Background: Secondary cortical degeneration caused by the remote effects of subcortical infarction has been implicated in long-term outcomes following acute ischemic stroke. However, this phenomenon remains insufficiently studied in recent small subcortical infarcts (RSSI). The aim of this study was to verify cortical damage induced by RSSI, examine whether this damage could be captured by other neuroimaging markers, and explore its association with functional outcomes, cognitive decline, and affective symptoms in RSSI patients. Methods: RSSI patients with longitudinal Magnetic Resonance Imaging (MRI) data were included in this study. Cortical degeneration driven by RSSI lesions was assessed using linear mixed-effects models, incorporating both a direct approach based on follow-up individual diffusion tensor imaging (DTI) and an indirect approach using a normative connectome from the Human Connectome Project (HCP) dataset. Principal component analysis (PCA) was employed to extract features of cortical alterations. The resulting component scores were then used in general linear models to assess their associations with other imaging markers and changes in clinical outcomes. Results: A total of 76 RSSI patients were included. RSSI was found to induce progressive cortical alterations in structurally connected regions. PCA identified a principal component reflecting parenchymal atrophy, which was associated with imaging features including peak width of skeletonized mean diffusivity (PSMD), track/cap sign, and fractional anisotropy (FA)/mean diffusivity (MD) values. Moreover, faster cortical thinning in lesion-connected regions was significantly associated with an increase in Hamilton Anxiety Rating Scale (HAMA) scores (β = -2.38, 95% CI = -4.30 – -0.47, p = 0.017). Conclusions: RSSI can induce secondary cortical damage through structurally connected fiber tracts, and this damage can be captured by neuroimaging markers that reflect white matter integrity. Furthermore, RSSI-induced regional cortical degeneration might be linked to post-stroke clinical outcomes, such as anxiety symptoms.
Wang et al. (Thu,) studied this question.