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


and he preferred to know the potencies of herbs, and the practice of healing, and to ply this quiet art, resigning fame.' (Virgil, 19 BCE).

Thrombolysis using rt-PA remains the only approved treatment for acute ischaemic stroke. Rt-PA changed the world, not just of stroke treatment, but of neurology in general. The availability of an effective therapy has dramatically changed the management of patients presenting with neurological symptoms, leading to quick assessment and application of therapeutic protocols in those patients with a high diagnostic probability of stroke. Evidence is now accumulating for its benefit in clinical practice, both within standard guidelines and potentially outside them. By combining both clinical and imaging criteria, patient selection can be improved, enhancing the benefits while reducing the risk of complications. The main clinical parameters are age, NIHSS, serum glucose, systolic blood pressure and onset-to-treatment time. ASPECTS, a widely used and validated tool, can be used to standardize and quantify imaging analysis to predict clinical outcome.

Although there is evidence from randomized controlled trials for the benefit of intravenous thrombolysis or other acute interventions in restoring blood flow and salvaging the ischaemic penumbra following acute ischaemic stroke, there remains a need for trials and meta-analyses to help provide additional evidence-based guidelines. These will help in patient selection, determining when the benefits outweigh the risks in those patients that fall into the exclusionary areas surrounding the current guidelines, such as onset-to-treatment times >4.5 h, seizure at stroke onset, anticoagulation, or mild/rapidly improving symptoms. Likewize, little is known about the risk of thrombolysis in conditions that fall into therapeutic 'grey areas' such as wake-up stroke/stroke of indeterminate onset, dementia, malignancy, and pregnancy, as these patients are often excluded from clinical trials and observational studies. The relatively disappointing results of the studies comparing intra-arterial therapy to intravenous thrombolysis may be due to improper patient stratification. Meta-analysis is warranted to see if the established quantitative metrics, particularly imaging scoring systems, can identify subgroups of patients who can potentially benefit.

More research will hopefully lead to the identification and inclusion of a greater number of suitable patients for thrombolysis, maximizing the number benefiting from rt-PA therapy. Evidence-based support for definite exclusion criteria is valuable, but must be adaptable to an acute clinical setting—stringent additional testing for rigorous exclusion of potential stroke mimics can be counterproductive if it results in closure of the therapeutic time window.

Patient selection is both science and art. The science arises from meta-analysis of the predictive value of quantitative metrics in determining response to therapy. The art arises from the gradual accumulation of clinical experience that reassures the clinician that they are treating the patient not just because they can, but because they expect to see a real benefit.

The chemical neurosurgery that rt-PA provides is the most validated tool in our arsenal of acute ischaemic stroke treatments. Despite the advent of several endovascular approaches, intravenous thrombolysis remains the treatment of choice in eligible patients. Only by combining thrombolysis with the quiet art of patient selection can we ameliorate outcomes for patients who may fall outside the guidelines, or in the many grey areas within the standard guidelines, and identify the patients that truly have the best chance of a positive outcome.