Impaired Perfusion and Early Ischemic Stroke Recurrence in Symptomatic Intracranial Atherosclerosis: BIORISK ICAS Study

Shadi Yaghi^{1

2}, Farhan Khan¹, Skylar Lewis¹, Ava Stipanovich¹, Richard Choi³, Richard Baker⁴, Sami Al Kasab⁵, Ahmad Abu Qdais⁵, Sridhara S Yaddanapudi⁶, Sabiha Sultana⁶, Muhib Khan⁷, Maarij Malik⁷, James Klaas⁸, Ekaterina Bakradze⁸, Muhammad Aemaz Ur Rehman⁸, Christopher Leon Guerrero⁹, Hadley Walsh Ressler¹⁰, Faddi G Saleh Velez¹¹, Cameron Owens¹¹, Camila Bonin Pinto¹¹, Margy McCullough-Hicks¹², Dawson Cooper¹², Abhiram Parameswaran Pillai¹², Praveen Hariharan¹², Shaista Alam¹³, Morgan Mayer¹³, Mirjam R Heldner¹⁴, Irina Kugler¹⁴, Kateryna Antoneko¹⁴, William Almiri¹⁵, Sheila Martins^{16

17}, Thais L Secchi¹⁷, Gabriel Mantovani¹⁶, Aaron Rothstein¹⁸, Kelly Sloane¹⁸, Balaji Krishnaiah¹⁹, Linda Alfred¹⁹, Cheran Elangovan¹⁹, Venugopalan Y Vishnu²⁰, Meena Chandu²⁰, Ayush Agarwal²⁰, Michele Romoli²¹, Nicola Marrone²¹, Stefano Vozzi²¹, Malik Ghannam²², Mohamed Elshikh²², Mahmoud Dibas²², Yan Hou²³, Krithika Peshwe²³, Ajay Tunguturi²³, João Pedro Marto²⁴, Rui Duarte Armindo²⁵, Jennifer Frontera²⁶, Lindsey Kuohn²⁶, Mohammad AlMajali²⁷, Osama O Zaidat²⁷, Benan Barakat²⁷, Niha Khan²⁷, Alexis N Simpkins²⁸, Shayak Sen²⁸, Mariana Coelho²⁹, Joao Sargento Fritas²⁹, Joao Andre Sousa²⁹, Diana Aguiar de Sousa^{30

31}, Mafalda Soares³⁰, Amanda Lima^{30

32}, Aditya Jhaveri³³, Rami Z Morsi³³, James Siegler³³, Yasmin N Aziz³⁴, Pablo Harker³⁴, Sonia Bhati³⁴, Sophia Vassilopoulou³⁵, Argyro Tountopoulou³⁵, Adam de Havenon³⁶, Varsha Muddasani³⁷, Nils Henninger³⁸, Hieu Tran³⁸, Johanna Helenius^{38

39}, Mohammad Khasawneh, Ananth Vellimana^{40

41}, Ryan Apfel⁴², Amir Molaie⁴², Marina Mannino⁴³, Valeria Terruso⁴³, Tarek El Halabi⁴⁴, Mahasen Reda⁴⁴, Christel Tamer⁴⁵, Piers Klein⁴⁶, Liqi Shu¹, Pooja Khatri³⁶, Karen Furie¹, Thanh N Nguyen⁴⁶, David S Liebeskind^{40

41}, Shyam Prabhakaran³³

Affiliations

¹ Department of Neurology, The Warren Alpert Medical School of Brown University, Providence, RI (S.Y., F.K., S.L., A.S., L.S., K.F.).
² Department of Neurology, Jersey Shore University Medical Center, Neptune, NJ (S.Y.).
³ Department of Neurology, Medstar Health, Washington, District of Columbia (R.C.).
⁴ Department of Neurology, Christiana Care, Newark, DE (R.B.).
⁵ Department of Neurology, Medical University of South Carolina, Charleston (S.A.K., A.A.Q.).
⁶ Department of Neurology, University of Maryland, Baltimore (S.S.Y., S. Sultana).
⁷ Department of Neurology, Mayo Clinic, Rochester, MN (M. Khan, M. Malik).
⁸ Department of Neurology, University of Alabama at Birmingham (J.K., E.B., M.A.U.R.).
⁹ Department of Neurology, Atrium Health, Charlotte, NC (C.L.G.).
¹⁰ Wake Forest University School of Medicine, NC (H.W.R.).
¹¹ Brain Stimulation and Neurorehabilitation Laboratory, Department of Neurology, University of Oklahoma, Oklahoma City (F.G.S.V., C.O., C.B.P.).
¹² Department of Neurology, University of Minnesota Twin Cities, Minneapolis (M.M.-H., D.C., A.P.P., P. Hariharan).
¹³ Department of Neurology, Thomas Jefferson University, Philadelphia, PA (S.A., M. Mayer).
¹⁴ Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Switzerland. (M.R.H., I.K., K.A.).
¹⁵ Institute of Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital, University of Bern, Switzerland. (W.A.).
¹⁶ Department of Neurology, Hospital de Clínicas de Porto Alegre, Brazil (S.M., G.M.).
¹⁷ Department of Neurology, Hospital Moinhos de Vento, Porto Alegre, Brazil (S.M., T.L.S.).
¹⁸ Department of Neurology, University of Pennsylvania, Philadelphia (A.R., K.S.).
¹⁹ Department of Neurology, University of Tennessee at Memphis (B.K., L.A., C.E.).
²⁰ Department of Neurology, All India Institute of Medical Sciences, New Delhi (V.Y.V., M. Chandu, A.A.).
²¹ Department of Neurosciences, Neurology and Stroke Unit, Bufalini Hospital, Cesena, Italy (M. Romoli, N.M., S. Vozzi).
²² Department of Neurology, University of Iowa, Iowa City (M.G., M.E., M.D.).
²³ Department of Neurology, Hartford Hospital, CT (Y.H., K.P., A. Tunguturi).
²⁴ Department of Neurology, Hospital de Egas Moniz, ULS Lisboa Ocidental, Portugal. (J.P.M.).
²⁵ Department of Neuroradiology, Hospital de Egas Moniz, ULS Lisboa Ocidental, Portugal. (R.D.A.).
²⁶ Department of Neurology, New York University, NY (J.F., L.K.).
²⁷ Department of Neurology, Mercy Health-Saint Vincent Medical Center, Toledo, OH (M.A., O.O.Z., B.B., N.K.).
²⁸ Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA (A.N.S., S. Sen).
²⁹ Department of Neurology, Coimbra University, Portugal (M. Coelho, J.S.F., J.A.S.).
³⁰ Stroke Center, Centro Hospitalar Universitário Lisboa Central, and Institute of Anatomy, Faculdade de Medicina da Universidade de Lisboa, Portugal (D.A.d.S., M.S., A.L.).
³¹ Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal (D.A.d.S.).
³² Department of Neurology, University of North Carolina at Chapel Hill (A.L.).
³³ Department of Neurology, University of Chicago, IL (A.J., R.Z.M., J.S., S.P.).
³⁴ Department of Neurology and Rehabilitation Medicine, University of Cincinnati, OH (Y.N.A., P. Harker, S.B.).
³⁵ 1st Department of Neurology, National and Kapodistrian University of Athens, Greece (S. Vassilopoulou, A. Tountopoulou).
³⁶ Department of Neurology, Yale University, New Haven, CT (A.d.H., P. Khatri).
³⁷ Department of Neurology, University of Texas, Houston (V.M.).
³⁸ Department of Neurology, University of Massachusetts Chan Medical School, Worcester (N.H., H.T., J.H.).
³⁹ Department of Neurology, Lahey Hospital and Medical Center, Burlington, MA (J.H.).
⁴⁰ Department of Neurology, Washington University in St. Louis, MO. (M. Khasawneh).
⁴¹ Department of Neurosurgery, Washington University in St. Louis, MO. (A.V., D.S.L.).
⁴² Department of Neurology, University of California, Los Angeles (R.A., A.M.).
⁴³ Department of Neurology and Stroke Unit, Azienda Ospedaliera Ospedali Riuniti (AOOR) Villa Sofia-V. Cervello, Palermo, Italy (M. Mannino, V.T.).
⁴⁴ Department of Neurology, American University of Beirut Medical Center, Lebanon. (T.E.H., M. Reda).
⁴⁵ Department of Radiology, American University of Beirut Medical Center, Lebanon. (C.T.).
⁴⁶ Department of Neurology, Boston University, MA (P. Klein, T.N.N.).

PMID: 41128719
PMCID: PMC12616403 (available on 2026-10-23)
DOI: 10.1161/STROKEAHA.125.053160

Impaired Perfusion and Early Ischemic Stroke Recurrence in Symptomatic Intracranial Atherosclerosis: BIORISK ICAS Study

Shadi Yaghi et al. Stroke. 2025.

. 2025 Oct 23:10.1161/STROKEAHA.125.053160.

doi: 10.1161/STROKEAHA.125.053160. Online ahead of print.

Authors

Affiliations

¹ Department of Neurology, The Warren Alpert Medical School of Brown University, Providence, RI (S.Y., F.K., S.L., A.S., L.S., K.F.).
² Department of Neurology, Jersey Shore University Medical Center, Neptune, NJ (S.Y.).
³ Department of Neurology, Medstar Health, Washington, District of Columbia (R.C.).
⁴ Department of Neurology, Christiana Care, Newark, DE (R.B.).
⁵ Department of Neurology, Medical University of South Carolina, Charleston (S.A.K., A.A.Q.).
⁶ Department of Neurology, University of Maryland, Baltimore (S.S.Y., S. Sultana).
⁷ Department of Neurology, Mayo Clinic, Rochester, MN (M. Khan, M. Malik).
⁸ Department of Neurology, University of Alabama at Birmingham (J.K., E.B., M.A.U.R.).
⁹ Department of Neurology, Atrium Health, Charlotte, NC (C.L.G.).
¹⁰ Wake Forest University School of Medicine, NC (H.W.R.).
¹¹ Brain Stimulation and Neurorehabilitation Laboratory, Department of Neurology, University of Oklahoma, Oklahoma City (F.G.S.V., C.O., C.B.P.).
¹² Department of Neurology, University of Minnesota Twin Cities, Minneapolis (M.M.-H., D.C., A.P.P., P. Hariharan).
¹³ Department of Neurology, Thomas Jefferson University, Philadelphia, PA (S.A., M. Mayer).
¹⁴ Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Switzerland. (M.R.H., I.K., K.A.).
¹⁵ Institute of Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital, University of Bern, Switzerland. (W.A.).
¹⁶ Department of Neurology, Hospital de Clínicas de Porto Alegre, Brazil (S.M., G.M.).
¹⁷ Department of Neurology, Hospital Moinhos de Vento, Porto Alegre, Brazil (S.M., T.L.S.).
¹⁸ Department of Neurology, University of Pennsylvania, Philadelphia (A.R., K.S.).
¹⁹ Department of Neurology, University of Tennessee at Memphis (B.K., L.A., C.E.).
²⁰ Department of Neurology, All India Institute of Medical Sciences, New Delhi (V.Y.V., M. Chandu, A.A.).
²¹ Department of Neurosciences, Neurology and Stroke Unit, Bufalini Hospital, Cesena, Italy (M. Romoli, N.M., S. Vozzi).
²² Department of Neurology, University of Iowa, Iowa City (M.G., M.E., M.D.).
²³ Department of Neurology, Hartford Hospital, CT (Y.H., K.P., A. Tunguturi).
²⁴ Department of Neurology, Hospital de Egas Moniz, ULS Lisboa Ocidental, Portugal. (J.P.M.).
²⁵ Department of Neuroradiology, Hospital de Egas Moniz, ULS Lisboa Ocidental, Portugal. (R.D.A.).
²⁶ Department of Neurology, New York University, NY (J.F., L.K.).
²⁷ Department of Neurology, Mercy Health-Saint Vincent Medical Center, Toledo, OH (M.A., O.O.Z., B.B., N.K.).
²⁸ Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA (A.N.S., S. Sen).
²⁹ Department of Neurology, Coimbra University, Portugal (M. Coelho, J.S.F., J.A.S.).
³⁰ Stroke Center, Centro Hospitalar Universitário Lisboa Central, and Institute of Anatomy, Faculdade de Medicina da Universidade de Lisboa, Portugal (D.A.d.S., M.S., A.L.).
³¹ Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal (D.A.d.S.).
³² Department of Neurology, University of North Carolina at Chapel Hill (A.L.).
³³ Department of Neurology, University of Chicago, IL (A.J., R.Z.M., J.S., S.P.).
³⁴ Department of Neurology and Rehabilitation Medicine, University of Cincinnati, OH (Y.N.A., P. Harker, S.B.).
³⁵ 1st Department of Neurology, National and Kapodistrian University of Athens, Greece (S. Vassilopoulou, A. Tountopoulou).
³⁶ Department of Neurology, Yale University, New Haven, CT (A.d.H., P. Khatri).
³⁷ Department of Neurology, University of Texas, Houston (V.M.).
³⁸ Department of Neurology, University of Massachusetts Chan Medical School, Worcester (N.H., H.T., J.H.).
³⁹ Department of Neurology, Lahey Hospital and Medical Center, Burlington, MA (J.H.).
⁴⁰ Department of Neurology, Washington University in St. Louis, MO. (M. Khasawneh).
⁴¹ Department of Neurosurgery, Washington University in St. Louis, MO. (A.V., D.S.L.).
⁴² Department of Neurology, University of California, Los Angeles (R.A., A.M.).
⁴³ Department of Neurology and Stroke Unit, Azienda Ospedaliera Ospedali Riuniti (AOOR) Villa Sofia-V. Cervello, Palermo, Italy (M. Mannino, V.T.).
⁴⁴ Department of Neurology, American University of Beirut Medical Center, Lebanon. (T.E.H., M. Reda).
⁴⁵ Department of Radiology, American University of Beirut Medical Center, Lebanon. (C.T.).
⁴⁶ Department of Neurology, Boston University, MA (P. Klein, T.N.N.).

PMID: 41128719
PMCID: PMC12616403 (available on 2026-10-23)
DOI: 10.1161/STROKEAHA.125.053160

Abstract

Background: 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.

Methods: 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_max (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 (P<0.1).

Results: 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]).

Conclusions: 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.

Keywords: infarction; intracranial atherosclerosis; ischemic stroke; perfusion imaging; recurrence.

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Impaired Perfusion and Early Ischemic Stroke Recurrence in Symptomatic Intracranial Atherosclerosis: BIORISK ICAS Study

Affiliations

Impaired Perfusion and Early Ischemic Stroke Recurrence in Symptomatic Intracranial Atherosclerosis: BIORISK ICAS Study

Authors

Affiliations

Abstract

References

Grants and funding

LinkOut - more resources

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Medical