Life-threatening parkinsonism-hyperpyrexia syndrome following bilateral deep brain stimulation of the subthalamic nucleus

Parkinsonism-hyperpyrexia syndrome (PHS), or neuroleptic malignant syndrome (NMS), is a neurophysiologic reaction to the acute withdrawal/decrease of central dopamine levels. It is a severe complication characterized by rigidity, change in consciousness level, fever, hypertension, and autonomic instability, that can be fatal. To the best of our knowledge, PHS following deep brain stimulation (DBS) of subthalamic nucleus (STN) surgery due to anti-Parkinson drug discontinuation has been previously reported only six times. Half of these cases resulted in fatalities. Herein, we report on an early diagnosed case of PHS following bilateral STN-DBS which was successfully treated with the administration of dopamine agonists, fluid replacement, and activation of DBS.     

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.     

Cognitive change on the repeatable battery of neuropsychological status (RBANS) in Parkinson's disease with and without bilateral subthalamic nucleus deep brain stimulation surgery

Cognitive change following bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) surgery in those with Parkinson's disease (PD) has led to equivocal results. The current study applied a standardized regression-based (SRB) method based on 20 medically managed PD patients and 20 STN DBS PD surgical patients who were administered the Repeatable Battery of Neuropsychological Status (RBANS). Of the medically managed PD participants, 94% remained stable compared to 73% of the DBS group. In the DBS group cognitive change was noted on the Total scale and the Immediate Memory Index. A secondary analysis also revealed reliable change on several subtest scores. Although preliminary, the current study provides change parameters for post DBS surgery on this brief battery.     

Caregiver burden worsens in the second year after subthalamic nucleus deep brain stimulation for Parkinson's disease

BackgroundCaregiver burden (CB) in Parkinson's disease (PD) does not improve in the short term after bilateral subthalamic nucleus (STN) deep brain stimulation (DBS), despite motor improvement. This may be due to increased caregiver demands after surgery or the possibility that DBS unresponsive non-motor factors, such as executive dysfunction, contribute to CB.ObjectiveTo evaluate the trajectory of CB in year 2 following bilateral STN DBS surgery for PD, and to test whether post-operative CB changes correlate with changes in executive function in a subgroup with available neuropsychological testing.MethodsThis retrospective analysis included 35 patients with PD whose caregivers completed the Caregiver Burden Inventory (CBI) at baseline and between 9 and 24 months after bilateral STN DBS. 14 of these patients had neuropsychological testing both at baseline and within 6 months of their follow up CBI assessment.ResultsCBI scores showed worsened CB from baseline to follow-up (16.4–21.5, p = 0.006). There was no correlation between change in executive function and change in CBI in the smaller subsample.ConclusionCB worsens in the 2 years after bilateral STN DBS despite improvement in motor symptoms and is not associated with change in executive dysfunction in the setting of advancing PD. These findings have implications on pre-operative counselling for patients and caregivers considering DBS for PD.     

双侧丘脑底核脑深部电刺激治疗帕金森病

目的 应用双侧丘脑底核脑深部电刺激（DBS）治疗难治性帕金森病（PD），并对其疗效作出评价。方法 对7例帕金森病患者采用磁共振导向立体定向及术中电生理验证方法，将刺激电极分别植入丘脑底核，采用同期或分期植入刺激发生器。术后1周用程控计算机在体外调速刺激参数，以达到最佳疗效。结果 6例患者术后均获得了显著的疗效。震颤完全消失，肌强直、步态、姿障碍以及药物所致的并发症明显,面时多巴胺类药物用量明显减少，1例曾接爱双侧丘脑腹中间核及一侧苍白球毁损后的患者只得到了轻度改善。结论 DBS法治疗中晚期PD，具有安全，副作用可逆转的优点，且可根据患者的不同状况及病情发展调节刺激参数达到最佳症状控制，完全控制震颤，明显改善肌张力障碍、步态、资势等运动障碍及药物所致的并发症，另外多巴胺类药物的用量也明显减少。     

丘脑底核脑深部刺激术治疗帕金森病的手术方法和疗效分析

目的 总结帕金森病(PD)脑深部刺激术(DBS)治疗的手术方法和效果。方法 对25例帕金森病患者进行了丘脑底核DBS治疗,其中单侧17例,双侧8例。采用磁共振扫描结合微电极记录技术进行靶点定位。术后用UPDRS运动评分评价刺激效果。结果 25例PD患者术后随访5～34个月,平均8.3个月。脉冲发生器开启时,在“关”状态下,UPDRS运动评分改善率50.2％;在“开”状态下,UPDRS运动评分改善率20.7％,未发现任何并发症。结论 丘脑底核DBS是改善PD患者运动功能较为理想的治疗方法。     

Long-term effects of bilateral deep brain stimulation of the subthalamic nucleus on depression in patients with Parkinson's disease

ObjectiveTo study the long-term effects of deep brain stimulation (DBS) of the bilateral subthalamic nucleus (STN) on depression in patients with Parkinson's disease (PD) and to discuss the mechanism.MethodsA STN–DBS group (n = 27) and anti-Parkinson's medication control group with paired designing were set up. The evaluation of the depression and motor function was performed a total of six times. Depression was evaluated by the Self-Rating Depression Scale (SDS) and Hamilton Rating Scale for Depression (HAMD). Motor function was evaluated by the third part of the Unified Parkinson's Disease Rating Scale (UPDRS-III).ResultsCompared with the preoperative and the medication control group, the UPDRS-III scores of the STN–DBS group decreased remarkably within 18 months postoperatively (P ≤ 0.001), and the SDS scores decreased notably within 6 months postoperatively (P ≤ 0.05), and the HAMD scores decreased notably within 3 months postoperatively (P ≤ 0.05). The UPDRS-III scores were strongly correlated with their SDS scores within 6 months postoperatively (P ≤ 0.05), especially at 5 weeks postoperation (P ≤ 0.001). UPDRS-III scores were also strongly correlated with HAMD scores at 5 weeks postoperation (P ≤ 0.05). The mean value of the bilateral voltages was obviously correlated with SDS and HAMD scores (P ≤ 0.05) within 18 months postoperatively.ConclusionThe improvement in motor symptoms resulting from STN–DBS can improve depression in PD patients, but its long-term effects were unremarkable. Within the treatment range, the higher the mean value of bilateral voltages then the more severe was the depression in PD patients.     

Parkinsonian gait improves with bilateral subthalamic nucleus deep brain stimulation during cognitive multi-tasking

BackgroundGait impairment in Parkinson's disease reduces mobility and increases fall risk, particularly during cognitive multi-tasking. Studies suggest that bilateral subthalamic deep brain stimulation, a common surgical therapy, degrades motor performance under cognitive dual-task conditions, compared to unilateral stimulation.ObjectiveTo measure the impact of bilateral versus unilateral subthalamic deep brain stimulation on walking kinematics with and without cognitive dual-tasking.MethodsGait kinematics of seventeen patients with advanced Parkinson's disease who had undergone bilateral subthalamic deep brain stimulation were examined off medication under three stimulation states (bilateral, unilateral left, unilateral right) with and without a cognitive challenge, using an instrumented walkway system.ResultsConsistent with earlier studies, gait performance declined for all six measured parameters under cognitive dual-task conditions, independent of stimulation state. However, bilateral stimulation produced greater improvements in step length and double-limb support time than unilateral stimulation, and achieved similar performance for other gait parameters.ConclusionsContrary to expectations from earlier studies of dual-task motor performance, bilateral subthalamic deep brain stimulation may assist in maintaining temporal and spatial gait performance under cognitive dual-task conditions.     

脑深部电刺激术治疗Hallervorden-Spatz病一例及文献复习

目的 观察双侧丘脑底核脑深部电刺激术治疗1例Hallervorden-Spatz病的手术效果.方法 将脑深部刺激电极植入双侧丘脑底核,分别于术前、开机后1个月、开机后3个月,12个月时对其进行BFM及BFMDMS评分,评价治疗效果.结果 术前、开机后1个月、开机后3个月、12个月的BFMDMS评分分别为114、35、28、14分,症状改善率刺激1个月时为69%、3个月为75%、12个月为88%.持续刺激未引起任何不良反应,患者不再服用相关药物.结论 双侧丘脑底核脑深部电刺激术能够有效的改善严重的全身性肌张力障碍Hallervorden-Spatz病症状,是一种可供选择的安全有效的治疗方法.     

Freezing of gait after bilateral subthalamic nucleus stimulation for Parkinson's disease

OBJECTIVE: To determine the long-term effect of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) on freezing of gait in Parkinson's disease patients. PATIENTS AND METHODS: Sixty-seven patients were followed 12 months after bilateral STN DBS and 32 patients were followed 24 months post-surgery. Patients were evaluated with the Unified Parkinson's Disease Rating Scale (UPDRS) with medications on and off at baseline and again in both conditions with stimulation on at follow-up. Specific attention was paid to the freezing item of the ADL section. RESULTS: Freezing scores in the medication off state improved significantly with stimulation at 1 and 2 years. In the medication on state there were no significant improvements in freezing. CONCLUSION: Off period freezing of gait is significantly improved with STN DBS up to 24 months; however, on period freezing is not affected by STN DBS.     

Influence of chronic bilateral stimulation of the subthalamic nucleus on cognitive function in Parkinson's disease

Background: The clinical efficacy of chronic deep brain stimulation in the treatment of parkinsonian patients with severe levodopa-related motor adverse effects has been repeatedly shown. Bilateral subthalamic nucleus (STN) stimulation has been shown to present an advantage over pallidal stimulation as it induces a higher antiakinetic effect and has positive effects on all parkinsonian symptoms. The morbidity of such surgery is usually considered to be very low. However, few studies have extensively examined the effects of chronic STN stimulation on cognitive function. Objective: The aim of the present study was to assess the effects of chronic bilateral STN stimulation on performance in an extensive battery of neuropsychological tests, three months and one year after surgery. Methods: Nine patients with Parkinson's disease were selected for STN electrodes implantation. They underwent a neuropsychological evaluation at one month before and at three months after surgery. Six of them were examined again at one year after surgery. Results: Before surgery, no patient showed cognitive decline. At three months after surgery, no modification was observed for most tasks. The information processing speed tended to improve. There was a significant reduction of the performance in a delayed free recall test and a trend toward a significant reduction of categorial word fluency. At one year after surgery, most task measures did not change. Slight impairment was observed for tasks evaluating executive function. Examination of individual results showed that some patients (30 % at 3 months after surgery) showed an overall cognitive decline. Behavioural changes were also observed in 4 patients with overall cognitive decline in one of them. Conclusion: In general, STN deep brain stimulation can be considered as a significant contribution to the treatment of severe Parkinson's disease However, in some patients it can induce overall cognitive decline or behavioural changes. Received: 4 May 2000 / Received in revised form: 31 January 2001 / Accepted: 6 February 2001     

丘脑底核脑深部电刺激治疗帕金森病合并抑郁障碍的长期疗效

目的研究丘脑底核（STN）脑深部电刺激（DBS）治疗帕金森病（PD）合并抑郁障碍的长期疗效并探讨其神经机制。方法对15例合并抑郁障碍的PD患者实施STN脑深部电极植入，术后3个月、6个月和12个月进行随访和临床评价。结果术后运动功能症状如肢体僵硬、震颤、运动迟缓和姿势平衡障碍改善良好，停药后PD分级量表运动评分显著下降（P〈0．01）。术后抑郁障碍症状如焦虑、绝望和激越症状改善良好，停药后汉密尔顿抑郁量表评分显著下降（P〈0．05）。结论STN-DBS能显著改善PD的抑郁障碍症状，STN在PD抑郁障碍神经机制中起重要作用。     

Instability of speech in Parkinson disease patients with subthalamic nucleus deep brain stimulation

IntroductionThe impact of deep brain stimulation (DBS) on speech rhythm and its mechanism remains unclear. We investigated speech rhythm characteristics of patients with Parkinson's disease (PD) treated with subthalamic nucleus (STN) DBS to understand the underlying pathophysiology better.MethodsWe enrolled a total of 105 participants and evaluated speech rhythm performances among patients with PD who had undergone STN-DBS (the PD-DBS group), patients with PD treated only with medication (the PD-Med group), patients with cerebellar ataxia (the CA group), and healthy controls (the HC group). Each participant was asked to repeat the syllable/pa/at a comfortable self-chosen steady pace. A widely-used software (the Motor Speech Profile) program performed an acoustic analysis.ResultsCompared to the PD-Med and HC groups, speech rate instability (DDKjit) was significantly higher in the PD-DBS and CA groups (p < 0.01). However, after DBS was turned off, the DDKjit of the PD-DBS group improved to a level comparable to that of the PD-Med and HC groups. In contrast to the significantly higher variability of speech volume (DDKcvi) in the CA group, the PD-DBS group showed similar DDKcvi to the PD-Med and HC groups.ConclusionsSTN-DBS affects the speech rate stability of patients with PD. Speech rhythm disorders caused by STN-DBS were phenotypically similar to that in CA in terms of interval variability but different regarding amplitude variability. Further studies are warranted to elucidate the underlying pathophysiology of speech rhythm disorders in PD patients treated with DBS.     

双侧丘脑底核脑深部电刺激对PD患者焦虑症状的短期影响

目的探讨双侧丘脑底核脑深部电刺激(STN-DBS)对帕金森病(PD)患者焦虑症状及生活质量的短期影响。方法对上海交通大学附属瑞金医院功能神经外科中心自2017年8月至2019年8月行双侧STN-DBS治疗的39例PD患者,分别于术前、术后1个月和末次随访时进行贝克焦虑自评量表(BAI)、贝克抑郁自评量表(BDI)评分,于术前和术后末次随访时进行帕金森病患者生活质量问卷-8项(PDQ-8)评分,采用统计学方法分析各节点间评分的差异,以及评分改善程度间的相关性;并进一步依据术前BAI评分将患者分为无焦虑组(n=18)、轻度焦虑组(n=10)、中度焦虑组(n=8)和重度焦虑组(n=3),以进行亚组分析。结果(1)39例患者术后1个月及末次随访时的BAI评分[14(8,20)分、9(3,14)分]均明显低于术前[16(9,27)分],术后末次随访时的BDI评分[8(6,16)分]及PDQ-8评分[3(2,6)分]均明显低于术前[15(8,21)分、9(6,13)分],差异均有统计学意义(P<0.05)。(2)相关性分析显示,术后末次随访时的BAI评分较术前的改善程度与BDI评分的改善程度呈正相关关系(rs=0.722,P=0.000),也与术前BDI评分及术前PDQ-8评分呈负相关关系(rs=-0.714,P=0.000;rs=-0.378,P=0.018)。(3)亚组分析显示,轻度焦虑组和中度焦虑组患者中,术后末次随访时的BAI评分均明显低于术前,差异均有统计学意义(P<0.05);轻度焦虑组、中度焦虑组与重度焦虑组患者的术后末次随访时的BAI评分较术前的改善程度均明显高于无焦虑组,差异均有统计学意义(P<0.05)。结论双侧STN-DBS能在短期内显著改善PD患者的焦虑症状,提高其生活质量,提示STN参与了PD患者焦虑症状的神经机制。     

双侧丘脑底核脑深部刺激术治疗帕金森病13例报告

目的 探讨双侧丘脑底核（STN）脑深部刺激术（DBS）治疗帕金森病的临床经验。方法 从2002年到2005年共完成了13例帕金森病的双侧丘脑底核DBS，根据STN解剖学定位，靶点的理论坐标值是X=11-13mm，Y=0-2mm，Z=0-4mm，通过立体定向技术在双侧丘脑底核植入刺激电极，并于锁骨下方植入脑深部电刺激器。结果 随访时间为6个月到3年，3例震颤为主病人的症状完全缓解，即震颤完全消失；僵直和运动迟缓为主要症状者的症状缓解程度达90％以上，其中以四肢肌肉僵直的效果较好，运动迟缓也有明显缓解，但是有1例病人双侧肢运动协调性差。所有患者植物神经功能症状有较明显改善，如便秘、流涎、出汗和浮肿等均有改善。结论 DBS治疗帕金森病，是帕金森病治疗的一个里程碑似的进步。它可以明显地缓解帕金森病的主要症状和体征，对运动迟缓、僵直和震颤等均有较理想的效果。     

A quantitative analysis of the effect of bilateral subthalamic nucleus-deep brain stimulation on subjective and objective sleep parameters in Parkinson's disease

ObjectiveTo explore how subjective and objective sleep parameters respond to bilateral subthalamic nucleus-deep brain stimulation (STN-DBS) in patients with Parkinson's disease (PD).MethodsThirty DBS sleep studies were included by searching PubMed, Embase, and the Cochrane Library, and only 21 prospectively designed studies, including 541 patients, were eligible for the main analysis. We evaluated sleep disturbance using 1 objective measurement, polysomnography (PSG), and 4 subjective scales, including PD Sleep Scale (PDSS), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and restless legs syndrome (RLS). We pooled data using the standard mean difference (SMD). The primary outcome was a change in sleep parameters 6 months postoperatively. Outcomes from <12 months to ≥12 months follow-up were compared in the subgroup analysis. Meta-regression was further conducted.ResultsSTN-DBS significantly improved all 4 subjective sleep scales in the 6-month follow-up: ESS (SMD = 0.234), PDSS (SMD = 0.724), PSQI (SMD = 1.374) and RLS (SMD = 1.086), while most PSG parameters remained unchanged, except for shortened rapid eye movement sleep latency (RSL) (SMD = 0.520). In the over-12-month follow-up, improvement persisted in PDSS but not in ESS. Dopamine drug reduction (p = 0.009) and motor improvement (p = 0.036) were correlated with ESS improvement and PDSS improvement, respectively.ConclusionsBilateral STN-DBS continuously improved subjective nocturnal sleep, while its effect on ESS lasted for only 1 year. Medication reduction and motor improvement may contribute to improved daytime sleepiness and better subjective nocturnal sleep, respectively. Except for a shortened RSL, STN-DBS did not change PSG parameters, including sleep efficiency and sleep architecture.RegistrationOpen Science Framework: DOI 10.17605/OSF.IO/3EGRC.     

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。