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Neurodegener Dis. 2013;12(1):23-35. doi: 10.1159/000339528. Epub 2012 Aug 23.

Consistent neurodegeneration and its association with clinical progression in Huntington's disease: a coordinate-based meta-analysis.

Dogan I#1,2,3, Eickhoff SB#2,4, Schulz JB1,3, Shah NJ1,2,3, Laird AR5, Fox PT5, Reetz K1,2,3.

Author information

Department of Neurology, RWTH Aachen University, Aachen.
Institute of Neuroscience and Medicine, Research Center Jülich GmbH, Jülich.
Translational Brain Medicine, Jülich Aachen Research Alliance, Jülich.
Institute of Clinical Neuroscience and Medical Psychology, Heinrich Heine University, Düsseldorf , Germany.
Research Imaging Center, University of Texas Health Science Center San Antonio, San Antonio, Tex. , USA.
Contributed equally



The neuropathological hallmark of Huntington's disease (HD) is progressive striatal loss starting several years prior to clinical onset. In the past decade, whole-brain magnetic resonance imaging (MRI) studies have provided accumulating evidence for widely distributed cortical and subcortical atrophy in the early course of the disease.


In order to synthesize current morphometric MRI findings and to investigate the impact of clinical and genetic features on structural changes, we performed a coordinate-based meta-analysis of voxel-based morphometry (VBM) studies in HD.


Twenty HD samples derived from 17 studies were integrated in the analysis comparing a total of 685 HD mutation carriers [345 presymptomatic (pre-HD) and 340 symptomatic (symp-HD) subjects] and 507 controls. Convergent findings across studies were delineated using the anatomical likelihood estimation approach. Effects of genetic and clinical parameters on the likelihood of observing VBM findings were calculated by means of correlation analyses.


Pre-HD studies featured convergent evidence for neurodegeneration in the basal ganglia, amygdala, thalamus, insula and occipital regions. In symp-HD, cerebral atrophy was more pronounced and spread to cortical regions (i.e., inferior frontal, premotor, sensorimotor, midcingulate, frontoparietal and temporoparietal cortices). Higher cytosine-adenosine-guanosine repeats were associated with striatal degeneration, while parameters of disease progression and motor impairment additionally correlated with cortical atrophy, especially in sensorimotor areas.


This first quantitative meta-analysis in HD demonstrates the extent of striatal atrophy and further consistent extrastriatal degeneration before clinical conversion. Sensorimotor areas seem to be core regions affected in symp-HD and, along with widespread cortical atrophy, may account for the clinical heterogeneity in HD.

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