适宜的迷走神经刺激参数对癫痫的控制作用

背景迷走神经刺激参数直接关系到迷走神经刺激的抗痫效果及患者使用的安全性,选择适宜的迷走神经刺激参数组合是实现迷走神经刺激抗痫作用的关键因素.目的观察电刺激参数包括输出电流、波宽、频率、开启时间、关闭时间、何时启动等在迷走神经刺激控制癫痫中的作用.设计单一样本实验.单位首都医科大学基础医学院神经生物学系.材料实验于2000-09/2002-09在首都医科大学基础医学院神经生物学系电生理实验室完成.选择健康成年Wistar大鼠36只.方法36只大鼠经海人藻酸复制大鼠癫痫模型,通过采用不同的迷走神经刺激参数组合,以大鼠行为学、心电图、皮层电图、海马神经元放电活动为观测指标,观察迷走神经刺激参数在控制致痫大鼠中的作用,并从中筛选适宜的刺激参数组合.主要观察指标①海人藻酸致痫效应.②迷走神经刺激参数组合及其抗痫效应.结果36只大鼠均进入结果分析.①迷走神经刺激的抗痫效应的观察主要在痫性发作4 h以内.②当波宽为2 ms,刺激强度为3～3.5 mA,频率为30～35 Hz,开启1 min,关闭2 min时,连续刺激迷走神经50 min时,抗痫效果显著,痫性皮层电图的发作时间明显缩短,严重程度显著降低;致痫大鼠海马CA1区神经元暴发性放电频率降低(P＜0.05).结论在保证受试者心电活动正常的前提下,能有效控制痫性发作的最小刺激参数组合为最适参数组合,且对心脏功能没有影响.     

迷走神经刺激的启动时间对抗癫痫作用的影响

背景长期反复痫性发作可影响记忆功能以及发生许多意料不到的并发症.如何控制和预防其发作是临床和康复医学研究的重点.目的应用大鼠癫痫模型,探讨迷走神经刺激(vagus nerve stimulation.VNS)治疗癫痫的最佳启动时间.设计随机对照的实验研究.地点和对象实验地点首都医科大学神经生物学研究室.实验对象Wistar大鼠34只,二级,首都医科大学实验动物中心提供.方法应用海人酸(kainic acid,KA)复制大鼠癫痫模型,以大鼠皮质电图(electrocorticographic,ECoG)和行为学为观测指标,在癫痫发作前后分别刺激左侧迷走神经,比较两组迷走神经刺激不同的启动时间对癫痫发作持续时间的影响,确定迷走神经刺激输出的最佳时机.主要观察指标①海人酸诱发癫痫的潜伏期和持续期.②VNS的启动时间对控制癫痫发作的影响.结果在癫痫发作前,间断刺激迷走神经50 min,可显著降低癫痫发作的严重程度、缩短发作的持续时间,甚至完全抑制癫痫发作.而发作一旦发生再行该组合刺激,则只能降低发作的严重程度、缩短发作的持续期,而不能完全阻抑癫痫发作.发作前后进行迷走神经刺激的抗痫效果之间存在显著性差异(F=27.320,P＜0.01).结论在癫痫发作前及时启动VNS可以显著提高VNS的抗痫效果,适宜的刺激参数组合是控制癫痫发作的关键,并为其预防发作奠定实验基础.     

脑电图动态非线性分析对癫痫发作预报的评估意义

目的：从非线性动力学角度探索在癫痫发作间期、发作期及发作前期脑电图活动的动态非线性变化特征，以期为癫痫发作的短期预报提供临床实验依据。方法：于2004—10选取天津医科大学总医院癫痫专科门诊男性癫痫患者1例，连续记录其在发作前、发作中及发作后的脑电图，选择其中异常度较高，伪差较少的导联（前额FP2导联）的脑电图进行2048点的相关维数计算（窗口移动2s／次，窗口长度8s），相关维数嵌入维为12，采用时间延迟重构相空间技术，延迟时间τ选用自相关函数第1个过零点时的时移量。对其癫痫发作间期、发作前期、发作期及发作后期脑电图进行连续动态非线性分析。结果：从发作间期至发作前期、发作期相关维数依次显著下降，与发作间期比较，发作前期与发作期的平均相关维数明显降低[（5．501&;#177;0．602），（4．602&;#177;0．517），（3．640&;#177;0．345），P〈0．01]。至发作后期（5．229&;#177;0．364）又升高至接近发作间期水平，即癫痫发作时脑电图相关维数最低，且发作前约120s处，脑电图相关维数已开始呈波动性下降。至发作开始，下降更为迅速，相关维数最低处仅为2．52，低于发作间期的平均值5．501。此后在脑电波幅下降至间期二分之一前约60-70s，相关维数再次上升至接近发作间期水平，并保持相对稳定。结论：癫痫发作的不同时期其脑电图的相关维数不同，以发作期最低。并且在临床尚无发作表现时脑电图的相关维数已呈波动性下降，即采用脑电图动态非线性分析可能在癫痫发作前至少120s进行预报。     

迷走神经刺激对致痫动物的抗痫作用及其机理研究

目的 研究迷走神经刺激(VNS)对致痫动物的抗痫作用及机理。方法 分别用青霉素、海人藻酸(KA)、士的宁对34只大鼠和8只家兔致痫，以动物大脑皮层电图(ECoG)、海马神经元电活动及行为学表现为观测指标，观察间断性左侧VNS对致病动物痫性发作的影响。结果 VNS可以阻抑致痫动物的痫性发作，对痫性ECoG、海马神经元电活动及行为学表现均呈现有显著的抑制。结论 内脏传入信息可能通过大脑皮层、海马部位的整合作用达到有效阻抑躯体痫性活动。     

脑电图动态非线性分析对癫痫发作预报的评估意义

目的:从非线性动力学角度探索在癫痫发作间期、发作期及发作前期脑电图活动的动态非线性变化特征,以期为癫痫发作的短期预报提供临床实验依据。方法:于2004-10选取天津医科大学总医院癫痫专科门诊男性癫痫患者1例,连续记录其在发作前、发作中及发作后的脑电图,选择其中异常度较高,伪差较少的导联(前额FP2导联)的脑电图进行2048点的相关维数计算(窗口移动2s/次,窗口长度8s),相关维数嵌入维为12,采用时间延迟重构相空间技术,延迟时间τ选用自相关函数第1个过零点时的时移量。对其癫痫发作间期、发作前期、发作期及发作后期脑电图进行连续动态非线性分析。结果:从发作间期至发作前期、发作期相关维数依次显著下降,与发作间期比较,发作前期与发作期的平均相关维数明显降低[(5.501±0.602),(4.602±0.517),(3.640±0.345),P<0.01]。至发作后期(5.229±0.364)又升高至接近发作间期水平,即癫痫发作时脑电图相关维数最低,且发作前约120s处,脑电图相关维数已开始呈波动性下降。至发作开始,下降更为迅速,相关维数最低处仅为2.52,低于发作间期的平均值5.501。此后在脑电波幅下降至间期二分之一前约60～70s,相关维数再次上升至接近发作间期水平,并保持相对稳定。结论:癫痫发作的不同时期其脑电图的相关维数不同,以发作期最低。并且在临床尚无发作表现时脑电图的相关维数已呈波动性下降,即采用脑电图动态非线性分析可能在癫痫发作前至少120s进行预报。     

迷走神经刺激的启动时间对抗癫痫作用的影响

背景：长期反复痫性发作可影响记忆功能以及发生许多意料不到的并发症。如何控制和预防其发作是临床和康复医学研究的重点。目的：应用大鼠癫痫模型，探讨迷走神经刺激(vagus nerve stimulation，VNS)治疗癫痫的最佳启动时间。设计：随机对照的实验研究。地点和对象：实验地点：首都医科大学神经生物学研究室。实验对象：Wistar大鼠34只，二级，首都医科大学实验动物中心提供。方法：应用海人酸(kainic acid，KA)复制大鼠癫痫模型，以大鼠皮质电图(electrocordcographic，ECoG)和行为学为观测指标，在癫痫发作前后分别刺激左侧迷走神经，比较两组迷走神经刺激不同的启动时间对癫痫发作持续时间的影响，确定迷走神经刺激输出的最佳时机。主要观察指标：①海人酸诱发癫痫的潜伏期和持续期。②VNS的启动时间对控制癫痫发作的影响。结果：在癫痫发作前，间断刺激迷走神经50min，可显著降低癫痫发作的严重程度、缩短发作的持续时间，甚至完全抑制癫痫发作。而发作一旦发生再行该组合刺激，则只能降低发作的严重程度、缩短发作的持续期，而不能完全阻抑癫痫发作。发作前后进行迷走神经刺激的抗痫效果之间存在显著性差异(F=27．320．P&;lt;0．01)。结论：在癫痫发作前及时启动VNS可以显著提高VNS的抗痫效果，适宜的刺激参数组合是控制癫痫发作的关键，并为其预防发作奠定实验基础。     

癫痫发作前后脑电变化的临床价值

脑电图(EEG)是癫痫诊断中不可缺少的手段,特别是发作时的EEG,对癫痫的准确分型及治疗有重要的意义。但发作时绝大多数EEG因大量的肌电干扰而无法判读,而发作前后伪差少,便于观察从发作间期到发作期及发作结束时脑电变化的特点,为临床诊治提供更好的资料。作者对1995年1月至2003年1月收集的21例临床发作前后的EEG资料总结报道如下。     

两小时脑电图监测对癫痫的诊断价值

【目的】探讨2h脑电图（EEG）监测在癫痫诊断中的应用价值。【方法】对112例临床拟诊癫痫的患者作常规EEG与2hEEG监测。【结果】常规EEG异常率为26．8％,2h EEG监测为90．2％,后者明显高于前者（P〈0．05）;常规EEG痫样放电检出率为0.2h EEG监测检出率为68．7％,两者差异有显著性（P〈0．05）;2h EEG监测痫样放电主要集中在睡眠期,达89．6％,且以第Ⅰ～Ⅱ睡眠周期最多见,达87．5％,清醒期为19．5％,两者差异有显著性（P〈0．05）。【结论】2h EEG监测可以提高癫痫样放电的检出率。     

24小时脑电监测提高可疑癫痫诊断率

脑电图(EEG)是诊断癫痫的重要手段。常规EEG的记录时间有限，描记时恰逢癫痫发作的机会不多，大多数患者在发作的间期描记，癫痫波检出率仅40％～50％。随着计算机数字化脑电图(QEEG)技术的发展，动态脑电图(AEEG)和视频脑电图(VEEG)相继问世，实现了对脑电波的长时间不间断监测，使脑电图技术产生质的飞跃。几年来我科开展了     

癫痫和非癫痫临床发作的动态脑电图监测

目的：探讨癫痫和非癫痫临床发作的动态脑电图监测。方法：对100例有临床症状的患者均先做普通脑电图（EEG），再做24h动态脑电图（AEEG）检查。结果：AEEG阳性率明显高于EEG。结论：AEEG作为长程监测，对于癫痫的诊断起着重要作用，提高了发作期间痫样放电的检出率，为诊断癫痫提供了可靠的依据。     

Noninvasive vagus nerve stimulation as treatment for trigeminal allodynia

Implanted vagus nerve stimulation (VNS) has been used to treat seizures and depression. In this study, we explored the mechanism of action of noninvasive vagus nerve stimulation (nVNS) for the treatment of trigeminal allodynia. Rats were repeatedly infused with inflammatory mediators directly onto the dura, which led to chronic trigeminal allodynia. Administration of nVNS for 2 minutes decreased periorbital sensitivity in rats with periorbital trigeminal allodynia for up to 3.5 hours after stimulation. Using microdialysis, we quantified levels of extracellular neurotransmitters in the trigeminal nucleus caudalis (TNC). Allodynic rats showed a 7.7 ± 0.9-fold increase in extracellular glutamate in the TNC after i.p. administration of the chemical headache trigger glyceryl trinitrate (GTN; 0.1 mg/kg). Allodynic rats that received nVNS had only a 2.3 ± 0.4-fold increase in extracellular glutamate after GTN, similar to the response in control naive rats. When nVNS was delayed until 120 minutes after GTN treatment, the high levels of glutamate in the TNC were reversed after nVNS. The nVNS stimulation parameters used in this study did not produce significant changes in blood pressure or heart rate. These data suggest that nVNS may be used to treat trigeminal allodynia.     

Electrical vagus nerve stimulation for the treatment of chronic heart failure

Autonomic dysregulation is a feature of chronic heart failure (HF) and is characterized by a sustained increase of sympathetic drive and by withdrawal of parasympathetic activity. Both sympathetic overdrive and increased heart rate are predictors of poor long-term outcome in patients with HF. Pharmacologic agents that partially inhibit sympathetic activity, such as beta-adrenergic receptor blockers, effectively reduce mortality and morbidity in patients with chronic HF. In contrast, modulation of parasympathetic activation as a potential therapy for HF has received only limited attention because of its inherent complex cardiovascular effects. This review examines results of experimental animal studies that provide support for the possible use of electrical vagus nerve stimulation (VNS) as a long-term therapy for the treatment of chronic HF. The review also addresses the effects of VNS on potential modifiers of the HF state, including proinflammatory cytokines, nitric oxide elaboration, and myocardial expression of gap junction proteins. Finally, the safety, feasibility, and efficacy trends of VNS in patients with advanced HF are reviewed.     

Trigeminal pain under vagus nerve stimulation

Three epilepsy patients treated by cyclic continuous vagus nerve stimulation (VNS) experienced trigeminal pain during the periods of stimulation, which was reported as toothache in the left lower jaw, ipsilateral to the side of stimulation. The symptom occurred with a latency of days to weeks following an increase in stimulation current intensity (SCI). Trigeminal pain was reversible with decrease in SCI, or subsided due to habituation. These findings show that clinically relevant effects of VNS on nociception may occur. Because of the late onset and variable form of this side effect, trigeminal pain may not be regarded as VNS-related which may result in unnecessary diagnostic and therapeutic procedures.     

迷走神经刺激治疗癫痫的实验和临床研究

目的通过动物实验,探讨迷走神经刺激治疗癫痫的有效性和最佳刺激参数,并对临床上癫痫持续状态病人进行疗效研究。方法应用士的宁制成动物癫痫模型,手术后直接刺激左侧迷走神经,应用不同的刺激参数组合进行刺激。对临床上癫痫持续状态的病人,经皮间接刺激迷走神经进行疗效观察。结果应用波宽２ｍｓ、频率１００Ｈｚ、电压１０Ｖ的组合参数刺激,全部实验动物的强直性发作立刻得到控制、痫样放电立即消失,脑电图恢复正常。选择病人可以耐受的电压幅度连续电脉冲刺激左侧颈部迷走神经体表投影区,进行经皮间接刺激治疗不同类型癫痫持续状态,结果完全控制率为８３．３％。有效率达１００％。结论刺激左侧迷走神经治疗癫痫和经皮刺激迷走神经治疗癫痫持续状态有效,但刺激参数至关重要。     

Left-sided vagus nerve stimulation improves cardiopulmonary resuscitation outcomes in rats as effectively as right-sided vagus nerve stimulation

BACKGROUND: Our group previously reported that right-sided vagus nerve stimulation (RVNS) significantly improved outcomes after cardiopulmonary resuscitation (CPR) in a rat model of cardiac arrest (CA). However, whether left-sided vagus nerve stimulation (LVNS) could achieve the same effect as RVNS in CPR outcomes remains unknown. METHODS: A rat model of CA was established using modified percutaneous epicardial electrical stimulation to induce ventricular fibrillation (VF). Rats were treated with LVNS or RVNS for 30 minutes before the induction of VF. All animals were observed closely within 72 hours after return of spontaneous circulation (ROSC), and their health and behavior were evaluated every 24 hours. RESULTS: Compared with those in the RVNS group, the hemodynamic measurements in the LVNS group decreased more notably. Vagus nerve stimulation (VNS) decreased the serum levels of tumor necrosis factor-alpha (TNF-α) and the arrhythmia score, and attenuated inflammatory infiltration in myocardial tissue after ROSC, regardless of the side of stimulation, compared with findings in the CPR group. Both LVNS and RVNS ameliorated myocardial function and increased the expression of α-7 nicotinic acetylcholine receptor in the myocardium after ROSC. Moreover, a clear improvement in 72-hour survival was shown with VNS pre-treatment, with no significant difference in efficacy when comparing the laterality of stimulation. CONCLUSIONS: LVNS may have similar effects as RVNS on improving outcomes after CPR.     

The effect of vagus nerve stimulation on migraines

Vagus nerve stimulation (VNS) inhibits nociceptive behavior in animals. VNS might reduce pain in patients with VNS device implanted for intractable seizures. One case report described possible benefits on migraines. We contacted all patients who received VNS therapy for intractable epilepsy between 1993 and 1999 at Southern Illinois University, Springfield, Illinois. Patients who had concomitant chronic pain were subsequently interviewed. Pain intensity before and after VNS implantation was rated by the patient as average, worst, and least and on numeric rating scale from 1 to 10. Current pain measurements were compared to preimplantation by using Global Pain Relief Rating Scale. Of 62 patients who received VNS, 27 patients were interviewed; 4 patients had common migraine, and no other chronic pain syndromes were identified. All patients with migraine reported reductions in headache frequency and numeric rating scale score for average and least headache intensity. One patient reported complete relief of headaches. Improvement was reported to start 1 to 3 months after initiation of therapy. On Global Pain Relief Rating Scale, 1 patient reported complete pain relief, 2 reported a lot of pain relief, and 1 reported slight pain relief. Concomitant antiepileptic drugs were decreased in 3 patients and slightly increased in 1. VNS might be beneficial for prophylactic therapy of migraine.