Subcortical T1-Rho MRI Abnormalities in Juvenile-Onset Huntington’s Disease

Abstract

Huntington’s disease (HD) is a fatal neurodegenerative disease caused by the expansion of cytosine-adenine-guanine (CAG) repeats in the huntingtin gene. An increased CAG repeat length is associated with an earlier disease onset. About 5% of HD cases occur under the age of 21 years, which are classified as juvenile-onset Huntington’s disease (JOHD). Our study aims to measure subcortical metabolic abnormalities in JOHD participants. T1-Rho (T1ρ) MRI was used to compare brain regions of 13 JOHD participants and 39 controls. Region-of-interest analyses were used to assess differences in quantitative T1ρ relaxation times. We found that the mean relaxation times in the caudate (p < 0.001), putamen (p < 0.001), globus pallidus (p < 0.001), and thalamus (p < 0.001) were increased in JOHD participants compared to controls. Furthermore, increased T1ρ relaxation times in these areas were significantly associated with lower volumes amongst participants in the JOHD group. These findings suggest metabolic abnormalities in brain regions previously shown to degenerate in JOHD. We also analyzed the relationships between mean regional T1ρ relaxation times and Universal Huntington’s Disease Rating Scale (UHDRS) scores. UHDRS was used to evaluate participants’ motor function, cognitive function, behavior, and functional capacity. Mean T1ρ relaxation times in the caudate (p = 0.003), putamen (p = 0.005), globus pallidus (p = 0.009), and thalamus (p = 0.015) were directly proportional to the UHDRS score. This suggests that the T1ρ relaxation time may also predict HD-related motor deficits. Our findings suggest that subcortical metabolic abnormalities drive the unique hypokinetic symptoms in JOHD.

Huntington’s disease across the lifespan.

“…Evidence from the Kids-HD study using resting-state functional magnetic resonance imaging (fMRI) adds to this picture. Striatal-cerebellar hyperconnectivity was observed across some connection pathways from age 6 to age 12, followed by hypoconnectivity in the years that followed through age 20 (Tereshchenko et al, 2020). This effect suggests an early compensatory increase in connectivity that gives way to reduced connectivity as children move into and through their teenage years.…”

Longitudinal Clinical and Biological Characteristics in Juvenile‐Onset Huntington's Disease

“…9 Cross-sectional analyses have demonstrated that patients with JOHD have significant neurodegeneration in cortical and subcortical brain regions shortly after receiving a diagnosis of JOHD. 10,11 However, quantifying clear measures of longitudinal disease progression in JOHD is an imperative step in the planning and conduct of clinical trials in this population. This study aimed to evaluate longitudinal clinical and neuroimaging changes in a relatively large cohort of JOHD patients.…”

“…Unfortunately, the same cannot be said for patients with JOHD 9 . Cross‐sectional analyses have demonstrated that patients with JOHD have significant neurodegeneration in cortical and subcortical brain regions shortly after receiving a diagnosis of JOHD 10,11 . However, quantifying clear measures of longitudinal disease progression in JOHD is an imperative step in the planning and conduct of clinical trials in this population.…”