Case Report: Nakalanga Syndrome Revisited: Long-Term Follow-Up of a Patient Living in Western Uganda, 1994-2018.

Nakalanga syndrome is a childhood developmental disorder that has been reported from various parts of sub-Saharan Africa with the major sign of retarded growth, regularly combined with physical deformities, impaired mental and pubertal development, and epilepsy. We present a follow-up over a 24-year period of a patient living in the Itwara onchocerciasis focus of western Uganda. We demonstrate the strong similarity of Nakalanga syndrome to the more recently described Nodding syndrome, and we discuss the possible causation of both disorders by onchocerciasis. We suggest that the growing knowledge about the tight interconnections between Nakalanga and nodding syndrome, other forms of epilepsy, and onchocerciasis should be taken into consideration in a revised classification system.

Changes in epilepsy burden after onchocerciasis elimination in a hyperendemic focus of western Uganda: a comparison of two population-based, cross-sectional studies.

BACKGROUND: In 1994, prevalence and incidence of epilepsy were high in the Itwara onchocerciasis focus (western Uganda), and cases of nodding and Nakalanga syndrome were documented. Onchocerciasis transmission was interrupted successfully in 2001. 17 years later, we re-investigated the epilepsy burden in this area. METHODS: From Dec 11 to Dec 15, 2018, a door-to-door survey was done in the three villages (Kabende Centre, Masongora South, and Rwesenene) with the highest epilepsy rates in 1994 to identify people with suspected epilepsy. Epilepsy diagnoses were confirmed by an interview and physical examination by a study clinician. The prevalence and incidence of epilepsy were measured using methods consistent with those used in 1994. Results from 2018 were compared with those from 1994. FINDINGS: The overall crude prevalence of epilepsy in the study villages decreased from 3·0% (35 of 1169) in 1994 to 1·2% (27 of 2325) in 2018 (p=0·0002), with a concomitant decrease in the proportion of people with epilepsy with unknown cause (p=0·037). Between 1994 and 2018, the overall incidence of epilepsy decreased from 418 cases per 100 000 person-years (95% CI 265-626) to 73 new cases per 100 000 person-years (32-114; p<0·0001); this reduction was more pronounced for cases having the first seizure between ages 3 years and 18 years (p<0·0001). No new case of nodding or Nakalanga syndromes had occurred since the interruption of onchocerciasis transmission. INTERPRETATION: Our findings support the existence of a negative association between onchocerciasis elimination and epilepsy burden in previously hyperendemic areas. Therefore, onchocerciasis elimination efforts should be intensified in endemic regions with a high prevalence of epilepsy, which might reduce the burden of epilepsy. FUNDING: Flemish University Development Cooperation and the European Research Council.

Onchocerciasis-Associated Epilepsy with Head Nodding Seizures-Nodding Syndrome: A Case Series of 15 Patients from Western Uganda, 1994.

Nodding syndrome (NS) is an encephalopathy characterized by the core symptom of epileptic head nodding seizures, affecting children at the age between 3 and 18 years in distinct areas of tropical Africa. A consistent correlation with onchocerciasis was found, but so far, the causation of NS has not been fully clarified. With a systematic analysis of features of a cohort of epilepsy patients examined in the Itwara onchocerciasis focus of western Uganda in 1994, we provide evidence that NS actually occurred in this area at this time, and we demonstrate a correlation between prevalence of NS and that of onchocerciasis in different villages. Following the elimination of onchocerciasis by community-directed treatment with ivermectin and ground larviciding, our data provide a baseline to examine the question whether NS will disappear once its putative cause has been removed.

Nodding syndrome, western Uganda, 1994.

Nodding syndrome (NS) is a poorly understood condition, which was delineated in 2008 as a new epilepsy syndrome. So far, confirmed cases of NS have been observed in three circumscribed African areas: southern Tanzania, southern Sudan, and northern Uganda. Case-control studies have provided evidence of an association between NS and infection with Onchocerca volvulus, but the causation of NS is still not fully clarified. We report a case of a 15-year old boy with head nodding seizures and other characteristic features of NS from an onchocerciasis endemic area in western Uganda, with no contiguity to the hitherto known areas. We suggest that the existence of NS should be systematically investigated in other areas.

Association between onchocerciasis and epilepsy in the Itwara hyperendemic focus, West Uganda: controlling for time and intensity of exposure.

In 38 pairs of epilepsy patients and controls matched for time and intensity of exposure to transmission of onchocerciasis, the presence of microfilariae in the skin of epilepsy patients was found insignificantly elevated compared with controls (odds ratio = 1.68; 95% confidence interval [CI] = 0.60-4.57; P = 0.31). This difference was more pronounced when detection of subcutaneous nodules was used as indication of infection with Onchocerca volvulus (odds ratio = 2.77; 95% CI = 0.92-8.33; P = 0.065). These findings from a patient group of limited size suggest that intensity of infection may play a substantial role in the development of onchocerciasis-associated epilepsy. Our results are in contrast to the results of two other independent studies from the identical endemic area; one case concluded a significant positive correlation between onchocerciasis and epilepsy, and the other case concluded a clearly negative correlation. Studies with a greater sample size are needed to confirm this possible relationship.