Evidence of Neuroinflammation and Excitotoxicity in ME/CFS using Single-Voxel MRS

Brisbane Convention & Exhibition Centre 

Neuroinflammation is implicated in various brain pathologies and is proposed as a mechanism underlying Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), a condition with largely unknown pathophysiology. The neuroinflammatory response is difficult to image non-invasively. However, magnetic resonance spectroscopy (MRS) offers a suitable approach to address this gap by enabling the measurement of metabolites that can serve as markers of neuroinflammation. Specifically, glutamine and glutamate (combined as Glx) are relevant due to their role in excitotoxicity and neuroinflammatory activation (Velu et al., 2024), while total N-acetylaspartate (tNAA) serves as a marker of neuronal integrity and a mitigating factor regarding inflammatory responses (Felice et al., 2024). Myo-inositol (mI), a recognized glial marker, reflects astrocytic activation and proliferation, central to the neuroinflammatory process (Harris et al., 2015). Total choline (tCho) indicates membrane turnover and is associated with neuroinflammation (Mueller et al., 2024). Additionally, lactate (Lac) may modulate immune responses, potentially affecting the hypothesised neuroinflammatory response in ME/CFS (Manosalva et al., 2022). This study investigated whether neurochemical concentrations of these metabolites are associated with a ME/CFS diagnosis. We hypothesise Glx, tCho, mI and lactate to be elevated, and tNAA to be downregulated in individuals with ME/CFS.