Although the levels of TNFR1 and TNFR2 protein were not significantly different between F+ SPMS and F− SPMS cases, our further analysis of the downstream pathways suggests that the increased pro-inflammatory reactions in the MS meninges, indicated by increased levels in patient CSF [35], direct soluble TNF/TNFR1 interaction towards RIPK1/RIPK3/MLKL-mediated necroptosis, rather than caspase 8-dependent apoptosis or IKK/NFkB-dependent cell survival. This evidence concerns the gene TNFRSF1B and myeloid sarcoma.