Long-Term Imaging and Clinical Outcomes After Recent Small Subcortical Infarct

Background and Objectives Recent small subcortical infarcts (RSSI) are common, but little is known about their tissue fates and relevance for clinical outcomes. We assessed predictors for long-term morphologic changes of symptomatic RSSI, and whether size and cavitation are associated with cognitive and functional outcomes after lacunar ischemic stroke. Methods We included participants with lacunar stroke from 2 prospective nonoverlapping studies, the Mild Stroke Study-2 (MSS-2) and MSS-3, with CT-confirmed and/or 1.5/3T MRI-confirmed RSSI at symptom onset (“index-RSSI”); and at least a follow-up brain MRI at 1 year. Demographic, clinical, cognitive, and imaging assessments were performed. We visually evaluated the morphologic changes of RSSI from diagnosis to 1 year, assessing maximum diameters (mm) and degrees of cavitation (cavitation status). Using multivariable mixed-effects analyses, we assessed predictors of index-RSSI size, any resulting lacune’s diameter, cavitation status, and associations with cognitive (Montreal cognitive assessment, MoCA), and functional (modified Rankin Scale) outcomes at 1 year. Results Downloaded from https://www.neurology.org by 86.31.113.121 on 11 August 2026 Among 173 participants (mean age 65 ± 11.2 years, 33% female), 10/173 (6%) index RSSI disappeared, 150/173 (87%) showed some degree of lacune formation at 1 year, of which 23/ 150 (15%) were <3 mm in diameter, and 4/173 (2%) partially cavitated regressed by 1 year. In multivariable analyses, index RSSI diameter at diagnosis (β = 0.6, 95% CI [0.5–0.7]) and supraventricular white matter location (i.e., centrum semiovale, β = 1.5, 95% CI [0.2–2.7]) predicted RSSI size at 1 year. Larger RSSI diameter at diagnosis (OR 1.4, 95% CI [1.2–1.7]) was associated with larger (≥3 mm) lacunes at 1 year. RSSI located in deep white matter (e.g., internal/external capsule) had better MoCA scores at 1 year (β = 1.9, 95% CI [0.6–3.2]) than other locations. No other RSSI long-term changes influenced clinical outcomes. Discussion RSSI and resulting lacunes evolve over a year, with 15% shrinking to <3 mm diameter, 6% disappearing, and 2% regressing, potentially masking small vessel disease burden. The determinants of RSSI that apparently do no leave a trace remain unknown. Apart from RSSI location, the lack of effect of index RSSI internal long-term changes on clinical outcomes suggests that secondary perilesional RSSI changes or preexisting brain microstructural health may be more relevant. Future research should consider neuroimaging heterogeneity, larger sample size