Abstract
ObjectiveNodding syndrome is a poorly understood epileptic encephalopathy characterized by a unique seizure type—head nodding—and associated with Onchocerca volvulus infection. We hypothesized that altered immune activation in the cerebrospinal fluid (CSF) and plasma of children with nodding syndrome may yield insights into the pathophysiology and progression of this seizure disorder.MethodWe conducted a case‐control study of 154 children (8 years or older) with long‐standing nodding syndrome and 154 healthy age‐matched community controls in 3 districts of northern Uganda affected by nodding syndrome. Control CSF samples were obtained from Ugandan children in remission from hematological malignancy during routine follow‐up. Markers of immune activation and inflammation (cytokines and chemokines) and complement activation (C5a) were measured in plasma and CSF using ELISA or Multiplex Luminex assays. O volvulus infection was assessed by serology for anti–OV‐16 IgG levels.ResultsThe mean (SD) age of the population was 15.1 (SD: 1.9) years, and the mean duration of nodding syndrome from diagnosis to enrollment was 8.3 (SD: 2.7) years. The majority with nodding syndrome had been exposed to O volvulus (147/154 (95.4%)) compared with community children (86/154 (55.8%)), with an OR of 17.04 (95% CI: 7.33, 45.58), P < .001. C5a was elevated in CSF of children with nodding syndrome compared to controls (P < .0001). The levels of other CSF markers tested were comparable between cases and controls after adjusting for multiple comparisons. Children with nodding syndrome had lower plasma levels of IL‐10, APRIL, CCL5 (RANTES), CCL2, CXCL13, and MMP‐9 compared with community controls (P < .05 for all; multiple comparisons). Plasma CRP was elevated in children with nodding syndrome compared to community children and correlated with disease severity.SignificanceNodding syndrome is associated with exposure to O. volvulus. Compared to controls, children with long‐standing symptoms of nodding syndrome show evidence of complement activation in CSF and altered immune activation in plasma.
Highlights
Nodding syndrome is a poorly understood severe neurological disorder characterized by a unique seizure manifesting as repeated head nods and complicated by other generalized seizures, motor, neuropsychiatric, and cognitive impairments[1,2]
This study aimed to examine pathways of immune and complement activation in children with chronic nodding syndrome
The findings suggest a possible role of central nervous system complement activation in the pathogenesis of chronic nodding syndrome
Summary
Nodding syndrome is a poorly understood severe neurological disorder characterized by a unique seizure manifesting as repeated head nods and complicated by other generalized seizures, motor, neuropsychiatric, and cognitive impairments[1,2]. Undernutrition, delayed development of sexual characteristics and stunting is observed in a proportion of affected children. Nodding syndrome was initially reported in southern Tanzania, followed by South Sudan and later in northern Uganda[3,4,5]. More recently cases have been reported in central Africa[6]. Nodding syndrome occurs in previously normal children between the ages of 318 years, it is chronic, shows progression in some, and frequently occurs in epidemics with clusters of cases observed in geographically distinct regions[7,8]. Clinical and electrophysiological studies suggest nodding syndrome may be an epileptic encephalopathy[9]
Sign-in/Register to view highlights & summary 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.
