Early tissue damage and microstructural reorganization predict disease severity in experimental epilepsy
Philipp Janz,
Niels Schwaderlapp,
Katharina Heining,
Ute Häussler,
Jan G Korvink,
Dominik von Elverfeldt,
Jürgen Hennig,
Ulrich Egert,
Pierre LeVan,
Carola A Haas
Affiliations
Philipp Janz
Experimental Epilepsy Research, Department of Neurosurgery, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Faculty of Biology, University of Freiburg, Freiburg, Germany
Niels Schwaderlapp
Medical Physics, Department of Radiology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
Katharina Heining
Faculty of Biology, University of Freiburg, Freiburg, Germany; Laboratory for Biomicrotechnology, Department of Microsystems Engineering, University of Freiburg, Freiburg, Germany
Experimental Epilepsy Research, Department of Neurosurgery, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; BrainLinks-BrainTools Cluster of Excellence, University of Freiburg, Freiburg, Germany
Institute of Microstructure Technology, Karlsruhe Institute of Technology, Karlsruhe, Germany
Dominik von Elverfeldt
Medical Physics, Department of Radiology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
Jürgen Hennig
Medical Physics, Department of Radiology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; BrainLinks-BrainTools Cluster of Excellence, University of Freiburg, Freiburg, Germany
Laboratory for Biomicrotechnology, Department of Microsystems Engineering, University of Freiburg, Freiburg, Germany; BrainLinks-BrainTools Cluster of Excellence, University of Freiburg, Freiburg, Germany; Bernstein Center Freiburg, University of Freiburg, Freiburg, Germany
Pierre LeVan
Medical Physics, Department of Radiology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; BrainLinks-BrainTools Cluster of Excellence, University of Freiburg, Freiburg, Germany
Experimental Epilepsy Research, Department of Neurosurgery, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; BrainLinks-BrainTools Cluster of Excellence, University of Freiburg, Freiburg, Germany; Bernstein Center Freiburg, University of Freiburg, Freiburg, Germany
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.
