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

• Published in: Brain (London, England : 1878) England : 1878), 2023-03, Vol.146 (3), p.954-967
• Main Authors: Pollanen, Michael S, Onzivua, Sylvester, McKeever, Paul M, Robertson, Janice, Mackenzie, Ian R, Kovacs, Gabor G, Olwa, Francis, Kitara, David L, Fong, Amanda
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Child; Epilepsy - pathology; Humans; Neurofibrillary Tangles - pathology; Nodding Syndrome - complications; Nodding Syndrome - epidemiology; Nodding Syndrome - pathology; Original; Seizures - complications; Uganda - epidemiology; Young Adult
• ISSN: 0006-8950; 1460-2156
• DOI: 10.1093/brain/awac137

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. Nodding syndrome is a rare neurological disorder that begins with nodding of the head, and often follows a progressive course leading ultimately to death. Based on neuropathological analysis of a cluster of cases in children in northern Uganda, Pollanen et al. show that nodding syndrome is likely an acquired tau proteinopathy.