Department of Neurology, University of Campinas, Campinas, Brazil.
Department of Pathology, University of Campinas, Campinas, Brazil.
Epilepsia. 2020 May;61(5):1008-1018. doi: 10.1111/epi.16509. Epub 2020 Apr 29.
To evaluate the interactions of metabolic neuronal-glial changes with the presence and hemispheric-side of hippocampal sclerosis (HS) and its potential role in predicting pharmacoresistance in temporal lobe epilepsy (TLE).
We included structural magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy ( H-MRS) metabolic data for 91 patients with unilateral TLE and 50 healthy controls. We measured the values of total N-acetyl aspartate/total creatine (tNAA/tCr), glutamate/tCr (Glu/tCr), and myo-inositol/tCr (mIns/tCr). To assess the influence of the pharmacoresponse and hemispheric-side of HS on metabolic data, the relationship between clinical and MRI data, and the predictive value of NAA/Cr, we used analysis of variance/covariance and built a logistic regression model. We used bootstrap simulations to evaluate reproducibility.
Bilateral tNAA/tCr reduction was associated with pharmacoresistance and with left HS, a decrease of Glu/tCr ipsilateral to the seizure focus was associated with pharmacoresistance, and ipsilateral mIns/tCr increase was related to pharmacoresistance and the presence of left HS. The logistic regression model containing clinical and H-MRS data discriminated pharmacoresistance (area under the curve [AUC] = 0.78). However, the reduction of tNAA/tCr was the main predictor, with the odds 2.48 greater for pharmacoresistance.
Our study revealed a spectrum of neuronal-glial changes in TLE, which was associated with pharmacoresistance, being more severe in left-sided HS and less severe in MRI-negative TLE. These noninvasive, in vivo biomarkers provide valuable additional information about the interhemispheric differences in metabolic dysfunction, seizure burden, and HS, and may help to predict pharmacoresistance.
评估代谢性神经元-神经胶质变化与海马硬化（HS）的存在和半球侧之间的相互作用，及其在预测颞叶癫痫（TLE）药物抵抗中的潜在作用。
我们纳入了 91 例单侧 TLE 患者和 50 例健康对照者的结构磁共振成像（MRI）和质子磁共振波谱（ 1 H-MRS）代谢数据。我们测量了总 N-乙酰天冬氨酸/总肌酸（tNAA/tCr）、谷氨酸/肌酸（Glu/tCr）和肌醇/肌酸（mIns/tCr）的比值。为了评估药物反应和 HS 的半球侧对代谢数据的影响，我们使用方差分析/协方差和构建逻辑回归模型，分析了临床和 MRI 数据之间的关系，以及 NAA/Cr 的预测价值。我们使用自举模拟来评估可重复性。
双侧 tNAA/tCr 降低与药物抵抗有关，与左侧 HS 有关；痫灶对侧的 Glu/tCr 降低与药物抵抗有关；同侧 mIns/tCr 升高与药物抵抗和左侧 HS 有关。包含临床和 1 H-MRS 数据的逻辑回归模型可以区分药物抵抗（曲线下面积[AUC] = 0.78）。然而，tNAA/tCr 的降低是主要的预测因子，药物抵抗的可能性增加了 2.48 倍。
我们的研究揭示了 TLE 中存在神经元-神经胶质变化的谱，其与药物抵抗有关，在左侧 HS 中更为严重，在 MRI 阴性的 TLE 中则较轻。这些非侵入性、活体生物标志物提供了关于代谢功能障碍、痫性发作负担和 HS 的半球间差异的有价值的额外信息，可能有助于预测药物抵抗。
