We have described the above enigmatic disorder of young children in East Africa before; a degenerative brain disease characterised by repetitive nodding movement, an inability to swallow, and eventually global brain failure. Authors of a recent study hypothesised that the disease may be caused by an autoimmune response to the river blindness parasite. They detected auto-antibodies to the parasite more often in cases than age-matched controls from the same village. The antibody attacks various cell markers in the mouse brain among neural networks that are affected in nodding syndrome. But only about half the patients with nodding syndrome exhibited the antibodies. The authors speculate that a number of yet to be identified antibodies may also be involved. I wonder why the disease does not map onto the geography of river blindness, which appears to be much broader than that of nodding syndrome.
So, here is my hypothesis. Remember, a few News Blogs ago, I articulated a ‘three hits hypothesis’ as the cause of many diseases. One example was cytomegalovirus infection, which in the presence of the malaria parasite, and along with genetic predisposition, leads to Burkitt’s lymphoma. So I suspect that exposure to river blindness may be a sensitising event, and propose a search for a further exposure that is more specific to the ‘nodding syndrome belt’ extending from South Sudan, through Uganda to North Tanzania (see Figure).
At the recent CAHRD (Centre for Applied Health Research and Delivery) Consultation in Liverpool, the CLAHRC WM Director was reminded of a curious tropical disease, which he would like to share with readers of our blog.
Children being tied to a tree, or chained in their home while their parents work in the nearby fields. Neglect? Or a sad necessity in some parts of Africa where a little known disease has been devastating communities? A growing number of children in late childhood/early adolescence are being afflicted by nodding disease – suffering from, among other things, seizures and cognitive difficulties. Many parents fear that without taking drastic measures they will return to find their child has wandered into the bush, unlikely to ever return, or has accidentally injured herself. Crucially, the medical community have not been able to pinpoint a definite cause, let alone a cure.
Nodding disease has only been diagnosed in three, non-contiguous rural areas of Africa – western and central South Sudan, southern Tanzania and northern Uganda (Figure 1). Estimates suggest 3,000–8,000 cases have already been reported  – figures higher than recorded Ebola cases. Although nodding disease has only recently come to the attention of the wider medical community (the Center for Disease Control (CDC) began to study the disease in 2009), it first emerged in the 1960s.
Its name comes from the characteristic symptom of the disease – an uncontrollable nodding of the head that is a direct result of seizures causing a brief lapse in muscle tone. These seizures are of various severities, and often begin when the child eats or the ambient temperature drops, generally not stopping until the child has finished eating or has warmed up. In latter stages of the disease this can lead to severe malnutrition as children are no longer able to eat. (Curiously it has been reported that no seizures occur when an affected child is given an unfamiliar food, such as chocolate.) Over time the symptoms worsen – from a few times a week, the nodding episodes begin to happen daily, then every few hours, and are followed by increasingly worse bouts of confusion, lethargy and convulsions. Eventually there is permanent and completely stunted growth of the body and the brain, leading to mental retardation. MRI scans of affected children have shown significant brain atrophy and damage to the hippocampus and glial cells.
There is currently no cure, with treatment confined to managing the symptoms. Anticonvulsants, such as sodium valproate, have been administered in an attempt to control the nodding, and although there has been some indication that this has helped, with children regaining some degree of normality – once again being able to talk or walk – the underlying damage remains and the condition continues to worsen.
A number of causes have been looked into, and subsequently ruled out – exposure to wartime chemicals, consumption of meat from monkeys, ingestion of toxic substances (e.g. coated seeds distributed by relief agencies that were meant for planting), or contaminated relief foods.
A potential cause that is still being considered is a possible autoimmune response linked to infection with microfilaria parasites – the age range of sufferers (5-15 years old), is similar to certain parasitic infections and epilepsy syndromes. Originally researchers thought it could be linked to Onchocerca volvulus, a parasitic worm that is carried by black fly. Victims have generally been concentrated near fast-flowing rivers, such as the Yei in South Sudan, which are home to black fly. Further, infection with O. volvulus is prevalent in areas of outbreak, with 93% of sufferers in some areas estimated to harbour the parasite, a figure significantly higher than those without the disease.O. volvulus also causes river blindness (onchocerciasis), which has been tentatively linked to other forms of epilepsy, as well as stunted growth. However, O. volvulus is very common in many areas which have not seen the disease, and a study in Tanzania found no significantly elevated levels of antibodies in the cerebrospinal fluid of patients. Perhaps the cause lies in a closely-related or variant strain of the parasite, or there is an unidentified co-factor that is needed in combination with O. volvulus infection. A second potential cause that is being looked into is linked to malnutrition (many of the affected populations have recently been displaced, or are amongst the poorest in the region) and/or vitamin B6 (pyridoxine) deficiency. A trial administering vitamin B6 to patients has been set up to study this possibility.
Although the local governments are trying to help – the Uganda Ministry of Health allocated $1.4 million of their budget to mount a response, and deployed teams of health workers to affected areas to distribute anticonvulsants  – outside donors and non-governmental organisations are needed if there is to be a solution any time soon.
— Peter Chilton, CLAHRC WM Research Associate
Dowell SF, Sejvar JJ, Riek L, et al. Nodding Syndrome. Emerg Infect Dis. 2013; 19(9): 1374-84.