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Introduction: We present our surgical complications resulting in neurological deficit or additional surgery during 25 years of DBS of the subthalamic nucleus (STN) for Parkinson's disease (PD). Methods: We conducted a retrospective chart review of all PD patients that received STN DBS in our DBS center between 1998 and 2023. Outcomes were complications resulting in neurological deficit or additional surgery. Potential risk factors (number of microelectrode recording tracks, age, anesthesia method, hypertension, and sex) for symptomatic intracerebral hemorrhage (ICH) were analyzed. Furthermore, lead fixation techniques were compared. Results: Eight hundred PD patients (507 men, 293 women) received unilateral (n = 11) or bilateral (n = 789) implantation of STN electrodes. Neurological deficit due to ICH, edema, delirium, or infarction was seen in 8.4% of the patients (7.4% transient, 1.0% permanent). Twenty-two patients (2.8%) had a symptomatic ICH following STN DBS, for which we did not find any risk factors, and five had permanent sequelae due to ICH (0.6%). Of all patients, 18.4% required additional surgery; the proportion was reduced from 27% in the first 300 cases to 13% in the last 500 cases (p < 0.001). The infection rate was 3.5%, which decreased from 5.3% in the first 300 cases to 2.2% in the last 500 cases. The use of a lead anchoring device led to significantly less lead migrations than miniplate fixation. Conclusion: STN DBS leads to permanent neurological deficit in a small number of patients (1.0%), but a substantial proportion needs some additional surgical procedure after the first DBS system implantation. The risk of revision surgery was reduced over time but remained significant. These findings need to be discussed with the patient in the preoperative informed consent process in addition to the expected health benefit. [ABSTRACT FROM AUTHOR]

Deep Brain Stimulation can improve tremor, bradykinesia, rigidity, and axial symptoms in patients with Parkinson's disease. Potentially, improving each symptom may require stimulation of different white matter tracts. Here, we study a large cohort of patients (N = 237 from five centers) to identify tracts associated with improvements in each of the four symptom domains. Tremor improvements were associated with stimulation of tracts connected to primary motor cortex and cerebellum. In contrast, axial symptoms are associated with stimulation of tracts connected to the supplementary motor cortex and brainstem. Bradykinesia and rigidity improvements are associated with the stimulation of tracts connected to the supplementary motor and premotor cortices, respectively. We introduce an algorithm that uses these symptom-response tracts to suggest optimal stimulation parameters for DBS based on individual patient's symptom profiles. Application of the algorithm illustrates that our symptom-tract library may bear potential in personalizing stimulation treatment based on the symptoms that are most burdensome in an individual patient. Different motor symptoms respond variably to deep brain stimulation in Parkinson's Disease. Rajamani et al. suggest that this variability may be due to tremor, bradykinesia, rigidity, and axial symptoms being associated with a gradient of brain circuits. [ABSTRACT FROM AUTHOR]

Background: Primary orthostatic tremor (OT) can affect patients' life. Treatment of OT with deep brain stimulation (DBS) of the thalamic ventral intermediate nucleus (Vim) is described in a limited number of patients. The Vim and posterior subthalamic area (PSA) can be targeted in a single trajectory, allowing both stimulation of the Vim and/or dentatorubrothalamic tract (DRT). In essential tremor this is currently often used with positive effects. Objective: To evaluate the efficacy of Vim/DRT‐DBS in OT‐patients, based on standing time and Quality of Life (QoL), also on the long‐term. Furthermore, to relate stimulation of the Vim and DRT, medial lemniscus (ML) and pyramidal tract (PT) to beneficial clinical and side‐effects. Methods: Nine severely affected OT‐patients received bilateral Vim/DRT‐DBS. Primary outcome measure was standing time; secondary measures included self‐reported measures, neurophysiological measures, structural analyses, surgical complications, stimulation‐induced side‐effects, and QoL up to 56 months. Stimulation of volume of tissue activated (VTA) were related to outcome measures. Results: Average maximum standing time increased from 41.0 s ± 51.0 s to 109.3 s ± 65.0 s after 18 months, with improvements measured in seven of nine patients. VTA (n = 7) overlapped with the DRT in six patients and with the ML and/or PT in six patients. All patients experienced side‐effects and QoL worsened during the first year after surgery, which improved again during long‐term follow‐up, although remaining below age‐related normal values. Most patients reported a positive effect of DBS. Conclusion: Vim/DRT‐DBS improved standing time in patients with severe OT. Observed side‐effects are possibly related to stimulation of the ML and PT. [ABSTRACT FROM AUTHOR]

Background: Deep brain stimulation (DBS) is efficacious for treating motor symptoms in Parkinson's disease (PD). Objectives: The aim is to evaluate the evidence regarding DBS effectiveness after postoperative cognitive deterioration, the impact of preoperative cognition on DBS effectiveness, and the impact of DBS on cognition. Methods: Literature searches were performed on MEDLINE, EMBASE, and CENTRAL (Cochrane library). Primary outcomes were OFF‐drug Unified Parkinson Disease Rating Scale Part III score and cognitive test scores. Results: DBS effectiveness did not differ in patients with postoperative declining compared to stable cognition (n = 5 studies). Preoperative cognition did not influence DBS effectiveness (n = 1 study). DBS moderately decreased verbal fluency compared to the best medical treatment (n = 24 studies), which may be transient. Conclusion: DBS motor effectiveness in PD does not appear to be influenced by cognition. DBS in PD seems cognitively safe, except for a moderate decline in verbal fluency. Further research is warranted. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background: Identifying the dorsolateral subthalamic nucleus (STN) for deep brain stimulation (DBS) in Parkinson's disease (PD) can be challenging due to the size and double‐oblique orientation. Since 2015 we implemented 7‐Tesla T2 weighted magnetic resonance imaging (7 T T2) for improving visualization and targeting of the dorsolateral STN. We describe the changes in surgical planning and outcome since implementation of 7 T T2 for DBS in PD. Methods: By comparing two cohorts of STN DBS patients in different time periods we evaluated the influence of 7 T T2 on STN target planning, the number of microelectrode recording (MER) trajectories, length of STN activity and the postoperative motor (UPDRS) improvement. Results: From February 2007 to January 2014, 1.5 and 3‐Tesla T2 guided STN DBS with 3 MER channels was performed in 76 PD patients. Average length of recorded STN activity in the definite electrode trajectory was 3.9 ± 1.5 mm. From January 2015 to January 2022 7 T T2 and MER‐guided STN DBS was performed in 182 PD patients. Average length of recorded STN activity in the definite electrode trajectory was 5.1 ± 1.3 mm and used MER channels decreased from 3 to 1. Average UPDRS improvement was comparable. Conclusion: Implementation of 7 T T2 for STN DBS enabled a refinement in targeting. Combining classical DBS targeting with dorsolateral STN alignment may be used to determine the optimal trajectory. The improvement in dorsolateral STN visualization can be used for further target refinements, for example adding probabilistic subthalamic connectivity, to enhance clinical outcome of STN DBS. [ABSTRACT FROM AUTHOR]

This document provides information about a study on deep brain stimulation (DBS) surgery for Parkinson's disease (PD). It discusses the types of analyses and data availability for the study, as well as references and assessments used. The document includes a disclaimer stating that the content has not been vetted or peer-reviewed. [Extracted from the article]

12 Merello M, Nouzeilles MI, Cammarota A, Betti O, Leiguarda R. Comparison of 1-year follow-up evaluations of patients with indication for pallidotomy who did not undergo surgery versus patients with Parkinson's disease who did undergo pallidotomy: a case control study. Deep brain stimulation plus best medical therapy versus best medical therapy alone for advanced Parkinson's disease (PD SURG trial): a randomised, open-label trial. [[5]] Indeed, it was the solid and robust effect of posteroventral pallidotomy on dopa-induced dyskinesias and dystonia in subjects with advanced Parkinson's disease (PD) that paved the way for using this very same brain target in the surgical treatment of non-parkinsonian dystonia, whether by pallidotomy or by pallidal DBS[[20]]. [Extracted from the article]

Background: Subthalamic nucleus deep brain stimulation (STN DBS) is an established therapy for Parkinson's disease (PD) patients suffering from motor response fluctuations despite optimal medical treatment, or severe dopaminergic side effects. Despite careful clinical selection and surgical procedures, some patients do not benefit from STN DBS. Preoperative prediction models are suggested to better predict individual motor response after STN DBS. We validate a preregistered model, DBS-PREDICT, in an external multicenter validation cohort. Methods: DBS-PREDICT considered eleven, solely preoperative, clinical characteristics and applied a logistic regression to differentiate between weak and strong motor responders. Weak motor response was defined as no clinically relevant improvement on the Unified Parkinson's Disease Rating Scale (UPDRS) II, III, or IV, 1 year after surgery, defined as, respectively, 3, 5, and 3 points or more. Lower UPDRS III and IV scores and higher age at disease onset contributed most to weak response predictions. Individual predictions were compared with actual clinical outcomes. Results: 322 PD patients treated with STN DBS from 6 different centers were included. DBS-PREDICT differentiated between weak and strong motor responders with an area under the receiver operator curve of 0.76 and an accuracy up to 77%. Conclusion: Proving generalizability and feasibility of preoperative STN DBS outcome prediction in an external multicenter cohort is an important step in creating clinical impact in DBS with data-driven tools. Future prospective studies are required to overcome several inherent practical and statistical limitations of including clinical decision support systems in DBS care. [ABSTRACT FROM AUTHOR]

The subthalamic nucleus and internal pallidum are main target sites for deep brain stimulation in Parkinson's disease. Multiple trials that investigated subthalamic versus pallidal stimulation were unable to settle on a definitive optimal target between the two. One reason could be that the effect is mediated via a common functional network. To test this hypothesis, we calculated connectivity profiles seeding from deep brain stimulation electrodes in 94 patients that underwent subthalamic and 28 patients with pallidal treatment based on a normative connectome atlas calculated from 1000 healthy subjects. In each cohort, we calculated connectivity profiles that were associated with optimal clinical improvements. The two maps showed striking similarity and were able to cross-predict outcomes in the respective other cohort (R = 0.37 at P < 0.001; R = 0.34 at P = 0.032). Next, we calculated an agreement map, which retained regions common to both target sites. Crucially, this map was able to explain an additional amount of variance in clinical improvements of either cohort when compared to the maps calculated on each cohort alone. Finally, we tested profiles and predictive utility of connectivity maps calculated from different motor symptom subscores with a specific focus on bradykinesia and rigidity. While our study is based on retrospective data and indirect connectivity metrics, it may deliver empirical data to support the hypothesis of a largely overlapping network associated with effective deep brain stimulation in Parkinson's disease irrespective of the specific target. [ABSTRACT FROM AUTHOR]

Notwithstanding the large improvement in motor function in Parkinson's disease (PD) patients treated with deep brain stimulation (DBS), apathy may increase. Postoperative apathy cannot always be related to a dose reduction of dopaminergic medication and stimulation itself may play a role. We studied whether apathy in DBS-treated PD patients could be a stimulation effect. In 26 PD patients we acquired apathy scores before and >6 months after DBS of the subthalamic nucleus (STN). Magnetoencephalography recordings (ON and OFF stimulation) were performed ≥6 months after DBS placement. Change in apathy severity was correlated with (i) improvement in motor function and dose reduction of dopaminergic medication, (ii) stimulation location (merged MRI and CT-scans) and (iii) stimulation-related changes in functional connectivity of brain regions that have an alleged role in apathy. Average apathy severity significantly increased after DBS (p < 0.001) and the number of patients considered apathetic increased from two to nine. Change in apathy severity did not correlate with improvement in motor function or dose reduction of dopaminergic medication. For the left hemisphere, increase in apathy was associated with a more dorsolateral stimulation location (p = 0.010). The increase in apathy severity correlated with a decrease in alpha1 functional connectivity of the dorsolateral prefrontal cortex (p = 0.006), but not with changes of the medial orbitofrontal or the anterior cingulate cortex. The present observations suggest that apathy after STN-DBS is not necessarily related to dose reductions of dopaminergic medication, but may be an effect of the stimulation itself. This highlights the importance of determining optimal DBS settings based on both motor and non-motor symptoms. • Apathy severity increases after deep brain stimulation (DBS) of the subthalamic nucleus in Parkinson's disease. • Post-DBS apathy does not correlate with dose reduction of dopaminergic medication. • Increased post-operative apathy scores correlate with stimulation position. • And with stimulation-induced changes in functional connectivity (MEG). • Apathy after DBS may be an effect of the stimulation itself. [ABSTRACT FROM AUTHOR]

Introduction: For deep brain stimulation (DBS) surgery of the subthalamic nucleus (STN) in Parkinson's disease (PD), many centers employ visualization of the nucleus on magnetic resonance imaging (MRI), intraoperative microelectrode recordings (MER), and test stimulation in awake patients. The value of these steps is a subject for ongoing debate. In the current study, we determined the relative contribution of MRI targeting, multitrack MER, and awake test stimulation in final lead placement during STN DBS surgery for PD. Methods: Data on PD patients undergoing MRI-targeted STN DBS surgery with three-channel MER and awake test stimulation between February 2010 and January 2014 were analyzed to determine in which MER trajectory final leads were implanted and why this tract was chosen. Results: Seventy-six patients underwent implantation of 146 DBS leads. In 92% of the STN, the final leads were implanted in one of the three planned channels. In 6%, additional channels were needed. In 2%, surgery was aborted before final lead implantation due to anxiety or fatigue. The final leads were implanted in the channels with the longest STN MER signal trajectory in 60% of the STN (38% of the bilaterally implanted patients). This was the central channel containing the MRI target in 39% of the STN (18% bilaterally). The most frequently noted reasons why another channel than the central channel was chosen for final lead placement were (1) a lower threshold for side effects (54%) and (2) no or a too short trajectory of the STN MER signal (40%) in the central channel. The latter reason correlated with larger 2D (x and y) errors in our stereotactic method. Conclusions: STN DBS leads were often not implanted in the MRI-planned trajectory or in the trajectory with the longest STN MER signal. Thresholds for side effects during awake test stimulation were decisive for final target selection in the majority of patients. [ABSTRACT FROM AUTHOR]

When oral dopaminergic medication falls short in the treatment of Parkinson's disease, patients are left with motor response fluctuations and dyskinesias that may have a large impact on functioning in daily life. They may benefit from one of the currently available advanced treatments, namely deep brain stimulation, continuous levodopa-carbidopa intestinal gel, and continuous subcutaneous apomorphine infusion. The indication, choice between the separate advanced treatments and the timing can be challenging and will be discussed against the background of the progressive nature of the disease, the heterogeneity of disease manifestation and variable patient characteristics. [ABSTRACT FROM AUTHOR]

Background: 7.0-T T2-weighted MRI offers excellent visibility of the subthalamic nucleus (STN), which is used as a target for deep brain stimulation (DBS) in Parkinson's disease (PD). A comparison of 7.0-T MRI to microelectrode recordings (MER) for STN border identification has not been performed. Objective: To compare representation of STN borders on 7.0-T T2 MRI with the borders identified during MER in patients undergoing DBS for PD and to evaluate whether STN identification on 7.0-T T2 MRI leads to alterations in stereotactic target planning. Design/Methods: STN border identification was done using volumetric 7.0-T T2 MRI acquisitions. This was compared to the STN borders identified by MER. STN target planning was independently performed by 3 DBS surgeons on T2 imaging using 1.5-, 3.0-, and 7.0-T MRI. Results: A total of 102 microelectrode tracks were evaluated in 19 patients. Identification of the dorsal STN border was well feasible on 7-T T2, whereas the ventral STN was un-distinguishable from the substantia nigra. The dorsal STN border on MRI was located more dorsal than MER in 73% of trajectories. The average distance from MRI to MER border was 0.9 mm (range –4.4 to +3.5 mm). STN target planning showed high correspondence between the 3 field strengths. Conclusion: 7.0-T T2 MRI offers the possibility of easy identification of the dorsal border of the STN. However, higher field strength MRI does not change the planning of the target. Compared to MER, the dorsal border on MRI was located more dorsal in the majority of cases, situating MER activity within STN representation. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the possible influence of electrode trajectories penetrating the caudate nucleus (CN) on cognitive outcomes in deep brain stimulation (DBS) surgery for Parkinson's disease (PD). Background: It is currently unclear how mandatory CN avoidance during trajectory planning is. Design/Methods: Electrode trajectories were determined to be inside, outside, or in border region of the CN. Pre- and postoperative neuropsychological tests of each trajectory group were compared in order to evaluate possible differences in cognitive outcomes 12 months after bilateral STN DBS. Results: One hundred six electrode tracks in 53 patients were evaluated. Bilateral penetration of the CN occurred in 15 (28%) patients, while unilateral penetration occurred in 28 (53%). In 19 (36%) patients tracks were located in the border region of the CN. There was no electrode penetration of the CN in 10 (19%) patients. No difference in cognitive outcomes was found between the different groups. Conclusion: Cognitive outcome was not influenced by DBS electrode tracks penetrating the CN. It is both feasible and sensible to avoid electrode tracks through the CN when possible, considering its function and anatomical position. However, penetration of the CN can be considered without major concerns regarding cognitive decline when this facilitates optimal trajectory planning due to specific individual anatomical variations. [ABSTRACT FROM AUTHOR]

Objective: The objective of this review was to update evidence-based medicine recommendations for treating motor symptoms of Parkinson's disease (PD).Background: The Movement Disorder Society Evidence-Based Medicine Committee recommendations for treatments of PD were first published in 2002 and updated in 2011, and we continued the review to December 31, 2016.Methods: Level I studies of interventions for motor symptoms were reviewed. Criteria for inclusion and quality scoring were as previously reported. Five clinical indications were considered, and conclusions regarding the implications for clinical practice are reported.Results: A total of 143 new studies qualified. There are no clinically useful interventions to prevent/delay disease progression. For monotherapy of early PD, nonergot dopamine agonists, oral levodopa preparations, selegiline, and rasagiline are clinically useful. For adjunct therapy in early/stable PD, nonergot dopamine agonists, rasagiline, and zonisamide are clinically useful. For adjunct therapy in optimized PD for general or specific motor symptoms including gait, rivastigmine is possibly useful and physiotherapy is clinically useful; exercise-based movement strategy training and formalized patterned exercises are possibly useful. There are no new studies and no changes in the conclusions for the prevention/delay of motor complications. For treating motor fluctuations, most nonergot dopamine agonists, pergolide, levodopa ER, levodopa intestinal infusion, entacapone, opicapone, rasagiline, zonisamide, safinamide, and bilateral STN and GPi DBS are clinically useful. For dyskinesia, amantadine, clozapine, and bilateral STN DBS and GPi DBS are clinically useful.Conclusions: The options for treating PD symptoms continues to expand. These recommendations allow the treating physician to determine which intervention to recommend to an individual patient. © 2018 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background: Individual motor improvement after deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson's disease (PD) varies considerably. Stereotactic targeting of the dorsolateral sensorimotor part of the STN is considered paramount for maximising effectiveness, but studies employing the midcommissural point (MCP) as anatomical reference failed to show correlation between DBS location and motor improvement. The medial border of the STN as reference may provide better insight in the relationship between DBS location and clinical outcome.Methods: Motor improvement after 12 months of 65 STN DBS electrodes was categorised into non-responding, responding and optimally responding body-sides. Stereotactic coordinates of optimal electrode contacts relative to both medial STN border and MCP served to define theoretic DBS 'hotspots'.Results: Using the medial STN border as reference, significant negative correlation (Pearson's correlation -0.52, P<0.01) was found between the Euclidean distance from the centre of stimulation to this DBS hotspot and motor improvement. This hotspot was located at 2.8 mm lateral, 1.7 mm anterior and 2.5 mm superior relative to the medial STN border. Using MCP as reference, no correlation was found.Conclusion: The medial STN border proved superior compared with MCP as anatomical reference for correlation of DBS location and motor improvement, and enabled defining an optimal DBS location within the nucleus. We therefore propose the medial STN border as a better individual reference point than the currently used MCP on preoperative stereotactic imaging, in order to obtain optimal and thus less variable motor improvement for individual patients with PD following STN DBS. [ABSTRACT FROM AUTHOR]

We thank Weill and colleagues for their valuable comments.1 Their observations corroborate our findings of cognitive decline post-deep brain stimulation (DBS) in PD patients carrying I GBA i mutations ( I GBA i -PD) and they, like us, question the long-term risk-to-benefit of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) in these patients. We do not claim that STN-DBS be categorically avoided in I GBA i -PD patients, rather, approached cautiously, and I GBA i status may be a factor that is useful when considering the risk-benefit profile of STN-DBS. They caution, however, against a potential bias introduced by our use of nonoperated I GBA i -PD patients accessed through the Parkinson's Progression Marker's Initiative,2 as these patients may have had a milder clinical profile than the I GBA i -PD patients who underwent STN-DBS, and we acknowledge this limitation of our study. [Extracted from the article]

Aims: To investigate whether deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) or the subthalamic nucleus (STN) improve lower urinary tract symptoms (LUTS) in advanced Parkinson's disease (PD). Methods: An exploratory post‐hoc analysis was performed of specific LUTS items of questionnaires used in a randomized clinical trial with 128 patients (NSTAPS study). First, we compared scores on LUTS items at baseline and 12 months for the GPi DBS and STN DBS group separately. Second, we divided the group by sex, instead of DBS location; to assess a possible gender associated influence of anatomical and pathophysiological differences, again comparing scores at baseline and 12 months. Third, we reported on Foley‐catheter use at baseline and after 12 months. Results: Urinary incontinence and frequency improved after both GPi DBS and STN DBS at 12 months, postoperatively, but this was only statistically significant for the STN DBS group (P = 0.004). The improvements after DBS were present in both men (P = 0.01) and women (P = 0.05). Nocturia and urinary incontinence did not improve significantly after any type of DBS, irrespective of sex. At 12 months, none of the patients had a Foley‐catheter. Conclusions: Urinary incontinence and frequency significantly improved after STN DBS treatment in male and female patients with PD. Nocturia and nighttime incontinence due to parkinsonism did not improve after DBS, irrespective of gender. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to assess psychiatric and social outcome 12 months after bilateral deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) and subthalamic nucleus (STN) for advanced Parkinson's disease (PD).Methods: We randomly assigned patients to receive GPi DBS (n = 65) or STN DBS (n = 63). Standardized psychiatric and social questionnaires were assessed at baseline and after 12 months.Results: No differences were found between GPi DBS and STN DBS on psychiatric evaluation. Within-group comparisons showed small but statistically significant changes on several measures in both groups. Descriptive statistics indicated slight changes in social functioning. Marital satisfaction of patients and partners remained relatively stable after GPi and STN DBS.Conclusions: We found neither differences in psychiatric and social outcome between GPi DBS and STN DBS nor any relevant within-group differences. The decision for GPi DBS or STN DBS cannot be based on expected psychiatric or social effects. [ABSTRACT FROM AUTHOR]

Background: Tinnitus is a disorder of the nervous system that cannot be adequately treated with current therapies. The effect of neuromodulation induced by deep brain stimulation (DBS) on tinnitus has not been studied well. This study investigated the effect of DBS on tinnitus by use of a multicenter questionnaire study. Methods: Tinnitus was retrospectively assessed prior to DBS and at the current situation (with DBS). From the 685 questionnaires, 443 were returned. A control group was one-to-one matched to DBS patients who had tinnitus before DBS (n = 61). Tinnitus was assessed by the tinnitus handicap inventory (THI) and visual analog scales (VAS) of loudness and burden. Results: The THI decreased significantly during DBS compared to the situation prior to surgery (from 18.9 to 15.1, P < .001), which was only significant for DBS in the subthalamic nucleus (STN). The THI in the control group (36.9 to 35.5, P = 0.50) and other DBS targets did not change. The VAS loudness increased in the control group (5.4 to 6.0 P < .01). Conclusion: DBS might have a modulatory effect on tinnitus. Our study suggests that DBS of the STN may have a beneficial effect on tinnitus, but most likely other nuclei linked to the tinnitus circuitry might be even more effective [ABSTRACT FROM AUTHOR]

Animal studies have shown that central dopamine signaling influences glucose metabolism. As a first step to show this association in an experimental setting in humans, we studied whether deep brain stimulation (DBS) of the subthalamic nucleus (STN), which modulates the basal ganglia circuitry, alters basal endogenous glucose production (EGP) or insulin sensitivity in patients with Parkinson's disease (PD). We studied 8 patients with PD treated with DBS STN, in the basal state and during a hyperinsulinemic euglycemic clamp using a stable glucose isotope, in the stimulated and non-stimulated condition. We measured EGP, hepatic insulin sensitivity, peripheral insulin sensitivity (Rd), resting energy expenditure (REE), glucoregulatory hormones, and Parkinson symptoms, using the Unified Parkinson's Disease Rating Scale (UPDRS). Basal plasma glucose and EGP did not differ between the stimulated and non-stimulated condition. Hepatic insulin sensitivity was similar in both conditions and there were no significant differences in Rd and plasma glucoregulatory hormones between DBS on and DBS off. UPDRS was significantly higher in the non-stimulated condition. DBS of the STN in patients with PD does not influence basal EGP or insulin sensitivity. These results suggest that acute modulation of the motor basal ganglia circuitry does not affect glucose metabolism in humans. [ABSTRACT FROM AUTHOR]

Background: Subthalamic nucleus (STN) deep brain stimulation effectively improves parkinsonian symptoms. It is hypothesized that distinct functional territories with different neurophysiologic activity within the STN relate to different symptoms. Objective: The aim of the study was to identify distinctive characteristics of STN neuronal activity related to tremor by directly comparing tremor sides with no-tremor sides. In addition, we studied the spatial pattern of frequency distributions within the STN in more detail. Methods: We analyzed intraoperative STN single/multiunit recordings from 33 tremor sides and 23 no-tremor sides. STN tracks were normalized to a length of 1 and subdivided into eight successive layers. The power spectral density was split into six frequency bands: theta (3-8 Hz), alpha (9-12 Hz), lower beta (13-20 Hz), upper beta (21-30 Hz), lower gamma (31-59 Hz), and upper gamma (60-100 Hz). Results: Tremor sides presented predominant theta frequency oscillations in the most dorsal layers of the STN, whereas in no-tremor sides beta frequencies predominated. Oscillatory activity was stronger in the dorsal STN than in the ventral, and this pattern was specific for frequencies in the theta, alpha, and beta bands, but not in the gamma bands. Conclusions: Our study supports the hypothesis that the presence of tremor is associated with a distinctive neuronal oscillations pattern. In particular, we demonstrate the specificity of the association of theta frequencies in the dorsal STN with tremor. Identification of symptom-specific characteristics of intraoperative microrecordings in the STN may lead to refinement of targeting for each patient, tailored to the specific clinical presentation. [ABSTRACT FROM AUTHOR]

Parkinsonian patients, who have had a unilateral pallidotomy, may require bilateral deep brain stimulation of the subthalamic nucleus (STN), due to disease progression. The current model of the basal ganglia circuitry does not predict a direct effect of pallidotomy on the neuronal activity of the ipsilateral STN. To date, only three studies have investigated the effect of pallidotomy on overall activity of the STN or neuronal firing rate, but not on the spectral content of the neuronal oscillatory activity. Moreover, none of these studies attempted to differentiate the effects on the dorsal (sensory-motor) and ventral (associative-limbic) parts of the STN. We studied the effect of pallidotomy on spectral power in six frequency bands in the STN ipsilateral and contralateral to pallidotomy from seven patients and in 60 control nuclei of patients without prior functional neurosurgery, and investigated whether this effect is different on the dorsal and ventral STN. The data show that pallidotomy suppresses beta power (13-30 Hz) in the ipsilateral STN. This effect tends predominantly to be present in the dorsal part of the STN. In addition, spectral power in the frequency range 3-30 Hz is significantly higher in the dorsal part than in the ventral part. The effect of pallidotomy on STN neural activity is difficult to explain with the current model of basal ganglia circuitry and should be envisaged in the context of complex modulatory interactions in the basal ganglia. [ABSTRACT FROM AUTHOR]

There is a growing interest in deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) as a potential therapeutic modality for Parkinson's disease dementia (PDD). Low-frequency stimulation has yielded encouraging results in individual patients; however, these are not yet sustained in larger studies. With the aim to expand the understanding of NBM-DBS, we share our experience with serendipitous NBM-DBS in patients treated with DBS of the internal Globus pallidus (GPi) for Parkinson's disease. Since NBM is anatomically located ventral to GPi, several GPi-treated patients appeared to have the distal contact of DBS-electrode(s) positioned in the NBM. We hypothesized that unintentional high-frequency NBM-DBS over a period of one year would result in the opposite effect of low-frequency NBM-stimulation and cause cognitive decline. We studied a cohort of 33 patients with bilateral high-frequency DBS in the GPi for Parkinson's disease, of which twelve were unintentionally co-stimulated in NBM. The subgroups of unintentional unilateral (N = 7) and bilateral NBM-DBS (N = 5) were compared to the control group of bilateral GPi-DBS (N = 11). Here, we show that unintentional high-frequency NBM-DBS did not cause a significantly faster decline in cognitive function. Further research is warranted for characterizing the therapeutic role of NBM-DBS. [ABSTRACT FROM AUTHOR]

In 2018, developments in Parkinson disease (PD) research yielded improved diagnostic criteria and provided evidence for the effects of some treatments, both old and new. These developments enrich the treatment options available for PD and are likely to change important guideline recommendations. The new diagnostic criteria for Parkinson disease (PD) yield high diagnostic specificity, but modest sensitivity2.Although many drugs have failed to protect against disease progression in trials, exenatide is a promising new candidate5.Subcutaneous infusion of apomorphine, a dopamine agonist, shortens the off-time of patients with advanced PD according to a confirmatory double-blind study6.A secondary analysis of a trial testing deep brain stimulation of the subthalamic nucleus against the best available medical treatment has shown that it improves impulse control disorders8.Pulsed focused ultrasound lesioning, an invasive procedure without incision, was successfully used in the subthalamic nucleus as a treatment of PD with motor response fluctuations10. [ABSTRACT FROM AUTHOR]

(1) Background: Deep brain stimulation (DBS) and continuous intrajejunal levodopa infusion (CLI) are efficacious treatments of medication related motor response fluctuations in advanced Parkinson's disease (PD). Literature regarding the use of both advanced treatments within one patient is scarce. (2) Methods: We present a retrospective single center case series and a review of the literature. Patients with PD who were treated with both DBS and CLI in our tertiary referral center between 2005 and 2020 were identified and medical records were assessed. Additionally, literature on patients treated with both therapies was systematically searched for in Medline and Embase. (3) Results: Nineteen patients were included. Medication related motor response fluctuations were a major indication for the second therapy in all but one. Of nine patients initially treated with DBS, five reported improvement with CLI. Seven of ten patients initially treated with CLI experienced benefits from DBS. The systematic literature search resulted in fifteen previous publications comprising 66 patients. Of the 59 patients, for whom the effect of the second treatment was known, 57 improved. (4) Conclusions: PD patients, who have persisting medication related motor response fluctuations, despite DBS or CLI treatment, may benefit from an additional or alternative treatment with either CLI or DBS. [ABSTRACT FROM AUTHOR]

Motor improvement after deep brain stimulation (DBS) in the subthalamic nucleus (STN) may vary substantially between Parkinson's disease (PD) patients. Research into the relation between improvement and active contact location requires a correction for anatomical variation. We studied the relation between active contact location relative to the neurophysiological STN, estimated by the intraoperative microelectrode recordings (MER-based STN), and contralateral motor improvement after one year. A generic STN shape was transformed to fit onto the stereotactically defined MER sites. The location of 43 electrodes (26 patients), derived from MRI-fused CT images, was expressed relative to this patient-specific MER-based STN. Using regression analyses, the relation between contact location and motor improvement was studied. The regression model that predicts motor improvement based on levodopa effect alone was significantly improved by adding the one-year active contact coordinates (R2 change = 0.176, p = 0.014). In the combined prediction model (adjusted R2 = 0.389, p < 0.001), the largest contribution was made by the mediolateral location of the active contact (standardized beta = 0.490, p = 0.002). With the MER-based STN as a reference, we were able to find a significant relation between active contact location and motor improvement. MER-based STN modeling can be used to complement imaging-based STN models in the application of DBS. [ABSTRACT FROM AUTHOR]

Introduction: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a widely used surgical treatment for severe Parkinson's disease (PD). However, post-operative motor improvement can vary greatly between patients, which might be caused by varying locations of the stimulating contact point. Research into the relation between motor improvement and active contact point (ACP) location using standard anatomical landmarks (AC-PC) may suffer from inaccuracy caused by anatomical variations between patients. Studies using the MRI-defined STN may also suffer from inaccuracy because the STN can be hard to identify in preoperative MRI. Therefore, in this study, we use the intraoperative microelectrode recordings (MER) to create a detailed estimation of STN size and location and then study the relation between motor improvement and ACP location relative to this MER-defined STN. Methods: For this study, we used 43 STNs of 26 patients, from the Dutch NSTAPS trial that had 1) assessment of PD motor symptoms preoperative and one year postoperative, 2) CT imaging of the implanted lead one year postoperative and 3) intraoperative MER that measured STN activity on at least three channels. STN size and location was estimated by automatically transforming a general biconvex lens-shaped STN to fit optimally on the MER measurement sites scored as either inside or outside the STN. The one year postoperative CT was fused with preoperative T1 MRI including stereotactic frame, stereotactic ACP location was manually determined and combined with the patient specific MER-defined STN. Finally, the STN and the ACP location together were transformed back to the original biconvex lens shape. This way, the ACP locations of the entire group could all be studied relative to one general STN shape. Per STN, the DBS-induced motor improvement was defined as the combined off-levodopa improvement on the UPDRS III of strictly contralateral motor symptoms as a percentage of the preoperative combined contralateral off-levodopa UPDRS III score. Location data was statistically analyzed using both standard multiple regression and independent samples T-tests. For the latter, two groups were defined based on the percentage of motor improvement: DBS-responders who showed a contralateral improvement of 50% or more (n = 27) and non-responders who improved less than 50% (n = 16). Results: For the group of DBS-responders, the mean ACP location one year after surgery was 0.8 mm lateral, 1.5 mm anterior and 2.1 mm dorsal to the center of the MER-defined STN. Independent samples T-tests showed that the ACP location relative to the general STN in the non-responder group was significantly more medial (smaller x-coordinate) than in the responder group (p = 0.045). No significant differences were found in the y- and zcoordinates representing the anterior-posterior and the dorsal-ventral directions respectively. Standard multiple regression showed that the x-, y- and z-coordinates of the ACP location together explain 37% of the variance in contralateral motor improvement (adjusted R square = 0.365, p < 0.0005). Further evaluation of the three directions in this regression showed that both the x- and the z-coordinates of ACP location made a significant unique contribution to the prediction of motor improvement. A more medial ACP location had the most pronounced negative contribution to the prediction of motor improvement (beta = -0.66, p < 0.0005), thus predicting less motor improvement. A more dorsal ACP location also predicted less motor improvement although its contribution was smaller (beta = -0.36, p = 0.016). Discussion: In this study we showed that a relation between ACP location and motor improvement can be found when determining the ACP locations relative to the MER-defined STN. The advantage of this method is that it takes into account the anatomical variations in STN location without depending on high quality MRI images. In DBS surgery it is important to target the anterior part of the dorsolateral STN, which corresponds to the sensorimotor area. Stimulation on contacts that are located more medial or more dorsal results in significantly less motor improvement. This has implications for both the lead placement during surgery and the postoperative selection of contacts for stimulation. During surgery, the MER-defined STN could be helpful in preventing too medial implantation and during contact selection the MER-defined STN could be used to prevent too dorsal stimulation. [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is the most effective surgical procedure for patients with advanced Parkinson's disease (PD). Precise targeting of the STN is paramount for maximizing therapeutic benefits while minimizing side effect. In most DBS centers, preoperative visualization of the STN on stereotactic T2-weighted magnetic resonance imaging (MRI), neurophysiological mapping of the target region through microelectrode recordings (MER) and intraoperative test stimulation in awake patients are performed to optimize STN targeting. However, it is unclear to what extent these different operative steps influence the decision where to implant the final electrode during DBS surgery. In the current study we retrospectively analyzed the relative value of these three operative steps in final electrode placement in 76 patients with advanced PD undergoing stereotactic Leksell frame-based implantation of 147 STN electrodes. In all patients, we used 3-channel MER with the planned MRI trajectory as the central channel, with additional anterior and lateral channels at 2-mm distance from the central channel. The central channel (=planned MRI trajectory) was chosen for final electrode placement in 39% of all leads, the anterior channel in 46%, and the lateral channel in 10%. In 5%, final electrodes were implanted in another channel (medial or anteromedial). In only 12 of 71 bilaterally operated patients (17%), final electrodes were implanted bilaterally in the planned MRI trajectory. In 50% of all leads, the channel chosen for final electrode placement was the channel with the longest STN-MER signal. The reason for not choosing the planned MRI trajectory for final electrode placement was most often low threshold for lateral (internal capsule) side effects during test stimulation, followed by no or very short STN-MER signal or medial (autonomic and oculomotor) side effects. The reason for not choosing the channel with longest STN-MER signal for final electrode placement was low threshold for lateral (internal capsule) side effects during test stimulation for almost all cases. In conclusion, the results of the current analysis suggest that both MRI, MER and awake test stimulation all contribute to the decision where to implant the final electrode during STN DBS surgery. Their relative values should be kept in mind when considering performing STN DBS surgery without MER or under general anesthesia. [ABSTRACT FROM AUTHOR]

Background: 7-Tesla T2-weighted Magnetic Resonance Imaging (MRI) offers improved visibility of the dorsolateral subthalamic nucleus (STN), which is considered the optimal location for deep brain stimulation (DBS) in Parkinson's Disease (PD). However, it is unknown whether the dorsolateral STN on 7-Tesla T2 corresponds to the neurophysiological location. Objective: To compare dorsolateral STN border identified on 7.0-Tesla T2-weighted MRI with the border obtained during microelectrode recordings (MER) in patients undergoing DBS for PD. Methods: Dorsolateral border identification was done using axial and coronal orientated 7.0-Tesla T2-weigthed MRI. This was compared to dorsolateral border identified by MER. Results: A total of 108 microelectrode tracks were evaluated in 19 patients. For the central and anterior microelectrode channel, the dorsolateral STN border on MRI was located more superior in 74% of trajectories compared to MER. Average distance from MRI to MER border was 1.0 millimeter. Conclusion: 7-Tesla T2 MRI offers the possibility of dorsolateral STN identification. In the vast majority of cases this border was located more superior compared to MER. For STN DBS, the optimal location on 7-Tesla MRI is located just below the dorsolateral border. [ABSTRACT FROM AUTHOR]

Objective: Relating active contact localization in subthalamic nucleus deep brain stimulation (STN DBS) to long-term motor symptom outcome by using midcommisural point (MCP) and medial border of STN as anatomical reference point. Background: Good motor symptom outcome after STN DBS is assumed to require accurate implantation of DBS electrodes. However, thus far several studies found no difference in mean stereotactic coordinates of active contact relative to MCP between patient that do or do not improve well after DBS. Anatomical variance in STN size and location relative to MCP have potentially hampered such analyses. Medial border of STN may serve as a landmark less subjected to anatomical variance and could provide more insight in individual optimal point of stimulation. Design/Methods: Stereotactic coordinates active electrode contact relative to both MCP and medial STN border were determined using preoperative stereotactic 1.5-Tesla MRI and postoperative CT. Medial STN border was determined on axial orientated MRI at the level of anterior border of the RN (Bejjani line). Resulting coordinates in X (medial-lateral), Y (anterior-posterior) and Z (dorsal-ventral) were plotted using 2D graphs. Change in off phase UPDRS motor score after 12 months of STN DBS was categorized into three groups: non-responding (less than 30%), responding (between 30 and 70%) and optimally responding (more than 70%) contralateral body-sides. Corresponding change in unilateral UPDRS motor score for individual coordinate points were subsequently integrated into the plots. Results: A total of 50 DBS leads were evaluated in 25 patients with PD. Unilateral off phase UPDRS motor score for responding and optimally responding body-sides showed average improvement of 57% and 89%, respectively. Average change in unilateral off phase UPDRS motor score was 8% deterioration for non-responding body-sides. Active electrode contacts of optimal response were located significantly more lateral, anterior and dorsal relative to medial STN border in comparison to non-response. This 'hot spot' was situated in superolateral STN. Plots based on MCP did not show differences in contact point localization between groups. Conclusion: Medial STN border proved to be superior compared to MCP as anatomical reference point for relating active contact localization in STN DBS to long-term motor symptom outcome. Stereotactic coordinates of stimulation points relative to medial STN border indicate an optimal area of stimulation in the nucleus. Unsatisfactory effect of DBS could be evaluated with the aid of this area and the contact point most closely situated considered for stimulation. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the clinical effect of re-operation to another target after failure of initial deep brain stimulation (DBS) for Parkinson's disease (PD). Methods: We descriptively analyzed the baseline characteristics, the effect of initial surgery and re-operation of NSTAPS (Netherlands SubThalamic and Pallidal Stimulation) patients and previously published cases that underwent re-operation to a different target. The evaluation included motor symptoms at baseline (off-drug and on-drug), after initial DBS surgery (on-stimulation, off-drug), before re-operation (on-stimulation, off-drug), and after re-operation (on-stimulation, off-drug). We evaluated motor symptoms using the Unified Parkinson's Disease Rating Scale motor examination (UPDRS-III). For the NSTAPS, blinded assessments were available at 12 and 36 months after the initial surgery. We dichotomized motor outcome: an off-drug UPDRS-III score improvement of 30% or more one year after DBS compared to baseline is considered a treatment success and less than 30% is considered unsuccessful. Results: A total of 14 patients were identified in the NSTAPS (n = 8) study and literature review (n = 6). NSTAPS Trial: The mean off-drug UPDRS-III before the first surgery (baseline) was 45 (range 24-88), and the mean percentage of improvement with levodopa was 71% (range 49-82%). Re-operation occurred between 12 and 67 months after start of DBS therapy. The mean pre-re-operation off-drug UPDRS-III score was 39 (range 22-56) and the mean score after re-operation was 31 (range 18-40), with two postoperative scores missing. In quantitative terms, two of the eight re-operations were considered a success, that is, a UPDRS-III improvement greater than 30%. Subjectively, five of the eight patients considered their re-operation a success. Literature Review: three articles were identified that describe a total of six cases, of which three patients initially received bilateral GPi DBS and three received STN DBS (supplement 1). The off-drug UPDRS-III score at baseline was not available in most patients and the percentage of improvement on levodopa was available in three patients only (57%, 81%, 74%). Of the patients who were re-operated from STN to GPi none had improvement of their off-drug UPDRS-III scores (-3%, -11%, -22%), but two of them reported subjective improvement. All patients who were reoperated from GPi to STN had a post-operative improvement of the off-drug UPDRS-III (37%, 59%, 64%) and also subjectively experienced improvement. Summary of all cases: Five out of 11 patients that were re-operated from GPi DBS to STN DBS showed more than 30% improvement of off-drug motor symptoms. Of the three patients reoperated from STN DBS to GPi DBS, none showed more than 30% off-drug motor improvement. Conclusions: Half the patients re-operated to STN DBS showed objective clinical improvement of more than 30% on the off-drug UPDRS-III score. However, three out of five of these improved cases were from the systematic review, so this finding is prone to a publication bias. None of the three patients re-operated to GPi DBS showed objective improvement. In conclusion, if insufficient clinical improvement is obtained after GPi DBS and patient selection and electrode placement were correct, re-operation to the STN is worth considering. Currently, there are insufficient data that indicate if re-operating from STN to GPi has a comparable effect. [ABSTRACT FROM AUTHOR]

Objective: Evaluating aligning ventral intermediate nucleus (VIM) and posterior subthalamic area (PSA) in one surgical trajectory for deep brain stimulation (DBS) in essential tremor (ET). Background: Both VIM DBS and more recent PSA DBS have shown to suppress tremor for ET. Considering it is currently not clear which target is optimal for individual patients we wanted to explore both during intraoperative test stimulation. For this, we applied the technique of aligning both targets in one surgical trajectory. Design/Methods: Technical aspects of planned trajectories, intraoperative test stimulation findings, final lead placement, target used for chronic stimulation and adverse and beneficial effects were evaluated. Results: In 17 patients representing 33 planned trajectories (16 bilateral, one unilateral), we successfully aligned VIM and PSA targets in one surgical trajectory in 26 (79%) trajectories (15 patients). Average trajectory distance between both targets was 7.5 mm (range 6-10). In 17 aligned trajectories, optimal intraoperative tremor suppression was obtained in PSA. During follow up, optimal active electrode contacts of these leads were in or just above PSA in the large majority of cases. In the remaining 9 aligned trajectories, optimal intraoperative tremor suppression was obtained in VIM (n = 3) or the area just above PSA (n = 6). During follow up, most active electrode contacts of these latter six leads were in VIM. Overall, successful tremor control was achieved in 74% of contralateral body sides, or 69% of patients. Stimulation-induced dysarthria or gait ataxia occurred in, respectively, 56% and 19%. No difference in tremor suppression efficacy or side effect profile was noted between aligned and non-aligned leads, nor between the different anatomical locations of active stimulation. Conclusion: Alignment of VIM and PSA for DBS in ET is well feasible and enables intraoperative exploration of both in one single trajectory. This facilitates optimal positioning of electrode contacts in these adjacent areas, where multiple optimal points of stimulation can be found. In the majority of aligned leads, both optimal intraoperative tremor suppression and active contacts used for chronic stimulation were in or just above PSA. [ABSTRACT FROM AUTHOR]