The Neurocognitive Burden of Onchocerciasis-associated Epilepsy in an onchocerciasis-endemic zone in Cameroon: a case-control study

The Neurocognitive Burden of Onchocerciasis-associated Epilepsy in an onchocerciasis-endemic zone in Cameroon: a case-control study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The Neurocognitive Burden of Onchocerciasis-associated Epilepsy in an onchocerciasis-endemic zone in Cameroon: a case-control study Mundih Noelar Njohjam This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4774080/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background A specific form of epilepsy called onchocerciasis-associated epilepsy (OAE) is common in onchocerciasis-endemic communities. Data on the prevalence and pattern of neurocognitive impairment caused by OAE is sparse in Africa. This aim of this study was to determine the spectrum and severity neurocognitive impairment among patients with OAE in two onchocerciasis-endemic communities. Methods A case-control study was conducted in two rural villages in an onchocerciasis-endemic zone in the central region of Cameroon. Based on diagnostic criteria established in other studies, we diagnosed patients with onchocerciasis-associated epilepsy and matched by age, sex, and educational level to controls. Neurocognitive functions were assessed using the Montreal Cognitive Assessment Test, Frontal Assessment Battery, International HIV Dementia Scale, Dubois’ Five Words Tests and Isaac Set’s tests. Data were analyzed using SPSS software version 19. The threshold for statistical significance was set at P < 0.05. Results The study included fifty people with OAE and fifty healthy controls. The mean age for the cases was 26.3 years, and for the controls, it was 26.4 years. Cases were more impaired cognitively than the controls, 96% for the cases vs. 78% for the controls (P = 0.007, OR;7.7). The main cognitive functions affected were memory (86% of cases Vs 30% of controls, P < 0.001, OR = 34.4), verbal fluency (80% of cases Vs 42% of controls, P < 0.001, OR = 15.6), attention, and executive functions (80% of cases as against 42% of controls, P < 0.001). The main factors associated with poorer neurocognitive outcomes were longer duration of epilepsy (P < 0.001), frequent seizures (P < 0.001), low educational level (P = 0.027), generalized tonic-clonic seizures (P < 0.001) and early age of onset of epilepsy (0.001) Conclusion Onchocerciasis-associated epilepsy causes severe neurocognitive impairment in those affected. The need to eliminate onchocerciasis and, hence, reduce the prevalence of OAE has never been more imperative. Onchocerciasis-associated epilepsy neurocognitive impairment Onchocerciasis Figures Figure 1 Figure 2 Figure 3 Background Epilepsy is one of the oldest known neurological disorders and a public health imperative in Africa( 1 , 2 ). Infectious causes of epilepsy are reported to be the leading cause of epilepsy in Africa( 2 ). Until recent years, neurocysticercosis was thought to be the leading infectious cause of epilepsy in Africa. However, there is a growing body of evidence from across Africa suggesting a causal relationship between onchocerciasis and epilepsy in onchocerciasis-endemic zones( 3 – 8 ). This form of epilepsy has been referred to as onchocerciasis-associated epilepsy (OAE) and has been identified as a public health imperative in Africa ( 7 ). Onchocerciasis-associated epilepsy is particularly common in onchocerciasis-endemic communities and is associated with neurocognitive impairment( 9 ). Researchers have identified wo specific forms of OAE: Nodding and Nakalanga syndromes. Nodding syndrome is characterized by repetitive head nodding with decreased responsiveness, stunted growth, cognitive impairment, and mental retardation( 10 – 12 ). On the other hand, people with Nakalanga syndrome have significant growth retardation and delayed or absent development of external signs of sexual development without an obvious cause for the growth retardation ( 13 ). The exact mechanisms underlying OAE are not fully understood, and there is no diagnostic test that can confirm if the epilepsy in an Onchocerciasis-infected patient is solely due to Onchocerciasis. The only cohort study that looked at a possible link between onchocerciasis and epilepsy found that people in an onchocerciasis focus in Cameroon who had higher microfilaria density were more likely to have seizures or epilepsy in an onchocerciasis focus in Cameroon( 5 ). Several other studies, including systematic reviews with meta-analysis and case controls, have further supported this causal relationship( 6 , 14 , 15 ). Clinical criteria for the diagnosis of OAE have been established( 11 ). Based on these criteria, a case of OAE is defined as any person(s) who meet all of the following six criteria( 11 ): ( 1 ) a history of two or more unprovoked epileptic seizures occurring at least 24 h apart; ( 2 ) living in an onchocerciasis-endemic region for at least three years; ( 3 ) living in a village with a high prevalence of epilepsy and persons with epilepsy often clustered within certain households, that is, families having more than one child with epilepsy; ( 4 ) no other obvious cause of epilepsy (e.g., perinatal asphyxia, history of severe malaria, measles, encephalitis or meningitis, or head injury with loss of consciousness in the five years before the onset of epileptic seizures); ( 5 ) onset of seizures in childhood or adolescence (3 to 18 years); ( 6 ) normal neurological development before the onset of epilepsy. Additional criteria suggesting OAE ( 1 ) A history of head nodding seizures, cognitive impairment or Nakalanga features+ ( 2 ) persons with these features in the same village ( 3 ) seropositivity for Ov16 onchocerciasis antibodies ( 4 ) for a person who has never taken ivermectin: a.skin test positivity for microfilaria (microscopy or polymerase chain reaction test) b. clinical manifestations of onchocerciasis, including leopard skin, onchodermatitis, ocular onchocerciasis and/or nodules. Patients with OAE reportedly have cognitive and behavioural problems ( 9 ) but the descriptions of these problems have been sparse and understudied. Our study aimed to address this research gap by determining the severity and spectrum of neurocognitive impairment among patients with OAE. The study also aimed to identify predictive factors that could be addressed to improve the cognitive function of patients with OAE. Knowledge of the spectrum and severity, and factors associated with neurocognitive impairment will inform clinical practice and allow for the provision of comprehensive care to patients with OAE. Evidence from our study will also support and strengthen policies pushing for the elimination of onchocerciasis in Sub-Saharan Africa. Materials and methods Study sites The cases and controls for this study were recruited from two villages, Nkongmessa and Mong, in the Monatele health district, an onchocerciasis endemic zone in the Lekie division of the Central region of Cameroon. The Monatelee health district is located in Monatele, the capital city of the Lekie division in the centre region( 16 ). It is located in the north of the central region, about 90km from Yaoundé. It is bordered on the: north by the Ebebda health district, the –East by the Sa’a health district, the south-west by the Evodoula health district, the east by the Obala health district, and the west by the Rivers Sanaga and Lekie. This district covers a total of 73 villages, among which are the study sites, and is known to be an endemic focus for onchocerciasis( 17 ) due to the presence of several falls and rapids that are found along the course of the Sanaga River. These rapids are excellent breeding grounds for the black flies, as they provide the oxygenated water that is indispensable for the survival of the larvae of the black fly. Mong is a rural village located about 500m from the Sanaga River and the Lekie rivers. Both of the Sanaga and Lekie rivers are well-known breeding sites for the multiplication of blackflies, which are vectors of O. volvulus. It has a total population size of about 450. The main income-generating activity of the people is agriculture. Other income-generating activities include fishing, animal rearing, and sand extraction. This village is known to the local inhabitants of this district as an “epilepsy settlement” due to the numerous cases of epilepsy found in the village. Nkongmessa is also a rural village located close to Sanaga but farther from it than Mong. It is located about 1km from the Sanaga River. It has a total population size of about 1500. Like in the village of Mong, the main income-generating activity of the people is agriculture. Study design This was a community-based case-control study. Patients with OAE living in the study site served as cases, while persons without OAE, matched for age, sex, and level of education served as controls. Study Activities After obtaining ethical clearance, authorizations were obtained from the local chief of each village after presenting the study objectives and procedures to the chef and his collaborators. Community relay agents assisted in conducting door-to-door visits to the homes of people with epilepsy. Each village's chief delegated these relay agents were delegated by the chief of each village. These relay agents also served as interpreters where needed. Before conducting any interviews or tests during the house-hold visits, we obtained written informed consent from the household head or his representative and from the final respondent. A pre-screening for epilepsy was done using a 5-item questionnaire that has been validated for the screening of epilepsy in the tropics We further interrogated and assessed all suspected cases of epilepsy identified during the pre-screening, applying the International League Against Epilepsy (ILAE) criteria for epilepsy diagnosis ( 18 ). We applied the diagnostic criteria for OAE to all cases confirmed to have epilepsy based on the ILAE criteria. We subsequently paired confirmed OAE patients with healthy controls living in the same household or community, matching them for sex, age, and educational level. Neurocognitive tests were conducted on both cases and controls to assess the neurocognitive impairment. We collected sociodemographic data for both cases and controls, as well as clinical data on OAE for cases, using a pre-established questionnaire that underwent pretesting and validation. For the assessment of neurocognitive impairment, the Montreal Cognitive Assessment, the International HIV dementia scale, Dubois’ five-word testing, the Frontal assessment battery (FAB) and the Isaac Set’s Test. The Montreal cognitive assessment is a 10-minute questionnaire designed to detect mild cognitive impairment in adults. It contains 30 items assessing multiple cognitive domains like short-term memory, visuospatial abilities, concentration, and verbal fluency( 19 ). It has been cross-culturally validated and is currently available in 74 different translations( 20 – 22 ). : The FAB, a brief battery, comprises six neuropsychological tasks specifically designed to evaluate frontal lobe function at the bedside. It assesses cognitive and behavioural domains controlled by the frontal lobes( 23 ). The Dubois’ test is a five-word verbal memory test that assesses verbal episodic memory and is widely used as a tool for the screening of memory disorders. It assesses immediate, delayed, and cued-recall memory test( 24 ). Dubois’s test has been tested and validated in healthy controls in Tunisia( 25 ). The Isaac’s Set Test is a validated test for the assessment of verbal fluency( 26 ). The International HIV Dementia Scale (IHDS) is a screening tool that was developed to detect probable HIV-associated dementia( 27 ). These tests were specifically chosen because of their feasibility, accuracy, and reproducibility. They have also been used in a previous study to assess neurocognitive impairment in patients with suspected OAE in Cameroon( 9 ). Eligibility criteria Cases The patient must meet the diagnostic criteria for epilepsy and OAE Does not have any other disease that can affect cognition Participants have willingly consented to participate, or those under the age of 18 have received parental consent. Is able and willing to participate in all neurocognitive tests Has been living in the study site from birth Controls Must not have epilepsy, OAE or any other disease that can affect cognition Participants have willingly consented to participate, or those under the age of 18 have received parental consent. Is able and willing to participate in all neurocognitive tests Has been living in the study site from birth All participants who refused to consent or who could not perform the different tasks in the tests were excluded. Bias The study included a representative sample of OAE cases due to the door-to-door approach to participant recruitment. Also, the controls were recruited from the same household or residential area as the cases: We also matched the cases based on sex, age, and education level to mitigate any potential confounding factors arising from these factors. Moreover, controls were screened to ensure that they had no health conditions that could influence their cognitive performance. Furthermore, the author had to undergo training on how to conduct all the neurocognitive tests before administering them to the patients. Lastly, the author used local translators when necessary to ensure that patients understood the instructions clearly before performing the various tasks. Definitions Using the criteria proposed by the ILAE for the diagnosis of epilepsy( 18 ), a case of epilepsy was defined as either: The presence of at least two unprovoked (or reflex) seizures occurring greater than 24 hours apart A diagnosis of an epilepsy syndrome. A single, unprovoked seizure with a probability of recurrence greater than 60%. OAE was defined using clinical criteria listed in the background section ( 11 ). Cognitive performance: Cognitive impairment was defined as a MoCA score of < 26 and an IHDS score ≤ 10 Executive dysfunction was defined as a FAB score < 16 for educated participants and < 15 for uneducated participants A Dubois' five-word test score of less than nine was used to define impaired memory. An Isaac Set Test score of less than 30 was defined as impairment in verbal fluency. Sample size calculation We determined the sample size of our cases and controls using the following formula, commonly used in the calculation of sample sizes in case-control studies. Where; n = = sample size in the case group r = ratio of controls to cases ṗ= proportion of cases in the exposed group P 1 -P 2 = Effect Size (the difference in proportions) Z β represents the desired power (typically 80% power). Z α/2 represents the desired level of confidence interval (typically 1.96 for 95% confidence). P 1 = risk of exposure in the case group In the control group, P2 = exposure risk. A previous study reported an 87.5% prevalence of neurocognitive impairment in patients with OAE and 37.5% in controls. To test for cognitive impairment, at least 12 persons are needed: 6 cases and 6 controls. This is based on the ratio of controls to cases (r = 1), the power of 80%, and the required level of statistical significance (5%, Z² = 0.84, Z±/2 = 1.96). Data management and analysis Data was collected in the field using paper forms and entered into SPSS version 20.0. Data was analyzed using SPSS version 20.0 based on study objectives. Continuous data were expressed as means ± standard deviation (SD). Frequencies and percentages were used to summarize data and evaluate sociodemographic variables' differences. We used the independent sample t test was to determine if there was a statistically significant difference between neurocognitive impairment in cases versus controls. The level of statistical significance was set at p < 0.05. To identify factors associated with cognitive impairment, a multivariate analysis was conducted. Results The pre-screening identified a total of 65 suspected cases of epilepsy, 26 from Nkongmessa and 39 from Mong. Fifty cases were confirmed as OAE. Fifteen cases were excluded: 12 were untraceable, 1 refused to consent, and 2 had epilepsy due to other causes. We subsequently matched these cases to 50 controls, resulting in a total of 100 study participants. The mean age was 26.26 ± 9.25 years for cases and 26.36 ± 9.08 years for controls. Fifty-two percent of the cases were males, while 47% were females. Table 1 shows the sociodemographic profile of the study participants. Table 1 Sociodemographic profile of study population Variable Cases Controls N % N % Male 26 52 26 52 Female 24 48 24 48 Total 50 100 50 100 Marital Status Married 0 0 25 50 Single 45 90 22 44 Divorced/Separated 1 2 0 0 Concubinage 4 8 3 6 Total 50 100 50 100 Occupation Farmer 23 46 31 62 Student/pupil 9 18 9 18 Sand dealer 3 6 4 8 Trader 7 14 6 12 None 8 16 0 0 Total 50 100 50 100 Level of Education Primary 35 70 35 70 Secondary 15 30 15 30 Total 50 100 50 100 The majority of cases (64%) were discovered in Mong. Most participants had only reached the primary level of education (70%). Clinical characteristics Table 2 shows the clinical characteristics of OAE for the cases. Generalized tonic-clonic seizures were the most common seizure type. We identified probable nodding syndrome was in 2 patients who had a history of head nodding and other forms of seizures, primarily generalised tonic-clonic seizures. We also identified probable Nakalanga syndrome in 2 (4%) patients who presented with severe stunting and delayed development of external signs of sexual and generalised tonic-clonic seizures. The majority of epilepsy patients experienced their first seizure between the ages of 3–18 years, with a peak around 5–11 years. Table 2 Clinical Characteristics of Epilepsy Variables Total N % Age of onset of epilepsy < 3 years of age 0 0 3–18 years of age 48 96 ≥ 19 years of age 2 4 Total 50 100 Seizure Type Generalized tonic clonic 37 74 Absence 7 14 Focal onset 1 2 Probable Noddling syndrome 2 4 Probable Nakalanga syndrome 2 4 Generalized atonic 1 2 Total 50 100 Seizure frequency Once a week 2 4 More than once a week 9 18 Once a month 11 22 More than once a month 14 28 Once every 3 months 13 26 Once every 6 months 1 2 Total 50 100 Neurocognitive Profile Severity of neurocognitive impairment. Using the cutoff of > 26 for the Montreal cognitive test, the prevalence of global cognitive was 96% for cases as against 78% for controls (Fig. 1 ). This difference was statistically significant (P = 0.007). The study participants were further grouped into the following categories: normal, mild, moderate, and severe, using cut-off values for each category proposed by the Quebec national institute for excellence in health and social sciences( 28 ). Thirty percent of the cases had severe cognitive impairment, as opposed to 0% for the controls. Table 3 shows the classification of cognitive impairment based on severity. Table 3 Cognitive impairment based on severity Cognitive Impairment Cases Controls N % N % Mild 16 33.3 46 92 Moderate 17 35.4 9 18 Severe 15 31.3 0 0 Total 50 100 50 100 Using the IHDS, the prevalence of cognitive impairment was 70% for cases as against 10% for controls (Fig. 2 ). This difference was statistically significant (P < 0.001). Spectrum of Neurocognitive Impairment The main cognitive functions affected were; memory, verbal fluency, attention, and executive function (Fig. 3 ). Our cases had more difficulties retaining than their controls (86% vs 30%, P < 0.001). The cases were also less fluent than the controls (80% vs 42%, P < 0.001). Factors associated with neurocognitive impairment. To identify independent factors associated with cognitive impairment, we performed a multivariate analysis. Table 4 shows the different factors associated with cognitive impairment. Table 4 Factors associated with cognitive impairment Variable P Value OR Age 0.151 0.4 Level of education 0.027 5.01 Sex 0.166 0.5 Village 0.054 4.2 Age of onset of epilepsy 0.001 4.3 Seizure type < 0.001 7.6 Most recent seizure 0.979 1.7 Seizure frequency < 0.001 9.5 Duration of epilepsy < 0.001 7.2 ASM type 0.708 1.5 Adherence to ASM 0.78 0.7 ASM: Antiseizure medications We found strong associations between cognitive impairment and factors such as low level education, early age of onset of epilepsy, generalized tonic-clonic seizure, frequent seizures, and longer duration of epilepsy. We also found a borderline association between cognitive impairment and village of origin. Discussion We found severe cognitive impairment in our study, and the main factors associated with cognitive impairment were level of education, village, age of onset of epilepsy, seizure type, seizure frequency, and duration of epilepsy. Our results are similar to those reported in a similar study in Cameroon( 9 ). Several factors could account for this high prevalence. Firstly, the high occurrence of uncontrolled or frequent seizures could have induced significant brain damag, leading to severe cognitive deficits. In various types of epilepsy, uncontrolled seizures have been linked to neurodegenerative changes and cognitive decline. With each seizure, there is a risk of neuronal injury. Uncontrolled seizures can cause cumulative neuronal injury, which over time can lead to severe cognitive decline. Furthermore, onchocerciasis-associated epilepsy may be a manifestation of central nervous system involvement by the parasite itself. The antigens and/or microfilaria of O. volvulus could potentially be neurotoxic and may directly contribute to neuronal damage and cognitive impairment. A study looked at the link between having an Ov16 (antibody against O. volvulus) and neurocognitive performance in children from three villages in Cameroon. It found that having an Ov16 was significantly linked to lower semantic verbal fluency and lower scores on the IHDS( 29 ). Future prospective studies to explore the possible relationship between Onchocerciasis and cognition should be considered Also, the high prevalence of cognitive impairment could have been influenced by socio-economic disadvantages common in rural areas, such as limited access to healthcare, educational opportunities, and adequate nutrition. Access to healthcare services for epilepsy management is particularly poor in many low- and middle-income countries( 1 , 30 ). Most people with epilepsy in these regions may only receive suboptimal or no treatment, leading to frequent and uncontrolled seizures and progressive brain damage. The low level of educational attainment in this study may also be a contributing factor. Education has been shown to be a protective factor against cognitive decline( 31 – 33 ). People with a high level of educational attainment tend to have greater cognitive reserves, which can help mitigate the effects of neuronal insults( 31 ). The majority of cases in this study had only completed the primary level of education, possibly due to limited access to educational opportunities, high levels of stigma that often result in early school dropouts, and the disabling effects of seizures on school attendance( 1 ). With a low level of educational attainment, cognitive reserves are lower, and cognitive decline is more likely to occur( 31 ). Additionally, the high cutoff value of > 26 for the MoCA could have led to high false positives. A previous study suggested that the current MoCA cutoff of 26 is too global and too high for the detection of mild cognitive impairment( 34 , 35 ). According to certain authors, a 3-class model (normal, mildly impaired, and severely impaired) may more accurately reflect cognitive impairment best( 35 ). Moreover, the negative psychotropic effects of anti-seizure drugs such as phenobarbitone could have also contributed to the high prevalence of neurocognitive impairment in the study cohort ( 36 ). Anti-seizure medications, particularly phenobarbitol, consistently increase the incidence of cognitive complications in people with epilepsy, and this effect is dose-dependent ( 36 , 37 ). Memory, verbal fluency, attention, and executive function were more impaired in patients with OAE than in the controls. Memory, attention, and executive function are the most commonly affected cognitive functions in people with epilepsy, irrespective of the underlying etiology( 38 , 39 ). Temporal and frontal lobe epilepsies are the most common forms of epilepsy in adults with epilepsy. In temporal lobe epilepsy, recurrent and/or prolonged seizures lead to atrophy and sclerosis of the hippocampus, a very important structure for memory formation, consolidation, and retrieval( 40 ). The long-term consequence of hippocampal sclerosis is significant cognitive impairment, with memory being the most affected cognitive function( 41 ). The different parts of the frontal lobe work to support executive functions and working memory, as well as emotional control and inhibition ( 42 ). Seizures originating from the frontal lobe can disrupt and damage frontal lobe networks responsible for executive function and working memory, leading to executive dysfunction and behavioural disorders( 38 , 39 ). Focal seizures, which could mean either temporal or frontal lobe epilepsy, were not common in our study group. However, generalized seizures can damage neuronal networks in the temporal and frontal lobes and lead to cognitive problems similar to those seen in people with temporal and frontal lobe epilepsy ( 43 ). Cases from Mong village were more cognitively impaired compared to those from Nkongmessa. Inhabitants of Mong are closest to and in direct contact with the Sanaga River, which is an excellent breeding ground for the black fly, which is the vector for O. volvulus . Because they are more likely to come into contact with the O. volvulus vector, they are more likely to have higher microfilaria loads, which can lead to more severe and frequent seizures, all of which make cognitive impairment worse.. Furthermore, if O. volvulus causes cognitive impairment separate from seizures ( 29 ), the close proximity of Mong participants to the black fly's breeding site could potentially lead to a higher microfilaria load and consequently, greater onchocerciasis-induced cognitive impairment The onset of seizures at an early age was significantly associated with greater cognitive impairment. Early seizure onset can disrupt critical periods of brain development and maturation, causing abnormal neural connections and network formation( 38 , 44 ). A review by Marco Mula reported that an age of onset of epilepsy younger than 5 years old is associated with greater cognitive impairment( 45 ). Cases with poor seizure control or frequent seizures were more cognitively impaired than those with fewer frequent seizures. Poorly controlled seizures can cause cognitive decline in a number of ways, such as inducing significant neuroinflammation, disruption of brain connections that are important for neuroplasticity, increased risk of comorbidities such as depression and sleep disorders, and decreased cognitive reserves( 46 , 47 ). A longer duration of epilepsy was associated with poorer cognitive performance. People with prolonged epilepsy are exposed to chronic neuroinflammation and progressive neurodegeneration for a long time, which can affect cognition ( 45 ). Also, with a longer duration of epilepsy, there is a higher risk of comorbidities such as depression, anxiety, and sleep disorders, which may exacerbate cognitive impairment( 44 ). Moreover, there is prolonged exposure to the cognitive side effects of anti-seizure medications with a longer duration of epilepsy( 46 ). Furthermore, a longer duration of epilepsy can affect daily life, social relationships, and emotional well-being, leading to additional cognitive decline( 38 , 44 ). Contrary to other studies, we didn’t find any significant association between antiseizure medication and neurocognitive impairment. This may be due to the small sample size and the low level of medication adherence in the study population. A low level of adherence reduces exposure to the negative side effects of antiseizure medications. Limitations Our neurocognitive assessment screening tools (with the exception of the international HIV dementia scale) were linguistically and culturally inappropriate for our study population. This may have led to an overestimation of cognitive impairment. Future studies to adapt these tests to our context are needed. No brain imaging or genetic tests were done to rule out other causes of epilepsy. A multifaceted approach was used to thoroughly check for the presence of other risk factors. This included questioning the participants, their parents, caregivers, or guardians, looking through the patient's medical records, and doing a full neurological assessment. Moreover, we did not assess other factors that could have affected cognition, such as sleep, nutrition, stress, social engagement, and sleep disorders. Conclusion The neurocognitive burden of onchocerciasis-associated epilepsy is substantial, highlighting the need for early diagnosis, effective seizure control, and integrated management approaches that address both the parasitic infection and its neurological sequelae. The need to eliminate onchocerciasis and, hence, reduce the prevalence of OAE has never been more imperative. Further studies to assess the impact of onchocerciasis on neurocognition in those without epilepsy are needed. Abbreviations ASM antiseizure medication FAB Frontal Assessment Battery FWT Five words test HIV Human immunodeficiency Virus IHDS International HIV dementia scale ILAE International League Against Epilepsy MoCA Montréal Cognitive Assessment OAE Onchocerciasis-associated epilepsy Declarations Ethics approval and consent to participate Participant confidentiality was strictly respected throughout this study. We obtained ethical approvals from the institutional ethical review board of the faculty of medicine and biomedical sciences of the University of Yaoundé 1 (Ref. No. 169/UY1/FMSB/VDRC/CSD) and the Cameroonian National Ethics Committee for Human Health Research (Registration number: 2018/12/1123/CE/CNERSH/SP) prior to the commencement of this study. We also got approvals (verbal and written) from the chiefs of the villages/communities We also obtained authorization from the Ministry of Public Health (D30–864LS/MINSANTE/SG/DLMEP/SDLCNT). Informed consent was also obtained from household heads or his representatives, as well as from the final respondents. Consent for publication : Not applicable Competing interests : The authors declare that they have no competing interests Funding: Not applicable Author Contribution MNN designed the study, collected, analysed and interpreted data, and wrote the manuscript text. Acknowledgement Our gratitude goes to all the chiefs and local authorities at the study sites for their active participation and collaboration. We are also grateful to the epilepsy patients for their collaboration and hospitality. We are particularly grateful to the executive director of Brain Research Africa for supervising this work. Data Availability The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. References Beghi E, Giussani G, Nichols E, Abd-Allah F, Abdela J, Abdelalim A, et al. 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[cited 2024 Jul 7]; Available from: https://www.academia.edu/115515712/LOGIQUES_DACTEURS_EN_SANT%C3%89_COMMUNAUTAIRE_DANS_LA_ LUTTE_CONTRE_LONCHOCERCOSE_%C3%80_MONAT%C3%89L%C3%89_CAMEROUN Fisher RS, Cross JH, French JA, Higurashi N, Hirsch E, Jansen FE, et al. Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017 Apr;58(4):522–30. Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, et al. The Montreal Cognitive Assessment, MoCA: A Brief Screening Tool For Mild Cognitive Impairment. Journal of the American Geriatrics Society. 2005;53(4):695–9. Cova I, Nicotra A, Maestri G, Canevelli M, Pantoni L, Pomati S. Translations and cultural adaptations of the Montreal Cognitive Assessment: a systematic and qualitative review. Neurol Sci. 2022 Jan 1;43(1):113–24. Islam N, Hashem R, Gad M, Brown A, Levis B, Renoux C, et al. Accuracy of the Montreal Cognitive Assessment tool for detecting mild cognitive impairment: A systematic review and meta-analysis. Alzheimer’s & Dementia. 2023;19(7):3235–43. O’Driscoll C, Shaikh M. Cross-Cultural Applicability of the Montreal Cognitive Assessment (MoCA): A Systematic Review. J Alzheimers Dis. 2017;58(3):789–801. Dubois, Slachevsky, Litvan, Pillon. Frontal Assessment Battery (FAB). In: A Compendium of Tests, Scales and Questionnaires. Psychology Press; 2010. Dubois B, Touchon J, Portet F, Ousset PJ, Vellas B, Michel B. ["The 5 words": a simple and sensitive test for the diagnosis of Alzheimer’s disease]. Presse Med. 2002 Nov 9;31(36):1696–9. Bouattour N, Nouha F, Hanen H, Olfa H, Salma S, Dammak M, et al. Étalonnage du test des cinq mots dans une population tunisienne de sujets sains. The Pan African Medical Journal [Internet]. 2019 Sep 30 [cited 2024 Jul 7];34(58). Available from: https://www.panafrican-med-journal.com/content/article/34/58/full Isaacs B, Kennie AT. The Set test as an aid to the detection of dementia in old people. Br J Psychiatry. 1973 Oct;123(575):467–70. Sacktor N, Wong M, Nakasujja N, Skolasky R, Selnes O, Musisi S, et al. The International HIV Dementia Scale: A new rapid screening test for HIV dementia. AIDS (London, England). 2005 Oct 1;19:1367–74. INESSS [Internet]. [cited 2024 Jul 7]. INESSS. Available from: https://www.inesss.qc.ca/ Siewe Fodjo JN, Njamnshi WY, Ngarka L, Nfor LN, Ayuk C, Mundih NN, et al. Association Between Ov16 Seropositivity and Neurocognitive Performance Among Children in Rural Cameroon: a Pilot Study. J Pediatr Neuropsychol. 2021;7(4):192–202. Singh G, Sander JW. The global burden of epilepsy report: Implications for low- and middle-income countries. Epilepsy Behav [Internet]. 2020 Apr 1 [cited 2023 Sep 6];105. Available from: https://www.epilepsybehavior.com/article/S1525-5050(19)31415-5/fulltext Lövdén M, Fratiglioni L, Glymour MM, Lindenberger U, Tucker-Drob EM. Education and Cognitive Functioning Across the Life Span. Psychol Sci Public Interest. 2020 Aug 1;21(1):6–41. Ramos J, Chowdhury AR, Caywood LJ, Prough M, Denise Fuzzell M, Fuzzell S, et al. Lower Levels of Education Are Associated with Cognitive Impairment in the Old Order Amish. J Alzheimers Dis. 2021;79(1):451–8. Zhong T, Li S, Liu P, Wang Y, Chen L. The impact of education and occupation on cognitive impairment: a cross-sectional study in China. Front Aging Neurosci [Internet]. 2024 Jul 11 [cited 2024 Jul 18];16. Available from: https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2024.1435626/full Milani SA, Marsiske M, Cottler LB, Chen X, Striley CW. Optimal cutoffs for the Montreal Cognitive Assessment vary by race and ethnicity. Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring. 2018 Jan 1;10:773–81. Yang C, Wang L, Hu H, Dong X, Wang Y, Yang F. Montreal Cognitive Assessment: Seeking a Single Cutoff Score May Not Be Optimal. Evidence-Based Complementary and Alternative Medicine. 2021;2021(1):9984419. Hirsch E, Schmitz B, Carreño M. Epilepsy, antiepileptic drugs (AEDs) and cognition. Acta Neurologica Scandinavica. 2003;108(s180):23–32. Witt JA, Elger CE, Helmstaedter C. Adverse cognitive effects of antiepileptic pharmacotherapy: Each additional drug matters. European Neuropsychopharmacology. 2015 Nov 1;25(11):1954–9. Aldenkamp AP, Bodde N. Behaviour, cognition and epilepsy. Acta Neurologica Scandinavica. 2005;112(s182):19–25. Helmstaedter C, Witt JA. Epilepsy and cognition – A bidirectional relationship? Seizure. 2017 Jul;49:83–9. Knierim JJ. The hippocampus. Current Biology. 2015 Dec 7;25(23):R1116–21. Vrinda M, Arun S, Srikumar BN, Kutty BM, Shankaranarayana Rao BS. Temporal lobe epilepsy-induced neurodegeneration and cognitive deficits: Implications for aging. Journal of Chemical Neuroanatomy. 2019 Jan 1;95:146–53. Hoffmann M. The Human Frontal Lobes and Frontal Network Systems: An Evolutionary, Clinical, and Treatment Perspective. International Scholarly Research Notices. 2013;2013(1):892459. Sayed NM, Aldin MTK, Ali SE, Hendi AE. Cognitive functions and epilepsy-related characteristics in patients with generalized tonic–clonic epilepsy: a cross-sectional study. Middle East Current Psychiatry. 2023 Feb 3;30(1):15. Mwangala PN, Kariuki SM, Nyongesa MK, Mwangi P, Chongwo E, Newton CR, et al. Cognition, mood and quality-of-life outcomes among low literacy adults living with epilepsy in rural Kenya: A preliminary study. Epilepsy Behav. 2018 Aug;85:45–51. Medscape [Internet]. [cited 2024 Jul 18]. Cognitive Dysfunction in Patients With Epilepsy: Focus on Clinical Variables. Available from: http://www.medscape.org/viewarticle/837686 Lenck-Santini PP, Scott RC. Mechanisms Responsible for Cognitive Impairment in Epilepsy. Cold Spring Harb Perspect Med. 2015 Jan 10;5(10):a022772. Holmes GL. Effect of Seizures on the Developing Brain and Cognition. Semin Pediatr Neurol. 2016 May;23(2):120–6. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4774080","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":330739534,"identity":"7442ace6-89cc-4486-ac3a-4a54228d26c9","order_by":0,"name":"Mundih Noelar Njohjam","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6ElEQVRIiWNgGAWjYFCCA2wMEhCWwWGGCiBJopYzRGlhYIMxDJgZ24jQYs54+NgDi5pt0Qa3mzceLpx3WN6cvfkAw4+KbTi1WDYcSzeQOHY7d8OdYwWHZ247bLiz51gCY8+Z2zi1GBw4YyYhwQbUciPH4DDvtsOMIAbQhYS0/INpmXPYnjgtkm0wLQ2HE4nQcixNQrLvdu7MG2kFh3mOpSdvOHMs4SBev9w4fExa4tvt3L4byZs/89RY22443nzwwY8K3FoYJA4wMEsguM1g8gBu9UDA38DA+AHBrcOreBSMglEwCkYmAABMo2fAA7Fx3wAAAABJRU5ErkJggg==","orcid":"","institution":"Cheikh Anta Diop University","correspondingAuthor":true,"prefix":"","firstName":"Mundih","middleName":"Noelar","lastName":"Njohjam","suffix":""}],"badges":[],"createdAt":"2024-07-20 17:08:20","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4774080/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4774080/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":62799693,"identity":"f5acd7b4-eb86-41da-a23a-a69bb53227f7","added_by":"auto","created_at":"2024-08-19 15:45:45","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":36151,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePrevalence of Cognitive impairment based on MoCA\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4774080/v1/f4b6ac0a3463ea3ccc0c4c63.jpg"},{"id":62799694,"identity":"e3b3babf-6829-48df-bfc8-c113dca5ba7f","added_by":"auto","created_at":"2024-08-19 15:45:46","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":36505,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePrevalence of Cognitive impairment based on IHDS\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4774080/v1/0b3c2e0fa379110ecf80f935.jpg"},{"id":62799692,"identity":"9299a555-bae9-4c67-a1dc-45835bb69c81","added_by":"auto","created_at":"2024-08-19 15:45:45","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":46960,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSpectrum of neurocognitive impairment\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4774080/v1/73c8363e81f9fcfbbe43eb14.jpg"},{"id":65177505,"identity":"5610c40c-5f4a-4f70-96bb-317e1e2f4406","added_by":"auto","created_at":"2024-09-24 12:09:11","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":854397,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4774080/v1/3f4bc0f0-cfef-475a-b745-373fe93c5a49.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The Neurocognitive Burden of Onchocerciasis-associated Epilepsy in an onchocerciasis-endemic zone in Cameroon: a case-control study","fulltext":[{"header":"Background","content":"\u003cp\u003eEpilepsy is one of the oldest known neurological disorders and a public health imperative in Africa(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Infectious causes of epilepsy are reported to be the leading cause of epilepsy in Africa(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Until recent years, neurocysticercosis was thought to be the leading infectious cause of epilepsy in Africa. However, there is a growing body of evidence from across Africa suggesting a causal relationship between onchocerciasis and epilepsy in onchocerciasis-endemic zones(\u003cspan additionalcitationids=\"CR4 CR5 CR6 CR7\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). This form of epilepsy has been referred to as onchocerciasis-associated epilepsy (OAE) and has been identified as a public health imperative in Africa (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Onchocerciasis-associated epilepsy is particularly common in onchocerciasis-endemic communities and is associated with neurocognitive impairment(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Researchers have identified wo specific forms of OAE: Nodding and Nakalanga syndromes. Nodding syndrome is characterized by repetitive head nodding with decreased responsiveness, stunted growth, cognitive impairment, and mental retardation(\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). On the other hand, people with Nakalanga syndrome have significant growth retardation and delayed or absent development of external signs of sexual development without an obvious cause for the growth retardation (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). The exact mechanisms underlying OAE are not fully understood, and there is no diagnostic test that can confirm if the epilepsy in an Onchocerciasis-infected patient is solely due to Onchocerciasis. The only cohort study that looked at a possible link between onchocerciasis and epilepsy found that people in an onchocerciasis focus in Cameroon who had higher microfilaria density were more likely to have seizures or epilepsy in an onchocerciasis focus in Cameroon(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Several other studies, including systematic reviews with meta-analysis and case controls, have further supported this causal relationship(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Clinical criteria for the diagnosis of OAE have been established(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Based on these criteria, a case of OAE is defined as any person(s) who meet all of the following six criteria(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e):\u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) a history of two or more unprovoked epileptic seizures occurring at least 24 h apart;\u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) living in an onchocerciasis-endemic region for at least three years;\u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) living in a village with a high prevalence of epilepsy and persons with epilepsy often clustered within certain households, that is, families having more than one child with epilepsy;\u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) no other obvious cause of epilepsy (e.g., perinatal asphyxia, history of severe malaria, measles, encephalitis or meningitis, or head injury with loss of consciousness in the five years before the onset of epileptic seizures);\u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) onset of seizures in childhood or adolescence (3 to 18 years);\u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) normal neurological development before the onset of epilepsy.\u003c/p\u003e \u003cp\u003eAdditional criteria suggesting OAE\u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) A history of head nodding seizures, cognitive impairment or Nakalanga features+\u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) persons with these features in the same village\u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) seropositivity for Ov16 onchocerciasis antibodies\u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) for a person who has never taken ivermectin:\u003c/p\u003e \u003cp\u003ea.skin test positivity for microfilaria (microscopy or polymerase chain reaction test)\u003c/p\u003e \u003cp\u003eb. clinical manifestations of onchocerciasis, including leopard skin, onchodermatitis, ocular onchocerciasis and/or nodules.\u003c/p\u003e \u003cp\u003ePatients with OAE reportedly have cognitive and behavioural problems (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) but the descriptions of these problems have been sparse and understudied. Our study aimed to address this research gap by determining the severity and spectrum of neurocognitive impairment among patients with OAE. The study also aimed to identify predictive factors that could be addressed to improve the cognitive function of patients with OAE. Knowledge of the spectrum and severity, and factors associated with neurocognitive impairment will inform clinical practice and allow for the provision of comprehensive care to patients with OAE. Evidence from our study will also support and strengthen policies pushing for the elimination of onchocerciasis in Sub-Saharan Africa.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy sites\u003c/h2\u003e \u003cp\u003eThe cases and controls for this study were recruited from two villages, Nkongmessa and Mong, in the Monatele health district, an onchocerciasis endemic zone in the Lekie division of the Central region of Cameroon. The Monatelee health district is located in Monatele, the capital city of the Lekie division in the centre region(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). It is located in the north of the central region, about 90km from Yaound\u0026eacute;. It is bordered on the: north by the Ebebda health district, the \u0026ndash;East by the Sa\u0026rsquo;a health district, the south-west by the Evodoula health district, the east by the Obala health district, and the west by the Rivers Sanaga and Lekie. This district covers a total of 73 villages, among which are the study sites, and is known to be an endemic focus for onchocerciasis(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e) due to the presence of several falls and rapids that are found along the course of the Sanaga River. These rapids are excellent breeding grounds for the black flies, as they provide the oxygenated water that is indispensable for the survival of the larvae of the black fly.\u003c/p\u003e \u003cp\u003eMong is a rural village located about 500m from the Sanaga River and the Lekie rivers. Both of the Sanaga and Lekie rivers are well-known breeding sites for the multiplication of blackflies, which are vectors of O. volvulus. It has a total population size of about 450. The main income-generating activity of the people is agriculture. Other income-generating activities include fishing, animal rearing, and sand extraction. This village is known to the local inhabitants of this district as an \u0026ldquo;epilepsy settlement\u0026rdquo; due to the numerous cases of epilepsy found in the village.\u003c/p\u003e \u003cp\u003eNkongmessa is also a rural village located close to Sanaga but farther from it than Mong. It is located about 1km from the Sanaga River. It has a total population size of about 1500. Like in the village of Mong, the main income-generating activity of the people is agriculture.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStudy design\u003c/h2\u003e \u003cp\u003eThis was a community-based case-control study. Patients with OAE living in the study site served as cases, while persons without OAE, matched for age, sex, and level of education served as controls.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStudy Activities\u003c/h2\u003e \u003cp\u003eAfter obtaining ethical clearance, authorizations were obtained from the local chief of each village after presenting the study objectives and procedures to the chef and his collaborators. Community relay agents assisted in conducting door-to-door visits to the homes of people with epilepsy. Each village's chief delegated these relay agents were delegated by the chief of each village. These relay agents also served as interpreters where needed. Before conducting any interviews or tests during the house-hold visits, we obtained written informed consent from the household head or his representative and from the final respondent.\u003c/p\u003e \u003cp\u003eA pre-screening for epilepsy was done using a 5-item questionnaire that has been validated for the screening of epilepsy in the tropics We further interrogated and assessed all suspected cases of epilepsy identified during the pre-screening, applying the International League Against Epilepsy (ILAE) criteria for epilepsy diagnosis (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). We applied the diagnostic criteria for OAE to all cases confirmed to have epilepsy based on the ILAE criteria. We subsequently paired confirmed OAE patients with healthy controls living in the same household or community, matching them for sex, age, and educational level. Neurocognitive tests were conducted on both cases and controls to assess the neurocognitive impairment.\u003c/p\u003e \u003cp\u003eWe collected sociodemographic data for both cases and controls, as well as clinical data on OAE for cases, using a pre-established questionnaire that underwent pretesting and validation. For the assessment of neurocognitive impairment, the Montreal Cognitive Assessment, the International HIV dementia scale, Dubois\u0026rsquo; five-word testing, the Frontal assessment battery (FAB) and the Isaac Set\u0026rsquo;s Test. The Montreal cognitive assessment is a 10-minute questionnaire designed to detect mild cognitive impairment in adults. It contains 30 items assessing multiple cognitive domains like short-term memory, visuospatial abilities, concentration, and verbal fluency(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). It has been cross-culturally validated and is currently available in 74 different translations(\u003cspan additionalcitationids=\"CR21\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). : The FAB, a brief battery, comprises six neuropsychological tasks specifically designed to evaluate frontal lobe function at the bedside. It assesses cognitive and behavioural domains controlled by the frontal lobes(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). The Dubois\u0026rsquo; test is a five-word verbal memory test that assesses verbal episodic memory and is widely used as a tool for the screening of memory disorders. It assesses immediate, delayed, and cued-recall memory test(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Dubois\u0026rsquo;s test has been tested and validated in healthy controls in Tunisia(\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). The Isaac\u0026rsquo;s Set Test is a validated test for the assessment of verbal fluency(\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). The International HIV Dementia Scale (IHDS) is a screening tool that was developed to detect probable HIV-associated dementia(\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). These tests were specifically chosen because of their feasibility, accuracy, and reproducibility. They have also been used in a previous study to assess neurocognitive impairment in patients with suspected OAE in Cameroon(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eEligibility criteria\u003c/h2\u003e \u003cdiv id=\"Sec7\" class=\"Section3\"\u003e \u003ch2\u003eCases\u003c/h2\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eThe patient must meet the diagnostic criteria for epilepsy and OAE\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eDoes not have any other disease that can affect cognition\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eParticipants have willingly consented to participate, or those under the age of 18 have received parental consent.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eIs able and willing to participate in all neurocognitive tests\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eHas been living in the study site from birth\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section3\"\u003e \u003ch2\u003eControls\u003c/h2\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eMust not have epilepsy, OAE or any other disease that can affect cognition\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eParticipants have willingly consented to participate, or those under the age of 18 have received parental consent.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eIs able and willing to participate in all neurocognitive tests\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eHas been living in the study site from birth\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eAll participants who refused to consent or who could not perform the different tasks in the tests were excluded.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section3\"\u003e \u003ch2\u003eBias\u003c/h2\u003e \u003cp\u003eThe study included a representative sample of OAE cases due to the door-to-door approach to participant recruitment. Also, the controls were recruited from the same household or residential area as the cases: We also matched the cases based on sex, age, and education level to mitigate any potential confounding factors arising from these factors. Moreover, controls were screened to ensure that they had no health conditions that could influence their cognitive performance. Furthermore, the author had to undergo training on how to conduct all the neurocognitive tests before administering them to the patients. Lastly, the author used local translators when necessary to ensure that patients understood the instructions clearly before performing the various tasks.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section3\"\u003e \u003ch2\u003eDefinitions\u003c/h2\u003e \u003cp\u003eUsing the criteria proposed by the ILAE for the diagnosis of epilepsy(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e), a case of epilepsy was defined as either:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eThe presence of at least two unprovoked (or reflex) seizures occurring greater than 24 hours apart\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eA diagnosis of an epilepsy syndrome.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eA single, unprovoked seizure with a probability of recurrence greater than 60%.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eOAE was defined using clinical criteria listed in the \u003cspan refid=\"Sec1\" class=\"InternalRef\"\u003ebackground\u003c/span\u003e section (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eCognitive performance:\u003c/h2\u003e \u003cp\u003eCognitive impairment was defined as a MoCA score of \u0026lt;\u0026thinsp;26 and an IHDS score\u0026thinsp;\u0026le;\u0026thinsp;10\u003c/p\u003e \u003cp\u003eExecutive dysfunction was defined as a FAB score\u0026thinsp;\u0026lt;\u0026thinsp;16 for educated participants and \u0026lt;\u0026thinsp;15 for uneducated participants\u003c/p\u003e \u003cp\u003eA Dubois' five-word test score of less than nine was used to define impaired memory.\u003c/p\u003e \u003cp\u003eAn Isaac Set Test score of less than 30 was defined as impairment in verbal fluency.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eSample size calculation\u003c/h2\u003e \u003cp\u003eWe determined the sample size of our cases and controls using the following formula, commonly used in the calculation of sample sizes in case-control studies.\u003c/p\u003e \u003cp\u003e\u003cimg 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\" style=\"width: 281px; height: 69.0726px;\" width=\"281\" height=\"69.0726\"\u003e\u003c/p\u003e \u003cp\u003eWhere;\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;=\u0026thinsp;sample size in the case group\u003c/p\u003e \u003cp\u003er\u0026thinsp;=\u0026thinsp;ratio of controls to cases\u003c/p\u003e \u003cp\u003e \u003cem\u003eṗ=\u003c/em\u003e proportion of cases in the exposed group\u003c/p\u003e \u003cp\u003e \u003cem\u003eP\u003c/em\u003e \u003csub\u003e \u003cem\u003e1\u003c/em\u003e \u003c/sub\u003e \u003cem\u003e-P\u003c/em\u003e \u003csub\u003e \u003cem\u003e2\u003c/em\u003e \u003c/sub\u003e\u0026thinsp;\u003cem\u003e=\u003c/em\u003e\u0026thinsp;\u003cb\u003eEffect Size\u003c/b\u003e (the difference in proportions)\u003c/p\u003e \u003cp\u003eZ\u003csub\u003eβ\u003c/sub\u003e represents the \u003cb\u003edesired power\u003c/b\u003e (typically 80% power).\u003c/p\u003e \u003cp\u003eZ\u003csub\u003eα/2\u003c/sub\u003e represents the desired \u003cb\u003elevel of confidence interval\u003c/b\u003e (typically 1.96 for 95% confidence).\u003c/p\u003e \u003cp\u003eP\u003csub\u003e1\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;risk of exposure in the case group\u003c/p\u003e \u003cp\u003eIn the control group, P2\u0026thinsp;=\u0026thinsp;exposure risk.\u003c/p\u003e \u003cp\u003eA previous study reported an 87.5% prevalence of neurocognitive impairment in patients with OAE and 37.5% in controls. To test for cognitive impairment, at least 12 persons are needed: 6 cases and 6 controls. This is based on the ratio of controls to cases (r\u0026thinsp;=\u0026thinsp;1), the power of 80%, and the required level of statistical significance (5%, Z\u0026sup2; = 0.84, Z\u0026plusmn;/2\u0026thinsp;=\u0026thinsp;1.96).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eData management and analysis\u003c/h2\u003e \u003cp\u003eData was collected in the field using paper forms and entered into SPSS version 20.0. Data was analyzed using SPSS version 20.0 based on study objectives. Continuous data were expressed as means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD). Frequencies and percentages were used to summarize data and evaluate sociodemographic variables' differences. We used the independent sample t test was to determine if there was a statistically significant difference between neurocognitive impairment in cases versus controls. The level of statistical significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05. To identify factors associated with cognitive impairment, a multivariate analysis was conducted.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe pre-screening identified a total of 65 suspected cases of epilepsy, 26 from Nkongmessa and 39 from Mong. Fifty cases were confirmed as OAE. Fifteen cases were excluded: 12 were untraceable, 1 refused to consent, and 2 had epilepsy due to other causes. We subsequently matched these cases to 50 controls, resulting in a total of 100 study participants. The mean age was 26.26\u0026thinsp;\u0026plusmn;\u0026thinsp;9.25 years for cases and 26.36\u0026thinsp;\u0026plusmn;\u0026thinsp;9.08 years for controls. Fifty-two percent of the cases were males, while 47% were females. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the sociodemographic profile of the study participants.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSociodemographic profile of study population\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCases\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eControls\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eN\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eN\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eTotal\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e50\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e100\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e50\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e100\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMarital Status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMarried\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSingle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDivorced/Separated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eConcubinage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eTotal\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e50\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e100\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e50\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e100\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOccupation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFarmer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e62\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStudent/pupil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSand dealer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTrader\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eTotal\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e50\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e100\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e50\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e100\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLevel of Education\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePrimary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e70\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSecondary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eTotal\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e50\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e100\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e50\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e100\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe majority of cases (64%) were discovered in Mong. Most participants had only reached the primary level of education (70%).\u003c/p\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eClinical characteristics\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows the clinical characteristics of OAE for the cases. Generalized tonic-clonic seizures were the most common seizure type. We identified probable nodding syndrome was in 2 patients who had a history of head nodding and other forms of seizures, primarily generalised tonic-clonic seizures. We also identified probable Nakalanga syndrome in 2 (4%) patients who presented with severe stunting and delayed development of external signs of sexual and generalised tonic-clonic seizures. The majority of epilepsy patients experienced their first seizure between the ages of 3\u0026ndash;18 years, with a peak around 5\u0026ndash;11 years.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical Characteristics of Epilepsy\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eN\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge of onset of epilepsy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;3 years of age\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u0026ndash;18 years of age\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e96\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;19 years of age\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e50\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e100\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSeizure Type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGeneralized tonic clonic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbsence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFocal onset\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProbable Noddling syndrome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProbable Nakalanga syndrome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGeneralized atonic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e50\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e100\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSeizure frequency\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOnce a week\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMore than once a week\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOnce a month\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMore than once a month\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOnce every 3 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOnce every 6 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e50\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e100\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eNeurocognitive Profile\u003c/h2\u003e \u003cp\u003e \u003cb\u003eSeverity of neurocognitive impairment.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eUsing the cutoff of \u0026gt;\u0026thinsp;26 for the Montreal cognitive test, the prevalence of global cognitive was 96% for cases as against 78% for controls (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). This difference was statistically significant (P\u0026thinsp;=\u0026thinsp;0.007).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe study participants were further grouped into the following categories: normal, mild, moderate, and severe, using cut-off values for each category proposed by the Quebec national institute for excellence in health and social sciences(\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Thirty percent of the cases had severe cognitive impairment, as opposed to 0% for the controls. Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows the classification of cognitive impairment based on severity.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCognitive impairment based on severity\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCognitive Impairment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eCases\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eControls\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eN\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eN\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMild\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e92\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModerate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSevere\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e50\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e100\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e50\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e100\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eUsing the IHDS, the prevalence of cognitive impairment was 70% for cases as against 10% for controls (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). This difference was statistically significant (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eSpectrum of Neurocognitive Impairment\u003c/h2\u003e \u003cp\u003eThe main cognitive functions affected were; memory, verbal fluency, attention, and executive function (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Our cases had more difficulties retaining than their controls (86% vs 30%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The cases were also less fluent than the controls (80% vs 42%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eFactors associated with neurocognitive impairment.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eTo identify independent factors associated with cognitive impairment, we performed a multivariate analysis. Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e shows the different factors associated with cognitive impairment.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eFactors associated with cognitive impairment\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eP Value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOR\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.151\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLevel of education\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.027\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.166\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVillage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.054\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge of onset of epilepsy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSeizure type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMost recent seizure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.979\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSeizure frequency\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of epilepsy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASM type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.708\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdherence to ASM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eASM: Antiseizure medications\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eWe found strong associations between cognitive impairment and factors such as low level education, early age of onset of epilepsy, generalized tonic-clonic seizure, frequent seizures, and longer duration of epilepsy. We also found a borderline association between cognitive impairment and village of origin.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe found severe cognitive impairment in our study, and the main factors associated with cognitive impairment were level of education, village, age of onset of epilepsy, seizure type, seizure frequency, and duration of epilepsy. Our results are similar to those reported in a similar study in Cameroon(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Several factors could account for this high prevalence. Firstly, the high occurrence of uncontrolled or frequent seizures could have induced significant brain damag, leading to severe cognitive deficits. In various types of epilepsy, uncontrolled seizures have been linked to neurodegenerative changes and cognitive decline. With each seizure, there is a risk of neuronal injury. Uncontrolled seizures can cause cumulative neuronal injury, which over time can lead to severe cognitive decline. Furthermore, onchocerciasis-associated epilepsy may be a manifestation of central nervous system involvement by the parasite itself. The antigens and/or microfilaria of \u003cem\u003eO. volvulus\u003c/em\u003e could potentially be neurotoxic and may directly contribute to neuronal damage and cognitive impairment. A study looked at the link between having an Ov16 (antibody against O. volvulus) and neurocognitive performance in children from three villages in Cameroon. It found that having an Ov16 was significantly linked to lower semantic verbal fluency and lower scores on the IHDS(\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). Future prospective studies to explore the possible relationship between Onchocerciasis and cognition should be considered\u003c/p\u003e \u003cp\u003eAlso, the high prevalence of cognitive impairment could have been influenced by socio-economic disadvantages common in rural areas, such as limited access to healthcare, educational opportunities, and adequate nutrition. Access to healthcare services for epilepsy management is particularly poor in many low- and middle-income countries(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). Most people with epilepsy in these regions may only receive suboptimal or no treatment, leading to frequent and uncontrolled seizures and progressive brain damage. The low level of educational attainment in this study may also be a contributing factor. Education has been shown to be a protective factor against cognitive decline(\u003cspan additionalcitationids=\"CR32\" citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). People with a high level of educational attainment tend to have greater cognitive reserves, which can help mitigate the effects of neuronal insults(\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). The majority of cases in this study had only completed the primary level of education, possibly due to limited access to educational opportunities, high levels of stigma that often result in early school dropouts, and the disabling effects of seizures on school attendance(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). With a low level of educational attainment, cognitive reserves are lower, and cognitive decline is more likely to occur(\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAdditionally, the high cutoff value of \u0026gt;\u0026thinsp;26 for the MoCA could have led to high false positives. A previous study suggested that the current MoCA cutoff of 26 is too global and too high for the detection of mild cognitive impairment(\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e). According to certain authors, a 3-class model (normal, mildly impaired, and severely impaired) may more accurately reflect cognitive impairment best(\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e). Moreover, the negative psychotropic effects of anti-seizure drugs such as phenobarbitone could have also contributed to the high prevalence of neurocognitive impairment in the study cohort (\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e). Anti-seizure medications, particularly phenobarbitol, consistently increase the incidence of cognitive complications in people with epilepsy, and this effect is dose-dependent (\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMemory, verbal fluency, attention, and executive function were more impaired in patients with OAE than in the controls. Memory, attention, and executive function are the most commonly affected cognitive functions in people with epilepsy, irrespective of the underlying etiology(\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e). Temporal and frontal lobe epilepsies are the most common forms of epilepsy in adults with epilepsy. In temporal lobe epilepsy, recurrent and/or prolonged seizures lead to atrophy and sclerosis of the hippocampus, a very important structure for memory formation, consolidation, and retrieval(\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e). The long-term consequence of hippocampal sclerosis is significant cognitive impairment, with memory being the most affected cognitive function(\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e). The different parts of the frontal lobe work to support executive functions and working memory, as well as emotional control and inhibition (\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e). Seizures originating from the frontal lobe can disrupt and damage frontal lobe networks responsible for executive function and working memory, leading to executive dysfunction and behavioural disorders(\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e). Focal seizures, which could mean either temporal or frontal lobe epilepsy, were not common in our study group. However, generalized seizures can damage neuronal networks in the temporal and frontal lobes and lead to cognitive problems similar to those seen in people with temporal and frontal lobe epilepsy (\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eCases from Mong village were more cognitively impaired compared to those from Nkongmessa. Inhabitants of Mong are closest to and in direct contact with the Sanaga River, which is an excellent breeding ground for the black fly, which is the vector for \u003cem\u003eO. volvulus\u003c/em\u003e. Because they are more likely to come into contact with the O. \u003cem\u003evolvulus\u003c/em\u003e vector, they are more likely to have higher microfilaria loads, which can lead to more severe and frequent seizures, all of which make cognitive impairment worse.. Furthermore, if O. \u003cem\u003evolvulus\u003c/em\u003e causes cognitive impairment separate from seizures (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e), the close proximity of Mong participants to the black fly's breeding site could potentially lead to a higher microfilaria load and consequently, greater onchocerciasis-induced cognitive impairment\u003c/p\u003e \u003cp\u003eThe onset of seizures at an early age was significantly associated with greater cognitive impairment. Early seizure onset can disrupt critical periods of brain development and maturation, causing abnormal neural connections and network formation(\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e). A review by Marco Mula reported that an age of onset of epilepsy younger than 5 years old is associated with greater cognitive impairment(\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eCases with poor seizure control or frequent seizures were more cognitively impaired than those with fewer frequent seizures. Poorly controlled seizures can cause cognitive decline in a number of ways, such as inducing significant neuroinflammation, disruption of brain connections that are important for neuroplasticity, increased risk of comorbidities such as depression and sleep disorders, and decreased cognitive reserves(\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e, \u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eA longer duration of epilepsy was associated with poorer cognitive performance. People with prolonged epilepsy are exposed to chronic neuroinflammation and progressive neurodegeneration for a long time, which can affect cognition (\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e). Also, with a longer duration of epilepsy, there is a higher risk of comorbidities such as depression, anxiety, and sleep disorders, which may exacerbate cognitive impairment(\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e). Moreover, there is prolonged exposure to the cognitive side effects of anti-seizure medications with a longer duration of epilepsy(\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e). Furthermore, a longer duration of epilepsy can affect daily life, social relationships, and emotional well-being, leading to additional cognitive decline(\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eContrary to other studies, we didn\u0026rsquo;t find any significant association between antiseizure medication and neurocognitive impairment. This may be due to the small sample size and the low level of medication adherence in the study population. A low level of adherence reduces exposure to the negative side effects of antiseizure medications.\u003c/p\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eOur neurocognitive assessment screening tools (with the exception of the international HIV dementia scale) were linguistically and culturally inappropriate for our study population. This may have led to an overestimation of cognitive impairment. Future studies to adapt these tests to our context are needed.\u003c/p\u003e \u003cp\u003eNo brain imaging or genetic tests were done to rule out other causes of epilepsy. A multifaceted approach was used to thoroughly check for the presence of other risk factors. This included questioning the participants, their parents, caregivers, or guardians, looking through the patient's medical records, and doing a full neurological assessment. Moreover, we did not assess other factors that could have affected cognition, such as sleep, nutrition, stress, social engagement, and sleep disorders.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe neurocognitive burden of onchocerciasis-associated epilepsy is substantial, highlighting the need for early diagnosis, effective seizure control, and integrated management approaches that address both the parasitic infection and its neurological sequelae. The need to eliminate onchocerciasis and, hence, reduce the prevalence of OAE has never been more imperative. Further studies to assess the impact of onchocerciasis on neurocognition in those without epilepsy are needed.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eASM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eantiseizure medication\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFAB\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eFrontal Assessment Battery\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFWT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eFive words test\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHIV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHuman immunodeficiency Virus\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIHDS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInternational HIV dementia scale\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eILAE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInternational League Against Epilepsy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMoCA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMontr\u0026eacute;al Cognitive Assessment\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOAE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOnchocerciasis-associated epilepsy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e \u003cp\u003eParticipant confidentiality was strictly respected throughout this study. We obtained ethical approvals from the institutional ethical review board of the faculty of medicine and biomedical sciences of the University of Yaound\u0026eacute; 1 (Ref. No. 169/UY1/FMSB/VDRC/CSD) and the Cameroonian National Ethics Committee for Human Health Research (Registration number: 2018/12/1123/CE/CNERSH/SP) prior to the commencement of this study. We also got approvals (verbal and written) from the chiefs of the villages/communities We also obtained authorization from the Ministry of Public Health (D30\u0026ndash;864LS/MINSANTE/SG/DLMEP/SDLCNT). Informed consent was also obtained from household heads or his representatives, as well as from the final respondents.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003e \u003cb\u003eConsent for publication\u003c/b\u003e :\u003c/strong\u003e \u003cp\u003eNot applicable\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003e \u003cb\u003eCompeting interests\u003c/b\u003e:\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no competing interests\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eNot applicable\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eMNN designed the study, collected, analysed and interpreted data, and wrote the manuscript text.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e \u003cp\u003eOur gratitude goes to all the chiefs and local authorities at the study sites for their active participation and collaboration. We are also grateful to the epilepsy patients for their collaboration and hospitality. We are particularly grateful to the executive director of Brain Research Africa for supervising this work.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBeghi E, Giussani G, Nichols E, Abd-Allah F, Abdela J, Abdelalim A, et al. Global, regional, and national burden of epilepsy, 1990\u0026ndash;2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet Neurology. 2019 Apr 1;18(4):357\u0026ndash;75. \u003c/li\u003e\n\u003cli\u003eBa-Diop A, Marin B, Druet-Cabanac M, Ngoungou EB, Newton CR, Preux PM. Epidemiology, causes, and treatment of epilepsy in sub-Saharan Africa. 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Middle East Current Psychiatry. 2023 Feb 3;30(1):15. \u003c/li\u003e\n\u003cli\u003eMwangala PN, Kariuki SM, Nyongesa MK, Mwangi P, Chongwo E, Newton CR, et al. Cognition, mood and quality-of-life outcomes among low literacy adults living with epilepsy in rural Kenya: A preliminary study. Epilepsy Behav. 2018 Aug;85:45\u0026ndash;51. \u003c/li\u003e\n\u003cli\u003eMedscape [Internet]. [cited 2024 Jul 18]. Cognitive Dysfunction in Patients With Epilepsy: Focus on Clinical Variables. Available from: http://www.medscape.org/viewarticle/837686\u003c/li\u003e\n\u003cli\u003eLenck-Santini PP, Scott RC. Mechanisms Responsible for Cognitive Impairment in Epilepsy. Cold Spring Harb Perspect Med. 2015 Jan 10;5(10):a022772. \u003c/li\u003e\n\u003cli\u003eHolmes GL. Effect of Seizures on the Developing Brain and Cognition. Semin Pediatr Neurol. 2016 May;23(2):120\u0026ndash;6. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Onchocerciasis-associated epilepsy, neurocognitive impairment, Onchocerciasis","lastPublishedDoi":"10.21203/rs.3.rs-4774080/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4774080/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eA specific form of epilepsy called onchocerciasis-associated epilepsy (OAE) is common in onchocerciasis-endemic communities. Data on the prevalence and pattern of neurocognitive impairment caused by OAE is sparse in Africa. This aim of this study was to determine the spectrum and severity neurocognitive impairment among patients with OAE in two onchocerciasis-endemic communities.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA case-control study was conducted in two rural villages in an onchocerciasis-endemic zone in the central region of Cameroon. Based on diagnostic criteria established in other studies, we diagnosed patients with onchocerciasis-associated epilepsy and matched by age, sex, and educational level to controls. Neurocognitive functions were assessed using the Montreal Cognitive Assessment Test, Frontal Assessment Battery, International HIV Dementia Scale, Dubois\u0026rsquo; Five Words Tests and Isaac Set\u0026rsquo;s tests. Data were analyzed using SPSS software version 19. The threshold for statistical significance was set at P\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe study included fifty people with OAE and fifty healthy controls. The mean age for the cases was 26.3 years, and for the controls, it was 26.4 years. Cases were more impaired cognitively than the controls, 96% for the cases vs. 78% for the controls (P\u0026thinsp;=\u0026thinsp;0.007, OR;7.7). The main cognitive functions affected were memory (86% of cases Vs 30% of controls, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001, OR\u0026thinsp;=\u0026thinsp;34.4), verbal fluency (80% of cases Vs 42% of controls, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001, OR\u0026thinsp;=\u0026thinsp;15.6), attention, and executive functions (80% of cases as against 42% of controls, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The main factors associated with poorer neurocognitive outcomes were longer duration of epilepsy (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), frequent seizures (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), low educational level (P\u0026thinsp;=\u0026thinsp;0.027), generalized tonic-clonic seizures (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and early age of onset of epilepsy (0.001)\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eOnchocerciasis-associated epilepsy causes severe neurocognitive impairment in those affected. The need to eliminate onchocerciasis and, hence, reduce the prevalence of OAE has never been more imperative.\u003c/p\u003e","manuscriptTitle":"The Neurocognitive Burden of Onchocerciasis-associated Epilepsy in an onchocerciasis-endemic zone in Cameroon: a case-control study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-19 15:45:38","doi":"10.21203/rs.3.rs-4774080/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"48aec88b-4b86-4ee2-a8d5-1437756cc429","owner":[],"postedDate":"August 19th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-09-24T12:08:57+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-19 15:45:38","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4774080","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4774080","identity":"rs-4774080","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}