Why Are Only Some Subcortical Ischemic Lesions on Diffusion Magnetic Resonance Imaging Associated With Stroke Symptoms in Small Vessel Disease?

Background and Purpose— In cerebral small vessel diseases, small subcortical ischemic lesions (SSIL) on diffusion imaging are responsible for stroke manifestations but can also be occasionally observed in the absence of overt neurological symptoms. We aimed to determine, in a large cohort of young patients with CADASIL (Cerebral Autosomal-Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy), a severe monogenic condition leading to SSIL in young patients, the characteristics of SSIL and of surrounding cerebral tissue associated with the presence of stroke symptoms. Methods— Among a cohort of 323 genetically confirmed CADASIL patients who were systematically evaluated every 18 months clinically and with magnetic resonance imaging, we studied all visible SSIL and documented ischemic stroke events with available magnetic resonance imaging data. We used mixed-effect logistic regression models to determine whether the presence of stroke symptoms was associated with age, sex, the volume of SSIL, their location with respect to preexisting white matter hyperintensities and with the load of the different magnetic resonance imaging markers of small vessel disease. Results— We identified 73 SSIL (30 with stroke symptoms and 43 without) in 55 patients. In multivariable models, stroke symptoms were more frequent in male patients (estimate=1.94; SE=0.82;P =0.03) and less frequent when SSIL appeared in contact to preexisting white matter hyperintensities (estimate=−2.12; SE=0.83;P =0.01). Within pyramidal tracts, stroke symptoms were more frequent in patients with extensive white matter hyperintensities (estimate=3.8×10−5 ; SE=9.3×10−6 ;P <10−4 ).Conclusions— Altogether, our results suggest that when SSIL occur, the presence of stroke symptoms may depend on sex and alterations of the surrounding brain tissue rather than on the characteristics of the SSIL itself.