RESUMO
Following previous reports of very high epilepsy prevalence in the onchocerciasis-endemic villages in Maridi County, South Sudan, a study was conducted to investigate the association between the level of Onchocerca volvulus infection, epilepsy, and related outcomes. In December 2018, persons with epilepsy (PWE) were recruited from villages where an epilepsy prevalence of 4.4% (range: 3.5-11.9%) was documented. We enrolled 318 participants from whom two skin snips were taken for microscopic detection of O. volvulus microfilariae (mf). Seizure history was obtained for all PWE and their degree of disability assessed using the modified Rankin scale. Almost all (84.9%) PWE had detectable mf in their skin snips. Onchocerciasis-infected PWE experienced nodding seizures more often than uninfected PWE (p=0.034). Moreover, persons with nodding seizures had more frequent seizures (p<0.001) and higher disability scores (p<0.001), and were more often cognitively impaired and younger at the time of their first epileptic seizure (nine years vs 12 years, p<0.001) compared to PWE without nodding seizures. Based on multivariate models, nodding seizures were associated with higher mf densities (aOR: 1.022; 95% CI: 1.005-1.041). Epilepsy onset at a younger age was associated with a worse outcome. Higher frequency of seizures, longer duration of epilepsy and younger age were associated with increased disability. Regular antiepileptic drug use was associated with better cognitive and disability outcomes. PWE with nodding seizures have a more severe form of onchocerciasis-associated epilepsy, with earlier seizure onset and higher levels of O. volvulus infection. Younger PWE were prone to worse epilepsy outcomes, which would be prevented with regular antiepileptic treatment.
Assuntos
Disfunção Cognitiva , Epilepsia , Microfilárias/patogenicidade , Onchocerca volvulus/patogenicidade , Oncocercose , Pele/parasitologia , Adolescente , Adulto , Fatores Etários , Animais , Criança , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Epilepsia/complicações , Epilepsia/parasitologia , Epilepsia/fisiopatologia , Feminino , Humanos , Masculino , Síndrome do Cabeceio/complicações , Síndrome do Cabeceio/parasitologia , Síndrome do Cabeceio/fisiopatologia , Oncocercose/complicações , Oncocercose/diagnóstico , Oncocercose/parasitologia , Índice de Gravidade de Doença , Sudão do Sul , Adulto JovemRESUMO
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.
Assuntos
Síndrome do Cabeceio/diagnóstico , Adolescente , Criança , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Masculino , Síndrome do Cabeceio/fisiopatologia , Estudos Retrospectivos , Avaliação de SintomasRESUMO
INTRODUCTION: Nodding syndrome (NS) is associated with high anion gap, biotinidase and acetyl carnitine deficiency, vitamin B6 and D deficiency and internal displacement. The objective of this study was to conduct a metabolic analysis on NS children and review literature on its similarities with ASD. METHODS: We conducted biochemical analysis on blood and urine of NS children at Hope for HumaNs (HfH) centre in 2014 and reviewed literature on its similarities with ASD. Ethical approval was obtained from an IRB. Data analysis was conducted using STATA version 12 and a p-value less than 0.05 was considered significant. RESULTS: We found biotinidase deficiency in NS with a mean 1.98 95% CI(1.61, 2.34; p < 0.001); Acetyl carnitine deficiency 16.92 95% CI(16.10,17.75; p<0.001); Low BMI-for-age 16.92 95% CI(16.10,17.75; p = 0.42); Age 14.08 95% CI(0.78,4.660; p = 0.007); IDP duration 4.82 95% CI(4.48, 5.21; p = 0.92); Age at NS onset 8.02 95% CI(7.03, 9.01; p = 0.001); NS associated with multiple nodding episodes (χ2)=22.15, p=0.005; NS siblings with NS (χ2) = 9.68, p = 0.004; NS were in IDPs (χ2) = 22.15, p = 0.005. CONCLUSION: These findings are indicative that NS is associated with biotinidase and acetyl carnitine deficiency, IDPs, and environmental exposures. There are no new cases of NS reported by Ugandan MOH and WHO since 2012 when the IDP camps were disbanded and communities resettled in their own communities and feed on their own grown foods. Perhaps NS may be akin to Autism Spectrum Disorder (ASD). This finding will help support all efforts towards the treatment and rehabilitation of NS children.
Assuntos
Acetilcarnitina/deficiência , Transtorno do Espectro Autista/epidemiologia , Deficiência de Biotinidase/epidemiologia , Síndrome do Cabeceio/epidemiologia , Adolescente , Transtorno do Espectro Autista/fisiopatologia , Deficiência de Biotinidase/complicações , Criança , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Masculino , Síndrome do Cabeceio/etiologia , Síndrome do Cabeceio/fisiopatologia , Uganda/epidemiologia , Adulto JovemRESUMO
Nodding syndrome is an epidemic neurologic disorder of unknown cause that affects children in the subsistence-farming communities of East Africa. We report the neuropathologic findings in five fatal cases (13-18 years of age at death) of nodding syndrome from the Acholi people in northern Uganda. Neuropathologic examination revealed tau-immunoreactive neuronal neurofibrillary tangles, pre-tangles, neuropil threads, and dot-like lesions involving the cerebral cortex, subcortical nuclei and brainstem. There was preferential involvement of the frontal and temporal lobes in a patchy distribution, mostly involving the crests of gyri and the superficial cortical lamina. The mesencephalopontine tegmental nuclei, substantia nigra, and locus coeruleus revealed globose neurofibrillary tangles and threads. We conclude that nodding syndrome is a tauopathy and may represent a newly recognized neurodegenerative disease.
Assuntos
Encéfalo/patologia , Emaranhados Neurofibrilares/patologia , Síndrome do Cabeceio/patologia , Síndrome do Cabeceio/fisiopatologia , Tauopatias/fisiopatologia , Adolescente , Encéfalo/metabolismo , Feminino , Humanos , Masculino , Síndrome do Cabeceio/epidemiologia , Tauopatias/epidemiologia , Uganda/epidemiologiaRESUMO
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.
Assuntos
Síndrome do Cabeceio/epidemiologia , Criança , Eletroencefalografia , Feminino , Humanos , Índia/epidemiologia , Síndrome do Cabeceio/diagnóstico , Síndrome do Cabeceio/patologia , Síndrome do Cabeceio/fisiopatologiaRESUMO
Nodding Syndrome (NS) is a childhood neurological disorder characterized by atonic seizures, cognitive decline, school dropout, muscle weakness, thermal dysfunction, wasting and stunted growth. There are recent published information suggesting associations between Nodding Syndrome (NS) with cerebrospinal fluid (CSF) VGKC antibodies and serum leiomidin-1 antibody cross reacting with Onchocerca Volvulus (OV). These findings suggest a neuro-inflammatory cause of NS and they are important findings in the search for the cause of Nodding Syndrome. These observations perhaps provide further, the unique explanation for the association between Nodding Syndrome and Onchocerca Volvulus. Many clinical and epidemiological studies had shown a significant correlation between NS and infestation with a nematode, Onchocerca volvulus which causes a disease, Onchocerciasis, some of which when left untreated can develop visual defect ("River Blindness"). While these studies conducted in Northern Uganda and Southern Sudan indicate a statistically significant association with (OV infection (using positive skin snips), we observe that (OV is generally endemic in many parts of Sub Saharan Africa and Latin America and that to date, no NS cases have been recorded in those regions. This letter to the Editor is to provide additional information on the current view about the relationship between Nodding Syndrome and Onchocerca Volvulus as seen in Northern Uganda.
Assuntos
Síndrome do Cabeceio/epidemiologia , Onchocerca volvulus/isolamento & purificação , Oncocercose Ocular/epidemiologia , Oncocercose/epidemiologia , Animais , Humanos , Síndrome do Cabeceio/fisiopatologia , Uganda/epidemiologiaRESUMO
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.
Assuntos
Pesquisa Biomédica/organização & administração , Doenças Negligenciadas/epidemiologia , Síndrome do Cabeceio/epidemiologia , África Oriental/epidemiologia , Pesquisa Biomédica/economia , Comportamento Cooperativo , Humanos , Disseminação de Informação , Doenças Negligenciadas/fisiopatologia , Síndrome do Cabeceio/fisiopatologia , Projetos de PesquisaRESUMO
PURPOSE: To describe the neurophysiological and clinical features of Nodding Syndrome (NS) in South Sudan. METHODS: The study was performed at the Epilepsy Service of "Usratuna" sited in Juba, South Sudan. The clinical history of each subject was collected along with an EEG tracing. RESULTS: Twenty-one children (10 females) were diagnosed with NS. Fifteen (72%) children were classified as Probable NS and six (28%) as Confirmed NS. They ranged in age between 6 and 14 years, and age at seizure onset ranged from 5 to 12 years. All the subjects presented with intellectual disability which was mild in severity in 12 (57%) cases, moderate in seven (33%) cases and severe in two (10%) cases. Interictal EEG was abnormal in 20 subjects. In 18 (85%) subjects, the EEG showed 2-3.5 Hz spike-and-wave discharges often intermingled with sharp waves. Intermittent light stimulation was normal. In 12 (57%) children, interictal abnormalities were activated by hyperventilation. Ictal EEG was obtained in three patients. In all ictal EEGs head nodding episodes came in clusters during hyperventilation. None of the patients achieved good seizure control even if all of them received antiepileptic treatment (carbamazepine alone [43%] or in association with phenobarbitone or phenytoin). CONCLUSION: This study confirms that NS is an encephalopathy and intellectual disabilities are partially independent of seizure frequency and EEG pathological activity. Based on interictal and ictal EEG patterns and on the experience of other researchers, valproic acid would seem to be the first-choice antiepileptic drug. NS in South Sudan presents with clinical and neurophysiological features which are similar to those described in northern Uganda and more severe than in Tanzania.
Assuntos
Encéfalo/fisiopatologia , Síndrome do Cabeceio/fisiopatologia , Adolescente , Anticonvulsivantes/uso terapêutico , Criança , Eletroencefalografia , Feminino , Seguimentos , Humanos , Masculino , Síndrome do Cabeceio/tratamento farmacológico , Síndrome do Cabeceio/epidemiologia , Índice de Gravidade de Doença , Sudão do Sul/epidemiologia , Tanzânia/epidemiologia , Uganda/epidemiologia , Ácido Valproico/uso terapêuticoRESUMO
BACKGROUND: Nodding syndrome is an epidemic symptomatic generalized epilepsy syndrome of unknown cause in Eastern Africa. Some patients have extreme short stature. We hypothesized that growth failure in nodding syndrome is associated with specific endocrine dysfunctions. In this pilot study, we examined the relationship between serum hormone levels and stature, bone age and sexual development. RESULTS: We recruited ten consecutive children, 13 years or older, with World Health Organization defined nodding syndrome and assessed physical growth, bone age, development of secondary sexual characteristics and serum hormone levels. Two children with incomplete results were excluded. Of the eight remaining, two had severe stunting (height for age Z [HAZ] score<-3) and three had moderate stunting (HAZ score between-3 and -2). The bone age was delayed by a median 3(range 0-4) years. Serum growth hormone levels were normal in all eight but the two patients with severe stunting and one with moderate stunting had low levels of Somatomedin C (Insulin like Growth Factor [IGF1]) and/or IGF binding protein 3 (IGFBP3), mediators of growth hormone function. A linear relationship was observed between serum IGF1 level and HAZ score. With the exception of one child, all were either pre-pubertal or in early puberty (Tanner stages 1 and 2) and in the seven, levels of the gonadotrophins (luteinising and follicle stimulating hormone) and the sex hormones (testosterone/oestrogen) were all within pre-pubertal ranges or ranges of early puberty. Thyroid function, prolactin, adrenal, and parathyroid hormone levels were all normal. CONCLUSIONS: Patients with nodding syndrome may have dysfunctions in the pituitary growth hormone and pituitary gonadal axes that manifest as stunted growth, delayed bone age and puberty. Studies are required to determine if such endocrine dysfunction is a primary manifestation of the disease or a secondary consequence of chronic ill health and malnutrition and if so, whether targeted interventions can improve outcome.
Assuntos
Osso e Ossos/fisiopatologia , Gônadas/metabolismo , Síndrome do Cabeceio/fisiopatologia , Sistema Hipófise-Suprarrenal/metabolismo , Puberdade/sangue , Adolescente , Estatura , Osso e Ossos/metabolismo , Estrogênios/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Gônadas/fisiopatologia , Hormônio do Crescimento/sangue , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Hormônio Luteinizante/sangue , Masculino , Síndrome do Cabeceio/sangue , Hormônio Paratireóideo/sangue , Projetos Piloto , Sistema Hipófise-Suprarrenal/fisiopatologia , Prolactina/sangue , Testosterona/sangue , Glândula Tireoide/metabolismoRESUMO
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.
Assuntos
Síndrome do Cabeceio/fisiopatologia , Adolescente , Adulto , África Subsaariana/epidemiologia , Idade de Início , Encéfalo/fisiopatologia , Criança , Progressão da Doença , Eletroencefalografia , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Síndrome do Cabeceio/epidemiologia , Convulsões/fisiopatologia , Inquéritos e Questionários , Adulto JovemRESUMO
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.