Contributions
Abstract: P594
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Introduction: In Multiple Sclerosis (MS), numerous findings suggest that axonal loss is ultimately responsible for the development of irreversible neurological deficits, which is likely to emerge as a consequence of nerve injury starting in early phases of the disease.
Objective: The aim of our study was to investigate the prognostic role of cerebrospinal fluid (CSF) biomarkers related to axonal damage and glial activation such as neurofilaments (NFL), total-tau and chitinase-3-like 1 (CHI3L1) in patients with Clinically Isolated Syndrome (CIS).
Methods and materials: CSF of patients with CIS was examined for the presence of NFL, total-tau and CHI3L1. The median biomarker level was used as a cut-off to define high or low levels. Outcomes for logistic regression and survival analysis were: diagnosis of Clinically Definite MS (CDMS), defined by a clinical relapse, and disability milestones defined as an EDSS of 3, 4 and 6. Correlations between biomarkers and clinical, MRI and CSF parameters, including IgMOB, were analyzed using Spearman"s rank test (with Bonferroni correction).
Results: We included 101 patients in the study (64F, mean age: 35±10 years). Mean follow-up duration was 72 months (24-109). A relapse occurred in 52% of patients. Median CSF amounts of NFL, CHI3L1 and tau were: 995ng/ml, 118ng/ml and 156pg/ml, respectively. NFL levels correlated with number of baseline brain and spinal cord MRI lesions, with the number of brain gadolinium-enhancing lesion and with EDSS at two years and at final follow-up. CHI3L1 correlated with age at onset, IgG Index and with EDSS at two years. Tau correlated with number of baseline brain gadolinium-enhancing MRI lesions, with CSF/serum albumin and with EDSS at final follow-up. Only high NFL values were associated with an increased risk of a relapse (OR: 3.9 CI95: 1.7-8.9; p=0.001) and with a shorter time to a relapse during follow-up (Log-rank test: p=0.002) or to an EDSS of 3 or 4 (Log-rank test: p=0.004 and: p=0.01, respectively).
Conclusion: In patients with CIS, high CSF NFL levels, but not high CHI3L1 or tau levels, were shown to increase the risk of a CDMS diagnosis and were associated with a shorter time to a CDMS diagnosis and to disability milestones during follow-up.
Disclosure:
Diana Ferraro has nothing to disclose in relation to the study.
Anna Maria Simone has nothing to disclose in relation to the study.
Roberta Bedin has nothing to disclose in relation to the study.
Francesca Vitetta has nothing to disclose in relation to the study.
Alessio Canovi has nothing to disclose in relation to the study.
Paolo Frigio Nichelli has nothing to disclose in relation to the study.
Patrizia Sola has nothing to disclose in relation to the study.
Abstract: P594
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Introduction: In Multiple Sclerosis (MS), numerous findings suggest that axonal loss is ultimately responsible for the development of irreversible neurological deficits, which is likely to emerge as a consequence of nerve injury starting in early phases of the disease.
Objective: The aim of our study was to investigate the prognostic role of cerebrospinal fluid (CSF) biomarkers related to axonal damage and glial activation such as neurofilaments (NFL), total-tau and chitinase-3-like 1 (CHI3L1) in patients with Clinically Isolated Syndrome (CIS).
Methods and materials: CSF of patients with CIS was examined for the presence of NFL, total-tau and CHI3L1. The median biomarker level was used as a cut-off to define high or low levels. Outcomes for logistic regression and survival analysis were: diagnosis of Clinically Definite MS (CDMS), defined by a clinical relapse, and disability milestones defined as an EDSS of 3, 4 and 6. Correlations between biomarkers and clinical, MRI and CSF parameters, including IgMOB, were analyzed using Spearman"s rank test (with Bonferroni correction).
Results: We included 101 patients in the study (64F, mean age: 35±10 years). Mean follow-up duration was 72 months (24-109). A relapse occurred in 52% of patients. Median CSF amounts of NFL, CHI3L1 and tau were: 995ng/ml, 118ng/ml and 156pg/ml, respectively. NFL levels correlated with number of baseline brain and spinal cord MRI lesions, with the number of brain gadolinium-enhancing lesion and with EDSS at two years and at final follow-up. CHI3L1 correlated with age at onset, IgG Index and with EDSS at two years. Tau correlated with number of baseline brain gadolinium-enhancing MRI lesions, with CSF/serum albumin and with EDSS at final follow-up. Only high NFL values were associated with an increased risk of a relapse (OR: 3.9 CI95: 1.7-8.9; p=0.001) and with a shorter time to a relapse during follow-up (Log-rank test: p=0.002) or to an EDSS of 3 or 4 (Log-rank test: p=0.004 and: p=0.01, respectively).
Conclusion: In patients with CIS, high CSF NFL levels, but not high CHI3L1 or tau levels, were shown to increase the risk of a CDMS diagnosis and were associated with a shorter time to a CDMS diagnosis and to disability milestones during follow-up.
Disclosure:
Diana Ferraro has nothing to disclose in relation to the study.
Anna Maria Simone has nothing to disclose in relation to the study.
Roberta Bedin has nothing to disclose in relation to the study.
Francesca Vitetta has nothing to disclose in relation to the study.
Alessio Canovi has nothing to disclose in relation to the study.
Paolo Frigio Nichelli has nothing to disclose in relation to the study.
Patrizia Sola has nothing to disclose in relation to the study.