Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy

• Published in: Brain imaging and behavior Vol. 14; no. 2; pp. 562 - 572
• Main Authors: Mueller, Christina, Lin, Joanne C., Sheriff, Sulaiman, Maudsley, Andrew A., Younger, Jarred W.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.04.2020; Springer Nature B.V
• Subjects: Abnormalities; Adult; Aspartic Acid - analogs & derivatives; Aspartic Acid - analysis; Biomedical and Life Sciences; Biomedicine; Body temperature; Brain; Brain - pathology; Cerebellum; Choline; Choline - analysis; Chronic fatigue syndrome; Cortex (frontal); Creatine; Creatine - metabolism; Encephalomyelitis; Fatigue; Fatigue - metabolism; Fatigue Syndrome, Chronic - diagnostic imaging; Fatigue Syndrome, Chronic - metabolism; Fatigue Syndrome, Chronic - physiopathology; Female; Humans; Inflammation; Inositol; Inositol - analysis; Lactic acid; Lactic Acid - analysis; Magnetic Resonance Imaging - methods; Magnetic resonance spectroscopy; Magnetic Resonance Spectroscopy - methods; Male; Medical imaging; Metabolites; Middle Aged; Mood; N-Acetylaspartate; Neuroimaging; Neuroimaging - methods; Neuroimmunomodulation - physiology; Neurology; Neuropsychology; Neuroradiology; Neurosciences; Original Research; Patients; Perfusion; Psychiatry; Putamen; Spectrum analysis; Temperature effects; Thalamus; Magnetic resonance spectroscopy; Anterior cingulate; Neuroinflammation; Brain temperature; Metabolites; Chronic fatigue syndrome
• ISSN: 1931-7557; 1931-7565; 1931-7565
• DOI: 10.1007/s11682-018-0029-4

Previous neuroimaging studies have detected markers of neuroinflammation in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Magnetic Resonance Spectroscopy (MRS) is suitable for measuring brain metabolites linked to inflammation, but has only been applied to discrete regions of interest in ME/CFS. We extended the MRS analysis of ME/CFS by capturing multi-voxel information across the entire brain. Additionally, we tested whether MRS-derived brain temperature is elevated in ME/CFS patients. Fifteen women with ME/CFS and 15 age- and gender-matched healthy controls completed fatigue and mood symptom questionnaires and whole-brain echo-planar spectroscopic imaging (EPSI). Choline (CHO), myo-inositol (MI), lactate (LAC), and N-acetylaspartate (NAA) were quantified in 47 regions, expressed as ratios over creatine (CR), and compared between ME/CFS patients and controls using independent-samples t-tests. Brain temperature was similarly tested between groups. Significant between-group differences were detected in several regions, most notably elevated CHO/CR in the left anterior cingulate ( p  < 0.001). Metabolite ratios in seven regions were correlated with fatigue ( p  < 0.05). ME/CFS patients had increased temperature in the right insula, putamen, frontal cortex, thalamus, and the cerebellum (all p  < 0.05), which was not attributable to increased body temperature or differences in cerebral perfusion. Brain temperature increases converged with elevated LAC/CR in the right insula, right thalamus, and cerebellum (all p  < 0.05). We report metabolite and temperature abnormalities in ME/CFS patients in widely distributed regions. Our findings may indicate that ME/CFS involves neuroinflammation.