Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system and the most common cause of non-traumatic neurological disability in young adults. Magnetic resonance imaging (MRI) is the most important paraclinical investigation used in the diagnosis and monitoring of the disease. In the past years, spinal cord MRI has improved significantly and has become an important part of the diagnostic workup for MS. Presently, follow-up imaging of the spinal cord is only performed when spinal cord related symptoms occur. However, there is increasing evidence that asymptomatic spinal cord lesions can occur, independently of brain disease activity. Despite these cord lesions being asymptomatic, they impact disability accrual in the long term. Although this might be an imaging marker for monitoring and treatment, it is not yet applied in the clinical setting.

The investigators will prospectively collect spinal cord MRI data (in addition to routine brain MRI), and blood-based biomarkers (plus cerebral spinal fluid markers, if available), in recently diagnosed MS patients, to address the following research questions:

• What is the incidence of asymptomatic spinal cord lesions in patients commencing DMT?
• And in the absence of radiological progression on brain imaging, how frequently do asymptomatic spinal cord lesions occur? In other words, how often is disease activity solely proven by spinal cord MRI and what is the number-needed-to-scan?
• A secondary objective is to investigate which patients are predisposed to developing new spinal cord lesions during follow-up in the early stages of the disease. For this question, factors such as cerebrospinal fluid (CSF) profiles, B-cell composition in blood, soluble blood markers, and clinical features will be focused on.

The investigators aim to prospectively collect spinal cord MRI data (in addition to routine brain MRI), in recently diagnosed MS patients, to address the following research questions:

What is the incidence of asymptomatic spinal cord lesions in patients commencing DMT?

And in the absence of radiological progression on brain imaging, how frequently do asymptomatic spinal cord lesions occur? In other words, how often is disease activity solely proven by spinal cord MRI and what is the number-needed-to-scan?

1. What is the incidence of asymptomatic spinal cord lesions in patients commencing DMT?
2. In the absence of radiological progression on brain imaging, how frequently do asymptomatic spinal cord lesions occur? In other words, how often is disease activity solely proven by spinal cord MRI and what is the number-needed-to-scan?

Hypothesis: The hypothesis is that the detected incidence of asymptomatic cord lesions independent of brain MRI activity will be higher than the approximately 10% per year reported in retrospective studies.

A secondary objective is to investigate which patients are predisposed to developing new spinal cord lesions during follow-up in the early stages of the disease. For this question, factors such as cerebrospinal fluid (CSF) profiles, B-cell composition in blood, soluble blood markers, and clinical features will be focused on.

2. What subgroups are prone to new spinal cord lesions at follow-up in early disease? In particular:

• Can disease activity on spinal cord MRI be predicted by baseline CSF profiles, i.e. is there an association between intrathecal IgM/IgG synthesis, number of oligoclonal bands and/or kappa free light chains at baseline and formation of new spinal cord lesions at follow-up?
• Is there an association between low number of transitional B cells in blood at baseline and formation of new spinal cord lesions?
• Is there an association between soluble blood markers and other blood biomarkers at baseline and formation of new spinal cord lesions at follow-up?
• What subtype of clinical presentation or certain physical complaints are associated with new spinal cord lesions during follow-up?

Hypothesis: The hypothesis is that more new spinal cord lesions occur in patients with CSF profile positive for intrathecal IgM, IgG synthesis and higher number oligoclonal bands, a low number of transitional B cells at baseline, a low number of CD56bright NK cells, high levels of activating sICPs and low levels of inhibitory sICPs at baseline, and/or a presenting syndrome of optic neuritis or myelitis.

To investigate the research questions, MS patients will be enrolled from five Dutch MS centres in an observational study with a follow-up of 27 months. Patients will be asked to participate when they are being screened for DMT initiation and given 7 days to consider. Informed consent will be obtained by a doctor, part of the research team. Next to routine regular follow-up with brain MRI and outpatient clinic visits, patients will receive spinal cord MRI and a structured registration of clinical parameters and collection of blood samples. Towards the end of follow-up, it will be evaluated whether starting an extension study is of additional value.

Inclusion Criteria:

• Patients between 18 and 65 years old
• Patients diagnosed with relapsing-remitting MS (≤5 years of first clinical event)
• Treatment-naïve patients starting (currently in the Netherlands approved) DMT

Exclusion Criteria:

• Patients who presented first clinical event more than five years ago
• Patients who have already started DMT
• Patients who are incapable of giving informed consent
• Patients who are unable to undergo local MRI scan, due to for instance
• Physical problems, for instance due to size/obesity (not fitting in regular MRI scanner), not being able to lie flat for extended periods of time (e.g. due to pain, shortness of breath)
• Due to claustrophobia
• Patients who have contraindications for MRI scan, for instance
• Due to MRI-unsafe or non-compatible implanted material/devices, such as pacemakers or ocular metal splinters
• Patients who are pregnant at inclusion

Population of treatment-naïve relapsing-remitting MS patients, early in the disease course (within 5 years of first clinical event) between 18 - 65 years old, where a first DMT is initiated.