So far, unequivocal risk factors have not been found for NS apart from its geographical confinement in Northern Uganda and neighbouring areas in South Sudan, impoverished areas that have endured devastating war conflicts during the last decade that has taking an enormous toll on its inhabitants. NS has been associated with onchocerciasis, and infection with onchocerca volvulus yet a clear pathophysiological mechanism has not been elucidated.
The isolation of a single etiology of NS may be elusive. History shows that, with a few exceptions such as neurosyphilis, most neuropsychiatric entities have defied attempts of verification and substantiation by pathogenetical or etiological evidence, through epidemiological, toxicological, and biomedical methods.
We recommend that the aftermath of traumatic events and deprivation should be assessed as risk factors for NS conjointly with a host of other plausible medical conditions. A similar panorama of medical and psychological risk factors has been suggested for pediatric catatonia [17,18].
Nodding Syndrome is a Dead Ringer of Pediatric Catatonia
NS may be a form of pediatric catatonia caused by a number of risk factors including medical conditions that are yet to be determined and the legacy of personal, familial, and community trauma predisposing vulnerable youth to a withdrawal condition with associated psychomotor and autonomic abnormalities rendering a clinical diagnosis of catatonia in most cases of NS.
Pediatric catatonia is treatable and exquisitely responsive to benzodiazepines and electroconvulsive therapy. Any associated conditions may require additional treatment.
This hypothesis should be investigated vigorously and the number of NS patients that meet criteria of catatonia should be assessed by applying standardized criteria of catatonia in NS patients and conducting a catatonia test  using test doses of lorazepam, another benzodiazepine such as alprazolam, or zolpidem , a nonbenzodiazepine GABA-an agonist. A positive catatonia test, i.e., when a significant reduction of symptoms follows acute administration of these agents, verifies the presence of catatonia. This would guide further steps towards sustained relief and remission of symptoms using treatment algorithms that have shown beneficial results in other pediatric cases with catatonia [6,19].
A trial of Benzodiazepines is Warranted
Despite the lack of etiological and pathophysiological knowledge of NS, the identification of clinical syndromes provides targets for treatment and symptomatic relief. Anticonvulsant medications can be used for epilepsy. Antipsychotic medications alleviate symptoms of autism but carry a risk of exacerbating catatonia and precipitating neuroleptic malignant syndrome. Benzodiazepines as first-line treatment remit catatonia in most instances. In refractory cases, electroconvulsive therapy is used.
Controlled treatment studies in NS are underway. The use of anticonvulsant medications, especially valproic acid, has been supported but preliminary observations suggest its effects to be limited. Trials of antipsychotics and benzodiazepines have not been done yet. There is less evidence of efficacy of non-benzodiazepine anticonvulsants such as valproic acid , carbamazepine  or topiramate  in alleviating catatonia compared to benzodiazepines.
A trial of benzodiazepines (or zolpidem) in children and adolescents with NS who meet criteria for catatonia is warranted given the clinical overlap between NS and pediatric catatonia. Pediatric use of benzodiazepines is generally deemed safe and effective, and may also improve associated seizures.