急性丘脑损伤作为创伤后癫痫发生的预后生物标志物。

Acute thalamic damage as a prognostic biomarker for post-traumatic epileptogenesis.

机构信息

A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.

出版信息

Epilepsia. 2021 Aug;62(8):1852-1864. doi: 10.1111/epi.16986. Epub 2021 Jul 9.

DOI:10.1111/epi.16986

PMID:34245005

Abstract

OBJECTIVE

To identify magnetic resonance imaging (MRI) biomarkers for post-traumatic epilepsy.

METHODS

The EPITARGET (Targets and biomarkers for antiepileptogenesis, epitarget.eu) animal cohort completing T relaxation and diffusion tensor MRI follow-up and 1-month-long video-electroencephalography monitoring included 98 male Sprague-Dawley rats with traumatic brain injury and 18 controls. T imaging was performed on day (D) 2, D7, and D21 and diffusion tensor imaging (DTI) on D7 and D21 using a 7-Tesla Bruker PharmaScan MRI scanner. The mean and standard deviation (SD) of the T relaxation rate, multiple diffusivity measures, and diffusion anisotropy at each time-point within the ventroposterolateral and ventroposteromedial thalamus were used as predictor variables in multi-variable logistic regression models to distinguish rats with and without epilepsy.

RESULTS

Twenty-nine percent (28/98) of the rats with traumatic brain injury (TBI) developed epilepsy. The best-performing logistic regression model utilized the D2 and D7 T relaxation time as well as the D7 diffusion tensor data. The model distinguished rats with and without epilepsy (Bonferroni-corrected p-value < .001) with a cross-validated concordance statistic of 0.74 (95% confidence interval [CI] 0.60-0.84). In a cross-validated classification test, the model exhibited 54% sensitivity and 91% specificity, enriching the epilepsy rate within the study population from the expected 29% to 71%. A model using the D2 T data only resulted in a 73% enriched epilepsy rate (regression p-value .007, cross-validated concordance 0.70, 95% CI 0.56-0.80, sensitivity 29%, specificity 96%).

SIGNIFICANCE

An MRI parameter set reporting on acute and subacute neuropathologic changes common to experimental and human TBI presents a diagnostic biomarker for post-traumatic epileptogenesis. Significant enrichment of the study population was achieved even when using a single time-point measurement, producing an expected epilepsy rate of 73%.

摘要

目的

确定创伤后癫痫的磁共振成像（MRI）生物标志物。

方法

EPITARGET（抗癫痫发生的靶点和生物标志物，epitarget.eu）动物队列完成 T 弛豫和弥散张量 MRI 随访以及 1 个月长的视频脑电图监测，包括 98 只创伤性脑损伤雄性 Sprague-Dawley 大鼠和 18 只对照大鼠。T 成像在第 2 天（D2）、第 7 天（D7）和第 21 天（D21）进行，弥散张量成像（DTI）在第 7 天和第 21 天进行，使用 7T Bruker PharmaScan MRI 扫描仪。每个时间点的 T 弛豫率、多个弥散度测量值和腹后外侧和腹后内侧丘脑的扩散各向异性的平均值和标准差（SD）被用作多变量逻辑回归模型中的预测变量，以区分有和无癫痫的大鼠。

结果

98 只创伤性脑损伤（TBI）大鼠中有 29%（28/98）发生癫痫。表现最好的逻辑回归模型利用 D2 和 D7 的 T 弛豫时间以及 D7 的弥散张量数据。该模型能够区分有和无癫痫的大鼠（经 Bonferroni 校正的 p 值<.001），交叉验证一致性为 0.74（95%置信区间[CI] 0.60-0.84）。在交叉验证分类测试中，该模型的灵敏度为 54%，特异性为 91%，使研究人群中的癫痫发生率从预期的 29%提高到 71%。仅使用 D2 T 数据的模型导致癫痫发生率提高 73%（回归 p 值<.007，交叉验证一致性为 0.70，95%CI 0.56-0.80，灵敏度 29%，特异性 96%）。