Browsing by Author "Hotterbeekx, An"

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    Histological examination of post-mortem brains of children with nodding syndrome
    (Annals of Translational Medicine, 2018) Hotterbeekx, An; Onzivua, Sylvester; Menon, Sonia; Colebunders, Robert
    We read with interest the editorial by Boivin about the aetiology of nodding syndrome (1). In this paper the author mentions that histological examination of post-mortem brains of children with nodding syndrome revealed polarizable material which proved difficult to characterize or identify in the majority of specimens (1). We recently performed a post-mortem study on a person with nodding syndrome in Uganda but we did not observe polarized material in the brain. Moreover, these polarized crystal-like structures were not described on MRI scans of persons with nodding syndrome (2), suggesting that they appeared post mortem. Indeed, polarized material has been seen in brain tissue that was not processed in an appropriate way and these crystalized structures have been called Buscaino bodies, representing myelin altered by fixation and handling (3). This was most likely what happened with previous post-mortem studies performed in patients with nodding syndrome. During these studies the composition of the formaldehyde used in preserving these brains was not documented. Currently, in onchocerciasis endemic districts of northern Uganda, a state of the art post-mortem study is ongoing, investigating the histopathological abnormalities in the brains of persons with epilepsy, including nodding syndrome. Hopefully this study will help us to obtain a better understanding of how the Onchocerca volvulus parasite is able to cause epilepsy.
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    Neuroinflammation and Not Tauopathy Is a Predominant Pathological Signature of Nodding Syndrome
    (Journal of Neuropathology & Experimental Neurology, 2019) Hotterbeekx, An; Lammens, Martin; Idro, Richard; Akun, Pamela R.; Lukande, Robert; Akena, Geoffrey; Nath, Avindra; Olwa, Francis; Colebunders, Robert
    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, α-synuclein, p62, TDP-43, amyloid β, 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 β, α-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.
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    Neuropathological Changes in Nakalanga Syndrome—A Case Report
    (Pathogens, 2021) Hotterbeekx, An; Lammens, Martin; Onzivua, Sylvester; Lukande, Robert; Olwa, Francis; Kumar-Singh, Samir; Hees, Stijn Van; Idro, Richard; Colebunders, Robert
    Nakalanga syndrome is a clinical manifestation of onchocerciasis-associated epilepsy characterized by stunting, delayed or absent secondary sexual development and skeletal deformities, and is often accompanied by epileptic seizures. The pathophysiology of Nakalanga syndrome is unknown. Here, we describe the post-mortem findings of a 17-year-old female who died with Nakalanga syndrome in northern Uganda. Macroscopic and histopathological examination of all major organs (liver, lungs, kidney and heart), including the brain and the pituitary gland, was performed. The suspected cause of death was malaria, and all major organs and pituitary gland appeared normal, except the lungs, which were edematous consistent with the malaria. Neuropathological changes include signs of neuro-inflammation (gliosis and activated microglia), which co-localized with tau-reactive neurofibrillary tangles and threads. The pathology was most abundant in the frontal cortex, thalamic and hypothalamic regions, and mesencephalon. The choroid plexus showed psammoma bodies. These findings indicate accelerated aging, probably due to repeated seizures. The neuropathological findings were similar to other persons who died with onchocerciasis-associated epilepsy. Examination of the pituitary gland did not reveal new information concerning the underlying pathophysiological mechanism of Nakalanga syndrome. Therefore, more post-mortem studies should be performed.
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    Prevalence and incidence of nodding syndrome and other forms of epilepsy in onchocerciasis-endemic areas in northern Uganda after the implementation of onchocerciasis control measures
    (Infectious Diseases of Poverty, 2020) Gumisiriza, Nolbert; Mubiru, Frank; Siewe Fodjo, Joseph Nelson; Mbonye Kayitale, Martin; Hotterbeekx, An; Idro, Richard; Makumbi, Issa; Lakwo, Tom; Opar, Bernard; Kaducu, Joice; Wamala, Joseph Francis; Colebunders, Robert
    Around 2007, a nodding syndrome (NS) epidemic appeared in onchocerciasis-endemic districts of northern Uganda, where ivermectin mass distribution had never been implemented. This study evaluated the effect of community-directed treatment with ivermectin (CDTI) and ground larviciding of rivers initiated after 2009 and 2012 respectively, on the epidemiology of NS and other forms of epilepsy (OFE) in some districts of northern Uganda. Methods: In 2012, a population-based community survey of NS/epilepsy was carried out by the Ugandan Ministry of Health in Kitgum and Pader districts. In August 2017, we conducted a new survey in selected villages of these districts and compared our findings with the 2012 data. In addition, two villages in Moyo district (where CDTI was ongoing since 1993) served as comparative onchocerciasis-endemic sites in which larviciding had never been implemented. The comparison between 2012 and 2017 prevalence and cumulative incidence were done using the Fisher’s and Pearson’s Chi-square tests at 95% level of significance. Results: A total of 2138 individuals in 390 households were interviewed. In the selected villages of Kitgum and Pader, there was no significant decrease in prevalence of NS and OFE between 2012 and 2017. However, the cumulative incidence of all forms of epilepsy decreased from 1165 to 130 per 100 000 persons per year (P = 0.002); that of NS decreased from 490 to 43 per 100 000 persons per year (P = 0.037); and for OFE from 675 to 87 per 100 000 persons per year (P = 0.024). The median age of affected persons (NS and OFE) shifted from 13.5 (IQR: 11.0–15.0) years in 2012 to 18.0 (IQR: 15.0–20.3) years in 2017; P < 0.001. The age-standardized prevalence of OFE in Moyo in 2017 was 4.6%, similar to 4.5% in Kitgum and Pader. Conclusions: Our findings support the growing evidence of a relationship between infection by Onchocerca volvulus and some types of childhood epilepsy, and suggest that a combination of bi-annual mass distribution of ivermectin and ground larviciding of rivers is an effective strategy to prevent NS and OFE in onchocerciasis-hyperendemic areas.