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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.
摘要：
目的：慢性癫痫发作间期血脑屏障功能障碍在动物模型和病理标本中得到证实。已使用实验性定量磁共振成像（MRI）方案在体内显示了人体的血脑屏障功能障碍。这里,我们假设在耐药癫痫患者中也存在发作间血脑屏障功能障碍.
方法：39人（21名女性，前瞻性招募了患有耐药癫痫的MRI±SD=30±8岁）的平均年龄，并在给药顺磁性造影剂前后进行了发作间期T1弛豫测量。同样，在29名无癫痫患者中获得了定量T1(12名女性，MRI年龄=48±18岁）。计算了定量T1差异图，并将其用作血脑屏障功能障碍的替代成像标记。然后比较假定的癫痫发作区同侧半球内的定量T1差异图的值，在体素水平上，在假定的癫痫发作区域内，癫痫患者和无癫痫患者的对侧。
结果：与对侧相比，同侧T1差异值显着高于白质（校正p<0.05），灰质（未校正p<.05），癫痫患者的癫痫发作区（p=.04）。与没有癫痫的人相比，在假定的癫痫发作区的解剖学附近发现了显着更高的T1差异值（p=.004）。与没有癫痫的人相比，海马硬化的一个亚组在同侧海马和与海马强烈相关的区域显示出明显更高的T1差异值（校正p<0.01）。最后,反映假定癫痫发作区内T1差值偏差的z评分与颞叶癫痫患者的言语记忆表现(p=.02)相关。
结论：我们的结果表明，在体内可相互检测到的耐药性癫痫中存在血脑屏障功能障碍，解剖学上与假定的癫痫发作区有关，并与认知缺陷有关。
方法：39人（21名女性，前瞻性招募了患有耐药癫痫的MRI±SD=30±8岁）的平均年龄，并在给药顺磁性造影剂前后进行了发作间期T1弛豫测量。同样，在29名无癫痫患者中获得了定量T1(12名女性，MRI年龄=48±18岁）。计算了定量T1差异图，并将其用作血脑屏障功能障碍的替代成像标记。然后比较假定的癫痫发作区同侧半球内的定量T1差异图的值，在体素水平上，在假定的癫痫发作区域内，癫痫患者和无癫痫患者的对侧。
结果：与对侧相比，同侧T1差异值显着高于白质（校正p<0.05），灰质（未校正p<.05），癫痫患者的癫痫发作区（p=.04）。与没有癫痫的人相比，在假定的癫痫发作区的解剖学附近发现了显着更高的T1差异值（p=.004）。与没有癫痫的人相比，海马硬化的一个亚组在同侧海马和与海马强烈相关的区域显示出明显更高的T1差异值（校正p<0.01）。最后,反映假定癫痫发作区内T1差值偏差的z评分与颞叶癫痫患者的言语记忆表现(p=.02)相关。
结论：我们的结果表明，在体内可相互检测到的耐药性癫痫中存在血脑屏障功能障碍，解剖学上与假定的癫痫发作区有关，并与认知缺陷有关。
