Motor cortex metabolite alterations in amyotrophic lateral sclerosis assessed in vivo using edited and non-edited magnetic resonance spectroscopy

• Published in: Brain research 2019-09, Vol.1718, p.22-31
• Main Authors: Weerasekera, A., Peeters, R., Sima, D., Dresselaers, T., Sunaert, S., De Vocht, J., Claeys, K., Van Huffel, S., Van Damme, P., Himmelreich, U.
• Format: Article
• Language: English
• Subjects: Amyotrophic lateral sclerosis; Edited MRS; HERMES; Magnetic resonance spectroscopy; Neurodegeneration
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2019.04.018

•Glutathione in ALS patients decreased compared to controls as assessed by HERMES MR spectroscopy.•Significant changes in NAA, Glx and myo-inositol were found in the motor cortex of ALS patients.•NAA levels in bulbar-onset patients were found to be significantly lower compared to limb-onset patients.•Changes in myo-inositol and Glx correlates with ALSFR-R score and FVC. Previous MRI and proton spectroscopy (1H-MRS) studies have revealed impaired neuronal integrity and altered neurometabolite concentrations in the motor cortex of patients with amyotrophic lateral sclerosis (ALS). Here, we aim to use MRI with conventional and novel MRS sequences to further investigate neurometabolic changes in the motor cortex of ALS patients and their relation to clinical parameters. We utilized the novel HERMES (Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy) MRS sequence to simultaneously quantify the inhibitory neurotransmitter GABA and antioxidant glutathione in ALS patients (n = 7) and healthy controls (n = 7). In addition, we have also quantified other MRS observable neurometabolites using a conventional point-resolved MR spectroscopy (PRESS) sequence in ALS patients (n = 20) and healthy controls (n = 20). We observed a trend towards decreasing glutathione concentrations in the motor cortex of ALS patients (p = 0.0842). In addition, we detected a 11% decrease in N-acetylaspartate (NAA) (p = 0.025), a 15% increase in glutamate + glutamine (Glx) (p = 0.0084) and a 21% increase in myo-inositol (mIns) (p = 0.0051) concentrations for ALS patients compared to healthy controls. Furthermore, significant positive correlations were found between GABA-NAA (p = 0.0480; Rρ = 0.7875) and NAA-mIns (p = 0.0448; Rρ = −0.4651) levels among the patients. NAA levels in the bulbar-onset patient group were found to be significantly (p = 0.0097) lower compared to the limb-onset group. A strong correlation (p