Evidence for peri-ictal blood-brain barrier dysfunction in patients with epilepsy
| Autor: | Gottfried Schlaug, Guido Lüchters, Bernd Weber, Elke Hattingen, Alon Friedman, Christian E. Elger, Robert D. Nass, Rainer Surges, Bastian David, Tony Stöcker, Theodor Rüber, Ralf Deichmann |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male medicine.medical_specialty Peri Blood–brain barrier Epileptogenesis pathology [Epilepsy] 030218 nuclear medicine & medical imaging 03 medical and health sciences Epilepsy Young Adult 0302 clinical medicine MMP9 protein human Internal medicine medicine Humans Ictal ddc:610 Young adult blood [Matrix Metalloproteinase 9] blood [Biomarkers] medicine.diagnostic_test business.industry diagnostic imaging [Blood-Brain Barrier] S100 Proteins Magnetic resonance imaging pathology [Blood-Brain Barrier] Middle Aged medicine.disease blood [S100 Proteins] Magnetic Resonance Imaging Functional imaging medicine.anatomical_structure Matrix Metalloproteinase 9 Blood-Brain Barrier Cardiology diagnostic imaging [Epilepsy] Female Neurology (clinical) business 030217 neurology & neurosurgery Biomarkers |
| Zdroj: | Brain 141(10), 2952-2965 (2018). doi:10.1093/brain/awy242 |
| DOI: | 10.1093/brain/awy242 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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