1H magnetic resonance spectroscopy in preclinical Huntington disease

Huntington disease (HD) is a hereditary brain disease, causing progressive deterioration after a preclinical phase. The pathophysiology of early brain abnormalities around disease onset is largely unknown. Some preclinical mutation carriers (PMC) show structural or metabolic changes on brain imaging but the most sensitive imaging modality has not been determined. (1)H magnetic resonance spectroscopy (MRS) studies in PMC have reported conflicting results. We studied 19 PMC and 8 controls with MRS and determined relative metabolite peak areas for choline, creatine and N-acetyl aspartate (NAA) in putamen and thalamus. We found no significant differences in metabolite signals between PMC and controls. Decreases in the NAA concentration ratio of putamen relative to thalamus correlated weakly (R(2)=0.22, p=0.04) with increases in the product of CAG repeat length and age, a predictor of striatal damage. Since other brain imaging methods have shown changes in these study subjects, MRS is not a very sensitive detector of early HD brain pathology.