Quantification of brain metabolites in amyotrophic lateral sclerosis by localized proton magnetic resonance spectroscopy

Abstract

Article abstract-We performed proton magnetic resonance spectroscopy ('H-MRS) in patients with motor neuron disease (MND) to determine the absolute in vivo concentrations in the brain of the metabolites N-acetyl aspartate (NAA), choline (Cho), and creatine (CrPCr). We examined the spectra acquired from a 20 X 20 X 20-mm3 voxel placed in the motor cortex and in the cerebellum from seven patients with clinically probable or definite amyotrophic lateral sclerosis (ALS) according to the El Escorial criteria, from three patients with suspected ALS (progressive muscular atrophy), and from eight normal control subjects. We estimated the concentrations of the metabolites using the water signal as an internal standard. The concentrations of Cho and Cr/PCr in both brain regions, a s well as the concentration of NAA in the cerebellum, were unaltered in the MND patients compared with the controls. Only MND patients with both upper and lower motor neuron signs had a significantly decreased concentration of NAA (9.13 5 0.28 mM, mean t SEM) in the primary motor cortex when compared with healthy controls (10.03 2 0.22 mM). In conclusion, the slightly decreased concentration of NAA in the primary motor cortex from ALS patients may represent a loss of neurons in this region.

Degeneration of the Mid-Cingulate Cortex in Amyotrophic Lateral Sclerosis Detected In Vivo with MR Spectroscopy

“…Previous studies measuring absolute metabolites in ALS have inconsistently found increased Cho, yet all additionally documented decreased NAA. 14,23,[48][49][50] Compared with absolute quantitation, ratio determination provides a simpler and more reliable method with less experimental error. It would be worthwhile to follow up these findings with a study that incorporates absolute quantitation but with a larger sample size.…”

The neurochemical profile quantified by in vivo 1H NMR spectroscopy

“…The neuronal marker NAA has been shown to be associated to reduced neuronal integrity and neurodegeneration in ALS. Compared to healthy individuals, ALS patients show reduced levels of NAA the primary motor cortex (Gredal et al, 1997;Han and Ma, 2010;Nelles et al, 2008;Pioro et al, 1994;Pohl et al, 2001;Sarchielli et al, 2001;Suhy et al, 2002;Wang et al, 2006) and brain stem (Cwik et al, 1998;Pioro et al, 1999). Reduced NAA to total creatine ratio in motor cortex of ALS patients correlates with ALS Functional Rating Scale that depicts ALS progression (Sivák et al, 2010).…”

Presymptomatic spinal cord neurometabolic findings in SOD1 -positive people at risk for familial ALS

“…A number of studies have demonstrated a reduction in N-acetylaspartate (NAA), a marker of neuronal loss, in patients with ALS compared to controls expressed as absolute concentrations, 11,12 or as ratios of other metabolites like choline (Cho) and creatine (Cr) 10,[13][14][15][16][17][18][19][20][21][22][23][24] in the primary motor cortex, 13,17,19,23,25,26 centrum semiovale, internal capsule, corticospinal tract, cervical spine, 10,12,23 medulla, 5 and brainstem. Whether similar findings might be evident in people at risk for developing ALS, however, remains an unanswered question.…”