Neuropsychology and Cognition Late Breaking Abstracts

LB1210 - Cerebrospinal fluid inflammatory profile of cognitive dysfunction in newly diagnosed multiple sclerosis patients (ID 2066)

Speakers
  • M. Pitteri
Authors
  • M. Pitteri
  • R. Magliozzi
  • S. Ziccardi
  • A. Pisani
  • M. Calabrese
Presentation Number
LB1210
Presentation Topic
Neuropsychology and Cognition

Abstract

Background

Increased cerebrospinal fluid (CSF) expression of proinflammatory cytokines (IFNG, TNF, IL2, and IL22) and molecules related to sustained B-cell activity and lymphoid-neogenesis (CXCL13, CXCL10, LTa, IL6, and IL10) was found associated to increase cortical grey matter (GM) pathology and more active and severe disease outcome either in naive MS patients or in post-mortem MS cases. Cognitive impairment (CI) is one of the main features of GM damage in MS and can be early observed in newly diagnosed MS patients.

Objectives

To investigate whether a potential link between CSF inflammatory profile and CI exists in newly diagnosed MS patients.

Methods

Sixty-nine, treatment-naïve MS patients (54 F, age=37.3±11.6 ys; education=14.4±3.5 years) underwent an extended battery of neuropsychological tests (median time between LP and neuropsychological assessment: 1 month) and the protein analysis of the levels of 57 inflammatory mediators by using customized immune-assay multiplex Bio-Plex X200. MS patients were classified into three groups (Cognitively Normal: CN; mild CI: mCI; severe CI: sCI) according to the number of neuropsychological tests below the cut-off (5th percentile).

Results

Increased CSF levels of CXCL13 were detected in sCI (mean=29.6pg/ml±SD=59.3) compared to both CN (5.5±9.6) and mCI (6.7±6.3) patients. Furthermore, in mCI compared to CN patients were found higher levels of CHI3L1 (mCI: 5431.7±31942.7; CN: 32743.6±18050.9), CX3CL1 (mCI: 550.7±402.2; CN: 311.7±146.1), IL8 (mCI: 116.5±128.6; CN: 43.1±30.5), CCL3 (mCI: 8.8±7.7; CN: 4.7±2.7), CCL19 (mCI: 164.5±117.0; CN: 83.8±93.4), sTNFr2 (mCI: 1017.9±761.3; CN: 550.1±366.6), and CCL8 (mCI: 590.4±1097.6; CN: 97.4±194.5). Finally, in sCI compared to CN patients were found higher levels of IL22 (sCI: 46.5±43.7; CN: 17.1±15.2), IL35 (sCI: 330.0±214.2; CN: 192.1±133.2), IL12 (sCI: 31.0±37.1; CN: 9.6±11.9), and LIGHT (sCI: 291.3±519.3; CN: 61.6±100.1). In particular, significant correlations were found between the cytokines-chemokines and tests of memory, attention/executive functions, and information processing speed. No significant difference in the CSF Nf-L level was found among the three groups (p=.96).

Conclusions

The presence of CI might be reflected by increased CSF levels of inflammatory mediators. In particular, we found a specific molecular pattern discriminating CN (innate immunity) from mCI and sCI (B-cell chemotaxis and activity). These results demonstrate, for the first time, that specific intrathecal inflammatory milieu might possibly contribute to the MS-related cognitive impairment since the early phases of MS disease.

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