Active clinical trials for "Nodding Syndrome"

Nodding Syndrome (NS) is a novel form of epilepsy seen predominantly among children aged 5-15 years and characterized by head nodding, progressively worsening seizures, and cognitive impairment. To date, the cause of NS remains unclear. A recent assessment by the Uganda Ministry of Health (MOH), World Health Organization (WHO), and US CDC conducted in Kitgum District in northern Uganda documented that the nodding episodes themselves resulted from atonic seizures, and that the children also exhibit multiple different seizure types, both clinically and electrographically. The investigation also found that there was significantly greater sero-positivity for onchocerciasis among children with NS compared with control children, and demonstrated low serum concentrations of vitamin B6 (pyridoxine) among both cases and controls. Vitamin B6 is involved in neurotransmission and has been an effective treatment of seizures for certain rare type of epileptic syndrome. Children with nodding syndrome in Kitgum have been episodically treated with multivitamins, ivermectin, and anti-epileptic medications including phenobarbital, phenytoin, carbamazepine, and valproate, but the possible beneficial or harmful effects of any of these medications for nodding syndrome has not been systematically assessed, and reports from parents and guardians about apparent effectiveness are varied. The investigators propose a randomized blinded four group clinical trial with crossover design to study the effect and response to therapeutic doses of oral pyridoxine (vitamin B6) and treatment with currently used conventional anti-epileptics including phenytoin and sodium valproate, among children with nodding syndrome.

Nodding syndrome (NS) is a devastating neurologic disorder affecting thousands of children in Africa. A number of toxic, nutritional, infectious, para-infectious and environmental causes have been studied but the only consistent association has been with infection by the parasite Onchocerca volvulus. There is no specific treatment for NS and also for the adult onchocerca. However, antibiotic depletion of the Onchocerca volvulus co-symbiotic bacteria Wolbachia with tetracyclines such as doxycycline results in sterilisation and premature death of the adult worm and marked reductions in dermal microfilaria density. Potentially, such therapy that kills adult onchocerca volvulus may improve the outcome of NS if the association were true.

Nodding Syndrome is an enigmatic neuropsychiatric syndrome affecting children and adolescents mostly in Eastern Africa. The symptoms of Nodding Syndrome and catatonia seem to overlap. The researchers' objectives in this study were to investigate the presence and types of catatonic symptoms in children with Nodding Syndrome and observe their response to one or two doses of lorazepam, the first-line treatment for catatonia.

Background: Childhood epilepsy disorders are particular frequent in the area around Mahenge, southern Tanzania and recent studies have described a novel type of epilepsy with repetitive head nodding episodes and often progressive cognitive dysfunction. Despite the disease affecting thousands in Tanzania, Uganda and South Sudan, etiology and pathogenesis of the disorder termed Nodding Syndrome (NS) is still obscure as the phenotype remains imprecisely described. Epidemiological associations with Onchocerca volvulus and Mansonella spp. were noted at different African sites and remain robust even though no evidence for the presence of O. volvulus in CSF or any previous contact with the CSF was found. Hypothesis: With regard to the complex host immune reaction to O. volvulus, the investigators hypothesize that the immune response against filariae might contribute to NS and epilepsy. The investigators further assume that specific genetic traits might play a role in the pathogenesis of NS. Aims In the present study the investigators aim to examine if and how O. volvulus and/or Mansonella spp. contribute to the pathology of NS/epilepsy and therefore intend to analyze the filarial infection and the host immune response in affected children. To identify inherited traits predisposing for epilepsy, NS or specific immune responses, a genetic workup that includes whole-exome sequencing (WES) is performed. The clinical and EEG characteristics are further defined. Cognitive impairment of people with epilepsy and NS is assessed using the Wechsler Nonverbal Scale of Ability (WNV). Study design: A cross-sectional observational (groups I-III) and a case-control (groups I-V) study recruiting in total 250 patients and controls (I: people with NS, n=50; II: people with epilepsy (PWE) and onchocerciasis, n=50; III: PWE without onchocerciasis, n=50; IV: controls with onchocerciasis but otherwise healthy, n= 50; healthy controls without evidence for onchocerciasis, n= 50) is performed to describe the clinical characteristics in children with NS/epilepsy and to evaluate differences in infection and immune response between groups, respectively. The WNV should be validated in 500 healthy controls to obtain reference data in rural Africa. Summary: In summary, the study aims to elucidate clinical characteristics and the pathogenesis of NS/epilepsy in children of southern Tanzania and role of parasitic infection as a cause for NS/epilepsy.