PET scan investigations of Huntington's disease: Cerebral metabolic correlates of neurological features and functional decline

Abstract

Fifteen drug-free patients with early to midstage Huntington's disease were evaluated with quantitative neurological examinations, scales for functional capacity, computed tomographic (CT) scans, and positron emission tomographic (PET) scans of 18F-2-fluoro-2-deoxyglucose (18F-FDG) uptake. All patients had abnormal indices of caudate metabolism on PET scanning, whereas in patients with early disease indices of putamen metabolism and CT measures of caudate atrophy were normal. Indices of caudate metabolism correlated highly with the patients' overall functional capacity (r = 0.906; p less than 0.001) and bradykinesia/rigidity (r = -0.692; p less than 0.01). Indices of putamen metabolism correlated highly with motor functions: chorea (r = -0.841; p less than 0.01), oculomotor abnormalities (r = -0.849; p less than 0.01), and fine motor coordination (r = -0.866; p less than 0.01). Indices of thalamic metabolism correlated positively with dystonia (r = 0.559; p less than 0.05). The data suggest that PET scanning with 18F-FDG is a sensitive measure of brain dysfunction in Huntington's disease and that basal ganglia metabolism is highly correlated with the overall functional capacity of individual patients and with the degree of their motor abnormalities.

How reliable is 18FDG PET for predicting the onset of Huntington’s disease?

“…This study showed significant hypometabolism in the caudate nucleus of gene mutation carriers as compared with mutation-negative subjects [9]. These first discoveries were followed by several years of relevant scientific research activity on HD which confirmed the preliminary reports and showed a significant relationship between striatal and cortical hypometabolism and motor impairment progression and cognitive changes [10][11][12]. Hayden et al found significant caudate nucleus hypometabolism in a cohort of mutation-positive subjects with no signs of cortical or striatal atrophy [13], and later Ciarmiello et al found that striatal hypometabolism is significantly correlated with the estimated age at onset [14].…”

Selective defect of in vivo glycolysis in early Huntington's disease striatum

“…Previous studies of cerebral metabolism in vivo in HD have not addressed this issue. They have almost exclusively concentrated on measurements of glycolytic, not oxidative, metabolism, reporting early reductions in both the caudate and putamen (11)(12)(13)(14). Only a single case study has reported measurements of striatal oxidative metabolism (15).…”

Positron emission tomography imaging of transplant function

“…40 -42 Levels of resting putamen metabolism correlate with locomotor function and caudate metabolism with performance on tests sensitive to frontal lobe function. 43,44 In early HD, cortical metabolism is preserved but as the disease progresses and dementia becomes prominent it also declines, with the frontal cortex being targeted. 45 Reduced caudate glucose metabolism has been reported in between 38% and 75% of asymptomatic adult HD gene carriers in various series.…”