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Looking Beyond the Surface of Adult Moyamoya Disease: Brain Magnetic Resonance Imaging Microstructural Changes and Cognitive Dysfunction
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
SC
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
TE D
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
EP
neurocognitive function. The results of the study were published in the February 2015 issue of
AC C
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
ACCEPTED MANUSCRIPT
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
RI PT
compromise when cerebrovascular reactivity was <15% in the left or right MCA territories. They also performed blinded neuropsychological assessment using Wechsler Adult Intelligent ScaleIII, Wisconsin Card Sorting test, Trail Making test (TMT; parts A and B), continuous performance task, Stroop test and reading span test. Lastly, they correlated the changes in gray
SC
and white matters with age, presence of ischemic symptoms, hemodynamic compromise and
M AN U
neuropsychological performance.
The authors observed significant reduction in gray matter density of bilateral posterior cingulate cortex (PCC) in MMD patients compared to controls. White matter alterations were reflected by a significant decrease in FA (55.2%) and increase in RD (42.5%). Changes in gray matter were significantly correlated with the mean FA (r=0.54) and RD (r=-.041) of the white matter skeleton, and both gray and white matter were inversely associated with age (r=-0.43 and
TE D
r=-0.57, respectively). Hemodynamic analysis revealed an association between hemodynamic compromise and reduced bilateral PCC density. Neuropsychological testing showed that the mean FA values of white matter tracts of the dorsolateral prefrontal, cingulate and inferior
EP
parietal regions were significantly associated with impaired cognitive performance.
We commend Kazumata et al. on their work. The results of this study suggest that MRI
AC C
imaging can be used to assess gray and white matter abnormalities in Moyamoya disease, and these abnormalities may underlie cognitive dysfunction. While obvious ischemic stroke and hemorrhage have been used to define “symptomatic disease”, this study supports the growing body of evidence that cognitive dysfunction and imaging biomarkers may be equally important in defining active Moyamoya disease. Future studies assessing the efficacy of revascularization should factor in cognitive dysfunction and its potential reversal as endpoints. Imaging should also be thoughtfully integrated into patient selection, disease monitoring and endpoint assessment paradigms. It is clear that the future vascular neurosurgery practice should
ACCEPTED MANUSCRIPT
incorporate cognitive testing and advanced imaging as important dimensions for screening, monitoring and assessment.
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SC
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1. Festa JR, Schwarz LR, Pliskin N, et al. Neurocognitive dysfunction in adult moyamoya disease. Journal of neurology 2010;257:806-15. 2. Karzmark P, Zeifert PD, Bell-Stephens TE, Steinberg GK, Dorfman LJ. Neurocognitive impairment in adults with moyamoya disease without stroke. Neurosurgery 2012;70:634-8. 3. Kazumata K, Tha KK, Narita H, et al. Chronic ischemia alters brain microstructural integrity and cognitive performance in adult moyamoya disease. Stroke; a journal of cerebral circulation 2015;46:354-60. 4. Suzuki J, Kodama N. Moyamoya disease--a review. Stroke; a journal of cerebral circulation 1983;14:104-9. 5. Suzuki J, Takaku A. Cerebrovascular "moyamoya" disease. Disease showing abnormal net-like vessels in base of brain. Archives of neurology 1969;20:288-99.
Figure Legends
Figure 1: Gradient echo images showing decreased gray matter density of posterior cingulate cortex in Moyamoya disease patients compared to controls (color regions represent P values).
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Figure 2: Differential correlation of white matter fractional anisotropy with cognitive testing (color regions represent P values).
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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
RI PT
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
SC
2. Department of Neurological Surgery, Northwestern University, Chicago, IL
Moyamoya disease (MMD) is a cerebrovascular condition characterized by progressive
M AN U
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
TE D
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
EP
neurocognitive function. The results of the study were published in the February 2015 issue of
AC C
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
ACCEPTED MANUSCRIPT
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
RI PT
compromise when cerebrovascular reactivity was <15% in the left or right MCA territories. They also performed blinded neuropsychological assessment using Wechsler Adult Intelligent ScaleIII, Wisconsin Card Sorting test, Trail Making test (TMT; parts A and B), continuous performance task, Stroop test and reading span test. Lastly, they correlated the changes in gray
SC
and white matters with age, presence of ischemic symptoms, hemodynamic compromise and
M AN U
neuropsychological performance.
The authors observed significant reduction in gray matter density of bilateral posterior cingulate cortex (PCC) in MMD patients compared to controls. White matter alterations were reflected by a significant decrease in FA (55.2%) and increase in RD (42.5%). Changes in gray matter were significantly correlated with the mean FA (r=0.54) and RD (r=-.041) of the white matter skeleton, and both gray and white matter were inversely associated with age (r=-0.43 and
TE D
r=-0.57, respectively). Hemodynamic analysis revealed an association between hemodynamic compromise and reduced bilateral PCC density. Neuropsychological testing showed that the mean FA values of white matter tracts of the dorsolateral prefrontal, cingulate and inferior
EP
parietal regions were significantly associated with impaired cognitive performance.
We commend Kazumata et al. on their work. The results of this study suggest that MRI
AC C
imaging can be used to assess gray and white matter abnormalities in Moyamoya disease, and these abnormalities may underlie cognitive dysfunction. While obvious ischemic stroke and hemorrhage have been used to define “symptomatic disease”, this study supports the growing body of evidence that cognitive dysfunction and imaging biomarkers may be equally important in defining active Moyamoya disease. Future studies assessing the efficacy of revascularization should factor in cognitive dysfunction and its potential reversal as endpoints. Imaging should also be thoughtfully integrated into patient selection, disease monitoring and endpoint assessment paradigms. It is clear that the future vascular neurosurgery practice should
ACCEPTED MANUSCRIPT
incorporate cognitive testing and advanced imaging as important dimensions for screening, monitoring and assessment.
M AN U
SC
RI PT
1. Festa JR, Schwarz LR, Pliskin N, et al. Neurocognitive dysfunction in adult moyamoya disease. Journal of neurology 2010;257:806-15. 2. Karzmark P, Zeifert PD, Bell-Stephens TE, Steinberg GK, Dorfman LJ. Neurocognitive impairment in adults with moyamoya disease without stroke. Neurosurgery 2012;70:634-8. 3. Kazumata K, Tha KK, Narita H, et al. Chronic ischemia alters brain microstructural integrity and cognitive performance in adult moyamoya disease. Stroke; a journal of cerebral circulation 2015;46:354-60. 4. Suzuki J, Kodama N. Moyamoya disease--a review. Stroke; a journal of cerebral circulation 1983;14:104-9. 5. Suzuki J, Takaku A. Cerebrovascular "moyamoya" disease. Disease showing abnormal net-like vessels in base of brain. Archives of neurology 1969;20:288-99.
Figure Legends
Figure 1: Gradient echo images showing decreased gray matter density of posterior cingulate cortex in Moyamoya disease patients compared to controls (color regions represent P values).
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EP
TE D
Figure 2: Differential correlation of white matter fractional anisotropy with cognitive testing (color regions represent P values).
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