Effect of creatine supplementation on metabolite levels in ALS motor cortices.

Mitochondrial pathology is an early observation in motor neurons and skeletal muscle of patients with amyotrophic lateral sclerosis (ALS). To clarify the relevance of this finding, we determined the effects of a 1-month oral administration of creatine on (1)H NMR-visible metabolites in the motor cortices of 15 controls and 15 patients with sporadic ALS, most of whom had mitochondrial pathology in skeletal muscle. In the motor cortex of the ALS group the N-acetylaspartate (NAA)/creatine (Cr(t)) metabolite ratio was lower than in our control group, indicating NAA loss. Upon creatine supplementation we observed in the controls a decline in the NAA/Cr(t), NAA/choline (Cho), glutamate + glutamine (Glx)/Cr(t), and Glx/Cho metabolite ratios. In contrast, in the ALS patient group the NAA/Cr(t) and the NAA/Cho metabolite ratios remained unchanged, while the Glx/Cr(t) and Glx/Cho metabolite ratios decreased. These data are compatible with the interpretation that creatine supplementation causes an increase in the diminished NAA levels in ALS motor cortex as well as an increase of choline levels in both ALS and control motor cortices. Because NAA is synthesized by mitochondria in an energy-dependent manner and the NAA/Cho metabolite ratios in the ALS motor cortices were found to be correlated to the degree of mitochondrial pathology in ALS skeletal muscle, our results can be explained by a deficiency of enzymes of mitochondrial respiratory chain in the ALS motor cortex which might affect motor neuron survival.

Vielhaber S ，Kaufmann J ，Kanowski M ，Sailer M ，Feistner H ，Tempelmann C ，Elger CE ，Heinze HJ ，Kunz WS ... -  《EXPERIMENTAL NEUROLOGY》

Study of the features of proton MR spectroscopy ((1)H-MRS) on amyotrophic lateral sclerosis.

Han J ，Ma L 《-》

Proton magnetic resonance spectroscopy of the motor cortex in 70 patients with amyotrophic lateral sclerosis.

Pohl C ，Block W ，Karitzky J ，Träber F ，Schmidt S ，Grothe C ，Lamerichs R ，Schild H ，Klockgether T ... -  《archives of neurology》

Combined structural and neurochemical evaluation of the corticospinal tract in amyotrophic lateral sclerosis.

Pyra T ，Hui B ，Hanstock C ，Concha L ，Wong JC ，Beaulieu C ，Johnston W ，Kalra S ... -  《-》

Relationship between cervical cord 1H-magnetic resonance spectroscopy and clinoco-electromyographic profile in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of motor neurons, leading to limb paralysis and respiratory failure. C1-C3 cord (1) H-magnetic resonance spectroscopy ((1) H-MRS) was performed in 19 patients with ALS and 20 controls. N-acetylaspartate (NAA), choline-containing compounds, creatine plus phosphocreatine (Cr), and myo-Inositol (m-Ins) were measured. ALS functional rating scale-revised (ALSFRS) and forced vital capacity (FVC) were assessed. The rates of decline were calculated at 6 months before and after (1) H-MRS. NAA/Cr and NAA/m-Ins were decreased significantly, and m-Ins/Cr was increased significantly in ALS patients compared with controls. NAA/Cr and NAA/m-Ins were correlated with ALSFRS and FVC and inversely linked to the decline rates. NAA/Cr, NAA/m-Ins, and m-Ins/Cr were altered markedly in 9 patients with denervation and neurogenic changes in both C2 paraspinal and upper limb muscles. These metabolite ratios were associated with disease progression and ongoing denervation in neck and hand muscles. C1-C3 cord (1) H-MRS might reflect anterior horn cell damage causing neck/arm weakness and respiratory dysfunction in ALS patients.

Ikeda K ，Murata K ，Kawase Y ，Kawabe K ，Kano O ，Yoshii Y ，Takazawa T ，Hirayama T ，Iwasaki Y ... -  《-》