Case report: Cerebellar sparing in juvenile Huntington's disease

Abstract

Juvenile Huntington's disease is an early-onset variant of Huntington's disease, generally associated with large CAG repeats and distinct clinical symptoms. The role of the cerebellum in Huntington's disease has been reevaluated, based on the presence of ataxia and findings on the impact of the disease on cerebellar volume. Recent studies showed a hyperconnectivity between the cerebellum and the basal ganglia in premanifest children with expanded CAG repeats, as well as an enlargement of the cerebellum in adolescence-onset Huntington's disease. We report a 21-year-old Brazilian female with Huntington's disease (age at disease onset 16 years) with Parkinsonism and no ataxic features. There was no reduction of cerebellar volume over 3 years of follow-up, despite the brain atrophy in other regions and clinical worsening. Furthermore, the cerebellar volume of the patient was similar to age- and sex-matched controls. These findings support the existence of compensatory mechanisms involving the cerebellum in individuals with a moderate-to-high number of CAG repeats (50-100 copies) in the early stages of life.

Keywords: atrophy; case report; cerebellum; juvenile Huntington's disease; magnetic resonance imaging.

Figure 1

Heat maps showing the volume of brain structures of the patient with juvenile Huntington's disease at 18 years (t1) and 21 years (t2). Brain structures were clustered in seven regions (summary, frontal lobe, temporal lobe, parietoccipital lobe, limbic and insular cortex, subcortical region, and the cerebellum). The blue-to-red scale indicates lower to higher intensity levels based on a Z-score of normalized volumes for each structure. Red/orange squares represent that the patient's structure volume is higher than its mean volume in controls, and yellow/blue squares represent that the patient's structure volume is lower than its mean volume in controls.

Figure 2

Brain magnetic resonance imaging segmentation maps of the patient with juvenile Huntington's disease at 18 years and 21 years. (A, B) Whole brain images (in red) of the patient in axial, coronal, and sagittal planes show an atrophy of the striatum at 18 years (A), progressing to a more diffuse process of atrophy, including subcortical structures and neocortical areas like the frontal and parietal lobes at 21 years (B). White matter volume was relatively preserved as compared to gray matter. (C, D) Cerebellum images of the patient in axial, coronal, and sagittal planes show a normal cerebellar volume and a volumetric stability at 18 years (C) and 21 years (D). The Roman numerals of the cerebellar lobules were added. CI, Crus I; CII: Crus II.