Background: The molecular abnormality responsible for Machado-Joseph disease (MJD), a neurodegenerative disorder, has recently been described. It has also been previously documented using positron emission tomography (PET) with [18F]-2-fluoro-2-deoxy-D-glucose (FDG) to record the metabolic changes in the brains of symptomatic subjects affected with MJD. The present study evaluated these changes in asymptomatic MJD gene carriers, previously identified by molecular analysis.
Methods: PET with FDG was used to study glucose metabolism in the brains of three asymptomatic MJD gene carriers who were identified by molecular analysis, and in 10 normal control subjects.
Results: By comparison with data obtained from normal control subjects, significantly decreased glucose utilization was found in the cerebellar hemisphere and occipital cortex of these three asymptomatic MJD gene carriers, suggesting preclinical disease activity. The sensitivity of diagnosis based on PET examination alone was 100% in this study, using significant decrease in glucose metabolism in the cerebellar hemisphere as a criterion.
Conclusions: Measurement of regional brain metabolism by PET is noninvasive, and subclinical reduction of FDG consumption in the cerebellar hemisphere and occipital cortex is found to act as an objective marker of disease activity. Based on the results from a limited number of patients, the sensitivity of PET is sufficient to justify its routine use in the investigation of asymptomatic at-risk MJD subjects.