Accepted Manuscript Looking Beyond the Surface of Adult Moyamoya Disease: Brain MRI Microstructural Changes and Cognitive Dysfunction Youssef J. Hamade, MD, MSCI, Rami James N. Aoun, MD, MPH, Samer G. Zammar, MD, Stacie E. DeMent, PA-C, Naresh P. Patel, MD, Bernard R. Bendok, MD, MSCI PII:

S1878-8750(15)00482-9

DOI:

10.1016/j.wneu.2015.05.001

Reference:

WNEU 2878

To appear in:

World Neurosurgery

Please cite this article as: Hamade YJ, Aoun RJN, Zammar SG, DeMent SE, Patel NP, Bendok BR, Looking Beyond the Surface of Adult Moyamoya Disease: Brain MRI Microstructural Changes and Cognitive Dysfunction, World Neurosurgery (2015), doi: 10.1016/j.wneu.2015.05.001. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT

Looking Beyond the Surface of Adult Moyamoya Disease: Brain MRI Microstructural Changes and Cognitive Dysfunction

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Youssef J. Hamade, MD, MSCI1; Rami James N. Aoun, MD, MPH1; Samer G. Zammar, MD2; Stacie E. DeMent, PA-C1; Naresh P. Patel, MD1; Bernard R. Bendok, MD, MSCI1

1. Department of Neurological Surgery, Mayo Clinic, Phoenix, AZ

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2. Department of Neurological Surgery, Northwestern University, Chicago, IL

Moyamoya disease (MMD) is a cerebrovascular condition characterized by progressive

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stenosis or occlusion of arteries of the anterior circulation with associated hypertrophy of deep penetrating arteries and development of extracranial-intracranial collateral vessels.4,5 Recent studies have suggested an association between adult MMD and cognitive impairment, with possible relation to reduced cerebral blood flow and microstructural changes in brain tissue.1,2 While both gray and white matter can be affected by ischemic changes, there are currently no reports evaluating gray matter integrity in MMD patients, and only a few assessing white matter

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changes. Furthermore, the relationship of these changes to cognitive function has not been well established. Kazumata et al. conducted a prospective study to investigate the microstructural alterations in MMD patients and their correlation with hemodynamic compromise and Stroke.3

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neurocognitive function. The results of the study were published in the February 2015 issue of

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The authors used 3D MRI for assessment of brain microstructural alterations. They used voxel by voxel density analysis to detect subtle gray matter changes, and diffusion tension imaging (DTI) with tractography for evaluation of white matter integrity. The four major DTI indices incorporated were fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). They enrolled 23 patients with clinical diagnosis of idiopathic MMD according to the criteria proposed by the Research Committee on Spontaneous Occlusion of the Circle of Willis, and age > 20, as well as 23 control patients who had normal intelligence quotient and no evidence of neurological or psychiatric disorders. For gray matter alterations, the authors compared density images between MMD and control patients. For white matter

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alterations, they tested the differences in DTI indices and calculated the mean value and number of voxels for each index reaching statistical significance. In both analyses, age was considered as a covariate and results were corrected. Furthermore, the authors assessed the hemodynamic status with single positron emission computed tomography and considered hemodynamic

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compromise when cerebrovascular reactivity was