Gefferie Silvano R, van Nieuw Amerongen Arthur R, Visser Gerhard H, Zijlmans Maeike, Tolner Else A, van de Ruit Mark, van den Maagdenberg Arn M J M, Thijs Roland D
Stichting Epilepsie Instellingen Nederland (SEIN), Heemstede, the Netherlands.
Department of Neurology, Leiden University Medical Centre, Leiden, the Netherlands.
Ann Clin Transl Neurol. 2025 Jun;12(6):1265-1275. doi: 10.1002/acn3.70045. Epub 2025 Apr 21.
Quantitative markers of cortical excitability may help identify responders to anti-seizure medications (ASMs). We studied the relationship between ASM load and two electroencephalography (EEG) markers of cortical excitability in people with refractory epilepsy.
We included individuals with refractory focal epilepsy undergoing presurgical evaluation, involving ASM tapering and sleep deprivation. We obtained daily resting state EEG and EEG responses to visual stimulation at linearly increasing flash frequency (10-40 Hz chirp). We extracted the aperiodic exponent from resting state EEG power spectra and analysed chirp response at driving and second-order harmonic frequencies. We modelled ASM load, which we related to the EEG markers using linear mixed-effects regression.
Forty-eight subjects (median age 34 years, age range 16-62 years, 19 females) participated. The spectral exponent became less negative with ASM load reduction (p = 0.02), mainly attributable to reduced low-frequency power. Lowering ASM load increased the harmonic response to chirp stimulation (p = 0.004), also after accounting for sleep deprivation (p = 0.02), but did not affect the driving response. ASM tapering specifically increased harmonic responses to high stimulation frequencies (27-40 Hz, p = 0.01).
Resting state EEG spectral exponents and visual chirp responses reflect ASM load in refractory epilepsy. Low-frequency spectral changes in resting state EEG may only mirror ASM-induced spectral slowing. Visual chirp stimulation reveals enhanced harmonic EEG responses during low ASM loads, likely due to both increased high gamma activity and increased response to visual perturbations. Implementation of the markers would need normative values to reduce the delay to individually optimised treatment regimens.
皮质兴奋性的定量指标可能有助于识别抗癫痫药物(ASM)的反应者。我们研究了难治性癫痫患者中ASM负荷与两种皮质兴奋性脑电图(EEG)指标之间的关系。
我们纳入了正在接受术前评估的难治性局灶性癫痫患者,评估过程包括逐渐减少ASM剂量和睡眠剥夺。我们获取了每日静息状态EEG以及在闪光频率线性增加(10 - 40Hz啁啾)时对视觉刺激的EEG反应。我们从静息状态EEG功率谱中提取非周期性指数,并分析了在驱动频率和二次谐波频率下的啁啾反应。我们对ASM负荷进行建模,并使用线性混合效应回归将其与EEG指标相关联。
48名受试者(中位年龄34岁,年龄范围16 - 62岁,19名女性)参与了研究。随着ASM负荷的降低,频谱指数的负值减小(p = 0.02),这主要归因于低频功率降低。降低ASM负荷增加了对啁啾刺激的谐波反应(p = 0.004),在考虑睡眠剥夺因素后也是如此(p = 0.02),但不影响驱动反应。逐渐减少ASM剂量特别增加了对高刺激频率(27 - 40Hz,p = 0.01)的谐波反应。
静息状态EEG频谱指数和视觉啁啾反应反映了难治性癫痫中的ASM负荷。静息状态EEG中的低频频谱变化可能仅反映了ASM引起的频谱减慢。视觉啁啾刺激显示在低ASM负荷期间EEG谐波反应增强,这可能是由于高伽马活动增加以及对视觉干扰的反应增加所致。这些指标的应用需要规范值,以减少实现个体化优化治疗方案的延迟。