Evaluation of the role of estimation of serum level of miRNAs223 and HMGB1in detection of patient with drug resistant epilepsy.

Early detection of the prognosis might help in guiding patients for proper management and treatment strategy.

This may open the door for new drug trials.

Epilepsy is the most prevalent neurological disorders (1). Drug-resistant epilepsy (DRE) represent approximately 30% of epilepsy..DRE is defined as failure to achieve sustained seizure freedom after adequate and well tolerated trials of two antiseizure medications( ASMs).The identification of circulating biomarkers for DRE could give an early idea about the prognosis and improve the choice of correct treatment.

MiRNAs are small noncoding RNAs that span between 19 and 24 nucleotide bases((2).They gain biological activity through base pairing in the 30-untranslated regions of target messenger RNA (mRNA) , thereby guiding a protein complex termed the RNA-induced silencing complex (RISC) that bind to the mRNA sequence and results in either the inhibition of translational processes or the degradation of the mRNA (3). Dysregulated miRNA expression has been associated with inflammatory pathways, cell death, neuronal excitability, and synaptic reorganization, which underlie epileptogenesis (4).

High- mobility group box 1(HMGB1) is a chromatin component that is physiologically attached to nuclei. However, following CNS insult, it can promptly be migrated towards cytoplasm and is discharged extracellularly. HMGB1mediates sterile neuro-inflammation evoked by epileptogenic injury and recurrent seizures(5) .HMGB1 increases in neurons, glia, and endothelial cells of the blood brain barrier (BBB) in DRE.

The HMGB1 contributes to the overexpression of P-glycoprotein, a BBB protein, which is induced in DRE foci and extrudes various ASMs from the brain(6) .

Inclusion Criteria:

• Patients diagnosed as drug resistant epilepsy .
• Control group: patients diagnosed as medically controlled epilepsy

Exclusion Criteria:

• Symptomatic epilepsy (vascular, tumor, post encephalitic, syndromic and febrile seizures).
• Alzheimers disease
• Parkinsons disease
• amyotrophic lateral sclerosis
• major depression disorder
• Non neurological criteria: tumors and cardiovascular

Drug resistant epilepsy defined as(failure to achieve sustained seizure freedom after adequate and well tolerated trials of two anti-seizure medications) Well controlled epilepsy defined as(seizure freedom for at least the last 6months) matched in sex and age.