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

The aim of this study was to examine basal ganglia volumes and regional cer ebral blood flow in asymptomatic subjects at-risk for Huntington's disease who had undergone genetic testing, We determined which measures were the be st 'markers' for the presence of the mutation and for the onset of symptoms , Twenty subjects who were Huntington's disease gene mutation-positive and 24 Huntington's disease gene mutation-negative participants, all of whom ha d a parent with genetically confirmed Huntington's disease, and were theref ore 50% at-risk for inheriting the Huntington's disease gene mutation, were included in the study, To evaluate basal ganglia structure and function, M RI and single photon emission computed tomography (SPECT) were used. Quanti tative measures of regional volumes and relative measures of regional perfu sion were calculated. SPECT and MRI scans were co-registered so that MRI an atomy could be used accurately to place SPECT regions, Estimated years-to-o nset in the mutation-positive subjects was calculated based on a regression formula that included gene (CAG)(n) repeat length and parental age of onse t, Changes in imaging measures in relation to estimated years-to-onset were assessed. The imaging measure that was most affected in mutation-positive subjects was putamen volume, This was also the measure that correlated most strongly with approaching onset. In subjects greater than or equal to 7 ye ars from estimated onset age, the putamen volume measures n ere similar to those of the mutation-negative subjects, However, in subjects 56 years from estimated onset age, there were dramatic reductions in putamen volume, res ulting in >90% discrimination from both the far-from-onset and the mutation -negative subjects. Caudate volume and bicaudate ratio also showed a signif icant decline in the close-to-onset subjects, although to a lesser degree t han putamen volume reductions. Furthermore, SPECT basal ganglia perfusion d eficits were observed in mutation-positive subjects. Imaging markers of neu ropathological decline preceding clinical onset are important for assessing the effects of treatments aimed at slowing the course of Huntington's dise ase. The current study suggests that quantitative assessment of basal gangl ia may provide a means to track early signs of decline in individuals with the Huntington's disease gene mutation prior to clinical onset.