Multicenter Study

. 2023 Nov 21;101(21):e2126-e2137.

doi: 10.1212/WNL.0000000000207908. Epub 2023 Oct 9.

Factors Associated With Fast Early Infarct Growth in Patients With Acute Ischemic Stroke With a Large Vessel Occlusion

Pierre Seners¹, Nicole Yuen², Jean-Marc Olivot², Michael Mlynash², Jeremy J Heit², Soren Christensen², José Bernardo Escribano-Paredes², Emmanuel Carrera², Davide Strambo², Patrik Michel², Alexander Salerno², Max Wintermark², Hui Chen², Jean-François Albucher², Christophe Cognard², Igor Sibon², Michael Obadia², Julien Savatovsky², Maarten G Lansberg², Gregory W Albers²; for Mismatch Prevalence

Collaborators, Affiliations

Collaborators

for Mismatch Prevalence:
Stephanie Kemp, Mikael Mazighi, Michel Piotin, Guillaume Bellanger, Thomas Tourdias, Anne-Christine Januel, Fabrice Bonneville, Nicolas Raposo, Alan Viguier, Lionel Calviére, Paolo Machi, Gianmarco Bernava, Elisabeth Dirren, Manuela Buehrer, Fanny Simonnet

Affiliations

¹ From the Stanford Stroke Center (P.S., N.Y., M.M., S.C., G.W.A.), Palo Alto, CA; Neurology Department (P.S., M.O.), Hôpital Fondation A. de Rothschild; Institut de Psychiatrie et Neurosciences de Paris (IPNP) (P.S.), U1266, INSERM, Paris; Acute Stroke Unit (J.M.O., J.-F.A.), Hôpital Pierre-Paul Riquet, CHU Toulouse and CIC 1436, Toulouse University, INSERM, UPS, France; Radiology Department (J.J.H.), Stanford University, Palo Alto, CA; Neurology Department (J.B.E.P., E.C.), Geneva University Hospital, Switzerland; Stroke Center (D.S., P.M., A.S.), Neurology Service, Lausanne University Hospital and University of Lausanne, Switzerland; Neuroradiology Department (M.W., H.C.), MD Anderson Cancer Center, University of Texas, Houston; Neuroradiology Department (C.C.), Toulouse University Hospital; Stroke Unit (I.S., J.S.), Bordeaux University Hospital; and Radiology Department (M.G.L.), Hôpital Fondation A. de Rothschild, Paris, France. pierre.seners@gmail.com.
² From the Stanford Stroke Center (P.S., N.Y., M.M., S.C., G.W.A.), Palo Alto, CA; Neurology Department (P.S., M.O.), Hôpital Fondation A. de Rothschild; Institut de Psychiatrie et Neurosciences de Paris (IPNP) (P.S.), U1266, INSERM, Paris; Acute Stroke Unit (J.M.O., J.-F.A.), Hôpital Pierre-Paul Riquet, CHU Toulouse and CIC 1436, Toulouse University, INSERM, UPS, France; Radiology Department (J.J.H.), Stanford University, Palo Alto, CA; Neurology Department (J.B.E.P., E.C.), Geneva University Hospital, Switzerland; Stroke Center (D.S., P.M., A.S.), Neurology Service, Lausanne University Hospital and University of Lausanne, Switzerland; Neuroradiology Department (M.W., H.C.), MD Anderson Cancer Center, University of Texas, Houston; Neuroradiology Department (C.C.), Toulouse University Hospital; Stroke Unit (I.S., J.S.), Bordeaux University Hospital; and Radiology Department (M.G.L.), Hôpital Fondation A. de Rothschild, Paris, France.

PMID: 37813579
PMCID: PMC10663035
DOI: 10.1212/WNL.0000000000207908

Multicenter Study

Factors Associated With Fast Early Infarct Growth in Patients With Acute Ischemic Stroke With a Large Vessel Occlusion

Pierre Seners et al. Neurology. 2023.

. 2023 Nov 21;101(21):e2126-e2137.

doi: 10.1212/WNL.0000000000207908. Epub 2023 Oct 9.

Authors

Collaborators

for Mismatch Prevalence:
Stephanie Kemp, Mikael Mazighi, Michel Piotin, Guillaume Bellanger, Thomas Tourdias, Anne-Christine Januel, Fabrice Bonneville, Nicolas Raposo, Alan Viguier, Lionel Calviére, Paolo Machi, Gianmarco Bernava, Elisabeth Dirren, Manuela Buehrer, Fanny Simonnet

Affiliations

¹ From the Stanford Stroke Center (P.S., N.Y., M.M., S.C., G.W.A.), Palo Alto, CA; Neurology Department (P.S., M.O.), Hôpital Fondation A. de Rothschild; Institut de Psychiatrie et Neurosciences de Paris (IPNP) (P.S.), U1266, INSERM, Paris; Acute Stroke Unit (J.M.O., J.-F.A.), Hôpital Pierre-Paul Riquet, CHU Toulouse and CIC 1436, Toulouse University, INSERM, UPS, France; Radiology Department (J.J.H.), Stanford University, Palo Alto, CA; Neurology Department (J.B.E.P., E.C.), Geneva University Hospital, Switzerland; Stroke Center (D.S., P.M., A.S.), Neurology Service, Lausanne University Hospital and University of Lausanne, Switzerland; Neuroradiology Department (M.W., H.C.), MD Anderson Cancer Center, University of Texas, Houston; Neuroradiology Department (C.C.), Toulouse University Hospital; Stroke Unit (I.S., J.S.), Bordeaux University Hospital; and Radiology Department (M.G.L.), Hôpital Fondation A. de Rothschild, Paris, France. pierre.seners@gmail.com.
² From the Stanford Stroke Center (P.S., N.Y., M.M., S.C., G.W.A.), Palo Alto, CA; Neurology Department (P.S., M.O.), Hôpital Fondation A. de Rothschild; Institut de Psychiatrie et Neurosciences de Paris (IPNP) (P.S.), U1266, INSERM, Paris; Acute Stroke Unit (J.M.O., J.-F.A.), Hôpital Pierre-Paul Riquet, CHU Toulouse and CIC 1436, Toulouse University, INSERM, UPS, France; Radiology Department (J.J.H.), Stanford University, Palo Alto, CA; Neurology Department (J.B.E.P., E.C.), Geneva University Hospital, Switzerland; Stroke Center (D.S., P.M., A.S.), Neurology Service, Lausanne University Hospital and University of Lausanne, Switzerland; Neuroradiology Department (M.W., H.C.), MD Anderson Cancer Center, University of Texas, Houston; Neuroradiology Department (C.C.), Toulouse University Hospital; Stroke Unit (I.S., J.S.), Bordeaux University Hospital; and Radiology Department (M.G.L.), Hôpital Fondation A. de Rothschild, Paris, France.

PMID: 37813579
PMCID: PMC10663035
DOI: 10.1212/WNL.0000000000207908

Abstract

Background 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.

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Conflict of interest statement

P. Seners and N. Yuen report no disclosures relevant to the manuscript. J.-M. Olivot reports grants from French department of Health; compensation from ACTICOR; ABBVIE and APTOLL for consultant services et Boehringer; and Bristol Myers Squibb for speakers fees. M. Mlynash reports no disclosures relevant to the manuscript. J.J. Heit reports consulting fees from Medtronic and MicroVention, and he is a member of the medical and scientific advisory board for iSchemaView. S. Christensen, J.B. Escribano-Paredes, E. Carrera, and D. Strambo report no disclosures relevant to the manuscript. P. Michel reports grants from University of Lausanne, Swiss Heart Foundation, and Swiss National Science Foundation. A. Salerno reports no disclosures relevant to the manuscript. M. Wintermark reports consulting fees for Icometrix, Subtle Medical, EMTensor, and Magnetic Insights, none relevant to this project. H. Chen, J.-F Albucher, C. Cognard, I. Sibon, M. Obadia, J. Savatovsky, and M.G. Lansberg report no disclosures relevant to the manuscript. G.W. Albers reports stock holdings in iSchemaView and compensation from Biogen, iSchemaView, and Genentech for consultant services. Go to Neurology.org/N for full disclosures.

Figures

**Figure 1. Relationship Between HIR Quartiles and Early Infarct Growth Rate**
Panels A and C show box-plot diagram of the early infarct growth rate in each HIR quartile in the CT (panel A) and MRI (panel C) cohorts. The box represents the upper and lower quartiles, the short black line within the box represents the median, and the whiskers represent the 5th and 95th percentiles. Panels B and D show the rate of fast progressors (early infarct growth rate ≥10 mL/h) in each HIR quartile in the CT (panel B) and MRI (panel D) cohorts. Error bars indicate 95% CIs. HIR = hypoperfusion intensity ratio.

**Figure 2. Representative Images of Fast and Slow Progressors**
Fast progressor: 56-year-old patient with right hemiparesis and aphasia. The CT perfusion obtained 1 hour after stroke onset (NIHSS 17) showed a proximal M1 occlusion and a large left-sided infarct of 79 mL. The early infarct growth rate is 79 mL/h. The hypoperfusion intensity ratio on perfusion imaging was high (0.7), reflecting poor collaterals. Slow progressor: 86-year-old patient with right hemiparesis and aphasia. The MRI obtained 5 hours after stroke onset (NIHSS 16) showed a proximal M1 occlusion and a deep left-sided infarct of 22 mL on DWI. The early infarct growth rate is 4.4 mL/h. The hypoperfusion intensity ratio on perfusion imaging was low (0.1), reflecting excellent collaterals. ADC = apparent diffusion coefficient; CBF = cerebral blood flow; DWI = diffusion-weighted imaging; NIHSS = NIH Stroke Scale; Tmax = time to maximum.

**Figure 3. Three-Month mRS Scores in Fast and Slow Progressors**
Panels A and B represent 3-month mRS scores according to the fast and slow progressor profile in the CT (panel A) and MRI (panel B) cohorts. Panel C represents the predicted probability of 3-month mRS score 0 to 2 according to the time from symptom onset to endovascular reperfusion in patients with slow (red curve, n = 407) and fast (blue curve, n = 233) progression profile. The shaded area corresponds to the 95% CI (logistic regression model). mRS = modified Rankin scale; mTICI = modified thrombolysis in cerebral infarction.

See this image and copyright information in PMC

References

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1. Wheeler HM, Mlynash M, Inoue M, et al. ; DEFUSE 2 Investigators. The growth rate of early DWI lesions is highly variable and associated with penumbral salvage and clinical outcomes following endovascular reperfusion. Int J Stroke. 2015;10(5):723-729. doi:10.1111/ijs.12436 - DOI - PMC - PubMed
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Factors Associated With Fast Early Infarct Growth in Patients With Acute Ischemic Stroke With a Large Vessel Occlusion

Collaborators

Affiliations

Factors Associated With Fast Early Infarct Growth in Patients With Acute Ischemic Stroke With a Large Vessel Occlusion

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources

Medical