Marchi Nicola, Angelov Lilyana, Masaryk Thomas, Fazio Vincent, Granata Tiziana, Hernandez Nadia, Hallene Kerri, Diglaw Tammy, Franic Linda, Najm Imad, Janigro Damir
Cerebrovascular Research Center, Department of Neurological Surgery, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Epilepsia. 2007 Apr;48(4):732-42. doi: 10.1111/j.1528-1167.2007.00988.x. Epub 2007 Feb 23.
It is generally accepted that blood-brain barrier (BBB) failure occurs as a result of CNS diseases, including epilepsy. However, evidences also suggest that BBB failure may be an etiological factor contributing to the development of seizures.
We monitored the onset of seizures in patients undergoing osmotic disruption of BBB (BBBD) followed by intraarterial chemotherapy (IAC) to treat primary brain lymphomas. Procedures were performed under barbiturate anesthesia. The effect of osmotic BBBD was also evaluated in naive pigs.
Focal motor seizures occurred immediately after BBBD in 25% of procedures and originated contralateral to the hemisphere of BBBD. No seizures were observed when BBB was not breached and only IAC was administered. The only predictors of seizures were positive indices of BBBD, namely elevation of serum S100beta levels and computed tomography (CT) scans. In a porcine model of BBBD, identical procedures generated an identical result, and sudden behavioral and electrographic (EEG) seizures correlated with successful BBB disruption. The contribution of tumor or chemotherapy to acute seizures was therefore excluded.
This is the first study to correlate extent of acute BBB openings and development of seizures in humans and in a large animal model of BBB opening. Acute vascular failure is sufficient to cause seizures in the absence of CNS pathologies or chemotherapy.
人们普遍认为血脑屏障（BBB）功能障碍是包括癫痫在内的中枢神经系统疾病的结果。然而，也有证据表明血脑屏障功能障碍可能是导致癫痫发作的一个病因。
我们监测了接受血脑屏障渗透性破坏（BBBD）联合动脉内化疗（IAC）治疗原发性脑淋巴瘤患者的癫痫发作情况。手术在巴比妥类麻醉下进行。还在未经处理的猪身上评估了渗透性BBBD的效果。
在25%的手术中，BBBD后立即出现局灶性运动性癫痫发作，发作起源于BBBD半球的对侧。当血脑屏障未被破坏且仅给予IAC时，未观察到癫痫发作。癫痫发作的唯一预测因素是BBBD的阳性指标，即血清S100β水平升高和计算机断层扫描（CT）。在BBBD猪模型中，相同的操作产生了相同的结果，突然的行为和脑电图（EEG）癫痫发作与血脑屏障的成功破坏相关。因此排除了肿瘤或化疗对急性癫痫发作的影响。
这是第一项在人类和大型血脑屏障开放动物模型中，将急性血脑屏障开放程度与癫痫发作发展相关联的研究。在没有中枢神经系统病变或化疗的情况下，急性血管功能障碍足以导致癫痫发作。
