Thalamic metabolism and symptom onset in preclinical Huntington's disease

A Feigin, C Tang, Y Ma, P Mattis, D Zgaljardic… - Brain, 2007 - academic.oup.com
A Feigin, C Tang, Y Ma, P Mattis, D Zgaljardic, M Guttman, JS Paulsen, V Dhawan…
Brain, 2007academic.oup.com
The neural basis for the transition from preclinical to symptomatic Huntington's disease (HD)
is unknown. We used serial positron emission tomography (PET) imaging in preclinical HD
gene carriers (p-HD) to assess the metabolic changes that occur during this period. Twelve
p-HD subjects were followed longitudinally with [11C]-raclopride and [18F]-
fluorodeoxyglucose PET imaging, with scans at baseline, 18 and 44 months. Progressive
declines in striatal D2-receptor binding were correlated with concurrent changes in regional …
Abstract
The neural basis for the transition from preclinical to symptomatic Huntington's disease (HD) is unknown. We used serial positron emission tomography (PET) imaging in preclinical HD gene carriers (p-HD) to assess the metabolic changes that occur during this period. Twelve p-HD subjects were followed longitudinally with [11C]-raclopride and [18F]-fluorodeoxyglucose PET imaging, with scans at baseline, 18 and 44 months. Progressive declines in striatal D2-receptor binding were correlated with concurrent changes in regional metabolism and in the activity of an HD-related metabolic network. We found that striatal D2 binding declined over time (P< 0.005). The activity of a reproducible HD-related metabolic covariance pattern increased between baseline and 18 months (P< 0.003) but declined at 44 months (P< 0.04). These network changes coincided with progressive declines in striatal and thalamic metabolic activity (P< 0.01). Striatal metabolism was abnormally low at all time points (P< 0.005). By contrast, thalamic metabolism was elevated at baseline (P < 0.01), but fell to subnormal levels in the p-HD subjects who developed symptoms. These findings were confirmed with an MRI-based atrophy correction for each individual PET scan. Increases in network expression and thalamic glucose metabolism may be compensatory for early neuronal losses in p-HD. Declines in these measures may herald the onset of symptoms in gene carriers.
Oxford University Press