In Reply to the Letter to the Editor Regarding “Pediatric Moyamoya Presenting as a Subarachnoid Hemorrhage from a Ruptured Anterior Cerebral Artery Aneurysm” W e would like to thank Yu et al 1 for their thoughtful and noteworthy comments on our manuscript. The authors raised 2 points: 1) the atypical location and hemorrhage type associated with the aneurysm and 2) the potential presence of PHACE syndrome (posterior fossa brain malformations, hemangioma, arterial lesions, cardiac abnormalities, eye abnormalities, sternal cleft) in our patient. Concerning the first point, we agree that the development of an aneurysm on anterior cerebral artery cannot be explained by the flow-related burden that is imposed by the architectural changes in the intracranial vascular tree. This is especially true in cases of moyamoya disease (MMD), where narrowing of the intracranial internal carotid arteries is bilateral as opposed to the unilateral involvement in our patient. In bilateral MMD, the hemodynamic load is shifted toward the posterior circulation, which may explain the high prevalence of aneurysms in the posterior cerebral vasculature. 2 Of interest, a recent article by Kim et al 3 reported exclusive localization of aneurysms to the anterior circulation in adult patients with unilateral moyamoya-like pathology, and subarachnoid hemorrhage was expectedly the presenting hemor- rhage type. This observation prompts further investigations about the hemodynamic changes in unilateral moyamoya. Regarding the second point, MMD is not uncommonly associated with various syndromes and congenital conditions including congenital cardiac anomalies. 4 Although our patient does not have PHACE syndrome features other than the patent foramen ovale and unilateral moyamoya-like pathology, she did have mild Down syndrome facies (flat nasal bridge, upslanting palpebral fissures, relatively short neck). However, her karyotype analysis was normal, which has also been reported in some patients with Down syndrome phenotypes. 5 Mohammad Hassan A. Noureldine 1 , Ibrahim Saikali 2 , Anis Nassif 3 , Rita Chahinian 3 , Ahmad Sweid 4 , Raghid Kikano 3 , Michel Mawad 3 From the 1 Department of Neurosurgery, Johns Hopkins University School of Medicine, Institute for Brain Protection Sciences, Johns Hopkins All Children’s Hospital, Saint Petersburg, Florida, USA; and 2 Division of Neurosurgery, 3 Department of Radiology, Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Beirut, Lebanon; and 4 Department of Neurosurgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, USA To whom correspondence should be addressed: Mohammad Hassan A. Noureldine, M.D. [E-mail: mohammadhassan.noureldine@lau.edu; mnourel2@jhmi.edu] Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. https://doi.org/10.1016/j.wneu.2020.02.175. REFERENCES 1. Noureldine MHA, Saikali I, Nassif A, et al. Pediatric moyamoya presenting as a subarachnoid hemorrhage from a ruptured anterior cerebral artery aneurysm. World Neurosurg. 2020;134:123-127. 2. Furtado SV, Medress ZA, Teo M, Steinberg GK. Pathogenesis of aneurysms on major vessels in moyamoya disease and management outcome. J Clin Neurosci. 2019;61:219-224. 3. Kim JH, Kwon T-H, Kim JH, Chong K, Yoon W. Intracranial aneurysms in adult moyamoya disease. World Neurosurg. 2018;109:e175-e182. 4. Scott RM, Smith JL, Robertson RL, Madsen JR, Soriano SG, Rockoff MA. Long- term outcome in children with moyamoya syndrome after cranial revasculariza- tion by pial synangiosis. J Neurosurg Pediatr. 2004;100:142-149. 5. Ahlbom BE, Goetz P, Korenberg JR, et al. Molecular analysis of chromosome 21 in a patient with a phenotype of Down syndrome and apparently normal karyotype. Am J Med Genet. 1996;63:566-572. 492 www.SCIENCEDIRECT.com 137: 492, MAY 2020 WORLD NEUROSURGERY Letter to the Editor