Decreased Metabolism in the Cerebral Cortex in Early-Stage Huntington's Disease: A Possible Biomarker of Disease Progression?

Background and Purpose Huntington's disease (HD) is an autosomal-dominant inherited neurodegenerative disorder. Genetic analysis of abnormal CAG expansion in the IT15 gene allows disease confirmation even in the preclinical stage. However, because there is no treatment to cure or delay the progression of this disease, monitoring of biological markers that predict progression is warranted. Methods FDG-PET was applied to 13 patients with genetically confirmed HD in the early stage of the disease. We recorded the initial and follow-up statuses of patients using the Independence Scale (IS) of the Unified Huntington's Disease Rating Scale. The progression rate (PR) was calculated as the annual change in the IS. The patients were divided into two groups with faster and slower progression, using the median value of the PR as the cut-off. FDG-PET data were analyzed using regions of interest, and compared among the two patient groups and 11 age- and sex-matched controls. Results The mean CAG repeat size in patients was 44.7. The CAG repeat length was inversely correlated with the age at onset as reported previously, but was not correlated with the clinical PR. Compared with normal controls, hypometabolism was observed even at very early stages of the disease in the bilateral frontal, temporal, and parietal cortices on FDG-PET. The decreases in metabolism in the bilateral frontal, parietal, and right temporal cortices were much greater in the faster-progression group than in the slower-progression group. Conclusions A decrease in cortical glucose metabolism is suggested as a predictor for identifying a more rapid form of progression in patients with early-stage HD. J Clin Neurol 2013;9:21-25