Format

Send to

Choose Destination
Brain. 2018 Oct 1;141(10):2952-2965. doi: 10.1093/brain/awy242.

Evidence for peri-ictal blood-brain barrier dysfunction in patients with epilepsy.

Author information

1
Department of Epileptology, University of Bonn Medical Center, Bonn, Germany.
2
Center for Development Research, University of Bonn, Bonn, Germany.
3
Department of Medical Neuroscience, Faculty of Medicine, Dalhousie University, Halifax, Canada.
4
Departments of Physiology and Cell Biology, Cognitive and Brain Sciences, Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
5
Section of Epileptology, Department of Neurology, University Hospital RWTH Aachen, Aachen, Germany.
6
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
7
Brain Imaging Center, Goethe University Frankfurt, Frankfurt, Germany.
8
Stroke Recovery Laboratory, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA, USA.
9
Department of Radiology, University of Bonn Medical Center, Bonn, Germany.

Abstract

Epilepsy has been associated with a dysfunction of the blood-brain barrier. While there is ample evidence that a dysfunction of the blood-brain barrier contributes to epileptogenesis, blood-brain barrier dysfunction as a consequence of single epileptic seizures has not been systematically investigated. We hypothesized that blood-brain barrier dysfunction is temporally and anatomically associated with epileptic seizures in patients and used a newly-established quantitative MRI protocol to test our hypothesis. Twenty-three patients with epilepsy undergoing inpatient monitoring as part of their presurgical evaluation were included in this study (10 females, mean age ± standard deviation: 28.78 ± 8.45). For each patient, we acquired quantitative T1 relaxation time maps (qT1) after both ictal and interictal injection of gadolinium-based contrast agent. The postictal enhancement of contrast agent was quantified by subtracting postictal qT1 from interictal qT1 and the resulting ΔqT1 was used as a surrogate imaging marker of peri-ictal blood-brain barrier dysfunction. Additionally, the serum concentrations of MMP9 and S100, both considered biomarkers of blood-brain barrier dysfunction, were assessed in serum samples obtained prior to and after the index seizure. Fifteen patients exhibited secondarily generalized tonic-clonic seizures and eight patients exhibited focal seizures at ictal injection of contrast agent. By comparing ΔqT1 of the generalized tonic-clonic seizures and focal seizures groups, the anatomical association between ictal epileptic activity and postictal enhancement of contrast agent could be probed. The generalized tonic-clonic seizures group showed significantly higher ΔqT1 in the whole brain as compared to the focal seizures group. Specific analysis of scans acquired later than 3 h after the onset of the seizure revealed higher ΔqT1 in the generalized tonic-clonic seizures group as compared to the focal seizures group, which was strictly lateralized to the hemisphere of seizure onset. Both MMP9 and S100 showed a significantly increased postictal concentration. The current study provides evidence for the occurrence of a blood-brain barrier dysfunction, which is temporally and anatomically associated with epileptic seizures. qT1 after ictal contrast agent injection is rendered as valuable imaging marker of seizure-associated blood-brain barrier dysfunction and may be measured hours after the seizure. The observation of the strong anatomical association of peri-ictal blood-brain barrier dysfunction may spark the development of new functional imaging modalities for the post hoc visualization of brain areas affected by the seizure.

PMID:
30239618
DOI:
10.1093/brain/awy242
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center