G04 Brain structure in children at risk for Huntington's disease

Background There has been growing evidence that the aetiology of Huntington9s disease (HD) has an important component of abnormal brain development. To assess this, the current study was designed to evaluate brain structure in children at risk for HD. Methods Children ages 6–18 years who have a parent with HD are enrolled in the study only if they are currently not manifesting symptoms of the disease. Participants are tested for gene-expansion for research purposes only. The sample included 21 children (age range 6–18 years) who were gene-expanded (GE). The gene non-expanded (GNE) group included 22 children. Each at-risk participant was age and sex matched to three healthy control (HC) children. All participants underwent a brain MRI scan with a 3T magnet using the same protocol. To eliminate effects of outliers, non-parametric methods were used to evaluate brain morphology between groups. Measures included intra-cranial volume (ICV), total brain tissue, CSF (divided into surface CSF and ventricular volume), grey and white matter volume of the four cerebral lobes, volume of caudate, putamen, thalamus and cerebellum. Results GE participants had substantially smaller ICV and total brain tissue volumes (a decrease of roughly 5%) compared to controls. Total CSF was increased. After controlling for ICV, the cortex was decreased in volume and this was most prominent in the parietal lobe. The volume of the putamen was also decreased in the GE group however the volume of the caudate and cerebellum were not different than the controls. The GE group had no significant differences compared to the controls in any measure. Conclusion In this sample of children who are gene-expanded yet greater than an estimated 30 years from onset, global measures of brain growth (ICV) as well as regional tissues (cortex, putamen) are different from controls. This supports the notion that aberrant brain development may play an important role in the pathophysiology of the disease.