Abnormal response to cortical activation in early stages of Huntington disease

Background:: We wished to identify noninvasive in vivo biomarkers of brain energy deficit in Huntington disease. Methods:: We studied 15 early affected patients (mean motor United Huntington Disease Rating Scale, 18 ± 9) and 15 age- and sex-matched controls. We coupled ³¹phosphorus nuclear magnetic resonance spectroscopy with activation of the occipital cortex in order to measure the relative concentrations of adenosine triphosphate, phosphocreatine, and inorganic phosphate before, during, and after visual stimulation. Results:: In controls, we observed an 11% increase in the inorganic phosphate/phosphocreatine ratio (P =024) and a 13% increase in the inorganic phosphate/adenosine triphosphate ratio (P =016) during brain activation, reflecting increased adenosine diphosphate concentrations. Subsequently, controls had a return to baseline levels during recovery (P =012 and 022, respectively). In contrast, both ratios were unchanged in patients during and after visual stimulation. Conclusions:: ³¹Phosphorus nuclear magnetic resonance spectroscopy could provide functional biomarkers of brain energy deficit to monitor therapeutic efficacy in Huntington disease.