Deep-brain stimulation in the subthalamic nuclei improves balance performance in patients with Parkinson's disease, when tested without anti-parkinsonian medication

OBJECTIVE: To evaluate the effect of bilateral deep-brain stimulation (DBS) in the subthalamic nucleus (STN) on balance performance in patients with severe Parkinson's disease (PD), when tested without anti-parkinsonian medication. MATERIAL AND METHODS: Thirty-one patients (median age 65 years, range 50-77) were included. Assessments were made after 10-12 h withdrawal of medication, before and 6 and 12 months after surgery. Postoperative evaluations were performed with DBS on and off. Balance performance was evaluated with the Berg Balance Scale (BBS). Motor symptoms and postural stability (item 30) were assessed with the Unified Parkinson's Disease Rating Scale (UPDRS III). RESULTS: DBS in STN improved balance performance as well as postural stability and motor symptoms significantly (P 相似文献   

Deep brain stimulation of the subthalamic nucleus for control of extrapyramidal features in advanced idiopathic Parkinson's disease: one year follow-up

Summary. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) with a quadripolar electrode was carried out in 9 patients with advanced idiopathic Parkinson's disease (PD) affected with severe diurnal motor fluctuations. The effect of bilateral STN stimulation was evaluated by clinical methods in all patients after 3 and 12 months. Assessment was based on the Unified Parkinson's Disease Rating Scale (UPDRS), timed motor tests, the Schwab and England Activities of Daily Living and a diary chart to document motor fluctuations. Alterations in parkinsonian signs, motor performance and functional outcome were recorded postoperatively (1) under temporary complete withdrawal of both STN stimulation and medication; (2) in the presence of STN stimulation only; and (3) in the presence of both STN stimulation and medication. The results were compared with the preoperative data assessed in defined on-phase and defined off-phase. STN stimulation on (compared to STN stimulation off) results in a significant improvement in UPDRS motor scores: after 3 months from 50.5 ± 14.3 to 27.8 ± 5.8, and after 12 months from 49.4 ± 14.1 to 27.1 ± 7.1 (p < 0.01). There was a significant decrease in the average duration of off-periods from 8.82 ± 2.47 hours to 1.00 ± 1.06 hours (p < 0.001), a marked increase in on-periods without dyskinesia from 4.62 ± 2.72 to 14.62 ± 1.51 hours (p < 0.01), and a sharp drop in on-periods with dyskinesia from 2.87 (± 4.18) to 0.25 (± 0.97) hours (p < 0.05), which remained stable up to 12 months (off-periods: 1.25 ± 1.58 hours, p < 0.001; on-periods without: 13.87 ± 1.95 hours, p < 0.001; and on-periods wth dyskinesia: 0.37 ± 1.06 hours, p < 0.05). However, our first PD patient with an implanted DBS electrode within the STN died from cardiac infarction two days after surgery. This sudden death was not linked either to surgery nor to stimulation – and happened by chance. Our findings confirm that STN stimulation is a suitable functional neurosurgical procedure for the modulation and control of PD signs associated with severe motor fluctuations, in that they demonstrate a beneficial effect which was fully sustained over a one year follow-up period. Received June 25, 1998; accepted February 3, 1999     

3D left hyperschematia after right brain damage

ABSTRACT

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves the motor symptoms of Parkinson’s disease (PD). The STN may represent an important relay station not only in the motor but also the associative cortico-striato-thalamocortical pathway. Therefore, STN stimulation may alter cognitive functions, such as working memory (WM). We examined cortical effects of STN-DBS on WM in early PD patients using functional near-infrared spectroscopy. The effects of dopaminergic medication on WM were also examined. Lateral frontal activity during WM maintenance was greater when patients were taking dopaminergic medication. STN-DBS led to a trend-level worsening of WM performance, accompanied by increased lateral frontal activity during WM maintenance. These findings suggest that STN-DBS in PD might lead to functional modifications of the basal ganglia-thalamocortical pathway during WM maintenance.     

Unilateral vs. bilateral STN DBS effects on working memory and motor function in Parkinson disease

Bilateral subthalamic nucleus deep brain stimulation (STN DBS) can reduce working memory while improving motor function in Parkinson disease (PD), but findings are variable. One possible explanation for this variability is that the effects of bilateral STN DBS on working memory function depend in part on functional or disease asymmetry. The goal of this study was to determine the relative contributions of unilateral DBS to the effects seen with bilateral DBS. Motor (Unified Parkinson Disease Rating Scale Part III, UPDRS) and working memory function (Spatial Delayed Response, SDR) were measured in 49 PD patients with bilateral STN DBS while stimulators were Both-off, Left-on, Right-on and Both-on in a randomized, double-blind manner. Patients were off PD medications overnight. Effects of unilateral DBS were compared to effects of bilateral STN DBS. Mean UPDRS and SDR responses to Left-on vs. Right-on conditions did not differ (p>.20). However, improvement in contralateral UPDRS was greater and SDR performance was more impaired by unilateral DBS in the more affected side of the brain than in the less affected side of the brain (p=.008). The effect of unilateral DBS on the more affected side on contralateral UPDRS and SDR responses was equivalent to that of bilateral DBS. These results suggest that motor and working memory function respond to unilateral STN DBS differentially depending on the asymmetry of motor symptoms.     

Disease progression continues in patients with advanced Parkinson's disease and effective subthalamic nucleus stimulation

OBJECTIVES: Glutamate mediated excitotoxicity of the hyperactive subthalamic nucleus (STN) has been reported to contribute to nigral degeneration in Parkinson's disease (PD). Deep brain stimulation of the STN (STN DBS), in its role as a highly effective treatment of severe PD motor complications, has been thought to inhibit STN hyperactivity and therefore decrease progression of PD. METHODS: In a prospective two centre study, disease progression was determined by means of serial (18)F-fluorodopa (F-dopa) positron emission tomography (PET) in 30 patients with successful STN DBS over the first 16 (SD 6) months after surgery. RESULTS: Depending on the method of PET data analysis used in the two centres, annual progression rates relative to baseline were 9.5-12.4% in the caudate and 10.7-12.9% in the putamen. CONCLUSIONS: This functional imaging study is the first to demonstrate a continuous decline of dopaminergic function in patients with advanced PD under clinically effective bilateral STN stimulation. The rates of progression in patients with STN DBS were within the range of previously reported data from longitudinal imaging studies in PD. Therefore this study could not confirm the neuroprotective properties of DBS in the STN target.     

Subthalamic nucleus stimulation is efficacious in patients with Parkinsonism and LRRK2 mutations.

Stimulation of the subthalamic nucleus (STN) improves motor signs in patients with levodopa-responsive Parkinson's disease (PD). Mutations in the leucine-rich repeat kinase-2 (LRRK2) gene cause Parkinsonism. We assessed 69 patients under STN stimulation and found heterozygous LRRK2 mutations in 9 (G2019S in 8 and T2031S in 1). The age at onset of PD, the clinical characteristics before or after neurosurgery, and the clinical response to STN stimulation were similar in both groups. Two patients with the G2019S LRRK2 mutation still benefited from STN stimulation, 9 and 10 years after surgery. Patients with LRRK2 mutations are, therefore, good candidates for STN stimulation.     

Stimulation of the subthalamic region facilitates the selection and inhibition of motor responses in Parkinson's disease

The aim of the present study was to specify the involvement of the basal ganglia in motor response selection and response inhibition. Two samples were studied. The first sample consisted of patients diagnosed with Parkinson's disease (PD) who received deep-brain stimulation (DBS) of the subthalamic nucleus (STN). The second sample consisted of patients who received DBS for the treatment of PD or essential tremor (ET) in the ventral intermediate nucleus of the thalamus (Vim). Stop-signal task and go/no-go task performances were studied in both groups. Both groups performed these tasks with (on stimulation) and without (off stimulation) DBS to address the question of whether stimulation is effective in improving choice reaction time (RT) and stop-signal RT. The results show that DBS of the STN was associated with significantly enhanced inhibitory control, as indicated by shorter stop-signal RTs. An additional finding is that DBS of the STN led to significantly shorter choice RT. The effects of DBS on responding and response inhibition were functionally independent. Although DBS of the Vim did not systematically affect task performance in patients with ET, a subgroup of Vim-stimulated PD patients showed enhanced stop-signal RTs in on stimulation versus off stimulation. This result suggests that the change in performance to stop signals may not be directly related to STN function, but rather results from a change in PD function due to DBS in general. The findings are discussed in terms of current functional and neurobiological models that relate basal ganglia function to the selection and inhibition of motor responses.     

Ten-Hertz stimulation of subthalamic nucleus deteriorates motor symptoms in Parkinson's disease.

Recently, a pathological oscillatory network at 10 Hz including several motor areas was described in patients with idiopathic Parkinson's disease (PD). In 7 PD patients, we tested the clinical effect of subthalamic nucleus (STN) stimulation at varying frequencies 1 to 3 years after implantation of electrodes. STN stimulation at 10 Hz induced significant worsening of motor symptoms, especially akinesia, compared with no stimulation and therapeutic stimulation (> or =130 Hz). This finding indicates the clinical relevance of pathological 10 Hz synchronization in PD.     

Bilateral subthalamic nucleus stimulation improves balance control in Parkinson's disease

BACKGROUND: Parkinson's disease (PD), the most common basal ganglia degenerative disease, affects balance control, especially when patients change balance strategy during postural tasks. Bilateral chronic stimulation of the subthalamic nucleus (STN) is therapeutically useful in advanced PD, and reduces the motor signs of patients. Nevertheless, the effects of STN stimulation on postural control are still debatable. AIMS: To assess the impact of bilateral STN stimulation on balance control in PD and to determine how basal ganglia related sensorimotor modifications act on neurosensorial organisation of balance and motor postural programming. METHODS: Twelve subjects aged 45-70 years underwent unified Parkinson's disease rating scale motor (part III) clinical tests, static and dynamic posturography, including sensory organisation and adaptation tests, shortly before and six months after bilateral implantation of electrodes into the STN. RESULTS: The postoperative static test showed an improvement in postural control precision both in eyes open and eyes closed conditions. The dynamic test highlighted the decreased number of falls and the ability of the patients to develop more appropriate sensorimotor strategies when stimulated. The sensory organisation test showed an improvement of equilibrium score and, thus, a better resolution of sensorial conflicts. CONCLUSIONS: STN stimulation allowed a reduction in rigidity and therefore an improvement in the ability to use muscular proprioception as reliable information, resulting in vestibulo-proprioceptive conflict suppression. STN stimulation has a synergistic effect with levodopa for postural control. Accordingly, non-dopaminergic pathways could be involved in postural regulation and STN stimulation may influence the functioning of these pathways.     

Effects of levodopa and subthalamic nucleus stimulation on cognitive and affective functioning in Parkinson's disease.

In Parkinson's disease (PD), levodopa and subthalamic nucleus (STN) stimulation lead to major improvement in motor symptoms. Effects of both treatments on cognition and affective status are less well understood. Motor, cognitive, and affective symptoms may relate to the dysfunctioning of parallel cortico-striatal loops. The aim of this study was to assess cognition, behavior, and mood, with and without both treatments in the same group of PD patients. A group of 22 nondemented PD patients was included in this study. Patients were tested twice before surgery (off and on levodopa) and twice 3 months after surgery (OFF and ON STN stimulation, off levodopa). Cognitive and affective effects of STN stimulation and levodopa had some common, but also different, effects. STN stimulation improved performance on the planning test, associated with the dorsolateral prefrontal cortex. However, the treatments had opposite effects on tests associated with the orbitofrontal cortex; specifically, levodopa impaired while STN stimulation improved performance on the extinction phase of a reversal/extinction task. Acutely, both treatments improved motivation and decreased fatigue and anxiety. On chronic treatment (3 months after surgery), depression improved, whereas apathy worsened 3 months after surgery. To conclude, there were significant but contrasting effects of levodopa and STN stimulation on cognition and affective functions.     

Effects of subthalamic nucleus stimulation on actual and imagined movement in Parkinson's disease : a PET study

BACKGROUND: PET studies in moderately affected Parkinson's disease (PD) patients reveal abnormal cerebral activation during motor execution and imagery, but the effects of subthalamic nucleus (STN) stimulation are not well established. OBJECTIVES: to assess the effect of STN stimulation on cerebral activation during actual and imagined movement in patients with advanced PD. METHODS: seven severely affected PD patients treated with bilateral STN stimulation were studied with PET and H(2)(15)O. The following conditions were investigated: (1). rest; (2). motor execution of a sequential predefined joystick movement with the right hand and (3). motor imagery of the same task. Patients were studied with and without left STN stimulation while right stimulator remained off. RESULTS: Without STN stimulation, the primary motor cortex was activated only during motor execution whereas the dorsolateral prefrontal cortex (DLPFC) was activated only during motor imagery. An activation of the supplementary motor area (SMA) was seen during both motor execution and motor imagery. Left STN stimulation during motor execution increased the regional cerebral blood flow (rCBF) bilaterally in the prefrontal cortex including DLPFC, in the left thalamus and putamen. In addition, a reduction of rCBF was noted in the right primary motor cortex, inferior parietal lobe and SMA. Under left STN stimulation, during motor imagery, rCBF increased bilaterally in the DLPFC and in the left thalamus and putamen and decreased in the left SMA and primary motor cortex. CONCLUSION: STN stimulation during both motor execution and imagery tends to improve the functioning of the frontal-striatal-thalamic pathway and to reduce the recruitment of compensatory motor circuits notably in motor, premotor and parietal cortical areas.     

Improved asymmetry of gait in Parkinson's disease with DBS: Gait and postural instability in Parkinson's disease treated with bilateral deep brain stimulation in the subthalamic nucleus

Postural instability is a sign of progression of Parkinson's disease (PD) and often resistant to levodopa treatment. To explore the effect of bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) on postural stability and gait, full body gait analyses were performed without medication, OFF and ON DBS in eight PD patients and 12 healthy age‐matched controls. DBS setting was changed at least 3 hours before gait analysis. To describe asymmetry most and least affected sides (MAS and LAS) were rated with the Unified Parkinson's Disease Rating Scale, motor part and quantitative gait analysis with the Vicon 612 gait analysis system. Stride length and gait velocity but not cadence improved ON DBS. The distances between the heel markers and center of mass (COM) were asymmetric and reduced OFF DBS. STN DBS increased the distances significantly and reduced asymmetry. The improvement in heel to COM distance was larger on the MAS compared with the LAS. OFF DBS knee momentum asymmetry was inversed so that LAS was more impaired than MAS. ON DBS asymmetry improved. PD patients OFF DBS place the heel too close to COM. The most affected body side has the most impaired swing and the result is a smaller knee moment on the opposite and least affected body side and an asymmetric gait pattern with disturbed balance OFF STN DBS. The asymmetry OFF DBS improved ON DBS. We suggest that DBS facilitates symmetric gait and thereby improves balance during gait. © 2008 Movement Disorder Society     

Mortality in patients with Parkinson's disease treated by stimulation of the subthalamic nucleus.

Subthalamic nucleus (STN) stimulation improves motor disability and quality of life in patients with advanced Parkinson's disease (PD). Short-term mortality is low, but little is known about long-term mortality. We assessed mortality and causes of death in 171 consecutive PD patients treated by STN stimulation. Surgery was performed after a median lagtime of 13 years from PD onset at a median age of 57 years. The median follow-up after surgery was 41 months. Sixteen patients died 8 to 83 months after neurosurgery. Poorer cognitive function was the only predictive factor for mortality (standardized mortality ratio = 2.9; 95% confidence interval [CI], 1.6-4.7; P < 0.0001). Based on a historical comparison of 118 operated patients with 39 nonoperated patients from a different population, survival among operated patients was not better (hazard ratio = 1.2; 95% CI, 0.7-2.1).     

Pallidal vs subthalamic nucleus deep brain stimulation in Parkinson disease

BACKGROUND: Deep brain stimulation (DBS) of the globus pallidus interna (GPi) and subthalamic nucleus (STN) has been reported to relieve motor symptoms and levodopa-induced dyskinesia in patients with advanced Parkinson disease (PD). Although it has been suggested that stimulation of the STN may be superior to stimulation of the GPi, comparative trials are limited. OBJECTIVE: To extend our randomized, blinded pilot comparison of the safety and efficacy of STN and GPi stimulation in patients with advanced PD. DESIGN: This study represents the combined results from our previously published, randomized, blinded, parallel-group pilot study and additional patients enrolled in our single-center extension study. SETTING: Oregon Health and Science University in Portland.Patients Twenty-three patients with idiopathic PD, levodopa-induced dyskinesia, and response fluctuations were randomized to implantation of bilateral GPi or STN stimulators. Patients and evaluating clinicians were blinded to stimulation site. All patients were tested preoperatively while taking and not taking medications and after 3, 6, and 12 months of DBS. MAIN OUTCOME MEASURES: Postoperatively, response of symptoms to DBS, medication, and combined medication and DBS was evaluated. Twenty patients (10 in the GPi group and 10 in the STN group) completed 12-month follow-up. RESULTS: Off-medication Unified Parkinson's Disease Rating Scale motor scores were improved after 12 months of both GPi and STN stimulation (39% vs 48%). Bradykinesia tended to improve more with STN than GPi stimulation. No improvement in on-medication function was observed in either group. Levodopa dose was reduced by 38% in STN stimulation patients compared with 3% in GPi stimulation patients (P = .08). Dyskinesia was reduced by stimulation at both GPi and STN (89% vs 62%). Cognitive and behavioral complications were observed only in combination with STN stimulation. CONCLUSION: Stimulation of either the GPi or STN improves many features of advanced PD. It is premature to exclude GPi as an appropriate target for DBS in patients with advanced disease.     

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。     

Stimulation of the subthalamic nucleus in Parkinson's disease: a 5 year follow up

BACKGROUND: The short term benefits of bilateral stimulation of the subthalamic nucleus (STN) in patients with advanced levodopa responsive Parkinson's disease (PD) are well documented, but long term benefits are still uncertain. OBJECTIVES: This study provides a 5 year follow up of PD patients treated with stimulation of the STN. METHODS: Thirty seven consecutive patients with PD treated with bilateral STN stimulation were assessed prospectively 6, 24, and 60 months after neurosurgery. Parkinsonian motor disability was evaluated with and without levodopa treatment, with and without bilateral STN stimulation. Neuropsychological and mood assessments included the Mattis Dementia Rating Scale, the frontal score, and the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: No severe peri- or immediate postoperative side effects were observed. Six patients died and one was lost to follow up. Five years after neurosurgery: (i) activity of daily living (Unified Parkinson Disease Rating Scale (UPDRS) II) was improved by stimulation of the STN by 40% ("off" drug) and 60% ("on" drug); (ii) parkinsonian motor disability (UPDRS III) was improved by 54% ("off" drug) and 73% ("on" drug); (iii) the severity of levodopa related motor complications was decreased by 67% and the levodopa daily doses were reduced by 58%. The MADRS was unchanged, but cognitive performance declined significantly. Persisting adverse effects included eyelid opening apraxia, weight gain, addiction to levodopa treatment, hypomania and disinhibition, depression, dysarthria, dyskinesias, and apathy. CONCLUSIONS: Despite moderate motor and cognitive decline, probably due to disease progression, the marked improvement in motor function observed postoperatively was sustained 5 years after neurosurgery.     

Clinical and economic results of bilateral subthalamic nucleus stimulation in Parkinson's disease

BACKGROUND: High frequency stimulation of the subthalamic nucleus (STN) is an alternative but expensive neurosurgical treatment for parkinsonian patients with levodopa induced motor complications. OBJECTIVE: To assess the safety, clinical effects, quality of life, and economic cost of STN stimulation. METHODS: We conducted a prospective multicentre study in 95 consecutive Parkinson's disease (PD) patients receiving bilateral STN stimulation and assessed its effects over 12 months. A double blind randomised motor evaluation was carried out at 3 month follow up, and quality of life, self care ability, and predictive factors of outcome following surgery were assessed. The cost of PD was estimated over 6 months before and after surgery. RESULTS: The Unified Parkinson's Disease Rating Scale (UPDRS) motor score improved by 57% (p<0.0001) and activities of daily living improved by 48% (p<0.0001) at 12 month follow up. Double blind motor scoring improved by 51% at 3 month follow up (p<0.0001). The total PD Quality of Life Questionnaire (PDQL-37) score improved by 28% (p<0.001). The better the preoperative motor score after a levodopa challenge, the better the outcome after STN stimulation. Five patients developed an intracerebral haematoma during electrode implantation with permanent after effects in two. The 6 month costs of PD decreased from 10,087 euros before surgery to 1673 euros after surgery (p<0.0001) mainly because of the decrease in medication. These savings allowed a return on the procedure investment, estimated at 36,904 euros over 2.2 years. CONCLUSIONS: STN stimulation has good outcomes with relatively low risk and little cost burden in PD patients with levodopa induced motor complications.     

Bilateral subthalamic nucleus stimulation in advanced Parkinson’s disease

Objective To assess the long-term efficacy and safety of chronic bilateral stimulation of the subthalamic nucleus (STN) in patients with advanced Parkinson’s disease (PD). Methods 36 consecutive patients with idiopathic Parkinson’s disease treated with bilateral stimulation of the STN were studied. Parkinsonian status was assessed preoperatively and at 1 and 3 years postoperatively using the Unified Parkinson’s Disease Rating Scale (UPDRS) and neuropsychological evaluation in on and off-medication / on and off stimulation conditions. Results At 3 years follow-up, STN stimulation reduced the UPDRS motor score by 54.2 % compared to baseline in the off-medication conditions. Tremor, rigidity, bradykinesia, postural stability, and gait improved by 72.2 %, 62.4 %, 56.8 %, 40.5 % and 45.3 %, respectively. UPDRS part II scores were reduced by 41.4 %. The overall dopaminergic drugs dose was reduced by 48.6 % after surgery and four patients were no longer taking antiparkinsonian medication at three years. However, axial dopa-unresponsive signs worsened in some patients. The most frequent transient adverse event consisted in mood disorders in 23 patients. Conclusions Our data demonstrate that: 1) bilateral STN stimulation is relatively safe, improves the motor symptoms and drug-related motor complications of PD, and reduces the daily dosage of medication; 2) this benefit is sustained over time despite the occurrence of axial doparesistant signs in some patients.     

丘脑底核与苍白球内侧部电刺激术治疗帕金森病疗效的Meta分析

目的 系统评价脑深部电刺激术（DBS）作用丘脑底核（STN）与苍白球内侧部（GPi）治疗帕金森病（PD）的疗效。方法 计算机检索2015年6月之前在PubMed、Cochrane Library、Embase、CNKI及VIP等数据库中DBS作用STN或GPi治疗PD的随机临床对照研究,按纳入排除标准进行资料的筛选和提取,利用RevMan 5.3软件进行Meta分析。结果 纳入7个研究共613例患者,其中STN组331例,GPi组282例。Meta分析显示,STN-DBS与GPi-DBS治疗后,患者运动症状改善效果（SMD=0.36;95% CI为-0.07~0.78;P=0.10）及生活质量改善（SMD=-0.20,95%CI为-0.78~0.39;P=0.51）相似,且术后3年均效果稳定。STN组较GPi组能明显减少术后药物用量（SMD=0.37;95% CI为0.19~0.55;P<0.0001）;gpi组抑郁发生率较stn组明显减少（rr ci为="" 1.28~2.27;p="0.0003）。结论 STN-DBS与GPi-DBS治疗PD后,患者运动症状改善效果与生活质量改善效果相似,STN -DBS能有效减少术后用药量,GPi-DBS术后抑郁发生率更低。