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Nodding Syndrome (NS) is a debilitating neurodegenerative disease plaguing children in sub-Saharan Africa, with the highest prevalence in northern Uganda and South Sudan. The disease is characterized by head nodding, seizures, cognitive impairment, and physical wasting. Despite decades of research, the exact etiology of NS remains unclear. Some evidence suggests a link to Onchocerca volvulus infection, vitamin deficiency, and war-related displacement. Although the etiology remains unclear, effective treatment has been demonstrated with a combination of anticonvulsants, nutritional supplementation, and psychological/social therapy. Comprehensive care has been shown to slow disease progression and even reverse symptoms in some patients. NS presents complex challenges beyond its clinical scope, including stigma, caregiver burden, and political mistrust. Though researching the exact etiology of NS shall continue, sufficient resources should be allocated to implement multidisciplinary care programs and prioritize symptomatic treatment to improve the lives of children and families affected by this devastating condition.