Nodding Syndromein South Sudan
Nodding Syndromein South Sudan
Abstract and Commentary
By Anna Mrelashvili and Phillip R. Fischer MD, DTM&H
Dr. Mrelashvili is a resident and Dr. Fischer is Professor of Pediatrics in the Department of Pediatric and Adolescent Medicine at Mayo Clinic, Rochester, MN.
Neither Dr. Mrelashvili nor Dr. Fischer reports financial relationships to this field of study.
Synopsis: "Nodding syndrome" is a puzzling and poorly characterized neurologic condition of children characterized by progressive eating-related seizures with nodding of the head and encephalopathy. It mostly occurs in South Sudan, Uganda, and Tanzania.
Source:Centers for Disease Control and Prevention. "Nodding Syndrome — South Sudan, 2011." MMWR 2012; 61:52-54.
In May 2011, an emergency-response team from the US Centers for Disease Control and Prevention (CDC) traveled to South Sudan, attempting to assist in the investigation of the recent geographic clustering of an illness, suspected to be the nodding syndrome. A descriptive study was conducted in two different communities (Maridi and Witto), enrolling a total of 38 matched case-control pairs. While assessing various risk factors, researchers also tried to identify any possible link between the condition and infection with a nematode worm, Onchocerca volvulus.
Although current infection with the O. volvulus was more prevalent among case-patients in Maridi (88% among case-patients and 44% among controls, P < 0.001), no such difference was found in Witto (54% among case-patients and 54% among controls).
Nodding syndrome was not found to be associated with other risk factors, including exposure to munitions, parents' occupations, and various demographic characteristics. Additional analyses of case-series data and additional investigations of exposures related to nutrition are under way. Results of laboratory testing (for vitamins A, B6, and B12; Onchocerca antibodies; heavy metals; and genetic markers) are pending.
Commentary
Nodding syndrome or disease was recognized as a specific entity around the turn of the millennium in what is now South Sudan.1 Retrospectively, however, a similar sort of seizure disorder was reported in southern Tanzania in the 1960s.2,3 Affected children are also often identified in northern Uganda. The condition typically begins between the ages of 5 and 15 years, and the disease is slowly progressive, impairing physical growth and cognitive development and eventually leading to death.4
The hallmark of the condition, head nodding, is often brought on by eating [especially beans and starch1] or sometimes by cold exposure and occurs as a sudden loss of neck muscle tone and, possibly, upper extremity tone. Many patients go on to develop generalized seizures that are incompletely controlled with anti-epileptic therapy. As the initial events often occur while the child is sitting before a dish of food, children stop eating adequately, become undernourished, and are often mentally and physically stunted. Affected individuals are more prone to falls and injuries, often bound to their homes, isolated from the rest of the village. They often seem dull and uninterested in their surroundings, presumably due to encephalopathic changes.
An association between O. volvulus infection and nodding syndrome has been identified; however, causality still remains unclear. In Tanzania, more than half of the patients with head nodding seizures had glial lesions on magnetic resonance imaging, and the presence of such lesions was associated with positive O. volvulus results obtained on PCR testing of skin and/or the CSF. However, they were negative in these patients and there was no major abnormality in other CSF parameters, including the antibody index for O. volvulus.2 Last autumn, the CDC also sent scientists to Uganda to investigate more than 1,000 cases of nodding syndrome that had occurred there. Although the results have yet to be published, agency insiders say the association with the river blindness parasite is similar to that reported from the first South Sudanese community, with a positive association between the worm and the syndrome.5
The exact causes and triggers of nodding syndrome remain unclear. Nonetheless, the postulated association with Onchocerca infections can prompt renewed efforts for mass treatment with ivermectin in O. volvulus-endemic areas. At the same time, health care infrastructures should be reinforced so that children with seizures and/or encephalopathic changes can gain ready access to good medical care. The CDC is moving ahead with interventional drug trials, assessing the effectiveness of standard anti-seizure drugs as well as high doses of pyridoxine.5 Further studies and research data are pending, and multi-national collaboration between researchers is crucial in order to uncover the cause of this mystery illness, help affected children, and prevent future cases.
References
- Lacey M. Nodding disease: mystery of southern Sudan. Lancet Neurology 2003;2:714.
- Winkler AS, et al. The head nodding syndrome—clinical classification and possible causes. Epilepsia 2008;49:2008–15.
- Winkler AS, et al. Clinical characteristics of people with head nodding in southern Tanzania. Trop Doct 2010;40:173-175.
- Wadman M. African outbreak stumps experts. Nature 2011;475-148-149.
- Williams SCP. Nodding syndrome leaves baffled scientists shaking their heads. Nature Medicine 2012;18:334.
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