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.

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.

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.

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.

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.

Community perception of epilepsy and its treatment in onchocerciasis-endemic villages of Maridi county, western equatoria state, South Sudan.

OBJECTIVE: To assess the community's perception of epilepsy and its treatment in onchocerciasis-endemic villages of Maridi County, Western Equatoria State, South Sudan. The study was conducted prior to the setting up of a community-based intervention to manage the important disease burden caused by onchocerciasis-associated epilepsy in these villages. METHOD: Five focus group discussions (FGD) were conducted with community leaders and with persons with epilepsy (PWE) and their families between November and December 2019. RESULTS: Villages close to the Maridi dam were considered to be most affected by epilepsy. Misconceptions about the cause and treatment of epilepsy were identified. Most people believed that epilepsy is caused by bad spirits and is contagious, transmitted through saliva, air, and contact with PWE. Very few participants were aware of the link between onchocerciasis and epilepsy. Persons with epilepsy are restricted in their day-to-day activities and children with epilepsy are often denied going to school. Persons with epilepsy are stigmatized and seen as unfit for marriage. Most participants considered both traditional and medical treatment as ineffective. Uninterrupted anti-seizure treatment continuously was unaffordable for most families with one or more PWE. CONCLUSION: There is a need to establish a comprehensive epilepsy treatment program which addresses misconceptions about epilepsy and reduces epilepsy-related stigma. Explaining the link between onchocerciasis and epilepsy could lead to a reduction in epilepsy-related stigma.

'There Were Moments We Wished She Could Just Die': The Highly Gendered Burden of Nodding Syndrome in Northern Uganda.

Nodding Syndrome (NS) occurs within a wide spectrum of epilepsies seen in onchocerciasis endemic areas of sub-Saharan Africa. It has debilitating consequences on affected individuals and increases the socio-economic, physical and psychological burden on care-givers and their households, diminishing their standing within the community. Social science research on the disproportionate burden of the disease on females is limited. Based on ethnographic research over 3 years in northern Uganda, we explored the burden of being ill and care-giving for persons with NS from a gendered perspective. We found that NS-affected females were at greater risk of physical and psychological abuse, sexual violence, unwanted pregnancies, sexually transmitted infections and stigma, in a context of deteriorating socio-economic conditions. Primary care-givers of the NS-affected, mostly women, struggled to make ends meet and were subjected to stigma and abandonment. Targeted interventions, including legal protection for affected females, stigma reduction, and psycho-social and financial support are needed.

Dual-Targeted Autoimmune Sword in Fatal Epilepsy: Patient's glutamate receptor AMPA GluR3B peptide autoimmune antibodies bind, induce Reactive Oxygen Species (ROS) in, and kill both human neural cells and T cells.

Nodding Syndrome (NS) is a fatal pediatric epilepsy of unknown etiology, accompanied by multiple neurological impairments, and associated with Onchocerca volvulus (Ov), malnutrition, war-induced trauma, and other insults. NS patients have neuroinflammation, and ~50% have cross-reactive Ov/Leiomodin-1 neurotoxic autoimmune antibodies. RESULTS: Studying 30 South Sudanese NS patients and a similar number of healthy subjects from the same geographical region, revealed autoimmune antibodies to 3 extracellular peptides of ionotropic glutamate receptors in NS patients: AMPA-GluR3B peptide antibodies (86%), NMDA-NR1 peptide antibodies (77%) and NMDA-NR2 peptide antibodies (87%) (in either 1:10, 1:100 or 1:1000 serum dilution). In contrast, NS patients did not have 26 other well-known autoantibodies that target the nervous system in several autoimmune-mediated neurological diseases. We demonstrated high expression of both AMPA-GluR3 and NMDA-NR1 in human neural cells, and also in normal human CD3+ T cells of both helper CD4+ and cytotoxic CD8+ types. Patient's GluR3B peptide antibodies were affinity-purified, and by themselves precipitated short 70 kDa neuronal GluR3. NS patient's affinity-purified GluR3B peptide antibodies also bound to, induced Reactive Oxygen Species (ROS) in, and killed both human neural cells and T cells within 1-2 hours only. NS patient's purified IgGs, or serum (1:10 or 1:30), induced similar effects. In vivo video EEG experiments in normal mice, revealed that when NS patient's purified IgGs were released continuously (24/7 for 1 week) in normal mouse brain, they induced all the following: 1.Seizures, 2. Cerebellar Purkinje cell loss, 3. Degeneration in the hippocampus and cerebral cortex, and 4. Elevation of CD3+ T cells, and of activated Mac-2+microglia and GFAP+astrocytes in both the gray and white matter of the cerebral cortex, hippocampus, corpus calossum and cerebellum of mice. NS patient's serum cytokines: IL-1ß, IL-2, IL-6, IL-8, TNFα, IFNγ, are reduced by 85-99% compared to healthy subjects, suggesting severe immunodeficiency in NS patients. This suspected immunodeficiency could be caused by combined effects of the: 1. Chronic Ov infection, 2. Malnutrition, 3. Killing of NS patient's T cells by patient's own GluR3B peptide autoimmune antibodies (alike the killing of normal human T cells by the NS patient's GluR3B peptide antibodies found herein in vitro). CONCLUSIONS: Regardless of NS etiology, NS patients suffer from 'Dual-targeted Autoimmune Sword': autoimmune AMPA GluR3B peptide antibodies that bind, induce ROS in, and kill both neural cells and T cells. These neurotoxic and immunotoxic GluR3B peptide autoimmune antibodies, and also NS patient's NMDA-NR1/NR2A and Ov/Leiomodin-1 autoimmune antibodies, must be silenced or removed. Moreover, the findings of this study are relevant not only to NS, but also to many more patients with other types of epilepsy, which have GluR3B peptide antibodies in serum and/or CSF. This claim is based on the following facts: 1. The GluR3 subunit is expressed in neural cells in crucial brains regions, in motor neurons in the spinal cord, and also in other cells in the body, among them T cells of the immune system, 2. The GluR3 subunit has diverse neurophysiological role, and its deletion or abnormal function can: disrupt oscillatory networks of both sleep and breathing, impair motor coordination and exploratory activity, and increase the susceptibility to generate seizures, 3. GluR3B peptide antibodies were found so far in ~27% of >300 epilepsy patients worldwide, which suffer from various other types of severe, intractable and enigmatic epilepsy, and which turned out to be 'Autoimmune Epilepsy'. Furthermore, the findings of this study could be relevant to different neurological diseases besides epilepsy, since other neurotransmitter-receptors autoantibodies are present in other neurological and psychiatric diseases, e.g. autoimmune antibodies against other GluRs, Dopamine receptors, GABA receptors, Acetylcholine receptors and others. These neurotransmitter-receptors autoimmune autoantibodies might also act as 'Dual-targeted Autoimmune Sword' and damage both neural cells and T cells (as the AMPA-GluR3B peptide antibodies induced in the present study), since T cells, alike neural cells, express most if not all these neurotransmitter receptors, and respond functionally to the respective neurotransmitters - a scientific and clinical topic we coined 'Nerve-Driven Immunity'.

Doxycycline for the treatment of nodding syndrome (DONS); the study protocol of a phase II randomised controlled trial.

BACKGROUND: Nodding syndrome is a poorly understood neurological disorder of unknown aetiology, affecting several thousand children in Africa. There has been a consistent epidemiological association with infection by the filarial parasite, Onchocerca volvulus and antibodies to leiomodin and DJ-1, cross-reacting with O.volvulus proteins, have been reported. We hypothesized that nodding syndrome is a neuro-inflammatory disorder, induced by antibodies to O.volvulus or its symbiont, Wolbachia, cross-reacting with human neuron proteins and that doxycycline, which kills Onchocerca through effects on Wolbachia, may be used as treatment. METHODS: This will be a two-arm, double-blind, placebo-controlled, randomised phase II trial of doxycycline 100 mg daily for six weeks in 230 participants. Participants will be patients' ages≥8 years with nodding syndrome. They will receive standard of care supportive treatment. All will be hospitalised for 1-2 weeks during which time baseline measurements including clinical assessments, EEG, cognitive and laboratory testing will be performed and antiepileptic drug doses rationalised. Participants will then be randomised to either oral doxycycline (Azudox®, Kampala Pharmaceutical Industries) 100 mg daily or placebo. Treatment will be initiated in hospital and continued at home. Participants will be visited at home at 2, 4 and 6 weeks for adherence monitoring. Study outcomes will be assessed at 6, 12, 18 and 24-month visits. Analysis will be by intention to treat. The primary efficacy outcome measure will be the proportion of patients testing positive and the levels or titires of antibodies to host neuron proteins (HNPs) and/or leiomodin at 24 months. Secondary outcome measures will include effect of the intervention on seizure control, inflammatory markers, cognitive function, disease severity and quality of life. DISCUSSION: This trial postulates that targeting O.volvulus through drugs which kill Wolbachia can modify the pathogenic processes in nodding syndrome and improve outcomes. Findings from this study are expected to substantially improve the understanding and treatment of nodding syndrome. TRIAL REGISTRATION: Registered with clinicaltrials.gov ID: NCT02850913 on 1st August, 2016.

Universal classifications, national approaches and specific situations: a comparative study on the conceptualization of nodding syndrome in Uganda and Tanzania.

This paper presents a comparative study on conceptualizations of the poorly understood nodding syndrome (NS) in Uganda and Tanzania. NS has been constructed as a biomedical category to serve global health discourse as well as national contexts of managing the condition. The paper looks into the shifting meanings and conceptualizations of NS in the affected areas of Kitgum (UG) and Mahenge (TZ) district. The perceived universality of biomedical classifications is problematized as conflicting with the specific contexts of lucluc and kifafa cha kusinzia. Reconciliation proves to be challenging, poignantly evoking the cultural construction as such of any medical condition.

Psychological treatments delivered by community health workers in low-resource government health systems: effectiveness of group interpersonal psychotherapy for caregivers of children affected by nodding syndrome in Uganda.

BACKGROUND: Despite increasing evidence for the benefits of psychological treatments (PTs) in low- and middle-income countries, few national health systems have adopted PTs as standard care. We aimed to evaluate the effectiveness of a group interpersonal psychotherapy (IPT-G) intervention, when delivered by lay community health workers (LCHWs) in a low-resource government health system in Uganda. The intended outcome was reduction of depression among caregivers of children with nodding syndrome, a neuropsychiatric condition with high morbidity, mortality and social stigma. METHODS: A non-randomized trial design was used. Caregivers in six villages (n = 69) received treatment as usual (TAU), according to government guidelines. Caregivers in seven villages (n = 73) received TAU as well as 12 sessions of IPT-G delivered by LCHWs. Primary outcomes were caregiver and child depression assessed at 1 and 6 months post-intervention. RESULTS: Caregivers who received IPT-G had a significantly greater reduction in the risk of depression from baseline to 1 month [risk ratio (RR) 0.25, 95% confidence interval (CI) 0.10-0.62] and 6 months (RR 0.33, 95% CI 0.11-0.95) post-intervention compared with caregivers who received TAU. Children of caregivers who received IPT-G had significantly greater reduction in depression scores than children of TAU caregivers at 1 month (Cohen's d = 0.57, p = 0.01) and 6 months (Cohen's d = 0.54, p = 0.03). Significant effects were also observed for psychological distress, stigma and social support among caregivers. CONCLUSION: IPT-G delivered within a low-resource health system is an effective PT for common mental health problems in caregivers of children with a severe neuropsychiatric condition and has psychological benefits for the children as well. This supports national health policy initiatives to integrate PTs into primary health care services in Uganda.

An exploration of caregiver burden for children with nodding syndrome (lucluc) in Northern Uganda.

BACKGROUND: Caregivers of patients with chronic illnesses are often uncompensated for work that is physically demanding, time consuming and emotionally and economically draining. This is particularly true for caregivers of children with nodding syndrome, an emergent neurological disorder of unknown etiology in resource poor settings in Africa. We aimed to explore perceptions of caregivers regarding challenges that a typical caregiver faces when caring for a child with nodding syndrome. METHODS: We used a qualitative exploratory study design with focus group discussions and in-depth interviews to collect data. We analyzed data using the qualitative analysis software package of NVivo and thematic query building. RESULTS: Emergent themes centered on burden of care with emotional agony as the most prominent. Subthemes reflecting the burden of care giving included child and caregiver safety concerns, burnout, social isolation and rejection, and homicidal ideation. Caregivers also complained of physical and financial constraints associated with the care of children with nodding syndrome. CONCLUSIONS: The findings point to a high burden of care for caregivers of children with nodding syndrome and suggests the need to incorporate community-based psychosocial and mental health care services for the caregivers of affected children into the national health system response.

Financing and collaboration on research and development for nodding syndrome.

BACKGROUND: Nodding syndrome is a neurological disease with no known cure or treatment, impacting children aged 3-18 years old, mainly in East Africa. Children progressively develop varying degrees of cognitive impairment which may lead to severe wasting, a vegetative state and, eventually, death. Despite its 50-year existence, little is known about its cause, risk factors and prognosis. It is a disease where markets will not provide solutions because the patients are both too few and too poor, making it especially neglected. Open source innovation has been recommended as an approach to neglected disease research in order to maximize available funding through greater collaboration and openness to results. Nodding syndrome is a useful case to examine the relevance of open source innovation. METHODS: We assessed the magnitude of research related to nodding syndrome, its availability, financing and the amount of collaboration. We surveyed researchers regarding their motivations, attitudes toward open source innovation concepts and barriers to greater collaboration. RESULTS: Little research is occurring for nodding syndrome, but it is openly available and researchers are highly collaborative. The disease is largely unknown, which is partly attributed to WHO not classifying nodding syndrome as a neglected tropical disease and not including it in any formal programme. Impacted countries, particularly Uganda, demonstrate a strong degree of ownership through both authorship and research financing. Nodding syndrome researchers have been allocated a total of €5 million from 2013 to 2019 in grant funding. Annual financing, due to three new grants, doubled from 2014 to 2015. CONCLUSIONS: Nodding syndrome, a disease previously ignored by the international community, is starting to receive greater attention, although financing remains modest. If infectious, a larger epidemic could take the world by surprise. Open source innovation can likely help by sharing research protocols (to avoid duplication) and early research results (to adjust to the findings of others). The existing scientists have already endorsed open source innovation, but increased financing is needed. The support of just a few high-income countries could reap a large impact.

Nodding syndrome since 2012: recent progress, challenges and recommendations for future research.

We aim to review the current epidemiology of nodding syndrome (NS) and discuss relevant gaps in research. NS and convulsive epilepsy of unknown aetiology are clustered within the same villages and families in onchocerciasis-endemic areas. They are therefore potentially different clinical expressions of the same disease. It has been difficult to perform full autopsies on NS patients who die in remote villages. Adequate fixation of tissue immediately after death is critical for the examination of brain tissue. Therefore, post-mortem transsphenoidal brain biopsies, performed immediately after death by trained nurses, will provide the best option for obtaining tissue for analysis. We suspect that certain blackflies in onchocerciasis-endemic areas may transmit a novel pathogen that could cause NS and epilepsy. This is supported by a recent drop in the number of new NS cases coinciding with vector control activities aimed at reducing blackfly populations in northern Uganda. We propose that metagenomic studies of human samples, blackflies and microfilariae are conducted to screen for pathogens, and that a clinical trial is planned to evaluate the impact of larviciding against NS and epilepsy epidemics.

'These nodding people': Experiences of having a child with nodding syndrome in postconflict Northern Uganda.

BACKGROUND: Nodding syndrome, an epidemic epileptic encephalopathy of unknown etiology, has affected an estimated 1834 children in Northern Uganda. Children are being treated symptomatically but inconsistently with antiepileptic drugs. DESIGN: Ten semistructured interviews with caregivers of affected children and five focus group discussions with 23 relatives, teachers, and religious leaders were conducted to examine the experiences of affected families and communities in Kitgum and Pader districts. The researcher also did participant observation during MoH outreach clinics. Data collection was carried out from July to September 2012, and data were analyzed through inductive thematic analysis. RESULTS: Nodding syndrome severely affects the children's ability to participate in daily life activities. Daily seizures and physical features such as salivating and stunting make them unable to pass as normal, and mood changes make it difficult for some to interact with others. Caregivers of children with nodding syndrome feel confined to their homes, and economic activities are reduced, which affects entire families, especially the education of healthy siblings. The familial clustering and the unknown etiology made many separate from the affected children when eating, sleeping, and having seizures because of a fear of transmission through saliva. Families struggle to provide care with minimal resources and have experienced a reduction in visitors since their children were affected by nodding syndrome. There were signs of apathy in patterns of care, and, generally, parents felt that antiepileptic medicine had brought only slight improvement in their child's condition because many had begun treatment when developmental milestones had already been lost. CONCLUSIONS: A consistent supply of antiepileptic medication is likely to reduce the stigma and fear of transmission, as the affected children's acceptance among others was greatly compromised whenever they had seizures. The loss and suffering involved with nodding syndrome are seen as a continuation of the confinement and trauma once caused by war, and a good regimen of medication is not the whole answer.

A longitudinal study on nodding syndrome--a new African epilepsy disorder.

OBJECTIVES: Nodding syndrome (NS), a new epilepsy disorder of sub-Saharan Africa, has only recently been classified. In a study conducted in southern Tanzania in 2005, 62 patients with NS were analyzed in great detail. The present study, a follow-up investigation, was conducted to evaluate the progression of NS over time and to obtain serial electroencephalography (EEG) data. METHODS: Of the 62 NS patients, 53 (85.5%), the majority of whom were currently on some form of antiepileptic treatment, could be reevaluated in 2009 with a standardized questionnaire. A subset of these patients (25/53) underwent EEG investigation. RESULTS: In patients with "head nodding (HN) only" in 2005, 10 (43.5%) of 23 remained with the same diagnosis, whereas 5 (21.7%) of 23 had developed "HN plus" (i.e., HN and generalized tonic-clonic seizures). Six patients (26.1%) had seizures other than HN only, and two patients (8.7%) had fully recovered. In the "HN plus" group of 2005, 9 (30.0%) of 30 patients remained "HN plus," and 15 patients (50.0%) had seizures other than HN only. Four patients (13.3%) reverted to "HN only," and two patients (6.7%) stopped all seizures. In 11 (44.0%) of 25 patients, electroencephalography (EEG) showed generalized slowing. Six (54.6%) of these 11 abnormal EEG studies further showed generalized epileptiform discharges: (1) ictal electroencephalographic pattern with generalized 2.5 Hz spike and waves in two patients and (2) interictal bursts of 1.5-2 Hz spike and waves in four patients. SIGNIFICANCE: This follow-up study confirms that HN represents an epilepsy disorder, possibly of the atypical absence type with dynamic development over time.

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.

Poor neurodevelopment, nutritional and physical growth outcomes among children born to mothers with nodding syndrome.

INTRODUCTION: Nodding syndrome (NS), a poorly understood severe neurological disorder develops in children. In Uganda, some NS cases have grown into child-bearing adults. Babies born to mothers with NS may be prone to impaired neurodevelopmental outcomes. Cognitive deficits in mothers with NS may further inhibit care offered to their children hence compromising neurocognitive development, physical growth, and behaviour. OBJECTIVES: The study aimed to determine the neurodevelopmental, behavioural, nutritional, and physical growth outcomes of children whose mothers have nodding syndrome. METHODS: A comparative cross-sectional study was conducted between May 2021 and April 2022 in Northern Uganda. Children aged 0-5 years of mothers with NS were compared to those of mothers without NS, matched by age, gender and neighbouring residence. Neurodevelopment, behaviour, nutrition, and physical growth were assessed using standardized measures and t-tests employed for group comparisons of outcomes. RESULTS: Overall,106 children participated. Fifty-three (53) were offspring of mothers with NS and 53 of mothers without NS; having a mean age of 26.9 (2.22) and 27.5(2.12) months respectively. Children whose mothers have NS had significantly lower neurodevelopmental scores than those of NS-unaffected mothers in fine motor (37.5(12.1) vs 44.2(14.3), p = 0.011), receptive language (37.8(10.8) vs 43.9(12.9), p = 0.010), overall cognitive development (74.36(17.8) vs 83.34(19.6), p = 0.015), and attention (0.64(0.20) vs 0.76(0.15), p = 0.001). There were no differences in the behaviour scores. Children of mothers with NS also had significantly lower weight-for-age z scores (WAZ) (p = 0.003) and length/height-for-age z scores (LAZ/HAZ) (p = 0.001); with 19(35.9 %) of them stunted. CONCLUSION: Children whose mothers have NS have poorer neurodevelopmental, nutritional, and physical growth outcomes. Interventions to improve outcomes in these children are warranted.

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.