RESEARCH—HUMAN—CLINICAL STUDIES Incidental De Novo Cerebral Microhemorrhages are Predictive of Future Symptomatic Macrohemorrhages After Surgical Revascularization in Moyamoya Disease Yiping Li, MD Ignatius Esene, MD Mauricio Mandel, MD, PhD Mark Bigder, MD Gary K. Steinberg, MD, PhD Stanford Stroke Center, Department of Neurosurgery, Stanford University School of Medicine, Stanford, California Correspondence: Gary K. Steinberg, MD, PhD, Stanford University School of Medicine, 300 Pasteur Dr (R281), Stanford, CA 94305-5327, USA. Email: gsteinberg@stanford.edu Received, December 18, 2019. Accepted, May 24, 2020. Published Online, July 27, 2020. Copyright C  2020 by the Congress of Neurological Surgeons BACKGROUND: Patients with moyamoya disease who develop incidental cerebral micro- hemorrhages (CMHs) on magnetic resonance imaging (MRI) have higher risk of developing subsequent symptomatic repeat macro hemorrhages. OBJECTIVE: To evaluate the efect of surgical revascularization on development of de novo CMHs and assess its correlation with repeat hemorrhage rates and functional outcome in hemorrhagic onset moyamoya disease (HOMMD). METHODS: We retrospectively reviewed a prospectively managed departmental database of all patients presenting with HOMMD treated between 1987 and 2019. The search yielded 121 patients with adequate MRI follow-up for inclusion into the study. RESULTS: In total, 42 preoperative CMHs were identifed in 18 patients (15%). Patients presenting with preoperative CMH were more likely to develop de novo CMH after surgical revascularization. 7 de novo CHMs were identifed in 6 patients (5%) on routine postoper- ative MRI at distinct locations from previous sites of hemorrhage or CMH. Symptomatic repeat macro hemorrhage was confrmed radiographically in 15 patients (12%). A total 5 (83%) of 6 patients with de novo CMHs later sufered symptomatic repeat macro hemor- rhage with 4 of 5 (80%) hemorrhages occurring at sites of previous CMH. On univariate and multivariate analysis, de novo CMHs was the only signifcant variable predictive for devel- oping repeat symptomatic hemorrhage. Development of delayed repeat symptomatic hemorrhage was prognostic for higher modifed Rankin Score and therefore poorer functional status, whereas preoperative functional status was predictive of fnal outcome. CONCLUSION: De novo CMHs after surgical revascularization might serve as a radio- graphic biomarker for refractory disease and suggest patients are at risk for future symptomatic macro hemorrhage. KEY WORDS: Moyamoya disease, Microhemorrhage, Surgical revascularization Neurosurgery 88:74–81, 2021 DOI:10.1093/neuros/nyaa319 www.neurosurgery-online.com T he natural history of hemorrhagic onset moyamoya disease (HOMMD) is poor and directly related to high mortality after repeat hemorrhages. 1, 2 Despite optimal ABBREVIATIONS: CMHs, cerebral microhemor- rhages; CI, confdence interval; CT, computed tomography; HOMMD, hemorrhagic onset moyamoya disease; MR, magnetic resonance; MRI, magnetic resonance imaging; mRS, modifed Rankin score; MMD, moyamoya disease; RR, relative risks; STA, superfcial temporal artery; SWI, suscep- tibility weighted imaging medical management and surgical revascular- ization, the repeat hemorrhage rate of HOMMD remain as high as 20%. 3 Recent evidence suggests that patients with moyamoya disease (MMD) who develop incidental cerebral micro- hemorrhages (CMHs) identified on magnetic resonance imaging (MRI) have higher risk of developing subsequent symptomatic macro hemorrhages. 4- 6 CMHs are characterized as small circular foci on T2 ∗ weighted imaging (T2 ∗ WI) and susceptibility weighted imaging (SWI) and are often located in the basal ganglia, thalamus, and deep white matter. 7 These locations are also common sites of hemorrhage 74 | VOLUME 88 | NUMBER 1 | JANUARY 2021 www.neurosurgery-online.com Downloaded from https://academic.oup.com/neurosurgery/article/88/1/74/5876915 by guest on 24 December 2020