Welcome to PracticeUpdate! We hope you are enjoying temporary access to this content.
Please register today for a free account and gain full access
to all of our expert-selected content.
Already Have An Account? Log in Now
Factors Associated With Fast Early Infarct Growth in Patients With Acute Ischemic Stroke With a Large-Vessel Occlusion
TAKE-HOME MESSAGE
- This study retrospectively analyzed data from a few prospective registries to determine the imaging predictors of early infarct growth, or "fast progression," in patients with large-vessel occlusion in the anterior circulation. Approximately one-third of the patients experienced fast progression. The hypoperfusion intensity ratio (HIR; a surrogate marker of leptomeningeal collateral status; Tmax >10 s volume divided by Tmax >6 s volume) was the strongest predictor of fast progression. More than half of the patients with an HIR greater than 0.42 experienced fast progression. Expectedly, fast progression was associated with worse clinical outcomes.
- This study highlights the importance of the HIR in predicting early infarct growth in patients with anterior-circulation large-vessel occlusion. This marker may be used in decision-making for patients being transferred to a higher level of care because of lack of immediate access to endovascular thrombectomy.
abstract
This abstract is available on the publisher's site.
Access this abstract nowBACKGROUND AND OBJECTIVES
The optimal methods for predicting early infarct growth rate (EIGR) in acute ischemic stroke with a large vessel occlusion (LVO) have not been established. We aimed to study the factors associated with EIGR, with a focus on the collateral circulation as assessed by the hypoperfusion intensity ratio (HIR) on perfusion imaging, and determine whether the associations found are consistent across imaging modalities.
METHODS
Retrospective multicenter international study including patients with anterior circulation LVO-related acute stroke with witnessed stroke onset and baseline perfusion imaging (MRI or CT) performed within 24 hours from symptom onset. To avoid selection bias, patients were selected from (1) the prospective registries of 4 comprehensive stroke centers with systematic use of perfusion imaging and including both thrombectomy-treated and untreated patients and (2) 1 prospective thrombectomy study where perfusion imaging was acquired per protocol, but treatment decisions were made blinded to the results. EIGR was defined as infarct volume on baseline imaging divided by onset-to-imaging time and fast progressors as EIGR ≥10 mL/h. The HIR, defined as the proportion of time-to-maximum (Tmax) >6 second with Tmax >10 second volume, was measured on perfusion imaging using RAPID software. The factors independently associated with fast progression were studied using multivariable logistic regression models, with separate analyses for CT- and MRI-assessed patients.
RESULTS
Overall, 1,127 patients were included (CT, n = 471; MRI, n = 656). Median age was 74 years (interquartile range [IQR] 62-83), 52% were male, median NIH Stroke Scale was 16 (IQR 9-21), median HIR was 0.42 (IQR 0.26-0.58), and 415 (37%) were fast progressors. The HIR was the primary factor associated with fast progression, with very similar results across imaging modalities: The proportion of fast progressors was 4% in the first HIR quartile (i.e., excellent collaterals), ∼15% in the second, ∼50% in the third, and ∼77% in the fourth (p < 0.001 for each imaging modality). Fast progression was independently associated with poor 3-month functional outcome in both the CT and MRI cohorts (p < 0.001 and p = 0.030, respectively).
DISCUSSION
The HIR is the primary factor associated with fast infarct progression, regardless of imaging modality. These results have implication for neuroprotection trial design, as well as informing triage decisions at primary stroke centers.
Additional Info
Disclosure statements are available on the authors' profiles:
Factors Associated With Fast Early Infarct Growth in Patients With Acute Ischemic Stroke With a Large Vessel Occlusion
Neurology 2023 Nov 21;101(21)e2126-e2137, P Seners, N Yuen, JM Olivot, M Mlynash, JJ Heit, S Christensen, JB Escribano-Paredes, E Carrera, D Strambo, P Michel, A Salerno, M Wintermark, H Chen, JF Albucher, C Cognard, I Sibon, M Obadia, J Savatovsky, MG Lansberg, GW AlbersFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
The paradigm for endovascular thrombectomy (EVT) for anterior-circulation large-vessel occlusion (LVO) acute ischemic stroke (AIS) has evolved around the principle of collateral circulation affecting penumbral salvage. The DEFUSE 31 and DAWN2 trials selectively enrolled patients with relatively good collaterals and showed remarkable outcome benefits.
Seners et al conducted a recent retrospective study involving 1127 patients with a witnessed AIS due to LVO.3 The authors demonstrated that the hypoperfusion intensity ratio (HIR) measures leptomeningeal collateral support by computed tomography or magnetic resonance perfusion imaging. An elevated HIR on either diagnostic modality accurately predicted early infarct growth (EIG) by initial imaging evaluation, which occurred in 37% of the patients, and EIG was independently associated with a poor 3-month functional outcome. The degree of benefit of EVT lowered over time, but the rate of decline was more robust in fast progressors, with no apparent benefit after 12 hours of symptom onset. On the other hand, the time-dependent benefit persisted over 24 hours in patients with robust collaterals. This analysis provides distinct time windows for EVT based on the objective imaging biomarker, and this information can be utilized in EVT triage and patient selection for future neuroprotection clinical trials (eg, nerinetide within 12 hours of symptom onset in patients with poor collaterals).4
Nguyen et al presented a retrospective analysis involving 166 patients diagnosed with AIS due to LVO based on the DEFUSE 3 and DAWN criteria who underwent EVT in the “late [6–24 hours]” or “very late [>24 hours]” window since symptom onset.5 The median patient age was 63 years, and both groups experienced comparable rates of LVO recanalization, symptomatic intracerebral hemorrhage, favorable functional outcome, and mortality. The very-late group experienced longer door-to-perfusion and door-to–groin puncture times, suggesting delays in acute stroke care at play in the developing country. Although the study requires further validation with large-scale randomized controlled trials, the optimistic findings suggest that the current EVT window limit of 24 hours will need to be extended in select patient populations (eg, robust collateral supply based on the HIR), regardless of what led to delayed intervention.
As can be noted from these two publications, collateral circulation is a dynamic factor that determines the “tissue clock” around the arbitrary, clinical-trial defined EVT time window of 24 hours since stroke symptom onset. Using emerging markers of collateralization on perfusion imaging (eg, the HIR and the mismatch ratio), next steps should address the relationships between leptomeningeal collaterals and other components of LVO care (eg, general anesthesia,6 post-EVT management) over the treatment course, even beyond 24 hours. Practical challenges, such as the limited availability of perfusion imaging in under-resourced communities, remain.
References