Journal article
Impaired Perfusion and Early Ischemic Stroke Recurrence in Symptomatic Intracranial Atherosclerosis: BIORISK ICAS Study
Stroke (1970), Vol.57(1), pp.96-106
01/2026
DOI: 10.1161/STROKEAHA.125.053160
PMCID: PMC12616403
PMID: 41128719
Abstract
Intracranial atherosclerosis (ICAS) is associated with an increased risk of early recurrent ischemic stroke. We evaluated whether biomarkers of impaired distal perfusion-specifically, anterior circulation borderzone infarct, and hypoperfusion mismatch volume-were associated with recurrent ischemic stroke within 90 days.
The BIORISK ICAS (Biomarkers and Recurrence Risk in Symptomatic Intracranial Atherosclerosis) is a multicenter retrospective international study (35 sites) that included hospitalized patients with symptomatic ICAS (50%-99% luminal stenosis of the intracranial vertebral, basilar, distal internal carotid, or proximal middle cerebral artery) from January 2019 to June 2024. The primary outcome was recurrent ischemic stroke in the territory of the symptomatic artery within 90 days. In the primary analysis, the exposure was an acute anterior circulation borderzone infarct. In secondary analysis of the subset with presentation within 72 hours of last known normal and perfusion imaging completed, the exposure of interest was prespecified as hypoperfusion mismatch volume at T
(time to maximum) threshold of 6 seconds, dichotomized at the Youden index. We performed multivariable Cox regression to test associations between exposure variables and the outcome, adjusting for clinically relevant variables and those associated with the outcome (
<0.1).
Of 2050 patients with symptomatic ICAS, 1737 (84.7%) presented within 72 hours of symptom onset, among whom 509 (29.3%) underwent perfusion imaging. The primary analysis included 1891 patients; 174 (9.2%) patients had recurrent ischemic stroke in the symptomatic arterial territory. In adjusted Cox regression models, there was an association between anterior circulation borderzone infarct and recurrent ischemic stroke at 90 days (adjusted hazard ratio, 1.40 [95% CI, 1.02-1.93]). In the perfusion imaging analysis, hypoperfusion mismatch of ≥10 mL was associated with recurrent ischemic stroke (adjusted hazard ratio, 1.83 [95% CI, 1.03-3.28]).
Biomarkers of impaired distal perfusion, anterior circulation borderzone infarct, and hypoperfusion mismatch were associated with increased risk of recurrent ischemic stroke. These findings support the use of perfusion imaging in ICAS as well as future trials investigating early reperfusion in high-risk patients with ICAS.
Details
- Title: Subtitle
- Impaired Perfusion and Early Ischemic Stroke Recurrence in Symptomatic Intracranial Atherosclerosis: BIORISK ICAS Study
- Creators
- Shadi Yaghi - Brown UniversityFarhan Khan - Brown UniversitySkylar Lewis - Brown UniversityAva Stipanovich - Brown UniversityRichard Choi - MedStar HealthRichard Baker - Department of Neurology, Christiana Care, Newark, DE (R.B.)Sami Al Kasab - Medical University of South CarolinaAhmad Abu Qdais - Medical University of South CarolinaSridhara S Yaddanapudi - University of Maryland, BaltimoreSabiha Sultana - University of Maryland, BaltimoreMuhib Khan - Mayo ClinicMaarij Malik - Mayo ClinicJames Klaas - University of Alabama at BirminghamEkaterina Bakradze - University of Alabama at BirminghamMuhammad Aemaz Ur Rehman - University of Alabama at BirminghamChristopher Leon Guerrero - Department of Neurology, Atrium Health, Charlotte, NC (C.L.G.)Hadley Walsh Ressler - Wake Forest UniversityFaddi G Saleh Velez - University of OklahomaCameron Owens - University of OklahomaCamila Bonin Pinto - University of OklahomaMargy McCullough-Hicks - University of MinnesotaDawson Cooper - University of MinnesotaAbhiram Parameswaran Pillai - University of MinnesotaPraveen Hariharan - University of MinnesotaShaista Alam - Thomas Jefferson UniversityMorgan Mayer - Thomas Jefferson UniversityMirjam R Heldner - University Hospital of BernIrina Kugler - University of BernKateryna Antoneko - University of BernWilliam Almiri - University Hospital of BernSheila Martins - Hospital Moinhos de VentoThais L Secchi - Hospital Moinhos de VentoGabriel Mantovani - Hospital de Clínicas de Porto AlegreAaron Rothstein - University of PennsylvaniaKelly Sloane - University of PennsylvaniaBalaji Krishnaiah - University of Tennessee Health Science CenterLinda Alfred - University of Tennessee Health Science CenterCheran Elangovan - University of Tennessee Health Science CenterVenugopalan Y Vishnu - All India Institute of Medical SciencesMeena Chandu - All India Institute of Medical SciencesAyush Agarwal - All India Institute of Medical SciencesMichele Romoli - Ospedale “M. Bufalini” di CesenaNicola Marrone - Ospedale “M. Bufalini” di CesenaStefano Vozzi - Ospedale “M. Bufalini” di CesenaMalik Ghannam - University of IowaMohamed Elshikh - University of IowaMahmoud Dibas - University of IowaYan Hou - Hartford HospitalKrithika Peshwe - Hartford HospitalAjay Tunguturi - Hartford HospitalJoão Pedro Marto - Hospital de Egas MonizRui Duarte Armindo - Hospital de Egas MonizJennifer Frontera - New York UniversityLindsey Kuohn - New York UniversityMohammad AlMajali - Mercy HealthOsama O Zaidat - Mercy HealthBenan Barakat - Mercy HealthNiha Khan - B & BAlexis N Simpkins - Cedars-Sinai Medical CenterShayak Sen - Cedars-Sinai Medical CenterMariana Coelho - University of CoimbraJoao Sargento Fritas - Department of Neurology, Coimbra University, Portugal (M. Coelho, J.S.F., J.A.S.)Joao Andre Sousa - University of CoimbraDiana Aguiar de Sousa - Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal (D.A.d.S.)Mafalda Soares - Unidade Local de Saúde de São JoséAmanda Lima - University of North Carolina at Chapel HillAditya Jhaveri - University of ChicagoRami Z Morsi - University of ChicagoJames Siegler - University of ChicagoYasmin N Aziz - University of CincinnatiPablo Harker - University of CincinnatiSonia Bhati - University of CincinnatiSophia Vassilopoulou - National and Kapodistrian University of AthensArgyro Tountopoulou - National and Kapodistrian University of AthensAdam de Havenon - Yale UniversityVarsha Muddasani - University of HoustonNils Henninger - University of Massachusetts Chan Medical SchoolHieu Tran - University of Massachusetts Chan Medical SchoolJohanna Helenius - Lahey Hospital and Medical CenterMohammad KhasawnehAnanth Vellimana - Washington University in St. LouisRyan Apfel - University of California, Los AngelesAmir Molaie - University of California, Los AngelesMarina Mannino - Ospedale Vincenzo CervelloValeria Terruso - Ospedale Vincenzo CervelloTarek El Halabi - American University of Beirut Medical CenterMahasen Reda - American University of Beirut Medical CenterChristel Tamer - American University of Beirut Medical CenterPiers Klein - Boston UniversityLiqi Shu - Brown UniversityPooja Khatri - Yale UniversityKaren Furie - Brown UniversityThanh N Nguyen - Boston UniversityDavid S Liebeskind - Washington University in St. LouisShyam Prabhakaran - University of Chicago
- Resource Type
- Journal article
- Publication Details
- Stroke (1970), Vol.57(1), pp.96-106
- DOI
- 10.1161/STROKEAHA.125.053160
- PMID
- 41128719
- PMCID
- PMC12616403
- NLM abbreviation
- Stroke
- ISSN
- 0039-2499
- eISSN
- 1524-4628
- Publisher
- LIPPINCOTT WILLIAMS & WILKINS
- Grant note
- National Institutes of Health/National Institute of Neurological Disorders and Stroke: UH3NS130228, R01NS130189, R21NS138995, 3U54AG065141-04S1 Robert A. Winn Excellence in Clinical TrialsHeersink School of Medicine: MULTIPI8165
Dr de Havenon reports National Institutes of Health/National Institute of Neurological Disorders and Stroke funding (UH3NS130228, R01NS130189, and R21NS138995). Dr Simpkins funding (3U54AG065141-04S1, Robert A. Winn Excellence in Clinical Trials: Career Development Award Scholar) is unrelated to this manuscript. Dr Bakradze reports funding from Heersink School of Medicine: Equitable Precision Medicine for Brain Health-MULTIPI8165, unrelated to this article.
- Language
- English
- Electronic publication date
- 10/23/2025
- Date published
- 01/2026
- Academic Unit
- Neurology
- Record Identifier
- 9985019042702771
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