Pediatric Moyamoya Disease and Syndrome in Italy: A Multicenter Cohort

Abstract

BackgroundMoyamoya is a rare progressive cerebral arteriopathy, occurring as an isolated phenomenon (moyamoya disease, MMD) or associated with other conditions (moyamoya syndrome, MMS), responsible for 6–10% of all childhood strokes and transient ischemic attacks (TIAs).MethodsWe conducted a retrospective multicenter study on pediatric-onset MMD/MMS in Italy in order to characterize disease presentation, course, management, neuroradiology, and outcome in a European country.ResultsA total of 65 patients (34/65 women) with MMD (27/65) or MMS (38/65) were included. About 18% (12/65) of patients were asymptomatic and diagnosed incidentally during investigations performed for an underlying condition (incMMS), whereas 82% (53/65) of patients with MMD or MMS were diagnosed due to the presence of neurological symptoms (symptMMD/MMS). Of these latter, before diagnosis, 66% (43/65) of patients suffered from cerebrovascular events with or without other manifestations (ischemic stroke 42%, 27/65; TIA 32%, 21/65; and no hemorrhagic strokes), 18% (12/65) of them reported headache (in 4/12 headache was not associated with any other manifestation), and 26% (17/65) of them experienced multiple phenotypes (≥2 among: stroke/TIA/seizures/headache/others). Neuroradiology disclosed ≥1 ischemic lesion in 67% (39/58) of patients and posterior circulation involvement in 51% (30/58) of them. About 73% (47/64) of patients underwent surgery, and 69% (45/65) of them received aspirin, but after diagnosis, further stroke events occurred in 20% (12/61) of them, including operated patients (11%, 5/47). Between symptom onset and last follow-up, the overall patient/year incidence of stroke was 10.26% (IC 95% 7.58–13.88%). At last follow-up (median 4 years after diagnosis, range 0.5–15), 43% (26/61) of patients had motor deficits, 31% (19/61) of them had intellectual disability, 13% (8/61) of them had epilepsy, 11% (7/61) of them had behavioral problems, and 25% (13/52) of them had mRS > 2. The proportion of final mRS > 2 was significantly higher in patients with symptMMD/MMS than in patients with incMMS (p = 0.021). Onset age <4 years and stroke before diagnosis were significantly associated with increased risk of intellectual disability (p = 0.0010 and p = 0.0071, respectively) and mRS > 2 at follow-up (p = 0.0106 and p = 0.0009, respectively).ConclusionsMoyamoya is a severe condition that may affect young children and frequently cause cerebrovascular events throughout the disease course, but may also manifest with multiple and non-cerebrovascular clinical phenotypes including headache (isolated or associated with other manifestations), seizures, and movement disorder. Younger onset age and stroke before diagnosis may associate with increased risk of worse outcome (final mRS > 2).

European Stroke Organisation (ESO) Guidelines on Moyamoya angiopathy Endorsed by Vascular European Reference Network (VASCERN)

“…Recent single centre studies with 100 and 73 paediatric MMA patients respectively and a multicentre study of 63 MMA patients, all of mainly European ethnicity, confirmed the high risk of progression with recurrent strokes in MMA children and more so in the younger age groups as well as in those showing PCA involvement. 88,134,135 In an older publication with East Asian paediatric MMD patients, Kim et al reiterated this aggressive clinical course. 136 In a recent follow-up study of 415 paediatric MMD patients, the same authors showed a favourable clinical outcome in 81% of the patients about 3 years after revascularization surgery.…”

Epidemiology, causes, and morbidities of stroke in the young

“…It can occur as an isolated phenomenon or associated with conditions such as neurofibromatosis, sickle cell disease (SCD), and renovascular disease. Two retrospective studies reported that Moyamoya can present with various clinical phenotypes, including headache, seizures, movement disorder, and stroke [26,27]. Younger age at the time of diagnosis was associated with worse outcome [27].…”

“…Two retrospective studies reported that Moyamoya can present with various clinical phenotypes, including headache, seizures, movement disorder, and stroke [26,27]. Younger age at the time of diagnosis was associated with worse outcome [27].…”

Moyamoya disease/cerebral vasculopathy in osteopathia striata with cranial sclerosis: a rare but important complication

“…The most common bilateral cerebral vasculopathy in children is Moyamoya Disease (MMD), with 66% of paediatric MMD cases presenting with stroke (Po’ et al ., 2022). Moyamoya Disease is a cerebral vasculopathy, causing progressive narrowing of cerebral vessels, predisposing individuals to stroke.…”