Is brain lactate increased in Huntington's disease?

Abstract

Impaired brain energy metabolism with increased regional brain lactate may play a role in the pathogenesis of Huntington's disease (HD). Magnetic resonance spectroscopy (MRS) has provided conflicting evidence, however, regarding metabolic changes. Our objective was to evaluate the potential contribution of CSF lactate to the changes observed with MRS in HD. We performed single voxel MRS at 3 T in 23 patients with HD and 28 age-matched control subjects using a method to segment voxels into grey matter, white matter, and CSF, and to extrapolate regional lactate content to a hypothetical voxel containing 100% brain in order to control for differences in CSF lactate. Lactate/creatine and lactate/N-acetyl aspartate (Lac/NAA) ratios were significantly increased in parieto-occipital (p<0.05) and cerebellar (p<0.01) voxels in HD patients. After extrapolating group Lac/NAA results to a theoretical voxel containing 100% brain, this ratio was greater in the HD group than the control group, suggesting possibly increased lactate in this predicted voxel, although the difference between groups did not reach statistical significance. These results suggest an increase in brain lactate content in manifest HD, in a regionally non-specific fashion, although the possibility of a CSF contribution to this increase cannot be ruled out. Regardless, this supports the possibility of impaired mitochondrial function resulting in abnormal brain energy metabolism in HD.