The Italian Multiple Sclerosis and Related Disorders Register (Registro Italiano Sclerosi Multipla e Patologie Correlate - RISM) is an observational cohort study that aims to create an organised multicentre structure to collect data of all patients with multiple sclerosis (MS) followed in the various MS clinical centers in Italy (a near population-level).

RISM is promoted and funded by the Italian Multiple Sclerosis Foundation (Fondazione Italiana Sclerosi Multipla - FISM ETS). In 2014, FISM and the University of Bari constituted a "Research Unit", which manages the project and acts on behalf of the participating MS clinical centers. The governance of RISM includes an Executive Committee (chaired by FISM and the University of Bari) with administrative and organisational roles and a Scientific Committee, which oversees the scientific initiatives, promotes specific strategic projects, and approves requests for access to centralised data for further research projects.

RISM aims to address high-priority research areas pertaining to: public healthcare area (quality of care, health optimisation such as economic optimisation, social and welfare information, access to healthcare treatments and healthcare services) and research area (epidemiology, rare MS disease forms such as primary progressive MS, pediatric MS as well as early and preclinical/subclinical disease stages represented by clinically isolated syndromes and radiologically isolated syndromes, treatment optimisation such as prognostic factors and predictive models of disease course, adherence to treatments, treatment efficacy, and safety).

RISM also includes patients with Neuromyelitis Optica Spectrum Disorders (NMOSD) and Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease (MOGAD).

In 2000, the Italian collection of MS clinical data started at different Italian MS centres in the framework of the Italian Multiple Sclerosis Database Network (MSDN). At the end of 2014, the Italian Multiple Sclerosis and Related Disorders Register (RISM) was set up to create a national data source collecting demographic and clinical data on people with multiple sclerosis. Currently, data are collected through a web-based system - the RISM-App - developed ad hoc for the study. Each centre can enter the data after identification through a personalised password. In RISM, each patient is assigned to a specific centre and has a unique valid code identifier, obtained through the patient encrypted fiscal code.

The RISM-App includes 1,475 variables and is organised into sections and subsections. According to the current clinical practice, the following information is requested in the RISM-App: identification/personal data, onset and diagnosis (anamnesis), follow-up visits (EDSS, safety, and relapses), adverse events (clinical events), treatments, non-pharmacological treatments, risk assessment, pregnancies, COVID-19, co-morbidity, familiar anamnesis, tests and scales, laboratory exams, magnetic resonance, liquor, evoked potentials, EEG, ECG, blood pressure, eye examination, optical computerised tomography.

To harmonise data collection, the RISM-App integrates several standardised databases, including FarmaDati, MedDRA, ICD-9-CM, and EUROCAT (for congenital anomalies). Continuous data monitoring is ensured through regular communication with centres, biannual ad hoc reports providing both overall and centre-specific quality and descriptive indicators, data verification requests, and training on standardised data collection procedures. In addition, a set of built-in validation checks - such as consistency between date of birth, diagnosis, first visit, and treatment - is implemented in the RISM-App to prevent conflicting entries.

Inclusion Criteria:

• Clinical diagnosis of definite or probable multiple sclerosis
• Clinical diagnosis of CIS or RIS
• Clinical diagnosis of NMOSD or MOGAD
• Patient is able to understand and sign the informed consent to participate in the study

Exclusion Criteria:

• None

All the Italian clinical centers specialized in multiple sclerosis and related disorders who participate in RISM invite their patients to be part of the study. Only subjects with multiple sclerosis (including CIS and RIS), NMOSD or MOGAD are enrolled in RISM.