MRI-Proven Incident Ischemia: A New Marker of Disease Progression in Small Vessel Diseases

BACKGROUND: In ischemic cerebral small vessel diseases (cSVD), recurrent ischemic stroke is rare (2%–3% per year). Because acute ischemia may not always lead to stroke in cSVD due to the small size of lesions, acute stroke may not reliably reflect ischemic activity or the risk of further clinical worsening, as both incident lacunes and incidental diffusion-weighted imaging–positive lesions can occur without stroke symptoms. We aimed to evaluate the total ischemic activity by measuring the incidence of magnetic resonance imaging (MRI)–proven incident ischemia, independent of the presence of stroke symptoms in a large cohort of cSVD. METHODS: DHU-LAC is an ongoing French multicenter cohort study of MRI-proven ischemic stroke presumably due to cSVD. We report data on patients recruited between June 2018 and October 2023. In DHU-LAC, patients are enrolled within 15 days of stroke onset and are cared for according to current guidelines. During the first 6 months, patients are systematically reassessed clinically and by brain MRI: (1) at any time if stroke symptoms occur and (2) at the end of the period. We defined MRI-proven incident ischemia as either recurrent ischemic stroke or at least 1 incident lacune or incidental diffusion-weighted imaging–positive lesion on brain MRI at 6 months. RESULTS: Two hundred forty-nine patients were included, of whom 172 had available data at both inclusion and after 6 months. They were aged 63±6 years, 28% were women, and 65% had hypertension. Six (3%) had a recurrent ischemic stroke, but 25 more (15%) had at least 1 incident lacune or incidental diffusion-weighted imaging–positive lesion on brain MRI. MRI-proven ischemia occurs about 5× more frequently than ischemic stroke in cSVD. CONCLUSIONS: As data confirming the detrimental clinical effect of both incident lacunes and incidental diffusion-weighted imaging–positive lesions accumulate, MRI-proven incident ischemia may become a plausible outcome for future clinical trials in cSVD. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03552926.