Background: The mechanisms guiding the progression of neuronal damage in patients with Huntington disease (HD) are not completely understood. It is unclear if the genotype, i.e., the length of the CAG repeat, guides the location and speed of gray matter decline once HD is clinically manifested. Moreover, the relationship between cortical and subcortical gray matter atrophy and the severity of motor symptoms of HD is controversial.
Objectives: In this article, we longitudinally studied over the period of one year a cohort of 49 patients with HD. We investigated: first, the clinical relevance of regional progressive gray matter atrophy and second, the relationship between the ratio of atrophy progression and genotype.
Methods: The length of the CAG repeat was quantified for all patients and the United Huntington’s Disease Rating Scale (UHDRS) was used to rate severity of clinical symptoms. Gray matter atrophy was determined using voxel based morphometry (VBM) of brain magnetic resonance images (MRI). Progression of atrophy was quantified in 37 patients who were submitted to two different MRI scans, the second scan one year later than the first.
Results: Overall, patients exhibited progressive atrophy involving the caudate, pallidum, putamen, insula, cingulate cortex, cerebellum, orbitofrontal cortex, medial temporal lobes and middle frontal gyri. Patients with a larger UHDRS score exhibited selective atrophy of the caudate, thalamus, midbrain, insula and frontal lobes. Patients with a longer CAG repeat sequences showed faster rates and more widespread atrophy, particularly those patients with more than 55 CAG repeats.
Conclusions: These results confirm that brain atrophy progresses after the clinical onset of HD and that regional atrophy is related to symptom severity. Moreover, our results also indicate that intensity and rate of progression of brain atrophy are more pronounced in patients with larger CAG repeat sequences.
- CAG repeat
- Huntingtons disease
- voxel based morphometry