Association between paramagnetic rim lesions and pulvinar iron depletion in persons with multiple sclerosis

Jack A Reeves; Fahad Salman; Maryam Mohebbi; Niels Bergsland; Dejan Jakimovski; Simon Hametner; Bianca Weinstock-Guttman; Robert Zivadinov; Michael G Dwyer; Ferdinand Schweser

doi:10.1016/j.msard.2024.106187

Association between paramagnetic rim lesions and pulvinar iron depletion in persons with multiple sclerosis

Mult Scler Relat Disord. 2024 Nov 24:93:106187. doi: 10.1016/j.msard.2024.106187. Online ahead of print.

Authors

Affiliations

¹ Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, United States. Electronic address: jackreev@buffalo.edu.
² Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, United States.
³ Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, United States; Wynn Hospital, Mohawk Valley Health System, Utica, NY, 13502, USA.
⁴ Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria; Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna, Vienna, Austria.
⁵ Jacobs Neurological Institute, Buffalo, NY, United States.
⁶ Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, United States; Center for Biomedical Imaging at the Clinical Translational Science Institute, University at Buffalo, State University of New York, Buffalo, NY, United States.

PMID: 39644585
DOI: 10.1016/j.msard.2024.106187

Abstract

Background: The deep gray matter (DGM), especially the pulvinar, and the white matter surrounding chronic active lesions have demonstrated depleted iron levels, indicating a possible mechanistic link. However, no studies have investigated the potential relationship between these phenomena.

Objectives: The study aimed to determine whether PRLs were associated with pulvinar iron depletion and, if so, whether this relationship was spatially mediated.

Methods: This retrospective analysis included 139 people with MS (pwMS) and 43 healthy controls (HCs) scanned at 3T MRI at baseline and after 5.4 ± 0.6 years. Pulvinar iron concentrations (cFe) and iron masses (mFe) were estimated from quantitative susceptibility maps and tested for associations with PRLs. A separate cohort of 96 pwMS with PRLs and propensity-matched HCs was included to evaluate peri‑plaque normal-appearing white matter (NAWM) abnormalities.

Results: PRL number was associated with greater decline in pulvinar cFe (β = -0.265, p = 0.005) and mFe (β = -0.256, p = 0.006). Peri-plaque NAWM susceptibility was increased 11 mm surrounding PRLs, outside which shorter PRL-to-pulvinar distance was associated with greater decline in pulvinar cFe (β = 0.380, p = 0.005) and mFe (β = 0.348, p = 0.022).

Conclusions: Our findings support a spatially-mediated relationship between PRLs and chronic pulvinar iron depletion.

Keywords: Chronic active lesions; Iron; Multiple sclerosis; Paramagnetic rim lesion; Quantitative susceptibility mapping.