Tommaso Nuzzo, Mario Stampanoni Bassi, Roberta Fantozzi, Arianna De Rosa, Roberto Furlan, Luana Gilio, Francesco Errico, Mattia Miroballo, Giovanni Galifi, Fabio Buttari, Diego Centonze, Paolo Bellantonio, Alessandro Usiello, Anna Di Maio, Annamaria Finardi, Alessia Casamassa, Stampanoni Bassi, M., Nuzzo, T., Gilio, L., Miroballo, M., Casamassa, A., Buttari, F., Bellantonio, P., Fantozzi, R., Galifi, G., Furlan, R., Finardi, A., De Rosa, A., Di Maio, A., Errico, F., Centonze, D., and Usiello, A.
Excessive extracellular concentrations of L-glutamate (L-Glu) can be neurotoxic and contribute to neurodegenerative processes in multiple sclerosis (MS). The association between cerebrospinal fluid (CSF) L-Glu levels, clinical features, and inflammatory biomarkers in patients with MS remains unclear. In 179MS patients (relapsing remitting, RR, N=157; secondary progressive/primary progressive, SP/PP, N=22), CSF levels of L-Glu at diagnosis were determined and compared with those obtained in a group of 40 patients with non-inflammatory/non-degenerative disorders. Disability at the time of diagnosis, and after 1year follow-up, was assessed using the Expanded Disability Status Scale (EDSS). CSF concentrations of lactate and of a large set of pro-inflammatory and anti-inflammatory molecules were explored. CSF levels of L-Glu were slightly reduced in MS patients compared to controls. In RR-MS patients, L-Glu levels correlated with EDSS after 1year follow-up. Moreover, in MS patients, significant correlations were found between L-Glu and both CSF levels of lactate and the inflammatory molecules interleukin (IL)-2, IL-6, and IL-1 receptor antagonist. Altered expression of L-Glu is associated with disability progression, oxidative stress, and inflammation. These findings identify CSF L-Glu as a candidate neurochemical marker of inflammatory neurodegeneration in MS. (Figure presented.).