학술논문
Evidence for interictal blood-brain barrier dysfunction in people with epilepsy.
Document Type
Academic Journal
Author
Reiter JT; Department of Epileptology, University Hospital Bonn, Bonn, Germany.; Department of Neuroradiology, University Hospital Bonn, Bonn, Germany.; Schulte F; Department of Epileptology, University Hospital Bonn, Bonn, Germany.; Department of Neuroradiology, University Hospital Bonn, Bonn, Germany.; Bauer T; Department of Epileptology, University Hospital Bonn, Bonn, Germany.; Department of Neuroradiology, University Hospital Bonn, Bonn, Germany.; David B; Department of Epileptology, University Hospital Bonn, Bonn, Germany.; Endler C; Department of Diagnostic and Interventional Radiology, University Hospital Bonn, Bonn, Germany.; Isaak A; Department of Diagnostic and Interventional Radiology, University Hospital Bonn, Bonn, Germany.; Schuch F; Department of Epileptology, University Hospital Bonn, Bonn, Germany.; Bitzer F; Department of Epileptology, University Hospital Bonn, Bonn, Germany.; Department of Neuroradiology, University Hospital Bonn, Bonn, Germany.; Witt JA; Department of Epileptology, University Hospital Bonn, Bonn, Germany.; Hattingen E; Institute of Neuroradiology, University Hospital and Goethe University Frankfurt, Frankfurt am Main, Germany.; Deichmann R; Brain Imaging Center, Goethe University Frankfurt, Frankfurt am Main, Germany.; Attenberger U; Department of Diagnostic and Interventional Radiology, University Hospital Bonn, Bonn, Germany.; Becker AJ; Department of Neuropathology, University Hospital Bonn, Bonn, Germany.; Helmstaedter C; Department of Epileptology, University Hospital Bonn, Bonn, Germany.; Radbruch A; Department of Neuroradiology, University Hospital Bonn, Bonn, Germany.; Surges R; Department of Epileptology, University Hospital Bonn, Bonn, Germany.; Friedman A; Department of Medical Neuroscience, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.; Departments of Cognitive and Brain Sciences, Physiology, and Cell Biology, Ben-Gurion University of the Negev, Beer Sheva, Israel.; Rüber T; Department of Epileptology, University Hospital Bonn, Bonn, Germany.; Department of Neuroradiology, University Hospital Bonn, Bonn, Germany.
Source
Publisher: Blackwell Science Country of Publication: United States NLM ID: 2983306R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1528-1167 (Electronic) Linking ISSN: 00139580 NLM ISO Abbreviation: Epilepsia Subsets: MEDLINE
Subject
Language
English
Abstract
Objective: Interictal blood-brain barrier dysfunction in chronic epilepsy has been demonstrated in animal models and pathological specimens. Ictal blood-brain barrier dysfunction has been shown in humans in vivo using an experimental quantitative magnetic resonance imaging (MRI) protocol. Here, we hypothesized that interictal blood-brain barrier dysfunction is also present in people with drug-resistant epilepsy.
Methods: Thirty-nine people (21 females, mean age at MRI ± SD = 30 ± 8 years) with drug-resistant epilepsy were prospectively recruited and underwent interictal T1-relaxometry before and after administration of a paramagnetic contrast agent. Likewise, quantitative T1 was acquired in 29 people without epilepsy (12 females, age at MRI = 48 ± 18 years). Quantitative T1 difference maps were calculated and served as a surrogate imaging marker for blood-brain barrier dysfunction. Values of quantitative T1 difference maps inside hemispheres ipsilateral to the presumed seizure onset zone were then compared, on a voxelwise level and within presumed seizure onset zones, to the contralateral side of people with epilepsy and to people without epilepsy.
Results: Compared to the contralateral side, ipsilateral T1 difference values were significantly higher in white matter (corrected p < .05), gray matter (uncorrected p < .05), and presumed seizure onset zones (p = .04) in people with epilepsy. Compared to people without epilepsy, significantly higher T1 difference values were found in the anatomical vicinity of presumed seizure onset zones (p = .004). A subgroup of people with hippocampal sclerosis demonstrated significantly higher T1 difference values in the ipsilateral hippocampus and in regions strongly interconnected with the hippocampus compared to people without epilepsy (corrected p < .01). Finally, z-scores reflecting the deviation of T1 difference values within the presumed seizure onset zone were associated with verbal memory performance (p = .02) in people with temporal lobe epilepsy.
Significance: Our results indicate a blood-brain barrier dysfunction in drug-resistant epilepsy that is detectable interictally in vivo, anatomically related to the presumed seizure onset zone, and associated with cognitive deficits.
(© 2024 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)
Methods: Thirty-nine people (21 females, mean age at MRI ± SD = 30 ± 8 years) with drug-resistant epilepsy were prospectively recruited and underwent interictal T1-relaxometry before and after administration of a paramagnetic contrast agent. Likewise, quantitative T1 was acquired in 29 people without epilepsy (12 females, age at MRI = 48 ± 18 years). Quantitative T1 difference maps were calculated and served as a surrogate imaging marker for blood-brain barrier dysfunction. Values of quantitative T1 difference maps inside hemispheres ipsilateral to the presumed seizure onset zone were then compared, on a voxelwise level and within presumed seizure onset zones, to the contralateral side of people with epilepsy and to people without epilepsy.
Results: Compared to the contralateral side, ipsilateral T1 difference values were significantly higher in white matter (corrected p < .05), gray matter (uncorrected p < .05), and presumed seizure onset zones (p = .04) in people with epilepsy. Compared to people without epilepsy, significantly higher T1 difference values were found in the anatomical vicinity of presumed seizure onset zones (p = .004). A subgroup of people with hippocampal sclerosis demonstrated significantly higher T1 difference values in the ipsilateral hippocampus and in regions strongly interconnected with the hippocampus compared to people without epilepsy (corrected p < .01). Finally, z-scores reflecting the deviation of T1 difference values within the presumed seizure onset zone were associated with verbal memory performance (p = .02) in people with temporal lobe epilepsy.
Significance: Our results indicate a blood-brain barrier dysfunction in drug-resistant epilepsy that is detectable interictally in vivo, anatomically related to the presumed seizure onset zone, and associated with cognitive deficits.
(© 2024 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)