Brain Structure in Preclinical Huntington’s Disease

doi:10.1016/j.biopsych.2005.06.003

Biological Psychiatry

Volume 59, Issue 1, 1 January 2006, Pages 57-63

https://doi.org/10.1016/j.biopsych.2005.06.003 Get rights and content

Background

Huntington’s disease (HD) is traditionally conceptualized as a degenerative disease of the striatum. Recent scientific advances, however, have suggested neurodevelopmental contributions and extrastriatal brain abnormalities. This study was designed to assess the morphology of the brain in participants who had previously undergone elective DNA analyses for the HD mutation who did not currently have a clinical diagnosis of HD (preclinical HD subjects).

Methods

Twenty-four preclinical participants with the gene expansion for HD underwent brain magnetic resonance imaging and were compared with a group of 24 healthy control subjects, matched by gender and age.

Results

Huntington’s disease preclinical participants had substantial morphologic differences from controls throughout the cerebrum. Volume of the cerebral cortex was significantly increased in preclinical HD, whereas the basal ganglia and cerebral white matter volume were substantially decreased.

Conclusions

In individuals with the HD gene mutation who are considered healthy (preclinical for manifest disease), the morphology of the brain is substantially altered compared with matched control subjects. Although decreased volumes of the striatum and cerebral white matter could represent early degenerative changes, the novel finding of enlarged cortex suggests that developmental pathology occurs in HD.

Section snippets

Procedure

Participants who had previously undergone elective presymptomatic genetic testing and found to have the HD gene mutation were recruited from the HD Registry at the University of Iowa (n = 24). Subjects were excluded if they had a diagnosis of manifest HD, history of learning disorder or mental retardation, unstable medical or psychiatric illness, history of alcohol or drug abuse within the previous year, history of other central nervous system disease or event, or pacemaker or metallic

Results

Table 2 displays the results of the brain measure analysis. General measures of intracranial volume, total brain volume, cerebral volume, and cerebellar volume did not differ between preHD participants and control subjects. Although total CSF was greater in the preHD participants, the excess CSF was found to be supratentorial and limited to the surface of the cerebrum as there was no enlargement of the ventricle volume.

Although the volume of the cerebrum as a whole was not different from

Discussion

This is the first comprehensive, quantitative study of brain morphology in preclinical HD. The findings indicate widespread abnormalities in brain morphology including a tissue distribution abnormality with reduced volume of the cerebral white matter and increased volume of the cortical gray matter. These tissue abnormalities were not regionally specific to any lobe of the cerebrum, indicating a generalized phenomenon.

There have been several studies of striatal volume in preclinical HD, and all

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Original articleBrain Structure in Preclinical Huntington’s Disease

Background

Methods

Results

Conclusions

Section snippets

Procedure

Results

Discussion

Neuron

Biol Psychiatry

Comput Med Imaging Graph

Trends Neurosci

Exp Neurol

J Am Acad Child Adolesc Psychiatry

Lancet

Neuroimage

Exp Neurol

Automatic atlas-based volume estimation of human brain regions from MR images

J Comput Assist Tomogr

Frontal lobe volume in patients with Huntington’s disease

Neurology

Reduced basal ganglia volume associated with the gene for Huntington’s disease in asymptomatic at-risk persons

Neurology

Basal ganglia volume and proximity to onset in presymptomatic Huntington disease

Arch Neurol

Rate of caudate atrophy in presymptomatic and symptomatic stages of Huntington’s disease

Mov Disord

Onset and rate of striatal atrophy in preclinical Huntington disease

Neurology

White matter volume and cognitive dysfunction in early Huntington’s disease

Cogn Behav Neurology

Expression of normal and mutant huntingtin in the developing brain

J Neurosci

Automatic 3D intersubject registration of MR volumetric data in standardized Talairach space

J Comput Assist Tomogr

Morphometric demonstration of atrophic changes in the cerebral cortex, white matter, and neostriatum in Huntington’s disease

J Neuropathol Exp Neurol

Anomalous anatomy of speech–language areas in adults with persistent developmental stuttering

Neurology

Brain development during childhood and adolescenceA longitudinal MRI study

Nat Neurosci

Quantitative neuropathological changes in presymptomatic Huntington’s disease

Ann Neurol

Improving tissue segmentation in MRIA three-dimensional multispectral discriminant analysis method with automated training class selection

J Comput Assist Tomogr

Reduced basal ganglia blood flow and volume in pre-symptomatic, gene-tested persons at-risk for Huntington’s disease

Brain

Original article
Brain Structure in Preclinical Huntington’s Disease