We will design small substudies as ideas arise in the course of our work that are pertinent to the theme of the pathophysiology of MS (or of diseases that share features with MS). If a hypothesis testing sub-study leads to results of interest and if a larger population is necessary to reach statistical significance, a separate protocol will be submitted with a priori hypotheses, specific study design and power analysis adapted from the pilot or exploratory substudies performed in the present protocol.