The etiology of multiple sclerosis is still elusive despite an extended patchwork of mechanistic events has been accumulated. In this article, are tentatively identified from scattered literature sources new factors that may link well known characteristic of MS such as the central alteration of BBR selectivity, its association with EBV status and its biased distribution of the globe more comprehensively. The hypothesis proposes that the concomitant important rise in some heterophilic antibodies (anti Neu5Gc) which activate BBB endothelial cells and in the frequency of anti EBV committed T cells and of memory B infected cells with EBV contemporary to EBV infection play a major role in MS etiology. In addition, the hypothesis proposes new possible explanations for the elevated risk of MS in specific geographical area.