University Medical Center Utrecht, Utrecht, The Netherlands.
Department of Pediatric Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
Epilepsia. 2018 Jan;59(1):179-189. doi: 10.1111/epi.13947. Epub 2017 Nov 10.
The most common reported seizure-precipitant is stress. We recently showed a biologic basis for stress sensitivity of seizures: cortisol levels in people with stress-sensitive epilepsy correlated with focal interictal epileptiform discharges (IEDs) on electroencephalography (EEG). Here we aimed to determine whether the effect of cortisol on the epileptic brain is global or focal, and whether cortisol affects all brains or just those of stress-sensitive people. Because epilepsy is associated with changes in functional brain connectivity, we studied the relationship between cortisol and changes in global and focal (node-centered) functional connectivity measures for individuals with stress-sensitive and non-stress-sensitive epilepsy.
Seventeen people with epilepsy underwent long-term (>24 h) EEG recording. During the first 5 h after waking, saliva was collected every 15 min for cortisol measurements. Theta-band functional connectivity was assessed for every 15 min of the recording. We calculated the average phase-lag index (PLI) between all channels as a measure of global functional connectivity. We used network Strength, the averaged PLI per channel, as focal functional connectivity measure. We correlated cortisol, global, and focal functional connectivity (Strength) with IED frequency using linear mixed models. Analyses were split for people with and without stress-sensitivity of seizures.
Cortisol was negatively correlated with global functional connectivity in people with stress-sensitive seizures (estimate -0.0020; P < .01), whereas not in those without stress-sensitivity (estimate -0.0003; P = .46). This relationship occurred irrespective of the presence of IEDs on a channel (channels without IEDs and stress-sensitivity: estimate -0.0019; P < .01, non-stress-sensitive -0.0003; P = .41). Global and focal functional connectivity were negatively correlated with IED frequency, irrespective of stress sensitivity of seizures or channel type.
People with stress-sensitive epilepsy have a whole-brain neuronal response to cortisol that is different from that of people with non-stress-sensitive epilepsy. This offers a basis for understanding seizure genesis in stress-sensitive epilepsy, which might require a different treatment approach.
最常见的诱发癫痫发作的因素是压力。我们最近发现了癫痫发作对压力敏感的生物学基础：皮质醇水平与脑电图（EEG）上的局灶性发作间期癫痫样放电（IED）相关。在这里，我们旨在确定皮质醇对癫痫大脑的影响是全局性的还是局灶性的，以及皮质醇是否影响所有大脑，还是仅影响那些对压力敏感的人。由于癫痫与功能性脑连接的变化有关，我们研究了皮质醇与应激敏感和非应激敏感癫痫患者的全局和局灶（以节点为中心）功能连接测量值之间的关系。
17 名癫痫患者进行了长期（>24 小时）EEG 记录。在醒来后的前 5 小时内，每 15 分钟采集一次唾液以测量皮质醇。在记录的每 15 分钟评估 theta 波段功能连接。我们计算了所有通道之间的平均相位滞后指数（PLI），作为全局功能连接的指标。我们使用网络强度（每个通道的平均 PLI）作为局灶功能连接的测量值。我们使用线性混合模型将皮质醇、全局和局灶功能连接（强度）与 IED 频率相关联。分析按有无癫痫发作压力敏感性进行划分。
皮质醇与应激敏感癫痫患者的全局功能连接呈负相关（估计值-0.0020；P<.01），而与无应激敏感癫痫患者则无相关性（估计值-0.0003；P=.46）。这种关系发生在通道上有无 IED 存在的情况下（无 IED 和应激敏感通道：估计值-0.0019；P<.01，非应激敏感通道-0.0003；P=.41）。全局和局灶功能连接与 IED 频率呈负相关，与癫痫发作压力敏感性或通道类型无关。
应激敏感型癫痫患者的皮质醇反应与非应激敏感型癫痫患者不同，这为理解应激敏感型癫痫发作的发病机制提供了依据，可能需要不同的治疗方法。
