Determinants of long‐term paramagnetic rim lesion evolution in people with multiple sclerosis
Abstract Objective Baseline paramagnetic rim lesion (PRL) load predicts disease progression in people with multiple sclerosis (pwMS). Understanding how PRLs relate to other known MS‐related factors, and the practical utility of PRLs in clinical trials, is crucial for informing clinical decision‐maki...
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| Format: | Article |
| Language: | English |
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Wiley
2025-02-01
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| Series: | Annals of Clinical and Translational Neurology |
| Online Access: | https://doi.org/10.1002/acn3.52253 |
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| author | Jack A. Reeves Alexander Bartnik Maryam Mohebbi Murali Ramanathan Niels Bergsland Dejan Jakimovski Gregory E. Wilding Fahad Salman Ferdinand Schweser Bianca Weinstock‐Guttman David Hojnacki Svetlana Eckert Francesca Bagnato Michael G. Dwyer Robert Zivadinov |
| author_facet | Jack A. Reeves Alexander Bartnik Maryam Mohebbi Murali Ramanathan Niels Bergsland Dejan Jakimovski Gregory E. Wilding Fahad Salman Ferdinand Schweser Bianca Weinstock‐Guttman David Hojnacki Svetlana Eckert Francesca Bagnato Michael G. Dwyer Robert Zivadinov |
| author_sort | Jack A. Reeves |
| collection | DOAJ |
| description | Abstract Objective Baseline paramagnetic rim lesion (PRL) load predicts disease progression in people with multiple sclerosis (pwMS). Understanding how PRLs relate to other known MS‐related factors, and the practical utility of PRLs in clinical trials, is crucial for informing clinical decision‐making and guiding development of novel disease‐modifying treatments (DMTs). Methods This study included 152 pwMS enrolled in a larger prospective, longitudinal cohort study who had 3T MRI scans and clinical assessments at baseline and 5‐ or 10‐year follow‐ups. PRLs were identified on baseline 3T quantitative susceptibility maps and classified as persisting, disappearing, or newly appearing at follow‐up. The relationships between PRL evolution and clinical, radiological, environmental, and genetic characteristics were assessed, and clinical trial sample sizes were estimated using PRL appearance or disappearance as outcome measures. Results DMT use was associated with lower odds of new PRL appearance (for high‐efficacy DMTs: odds ratio = 0.088, p = 0.024), but not disappearance. Current smoking status was associated with greater baseline PRL number (B = 0.527 additional PRLs, p = 0.013). A 24‐month clinical trial in people with progressive MS for a DMT that doubles the rate of PRL rim disappearance would require an estimated 118 people with progressive MS per group at 80% statistical power. Interpretation Early MS diagnosis and subsequent DMT initiation may reduce new chronic active inflammation. However, the utility of PRL disappearance or new PRL appearance as outcome measures in clinical trials is limited by potentially large sample sizes that are needed for moderate efficacy drugs. |
| format | Article |
| id | doaj-art-bb3bcbf310fc4db887472b21bd9afa1b |
| institution | OA Journals |
| issn | 2328-9503 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Annals of Clinical and Translational Neurology |
| spelling | doaj-art-bb3bcbf310fc4db887472b21bd9afa1b2025-08-20T02:28:00ZengWileyAnnals of Clinical and Translational Neurology2328-95032025-02-0112226727910.1002/acn3.52253Determinants of long‐term paramagnetic rim lesion evolution in people with multiple sclerosisJack A. Reeves0Alexander Bartnik1Maryam Mohebbi2Murali Ramanathan3Niels Bergsland4Dejan Jakimovski5Gregory E. Wilding6Fahad Salman7Ferdinand Schweser8Bianca Weinstock‐Guttman9David Hojnacki10Svetlana Eckert11Francesca Bagnato12Michael G. Dwyer13Robert Zivadinov14Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences University at Buffalo, State University of New York Buffalo New York USABuffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences University at Buffalo, State University of New York Buffalo New York USABuffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences University at Buffalo, State University of New York Buffalo New York USADepartment of Pharmaceutical Sciences State University of New York Buffalo New York USABuffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences University at Buffalo, State University of New York Buffalo New York USABuffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences University at Buffalo, State University of New York Buffalo New York USADepartment of Biostatistics, School of Public Health and Health Professions State University of New York at Buffalo Buffalo New York USABuffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences University at Buffalo, State University of New York Buffalo New York USABuffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences University at Buffalo, State University of New York Buffalo New York USAJacobs Neurological Institute Buffalo New York USADepartment of Neurology, Jacobs School of Medicine and Biomedical Sciences University at Buffalo, State University of New York Buffalo New York USADepartment of Neurology, Jacobs School of Medicine and Biomedical Sciences University at Buffalo, State University of New York Buffalo New York USANeuroimaging Unit, Neuroimmunology Division, Department of Neurology Vanderbilt University Medical Center Nashville Tennessee USABuffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences University at Buffalo, State University of New York Buffalo New York USABuffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences University at Buffalo, State University of New York Buffalo New York USAAbstract Objective Baseline paramagnetic rim lesion (PRL) load predicts disease progression in people with multiple sclerosis (pwMS). Understanding how PRLs relate to other known MS‐related factors, and the practical utility of PRLs in clinical trials, is crucial for informing clinical decision‐making and guiding development of novel disease‐modifying treatments (DMTs). Methods This study included 152 pwMS enrolled in a larger prospective, longitudinal cohort study who had 3T MRI scans and clinical assessments at baseline and 5‐ or 10‐year follow‐ups. PRLs were identified on baseline 3T quantitative susceptibility maps and classified as persisting, disappearing, or newly appearing at follow‐up. The relationships between PRL evolution and clinical, radiological, environmental, and genetic characteristics were assessed, and clinical trial sample sizes were estimated using PRL appearance or disappearance as outcome measures. Results DMT use was associated with lower odds of new PRL appearance (for high‐efficacy DMTs: odds ratio = 0.088, p = 0.024), but not disappearance. Current smoking status was associated with greater baseline PRL number (B = 0.527 additional PRLs, p = 0.013). A 24‐month clinical trial in people with progressive MS for a DMT that doubles the rate of PRL rim disappearance would require an estimated 118 people with progressive MS per group at 80% statistical power. Interpretation Early MS diagnosis and subsequent DMT initiation may reduce new chronic active inflammation. However, the utility of PRL disappearance or new PRL appearance as outcome measures in clinical trials is limited by potentially large sample sizes that are needed for moderate efficacy drugs.https://doi.org/10.1002/acn3.52253 |
| spellingShingle | Jack A. Reeves Alexander Bartnik Maryam Mohebbi Murali Ramanathan Niels Bergsland Dejan Jakimovski Gregory E. Wilding Fahad Salman Ferdinand Schweser Bianca Weinstock‐Guttman David Hojnacki Svetlana Eckert Francesca Bagnato Michael G. Dwyer Robert Zivadinov Determinants of long‐term paramagnetic rim lesion evolution in people with multiple sclerosis Annals of Clinical and Translational Neurology |
| title | Determinants of long‐term paramagnetic rim lesion evolution in people with multiple sclerosis |
| title_full | Determinants of long‐term paramagnetic rim lesion evolution in people with multiple sclerosis |
| title_fullStr | Determinants of long‐term paramagnetic rim lesion evolution in people with multiple sclerosis |
| title_full_unstemmed | Determinants of long‐term paramagnetic rim lesion evolution in people with multiple sclerosis |
| title_short | Determinants of long‐term paramagnetic rim lesion evolution in people with multiple sclerosis |
| title_sort | determinants of long term paramagnetic rim lesion evolution in people with multiple sclerosis |
| url | https://doi.org/10.1002/acn3.52253 |
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