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

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

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.

Publication types

  • Comparative Study
  • Controlled Clinical Trial
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Axons / drug effects*
  • Axons / metabolism*
  • Axons / pathology
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / pathology
  • Early Medical Intervention
  • Energy Metabolism / drug effects*
  • Female
  • Glatiramer Acetate / therapeutic use
  • Humans
  • Image Enhancement / methods*
  • Image Interpretation, Computer-Assisted / methods*
  • Interferon-beta / therapeutic use
  • Longitudinal Studies
  • Magnetic Resonance Spectroscopy / methods*
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / metabolism*
  • Natalizumab / therapeutic use*

Substances

  • Natalizumab
  • Glatiramer Acetate
  • Interferon-beta