Non-invasive PET imaging of brain inflammation at disease onset predicts spontaneous recurrent seizures and reflects comorbidities
Non-invasive PET imaging of brain inflammation at disease onset predicts spontaneous recurrent seizures and reflects comorbidities
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DOI：
10.1016/j.bbi.2016.12.015
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发表时间：
2017-03-01
影响因子：
15.1
通讯作者：
Dedeurwaerdere, Stefanie
中科院分区：
文献类型：
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作者：
Bertoglio, Daniele;Verhaeghe, Jeroen;Dedeurwaerdere, Stefanie
脑炎症是健康大脑转化为癫痫的重要因素，这种现象称为癫痫发生，为预后工具提供了一个新的切入点。由于我们无法预测疾病结果的严重程度，因此在疾病发作前或发作时进行抗癫痫治疗的发展受到阻碍。在颞叶癫痫大鼠模型中，我们旨在评估疾病发作时脑炎症的体内非侵入性成像是否可预测抑郁样和感觉运动相关共病的自发性复发性癫痫发作（SRS）频率和严重程度。为此，使用[F-18]-PBR 111通过癫痫持续状态后2周和4周的正电子发射断层扫描（PET）对炎症生物标志物转运蛋白进行成像。癫痫持续状态后2周，转运蛋白在边缘结构中高度上调（与颞叶对照相比，增加高达2.1倍，P < 0.001），而癫痫持续状态后4周，上调减少（与对照相比，增加高达1.6倍颞叶，P < 0.01），并且仅在这些区域的一个子集中明显。在疾病的所有阶段（癫痫持续状态后2周左右出现的急性、潜伏期首次癫痫发作和慢性阶段），用视频脑电图监测动物，共12周，以确定每例受试者的SRS频率（范围为0.00-0.83 SRS/天）。我们发现，癫痫持续状态后2周和4周的局部PET摄取与慢性癫痫期间抑郁样和感觉运动相关共病的严重程度相关（每个测试P < 0.05）。区域PET成像与SRS频率无关，然而，通过应用基于癫痫持续状态后2周转运蛋白PET成像的多变量数据驱动建模方法，我们准确预测了癫痫发作时SRS的频率（R = 0.92; R-2 = 0.86; P < 0.0001）。这项研究不仅证明了转运蛋白作为一种预后生物标志物的非侵入性成像，以确定SRS频率，而且还显示了其反映抑郁样和感觉运动相关合并症严重程度的能力。我们的研究结果是一个令人鼓舞的一步，抗癫痫治疗的发展，提供早期定量评估SRS的频率和严重程度的合并症具有高度的临床相关性。(C)2016 Elsevier Inc. All rights reserved.
Brain inflammation is an important factor in the conversion of a healthy brain into an epileptic one, a phenomenon known as epileptogenesis, offering a new entry point for prognostic tools. The development of anti-epileptogenic therapies to treat before or at disease onset is hampered by our inability to predict the severity of the disease outcome. In a rat model of temporal lobe epilepsy we aimed to assess whether in vivo non-invasive imaging of brain inflammation at disease onset was predictive of spontaneous recurrent seizures (SRS) frequency and severity of depression-like and sensorimotor-related comorbidities. To this end, translocator protein, a biomarker of inflammation, was imaged by means of positron emission tomography (PET) 2 and 4 weeks post-status epilepticus using [F-18]-PBR111. Translocator protein was highly upregulated 2 weeks post-status epilepticus in limbic structures (up to 2.1-fold increase compared to controls in temporal lobe, P < 0.001), whereas 4 weeks post-status epilepticus, upregulation decreased (up to 1.6-fold increase compared to controls in temporal lobe, P < 0.01) and was only apparent in a subset of these regions. Animals were monitored with video-electroencephalography during all stages of disease (acute, latent-first seizures appearing around 2 weeks post-status epilepticus-and chronic phases), for a total of 12 weeks, in order to determine SRS frequency for each subject (range 0.00-0.83 SRS/day). We found that regional PET uptake at 2 and 4 weeks post-status epilepticus correlated with the severity of depression-like and sensorimotor-related comorbidities during chronic epilepsy (P < 0.05 for each test). Regional PET imaging did not correlate with SRS frequency, however, by applying a multivariate data-driven modeling approach based on translocator protein PET imaging at 2 weeks post-status epilepticus, we accurately predicted the frequency of SRS (R = 0.92; R-2 = 0.86; P < 0.0001) at the onset of epilepsy. This study not only demonstrates non-invasive imaging of translocator protein as a prognostic biomarker to ascertain SRS frequency, but also shows its capability to reflect the severity of depression-like and sensorimotor-related comorbidities. Our results are an encouraging step towards the development of anti-epileptogenic treatments by providing early quantitative assessment of SRS frequency and severity of comorbidities with high clinical relevance.(C) 2016 Elsevier Inc. All rights reserved.