Longitudinal 1H MRS in advanced amyotrophic lateral sclerosis

Abstract

Background: Standard MRI in patients suffering from amyotrophic lateral sclerosis (ALS) provides only little information on stage of disease and its progression. Besides the description of non-specific hyperintense signal alterations of the corticospinal tracts (CST), there are variable findings of enlargements of the central sulcus. Objectives: Several approaches have been made to investigate whether or not proton magnetic resonance spectroscopy (1H MRS) may serve in detecting upper motor neuron degeneration in ALS. Even so, lowered concentrations of N-acetyl-aspartate (NAA) in cortical motor regions as well as raised concentrations of creatine (Cr) and choline (Cho) in the internal capsule have been observed in patients with ALS compared to healthy controls. According to progression of disease, longitudinal decrease of NAA-concentrations was detected. The objective of this study was to investigate the longitudinal development of the concentration of brain metabolites in defined motor regions in advanced ALS. Methods: Ten patients with definite ALS according to Revised El Escorial criteria underwent standard single-voxel spectroscopy of the left- and right-hemispheric motor cortex and of the white matter including the CST in a six month follow-up series of three measurements. 1H MRS data were coregistered with tissue-segmented MRI data to obtain concentrations of the metabolites while fully automated post-processing included spectral fitting of the peak areas of NAA, Cr, and Cho. Results: In a cross-sectional view, the NAA/(Cr + Cho)-ratio of the motor cortex was reduced as expected, as a reflection of decreased NAA. All patients showed a markable decline of NAA in the motor cortex areas with nearly stable concentrations of Cr and Cho in the longitudinal follow-up. In contrast, neither the concentration of NAA nor the NAA/(Cr + Cho)-ratio showed comparable dynamics in paraventricular white matter areas. Conclusions: The NAA/(Cr + Cho)-ratio of the motor cortex is in a continuous decline corresponding proportionally to a decrease of NAA as a neuron-specific marker. Consecutively, NAA seems to be a promising candidate as a surrogate marker for in-vivo detection of disease progression and staging.