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Insight into Metabolic 1H-MRS Changes in Natalizumab Induced Progressive Multifocal Leukoencephalopathy Brain Lesions
Ruth Schneider1, Barbara Bellenberg2, Robert Hoepner1
1Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany.
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 described 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 T 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) 1 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). By 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 four 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 ρ = 0.481, p = 0.018; ρ = -0.505, p = 0.014; and ρ = -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.
Insights
This study used 1H-MRS to track metabolic changes in progressive multifocal leukoencephalopathy (PML) lesions in multiple sclerosis (MS) patients treated with natalizumab. Metabolic profiles dynamically changed during PML and immune reconstitution inflammatory syndrome (IRIS), correlating with clinical worsening.
Area of Science:
- Neuroimaging
- Neuroimmunology
- Metabolic studies
Background:
- Progressive multifocal leukoencephalopathy (PML) is a severe complication of immunosuppressive therapies, particularly natalizumab in relapsing-remitting multiple sclerosis (MS).
- Metabolic alterations within PML lesions in natalizumab-associated PML (PML-IRIS) in MS patients remain underexplored.
Purpose of the Study:
- To investigate metabolic profiles in natalizumab-associated PML lesions using 1H magnetic resonance spectroscopy (1H-MRS) across different PML disease stages.
- To analyze metabolic changes associated with the onset of immune reconstitution inflammatory syndrome (IRIS) in PML patients.
Main Methods:
- Utilized 1H-MRS and 3T imaging in 20 MS patients with PML at various stages: pre-IRIS, IRIS, early post-PML, and late post-PML.
- Assessed clinical status using Karnofsky Performance Scale (KPS) and expanded disability status scale (EDSS), with follow-up examinations for five patients.
Main Results:
- Elevated Lip/Cr ratios were observed in PML lesions before IRIS, peaking during IRIS. Marked Cho/Cr increases were specific to the IRIS phase.
- Lip/Cr ratios normalized in late-stage PML. Reduced NAA/Cho and NAA/Cr were noted in early PML stages.
- Metabolic changes (NAA/Cho, Cho/Cr, lipid levels) correlated significantly with residual clinical worsening post-PML.
Conclusions:
- 1H-MRS revealed dynamic metabolic pattern shifts in PML lesions throughout natalizumab-associated PML in MS patients.
- Lip/Cr and Cho/Cr ratios may serve as biomarkers for detecting IRIS onset during PML progression.
