Nodding syndrome: A key role for sources of nutrition?

Nodding Syndrome (NS) has occurred among severely food-stressed communities in northern Uganda and several other East African populations that, with their forced physical displacement, have resorted to nutritional support from available wild plants and fungi, some of which have neurotoxic potential. Among the latter is an agaric mushroom with an unknown content of hydrazine-generating agaritine, namely Agaricus bingensis, the unusually wide consumption of which may relate to the low serum levels of vitamin B6 in Ugandan NS subjects relative to controls. Hydrazine-related compounds induce patterns of DNA damage that promote neuropathological changes (tauopathy) reminiscent of those associated with established NS. While the cause of this childhood brain disease is unknown, we encourage increased attention to the role of malnutrition and B6 hypovitaminosis in the etiology of this devastating brain disease. •Idiopathic epileptic encephalopathy with tauopathy (Nodding syndrome) impacts East African children•Associated factors include nematode infection, food insecurity, and food use of wild plants and fungi•Food use of hydrazinic fungi induces B6 hypovitaminosis, which may be marked in Nodding syndrome•Vitamin B6 deficiency promotes tau phosphorylation in mouse models of human tauopathy•Hydrazine generates carbon free radicals associated with DNA-damage and neurodegenerative disease•Increased research attention to nutritional practices associated with Nodding syndrome is merited.