Metabolic profiles by ¹H-magnetic resonance spectroscopy in natalizumab-associated post-PML lesions of multiple sclerosis patients who survived progressive multifocal leukoencephalopathy (PML)

<div><p>Purpose</p><p>Early diagnosis and treatment of multiple sclerosis-related progressive multifocal leukoencephalopathy (PML) significantly improve clinical outcomes. However, there is a lack of information regarding the restart of immunomodulatory therapy in the post-PML setting, when multiple sclerosis activity reappears. We aimed at the examination of metabolic differences using ¹H-magnetic resonance spectroscopy (¹H-MRS) in multiple sclerosis patients at various post-PML stages and at the exploration of differences according to their disease and JC virus (JCV) status.</p><p>Methods</p><p>¹H-MRS of PML lesions was carried out on 15 relapsing-remitting multiple sclerosis patients with natalizumab-associated PML. Patients were grouped according to their stage after PML infection as early post-PML, less than 19 months after PML onset (<i>n</i> = 5), or late post-PML group, more than 23 months after PML onset (<i>n</i> = 10). The latter group was further categorized according to persisting JCV load in the cerebrospinal fluid.</p><p>Results</p><p>Early post-PML patients showed significantly higher Lipid/Creatine ratios within PML lesions than late post-PML (<i>p</i> = 0.036). Furthermore, N-Acetyl-Aspartate/Creatine and N-Acetyl-Aspartate/Choline were significantly reduced in early post-PML and late post-PML lesions relative to normal-appearing white matter. In late post-PML, virus-positive patients showed significantly higher ratios of Choline/Creatine (<i>p</i> = 0.019) and consequently a reduced N-Acetyl- Aspartate/Choline ratio (<i>p</i> = 0.010) in contrast to virus-negative patients. In late post-PML patients with persisting viral load, an elevated Choline/Creatine ratio correlated significantly with higher disability.</p><p>Conclusions</p><p>¹H-MRS may provide additional information related to underlying PML disease activity in various post-PML stages. In particular, Choline/Creatine levels, Lipid levels, and N-Acetyl- Aspartate/Choline are relevant markers in the post-PML setting, taking also the JCV status into account.</p></div

Association between Cho/Cr (in PML lesions) and the PML-related change in KPS in late post-PML patients (L-pPML).

<p>The KPS change was calculated as the difference between the time points: one year before PML diagnosis and the time of the MRS examination. The dotted line depicts a linear regression.</p

Exemplary ¹H-spectra (2D-PRESS, TR/TE: 2000 / 45 ms).

<p>(A) PML lesion early post-PML (E-pPML, male, aged 62 years, 8 months post-PML); (B) PML lesion late post-PML (L-pPML, female, aged 38 years, 27 months post-PML); (C) NAWM (same patient as (A)); (D) MS lesion (same patient as (B)). The location of the spectra is marked by yellow squares on the inserted axial FLAIR images.</p

Spectroscopy results.

<p>Metabolite ratios in subgroups of PML lesions, MS lesions, and NAWM.</p

MSJ763541_supplementary_material – Supplemental material for Association of smoking but not HLA-DRB1*15:01, <i>APOE</i> or body mass index with brain atrophy in early multiple sclerosis

<p>Supplemental material, MSJ763541_supplementary_material for Association of smoking but not HLA-DRB1*15:01, <i>APOE</i> or body mass index with brain atrophy in early multiple sclerosis by Christiane Graetz, Adriane Gröge, Felix Luessi, Anke Salmen, Daniela Zöller, Janine Schultz, Nelly Siller, Vinzenz Fleischer, Barbara Bellenberg, Achim Berthele, Viola Biberacher, Joachim Havla, Michael Hecker, Reinhard Hohlfeld, Carmen Infante-Duarte, Jan S Kirschke, Tania Kümpfel, Ralf Linker, Friedemann Paul, Steffen Pfeuffer, Philipp Sämann, Gerrit Toenges, Frank Weber, Uwe K Zettl, Antje Jahn-Eimermacher, Gisela Antony, Sergiu Groppa, Heinz Wiendl, Bernhard Hemmer, Mark Mühlau, Carsten Lukas, Ralf Gold, Christina M Lill and Frauke Zipp in Multiple Sclerosis Journal</p