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.
Abbreviations
- GA
- glatiramer acetate
- Glu
- glutamate
- IFNb
- interferon β
- LWM
- lesional white matter
- NAWM
- normal-appearing white matter
- MRSI
- MR spectroscopic imaging
- PVE
- partial volume estimation
- tCr
- total creatine (creatine and phosphocreatine)
- tNAA
- total N-acetylaspartate
- RRMS
- relapsing-remitting multiple sclerosis
Footnotes
O.T. Wiebenga and A.M. Klauser contributed equally to this article.
- © 2015 American Society of Neuroradiology