Staged Bilateral MRI-Guided Focused Ultrasound Subthalamotomy for Parkinson Disease.

Importance: Unilateral magnetic resonance imaging (MRI)-guided focused ultrasound subthalamotomy (FUS-STN) improves cardinal motor features among patients with asymmetrical Parkinson disease (PD). The feasibility of bilateral FUS-STN is as yet unexplored. Objective: To assess the safety and effectiveness of staged bilateral FUS-STN to treat PD. Design, Setting, and Participants: This prospective, open-label, case series study was conducted between June 18, 2019, and November 7, 2023, at HM-CINAC, Puerta del Sur University Hospital, Madrid, Spain, and included 6 patients with PD who had been treated with unilateral FUS-STN contralateral to their most affected body side and whose parkinsonism on the untreated side had progressed and was not optimally controlled with medication. Intervention: Staged bilateral FUS-STN. Main Outcomes and Measures: Primary outcomes were assessed 6 months after the second treatment and included safety (incidence and severity of adverse events after second treatment) and effectiveness in terms of motor change (measured with the Movement Disorders Society Unified Parkinson's Disease Rating Scale part III [MDS-UPDRS III]) in the off-medication state (ie, after at least 12 hours of antiparkinsonian drug withdrawal) compared with baseline (ie, prior to the first side ablation). Secondary outcomes included motor change in patients in the on-medication state (ie, after usual antiparkinsonian medication intake), motor complications (measured with the MDS-UPDRS IV), daily living activities (measured with the MDS-UPDRS I-II), quality of life (measured with the 39-item Parkinson's Disease Questionnaire), change in dopaminergic treatment, patient's global impression of change (measured with the Global Impression of Change [PGI-C] scale), and long-term (24-month) follow-up. Results: Of 45 patients previously treated with unilateral FUS-STN, 7 were lost to follow-up, and 4 were excluded due to adverse events. Of the remaining 34 patients, 6 (median age at first FUS-STN, 52.6 years [IQR, 49.0-57.3 years]; 3 women [50%]) experienced progression of parkinsonism on the untreated body side and were included. At the time of the first FUS-STN, patients' median duration of disease was 5.7 years (IQR, 4.7-7.3 years). The median time between procedures was 3.2 years (IQR, 1.9-3.5 years). After the second FUS-STN, 4 patients presented with contralateral choreic dyskinesia, which resolved by 3 months. Four patients developed speech disturbances, which gradually improved but remained in a mild form for 2 patients at 6 months; 1 patient experienced mild imbalance and dysphagia during the first week after treatment, which subsided by 3 months. No behavioral or cognitive disturbances were found on neuropsychological testing. For patients in the off-medication state, MDS-UPDRS III scores improved by 52.6% between baseline and 6 months after the second FUS-STN (from 37.5 [IQR, 34.2-40.0] to 20.5 [IQR, 8.7-24.0]; median difference, 23.0 [95% CI, 7.0-33.7]; P = .03). The second treated side improved by 64.3% (MDS-UPDRS III score, 17.0 [IQR, 16.0-19.5] prior to the second treatment vs 5.5 [IQR, 3.0-10.2]; median difference, 9.5 [95% CI, 3.2-17.7]; P = .02). After the second procedure, all self-reported PGI-C scores were positive. Conclusions: Findings of this pilot study suggest that staged bilateral FUS-STN was safe and effective for the treatment of PD, although mild but persistent speech-related adverse events were observed among a small number of patients.

Delayed-onset seizures after subthalamic nucleus deep brain stimulation surgery for Parkinson's disease.

BACKGROUND: Delayed-onset seizures after deep brain stimulation (DBS) surgery were seldom reported. This study summarized the clinical characteristics of delayed-onset seizures after subthalamic nucleus (STN) DBS surgery for Parkinson's disease (PD) and analyzed risk factors. METHODS: A single-center retrospective study containing consecutive STN-DBS PD patients from 2006 to 2021 was performed. Seizures occurred during the DBS surgery or within one month after DBS surgery were identified based on routine clinical records. Patients with postoperative magnetic resonance imaging (MRI) were included to further analyze the risk factors for postoperative seizures with univariate and multivariate statistical methods. RESULTS: 341 consecutive PD patients treated with bilateral STN-DBS surgery wereidentified, and five patients experienced seizures after DBS surgery with an incidence of 1.47 %. All seizures of the five cases were characterized as delayed onset with average 12 days post-operatively. All seizures presented as generalized tonic-clonic seizures and didn't recur after the first onset. In those seizures cases, peri-electrode edema was found in both hemispheres without hemorrhage and infarction. The average diameter of peri-electrode edema of patients with seizures was larger than those without seizures (3.15 ± 1.00 cm vs 1.57 ± 1.02 cm, p = 0.005). Multivariate risk factor analysis indicated that seizures were only associated with the diameter of peri-electrode edema (OR 4.144, 95 % CI 1.269-13.530, p = 0.019). CONCLUSIONS: Delayed-onset seizures after STN-DBS surgery in PD patients were uncommon with an incidence of 1.47 % in this study. The seizures were transient and self-limiting, with no developing into chronic epilepsy. Peri-electrode edema was a risk factor for delayed-onset seizures after DBS surgery. Patients with an average peri-electrode edema diameter > 2.70 cm had a higher risk to develop seizures.

Magnetic Resonance-Guided Focused Ultrasound for Treatment of Essential Tremor: Ventral Intermediate Nucleus Ablation Alone or Additional Posterior Subthalamic Area Lesioning?

BACKGROUND: Magnetic resonance-guided focused ultrasound (MRgFUS) for treatment of essential tremor (ET) traditionally targets the ventral intermediate (Vim) nucleus. Recent strategies include a secondary lesion to the posterior subthalamic area (PSA). OBJECTIVE: The aim was to compare lesion characteristics, tremor improvement, and adverse events (AE) between patients in whom satisfactory tremor suppression was achieved with lesioning of the Vim alone and patients who required additional lesioning of the PSA. METHODS: Retrospective analysis of data collected from ET patients treated with MRgFUS at St Vincent's Hospital Sydney was performed. Clinical Rating Scale for Tremor (CRST), hand tremor score (HTS), and Quality of Life in Essential Tremor Questionnaire (QUEST) were collected pre- and posttreatment in addition to the prevalence of AEs. The lesion coordinates and overlap with the dentatorubrothalamic tract (DRTT) were evaluated using magnetic resonance imaging. RESULTS: Twenty-one patients were treated in Vim only, and 14 were treated with dual Vim-PSA lesions. Clinical data were available for 29 of the 35 patients (19 single target and 10 dual target). At follow-up (mean: 18.80 months) HTS, CRST, and QUEST in single-target patients improved by 57.97% (P < 0.001), 36.71% (P < 0.001), and 58.26% (P < 0.001), whereas dual-target patients improved by 68.34% (P < 0.001), 35.37% (P < 0.003), and 46.97% (P < 0.005), respectively. The Vim lesion of dual-target patients was further anterior relative to the posterior commissure (PC) (7.84 mm), compared with single-target patients (6.92 mm), with less DRTT involvement (14.85% vs. 23.21%). Dual-target patients exhibited a greater proportion of patients with acute motor AEs (100% vs. 58%); however, motor AE prevalence was similar in both groups at long-term follow-up (33% vs. 38%). CONCLUSION: Posterior placement of lesions targeting the Vim may confer greater tremor suppression. The addition of a PSA lesion, in patients with inadequate tremor control despite Vim lesioning, had a trend toward better long-term tremor suppression; however, this approach was associated with greater prevalence of gait disturbance in the short term.

Overlapping stimulation of subthalamic nucleus and dentato-rubro-thalamic tract in Parkinson's disease after deep brain stimulation.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reduces tremor, rigidity, and akinesia. According to the literature, the dentato-rubro-thalamic tract (DRTt) is verified target for DBS in essential tremor; however, its role in the treatment of Parkinson's disease is only vaguely described. The aim of our study was to identify the relationship between symptom alleviation in PD patients and the distance of the DBS electrode electric field (EF) to the DRTt. METHODS: A single-center retrospective analysis of patients (N = 30) with idiopathic Parkinson's disease (PD) who underwent DBS between November 2018 and January 2020 was performed. DRTt and STN were visualized using diffusion-weighted imaging (DWI) and tractography protocol of magnetic resonance (MR). The EF was calculated and compared with STN and course of DRTt. Evaluation of patients before and after surgery was performed with use of UPDRS-III scale. The association between distance from EF to DRTt and clinical outcomes was examined. To confirm the anatomical variation between DRTt and STN observed in tractography, white matter dissection was performed with the Klingler technique on ten human brains. RESULTS: Patients with EF overlapping STN and DRTt benefited from significant motor symptoms improvement. Anatomical findings confirmed the presence of population differences in variability of the DRTt course and were consistent with the DRTt visualized by MR. CONCLUSIONS: DRTt proximity to STN, the main target in PD DBS surgery, confirmed by DWI with tractography protocol of MR combined with proper predefined stimulation parameters may improve efficacy of DBS-STN.

The Use of Image Guided Programming to Improve Deep Brain Stimulation Workflows with Directional Leads in Parkinson's Disease.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a preferred treatment for parkinsonian patients with severe motor fluctuations. Proper targeting of the STN sensorimotor segment appears to be a crucial factor for success of the procedure. The recent introduction of directional leads theoretically increases stimulation specificity in this challenging area but also requires more precise stimulation parameters. OBJECTIVE: We investigated whether commercially available software for image guided programming (IGP) could maximize the benefits of DBS by informing the clinical standard care (CSC) and improving programming workflows. METHODS: We prospectively analyzed 32 consecutive parkinsonian patients implanted with bilateral directional leads in the STN. Double blind stimulation parameters determined by CSC and IGP were assessed and compared at three months post-surgery. IGP was used to adjust stimulation parameters if further clinical refinement was required. Overall clinical efficacy was evaluated one-year post-surgery. RESULTS: We observed 78% concordance between the two electrode levels selected by the blinded IGP prediction and CSC assessments. In 64% of cases requiring refinement, IGP improved clinical efficacy or reduced mild side effects, predominantly by facilitating the use of directional stimulation (93% of refinements). CONCLUSIONS: The use of image guided programming saves time and assists clinical refinement, which may be beneficial to the clinical standard care for STN-DBS and further improve the outcomes of DBS for PD patients.

A Systematic Review of Neurophysiology-Based Localization Techniques Used in Deep Brain Stimulation Surgery of the Subthalamic Nucleus.

OBJECTIVE: This systematic review is conducted to identify, compare, and analyze neurophysiological feature selection, extraction, and classification to provide a comprehensive reference on neurophysiology-based subthalamic nucleus (STN) localization. MATERIALS AND METHODS: The review was carried out using the methods and guidelines of the Kitchenham systematic review and provides an in-depth analysis on methods proposed on STN localization discussed in the literature between 2000 and 2021. Three research questions were formulated, and 115 publications were identified to answer the questions. RESULTS: The three research questions formulated are answered using the literature found on the respective topics. This review discussed the technologies used in past research, and the performance of the state-of-the-art techniques is also reviewed. CONCLUSION: This systematic review provides a comprehensive reference on neurophysiology-based STN localization by reviewing the research questions other new researchers may also have.

Long-term safety and efficacy of frameless subthalamic deep brain stimulation in Parkinson's disease.

BACKGROUND: Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) is standard of care for Parkinson's disease (PD) patients and a correct lead placement is crucial to obtain good clinical outcomes. Evidence demonstrating the targeting accuracy of the frameless technique for DBS, along with the advantages for patients and clinicians, is solid, while data reporting long-term clinical outcomes for PD patients are still lacking. OBJECTIVES: The study aims to assess the clinical safety and efficacy of frameless bilateral STN-DBS in PD patients at 5 years from surgery. METHODS: Consecutive PD patients undergoing bilateral STN-DBS with a frameless system were included in this single-center retrospective study. Clinical features, including the Unified Parkinson's Disease Rating Scale (UPDRS) in its total motor score and axial sub-scores, and pharmacological regimen were assessed at baseline, 1 year, 3 years, and 5 years after surgery. The adverse events related to the procedure, stimulation, or the presence of the hardware were systematically collected. RESULTS: Forty-one PD patients undergone bilateral STN-DBS implantation were included in the study and fifteen patients already completed the 5-year observation. No complications occurred during surgery and the perioperative phase, and no unexpected serious adverse event occurred during the entire follow-up period. At 5 years from surgery, there was a sustained motor efficacy of STN stimulation: STN-DBS significantly improved the off-stim UPDRS III score at 5 years by 37.6% (P < 0.001), while the dopaminergic medications remained significantly reduced compared to baseline (- 21.6% versus baseline LEDD; P = 0.036). CONCLUSIONS: Our data support the use of the frameless system for STN-DBS in PD patients, as a safe and well-tolerated technique, with long-term clinical benefits and persistent motor efficacy at 5 years from the surgery.

Deep Brain Stimulation of Subthalamic Nucleus Improves Quality of Life in General and Mental Health Domains in Parkinson's Disease to the Level of the General Population.

OBJECTIVES: Parkinson's disease (PD) leads to significant impairment in quality of life (QoL) across various domains. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is known to improve motor and nonmotor symptoms in PD. The aim was to study whether STN-DBS could improve the QoL of patients with PD to the level of the general population, and to determine factors predicting better motor outcomes. MATERIALS AND METHODS: The retrospective analysis included 43 patients who underwent either primary or revision STN-DBS. Patients filled out a general QoL questionnaire (RAND 36-item health survey) before and 12 months after surgery, and scores were compared with age- and sex-adjusted national population values. In addition, motor scores were calculated using Unified Parkinson Disease Rating Scale part 3 (UPDRS 3) with the best PD medication. Levodopa equivalent daily dose (LEDD) was also collected. Changes in the QoL were compared with operation age, disease duration, and preoperative QoL. RESULTS: Preoperatively, patients had significantly impaired QoL in all subsections compared with that of the general population. The mean postoperative UPDRS 3 improvement was 50.0%, and reduction in LEDD was 69.0%. Statistically significant QoL improvements were found in Physical Function, Mental Health, Social Function, Vitality, and Role Physical 12 months postoperatively compared with baseline. The mean differences compared with a healthy population were not statistically significant in General Health, Mental Health, Vitality, and Role Emotional. Furthermore, disease duration was found to be negatively correlated with improvements in UPDRS 3 score, and worse preoperative QoL positively correlated with changes in Physical Function. CONCLUSIONS: Patients experienced significant QoL improvements after STN-DBS. The General Health and Mental Health of patients were postoperatively most comparable with age- and sex-adjusted population values. Moreover, earlier stimulation predicted better motor improvements, which emphasizes the importance of earlier timing of STN-DBS surgery and minimizing loss of function at a critical disease stage.

Susceptibility-Weighted MRI Approximates Intraoperative Microelectrode Recording During Deep Brain Stimulation of the Subthalamic Nucleus for Parkinson's Disease.

BACKGROUND: Deep brain stimulation of the subthalamic nucleus (STN-DBS) for Parkinson's disease can be performed with intraoperative neurophysiological and radiographic guidance. Conventional T2-weighted magnetic resonance imaging sequences, however, often fail to provide definitive borders of the STN. Novel magnetic resonance imaging sequences, such as susceptibility-weighted imaging (SWI), might better localize the STN borders and facilitate radiographic targeting. We compared the radiographic location of the dorsal and ventral borders of the STN using SWI with intraoperative microelectrode recording (MER) during awake STN-DBS for Parkinson's disease. METHODS: Thirteen consecutive patients who underwent placement of 24 STN-DBS leads for Parkinson's disease were analyzed retrospectively. Preoperative targeting was performed with SWI, and MER data were obtained from intraoperative electrophysiology records. The boundaries of the STN on SWI were identified by a blinded investigator. RESULTS: The final electrode position differed significantly from the planned coordinates in depth but not in length or width, indicating that MER guided the final electrode depth. When we compared the boundaries of the STN by MER and SWI, SWI accurately predicted the entry into the STN but underestimated the length and ventral boundary of the STN by 1.2 mm. This extent of error approximates the span of a DBS contact and could affect the placement of directional contacts within the STN. CONCLUSIONS: MER might continue to have a role in STN-DBS. This could potentially be mitigated by further refinement of imaging protocols to better image the ventral boundary of the STN.

Evaluation of the PaCER Algorithm for Postoperative Subthalamic Nucleus Deep Brain Stimulation Electrode Localization.

Deep Brain Stimulation (DBS) is an established therapy for many movement disorders. DBS entails electrical stimulation of precise brain structures using permanently implanted electrodes. Following implantation, locating the electrodes relative to the target brain structure assists patient outcome optimization. Here we evaluated an open-source automatic algorithm (PaCER) to localize individual electrodes on Computed Tomography imaging (co-registered to Magnetic Resonance Imaging). In a dataset of 111 participants, we found a modified version of the algorithm matched manual-markups with median error less than 0.191 mm (interquartile range 0.698 mm). Given the error is less than the voxel resolution (1 mm3) of the images, we conclude that the automatic algorithm is suitable for DBS electrode localizations.Clinical Relevance- Automated DBS electrode localization identifies the closest electrode to the target brain structure; allowing the neurologist to direct electrical stimulation to maximize patient outcomes. Further, if none of the electrodes are deemed suitable, localization will guide re-implantation.

[Early brain imaging changes and its influence on electrode impedance after implantation of 3.0 T MRI-compatible deep brain stimulation system in Parkinson's disease subthalamic nucleus].

Objective: To analyze the imaging changes of in the early period after subthalamic nucleus (STN) deep brain stimulation (DBS) surgery for Parkinson's disease (PD) and its impact on electrode impedance by the application of 3.0T MRI-compatible devices. Methods: A retrospective analysis was performed for the data of 43 PD patients who underwent 3.0T MRI-compatible STN-DBS surgery from October 2022 to April 2023 at the First Affiliated Hospital of USTC(Anhui Provincial Hospital), including 27 males and 16 females, aged 43-68 (56±5) years. All patients underwent postoperative 3.0T MRI, CT scans,and impedance measurements 1 week postoperatively.Fifteen patients underwent 3.0T MRI and impedance measurements 1 month postoperatively. The differences in impedance of electrode contacts before and after the 3.0T MRI scans were compared. The occurrence of peri-lead cerebral edema (PLE) in patients was analyzed, as well as the differences in PLE detection rates between the two imaging methods, and the differences in the incidence and volume of PLE at different microelectrode recordings, the occurrence and detection of postoperative PLE, and different microelectrode recording (MER) times and different time nodes were compared. The correlation between electrode impedance and the volume of edema around the nucleus was analyzed. Results: All 43 patients successfully underwent surgery, with a total of 86 electrodes implanted. There was no significant difference in electrode impedance values before and after the 3.0T MRI examinations at 1 week and 1 month postoperatively. The PLE detection rate with 3.0T MRI was 95.12%(39/43), which is significantly higher than that of CT imaging 17.07% (7/43)(χ2=50.705, P<0.001). One week after surgery, the incidence and volume of PLE were higher in the multiple MER group compared with the single MER group, but the difference was not statistically significant. The volume of PLE [M(Q1, Q3) 0 (0, 1.211) cm3] at 1 month was significantly smaller than that at 1 week [0.243 (0, 2.914) cm3] (Z=-3.408, P=0.001). The impedance of electrode contacts within 1 month postoperatively showed a trend of initial decrease followed by an increase, which was negatively correlated with SE volume(r=-0.317, P=0.014). Conclusions: The application of 3.0T MRI-compatible DBS devices in the surgical treatment of PD patients improves the accuracy of early postoperative imaging assessment. The electrode impedance is more stable as the edema around the nucleus subsided at 1 month after surgery, which is suitable for the first program control.

Combining ultrasound and microelectrode recordings for postoperative localization of subthalamic electrodes in Parkinson's disease.

OBJECTIVE: To assess transcranial sonography (TCS) as stand-alone tool and in combination with microelectrode recordings (MER) as a method for the postoperative localization of deep brain stimulation (DBS) electrodes in the subthalamic nucleus (STN). METHODS: Individual dorsal and ventral boundaries of STN (n = 12) were determined on intraoperative MER. Postoperatively, a standardized TCS protocol was applied to measure medio-lateral, anterior-posterior and rostro-caudal electrode position using visualized reference structures (midline, substantia nigra). TCS and combined TCS-MER data were validated using fusion-imaging and clinical outcome data. RESULTS: Test-retest reliability of standard TCS measures of electrode position was excellent. Computed tomography and TCS measures of distance between distal electrode contact and midline agreed well (Pearson correlation; r = 0.86; p < 0.001). Comparing our "gold standard" of rostro-caudal electrode localization relative to STN boundaries, i.e. combining MRI-based stereotaxy and MER data, with the combination of TCS and MER data, the measures differed by 0.32 ± 0.87 (range, -1.35 to 1.25) mm. Combined TCS-MER data identified the clinically preferred electrode contacts for STN-DBS with high accuracy (Cohens kappa, 0.86). CONCLUSIONS: Combined TCS-MER data allow for exact localization of STN-DBS electrodes. SIGNIFICANCE: Our method provides a new option for monitoring of STN-DBS electrode location and guidance of DBS programming in Parkinson's disease.

Stereotactic Staged Asymmetric Bilateral Radiofrequency Lesioning for Parkinson's Disease.

INTRODUCTION: Parkinson's disease (PD) is one of the most common neurodegenerative progressive disorders. Despite the dominance of neurostimulation technology, stereotactic lesioning operations play a significant role in the treatment of PD. The aim of the study was to evaluate the effectiveness and safety of staged bilateral asymmetric radiofrequency (RF) stereotactic lesioning in a highly selected group of PD patients. MATERIAL AND METHODS: A retrospective review of 418 consecutive patients undergoing stereotactic ablation for advanced PD at our institution revealed 28 patients who underwent staged asymmetric bilateral ablation. In this subset, after initial RF thalamotomy, contralateral pallidotomy was performed in 16 (57.1%) patients (group Vim-GPi), and contralateral lesion of the subthalamic nucleus (STN) was performed in 12 (32.9%) patients (group Vim-STN). The mean duration of disease before the first surgery was 9.9 ± 0.8 years. The mean interval between the two operations was 3.5 ± 0.4 years (range, 1-10 years); in the Vim-GPi group, it was 3.1 ± 0.4 years; and in the Vim-STN group, it was 4.3 ± 0.1 years. After the second operation, the long-term follow-up lasted from 1 to 8 years (mean 4.8 ± 0.5 years). All patients were evaluated 1 year after the second operation. RESULTS: One year after staged bilateral lesioning, the mean tremor score improved from baseline, prior to the first operation, from 19.8 to 3.8 (improvement of 81%), the overall mean rigidity score improved from 11.0 to 3.7 (improvement of 66%), and hypokinesia improved from 14.8 to 8.9 (improvement of 40%). One year after staged bilateral lesioning, the total UPDRS score improved in the Vim-GPi group by 47% in the OFF and 45.9% in the ON states. In the Vim-STN group, the total UPDRS score improved from baseline, prior to the first operation, by 44.8% in the OFF and 51.6% in the ON states. Overall, levodopa dose was reduced by 43.4%. Neurological complications were observed in 4 (14.3%) cases; among them, 1 (3.6%) patient had permanent events related to local ischemia after pallidotomy. CONCLUSION: Staged asymmetric bilateral stereotactic RF lesioning can be a safe and effective method in highly selected patients with advanced PD, particularly where deep brain stimulation is not available or desirable. Careful identification and selection of patients for ablative surgery allow achieving optimal results in the treatment of PD with bilateral symptoms.

Thirty Years of Global Deep Brain Stimulation: "Plus ça change, plus c'est la même chose"?

BACKGROUND: The advent of deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson's disease 30 years ago has ushered a global breakthrough of DBS as a universal method for therapy and research in wide areas of neurology and psychiatry. The literature of the last three decades has described numerous concepts and practices of DBS, often branded as novelties or discoveries. However, reading the contemporary publications often elicits a sense of déjà vu in relation to several methods, attributes, and practices of DBS. Here, we review various applications and techniques of the modern-era DBS and compare them with practices of the past. SUMMARY: Compared with modern literature, publications of the old-era functional stereotactic neurosurgery, including old-era DBS, show that from the very beginning multidisciplinarity and teamwork were often prevalent and insisted upon, ethical concerns were recognized, brain circuitries and rational for brain targets were discussed, surgical indications were similar, closed-loop stimulation was attempted, evaluations of surgical results were debated, and controversies were common. Thus, it appears that virtually everything done today in the field of DBS bears resemblance to old-time practices, or has been done before, albeit with partly other tools and techniques. Movement disorders remain the main indications for modern DBS as was the case for lesional surgery and old-era DBS. The novelties today consist of the STN as the dominant target for DBS, the tremendous advances in computerized brain imaging, the sophistication and versatility of implantable DBS hardware, and the large potential for research. KEY MESSAGES: Many aspects of contemporary DBS bear strong resemblance to practices of the past. The dominant clinical indications remain movement disorders with virtually the same brain targets as in the past, with one exception: the STN. Other novel brain targets - that are so far subject to DBS trials - are the pedunculopontine nucleus for gait freezing, the anteromedial internal pallidum for Gilles de la Tourette and the fornix for Alzheimer's disease. The major innovations and novelties compared to the past concern mainly the unmatched level of research activity, its high degree of sponsorship, and the outstanding advances in technology that have enabled multimodal brain imaging and the miniaturization, versatility, and sophistication of implantable hardware. The greatest benefit for patients today, compared to the past, is the higher level of precision and safety of DBS, and of all functional stereotactic neurosurgery.

Deep Brain Stimulation of the Globus Pallidus Internus and Externus in Multiple System Atrophy.

BACKGROUND: Multiple system atrophy with parkinsonism (MSA-P) is a progressive condition with no effective treatment. OBJECTIVE: The aim of this study was to describe the safety and efficacy of deep brain stimulation (DBS) of globus pallidus pars interna and externa in a cohort of patients with MSA-P. METHODS: Six patients were included. Changes in Movement Disorders Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III), Parkinson's Disease Questionnaire (PDQ-39) scores, and levodopa equivalent daily dose were compared before and after DBS. Electrode localization and volume tissue activation were calculated. RESULTS: DBS surgery did not result in any major adverse events or intraoperative complications. Overall, no differences in MDS-UPDRS III scores were demonstrated (55.2 ± 17.6 preoperatively compared with 67.3 ± 19.2 at 1 year after surgery), although transient improvement in mobility and dyskinesia was reported in some subjects. CONCLUSIONS: Globus pallidus pars interna and externa DBS for patients with MSA-P did not result in major complications, although it did not provide significant clinical benefit as measured by MDS-UPDRS III. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Automatic Localization of Key Structures for Subthalamic Nucleus-Deep Brain Stimulation Surgery via Prior-Enhanced Multi-Object Magnetic Resonance Imaging Segmentation.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established and effective neurosurgical treatment for relieving motor symptoms in Parkinson disease. The localization of key brain structures is critical to the success of DBS surgery. However, in clinical practice, this process is heavily dependent on the radiologist's experience. METHODS: In this study, we propose an automatic localization method of key structures for STN-DBS surgery via prior-enhanced multi-object magnetic resonance imaging segmentation. We use the U-Net architecture for the multi-object segmentation, including STN, red nucleus, brain sulci, gyri, and ventricles. To address the challenge that only half of the brain sulci and gyri locate in the upper area, potentially causing interference in the lower area, we perform region of interest detection and ensemble joint processing to enhance the segmentation performance of brain sulci and gyri. RESULTS: We evaluate the segmentation accuracy by comparing our method with other state-of-the-art machine learning segmentation methods. The experimental results show that our approach outperforms state-of-the-art methods in terms of segmentation performance. Moreover, our method provides effective visualization of key brain structures from a clinical application perspective and can reduce the segmentation time compared with manual delineation. CONCLUSIONS: Our proposed method uses deep learning to achieve accurate segmentation of the key structures more quickly than and with comparable accuracy to human manual segmentation. Our method has the potential to improve the efficiency of surgical planning for STN-DBS.

Quantifying the Variability Associated with Postoperative Localization of Deep Brain Stimulation Electrodes.

INTRODUCTION: Computational models of deep brain stimulation (DBS) have become common tools in clinical research studies that attempt to establish correlations between stimulation locations in the brain and behavioral outcome measures. However, the accuracy of any patient-specific DBS model depends heavily upon accurate localization of the DBS electrodes within the anatomy, which is typically defined via co-registration of clinical CT and MRI datasets. Several different approaches exist for this challenging registration problem, and each approach will result in a slightly different electrode localization. The goal of this study was to better understand how different processing steps (e.g., cost-function masking, brain extraction, intensity remapping) affect the estimate of the DBS electrode location in the brain. METHODS: No "gold standard" exists for this kind of analysis, as the exact location of the electrode in the living human brain cannot be determined with existing clinical imaging approaches. However, we can estimate the uncertainty associated with the electrode position, which can be used to guide statistical analyses in DBS mapping studies. Therefore, we used high-quality clinical datasets from 10 subthalamic DBS subjects and co-registered their long-term postoperative CT with their preoperative surgical targeting MRI using 9 different approaches. The distances separating all of the electrode location estimates were calculated for each subject. RESULTS: On average, electrodes were located within a median distance of 0.57 mm (0.49-0.74) of one another across the different registration approaches. However, when considering electrode location estimates from short-term postoperative CTs, the median distance increased to 2.01 mm (1.55-2.78). CONCLUSIONS: The results of this study suggest that electrode location uncertainty needs to be factored into statistical analyses that attempt to define correlations between stimulation locations and clinical outcomes.

Factors influencing the reliability of intraoperative testing in deep brain stimulation for Parkinson's disease.

BACKGROUND: Several meta-analyses comparing the outcome of awake versus asleep deep brain stimulation procedures could not reveal significant differences concerning the postoperative improvement of motor symptoms. Only rarely information on the procedural details is provided for awake operations and how often somnolence and disorientation occurred, which might hamper the reliability of intraoperative clinical testing. The aim of our study was to investigate possible influencing factors on the occurrence of somnolence and disorientation in awake DBS procedures. METHODS: We retrospectively analyzed 122 patients with Parkinson's disease having received implantation of a DBS system at our centre. Correlation analyses were performed for the duration of disease prior to surgery, number of microelectrode trajectories, AC-PC-coordinates of the planned target, UPDRS-scores, intraoperative application of sedative drugs, duration of the surgical procedure, perioperative application of apomorphine, and the preoperative L-DOPA equivalence dosage with the occurrence of intraoperative somnolence and disorientation. RESULTS: Patients with intraoperative somnolence were significantly older (p=0.039). Increased duration of the DBS procedure (p=0.020), delayed start of the surgery (p=0.049), higher number of MER trajectories (p=0.041), and the patients' % UPDRS improvement (p=0.046) also correlated with the incidence of intraoperative somnolence. We identified the main contributing factor to intraoperative somnolence as the use of sedative drugs applied during skin incision and burr hole trepanation (p=0.019). Perioperatively applied apomorphine could reduce the occurrence of somnolent phases during the operation (p=0.026). CONCLUSION: Several influencing factors were found to seemingly increase the risk of intraoperative somnolence and disorientation, while the use of sedative drugs seems to be the main contributing factor. We argue that awake DBS procedures should omit the use of sedatives for best clinical outcome. When reporting on awake DBS surgery these factors should be considered and adjusted for, to permit reliable interpretation and comparison of DBS study results.