Insight into Metabolic 1H-MRS Changes in Natalizumab Induced Progressive Multifocal Leukoencephalopathy Brain Lesions
BackgroundProgressive 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....
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Frontiers Media S.A.
2017-09-01
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| Series: | Frontiers in Neurology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fneur.2017.00454/full |
| _version_ | 1819090700676890624 |
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| author | Ruth Schneider Barbara Bellenberg Robert Hoepner Gisa Ellrichmann Ralf Gold Carsten Lukas |
| author_facet | Ruth Schneider Barbara Bellenberg Robert Hoepner Gisa Ellrichmann Ralf Gold Carsten Lukas |
| author_sort | Ruth Schneider |
| collection | DOAJ |
| description | BackgroundProgressive 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.ObjectiveTo 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).Methods20 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.ResultsIn 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).Conclusion1H-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. |
| first_indexed | 2024-12-21T22:28:00Z |
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| language | English |
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| publishDate | 2017-09-01 |
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| spelling | doaj.art-3c0a044709804a69a11106f5f1178cb82022-12-21T18:48:09ZengFrontiers Media S.A.Frontiers in Neurology1664-22952017-09-01810.3389/fneur.2017.00454274621Insight into Metabolic 1H-MRS Changes in Natalizumab Induced Progressive Multifocal Leukoencephalopathy Brain LesionsRuth Schneider0Barbara Bellenberg1Robert Hoepner2Gisa Ellrichmann3Ralf Gold4Carsten Lukas5Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, GermanyDepartment of Diagnostic and Interventional Radiology and Nuclear Medicine, St. Josef Hospital, Ruhr University Bochum, Bochum, GermanyDepartment of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, GermanyDepartment of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, GermanyDepartment of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, GermanyDepartment of Diagnostic and Interventional Radiology and Nuclear Medicine, St. Josef Hospital, Ruhr University Bochum, Bochum, GermanyBackgroundProgressive 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.ObjectiveTo 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).Methods20 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.ResultsIn 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).Conclusion1H-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.http://journal.frontiersin.org/article/10.3389/fneur.2017.00454/full1H magnetic resonance spectroscopymultiple sclerosisnatalizumabprogressive multifocal leukoencephalopathyPML lesionsimmune reconstitution inflammatory syndrome |
| spellingShingle | Ruth Schneider Barbara Bellenberg Robert Hoepner Gisa Ellrichmann Ralf Gold Carsten Lukas Insight into Metabolic 1H-MRS Changes in Natalizumab Induced Progressive Multifocal Leukoencephalopathy Brain Lesions Frontiers in Neurology 1H magnetic resonance spectroscopy multiple sclerosis natalizumab progressive multifocal leukoencephalopathy PML lesions immune reconstitution inflammatory syndrome |
| title | Insight into Metabolic 1H-MRS Changes in Natalizumab Induced Progressive Multifocal Leukoencephalopathy Brain Lesions |
| title_full | Insight into Metabolic 1H-MRS Changes in Natalizumab Induced Progressive Multifocal Leukoencephalopathy Brain Lesions |
| title_fullStr | Insight into Metabolic 1H-MRS Changes in Natalizumab Induced Progressive Multifocal Leukoencephalopathy Brain Lesions |
| title_full_unstemmed | Insight into Metabolic 1H-MRS Changes in Natalizumab Induced Progressive Multifocal Leukoencephalopathy Brain Lesions |
| title_short | Insight into Metabolic 1H-MRS Changes in Natalizumab Induced Progressive Multifocal Leukoencephalopathy Brain Lesions |
| title_sort | insight into metabolic 1h mrs changes in natalizumab induced progressive multifocal leukoencephalopathy brain lesions |
| topic | 1H magnetic resonance spectroscopy multiple sclerosis natalizumab progressive multifocal leukoencephalopathy PML lesions immune reconstitution inflammatory syndrome |
| url | http://journal.frontiersin.org/article/10.3389/fneur.2017.00454/full |
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