Cerebral cortex and the clinical expression of Huntington's disease: complexity and heterogeneity

• Published in: Brain (London, England : 1878) Vol. 131; no. 4; pp. 1057 - 1068
• Main Authors: Rosas, H. Diana, Salat, David H., Lee, Stephanie Y., Zaleta, Alexandra K., Pappu, Vasanth, Fischl, Bruce, Greve, Doug, Hevelone, Nathanael, Hersch, Steven M.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.04.2008; Oxford Publishing Limited (England)
• Subjects: Adult; Atrophy; Biological and medical sciences; biomarker; Brain Mapping - methods; Cerebral Cortex - pathology; Cerebral Cortex - physiopathology; Cognition Disorders - etiology; Cognition Disorders - pathology; cortex; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Progression; Female; Humans; Huntington Disease - pathology; Huntington Disease - physiopathology; Huntington Disease - psychology; Huntington's disease; Image Interpretation, Computer-Assisted - methods; Magnetic Resonance Imaging - methods; Male; Medical sciences; Middle Aged; Models, Neurological; Neurology; Neuropsychological Tests; Phenotype; phenotypic variability; cortex; phenotypic variability; Huntington's disease; biomarker; Cerebral cortex; Nervous system diseases; Variability; Central nervous system; Huntington disease; Encephalon; Genetic disease; Cerebral disorder; Complexity; Heterogeneity; Central nervous system disease; Degenerative disease; Extrapyramidal syndrome
• ISSN: 0006-8950; 1460-2156
• DOI: 10.1093/brain/awn025

The clinical phenotype of Huntington's disease (HD) is far more complex and variable than depictions of it as a progressive movement disorder dominated by neostriatal pathology represent. The availability of novel neuro-imaging methods has enabled us to evaluate cerebral cortical changes in HD, which we have found to occur early and to be topographically selective. What is less clear, however, is how these changes influence the clinical expression of the disease. In this study, we used a high-resolution surface based analysis of in vivo MRI data to measure cortical thickness in 33 individuals with HD, spanning the spectrum of disease and 22 age- and sex-matched controls. We found close relationships between specific functional and cognitive measures and topologically specific cortical regions. We also found that distinct motor phenotypes were associated with discrete patterns of cortical thinning. The selective topographical associations of cortical thinning with clinical features of HD suggest that we are not simply correlating global worsening with global cortical degeneration. Our results indicate that cortical involvement contributes to important symptoms, including those that have been ascribed primarily to the striatum, and that topologically selective changes in the cortex might explain much of the clinical heterogeneity found in HD. Additionally, a significant association between regional cortical thinning and total functional capacity, currently the leading primary outcome measure used in neuroprotection trials for HD, establishes cortical MRI morphometry as a potential biomarker of disease progression.