De novo ADGRV1 variant in a patient with ictal asystole provides novel clues for increased risk of SUDEP

Background Various cardiac and autonomic manifestations are frequently reported during seizures.Among the seizure-related arrhythmia,ictal tachycardia is the most common,followed by ictal bradycardia,with ictal asystole being the rarest.The occurrence of ictal asystole may obscure the clinical presentation and delay the diagnosis,representing a life-threatening presentation of epilepsy,with an elevated risk of sudden unexpected death in epilepsy patients(SUDEP).These cardiac abnormalities are being increasingly recognized as the key to elucidating the mechanisms of SUDEP.Case presentation We present a 35-year-old man with a history of focal-onset seizures with impaired consciousness since his mid-20 s.He developed different types of seizures for 2 years,described as tonic seizure and atonic seizure(drop attack).During such clinical events,he suffered from falls and cardiac arrest.However,thorough cardiac electrophysiology and imaging workup failed to reveal a cardiac etiology.Subsequent video electroencephalograph(EEG)monitoring was performed,and ictal bradycardia and ictal asystole were discovered.A cardiac pacemaker was implanted,and at 3-year follow-up,the patient did not suffer more atonic seizures,or falls.Genetic tests discovered a de novo variant of Adhesion G Protein-Coupled Receptor V1(ADGRV1),which may provide a clue for the patient’s ictal asystole and the increased risk of SUDEP.Conclusions Considering the important impact of ictal bradycardia and asystole on the morbidity and potential mortality of epileptic patients,it is important to simultaneously utilize EEG and electrocardiogram to confirm the diagnosis.This case report highlights the link between the de novo variant of ADGRV1 and the ictal bradycardia/asystole phenotype and implicates the importance of genetic testing in adult epilepsy patients.

SUDEP病1例

SUDEP（Sudden Unexpected Death in Epilepsy）是近几年才逐渐被认识及重视的一种临床病征，即癫痫性猝死。截止目前，国内报告较少，本文报告1例。患者男，59岁，因反复发生意识丧失，在外院多次行心肺复苏转入我院急诊科。追问病史，反复意识丧失起始于2014年10月，晨起无诱因的情况下突发面色苍白、口唇紫绀、意识丧失伴四肢抽搐数分钟后意识恢复。

癫痫发作后全面性脑电波抑制及其在癫痫性猝死中的意义

癫痫性猝死(sudden unexpected death in epilepsy,SUDEP)是癫痫患者意外死亡的主要原因。癫痫发作后全面性脑电波抑制(postictal generalized EEG suppression,PGES)与SUDEP具有一定的相关性;PGES的出现具有显著的个体差异,其发生与患者年龄、发作类型、强直性发作/肌强直、发作时及发作后呼吸功能障碍、发作时和发作后的自主神经功能障碍相关。全面性强直-阵挛发作作中阵挛期进行性慢波(progressive slowing of clonic phase,PSCP)是PGES发生和延长的独立预测因子。

9例癫痫猝死法医学分析

目的分析癫痫猝死(sudden unexpected death in epilepsy,SUDEP)的案情、现场特征及法医病理学特点,为法医学鉴定提供实践依据。方法收集SUDEP尸体检验案例9例,分析案件的基本信息、现场特征、法医病理学改变、常规毒(药)物和抗癫痫药物检验结果以及心包液生物化学检验结果。结果9例均为男性癫痫患者,均在夜间睡眠时间段死亡,死亡年龄(37.1±8.6)岁,癫痫病程(21.3±5.6)年。6例尸体呈俯卧位,3例呈左侧卧位。有胸锁乳突肌、胸骨甲状肌、胸骨舌骨肌出血的分别为8例、5例及4例,均为单侧性;6例出现双侧胸小肌出血。脑水肿、额颞叶噬神经现象及胶质细胞增生、心肌纤维波浪样变及嗜伊红染色增强、肺水肿、肺淤血、肺泡内出血、肺内细小支气管管壁皱缩、肾小管蛋白管型、胰腺实质出血是较多见的组织病理学改变。心包液生物化学检验结果提示存在心肌缺血性损害。结论青年男性、起病早、病程长、俯卧位睡眠、药物依从性差或联合用药、癫痫发作可能是SUDEP的危险因素,心功能障碍和呼吸抑制可能是SUDEP的主要死亡机制。

癫痫患者突然意外死亡4例报告并文献复习

癫痫患者突然意外死亡（SUDEP ）是难治性癫痫患者抽搐相关死亡最常见原因。SUDEP是癫痫患者突然出现不能解释的死亡现象，死前身体状态良好，伴或不伴发作证据，非癫痫持续状态、癫痫发作导致的外伤或溺水引起的死亡，尸解未发现解剖和毒理学原因所致癫痫患者的突然死亡。如果未尸解，考虑为可能SUDEP［1-3］。研究表明，随着癫痫患病时间及严重程度增加，SUDEP发生率逐渐增加，每年普通癫痫人群中SUDEP的发生率为0.9～2.3／1000人，而每年难治性癫痫人群中发生率为1.1～5.9／1000人［1-3］。本文对我院就诊癫痫患者中出现的4例SUDEP的临床特征报告如下。

癫痫模型大鼠心肌组织钠氢交换体1的表达及与凋亡的关系

目的探讨癫痫模型大鼠心肌组织钠氢交换体1(NHE1)的表达及凋亡情况。方法选取SD雄性大鼠共40只纳入研究,采用氯化锂-匹罗卡品构建癫痫模型作为模型组(n=22),采用腹腔注射生理盐水作为对照组(n=18);模型成功后第60天,麻醉处死后取心肌组织,应用蛋白印迹和RT-PCR检测NHE1的表达,进一步应用流式细胞仪检测大鼠心肌细胞凋亡情况。结果制作模型过程中3只大鼠死亡,死亡率为14%。与对照组比较,蛋白印迹结果显示第60天时模型组大鼠心肌组织NHE1蛋白表达增高(P<0.05)。RT-PCR结果显示造模后第60天时,模型组大鼠心肌组织NHE1mRNA表达增高(P<0.05)。流式细胞检测结果显示模型组大鼠心肌细胞凋亡明显增多(P<0.05)。结论癫痫模型大鼠在癫痫慢性病程中,心肌组织的NHE1表达增高可能与心肌细胞凋亡增多相关。

癫癎猝死与心脏的相关性

癫癎为多种原因（如脑发育障碍、脑外伤、中枢神经系统感染、脑血管病等）导致脑部神经元高度同步化异常放电所致的感觉、运动、意识、精神、行为和自主神经功能障碍，

Arterial spin labeling perfusion MRI applications in drug‑resistant epilepsy and epileptic emergency

Epilepsy affects all age groups and is one of the most common and disabling neurological disorders worldwide.Drug-resistant epilepsy(DRE),status epilepticus(SE),and sudden unexpected death in epilepsy(SUDEP),which are associated with considerable healthcare costs and mortality,have always been difficult to address and become the focus of clinical research.The rapid identification of seizure onset and accurate localization of epileptic foci are crucial for the treatment and prognosis of people with DRE,SE,or near-SUDEP.However,most of the conventional neuroimaging techniques for assessing cerebral blood flow of people with epilepsy are restricted by time consumption,limited resolution,and ionizing radiation.Arterial spin labeling(ASL)is a newly powerful non-contrast magnetic resonance imaging technique that enables the quantitative evaluation of brain perfusion,characterized by its unique advantages of reproducibility and easy accessibility.Recent studies have demonstrated the potential advantages of ASL for the diagnosis and evaluation of epilepsy.Therefore,in this review,we discussed the complementary value of ASL in evaluating and characterizing the basic substrates underlying refractory epilepsy and epileptic emergencies.

Sudden unexpected death after acute symptomatic seizures in a patient on mechanical ventilation

Background:The mechanism of sudden unexpected death in epilepsy remains poorly understood.Seizure induced cardiac arrhythmia,central and obstructive apneas have been proposed as possible causes of death.Here we report a unique case of seizure related sudden unexpected death in a patient whose airway was fully protected by intubation and mechanic ventilation in the absence of fatal cardiac arrhythmia.Case presentation:A 70-year-old woman was undergoing mechanical ventilation and videoelectroencephalography(EEG)monitoring following two convulsive seizures with ictal hypoventilation and hypoxemia.Several hours after intubation,she suffered another generalized tonic clonic seizure lasted for 3 min and developed postictal generalized EEG suppression in the presence of stable vital signs with SpO2>90%.EEG suppression persisted throughout the postictal phase.There was a significant fluctuation of systolic blood pressure between 50 and 180 mmHg with several bouts of hypotension<60 mmHg.She remained unresponsive after the convulsive seizure and died of diffuse cerebral edema 12 h later.Autopsy revealed no clear cause of death,except for possible hypoxic and ischemic injury leading to the diffuse cerebral edema.Conclusion:Given the reliable periictal airway protection,neither seizure induced central apnea nor obstructive apnea appeared to be the direct cause of death in this unique case.In the absence of fatal cardiac arrhythmia,diffuse cerebral edema secondary to seizure-induced autonomic dysfunction,hypotension and hypoxemia might be the cause of death,highlighting the etiological heterogeneity of sudden unexpected death in epilepsy.

癫痫猝死高危人群的静息态功能磁共振低频振幅研究

目的既往报道认为癫痫猝死(Sudden unexpected death in epilepsy,SUDEP)的直接原因可能是痫性发作相关的心肺功能障碍,但越来越多的研究却发现这种心肺功能的改变很可能是继发于痫性发作后的弥漫性脑功能抑制。但目前痫性发作后脑功能抑制的神经网络基础尚不清楚。探讨运用血氧水平依赖(Blood oxygen level dependent,BOLD)的静息态功能磁共振技术对SUDEP高危人群的神经网络特征进行研究。方法 2012年9月-2013年3月四川大学华西医院神经内科癫痫专科门诊就诊患者纳入SUDEP高危患者13例,低危患者12例,进行静息态磁共振数据采集。采用低频振幅(Amplitude of low-frequency fluctuations,ALFF)作为测量指标,比较两组被试患者的局部静息态脑活动差异。结果与低危患者相比,SUDEP高危组患者的ALFF值在右侧背外侧额上回、左侧眶部额上回、左侧岛叶及左侧丘脑的部分区域降低,而在右侧内侧和旁扣带回、右侧补充运动区及左侧丘脑的部分区域增高。结论研究发现SUDEP高危患者确有功能神经网络的异常存在。从神经网络的角度展开对SUDEP的机制研究,为SUDEP的预警提供了可能的影像学标记。