AUTHOR=Schneider Ruth , Bellenberg Barbara , Hoepner Robert , Ellrichmann Gisa , Gold Ralf , Lukas Carsten 

TITLE=Insight into Metabolic 1H-MRS Changes in Natalizumab Induced Progressive Multifocal Leukoencephalopathy Brain Lesions

JOURNAL=Frontiers in Neurology

VOLUME=Volume 8 - 2017

YEAR=2017

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2017.00454

DOI=10.3389/fneur.2017.00454

ISSN=1664-2295

ABSTRACT=Background: Progressive multifocal leukoencephalopathy (PML) is a severe complication of immunosuppressive therapies, especially of natalizumab in relapsing-remitting multiple sclerosis (MS). Metabolic changes within PML lesions have not yet been decribed in natalizumab-associated PML in MS patients.
Objective: To study metabolic profiles in natalizumab-associated PML lesions of MS patients by 1H magnetic resonance spectroscopy (1H-MRS) at different stages during the PML course. To assess changes associated with the occurrence of the immune reconstitution inflammatory syndrome (IRIS) 
Methods: 20 patients received 1H-MRS and imaging at 3 Tesla either in the pre-IRIS, IRIS, early-post-PML or late post-PML setting. Five of these patients received individual follow-up examinations including the pre-IRIS or IRIS phase. Clinical worsening was described by changes in the Karnofsky-Performance Scale (KPS) and the expanded disability status scale (EDSS) one year before PML and scoring at the time of 1H-MRS.
Results: In PML lesions increased levels of the Lip/Cr ratio, driven by rising of lipid and reduction of Creatine were found before the occurrence of IRIS (p=0.014) with a maximum in the PML-IRIS group (P=0.004). In contrast, marked rises of Cho/Cr in PML lesions were detected exclusively during the IRIS phase (p=0.003). The Lip/Cr ratio decreased to above-normal levels in early-post-PML (p=0.007, compared to normal appearing white matter (NAWM)) and to normal levels in the late-post-PML group. NAA/Cho was reduced compared to NAWM in the pre-IRIS, IRIS and early-post-PML group.  In NAA/Cr the same effect was seen in the pre-IRIS and early-post-PML group. These cross-sectional results were confirmed by the individual follow-up examinations of 4 patients. NAA/Cho , Cho/Cr and the lipid rise relative to NAWM in PML lesions were significantly correlated with the residual clinical worsening (KPS change) in post-PML patients (Spearman correlations rho= 0.481, p= 0.018, rho=-0.505, p= 0.014 and  rho=-0.488, p= 0.020).  
Conclusion: 1H-MRS detected clinically significant dynamic changes of metabolic patterns in PML lesions during the course of natalizumab-associated PML in MS patients. Lip/Cr and Cho/Cr may provide additional information for detecting the onset of the IRIS phase in the course of the PML disease.