Biomarkers of Impaired Distal Perfusion in ICAS

Hopefully your competent? doctor knows EXACTLY WHAT TO DO WITH THIS TO PREVENT YOUR NEXT STROKE!

Do you prefer your doctor, hospital and board of director's incompetence NOT KNOWING? OR NOT DOING?

My doctor told me I had a bunch of white matter hyperintensities but never showed me them on any scan, so I don't know the size, location or any intervention needed, because my doctor knew nothing and did nothing.

Biomarkers of Impaired Distal Perfusion in ICAS

Johanna Seiden

, MD, MPH, @JohannaSeidenMDYaghi S, Khan F, Lewis S, Stipanovich A, Choi R, Baker R, Al Kasab S, Abu Qdais A, Yaddanapudi SS, Sultana S, et al. Impaired Perfusion and Early Ischemic Stroke Recurrence in Symptomatic Intracranial Atherosclerosis: BIORISK ICAS Study. Stroke. 2025. 

The risk of recurrent ischemic stroke due to intracranial atherosclerosis (ICAS) among medically treated patients is higher than other etiologies.¹ There are a number of different submechanisms within ICAS — distal embolization, perforator disease, and hypoperfusion — and risk of subsequent ischemic stroke may not be the same for all causes. Prior studies suggest that impaired distal perfusion may be associated with increased risk of stroke recurrence,^2,3 but these studies did not acutely enroll patients after their index events. They beg the question: Are specific biomarkers of impaired distal perfusion — Anterior Circulation borderzone infarcts (ACBI) and hypoperfusion mismatch volume — associated with higher risk of recurrence within 90 days? The Biomarkers and Recurrence Risk in Symptomatic Intracranial Atherosclerosis (BIORISK ICAS) is a multicenter retrospective international study of 2050 patients with symptomatic ICAS (50-99% luminal stenosis of the intracranial vertebral, basilar, distal ICA or proximal MCA) who did not receive endovascular therapy as first line therapy. The study was conducted between 2019 and 2024. The primary outcome was recurrent ischemic stroke in the territory of the symptomatic artery within 90 days. The primary analysis examined acute ACBI, and secondary analysis performed on patients presenting within 72 hours of last known normal with perfusion imaging studied hypoperfusion mismatch volume at Tmax of 6 seconds. The primary analysis included 1891 patients. Mean age was 67 years, and 54.7% were men. ACBI was seen in 31.7% of patients, and 71.7% had 70-99% stenosis. 174 (9.2%) patients had recurrent ischemic stroke in the symptomatic arterial territory within 90 days. In univariate analysis, ACBI was associated with recurrent stroke at 90 days (38.5% [67/174] vs. 31% [532/1717], p=0.042). Hyperlipidemia, degree of stenosis 70-99% vs 50-69%, and nonsmokers had increased risk of recurrent stroke. Among patients who underwent perfusion imaging (509 patients), hypoperfusion mismatch was also associated with increased risk of recurrent stroke within 90 days (67.7% [42/62] vs. 53.5% [221/413], p=0.036). Hyperlipidemia and atrial fibrillation were also associated with increased risk of recurrent stroke. Patients with ACBI had increased risk of recurrent stroke within 90 days; this finding persisted even after adjustment for variables associated with recurrent ischemic stroke risk (aHR 1.40, 95% CI 1.02-1.93, p=0.038). In the interaction analyses, the association between ACBI and recurrent stroke was more pronounced in patients with 50-69% stenosis (aHR 3.10 95% CI 1.47-6.52) versus 70-99% stenosis (aHR 1.18 95% CI 0.83-1.68), P Interaction=0.026. In the perfusion imaging analysis, hypoperfusion mismatch >10 mL at Tmax 6 seconds was associated with recurrent stroke at 90 days even after adjustment (aHR 1.83, 95% CI 1.03-3.28, p=0.041). This multicenter international study of patients with symptomatic ICAS demonstrated that patients with impaired distal perfusion, measured either directly (through perfusion imaging) or indirectly (via evidence of ACBI), were at a higher risk of recurrent stroke at 90 days. Interestingly, this study found that the association between ACBI and recurrent ischemic stroke was more pronounced in patients with moderate stenosis versus severe stenosis. This finding could very well be due to chance, but the authors also hypothesize that the presence of borderzone infarcts in patients with severe stenosis may not be as helpful in risk stratification because they are inherently more common; however, in those with moderate stenosis, borderzone infarcts may portend a higher recurrence risk. Future studies will be important to further evaluate this finding. Limitations of this study include the retrospective and observational nature, while strengths include the large sample size and multicenter international population. Methods to risk stratify ICAS patients could help determine which patients might benefit from angioplasty, stenting, or other targeted interventions. Randomized trials testing maximal medical therapy against early reperfusion in these high-risk patients will be important moving forward.

References:Derdeyn CP, Chimowitz MI, Lynn MJ, Fiorella D, Turan TN, Janis LS,Montgomery J, Nizam A, Lane BF, Lutsep HL, et al. Aggressive medical treatment with or without stenting in high-risk patients with intracranial artery stenosis (SAMMPRIS): The final results of a randomised trial. Lancet (London, England). 2014;383:333-341

Wabnitz AM, Derdeyn CP, Fiorella DJ, Lynn MJ, Cotsonis GA, Liebeskind DS, Waters MF, Lutsep H, López-Cancio E, Turan TN, et al. Hemodynamic markers in the anterior circulation as predictors of recurrent stroke in patients with intracranial stenosis. Stroke. 2018:Strokeaha11802084

Wang T, Yang Y, Wang H, Liu D, Wang J, Luo J, Yang R, Li T, Gong H, Sun X, et al. Ct perfusion for predicting ischemic stroke in patients with symptomatic carotid or middle cerebral artery occlusion: A post hoc analysis of the CMOSS study. Stroke. 2025;56:2579-2587