Multiple simultaneous acute infarcts in CADASIL: a retrospective cohort study and systematic review

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic cause of stroke and typically presents with single lacunar infarcts. However, multiple simultaneous acute infarcts have increasingly been reported. Methods: We retrospectively reviewed a prospectively recruited CADASIL registry from a British National Referral Clinic to identify cases with multiple simultaneous acute infarcts. We combined this with data from a systematic review on MEDLINE, Embase, Web of Science, and Cochrane Library from inception to 16th February 2026. Multiple simultaneous infarcts were defined as multiple diffusion-restricted lesions on brain MRI. Results: Eight cases (5 male) were identified from 612 symptomatic CADASIL patients, corresponding to 1.3% of the cohort (95% CI 0.6–2.6%). Mean (SD) age 49.6±13.1 compared with 49.5±9.8 for 291 stroke patients with single lacunar infarct. All had a recent infection (COVID-19 3, unspecified respiratory tract infections 4, and Campylobacter infection 1), occurring 2–14 days before symptom onset. The systematic review identified an additional 36 cases (total n=44). Mean age was 48.3±10.2 years and 26 were male. Preceding events were identified in 31 cases, most commonly infection (n=25), followed by surgery (n=4), trauma (n=1), and severe anaemia (n=1). Most patients had infarcts involving bilateral internal watershed regions (90.9%). Conclusions: Multiple simultaneous acute infarcts are a rare but important CADASIL presentation, typically involving bilateral watershed regions and frequently preceded by acute systemic stressors, most commonly infection, but also surgery and hypotension. This pattern may reflect increased cerebral microvascular vulnerability in CADASIL patients and warrants further investigation.