Elsevier

The Lancet Neurology

Volume 5, Issue 8, August 2006, Pages 661-667
The Lancet Neurology

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MRI versus CT-based thrombolysis treatment within and beyond the 3 h time window after stroke onset: a cohort study

https://doi.org/10.1016/S1474-4422(06)70499-9Get rights and content

Summary

Background

Thrombolytic treatment with recombinant tissue plasminogen activator (rtPA) is approved for use within 3 h after stroke onset. Thus only a small percentage of patients can benefit. Meta-analyses and more recent studies suggest a benefit for a subset of patients beyond 3 h. We assessed the safety and efficacy of an MRI-based selection protocol for stroke treatment within and beyond 3 h compared with standard CT-based treatment.

Methods

We assessed clinical outcome and incidence of symptomatic intracerebral haemorrhage (ICH) in 400 consecutive patients treated with intravenous rtPA. Patients eligible for thrombolysis within 3 h were selected by CT or MRI and beyond 3 h only by MRI. 18 patients were excluded from analysis because of violation of that algorithm. The remaining 382 patients were divided into three groups: CT-based treatment within 3 h (n=209); MRI-based treatment within 3 h (n=103); and MRI-based treatment beyond 3 h (n=70).

Findings

Patients in group 3 (MRI >3 h) had a similar 90 day outcome to those in the other two groups (48% were independent in the CT ≤ 3 h group, 51% in the MRI ≤ 3 h group, and 56% in group 3), but without an increased risk for symptomatic ICH (9%, 1%, 6%) or mortality (21%, 13%, 11%). MRI-selected patients overall had a significantly lower risk than CT-selected patients for symptomatic ICH (3% vs 9%; p=0·013) and mortality (12% vs 21%; p=0·021). Time to treatment did not affect outcomes in univariate and multivariate analyses.

Interpretation

Our data suggest that beyond 3 h and maybe even within 3 h, patient selection is more important than time to treatment for a good outcome. Furthermore, MRI-based thrombolysis, irrespective of the time window, shows an improved safety profile while being at least as effective as standard CT-based treatment within 3 h.

Introduction

Thrombolytic treatment with recombinant tissue plasminogen activator (rtPA) is approved for use up to 3 h after onset of stroke symptoms. Therefore, all patients who present later than 3 h and those with an unknown time window are excluded from this treatment option. Up to now, randomised trials have not shown a benefit of rtPA beyond 3 h, but meta-analyses and other smaller studies have suggested an effect for selected patients after the narrow 3 h time window.1, 2, 3, 4 Multiparametric MRI with diffusion-weighted imaging (DWI) and perfusion sequences (PWI) could help identify patients who could benefit from treatment after 3 h.3, 4, 5 In a simplified approach, the area of decreased diffusion represents the ischaemic core of the infarct and the perfusion-diffusion mismatch is believed to be a marker for critically hypoperfused yet potentially salvageable brain tissue (presumptive ischaemic penumbra).6, 7, 8 Although ongoing research aims to refine this concept and improve the means to visualise the tissue at risk, the main advantage of this approach is that it is simple, sufficiently accurate, and therefore feasible to implement in emergency conditions.6, 9 Previous studies have implied that multiparametric MRI is a powerful diagnostic tool in acute ischaemic stroke and that patient selection for thrombolysis is improved with MRI compared with use of non-contrast CT scans.6, 8, 10, 11, 12 Therefore, several previous and ongoing phase II and III trials apply the PWI–DWI mismatch as an inclusion criterion.2, 3, 4, 13 We postulated that an MRI-based selection approach for thrombolytic treatment in the clinical routine is safe and effective within and beyond the rigid 3 h time window compared with the standard CT-based approach to treatment.

Section snippets

Patients and procedures

In total 400 patients with acute ischaemic stroke of the anterior circulation were treated with intravenous rtPA at our institution between March, 1998, and October, 2005. Data were prospectively obtained and entered into a local database, including information about age, sex, time of onset of symptoms, time of treatment, modified Rankin scale (mRS) score at 90 days, baseline National Institutes of Health stroke scale score (NIHSSS) at days 1 and 7, concomitant medication use, other relevant

Results

382 patients with a median age of 71 years (range 19–94) were treated with intravenous rtPA (table 1). Baseline stroke severity was closely similar in all three predefined subgroups (median NIHSSS=13). Patients in group 1 (CT ≤3 h) were older than patients in the other groups, but all other assessed parameters, including sex, affected hemisphere, baseline glucose concentrations, and cause of stroke, did not differ between groups. There was a significantly lower risk of symptomatic ICH in both

Discussion

Multiparametric MRI has been shown to be a useful tool for selection of patients for thrombolysis.2, 3, 4 Our data show that within a clinical routine setting in a large patient cohort, MRI-based thrombolysis within and beyond 3 h shows an increased safety profile and is as effective as standard CT-based treatment.

In the approval-relevant NINDS trial,15 39% of patients in the rtPA group had a favourable outcome (26% in the placebo group; odds ratio 1·7, 95% CI 1·1–2·6) and 43% were independent

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