Drug Resistant Epilepsy: Clinical and Genetic Study

Study Overview
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Brief Summary
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This study is to identify the clinical criteria of drug resistant epilepsy and to explore whether SCN1A c.3184 A/G (rs2298771) and ccl2(rs1024611) polymorphisms could serve as genetic based biomarkers to predict drug resistance among epileptic patient.

Detailed Description
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This retrospective case control study will be conducted on 120 epileptic patients treated with AEDs, 60 patients are drug responders and 60 patients are drug resistant. All epileptic patient will be recruited from outpatient epilepsy clinic, Department of Neurology, Mansoura University hospital. The control consists of 60 Age and gender matched healthy individual with negative past and family history of epilepsy and febrile convulsion. Subjects: Inclusion criteria: Patient with diagnosis of epilepsy (idiopathic or cryptogenic/symptomatic), according to the International League Against Epilepsy classification confirmed by electroencephalogram. Treatment with at least one AED, long enough to achieve the optimal dose; drug-resistance and drug-responsiveness, according to the criteria ILAE 2010. Written consent obtained from a patient or legal guardian. Exclusion criteria: Patient with severe adverse anti epileptic drug reactions. Patient with unreliable records of seizure frequency. Patient with poor compliance with AEDs,. Patient with significant psychiatric comor- bidity, Patient with progressive systemic disorders . Patient with history of alcohol or drug abuse. Epileptic patients in clinical remission or with gradual withdrawal of therapy. Epileptic patients with therapy titration phase. Methods: After an informed consent, all participants will be subjected to the following; A detailed history taking; including age, sex, age of onset , type of seizure, duration of epilepsy, pretreatment and post treatment seizure frequency , and drugs (antiepileptic drugs, others). Full laboratory investigation including (complete blood count, liver function test, serum creatinine, electrolyte assay, thyroid profile, blood sugar test). Serum level of antiepileptic drug. Electroencephalogram in order to localize site of paroxysmal activity. MRI brain: T1, T2 and FLAIR: axial and coronal cuts to detect any structural abnormalities, Both control and epileptic patient will underwent genetic study for SCN1A c.3184 A/G and CCL2-2518G>A polymorphism: DNA analysis: Genomic DNA will be extracted from EDTA-anticoagulated peripheral blood (QIAamp DNA Blood mini kit,QIAGEN).

Official Title
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Clinical and Genetic Factors Associated With Drug Resistance of Epilepsy

Conditions
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Epilepsy, Drug Resistant

Intervention / Treatment
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* Genetic: Genetic study for SCN1A c.3184 A/G and CCL2-2518G>A polymorphism:


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with diagnosis of epilepsy (idiopathic or cryptogenic/symptomatic), according to the International League Against Epilepsy classification confirmed by electroencephalogram. Treatment with at least one AED, long enough to achieve the optimal dose; drug-resistance and drug-responsiveness, according to the criteria ILAE 2010. Exclusion Criteria: Patient with severe adverse anti-epileptic drug reactions. Patient with unreliable records of seizure frequency. Patient with poor compliance with AEDs,. Patient with significant psychiatric comorbidity, Patient with progressive systemic disorders . Patient with history of alcohol or drug abuse. Epileptic patients in clinical remission or with gradual withdrawal of therapy. Epileptic patients with therapy titration phase.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Drug responders<br>60 patients are drug responders | Genetic: Genetic study for SCN1A c.3184 A/G and CCL2-2518G>A polymorphism:<br>* DNA analysis: Genomic DNA will be extracted from EDTA-anticoagulated peripheral blood (QIAamp DNA Blood mini kit,QIAGEN). Genotyping of SCN1A c.3184 A/G(rs2298771) polymorphism<br>|
| Drug resistant<br>60 patients are drug resistant | Genetic: Genetic study for SCN1A c.3184 A/G and CCL2-2518G>A polymorphism:<br>* DNA analysis: Genomic DNA will be extracted from EDTA-anticoagulated peripheral blood (QIAamp DNA Blood mini kit,QIAGEN). Genotyping of SCN1A c.3184 A/G(rs2298771) polymorphism<br>|
| The control<br>The control consists of 60 Age and gender matched healthy individual with negative past and family history of epilepsy and febrile convulsion. | Genetic: Genetic study for SCN1A c.3184 A/G and CCL2-2518G>A polymorphism:<br>* DNA analysis: Genomic DNA will be extracted from EDTA-anticoagulated peripheral blood (QIAamp DNA Blood mini kit,QIAGEN). Genotyping of SCN1A c.3184 A/G(rs2298771) polymorphism<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Genetic study for SCN1A c.3184 A/G and CCL2-2518G>A polymorphism: | • DNA analysis: Genomic DNA will be extracted from EDTA-anticoagulated peripheral blood (QIAamp DNA Blood mini kit,QIAGEN). • Genotyping of SCN1A c.3184 A/G(rs2298771) polymorphism | 5-7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epilepsy, genetic and drug resistant