美学者探讨癫痫患者猝死风险标志物

美国波士顿布里格姆妇女医院癫痫、神经生理与睡眠科的Milena Pavlova博士及其同事报告称，一项前瞻性研究的结果表明，成人比儿童更常出现癫痫发作后脑电图(EEG)全导电抑制(PGES)，这可能与成年癫痫患者意外猝死发生率高于儿童有关(Epilepsy Behav. 2013 Oct. 17 [doi:10.1016/j.yebeh.2013.09.026])。

这项研究纳入了26例平均年龄为10.6岁的儿童(年龄范围2~20岁)和22例平均年龄为37岁的成人(年龄范围22~62岁)，这些患者均被收治到2家医院的长期监测中心接受癫痫发作评估。他们接受了标准连续视频EEG监测以及心电图、呼吸感应性容积描记(RIP)和指尖脉搏血氧测定。研究者记录到了儿童患者的101次发作(人均3.9次)和成年患者的55次发作(人均2.55次)。

成年和儿童队列的患者特征(性别、体重指数、抗癫痫药物的使用、MRI病灶)以及癫痫发作参数(发作类型、持续时间、定位、定侧、 继发性全身发作、体位、睡眠-觉醒状态)均相似。不过，与成年患者相比，儿童患者的癫痫发作更多地累及额叶(47/101，47% vs. 11/55，20%)，而成年患者出现颞叶癫痫发作的几率几乎比儿童患者高5倍(37/55，67% vs. 29/101，29%)。

一次或多次发作后，22例成年患者中有13例(59%)出现了PGES，而26例儿童患者中只有1例(4%)出现PGES，差异有统计学意义，比值比为0.20。而且，PGES见于儿童患者的6次(6%)发作中，而成年患者多达13次(24%)。

研究者写道：“考虑到成年人比儿童更频发PGES以及年龄与PGES无关的事实，我们推测只有在大脑发育成熟至表现出PGES之前，年龄可能才会对PGES的发生率产生影响。一旦大脑成熟到可以表现出PGES时，年龄再增加可能就不会产生进一步的影响了。这项研究的结果进一步支持了发育中大脑的‘控制网络’不够成熟，不能表现出PGES的观点。”

此外，儿童出现发作时中枢性呼吸暂停的几率比成年人高3倍(比值比 = 3.36) (儿童78次发作中有39次[50%] ，RIP数据较好vs. 成年人55次发作中有17 次 [31%])。无论是儿童还是成年患者，记录到的呼吸暂停事件的性质都不是阻塞性的。

儿童出现发作时心动过缓的几率比成年人高将近5倍(儿童63次发作中有15次[24%] vs. 成年人55次发作中有4 次 [7%])。相反，儿童出现发作时心动过速的几率却比成年人低60%(儿童63次发作中有31次[49%] vs. 成年人55次发作中有35 次 [64%]；比值比=0.40)。

对于其他心肺异常(发作时呼吸过慢和呼吸过快，发作时和发作后心动过缓和心动过速)的发生率，儿童和成年患者之间无显著差异。

研究者指出：“就发作时心脏呼吸异常的演化过程而言，尚未系统研究过与年龄相关的结果。在关于成年患者的研究中，有一些证据表明PGES可能是癫痫患者意外猝死的一个风险标志物，而且与年龄相关的大脑发育成熟可能与PGES的表现有关，但是少有研究评估了这种与年龄相关的大脑发育成熟对于PGES的潜在影响。”

这项研究由Harvard Catalyst提供的研究经费资助。一名作者声明担任了Digitrace和Best Doctors的顾问。其他作者声明无相关利益冲突。

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By: JEFF EVANS, Internal Medicine News Digital Network

Postictal generalized EEG suppression occurs more often in adults than in children and might be related to why adults have a higher rate of sudden unexpected death in epilepsy than that of children, according to results from a prospective study.

Cardiopulmonary abnormalities involving ictal apnea and bradycardia happened more frequently in children, whereas ictal tachycardia occurred more often among adults. However, there was no difference in desaturation or ictal bradypnea or tachypnea in children versus adults, reported Dr. Milena Pavlova of the division of epilepsy, neurophysiology, and sleep at Brigham and Women’s Hospital, Boston, and her colleagues.

"The evolution of ictal cardiorespiratory abnormalities [had] not been systematically studied for age-related findings," the researchers noted. "There is some evidence in adults that postictal generalized EEG suppression (PGES) may potentially be a risk marker for SUDEP [sudden unexpected death in epilepsy] and that age related maturation of brain may be involved in the manifestation of PGES, but not many studies have looked into the possible effect of this age-related brain maturation on PGES," they wrote (Epilepsy Behav. 2013 Oct. 17 [doi:10.1016/j.yebeh.2013.09.026]).

The study involved 26 children with a mean age of 10.6 years (range of 2-20 years) and 22 adults with a mean age of 37 years (range of 22-62 years) who had been admitted to the long-term monitoring units at two hospitals for the evaluation of seizures. They underwent standard continuous video-EEG monitoring as well as electrocardiography, respiratory inductance plethysmography (RIP), and finger pulse oximetry. The investigators recorded 101 seizures in children (mean of 3.9) and 55 in adults (mean of 2.55).

After one or more seizures, 13 of 22 (59%) adults had PGES, compared with only 1 of 26 (4%) children. This was a significant difference with an odds ratio of 0.20. Furthermore, PGES occurred in 6 (6%) of the seizures recorded in children, compared with 13 (24%) in adults.

"The fact that PGES was more frequent in adults than in children and the fact that age had no correlation with PGES in adults lead us to hypothesize that age may play a role in the occurrence of PGES only up to a point where the brain is mature enough to exhibit PGES. Once the brain is mature enough to be capable of manifesting PGES, further increase in age may not have any additional effect. These findings further support the idea of a less mature ‘controlling network’ in the developing brain being less capable of exhibiting PGES," the investigators wrote.

Children had more than three times greater odds of developing ictal central apnea (odds ratio = 3.36) than those of adults (39 of 78 [50%] seizures in children with good RIP data vs. 17 of 55 [31%] in adults). None of the apnea events recorded in either children or adults were obstructive in nature.

Ictal bradycardia was nearly five times more likely to occur in children than in adults (15 of 63 [24%] vs. 4 of 55 [7%], respectively). In comparison, ictal tachycardia was 60% less likely to occur among children than in adults (31 of 63 [49%] vs. 35 of 55 [64%], respectively; OR = 0.40).

The rates of other cardiopulmonary abnormalities (ictal bradypnea and tachypnea, ictal and postictal bradycardia and tachycardia) did not differ significantly between children and adults.

The adult and pediatric cohorts had similar characteristics for patient (gender, body mass index, antiepileptic drug usage, MRI lesions) and seizure variables (seizure type, duration, localization, lateralization, secondary-generalization, body-position, sleep-wake state). However, seizures in children more often involved the frontal lobe (47 of 101, 47%) compared with adults (11 of 55, 20%), whereas temporal lobe seizures were nearly five times more likely to occur in adults (37 of 55, 67%) than in children (29 of 101, 29%).

The study was funded by a grant from the Harvard Catalyst. One author reported serving as a consultant for Digitrace and Best Doctors. No other authors had conflicts of interest to report.