Abstract
Nodding syndrome has been suggested to be triggered by neurotoxic leiomodin-1 auto-antibodies cross-reacting with Onchocerca volvulus. Here, we screened serum and CSF samples of persons with nodding syndrome and other forms of onchocerciasis-associated epilepsy (OAE) and African and European controls for leiomodin-1 antibodies by a cell-based assay (CBA) and Western blot (WB). These samples were also investigated for the presence of auto-antibodies cross-reacting with rat brain tissue by immunohistochemistry (IHC). Additionally, IHC was used to detect the leiomodin-1 protein in post-mortem brain samples of persons with OAE who died. Leiomodin-1 antibodies were detected by CBA in 6/52 (12%) and by WB in 23/54 (43%) persons with OAE compared to in 14/61 (23%) (p = 0.113) and 23/54 (43%) (p = 0.479) of controls without epilepsy. Multivariable exact logistic regression did not show an association between O. volvulus infection or epilepsy status and the presence of leiomodin-1. Leiomodin-1 antibodies were not detected in 12 CSF samples from persons with OAE or in 16 CSF samples from persons with acute-onset neurological conditions, as well as not being detected in serum from European controls. Moreover, the leiomodin-1 protein was only detected in capillary walls in post-mortem brain tissues and not in brain cells. IHC on rat brain slides with serum samples from persons with OAE or controls from persons with or without O. volvulus infection revealed no specific staining pattern. In conclusion, our data do not support OAE to be an autoimmune disorder caused by leiomodin-1 antibodies.
Highlights
Nodding syndrome and other forms of onchocerciasis-associated epilepsy (OAE) are characterized by an onset of seizures between the age of 3 and 18 years [1]
Serum samples were obtained from two village matched case–control studies in the DRC to identify risk factors for epilepsy in onchocerciasis-endemic areas, one in Ituri [12] and one in Bas Uéle [13], a clinical trial assessing the effect of ivermectin on the frequency of seizures in O. volvulus-infected persons with epilepsy [14], controls with and without O. volvulus infection from a rapid epidemiological mapping of onchocerciasis (REMO) study in Ituri [15] and a diagnostic study among patients admitted to the Mosango general hospital, in Kwilu Province [16] (Table 1)
cerebrospinal fluid (CSF) samples of cases were obtained from persons with OAE from Maridi, an onchocerciasis-endemic region in South Sudan, and from persons without O. volvulus infection with acute-onset neurological conditions from the Mosango general hospital in Kwilu, DRC (Table 2)
Summary
Nodding syndrome and other forms of onchocerciasis-associated epilepsy (OAE) are characterized by an onset of seizures between the age of 3 and 18 years [1]. The pathological mechanism of this type of epilepsy remains unknown but seems to be dependent on the O. volvulus microfilarial load. This suggests that O. volvulus may directly or indirectly trigger epilepsy. Post-mortem brains of people who died with nodding syndrome and other forms of OAE showed signs of neuro-inflammation and deposition of tau-reactive neurofibrillary tangles and threads, but no evidence of a parasitic infection [2,4]. It has been suggested that OAE is an autoimmune disease caused by cross-reacting antibodies against O. volvulus tropomyosin and human leimodin-1 [5,6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
