Wide Cytokine Analysis in Cerebrospinal Fluid at Diagnosis Identified CCL-3 as a Possible Prognostic Factor for Multiple Sclerosis

Background: Apart from IgG oligoclonal bands, no other biomarker has, to date, been validated for diagnostic and/or prognostic purposes in multiple sclerosis (MS). Aim: To investigate a wide panel of cytokines and chemokines in the cerebrospinal fluid (CSF) of relapsing\u2013remitting MS (RRMS) patients and evaluate their association with clinical and magnetic resonance imaging (MRI) parameters, as well as their predictive clinical value. Methods: Fifty-one RRMS at clinical onset and 17 other not inflammatory neurological disorders (ONINDs) underwent brain MRI (including 3D-T1, 3D-FLAIR, and 3-DIR sequences) and CSF examination. Eighty-seven cytokines and chemokines were analyzed in CSF by Multiplex technology. Results: Compared to ONIND, CXCL-10, CXCL-11, CXCL-13, CCL-1, CCL-2, CCL-3, CCL-22, IL-16, and BAFF were significantly (p < 0.05) increased in RRMS CSF. However, only CCL-3 was associated with both MS diagnosis and IgGOB detection. Based on a 95%CI in ONIND (cut-off value: 0.798 pg/ml) and ROC analysis (cut-off value: 0.495 pg/ml), RRMS patients were stratified in CCL-3high (>0.736 pg/mL), CCL-3medium, and CCL-3low (<0.495 pg/ml). Survival analysis disclosed a strong association between high CCL-3 values and disease reactivation (OR = 4.9, 95%CI: 1.8\u201313.3, p < 0.005) in the following 2 years. Conclusions: CCL-3 deserves further investigation as a candidate prognostic biomarker for RRMS

Association between the frailty index and vascular brain damage: The Treviso Dementia (TREDEM) registry

Purpose: An association between frailty and vascular brain damage (VBD) has been described in older adults. However, most studies have identified frailty according to the phenotypic model. It is less clear whether frailty, operationalized as an accumulation of health deficits, is associated with the presence and severity of VBD. The present study was therefore undertaken to verify whether a 50-item frailty index (FI) is related to VBD in a large and relatively unselected cohort of attendees of a memory clinic. Materials and methods: The TREDEM (Treviso Dementia) registry includes retrospective observational data of 1584 participants. A modified FI was calculated from 50 variables comprising diseases, disability, behavioral disorders, and blood biochemistry. The presence and severity of VBD, including leukoaraiosis, lacunes, larger infarctions and the hierarchical vascular rating scale (HVRS), were determined based on brain computerized tomography imaging. Multiple logistic regression models were built according to the stepwise method. Results: Mean age of the 1584 participants was 79.6 ± 7.5 years and 1033 (65.2 %) were females. The average number of health deficits was 11.6 ± 6.2, corresponding to an FI of 0.23 ± 0.12 (range: 0.00–0.56). Each 0.01-point increase in the FI was associated with an increased probability of leukoaraiosis (+2.3 %) and severe leukoaraiosis (+5 %), lacunas in the basal ganglia (+1.73 %), occipital lobes (+2.7 %), parietal lobes (+3 %), frontal lobes (+3.6 %), temporal lobes (+4.2 %), and thalamus (+4.4 %). Moreover, an increase of 0.01 points in the FI was associated with a 3.1 % increase in the probability of HVRS score (≥2). Conclusion: An FI based on routine clinical and laboratory variables was associated with the presence, degree, and some localizations of VBD in a population of older adults with cognitive decline. This frailty assessment tool may therefore be used to identify individuals at risk of developing cerebrovascular disease and, consequently, to implement strategies for vascular risk factor control