scholarly journals P.042 Dopamine Dysregulation Syndrome in Parkinson’s Disease and its Management with Advanced Therapies

Author(s):  
S Sasikumar ◽  
R Matta ◽  
A Fasano

Background: Dopamine Dysregulation Syndrome (DDS) is an adverse non-motor complication of dopamine replacement therapy in Parkinson’s Disease. The current literature on DDS is limited, and it remains underdiagnosed and challenging to manage. Methods: We performed a retrospective chart review and classified patients according to risk factors that have been identified in the literature, UPDRS scores, intervention and outcome. Univariate analyses were performed to quantify these characteristics. Results: Prior psychiatric illness was identified in 70% of patients, impulse control disorder in 89% and substance abuse in 3.7%. Interventions included reduction of dopamine therapy (88.9%), deep brain stimulation (DBS) of the subthalamic nucleus (STN, 48.1%) or globus pallidus interna (GPi, 7.4%), and levodopa-carbidopa intestinal gel (LCIG) infusion (11.1%). Baseline UPDRS IV before treatment and MDS III after treatment were not significant between intervention groups (p=0.09 and p=0.13 respectively). Overall 88.9% patients improved at follow up, with medication only (75%), STN DBS (100%), GPi DBS (100%) and LCIG (33%). Relapse rate was 18.2%, in the STN group only. Conclusions: Our results suggest that GPi DBS, in concurrence with dopaminergic medication reduction, is the most effective intervention. STN DBS might be also beneficial although the associated medications reduction causes DDS relapse in a subgroup of patients.

Author(s):  
Azari H ◽  

Background: Deep Brain Stimulation (DBS) is regarded as a viable therapeutic choice for Parkinson’s Disease (PD). The two most common sites for DBS are the Subthalamic Nucleus (STN) and Globus Pallidus (GPi). In this study, the clinical effectiveness of these two targets was compared. Methods: A systematic literature search in electronic databases were restricted to English language publications 2010 to 2021. Specified MeSH terms were searched in all databases. Studies that evaluated the Unified Parkinson’s Disease Rating Scale (UPDRS) III were selected by meeting the following criteria: (1) had at least three months follow-up period; (2) compared both GPi and STN DBS; (3) at least five participants in each group; (4) conducted after 2010. Study quality assessment was performed using the Modified Jadad Scale. Results: 3577 potentially relevant articles were identified 3569 were excluded based on title and abstract, duplicate and unsuitable article removal. Eight articles satisfied the inclusion criteria and were scrutinized (458 PD patients). Majority of studies reported no statistically significant between-group difference for improvements in UPDRS III scores. Conclusions: Although there were some results in terms of action tremor, rigidity, and urinary symptoms, which indicated that STN DBS might be a better choice or regarding the adverse effects, GPi seemed better; but it cannot be concluded that one target is superior. Other larger randomized clinical trials with longer follow-up periods and control groups are needed to decide which target is more efficient for stimulation and imposes fewer adverse effects on the patients.


2021 ◽  
Author(s):  
Hushyar Azari

Abstract Background: Deep brain stimulation (DBS) is regarded as a viable therapeutic choice for Parkinson's disease (PD). The two most common sites for DBS are the subthalamic nucleus (STN) and globus pallidus (GPi). In this study, the clinical effectiveness of these two targets was compared.Methods: A systematic literature search in electronic databases were restricted to English language publications 2010 to 2021. Specified MeSH terms were searched in all databases. Studies that evaluated the Unified Parkinson's Disease Rating Scale (UPDRS) III were selected by meeting the following criteria: (1) had at least three months follow-up period; (2) compared both GPi and STN DBS; (3)at least five participants in each group; (4)conducted after 2010. Study quality assessment was performed using the Modified Jadad Scale.Results: 3577 potentially relevant articles were identified,3569 were excluded based on title and abstract, duplicate and unsuitable article removal. Eight articles satisfied the inclusion criteria and were scrutinized (458 PD patients). Majority of studies reported no statistically significant between-group difference for improvements in UPDRS ш scores.Conclusions: Although there were some results in terms of action tremor, rigidity, and urinary symptoms, which indicated that STN DBS might be a better choice or regarding the adverse effects, GPi seemed better; but it cannot be concluded that one target is superior. Other larger randomized clinical trials with longer follow-up periods and control groups are needed to decide which target is more efficient for stimulation and imposes fewer adverse effects on the patients.


2019 ◽  
Vol 131 (6) ◽  
pp. 1797-1804 ◽  
Author(s):  
Ryul Kim ◽  
Han-Joon Kim ◽  
Chaewon Shin ◽  
Hyeyoung Park ◽  
Aryun Kim ◽  
...  

OBJECTIVESubthalamic nucleus deep brain stimulation (STN DBS) is effective against freezing of gait (FOG) in Parkinson’s disease (PD); however, whether this effect persists over the long term is debated. The aim of the current study was to investigate the long-term effect of STN DBS on FOG in patients with PD.METHODSData on 52 cases in which PD patients received bilateral STN DBS were obtained from a prospective registry. The authors blindly analyzed FOG incidence and its severity from the videotapes of a 5-m walking task at the baseline and at the 1-, 2-, and 5- or 7-year follow-up visits. They also compared the axial score from the Unified Parkinson’s Disease Rating Scale (UPDRS) part III, UPDRS part II (UPDRS-II) item 14, and the FOG questionnaire (FOG-Q). Postoperatively, video-based FOG analysis and the axial score were evaluated under 4 conditions (off-medication/off-stimulation, off-medication/on-stimulation, on-medication/off-stimulation, and on-medication/on-stimulation), and UPDRS-II item 14 and the FOG-Q score were evaluated under 2 conditions (off-medication/on-stimulation and on-medication/on-stimulation).RESULTSDuring the off-medication state, the on-stimulation condition improved FOG outcomes, except for video-based FOG severity, up to the last follow-up compared with the baseline. Video-based FOG outcomes and the axial score during the off-medication state were improved with the on-stimulation condition up to the last follow-up compared with the off-stimulation condition. During the on-medication state, the on-stimulation condition did not improve any FOG outcome compared with the baseline; however, it improved video-based FOG outcomes up to the 2-year follow-up and the axial score up to the last follow-up compared with the off-stimulation condition.CONCLUSIONSOur findings suggest that STN DBS has a long-term effect on FOG in the off-medication state. However, STN DBS did not show a long-term effect on FOG in the on-medication state, although it had a short-term effect until the 2-year follow-up.


2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Christine Daniels ◽  
Frank Steigerwald ◽  
Philipp Capetian ◽  
Cordula Matthies ◽  
Uwe Malzahn ◽  
...  

Abstract Introduction Dementia in Parkinson’s disease (PDD) is a common non-motor symptom of advanced disease, associated with pronounced neocortical cholinergic deficits due to neurodegeneration of the nucleus basalis of Meynert (NBM) and its cholinergic terminals. In advanced PD, patients often require advanced therapies such as infusion therapy or deep brain stimulation (DBS) to improve motor control. However, patients with associated dementia are commonly excluded from DBS because of potential deterioration of cognitive functions. Yet marked reductions in dopaminergic medication and the subsequent risk of side effects (e.g., cognitive decline, psychosis, delirium) suggest that critical re-consideration of DBS of the subthalamic nucleus (STN-DBS) for advanced stages of PD and PDD is worthwhile. In this Phase 1b study, we will provide STN-DBS to a cohort of PDD patients with severe motor fluctuations and combine two additional electrodes for augmentative neurostimulation of the NBM. Methods We aim to include 12 patients with mild-to-moderately severe PDD who fulfill indication criteria regarding motor symptoms for STN-DBS. Eligible patients will undergo implantation of a neurostimulation system with bilateral electrodes in both the STN and NBM. After 12 weeks of STN-DBS (visit 1/V1), participants will be randomized to receive either effective neurostimulation of the NBM (group 1) or sham stimulation of the NBM (group 2). NBM-DBS will be activated in all participants after 24 weeks of blinded treatment (visit 2/V2). The primary outcome will be the safety of combined bilateral STN- and NBM-DBS, determined by spontaneously-reported adverse events. Other outcome measures will comprise changes on scales evaluating cognition, activities of daily living functioning and clinical global impression, as well as motor functions, mood, behavior, caregiver burden and health economic aspects, and several domain-specific cognitive tests. Changes in scores (V1 – V2) for both treatment arms will undergo analysis of covariances, with baseline scores as covariates. Perspective The feasibility and safety of combined STN-NBM-DBS in patients with PDD will be assessed to determine whether additional NBM-DBS improves or slows the progression of cognitive decline. Positive results would provide a basic concept for future studies evaluating the efficacy of NBM-DBS in larger PDD cohorts. Indirectly, proof-of-safety of STN-DBS in PDD might influence patient selection for this standard treatment option in advanced PD. Trial registration ClinicalTrials.gov identifier (NCT number): NCT02589925.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Zixiao Yin ◽  
Yutong Bai ◽  
Liangying Zou ◽  
Xin Zhang ◽  
Huimin Wang ◽  
...  

Abstract The effect of subthalamic nucleus deep brain stimulation (STN-DBS) on balance function in patients with Parkinson’s disease (PD) and the potential outcome predictive factors remains unclear. We retrospectively included 261 PD patients who underwent STN-DBS and finished the 1-month follow-up (M1) assessment in the explorative set for identifying postoperative balance change predictors, and 111 patients who finished both the M1 and 12-month follow-up (M12) assessment in the validation set for verifying the identified factors. Motor and balance improvement were evaluated through the UPDRS-III and the Berg balance scale (BBS) and pull test (PT), respectively. Candidate predictors of balance improvement included age, disease duration, motor subtypes, baseline severity of PD, cognitive status, motor and balance response to levodopa, and stimulation parameters. In the off-medication condition, STN-DBS significantly improved BBS and PT performance in both the M1 and M12, in both datasets. While in the on-medication condition, no significant balance improvement was observed. Higher preoperative BBS response to levodopa was significantly associated with larger postoperative off-medication, but not on-medication, BBS (p < 0.001) and PT (p < 0.001) improvement in both the M1 and M12. BBS subitems 8, 9, 11, 13, and 14 were the major contributors to the prediction of balance improvement after STN-DBS. STN-DBS improves short-term off-medication, but not on-medication, balance function assessed through BBS and PT. Preoperative BBS response to levodopa best predicts postoperative off-medication balance improvement. For patients who manifested severe balance problems, a levodopa challenge test on BBS or the short version of BBS is recommended.


2019 ◽  
Vol 131 (5) ◽  
pp. 1508-1513
Author(s):  
Gwanhee Ehm ◽  
Han-Joon Kim ◽  
Ji-Young Kim ◽  
Jee-Young Lee ◽  
Hee Jin Kim ◽  
...  

OBJECTIVEFor patients with highly asymmetrical Parkinson’s disease (PD), unilateral subthalamic nucleus (STN) deep brain stimulation (DBS) has been suggested as a reasonable treatment. However, the results of a previous 2-year follow-up study involving patients with prominently asymmetrical PD who had unilateral STN DBS suggested that simultaneous bilateral surgery should be performed. In the present study, the authors analyze 7-year follow-up data from the same patient group to examine changes in motor benefit from unilateral STN DBS over time and the interval between initial unilateral surgery and a second (contralateral) STN DBS surgery.METHODSEight patients with highly asymmetrical parkinsonism who underwent unilateral STN DBS were evaluated. The factors measured were scores on the motor part of the Unified Parkinson’s Disease Rating Scale (UPDRS III), Hoehn and Yahr (HY) stage, and levodopa equivalent daily dose (LEDD). Evaluations occurred at 3, 6, and 12 months after the initial surgery and annually thereafter.RESULTSThe mean follow-up period was 91.5 months (range 36–105 months). Three years after the initial unilateral surgery, motor benefits on the contralateral side continued; however, an aggravation of the ipsilateral parkinsonism attenuated the improvement in total UPDRS III scores, which reverted to baseline. Axial motor score, LEDD, and HY stage did not differ from the baseline. Seven of 8 patients (87.5%) were considered candidates for a second surgery to offer additional motor benefits. Of the 7 candidates, 4 patients (50% of total patients) underwent the second surgery at 58.5 ± 11.6 (mean ± SD) months after the initial surgery. Three patients were not able to have the second surgery: one patient died of gastric cancer, one patient was severely immobilized by an accident, and one patient could not afford the second surgery. One patient remained content with the initial unilateral surgery throughout the follow-up period.CONCLUSIONSSeven of 8 patients with unilateral STN DBS became candidates for second surgery before battery replacement surgery of the first implanted device. Baseline asymmetry alone may not predict appropriate candidates for unilateral STN DBS. This study provides further evidence that, from a long-term perspective, initial simultaneous bilateral STN DBS should be considered for PD patients with prominently asymmetrical motor symptoms.


2020 ◽  
Vol 77 (9) ◽  
pp. 1000-1002 ◽  
Author(s):  
Mehmet Şenol ◽  
Hakan Şimşek

Introduction. Parkinson's disease patients with impulse control disorders and dopamine dysregulation syndrome is increasingly recognized. There are reports that such disorders can sometimes be improved by using deep brain stimulation, but sometimes they can get worse. Case report. Our patient was a 30-year-old man with Parkinson's disease since the age of 23. The patient had motor fluctuations on the right with marked bradykinesia, bradymimia and rigidities in the off-periods. The patient's paraphilia and sexual indiscretions against women were apparent in the on-periods. The patient's eating habits were also changed. The patient underwent subthalamic nucleus-deep brain stimulation (STNDBS). Significant improvements were seen in the motor and behavior signs of the patient after this procedure had been performed. Conclusion. STN-DBS may be a reasonable option in patients with Parkinson's disease when unwanted dopaminergic side effects occur, and motor disorders and impulse control disorders cannot be improved with drugs.


2018 ◽  
Vol 128 (4) ◽  
pp. 1199-1213 ◽  
Author(s):  
Alireza Mansouri ◽  
Shervin Taslimi ◽  
Jetan H. Badhiwala ◽  
Christopher D. Witiw ◽  
Farshad Nassiri ◽  
...  

OBJECTIVEDeep brain stimulation (DBS) is effective in the management of patients with advanced Parkinson’s disease (PD). While both the globus pallidus pars interna (GPi) and the subthalamic nucleus (STN) are accepted targets, their relative efficacy in randomized controlled trials (RCTs) has not been established beyond 12 months. The objective of this study was to conduct a meta-analysis of RCTs to compare outcomes among adults with PD undergoing DBS of GPi or STN at various time points, including 36 months of follow-up.METHODSThe MEDLINE, Embase, CENTRAL, Web of Science, and CINAHL databases were searched. Registries for clinical trials, selected conference proceedings, and the table of contents for selected journals were also searched. Screens were conducted independently and in duplicate. Among the 623 studies initially identified (615 through database search, 7 through manual review of bibliographies, and 1 through a repeat screen of literature prior to submission), 19 underwent full-text review; 13 of these were included in the quantitative meta-analysis. Data were extracted independently and in duplicate. The Cochrane Collaboration tool was used to assess the risk of bias. The GRADE evidence profile tool was used to assess the quality of the evidence. Motor scores, medication dosage reduction, activities of daily living, depression, dyskinesias, and adverse events were compared. The influence of disease duration (a priori) and the proportion of male patients within a study (post hoc) were explored as potential subgroups.RESULTSThirteen studies (6 original cohorts) were identified. No difference in motor scores or activities of daily living was identified at 36 months. Medications were significantly reduced with STN stimulation (5 studies, weighted mean difference [WMD] −365.46, 95% CI −599.48 to −131.44, p = 0.002). Beck Depression Inventory scores were significantly better with GPi stimulation (3 studies; WMD 2.53, 95% CI 0.99–4.06 p = 0.001). The motor benefits of GPi and STN DBS for PD are similar.CONCLUSIONSThe motor benefits achieved with GPi and STN DBS for PD are similar. DBS of STN allows for a greater reduction of medication, but not as significant an advantage as DBS of GPi with respect to mood. This difference is sustained at 36 months. Further long-term studies are necessary.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yijie Lai ◽  
Yunhai Song ◽  
Daoqing Su ◽  
Linbin Wang ◽  
Chencheng Zhang ◽  
...  

AbstractCamptocormia is a common and often debilitating postural deformity in Parkinson’s disease (PD). Few treatments are currently effective. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) shows potential in treating camptocormia, but evidence remains limited to case reports. We herein investigate the effect of GPi-DBS for treating camptocormia in a retrospective PD cohort. Thirty-six consecutive PD patients who underwent GPi-DBS were reviewed. The total and upper camptocormia angles (TCC and UCC angles) derived from video recordings of patients who received GPi-DBS were used to compare camptocormia alterations. Correlation analysis was performed to identify factors associated with the postoperative improvements. DBS lead placement and the impact of stimulation were analyzed using Lead-DBS software. Eleven patients manifested pre-surgical camptocormia: seven had lower camptocormia (TCC angles ≥ 30°; TCC-camptocormia), three had upper camptocormia (UCC angles ≥ 45°; UCC-camptocormia), and one had both. Mean follow-up time was 7.3 ± 3.3 months. GPi-DBS improved TCC-camptocormia by 40.4% (angles from 39.1° ± 10.1° to 23.3° ± 8.1°, p = 0.017) and UCC-camptocormia by 22.8% (angles from 50.5° ± 2.6° to 39.0° ± 6.7°, p = 0.012). Improvement in TCC angle was positively associated with pre-surgical TCC angles, levodopa responsiveness of the TCC angle, and structural connectivity from volume of tissue activated to somatosensory cortex. Greater improvement in UCC angles was seen in patients with larger pre-surgical UCC angles. Our study demonstrates potential effectiveness of GPi-DBS for treating camptocormia in PD patients. Future controlled studies with larger numbers of patients with PD-related camptocormia should extend our findings.


2021 ◽  
Vol 15 ◽  
Author(s):  
Yu Diao ◽  
Yutong Bai ◽  
Tianqi Hu ◽  
Zixiao Yin ◽  
Huangguang Liu ◽  
...  

Pain from Parkinson's disease (PD) is a non-motor symptom affecting the quality of life and has prevalence of 20–80%. However, it is unclear whether subthalamic nucleus deep brain stimulation (STN–DBS), a well-established treatment for PD, is effective forPD-related pain. Thus, the objective of this meta-analysis was to investigate the efficacy of STN-DBS on PD-related pain and explore how its duration affects the efficacy of STN-DBS. A systematic search was performed using PubMed, Embase, and the Cochrane Library. Nine studies included numerical rating scale (NRS), visual analog scale (VAS), or non-motor symptom scale (NMSS) scores at baseline and at the last follow-up visit and therefore met the inclusion criteria of the authors. These studies exhibited moderate- to high-quality evidence. Two reviewers conducted assessments for study eligibility, risk of bias, data extraction, and quality of evidence rating. Random effect meta-analysis revealed a significant change in PD-related pain as assessed by NMSS, NRS, and VAS (P &lt;0.01). Analysis of the short and long follow-up subgroups indicated delayed improvement in PD-related pain. These findings (a) show the efficacy of STN-DBS on PD-related pain and provide higher-level evidence, and (b) implicate delayed improvement in PD-related pain, which may help programming doctors with supplement selecting target and programming.Systematic Review Registration: This study is registered in Open Science Framework (DOI: 10.17605/OSF.IO/DNM6K).


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