2024-12-11 バッファロー大学(UB)
<関連情報>
- https://www.buffalo.edu/news/releases/2024/UB-studies-paramagnetic-rim-lesions-MS.html
- https://onlinelibrary.wiley.com/doi/10.1002/acn3.52253
- https://www.neurology.org/doi/10.1212/WNL.0000000000210004
多発性硬化症患者における常磁性リム病変の長期的進展の決定因子 Determinants of long-term paramagnetic rim lesion evolution in people with multiple sclerosis
Jack A. Reeves, Alexander Bartnik, Maryam Mohebbi, Murali Ramanathan, Niels Bergsland, Dejan Jakimovski, Gregory E. Wilding, Fahad Salman, Ferdinand Schweser …
Annals of Clinical and Translational Neurology Published: 18 November 2024
DOI:https://doi.org/10.1002/acn3.52253
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.
多発性硬化症患者における常磁性縁病変の進展と臨床的および放射線学的疾患進行との関連性 Associations Between Paramagnetic Rim Lesion Evolution and Clinical and Radiologic Disease Progression in Persons With Multiple Sclerosis
Jack A. Reeves, PhD, Alexander Bartnik, PhD, Dejan Jakimovski, MD, PhD, Maryam Mohebbi, MSc, Niels Bergsland, PhD, Fahad Salman, MSc, Ferdinand Schweser, PhD, Gregory Wilding, PhD, Bianca Weinstock-Guttman, MD, Michael G. Dwyer, PhD, and Robert Zivadinov, MD, PhD
Neurology Published:October 24, 2024
DOI:https://doi.org/10.1212/WNL.0000000000210004
Abstract
Background and Objectives
Recent technological advances have enabled visualizing in vivo a subset of chronic active brain lesions in persons with multiple sclerosis (pwMS), referred to as “paramagnetic rim lesions” (PRLs), with iron-sensitive MRI. PRLs predict future clinical disease progression, making them a promising clinical and translational imaging marker. However, it is unknown how disease progression is modified by PRL evolution (PRL disappearance, new PRL appearance). This is key to understanding MS pathophysiology and may help inform selection of sensitive endpoints for clinical trials targeting chronic active inflammation. To this end, we assessed the longitudinal associations between PRL disappearance and new PRL appearance and clinical disability progression and brain atrophy.
Methods
PwMS and healthy controls (HCs) were included from a larger prospective, longitudinal cohort study at the University at Buffalo if they had available 3T MRI and clinical visits at baseline and follow-up timepoints. PwMS with sufficient clinical data for confirmed disability progression (CDP) analysis were included in a Disability Progression Cohort, and pwMS and HCs with brain volumetry data at baseline and follow-up were included in MS and HC Brain Atrophy cohorts. PRLs were assessed at baseline and follow-up and assigned as disappearing, newly appearing, or persisting at follow-up. Linear models were fit to compare annualized PRL disappearance rates or new PRL appearance (yes/no) with annualized rates of CDP and progression independent of relapse activity (PIRA) or with annualized rates of brain atrophy, adjusting for covariates including baseline PRL number and follow-up time. Statistical analyses were corrected for false discovery rate (FDR; i.e., q-value).
Results
In total, 160 pwMS (73.8% female; mean baseline age 46.6 ± 11.4 years; mean baseline disease duration 13.8 ± 10.6 years; median follow-up time 5.6 [interquartile range 5.2–7.8] years; 26.9% progressive MS) and 27 HCs (74.1% female; mean baseline age 43.9 ± 13.6 years; median follow-up time 5.4 [5.2–5.6] years) were enrolled. Greater PRL disappearance rates were associated with reduced rates of CDP (β mean = -0.262, 95% CI -0.475 to -0.049, q = 0.028) and PIRA (β mean = -0.283, 95% CI -0.492 to -0.073, q = 0.036), and new PRL appearance was associated with increased rates of PIRA (β mean = 0.223, 95% CI 0.049–0.398, q = 0.036). By contrast, no associations between new PRL appearance or PRL disappearance and brain volume changes survived FDR correction (q > 0.05).
Discussion
Our results show that resolution of existing PRLs and lack of new PRLs are associated with improved clinical outcomes. These findings further motivate the need for novel therapies targeting microglia-mediated brain inflammation and adoption of clinical strategies to prevent appearance of new PRL.
