Advances in Understanding the Pathogenesis of Lacunar Stroke: From Pathology and Pathophysiology to Neuroimaging.

Lacunar stroke (LS) accounts for about one-quarter of all acute ischemic strokes, represents an important marker of cerebral small vessel disease (CSVD), and has prognostic significance in terms of recurrent vascular events and vascular cognitive impairment. Our understanding of the etiology and pathogenesis of LS is largely based on the meticulous postmortem work of C. Miller Fisher in the late 1960s, with scarce subsequent pathological analysis of the "lacunar hypothesis" and no reliable approaches for direct in vivo imaging of the small intracranial vessels. The recent development of high-resolution MRI, which allows both large-vessel wall and perforating arteries to be imaged in one setting, provides the opportunity to advance understandings of the clinical mechanisms, imaging characteristics, and pathogenesis of LS. Given accumulating evidence of endothelial dysfunction and blood-brain-barrier disruption as early features of CSVD-related LS, advanced imaging may allow various underlying pathogenetic mechanisms to be defined and for better targeting of therapeutic approaches in LS. In this review, progress in understanding the pathogenesis of LS is outlined, covering pathology, pathophysiology, and imaging characteristics, with a focus toward future directions in the complex entity of LS.