熊磊教授基于“脾为痰源”辨治儿童癫痫临证思路探赜

熊磊教授以理脾为本，将治痰贯穿始终。根据小儿脾常不足、肾常虚、肝常有余的生理特点，癫痫发作期治疗主以涤痰开窍，辅以理气健脾，同时配合活血化瘀通窍与平肝息风潜阳。主要选方为柴芍温胆汤、天麻钩藤饮、桃红四物汤加减；缓解期则以补肾养肝为主，兼以健脾化痰，主要选方为杞菊地黄丸合定痫丸加减，取得较好临床疗效。     

中药对癫痫相关信号通路调控作用的研究进展

癫痫是一种常见的神经系统疾病，其反复发作，迁延难愈，对患者的身心造成极大危害。抗癫痫药带来良好的治疗作用的同时也伴发着诸多身心损伤的不良反应。中医药治疗癫痫由来已久，目前除不断丰富传统中医理论治疗癫痫的认知理论外，从分子生物学角度研究中医药治疗癫痫的细胞信号传导机制发展迅速。通过对国内外文献检索发现，癫痫发生与细胞增殖、凋亡、自噬、炎症反应、免疫应答等病理生理过程密切相关；同时中西药的现代医学研究表明，无论是中药单体、单味中药甚至中药复方治疗癫痫的机制的研究均与文中所述信号通路有着直接或间接的关系，其可以通过调控相应信号通路的关键分子表达，达到抑制癫痫发生，控制癫痫发作，保护癫痫脑损伤的作用。该文通过对国内外研究现状进行总结，具体如下：①桔皮素，银杏内酯B等能通过激活磷脂酰肌醇3-激酶/蛋白激酶B（PI3K/Akt）信号通路，抑制凋亡及氧化应激反应。②黄芩苷，蛇床子素等能通过抑制哺乳动物-雷帕霉素靶蛋白（mTOR）信号通路，抑制自噬。③灵芝多糖，黄芪甲苷等能通过抑制丝裂原活化蛋白激酶（MAPK）信号通路，减少细胞凋亡。④红景天苷，白藜芦醇等能通过激活核因子E2相关因子2/抗氧化反应元件/血红素加氧酶1（Nrf2/ARE/HO-1）信号通路，抗氧化应激反应及抑制凋亡。⑤姜黄素，黄芩苷等能通过抑制核转录因子-κB（NF-κB）信号通路，降低炎症反应及减少凋亡。以上总结旨在为中药治疗癫痫的深入研究提供参考依据，也为临床中药治疗癫痫提供新的思路。     

Epilepsy and pregnancy: What should the neurologists do?

Epilepsy is one of the most common chronic disorders affecting women of childbearing age. Unfortunately, many women with epilepsy (WWE) still report not receiving key information about pregnancy. They obviously need information about epilepsy and pregnancy prior to conception with a particular emphasis on effective birth control (i.e. contraception), necessity to plan pregnancy, antiepileptic drugs optimization, and folate supplementation. The risks associated with use of antiepileptic drugs during pregnancy have to be balanced against fetal and maternal risks associated with uncontrolled seizures. This report reviews evidence-based counseling and management strategies concerning maternal and fetal risks associated with seizures, teratogenic risks associated with antiepileptic drug exposure with a special emphasis on developmental and behavioural outcomes of children exposed to intra utero antiepileptic drugs.     

Differentiating ictal/subclinical spikes and waves in childhood absence epilepsy by spectral and network analyses: A pilot study

ObjectiveChildhood absence epilepsy (CAE) is a disease with distinct seizure semiology and electroencephalographic (EEG) features. Differentiating ictal and subclinical generalized spikes and waves discharges (GSWDs) in the EEG is challenging, since they appear to be identical upon visual inspection. Here, spectral and functional connectivity (FC) analyses were applied to routine EEG data of CAE patients, to differentiate ictal and subclinical GSWDs.MethodsTwelve CAE patients with both ictal and subclinical GSWDs were retrospectively selected for this study. The selected EEG epochs were subjected to frequency analysis in the range of 1–30 Hz. Further, FC analysis based on the imaginary part of coherency was used to determine sensor level networks.ResultsDelta, alpha and beta band frequencies during ictal GSWDs showed significantly higher power compared to subclinical GSWDs. FC showed significant network differences for all frequency bands, demonstrating weaker connectivity between channels during ictal GSWDs.ConclusionUsing spectral and FC analyses significant differences between ictal and subclinical GSWDs in CAE patients were detected, suggesting that these features could be used for machine learning classification purposes to improve EEG monitoring.SignificanceIdentifying differences between ictal and subclinical GSWDs using routine EEG, may improve understanding of this syndrome and the management of patients with CAE.     

A new cause of developmental and epileptic encephalopathy with continuous spike-and-wave during sleep: CDKL5 disorder

The CDKL5 disorder is characterized by early onset epilepsy, stereotypical hand movement, absent speech and severe hypotonia. Herein, we report epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS) in apatient with CDKL5 disorder. She admitted with complaints of frequently recurring generalized tonic and myoclonic seizures. The diagnoses were confirmed by de novo CDKL5 mutation, c.197_198delCT (p.L67QfsX23). Interictal EEG revealed generalized spike and slow-wave activity, occurring intermittently in wakefulness but present for at least 85% of non-REM sleep, consistent with the diagnosis of CSWS. To our knowledge, this is the first report of CSWS associated with CDKL5 disorder.     

Simultaneously recorded intracranial and scalp high frequency oscillations help identify patients with poor postsurgical seizure outcome

ObjectiveHigh frequency oscillations (HFO) between 80–500 Hz are markers of epileptic areas in intracranial and maybe also scalp EEG. We investigate simultaneous recordings of scalp and intracranial EEG and hypothesize that scalp HFOs provide important additional clinical information in the presurgical setting.MethodsSpikes and HFOs were visually identified in all intracranial scalp EEG channels. Analysis of correlation of event location between intracranial and scalp EEG as well as relationship between events and the SOZ and zone of surgical removal was performed.Results24 patients could be included, 23 showed spikes and 19 HFOs on scalp recordings. In 15/19 patients highest scalp HFO rate was located over the implantation side, with 13 patients having the highest scalp and intracranial HFO rate over the same region. 17 patients underwent surgery, 7 became seizure free. Patients with poor post-operative outcome showed significantly more regions with HFO than those with seizure free outcome.ConclusionsScalp HFOs are mostly located over the SOZ. Widespread scalp HFOs are indicative of a larger epileptic network and associated with poor postsurgical outcome.SignificanceAnalysis of scalp HFO add clinically important information about the extent of epileptic areas during presurgical simultaneous scalp and intracranial EEG recordings.     

不同类型抗癫痫药物对开颅手术患者术后早期高氨血症发病率的影响

目的：评价开颅手术患者应用左乙拉西坦、丙戊酸钠和卡马西平等3种不同抗癫痫药（AEDs）诱发高氨血症（AHA）的发生率、发作程度，并分析患者发生AHA的危险因素。方法：纳入2014年4月至2018年9月间在某院神经外科进行开颅手术的108患者，并将其随机分为左乙拉西坦组（n=36）、丙戊酸钠组（n=36）与卡马西平组（n=36）。3组患者术后分别口服左乙拉西坦片、丙戊酸钠片与卡马西平片进行癫痫预防治疗，在术前，手术当天，术后第1，3，7天检测并比较3组患者的血氨浓度、肝功能和凝血指标，评价3组患者术后AHA发生率、血氨浓度、血氨变化趋势及AEDs对患者肝功能和凝血功能的影响。根据术后患者是否发生AHA，将患者分为术后AHA组（n=70）与术后血氨正常组（n=38），比较2组患者的临床特征，评价患者发生AHA的危险因素。结果：左乙拉西坦组、丙戊酸组与卡马西平组分别有24（66.7%）例、29（80.6%）例及17（47.2%）例患者发生AHA，丙戊酸组患者AHA发生率显著高于卡马西平组（χ²=8.669，P=0.003）。丙戊酸钠组患者术后第3天和第7天血氨浓度及术后血氨的平均浓度均显著高于卡马西平组患者（P=0.023，<0.001，0.028）。术后第7天丙戊酸组患者ALT指标显著低于左乙拉西坦组与卡马西平组（均P<0.001）。影响患者术后发生AHA的危险因素包括：较低的年龄（t=2.061，P=0.042）与较高的术前血氨浓度（t=7.986，P<0.001）。AHA组患者术后总胆红素（t=3.788，P<0.001）、直接胆红素（t=3.329，P=0.001）和血清白蛋白（t=11.624，P<0.001）较术前显著降低，血浆凝血酶原时间显著延长（t=4.109，P<0.001）。而衡量急性肝炎的指标丙氨酸转氨酶没有显著变化（t=0.956，P=0.341）。结论：卡马西平对患者术后血氨浓度影响较小，是开颅手术患者的首选AEDs药物，而丙戊酸钠更适合肝脏氨基转移酶异常的患者。