Long-term observation and mortality of children with nodding syndrome in western Uganda, 1994 - 2018.

PURPOSE: To assess long-term mortality and causes of death in children with nodding syndrome, an epileptic disorder of sub-Sahara Africa. METHODS: Ten children with nodding syndrome were followed over 24 years. The mortality rate was determined as the number of deaths per 1000 person-years of observation. The standard mortality ratio (SMR) was calculated as the number of observed deaths divided by the number of expected deaths in the general population. Patients were started on phenobarbital and treatment response was monitored during the first 20 months of follow-up. RESULTS: During an observation period of 89.8 person-years, eight patients had died, one patient was found alive, and one patient had been lost to follow-up. This corresponded to a mortality rate of 89.1 deaths per 1000 person-years and a SMR of 21.4 (95 % CI 6.6-36.2). Five deaths were related to status epilepticus, in two cases occurring after inadvertent drug withdrawal. All patients responded on phenobarbital with a reduction of seizure frequency but only four reached a seizure-free period of at least 6 months. CONCLUSIONS: This long-term follow-up demonstrated high mortality in patients with nodding syndrome. Anti-seizure treatment with phenobarbital was of moderate efficacy. Abrupt interruption of phenobarbital was found leading to seizure aggravation, status epilepticus, and death. Our findings point out the importance of securing continuity of treatment access once anti-seizure therapy is included in health services in resource-poor settings. More rigorous observations and controlled studies are needed to improve the therapeutic options for nodding syndrome.

Evaluating epilepsy management in an onchocerciasis-endemic area: Case of Maridi, South Sudan.

PURPOSE: The epilepsy prevalence in Maridi County, South Sudan, in 2018 was 43.8 (95% CI: 40.9-47.0) per 1000 persons; 85.2% of the identified persons with epilepsy (PWE) met the criteria of onchocerciasis-associated epilepsy. To address this health problem, an epilepsy clinic was established at Maridi County Hospital in 2020. In August 2023, the impact of the clinic on the lives of PWE and their families was evaluated. METHODS: At the Maridi epilepsy clinic, data routinely collected by primary healthcare workers as part of patient care was reviewed. We also analyzed findings from two household surveys conducted in 2018 and 2022, which assessed the impact of the clinic on epilepsy care. Moreover, four households, each with four PWE, were visited in a high epilepsy prevalence area. PWE were examined by a neurologist, and in-depth interviews were conducted with family members. RESULTS: The proportion of PWE on anti-seizure medication increased by 39.7% (95%CI: 35.3-44.2) between 2018 and 2022. The proportion of PWE reporting daily seizures decreased from 27.3% in 2018 to 5.3% in 2022. Of the 754 PWE seen in the clinic in July 2023, only 17 (2.3%) reported side effects. During household visits in July 2023, 13/173 (7.5%) of the visited PWE were found without remaining anti-seizure medication. A high level of epilepsy-related stigma was observed in all visited households. CONCLUSION: The Maridi epilepsy clinic positively impacted the lives of PWE in Maridi. Similar initiatives should be accessible for all PWE living in onchocerciasis-endemic areas. Evidence-based information about OAE is needed to decrease misconceptions and epilepsy-related stigma.

Onchocerciasis-associated epilepsy: Charting a path forward.

This narrative review intends to inform neurologists and public health professionals about Onchocerciasis-Associated Epilepsy (OAE), a neglected public health problem in many remote onchocerciasis-endemic areas. For epidemiological purposes, we define OAE as sudden-onset of convulsive and non-convulsive seizure types, including head nodding seizures (nodding syndrome) in a previously healthy child aged 3 to 18 years in the absence of any other obvious cause for epilepsy, all happening within an area with high ongoing Onchocerca volvulus transmission. Several OAE pathophysiological mechanisms have been proposed, but none has been proven yet. Recent population-based studies showed that strengthening onchocerciasis elimination programs was followed by a significant reduction in the incidence of OAE and nodding syndrome. Treating epilepsy in onchocerciasis-endemic regions is challenging. More advocacy is needed to provide uninterrupted, free access to anti-seizure medication to persons with epilepsy in these remote, impoverished areas. It is crucial todevelop policies and increase funding for the prevention and treatment of OAE to reduce the associated burden of disease, notably via the establishment of morbidity management and disability prevention programs (MMDP). Moreover, effective collaboration between onchocerciasis elimination and mental health programs is imperative to alleviate the burden of OAE. This synergy promises reciprocal advantages and underscores the need for a comprehensive approach to address this multifaceted challenge.

Long-term clinical course and treatment outcomes of individuals with Nodding Syndrome.

Nodding Syndrome is a poorly understood epilepsy disorder in sub-Saharan Africa. The cause(s) of the disease, risk factors and long-term outcomes are unknown or controversial. The objectives of this study were to describe the long-term clinical course and treatment outcomes of individuals suffering from Nodding Syndrome. In addition, we aimed to provide a comprehensive characterization of the epileptological and social features of patients with Nodding Syndrome. From 11/2014 to 4/2015, we conducted a hospital-based, cross-sectional and observational study in Mahenge, Tanzania. Seventy-eight individuals (female:male ratio: 40:38, age at examination: 21.1 ± 6.39 (SD) years) have been enrolled, of whom 38 (49%) had also been examined in 2005 and in 2009. The 10-year clinical course analysis of this revisited subgroup revealed a calculated case fatality of 0.8-2.3%. Progressive physical or cognitive deterioration has not been observed in any of the 78 individuals and more than half of the people studied (38/69; 55%) managed to live and work independently. 14/78 individuals (18%) were seizure-free, (no head nodding, no other seizure types), 13 of whom were taking antiseizure medication. Phenytoin was more effective against head nodding seizures (14/19 (74%)) than monotherapy with other available antiseizure medication (phenobarbitone 12/25 (48%) and carbamazepine 7/22 (32%), p = 0.02, chi-square test). Our ten-year clinical outcome data show that Nodding Syndrome is not a fatal disease, however, the response to treatment is worse than in epilepsy patients in general. Phenytoin may be more effective than carbamazepine and phenobarbitone, but further studies are needed to confirm this observation.

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

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 gray literature. Commentaries, editorials, book chapters, books, conference paper, qualitative studies that mentioned NS cases were also included. Data retrieved included study location (with GPS coordinates searched), year of study and 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 (ORs) and visualized as forest 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 anti-epileptic drugs is a significant barrier to 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.

Treatment and prevention of epilepsy in onchocerciasis-endemic areas is urgently needed.

BACKGROUND: There is increasing epidemiological evidence supporting the association between onchocerciasis and seizures, reinforcing the concept of onchocerciasis-associated epilepsy (OAE). The aim of this paper is to provide an update on the new knowledge about OAE and to propose recommendations to the World Health Organization how to address this public health problem. MAIN TEXT: During the 2nd International Workshop on OAE held on 19-21 September, 2023, in Antwerp, Belgium, participants recognised OAE as a substantial yet neglected public health problem, particularly in areas of sub-Saharan Africa where onchocerciasis remains hyperendemic. Evidence from prospective population-based studies suggest that strengthening onchocerciasis elimination efforts leads to a significant reduction of OAE incidence. There is a need to validate an OAE case definition to estimate the burden of disease and identify onchocerciasis-endemic areas requiring intensification of onchocerciasis elimination programmes and integration of epilepsy care. It is expected that raising awareness about OAE will boost the population uptake of ivermectin. The implementation of a community-based epilepsy treatment programme offering free anti-seizure medications (ASMs) has shown high effectiveness in reducing the frequency of seizures and improving the overall quality of life of people with epilepsy. CONCLUSIONS: To reduce OAE burden, enhanced collaboration between onchocerciasis and mental health programmes at community, national, and international levels is required. Urgent efforts are needed to ensure the uninterrupted provision of free ASMs in onchocerciasis-endemic areas. Furthermore, OAE should be included in the quantification of the onchocerciasis disease burden.

Parasitic, bacterial, viral, immune-mediated, metabolic and nutritional factors associated with nodding syndrome.

Nodding syndrome is a neglected, disabling and potentially fatal epileptic disorder of unknown aetiology affecting thousands of individuals mostly confined to Eastern sub-Saharan Africa. Previous studies have identified multiple associations-including Onchocerca volvulus, antileiomodin-1 antibodies, vitamin B6 deficiency and measles virus infection-yet, none is proven causal. We conducted a case-control study of children with early-stage nodding syndrome (symptom onset <1 year). Cases and controls were identified through a household survey in the Greater Mundri area in South Sudan. A wide range of parasitic, bacterial, viral, immune-mediated, metabolic and nutritional risk factors was investigated using conventional and state-of-the-art untargeted assays. Associations were examined by multiple logistic regression analysis, and a hypothetical causal model was constructed using structural equation modelling. Of 607 children with nodding syndrome, 72 with early-stage disease were included as cases and matched to 65 household- and 44 community controls. Mansonella perstans infection (odds ratio 7.04, 95% confidence interval 2.28-21.7), Necator americanus infection (odds ratio 2.33, 95% confidence interval 1.02-5.3), higher antimalarial seroreactivity (odds ratio 1.75, 95% confidence interval 1.20-2.57), higher vitamin E concentration (odds ratio 1.53 per standard deviation increase, 95% confidence interval 1.07-2.19) and lower vitamin B12 concentration (odds ratio 0.56 per standard deviation increase, 95% confidence interval 0.36-0.87) were associated with higher odds of nodding syndrome. In a structural equation model, we hypothesized that Mansonella perstans infection, higher vitamin E concentration and fewer viral exposures increased the risk of nodding syndrome while lower vitamin B12 concentration, Necator americanus and malaria infections resulted from having nodding syndrome. We found no evidence that Onchocerca volvulus, antileiomodin-1 antibodies, vitamin B6 and other factors were associated with nodding syndrome. Our results argue against several previous causal hypotheses including Onchocerca volvulus. Instead, nodding syndrome may be caused by a complex interplay between multiple pathogens and nutrient levels. Further studies need to confirm these associations and determine the direction of effect.

Mortality among persons with epilepsy in onchocerciasis-endemic and non-endemic areas of sub-Saharan Africa: A systematic review and meta-analysis.

PURPOSE: To document epilepsy-related mortality in sub-Saharan Africa (SSA) and investigate possible associations with onchocerciasis endemicity. METHODS: Systematic review with meta-analysis. Searches were performed in PubMed and Google Scholar (search terms: 'epilepsy'; 'mortality/death'; 'sub-Saharan Africa'). Included studies were classified as high-risk or low-risk for onchocerciasis based on documented endemicity data. Pooled mortality rates and annual case fatality rates (CFR) were calculated, and risk factors for mortality among persons with epilepsy (PWE) were investigated using meta-regression analysis. RESULTS: The 28 eligible studies reported 30 epilepsy surveys, of which 9 (30.0%) were conducted in onchocerciasis high-risk sites. The pooled epilepsy mortality rate was 20.9 (95% CI: 5.9-74.4) per 100,000 person-years, and the pooled CFR was 36.2 (95% CI: 23.9-54.4) per 1,000 PWE per year, albeit with substantial between-study heterogeneity. Compared to onchocerciasis low-risk sites, high-risk sites had higher pooled mortality (342.9 versus 10.0 per 100,000 PY; p<0.001) and CFR (57.0 versus 26.6 per 1,000 PWE per year; p = 0.001). Mortality of PWE was almost five-fold that of people without epilepsy (mortality risk ratio: 4.9; 95% CI: 3.5-6.8). Studies in onchocerciasis high-risk sites and the study which recruited only PWE with nodding syndrome were associated with higher CFR (p = 0.044 and p = 0.002, respectively). The leading causes of epilepsy-related death were status epilepticus (58.5%), drowning (15.7%), and sudden unexpected death in epilepsy (10.1%). CONCLUSION: Epilepsy mortality remains high in SSA. Most reported causes of death among PWE might be averted by improving seizure control. Better epilepsy prevention and care are urgently needed, particularly in onchocerciasis-endemic settings.

Disability assessment among persons with epilepsy in Mahenge, an onchocerciasis-endemic area in Tanzania: A cross-sectional study.

BACKGROUND: A high prevalence of epilepsy has been observed in the onchocerciasis-endemic focus of Mahenge, Tanzania. This study sought to assess the degree of disability experienced by persons with epilepsy (PWE) in Mahenge and identify associations with sociodemographic and clinical features. METHOD: This cross-sectional study was conducted in Mahenge, Tanzania, between February and July 2020. PWE were recruited from the Mahenge epilepsy clinic and four neighbouring rural villages (Mdindo, Mzogezi, Mzelezi and Sali). Data were collected using the 36-item version of the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) questionnaire for adults. For children aged 5-17 years, we used the Module on Child Functioning developed by UNICEF and the Washington Group. Questionnaires were administered by trained research assistants. Descriptive statistics were performed, and multivariable analyses (gamma and logistic regressions) were conducted. RESULTS: A total of 321 adults (45.5% males) and 48 children (55.3% males) with epilepsy participated. The overall median WHODAS 2.0 score was 4.8% (IQR: 0.9-18.9). The most affected disability domain was 'participating in the society' (median score: 12.5%, IQR: 0-29.2). Fifteen (31.3%) of the children with epilepsy had a disability in at least one domain of the child functioning module, with the 'accepting change' domain harbouring the highest proportion of disabled children (12.5%). Higher seizure frequency and longer epilepsy duration were associated with more disability. CONCLUSION: PWE in Mahenge experience variable degrees of disability. The affected domains indicate the need for societal rehabilitation of PWE in various community and/or social activities. Peer-support groups were instituted at the study sites to address these needs.

Quality of life of persons with epilepsy in Mahenge, an onchocerciasis-endemic area in Tanzania: A cross-sectional study.

OBJECTIVE: This study investigated the quality of life (QoL) of adults with epilepsy living in Mahenge, an onchocerciasis-endemic area in Tanzania with a high prevalence of onchocerciasis-associated epilepsy (OAE). METHODS: Between February and December 2020, persons with epilepsy (PWE) were recruited from four rural villages in Mahenge: Mdindo, Msogezi, Mzelezi, and Sali. For PWE who could not answer the questionnaire due to their mental or physical disability, a family member was asked to answer the questions instead. The Quality of Life in Epilepsy Inventory-31 (QOLIE-31) questionnaire used contained seven domains. The raw domain scores were transformed to 0-100% subscales, with higher scores indicating better QoL. The global QoL was calculated from the subscales using the overall QOLIE-31 score formula. RESULTS: In total, 96 PWE were enrolled in the study with a median age of 28 (range: 18-60) years, of whom 45 (47%) were male. The questionnaires were answered by PWE (54.8%) or one of their family members (45.2%). Most PWE were single (81%), and half never attended school. About two-thirds (65%) of PWE were suspected of having OAE, and a third (31%) had a history of head nodding seizures. Most PWE were treated with phenobarbital (85.4%) and had high treatment adherence (96.9%). Still, the number of seizures per week ranged from 0 to 7, with a median of one. The mean global QOLIE-31 score was 66.9 (range: 38.3-92.1) out of 100.0. Predictors of lower QoL were living in Sali Village and experiencing seizures the week before the interview. In contrast, completing primary school and switching to second-line anti-seizure medication were predictors of higher QoL. CONCLUSION: In order to improve the QoL of PWE in Mahenge, it is vital to optimize anti-seizure medication regimens to decrease the frequency of seizures and to increase the schooling of PWE.

Excitatory amino acids, possible causative agents of nodding syndrome in eastern Africa.

BACKGROUND: Nodding syndrome (NS) is one type of epilepsy and a progressive disease characterized by nodding symptoms with children in sub-Saharan Africa. The burden for NS children is heavy, not only mentally but financially for themselves and their families, and yet, the cause and cure of NS remain unknown. The kainic acid-induced model in experimental animals is a well-known epilepsy model that is useful for studying human diseases. In this study, we examined similarities of clinical symptoms and histological brain changes between NS patients and kainic acid-treated rats. In addition, we argued for kainic acid agonist as one of the causes of NS. METHODS: Clinical signs in rats were studied after kainic acid administration, and histological lesions including the expression of tau protein and gliosis, were examined at 24 h, 8 days, and 28 days after dosing. RESULTS: Kainic acid-induced epileptic symptoms were observed in rats, including nodding accompanied by drooling and bilateral neuronal cell death in the hippocampus and piriform cortex regions. In the regions that exhibited neuronal cell death, an increase in tau protein expression and gliosis were found immunohistochemically. The symptoms and brain histology were similar in the NS and kainic acid-induced rat models. CONCLUSION: The results suggest that kainic acid agonist may be one of the causative substances for NS.

Case definitions for onchocerciasis-associated epilepsy and nodding syndrome: A focused review.

Onchocerciasis-associated epilepsy (OAE) is an important but neglected public health problem in onchocerciasis-endemic areas with insufficient or inadequate onchocerciasis control. Hence, there is a need for an internationally accepted, easy-to-use epidemiological case definition of OAE to identify areas of high Onchocerca volvulus transmission and disease burden requiring treatment and prevention interventions. By including OAE as a manifestation of onchocerciasis, we will considerably improve the accuracy of the overall onchocerciasis disease burden, which is currently underestimated. Hopefully, this will lead to increased interest and funding for onchocerciasis research and control interventions, notably the implementation of more effective elimination measures and treatment and support for affected individuals and their families.

Epidemiology of epilepsy and relationship with onchocerciasis prevalence in villages of the Ntui Health District of Cameroon.

BACKGROUND: A strong association between epilepsy and onchocerciasis endemicity has been reported. We sought to document the epidemiology of epilepsy in onchocerciasis-endemic villages of the Ntui Health District in Cameroon and investigate how this relates to the prevalence of onchocerciasis. METHODS: In March 2022, door-to-door epilepsy surveys were conducted in four villages (Essougli, Nachtigal, Ndjame, and Ndowe). Ivermectin intake during the 2021 session of community-directed treatment with ivermectin (CDTI) was investigated in all participating village residents. Persons with epilepsy (PWE) were identified through a two-step approach: administration of a 5-item epilepsy screening questionnaire followed by clinical confirmation by a neurologist. Epilepsy findings were analyzed together with onchocerciasis epidemiological data previously obtained in the study villages. RESULTS: We surveyed 1663 persons in the four study villages. The 2021 CDTI coverage for all study sites was 50.9%. Overall, 67 PWE were identified (prevalence of 4.0% (IQR: 3.2-5.1) with one new-onset case during the past 12 months (annual incidence of 60.1 per 100,000 persons). The median age of PWE was 32 years (IQR: 25-40), with 41 (61.2%) being females. The majority (78.3%) of PWE met the previously published criteria for onchocerciasis-associated epilepsy (OAE). Persons with a history of nodding seizures were found in all villages and represented 19.4% of the 67 PWE. Epilepsy prevalence was positively correlated with onchocerciasis prevalence (Spearman Rho = 0.949, p = 0.051). Meanwhile, an inverse relationship was observed between distance from the Sanaga river (blackfly breeding site) and the prevalence of both epilepsy and onchocerciasis. CONCLUSION: The high epilepsy prevalence in Ntui appears to be driven by onchocerciasis. It is likely that decades of CDTI have likely contributed to a gradual decrease in epilepsy incidence, as only one new case occurred in the past year. Therefore, more effective elimination measures are urgently needed in such endemic areas to curb the OAE burden.

Nodding Syndrome: Clinical Characteristics, Risks Factors, Access to Treatment, and Perceptions in the Greater Mundri Area, South Sudan.

We conducted a house-to-house survey in the Mundri, Western Equatoria state of South Sudan to investigate the clinical characteristics, risk factors, access to treatment and perceptions about nodding syndrome (NS). In total, 224 NS cases with median age of seizure onset of 10 years were identified. Head nodding only was reported in 50 (22.3%) cases, and head nodding plus other types of seizures in 174 (77.7%) cases. Wasting, stunted growth, delayed sexual development and speech and behavioral abnormalities were observed in 17 (23.6%), 16 (22.2%), 9 (17.3%), 14 (19.4%) and 4 (5.6%) cases, respectively. The consumption of rat meat, but not other bushmeat was associated with an increased risk of NS (OR 9.31, 95% CI 1.27-406.51). Children with NS were more likely to have taken ivermectin in the last 5 years (OR 2.40, 95% CI 1.33-4.43). NS cases were less likely to share a bedroom with other children (OR 0.06, 95% CI 0.02-0.16) or adults (OR 0.27, 95% CI 0.13-0.56). In conclusion, rat meat consumption is an unlikely risk factor for NS, and ivermectin intake was more common among NS cases than controls. Importantly, we documented that children with NS are stigmatized because of the misconception that NS is transmitted through direct contact.

Onchocerciasis-associated epilepsy: an update and future perspectives.

Onchocerciasis-associated epilepsy (OAE) is an important neglected public health problem in areas with high ongoing onchocerciasis transmission. The risk that children in such areas develop epilepsy is related to their Onchocerca volvulus microfilarial (mf) load. Before the implementation of mass treatment with ivermectin, microfilariae were detected in cerebrospinal fluid (CSF). More recently, neither O. volvulus microfilariae nor DNA were detected in CSF or brain tissue; however, these samples were obtained years after seizure onset. It is possible that during fever-induced increased blood-brain barrier permeability, microfilariae enter the brain and, upon dying, cause an inflammatory reaction inducing seizures. Including OAE in the onchocerciasis disease burden estimation may mobilise extra resources for onchocerciasis disease elimination and treatment/care of OAE-affected persons/families.

Impact of COVID-19 on the well-being of children with epilepsy including nodding syndrome in Uganda: A qualitative study.

OBJECTIVE: To investigate the impact of the COVID-19 pandemic and related restrictions on the access and use of health services by children with epilepsy including nodding syndrome in Uganda. METHODS: Four focus group discussions (FGD) with parents/caregivers of children with epilepsy and five in-depth interviews with key informants were conducted between April and May 2021 at Butabika National Mental Referral Hospital and Kitgum General Hospital. RESULTS: COVID-19-related restrictions, including the halting of non-essential services and activities, and suspension of public transport, created several challenges not only for children with epilepsy and their parents/caregivers but also for their healthcare providers. Study participants described extreme transport restrictions that reduced their access to healthcare care services, increased food insecurity and shortage or inability to afford essential medicines as consequences of COVID-19-related restrictions. However, parents/caregivers and healthcare workers adopted several coping strategies for these challenges. Parents/caregivers mentioned taking on casual work to earn an income to buy food, medicines, and other necessities. Healthcare workers intensified outreach services to affected communities. A positive impact of lockdown measures described by some FGD participants was that most family members stayed at home and were able to care for children with epilepsy in turn. CONCLUSIONS: Our study highlights the significant negative impact of the COVID-19 pandemic and related restrictions on access to health services and the general well-being of children with epilepsy. Decentralized epilepsy treatment services and nutritional support could reduce the suffering of children with epilepsy and their families during the ongoing COVID-19 pandemic and similar future emergencies.

High Prevalence of Glaucoma among Patients in an Onchocerciasis Endemic Area (Mahenge, Tanzania).

Onchocerciasis is known to cause skin lesions and blindness, but there is also epidemiological evidence that onchocerciasis is associated with epilepsy, including nodding syndrome. We carried out ocular exams in persons with epilepsy in Mahenge, an onchocerciasis endemic area with a high prevalence of epilepsy in Tanzania. We recruited 278 consecutive persons with epilepsy attending the epilepsy clinic at Mahenge hospital and satellite clinics in rural villages. They underwent a general physical and a detailed ocular examination and were tested for onchocerciasis Ov16 IgG4 antibodies. Glaucoma was defined by a raised intraocular pressure above 21 mmHg with evidence of typical glaucomatous disc changes in one or both eyes. Among the 278 participants, median age 27 (IQR 21-38) years, 55.4% were female; 151/210 (71.9%) (95% CI: 65.3-77.9) were Ov16 positive. The most frequent ophthalmic lesions were glaucoma (33.1%), vitreous opacities (6.5%) and cataracts (2.9%). In multivariate analysis, glaucoma (adjusted IRR = 1.46; 95% CI: 1.24-1.70) and age (adjusted IRR = 1.01; 95% CI: 1.01-1.02) were significantly associated with onchocerciasis. In conclusion, a high prevalence of glaucoma was observed among Ov16 positive persons with epilepsy. Persons with epilepsy with O. volvulus infection should undergo screening for glaucoma to prevent one of the causes of preventable blindness.

Preliminary seroprevalence study of neurotropic virus antibodies in Nodding syndrome.

Nodding syndrome (NS) is a mostly East African pediatric epileptiform encephalopathy of unknown etiology that shares some clinical features with measles-associated subacute sclerosing panencephalitis (SSPE) and progressive rubella panencephalitis. Two independent studies in northern Uganda identified an association between NS and prior measles infection, while an earlier study in South Sudan found an inverse association. We report preliminary serologic analyses of antibodies to measles (MV), rubella (RV), HSV-1, and CMV viruses in northern Ugandan children with NS and Household (HC) and Community (CC) Controls. Only MV-positive titers were significantly different (3-fold and > 2-fold) in NS relative to HC and HC + CC, respectively. While these results are consistent with greater prior measles infection in Ugandan persons with NS, further studies are needed to determine whether Measles virus (MV) plays any role in the etiology and pathogenesis of NS. Resolving this issue will be invaluable for the thousands of children at risk for this devastating yet often neglected condition.

The neurology of chronic nodding syndrome.

Nodding syndrome is an uncommon disorder of childhood onset and unknown cause, presenting with nodding seizures, and which appears to occur exclusively in clusters in sub-Saharan Africa. An endemic pattern of disease was initially described in Tanzania and in Liberia; epidemic occurrences were later reported in South Sudan and northern Uganda. Not the least significant of the many questions remaining about nodding syndrome concerns the common presence or otherwise of neurological features other than seizures-clearly relevant to the core issue of whether this is a focal, primary epileptic disease, or a multi-system CNS disorder, with, in turn implications for its aetiology. We had the opportunity to interview and clinically to examine 57 affected individuals in rural northern Uganda some 10 years after onset. In this observational cross-sectional study, nodding onset was invariably between the ages of 5 and 14, presenting with food-triggered nodding attacks in over 75% of cases; 86% went on to develop other seizure types. In 53 of 57 nodding syndrome individuals (93%), there was a definite history of the child and his or her family having resided in or been fed from an internally displaced person camp for some time prior to the onset of nodding. A half of nodding syndrome sufferers (28/57) had focal neurological abnormalities-mainly pyramidal signs (92%), often asymmetric, some with extrapyramidal abnormalities. Many individuals (28/57) were severely functionally disabled, ranging from 'sometimes can dig' to 'can do nothing at home' or 'cannot even feed herself'. Such sufferers tended more frequently to have significant burns, and clear cognitive impairment. We conclude that nodding syndrome is a unique multisystem CNS disorder of childhood onset and then slow progression over several years often followed by spontaneous stabilisation, consistent with an underlying self-limiting neurodegenerative process. We discuss the possibility that this might be triggered by food-related mycotoxins, within a fixed window of CNS vulnerability during childhood.