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

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.

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.

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±5.2 years (50.6% female), and MMS mean age was 7.4±3.0 years (54.5% female). Stroke at presentation was more common in DS-MMS (71.4% versus 20.7%; absolute difference, 50.7%), corresponding to an adjusted odds ratio of 14.50 ([95% CI, 6.65-31.60]; P<0.001). Children with DS-MMS experienced longer delays from symptom onset to presentation and from presentation to diagnostic confirmation (both P<0.001). Posterior circulation involvement was more frequent in DS-MMS (adjusted odds ratio, 2.18 [95% CI, 1.09-4.37]; P=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 (P<0.001). At 1 year, DS-MMS was associated with greater disability (adjusted odds ratio, 2.58 [95% CI, 1.45-4.57]; P<0.001) and spasticity (adjusted odds ratio, 6.33 [95% CI, 3.12-12.83]; P<0.001).

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.