Systemic and cerebrospinal fluid immune and complement activation in Ugandan children and adolescents with long‐standing nodding syndrome: A case‐control study

Ogwang, Rodney; Muhanguzi, Dennis; Mwikali, Kioko; Anguzu, Ronald; Kubofcik, Joe; Nutman, Thomas B.; Taylor, Mark J.; Newton, Charles R.; Vincent, Angela; Conroy, Andrea L.; Marsh, Kevin; Idro, Richard

doi:10.1002/epi4.12463

Cited by 14 publications

(6 citation statements)

References 47 publications

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“…In a previous study, higher levels of MCP-1 were found in brain tissue of patients with intractable epilepsy [ 57 ]. However, the findings are not comparable to the results of the study by Ogwang et al [ 58 ], in which decreased concentrations of MCP-1 were detected in plasma samples of nodding syndrome individuals compared to healthy controls. The different outcome of the measurements could be due to differences in patient inclusion; their study included individuals with nodding syndrome based on the presence of OV-16 antibodies, a marker for exposure to O .…”

Section: Discussioncontrasting

confidence: 99%

Epilepsy and nodding syndrome in association with an Onchocerca volvulus infection drive distinct immune profile patterns

Arndts,

Kegele,

Massarani

et al. 2023

PLoS Negl Trop Dis

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Previous studies have described the association of onchocerciasis (caused by Onchocerca volvulus) with epilepsy, including nodding syndrome, although a clear etiological link is still missing. Cases are found in different African countries (Tanzania, South Sudan, Uganda, Democratic Republic of the Congo, Central African Republic and Cameroon). In our study we investigated immunological parameters (cytokine, chemokine, immunoglobulin levels) in individuals from the Mahenge area, Tanzania, presenting with either epilepsy or nodding syndrome with or without O. volvulus infection and compared them to O. volvulus negative individuals from the same endemic area lacking neurological disorders. Additionally, cell differentiation was performed using blood smears and systemic levels of neurodegeneration markers, leiomodin-1 and N-acetyltyramine-O, β-glucuronide (NATOG) were determined. Our findings revealed that cytokines, most chemokines and neurodegeneration markers were comparable between both groups presenting with epilepsy or nodding syndrome. However, we observed elevated eosinophil percentages within the O. volvulus positive epilepsy/nodding syndrome patients accompanied with increased eosinophilic cationic protein (ECP) and antigen-specific IgG levels in comparison to those without an O. volvulus infection. Furthermore, highest levels of NATOG were found in O. volvulus positive nodding syndrome patients. These findings highlight that the detection of distinct biomarkers might be useful for a differential diagnosis of epilepsy and nodding syndrome in O. volvulus endemic areas. Trial-registration: NCT03653975.

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Section: Discussioncontrasting

confidence: 99%

Epilepsy and nodding syndrome in association with an Onchocerca volvulus infection drive distinct immune profile patterns

Arndts,

Kegele,

Massarani

et al. 2023

PLoS Negl Trop Dis

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“…NS has emerged in areas of hyper-endemicity for onchocerciasis (also known as river blindness), hence the interest in Onchocerca volvulus (OV). Six case-control studies have been conducted in Southern Sudan and Uganda and report a positive and significant association between onchocerciasis and NS [13][14][15][16][17][18]. The risk associated with onchocerciasis varies according to study areas and also to the tests used (Table 2).…”

Section: Associated Factors and Pathophysiology Of Ns Parasitic Infec...mentioning

confidence: 99%

“…These two post-mortem studies were not assessed by the NOS and were of fair quality according to the DCP scale. In addition, results from a study of good NOS quality and fair DCP quality suggest a possible role for central nervous system complement activation in the pathogenesis of chronic NS [16].…”

Section: Geneticsmentioning

confidence: 99%

Mapping, Associated Factors, and Pathophysiology of Nodding Syndrome in Africa: A Systematic Review

Metanmo,

Dossa,

Ahmat

et al. 2024

Neuroepidemiology

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Introduction: Nodding Syndrome (NS) remains a poorly understood disorder. For a long time, it has been thought to be restricted to East Africa, however cases in Central Africa have been increasing over time. The objective of this systematic review (SR) was to provide a summary of the state of knowledge on NS to date. Methods: All original articles published on NS up to November 2021 were searched in four major databases and in the grey literature. Commentaries, editorials, book chapters, books, conference paper, qualitative studies that mentioned NS cases were also included. Data retrieved included study location, year of study and of publication, population characteristics, definition and diagnosis of NS, associated factors, and treatment if applicable. A meta-analysis of associated factors was performed where possible and results were presented as Odds Ratios and visualized as Forrest Plots. Geographic information systems were used for cartographic representations. The quality of the articles included was assessed. Results: Of the 876 articles initially identified, 67 (corresponding to 59 studies) were included in the SR. NS is only present in Central and East Africa. Interestingly, there were reports of NS in Central Africa prior to 2010, earlier than previously thought. The way NS diagnosis was established varies according to studies, and the 2012 WHO classification was used in only 60% of the studies. Approximately 11% of the articles did not meet the quality requirements set for this review. In our meta-analysis, the main factor associated with NS was onchocerciasis (OR = 8.8 [4.8, 15.9]). However, the pathophysiology of the disease remains poorly understood. The lack of common antiepileptic drugs is a significant barrier for the management of head nodding and associated epileptic seizures. Discussion/conclusion: The lack of an operational definition of NS is an obstacle to its diagnosis and thus to its appropriate treatment. Indeed, diagnostic difficulties might have led to false positives and false negatives which could have altered the picture of NS presented in this article. Treatment should take into account nutritional and psychological factors, as well as associated infections. Some risk factors deserve further investigation; therefore, we suggest a multicentric study with an etiological focus using a more operational definition of NS.

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“…The symptoms develop in early childhood, and patients progressively develop neurocognitive and physical impairment [1]. It has been suggested that NS is one of the clinical presentations of onchocerciasis-associated epilepsy (OAE) [2][3][4].…”

Section: Introductionmentioning

confidence: 99%

Risk Factors for Nodding Syndrome and Other Forms of Epilepsy in Northern Uganda: A Case-Control Study

et al. 2021

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Epidemiological studies suggest a link between onchocerciasis and various forms of epilepsy, including nodding syndrome (NS). The aetiopathology of onchocerciasis associated epilepsy remains unknown. This case-control study investigated potential risk factors that may lead to NS and other forms of non-nodding epilepsy (OFE) in northern Uganda. We consecutively recruited 154 persons with NS (aged between 8 and 20 years), and age-frequency matched them with 154 with OFE and 154 healthy community controls. Participants’ socio-demography, medical, family, and migration histories were recorded. We tested participants for O. volvulus serum antibodies. The 154 controls were used for both OFE and NS separately to determine associations. We recruited 462 people with a median age of 15 years (IQR 14, 17); 260 (56.4%) were males. Independent risk factors associated with the development of NS were the presence of O. volvulus antibodies [aOR 8.79, 95% CI (4.15–18.65), p-value < 0.001] and preterm birth [aOR 2.54, 95% CI (1.02–6.33), p-value = 0.046]. Risk factors for developing OFE were the presence of O. volvulus antibodies [aOR 8.83, 95% CI (4.48–17.86), p-value < 0.001] and being born in the period before migration to IDP camps [aOR 4.28, 95% CI (1.20–15.15), p-value = 0.024]. In conclusion, O. volvulus seropositivity was a risk factor to develop NS and OFE; premature birth was a potential co-factor. Living in IDP camps was not a risk factor for developing NS or OFE.

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Systemic and cerebrospinal fluid immune and complement activation in Ugandan children and adolescents with long‐standing nodding syndrome: A case‐control study

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 14 publications

References 47 publications

Epilepsy and nodding syndrome in association with an Onchocerca volvulus infection drive distinct immune profile patterns

Epilepsy and nodding syndrome in association with an Onchocerca volvulus infection drive distinct immune profile patterns

Mapping, Associated Factors, and Pathophysiology of Nodding Syndrome in Africa: A Systematic Review

Risk Factors for Nodding Syndrome and Other Forms of Epilepsy in Northern Uganda: A Case-Control Study

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