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EBioMedicine. 2018 Dec;38:127-141. doi: 10.1016/j.ebiom.2018.10.068. Epub 2018 Nov 2.

Dual-center, dual-platform microRNA profiling identifies potential plasma biomarkers of adult temporal lobe epilepsy.

Author information

1
Department of Physiology & Medical Physics, RCSI, Dublin, Ireland; Department of Anatomy, Mosul Medical College, University of Mosul, Mosul, Iraq.
2
Epilepsy Center Hessen, Department of Neurology, Philipps University Marburg, Marburg, Germany; Epilepsy Center Frankfurt Rhine-Main, Neurocenter, Goethe-University Frankfurt, Frankfurt a.m., Germany; Center for Personalized Translational Epilepsy Research (CePTER), Frankfurt/Main, Germany.
3
Department of Physiology & Medical Physics, RCSI, Dublin, Ireland; Beaumont Hospital, Beaumont Road, Dublin, Ireland.
4
Department of Physiology & Medical Physics, RCSI, Dublin, Ireland.
5
School of Chemical Sciences, National Centre for Sensor Research, Dublin City University, Dublin, Ireland.
6
School of Chemical Sciences, National Centre for Sensor Research, Dublin City University, Dublin, Ireland; FutureNeuro Research Centre, RCSI, Dublin, Ireland.
7
Department of Physiology & Medical Physics, RCSI, Dublin, Ireland; FutureNeuro Research Centre, RCSI, Dublin, Ireland.
8
Epilepsy Centre, Department of Neurology, University of Erlangen, Erlangen, Germany.
9
Beaumont Hospital, Beaumont Road, Dublin, Ireland; FutureNeuro Research Centre, RCSI, Dublin, Ireland; Department of Molecular & Cellular Therapeutics, RCSI, Dublin, Ireland.
10
FutureNeuro Research Centre, RCSI, Dublin, Ireland; School of Computer Science, UCD, Dublin, Ireland.
11
Department of Physiology & Medical Physics, RCSI, Dublin, Ireland; FutureNeuro Research Centre, RCSI, Dublin, Ireland. Electronic address: dhenshall@rcsi.ie.

Abstract

BACKGROUND:

There are no blood-based molecular biomarkers of temporal lobe epilepsy (TLE) to support clinical diagnosis. MicroRNAs are short noncoding RNAs with strong biomarker potential due to their cell-specific expression, mechanistic links to brain excitability, and stable detection in biofluids. Altered levels of circulating microRNAs have been reported in human epilepsy, but most studies collected samples from one clinical site, used a single profiling platform or conducted minimal validation.

METHOD:

Using a case-control design, we collected plasma samples from video-electroencephalogram-monitored adult TLE patients at epilepsy specialist centers in two countries, performed genome-wide PCR-based and RNA sequencing during the discovery phase and validated findings in a large (>250) cohort of samples that included patients with psychogenic non-epileptic seizures (PNES).

FINDINGS:

After profiling and validation, we identified miR-27a-3p, miR-328-3p and miR-654-3p with biomarker potential. Plasma levels of these microRNAs were also changed in a mouse model of TLE but were not different to healthy controls in PNES patients. We determined copy number of the three microRNAs in plasma and demonstrate their rapid detection using an electrochemical RNA microfluidic disk as a prototype point-of-care device. Analysis of the microRNAs within the exosome-enriched fraction provided high diagnostic accuracy while Argonaute-bound miR-328-3p selectively increased in patient samples after seizures. In situ hybridization localized miR-27a-3p and miR-328-3p within neurons in human brain and bioinformatics predicted targets linked to growth factor signaling and apoptosis.

INTERPRETATION:

This study demonstrates the biomarker potential of circulating microRNAs for epilepsy diagnosis and mechanistic links to underlying pathomechanisms.

KEYWORDS:

Biofluids; Dissociative seizures; Noncoding RNA; Serum; Status epilepticus; Temporal lobe epilepsy

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