Biomarkers of Intrathecal Synthesis May Be Associated with Cognitive Impairment at MS Diagnosis
Eleonora Virgilio1,2, Valentina Ciampana3, Chiara Puricelli4
1Neurology Unit, Department of Clinical and Biological Sciences, University Hospital San Luigi Gonzaga, University of Turin, 10043 Turin, Italy.
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 p: 0.0003 and p: 0.003) and kappa-Index (respectively p: 0.01 and p: 0.02) compared to those with normal verbal memory and no CI. Patients with CI also displayed lower CSF LFLCs (p: 0.04) and lambda-Index (p: 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 p: 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.
Insights
Intrathecal B cell activity, indicated by cerebrospinal fluid kappa free light chains (KFLC), is linked to cognitive impairment (CI) in multiple sclerosis (MS) patients, particularly affecting verbal memory.
Area of Science:
- Neuroimmunology
- Neurology
- Biochemistry
Background:
- The mechanisms underlying cognitive impairment (CI) in multiple sclerosis (MS) are not fully understood.
- Meningeal B cell aggregates are hypothesized to play a role in cortical grey matter pathology in MS.
- Cerebrospinal fluid (CSF) kappa free light chains (KFLC) and kappa-Index are established markers of intrathecal synthesis, but their association with CI in MS is underexplored, with no data on lambda free light chains (LFLC).
Purpose of the Study:
- To investigate the association between intrathecal synthesis markers, specifically CSF KFLC, kappa-Index, LFLC, and lambda-Index, and cognitive function in newly diagnosed, drug-naïve MS patients.
- To determine if CSF KFLC and kappa-Index predict verbal memory performance in MS.
Main Methods:
- Cognitive function was assessed using the Brief International Cognitive Assessment for MS (BICAMS) battery.
- Serum and CSF samples were collected at diagnosis from newly diagnosed, drug-naïve MS patients.
- CSF KFLC, kappa-Index, LFLC, and lambda-Index levels were quantified and correlated with cognitive performance, including verbal memory, adjusting for age, sex, educational level, and EDSS score.
Main Results:
- Patients with impaired verbal memory and overall CI exhibited significantly higher CSF KFLCs and kappa-Index compared to those without CI.
- Patients with CI showed lower CSF LFLCs and lambda-Index.
- CSF KFLC demonstrated a significant negative correlation with verbal memory performance, even after adjusting for covariates.
- CSF KFLC and kappa-Index were identified as significant predictors of verbal memory in multivariate analysis.
Conclusions:
- Intrathecal B cell activity, as indicated by elevated CSF KFLC and kappa-Index, may contribute to the development of cognitive impairment, particularly verbal memory deficits, in MS patients.
- These findings highlight the potential role of B cell-mediated inflammation in MS-related cognitive dysfunction.
