Persistent Target Mismatch Profile >24 Hours After Stroke Onset in DEFUSE 3

Abstract

Background and Purpose— Efficacy of endovascular thrombectomy has been demonstrated up to 24 hours after stroke onset in patients selected with perfusion imaging. We hypothesized that a persistent favorable perfusion profile exists in some patients beyond 24 hours from the onset and can be predicted by a lower baseline hypoperfusion intensity ratio, which indicates favorable collaterals. Methods— We identified control arm patients from the DEFUSE 3 trial (The Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) with a diffusion weighted imaging and perfusion magnetic resonance imaging performed 24 hours following randomization and compared imaging and clinical variables between patients with persistent mismatch versus patients who no longer had a mismatch 24 hours after randomization. Results— Eighteen percent of the control arm patients had a persistent favorable profile >38 hours after last known well time. These patients had similar baseline diffusion weighted imaging and Tmax >6 seconds volumes as patients whose initially favorable perfusion profile became unfavorable (diffusion weighted imaging lesion 7 versus 17 mL; P =0.17, Tmax >6 seconds 98 versus 100 mL; P =0.48) yet experienced less infarct growth (15 versus 59 mL; P <0.001) and had 3-fold smaller infarct volumes (15 versus 59 mL; P <0.001) 24 hours after randomization. Patients with a persistent favorable perfusion profile had a significantly lower hypoperfusion intensity ratio on baseline imaging (0.2 versus 0.4; P <0.01). Favorable clinical outcome at 90 days occurred in only 10% of the persistent mismatch patients. Conclusions— About 20% of patients with a middle cerebral artery or internal carotid artery occlusion who present in an extended time window and are not treated with thrombectomy have a persistent mismatch for at least an additional 24 hours. These patients have a favorable hypoperfusion intensity ratio at presentation, may experience delayed infarct expansion, and have poor clinical outcomes. Clinical trials are needed to determine if patients with a favorable perfusion profile benefit from reperfusion beyond 24 hours. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT02586415.

Response by de Havenon et al to Letter Regarding Article, “Results From DEFUSE 3: Good Collaterals Are Associated With Reduced Ischemic Core Growth but Not Neurologic Outcome”

“…We would draw attention to our recent publication that examined imaging profiles 24 hours after randomization in the DEFUSE 3 study. 3 This study found that approximately 20% of patients retain a Target Mismatch 24 hours after enrollment, which indicates that robust collaterals can persist for prolonged periods of time. 3 As we said in our article, "until we better understand collateral evolution, we will not fully appreciate their effect on neurological outcome or comprehend how to therapeutically modify that effect."…”

“…3 This study found that approximately 20% of patients retain a Target Mismatch 24 hours after enrollment, which indicates that robust collaterals can persist for prolonged periods of time. 3 As we said in our article, "until we better understand collateral evolution, we will not fully appreciate their effect on neurological outcome or comprehend how to therapeutically modify that effect." Additional research is needed, with follow-up imaging at time points past 24 or 48 hours from last known normal, to validate or refute the findings of this analysis and, more importantly, to provide a viable pathway forward for translational collateral research.…”

Mechanical Thrombectomy for Acute Stroke: Early versus Late Time Window Outcomes

“…A significant number of patients presenting in the extended window do not have favorable imaging profile 35 . Moreover, those with favorable profile (slow progressors), become ineligible for treatment if not recanalized immediately after onset and develop extensive infarction leading to poor outcomes 36,37 . Patient presenting with favorable penumbral pattern on imaging should receive thrombectomy expeditiously with careful monitoring of imaging‐to‐skin puncture and imaging‐to‐recanalization time metrics.…”

Endovascular thrombectomy: 31 hours from symptom onset

“…There was no difference in the rate of symptomatic intracranial haemorrhage (5% vs 6%, p=0.87) or of good outcome (90 day mRS score of 0–2, 43% vs 48%, p=0.68) when compared with the intervention arm patients 1. This study together with data from DEFUSE 3 suggest that intervention for patients with large intracranial vessel occlusion presenting beyond 24 hours is justified on an individualised basis 1 2. The decision to proceed with off-label treatment in our patient was also based on MRI demonstration of viable symptomatic brain tissue despite established insular infarction and the likely eventual demise of eloquent penumbral tissue.…”

“…In two patients, the follow-up imaging at 4 days from stroke onset showed progression of expansion of infarct core; both had poor outcomes. One patient (10%) had a good outcome (modified Rankin Scale (mRS) score of 0–1) and most (60%) were dead or severely disabled (mRS score 5–6) at 90 days, probably reflecting progressive penumbral demise and infarct core expansion without reperfusion 2…”