Subthalamic Deep Brain Stimulation Research Articles

Long-Term Medication Profiles in Parkinson's Disease under Subthalamic Deep Brain Stimulation: A Controlled Study.

Subthalamic deep brain stimulation (STN-DBS) reduces antiparkinsonian medications in Parkinson's disease (PD) compared with the preoperative state. Longitudinal and comparative studies on this effect are lacking. To compare longitudinal trajectories of antiparkinsonian medication in STN-DBS treated patients to non-surgically treated control patients. We collected retrospective information on antiparkinsonian medication from PD patients that underwent subthalamic DBS between 1999 and 2010 and control PD patients similar in age at onset and baseline, sex-distribution, and comorbidities. In 74 DBS patients levodopa-equivalent daily dose (LEDD) were reduced by 33.9-56.0% in relation to the preoperative baseline over the 14-year observational period. In 61 control patients LEDDs increased over approximately 10 years, causing a significant divergence between groups. The largest difference amongst single drug-classes was observed for dopamine agonists. In PD patients, chronic STN-DBS was associated with a lower LEDD compared with control patients over 14 years.

Exploring Cardiovascular Autonomic Function before and after Chronic Deep Brain Stimulation in Parkinson's Disease.

Blood pressure control in Parkinson's disease (PD) under subthalamic deep brain stimulation (STN-DBS) is influenced by several intertwined aspects, including autonomic failure and levodopa treatment. To evaluate the effect of chronic STN-DBS, levodopa, and their combination on cardiovascular autonomic functions in PD. We performed cardiovascular reflex tests (CRTs) before and 6-months after STN-DBS surgery in 20 PD patients (pre-DBS vs. post-DBS). CRTs were executed without and with medication (med-OFF vs. med-ON). CRT results and occurrence of neurogenic orthostatic hypotension (OH) did not differ between pre- and post-DBS studies in med-OFF condition. After levodopa intake, the BP decrease during HUTT was significantly greater compared to med-OFF, both at pre-DBS and post-DBS evaluation. Levodopa-induced OH was documented in 25% and 5% of patients in pre-DBS/med-ON and post-DBS/med-ON study. Chronic stimulation did not influence cardiovascular responses, while levodopa exerts a relevant hypotensive effect. The proportion of patients presenting levodopa-induced OH decreases after STN-DBS surgery.

Clinical and Brain Morphometry Predictors of Deep Brain Stimulation Outcome in Parkinson's Disease.

Subthalamic deep brain stimulation (STN-DBS) is known to improve motor function in advanced Parkinson's disease (PD) and to enable a reduction of anti-parkinsonian medication. While the levodopa challenge test and disease duration are considered good predictors of STN-DBS outcome, other clinical and neuroanatomical predictors are less established. This study aimed to evaluate, in addition to clinical predictors, the effect of patients' individual brain topography on DBS outcome. The medical records of 35 PD patients were used to analyze DBS outcomes measured with the following scales: Part III of the Unified Parkinson's Disease Rating Scale (UPDRS-III) off medication at baseline, and at 6-months during medication off and stimulation on, use of anti-parkinsonian medication (LED), Abnormal Involuntary Movement Scale (AIMS) and Non-Motor Symptoms Questionnaire (NMS-Quest). Furthermore, preoperative brain MRI images were utilized to analyze the brain morphology in relation to STN-DBS outcome. With STN-DBS, a 44% reduction in the UPDRS-III score and a 43% decrease in the LED were observed (p<0.001). Dyskinesia and non-motor symptoms decreased significantly [median reductions of 78,6% (IQR 45,5%) and 18,4% (IQR 32,2%) respectively, p=0.001 - 0.047]. Along with the levodopa challenge test, patients' age correlated with the observed DBS outcome measured as UPDRS-III improvement (ρ= -0.466 - -0.521, p<0.005). Patients with greater LED decline had lower grey matter volumes in left superior medial frontal gyrus, in supplementary motor area and cingulum bilaterally. Additionally, patients with greater UPDRS-III score improvement had lower grey matter volume in similar grey matter areas. These findings remained significant when adjusted for sex, age, baseline LED and UPDRS scores respectively and for total intracranial volume (p=0.0041- 0.001). However, only the LED decrease finding remained significant when the analyses were further controlled for stimulation amplitude. It appears that along with the clinical predictors of STN-DBS outcome, individual patient topographic differences may influence DBS outcome. Clinical Trial Registration Number: NCT06095245, registration date October 23, 2023, retrospectively registered.

Sleep macro-architecture in patients with Parkinson's disease does not change during the first night of neurostimulation in a pilot study.

A growing body of literature suggests that deep brain stimulation (DBS) to treat motor symptoms of Parkinson's disease (PD) may also ameliorate certain sleep deficits. Many foundational studies have examined the impact of stimulation on sleep following several months of therapy, leaving an open question regarding the time course for improvement. It is unknown whether sleep improvement will immediately follow onset of therapy or accrete over a prolonged period of stimulation. The objective of our study was to address this knowledge gap by assessing the impact of DBS on sleep macro-architecture during the first nights of stimulation. Polysomnograms were recorded for three consecutive nights in 14 patients with advanced PD (10 male, 4 female; age: 53-74 years), with intermittent, unilateral subthalamic nucleus DBS on the final night or two. Sleep scoring was determined manually by a consensus of four experts. Sleep macro-architecture was objectively quantified using the percentage, latency, and mean bout length of wake after sleep onset (WASO) and on each stage of sleep (REM and NREM stages N1, N2, N3). Sleep was found to be highly disrupted in all nights. Sleep architecture on nights without stimulation was consistent with prior results in treatment naive patients with PD. No statistically significant difference was observed due to stimulation. These objective measures suggest that one night of intermittent subthreshold stimulation appears insufficient to impact sleep macro-architecture. Name: Adaptive Neurostimulation to Restore Sleep in Parkinson's Disease; URL: https://clinicaltrials.gov/ct2/show/NCT04620551; Identifier: NCT04620551.

A Retrospective Comparison of Multiple Approaches to Anatomically Informed Contact Selection in Subthalamic Deep Brain Stimulation for Parkinson's Disease.

Conventional deep brain stimulation (DBS) programming via trial-and-error warrants improvement to ensure swift achievement of optimal outcomes. The definition of a sweet spot for subthalamic DBS in Parkinson's disease (PD-STN-DBS) may offer such advancement. This investigation examines the association of long-term motor outcomes with contact selection during monopolar review and different strategies for anatomically informed contact selection in a retrospective real-life cohort of PD-STN-DBS. We compared contact selection based on a monopolar review (MPR) to multiple anatomically informed contact selection strategies in a cohort of 28 PD patients with STN-DBS. We employed a commercial software package for contact selection based on visual assessment of individual anatomy following two predefined strategies and two algorithmic approaches with automatic targeting of either the sensorimotor STN or our previously published sweet spot. Similarity indices between chronic stimulation and contact selection strategies were correlated to motor outcomes at 12 months follow-up. Lateralized motor outcomes of chronic DBS were correlated to the similarity between chronic stimulation and visual contact selection targeting the dorsal part of the posterior STN (rho = 0.36, p = 0.007). Similar relationships could not be established for MPR or any of the other investigated strategies. Our data demonstrates that a visual contact selection following a predefined strategy can be linked to beneficial long-term motor outcomes in PD-STN-DBS. Since similar correlations could not be observed for the other approaches to anatomically informed contact selection, we conclude that clear definitions and prospective validation of any approach to imaging-based DBS-programming is warranted.

Effects of deep brain stimulation and verbal suggestions on pain in Parkinson's disease.

In Parkinson's disease (PD) patients, verbal suggestions have been shown to modulate motor and clinical outcomes in treatment with subthalamic deep brain stimulation (DBS). Furthermore, DBS may alleviate pain in PD. However, it is unknown if verbal suggestions influence DBS' effects on pain. Twenty-four people with PD and DBS had stimulation downregulated (80-60 to 20%) and upregulated (from 20-60 to 80%) in a blinded manner on randomized test days: (1) with negative and positive suggestions of pain for down- and upregulation, respectively, and (2) with no suggestions to effect (control). Effects of DBS and verbal suggestions were assessed on ongoing and evoked pain (hypertonic saline injections) via 0-10 numerical rating scales along with motor symptoms, expectations, and blinding. Stimulation did not influence ongoing and evoked pain but influenced motor symptoms in the expected direction. Baseline and experimental pain measures showed no patterns in degree of pain. There was a trend toward negative suggestions increasing pain and positive suggestions decreasing pain. Results show significant differences in identical stimulation with negative vs positive suggestions (60% conditions AUC 38.75 vs 23.32, t(13) = 3.10, p < 0.001). Expectations to pain had small to moderate effects on evoked pain. Patients estimated stimulation level correctly within 10 points. Stimulation does not seem to influence ongoing and evoked pain, but verbal suggestions may influence pain levels. Patients appear to be unblinded to stimulation level which is an important consideration for future studies testing DBS in an attempted blind fashion.

Modulation of DBS-induced cortical responses and movement by the directionality and magnitude of current administered

Subthalamic deep brain stimulation (STN-DBS) is an effective therapy for alleviating motor symptoms in people with Parkinson’s disease (PwP), although some may not receive optimal clinical benefits. One potential mechanism of STN-DBS involves antidromic activation of the hyperdirect pathway (HDP), thus suppressing cortical beta synchrony to improve motor function, albeit the precise mechanisms underlying optimal DBS parameters are not well understood. To address this, 18 PwP with STN-DBS completed a 2 Hz monopolar stimulation of the left STN during MEG. MEG data were imaged in the time-frequency domain using minimum norm estimation. Peak vertex time series data were extracted to interrogate the directional specificity and magnitude of DBS current on evoked and induced cortical responses and accelerometer metrics of finger tapping using linear mixed-effects models and mediation analyses. We observed increases in evoked responses (HDP ~ 3–10 ms) and synchronization of beta oscillatory power (14–30 Hz, 10–100 ms) following DBS pulse onset in the primary sensorimotor cortex (SM1), supplementary motor area (SMA) and middle frontal gyrus (MFG) ipsilateral to the site of stimulation. DBS parameters significantly modulated neural and behavioral outcomes, with clinically effective contacts eliciting significant increases in medium-latency evoked responses, reductions in induced SM1 beta power, and better movement profiles compared to suboptimal contacts, often regardless of the magnitude of current applied. Finally, HDP-related improvements in motor function were mediated by the degree of SM1 beta suppression in a setting-dependent manner. Together, these data suggest that DBS-evoked brain-behavior dynamics are influenced by the level of beta power in key hubs of the basal ganglia-cortical loop, and this effect is exacerbated by the clinical efficacy of DBS parameters. Such data provides novel mechanistic and clinical insight, which may prove useful for characterizing DBS programming strategies to optimize motor symptom improvement in the future.

Kinematic Effects of Combined Subthalamic and Dorsolateral Nigral Deep Brain Stimulation in Parkinson's Disease.

Additional stimulation of the substantia nigra (SNr) has been proposed to target axial symptoms and gait impairment in patients with Parkinson's disease (PD). This study aimed to characterize effects of combined deep brain stimulation (DBS) of the subthalamic nucleus (STN) and SNr on gait performance in PD and to map stimulation sites within the SNr. In a double-blinded crossover design, 10 patients with PD and gait impairment underwent clinical examination and kinematic assessment with STN DBS, combined STN+SNr DBS and OFF DBS 30 minutes after reprogramming. To confirm stimulation within the SNr, electrodes, active contacts, and stimulation volumes were modeled in a common space and overlap with atlases of SNr was computed. Overlap of stimulation volumes with dorsolateral SNr was confirmed for all patients. UPDRS III, scoring of freezing during turning and transitioning, stride length, stride velocity, and range of motion of shank, knee, arm, and trunk as well as peak velocities during turning and transitions and turn duration were improved with STN DBS compared to OFF. On cohort level, no further improvement was observed with combined STN+SNr DBS but additive improvement of spatiotemporal gait parameters was observed in individual subjects. Combined high frequency DBS of the STN and dorsolateral SNr did not consistently result in additional short-term kinematic or clinical benefit compared to STN DBS. Stimulation intervals, frequency, and patient selection for target symptoms as well as target region within the SNr need further refinement in future trials.

Pallidal versus subthalamic deep brain stimulation for Meige syndrome: A systematic review and meta-analysis

BackgroundGlobus pallidus internus (GPi) and subthalamic nucleus (STN) are two common deep brain stimulation (DBS) targets. This meta-analysis was to compared the efficacy and safety of these two DBS targets for the treatment of Meige syndrome (MS). MethodsA systematic search was performed using EMBASE, MEDLINE, the Cochrane Library, and ClinicalTrials.gov to identify DBS trials for MS. Review Manager 5.3 was used to perform meta-analysis and the mean difference (MD) was analyzed and calculated with a random effect model. Pearson's correlation coefficients and meta-regression analyses were utilized to identify relevant predictive markers. ResultsTwenty trials involving 188 participants with GPi-DBS and 110 individuals with STN-DBS were eligible. Both groups showed improvement of the Burke-Fahn-Marsden Dystonia Rating Scale-Movement (BFMDRS-M) and Disability (BFMDRS-D) scores (BFMDRS-M: MD = 10.57 [7.74–13.41] for GPi-DBS, and MD = 8.59 [4.08–13.11] for STN-DBS; BFMDRS-D: MD = 5.96 [3.15–8.77] for GPi-DBS, and MD = 4.71 [1.38–8.04] for STN-DBS; all P < 0.001) from baseline to the final follow-up, while no notable disparity in improvement rates was observed between them. Stimulation-related complications occurrence was also similar between two groups (38.54 ± 24.07% vs. 43.17 ± 29.12%, P = 0.7594). Simultaneously, preoperative BFMDRS-M score and disease duration were positively connected with the relative changes in BFMDRS-M score at the final visit. ConclusionBoth GPi-DBS and STN-DBS are effective MS therapies, with no differences in efficacy or the frequency of stimulation-related problems. Higher preoperative scores and longer disease duration probably predict greater improvement.

Interleaved Propofol-Ketamine Maintains DBS Physiology and Hemodynamic Stability: A Double-Blind Randomized Controlled Trial.

The gold standard anesthesia for deep brain stimulation (DBS) surgery is the "awake" approach, using local anesthesia alone. Although it offers high-quality microelectrode recordings and therapeutic-window assessment, it potentially causes patients extreme stress and might result in suboptimal surgical outcomes. General anesthesia or deep sedation is an alternative, but may reduce physiological testing reliability and lead localization accuracy. The aim is to investigate a novel anesthesia regimen of ketamine-induced conscious sedation for the physiological testing phase of DBS surgery. Parkinson's patients undergoing subthalamic DBS surgery were randomly divided into experimental and control groups. During physiological testing, the groups received 0.25 mg/kg/h ketamine infusion and normal saline, respectively. Both groups had moderate propofol sedation before and after physiological testing. The primary outcome was recording quality. Secondary outcomes included hemodynamic stability, lead accuracy, motor and cognitive outcome, patient satisfaction, and adverse events. Thirty patients, 15 from each group, were included. Intraoperatively, the electrophysiological signature and lead localization were similar under ketamine and saline. Tremor amplitude was slightly lower under ketamine. Postoperatively, patients in the ketamine group reported significantly higher satisfaction with anesthesia. The improvement in Unified Parkinson's disease rating scale part-III was similar between the groups. No negative effects of ketamine on hemodynamic stability or cognition were reported perioperatively. Ketamine-induced conscious sedation provided high quality microelectrode recordings comparable with awake conditions. Additionally, it seems to allow superior patient satisfaction and hemodynamic stability, while maintaining similar post-operative outcomes. Therefore, it holds promise as a novel alternative anesthetic regimen for DBS. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Restless legs syndrome in the dominant Parkinson's side related to subthalamic deep-brain stimulation

BackgroundRestless legs syndrome (RLS) has an increased estimated prevalence in patients with Parkinson’s disease (PS). RLS frequently mimics symptoms intrinsic to PD, such as motor restlessness, contributing to making its diagnosis challenging in this population. We report the case of a patient with new-onset RLS following subthalamic deep-brain stimulation (DBS-STN). We assessed symptoms using suggested immobilization test (SIT) with both DBS-STN activated and switched off. Case descriptionA 59-year-old man with idiopathic PD developed disabling RLS following DBS-STN at age 58, with PD onset at 50 manifesting as left arm tremor. Despite improved motor symptoms during the month following surgery, the patient experienced left leg discomfort at rest, transiently alleviated by movements due to an irrepressible urge to move, and worsened at night. Symptoms had no temporal relationship with oral dopa-therapy and disappeared when DBS-STN was deactivated. A 1 h SIT assessed motor behavior with irrepressible urge to move, as well as sensory symptoms by visual analog scale. After 30 m DBS-STN was switched off followed by the appearance of tremor in the left arm while both motor and sensory symptoms of RLS disappeared in the left leg. DiscussionThe mechanisms of DBS-STN’s impact on RLS remain controversial. We hypothesize the DBS-STN to induce in our patient a hyperdopaminergic tone. DBS-induced and DBS-ameliorated RLS represent interesting conditions to further understand the pathophysiology of RLS. Moreover, the present observation suggests that SIT can be a valuable tool to assess RLS in PD patients before and after DBS-STN in future prospective studies.

The impact of subthalamic deep-brain stimulation in restoring motor symmetry in Parkinson's disease patients: a prospective study.

The impact of subthalamic deep-brain stimulation (STN-DBS) on motor asymmetry and its influence on both motor and non-motor outcomes remain unclear. The present study aims at assessing the role of STN-DBS on motor asymmetry and how its modulation translates into benefits in motor function, activities of daily living (ADLs) and quality of life (QoL). Postoperative motor asymmetry has been assessed on the multicentric, prospective Predictive Factors and Subthalamic Stimulation in Parkinson's Disease cohort. Asymmetry was evaluated at both baseline (pre-DBS) and 1year after STN-DBS. A patient was considered asymmetric when the right-to-left MDS-UPDRS part III difference was ≥ 5. In parallel, analyses have been carried out using the absolute right-to-left difference. The proportion of asymmetric patients at baseline was compared to that in the post-surgery evaluation across different medication/stimulation conditions. 537 PD patients have been included. The proportion of asymmetric patients was significantly reduced after both STN-DBS and medication administration (asymmetric patients: 50% in pre-DBS MedOFF, 35% in MedOFF/StimON, 26% in MedON/StimOFF, and 12% in MedON/StimON state). Older patients at surgery and with higher baseline UPDRS II scores were significantly less likely to benefit from STN-DBS at the level of motor asymmetry. No significant correlation between motor asymmetry and ADLs (UPDRS II) or overall QoL (PDQ-39) score was observed. Asymmetric patients had significantly higher mobility, communication, and daily living PDQ-39 sub-scores. Both STN-DBS and levodopa lead to a reduction in motor asymmetry. Motor symmetry is associated with improvements in certain QoL sub-scores.

Motor and Non-motor Outcomes of Deep Brain Stimulation across the Genetic Panorama of Parkinson's Disease: A Multi-Scale Meta-Analysis.

In the era of modern medicine, where high-throughput sequencing techniques are readily available, it is desirable to elucidate the role of genetic background in patients with Parkinson's Disease (PD) undergoing Deep Brain Stimulation (DBS). Genetic stratification of PD patients undergoing DBS may assist in patient selection and prediction of clinical outcomes and complement existing selection procedures such as levodopa challenge testing. To capture a broad spectrum of motor and non-motor DBS outcomes in genetic PD patients with data from the recently updated literature. A multi-scale meta-analysis with 380 genetic PD cases was conducted using the Cochrane Review Manager, JASP software and R. This meta-analysis revealed that overall, patients with genetic PD are good candidates for DBS but the outcomes might differ depending on the presence of specific mutations. PRKN carriers benefited the most regarding motor function, daily dose medication and motor complications. However, GBA carriers appeared to be more prone to cognitive decline after subthalamic nucleus DBS accompanied by a low quality of life with variable severity depending on genetic variants and concomitant alterations in other genes. Apart from GBA, cognitive worsening was also observed in SNCA carriers. Pre-operative levodopa responsiveness and a younger age of onset are associated with a favorable motor outcome. A personalized approach with a variant-based risk stratification within the emerging field of surgicogenomics is needed. Integration of polygenic risk scores in clinical-decision making should be encouraged.

Impact of deep brain stimulation on gait in Parkinson disease: A kinematic study

BackgroundThe effect of Deep Brain Stimulation (DBS) on gait in Parkinson’s Disease (PD) is poorly understood. Kinematic studies utilizing quantitative gait outcomes such as speed, cadence, and stride length have shown mixed results and were done mostly before and after acute DBS discontinuation. ObjectiveTo examine longitudinal changes in kinematic gait outcomes before and after DBS surgery. MethodWe retrospectively assessed changes in quantitative gait outcomes via motion capture in 22 PD patients before and after subthalamic (STN) or globus pallidus internus (GPi) DBS, in on medication state. Associations between gait outcomes and clinical variables were also assessed. ResultGait speed reduced from 110.7 ± 21.3 cm/s before surgery to 93.6 ± 24.9 after surgery (7.7 ± 2.9 months post-surgery, duration between assessments was 15.0 ± 3.8 months). Cadence, step length, stride length, and single support time reduced, while total support time, and initial double support time increased. Despite this, there was overall improvement in the Movement Disorder Society-Unified Parkinson Disease Rating Scale-Part III score “on medication/on stimulation” score (from 19.8 ± 10.7–13.9 ± 8.6). Change of gait speed was not related to changes in levodopa dosage, disease duration, unilateral vs bilateral stimulation, or target nucleus. ConclusionQuantitative gait outcomes in on medication state worsened after chronic DBS therapy despite improvement in other clinical outcomes. Whether these changes reflect the effects of DBS as opposed to ongoing disease progression is unknown.

The advantages of general anesthesia subthalamic deep brain stimulation for Parkinson's disease in the enhanced recovery after surgery: A randomized clinical trial

AbstractBackground and AimsWith advancements in imaging and microelectrode recording techniques, general anesthesia (GA) has emerged as an alternative option for Parkinson's disease (PD) patients undergoing subthalamic nucleus deep brain stimulation (STN‐DBS). In this study, we compared the advantages and disadvantages of using GA and local anesthesia for STN‐DBS in enhanced recovery after surgery (ERAS).MethodsSurgical outcomes of STN‐DBS were evaluated using the unified PD rating scales (UPDRS). CT and magnetic resonance imaging scans are used to evaluate intracranial conditions. State‐trait anxiety inventory and hospital anxiety and depression scale are used to evaluate patients' perioperative psychology.ResultsAnesthesia method does not significantly impact the accuracy of microelectrode placement or the improvement of postoperative symptoms. However, the local anesthesia group had a higher incidence of intracranial air, as well as higher rates of postoperative complications such as headache, dizziness, vomiting, and delirium. GA effectively alleviated preoperative anxiety and resulted in lower levels of perioperative anxiety and psychological stress compared to local anesthesia. Additionally, the GA group had shorter surgery duration, earlier ambulation, and a shorter average hospital stay.ConclusionDBS under GA is safe and effective. Due to shorter surgical duration, reduced occurrence of perioperative complications, effective reduction of preoperative anxiety, and faster postoperative recovery, DBS under GA is better aligned with the concept of ERAS.

Subthalamic nucleus deep brain stimulation in primary Meige syndrome: motor and non-motor outcomes.

Deep brain stimulation (DBS) has emerged as a promising treatment for movement disorders. This prospective study aims to evaluate the effects of bilateral subthalamic nucleus DBS (STN-DBS) on motor and non-motor symptoms in patients with primary Meige syndrome. Thirty patients who underwent bilateral STN-DBS between April 2017 and June 2020 were included. Standardized and validated scales were utilized to assess the severity of dystonia, health-related quality of life, sleep, cognitive function and mental status at baseline and at 1 year and 3 years after neurostimulation. The Burke-Fahn-Marsden Dystonia Rating Scale movement scores showed a mean improvement of 63.0% and 66.8% at 1 year and 3 years, respectively, after neurostimulation. Similarly, the Burke-Fahn-Marsden Dystonia Rating Scale disability scores improved by 60.8% and 63.3% at the same time points. Postoperative quality of life demonstrated a significant and sustained improvement throughout the follow-up period. However, cognitive function, mental status, sleep quality and other neuropsychological functions did not change after 3 years of neurostimulation. Eight adverse events occurred in six patients, but no deaths or permanent sequelae were reported. Bilateral STN-DBS is a safe and effective alternative treatment for primary Meige syndrome, leading to improvements in motor function and quality of life. Nevertheless, it did not yield significant amelioration in cognitive, mental, sleep status and other neuropsychological functions after 3 years of neurostimulation.

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

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

Mechanical behavior and microstructure of porcine brain tissues under pulsed electric fields.

Pulsed electric fields are extensively utilized in clinical treatments, such as subthalamic deep brain stimulation, where electric field loading is in direct contact with brain tissue. However, the alterations in brain tissue's mechanical properties and microstructure due to changes in electric field parameters have not received adequate attention. In this study, the mechanical properties and microstructure of the brain tissue under pulsed electric fields were focused on. Herein, a custom indentation device was equipped with a module for electric field loading. Parameters such as pulse amplitude and frequency were adjusted. The results demonstrated that following an indentation process lasting 5s and reaching a depth of 1000 μm, and a relaxation process of 175s, the average shear modulus of brain tissue was reduced, and viscosity decreased. At the same amplitude, high-frequency pulsed electric fields had a smaller effect on brain tissue than low-frequency ones. Furthermore, pulsed electric fields induced cell polarization and reduced the proteoglycan concentration in brain tissue. As pulse frequency increased, cell polarization diminished, and proteoglycan concentration decreased significantly. High-frequency pulsed electric fields applied to brain tissue were found to reduce impedance fluctuation amplitude. This study revealed the effect of pulsed electric fields on the mechanical properties and microstructure of ex vivo brain tissue, providing essential information to promote the advancement of brain tissue electrotherapy in clinical settings.

Directional versus ring-mode deep brain stimulation for Parkinson’s disease: protocol of a multi-centre double-blind randomised crossover trial

BackgroundThe effectiveness of Deep Brain Stimulation (DBS) therapy for Parkinson’s disease can be limited by side-effects caused by electrical current spillover into structures adjacent to the target area. The objective of the STEEred versus RING-mode DBS for Parkinson’s disease (STEERING) study is to investigate if directional DBS for Parkinson’s disease results in a better clinical outcome when compared to ring-mode DBS.MethodsThe STEERING study is a prospective multi-centre double-blind randomised crossover trial. Inclusion criteria are Parkinson’s disease, subthalamic nucleus DBS in a ‘classic’ ring-mode setting for a minimum of six months, and optimal ring-mode settings have been established. Participants are categorised into one of two subgroups according to their clinical response to the ring-mode settings as ‘responders’ (i.e., patient with a satisfactory effect of ring-mode DBS) or ‘non-responder’ (i.e., patient with a non-satisfactory effect of ring-mode DBS). A total of 64 responders and 38 non-responders will be included (total 102 patients). After an optimisation period in which an optimal directional setting is found, participants are randomised to first receive ring-mode DBS for 56 days (range 28–66) followed by directional DBS for 56 days (28–66) or vice-versa. The primary outcome is the difference between ring-mode DBS and directional DBS settings on the Movement Disorders Society Unified Parkinson’s Disease Rating Scale – Motor Evaluation (MDS-UPDRS-ME) in the off-medication state. Secondary outcome measures consist of MDS-UPDRS-ME in the on-medication state, MDS-UPDRS Activities of Daily Living, MDS-UPDRS Motor Complications–Dyskinesia, disease related quality of life measured with the Parkinson’s Disease Questionnaire 39, stimulation-induced side-effects, antiparkinsonian medication use, and DBS-parameters. Participants’ therapy preference is measured at the end of the study. Outcomes will be analysed for both responder and non-responder groups, as well as for both groups pooled together.DiscussionThe STEERING trial will provide insights into whether or not directional DBS should be standardly used in all Parkinson’s disease DBS patients or if directional DBS should only be used in a case-based approach.Trial registrationThis trial was registered on the Netherlands Trial Register, as trial NL6508 (NTR6696) on June 23, 2017.

Subthalamic deep brain stimulation improves vascular endothelial function in Parkinson's disease

ObjectivesVascular health (white matter change, vascular risk factor, angiogenesis, microvascular alteration) is associated with clinical progression or levodopa-induced dyskinesia in PD. Vascular endothelial function is known to reflect the earliest vascular change. While DBS can improve motor and non-motor symptoms, the effect of DBS on vascular endothelial function is unknown. Thus, we aimed to investigate whether DBS surgery could impact vascular endothelial function in PD. MethodA total of 20 PD patients were recruited. Vascular endothelial function was evaluated with flow-mediated dilation (FMD). FMD was investigated before and after one year of DBS surgery. ResultsFMD improved (6.01 ± 1.58 to 6.84 ± 1.57, p = 0.027). While the level of homocysteine slightly decreased (13.8 ± 4.1 to 13.0 ± 3.2, p = 0.05), there was no significant correlation between FMD changes and homocysteine levels (r = 0.42, p = 0.065). FMD change was associated with baseline age (r = −0.59, p = 0.006) but not with disease duration (p = 0.73), baseline UPDRS III (p = 0.81), change of UPDRS III and dyskinesia, and LEDD change (p = 0.94). Multivariate linear regression analysis revealed that only age (B = −0.139; p = 0.024) was significantly and inversely correlated with the change of FMD. ConclusionsWe found that STN-DBS improves vascular endothelial function in PD. Further studies are needed to clarify the exact pathogenesis and clinical implication of beneficial effects on vascular endothelial dysfunction in PD.