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Background and objectiveNodding syndrome (NS) is a unique childhood-onset epileptic disorder that occurs predominantly in several regions of sub-Saharan Africa. The disease has been associated with Onchocerca volvulus (Ov)-induced immune responses and possible cross-reactivity with host proteins. The aim of this study was to compare structural changes in the brain on MRI between NS and other forms of onchocerciasis-associated epilepsies (OAEs) and to relate structural changes to the Ov-induced immune responses and level of disability.MethodsThirty-nine children with NS and 14 age-matched participants with other forms of OAE from an endemic region in Uganda underwent detailed clinical examination, serologic evaluation (including Ov-associated antibodies to Ov-16 and Hu-leiomodin-1) and quantitative volumetric analysis of brain MRIs (1.5 T scanner) using Neuroreader, a cloud-based software.ResultsCerebral and cerebellar atrophy were the predominant features in both NS and OAE. On quantitative volumetric analysis, participants with NS had larger ventricular volumes compared with participants with OAE, indicative of increased global cortical atrophy (pcorr = 0.036). Among children with NS, severe disability correlated with higher degree of atrophy in the gray matter volume (pcorr = 0.009) and cerebellar volume (pcorr = 0.009). NS cases had lower anti-Ov-16 IgG signal-to-noise ratios than the OAE cases (p < 0.01), but no difference in the levels of the Hu-leiomodin-1 antibodies (p = 0.64). The levels of Ov-associated antibodies did not relate to the degree of cerebral or cerebellar atrophy in either NS or OAE cases.DiscussionThis is the first study to show that cerebral and cerebellar atrophy correlated with the severity of NS disability, providing an imaging marker for these endemic epileptic disorders that until now have remained poorly characterized. Both NS and OAE have cerebral and cerebellar atrophy, and the levels of Ov-associated antibodies do not seem to be related to the structural changes on MRI.

Original publication





Neurology(R) neuroimmunology & neuroinflammation

Publication Date





From the Department of Neurology (R.M.), David Geffen School of Medicine at University of California Los Angeles; Kampala MRI Centre (S.K.L., M.K.), Uganda; Department of Radiological Sciences (N.S.), David Geffen School of Medicine, University of California Los Angeles, CA; Division of General Internal Medicine and Health Services Research (N.J.J.), David Geffen School of Medicine at UCLA; Centre of Tropical Neuroscience (P.R.A., R.A., R.I.), Kitgum Site, Uganda; Makerere University (R.A., R.J.O., R.I.), College of Health Sciences, Kampala, Uganda; Laboratory of Parasitic Diseases (J.K., T.N.), National Institutes of Health, Bethesda, MD; Centre for Tropical Medicine and Global Health (K.M., R.I.), Nuffield Department of Medicine, University of Oxford, United Kingdom; Department of Psychiatry (C.N.), University of Oxford, United Kingdom; and Nuffield Department of Clinical Neurosciences (A.V.), University of Oxford, United Kingdom.


Animals, Humans, Onchocerca volvulus, Onchocerciasis, Epilepsy, Antibodies, Antinuclear, Child, Nodding Syndrome