Nodding syndrome in Ugandan children—clinical features, brain imaging and complications: a case series

Abstract

ObjectivesNodding syndrome is a devastating neurological disorder of uncertain aetiology affecting children in Africa. There is no diagnostic test, and risk factors and symptoms that would allow early diagnosis are poorly documented. This study aimed to describe the clinical, electrophysiological and brain imaging (MRI) features and complications of nodding syndrome in Ugandan children.DesignCase series.Participants22 children with nodding syndrome brought to Mulago National Referral Hospital for assessment.Outcome measuresClinical features, physical and functional disabilities, EEG and brain MRI findings and a staging system with a progressive development of symptoms and complications.ResultsThe median age of symptom onset was 6 (range 4–10) years and median duration of symptoms was 8.5 (range 2–11) years. 16 of 22 families reported multiple affected children. Physical manifestations and complications included stunting, wasting, lip changes and gross physical deformities. The bone age was delayed by 2 (range 1–6) years. There was peripheral muscle wasting and progressive generalised wasting. Four children had nodding as the only seizure type; 18 in addition had myoclonic, absence and/or generalised tonic–clonic seizures developing 1–3 years after the onset of illness. Psychiatric manifestations included wandering, aggression, depression and disordered perception. Cognitive assessment in three children demonstrated profound impairment. The EEG was abnormal in all, suggesting symptomatic generalised epilepsy in the majority. There were different degrees of cortical and cerebellar atrophy on brain MRI, but no hippocampal changes. Five stages with worsening physical, EEG and brain imaging features were identified: a prodrome, the development of head nodding and cognitive decline, other seizure types, multiple complications and severe disability.ConclusionsNodding syndrome is a neurological disorder that may be characterised as probably symptomatic generalised epilepsy. Clinical manifestations and complications develop in stages which might be useful in defining treatment and rehabilitation. Studies of risk factors, pathogenesis, management and outcome are urgently needed.

Unravelling the mysterious onchocerciasis—nodding syndrome link: new developments and future challenges

“…It could also be related to genetic susceptibility. In a case series in Uganda, we observed that over 70% of families with children with NS reported multiple affected children (7). In view of these varied possibilities, further studies are of necessity to explain this discrepancy.…”

“…Some cases having NS-like clinical features have been described in a number of onchocerciasis-endemic African countries (1), however it is in Northern Uganda (2) and Southern Sudan (3) were epidemic proportions have been noted. First described by Louise Jilek-Aall in Tanzania in the 1960s (4), NS core clinical features are the atonic seizures manifesting as repetitive head nodding episodes (5), often occurring in association with taking a meal or by cold weather, and may be trailed or heralded by other seizure types, behavioural difficulties and deteriorating cognitive function (5)(6)(7). In addition, patients may progressively develop other features such as growth decline, delayed sexual development, malnutrition, and psychiatric manifestations such as aggression, catatonia and/or disordered perception (7)(8)(9).…”

“…First described by Louise Jilek-Aall in Tanzania in the 1960s (4), NS core clinical features are the atonic seizures manifesting as repetitive head nodding episodes (5), often occurring in association with taking a meal or by cold weather, and may be trailed or heralded by other seizure types, behavioural difficulties and deteriorating cognitive function (5)(6)(7). In addition, patients may progressively develop other features such as growth decline, delayed sexual development, malnutrition, and psychiatric manifestations such as aggression, catatonia and/or disordered perception (7)(8)(9). The consensus case definitions include suspected, probable (further divided in major and minor criteria) and confirmed NS (10).…”

Reducing neurodevelopmental disorders and disability through research and interventions

“…Nodding syndrome is most prevalent in areas with high infection rates of the parasitic worm Onchocerca volvulus -a nematode carried by black fly of the genus Simulium -the bites of which can cause onchocerciasis, a highly prevalent type of blindness caused by infection. Other reports suggest an association between the syndrome and malnutrition 35 . Future research of this S157 syndrome must focus on understanding the aetiology so that it can be prevented, diagnosed early and treated effectively.…”

Setting up a clinical trial for a novel disease: a case study of the Doxycycline for the Treatment of Nodding Syndrome Trial – challenges, enablers and lessons learned

“…Head nodding is the pathognomonic symptom with onset in children aged 3 to 18 years [13]. Subsequent complications include multiple seizure types, cognitive decline, behavioural problems, psychiatric disorders, severe physical disability, malnutrition, and delayed physical growth and sexual development [14]. Symptoms, however, improve with symptomatic treatment [15].…”