الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Epilepsy is a group of chronic neurological disorders characterized by spontaneous, recurrent, and unpredictable seizures. It is one of the most common central nervous system diseases affecting people of all ages, races, and geographical regions. It affects approximately 50 million individuals worldwide. Around 80% of epileptic patients are present in developing countries. Moreover, three quarters of these patients do not take proper treatment. Current interventions and AED are considered ineffective in more than thirty percent of patients. The pathogenic mechanisms underlying drug-resistant epilepsy remain unknown.
Conclusive diagnosis of drug resistant epileptic patients always needs a prolonged treatment cycle of many years. During this period, recurrent fits may not only worsen their cerebral function but also results in delaying optimal opportunity for thorough treatment, including surgery. Therefore, researchers aim to validate a rapid, noninvasive and inexpensive marker for early identification of drug resistant epilepsy.
MiRNAs are a group of small non-coding RNAs of about 22 nucleotides that negatively regulate specific gene expression, mainly through interaction with target mRNAs leading to their degradation or inhibiting their translation, resulting in overall lower protein levels in cells. In recent years, the role of miRNAs in epilepsy is a fast- expanding area of research.
The aims of this study were to assess the roles of miRNAs 153 and 199a in epilepsy, and their relation to hypoxia inducible factor 1. Also, the possible use of miRNAs 153 and 199a as predictive biomarkers for drug resistance in generalized and focal epilepsy was assessed.
Our study comprised 20 patients with generalized epilepsy, 20 patients diagnosed with focal epilepsy and 20 healthy controls. In generalized epilepsy group, 11 patients were drug responsive and 9 patients were drug resistant. While in the focal group, 9 patients were drug responsive and 11 were drug resistant.
The following investigations were performed for all patients and healthy subjects:
• Total RNA was extracted from serum samples followed by reverse transcription real time PCR. Then expression of serum miRNAs 153 and 199a was calculated.
• Serum Hypoxia inducible factor 1α (HIF-1α) level using Enzyme Linked Immunosorbent Assay.
Statistical analysis of the studied parameters showed that:
• Serum levels of both miRNAs 153 and 199a are significantly downregulated in patients with generalized epilepsy as compared with healthy controls. But, There was statistically non-significant upregulation of both miRNAs in focal group when compared to control group.
• Accordingly the possible use of miRNAs 153 and 199a for diagnosis of generalized epilepsy was assessed. It was found that the combination of both miRNAs had the best diagnostic value reaching 90% sensitivity in addition to 70% specificity.
• Serum miRNAs 153 and 199a expression levels cannot be used as markers for the diagnosis of focal epilepsy as they showed nonsignificant difference between focal epilepsy group and control group.
• No significant difference was detected among the studied groups regarding serum level of HIF-1α.
• The mean expression of miRNA 153 in generalized epilepsy patients was downregulated in drug resistant patients compared to drug responders. While in focal epilepsy group, it was significantly upregulated in refractory patients compared to drug responsive group. However, the mean expression of miRNA 199a was non-significantly deregulated in refractory patients compared to drug responsive patients in both generalized and focal epilepsy groups.
• Our results revealed that combination of miRNAs 153 and 199a can predict drug resistance in generalized epilepsy with 100% sensitivity and specificity.
• In focal epilepsy group, miRNA 153 showed better results in predicting drug resistance than the combination of both miRNAs with sensitivity 100% and 66.67% specificity.
Our results revealed that serum expression level of miRNAs 153 and 199a may have a diagnostic role for generalized epilepsy as well as a predictive role for drug resistance in both focal and generalized epilepsy.