宁夏农村地区惊厥性癫痫患者死亡原因分析

目的分析宁夏农村地区惊厥性癫痫患者可能的死亡原因,为预防癫痫患者死亡及降低癫痫死亡率提供依据。方法收集2012年1月1日~2014年12月31日宁夏农村地区癫痫示范项目区内死亡癫痫患者的临床资料,并进行回顾性分析,用Excel表格建立数据库,SPSS17.0软件统计分析,计数资料比较采用χ2检验,P0.05为差异有统计学意义。结果 3 y间,宁夏农村地区癫痫示范项目区内死亡患者共计137例。癫痫发作在死因构成中居于首位(32.8%),其次为意外死亡(26.9%)、脑血管病(11.0%)、不明原因死亡(8.0%)、呼吸系统疾病(6.5%)、循环系统疾病(5.1%)、消化系统疾病(4.3%)及自杀(2.9%);癫痫患者的死亡年龄主要分布在30~39岁之间(21.9%);以脑血管病为主要死亡原因者主要分布在60~69岁之间;以癫痫发作为死亡原因者20~69岁年龄组占86.7%;意外死亡的患者年龄分布在10~79岁之间,其中,40~59岁者占37.9%。宁夏农村地区癫痫患者年平均死亡率为1.4/10万,男性死亡率为1.7/10万,女性为1.1/10万,男、女性死亡率有显著性差异(P0.05);在神经系统疾病死因统计中,癫痫死亡率仅次于脑血管病。结论癫痫发作、意外(溺水及车祸为主)、脑血管病、不明原因死亡是宁夏农村地区癫痫示范项目区内癫痫患者死亡的主要原因。宁夏农村地区癫痫示范项目区内癫痫患者的死亡率为1.4/10万。男性癫痫患者的死亡率(1.7/10万)高于女性(1.1/10万)。     

癫痫猝死的危险因素及预防

<正> 癫痫患者的死亡率是健康人群的2～5倍。癫痫猝死(sudden unexpected death in epilepsy,SUDEP)是癫痫最常见的直接死因,常发生于慢性癫痫患者。1 SUDEP 的诊断及发生率 SUDEP是突然的     

癫痫猝死的生物学标志物及危险因素研究进展

癫痫是一种常见的神经系统疾病，患者常表现出不可预测的自发性癫痫发作，尽管现已存在数十种治疗癫痫发作的药物和干预手段，但仍有约30%的癫痫转为难治性癫痫。癫痫猝死(SUDEP)是难治性癫痫患者死亡的主要原因，然而其确切发病机制尚不清楚。已有的研究表明，呼吸、心脏和自主神经功能障碍、大脑觉醒抑制等机制参与了SUDEP的发生。现基于SUDEP的发病机制，对SUDEP生物学标志物及危险因素的研究进展做一综述。 [国际神经病学神经外科学杂志, 2022, 49(3): 102-106.]     

癫痫猝死的研究进展

癫痫猝死(sudden unexpected death in epilepsy,SUDEP)是癫痫患者突然发生的无法解释的死亡,一般认为大部分SUDEP与癫痫发作有关.其发病机制仍不明确,现对SUDEP的相关文献进行系统综述,旨在提高对该现象的认识并促进其研究.     

急性缺血性卒中影像学研究进展

在我国,随着生活水平的不断提高、工作节奏的加快,以及高血压、糖尿病患者的增多,脑血管病的发病率呈现逐年上升趋势。根据2008年公布的第3次全国死因调查结果,我国居民前5位死因依次为脑血管病、恶性肿瘤、呼吸系统疾病、心脏病,以及损伤和中毒。以13亿人口计,全国每年新发病例约为250万例,死于脑血管病者超过150万例,幸存者600～700万例,病残率高达75%。更为严重的     

癫痫患者的突然意外死亡

癫痫患者突然意外死亡(sudden unexpected death in epilepsy,SUDEP)是指检证明没有解剖和毒理学原因的癫痫患者的突然死亡,它是慢性癫痫患者抽搐相关死亡最常见的原因.     

大鼠癫痫持续状态后认知功能变化模式及海马脑红蛋白表达水平的实验研究

目的观察大鼠癫痫持续状态(SE)后学习记忆功能改变情况及海马组织脑红蛋白(NGB)表达水平,探讨癫痫发作对认知功能影响的可能机制。方法健康成年雄性SD大鼠40只,随机分为对照组(n=5)、癫痫模型实验组(n=35),模型组再依据观察时间分为:0 h、1 h、3 h、12 h、24 h、10 d、30 d。应用氯化锂-匹罗卡品(Li-Pilo)建立SE模型,观察致痫期间大鼠行为学变化;采用Nissl染色检测神经元损伤情况;SABC免疫组化法检测NGB表达水平。同时随机选取同期相同品系SD大鼠40只,在造模前及造模后第5d、10 d、15 d、25 d、35 d进行RMT-100迷宫实验,以评价大鼠SE前后学习记忆功能变化情况。结果大鼠SE后,海马CA1、CA3区和DG区均出现不同程度神经元细胞损伤坏死,且NGB表达上调,而海马CA1和CA3区神经元存活数与NGB表达水平呈正相关(r=0.206,P=0.015;r=0.306,P=0.011)。迷宫实验显示工作记忆错误(WME)和参照记忆错误(RME)次数随SE后时间延长均呈递增趋势。相关性分析证实RME次数与CA1和CA3区神经元存活数呈负相关(r=-0.579,P=0.000;r=-0.454,P=0.002),WME次数与CA1和CA3区神经元存活数也呈负相关(r=-0.470,P=0.001;r=-0.507,P=0.000)。结论 SE后NGB表达上调,且与海马组织神经元存活数呈正相关,提示其可能是SE所致缺血缺氧损害的一种代偿神经保护机制。SE后可导致明显认知功能损害,其可能与SE所致海马组织神经元的病理改变相关。     

急性缺血性卒中影像学研究进展

在我国，随着生活水平的不断提高、工作节奏的加快，以及高血压、糖尿病患者的增多，脑血管病的发病率呈现逐年上升趋势。根据2008年公布的第3次全国死因调查结果，我国居民前5位死因依次为脑血管病、恶性肿瘤、呼吸系统疾病、心脏病，以及损伤和中毒。以13亿人口计，全国每年新发病例约为250万例，死于脑血管病者超过150万例，     

癫痫性猝死之管见

<正>癫痫性猝死（sudden unexpected death in epilepsy,SUDEP）是癫痫患者整体死亡风险较普通人群显著增高的重要原因，由SUDEP所致的癫痫性死亡已成为重大公共卫生问题。笔者检索国内文献发现，目前关于SUDEP的报道甚少，有关SUDEP命名不一，如“癫痫不明原因猝死”、“癫痫患者突然意外死亡”、“癫痫猝死”等。随着长程视频脑电监测的普及、基因检测技术及分子水平尸检的开展等，人们对SUDEP有了进一步认识，有必要再次探讨SUDEP的科学定义和解读，这对未来研究SUDEP具有重要意义。癫痫性猝死的概念由Nashef于1997首次提出。为了方便临床应用，2012年再次对其重新修订。     

腹腔注射脂多糖对幼鼠癫痫发作及海马TLR4/HMGB1/P-IκB-α表达的影响

目的探讨脂多糖(LPS)预处理对幼鼠癫痫发作及海马炎症介质Toll样受体4/高迁移率族蛋白1/磷酸化核因子抑制蛋白α(TLR4/HMGB1/P-IκB-α)表达的影响。方法出生21d的SD鼠随机分为生理盐水组(对照组),模型Ⅰ组和模型Ⅱ组,模型Ⅰ组采用海人酸(KA)诱导癫痫发作,模型Ⅱ组在应用KA前2h腹腔注射LPS,观察幼鼠癫痫发作的行为学表现,荧光定量PCR检测癫痫持续状态(SE)后3h和24h各组海马TLR4和HMGB1基因的表达,Westernblot法检测SE后3h、24h各组海马TLR4、HMGB1、P-IκB-α蛋白的表达。结果与对照组相比:模型Ⅰ组、模型Ⅱ组海马TLR4基因在SE后3h表达均显著增加(t=4.806,P0.05;t=4.954,P0.05),SE后24h也显著增加(t=3.924,P0.05;t=3.792,P0.05),模型Ⅰ组、模型Ⅱ组海马TLR4蛋白表达在SE后3h均显著增加(t=7.804,P0.05;t=8.385,P0.05),SE后24h也显著增加(t=4.256,P0.05;t=4.262,P0.05);模型Ⅰ组、模型Ⅱ组海马HMGB1基因在SE后3h表达均显著增加(t=3.626,P0.05;t=5.255,P0.05),SE后24h也显著增加(t=4.046,P0.05;t=2.836,P0.05),模型Ⅰ组、模型Ⅱ组海马HMGB1蛋白在SE后3h均无显著性增加(t=0.389,P0.05;t=0.213,P0.05),SE后24h也无显著性增加(t=0.106,P0.05;t=0.279,P0.05)。模型Ⅰ组、模型Ⅱ组海马P-IκB-α蛋白表达在SE后3h均显著增加(t=4.383,P0.05;t=6.627,P0.05),SE后24h也显著增加(t=14.521,P0.05;t=19.458,P0.05)。模型Ⅱ组与模型Ⅰ组相比,LPS预处理可显著增加海马TLR4基因在SE后3h的水平(t=2.362,P0.05),及SE后3hTLR4蛋白表达(t=4.284,P0.05);且显著增加SE后3h、24hPIκB-α蛋白表达(t=4.249,P0.05;t=9.120,P0.05);但对SE后3h、24hHMGB1基因水平无显著性影响(t=0.569,P0.05;t=0.691,P0.05),对SE后3h、24hHMGB1蛋白表达也无显著性影响(t=0.168,P0.05;t=0.385,P0.05)。结论LPS预处理加重幼鼠癫痫发作,使TLR4/P-IκB-α表达升高,对HMGB1表达无显著改变。     

Mortality in epilepsy

All studies report an increased mortality risk for people with epilepsy compared with the general population. Population-based studies have demonstrated that the increased mortality is often related to the cause of the epilepsy. Common etiologies include neoplasia, cerebrovascular disease, and pneumonia. Deaths in selected cohorts, such as sudden unexpected death in epilepsy (SUDEP), status epilepticus (SE), suicides, and accidents are more frequently epilepsy-related. SUDEP is a particular cause for concern in younger people, and whether and when SUDEP should be discussed with patients with epilepsy remain problematic issues. Risk factors for SUDEP include generalized tonic-clonic seizures, increased seizure frequency, concomitant learning disability, and antiepileptic drug polypharmacy. The overall incidence of SE may be increasing, although case fatality rates remain constant. Mortality is frequently secondary to acute symptomatic disorders. Poor compliance with treatment in patients with epilepsy accounts for a small proportion of deaths from SE. The incidence of suicide is increased, particularly for individuals with epilepsy and comorbid psychiatric conditions. Late mortality figures in patients undergoing epilepsy surgery vary and are likely to reflect differences in case selection. Future studies of mortality should be prospective and follow agreed guidelines to better quantify risk and causation in individual populations.     

Premature mortality risk in people with convulsive epilepsy: Long follow‐up of a cohort in rural China

Purpose: Detailed data on the mortality of epilepsy are still lacking from resource‐poor settings. We conducted a long‐term follow‐up survey in a cohort of people with convulsive epilepsy in rural areas of China. In this longitudinal prospective study we investigated the causes of death and premature mortality risk among people with epilepsy. Methods: We attempted to trace all 2,455 people who had previously participated in a pragmatic assessment of epilepsy management at the primary health level. Putative causes of death were recorded for those who died, according to the International Classification of Diseases. We estimated proportional mortality ratios (PMRs) for each cause, and standardized mortality ratios (SMRs) for each age‐group and cause. Survival analysis was used to detect risk factors associated with increased mortality. Key Findings: During 6.1 years of follow‐up there were 206 reported deaths among the 1,986 people with epilepsy who were located. The highest PMRs were for cerebrovascular disease (15%), drowning (14%), self‐inflicted injury (13%), and status epilepticus (6%), with probable sudden unexpected death in epilepsy (SUDEP) in 1%. The risk of premature death was 2.9 times greater in people with epilepsy than in the general population. A much higher risk (SMRs 28–37) was found in young people. Duration of epilepsy and living in a waterside area were independent predictors for drowning. Significance: Drowning and status epilepticus were important, possibly preventable, causes of death. Predictors of increasing mortality suggest interventions with efficient treatment and education to prevent premature mortality among people with epilepsy in resource‐poor settings.     

Risk factors for fatality and neurological sequelae after status epilepticus in children

Using multivariate regression analysis, we examined risk factors for fatality and neurological sequelae after status epilepticus (SE) in children. Possible risk factors included sex, age at onset, the cause of SE, pyrexia, asthmatic attack during SE, past history of seizure, predisposing neurological abnormality, seizure duration, type of seizure, and medication with theophylline. Consecutive patients with SE, aged 1 month to 18 years, who were referred to Tottori University Hospital from 1984 to 2002 were reviewed. Of the 234 patients enrolled, 45 patients (19.2 %) showed poor outcomes, namely early death in 9 and neurological sequela in 36. Acute neurological insult and progressive neurological disease as the cause of SE were very significantly related to poor outcome (OR = 33.68, p = 0.000). We excluded 21 patients with the etiology of acute neurological insult and progressive neurological disease and then reanalyzed risk factors in the remaining 213 patients. Twenty-nine patients (13.6 %) showed poor outcome, namely early death in 6 and neurological sequela in 23. Seizure duration of more than 2 hours (OR = 12.73, p = 0.000) and moderate to severe asthmatic attack (OR = 31.61, p = 0.010) were associated with poor outcome. These results indicate that long-lasting seizure activity and asthmatic attack can exacerbate SE-associated brain injury.     

Status epilepticus in Hong Kong Chinese: aetiology, outcome and predictors of death and morbidity.

The majority of patients with epilepsy live in developing countries but there is limited information on status epilepticus (SE) from these regions. We evaluated the clinical profile and predictors of poor outcome in a group of Chinese patients with SE. Patients with SE were ascertained from the medical, intensive care and emergency departments of a large urban hospital from 1996 to 2001. Factors for poor outcome, defined as death or morbidity as measured by deterioration in functional status using the Glasgow Outcome Score were analysed in a multivariate logistic regression model. A total of 107 episodes of SE occurring in Chinese patients were studied. The three most common underlying causes were cerebrovascular disease, metabolic derangement and anti-convulsant withdrawal but alcohol-related SE was infrequent. Twenty-six percent had worsened functional ability and the mortality rate was 16%. Predictors of poor outcome were older age (odds ratio (OR)=1.04, 95% CI 1.01-1.07), delay in treatment (OR=3.52, 95%CI 1.01-12.18), SE due to cerebrovascular disease (OR=9.73, 95% CI 1.58-59.96) and CNS infection (OR=30.27, 95% CI 3.14-292.19).     

Sudden and unexpected death in epilepsy (SUDEP): evidence of acute neuronal injury using HSP-70 and c-Jun immunohistochemistry

Post-mortem and neuropathological examination in sudden and unexpected death in epilepsy (SUDEP) shows no specific lesions and the exact cause and mechanism of death in these cases remains undetermined. There is clinical evidence to support the fact that SUDEP is a seizure-mediated event, and patients with poorly controlled seizures are at higher risk. We aimed to identify any evidence of acute neuronal injury in SUDEP cases at post-mortem to support that a recent seizure had occurred. We analysed the distribution and frequency of heat shock protein (HSP)-70 and c-Jun immunopositive neurones in the hippocampus in 18 SUDEP cases and 22 control cases, both markers being nonspecific but early and reliable indicators of acute neuronal injury. Post-mortem control groups included patients with epilepsy with cause of death other than SUDEP (including status epilepticus and accidental death), and patients with sudden cardiac death without an epilepsy history. An additional surgical control group included patients with refractory epilepsy and hippocampal sclerosis who had undergone temporal lobectomy. Semiquantitative analysis of the distribution of HSP-70 staining showed significantly more SUDEP cases with positively labelled neurones in hippocampal subfields compared to epilepsy and cardiac post-mortem controls (P < 0.001) but not compared to the epilepsy surgical controls (P = 0.4). No significant difference in immunostaining patterns between groups was seen in the parahippocampal gyrus with HSP-70 or with c-Jun in either the hippocampus or parahippocampal gyrus regions. The detection of HSP-70 positive neurones in the hippocampus in SUDEP is supportive of ante-mortem neuronal injury including a recent seizure prior to death.     

Sudden Unexplained Death and Injury in Epilepsy

Summary: Seizures may be associated with risk of injury or death. Injuries are common in patients with epilepsy, with up to 30% of patients reporting injuries, most commonly blunt trauma and lacerations. Seizures associated with falls increase the risk of injury, but any seizure that is associated with alteration in consciousness may cause injury. Patients with seizures may injure others, especially by causing motor vehicle accidents. Each state has restrictions on driving, requiring seizure-free intervals that range from 3 to 18 months. Mortality is increased in patients with epilepsy. The standardized mortality ratio is increased two to three times in epilepsy cohorts. Sudden unexplained death in epilepsy (SUDEP) is responsible for 2% to 17% of all deaths in patients with epilepsy, depending on the cohort studied. Population-based studies of SUDEP show a lower overall SUDEP rate compared with clinical trials or epilepsy referral center cohorts. Overall, the risk of sudden death is increased in the epilepsy population by 24 times compared with the general population. Risk factors for SUDEP may include poorly controlled seizures, early onset of epilepsy, and generalized tonic-clonic seizures. The pathophysiology of SUDEP is unknown, but animal data suggest apnea may be the initial factor that results in sudden death.     

Mortality in a population-based cohort of epilepsy surgery patients

PURPOSE: To investigate mortality and especially the incidence of sudden unexpected death in epilepsy (SUDEP) in a population-based cohort of epilepsy surgery patients. METHODS: All patients who underwent epilepsy surgery treatment between January 1990 and December 1998 (surgery patients) or whose presurgical evaluation started, although not leading to an operation, during the same period (nonsurgery patients) were identified through the Swedish National Epilepsy register. All subjects were followed up through the Cause of Death Register until December 1998. Standardized mortality ratios (SMRs) for all causes of death and incidence of SUDEP were calculated. RESULTS: During the study period, 651 surgical operations were carried out on 596 patients (316 male). Of those, 14 patients died (six in SUDEP), rendering a total SMR of 4.9 [95% confidence interval (CI), 2.7-8.3]. SUDEP incidence was 2.4 per 1,000 person years. No major differences were found in SMRs or SUDEP rates between subgroups when stratifying for type of operation and for seizure outcome 2 years after surgery. SMR and SUDEP rates were higher in right-sided temporal lobe resections for gliosis than in left-sided, but the number of deaths was small. Among 212 nonsurgery patients, five died (four in SUDEP). The SMR for all causes was 7.9 (2.6-18.4), and SUDEP incidence, 6.3 per 1,000 person years. CONCLUSIONS: In this large and strictly population-based cohort, SMR for all causes and SUDEP incidence among surgery patients were similar to those of other studies. No differences in overall mortality emerged by seizure outcome, but none of the SUDEP cases was seizure free at the time of death. Four of five deaths in the nonsurgery group occurred during the surgery evaluation period. Mortality appeared to be lower for surgery than for nonsurgery patients, and the interpretation of this finding is discussed.     

Risk of sudden unexpected death in epilepsy in patients given adjunctive antiepileptic treatment for refractory seizures: a meta-analysis of placebo-controlled randomised trials

Background

Sudden unexpected death in epilepsy (SUDEP) represents the main cause of death in patients with refractory epilepsy. No evidence-based intervention to prevent SUDEP exists. We postulated that pooling data from randomised placebo-controlled trials in patients with refractory epilepsy might show a lower incidence of SUDEP in patients receiving antiepileptic drugs (AEDs) at efficacious doses than in those receiving placebo.

Methods

We searched Medline and the Cochrane Library for randomised trials investigating any AED in the add-on treatment of drug-resistant epilepsy in adults. We extracted the number and causes of death in patients allocated to AEDs at doses that were more efficacious than placebo against seizures, AEDs at non-efficacious doses, and placebo. In our primary analysis, we compared the occurrence of definite or probable SUDEP between patients given efficacious AED doses and those given placebo using the Mantel-Haenszel method, with exclusion of trials with no event.

Findings

Data of 33 deaths, including 20 deemed as SUDEP, were extracted from 112 eligible randomised trials. 18 deaths were classified as definite or probable SUDEP and two as possible SUDEP. Definite or probable SUDEP, all SUDEP, and all causes of death were significantly less frequent in the efficacious AED group than in the placebo group, with odds ratios of 0·17 (95% CI 0·05–0·57, p=0·0046), 0·17 (0·05–0·57, p=0·0046), and 0·37 (0·17–0·81, p=0·0131), respectively. Rates of definite or probable SUDEP per 1000 person-years were 0·9 (95% CI 0·2–2·7) in patients who received efficacious AED doses and 6·9 (3·8–11·6) in those allocated to placebo.

Interpretation

Treatment with adjunctive AEDs at efficacious doses may have reduced the incidence of definite or probable SUDEP by more than seven times compared with placebo in patients with previously uncontrolled seizures. This result provides evidence in favour of active treatment revision for patients with refractory epilepsy.

Funding

None.     

Sudden Unexplained Death in Epilepsy: Observations from a Large Clinical Development Program

Summary: Purpose: The present study was conducted to determine the rate of sudden unexplained death in epilepsy (SUDEP) in a well-defined cohort of patients included in the lamotrigine (LTG) clinical development database.
Methods: A panel of scientists experienced in the area of SUDEP was assembled and provided with case summaries on all deaths (n = 45) reported during the initial clinical development of LTG. The panel developed a set of criteria for classifying cases as SUDEP (definite or highly probable), possible SUDEP, or non-SUDEP. This classification algorithm was then applied to the LTG cases, and SUDEP rates were calculated using patient-years of exposure as the denominator.
Results: At the time of the study, 4,700 patients (5,747 patient-years of exposure) were included in the worldwide LTG clinical trials database. In this cohort, 45 deaths were reported. Eighteen were judged by the panel to be SUDEP, 6 were defined as possible SUDEP, 20 were judged to be due to other causes (non-SUDEP), and 1 lacked sufficient data from which to make a classification. The overall SUDEP rate (definite/highly probable SUDEP and possible SUDEP combined) was calculated to be 3.5 in 1,000 patient-years of exposure to LTG.
Conclusions: The rate of SUDEP in this cohort of patients was comparable to the rate that would be expected in young adults with severe epilepsy (the subgroup of patients believed to be at highest risk of SUDEP). The data suggest that the rate of SUDEP in the LTG clinical development program is a function of the clinical trial population and is unrelated to drug treatment.