Ictal Electroencephalographic Characteristics of Nodding Syndrome: A Comparative Case-Series from South Sudan, Tanzania, and Uganda.

Nodding syndrome (NS) is a poorly understood form of childhood-onset epilepsy that is characterized by the pathognomonic ictal phenomenon of repetitive vertical head drops. To evaluate the underlying ictal neurophysiology, ictal EEG features were evaluated in nine participants with confirmed NS from South Sudan, Tanzania, and Uganda and ictal presence of high frequency gamma oscillations on scalp EEG were assessed. Ictal EEG during the head nodding episode predominantly showed generalized slow waves or sharp-and-slow wave complexes followed by electrodecrement. Augmentation of gamma activity (30-70 Hz) was seen during the head nodding episode in all the participants. We confirm that head nodding episodes in persons with NS from the three geographically distinct regions in sub-Saharan Africa share the common features of slow waves with electrodecrement and superimposed gamma activity. ANN NEUROL 2022;92:75-80.

First description of Nodding Syndrome in the Central African Republic.

BACKGROUND: The term Nodding Syndrome (NS) refers to an atypical and severe form of childhood epilepsy characterized by a repetitive head nodding (HN). The disease has been for a long time limited to East Africa, and the cause is still unknown. The objective of this study was to confirm the existence of NS cases in Central African Republic (CAR). METHODOLOGY/PRINCIPAL FINDINGS: This was a cross-sectional descriptive study in the general population. The identification of NS cases was conducted through a door-to-door survey in a village near Bangui along the Ubangui River. Based on Winkler's 2008 and the World Health Organization (WHO)'s 2012 classifications, the confirmation of cases was done by a neurologist who also performed the electroencephalograms. No laboratory tests were done during this investigation. Treatment was offered to all patients. A total of 6,175 individuals was surveyed in 799 households. After reviewing the cases, we identified 5 NS cases in girls aged between 8 and 16. The age of onset of the seizures was between 5 and 12 years of age. Two cases were classified as "HN plus" according to Winkler's 2008 classification. Four NS cases were classified as probable and one as confirmed according to the WHO's 2012 classification. Three of them presented with developmental delay and cognitive decline, and one had an abnormally low height-for-age z-score. Electroencephalographic abnormalities were found in four patients. CONCLUSIONS/SIGNIFICANCE: Nodding Syndrome cases were described in CAR for the first time. Despite certain peculiarities, these cases are similar to those described elsewhere. Given that only a small part of the affected area was investigated, the study area along the Ubangui River needs to be expanded in order to investigate the association between Onchocerca volvulus and NS and also evaluate the real burden of NS in CAR.

The Pathogenesis of Nodding Syndrome.

Nodding syndrome is a rare, enigmatic form of pediatric epilepsy that has occurred in an epidemic fashion beginning in the early 2000s in geographically distinct regions of Africa. Despite extensive investigation, the etiology of nodding syndrome remains unclear, although much progress has been made in understanding the pathogenesis of the disease, as well as in treatment and prevention. Nodding syndrome is recognized as a defined disease entity, but it is likely one manifestation along a continuum of Onchocerca volvulus-associated neurological complications. This review examines the epidemiology of nodding syndrome and its association with environmental factors. It provides a critical analysis of the data that support or contradict the leading hypotheses of the etiologies underlying the pathogenesis of the syndrome. It also highlights the important progress made in treating and preventing this devastating neurological disease and prioritizes important areas for future research.

Nodding syndrome phenotypes.

Nodding syndrome (NS) is a progressive encephalopathy of children and adolescents characterized by seizures, including periodic vertical head nodding. Epidemic NS, which has affected parts of East Africa, appears to have clinical overlap with sub-Saharan Nakalanga syndrome (NLS), a brain disorder associated with pituitary dwarfism that appears to have a patchy distribution across sub-Sahara. Clinical stages of NS include inattention and blank stares, vertical head nodding, convulsive seizures, multiple impairments, and severe cognitive and motorsystem disability, including features suggesting parkinsonism. Head nodding episodes occur in clusters with an electrographic correlate of diffuse high-amplitude slow waves followed by an electrodecremental pattern with superimposed diffuse fast activity. Brain imaging reveals differing degrees of cerebral cortical and cerebellar atrophy. Brains of NS-affected children with mild frontotemporal cortical atrophy display neurofibrillary pathology and dystrophic neurites immunopositive for tau, consistent with a progressive neurodegenerative disorder. The etiology of NS and NLS appears to be dominated by environmental factors, including malnutrition, displacement, and nematode infection, but the specific cause is unknown.

"Those who died are the ones that are cured". Walking the political tightrope of Nodding Syndrome in northern Uganda: Emerging challenges for research and policy.

BACKGROUND: Nodding Syndrome was first reported from Tanzania in the 1960s but appeared as an epidemic in Northern Uganda in the 1990s during the LRA civil war. It is characterized by repetitive head nodding, often followed by other types of seizures, developmental retardation and growth faltering with onset occurring in children aged 5-15 years. More than 50 years after the first reports, the aetiology remains unknown and there is still no cure. The recent hypothesis that Nodding Syndrome is caused by onchocerciasis also increases the relevance of onchocerciasis control. Northern Uganda, with its unique socio-political history, adds challenges to the prevention and treatment for Nodding Syndrome. This article aims to show how and why Nodding Syndrome has been politicised in Uganda; how this politicisation has affected health interventions including research and dissemination; and, the possible implications this can have for disease prevention and treatment. METHODOLOGY: Ethnographic research methods were used triangulating in-depth interviews, focus group discussions, informal conversations and participant observation, for an understanding of the various stakeholders' perceptions of Nodding Syndrome and how these perceptions impact future interventions for prevention, treatment and disease control. PRINCIPAL FINDINGS: Distrust towards the government was a sentiment that had developed in Northern Uganda over several decades of war and was particularly linked to the political control and ethnic divisions between the north and south. This coincided with the sudden appearance of Nodding Syndrome, an unknown epidemic disease of which the cause could not be clearly identified and optimal treatment had not clearly been established. Additionally, the dissemination of the inconclusive results of research conducted in the area lacked sufficient community involvement which further fueled this political distrust. Disease perceptions revolved around rumours that the entire Acholi ethnic group of the north would be annihilated, or that international researchers were making money by stealing study samples. This discouraged some community members from participating in research or from accepting the mass drug administration of ivermectin for prevention and treatment of onchocerciasis. Such rumour and distrust led to suspicions concerning the integrity of the disseminated results, which may negatively impact future disease management and control interventions. CONCLUSIONS AND RECOMMENDATIONS: Trust must be built up gradually through transparency and by de-politicising interventions. This can be done by engaging the community at regular intervals during research and data collection and the dissemination of results in addition to involvement during service delivery for prevention and treatment. Maintaining a regular feedback loop with the community will help control rumours, build trust, and improve the preparations for adequate dissemination.

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.

The natural history of nodding syndrome.

Nodding syndrome is a poorly understood acquired disorder affecting children in sub-Saharan Africa. The aetiology and pathogenesis are unknown, and no specific treatment is available. Affected children have a distinctive feature (repeated clusters of head nodding) and progressively develop many other features. In an earlier pilot study, we proposed a five-level clinical staging system. The present study aimed to describe the early features and natural history of nodding syndrome and refine the proposed clinical stages. This was a retrospective study of the progressive development of symptoms and complications of nodding syndrome. Participants were a cohort of patients who had been identified by community health workers and were referred for treatment. A detailed history was obtained to document the chronological development of symptoms before and after onset of head nodding and a physical examination and disability assessment performed by a team of clinicians and therapists. A total of 210 children were recruited. The mean age at the onset of head nodding was 7.5 (SD: 3.0) years. Five overlapping clinical stages were recognised: prodromal, head nodding, convulsive seizures, multiple impairments, and severe disability stages. Clinical features before the onset of head nodding (prodromal features) included periods of staring blankly or being inattentive, complaints of dizziness, excessive sleepiness, lethargy, and general body weakness, all occurring two weeks to 24 months before nodding developed. After the onset of head nodding, patients progressively developed convulsive seizures, cognitive and psychiatric dysfunction, physical deformities, growth arrest, and eventually, in some patients, severe disability. The description of the natural history of nodding syndrome and especially the prodromal features has the potential of providing a means for the early identification of at-risk patients and the prompt initiation of interventions before extensive brain injury develops. The wide spectrum of symptoms and complications emphasises the need for multi-disciplinary investigations and care.

Nodding syndrome- an Indian case.

BACKGROUND: Although nodding syndrome is a catastrophic epileptic encephalopathy, it is reported only from Africa so far. We describe the first case from the Indian sub-continent. METHODS: A ten-year-old child who had an episode of Guillain Barre syndrome with incomplete recovery developed emaciation secondary to bulbar palsy and depression. Subsequently, nine months later she developed head nodding, spastic quadriparesis, choreo-athetoid movement disorder, global aphasia and depression. She improved with sodium valproate, nutritional rehabilitation and anti-spasticity and anti-depressant medications. RESULTS: First case of nodding syndrome is described from India where possible etiology is malnutrition. She had anemia, her electroencephalography revealed parieto-occipital inter-ictal epileptiform discharges and Magnetic Resonance Imaging showed diffuse cerebral atrophy. CONCLUSION: Nodding syndrome is an epileptic encephalopathy of nutritional origin beyond geographical barriers but amenable to anti-convulsants and nutritional rehabilitation.

Nodding Syndrome in the Spotlight - Placing Recent Findings in Perspective.

Nodding syndrome (NS) is a debated scientific topic. A recently published study suggests that NS is an autoimmune disorder based on findings of cross-reacting antibodies between neuronal structures and a protein present in Onchocerca volvulus (OV). In our opinion, the proposed causal relationship between OV infection and NS has yet to be demonstrated and, instead, OV infection in NS may be opportunistic.

Nodding syndrome, western Uganda, 1994.

Nodding syndrome (NS) is a poorly understood condition, which was delineated in 2008 as a new epilepsy syndrome. So far, confirmed cases of NS have been observed in three circumscribed African areas: southern Tanzania, southern Sudan, and northern Uganda. Case-control studies have provided evidence of an association between NS and infection with Onchocerca volvulus, but the causation of NS is still not fully clarified. We report a case of a 15-year old boy with head nodding seizures and other characteristic features of NS from an onchocerciasis endemic area in western Uganda, with no contiguity to the hitherto known areas. We suggest that the existence of NS should be systematically investigated in other areas.

Nodding syndrome or disease? On the conceptualization of an illness-in-the-making.

OBJECTIVE: To explore processes of conceptualizing nodding syndrome (NS), an unknown illness which has been reported to affect thousands of children in post-conflict northern Uganda, in South Sudan and in Tanzania. DESIGN: This qualitative study comprised 40 in-depth interviews with affected families, health workers and politicians during five months of fieldwork in northern Uganda and a review of available reports, newspapers and academic literature on NS. In addition, observations have been made at treatment centers and during outreaches and meetings. Focus is put on how meanings of key terms related to NS are produced and negotiated. Attention is being paid to the circulation of different discourses and explanatory models. RESULTS: Discourses and explanatory models play an active role in the conceptualization of illness, as much by medical personnel as by affected families and the media. The prominent use of biomedical terms in the academic discourse on NS is striking; links are suggested with onchocerciasis and epilepsy. In contrast, the local discourse associates NS with social issues. The illness experiences are connected to the trauma of past conflict, to poverty and to (region-bound) frustration over neglect. The cultural significance of physical symptoms raises the question of the impact of culture on health. CONCLUSION: By only looking at the biomedical significance of this new syndrome, we will miss important aspects of how this illness is being experienced and understood. In our future dealings with NS, we will have to consider and re-conceive the relation between culture and neurobiology.

Nodding syndrome.

An epidemic illness characterized by head nodding associated with onchocerciasis has been described in eastern Africa since the early 1960s; we summarize published reports and recent studies. Onset of nodding occurs in previously healthy 5-15-year-old children and is often triggered by eating or cold temperatures and accompanied by cognitive impairment. Its incidence has increased in Uganda and South Sudan over the past 10 years. Four case-control studies identified modest and inconsistent associations. There were nonspecific lesions seen by magnetic resonance imaging, no cerebrospinal fluid inflammation, and markedly abnormal electroencephalography results. Nodding episodes are atonic seizures. Testing has failed to demonstrate associations with trypanosomiasis, cysticercosis, loiasis, lymphatic filariasis, cerebral malaria, measles, prion disease, or novel pathogens; or deficiencies of folate, cobalamin, pyridoxine, retinol, or zinc; or toxicity from mercury, copper, or homocysteine. There is a consistent enigmatic association with onchocerciasis detected by skin snip or serologic analysis. Nodding syndrome is an unexplained epidemic epilepsy.

Pyomyositis in Nodding Syndrome (NS) patient--a case report.

We report a case of Pyomyositis in a 13-year-old boy diagnosed using WHO surveillance definition of Probable Nodding syndrome. Complete blood count showed Leukocytosis with immature granulocytes and atypical lymphocytes. Except for the liver enzymes which were high the renal functions and serum electrolytes were within normal range values. Culture of a pus-swab grew Staphylococcus aureus. Abdominal ultrasound scan showed a focal mass on the internal and external oblique muscles of the right abdominal wall. Incision and drainage was performed. Histology of the muscle showed non-specific inflammation of the external and internal oblique muscles. This finding may highlight some of the other tropical diseases that occur in children with Nodding syndrome.