F009 Distinct morphologic and metabolic brain traits in pediatric-Onset Huntington disease: evidence from RAREST-JHD study
Year: 2024
Type: conference-abstract
Abstract: Background Pediatric-onset (PO) Huntington disease (HD) displays a phenotype different to adult-onset HD (AOHD), with hypokinetic movement disorders (e.g. rigidity, bradykinesia and dystonia) rather than chorea typical of AOHD. Objectives To uncover pathophysiologic-based biomarkers specific to POHD. Methods RAREST-JHD is a 3-year prospective study assessing clinical, genetic and imaging characteristics of young HD patients, to identify potential biomarkers of disease. We included adult patients (aged >18 years) previously diagnosed with POHD (adolescent onset) only if with an HTT mutation >60 CAG repeats, and adult patients previously diagnosed with AOHD (adult onset) with an HTT mutation <60 CAG repeats. All patients were included in the ENROLL-HD platform. RAREST-JHD included AOHD patients matched for disease duration. Simultaneous hybrid imaging using [18F]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography plus magnetic resonance imaging (FDG-PET/MRI), alongside clinical assessment using standardized HD scales. Exploratory longitudinal analyses were also performed. Results Striatal volume loss was remarkable and more severe in POHD (n=5) than AOHD (n=14). Widespread, markedly altered glucose metabolism occurred in POHD cortex, but not AOHD cortex, consistent with differences in clinical progression. While brain volume changes were relatively similar among the three, longitudinally followed-up, POHD patients, alterations in glucose metabolism were highly individualized, with greater annual changes in metabolism linked to more severe worsening in annualized dystonia, parkinsonism and independence scores. Conclusions POHD patients’ brains displayed distinct morphologic and metabolic traits versus AOHD, 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 POHD is a distinct disease from AOHD.
Institutions: Casa Sollievo della Sofferenza, Magna Graecia University
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4402374539