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.
Pediatric Huntington Disease Brains Have Distinct Morphologic and Metabolic Traits: the RAREST‐JHD Study
Caligiuri, Maria Eugenia;Tinelli, Emanuele;Vizza, Patrizia;Cicone, Francesco;Cascini, Giuseppe Lucio;Sabatini, Umberto;
2024-01-01
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
