1H-magnetic resonance spectroscopy in amyotrophic lateral sclerosis

1H-magnetic resonance spectroscopy (MRS) is potentially a powerful tool for the investigation of the chemicals of the brain in vivo in health and disease. Levels of N-acetyl-aspartate (NAA) in the motor cortex and brainstem of patients with amyotrophic lateral sclerosis (ALS) have been reported to be reduced by up to 68%, and in one report the level of glutamate in the brainstem was increased by 58%. We studied levels of metabolites in the cerebral cortex and brainstem of 20 ALS patients and 14 age-matched controls with a 1.5 Tesla Picker magnet using MRS. We used the same spectra for determining both the area of the metabolite peaks expressed as a ratio of the area of the creatine (Cr) peak, and the absolute concentrations using the Provencher LC model. These produced different results. With the LC model, the NAA content of the motor cortex of ALS patients was reduced by 7.7% (P=0.015), and that of the brainstem was reduced by 21.5% (P=0.035), compared with controls. The degree of reduction of NAA was related to the severity of upper motor neuron abnormalities. No effect of treatment with anti-glutamate agents on NAA concentration could be detected. Concentrations of other metabolites were not affected in ALS. It appears that MRS is a technique that is still in development, and that further refinement is required before it can be used to understand disease mechanisms and investigate treatment in ALS.