Nodding Syndrome – a critical note and a plea to join forces

In August 2012, a meeting on Nodding Disease/Nodding Syndrome/Head Nodding was organised by the WHO in Kampala, Uganda. Different perceptions, impressions, scientific results and even speculative discussions on a presumed new disease entity were discussed. So far, it seems to only occur in eastern Africa, that is Tanzania, Uganda and South Sudan, although anecdotal reports have emerged from Liberia, Democratic Republic of Congo and Cameroon. At the meeting in Kampala, experts devised a clear definition of the disease, calling it Nodding Syndrome. As the publication of a WHO report and potential management guidelines (WHO 2012; Idro et al. 2013a), many more scientists have tried to describe or define the disease and to adapt its appearance to regional or local concepts. The resulting ideas and novel descriptions of pathogenic mechanisms give rise to discussions and controversies (van der Waals et al. 1983; Prischich et al. 2008; Winkler et al. 2008, 2010, 2013, 2014; Kaiser et al. 2009; Nyungura et al. 2011; Tumwine et al. 2012; Dowell et al. 2013; Foltz et al. 2013; Idro et al. 2013b; Sejvar et al. 2013; Spencer et al. 2013a,b; Colebunders et al. 2014; Iyengar et al. 2014). A syndrome in which nodding of the head occured as the major feature in previously healthy children or adolescents, triggered by cold temperatures, eating or other external factors, in some cases accompanied by cognitive impairment and/or progressive cognitive decline, in others evolving into tonic clonic generalised epilepsy, was described in the early 1960s in the Mahenge area of central/southern Tanzania (Aall-Jilek 1965; Jilek & Jilek-Aall 1970; Aall 1992; Spencer et al. 2013a). Before that, a non-specified disease, called Nakalanga Syndrome with similar signs/symptoms, was reported (Raper & Ladkin 1950). Perhaps it was the same as, or at least similar to, Nodding Syndrome (Gottlob et al. 1990; Ovuga et al. 1992; Doummar et al. 1998). Several case–control studies identified inconsistent to modest associations with infectious agents, mainly Onchocerca volvulus. Although onchocerciasis was more prevalent in children with Nodding Syndrome in three study locations in South Sudan and one in northern Uganda, it was not possible to state whether infection preceded or followed Nodding Syndrome onset. In another study location in South Sudan, such an association was not found (Centers for Disease Control and Prevention (CDC) 2012; Tumwine et al. 2012; Foltz et al. 2013). Testing for other pathogens (viral and bacterial), toxins, vitamin and micronutrient deficiencies, genetic causes and auto-immune antibodies has so far yielded negative results (Tumwine et al. 2012; Dowell et al. 2013; Foltz et al. 2013; Sejvar et al. 2013; Spencer et al. 2013b; Dietmann et al. 2014). Cerebrospinal fluid studies and magnetic resonance imaging of the brain did not render any specific results (Winkler et al. 2008, 2013; K€ onig et al. 2010; Idro et al. 2013b; Sejvar et al. 2013). Electroencephalography was abnormal or even markedly abnormal, showing a typical 2.5 spike wave pattern when recorded immediately after a nodding episode in two cases and electrical depression during nodding episodes in two other children (Sejvar et al. 2013; Winkler et al. 2014). The epidemiology of Nodding Syndrome is of great scientific interest. In central and southern Tanzania (Mahenge area), Nodding Syndrome seems to be endemic (Winkler et al. 2008, 2014), whereas in northern Uganda and South Sudan, it seems to be epidemic. In northern Uganda, incidence rates reached an all-time high between 2006 and 2012 (Idro et al. 2013b; Mitchell et al. 2013; Sejvar et al. 2013), and then dropped to almost zero new cases per week or month after the publication of the WHO Nodding Syndrome definition (Weekly Epidemiological Bulletin, Ministry of Health Uganda 2014). The first community-based study on prevalence of Nodding Syndrome, conducted in northern Uganda in March 2013, found 6.8 probable cases of Nodding Syndrome per 1000 children, giving for the first time a precise figure instead of the