Absolute metabolite concentrations in cerebral white matter of multiple sclerosis patients with beta interferon treatment

• Background: A few investigations concern interferon (IFN)-treated multiple sclerosis (MS) patients using proton spectroscopy, however not with an absolute quantitation or during extended treatment.Objective: To quantify metabolite changes during IFN therapy using magnetic resonance spectroscopy.Methods: We included 14 MS patients, (9 men, 5 women, mean age 41.8 years, mean disease duration 10.9 years, 9 with relapsing-remitting MS, 6 with secondary progressive and bouts) scheduled for immunomodulatory treatment (5 IFN1A, 9 IFN1B) as well as 14 healthy controls, (8 men, 6 women, mean age 40.2 years). All patients had clinically definite MS (Poser criteria). Measurements were performed in white matter (four voxels).Results: Longitudinal results: N-acetylaspartate + Nacetylapartylglutamate (NAA+NAAG) showed a trend to higher values before treatment. Myo-inositol concentrations were significantly and increasingly elevated (p=0.03). Glutamine and glutamate concentrations dropped significantly (p=0.009) after treatment started but raised later. MS patients/ healthy controls: Creatine and myo-inositol concentrations were significantly higher in MS patients before and after treatment. NAA + NAAG concentrations were significantly lower before and after treatment. Glutamine and glutamate concentrations were higher before therapy, later equal to healthy controls.Conclusions: IFN-treated patients demonstrate increasing myoinositol, a marker of progressive glial proliferation. Also, decreasing concentrations of total NAA derivatives despite IFN therapy suggest ongoing progressive pathology and constant neuronal loss in the course of MS. MS patients compared with matched healthy controls show highly significant differences regarding metabolites (Cr, myo- Ins, NAA) that increase during the therapy period, also indicating that the medication can only moderately influence the metabolites. The most interesting finding is related the excitatory molecules, glutamine and glutamate. Before IFN therapy statistical analysis showed significant elevation in the concentrations; however after IFN therapy this difference is no longer observed. This finding underlines a possible role of IFN in the expression of down-regulating excitotoxic molecules.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)

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art (subject category)