Neural selectivity,efficiency, and dose equivalence in deep brain stimulation through pulse width tuning and segmented electrodes

BackgroundAchieving deep brain stimulation (DBS) dose equivalence is challenging, especially with pulse width tuning and directional contacts. Further, the precise effects of pulse width tuning are unknown, and recent reports of the effects of pulse width tuning on neural selectivity are at odds with classic biophysical studies.MethodsWe created multicompartment neuron models for two axon diameters and used finite element modeling to determine extracellular influence from standard and segmented electrodes. We analyzed axon activation profiles and calculated volumes of tissue activated.ResultsWe find that long pulse widths focus the stimulation effect on small, nearby fibers, suppressing distant white matter tract activation (responsible for some DBS side effects) and improving battery utilization when equivalent activation is maintained for small axons. Directional leads enable similar benefits to a greater degree. Reexamining previous reports of short pulse stimulation reducing side effects, we explore a possible alternate explanation: non-dose equivalent stimulation may have resulted in reduced spread of neural activation. Finally, using internal capsule avoidance as an example in the context of subthalamic stimulation, we present a patient-specific model to show how long pulse widths could help increase the biophysical therapeutic window.DiscussionWe find agreement with classic studies and predict that long pulse widths may focus the stimulation effect on small, nearby fibers and improve power consumption. While future pre-clinical and clinical work is necessary regarding pulse width tuning, it is clear that future studies must ensure dose equivalence, noting that energy- and charge-equivalent amplitudes do not result in equivalent spread of neural activation when changing pulse width.     

A practical guide to troubleshooting pallidal deep brain stimulation issues in patients with dystonia

High frequency deep brain stimulation (DBS) of the internal portion of the globus pallidus has, in the last two decades, become a mainstream therapy for the management of medically-refractory dystonia syndromes. Such increasing uptake places an onus on movement disorder physicians to become familiar with this treatment modality, in particular optimal patient selection for the procedure and how to troubleshoot problems relating to sub-optimal efficacy and therapy-related side effects.Deep brain stimulation for dystonic conditions presents some unique challenges. For example, the frequent lack of immediate change in clinical status following stimulation alterations means that programming often relies on personal experience and local practice rather than real-time indicators of efficacy. Further, dystonia is a highly heterogeneous disorder, making the development of unifying guidelines and programming algorithms for DBS in this population difficult. Consequently, physicians may feel less confident in managing DBS for dystonia as compared to other indications e.g. Parkinson's disease.In this review, we integrate our years of personal experience of the programming of DBS systems for dystonia with a critical appraisal of the literature to produce a practical guide for troubleshooting common issues encountered in patients with dystonia treated with DBS, in the hope of improving the care for these patients.     

丘脑底核电刺激治疗帕金森病及其术后管理

目的探讨丘脑底核电刺激治疗帕金森病术后症状缓解特点,为提高术后患者管理质量提供依据。方法自2008年1月至2009年12月,共34例帕金森病患者于我院接受丘脑底核电刺激手术治疗,其中单侧植入3例,双侧植入31例。术后由神经内外科医师配合对患者进行患者管理。分别于患者首次开机、术后半年和1年时对患者进行UPDRS运动评分,并记录副反应发生情况。结果 34例患者手术顺利,术后平均随访10.6个月。所有患者术后均出现微毁损效应。患者在不服药状态下,术前、首次开机、术后半年和术后1年UPDRS运动评分分别为:46.8±8.9,20.1±9.7,23.1±9.4和22.3±8.9;刺激器打开并服药后,患者症状得到进一步缓解。1例患者术后发生皮肤感染,1例患者发生胸前囊袋积液,经妥善处理后症状控制。结论丘脑底核电刺激治疗帕金森病疗效肯定,高质量的术后患者管理是维持手术疗效的重要环节。     

Deep brain stimulation fine-tuning in Parkinson's disease: Short pulse width effect on speech

Backgroundsubthalamic nucleus deep brain stimulation (STN-DBS) may have a detrimental effect on speech in Parkinson's disease (PD) patients and new stimulation technologies may help in addressing this issue.Objectiveto evaluate the STN-DBS acute effect of 30 μs pulse width (30PW) versus conventional 60 μs PW (60PW) on speech and identify the core features of voice modified by 30PW.Methodsseven STN-DBS treated PD patients participated into a pilot cross-sectional study. Motor and speech performances were tested by means of both automatic analysis and blinded clinical evaluations in four stimulation conditions: 30PW and 60PW both at the usual amplitude and at an amplitude just below the threshold for stimulation-related side effects.Resultsat the threshold amplitude, 30PW stimulation improved speech intelligibility for both words (p = 0.02) and sentences (p = 0.04), without worsening motor performance. A lower but not statistically significant voice variability and instability and percentage of stuttering disfluencies was also observed. The beneficial effect of 30PW detected by automatic analysis, was confirmed by patients’ perception.ConclusionsSTN-DBS treated patients experiencing low speech intelligibility may benefit from a 30PW stimulation trial at a higher amplitude. Deep characterization of PD speech profiles may help in a better application of recent DBS hardware advances.     

3D X-ray based visualization of directional deep brain stimulation lead orientation

Knowing the orientation of directional deep brain stimulation electrodes enables imaging-based adjustment of the stimulation settings. A rotational X-ray based examination was developed to determine the electrodes orientation. By identifying the patient´s 0° axis and the electrode´s rotation using the “iron sights”-sign, the exact orientation of the electrode in relation to the ACPC-line is given. The presented imaging approach offers a reliable diagnostic tool for visualization of the implanted DBS electrode orientation in clinical routine.     

Foreign body granuloma around implantable pulse generator for deep brain stimulation: Two case reports

We report two cases of granuloma that occurred around an implantable pulse generator (IPG) for deep brain stimulation. Both cases showed no signs of infection and disappeared after moving the IPG and removing the granulation. If a noninfectious mass is formed, the relocation of IPG may improve it.     

Predictors of deep brain stimulation outcome in tremor patients

Background

Deep brain stimulation of the ventro-intermedius nucleus of the thalamus is an established treatment for tremor of differing etiologies but factors that may predict the short- and especially long-term outcome of surgery are still largely unknown.

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.     

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。     

Imaging-based programming of subthalamic nucleus deep brain stimulation in Parkinson's disease

BackgroundThe need for imaging-guided optimization of Deep Brain Stimulation (DBS) parameters is increasing with recent developments of sophisticated lead designs offering highly individualized, but time-consuming and complex programming.ObjectiveThe objective of this study was to compare changes in motor symptoms of Parkinson's Disease (PD) and the corresponding volume of the electrostatic field (VEsF) achieved by DBS programming using GUIDE XT™, a commercially available software for visualization of DBS leads within the patient-specific anatomy from fusions of preoperative magnetic resonance imaging (MRI) and postoperative computed tomography (CT) scans, versus standard-of-care clinical programming.MethodsClinical evaluation was performed to identify the optimal set of parameters based on clinical effects in 29 patients with PD and bilateral directional leads for Subthalamic Nucleus (STN) DBS. A second DBS program was generated in GUIDE XT™ based on a VEsF optimally located within the dorsolateral STN. Reduction of motor symptoms (Movement Disorders Society Unified Parkinson's Disease Rating Scale, MDS-UPDRS) and the overlap of the corresponding VEsF of both programs were compared.ResultsClinical and imaging-guided programming resulted in a significant reduction in the MDS-UPDRS scores compared to off-state. Motor symptom control with GUIDE XT™-derived DBS program was non-inferior to standard clinical programming. The overlap of the two VEsF did not correlate with the difference in motor symptom reduction by the programs.ConclusionsImaging-guided programming of directional DBS leads using GUIDE XT™ is possible without computational background and leads to non-inferior motor symptom control compared with clinical programming. DBS programs based on patient-specific imaging data may thus serve as starting point for clinical testing and may promote more efficient DBS programming.     

The cognitive effects of amygdalohippocampal deep brain stimulation in patients with temporal lobe epilepsy

The aim of this study was to examine the effects of amygdalohippocampal deep brain stimulation (AH-DBS) on cognitive functioning in patients with refractory temporal lobe epilepsy. The population consisted of 10 patients (7 men) who underwent ipsilateral (n = 8) or bilateral (n = 2) AH-DBS. Intellectual and neuropsychological evaluation was performed before and 6 months after initiation of AH-DBS. Group analyses revealed no overall pattern of change in cognitive measures, but improvement was seen in emotional well-being. Individual results varied over a broad spectrum ranging from no cognitive effects to negative effects on intelligence capacities, divided attention, and concept formation, to positive effects on speed of information processing and speed of finger movements. AH-DBS is a valuable treatment alternative for patients with refractory epilepsy that appears to have no major adverse neuropsychological consequences and enhances emotional well-being on the group level. Individual results are too diverse at this moment to allow viable interpretation. Additional studies are needed to confirm these preliminary results.     

微电极引导立体定向核团毁损和脑深部电刺激治疗帕金森病

目的研究微电极引导立体定向颅内核团毁损和脑深部电刺激手术(deep brain stimulation,DBS)治疗帕金森病的临床疗效。方法分析我院116例应用微电极引导立体定向核团毁损术和85例应用脑深部电刺激术治疗的帕金森病患者的临床资料,获得术前、术后和DBS开启后6个月、1年、3年及5年的不同服药状态下帕金森病联合评分量表(UPDRS)的评分,比较手术前后UPDRS运动评分的差异。结果核团毁损术和DBS在术后6个月、1年和3年的随访中均能显著改善患者术前UPDRS运动评分,在第5年仅DBS组UPDRS运动评分较术前有改善,同时DBS组患者术后抗帕金森病药物用量较术前减少。结论核团毁损和脑深部电刺激手术均能显著改善帕金森病患者的UPDRS运动评分,DBS疗效更为长久。     

丘脑底核脑深部电刺激治疗原发性帕金森病的不良事件

目的观察原发性帕金森病(Parkinson disease,PD)患者行丘脑底核脑深部电刺激术(deep brain stimulation of subthalamic nucleus,STN DBS)的不良事件。方法纳入行STN DBS的原发性帕金森病45例,收集患者一般临床资料,术后随访至3~9年,观察术后不良事件。结果手术相关不良事件:微毁损效应44例、囊袋积液2例、颅内出血1例、嗜睡1例;未观察到任何装置相关不良事件;刺激或疾病相关不良事件:异动症15例、步态平衡障碍12例,焦虑抑郁状态6例,构音障碍与多巴胺失调综合征各4例,智能减退2例,少数患者出现体重增加、幻觉、睁眼困难等。7例患者因共存疾病死亡。结论 STN DBS大部分不良事件可以控制,术后个体化调整参数及药物,有利于减少STN DBS不良事件。     

脑深部电刺激术治疗成人抽动秽语综合征长期疗效观察

目的 研究苍白球腹后内侧部(Gpi)脑深部电刺激术(DBS)治疗成人抽动秽语综合征(TS)的长期疗效. 方法 首都医科大学宣武医院功能神经外科自2007年5月至2008年5月应用Gpi DBS治疗5例药物难治性TS患者,分别于术前,术后3月、6月、1年及1年以上应用耶鲁综合抽动严重程度评分量表(YGTSS)进行症状评估. 结果 患者随访时间21～33月.与术前比较,患者最后随访时运动、发声、总体损害程度、YGTSS评分均降低,差异有统计学意义(P＜0.05);与术前、术后3月比较,患者其余各个时间点YGTSS评分均降低,差异有统计学意义(P＜0.05).所有患者症状逐渐改善,前6月症状改善明显,6月后基本平稳,仍会有轻度改善.术后3月、6月、1年、1年以上YGTSS评分的最终改善率分别为28.5％、52.35％、57.62％、62.88％.最后随访时YGTSS评分中运动抽动改善率为51.38％,发声抽动改善率为46.16％,总体损害程度改善率为71％.没有严重并发症. 结论 Gpi DBS是一种治疗成人药物难治性TS安全有效的方法,能够全面缓解TS运动抽动、发声抽动及总体损害,长期效果稳定.     

国产脑深部电刺激系统治疗帕金森病的临床初步研究

目的 验证清华大学航天航空学院自主研发的国产脑深部电刺激(DBS)系统用于治疗原发性帕金森病(PD)临床应用的安全性和有效性.方法 对33例PD患者实施了国产脑深部电刺激系统(PINS系统)植入术.分别于术前、术后对用药情况,UPDRS评分量表,日常生活能力评分量表等情况进行评估和分析.结果 33例PD患者平均年龄(56.3±8.6)岁,平均病程(10.4±4.3)年.术后患者症状均得到显著改善,UPDRS运动评分较术前改善78％,症状控制稳定.结论 国产脑深部电刺激器PINS系统生物安全性、系统稳定性、刺激作用有效性均能够满足临床应用的要求.     

Outcomes,management, and potential mechanisms of interleaving deep brain stimulation settings

IntroductionDBS is a therapeutic option for patients with Parkinson disease (PD), tremor and dystonia. In patients who experience suboptimal clinical results with conventional programming (monopolar, double monopolar or bipolar settings), interleaved pulses can sometimes be used to provide differential therapeutic benefits with the possibility of fewer side effects. Interleaving allows a clinician to define two “programs” that automatically alternate. The goal of this paper is to 1) present clinical scenarios where DBS interleaving was used across two clinics to provide improved symptom control in three patients with suboptimal results from conventional programming; 2) address the potential mechanisms of interleaving; and 3) provide practical tips on the use of interleaving.MethodsThree patients were formally compared for therapeutic benefit on interleaved and conventional parameter settings.ResultsInterleaving is most likely to be useful in two clinical scenarios: 1) different contacts are beneficial for specific symptoms, but each at a different stimulation amplitude; or 2) symptoms are resolved incompletely, and further voltage increase is limited by side effects. The factors underpinning the differences in outcomes with interleaving are unknown but may be highly dependent on specific symptoms and to electrode positioning. Interleaving is a relatively new programming platform and there is no data to demonstrate long-term benefits.ConclusionsInterleaving is a tool that may augment outcomes, and possibly obviate the need for surgical revisions, although in our experience across two large centers it has been effective for only a small number of patients.     

Adverse events associated with deep brain stimulation in patients with childhood-onset dystonia

BackgroundData on pediatric DBS is still limited because of small numbers in single center series and lack of systematic multi-center trials.ObjectivesWe evaluate short- and long-term adverse events (AEs) of patients undergoing deep brain stimulation (DBS) during childhood and adolescence.MethodsData collected by the German registry on pediatric DBS (GEPESTIM) were analyzed according to reversible and irreversible AEs and time of occurrence with relation to DBS-surgery: Intraoperative, perioperative (<4 weeks), postoperative (4 weeks < 6 months) and long term AEs (>6 months).Results72 patients with childhood-onset dystonia from 10 DBS-centers, who received 173 DBS electrodes and 141 implantable pulse generators (IPG), were included in the registry. Mean time of postoperative follow-up was 4.6 ± 4 years. In total, 184 AEs were documented in 53 patients (73.6%). 52 DBS-related AEs in 26 patients (36.1%) required 45 subsequent surgical interventions 4.7 ± 4.1 years (range 3 months–15 years) after initial implantation. The total risk of an AE requiring surgical intervention was 7.9% per electrode-year. Hardware-related AEs were the most common reason for surgery. There was a tendency of a higher rate of AEs in patients aged 7–9 years beyond 6 months after implantation.DiscussionThe intraoperative risk of AEs in pediatric patients with dystonia undergoing DBS is very low, whereas the rate of postoperative hardware-related AEs is a prominent feature with a higher occurrence compared to adults, especially on long-term follow-up.ConclusionFactors leading to such AEs must be identified and patient management has to be focused on risk minimization strategies in order to improve DBS therapy and maximize outcome in pediatric patients.     

规范脑深部电刺激术术前评估已是当务之急

<正>2014年,法国约瑟夫傅立叶大学Alim LouisBenabid教授和美国埃默里大学医学院Mahlon R.De Long教授荣获号称诺贝尔医学奖风向标的拉斯克临床医学奖,原因是发现丘脑底核(STN)脑深部电刺激术(DBS)有助于减少帕金森病(PD)患者静止性震颤和恢复运动功能。这一历史性时刻表明,脑深部电刺激术用于治疗帕金森病已在全世界范围内完全认可。据不完全统计,截至2005年,全球约有帕金森