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

Abstract

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.

• Authors: Ruth Schneider, Barbara Bellenberg, Robert Hoepner, Eva-Maria Kolb, Gisa Ellrichmann, Aiden Haghikia, Ralf Gold, Carsten Lukas
• Journal: PloS one (PLoS One) Vol. 12 Issue 4 Pg. e0176415 ( 2017) ISSN: 1932-6203 [Electronic] United States
• PMID: 28445498 (Publication Type: Journal Article)

Chemical References

• Immunologic Factors
• Lipids
• Natalizumab
• Aspartic Acid
• N-acetylaspartate
• Creatine
• Choline

Topics

• Adult
• Aspartic Acid (analogs & derivatives, analysis, metabolism)
• Brain (diagnostic imaging)
• Choline (analysis, metabolism)
• Creatine (analysis, metabolism)
• Female
• Humans
• Immunologic Factors (therapeutic use)
• JC Virus (isolation & purification, physiology)
• Leukoencephalopathy, Progressive Multifocal (complications, pathology, virology)
• Lipids (analysis)
• Magnetic Resonance Imaging
• Magnetic Resonance Spectroscopy
• Male
• Metabolome
• Middle Aged
• Multiple Sclerosis, Relapsing-Remitting (complications, drug therapy)
• Natalizumab (therapeutic use)
• Viral Load