Merlet Isabelle, Ostrowsky Karine, Costes Nicolas, Ryvlin Philippe, Isnard Jean, Faillenot Isabelle, Lavenne Franck, Dufournel Damien, Le Bars Didier, Mauguière François
EA1880, Federal Institute of Neurosciences (IFR19), Lyon, France.
Brain. 2004 Apr;127(Pt 4):900-13. doi: 10.1093/brain/awh109. Epub 2004 Feb 25.
The aim of our study was to assess abnormalities in 5-hydroxytryptamine-1A (5-HT1A) receptor density in patients suffering from refractory temporal lobe epilepsy (TLE). Experimental data in animals show that 5-HT1A receptors are predominantly located in limbic areas, and that serotonin, via these receptors, mediates an antiepileptic and anticonvulsant effect. In TLE patients, we quantified 5-HT1A receptor density in epileptogenic and non-epileptogenic areas, as defined by intracranial recordings with stereo-electroencephalography (SEEG). Nine TLE patients and 53 control subjects were studied by PET using a 5-HT1A receptor antagonist ([18F]MPPF). Anatomical regions of interest (ROIs) were drawn on patient and control MRIs co-registered with PET. PET data were quantified using a simplified model to assess binding potential (BP) values in each ROI, with cerebellum as reference. For each patient, a normalized percentage BP change was calculated as the relative variation of BP in each ROI compared with the corresponding ROI in control subjects. In patients, ROIs explored by SEEG were categorized according to their degree of epileptic activity (ictal onset, ictal spreading, interictal spikes, no epileptic activity) and according to their lesional aspect and volume (lesional with volume loss, lesional without volume loss, non-lesional). Compared with control values, the binding to 5-HT1A receptors in TLE patients was decreased in the epileptogenic temporal lobe. BP decrease was significantly greater in: (i) regions involved in the seizure onset than regions where only interictal paroxysms or no epileptic activity was recorded; and (ii) regions where the discharge propagated than regions where only interictal paroxysms or no epileptic activity was recorded. BP decrease was shown to be significantly influenced by the existence of a lesion on MRI. However, in the group of ROIs with normal quantitative and qualitative MRI aspect, BP decrease remained strongly correlated to the degree of epileptic activity. This study shows that in vivo availability of 5-HT1A receptors is decreased in epileptic patients compared with normal subjects. This decrease is highly correlated to the degree of epileptogenicity of cortical areas explored by intracerebral recordings, and does not reflect only pathological changes or neuronal loss in the epileptic focus.
我们研究的目的是评估难治性颞叶癫痫（TLE）患者5-羟色胺-1A（5-HT1A）受体密度的异常情况。动物实验数据表明，5-HT1A受体主要位于边缘系统区域，血清素通过这些受体介导抗癫痫和抗惊厥作用。在TLE患者中，我们通过立体脑电图（SEEG）颅内记录来定义致痫区和非致痫区，并对其中的5-HT1A受体密度进行量化。我们使用5-HT1A受体拮抗剂（[18F]MPPF），通过正电子发射断层扫描（PET）对9例TLE患者和53名对照者进行了研究。在与PET共同配准的患者和对照者的磁共振成像（MRI）上绘制感兴趣的解剖区域（ROI）。使用简化模型对PET数据进行量化，以评估每个ROI中的结合潜能（BP）值，以小脑作为参照。对于每位患者，计算归一化的BP变化百分比，即每个ROI中BP相对于对照者相应ROI的相对变化。在患者中，通过SEEG探索的ROI根据癫痫活动程度（发作起始、发作扩散、发作间期棘波、无癫痫活动）以及病变情况和体积（有体积损失的病变、无体积损失的病变、无病变）进行分类。与对照值相比，TLE患者致痫性颞叶中5-HT1A受体的结合减少。BP降低在以下情况中显著更大：（i）发作起始涉及的区域比仅记录到发作间期阵发性活动或无癫痫活动的区域；（ii）放电扩散的区域比仅记录到发作间期阵发性活动或无癫痫活动的区域。结果显示，MRI上病变的存在对BP降低有显著影响。然而，在MRI定量和定性表现正常的ROI组中，BP降低仍与癫痫活动程度密切相关。这项研究表明，与正常受试者相比，癫痫患者体内5-HT1A受体的可用性降低。这种降低与通过脑内记录探索的皮质区域的致痫性程度高度相关，并且不仅仅反映癫痫灶中的病理变化或神经元丢失。
