Together with extensive subpial demyelination, the findings of glia limitans damage and of a gradient of neuronal loss and microglia activation from the pial membrane in the cerebral cortex of MS patients with prominent meningeal inflammation (Magliozzi et al., 2010) are compatible with diffusion of large amounts of pro-inflammatory cytokines and cytolytic enzymes produced by CD8+ T cells accumulating in the subarachnoid space and being continuously activated by a locally dysregulated EBV infection (Serafini et al., 2007, 2019; Veroni et al., 2018). This evidence concerns the gene CD8A and Epstein-Barr virus infection.