Nodding syndrome: recent insights into etiology, pathophysiology, and treatment

Abstract

Nodding syndrome is an enigmatic neuropsychiatric and epileptiform disorder associated with psychomotor, mental, and physical growth retardation. The disorder affects otherwise previously normal children aged 3–18 years, with a slight preponderance for the male child. Nodding syndrome has been described in rural regions of some low-income countries in sub-Saharan Africa including northern Uganda, South Sudan, and a mountainous region of southern Tanzania. The cause of the disorder has hitherto eluded scientists. Neuroimaging studies show involvement of the nervous system with associated severe cortical atrophy in the affected children. The affected communities have generated a number of perceived causes including some conspiracy theories related to intentional poisoning of water sources and foods, and causes related to fumes and chemicals from ammunitions used during civil wars in the affected regions. From biomedical perspectives, the treatment of the affected children is geared towards symptoms control and rehabilitation. There is evidence that seizures and behavioral problems including wandering and episodes of aggressions are controllable with anticonvulsants, especially sodium valproate and antipsychotics. No treatments have proven effective in reversing the course of the disorder, and cure remains a distant goal. Community members have used indigenous medicines, cleansing rituals, and prayer interventions, but have not perceived any reasonable improvements. A randomized controlled clinical trial is ongoing in northern Uganda to test the efficacy and effectiveness of doxycycline in the treatment of nodding syndrome. The hypothesis underlying the doxycycline trial underscores the role of antigenic mimicry: that antibodies generated against an antigen of a microorganism that resides inside the black fly-transmitted parasite, Onchocerca volvulus becomes directed against nervous tissue in the brain. This paper reviews some of the recent advances in researches on the etiologies, pathophysiology, and treatment of nodding syndrome.

Household poverty, schooling, stigma and quality of life in adolescents with epilepsy in rural Uganda

“…In agreement with our findings, nearly half of the children under fifteen years of age presenting with seizures in a health facility-based survey in rural Western Uganda were not attending school [27]. Similarly, another observational study among schoolgoing children in Kitgum showed that nodding syndrome, an epileptic disorder of childhood-onset in onchocerciasis endemic regions in Africa [44][45][46][47] was significantly associated with school dropout [48]. Further, individuals with epilepsy may have poorer academic achievement due to absenteeism or their inability to attend school.…”

Some New and Unexpected Tauopathies in Movement Disorders

“…Theories include intentional poisoning of water sources, exposure to chemicals, neurotropic viruses, and parainfectious autoimmune disorders. 34 Recent neuropathologic examination of 5 patients who had died of NS showed neuronal tau deposition (pretangles and neuropil threads) predominantly in the cortical and brainstem regions, with relative sparing of basal ganglia. 35 However, epilepsy is one of the clinical features of NS, and given that tau pathology is well known to occur in long-standing epileptics, 36 it could be that the observed changes are secondary to poorly controlled seizures.…”

The tau hypothesis of nodding syndrome in Africa

“…NS usually begins with spells of head bobbing [ 4 – 7 ], which have now been determined to represent atonic seizures. Clinical presentation with nodding is typically at 5 to 15 years of age with the progression to grand mal seizures within months or years of the initial presentation.…”