PT  - JOURNAL ARTICLE
AU  - Wiebenga, O.T.
AU  - Klauser, A.M.
AU  - Schoonheim, M.M.
AU  - Nagtegaal, G.J.A.
AU  - Steenwijk, M.D.
AU  - van Rossum, J.A.
AU  - Polman, C.H.
AU  - Barkhof, F.
AU  - Pouwels, P.J.W.
AU  - Geurts, J.J.G.
TI  - Enhanced Axonal Metabolism during Early Natalizumab Treatment in Relapsing-Remitting Multiple Sclerosis
AID  - 10.3174/ajnr.A4252
DP  - 2015 Jun 01
TA  - American Journal of Neuroradiology
PG  - 1116--1123
VI  - 36
IP  - 6
4099  - http://www.ajnr.org/content/36/6/1116.short
4100  - http://www.ajnr.org/content/36/6/1116.full
SO  - Am. J. Neuroradiol.2015 Jun 01; 36
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.GAglatiramer acetateGluglutamateIFNbinterferon βLWMlesional white matterNAWMnormal-appearing white matterMRSIMR spectroscopic imagingPVEpartial volume estimationtCrtotal creatine (creatine and phosphocreatine)tNAAtotal N-acetylaspartateRRMSrelapsing-remitting multiple sclerosis