PT - JOURNAL ARTICLE AU - O.T. Wiebenga AU - A.M. Klauser AU - M.M. Schoonheim AU - G.J.A. Nagtegaal AU - M.D. Steenwijk AU - J.A. van Rossum AU - C.H. Polman AU - F. Barkhof AU - P.J.W. Pouwels AU - J.J.G. Geurts TI - Enhanced Axonal Metabolism during Early Natalizumab Treatment in Relapsing-Remitting Multiple Sclerosis AID - 10.3174/ajnr.A4252 DP - 2015 Mar 05 TA - American Journal of Neuroradiology 4099 - http://www.ajnr.org/content/early/2015/03/05/ajnr.A4252.short 4100 - http://www.ajnr.org/content/early/2015/03/05/ajnr.A4252.full AB - BACKGROUND AND PURPOSE: The considerable clinical effect of natalizumab in patients with relapsing-remitting multiple sclerosis might be explained by its possible beneficial effect on axonal functioning. In this longitudinal study, the effect of natalizumab on absolute concentrations of total N-acetylaspartate, a marker for neuronal integrity, and other brain metabolites is investigated in patients with relapsing-remitting multiple sclerosis by using MR spectroscopic imaging. MATERIALS AND METHODS: In this explorative observational study, 25 patients with relapsing-remitting multiple sclerosis initiating natalizumab treatment were included and scanned every 6 months for 18 months. Additionally 18 matched patients with relapsing-remitting multiple sclerosis continuing treatment with interferon-β or glatiramer acetate were included along with 12 healthy controls. Imaging included short TE 2D-MR spectroscopic imaging with absolute metabolite quantification of total N-acetylaspartate, creatine and phosphocreatine, choline-containing compounds, myo-inositol, and glutamate. Concentrations were determined for lesional white matter, normal-appearing white matter, and gray matter. RESULTS: At baseline in both patient groups, lower concentrations of total N-acetylaspartate and creatine and phosphocreatine were found in lesional white matter compared with normal-appearing white matter and additionally lower glutamate in lesional white matter of patients receiving natalizumab. In those patients, a significant yearly metabolite increase was found for lesional white matter total N-acetylaspartate (7%, P < .001), creatine and phosphocreatine (6%, P = .042), and glutamate (10%, P = .028), while lesion volumes did not change. In patients receiving interferon-β/glatiramer acetate, no significant change was measured in lesional white matter for any metabolite, while whole-brain normalized lesion volumes increased. CONCLUSIONS: Patients treated with natalizumab showed an increase in total N-acetylaspartate, creatine and phosphocreatine, and glutamate in lesional white matter. These increasing metabolite concentrations might be a sign of enhanced axonal metabolism. Abbreviations GAglatiramer acetateGluglutamateIFNbinterferon βLWMlesional white matterNAWMnormal-appearing white matterMRSIMR spectroscopic imagingPVEpartial volume estimationtCrtotal creatine (creatine and phosphocreatine)tNAAtotal N-acetylaspartateRRMSrelapsing-remitting multiple sclerosis