Subclinical Vascular Brain Lesions in Young Adults With Acute Ischemic Stroke
Authors: De Giuli Valeria , Grassi Mario , Besana Michele , Zedde Marialuisa , Zini Andrea , Lodigiani Corrado , Marcheselli Simona , Cavallini Anna , Micieli Giuseppe , Rasura Maurizia , DeLodovici Maria Luisa , Tomelleri Giampaolo , Checcarelli Nicoletta , Chiti Alberto , Giorli Elisa , Del Sette Massimo , Tancredi Lucia , Toriello Antonella , Braga Massimiliano , Morotti Andrea , Pezzini Debora , Locatelli Martina , Mazzoleni Valentina , Bonacina Sonia , Gamba Massimo , Magoni Mauro , Patella Rosalba , Spalloni Alessandra , Maria Simone Anna , Pascarella Rosario , Beretta Sandro , Padovani Alessandro , Gasparotti Roberto , Pezzini Alessandro , Gilberti Nicola , Ferrazzi Paola , Banfi Elena , Librè Luca , Traverso Elisabetta , Schirinzi Erika , Carimati Federico , Cappellari Manuel , Locatelli Giampiero , Demelas Laura , Ferrario Davide , Persico Alessandra , Orlandi Giovanni , Napoli Manuela , Moratti Claudio , Guidotti Mario 
Published: November 2021

Background:
Subclinical vascular brain lesions are highly prevalent in elderly patients with stroke. Little is known about predisposing factors and their impact on long-term outcome of patients with stroke at a young age.

Methods:
We quantified magnetic resonance-defined subclinical vascular brain lesions, including lacunes and white matter hyperintensities, perivascular spaces and cerebral microbleeds, and assessed total small-vessel disease (SVD) score in patients with first-ever acute ischemic stroke aged 18 to 45 years, and followed them up, as part of the multicentre Italian Project on Stroke in Young Adults. The primary end point was a composite of ischemic stroke, transient ischemic attack, myocardial infarction, or other arterial events. We assessed the predictive accuracy of magnetic resonance features and whether the addition of these markers improves outcome prediction over a validated clinical tool, such as the Italian Project on Stroke in Young Adults score.

Results:
Among 591 patients (males, 53.8%; mean age, 37.5±6.4 years), 117 (19.8%) had subclinical vascular brain lesions. Family history of stroke was associated with lacunes (odds ratio, 2.24 [95% CI, 1.30–3.84]) and total SVD score (odds ratio, 2.06 [95% CI, 1.20–3.53] for score≥1), hypertension with white matter hyperintensities (odds ratio, 2.29 [95% CI, 1.22–4.32]). After a median follow-up of 36.0 months (25th–75th percentile, 38.0), lacunes and total SVD score were associated with primary end point (hazard ratio, 2.13 [95% CI, 1.17–3.90] for lacunes; hazard ratio, 2.17 [95% CI, 1.20–3.90] for total SVD score ≥1), and the secondary end point brain ischemia (hazard ratio, 2.55 [95% CI, 1.36–4.75] for lacunes; hazard ratio, 2.61 [95% CI, 1.42–4.80] for total SVD score ≥1). The predictive performances of the models, including magnetic resonance features were comparable to those of the random model. Adding individual magnetic resonance features to the Italian Project on Stroke in Young Adults score did not improve model prediction.

Conclusions:
Subclinical vascular brain lesions affect ≈2 in 10 young adults with ischemic stroke. Although lacunes and total SVD score are associated with thrombotic recurrence, they do not improve accuracy of outcome prediction over validated clinical predictors.