Short echo-time Magnetic Resonance Spectroscopy in ALS, simultaneous quantification of glutamate and GABA at 3 T

• Published in: Scientific reports Vol. 9; no. 1; pp. 17593 - 7
• Main Authors: Blicher, J. U., Eskildsen, S. F., Stærmose, T. G., Møller, A. T., Figlewski, K., Near, J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.11.2019; Nature Publishing Group
• Subjects: 59/57; 692/53/2422; 692/617/375/1917/1285; Aged; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - metabolism; Amyotrophic Lateral Sclerosis - pathology; Amyotrophic Lateral Sclerosis - physiopathology; Aspartic Acid - analogs & derivatives; Aspartic Acid - analysis; Atrophy; Choline - analysis; Cortex (motor); Creatine - analysis; Disease Progression; Female; gamma-Aminobutyric Acid - analysis; Glutamic Acid - analysis; Glutamine - analysis; Glutathione; Glutathione - analysis; Gray Matter - pathology; Hand Strength; Humanities and Social Sciences; Humans; Inositol - analysis; Magnetic resonance spectroscopy; Magnetic Resonance Spectroscopy - methods; Male; Metabolites; Middle Aged; Motor Cortex - chemistry; Motor Cortex - pathology; multidisciplinary; Neurotransmitters; Occipital lobe; Occipital Lobe - chemistry; Occipital Lobe - pathology; Pathogenesis; Pilot Projects; Science; Science (multidisciplinary); Severity of Illness Index; Single-Blind Method; Spectroscopy; Spectrum analysis; γ-Aminobutyric acid
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-53009-4

Cortical hyperexcitability has been found in early Amyotrophic Lateral Sclerosis (ALS) and is hypothesized to be a key factor in pathogenesis. The current pilot study aimed to investigate cortical inhibitory/excitatory balance in ALS using short-echo Magnetic Resonance Spectroscopy (MRS). Patients suffering from ALS were scanned on a 3 T Trio Siemens MR scanner using Spin Echo Full Intensity Acquired Localized (SPECIAL) Magnetic Resonance Spectroscopy in primary motor cortex and the occipital lobe. Data was compared to a group of healthy subjects. Nine patients completed the scan. MRS data was of an excellent quality allowing for quantification of a range of metabolites of interest in ALS. In motor cortex, patients had Glutamate/GABA and GABA/Cr- ratios comparable to healthy subjects. However, Glutamate/Cr (p = 0.002) and the neuronal marker N-acetyl-aspartate (NAA/Cr) (p = 0.034) were low, possibly due to grey-matter atrophy, whereas Glutathione/Cr (p = 0.04) was elevated. In patients, NAA levels correlated significantly with both hand strength (p = 0.027) and disease severity (p = 0.016). In summary SPECIAL MRS at 3 T allows of reliable quantification of a range of metabolites of interest in ALS, including both excitatory and inhibitory neurotransmitters. The method is a promising new technique as a biomarker for future studies on ALS pathophysiology and monitoring of disease progression.