Five-Year Stroke Risk and Its Predictors in Asymptomatic Moyamoya Disease: Asymptomatic Moyamoya Registry (AMORE)

Abstract

Background: Long-term outcomes are unknown in patients with asymptomatic moyamoya disease. In this report, we aimed to clarify their 5-year risk of stroke and its predictors. Methods: We are conducting a multicenter, prospective cohort study (Asymptomatic Moyamoya Registry) in Japan. Participants were eligible if they were 20 to 70 years, had bilateral or unilateral moyamoya disease, experienced no episodes suggestive of TIA and stroke; and were functionally independent (modified Rankin Scale score 0–1). Demographic and radiological information was collected at enrollment. In this study, they are still followed up for 10 years. In this interim analysis, we defined the primary end point as a stroke occurring during a 5-year follow-up period. Independent predictors for stroke were also determined, using a stratification analysis method. Results: Between 2012 and 2015, we enrolled 109 patients, of whom 103 patients with 182 involved hemispheres completed the 5-year follow-up. According to the findings on DSA and MRA, 143 hemispheres were judged as moyamoya disease and 39 hemispheres as questionable manifestations (isolated middle cerebral artery stenosis). The patients with questionable hemispheres were significantly older, more often male, and more frequently had hypertension than those with moyamoya hemisphere. Moyamoya hemispheres developed 7 strokes, including 6 hemorrhagic and 1 ischemic stroke, during the first 5 years. The annual risk of stroke was 1.4% per person, 0.8% per hemisphere, and 1.0% per moyamoya hemisphere. Independent predictor for stroke was Grade-2 choroidal anastomosis (hazard ratio, 5.05 [95% CI, 1.24–20.6]; P =0.023). Furthermore, microbleeds (hazard ratio, 4.89 [95% CI, 1.13-21.3]; P =0.0342) and Grade-2 choroidal anastomosis (hazard ratio, 7.05 [95% CI, 1.62–30.7]; P =0.0093) significantly predicted hemorrhagic stroke. No questionable hemispheres developed any stroke. Conclusions: The hemispheres with asymptomatic moyamoya disease may carry a 1.0% annual risk of stroke during the first 5 years, the majority of which are hemorrhagic stroke. Grade-2 choroidal anastomosis may predict stroke, and the microbleeds and Grade-2 choroidal anastomosis may carry the risk for hemorrhagic stroke. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: UMIN000006640.

Case report: Three characteristics of tyrosine kinase inhibitor-associated cerebrovascular stenosis. High threshold for infarction, atypical infarct area, and vascular recoverability under the use of ponatinib

“…In addition, radiological observations were also similar, as stenotic characteristics of moyamoya disease with donuts-like concentric pattern (Kim et al, 2013;Ya et al, 2020) were also reported in TKI-associated CVS (Hirschbuehl et al, 2019;Suzuki et al, 2019) and large vessel stenosis of the leg (Hirschbuehl et al, 2019), which differentiate from the typical eccentric atherosclerosis. Furthermore, clinical manifestations of moyamoya disease may also resemble the present TKI-associated case, featuring an extended asymptomatic period (Kuroda et al, 2023) possibly due to resistance to infarctions, atypical infarct areas irrespective of anatomical perfusion areas, and confined infarctions in gray matter (known as "gyral pattern, " especially in younger patients; Cho et al, 2011;Kuroda et al, 2023). Added to these similarities, some TKI-associated CVS was reported to be affected by the genetical abnormality (ring finger protein 213) of moyamoya disease (Uemura et al, 2020).…”

Twig-like middle cerebral artery as a variety of isolated middle cerebral artery disease with new vessel formation: illustrative case

“…The Asymptomatic Moyamoya Registry (AMORE) study, the largest prospective cohort study for asymptomatic MMD, is in progress. 20 In that study, questionable (Q) cases in which the stenosis existed only in the proximal portion of the MCA were enrolled, as well as typical MMD cases. The AMORE study group mentioned that the Q cases may be almost identical to isolated MCA disease, and we speculate that a Q case identical to T-MCA may be defined as a variety of isolated MCA disease with NVF.…”

Outcomes of Bypass Surgery in Adult Moyamoya Disease by Onset Type

“…Data on the long-term prognosis of conservative management for adult patients with MMD are limited. Some studies [17][18][19][20][21][22] have described the outcomes of conservative treatment for patients with asymptomatic or hemodynamically stable MMD. In a series of 113 adult patients with MMD, 17 the disease progression rate was reported to be approximately 20% over 6 years.…”

“…The reported annual stroke rate in patients with conservatively managed adult MMD is 3.2% to 15.0%. [18][19][20][21] In a recent multicenter study in Japan with 103 asymptomatic adult patients with MMD, 22 the annual risk of stroke was 1.0% in the first 5 years, predominantly hemorrhage in nature. In the present study, the annual rates of HS and IS were 1.21 and 0.56 per 100 person-years, respectively, in patients with asymptomatic MMD and conservative management (eTable 8 in Supplement 1).…”