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Abstract
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. 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. 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. 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.
Highlights
BACKGROUND AND PURPOSEThe considerable clinical effect of natalizumab in patients with relapsing-remitting multiple sclerosis might be explained by its possible beneficial effect on axonal functioning
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 lower glutamate in lesional white matter of patients receiving natalizumab
Patients treated with natalizumab showed an increase in total N-acetylaspartate, creatine and phosphocreatine, and glutamate in lesional white matter
Summary
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. 18 matched patients with relapsingremitting multiple sclerosis continuing treatment with interferon- or glatiramer acetate were included along with 12 healthy controls. Subjects Three groups of subjects were investigated in this observational study: patients with RRMS starting natalizumab at baseline, those continuing IFNb/GA, and healthy controls (Table 1), as described separately (O.T.W. et al, unpublished data, 2015). (TR/TE, 3000/30 ms) on a single 15-mm slab aligned to the sections of the proton-attenuation/T2 sequence, with the center touching the top of the corpus callosum.[17] Depending on head size, the FOV was 160 ϫ 160 or 140 ϫ 160 mm and the corresponding volume of interest was 70 ϫ 100 or 80 ϫ 100 mm. Exclusion criteria were a history of psychiatric or neurologic disease (other than MS for patients), contraindications for MR imaging, and a history of alcohol or drug abuse
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