We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation.

Chitinase 3-like 1 (CHI3L1) has been proposed as a biomarker associated with the conversion to clinically definite multiple sclerosis in patients with clinically isolated syndromes, based on the finding of increased cerebrospinal fluid CHI3L1 levels in clinically isolated syndrome patients who later converted to multiple sclerosis compared to those who remained as clinically isolated syndrome. Here, we aimed to validate CHI3L1 as a prognostic biomarker in a large cohort of patients with clinically isolated syndrome. This is a longitudinal cohort study of clinically isolated syndrome patients with clinical, magnetic resonance imaging, and cerebrospinal fluid data prospectively acquired. A total of 813 cerebrospinal fluid samples from patients with clinically isolated syndrome were recruited from 15 European multiple sclerosis centres. Cerebrospinal fluid CHI3L1 levels were measured by enzyme-linked immunosorbent assay. Multivariable Cox regression models were used to investigate the association between cerebrospinal fluid CHI3L1 levels and time to conversion to multiple sclerosis and time to reach Expanded Disability Status Scale 3.0. CHI3L1 levels were higher in patients who converted to clinically definite multiple sclerosis compared to patients who continued as clinically isolated syndrome (P = 8.1 × 10(-11)). In the Cox regression analysis, CHI3L1 levels were a risk factor for conversion to multiple sclerosis (hazard ratio = 1.7; P = 1.1 × 10(-5) using Poser criteria; hazard ratio = 1.6; P = 3.7 × 10(-6) for McDonald criteria) independent of other covariates such as brain magnetic resonance imaging abnormalities and presence of cerebrospinal fluid oligoclonal bands, and were the only significant independent risk factor associated with the development of disability (hazard ratio = 3.8; P = 2.5 × 10(-8)). High CHI3L1 levels were associated with shorter time to multiple sclerosis (P = 3.2 × 10(-9) using Poser criteria; P = 5.6 × 10(-11) for McDonald criteria) and more rapid development of disability (P = 1.8 × 10(-10)). These findings validate cerebrospinal fluid CHI3L1 as a biomarker associated with the conversion to multiple sclerosis and development of disability and reinforce the prognostic role of CHI3L1 in patients with clinically isolated syndrome. We propose that determining cerebrospinal fluid chitinase 3-like 1 levels at the time of a clinically isolated syndrome event will help identify those patients with worse disease prognosis.

We compared the calibration of hepatic iron based on R2* relaxometry and liver biopsy with similar studies that have already been published to investigate the transferability of published calibration curves. Materials and Methods: 17 patients with clinically suspected hepatic iron overload (HIO) were enrolled. All patients underwent liver biopsy and MRI of the liver using a multi-echo gradient echo sequence (TR = 200 ms; TE-initial 0.99 ms; Delta-TE 1.41 ms; 12 echos; flip-angle: 20°). R2* parameter maps were analyzed using manually placed regions of interest and R2* values were correlated with liver iron concentration (LIC) obtained from liver biopsy. In addition, the results of our study were compared with 6 similar, already published studies. Results: A linear relationship between R2* and LIC was found. Regression analysis yielded a correlation coefficient of 0.926, a slope of 0.024 (s mg/g) [95 % CI 0.013 -0.024] and an intercept of 0.277 (mg/g) [95 % CI -0.328 -2.49]. We found a significant correlation between the calibration curves obtained from our study in comparison to 3/6 similar studies. The other 3 studies used a different reference standard or sequence parameters which lead to a significant difference for slope, intercept or both in comparison to our data. Conclusion: Calibration curves from published studies that are based on a correlation of liver biopsy and R2* can be used for the estimation of liver iron concentration, although different scanning parameters and post-processing protocols were used. Low initial TEs might be a prerequisite for pooling data for liver iron quantification.

• Hepatic iron overload causes fibrosis, cirrhosis and increases hepatocellular carcinoma risk. • MRI detects iron because of the field heterogeneity generated by haemosiderin. • T2* relaxation is very accurate in diagnosing hepatic iron overload. • Additional information may be obtained by T1 and T2* mapping.