Risk Factors and Etiologies of Epilepsy in Urban and Rural Rwanda

Study Overview
=================
Brief Summary
-----------------
Epilepsy is one of the most common chronic brain disorders. Up to 85% of persons living with epilepsy (PwE) live in the developing world. In sub-Saharan Africa (SSA), Rwanda has one of the highest prevalence rates (±5%). Higher prevalence in low-and middle-income countries (LMICs) can partly be attributed to differences in risk factors for epilepsy of which a great number are preventable. Expanding knowledge on risk factors and etiologies of epilepsy in Rwanda can lower the portion of preventable epilepsies and decrease the high number of Rwandan PwE. This project will focus on the investigation of risk factors and etiologies of epilepsy in urban and rural Rwanda using a nationwide approach.

Detailed Description
-----------------
Risk factors and etiologies of epilepsy in the Rwandan population will be determined using two phases. The initial phase (Task 1) includes the recruitment of the study population using two separate surveys. The first survey (Task 1.1.) will be conducted in the general population by a door-to-door (D2D) approach. During D2D visits in 10 selected urban and rural villages throughout the country, one rural and one urban per province, persons of the households with permanent residence will be interviewed by enumerators to screen for epilepsy. In case of a positive screening, they will be assessed by a team of Rwandan and Belgian neurologists to confirm the epilepsy diagnosis. During a second survey (Task 1.2.), PwE will be matched with control persons defined as persons who screened negative during the Task 1.1 survey. The second phase of our study (Task 2) consists of the assessment of potential risk factors associated with epilepsy using the matched case-control group (Task 2.1.), and the identification of underlying etiology in PwE according to the International League Against Epilepsy (ILAE) etiology guidelines (Task 2.2.). Task 2.1. Both cases and controls will complete a structured questionnaire on a wide range of potential risk factors present before the onset of the epilepsy, administered by research assistants. In addition, blood samples from both PwE and controls will be collected as to measure the exposure to parasitic infections and HIV, and the presence of sickle cell disease, among others. Exposure will be measured by detection of IgG antibodies to parasitic antigens including Taenia solium, Toxoplasma gondii and Plasmodium falciparum as well as HIV in plasma samples of the participants. Task 2.2. Further, in order to classify PwE according to the ILAE etiology guidelines, we will use the detailed medical and epilepsy history including in-depth narrative of seizure description and frequency, clinical examination and narrative of epilepsy treatment assessed by the team of neurologists subsequent to the confirmation of the epilepsy diagnosis. In addition, all PwE will undergo EEG recording using a mobile device. Furthermore, PwE will undergo CT- or MRI-imaging unless previous imaging studies have been performed and are accessible for re-evaluation.

Official Title
-----------------
Risk Factors and Etiologies of Epilepsy in Urban and Rural Rwanda

Conditions
-----------------
Epilepsy

Intervention / Treatment
-----------------
* Diagnostic Test: EEG
* Diagnostic Test: Neuroimaging
* Diagnostic Test: Blood sample
* Other: Risk factor questionnaire


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Inhabitants of the selected villages who screen positive on the Limoges epilepsy screening questionnaire during the D2D visits and have a confirmed epilepsy diagnosis assessed by a team of Rwandan and Belgian neurologists, are included as PwE. Epilepsy will be defined as unprovoked recurrent seizures occurring more than 24h apart, including active and lifetime epilepsy. Persons with a negative screening during the D2D visits who match with a PwE for age and gender and have an absence of epilepsy confirmed during a clinical assessment by a team of Rwandan and Belgian neurologists, are included as control persons. Exclusion Criteria: Inhabitants of the selected villages who are unwilling to complete a verbal witnessed informed consent during D2D visits. For patients ≤18 years of age, verbal consent will be obtained from their parents/caregivers. PwE and selected control persons who are unwilling to sign a written informed consent upon referral for neurological assessment. PwE and control persons not meeting the inclusion criteria.
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| People living with epilepsy (PwE)<br>Study participants with epilepsy | Diagnostic Test: EEG<br>* EEG registration performed in PwE to confirm epilepsy diagnosis<br>Diagnostic Test: Neuroimaging<br>* Neuroimaging performed in PwE to diagnose epilepsy etiology<br>* Other names: CT/MRI;Diagnostic Test: Blood sample<br>* Blood samples from both PwE and controls will be collected to measure full blood count, IgM and IgG antibodies to parasitic antigens including Taenia solium, Toxoplasma gondii and Plasmodium falciparum, to perform ELISA for HIV1 and HIV2, to measure HIV viral load and to conduct an emmel test.<br>Other: Risk factor questionnaire<br>* Both PwE and control subjects will complete a structured questionnaire on a wide range of potential risk factors present before the onset of the epilepsy.<br>|
| Control subjects<br>Study participants without epilepsy | Diagnostic Test: Blood sample<br>* Blood samples from both PwE and controls will be collected to measure full blood count, IgM and IgG antibodies to parasitic antigens including Taenia solium, Toxoplasma gondii and Plasmodium falciparum, to perform ELISA for HIV1 and HIV2, to measure HIV viral load and to conduct an emmel test.<br>Other: Risk factor questionnaire<br>* Both PwE and control subjects will complete a structured questionnaire on a wide range of potential risk factors present before the onset of the epilepsy.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association between epilepsy and exposure of possible risk factors for epilepsy | The following risk factors will be assessed in both PwE and control subjects: family history of seizures, history of febrile seizures, history of head trauma, history of CNS infections and tuberculosis, history of perinatal events, cassava consumption and malnutrition, immunization status against common communicable diseases, history of cerebrovascular disease including hypertension, hypercholesterolemia and diabetes mellitus as primary risk factors and consumption of alcohol, drugs and tobacco; using a risk factor questionnaire. Additional risk factors including exposure to parasitic infections e.g., toxoplasmosis, malaria, neurocysticercosis and HIV, and the presence of sickle cell disease, among others, will be measured by analysis of blood samples. Primary risk factors associated with the mentioned parasitic infections and HIV are included in the questionnaire. | Baseline | 
| Etiologies of epilepsy | Etiologies of epilepsy in PwE will be classified according to the 2017 International League Against Epilepsy (ILAE) criteria using detailed medical and epilepsy history, clinical examination and paraclinical investigations including EEG recording and neuroimaging in PwE only. | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Male and female epilepsy risk factors and etiologies | A sub-analysis comparing male and female epilepsy risk factors and etiologies will be conducted. | Baseline | 
| Prevalence of epilepsy | Establishment of prevalence of epilepsy in selected villages | Baseline | 
| Diagnosis gap | Previous diagnosis of epilepsy if applicable, including who initially made the diagnosis and when, will be self-reported during epilepsy screening in the selected villages defining newly and previously diagnosed patients (diagnosis gap). | Baseline | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Epilepsy / etiology, Epilepsy / epidemiology, Seizures, Africa South of the Sahara, Risk Factors, Case-Control Studies, Epilepsy