Dataset Information

Neuroinflammation and Not Tauopathy Is a Predominant Pathological Signature of Nodding Syndrome.

ABSTRACT: Nodding syndrome (NS) is an epileptic disorder occurring in children in African onchocerciasis endemic regions. Here, we describe the pathological changes in 9 individuals from northern Uganda who died with NS (n?=?5) or other forms of onchocerciasis-associated epilepsy (OAE) (n?=?4). Postmortem examinations were performed and clinical information was obtained. Formalin-fixed brain samples were stained by hematoxylin and eosin and immunohistochemistry was used to stain astrocytes (GFAP), macrophages (CD68), ubiquitin, ?-synuclein, p62, TDP-43, amyloid ?, and tau (AT8). The cerebellum showed atrophy and loss of Purkinje cells with hyperplasia of the Bergmann glia. Gliosis and features of past ventriculitis and/or meningitis were observed in all but 1 participant. CD68-positive macrophage clusters were observed in all cases in various degrees. Immunohistochemistry for amyloid ?, ?-synuclein, or TDP-43 was negative. Mild to sparse AT8-positive neurofibrillary tangle-like structures and threads were observed in 4/5 NS and 2/4 OAE cases, preferentially in the frontal and parietal cortex, thalamic- and hypothalamic regions, mesencephalon and corpus callosum. Persons who died with NS and other forms of OAE presented similar pathological changes but no generalized tauopathy, suggesting that NS and other forms of OAE are different clinical presentations of a same disease with a common etiology.

SUBMITTER: Hotterbeekx A

PROVIDER: S-EPMC6839030 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Neuroinflammation and Not Tauopathy Is a Predominant Pathological Signature of Nodding Syndrome.

Hotterbeekx An A Lammens Martin M Idro Richard R Akun Pamela R PR Lukande Robert R Akena Geoffrey G Nath Avindra A Taylor Joneé J Olwa Francis F Kumar-Singh Samir S Colebunders Robert R

Journal of neuropathology and experimental neurology 20191101 11

Nodding syndrome (NS) is an epileptic disorder occurring in children in African onchocerciasis endemic regions. Here, we describe the pathological changes in 9 individuals from northern Uganda who died with NS (n = 5) or other forms of onchocerciasis-associated epilepsy (OAE) (n = 4). Postmortem examinations were performed and clinical information was obtained. Formalin-fixed brain samples were stained by hematoxylin and eosin and immunohistochemistry was used to stain astrocytes (GFAP), macroph ...[more]

PMID: 31553445

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Project description:Abstract 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. Nodding syndrome is a poorly understood, predominantly epileptic disorder identified almost exclusively in rural East Africa. Focal neurological signs have not been studied. Scolding et al. examined 57 individuals with chronic nodding syndrome in rural settings in northern Uganda and found pyramidal and/or extrapyramidal signs in almost half. Graphical Abstract Graphical Abstract

Project description:IntroductionNodding syndrome (NS) is an encephalopathy of unknown origin that affects children aged between 3 and 15 years old. Cases have been reported since the 1950 in Tanzania and South Sudan, the most heavily affected population is the Acholi community in Uganda. In response to the high incidence of the disease, the Ugandan Government has developed a management algorithm, but access to such measures in affected communities is limited. There is little funding for research on the disease, consequently, few studies have been conducted to date. Nevertheless, the number of scientific publications on NS has increased since 2013, reporting several aetiological hypotheses, management algorithms and cases of stigmatisation; however, none has obtained conclusive results.This document describes a protocol for a scoping review of NS to date aimed at obtaining a broad overview of the disease. The results will identify gaps in knowledge in order to better guide future research, intervention strategies, health policies in areas at risk and cooperation and development programmes.Methods and analysisTo identify the relevant data, we will conduct a literature search using the electronic databases PubMed/Medline, Embase, Social Science Citation Index Scopus, Scientific Electronic Library Online (SciELO), Literatura Latinoamericana y del Caribe en Ciencias de la Salud (LILACS), Social Science Citation Index Expanded and The Cochrane Library. We will also include grey literature. The search strategy will be designed by a librarian.Two members of the team will work independently to identify studies for inclusion and perform data extraction. The search results will be assessed by two independent reviewers and data from the included studies will be charted and summarised in duplicate. The data will be summarised in tables and figures to present the research landscape and describe and map gaps.Ethics and disseminationEthical approval is not required. The scoping review will adhere to the Preferred Reporting Items for Systematic Reviews andMeta-Analyses-ScR guidelines. The results will be disseminated at scientific congresses and meetings.

Project description: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.

Dataset Information

Neuroinflammation and Not Tauopathy Is a Predominant Pathological Signature of Nodding Syndrome.

Publications

Neuroinflammation and Not Tauopathy Is a Predominant Pathological Signature of Nodding Syndrome.

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