E32 A 36 Month Longitudinal Magnetic Resonance Spectroscopy Study In Pre-manifest And Early Huntington Disease Subjects From The Track-hd Study

Abstract

<h3>Background</h3> TRACK-HD is a multi-national longitudinal observational study of Huntington Disease (HD). Magnetic Resonance Spectroscopy (MRS) utilises MRI technology to measure brain metabolites. <h3>Aims</h3> Using MRS we aimed to define patterns of change in specific metabolite concentrations that reflect disease onset or progression in brain regions affected in HD. <h3>Methods</h3> Age and gender-matched subjects from a single TRACK-HD site (Vancouver) were evaluated by MRS at four visits over 36 months. Early HD was defined as UHDRS-TFC Stage 1 or 2, Pre-manifest HD (Pre-HD) individuals scored &lt;5 on UHDRS-TMS and controls were gene negative spouses or family members. The MRS protocol involved single voxel spectroscopy in the LEFT putamen using a 3T Philips Achieva MRI Scanners. Metabolites reported include: N-acetyl Aspartate (NAA) a marker of neuronal integrity; Creatine, a marker of brain energy metabolism; Choline, a marker for neuronal membrane turnover; Glutamate, a major CNS excitatory neurotransmitter; and Myo-inositol (mI), an astrocyte marker. MRS spectra were fit using the LCModel program, and metabolite concentrations were normalised to the unsuppressed water signal. <h3>Results</h3> At all time points, decreased putaminal NAA concentration was observed in Pre-HD and Early HD; the decrease in NAA concentration was independent of grey matter volume loss (putamen atrophy), showed longitudinal consistency, and correlated with motor performance at baseline. Putaminal mI concentration was increased in early HD at all time points. Additional findings for other metabolites will be presented. <h3>Conclusions</h3> We identify here a potentially useful role for MRS in measuring disease progression and disease onset in HD. These MRS measures are biologically relevant endpoints that should be further evaluated in large multi-site clinical trials.