Early tissue damage and microstructural reorganization predict disease severity in experimental epilepsy

Elife. 2017 Jul 26:6:e25742. doi: 10.7554/eLife.25742.

Abstract

Mesial temporal lobe epilepsy (mTLE) is the most common focal epilepsy in adults and is often refractory to medication. So far, resection of the epileptogenic focus represents the only curative therapy. It is unknown whether pathological processes preceding epilepsy onset are indicators of later disease severity. Using longitudinal multi-modal MRI, we monitored hippocampal injury and tissue reorganization during epileptogenesis in a mouse mTLE model. The prognostic value of MRI biomarkers was assessed by retrospective correlations with pathological hallmarks Here, we show for the first time that the extent of early hippocampal neurodegeneration and progressive microstructural changes in the dentate gyrus translate to the severity of hippocampal sclerosis and seizure burden in chronic epilepsy. Moreover, we demonstrate that structural MRI biomarkers reflect the extent of sclerosis in human hippocampi. Our findings may allow an early prognosis of disease severity in mTLE before its first clinical manifestations, thus expanding the therapeutic window.

Keywords: MRI; biomarker; epilepsy; granule cell dispersion; human; human biology; kainate; medicine; mouse; neurodegeneration; neuroscience.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Biomarkers / analysis
  • Dentate Gyrus / pathology*
  • Disease Models, Animal
  • Epilepsy, Temporal Lobe / physiopathology*
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Mice, Inbred C57BL
  • Neurodegenerative Diseases / pathology*
  • Prognosis

Substances

  • Biomarkers

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.