Serum neurofilaments increase at progressive multifocal leukoencephalopathy onset in natalizumab-treated multiple sclerosis patients.

This study analyzed serum neurofilament light chains (NfL) in 2 European cohorts of 312 multiple sclerosis (MS) patients to investigate whether NfL are biomarkers of progressive multifocal leukoencephalopathy (PML) during natalizumab treatment. The cohort comprised 25 PML, 136 natalizumab-treated, and 151 untreated MS patients. Patients subsequently developing PML had similar NfL to other natalizumab-treated MS patients. At PML onset, NfL were 10-fold higher than in the pre-PML condition and in natalizumab-treated or untreated MS patients, and NfL continued to increase until onset of immune reconstitution inflammatory syndrome. The results suggest that in natalizumab-treated patients, NfL may represent an early and accessible marker of PML. Ann Neurol 2019;85:606-610.

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

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 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. METHODS: 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 (n = 5), or late post-PML group, more than 23 months after PML onset (n = 10). The latter group was further categorized according to persisting JCV load in the cerebrospinal fluid. RESULTS: Early post-PML patients showed significantly higher Lipid/Creatine ratios within PML lesions than late post-PML (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 (p = 0.019) and consequently a reduced N-Acetyl- Aspartate/Choline ratio (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. CONCLUSIONS: 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.