Circulating MicroRNAs From Plasma Small Extracellular Vesicles as Potential Diagnostic Biomarkers in Pediatric Epilepsy and Drug-Resistant Epilepsy

Abstract

Pediatric epilepsy is a neurological condition that causes repeated and unprovoked seizures and is more common in 1–5-year-old children. Drug resistance has been indicated as a key challenge in improving the clinical outcomes of patients with pediatric epilepsy. In the present study, we aimed to identify plasma small extracellular vesicles (sEVs) derived microRNAs (miRNAs) from the plasma samples of children for predicting the prognosis in patients with epilepsy and drug-resistant epilepsy. A total of 90 children clinically diagnosed with epilepsy [46 antiepileptic drug (AED)-responsive epilepsy and 44 drug-resistant epilepsy] and 37 healthy controls (HCs) were enrolled in this study. RNA sequencing was performed to identify plasma sEVs derived miRNAs isolated from the children’s plasma samples. Differentially expressed plasma sEVs derived miRNAs were identified using bioinformatics tools and were further validated by reverse transcription-polymerase chain reaction and receiver operator characteristic (ROC) curve analysis. In the present study, 6 miRNAs (hsa-miR-125b-5p, hsa-miR-150-3p, hsa-miR-199a-3p, hsa-miR-584-5p hsa-miR-199a-5p, and hsa-miR-342-5p) were selected for further validation. hsa-miR-584-5p, hsa-miR-342-5p, and hsa-miR-150-5p with area under curve (AUC) values of 0.846, 0.835, and 0.826, respectively, were identified as promising biomarkers of epilepsy. A logistic model combining three miRNAs (hsa-miR-584-5p, hsa-miR-342-5p, and hsa-miR-199a-3p) could achieve an AUC of 0.883 and a six miRNAs model (hsa-miR-342-5p, hsa-miR-584-5p, hsa-miR-150-5p, hsa-miR-125b-5p, hsa-miR-199a-3p, and hsa-miR-199a-5p) could attain an AUC of 0.888. The predicted probability of multiple miRNA panels was evaluated for differentiating between drug-resistant children and drug-responsive children. The AUC of a six-miRNA panel (hsa-miR-342-5p, hsa-miR-584-5p, hsa-miR-150-5p, hsa-miR-125b-5p, hsa-miR-199a-3p, and hsa-miR-199a-5p) reached 0.823. We identified and confirmed plasma sEVs derived miRNA biomarkers that could be considered as potential therapeutic targets for pediatric epilepsy and drug-resistant epilepsy.

Smart Nanoscale Extracellular Vesicles in the Brain: Unveiling their Biology, Diagnostic Potential, and Therapeutic Applications

“…278 In another study of pediatric epilepsy, small EVs-associated hsa-miR-584-5p, hsa-miR-342-5p, and hsa-miR-150-5p were identified as promising biomarkers. 279 Similarly, serum exosomes containing miR-155 in epilepsy patients correlated to the disease states and abnormal EEG profiles. 280 BDEVs displayed altered profiles for miRNA-346 and miRNA-341-3p in the mice model for temporal lobe epilepsy.…”

Micro-RNAs from Plasma-Derived Small Extracellular Vesicles as Potential Biomarkers for Tic Disorders Diagnosis

“…In neurological disorders, nearly 70% of the miRNAs are expressed in the human cerebrum and many of them are particular to neurons [ 18 ]. Distinctive miRNA expression is involved in neuronal differentiation and morphological properties [ 19 ] and contributes to ir-regular cerebrum development and the mechanism of multiple neurodevelopmental disorders [ 20 ], such as Alzheimer’s disease [ 21 ], Parkinson’s disease [ 22 ], epilepsy [ 23 , 24 ], and Tourette Syndrome [ 25 ]. The assessment of miRNA expression level in patients with nervous system disorders may help diagnose related neurological disease.…”

Revisiting the concept of drug‐resistant epilepsy: A TASK1 report of the ILAE/AES Joint Translational Task Force

“…For example, several studies explored differences in the expression pattern of circulating miRNAs between patients with DRE and drug-sensitive epilepsy. [97][98][99] These differences may, for example, influence inflammatory mediators as regulatory factors, or may more contribute directly to alterations in the expression of ASM targets. 100 Evidence exists that pro-inflammatory mediators can contribute not only to intrinsic severity but can also directly affect pharmacokinetics and pharmacodynamics, for example, by effects on transporter expression or target subunit composition.…”