深部脑刺激技术及其对抑郁症治疗的研究进展

介绍深部脑刺激技术治疗抑郁症的进展.     

脑深部刺激治疗帕金森病

最近临床研究脑深部刺激(deep brain stimula tion,DBS)治疗PD近期效果与毁损术相近,疗效持久,手术安全.我院已采用DBS治疗3例PD病人,现报告如下:     

深部脑刺激治疗药物难治性癫痫的研究现状

癫痫是一种短暂性脑神经异常放电引起人体机能出现异常的一种疾病,该疾病目前已然波及全球5 000万余人,人们通常使用药物控制发作,尽管引入了各种新型抗癫痫发作药物(Anti-seizure medications,ASMs),仍有约1/3的患者无法通过ASMs正规治疗得到有效控制,进而发展为药物难治性癫痫(Drug-resistant epilepsy,DRE),持续的癫痫发作会对患者的身体、心理、家庭以及社会造成严重的负担。随着神经外科对立体定向技术的逐步深入研究,研究发现深部脑刺激(Deep brain stimulation,DBS)是一种广泛应用于精神和神经疾病的有效治疗手段,目前,DBS在治疗帕金森病(Parkinson’s disease,PD)方面已取得良好成效,同时该技术的可调节性、可逆性及良好的安全性促使人们通过DBS对精神神经系统疾病进行更深入的研究。目前世界各地已有一定数量的患有不同精神障碍或神经障碍的患者接受DBS治疗,其运用于DRE也得到了良好疗效,本文就DBS的神经调控机制、相关靶点、副作用及研究现状作如下概述,以期对DRE的治疗提供治疗新思路。     

深部脑刺激术治疗难治性癫痫的研究进展

外科切除性手术是难治性癫痫的一种有效治疗方式,但仍有不少患者因为各种原因无法接受切除性手术。而深部脑刺激术因其在神经系统疾病治疗上的有效性和相对安全性,正被逐步应用于难治性癫痫的治疗。本文就脑深部刺激术治疗难治性癫痫的神经调控机制、治疗靶点及其相关的研究进展作一综述。     

深部脑刺激技术在精神外科中的应用

深部脑刺激（deep brain stimulation,DBS）技术被广泛应用于难治性运动障碍性疾病的治疗,并尝试用于精神疾病的治疗。DBS的作用机制包括抑制作用、兴奋作用、复杂的重塑、代谢改变等,涉及复杂的神经网络活动,并与刺激部位、疾病状态和刺激参数等因素有关。DBS在难治性强迫症和抑郁症治疗中的应用处于起步阶段。本文综述了DBS在精神疾病临床应用的现状及前景。     

慢性深部脑刺激治疗帕金森病

帕金森病（Parkinson,sdisease,PD）治疗仍然是医学界的一大难题。丘脑切开术（thalamotomy）跨手术和左旋多巴队（L-Dopa）等药物的疗效均不够满意。近年来PD的慢性深部脑刺激（chronicdeePbrainstimulation,CDBS）疗法取得了较大进展,显示出良好前景,成为了PD的有效疗法     

脑深部刺激治疗帕金森病的研究进展

帕金森病(Parkinson’s disease，PD)多发于老年人，是以静止性震颤、肌强直及运动徐缓为主要临床表现的神经系统疾病，病情呈缓慢进行性加重，晚期常死于肺炎、尿路感染等并发症。其治疗目前仍以药物与手术相结合的综合治疗为主，本文仅就脑深部刺激术(deepbrain stimulation，DBS)的最新研究状况作一阐述。     

慢性难治性丛集性头痛的深部脑刺激治疗

丛集性头痛（cluster headache，CH）是一种剧烈的爆炸样原发性疼痛，位于一侧眼眶、球后和额颞部，并伴有同侧眼球结膜充血、流泪、鼻塞及Homer综合征等。此病人群发病率为（2～6）／10000，年龄20～50岁，平均约30岁，其中男性发病率高于女性。约10％的CH病人可发展为慢性CH（chronic cluster headache，CCH）并且持续1年以上不消退。对于急性发作的CH药物或者吸氧等治疗作用尚可，而对于一些难治性的CCH药物效果欠佳，外科使用三叉神经毁损术效果也不理想，且并发症较多。自用深部脑刺激术（deep brain stimulation，DBS）治疗运动障碍性疾病取得良好临床效果以来，一些学者尝试用DBS来治疗CCH，也取得了良好的效果。现就CCH的诊断、病理生理、DBS的治疗进展作一综述。     

脑深部电刺激治疗帕金森病

脑深部电刺激 (ｄｅｅｐｂｒａｉｎｓｔｉｍｕｌａｔｉｏｎ ,ＤＢＳ)自 90年代后期作为一种理想的手术方法治疗特发性震颤及帕金森病 ,在欧美国家已广泛应用 ,并基本取代了毁损手术。本中心自1999年 11月以来共为 31例患者植入 4 1侧深部电极 ,其中同期双侧丘脑底核 (ＳＴＮ)刺激 10例 ,单侧ＳＴＮ刺激 2 0例 (其中 4例为已作过对侧或同侧Ｖｉｍ毁损术 ) ,单侧苍白球内侧核 (ＧＰｉ )刺激 1例 ,现介绍如下。资料和方法 :(1)观察对象 :31例ＰＤ患者中男性 2 2例 ,女性 9例。年龄 37～ 82岁 ,平均年龄 (6 4 2± 7 5 )岁 ,排除各种原因引起的…     

脑深部电刺激治疗难治性癫癎

目的探讨脑深部电刺激（deep brain stimulation,DBS）在治疗难治性癫中的应用。方法回顾性分析接受DBS治疗的4例难治性癫病人的临床资料,1例选择丘脑前核电刺激,3例选择杏仁核-海马复合体电刺激。分析DBS治疗难治性癫的术前评估、手术方法及治疗效果。结果随访11-33个月,3例病人发作均减少50%以上,1例无效。结论对于不适合接受开颅切除性手术治疗的药物难治性癫病人,DBS治疗为安全而有效地治疗方式之一。靶点的选择主要依据癫癎样放电的部位及特点。     

A connectomic analysis of deep brain stimulation for treatment-resistant depression

ObjectiveDeep brain stimulation (DBS) has been used as a treatment of last resort for treatment-resistant depression (TRD) for more than a decade. Many DBS targets have been proposed and tested clinically, but the underlying circuit mechanisms remain unclear. Uncovering white matter tracts (WMT) activated by DBS targets may provide crucial information about the circuit substrates mediating DBS efficacy in ameliorating TRD.MethodsWe performed probabilistic tractography using diffusion magnetic resonance imaging datas from 100 healthy volunteers in Human Connectome Project datasets to analyze the structural connectivity patterns of stimulation targeting currently-used DBS target for TRD. We generated mean and binary fiber distribution maps and calculated the numbers of WMT streamlines in the dataset.ResultsProbabilistic tracking results revealed that activation of distinct DBS targets demonstrated modulation of overlapping but considerably distinct pathways. DBS targets were categorized into 4 groups: Cortical, Striatal, Thalamic, and Medial Forebrain Bundle according to their main modulated WMT and brain areas. Our data also revealed that Brodmann area 10 and amygdala are hub structures that are associated with all DBS targets.ConclusionsOur results together suggest that the distinct mechanism of DBS targets implies individualized target selection and formulation in the future of DBS treatment for TRD. The modulation of Brodmann area 10 and amygdala may be critical for the efficacy of DBS-mediated treatment of TRD.     

Tract-based analysis of target engagement by subcallosal cingulate deep brain stimulation for treatment resistant depression

BackgroundDeep brain stimulation (DBS) of subcallosal cingulate cortex (SCC) is a promising investigational therapy for treatment-resistant depression (TRD). However, outcomes vary, likely due to suboptimal DBS placement. Ideal placement is proposed to stimulate 4 SCC white matter bundles; however, no quantitative data have linked activation of these target tracts to response.ObjectiveHere we used the volume of tissue activated (VTA) and probabilistic diffusion tensor imaging (DTI) to quantify tract activation relating to response.MethodsDTI was performed in 19 TRD patients who received SCC-DBS. We defined clinical response as >48% reduction from baseline in the Hamilton Depression Rating Scale. Bilateral VTAs were generated based on subject-specific stimulation parameters. Patient-specific tract maps emanating from the VTAs were calculated using whole-brain probabilistic DTI. The four target tracts were isolated using tract-specific quantification and examined for overlap with DBS activated tissue.ResultsMedial frontal and temporal projections were stimulated in all responders at 6 and 12 months. Individual tract-based generalized linear mixed model analysis revealed a significant tract-by-response interaction at both 6 (F(1,135) = 3.828, p = 0.001) and 12 (F(1,135) = 5.688, p < 0.001) months, with post hoc tests revealing a response-related increase in cingulum activation at 6 months (t(135) = 2.418, p = 0.017) and decrease in forceps minor activation at 12 months (t(135) = -2.802, p = 0.006).ConclusionsA wider profile of white matter tracts, particularly to the medial frontal, was associated with DBS response. Cingulum bundle stimulation may promote early response and excess stimulation of the forceps minor might be detrimental. Our work supports prospective patient-specific targeting to inform personalized DBS.     

A pilot study of bed nucleus of the stria terminalis deep brain stimulation in treatment-resistant depression

Background

Studies are increasingly investigating the therapeutic effects of deep brain stimulation (DBS) applied to a variety of brain regions in the treatment of patients with highly treatment refractory depression. Limited research to date has investigated the therapeutic potential of DBS applied to the Bed Nucleus Of Stria Terminalis (BNST).

Clinical issues in considering vagus nerve stimulation for treatment-resistant depression

This review briefly discusses the clinical and basic science rationale for vagus nerve stimulation (VNS) in treatment-resistant depression (TRD). As the number of treatment failures for depression increases, the likelihood of achieving remission during acute treatment decreases, and the risk of relapse increases with the number of treatment failures. Two open trials of adjunctive VNS for TRD showed positive acute results and a growing benefit over time. The results of the acute randomized controlled trial were not significant for the primary outcome (response by HRSD-24), but the secondary measure (IDS-SR-30) was significant for VNS. A 12-month nonrandomized comparative analysis of patients receiving adjunctive VNS with TRD patients receiving treatment as usual showed significant results favoring VNS. Post hoc analyses found that this difference was not accounted for baseline differences nor by intercurrent treatment. While VNS is well tolerated, the optimal dosing strategies have not been determined nor have clinically useful predictors of who will respond to the treatment. Given the profound effects of TRD upon the daily lives of patients and that a substantial number of VNS patients receive benefit, VNS is a useful option for managing patients with TRD.     

脑深部电刺激在难治性强迫症治疗中的研究进展

强迫症是一组以强迫思维和(或)强迫行为为主要表现的精神疾病,目前临床上的一线治疗方案为5-羟色胺再摄取抑制剂和认知行为治疗。但仍有约40%~60%患者对一线治疗反应不佳或无效,称之为难治性强迫症。2009年美国及欧洲药监局批准的脑深部电刺激(deep brain stimulation,DBS)技术,作为一种神经调控的新型疗法能安全有效地改善难治性强迫症患者的症状。我们总结了现阶段对强迫症发病机制的了解,阐述了DBS应用于强迫症的历史和最新进展,并对其治疗机制、疗效、安全性、局限性及今后的发展方向等进行了综述。     

Deep brain stimulation in the treatment of depression

Blomstedt P, Sjöberg RL, Hansson M, Bodlund O, Hariz MI. Deep brain stimulation in the treatment of depression. Objective: To present the technique of deep brain stimulation (DBS) and to evaluate the studies conducted on DBS in the treatment of therapy‐refractory major depressive disorder (MDD). Method: A review of the literature on DBS in the treatment of MDD was conducted. Results: The results of DBS in MDD have been presented in 2 case reports and 3 studies of 47 patients operated upon in 5 different target areas. Positive effects have been presented in all studies and side effects have been minor. DBS in the nucleus accumbens resulted in a mean reduction of Hamilton depression rating scale (HDRS) of 36% after 1 year and 30% of the 10 patients achieved remission. DBS in the internal capsule/ventral striatum resulted in a reduction of 44% after 1 year, and at the last evaluation after in mean 2 years, 40% of the 15 patients were in remission. The 20 patients with subcallosal cingulated gyrus DBS had a reduction of HDRS of 52% after 1 year, and 35% were within 1 point from remission or in remission. Conclusion: DBS is a promising treatment for therapy‐refractory MDD. The published experience is, however, limited, and the method is at present an experimental therapy.     

Pallidal deep brain stimulation in the treatment of Meige syndrome

IntroductionMeige syndrome (MS) is characterized by blepharospasm, facial, oromandibular, and often cervical dystonia. The medical treatment of this condition is challenging and unsuccessful over long time. Recent case reports and small clinical series showed that bilateral deep brain stimulation (DBS) of globus pallidus pars interna (GPi) improves dystonic features of MS validated by Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS).Materials and methodsWe report on our experience in using bilateral GPi DBS in 3 cases of MS. We present short-term (3 months) follow-up as well long-term (from 8 months to 36 months) results.Preoperative and postoperative BFMDRS assessments were performed on each patient. The postoperative BFMDRS scores was done when both stimulators were switched on and compared to baseline scores.ResultsBilateral GPi DBS reduced the BFMDRS total movement score by 66% at short-term follow-up, and by 75% at long-term follow-up when compared to baseline scores. The BFMDRS total disability score was reduced by 34% at short-term follow-up, and by 47% at long-term follow-up when compared to baseline scores.ConclusionsOur results showed that bilateral GPi DBS in MS is effective and safe, if conservative treatment options failed. The benefit is not only observed at short-term 3 months period but is maintained at long-term follow-up ranging from 8 to 36 months.     

丘脑底核电刺激治疗继发性肌张力障碍

目的 探讨丘脑底核（STN）的脑深部电剌激（DBS）治疗继发性肌张力障碍的可行性、适应证和并发症。方法 5例行双侧STN—DBS，1例行单侧STN—DBS。结果 术中利用微电极记录的电信号获得STN的准确靶点定位，电刺激后患者肌张力有不同程度下降，但扭转改善不明显。随访半年至3年，6例患者中，药物引起的迟发性肌张力障碍及外伤性肌张力障碍的患者疗效理想，BFMDRS评分改善均在90％以上，且随着随访时间的延长，效果持续不断改善；其余4例患者疗效不佳，4例均肌张力略有改善，其中1例扭转略改善，1例语言及步态略有改善。手术后患者均无明显合并症，但1例术后16个月发现左侧电极折断，后取出。结论 DBS治疗迟发性和外伤性继发性肌张力障碍效果理想，而对于缺氧或脑基底节区弥漫性损害的继发性肌张力障碍效果不佳；STN可以成为治疗本病的理想靶点；术中应根据电生理记录结果和肌张力的轻度改善作为靶点定位的指标；手术无明显合并症。     

Unilateral deep brain stimulation of the nucleus accumbens in patients with treatment-resistant obsessive-compulsive disorder: Outcomes after one year

Objective

To investigate the effects of unilateral deep brain stimulation (DBS) in the right nucleus accumbens in patients with obsessive-compulsive disorder (OCD). Predominantly bilateral stimulation of the anterior limb of the internal capsule was utilized.

Methods

The study was designed as a double-blind sham-controlled crossover study. Patients received 3 months of deep brain stimulation followed by 3 months of sham stimulation, or vice versa. Subsequently, stimulation was continued unblinded for all patients. The primary outcome measure was the severity level of OCD, measured using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Secondary outcome measures were depressive symptoms, anxiety, psychological symptom severity, global functioning, quality of life, and cognitive function.

Results

The mean Y-BOCS scores decreased significantly from 32.2 (±4.0) at baseline to 25.4 (±6.7) after 12 months (p = 0.012). Five out of ten patients showed a decrease of more than 25%, indicating at least a partial response. One patient showed a decrease in Y-BOCS severity greater than 35%. Similarly, depression, global functioning and quality of life improved within one year. In contrast, anxiety, global symptom severity and cognitive function showed no significant changes. In general, DBS was well-tolerated.

Conclusions

DBS of the unilateral right nucleus accumbens showed encouraging results in patients with treatment-resistant OCD. Five out of ten patients reached at least a partial response after the first year.     

氟西汀合并奥氮平治疗难治性抑郁症的双盲对照研究

目的本研究探讨氟西汀合并奥氮平治疗难治性抑郁症的安全性和疗效。方法采用双盲对照研究,将52例诊断为难治性抑郁症的患者随机分为两组,一组采用氟西汀治疗,一组采用氟西汀合并奥氮平治疗,分别在治疗后第2、4、6、8周末,评定汉密顿抑郁量表(HAMD)和临床总体印象量表(CGI),同时采用Asberg抗抑郁剂副反应量表评定两组的药物副反应。结果氟西汀联合奥氮平治疗难治性抑郁症的疗效要明显优于单一应用氟西汀治疗(P<0.05),药物副反应两组间无明显差异(P>0.05)。结论氟西汀联合奥氮平治疗难治性抑郁症的疗效要明显优于单一应用氟西汀治疗(P<0.05),药物副反应两组间无明显差异(P>0.05)。