Reduced NAA in motor and non‐motor brain regions in amyotrophic lateral sclerosis: a cross‐sectional and longitudinal study

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Abstract
OBJECTIVES: After replication of previous findings we aimed to: 1) determine if previously reported 1H MRSI differences between ALS patients and control subjects are limited to the motor cortex; and 2) determine the longitudinal metabolic changes corresponding to varying levels of diagnostic certainty. METHODS: Twenty‐one patients with possible/suspected ALS, 24 patients with probable/definite ALS and 17 control subjects underwent multislice 1H MRSI co‐registered with tissue‐segmented MRI to obtain concentrations of the brain metabolites N‐acetylaspartate (NAA), creatine, and choline in the left and right motor cortex and in gray matter and white matter of non‐motor regions in the brain. RESULTS: In the more affected hemisphere, reductions in the ratios, NAA/Cho and NAA/Cre+Cho were observed both within (12.6% and 9.5% respectively) and outside (9.2% and 7.3% respectively) the motor cortex in probable/definite ALS. However, these reductions were significantly greater within the motor cortex (PPPP<0.005). However, there was no clear pattern of progressive change over time. CONCLUSIONS: NAA ratios are reduced in the motor cortex and outside the motor cortex in ALS, suggesting widespread neuronal injury. Longitudinal changes of NAA are not reliable, suggesting that NAA may not be a useful surrogate marker for treatment trials.