Disability Progression in Multiple Sclerosis: Determinants, Pathophysiology, and Global Health Impact

This study aims to identify clinical, biological, imaging, and environmental factors that predict the progression and severity of Multiple Sclerosis (MS). We will establish a prospective, highly phenotyped cohort of patients diagnosed with MS according to the 2024 criteria, regardless of disease form or stage.

We hypothesize that combining neurological, vascular, metabolic, neuropsychological, environmental, and imaging data (from the central nervous system and the eye) will improve the identification of markers associated with MS progression. This integrative approach will help clarify the respective roles of inflammation, vascular dysfunction, myelin repair, and neurodegeneration in disability accumulation.

The study will also evaluate the impact of MS, disability, and treatments on patients' physical, mental, and social health, as defined by the World Health Organization (WHO). These results are expected to support personalized patient management and identify modifiable risk factors to reduce disability and inform future therapeutic strategies.

The primary objective is to identify factors that worsen neurological disability in MS patients, including disease-related, comorbidity, and environmental factors. The main outcome measure is time to confirmed disability accumulation (CDA), defined as an increase in the EDSS (Expanded Disability Status Scale) score confirmed after at least 3 months.

This single-center, 5-year prospective cohort study will be conducted at Hôpital Fondation Adolphe de Rothschild (Paris, France), with annual visits. A linkage with national health data (SNDS) will be established for both MS patients and a matched control group (5:1 ratio).

Additional research procedures include:

Ophthalmologic exams (OCT, angio-OCT, fundus photography, pupillometry) at baseline, year 1, 3, and 5.

Brain MRI with additional non-contrast research sequences (annual).

Clinical assessments including arterial stiffness and hearing tests.

Blood sampling (up to 40 mL) for biomarker analyses and long-term biobanking (25 years).

Lumbar puncture if clinically indicated at baseline (with extra samples for research).

Physical activity and circadian rhythm monitoring using a wrist accelerometer for 9 consecutive days.

Standardized questionnaires assessing quality of life, education, and social/professional impact.

Inclusion criteria:

Age ≥ 18 years

Diagnosis of MS according to 2024 criteria