The findings that both TNF + IFNγ-treated microglial-conditioned medium and glutamate itself could mimic the paranodal changes and that the effects of the cytokines could be inhibited by the noncompetitive NMDA antagonist MK-801 strongly implicate glutamate signaling as a key molecular mediator driving paranodal pathology in the NAWM of the MS brain. The gene discussed is TNF; the disease is myeloid sarcoma.