Is nodding syndrome an Onchocerca volvulus-induced neuroinflammatory disorder? Uganda's story of research in understanding the disease

•Nodding syndrome is a complex epilepsy disorder characterized by atonic seizures.•It is associated with multiple physical and functional disabilities and psychiatric manifestations.•There is a consistent epidemiological association with infection by the parasite Onchocerca volvulus.•Preliminary studies suggest it is a neuroinflammatory disorder induced by antibodies to O. volvulus cross-reacting with neuron proteins.•Studies to confirm these observations and a treatment trial are planned for 2016.

SummaryNodding syndrome is a devastating neurological disorder, mostly affecting children in eastern Africa. An estimated 10 000 children are affected. Uganda, one of the most affected countries, set out to systematically investigate the disease and develop interventions for it. On December 21, 2015, the Ministry of Health held a meeting with community leaders from the affected areas to disseminate the results of the investigations made to date. This article summarizes the presentation and shares the story of studies into this peculiar disease. It also shares the results of preliminary studies on its pathogenesis and puts into perspective an upcoming treatment intervention. Clinical and electrophysiological studies have demonstrated nodding syndrome to be a complex epilepsy disorder. A definitive aetiological agent has not been established, but in agreement with other affected countries, a consistent epidemiological association has been demonstrated with infection by Onchocerca volvulus. Preliminary studies of its pathogenesis suggest that nodding syndrome may be a neuroinflammatory disorder, possibly induced by antibodies to O. volvulus cross-reacting with neuron proteins. Histological examination of post-mortem brains has shown some yet to be characterized polarizable material in the majority of specimens. Studies to confirm these observations and a clinical trial are planned for 2016.