Nodding syndrome is an epileptic disorder of unknown etiology that occurs in children in East Africa. There is an epidemiological association with Onchocerca volvulus, the parasitic worm that causes onchocerciasis (river blindness), but there is limited evidence that the parasite itself is neuroinvasive. We hypothesized that nodding syndrome may be an autoimmune-mediated disease. Using protein chip methodology, we detected autoantibodies to leiomodin-1 more abundantly in patients with nodding syndrome compared to unaffected controls from the same village. Leiomodin-1 autoantibodies were found in both the sera and cerebrospinal fluid of patients with nodding syndrome. Leiomodin-1 was found to be expressed in mature and developing human neurons in vitro and was localized in mouse brain to the CA3 region of the hippocampus, Purkinje cells in the cerebellum, and cortical neurons, structures that also appear to be affected in patients with nodding syndrome. Antibodies targeting leiomodin-1 were neurotoxic in vitro, and leiomodin-1 antibodies purified from patients with nodding syndrome were cross-reactive with O. volvulus antigens. This study provides initial evidence supporting the hypothesis that nodding syndrome is an autoimmune epileptic disorder caused by molecular mimicry with O. volvulus antigens and suggests that patients may benefit from immunomodulatory therapies.

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Nodding syndrome may be an autoimmune reaction to the parasitic worm Onchocerca volvulus .

Onchocerciasis-Associated Epilepsy, an Additional Reason for Strengthening Onchocerciasis Elimination Programs

Risk factors for epilepsy in Bas-Uélé Province, Democratic Republic of the Congo: a case–control study

A high prevalence of epilepsy is reported in many onchocerciasis-endemic regions. In this paper we discuss recent epidemiological and clinical aspects as well as public health implications of onchocerciasis-associated epilepsy (OAE) and propose a strategy to reduce the burden of disease. OAE probably presents in a variety of clinical manifestations, including the nodding syndrome and the Nakalanga syndrome. The most common clinical presentation, however, is generalized (primarily tonic-clonic) seizures. A characteristic of OAE is the onset of seizures between the ages of 3 and 18 years and clustering in certain families and villages close to rapid-flowing black-fly-infested rivers. A strategy combining active surveillance for epilepsy with early treatment with antiepileptic drugs and prevention of onchocerciasis by increasing the geographical and therapeutic coverage of community-directed treatment with ivermectin (CDTi) may considerably decrease the burden of disease.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/epi4.12054

Onchocerciasis-associated epilepsy: From recent epidemiological and clinical findings to policy implications.

Nakalanga syndrome is a condition that was described in Uganda and various other African countries decades ago. Its features include growth retardation, physical deformities, endocrine dysfunction, mental impairment, and epilepsy, amongst others. Its cause remains obscure. Nodding syndrome is a neurological disorder with some features in common with Nakalanga syndrome, which has been described mainly in Uganda, South Sudan, and Tanzania. It has been considered an encephalopathy affecting children who, besides head nodding attacks, can also present with stunted growth, delayed puberty, and mental impairment, amongst other symptoms. Despite active research over the last years on the pathogenesis of Nodding syndrome, to date, no convincing single cause of Nodding syndrome has been reported. In this review, by means of a thorough literature search, we compare features of both disorders. We conclude that Nakalanga and Nodding syndromes are closely related and may represent the same condition. Our findings may provide new directions in research on the cause underlying this neurological disorder.

/pdf/nakalanga-syndrome-clinical-characteristics-potential-causes-12frd67uks.pdf

Sylvester Onzivua

Papers

Is nodding syndrome an Onchocerca volvulus-induced neuroinflammatory disorder? Uganda's story of research in understanding the disease.