癫猝死的相关研究新进展

癫是一种脑部疾病,其特点是脑部有持续存在癫反复发作的易感性,以及因癫发作所引起的神经生化、认知、心理和社会后果。癫患者的早逝风险较同年龄普通人群高。癫猝死(SUDEP)是癫患者早逝风险增加的重要原因。文中就SUDEP的定义、发生率、发病机制、危险因素以及预防措施做综述。     

急性脑血管病并发癫（癎）的临床研究

目的 研究急性脑血管病并发癫（癎）的发病机制、疾病特征、治疗与预后.方法 选取2008-01-2011-12我院862例急性脑血管病患者,其中并发癫（癎）患者73例,给予正规原发疾病的治疗以及相应抗癫（癎）治疗,比较分析急性脑血管病并发癫（癎）的发病率、发作类型、发作时间、病死率等.结果 急性脑血管病并发癫（癎）的发病率为8.47%,其中脑梗死占8.03%（37/461）,脑出血占9.87 %（22/223）,蛛网膜下腔出血占9.86%（14/142）;单纯部分性发作病例比例最高（P〈0.05）;急性脑血管病并发癫（癎）患者中早期发作型癫（癎）比例较高;脑出血和蛛网膜下腔出血的患者更易并发早期发作型癫（癎）（P〈0.05）,而脑梗死的患者更容易并发迟发型癫（癎）（P〈0.05）;急性脑血管病并发癫（癎）患者总病死率为36.99%,明显高于未并发癫（癎）患者（P〈0.05）.结论 急性脑血管病并发癫（癎）的发病率为8.47%,以早期发作型癫（癎）比例较高,且病死率较高.     

哈密地区中老年人非癫（癎）性发作性疾病的病因及脑电图分析

癫（癎）是一种发作性疾病,是大脑皮质局限性或广泛性、间歇性的异常放电,在临床上可能与其他发作性疾病相混淆.长程视频录像脑电图（V-EEG）可通过直接观察发作的临床表现、睡眠结构EEG,并通过同步EEG监测来分析临床与EEG的关系,从而成为癫（癎）诊断与鉴别诊断非常可靠的监测方法.非癫（癎）性发作（NES）是指多种原因引起的阵发性临床发作,不伴有发作期EEG（癎）样放电.在国外癫（癎）中心所谓癫（癎）患者中10%～20%被证实为NES.现将哈密地区监测的54例中老年人NES患者的临床资料分析报告如下.     

长期应用抗癫癎药控制的颞叶癫癎患者发作间期SPECT异常灌注灶修复与长程视频脑电图变化的临床研究

目的：探讨抗癫癎药（AEDs）长期控制的颞叶癫癎患者发作期间应用单光子发射电子计算机断层扫描（SPECT）检查异常灌注灶的修复。方法：颞叶癫癎患者经AEDs、步长脑心通胶囊与尼莫地平治疗,并在两次发作间期行SPECT、长程视频脑电图（V-EEG）和CT/MRI检查。结果：44例癫癎患者平均年龄为25岁;平均病程为3.5年;44例患者中病因明确者为19例（家族史2例,围产期损伤1例,热性惊厥3例,颅脑损伤出血1例,颅脑外伤5例,脑膜脑炎3例,脑部手术2例,多病因2例）。癫癎发作控制平均为25个月。治疗前发作间期SPECT异常（颞叶和非颞叶）感兴趣区（ROI）为77.3%,长程V-EEG异常77.3%（其中癎样放电88.2%）,治疗前CT/MRI异常47.7%。治疗后发作间期SPECT正常增加4.5%（P〉0.05）,异常灶减少8.3%（P〉0.05）;长程V-EEG正常增加27.3%（P〈0.05）,癎样放电减少53.3%（P〈0.05）;结论：长期控制的颞叶癫癎患者的异常灌注灶修复明显低于其他类型癫癎,防治重点应放在颞叶癫癎症状出现之前的继发性全身强直阵挛发作。     

癫癎患者的家庭支持

癫癎是一种由多种病因引起的慢性脑部疾患,以脑部神经元异常放电所致的突然、反复和短暂的中枢神经系统能失常为特征。癫癎患者由于长期服药或者反复发作,严重影响其生活质量。有研究表明,癫癎患者的生活质量明显低于正常人[1],提高癫癎患者的家庭支持能改善患者的生活质量。     

难治性癫(癎):临床界定的难题

癫(癎)是由不同病因引起的一种脑部疾病,其预后不尽相同.大多数癫(癎)患者的发作可获得满意的控制,但有30%～40%的癫(癎)患者经适当的抗癫(癎)药物(anti-epileptic drugs,AEDs)治疗,在一定时期后仍未达到无发作,即难治性癫(癎)(refractory epilepsy,RE).     

山东省癫癎流行病学调查研究

目的 了解中国山东省的癫癎）病流行现况及其危险因素.方法 以调查问卷为基础,运用国际统一癫癎诊断标准,采用多级分层随机整群抽样方法,逐户进行调查.结果 调查人数251 492名,癫癎患者335例,癫（痫）患病率为1.33‰;男性患病率为1.35‰o,女性患病率为1.31‰;城市患病率为1.20‰,农村患病率为1.39‰,均差异无统计学意义.癫癎发病率为18.69/10万.发作类型以全面性发作为主为60.90％;部分性发作为34.33％;发作不能分类为4.78％.首次发病平均年龄为（15.37±15.77）岁.特发性癫癎为60.90％,症状性癫（痫）为39.10％.大部分患者未进行正规治疗,治疗缺口为54.33％.结论 山东省癫癎患病率、发病率处于全国较低水平,治疗缺口与国内文献报道一致.癫癎发作类型以全面性发作为主;癫癎发病以特发性癫（痫）为主,症状性癫癎病因中以脑炎为主.     

难治性癫(癎)的脑部电刺激治疗

癫癎是由多种病因引起的慢性脑部疾病，以脑部神经元过度放电所致的突然、反复和短暂的中枢神经系统功能失常为特征。据统计25％-30％的癫癎患者应用已有的抗癫癎药正规治疗后临床发作仍得不到有效控制，称为难治性癫癎。约50％的难治性癫癎患者不适合进行癫癎灶切除术，所以研究者们都在探索新的治疗方法，电刺激近年来成为人们研究的热点。     

抗癫(癎)药物对认知功能的影响

癫(癎)是脑部神经元异常放电高度同步化活动所引起的,由不同症状和体征组成的短暂性临床现象.其特点是脑部持续存在的导致癫(癎)反复发作的易感性,以及由于这种疾病引起的神经生物、认知、心理和社会功能障碍等方面的后果.     

卒中后癫癎发作时间分布及影响因素的研究

目的 分析卒中后癫癎发作时间分布特点,并对其影响因素进行研究.方法 将122例卒中后癫癎发作患者分为早发性癫癎发作组(卒中后2周内出现癫癎发作)60例;晚发性癫癎发作组(卒中2周后出现癫癎发作)62例.进行单因素及多因素分析,研究患者的基础情况,卒中的危险因素、卒中的类型、癫癎发作的类型、发作频次、治疗等情况与早发及晚发的关系.结果 性别、年龄、卒中危险因素以及脑电图改变在两组间无差异.缺血性卒中出血转化是卒中后癫癎发作早发的危险因素;早发性癫痫发作倾向于表现为全面性强直阵挛发作,晚发性癫癎发作倾向于表现为部分性发作;颞叶病变是卒中后癫癎发作晚发的危险因素;晚发性癫癎发作倾向于复发.早发性癫癎发作患者接受短期治疗的比例较高,晚发性癫癎发作患者接受长期治疗的比例较高.Logistic多元回归提示糖尿病是卒中后癫癎发作早发的危险因素(OR=2.664,95%CI=1.143～6.210,P=0.259).结论 糖尿病和缺血性卒中出血转化为卒中后癫癎发作早发的危险因素;而颞叶病变是卒中后癫癎发作晚发的危险因素,且晚发性癫癎发作更倾向于复发.     

Sudden Unexpected Death in Epilepsy: Addressing the Challenges

Epilepsy is associated with a higher rate of premature death than the general population, and the commonest cause of epilepsy mortality is sudden unexpected death in epilepsy (SUDEP). It is difficult to quantify because of the variable reporting of this cause of death. Death occurs due to autonomic deregulation of cardio-respiratory pathways as a result of seizures. Measures to reduce cardio-respiratory dysfunction are discussed together with the importance of seizure control in preventing SUDEP. The role of seizure detection devices, antiepileptic drugs and the importance of providing information about SUDEP to people with epilepsy are highlighted. There is increasing interest in SUDEP and some current initiatives are discussed.     

Sudden unexpected death in people with epilepsy: a pediatric perspective

The possibility of sudden unexpected death in people with epilepsy (SUDEP) is very frightening for parents of a child with epilepsy. The mechanism for SUDEP is unclear but is probably most commonly related to postictal respiratory insufficiency. Occasionally the cause is a cardiac arrhythmia induced by a seizure. Even though children with epilepsy have an increased risk of death, SUDEP is very rare (1-2/10,000 patient-years). Nearly all of the mortality in children with epilepsy is related to the underlying neurologic disorder, not the seizures. Normal children with epilepsy do not have an increased risk of death compared with the general population. There is no current proven strategy to prevent SUDEP, although its rarity precludes systematic trials. Common sense approaches include identifying patients with cardiac arrhythmias as the cause of misdiagnosed epilepsy and vigorous attempts to control resistant seizure disorders.     

Sudden unexpected death in epilepsy: ongoing challenges in finding mechanisms and prevention

ABSTRACT

Purpose/aim of the study: To summarize recent studies on the pathophysiology and preventive strategies for SUDEP.

Materials and methods: Databases and literature review.

Results: Patients with epilepsy have a significantly higher risk of death than the general population. Sudden unexpected death in epilepsy (SUDEP) is the leading cause of sudden death among patients with epilepsy. Despite on-going research, there are still deficits in our knowledge about the mechanisms, genetic factors, and prevention of SUDEP. Current evidence suggests that cardiac arrhythmias, respiratory dysfunction, and brainstem arousal system dysfunction are the major mechanisms of SUDEP, and animal models support the role of neurotransmitters, especially serotonin and adenosine, in pathophysiology of SUDEP. Several mutations in the neurocardiogenic channelopathy genes have been identified as a possible cause of epilepsy and increased SUDEP risk. The lack of awareness that SUDEP can be a potential cause of premature death has been found in several surveys. In addition, medical legal cases demonstrate the need for more education about this condition. Several preventive strategies to reduce SUDEP have been proposed, including effective seizure control, nocturnal supervision, seizure monitoring, devices to protect the airway, and selective serotonin reuptake inhibitors. Further research is needed to determine the efficacy of these interventions.

Conclusions: The major mechanisms of SUDEP include cardiac arrhythmias, respiratory dysfunction, and brainstem arousal system dysfunction. Effective control of seizures is the only effective strategy to prevent SUDEP. Other preventive interventions require more research.     

Sudden unexpected death in epilepsy

Mortality in people with epilepsy is two- to three-times that of the general population. This can be attributed to epilepsy itself (epilepsy-related death) or to the underlying cause of the epilepsy. Sudden unexpected death in epilepsy (SUDEP) is the commonest cause of epilepsy-related death. It is a syndrome where a person with epilepsy dies suddenly and no other cause of death is found. There are frequent reports of persons dying alone in their sleep. It is assumed that death occurs following a seizure but since the deaths are often unwitnessed this is only an assumption. The most important risk factor appears to be poor seizure control. Lately, SUDEP has received much public interest, has been the subject of international forums, ethical debates and comprises part of national guidelines on epilepsy management. Despite its high profile, the evidence for specific risk factors and pathophysiology is still not established. Poor incident case reporting, inaccurate death certification and fewer post-mortem examinations have limited the value of epidemiological data on SUDEP. Here, we review the characteristics of SUDEP, its likely risk factors, mechanisms and differential diagnosis, and consider possible strategies for prevention. We also explore the discussion of SUDEP with patients and the management of relatives of SUDEP patients.     

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.     

Sudden unexpected death in epilepsy associated with progressive deterioration in heart rate variability

We describe a patient with severe epilepsy who underwent serial measurements of heart rate variability (HRV) prior to his death from autopsy-confirmed sudden unexpected death in epilepsy (SUDEP). The significance of low HRV is discussed in relation to SUDEP risk. Progressive deterioration in HRV may be a risk factor for SUDEP.     

Knowing the risk of SUDEP: Two family's perspectives and The Danny Did Foundation

There is much debate in the epilepsy community about whether neurologists should discuss the risk of sudden unexpected death in epilepsy (SUDEP) with their patients and family members. Those in favor purport that patients have a right to know about SUDEP. Opponents say the risk is so low that discussions only worry patients and families, especially if there is nothing that can be done to prevent SUDEP. North American surveys show that the epilepsy community knows little about SUDEP and neurologists are unlikely to talk about it. However, surveys of those bereaved by SUDEP show that an overwhelming majority of the parents, spouses, and family members want to be told about SUDEP immediately after the diagnosis of epilepsy. This article is written by two families bereaved by SUDEP and their strong belief that neurologists should have the discussion about the risk of SUDEP soon after the diagnosis of epilepsy.     

心脏病变是癫癇猝死之重要原因

癫癇猝死系指癫癇患者在发作期或发作间期突发的无法解释的死亡,其风险是普通人群的20余倍。癫癇猝死存在多种机制,与心功能的相关性研究是目前研究的重要课题。癫癇和心脏离子通道病共存的遗传易感性、自主神经功能异常、抗癫癇药物等相关因素导致的心功能异常易诱发癫癇患者发生心源性猝死,进一步了解癫癇猝死发生过程中的心脏病变相关机制能够为制定预防和治疗策略提供理论基础。     

High‐resolution molecular genomic autopsy reveals complex sudden unexpected death in epilepsy risk profile

Advanced variant detection in genes underlying risk of sudden unexpected death in epilepsy (SUDEP) can uncover extensive epistatic complexity and improve diagnostic accuracy of epilepsy‐related mortality. However, the sensitivity and clinical utility of diagnostic panels based solely on established cardiac arrhythmia genes in the molecular autopsy of SUDEP is unknown. We applied the established clinical diagnostic panels, followed by sequencing and a high density copy number variant (CNV) detection array of an additional 253 related ion channel subunit genes to analyze the overall genomic variation in a SUDEP of the 3‐year‐old proband with severe myoclonic epilepsy of infancy (SMEI). We uncovered complex combinations of single nucleotide polymorphisms and CNVs in genes expressed in both neurocardiac and respiratory control pathways, including SCN1A, KCNA1, RYR3, and HTR2C. Our findings demonstrate the importance of comprehensive high‐resolution variant analysis in the assessment of personally relevant SUDEP risk. In this case, the combination of de novo single nucleotide polymorphisms (SNPs) and CNVs in the SCN1A and KCNA1 genes, respectively, is suspected to be the principal risk factor for both epilepsy and premature death. However, consideration of the overall biologically relevant variant complexity with its extensive functional epistatic interactions reveals potential personal risk more accurately.     

Sudden Unexpected Death in Epilepsy: A Review of Incidence and Risk Factors

Summary:  Sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death. However, SUDEP is rare in patients with new onset epilepsy and in patients in remission. Incidence is about 0.35 cases/1,000 person-years in population-based incidence cohort of epilepsy. Incidence is considerably higher in patients with chronic epilepsy, 1–2/1,000 person-years, and highest with severe, refractory seizures, 3–9/1,000. The highest rates occur from 20 to 40 years. Most SUDEP appears seizure-related. When witnessed, the fatal event generally occurred in association with generalized tonic–clonic seizure. Two recent case–control studies suggest that seizure frequency is the strongest risk factor for SUDEP: relative risk = 23 (95% CI = 3.2–170) for persons with ≥1 seizure during the year of observation versus seizure-free patients. Onset of epilepsy at an early age and long duration of the disorder are other risk factors. Although SUDEP has not been associated with the use of any particular antiepileptic drugs (AEDs), some case–control studies have pointed to an association between SUDEP and polytherapy with AEDs and frequent dose changes independent of seizure frequency. Although recent epidemiological studies have been helpful in identifying patients at risk for SUDEP, providing clues to mechanisms behind SUDEP, no single risk factor is common to all SUDEP, suggesting multiple mechanisms or trigger factors. Seizure control seems of paramount importance to prevent SUDEP. Further large-scale case–control studies are needed to assess the role of AEDs in order to form a basis for treatment strategies aiming at seizure control and prevention of SUDEP.