Biomarkers of Intrathecal Synthesis May Be Associated with Cognitive Impairment at MS Diagnosis

Overview

Journal Int J Mol Sci

Publisher MDPI

Date 2025 Jan 25

PMID 39859538

Authors

Eleonora Virgilio

Valentina Ciampana

Chiara Puricelli

Paola Naldi

Angelo Bianchi

Umberto Dianzani

Domizia Vecchio

Cristoforo Comi

Affiliations

Soon will be listed here.

Abstract

The pathophysiology of cognitive impairment (CI) in multiple sclerosis (MS) remains unclear. Meningeal B cell aggregates may contribute to cortical grey matter pathology. Cerebrospinal fluid (CSF), kappa free light chains (KFLC), and KFLCs-Index (kappa-Index) are reliable quantitative markers of intrathecal synthesis, but few data have been presented exploring the association with CI, and no data are present for lambda FLC (LFLC) in MS. We evaluated cognition using the Brief International Cognitive Assessment for MS (BICAMS) battery and collected serum and CSF at diagnosis in newly diagnosed drug-naïve MS patients. We observed that patients with impaired verbal memory and overall CI showed increased CSF KFLCs (respectively : 0.0003 and : 0.003) and kappa-Index (respectively : 0.01 and : 0.02) compared to those with normal verbal memory and no CI. Patients with CI also displayed lower CSF LFLCs (: 0.04) and lambda-Index (: 0.001); however, only CSF KFLC negatively correlated with normalized results of verbal memory (for age, sex, and educational levels), even after correction for EDSS (r: -0.27 : 0.01). Finally, CSF FKLC and kappa-Index were significant predictors of verbal memory in a multivariate analysis. Our results, suggest that intrathecal B cell activity might contribute to CI development in MS patients.

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