[Rethinking Lacunar Stroke: Beyond Fisher's Curse].

Area of Science:

• Neurology
• Vascular Neurology
• Neuroimaging

Background:

• Lipohyalinosis has been historically overemphasized in lacunar stroke etiology, causing diagnostic confusion.
• Antihypertensive therapies have reduced classical lipohyalinosis, making age-related hyaline atherosclerosis more prevalent.
• Lacunar stroke involves multiple etiopathogenetic factors beyond lipohyalinosis.

Purpose of the Study:

• To re-evaluate the role of lipohyalinosis in lacunar stroke.
• To identify alternative etiopathogenetic mechanisms contributing to lacunar stroke.
• To explore the significance of deep white matter hyperintensity on MRI and genetic factors in lacunar stroke.

Main Methods:

• Categorization of lacunar stroke based on atheroma detection, excluding cardiogenic embolism.
• Utilizing advanced atheroma imaging techniques.
• Conducting risk gene analysis in patients with lacunar stroke and deep white matter hyperintensity on MRI.

Main Results:

• Lacunar strokes without detectable atheroma are associated with deep white matter hyperintensity on MRI.
• Risk gene analysis identified specific extracellular matrix-associated genes linked to lacunar stroke with white matter changes.
• These findings suggest distinct pathogenetic pathways, particularly genetic contributors, for this subgroup of lacunar stroke.

Conclusions:

• Lacunar stroke pathogenesis is multifactorial, with lipohyalinosis playing a less dominant role than previously thought.
• Deep white matter hyperintensity on MRI in lacunar stroke may indicate unique pathogenetic mechanisms, often involving genetic factors.
• Future diagnostic and therapeutic strategies for lacunar stroke should consider these diverse etiologies, especially genetic contributions.