proposed a theory of pathophysiology of DS(a dozen of demons), but namely ischemia, blood-brain barrier dysfunction and neuroinflammation, oxidative stress and neurotoxicity, gemistocytopathy and astrocytic dysfunction, microhemorrhages and methemoglobin deposition, paramagnetic mineral deposition, cytotoxic edema and cellular swelling, myelinolysis, autoimmune and infectious etiology, gliosis, atrophy and structural changes and metabolic theory. Here, HBG2 is linked to ischemia.