lacunar or dissection, so long as baseline haemorrhage is ruled out, thrombolysis can be beneficial. It is vitally important that patients are rapidly assessed and imaged, and that a judgement be made as to whether there is viable tissue that will recover after reperfusion. Rapid diagnosis and quick decision-making are essential for treatment decisions in the hyperacute phase, decisions normally made before establishing the pathophysiology of the acute ischaemic stroke. The primary therapeutic goal is rapid restoration of blood flow through recanalization, which can be achieved through thrombolytic therapy or mechanical thrombectomy. The ideal thrombolytic therapy is intravenous recombinant human tissue-type plasminogen activator (rt-PA) administered adherent to the established American Heart Association/American Stroke Association (AHA/ASA) or European Stroke Organisation (ESO) guidelines (ESO, 2008; Jauch et al., 2013). Intra-arterial interventions have proven less successful, although meta-analysis is required to determine if these issues can be resolved with better patient stratification.

The evidence presented in this narrative review is limited to acute ischaemic stroke management. The aim of this review is to identify not only patients that fall within current guidelines for thrombolysis, but to distinguish between those who fall outside established guidelines, in whom thrombolysis is absolutely contraindicated, and those who lie within clinical 'grey areas' who, with good clinical acumen may be judged to nonetheless derive benefit from treatment.