Acute stroke management: from time window to tissue window?

Core/penumbra mismatch criteria for the extended time window for endovascular treatment were not met by about a third of stroke patients in the early time window (<6 hours). The absence of this mismatch was independently associated with an unfavourable outcome after 3 months. These results raise the question if, apart from a time window, a tissue window should also be considered in early arriving patients.

Treatment of acute ischaemic stroke (AIS) with mechanical thrombectomy is strongly time dependent and since 2018 it is mainly applied 6–30 hours after AIS. In this late time-window, patient selection is based on advanced neuroimaging, which needs to demonstrate a significant penumbra in order for a patient to be selected for thrombectomy. In the early time-window (<6 hours after AIS), there is no need for this type of advanced penumbra imaging; a CT-scan or MRI is sufficient. Dr Davide Strambo (University of Lausanne, Switzerland) and colleagues aimed to investigate whether pre-treatment perfusion parameters are associated with outcome in AIS patients treated with mechanical thrombectomy within 6 hours [1].

To this end, a retrospective, single-centre analysis based on the ASTRAL registry was performed, including AIS patients with anterior circulation large vessel occlusion (LVO), treated within 6 hours, and with available baseline perfusion data. CT and MRI data allowed for quantification of the volume of the core, i.e. tissue that is irreversibly injured, and of the penumbra, i.e. tissue at risk. Based on these data, the absence of a core/penumbra “mismatch” was assessed (according to EXTEND 1A, SWIFT/PRIME, DEFUSE 3, and DAWN trials criteria), as well as ischaemic core and penumbra volumes, and perfusion/core ratio. The primary outcome was the 3-month unfavourable shift on the modified Rankin Scale (mRS>2).

Included were 262 patients, with a mean age of 70 years and 40% were women. Median National Institutes of Health Stroke Scale (NIHSS) at admission was 16, median onset-to-imaging was 100 minutes, and median onset-to-groin was 190 minutes. Median core volume was 24.4 mL (95% CI 8.0–62.4) and median penumbra volume was 113.5 mL (95% CI 68.7–164.6). Calculating the mismatch ratio showed that 20% of patients had a penumbra/core ratio <1.2, 7% between 1.2–1.8, and 73% >1.8.

“About one third of patients lacked the favourable target mismatch according to the criteria of the EXTEND 1A, SWIFT/PRIME, and DEFUSE 3 criteria,” Dr Strambo noted. When comparing outcomes at 3 months, an unfavourable outcome was associated with a larger ischaemic core, a slightly smaller penumbra, and a lower core/penumbra ratio (see Table).

Table: Associations between perfusion parameters and unfavourable outcome at 3-months by modified Rankin Scale [1]



The absence of mismatch was independently associated with a significant shift towards worse disability at 3 months, with OR varying depending on trial criteria:

• EXTEND 1A trial: OR 2.77 (95 % CI 1.53–5.04; P=0.001);
• SWIFT/PRIME trial: OR 2.72 (95 % CI 1.54–4.81; P=0.001);
• DEFUSE-3 trial: OR 2.65 (95 % CI 1.49–4.70); P=0.001);
• DAWN trial: OR 3.26 (95 % CI 1.87–5.67; P=0.001).
• Any mismatch: OR 2.72 (95 % CI 1.45–5.07; P=0.002).

These results suggest there could be reason for a paradigm shift from time-window to tissue-window in acute stroke managements.

1. Schwarz G, et al. Perfusion imaging in large vessel occlusion stroke within 6 hours from onset: from time-window to tissue window. OPR-015, EAN 2022, 25–28 April, Vienna, Austria.

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Posted on 22 August 202222 February 2024