Enhanced axonal metabolism during early natalizumab treatment in relapsing-remitting multiple sclerosis

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.