What is the potential of paramagnetic rim lesions as diagnostic indicators in multiple sclerosis?

ABSTRACT

Introduction

In multiple sclerosis (MS), paramagnetic rim lesions (PRLs) on MRI identify a subset of chronic active lesions (CALs), which have been linked through clinical and pathological studies to more severe disease course and greater disability accumulation. Beside their prognostic relevance, increasing evidence supports the use of PRL as a diagnostic biomarker.

Areas covered

This review summarizes the most recent updates regarding the MRI pathophysiology of PRL, their prevalence in MS (by clinical phenotypes) vs mimicking conditions, and their potential role as diagnostic MS biomarkers. We searched PubMed with terms including ‘multiple sclerosis’ AND ‘paramagnetic rim lesions’ OR ‘iron rim lesions’ OR ‘rim lesions’ for manuscripts published between January 2008 and July 2022.

Expert opinion

Current research suggests that PRL can improve the diagnostic specificity and the overall accuracy of MS diagnosis when used together with the dissemination in space MRI criteria and the central vein sign. Nevertheless, future prospective multicenter studies should further define the real-world prevalence and specificity of PRL. International guidelines are needed to establish methodological criteria for PRL identification before its implementation into clinical practice.

KEYWORDS:

• multiple sclerosis
• diagnosis
• susceptibility-based MRI
• paramagnetic rim lesion
• biomarker

Article highlights

• In multiple sclerosis (MS), a subset of chronic active lesions can be identified in vivo on susceptibility-based MRI as paramagnetic rim lesions.

• Chronic active lesions have been associated on pathological and clinical studies with more aggressive disease course and worse clinical outcomes, but their performance as diagnostic biomarkers needs to be established.

• The 2017 revision of MS diagnostic criteria demonstrated similar accuracy and higher sensitivity, but lower specificity when compared with 2010 revision. Thus, there is need for lesion biomarkers that are specific to MS.

• PRLs are present in a high proportion of MS patients (about 50%) and have been found to be common in all MS phenotypes.

• PRL and perivenular lesion detection can be used to differentiate brain lesions between MS and MS-mimicking conditions with high diagnostic specificity.

• Preliminary evidence suggests that PRL can be used to predict MS conversion in radiologically isolated syndrome and clinically isolated syndrome patients.

Declaration of interest

M Absinta was supported by the Conrad N. Hilton Foundation (Marylin Hilton Bridging Award for Physician-Scientists, grant #17313), the International Progressive MS Alliance (PA-2107-38,081), the Roche Foundation for Independent Research, the Cariplo Foundation (grant #1677), and the FRRB Early Career Award (grant #1750327). She received compensation for consulting service and/or speaking activities from Celgene, GSK, Sanofi-Genzyme, and Abata Therapeutics. L Moiola received compensation for consulting services and/or speaking activities from Biogen, Celgene, Genzyme, Merck-Serono, Novartis, Roche, and Sanofi. MA Rocca received consulting fees from Biogen, Bristol Myers Squibb, Eli Lilly, Janssen, and Roche and speaker honoraria from Bayer, Biogen, Bristol Myers Squibb, Bromatech, Celgene, Genzyme, Merck Healthcare Germany, Merck Serono SpA, Novartis, Roche, and Teva. She received research support from the MS Society of Canada and Fondazione Italiana Sclerosi Multipla. She is an Associate Editor for Multiple Sclerosis and Related Disorders. M Filippi is the Editor-in-Chief of the Journal of Neurology and Associate Editor of Radiology, Human Brain Mapping and Neurological Sciences; received compensation for consulting services and/or speaking activities from Almiral, Alexion, Bayer, Biogen, Celgene, Eli Lilly, Genzyme, Merck-Serono, Novartis, Roche, Sanofi, Takeda, and Teva Pharmaceutical Industries; and received research support from Biogen Idec, Merck Serono, Novartis, Roche, Sanofi, Almiral, Eli Lilly, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers of this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper was funded by the Conrad N. Hilton Foundation and the Cariplo Foundation.