Bilateral STN-DBS Research Articles

Development of Clinical Milestones in Parkinson’s Disease After Bilateral Subthalamic Deep Brain Stimulation

Objective Deep brain stimulation of the subthalamic nucleus (STN-DBS) in Parkinson’s disease (PD) patients does not halt disease progression, as these patients will progress and develop disabling non-levodopa responsive symptoms. These features may act as milestones that represent the overall functionality of patients after DBS. The objective of this study was to investigate the development of clinical milestones in advanced PD patients who underwent bilateral STN-DBS.Methods The study evaluated PD patients who underwent STN-DBS at baseline up to their last follow-up using the Unified Parkinson’s Disease Rating Scale and Hoehn and Yahr scale. The symptoms of hallucinations, dysarthria, dysphagia, frequent falls, difficulty walking, cognitive impairment and the loss of autonomy were chosen as the clinical milestones.Results A total of 106 patients with a mean age of 47.21 ± 10.52 years at disease onset, a mean age of 58.72 ± 8.74 years at surgery and a mean disease duration of 11.51 ± 4.4 years before surgery were included. Initial improvement of motor symptoms was seen after the surgery with the appearance of clinical milestones over time. Using the moderately disabling criteria, 81 patients (76.41%) developed at least one clinical milestone, while 48 patients (45.28%) developed a milestone when using the severely disabling criteria.Conclusion STN-DBS has a limited effect on axial and nonmotor symptoms of the PD patients, in contrast to the effect on motor symptoms. These symptoms may serve as clinical milestones that can convey the status of PD patients and its impact on the patients and their caregivers. Therefore, advanced PD patients, even those treated with bilateral STN-DBS, will still require assistance and cannot live independently in the long run.

Effects of subthalamic deep brain stimulation on non‐motor symptoms of Parkinson's disease: A meta‐analysis

Deep brain stimulation (DBS) is a well-defined treatment for motor symptoms in advanced PD. Although several studies have investigated the DBS effect on non-motor symptoms (NMS), controversial results exist regarding this matter. The aim of this meta-analysis and systematic review was to assess the bilateral subthalamic nucleus (STN) DBS effect on NMS of PD. We conducted a systematic search on the literature of Web of Science (WOS), PubMed/MEDLINE, Scopus, Cochrane, and Embase. An additional hand search was also done. Finally, a meta-analysis was conducted on 10 studies containing pre- and post-bilateral STN-DBS data regarding NMS acquired using Non-Motor Symptoms Scale for Parkinson's Disease (NMSS) or Non-Motor Symptoms Questionnaire (NMSQ). A random-effects model was used to determine weighted mean differences, and the heterogeneity index was evaluated using Cochrane's Q test. Our study results indicated that bilateral STN-DBS significantly reduced total NMSS and NMSQ score (WMD -17.73; 95% confidence interval [CI] -20.28 to -15.18, WMD -2.19; 95% CI -2.98 to -1.40), respectively, and no publication bias was found. Regarding each of the NMSS domains, DBS significantly reduced the scores of following domains: sleep (WMD -5.98; 95% CI -6.82 to -5.15), miscellaneous (WMD -4.19; 95% CI -4.96 to -3.43), urinary (WMD -2.99; 95% CI -3.78 to -2.19), sexual (WMD -0.65; 95% CI -1.16 to -0.14), and attention/memory (WMD -0.59; 95% CI -1.15 to -0.03). This meta-analysis demonstrated that bilateral STN-DBS has beneficial effects on NMS of PD.

The Role of Microelectrode Recording and Stereotactic Computed Tomography in Verifying Lead Placement During Awake MRI-Guided Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease.

Background:Bilateral deep brain stimulation of the subthalamic nucleus (STN-DBS) has become a cornerstone in the advanced treatment of Parkinson’s disease (PD). Despite its well-established clinical benefit, there is a significant variation in the way surgery is performed. Most centers operate with the patient awake to allow for microelectrode recording (MER) and intraoperative clinical testing. However, technical advances in MR imaging and MRI-guided surgery raise the question whether MER and intraoperative clinical testing still have added value in DBS-surgery.Objective:To evaluate the added value of MER and intraoperative clinical testing to determine final lead position in awake MRI-guided and stereotactic CT-verified STN-DBS surgery for PD.Methods:29 consecutive patients were analyzed retrospectively. Patients underwent awake bilateral STN-DBS with MER and intraoperative clinical testing. The role of MER and clinical testing in determining final lead position was evaluated. Furthermore, interobserver variability in determining the MRI-defined STN along the planned trajectory was investigated. Clinical improvement was evaluated at 12 months follow-up and adverse events were recorded.Results:98% of final leads were placed in the central MER-track with an accuracy of 0.88±0.45 mm. Interobserver variability of the MRI-defined STN was 0.84±0.09. Compared to baseline, mean improvement in MDS-UPDRS-III, PDQ-39 and LEDD were 26.7±16.0 points (54%) (p < 0.001), 9.0±20.0 points (19%) (p = 0.025), and 794±434 mg/day (59%) (p < 0.001) respectively. There were 19 adverse events in 11 patients, one of which (lead malposition requiring immediate postoperative revision) was a serious adverse event.Conclusion:MER and intraoperative clinical testing had no additional value in determining final lead position. These results changed our daily clinical practice to an asleep MRI-guided and stereotactic CT-verified approach.

Synchronized Intracranial Electrical Activity and Gait Recording in Parkinson’s Disease Patients With Freezing of Gait

BackgroundThis study aimed to describe a synchronized intracranial electroencephalogram (EEG) recording and motion capture system, which was designed to explore the neural dynamics during walking of Parkinson’s disease (PD) patients with freezing of gait (FOG). Preliminary analysis was performed to test the reliability of this system.MethodsA total of 8 patients were enrolled in the study. All patients underwent bilateral STN-DBS surgery and were implanted with a right subdural electrode covering premotor and motor area. Synchronized electrophysiological and gait data were collected using the Nihon Kohden EEG amplifier and Codamotion system when subjects performed the Timed Up and Go (TUG) test. To verify the reliability of the acquisition system and data quality, we calculated and compared the FOG index between freezing and non-freezing periods during walking. For electrophysiological data, we first manually reviewed the scaled (five levels) quality during waking. Spectra comprising broadband electrocorticography (ECoG) and local field potential (LFP) were also compared between the FOG and non-FOG states. Lastly, connectivity analysis using coherence between cortical and STN electrodes were conducted. In addition, we also use machine learning approaches to classified FOG and non-FOG.ResultsA total of 8 patients completed 41 walking tests, 30 of which had frozen episodes, and 21 of the 30 raw data were level 1 or 2 in quality (70%). The mean ± SD walking time for the TUG test was 85.94 ± 47.68 s (range: 38 to 190.14 s); the mean ± SD freezing duration was 12.25 ± 7.35 s (range: 1.71 to 27.50 s). The FOG index significantly increased during the manually labeled FOG period (P < 0.05). The beta power of STN LFP in the FOG period was significantly higher than that in the non-FOG period (P < 0.05), while the band power of ECoG did not exhibit a significant difference between walking states. The coherence between the ECoG and STN LFP was significantly greater in high beta and gamma bands during the FOG period compared with the shuffled surrogates (P < 0.05). Lastly, STN-LFP band power features showed above-chance performance (p < 0.01, permutation test) in identifying FOG epochs.ConclusionIn this study, we established and verified the synchronized ECoG/LFP and gait recording system in PD patients with FOG. Further neural substrates underlying FOG could be explored using the current system.

818 Association Between Intraoperative LFP, Lead Location, and Outcomes in Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease

INTRODUCTION: Imaging-based, LFP-based and empirical programming strategies can be used to determine the optimal therapeutic contact for deep brain stimulation, but the most efficient strategy is unclear. METHODS: In this prospective, IRB-approved study, 10 awake patients were implanted with bilateral STN DBS using both an electrophysiologically- and imaged-confirmed technique. Once the DBS lead had been secured, LFP signals were recorded with a Grapevine Neural Amplifier (Ripple Neuro, UT) at 30 KHz and 16-bit A/D resolution, and LFPs were down-sampled to 2 KHz before further processing. Stereotactic CTs acquired two weeks postoperatively were fused to the pre-operative 3T, T2 weighted MRI and processed using the SureTune platform (Medtronic, MN). Therapeutic DBS programming parameters were obtained 6 months post-implantation, along with pre- and post-operative UPDRS Part III scores. RESULTS: There was a 54% reduction in the UPDRS score when comparing the preoperative OFF score, to the 6 month postoperative OFF Meds/ON Stimulation Score. 50% of the chosen contacts were in the STN only, 10% in the ZI only, and 35% in both. One lead was found to be outside the segmented STN and ZI; this patient did not experience clinical improvement based on their Part III UPDRS score. Beta (8-30Hz) power was 4.1 times higher for electrodes within the STN versus out, 1.4 times for ZI versus out, and 5.9 times higher for both versus neither. The average beta power was 15% higher in the chosen therapeutic contacts over those contacts not used. Lastly, we found that the number of electrodes within the STN correlated with the decrease in the UPDRS score (r=0.27). CONCLUSIONS: There is a strong correlation between image-based electrode localization, LFP characteristics, and clinical outcomes in patients undergoing STN DBS for Parkinson Disease. Focused programming strategies based on either imaging or LFP data can facilitate identification of the optimal therapeutic contact.

The Intraoperative Microlesion Effect Positively Correlates With the Short-Term Clinical Effect of Deep Brain Stimulation in Parkinson's Disease

ObjectiveDuring the surgical procedure of deep brain stimulation (DBS), insertion of an electrode in the subthalamic nucleus (STN) frequently causes a temporary improvement of motor symptoms, known as the microlesion effect (MLE). The objective of this study was to determine the correlation between the intraoperative MLE and the clinical effect of DBS. Materials and MethodsThirty Parkinson's disease (PD) patients with Movement Disorder Society (MDS) Unified Parkinson's Disease Rating Scale (UPDRS) part III (MDS-UPDRS III) scores during bilateral STN-DBS implantation were included in this retrospective study. MDS-UPDRS III subscores (resting tremor, rigidity, and bradykinesia) of the contralateral upper extremity were used. During surgery, these subscores were assessed directly before and after insertion of the electrode. Also, these subscores were determined in the outpatient clinic after 11 weeks on average (on-stimulation). All assessments were performed in an off-medication state (at least 12 hours of medication washout). ResultsPostinsertion MDS-UPDRS motor scores decreased significantly compared to preinsertion scores (p < 0.001 for both hemispheres). The MLE showed a positive correlation with the clinical effect of DBS in both hemispheres (rho = 0.68 for the primarily treated hemisphere, p < 0.001, and rho = 0.59 for the secondarily treated hemisphere, p < 0.01). ConclusionThe MLE has a clinically relevant correlation with the effect of DBS in PD patients. These results suggest that the MLE can be relied upon as evidence of a clinically effective DBS electrode placement.

P.155 Prospective cohort analysis of normal versus mild cognitive impairment for quality of life outcome following DBS for Parkinson’s disease

Background: All guidelines for DBS in Parkinson’s disease (PD) include a contraindication for ‘dementia’. It is unclear where this cut-off should occur and if patients with mild cognitive impairment (MCI) do not do as well. This prospective cohort analysis assessed if pre-operative cognition affected post-operative quality of life. Methods: PD patients receiving bilateral STN-DBS (n=100) were prospectively studied using STROBE guidelines. All had Montreal Cognitive Assessment (MoCA), motor (UPDRS), mood (BDI-II), and quality of life (Parkinson Disease Questionnaire summary index, PDQ-39-SI). Two cohorts, pre-operative MCI (MoCA:18-25) and normal cognition (MoCA:26-30), had post-operative PDQ-39-SI at 1-year. The primary outcome was the proportion of patients with an improved PDQ-39-SI at 1-year. Results: Cohorts were not significantly different in age, severity of illness, response to dopamine, or mood. MCI was present in 27/100. Improved quality of life at 1-year occurred in 75% with normal cognition and 70% with MCI (p=0.54) with RR=1.1 (95% CI, 0.8-1.5). Linear regression analysis showed no correlation between pre-operative cognition and post-operative outcome (R2=0.02). Conclusions: Parkinson’s patients with MCI should be offered DBS if their motor symptoms require surgery. Guidelines for DBS surgery in PD should change from “dementia is contraindicated” to “patients require adequate cognitive functioning, MoCA318”.

Anterior lead location predicts verbal fluency decline following STN-DBS in Parkinson's disease

IntroductionVerbal fluency (VF) decline is a well-documented cognitive effect of Deep Brain Stimulation of the subthalamic nucleus (STN-DBS) in patients with Parkinson's disease (PD). This decline may be associated with disruption to left-sided frontostriatal circuitry involving the anteroventral non-motor area of the STN. While recent studies have examined the impact of lead location in relation to functional STN subdivisions on VF outcomes, results have been mixed and methods have been limited by atlas-based location mapping. MethodsParticipants included 59 individuals with PD who underwent bilateral STN-DBS. Each participant's active contact location was determined in an atlas-independent fashion, relative to their individual MR-visualized STN midpoint. Multiple linear regression was used to examine lead location in each direction as a predictor of phonemic and semantic VF decline, controlling for demographic and disease variables. ResultsMore anterior lead locations relative to the STN midpoint in the left hemisphere predicted greater phonemic VF decline (B = −2.34, B SE = 1.08, β = −0.29, sr2 = 0.08). Lead location was not a significant predictor of semantic VF decline. ConclusionUsing an individualized atlas-independent approach, present findings suggest that more anterior stimulation of the left STN may uniquely contribute to post-DBS VF decline. This is consistent with models in which the anterior STN represents a “non-motor” functional subdivision with connections to frontal regions, e.g., the left dorsal prefrontal cortex. Future studies should investigate the effect of DBS lead trajectory on VF outcomes.

Early subthalamic nucleus deep brain stimulation in Parkinson’s disease reduces long-term medication costs

IntroductionSubthalamic nucleus (STN) deep brain stimulation (DBS) is recognized as a safe and effective treatment in mid- and advanced-staged Parkinson’s disease (PD) that decreases the need for PD medications and their associated costs. This study reports medication costs from the only clinical trial to evaluate DBS in patients with early-stage PD and projects costs through advanced-stage disease. MethodsThe DBS in early-stage PD pilot was a prospective, single-blind clinical trial that randomized 30 patients with early-stage PD 1:1 to receive bilateral STN-DBS plus optimal drug therapy (ODT) or ODT alone. Subjects who completed the trial participated in an observational follow-up study and were evaluated annually for five years after randomization. PD medication data collected at each study visit were used to calculate and project medication costs (n = 28). ResultsFive-year cumulative medication cost reduction with early DBS+ODT was $28,246. Mean annual medication cost for early DBS+ODT subjects was 2.4 times lower than early ODT subjects (β = 2.4, 95%CI:1.5–3.7, p = 0.0004). Early DBS+ODT is projected to reduce cumulative medication costs by $104,958 over 15 years of disease duration. ConclusionDBS in early-stage PD may provide long-term medication cost reduction compared to standard care.

Analysis of dysgraphia in advanced Parkinson's disease patients following bilateral STN-DBS – A prospective study

Parkinson's disease is characterized by varying intensities of bradykinesia, rigidity and tremor leading to disturbances in writing skills of the patient. We undertook this study to evaluate dysgraphia features in advanced Parkinson's disease cases and changes in these features after bilateral Subthalamic Nucleus Deep Brain Stimulation.

Predictors of short-term impulsive and compulsive behaviour after subthalamic stimulation in Parkinson disease

BackgroundThe effects of subthalamic stimulation (subthalamic nucleus-deep brain stimulation, STN-DBS) on impulsive and compulsive behaviours (ICB) in Parkinson’s disease (PD) are understudied.ObjectiveTo investigate clinical predictors of STN-DBS effects on ICB.MethodsIn...

Effects of Bilateral STN-DBS on Psychiatric Profile, Cognitive Aspects, and Quality of Life in Patients with Parkinson's Disease

Background: Apart from motor manifestations, Parkinson's disease (PD) and associated treatment modalities including DBS are associated with less studied psychiatric and cognitive symptoms. Aim: This study aims to evaluate psychiatric profile, cognition, and quality of life in patients with advanced PD and the effects on STN-DBS on them. Study Design: A prospective, single center, observational study using a direct, structured interview of PD patients. Materials and Methods: All consecutive patients undergoing bilateral STN-DBS between the period June 2017 and December 2019 were evaluated with mini international neuropsychiatric interview (MINI), Addenbrooke's Cognitive Examination (ACE), and PD questionnaire-39 (PDQ-39) before surgery. All these patients were evaluated at 6 weeks postsurgery with MINI and with MINI, ACE and PDQ-39 at 6 months postsurgery. Lead position in magnetic resonance imaging was correlated with psychiatric manifestations. Paired t-test and Wilcoxon sign-rank test were used to study the difference between means. Results: There were a total of 40 cases operated in the study period. There were two patients who had cerebral hemorrhage and two had leads removed due to infection and these patients were excluded from the final analysis. Out of 36 patients, depression was noted in 7 (19.4%), psychosis in 5 (13.8%), anxiety in 10 (27.7%), and suicidal ideation in 2 (5.5%) cases. Postoperatively, 85% of patients with depression, 80% with psychosis, and 80% of patients with anxiety disorders improved. One patient developed new-onset depression and one patient developed visual hallucination. Two patients had acute deterioration in the immediate postoperative period. The patient who developed depression and hallucination had their leads medially located. Mild cognitive decline was noted in verbal fluency which was significant (P = 0.003), and however, there was a significant improvement in quality of life (P = 0.001). Conclusions: Bilateral STN-DBS is a safe and effective therapeutic option and improves psychiatric disorders if the leads are appropriately placed. Although mild cognitive decline occurs, there is overall significant improvement in quality of life.

How accurately are subthalamic nucleus electrodes implanted relative to the ideal stimulation location for Parkinson's disease?

IntroductionThe efficacy of subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson’s disease (PD) depends on how closely electrodes are implanted relative to an individual’s ideal stimulation location. Yet, previous studies have assessed how closely electrodes are implanted relative to the planned location, after homogenizing data to a reference. Thus here, we measured how accurately electrodes are implanted relative to an ideal, dorsal STN stimulation location, assessed on each individual’s native imaging. This measure captures not only the technical error of stereotactic implantation but also constraints imposed by planning a suitable trajectory.MethodsThis cross-sectional study assessed 226 electrodes in 113 consecutive PD patients implanted with bilateral STN-DBS by experienced clinicians utilizing awake, microelectrode guided, surgery. The error (Euclidean distance) between the actual electrode trajectory versus a nominated ideal, dorsal STN stimulation location was determined in each hemisphere on native imaging and predictive factors sought.ResultsThe median electrode location error was 1.62 mm (IQR = 1.23 mm). This error exceeded 3 mm in 28/226 electrodes (12.4%). Location error did not differ between hemispheres implanted first or second, suggesting brain shift was minimised. Location error did not differ between electrodes positioned with (48/226), or without, a preceding microelectrode trajectory shift (suggesting such shifts were beneficial). There was no relationship between location error and case order, arguing against a learning effect.Discussion/ConclusionThe proximity of STN-DBS electrodes to a nominated ideal, dorsal STN, stimulation location is highly variable, even when implanted by experienced clinicians with brain shift minimized, and without evidence of a learning effect. Using this measure, we found that assessments on awake patients (microelectrode recordings and clinical examination) likely yielded beneficial intraoperative decisions to improve positioning. In many patients the error is likely to have reduced therapeutic efficacy. More accurate methods to implant STN-DBS electrodes relative to the ideal stimulation location are needed.

P 37. The cognitive course in Parkinson's disease patients treated with Deep Brain Stimulation of subthalamic nucleus – Correlations with qEEG

Objective. Deep brain stimulation of the subthalamic nucleus (STN-DBS) improve motor functioning in Parkinson“s disease patients– Additionally it can also influence cognitive functioning. In most patients, a decline of verbal fluency test performance after STN-DBS is often reported. The purpose of this study was to determine whether preoperative quantitative electroencephalography (qEEG) may be useful in the preoperative assessment predicting cognitive changes in PD patients treated with STN-DBS. Methods. We compared the cognitive performance of 16 PD patients who underwent bilateral STN-DBS and 15 PD controls (matched for age, sex and education) at baseline as well as after 24 months. Cognitive scores were calculated for all patients across 5 cognitive domains covered by different cognitive tests (attention, executive function, episodic & working memory, verbal fluency, visuo-construction). A preoperative 256-channels EEG was recorded of each patient at rest and global relative power spectra were computed. Correlation and linear regression models were used to assess the association of preoperative EEG measures with postoperative cognitive scores in stimulated PD patients compared to PD controls. Results. The decline of verbal fluency performance after two years in the PD group treated with STN-DBS was significant in comparison to the PD controls ( p < 0.001). All other cognitive domains declined in the same manner as in the PD controls or remained stable over the 24-months period. EEG frequency analyses revealed increased global theta power (4-8 Hz) at baseline to be associated with reduced postoperative verbal fluency performance ( r = 0.50, p < 0.05) at follow-up. Conclusion. Consistent with the results of former studies, STN stimulation deteriorates verbal fluency in the course of two years. Accordingly, we observed significant decline in tests measuring verbal fluency in the group of PD patients treated with STN-DBS compared to a control group of PD patients. The decline of verbal fluency performance could be predicted by a reduced theta power at baseline. No other significant differences in cognitive alterations between patients in the STN-DBS group and the PD control group occur over two years.

A prospective pilot study of the effects of deep brain stimulation on olfaction and constipation in Parkinson’s disease

BackgroundPrevious studies suggest deep brain stimulation of the subthalamic nucleus (STN-DBS) may improve olfaction and constipation in PD, using subjective measures. ObjectiveTo utilize objective measures to assess olfaction and constipation in PD following STN-DBS. MethodsIn this prospective pilot study, olfaction (University of Pennsylvania Smell Identification Test [UPSIT]), bowel symptoms (ROME III questionnaires, daily bowel diaries, 100 mm visual analog scales for satisfaction with treatment and bowel habits), and motor manifestations of PD were evaluated before and after STN-DBS. Levodopa equivalent daily dose (LEDD) was calculated. ResultsTen patients (8 men, mean age 67.4 ± 6.0 years) with mean PD duration of 7.5 ± 3.7 years underwent bilateral STN-DBS, with mean follow-up of 3 months for all measures, except 7 months follow-up for bowel diaries. There was improvement in the Unified Parkinson’s Disease Rating Scale motor “off” scores (33.7 ± 6.7 before and 16.1 ± 10.8 after, P = 0.001). Mean UPSIT scores (20.0 ± 6.6 versus 17.5 ± 5.7, P = 0.03) worsened from severe to total hyposmia. Seven patients had baseline constipation and completed bowel diaries. There was improvement in number of complete spontaneous bowel motions (CBSM) per week (2.2 ± 1.9 before versus 4.7 ± 2.4 after, P = 0.04), satisfaction with treatment of constipation (44 ± 27 before versus 64 ± 25 after, P = 0.02), and with bowel motions (33 ± 22 before and 48 ± 20 after, P = 0.2). However, laxative use (P = 0.15) and LEDD (P = 0.15) were unchanged. ConclusionOlfaction worsened while symptoms of constipation improved but did not resolve after STN-DBS.

Long-term effect of bilateral STN-DBS on non-motor symptoms in Parkinson's disease: A four-year observational, prospective study

BackgroundSeveral studies have shown beneficial effects of bilateral stimulation of the subthalamic nucleus (STN-DBS) on motor as well as on non-motor symptoms (NMS) up to 36 months post-surgery in advanced Parkinson's disease (PD) patients. We set to explore the long-term effect of STN-DBS on NMS in a four-year follow-up, prospective, observational study. MethodsForty patients were enrolled and assessed at baseline. Twenty-eight were followed-up at 6, 12, 24, 36 and 48 months after the operation. The effect of post-operative time on NMS was analyzed by six-level repeated measures ANOVA. In a post-hoc analysis the follow-up scores were compared to baseline using a paired t-test. ResultsThe following scores stayed improved up to 24 months after surgery, presented as baseline/24 months, p-value (t-test): total Non-Motor Symptoms Scale score (54.0 ± 5.6/44.9 ± 5.0, p = 0.029), Hamilton Anxiety Scale (14.3 ± 1.3/11.3 ± 1.2, p = 0.019) and PDQ39 (53.4 ± 4.5/40.2 ± 2.9, p = 0.012). PD Sleep Scale 2 remained improved throughout the study (17.4 ± 2.0/12.8 ± 1.3 at 48 months, p = 0.032), while Beck Depression Inventory only at six months post-surgery (9.5 ± 1.2/6.7 ± 0.7 at 6 months, p = 0.006). Montreal Cognitive Assessment remained stable up to 24 months and then declined at 36 months (26.3 ± 0.5/25.4 ± 0.5 at 36 months, p = 0.003), Starkstein Apathy Scale deteriorated throughout the study (7.6 ± 0.7/12.7 ± 0.9 at 48 months, p = 0.006). ConclusionsWe observed beneficial effect of STN-DBS in several but not all domains of NMS at least up to 24 months post-op in advanced PD. Further long-term studies on larger cohorts of PD patients and longer follow-up need to be conducted to better understand the long-term effect of STN-DBS on NMS.

The Effect of Deep Brain Stimulation of the Subthalamic Nucleus on Language Function in Parkinson's Disease: A Systematic Review.

Purpose This systematic review focuses on the effect of bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) on language function in Parkinson's disease (PD). It fills an important gap in recent reviews by considering other language tasks in addition to verbal fluency. Method We critically and systematically reviewed the literature on studies that investigated the effect of bilateral STN-DBS on language function in PD. All studies included a matched PD control group who were on best medical treatment, with language testing at similar baseline and follow-up intervals as the DBS PD group. Results Thirteen identified studies included a form of a verbal fluency task, seven studies included picture naming, and only two studies included more language-oriented tasks. We found that verbal fluency was negatively affected after DBS, whereas picture naming was unaffected. Studies investigating individual change patterns using reliable change indices showed that individual variability is larger for picture naming than for verbal fluency. Conclusions Verbal fluency is the most frequently investigated aspect of language function. Our analysis showed a pattern of decline in verbal fluency across multiple studies after STN-DBS, whereas picture naming was unaffected. Data on more language-oriented tests in a large DBS sample and best medical treatment control group are sparse. The investigation of language function in PD after DBS requires sensitive language tests (with and without time pressure) and experimental designs as used in the studies reviewed here. Reliable change index statistics are a promising tool for investigating individual differences in performance after DBS. Supplemental Material https://doi.org/10.23641/asha.14794458.

Optimized Propofol Anesthesia Increases Power of Subthalamic Neuronal Activity in Patients with Parkinson's Disease Undergoing Deep Brain Stimulation.

IntroductionPropofol is a general anesthetic option for deep brain stimulation (DBS) of the subthalamic nucleus (STN) of patients with Parkinson's disease (PD). However, its effects on STN activity and neuropsychological outcomes are controversial. The optimal propofol anesthesia for asleep DBS is unknown. This study investigated the safety and effectiveness of an optimized propofol anesthesia regimen in asleep DBS.MethodsThis retrospective study enrolled 68 PD patients undergoing bilateral STN-DBS surgery. All patients received local scalp anesthesia, with (asleep group, n = 35) or without (awake group, n = 33) propofol-remifentanil general anesthesia by target-controlled infusion under electroencephalogram monitoring. The primary outcome was subthalamic neuronal spiking characterization during microelectrode recording. The secondary outcomes were clinical outcomes including motor, cognition, mind, sleep, and quality of life at 6 months.ResultsSignificantly increased delta and theta power were obtained under propofol anesthesia (awake vs. asleep group, mean ± standard deviation; delta: 31.97 ± 9.87 vs. 39.77 ± 10.56, p < 0.01; theta: 21.09 ± 5.55 vs. 24.82 ± 6.63, p = 0.01). After excluding the influence of confounding factors of age and preoperative motor scores, there was a statistically significant influence on the delta, theta, and alpha power of STN neuronal activity under different anesthesia regimens (delta: β = 2.64, p < 0.01; theta: β = 2.11, p < 0.01; alpha: β = 1.42, p = 0.01). There were no differences in modified burst index, firing rate, tract numbers of microelectrode recording, and other clinical outcomes between the two groups.ConclusionOptimized propofol anesthesia enhanced the delta, theta, and alpha power in STN compared with the awake technique and likely contributed to target recognition under propofol anesthesia. These results demonstrate that propofol is suitable, but needs to be optimized, for asleep STN-DBS.Trial RegistrationChinese Clinical Trial Registry Identification number: ChiCTR2100045942. Registered 29 April 2021–Retrospectively registeredSupplementary InformationThe online version contains supplementary material available at 10.1007/s40120-021-00259-y.

Long-term Outcomes (15 Years) After Subthalamic Nucleus Deep Brain Stimulation in Patients With Parkinson Disease.

To evaluate the effects of deep brain stimulation of the subthalamic nucleus (STN-DBS) on motor complications in patients with Parkinson disease (PD) beyond 15 years after surgery. Data on motor complications, quality of life (QoL), activities of daily living, Unified Parkinson's Disease Rating Scale motor scores, dopaminergic treatment, stimulation measures, and side effects of STN-DBS were retrospectively retrieved and compared before surgery, at 1 year, and beyond 15 years after bilateral STN-DBS. Fifty-one patients with 17.06 ± 2.18 years STN-DBS follow-up were recruited. Compared to baseline, the time spent with dyskinesia and the time spent in the "off" state were reduced by 75% (p < 0.001) and by 58.7% (p < 0.001), respectively. Moreover, dopaminergic drugs were reduced by 50.6% (p < 0.001). Parkinson's Disease Quality of Life Questionnaire total score and the emotional function and social function domains improved 13.8% (p = 0.005), 13.6% (p = 0.01), and 29.9% (p < 0.001), respectively. Few and mostly manageable device-related adverse events were observed during the follow-up. STN-DBS is effective beyond 15 years from the intervention, notably with significant improvement in motor complications and stable reduction of dopaminergic drugs. Furthermore, despite the natural continuous progression of PD with worsening of levodopa-resistant motor and nonmotor symptoms over the years, patients undergoing STN-DBS could maintain an improvement in QoL. This study provides Class IV evidence that, for patients with PD, STN-DBS remains effective at treating motor complications 15 years after surgery.

Stimulation of the Subthalamic Nucleus Changes Cortical-Subcortical Blood Flow Patterns During Speech: A Positron Emission Tomography Study.

Background: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment for Parkinson's disease (PD) but can have an adverse effect on speech. In normal speakers and in those with spinocerebellar ataxia, an inverse relationship between regional cerebral blood flow (rCBF) in the left inferior frontal (IFG) region and the right caudate (CAU) is associated with speech rate. This pattern was examined to determine if it was present in PD, and if so, whether it was altered by STN-DBS.Methods: Positron Emission Tomography (PET) measured rCBF during speech in individuals with PD not treated with STN-DBS (n = 7), and those treated with bilateral STN-DBS (n = 7). Previously reported results from non-PD control subjects (n = 16) were reported for comparison. The possible relationships between speech rate during scanning and data from the left and right IFG and CAU head regions were investigated using a step-wise multiple linear regression to identify brain regions that interacted to predict speech rate.Results: The multiple linear regression analysis replicated previously reported predictive coefficients for speech rate involving the left IFG and right CAU regions. However, the relationships between these predictive coefficients and speech rates were abnormal in both PD groups. In PD who had not received STN-DBS, the right CAU coefficient decreased normally with increasing speech rate but the left IFG coefficient abnormally decreased. With STN-DBS, this pattern was partially normalized with the addition of a left IFG coefficient that increased with speech rate, as in normal controls, but the abnormal left IFG decreasing coefficient observed in PD remained. The magnitudes of both cortical predictive coefficients but not the CAU coefficient were exaggerated with STN-DBS.Conclusions: STN-DBS partially corrects the abnormal relationships between rCBF and speech rate found in PD by introducing a left IFG subregion that increases with speech rate, but the conflicting left IFG subregion response remained. Conflicting IFG responses may account for some of the speech problems observed after STN-DBS. Cortical and subcortical regions may be differentially affected by STN-DBS.