Nodding Syndrome is a brain seizure disorder found in hotspots in sub-Saharan Africa, including Mundri County, Western Equatoria Province, South Sudan, the setting of the proposed epidemiological study. Children typically develop an uncontrollable, rhythmic nodding of the head shortly after beginning to eat their local diet, a phenomenon termed "eating seizures/epilepsy". With time, head nodding may advance to tonic-clonic seizures, wasting, and cognitive deficits, eventually with a fatal outcome. Preliminary studies show that Nodding Syndrome is associated with skin infection with the nematode worm Onchocerca volvulus, the cause of onchocerciasis (River Blindness), but additional local environmental factors must participate because, in other parts of Africa, onchocerciasis is variably associated with epilepsy and rarely with Nodding Syndrome. We hypothesize that plant and/or fungal toxins in food, in the presence or absence of specific nutritional deficiencies, contribute in triggering eating epilepsy in children with Nodding Syndrome. We will test this hypothesis in a cohort of 1000 eligible subjects (males and females, aged 5-21 years), from which we will select 50 subjects with Nodding Syndrome (Cases) and 100 subjects with no history of head nodding or other seizure types (absence, grand mal) (Controls). We will carry out this nested Case:Control study of Nodding Syndrome to examine the relative contributions of exposure to environmental factors associated with epilepsy and other convulsive disorders. These include infectious agents (Onchocerca volvulus), nutritional status (vitamin B6, zinc), plant toxins (cyanogens) and fungal toxins (tremorgens, ergot). These factors will be analyzed in food, blood and urine collected from Cases and Controls and analyzed with respect to Nodding Syndrome. The results will be shared with families, community and health authorities. Recommendations will be made on food preparation and storage to minimize exposure to plant and fungal agents that may trigger seizure activity and thereby advance brain damage. Discovery that plant/fungal toxins can promote seizures in individuals prone to epileptic attacks would have relevance in the prevention and treatment of epileptic disorders worldwide.

Public Health Relevance

Epilepsy affects as many as 50 million people: 80% are estimated to live in low-income countries, notably sub- Saharan Africa where prevalence estimates range up to 58/1000, 70-90% of which do not have access to anticonvulsant therapy. Nodding Syndrome is a newly recognized form of epilepsy that is reportedly increasing in South Sudan, Uganda and Tanzania. If the present hypothesis is supported, namely that plant and fungal toxins in food can contribute to the onset of epileptic attacks in epilepsy-prone individual in South Sudan, diet composition may have great relevance in the prevention and treatment of individuals with epilepsy worldwide.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01NS079276-03
Application #
8709009
Study Section
Special Emphasis Panel (ZNS1)
Program Officer
Fureman, Brandy E
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Neurology
Type
Schools of Medicine
DUNS #
City
Portland
State
OR
Country
United States
Zip Code
97239
Landis, Jesa L; Palmer, Valerie S; Spencer, Peter S (2014) Nodding syndrome in Kitgum District, Uganda: association with conflict and internal displacement. BMJ Open 4:e006195
Spencer, P S; Vandemaele, K; Richer, M et al. (2013) Nodding syndrome in Mundri county, South Sudan: environmental, nutritional and infectious factors. Afr Health Sci 13:183-204
Spencer, P S; Palmer, V S; Jilek-Aall, L (2013) Nodding syndrome: origins and natural history of a longstanding epileptic disorder in sub-Saharan Africa. Afr Health Sci 13:176-82
Spencer, Peter S; Palmer, Valerie S (2012) Interrelationships of undernutrition and neurotoxicity: food for thought and research attention. Neurotoxicology 33:605-16