Subthalamic Nucleus Deep Brain Stimulation Improves Saccades in Parkinson's Disease

Objectives. The clinical efficacy of subthalamic nucleus (STN) deep brain stimulation (DBS) for major motor symptoms of Parkinson's disease (PD) is well established, but its effects on visually guided vs. internally generated eye movements in the medication off state need to be studied further. Since the basal ganglia are thought to be involved in the generation of voluntary movements under internal control, we hypothesized that voluntary saccades would show improvements with STN DBS. Materials and Methods. Seven PD patients with STN DBS performed visually guided and internally generated (anti‐ and memory‐guided) saccades with STN DBS on and off following 12 hours of levodopa withdrawal. The change in saccade reaction time, first saccade gain, and final saccade gain with STN DBS were measured. Results. STN DBS improved the reaction time of visually guided saccades but not of anti‐ or memory‐guided saccades. STN DBS also improved the first saccade gain of the anti‐ and memory‐guided saccades, but not of the visually guided saccades. Conclusions. These results demonstrate that STN DBS has differential effects on the parameters of visually guided and internally generated saccades. These effects may be mediated by the influence of STN DBS on cortical ocular motor areas, the basal ganglia, ocular motor loop, or downstream structures such as the brainstem saccade generating circuits.     

Effects of Subthalamic Deep Brain Stimulation With Different Frequencies in a Parkinsonian Rat Model

ObjectiveSubthalamic deep brain stimulation (STN-DBS) could be an effective alternative treatment for patients with Parkinson’s disease (PD). However, the mechanisms of deep brain stimulation (DBS) at different frequencies are still unclear. In this study, diffusion tensor imaging (DTI) was used to detect parameter changes in different regions of rat brains after DBS, and rat exercise capacity and brain tissue immunohistochemistry were evaluated.Materials and MethodsThe 6-hydroxydopamine-induced hemi-parkinsonian rat models were made and divided into four groups: a control group, sham group, low-frequency group, and high-frequency group. Low-frequency (30 Hz) and high-frequency (130 Hz) DBS were given to the STN in rats. First, an open-field experiment was used to evaluate changes in exercise performance. Then, the DTI was used to measure parameter changes in the substantia nigra (SN). Finally, immunohistochemistry was used to analyze the expression of tyrosine hydroxylase (TH), NeuN, and α-synuclein (α-syn) in the SN in the rats.ResultsThere were significant differences in movement distance changes between the high-frequency stimulation (HFS) group and low-frequency stimulation (LFS) group, the HFS group and Ctrl group, and the Sham group and Ctrl group (all p < 0.05) after one week of stimulation. In the HFS group, the fractional anisotropy value of the SN was significantly higher than that of the other groups (p < 0.05), and the apparent diffusion coefficient and radial diffusion coefficient values were significantly lower than those of the other groups (p < 0.01). Immunohistochemical analysis showed that the integral optical density values of SN TH staining (p < 0.01) and NeuN staining (p < 0.05) in the HFS group were both significantly higher than those in the other groups.ConclusionSTN-HFS (130 Hz) and sham operation for one week can significantly improve the exercise performance of PD rats. The exercise performance of PD rats in LFS group (30 Hz) is worse compared with HFS group (130 Hz). HFS plays a role in neuroprotection and improvement of exercise performance of PD rats. Moreover, DTI can be used as an effective technique to assess the therapeutic effects and severity of PD.     

Deep Brain Stimulation of the Subthalamic Area for Dystonic Tremor

The stereotactic surgical target for dystonic tremor is the subject of ongoing debate. Targeting the subthalamic area using deep brain stimulation has been regaining interest as a therapy for various types of involuntary movements. We describe the efficacy of stimulation of the subthalamic area in a patient with intractable dystonic tremor. Excellent control without neurological complications was achieved. This case report demonstrates that the subthalamic area is a valuable target for the control of dystonic tremor.     

Effects of Contralateral Deep Brain Stimulation and Levodopa on Subthalamic Nucleus Oscillatory Activity and Phase-Amplitude Coupling

BackgroundThe modulatory effects of medication and deep brain stimulation (DBS) on subthalamic nucleus (STN) neural activity in Parkinson's disease have been widely studied. However, effects on the contralateral side to the stimulated STN, in particular, changes in local field potential (LFP) oscillatory activity and phase-amplitude coupling (PAC), have not yet been reported.ObjectiveThe aim of this study was to examine changes in STN LFP activity across a range of frequency bands and STN PAC for different combinations of DBS and medication on/off on the side contralateral to the applied stimulation.Materials and MethodsWe examined STN LFPs that were recorded using externalized leads from eight parkinsonian patients during unilateral DBS from the side contralateral to the stimulation. LFP spectral power in alpha (5 to ～13 Hz), low beta (13 to ～20 Hz), high beta (20–30 Hz), and high gamma plus high-frequency oscillation (high gamma+HFO) (100–400 Hz) bands were estimated for different combinations of medication and unilateral stimulation (off/on). PAC between beta and high gamma+HFO in the STN LFPs was also investigated. The effect of the condition was examined using linear mixed models.ResultsPAC in the STN LFP was reduced by DBS when compared to the baseline condition (no medication and stimulation). Medication had no significant effect on PAC. Alpha power decreased with DBS, both alone and when combined with medication. Beta power decreased with DBS, medication, and DBS and medication combined. High gamma+HFO power increased during the application of contralateral DBS and was unaltered by medication.ConclusionsThe results provide new insights into the effects of DBS and levodopa on STN LFP PAC and oscillatory activity on the side contralateral to stimulation. These may have important implications in understanding mechanisms underlying motor improvements with DBS, including changes on both contralateral and ipsilateral sides, while suggesting a possible role for contralateral sensing during unilateral DBS.     

双侧丘脑底核电刺激对帕金森病患者抑郁状况的影响

目的 探讨双侧丘脑底核脑深部电刺激对帕金森病患者抑郁状况的影响.方法 设置STN-DBS组及药物治疗对照组,配对人组,有效病例27对.两组患者均只服用左旋多巴制剂且剂量前后无显著变化,均未服用抗抑郁药物.前后共6次分别评估其抑郁及运动状况.结果 与术前及药物治疗组相比,STN-DBS组术后运动功能改善,抑郁状况短期内(3～6个月)改善;STN-DBS组术后运动评分与抑郁评分短期内(5周～6个月)相关,双侧电压均值与其抑郁评分均相关;STN-DBS组术后电压均值对抑郁评分的标准回归方程及回归系数均显著,运动评分对抑郁评分的标准回归方程及同归系数在短期内(5周～3个月)显著.结论 STN-DBS对PD患者运动障碍症状的改善在短期内可改善其抑郁状况,但长期效应不明显.在STN-DBS治疗电压值范围内,双侧电压均值越高,PD患者的抑郁状况越严重.     

Imaging of the Subthalamic Nucleus for Deep Brain Stimulation: A Systematic Review

It is still debated which neuroimaging technique should be preferred in targeting the subthalamic nucleus (STN) for implantation of stimulating electrodes. In the present study, we systematically analyzed the different imaging techniques and their outcome in reports describing original data on bilateral STN stimulation in advanced Parkinson's disease. Five different imaging techniques to target the STN for implantation of stimulating electrodes were reported: magnetic resonance imaging (MRI), MRI in combination with ventriculography, MRI in combination with computed tomography (CT), CT, and CT in combination with ventriculography. We found that patients who underwent STN deep brain stimulation with MRI (regardless the use of an additional imaging technique) had a significantly better Unified Parkinson's Disease Rating Scale motor score (mean improvement 58%) as compared to patients who underwent STN deep brain stimulation with CT imaging (regardless the use of an additional imaging technique; mean improvement 47%).     

Cognitive Effects of Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease with GBA1 Pathogenic Variants

Genetic subtyping of patients with Parkinson's disease (PD) may assist in predicting the cognitive and motor outcomes of subthalamic deep brain stimulation (STN-DBS). Practical questions were recently raised with the emergence of new data regarding suboptimal cognitive outcomes after STN-DBS in individuals with PD associated with pathogenic variants in glucocerebrosidase gene (GBA1-PD). However, a variety of gaps and controversies remain. (1) Does STN-DBS truly accelerate cognitive deterioration in GBA1-PD? If so, what is the clinical significance of this acceleration? (2) How should the overall risk-to-benefit ratio of STN-DBS in GBA1-PD be established? (3) If STN-DBS has a negative effect on cognition in GBA1-PD, how can this effect be minimized? (4) Should PD patients be genetically tested before STN-DBS? (5) How should GBA1-PD patients considering STN-DBS be counseled? We aim to summarize the currently available relevant data and detail the gaps and controversies that exist pertaining to these questions. In the absence of evidence-based data, all authors strongly agree that clinicians should not categorically deny DBS to PD patients based solely on genotype (GBA1 status). We suggest that PD patients considering DBS may be offered genetic testing for GBA1, where available and feasible, so the potential risks and benefits of STN-DBS can be properly weighed by both the patient and clinician. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

Apathy Induced by Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease: A Meta-Analysis

Apathy, the loss of motivation, is a common problem in Parkinson's disease (PD) and often observed following deep brain stimulation (DBS) of the subthalamic nucleus (STN). The aim of this meta-analysis was to determine the occurrence of apathy following STN DBS in literature. Relevant articles were searched in PubMed/Medline, SCOPUS, EMBASE, and Web of Sciences electronic databases. Studies were included if they reported apathy scores pre- and post-DBS or the cross-sectional difference between PD patients receiving STN DBS and patients receiving medication only. Thirty-three articles were included in the meta-analyses from 6,658 screened articles by two authors independently. A total of 1,286 patients were included with a mean age (±standard deviation [SD]) of 58.4 ± 8.5 years and a disease duration of 11.0 ± 5.8 years. The apathy score measured by means of the Apathy Evaluation Scale (AES), Starkstein Apathy Scale (SAS), and the Lille Apathy Rating Scale (LARS) was significantly higher after DBS than pre-operatively (g = 0.34, 95% confidence interval [CI] = 0.19–0.48, P < 0.001). An equal, significant difference in severity of apathy was found between STN DBS and medication only (g = 0.36, 95% CI = 0.03–0.65; P = 0.004). Statistical heterogeneity was moderately high, but the effects stood strong after multiple analyses and were independent of tapering off dopaminergic medication. The findings of this meta-analysis indicate that apathy is increased after STN DBS compared to the pre-operative state and to medication only (systematic review registration number: PROSPERO CRD42019133932). © 2020 Universiteit van Amsterdam. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society     

丘脑底核脑深部刺激术治疗帕金森病137例报道

目的：总结丘脑底核脑深部刺激术（DBS）治疗帕金森病（PD）的经验。方法：自2000年3月至2007年12月应用DBS治疗PD137例，其中单侧丘脑底核刺激68例，双侧丘脑底核刺激69例。术后1年（108例）、3年（43例）和5年（20例）分别进行PD评定量表（UPDRS）运动评分。结果：脉冲发生器开启时，在“关”期和“开”期状态下，术后1，3和5年UPDRS运动评分症状改善率分别为55．8％、53．4％和45．2％及22．5％、23．2％和20．4％。手术并发症主要有：肺部感染1例，脉冲发生器植入处胸部皮下感染1例，积液3例，头部刺激电极和皮下导线连接处皮肤破溃1例。二次手术调整刺激电极深度2例。无永久性并发症。结论：掌握适应证，规范手术操作和术中影像学验证是提高DBS疗效，降低并发症的关键。     

Spectral Topography of the Subthalamic Nucleus to Inform Next-Generation Deep Brain Stimulation

Background

The landscape of neurophysiological symptoms and behavioral biomarkers in basal ganglia signals for movement disorders is expanding. The clinical translation of sensing-based deep brain stimulation (DBS) also requires a thorough understanding of the anatomical organization of spectral biomarkers within the subthalamic nucleus (STN).

Objectives

The aims were to systematically investigate the spectral topography, including a wide range of sub-bands in STN local field potentials (LFP) of Parkinson's disease (PD) patients, and to evaluate its predictive performance for clinical response to DBS.

Methods

STN-LFPs were recorded from 70 PD patients (130 hemispheres) awake and at rest using multicontact DBS electrodes. A comprehensive spatial characterization, including hot spot localization and focality estimation, was performed for multiple sub-bands (delta, theta, alpha, low-beta, high-beta, low-gamma, high-gamma, and fast-gamma (FG) as well as low- and fast high-frequency oscillations [HFO]) and compared to the clinical hot spot for rigidity response to DBS. A spectral biomarker map was established and used to predict the clinical response to DBS.

Results

The STN shows a heterogeneous topographic distribution of different spectral biomarkers, with the strongest segregation in the inferior-superior axis. Relative to the superiorly localized beta hot spot, HFOs (FG, slow HFO) were localized up to 2 mm more inferiorly. Beta oscillations are spatially more spread compared to other sub-bands. Both the spatial proximity of contacts to the beta hot spot and the distance to higher-frequency hot spots were predictive for the best rigidity response to DBS.

Conclusions

The spatial segregation and properties of spectral biomarkers within the DBS target structure can additionally be informative for the implementation of next-generation sensing-based DBS. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

Utilizing 7-Tesla Subthalamic Nucleus Connectivity in Deep Brain Stimulation for Parkinson Disease

BackgroundDeep brain stimulation (DBS) of the subthalamic nucleus (STN) is a highly effective surgical treatment for patients with advanced Parkinson disease (PD). Combining 7.0-Tesla (7T) T2- and diffusion-weighted imaging (DWI) sequences allows for selective segmenting of the motor part of the STN and, thus, for possible optimization of DBS.Materials and Methods7T T2 and DWI sequences were obtained, and probabilistic segmentation of motor, associative, and limbic STN segments was performed. Left- and right-sided motor outcome (Movement Disorders Society Unified Parkinson’s Disease Rating Scale) scores were used for evaluating the correspondence between the active electrode contacts in selectively segmented STN and the clinical DBS effect. The Bejjani line was reviewed for crossing of segments.ResultsA total of 50 STNs were segmented in 25 patients and proved highly feasible. Although the highest density of motor connections was situated in the dorsolateral STN for all patients, the exact partitioning of segments differed considerably. For all the active electrode contacts situated within the predominantly motor-connected segment of the STN, the average hemi-body Unified Parkinson’s Disease Rating Scale motor improvement was 80%; outside this segment, it was 52% (p < 0.01). The Bejjani line was situated in the motor segment for 32 STNs.ConclusionThe implementation of 7T T2 and DWI segmentation of the STN in DBS for PD is feasible and offers insight into the location of the motor segment. Segmentation-guided electrode placement is likely to further improve motor response in DBS for PD. However, commercially available DBS software for postprocessing imaging would greatly facilitate widespread implementation.     

Stimulation-Induced Dyskinesia After Subthalamic Nucleus Deep Brain Stimulation in Patients With Meige Syndrome

ObjectivesDeep brain stimulation of the subthalamic nucleus (STN-DBS) is increasingly used to treat Meige syndrome (MS) and markedly improves symptoms. Stimulation-induced dyskinesia (SID), which adversely affects surgical outcomes and patient satisfaction, may, however, occur in some patients. This study attempts to explore possible causes of SID.Materials and MethodsRetrospectively collected clinical data on 32 patients who underwent STN-DBS between October 2016 and April 2019 were analyzed. Clinical outcomes were assessed pre- and post-surgery, using the Burke–Fahn–Marsden dystonia rating scale (BFMDRS). Patients were divided into a dyskinesia group and a non-dyskinesia group, according to whether or not they experienced persistent SID during follow-up. The coordinates of the active contacts were calculated from post-operative computerized tomography or magnetic resonance imaging, using the inter-commissural line as a reference. At final follow-up, the main stimulatory parameters for further study included pulse width, voltage, and frequency.ResultsAt final follow-up (mean = 16.3 ± 7.2 months), MS patients had improved BFMDRS total scores compared with pre-surgical scores (mean improvement = 79.0%, p < 0.0001). The mean improvement in BFMDRS total scores in the dyskinesia (n = 10) and non-dyskinesia (n = 22) groups were 81.6 ± 8.8% and 77.9 ± 14.2%, respectively. The mean minimum voltage to induce dyskinesia was 1.7 ± 0.3 V. The programmed parameters of both groups were similar. When compared with the non-dyskinesia group, active stimulatory contact coordinates in the dyskinesia group were inferior (mean left side: z = −2.3 ± 1.7 mm vs. z = −1.2 ± 1.5 mm; p = 0.0282; mean right side: z = −2.7 ± 1.9 mm vs. z = −2.3 ± 1.7 mm; p = 0.0256). The x and y coordinates were similar.ConclusionSTN-DBS is an effective intervention for MS, providing marked improvements in clinical symptoms; SID may, however occur in the subsequent programming control process. Comparing patients with/without dyskinesia, the active contacts were located closer to the inferior part of the STN in patients with dyskinesia, which may provide an explanation for the dyskinesia.