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Cited by 54Parasitic Diseases Research and TreatmentEpilepsy research and treatmentNeuroinflammation and Neurodegeneration Mechanisms

Neuroinflammation and not tauopathy is a predominant pathological signature of nodding syndrome.

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Hotterbeekx, An, Lammens, Martin, Idro, Richard, Akun, Pamela R, Lukande, Robert, Akena, Geoffrey, Nath, Avindra, Taylor, Joneé +3 more·2019·Journal of Neuropathology & Experimental Neurology
DOI 10.1093/jnen/nlz090PMC PMC6839030
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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, 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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  • P-tau pathology is found in patients with temporal lobe epilepsy, Dravet syndrome, Nodding syndrome, Niemann-Pick type C disease, focal cortical dysplasia IIB, and tuberous sclerosis complex, as well as animal models of post-traumatic epilepsy, Lafora disease, and autism spectrum disorder.

    “These include patients with TLE, Dravet syndrome, Nodding syndrome (Thom et al., 2011; Pollanen et al., 2018; Hotterbeekx et al., 2019), Niemann-Pick type C disease (NPC) (Auer et al., 1995; Love et al., 1995; Suzuki et al., 1995; Malnar et al., 2014), focal cortical dysplasia IIB (FCDIIb) (Sen et al., 2007; Iyer et al., 2014), and tuberous sclerosis complex (TSC) (Sarnat and Flores-Sarnat, 2015;”

    From Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms (2022) · cites this paper as Hotterbeekx et al., 2019

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Authors
Hotterbeekx, A., Lammens, M., Idro, R., Akun, P. R., Lukande, R., Akena, G., Nath, A., Taylor, J., Olwa, F., Kumar-Singh, S., & Colebunders, R.
Affiliations
  • University of Antwerp (BE)
  • Antwerp University Hospital (BE)
  • Makerere University (UG)
  • Kitgum Hospital, Kitgum, Uganda
  • National Institutes of Health (US)
  • Department of Forensic Medicine, New York University, School of Medicine, New York City Office of the Chief Medical Examiner, New York, New York
  • Lira University (UG)
  • Molecular Pathology Group, Laboratory of Cell Biology & Histology, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
Corresponding author
Hotterbeekx, An
ORCID
Venue
Journal of Neuropathology & Experimental Neurology
Publisher
Oxford University Press (OUP)
Published
2019-09-06
Volume
78
Issue
11
Pages
1049-1058
ISSN
  • 0022-3069 (ISSN-L)
  • 1554-6578
DOI
10.1093/jnen/nlz090
PMC
PMC6839030
OpenAlex
W2976552244
Cited by
54
References
2
Citations by year
2026: 2 · 2025: 2 · 2024: 6 · 2023: 4 · 2022: 9 · 2021: 15 · 2020: 13 · 2019: 3
FWCI
7.67
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Neuropathology & Experimental Neurology (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
European Research Council (NSETHIO 671055)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Parasitic Diseases Research and Treatment
  • Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
nodding syndrome, onchocerciasis-associated epilepsy, neuroinflammation, tauopathy, neurofibrillary tangles, cerebellar atrophy, Purkinje cells, Bergmann glia, gliosis, macrophages, ventriculitis, meningitis, pediatric epilepsy, Northern Uganda
MeSH terms
Adolescent, Adult, Brain, Encephalitis, Female, Humans, Male, Onchocerciasis, Uganda, Neurofibrillary Tangles, Tauopathies, Young Adult, Nodding Syndrome

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