Cerebrospinal fluid–related tissue damage in multiple sclerosis patients with iron rim lesions

Wittayer, Matthias; Weber, Christian; Kittel, Maximilian; Platten, Michael; Schirmer, Lucas; Tumani, Hayrettin; Gass, Achim; Eisele, Philipp

doi:10.1177/13524585231155639

Cited by 4 publications

(1 citation statement)

References 39 publications

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“…Paramagnetic rim lesions (PRLs), also known as iron rim lesions (IRLs), are thought to reflect chronic active lesions with substantial microglia/macrophage inflammation [ 97 , 98 ]. Retrospective studies of patients with MS have found that, compared with patients without PRLs, patients with least one PRL had higher disability scores, T2 lesion volume, and intrathecal IgG synthesis were higher, and lower brain volume, and patients with 4 or more PRLs had more aggressive disease, and experienced greater motor and cognitive disability at an earlier age [ 97 , 98 ]. Also, PRLs have been detected in early RRMS [ 99 ].…”

Section: Biomarkers As Indicators Of “Silent” Diseasementioning

confidence: 99%

Identification and management of subclinical disease activity in early multiple sclerosis: a review

Ontaneda,

Chitnis,

Rammohan

et al. 2023

J Neurol

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Importance Early treatment initiation in multiple sclerosis (MS) is crucial in preventing irreversible neurological damage and disability progression. The current assessment of disease activity relies on relapse rates and magnetic resonance imaging (MRI) lesion activity, but inclusion of other early, often “hidden,” indicators of disease activity may describe a more comprehensive picture of MS. Observations Early indicators of MS disease activity other than relapses and MRI activity, such as cognitive impairment, brain atrophy, and fatigue, are not typically captured by routine disease monitoring. Furthermore, silent progression (neurological decline not clearly captured by standard methods) may occur undetected by relapse and MRI lesion activity monitoring. Consequently, patients considered to have no disease activity actually may have worsening disease, suggesting a need to revise MS management strategies with respect to timely initiation and escalation of disease-modifying therapy (DMT). Traditionally, first-line MS treatment starts with low- or moderate-efficacy therapies, before escalating to high-efficacy therapies (HETs) after evidence of breakthrough disease activity. However, multiple observational studies have shown that early initiation of HETs can prevent or reduce disability progression. Ongoing randomized clinical trials are comparing escalation and early HET approaches. Conclusions and relevance There is an urgent need to reassess how MS disease activity and worsening are measured. A greater awareness of “hidden” indicators, potentially combined with biomarkers to reveal silent disease activity and neurodegeneration underlying MS, would provide a more complete picture of MS and allow for timely therapeutic intervention with HET or switching DMTs to address suboptimal treatment responses.

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