Pediatric Moyamoya Disease and Syndrome in Italy: A Multicenter Cohort
Authors: Po' Chiara , Nosadini Margherita , Zedde Marialuisa , Pascarella Rosario , Mirone Giuseppe , Cicala Domenico , Rosati Anna , Cosi Alessandra , Toldo Irene , Colombatti Raffaella , Martelli Paola , Iodice Alessandro , Accorsi Patrizia , Giordano Lucio , Savasta Salvatore , Foiadelli Thomas , Sanfilippo Giuseppina , Lafe Elvis , Thyrion Federico Zappoli , Polonara Gabriele , Campa Serena , Raviglione Federico , Scelsa Barbara , Bova Stefania Maria , Greco Filippo , Cordelli Duccio Maria , Cirillo Luigi , Toni Francesco , Baro Valentina , Causin Francesco , Frigo Anna Chiara , Suppiej Agnese , Sainati Laura , Azzolina Danila , Agostini Manuela , Cesaroni Elisabetta , De Carlo Luigi , Di Rosa Gabriella , Esposito Giacomo , Grazian Luisa , Morini Giovanna , Nicita Francesco , Operto Francesca Felicia , Pruna Dario , Ragazzi Paola , Rollo Massimo , Spalice Alberto , Striano Pasquale , Skabar Aldo , Lanterna Luigi Alberto , Carai Andrea , Marras Carlo Efisio , Manara Renzo , Sartori Stefano 
Published: May 2022

Background

Moyamoya 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).

Methods

We 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.

Results

A 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 &gt; 2. The proportion of final mRS &gt; 2 was significantly higher in patients with symptMMD/MMS than in patients with incMMS (p = 0.021). Onset age &lt;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 &gt; 2 at follow-up (p = 0.0106 and p = 0.0009, respectively).

Conclusions

Moyamoya 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 &gt; 2).