Delayed Recognition and Stroke-Predominant Presentation in Down Syndrome-Associated Moyamoya Syndrome.

Abstract (English)

BACKGROUND: Children with Down syndrome (DS) are at high risk for moyamoya syndrome (MMS) and ischemic stroke, yet early detection strategies remain poorly defined despite the condition being surgically treatable. METHODS: We conducted a multicenter retrospective cohort study comparing children with Down syndrome-associated moyamoya syndrome (DS-MMS) and MMS without DS (MMS). The primary outcome was stroke as the primary presenting symptom. Secondary outcomes included diagnostic delays, angiographic features, prediagnostic systolic blood pressure percentiles, and 1-year neurological outcomes. Multivariable models adjusted for demographic and access-related covariates. RESULTS: In total, 271 patients were identified; 198 (73.1%) met inclusion criteria and comprised the analytic cohort. Among 198 patients (77 DS-MMS; 121 MMS), DS-MMS mean age was 9.5&#xb1;5.2 years (50.6% female patients), and MMS mean age was 7.4&#xb1;3.0 years (54.5% female patients). Stroke at presentation was more common in DS-MMS (71.4% versus 20.7%; absolute difference, 50.8%), corresponding to an adjusted odds ratio of 14.50 ([95% CI, 6.65-31.60]; <i>P</i><0.001). Children with DS-MMS experienced longer delays from symptom onset to presentation and from presentation to diagnostic confirmation (both <i>P</i><0.001). Posterior circulation involvement was more frequent in DS-MMS (adjusted odds ratio, 2.18 [95% CI, 1.09-4.37]; <i>P</i>=0.03), whereas angiographic severity was similar between groups. In the prediagnostic period, DS-MMS demonstrated a progressive rise in systolic blood pressure percentiles, exceeding the MMS cohort by 6 months (<i>P</i><0.001). At 1 year, DS-MMS was associated with greater disability (adjusted odds ratio, 2.58 [95% CI, 1.45-4.57]; <i>P</i><0.001) and spasticity (adjusted odds ratio, 6.33 [95% CI, 3.12-12.83]; <i>P</i><0.001). CONCLUSIONS: DS-MMS represents a high-risk cerebrovascular phenotype characterized by delayed recognition and a markedly increased likelihood of stroke at presentation. Rising blood pressure percentiles preceding diagnosis may serve as an early physiological signal. These findings support targeted early detection strategies and a lower threshold for vascular imaging in symptomatic patients.