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

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 of such an atypical POHD phenotype remain poorly understood.

To detect Midbrain and Substantia Nigra (SN) volumetric changes and their potential association with clinical parameters.

Cross-sectional study by 3 T high-field Magnetic Resonance Imaging and Unified Huntington Disease Rating Scales assays in POHD cohort with ≥60 CAG repeats and AOHD cohort with ≤59CAG repeats in HTT gene.

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.

Our findings suggest SN volume decrease as potential POHD brain signature contributing to the atypical HD parkinsonism.