Thalamic metabolic abnormalities in patients with Huntington's disease measured by magnetic resonance spectroscopy

Huntington's disease (HD) is a neurologic disorder that is not completely understood; its fundamental physiological mechanisms and chemical effects remain somewhat unclear. Among these uncertainties, we can highlight information about the concentrations of brain metabolites, which have been widely discussed. Concentration differences in affected, compared to healthy, individuals could lead to the development of useful tools for evaluating the progression of disease, or to the advance of investigations of different/alternative treatments. The aim of this study was to compare the thalamic concentration of metabolites in HD patients and healthy individuals using magnetic resonance spectroscopy. We used a 2.0-Tesla magnetic field, repetition time of 1500 ms, and echo time of 135 ms. Spectra from 40 adult HD patients and 26 control subjects were compared. Quantitative analysis was performed using the LCModel method. There were statistically significant differences between HD patients and controls in the concentrations of N-acetylaspartate+N-acetylaspartylglutamate (NAA+NAAG; t-test, P<0.001), and glycerophosphocholine+phosphocholine (GPC+PCh; t-test, P=0.001) relative to creatine+phosphocreatine (Cr+PCr). The NAA+NAAG/Cr+PCr ratio was decreased by 9% and GPC+PCh/Cr+PCr increased by 17% in patients compared with controls. There were no correlations between the concentration ratios and clinical features. Although these results could be caused by T1 and T2 changes, rather than variations in metabolite concentrations given the short repetition time and long echo time values used, our findings point to thalamic dysfunction, corroborating prior evidence.

Striatal and extrastriatal atrophy in Huntington's disease and its relationship with length of the CAG repeat

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder that affects the striatum most severely. However, except for juvenile forms, relative preservation of the cerebellum has been reported. The objective of the present study was to perform MRI measurements of caudate, putamen, cerebral, and cerebellar volumes and correlate these findings with the length of the CAG repeat and clinical parameters. We evaluated 50 consecutive patients with HD using MRI volumetric measurements and compared them to normal controls. Age at onset of the disease ranged from 4 to 73 years (mean: 43.1 years). The length of the CAG repeat ranged from 40 to 69 (mean: 47.2 CAG). HD patients presented marked atrophy of the caudate and putamen, as well as reduced cerebellar and cerebral volumes. There was a significant correlation between age at onset of HD and length of the CAG repeat, as well as clinical disability and age at onset. The degree of basal ganglia atrophy correlated with the length of the CAG repeat. There was no correlation between cerebellar or cerebral volume and length of the CAG repeat. However, there was a tendency to a positive correlation between duration of disease and cerebellar atrophy. While there was a negative correlation of length of the CAG repeat with age at disease onset and with striatal degeneration, its influence on extrastriatal atrophy, including the cerebellum, was not clear. Extrastriatal atrophy occurs later in HD and may be related to disease duration.