Plaque-Inflammation Identified by FDG-PET Associated With Recurrent Ipsilateral Stroke

The risk of 5-year ipsilateral recurrent stroke was 14.3% for those with Symptomatic Carotid Atheroma Inflammation Lumen-Stenosis scores of at least 3 compared with 2.6% for those with low-risk category scores.

Data pooled from 3 prospective studies suggest that use of fluordeoxyglucose (18FDG)-PET on plaque inflammation may improve the identification of patients with symptomatic carotid stenosis who are at high risk of late, as well as early, recurrent stroke. All told, use of the imaging technique was shown to be independently associated with recurrent ipsilateral stroke for up to 5 years in these patients.

A total of 183 eligible patients with nonsevere ischemic stroke/transient ischemic attack (TIA) and ipsilateral carotid stenosis who underwent carotid FDG-PET/CT angiography less than 14 days after recruitment were included in the analysis. 18FDG uptake was expressed as maximum standardized uptake value (SUVmax) in the axial single hottest splice (SHS) of symptomatic plaque.

Senior author Peter Kelly, MD, MS, FRCPI, clinical professor of neurology, University College Dublin, and codirector, stroke service, Mater Hospital, and colleagues defined recurrent stroke, the primary outcome, as a sudden-onset new focal neurologic deficit lasting more than 24 hours or focal neurologic deficits lasting less than 24 hours with imaging-confirmed acute infarction. Of eligible cohort, 181 (98.9%) completed follow-up for a median follow-up duration of 4.9 years (interquartile range [IQR], 3.3-6.4).

At follow-up, there were 18 recurrent ipsilateral ischemic strokes recorded among 17 patients (9.4% [95% CI, 5.6-14.6) after PET imaging, of which 11 (61%) stroke occurred after 30 days and 9 (50%) occurred at least 6 months after the index event. Among those who had an ipsilateral stroke, 8 individuals had severe carotid stenosis, and 5 patients had carotid endarterectomy (CEA) during the hospital admission for the qualifying stroke/TIA.

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Patients who had a recurrent ipsilateral stroke also demonstrated higher mean SUVmax in the SHS than those without recurrence (3.20 g/mL vs 2.84 g/mL; P = .04). After adjusting for age, sex, and carotid revascularization, data on multivariate Cox regression model showed that baseline plaque inflammation remained associated with 5-year ipsilateral stroke recurrence (adjusted HR per 1-g/mL increase in SUVmax, 1.94 [95% CI, 1.06-3.56]; P = .03). This association remained unchanged after inclusion of diabetes mellitus, stenosis severity, and National Institutes of Health Stroke Scale (NIHSS) scores (adjusted HR, 1.98 [95% CI, 1.10-3.56]; P = .02).

Kelly and colleagues noted that further research expanding on these findings, is needed. Mainly, "randomized controlled trials are needed to test the hypothesis that addition of plaque inflammation imaged by PET into current strategies for patient selection will improve clinical outcomes after carotid revascularization."

Symptomatic Carotid Atheroma Inflammation Lumen-Stenosis (SCAIL) score, a previously validated measure, was shown to predict 5-year recurrent ipsilateral ischemic stroke. For each 1-point increase in SCAIL score, the unadjusted HR after PET was 1.63 (95% CI, 1.00-2.65; P = .05). After adjusting for variables such as age, sex, carotid revascularization, diabetes mellitus, and NIHSS score, the SCAIL score independently predicted 5-year recurrent ipsilateral ischemic stroke (adjusted HR, 2.73 [95% CI, 1.52-4.90]; P = .001). this association remained consistent in an exploratory analysis that additionally adjusted for hyperlipidemia, hypertension, smoking and antiplatelet and statin treatment.

Once SCAIL was categorized into low-risk (0-2) and high-risk (3-5) scores, the 5-year ipsilateral recurrent stroke risk was 2.6% (2 of 76 patients [95% CI, 0.3-9.2]) for those in the low-risk group and 14.3% (15 of 103 patients [95% CI, 8.2-22.5]) for those with a score of at least 3 (P = .008). Furthermore, on a threshold analysis, SCAIL scores of at least 3 had 88.2% (95% CI, 63.9-98.5) sensitivity and 45.1% (95% CI, 37.4-53.1) specificity for discrimination of recurrent stroke.

A total of 37 patients had died by 5 years (20.4% [95% CI, 14.8-27.1]). Among surviving patients who had data on late medication use, high rates of statin (90.1%), antithrombotic (96%), and antihypertensive (85.2%) therapy were reported at late follow-up.

At 5 years, there were 55 post-PET recurrent vascular events, including 20 nonfatal coronary events, 14 ischemic vascular deaths, and 21 nonfatal ischemic strokes, occurring in 50 patients (27.6% [95% CI, 21.3-34.7]). Despite this, no association was observed between SUVmax and all late recurrent vascular events on bivariate (HR per 1 g/mL SUVmax, 0.84 [95% CI, 0.56-1.27]; P = .42) or multivariate (HR per 1 g/mL, 0.88 [95% CI, 0.58-1.33]; P = .54) Cox regression.

McCabe JJ, Camps-Renom P, Giannotti N, et al. Carotid plaque inflammation imaged by PET and prediction of recurrent stroke at 5 years. Neurology. 2021;97(23). doi:10.1212/WNL.0000000000012909