A Tale of Two Factors: What Determines the Rate of Progression in Huntington's Disease? A Longitudinal MRI Study
Identifieur interne : 002841 ( PascalFrancis/Curation ); précédent : 002840; suivant : 002842A Tale of Two Factors: What Determines the Rate of Progression in Huntington's Disease? A Longitudinal MRI Study
Auteurs : H. Diana Rosas [États-Unis] ; Martin Reuter [États-Unis] ; Gheorghe Doros [États-Unis] ; Stephanie Y. Lee [États-Unis] ; Tyler Triggs [États-Unis] ; Keith Malarick [États-Unis] ; Bruce Fischl [États-Unis] ; David H. Salat [États-Unis] ; Steven M. Hersch [États-Unis]Source :
- Movement disorders [ 0885-3185 ] ; 2011.
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Abstract
Over the past several years, increased attention has been devoted to understanding regionally selective brain changes that occur in Hunting-ton's disease and their relationships to phenotypic variability. Clinical progression is also heterogeneous, and although CAG repeat length influences age of onset, its role, if any, in progression has been less clear. We evaluated progression in Huntington's disease using a novel longitudinal magnetic resonance imaging analysis. Our hypothesis was that the rate of brain atrophy is influenced by the age of onset of Huntington's disease. We scanned 22 patients with Huntington's disease at approximately 1-year intervals; individuals were divided into 1 of 3 groups, determined by the relative age of onset. We found significant differences in the rates of atrophy of cortex, white matter, and subcortical structures; patients who developed symptoms earlier demonstrated the most rapid rates of atrophy compared with those who developed symptoms during middle age or more advanced age. Rates of cortical atrophy were topologically variable, with the most rapid changes occurring in sensorimotor, posterior frontal, and portions of the parietal cortex. There were no significant differences in the rates of atrophy in basal ganglia structures. Although both CAG repeat length and age influenced the rate of change in some regions, there was no significant correlation in many regions. Rates of regional brain atrophy seem to be influenced by the age of onset of Huntington's disease symptoms and are only partially explained by CAG repeat length. These findings suggest that other genetic, epigenetic, and environmental factors play important roles in neurodegeneration in Huntington's disease.
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">A Tale of Two Factors: What Determines the Rate of Progression in Huntington's Disease? A Longitudinal MRI Study</title>
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<affiliation wicri:level="1"><inist:fA14 i1="06"><s1>MIT Computer Science and Al Lab, Division of Health Sciences and Technology</s1>
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<author><name sortKey="Salat, David H" sort="Salat, David H" uniqKey="Salat D" first="David H." last="Salat">David H. Salat</name>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Center for Neuro-imaging of Aging and Neurodegenerative Diseases, Massachusetts General Hospital</s1>
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<affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Radiology, Massachusetts General Hospital, Charlestown, Massachusetts, USA, and Harvard Medical School</s1>
<s2>Boston, Massachusetts</s2>
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<author><name sortKey="Hersch, Steven M" sort="Hersch, Steven M" uniqKey="Hersch S" first="Steven M." last="Hersch">Steven M. Hersch</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Neurology, Massachusetts General Hospital</s1>
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<affiliation wicri:level="1"><inist:fA14 i1="03"><s1>MassGeneral Institute for Neurodegeneration, Massachusetts General Hospital</s1>
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<series><title level="j" type="main">Movement disorders</title>
<title level="j" type="abbreviated">Mov. disord.</title>
<idno type="ISSN">0885-3185</idno>
<imprint><date when="2011">2011</date>
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<seriesStmt><title level="j" type="main">Movement disorders</title>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Atrophy</term>
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<term>Variability</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Chorée de Huntington</term>
<term>Atrophie</term>
<term>Pathologie du système nerveux</term>
<term>Imagerie RMN</term>
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<front><div type="abstract" xml:lang="en">Over the past several years, increased attention has been devoted to understanding regionally selective brain changes that occur in Hunting-ton's disease and their relationships to phenotypic variability. Clinical progression is also heterogeneous, and although CAG repeat length influences age of onset, its role, if any, in progression has been less clear. We evaluated progression in Huntington's disease using a novel longitudinal magnetic resonance imaging analysis. Our hypothesis was that the rate of brain atrophy is influenced by the age of onset of Huntington's disease. We scanned 22 patients with Huntington's disease at approximately 1-year intervals; individuals were divided into 1 of 3 groups, determined by the relative age of onset. We found significant differences in the rates of atrophy of cortex, white matter, and subcortical structures; patients who developed symptoms earlier demonstrated the most rapid rates of atrophy compared with those who developed symptoms during middle age or more advanced age. Rates of cortical atrophy were topologically variable, with the most rapid changes occurring in sensorimotor, posterior frontal, and portions of the parietal cortex. There were no significant differences in the rates of atrophy in basal ganglia structures. Although both CAG repeat length and age influenced the rate of change in some regions, there was no significant correlation in many regions. Rates of regional brain atrophy seem to be influenced by the age of onset of Huntington's disease symptoms and are only partially explained by CAG repeat length. These findings suggest that other genetic, epigenetic, and environmental factors play important roles in neurodegeneration in Huntington's disease.</div>
</front>
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<fA08 i1="01" i2="1" l="ENG"><s1>A Tale of Two Factors: What Determines the Rate of Progression in Huntington's Disease? A Longitudinal MRI Study</s1>
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