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About 30% of patients with epilepsy have drug-resistant seizures. The aim of the current endeavor was to systematically review the existing evidence on the potential applications of microRNAs as biomarkers in people with difficult to treat temporal lobe epilepsy (TLE). MEDLINE (accessed from PubMed) and Scopus from inception to March 18, 2020 were systematically searched for related published articles. In both electronic databases, the following search strategy was implemented, and these keywords (in the title/abstract) were used "microR