Association between Change in Normal Appearing White Matter Metabolites and Intrathecal Inflammation in Natalizumab-Treated Multiple Sclerosis
2012 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 7, no 9, e44739- p.Article in journal (Refereed) Published
Background: Multiple sclerosis (MS) is associated not only with focal inflammatory lesions but also diffuse pathology in the central nervous system (CNS). Since there is no firm association between the amount of focal inflammatory lesions and disease severity, diffuse pathology in normal appearing white matter (NAWM) may be crucial for disease progression. Immunomodulating treatments for MS reduce the number of focal lesions, but possible effects on diffuse white matter pathology are less studied. Furthermore, it is not known whether intrathecal levels of inflammatory or neurodegenerative markers are associated with development of pathology in NAWM.
Methods: Quantitative proton magnetic resonance spectroscopy (1H-MRS) was used to investigate NAWM in 27 patients with relapsing MS before and after one year of treatment with natalizumab as well as NAWM in 20 healthy controls at baseline. Changes in 1H-MRS metabolite concentrations during treatment were also correlated with a panel of intrathecal markers of inflammation and neurodegeneration in 24 of these 27 patients.
Results: The group levels of 1H-MRS metabolite concentrations were unchanged pre-to posttreatment, but a pattern of high magnitude correlation coefficients (r = 0.43–0.67, p<0.0005–0.03) were found between changes in individual metabolite concentrations (total creatine and total choline) and levels of pro-inflammatory markers (IL-1β and CXCL8).
Conclusions: Despite a clinical improvement and a global decrease in levels of inflammatory markers in cerebrospinal fluid during treatment, high levels of pro-inflammatory CXCL8 and IL-1β were associated with an increase in 1H-MRS metabolites indicative of continued gliosis development and membrane turnover in NAWM.
Place, publisher, year, edition, pages
2012. Vol. 7, no 9, e44739- p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-84270DOI: 10.1371/journal.pone.0044739ISI: 000309742800016OAI: oai:DiVA.org:liu-84270DiVA: diva2:558412
funding agencies|Swedish Society of Neurologically Disabled||Swedish Society of Medicine||National Research Council (VR/NT)||University Hospital of Linkoping||County Council of Ostergotland||Teva||Biogen Idec||2012-10-032012-10-032014-10-02