Concurrent gliomas in patients with multiple sclerosis
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Published:2023-12-18
Issue:1
Volume:3
Page:
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ISSN:2730-664X
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Container-title:Communications Medicine
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language:en
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Short-container-title:Commun Med
Author:
Sahm KatharinaORCID, Kessler Tobias, Eisele Philipp, Ratliff MiriamORCID, Sperk Elena, König Laila, Breckwoldt Michael O.ORCID, Seliger Corinna, Mildenberger Iris, Schrimpf Daniel, Herold-Mende Christel, Zeiner Pia S., Tabatabai Ghazaleh, Meuth Sven G., Capper DavidORCID, Bendszus Martin, von Deimling AndreasORCID, Wick WolfgangORCID, Sahm FelixORCID, Platten MichaelORCID
Abstract
Abstract
Background
Concurrent malignant brain tumors in patients with multiple sclerosis (MS) constitute a rare but paradigmatic phenomenon for studying neuroimmunological mechanisms from both molecular and clinical perspectives.
Methods
A multicenter cohort of 26 patients diagnosed with both primary brain tumors and multiple sclerosis was studied for disease localization, tumor treatment-related MS activity, and molecular characteristics specific for diffuse glioma in MS patients.
Results
MS neither predisposes nor protects from the development of gliomas. Patients with glioblastoma WHO grade 4 without isocitratdehydrogenase (IDH) mutations have a longstanding history of MS, whereas patients diagnosed with IDH-mutant astrocytoma WHO grade 2 receive multiple sclerosis diagnosis mostly at the same time or later. Concurrent MS is associated with a lesser extent of tumor resection and a worse prognosis in IDH-mutant glioma patients (PFS 32 vs. 64 months, p = 0.0206). When assessing tumor-intrinsic differences no distinct subgroup-defining methylation pattern is identified in gliomas of MS patients compared to other glioma samples. However, differential methylation of immune-related genetic loci including human leukocyte antigen locus on 6p21 and interleukin locus on 5q31 is found in MS patients vs. matched non-MS patients. In line, inflammatory disease activity increases in 42% of multiple sclerosis patients after brain tumor radiotherapy suggesting a susceptibility of multiple sclerosis brain tissue to pro-inflammatory stimuli such as ionizing radiation.
Conclusions
Concurrent low-grade gliomas should be considered in multiple sclerosis patients with slowly progressive, expansive T2/FLAIR lesions. Our findings of typically reduced extent of resection in MS patients and increased MS activity after radiation may inform future treatment decisions.
Funder
Deutsche Forschungsgemeinschaft Gemeinnützige Hertie-Stiftung Else Kröner-Fresenius-Stiftung
Publisher
Springer Science and Business Media LLC
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