Basal ganglia volume and proximity to onset in presymptomatic Huntington disease.

Abstract

To determine in presymptomatic individuals who carry the gene mutation for Huntington disease whether proximity to estimated age at onset is associated with volume of basal ganglia, as measured on magnetic resonance imaging scans. Survey study involving correlations between basal ganglia volume, measured blind to subject status, and estimation of subjects' age at onset. Huntington's Disease Presymptomatic Testing Program at The Johns Hopkins University School of Medicine, Baltimore, Md. Subjects included 47 individuals at risk for Huntington disease (ie, off-spring of patients with Huntington disease). Twenty subjects tested positive for the gene mutation but were not symptomatic. Twenty-seven subjects tested negative. Estimated age at onset was calculated for each of 20 gene-positive individuals using an empirically derived formula based on the subject's trinucleotide repeat length and parental age at onset. Each subject's age at the time of the magnetic resonance imaging scan was subtracted from his or her estimated age at onset, yielding estimated years to onset. Volumes of caudate, putamen, and globus pallidus were measured on magnetic resonance imaging scans. After controlling for the subject's age at the time of the scan, significant correlations were found between volumes of all basal ganglia structures and years to onset. Gene-positive subjects who were far from onset had smaller basal ganglia volumes than gene-negative subjects for all structures except globus pallidus. Gene-positive subjects who were close to onset had smaller volumes than gene-negative subjects for all basal ganglia structures and had smaller volumes than subjects far from onset for all structures except caudate. The results suggest that atrophy of the basal ganglia occurs gradually, beginning years before symptom onset.