Disease progression, transient ischemic attack, and de novo parenchymal lesions in asymptomatic moyamoya disease: results of a 5-year interim analysis of the AMORE study
Authors: Kuroda Satoshi , Yamamoto Shusuke , Funaki Takeshi , Fujimura Miki , Kataoka Hiroharu , Hishikawa Tomohito , Takahashi Jun C. , Endo Hidenori , Nariai Tadashi , Osato Toshiaki , Saito Nobuhito , Sato Norihiro , Hori Emiko , Kashiwazaki Daina , Ito Yoichi M. , Miyamoto Susumu , Inaji Motoki , Morita Kenichi , Maruyama Daisuke , Nakagawara Jyoji , Hashimura Naoki , Hamano Eika , Iihara Koji , Hashimoto Nobuo , Honjo Kaori , Nakamura Hirohiko , Imai Hideaki , Miyawaki Satoru , Hongo Hiroki , Yoshida Kazumichi , Kikuchi Takayuki , Mineharu Yohei , Isozaki Makoto , Kikuta Kenichiro , Araki Yoshio , Kanamori Fumiaki , Date Isao , Ono Junichi , Machida Toshio , Mase Mitsuhito , Katano Hiroyuki , Yamaguchi Koji , Kawamata Takakazu , Tominaga Teiji , Uchino Haruto , Tokairin Kikutaro , Ito Masaki , Houkin Kiyohiro , Chida Kohei , Ogasawara Kuniaki , Nagata Izumi , Horie Nobutaka , Oka Hidehiro , Kumabe Toshihiro 
Published: October 2024

OBJECTIVE
Recently, the authors have reported the 5-year risk of stroke in patients with asymptomatic moyamoya disease (MMD). In this report, the aim was to clarify patients’ 5-year risk of disease progression, transient ischemic attack (TIA), and de novo parenchymal lesions and to identify their predictors.

METHODS
This multicenter, prospective cohort study (Asymptomatic Moyamoya Registry [AMORE]) in Japan is still ongoing. Participants were enrolled if they were 20–70 years of age, had bilateral or unilateral MMD, experienced no episodes suggestive of TIA and stroke, were functionally independent (modified Rankin Scale score of 0 or 1), and had been followed up for 10 years. Clinical and radiological data were obtained at enrollment and annually thereafter for 5 years. In this 5-year interim analysis, the authors defined disease progression, TIA, and de novo parenchymal lesions as the secondary endpoints. The predictors for these events were identified, using a stratification analysis method.

RESULTS
A total of 103 patients were enrolled and prospectively followed up for 5 years. On annual MRA examinations, disease progression occurred in 39 hemispheres in 26 patients. The incidence of disease progression was 5.9% per patient-year, and the predictors included younger age (OR 5.72, 95% CI 1.28–25.56; p = 0.0223) and hypercholesterolemia (OR 5.41, 95% CI 1.37–21.28; p = 0.0158). TIA occurred in 12 hemispheres in 10 patients, for an incidence of 2.3% per patient-year. The disease progression prior to TIA was a significant predictor for TIA (OR 5.00, 95% CI 1.31–19.0; p = 0.0184). De novo microbleeds were found in 11 hemispheres in 10 patients (2.3% per patient-year). The presence of microbleeds at enrollment was a significant predictor for de novo microbleeds (OR 5.53, 95% CI 1.17–26.13; p = 0.0309).

CONCLUSIONS
Patients with asymptomatic MMD may carry a significant risk of disease progression, TIA, and de novo microbleeds during the first 5 years after initial diagnosis. Practitioners should very carefully follow up with them to improve their outcome, using MRI and MRA at regular intervals.
Clinical trial registration no.: UMIN000006640 (https://www.umin.ac.jp).