Round Table Challenges in exposure and outcome definition in neuroepidemiology : the case of vitamin D and multiple sclerosis

4 Abstract For several neurological diseases, the relationship between onset of pathological changes and development of clinical symptoms is unclear. This makes it difficult to define ‘disease onset’ against which to evaluate potential risk factors, and increases the risk that associations are due to reverse causality. Equally it may be difficult to define the exposure of interest, for example, differentiating the effects of sun exposure from those of vitamin D status. Here it is important to consider the relevant time course of exposure and to critically evaluate the evidence linking it to the outcome of interest. Intervention studies provide a means to distinguish the contributions of closely related exposures, and interim markers of disease, such as radiological changes, may be needed to identify disease onset.