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

Abstract

$\bf Purpose$ 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 $^{1}$H-magnetic resonance spectroscopy ($^{1}$H-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. $\bf Methods$ $^{1}$H-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 ($\it n$ = 5), or late post-PML group, more than 23 months after PML onset ($\it n$ = 10). The latter group was further categorized according to persisting JCV load in the cerebrospinal fluid. $\bf Results$ Early post-PML patients showed significantly higher Lipid/Creatine ratios within PML lesions than late post-PML ($\it p$ = 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 ($\it p$ = 0.019) and consequently a reduced N-Acetyl-Aspartate/Choline ratio ($\it p$ = 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. $\bf Conclusions$ $^{1}$H-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