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AJNR Am J Neuroradiol. 2015 Jun;36(6):1116-23. doi: 10.3174/ajnr.A4252. Epub 2015 Mar 5.

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

Author information

1
From the Departments of Radiology and Nuclear Medicine (O.T.W., G.J.A.N., M.D.S., F.B.) Anatomy and Neurosciences (O.T.W., A.M.K., M.M.S., G.J.A.N., J.J.G.G.) o.wiebenga@vumc.nl.
2
Anatomy and Neurosciences (O.T.W., A.M.K., M.M.S., G.J.A.N., J.J.G.G.).
3
From the Departments of Radiology and Nuclear Medicine (O.T.W., G.J.A.N., M.D.S., F.B.) Anatomy and Neurosciences (O.T.W., A.M.K., M.M.S., G.J.A.N., J.J.G.G.).
4
From the Departments of Radiology and Nuclear Medicine (O.T.W., G.J.A.N., M.D.S., F.B.).
5
Neurology (J.A.v.R., C.H.P.).
6
Physics and Medical Technology (P.J.W.P.), Neuroscience Campus Amsterdam and VU University Medical Center, Amsterdam, the Netherlands.

Abstract

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.

PMID:
25742985
DOI:
10.3174/ajnr.A4252
[Indexed for MEDLINE]
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