Differential Effects of Fingolimod and Natalizumab on Magnetic Resonance Imaging Measures in Relapsing-Remitting Multiple Sclerosis.

Fingolimod and natalizumab are approved disease-modifying drugs in relapsing-remitting multiple sclerosis (RRMS). The two drugs have different modes of action and may therefore influence different aspects of MS-related tissue damage. In this retrospective cohort study, we longitudinally compared patients treated with fingolimod and patients treated with natalizumab by measures based on structural magnetic resonance imaging (MRI). We included patients with RRMS given that two standardized MRI scans under the same drug were available with an interval of at least 6 months both from therapy start to baseline scan and from baseline scan to follow-up scan. After matching for age, baseline and follow-up scans from 93 patients (fingolimod, 48; natalizumab, 45) were investigated. Mean follow-up time was 1.9 years. We determined the number of new white matter lesions as well as thalamic, cortical, and whole-brain atrophy. After scaling for time of the interscan interval, measures were analyzed by group comparisons and, to account for demographic and clinical characteristics, by multiple regression models and a binary logistic regression model. Compared to natalizumab, fingolimod treatment went along with more new white matter lesions (median [interquartile range, IQR] 0.0 [0.0; 0.7] vs. 0.0 [0.0; 0.0] /year; p < 0.01) whereas whole-brain atrophy was lower (median [IQR] 0.2 [0.0; 0.5] vs. 0.5 [0.2; 1.0] %/year; p = 0.01). These significant differences were confirmed by multiple regression models and the binary logistic regression model. In conclusion, our observation is compatible with stronger neuroprotective properties of fingolimod compared to natalizumab.

T1-Weighted Intensity Increase After a Single Administration of a Linear Gadolinium-Based Contrast Agent in Multiple Sclerosis.

PURPOSE: Through analysis of T1-weighted (T1w) images this study investigated gadolinium (Gd) deposition in the brain after administration of a linear (gadopentetic acid) and a cyclic (gadoteric acid) gadolinium-based contrast agent (GBCA) in patients with multiple sclerosis (MS), a disorder frequently requiring magnetic resonance imaging (MRI) scans over years. METHODS: A total of 3233 T1w images (unenhanced with respect to the same scanning session) of 881 MS patients were retrospectively analyzed. After spatial normalization and intensity scaling using a sphere within the pons, differences of all pairs of subsequent scans were calculated and attributed to either linear (n = 2718) or cyclic (n = 385) or no GBCA (n = 130) according to the first scan. Regional analyses were performed, focusing on the dentate nucleus, and whole brain analyses. By 1­sample t­tests, signal intensity increases within conditions were searched for; conditions were compared by 2­sample t­tests. Furthermore, recent hypotheses on the reversibility of GBCA deposition were tested. RESULTS: In the dentate nucleus, a significant increase was observed only after administration of linear GBCA even after a single GBCA administration. This increase differed significantly (p < 0.001) from the other conditions (cyclic and no GBCA). Whole brain analyses revealed T1w signal increases only after administration of linear GBCA within two regions, the dentate nucleus and globus pallidus. Additional analyses did not indicate any decline of Gd deposition in the brain. CONCLUSION: The data point towards Gd deposition in the brain after administration of linear GBCA even after a single administration.

Evidence for a white matter lesion size threshold to support the diagnosis of relapsing remitting multiple sclerosis.

BACKGROUND: The number of white matter lesions (WML) in brain MRI is the most established paraclinical tool to support the diagnosis of multiple sclerosis (MS) and to monitor its course. Diagnostic criteria have stipulated a minimum detectable diameter of 3 mm per WML, although this threshold is not evidence-based. We aimed to provide a rationale for a WML size threshold for three-dimensional MRI sequences at 3 T by comparing patients with relapsing-remitting MS (RRMS) to control subjects (CS). METHODS: We analyzed MR images from two cohorts, obtained at scanners from two different vendors, each comprising patients with RRMS and CS. Both cohorts were examined with FLAIR and T1w sequences. In total, 232 patients with RRMS (Expanded Disability Status Scale: mean = 1.6 ± 1.2; age: mean = 36 ± 10) as well as 116 age- and sex-matched CS were studied. We calculated odds ratios across WML volumes. The WML size threshold, which discriminated best between patients and CS, was estimated with receiver operating characteristic curve analysis. RESULTS: In both cohorts, odds ratios increased continuously with increasing WML volumes, and discriminative power was highest at a WML size threshold corresponding to a diameter of about 3 mm. CONCLUSION: The stipulated WML size threshold of 3 mm in diameter for the diagnostic criteria of MS seems a reasonable choice for three-dimensional MRI sequences at 3 T.