Substantia Nigra as Brainstem Signature in Pediatric‐Onset Huntington's Disease: The RAREST-JHD Study

Background: Pediatric-onset Huntington’s disease (POHD) is usually associated with signs and symptoms of parkinsonism and dystonia predominating on chorea, which is typical of adult-onset HD (AOHD). Brain changes responsible for such an atypical POHD phenotype remain poorly understood. Objectives: To detect Midbrain and Substantia Nigra (SN) volumetric changes and their potential association with clinical parameters. Methods: Cross-sectional study by 3T high field Magnetic Resonance Imaging and Unified Huntington Disease Rating Scales assays in POHD cohort with≥60 CAG repeats and AOHD cohort with≤59 CAG repeats in HTT gene. Results: POHD had volumes of SN lower than adult-onset HD (AOHD)(P=0.003), in addition to lower striatum volume (P<0.05). The lower SN volume of the whole HD population correlated significantly with clinical measures of UHDRS motor (P=0.009), functional capacity(P=0.001) and independence(P=0.021) scores. Conclusions: Our findings suggest SN volume decrease as potential POHD brain signature contributing to the atypical HD parkinsonism.