Nairismägi Jaak, Gröhn Olli H J, Kettunen Mikko I, Nissinen Jari, Kauppinen Risto A, Pitkänen Asla
National Bio-NMR Facility and Department of Biomedical NMR, University of Kuopio, Kuopio, Finland.
Epilepsia. 2004 Sep;45(9):1024-34. doi: 10.1111/j.0013-9580.2004.08904.x.
This study examined the hypothesis that neurodegeneration continues after status epilepticus (SE) ends and that the severity of damage at the early phase of the epileptogenic process predicts the outcome of epilepsy in a long-term follow-up.
SE was induced in rats by electrical stimulation of the amygdala, and the progression of structural alterations was monitored with multiparametric magnetic resonance imaging (MRI). Absolute T2, T1rho, and diffusion (Dav) images were acquired from amygdala, piriform cortex, thalamus, and hippocampus for < or = 4.5 months after SE. Frequency and type of spontaneous seizures were monitored with video-electroencephalography recordings. Histologic damage was assessed from Nissl, Timm, and Fluoro-Jade B preparations at 8 months.
At the acute phase (2 days after SE induction), quantitative MRI revealed increased T2, T1rho, and Dav values in the primary focal area (amygdala), reflecting disturbed water homeostasis and possible early structural damage. Pathologic T2 and T1rho were observed in mono- or polysynaptically connected regions, including the piriform cortex, midline thalamus, and hippocampus. The majority of acute MRI abnormalities were reversed by 9 days after SE. In later time points (> 20 days after induction), both the T1rho and diffusion MRI revealed secondarily affected areas, most predominantly in the amygdala and hippocampus. At this time, animals began to have spontaneous seizures. The initial pathology revealed by MRI had a low predictive value for the subsequent severity of epilepsy and tissue damage.
The results demonstrate progressive neurodegeneration after SE in the amygdala and the hippocampus and stress the need for continued administration of neuroprotectants in the treatment of SE even after electrographic seizure activity has ceased.
本研究检验了以下假设，即癫痫持续状态（SE）结束后神经退行性变仍会继续，并且致痫过程早期的损伤严重程度可预测癫痫在长期随访中的结局。
通过电刺激杏仁核在大鼠中诱导SE，并使用多参数磁共振成像（MRI）监测结构改变的进展。在SE后≤4.5个月内，从杏仁核、梨状皮质、丘脑和海马获取绝对T2、T1rho和扩散（Dav）图像。通过视频脑电图记录监测自发癫痫发作的频率和类型。在8个月时，从尼氏染色、Timm染色和氟玉髓B染色制剂评估组织学损伤。
在急性期（SE诱导后2天），定量MRI显示原发性病灶区域（杏仁核）的T2、T1rho和Dav值增加，反映了水稳态紊乱和可能的早期结构损伤。在单突触或多突触连接区域，包括梨状皮质、中线丘脑和海马，观察到病理性T2和T1rho。大多数急性MRI异常在SE后9天内恢复。在后期时间点（诱导后>20天），T1rho和扩散MRI均显示继发性受累区域，最主要在杏仁核和海马。此时，动物开始出现自发癫痫发作。MRI显示的初始病理对随后癫痫的严重程度和组织损伤的预测价值较低。
结果表明SE后杏仁核和海马中存在进行性神经退行性变，并强调即使在脑电图癫痫活动停止后，在SE治疗中仍需要持续给予神经保护剂。
