Early tissue damage and microstructural reorganization predict disease severity in experimental epilepsy
Early tissue damage and microstructural reorganization predict disease severity in experimental epilepsy
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DOI：
10.7554/elife.25742
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发表时间：
2017-07-26
期刊：
影响因子：
7.7
通讯作者：
Haas, Carola A.
中科院分区：
文献类型：
--
作者：
Janz, Philipp;Schwaderlapp, Niels;Haas, Carola A.
中颞叶癫痫（mTLE）是成人最常见的局灶性癫痫，通常难以治疗。到目前为止，切除致痫灶是唯一有效的治疗方法。目前尚不清楚癫痫发作前的病理过程是否为后来疾病严重程度的指标。利用纵向多模态MRI，我们监测了小鼠mTLE模型癫痫发生过程中的海马损伤和组织重组。MRI生物标志物的预后价值是通过与病理特征的回顾性相关性来评估的。在这里，我们首次表明，早期海马神经退行性变的程度和齿状回的进行性微结构变化转化为慢性癫痫海马硬化的严重程度和癫痫发作负担。此外，我们证明了结构MRI生物标志物反映了人类海马硬化的程度。我们的研究结果可能允许在mTLE首次临床表现之前对疾病严重程度进行早期预后，从而扩大治疗窗口。
Mesial temporal lobe epilepsy (mTLE) is the most common focal epilepsy in adults and is often refractory to medication. So far, resection of the epileptogenic focus represents the only curative therapy. It is unknown whether pathological processes preceding epilepsy onset are indicators of later disease severity. Using longitudinal multi-modal MRI, we monitored hippocampal injury and tissue reorganization during epileptogenesis in a mouse mTLE model. The prognostic value of MRI biomarkers was assessed by retrospective correlations with pathological hallmarks Here, we show for the first time that the extent of early hippocampal neurodegeneration and progressive microstructural changes in the dentate gyrus translate to the severity of hippocampal sclerosis and seizure burden in chronic epilepsy. Moreover, we demonstrate that structural MRI biomarkers reflect the extent of sclerosis in human hippocampi. Our findings may allow an early prognosis of disease severity in mTLE before its first clinical manifestations, thus expanding the therapeutic window.