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OBJECTIVE: Previous studies assessing seasonal variation of relapse onset in multiple sclerosis have had conflicting results. Small relapse numbers, differing diagnostic criteria, and single region studies limit the generalizability of prior results. The aim of this study was to determine whether there is a temporal variation in onset of relapses in both hemispheres and to determine whether seasonal peak relapse probability varies with latitude. METHODS: The international MSBase Registry was utilized to analyze seasonal relapse onset distribution by hemisphere and latitudinal location. All analyses were weighted for the patient number contributed by each center. A sine regression model was used to model relapse onset and ultraviolet radiation (UVR) seasonality. Linear regression was used to investigate associations of latitude and lag between UVR trough and subsequent relapse peak. RESULTS: A total of 32,762 relapses from 9,811 patients across 30 countries were analyzed. Relapse onset followed an annual cyclical sinusoidal pattern with peaks in early spring and troughs in autumn in both hemispheres. Every 10° of latitude away from the equator was associated with a mean decrease in UVR trough to subsequent relapse peak lag of 28.5 days (95% confidence interval = 3.29-53.71, p = 0.028). INTERPRETATION: We demonstrate for the first time that there is a latitude-dependent relationship between seasonal UVR trough and relapse onset probability peak independent of location-specific UVR levels, with more distal latitude associated with shorter gaps. We confirm prior meta-analyses showing a strong seasonal relapse onset probability variation in the northern hemisphere, and extend this observation to the southern hemisphere.

Signori, Alessio/0000-0001-6289-9144; Sajedi, Seyed Aidin/0000-0002-6704-9787; Jokubaitis, Vilija G./0000-0002-3942-4340; Shaygannejad, Vahid/0000-0002-6226-0161; Oreja-Guevara, Celia/0000-0002-9221-5716; amato, Maria Pia/0000-0003-3325-3760; Lugaresi, Alessandra/0000-0003-2902-5589; Majdinasab, Nastaran/0000-0001-5163-7210; Kalincik, Tomas/0000-0003-3778-1376; Butzkueven, Helmut/0000-0003-3940-8727; van Pesch, Vincent/0000-0003-2885-9004; pucci, eugenio/0000-0001-7606-7330; Petersen, Thor/0000-0001-5633-2600; Prat, Alexandre/0000-0001-6188-0580; Sanchez Menoyo, Jose Luis/0000-0003-2634-8294; Slee, Mark/0000-0003-4323-2453; SORMANI, MARIA PIA/0000-0001-6892-104X; Trojano, Maria/0000-0002-6329-8946 WOS: 000432098100013 PubMed: 28382837 Background: Several natural history studies on primary progressive multiple sclerosis (PPMS) patients detected a consistent heterogeneity in the rate of disability accumulation. Objectives: To identify subgroups of PPMS patients with similar longitudinal trajectories of Expanded Disability Status Scale (EDSS) over time. Methods: All PPMS patients collected within the MSBase registry, who had their first EDSS assessment within 5 years from onset, were included in the analysis. Longitudinal EDSS scores were modeled by a latent class mixed model (LCMM), using a nonlinear function of time from onset. LCMM is an advanced statistical approach that models heterogeneity between patients by classifying them into unobserved groups showing similar characteristics. Results: A total of 853 PPMS (51.7% females) from 24 countries with a mean age at onset of 42.4 years (standard deviation (SD): 10.8 years), a median baseline EDSS of 4 (interquartile range (IQR): 2.5-5.5), and 2.4 years of disease duration (SD: 1.5 years) were included. LCMM detected three different subgroups of patients with a mild (n = 143; 16.8%), moderate (n = 378; 44.3%), or severe (n = 332; 38.9%) disability trajectory. The probability of reaching EDSS 6 at 10 years was 0%, 46.4%, and 81.9% respectively. Conclusion: Applying an LCMM modeling approach to long-term EDSS data, it is possible to identify groups of PPMS patients with different prognosis. MSBase Foundation; Merck SeronoMerck SeronoMerck & Company; BiogenBiogen; Novartis Pharma; Bayer ScheringBayer AG; Sanofi-AventisSanofi-Aventis; BioCSL The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was funded by the MSBase Foundation. The MSBase Foundation is a not-for-profit organization that receives support from Merck Serono, Biogen, Novartis Pharma, Bayer Schering, Sanofi-Aventis and BioCSL. The study was conducted separately and apart from the guidance of the sponsors.

Limited data suggest that multiple sclerosis (MS) in Latin America (LA) could be less severe than in the rest of the world. The objective was to compare the course of MS between LA and other regions. Methods Centers from 18 countries with >20 cases enrolled in the MSBase Registry participated. Patients with MS with a disease duration of >1 year and Results A total of 9610 patients were included. Patients were from: Europe, 6290 (65.6%); North America, 1609 (16.7%); Australia, 1119 (11.6%); and LA, 592 (6.1%). The mean MSSS in patients from LA was 4.47 ± 2.8, 4.53 ± 2.8 in North America, 4.51 ± 2.8 in Europe and 4.49 ± 2.7 in Australia. Mean MSSS in the northern hemisphere was 4.51 ± 1.6 compared to 4.48 ± 1.9 in the southern hemisphere. No differences were found for MSSS among hemispheres ( p = 0.68), regions ( p = 0.96) or countries ( p = 0.50). Conclusions Our analyses did not discover any difference in mean MSSS among patients from different regions, hemispheres or countries.