Background: Pediatric-onset Huntington's disease (POHD) exhibits a phenotype different from adult-onset HD (AOHD), with hypokinetic movement disorders (eg, rigidity, bradykinesia, and dystonia) rather than chorea typical of AOHD.
Objectives: The aim was to identify pathophysiology-based biomarkers specific to POHD (≥60 CAG repeats).
Methods: Simultaneous hybrid imaging using [18F]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography plus magnetic resonance imaging (FDG-PET/MRI) and clinical assessment using standardized Huntington's disease (HD) scales were employed. Exploratory longitudinal analyses were also performed.
Results: Striatal volume loss was remarkable and more severe in POHD (n = 5) than in AOHD (n = 14). Widespread, significantly altered glucose metabolism occurred in several different POHD cortical areas and thalamus, but not AOHD cortex, consistent with differences in clinical progression.
Conclusions: POHD patients' brains exhibited distinct morphologic and metabolic traits compared to AOHD patients' brains, with longitudinal changes mirroring clinical progression. Hybrid FDG-PET/MRI highlighted a variable regional brain dysfunction in vivo, as a biological consequence of highly expanded CAG repeats. Findings provide further evidence that POHD is a distinct disease from AOHD.
Keywords: glucose metabolism; magnetic resonance imaging (MRI); pediatric‐onset Huntington's disease; positron emission tomography (PET); simultaneous imaging; striatal volume.
© 2024 The Author(s). Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.