The spectrum of disease and tau pathology of nodding syndrome in Uganda

Michael S Pollanen; Sylvester Onzivua; Paul M McKeever; Janice Robertson; Ian R Mackenzie; Gabor G Kovacs; Francis Olwa; David L Kitara; Amanda Fong

doi:10.1093/brain/awac137

The spectrum of disease and tau pathology of nodding syndrome in Uganda

Brain. 2023 Mar 1;146(3):954-967. doi: 10.1093/brain/awac137.

Authors

Michael S Pollanen^{1

2

3}, Sylvester Onzivua⁴, Paul M McKeever³, Janice Robertson^{1

3}, Ian R Mackenzie⁵, Gabor G Kovacs^{1

3

6}, Francis Olwa⁷, David L Kitara⁸, Amanda Fong²

Affiliations

¹ Department of Pathobiology and Laboratory Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
² Ontario Forensic Pathology Service, Toronto, Ontario M3M 0B1, Canada.
³ Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario M5G 2C4, Canada.
⁴ Department of Pathology, College of Health Sciences, Makerere University, Kampala PO 7072, East Africa.
⁵ Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 1Z7, Canada.
⁶ Laboratory Medicine Program and Krembil Brain Institute, University Health Network, Toronto, Ontario M5G 2C4, Canada.
⁷ Department of Pathology, Faculty of Medicine, Gulu University, Gulu, Uganda PO 166, East Africa.
⁸ Department of Surgery, Faculty of Medicine, Gulu University, Gulu, Uganda PO 166, East Africa.

Abstract

Nodding syndrome is an enigmatic recurrent epidemic neurologic disease that affects children in East Africa. The illness begins with vertical nodding of the head and can progress to grand mal seizures and death after several years. The most recent outbreak of nodding syndrome occurred in northern Uganda. We now describe the clinicopathologic spectrum of nodding syndrome in northern Uganda. The neuropathologic findings of 16 children or young adults with fatal nodding syndrome were correlated with the onset, duration and progression of their neurological illness. The affected individuals ranged in age from 14 to 25 years at the time of death with a duration of illness ranging from 6-15 years. All 16 cases had chronic seizures. In 10 cases, detailed clinical histories were available and showed that three individuals had a clinical course that was predominantly characterized by epilepsy, whereas the other seven individuals had progressive cognitive, behavioural and motor decline, in addition to epilepsy. The main neuropathologic findings included: tau pathology (16/16 cases), cerebellar degeneration (11/16 cases) and white matter degeneration (7/16 cases). The tau pathology was characterized by filamentous tau-positive deposits in the form of neurofibrillary tangles, pre-tangles and dot-like grains and threads in the neuropil. All cases showed some degree of tau pathology in the neocortex and in the locus coeruleus with frequent involvement of the substantia nigra and tegmental nuclei and lesser involvement of other grey matter sites, but there was a lack of glial tau pathology. The tau pathology in the neocortex showed a multifocal superficial laminar pattern. We conclude that nodding syndrome is a clinicopathological entity associated consistently with tau pathology, but our observations did not establish the cause of the disease, or an explanation for the tau pathology.

Keywords: dementia; encephalitis; neurodegeneration; onchocerciasis; tau.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Child
Epilepsy* / pathology
Humans
Neurofibrillary Tangles / pathology
Nodding Syndrome* / complications
Nodding Syndrome* / epidemiology
Nodding Syndrome* / pathology
Seizures / complications
Uganda / epidemiology
Young Adult