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Background: Epilepsy remains a leading chronic neurological disorder in Low- and Middle-Income Countries. In Uganda, the highest burden is among young rural people. We aimed to; (i) describe socio-economic status (including schooling), and household poverty in adolescents living with epilepsy (ALE) compared to unaffected counterparts in the same communities and (ii) determine the factors associated with the overall quality of life (QoL)., Methods: This was a cross-sectional survey nested within a larger study of ALE compared to age-matched healthy community children in Uganda. Between Sept 2016 to Sept 2017, 154 ALE and 154 healthy community controls were consecutively recruited. Adolescents recruited were frequency and age-matched based on age categories 10-14 and 15-19 years. Clinical history and standardized assessments were conducted. One control participant had incomplete assessment and was excluded. The primary outcome was overall QoL and key variables assessed were schooling status and household poverty. Descriptive and multivariable linear regression analysis were conducted for independent associations with overall QoL., Results: Mean (SD) age at seizure onset was 8.8 (3.9) years and median (IQR) monthly seizure burden was 2 (1-4). Epilepsy was associated with living in homes with high household poverty; 95/154 (61.7%) ALE lived in the poorest homes compared to 68/153 (44.5%) of the healthy adolescents, p = 0.001. Nearly two-thirds of ALE had dropped out of school and only 48/154 (31.2%) were currently attending school compared to 136/153 (88.9%) of healthy controls, p < 0.001. QoL was lowest among ALE who never attended school (p < 0.001), with primary education (p = 0.006) compared to those with at least secondary education. Stigma scores [mean(SD)] were highest among ALE in the poorest [69.1(34.6)], and wealthy [70.2(32.2)] quintiles compared to their counterparts in poorer [61.8(31.7)], medium [68.0(32.7)] and wealthiest [61.5(33.3)] quintiles, though not statistically significant (p = 0.75). After adjusting for covariates, ALE currently attending school had higher overall QoL compared to their counterparts who never attended school (β = 4.20, 95%CI: 0.90,7.49, p = 0.013). QoL scores were higher among ALE with ≥secondary education than those with no or primary education (β = 10.69, 95%CI: 1.65, 19.72)., Conclusions: ALE in this rural area are from the poorest households, are more likely to drop out of school and have the lowest QoL. Those with poorer seizure control are most affected. ALE should be included among vulnerable population groups and in addition to schooling, strategies for seizure control and addressing the epilepsy treatment gap in affected homes should be specifically targeted in state poverty eradication programs., Competing Interests: Declaration of Competing Interest All authors report no conflict of interest., (Copyright © 2020. Published by Elsevier Inc.)

BACKGROUND AND OBJECTIVE: Nodding 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. METHODS: Thirty-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. RESULTS: Cerebral 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. DISCUSSION: This 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.

Globally, epilepsy is the most common chronic neurological disorder. The incidence in sub-Saharan Africa is 2-3 times higher than that in high income countries. Infection by Onchocerca volvulus may be an underlying risk factor for the high burden and based upon epidemiological associations, has been proposed to cause a group of disorders-Onchocerca associated epilepsies (OAE) like nodding syndrome (NS). To improve our understanding of the disease spectrum, we described the clinical, electroencephalographic (EEG) and magnetic resonance imaging (MRI) features of children with epilepsy and sero-positive for Onchocerca volvulus (possible OAEs other than nodding syndrome). Twenty-nine children and adolescents with non-nodding syndrome OAE in northern Uganda were enrolled. A diagnosis of OAE was made in patients with epilepsy and seizure onset after age 3 years, no reported exposure to perinatal severe febrile illness or traumatic brain injury, no syndromic epilepsy diagnosis and a positive Ov-16 ELISA test. Detailed clinical evaluation including psychiatric, diagnostic EEG, a diagnostic brain MRI (in 10 patients) and laboratory testing were performed. Twenty participants (69%) were male. The mean age was 15.9 (standard deviation [SD] 1.9) years while the mean age at seizure onset was 9.8 (SD 2.9) years. All reported normal early childhood development. The most common clinical presentation was a tonic-clonic seizure. The median number of seizures was 2 (IQR 1-4) in the previous month. No specific musculoskeletal changes, or cranial nerve palsies were reported, neither were any vision, hearing and speech difficulties observed. The interictal EEG was abnormal in the majority with slow wave background activity in 52% (15/29) while 41% (12/29) had focal epileptiform activity. The brain MRI showed mild to moderate cerebellar atrophy and varying degrees of atrophy of the frontal, parietal and occipital lobes. The clinical spectrum of epilepsies associated with Onchocerca may be broader than previously described. In addition, focal onset tonic-clonic seizures, cortical and cerebellar atrophy may be important brain imaging and clinical features.