迷走神经电刺激治疗难治性癫的作用机制与临床应用

迷走神经电刺激是治疗难治性癫的一种新方法,能有效减少癫发作频率及严重程度,提高生活质量,但其抗癫作用的机制尚未明确。本文从神经解剖学、神经电生理学、功能影像学等方面阐述其作用机制,并对其临床应用的适应证、疗效、不良反应等方面的研究进展进行总结。     

脑电刺激治疗难治性癫

脑电刺激治疗为不适合手术的难治性癫病人提供了一种选择,主要包括脑深部刺激、迷走神经刺激和闭合环路刺激。前两者主要通过调控丘脑-皮质通路来抑制皮质兴奋性,减少癫发作;后者通过早期预警触发刺激来抑制发作的传播扩散。本文就几种脑电刺激治疗的原理、方法、疗效和并发症等方面内容进行简要回顾总结。     

迷走神经电刺激治疗难治性癫(癎)的作用机制与临床应用

迷走神经电刺激是治疗难治性癫(癎)的一种新方法,能有效减少癫(癎)发作频率及严重程度,提高生活质量,但其抗癫(癎)作用的机制尚未明确.本文从神经解剖学、神经电生理学、功能影像学等方面阐述其作用机制,并对其临床应用的适应证、疗效、不良反应等方面的研究进展进行总结.     

迷走神经刺激治疗难治性癫痫(附11例报告)

目的 探讨迷走神经刺激术治疗顽固性癫痫的治疗效果和机制.方法 2004年4月～2006年12月,11例顽固性癫痫进行了迷走神经刺激治疗,其中3例为脑炎后部分性继发全身发作,3例为Lenonx-Castaut Syndrome(LGS),另外5例为原因不明的全身强直阵挛性发作.手术在全麻下进行,在甲状软骨水平左侧胸锁乳突肌前缘作3cm皮肤切口,分离肌肉并显示左侧迷走神经干约3cm,将螺旋型迷走神经刺激电极缠绕于迷走神经干上,在左腋前线作一皮肤切口,将刺激器置入皮下并与刺激电极相连接及固定.术后2周开机,调试参数,刺激电流从0.25mA逐渐调至1.5mA,刺激模式为:刺激时间为30秒,间歇5分钟,脉宽为500～1000μs,频率为30Hz.结果 术后3个月～2年随访,癫痫发作频率平均减少60%,发作程度减轻,全身强直阵挛性发作明显减少,精神状态明显改善.结论 迷走神经刺激手术创伤小,副作用少,术后能减少病人发作的频率,提高病人生活质量,对不适合开颅手术的难治性癫痫是一种有效的治疗方法.     

致灶切除治疗难治性癫

目的探讨皮层脑电图扫描下致灶切除术治疗难治性癫的术前评估及致灶病理学意义。方法对67例经临床诊断为难治性癫的患者应用神经影像、神经电生理及功能性检查等方法进行术前综合评估,确定致灶。然后在皮层脑电图描记下行致灶切除,对切除的致灶组织送病理检查。结果术后综合疗效评定:1年内癫发作消失23例,显进进步18例,进步17例,无变化5例,失访4例,总有效率为84.6%;病理结果:有肿瘤、动静脉畸形、灰质异位、表皮样囊肿、炎性肉芽肿、脑软化、粘连性蛛网膜炎、海马硬化,其他还有蛛网膜增厚、脑组织神经变性、胶质细胞增生及变性,部分病例伴有陈旧性出血、含铁血黄素沉着、淋巴细胞浸润或者血管增生、管壁增厚,伴有小疤痕形成或继发性囊肿形成等。无1例无异常。结论神经电生理、影像学及功能检查的联合应用是术前评估致灶的重要方法。而脑电图、颅内电极与数字视频脑电结合,将患者的发作期表现与脑电信息同步记录保存是分析癫异常放电定位致灶的最佳方法。致灶切除术是难治性癫的有效治疗手段,致灶组织均存在结构性病理改变。     

皮质电刺激在难治性癫病人语言区定位的应用

目的探讨皮质电刺激在难治性癫病人语言区定位的作用。方法 10例癫病人经颅内电极行脑皮质电刺激,记录其语言行为学表现及相应电流强度,个体化定位语言区以指导剪裁式致灶切除术。术后评估病人语言功能。结果 5例病人应用皮质电刺激测得语言区,其分布变异大,但4例病人干扰语言功能的电流强度阈值之间无明显差异(P>0.05)。所有病人术后均未出现语言功能障碍。结论应用特定参数的脑皮质电刺激行个体化语言区定位,有利于降低难治性癫病人致灶切除术后发生语言障碍的风险。     

开创我国癫外科治疗的新局面

癫是由多种原因引起的常见病和多发病,在我国,癫患病率达7‰,其中活动性癫占5‰,也就是说,我国有近千万的癫病人,其中30%是药物难治性癫,该类病人如经综合术前评估,至少有1/2可选择适当的外科治疗并从中获益。近年来,随着神     

MRI阴性难治性儿童额叶癫的脑电图特点及外科治疗(附25例分析)

目的总结分析MRI阴性难治性儿童额叶癫的脑电图特点及手术治疗方法和预后。方法回顾性分析25例MRI阴性难治性儿童额叶癫病例的治疗经验。根据病儿发作的症状及头皮脑电图特点,在可疑的癫灶起源区植入颅内电极,行皮质脑电图(ECoG)监测,根据其间期、发作期特点制定癫灶切除计划。病灶位于功能区时术中行皮质电刺激,进行癫灶及功能区定位。结果本组行单纯前额叶切除7例,前额叶切除加局限性皮质切除4例,局限性皮质切除加皮质热灼6例,前额叶外侧切除加局限性皮质切除3例,前额叶内侧切除加局限性皮质切除5例(其中3例加胼胝体切开);对其中6例灶位于功能区病人于局限性皮质切除后加行皮质热灼。无手术死亡及严重并发症发生,随访12～24个月,手术后疗效按Wilson标准评判,癫发作完全消失7例,发作次数显著减少8例,发作程度减轻6例,无明显改善4例;优良率为84%。结论分析头皮脑电图初步定位癫灶后,再应用颅内电极进行精确致灶及功能区定位,制定个体化治疗计划,选择前额叶切除、局限性皮质切除、皮质热灼、胼胝体切开或根据需要联合多种术式,是治疗MRI阴性难治性儿童额叶癫的有效方法。     

难治性颞叶癫的手术治疗

目的 探讨难治性颞叶癫的手术疗效。方法 回顾性分析2003年7月至2007年2月我科手术治疗的72例难治性颞叶癫患者临床资料。结果 按我国谭氏标准,满意：59例;显著改善：2例;良好：3例;效差：2例;无改善：5例;死亡：1例。结论 手术治疗难治性颞叶癫疗效确切可靠,在有条件的医院可推广。     

脑电刺激治疗难治性癫(癎)

脑电刺激治疗为不适合手术的难治性癫(癎)病人提供了一种选择,主要包括脑深部刺激、迷走神经刺激和闭合环路刺激.前两者主要通过调控丘脑-皮质通路来抑制皮质兴奋性,减少癫(癎)发作;后者通过早期预警触发刺激来抑制发作的传播扩散.本文就几种脑电刺激治疗的原理、方法、疗效和并发症等方面内容进行简要回顾总结.     

迷走神经刺激术治疗难治性癫痫(附25例报告)

目的研究迷走神经刺激术治疗难治性癫痫的适应证选择、手术方法、术后程控及疗效。方法 2009年11月~2016年7月清华大学玉泉医院癫痫中心对25例难治性癫痫患者行迷走神经刺激术,术后给予程控管理控制癫痫发作;并通过随访回顾性分析术后疗效。结果术后随访患者4个月~7年,其中癫痫发作频率减少达McHughⅠ级6例、Ⅱ级12例、Ⅲ级4例、Ⅳ级1例、Ⅴ级2例。手术前后癫痫发作频率对比,差异有统计学意义(P0.05)。结论迷走神经刺激术作为一种安全有效的辅助治疗难治性癫痫的方法,其治疗效果可以随着参数的调整和时间延长而增强,并可以一定程度改善患者的认知行为和生活质量。     

Vagus nerve stimulation therapy in depression and epilepsy: therapeutic parameter settings

Vagus nerve stimulation (VNS) therapy is an effective adjunctive treatment for chronic or recurrent treatment-resistant depression in adults, and for pharmacoresistant epilepsy in adults and adolescents. VNS therapy is administered through an implanted pulse generator that delivers programmed electrical pulses through an implanted lead to the left vagus nerve. Programmable pulse parameters include output current, frequency, pulse width, and ON/OFF times. Within a range of typical values, individual patients respond best to different combinations of parameter settings. The physician must identify the optimum settings for each patient while balancing the goals of maximizing efficacy, minimizing side effects, and preserving battery life. Output current is gradually increased from 0.25 mA to the maximum tolerable level (maximum, 3.5 mA); typical therapeutic settings range from 1.0 to 1.5 mA. Greater output current is associated with increased side effects, including voice alteration, cough, a feeling of throat tightening, and dyspnea. Frequency is typically programmed at 20 Hz in depression and 30 Hz in epilepsy. Pulse width is typically 250 or 500 micros. The recommended initial ON time is 30 s, followed by 5 min OFF; OFF time > ON time is recommended. As with pharmacotherapy, VNS therapy must be adjusted in a gradual, systematic fashion to individualize therapy for each patient.     

迷走神经刺激术治疗五例顽固性癫痫及其随访研究

寻求顽固性癫痫的有效治疗方法。方法用迷走神经刺激术治疗５例顽固性癫痫患者，并进行１年的随访。结果４例患者的癫痫发作频率较术前减少５０％以上；另１例为失张力伴强直－阵挛发作，失张力发作无明显改变，但１年中未见强直－阵挛发作。所有患者的发作强度均有所减轻，持续时间缩短。迷走神经刺激术后血浆抗癫痫药物浓度未见明显改变。５例中４例患者的脑电图所见较术前有明显改进，表现为原有的棘波、尖波消失，阵发性异常消失或时间缩短；另１例脑电图改变不明显。５例患者除在植于体内脉冲发生器刺激时感到喉部有轻微震动感和声音略有低哑外，未见有其他副作用。心电图均正常。结论迷走神经刺激术治疗顽固性癫痫安全并可有一定效果，但其确切疗效仍有待于进一步研究。     

Vagus nerve stimulation for the treatment of bilateral independent temporal lobe epilepsy

PURPOSE: We studied the effect of vagus nerve stimulation (VNS) on seizure reduction in patients with intractable epilepsy with bilateral independent temporal lobe foci. METHODS: Ten patients who met the criterion of the presence of two distinctive clinical and ictal EEG seizure patterns were identified and followed up for 1 year. RESULTS: Six patients had >50% reduction in their seizure frequency that persisted up to > or =1 year of follow-up, whereas four patients reported small or no reduction in their partial seizures. CONCLUSIONS: VNS is often effective and well tolerated in this select group of intractable epilepsy patients.     

Vagus nerve stimulation in children with intractable epilepsy: indications,complications and outcome

Purpose  To analyze the indication, complications and outcome of vagus nerve stimulation in intractable childhood epilepsy. Materials and methods  We retrospectively reviewed the data of 69 children who had insertion of vagal nerve stimulator (VNS) between June 1995 and August 2006 for medically intractable epilepsy. Outcome was based on the Engel's classification. Statistical analysis of the data was also done to see if any of the parameters significantly influenced the outcome. Result  Thirty-eight patients (55.08 %) had a satisfactory outcome (Engel class I, II or III), and in 31 patients (44.92 %), there was no worthwhile improvement of seizures (Engel class IV). There was no statistical significance between the type of seizure and outcome (Fisher's exact test, p = 0.351). Statistical analysis also showed that the following parameters did not significantly influence the outcome (p > 0.05): age at insertion of VNS, age of first fit, duration between first fit and insertion of VNS and the length of follow-up. Complications included infection, lead fracture, fluid collection around the stimulator, neck pain and difficulty swallowing. Conclusion  Vagus nerve stimulation is a relatively safe and potentially effective treatment for children with medically intractable epilepsy.     

Is vagus nerve stimulation a treatment option for patients with drug-resistant idiopathic generalized epilepsy?

Background –   The value of vagus nerve stimulation (VNS) for treating patients with drug-resistant idiopathic generalized epilepsy (IGE) is not well documented.
Patients and methods –   Twelve patients (2 males, 10 females) with a mean age of 31 years (11–48 years) and with drug-resistant IGE had VNS implanted in the period 1995–2006. All had generalized seizures documented by video-electroencephalogram. Mean follow-up period was 23 months (9–54 months).
Results –   There was a total seizure reduction of 61% (P = 0.0002). There was 62% reduction of generalized tonic-clonic seizures (P = 0.0020), 58% of absences (P = 0.0003) and 40% of myoclonic seizures (P = 0.0156). Eight patients were considered responders (>50% seizure reduction); two of these patients became seizure-free. Five out of seven patients with juvenile myoclonic epilepsy were responders. At the last follow-up visit, the patients had reduced the anti-epileptic drug (AED) usage from an average of 2.3 to 1.7 AED per patient (P = 0.0625). Two patients are currently being treated with VNS therapy only. Nine patients reported side effects, which were mostly mild and tended to diminish over time.
Conclusion –   Our results indicate that adjunctive VNS therapy is a favourable treatment option for patients with drug-resistant IGE. Rapid cycling seems worth trying in some of the non-responders.     

Research progress of vagus nerve stimulation in the treatment of epilepsy

The International League Against Epilepsy (ILAE) defined drug‐resistant epilepsy (DRE) that epilepsy seizure symptoms cannot be controlled with two well‐tolerated and appropriately chosen antiepileptic drugs, whether they are given as monotherapy or in combination. According to the WHO reports, there is about 30%‐40% of epilepsy patients belong to DRE. These patients need some treatments other than drugs, such as epilepsy surgery, and neuromodulation treatment. Traditional surgical approaches may be limited by the patient's clinical status, pathological tissue location, or overall prognosis. Thus, neuromodulation is an alternative choice to control their symptoms. Vagus nerve stimulation (VNS) is one of the neuromodulation methods clinically, which have been approved by the Food and Drug Administration (FDA). In this review, we systematically describe the clinical application, clinical effects, possible antiepileptic mechanisms, and future research directions of VNS for epilepsy.     

迷走神经刺激治疗药物难治性癫痫的随访研究（附62例分析）

目的研究迷走神经刺激治疗药物难治性癫痫的疗效。方法回顾性分析62例接受迷走神经刺激（vNs）治疗的药物难治性癫痫患者的临床资料。通过患者来院或电话对患者的发作频率、持续时间和生活质量等进行随访。结果62例患者,失访5例,1例患者刺激时间小于2个月未纳入统计范围,对接受迷走神经刺激治疗3～40个月的56例患者进行统计分析,McHughⅠ级22例（39．3％）,Ⅱ级16例（28．6％）,Ⅲ级13例（23．2％）,Ⅳ级＋Ⅴ级5例（8．9％）。其中3例（5．4％）术后无发作,38例（67．9％）发作减少50％以上。结论迷走神经刺激是治疗药物难治性癫痫安全、有效的方法。VNS刺激时间和刺激参数可能是影响其对药物难治性癫痫疗效的重要因素,随刺激时间延长疗效增加。     

Vagus nerve stimulation: from epilepsy to the cholinergic anti‐inflammatory pathway

Background The brain and the gut communicate bidirectionally through the autonomic nervous system (ANS). The vagus nerve (VN), a major component of the ANS, plays a key role in the neuro‐endocrine‐immune axis to maintain homeostasia through its afferents (through the activation of the hypothalamic pituitary adrenal axis and the central ANS) and through its efferents (i.e. the cholinergic anti‐inflammatory pathway; CAP). The CAP has an anti‐TNF effect both through the release of acetylcholine at the distal VN acting on macrophages and through the connection of the VN with the spleen through the splenic sympathetic nerve. Vagus nerve stimulation (VNS) of vagal afferents at high frequency (20–30 Hz) is used for the treatment of drug‐resistant epilepsy and depression. Low‐frequency (5 Hz) VNS of vagal efferents activates the CAP for an anti‐inflammatory effect that is as an anti‐TNF therapy in inflammatory diseases were TNF is a key cytokine as represented by experimental sepsis, postoperative ileus, burn‐induced intestinal barrier injury, colitis. However, both vagal afferents and efferents are activated by VNS. Purpose The objective of this review was to explore the following: (i) the supporting evidence for the importance of VNS in epilepsy (and depression) and its mechanisms of action, (ii) the anti‐inflammatory characteristics of the VN, (iii) the experimental evidence that VNS impact on inflammatory disorders focusing on the digestive tract, and (iv) how VNS could potentially be harnessed therapeutically in human inflammatory disorders such as inflammatory bowel diseases, irritable bowel syndrome, postoperative ileus, rheumatoid arthritis as an anti‐inflammatory therapy.