To characterize the epidemiology of multiple sclerosis (MS) in Catalonia, a prospective registry of new cases of MS in Catalonia was set up in 2009 with the participation of 21 hospitals throughout Catalonia. Prevalence and incidence studies based on this population-based registry are being performed. Recently, and in collaboration with the Center of Multiple Sclerosis of Catalonia (Cemcat), we have set up a prospective registry of vaccination in patients with Immuno-Mediated Inflammatory Disease (IMID) who are candidates for biological treatment with the aim of evaluating vaccine immunogenicity and safety that will allow establishing the best vaccination strategy. In addition, we will study the prevalence and impact of comorbidity on Multiple Sclerosis prognosis.

2.1. Search for casual variants of genes associated with MS Lead scientist: Manuel Comabella This line of research seeks to identify causal variants responsible for the MS risk of genes found to be associated with the disease in GWAS by means if deep sequencing. 2.2. To develop dynamic risk scores according to dynamic prognostic models for MS based on clinical, biological and radiological variables Lead scientist: Mar Tintoré In particular: 1. Develop a dynamic risk score based on the evaluation of demographical, clinical, radiological, and biological factors that entail a higher risk of developing a second relapse after a clinically isolated syndrome (CIS), i.e. risk of CDMS, through building models of a dynamic nature. 2. Develop a dynamic risk score based on the evaluation of demographical, clinical, radiological, and biological factors entail a higher risk of progression of disability, as measured by the Expanded Disability Status Scale (EDSS) (Kurtzke Neurology 1983), in people who have suffered a CIS, also through building models of a dynamic nature. Since 1995, patients presenting with a CIS or first attack suggestive of MS are included in a prospective cohort study. One thousand and one hundred CIS patients with a median follow-up of almost 10 years, have been included up to now. Clinical variables (age, gender, topography of the syndrome), radiological variables (number of lesions, number of Barkhof criteria, topography of the lesions, atrophy measures), as well as biological markers (IgG and IgM oligoclonal bands). In a subgroup of patients additional biomarkers (neurofilaments light and heavy chains, fetuin A, GFAP, anti-neurofascin antibodies, anti-glycan panel, chitinase, S1P, etc.) are studied as predictors of conversion to MS and as predictors of disability progression. Mathematical and marginal structural models with different combinations of the variables listed above are investigated. 2.3. Neuropsychological assessment of neurocognitive deficits in patients with multiple sclerosis Lead scientist: Mª Jesús Arévalo Unified neuropsychological assessment is considered necessary to make comparisons between different groups of patients and to draw general conclusions as well as to evolve in the knowledge of cognitive impairment of patients. There is no consensus on protocols for neuropsychological assessment of people with MS in Catalonia and patient evaluations are performed disparately among different hospitals. Neurologists and neuropsychologists from 13 hospitals and patient foundations from Catalonia have held work meetings every two months since July 2012 to seek common work ground. Consensus has been reached as to a common neuropsychological protocol for the assessment of cognitive impairment in MS. We have set up a common database including clinical and neuropsychological variables recorded from interviews with patients introduced into one application. Our work group has been incorporated into the Neuropsychology Section of the Official College of Psychology of Catalonia. 2.4. Upper limbs function and psychometric properties of outcome measures Lead scientist: Núria Filló / Ingrid Galán Upper limbs impairment impacts on daily activities and social participation of persons with MS. Under-recognition of upper limb dysfunction may result in part from limited availability of performance-based and patient self-report measures that are validated for use in MS and that can be readily incorporated into clinical practice for screening and regularly scheduled assessments This line of research seeks to study the psychometric properties of outcome measures for upper limb function in MS. 2.5 EpidEMcat Lead scientist: Susana Otero The Multiple Sclerosis Centre of Catalonia (Cemcat) coordinates a project that aims to characterize the epidemiology of MS in Catalonia. For this purpose, a prospective registry of new cases of MS in Catalonia was set up in 2009 with the participation of 21 hospitals throughout Catalonia. Prevalence and incidence studies based on this population-based registry are being performed. A new research line on co-morbidity and healthcare resource utilization in MS patients is now starting. 2.6 Search of genetic modifiers associated with aggressive and benign disease courses Lead scientist: Manuel Comabella We aim to identify genetic variants that influence the course of the disease by means of exome sequencing of MS patients with divergent clinical courses, i.e. aggressive and benign disease courses. 2.7 Search of biomarkers for multiple sclerosis by RNA, microRNA and exome sequencing approaches Lead scientist: Manuel Comabella Biomarkers are needed in MS to understand the complex and multifactorial heterogeneity of the disease, particularly disease activity biomarkers that may help to distinguish between different MS clinical courses or activity phases of the disease. Here, we aimed to identify disease activity biomarkers in MS by applying RNA, microRNA, and DNA sequencing approaches.