Subthalamic Nucleus Stimulation in Parkinson's Disease: 5‐Year Extension Study of a Randomized Trial

Bjerknes, Silje; Toft, Mathias; Brandt, Reidun; Rygvold, Trine Waage; Konglund, Ane; Dietrichs, Espen; Andersson, Stein; Skogseid, Inger Marie

doi:10.1002/mdc3.13348

Cited by 7 publications

(7 citation statements)

References 58 publications

(124 reference statements)

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“…Clinical studies show STN-DBS may impact non-motor behaviour ( Bjerknes et al, 2021 ; Voruz et al, 2022 ). STN optogenetic stimulation or inhibition had no effect on the real time place preference assay ( Figure 2I ).…”

Section: Discussionmentioning

confidence: 99%

Bidirectional Optogenetic Modulation of the Subthalamic Nucleus in a Rodent Model of Parkinson’s Disease

2022

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Parkinson’s disease (PD) is a neurodegenerative disorder characterized by a range of motor symptoms. Treatments are focused on dopamine replacement therapy or deep brain stimulation (DBS). The subthalamic nucleus (STN) is a common target for DBS treatment of PD. However, the function of the STN in normal conditions and pathology is poorly understood. Here, we show in rats that optogenetic modulation of STN neuronal activity exerts bidirectional control of motor function, where inhibition of the STN increases movement and STN activation decreases movement. We also examined the effect of bidirectional optogenetic manipulation STN neuronal activity under dopamine depleted condition using the bilateral rodent 6-hydroxydopamine (6-OHDA) model of Parkinson’s disease. Optogenetic inhibition of the STN in the absence of dopamine had no impact on motor control yet STN excitation led to pronounced abnormal involuntary movement. Administration of levodopa rescued the abnormal involuntary movements induced by STN excitation. Although dopamine and STN dysfunction are well established in PD pathology, here we demonstrate simultaneous STN over activity and loss of dopamine lead to motor deficits. Moreover, we show the dysfunction of the STN is dependent on dopamine. This study provides evidence that the loss of dopamine and the over activity of the STN are key features of PD motor deficits. These results provide insight into the STN pathology in PD and therapeutic mechanism of targeting the STN for the treatment for PD.

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Section: Discussionmentioning

confidence: 99%

Bidirectional Optogenetic Modulation of the Subthalamic Nucleus in a Rodent Model of Parkinson’s Disease

2022

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“…The 42% LEDD reduction after STN-DBS at 5-year follow-up was well within the range reported in the literature. 6,49,51 Medication requirements in the MED group increased significantly during the 5year study.…”

Section: Motor Outcomes Medication Requirements Teed and Aesmentioning

confidence: 95%

“…Furthermore, one has to acknowledge that dropouts from long-term studies occur more frequently among poor-performing and more severely impaired patients (eg, nursing home residents). 6 Indeed, patients in nursing homes are often difficult to follow up in DBS clinics because in the later stages of the disease patients may already be too disabled to go to the hospital. However, the dropout rates in our study were well within the range of previous work.…”

Section: Jama Network Open | Neurologymentioning

confidence: 99%

“…[1][2][3] Long-term studies with more than 5 years of follow-up have provided evidence of the beneficial effects of STN-DBS on motor complications, 4 whereas conflicting results have been reported on long-term QOL outcomes up to 5 years after DBS surgery. 5,6 A recent meta-analysis 7 of studies of only patients undergoing STN-DBS reported a QOL improvement for up to 3 years after surgery, with subsequent decrements in these gains at a 5-year follow-up when QOL returns to preoperative status. In contrast, QOL worsens over time in patients treated with standardof-care medication (MED), irrespective of patients' PD stage.…”

Section: Introductionmentioning

confidence: 99%

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Neurostimulation for Advanced Parkinson Disease and Quality of Life at 5 Years

Jost,

Aloui,

Evans

et al. 2024

JAMA Netw Open

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ImportanceDeep brain stimulation of the subthalamic nucleus (STN-DBS) improves quality of life (QOL) in patients with advanced Parkinson disease (PD). However, controlled studies with more than 3 years of follow-up are lacking.ObjectiveTo investigate the long-term effects of STN-DBS on QOL compared with standard-of-care medication (MED).Design, Setting, and ParticipantsIn this prospective, observational, quasi-experimental, longitudinal nonrandomized controlled trial, 183 patients were screened for eligibility and 167 were enrolled from March 1, 2011, to May 31, 2017, at 3 European university centers. Propensity score matching for demographic and clinical characteristics was applied to 108 patients with PD (62 in the STN-DBS group and 46 in the MED group), resulting in a well-balanced, matched subcohort of 25 patients per group. Data analysis was performed from September 2022 to January 2023.ExposureTreatment for PD of STN-DBS or MED.Main Outcomes and MeasuresAssessments included Parkinson’s Disease Questionnaire 8 (PDQ-8), Unified PD Rating Scale–motor examination, Scales for Outcomes in PD–activities of daily living (ADL) and motor complications, and levodopa-equivalent daily dose. Within-group longitudinal outcome changes, between-group differences, and correlations of change scores were analyzed.ResultsThe study population in the analysis included 108 patients (mean [SD] age, 63.7 [8.3] years; 66 [61.1%] male). At 5-year follow-up, PDQ-8 and ADL worsened only in the MED group (PDQ-8 change, −10.9; 95% CI, −19.0 to −2.7; P = .01; ADL change: −2.0; 95% CI, −3.1 to −0.8; P = .002), whereas both outcomes remained stable in the STN-DBS group (PDQ-8 change, −4.3; 95% CI, −13.2 to 4.7; P = .34; ADL change, −0.8; 95% CI, −2.5 to 1.0; P = .38). Changes in PDQ-8 and ADL correlated moderately (rs = .40, P = .008). Furthermore, STN-DBS outcomes were favorable for motor complications (median difference in change scores between STN-DBS and MED, −2.0; 95% CI, −4.0 to −1.0; P = .003), mobility (−1.0; 95% CI, −2.0 to 0; P = .03), and levodopa-equivalent daily dose reduction (−821.4; 95% CI, −1111.9 to −530.8; P &lt; .001).Conclusions and RelevanceThis study provides evidence of differences in QOL outcomes at 5-year follow-up between STN-DBS (stable) and MED (worsened), mainly driven by the favorable effect of STN-DBS on mobility (class IIb evidence). The association between changes in QOL and ADL, but not motor impairment or complications, highlights the relative importance of ADL outcomes for long-term DBS assessments.Trial RegistrationGerman ClinicalTrials Registry: DRKS00006735

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“…Long-term data on STN-DBS suggest a sustained benefit on motor symptoms and complications, with a persistent reduction of dopaminergic medication [3][4][5][6]7]. However, non-motor outcome data at very long-term follow-up are scarce [8,9]. This is understandable, considering the difficulties of long-term follow-up for people living far away from the centers of investigation, as well as the old age and the comorbidities in patients with long disease duration.…”

Section: Introductionmentioning

confidence: 99%

Long‐term independence and quality of life after subthalamic stimulation in Parkinson disease

Castrioto

Debû

Cousin

et al. 2022

Euro J of Neurology

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Background and purpose Studies on long‐term nonmotor outcomes of subthalamic nucleus stimulation in Parkinson disease (PD) are scarce. This study reports on very long‐term non‐motor and motor outcomes in one of the largest cohorts of people with advanced PD, treated for >10 years with subthalamic nucleus stimulation. The main outcome was to document the evolution of independence in activities of daily living. The secondary outcomes were to measure the change in quality of life, as well as non‐motor and motor outcomes. Methods Patients were studied preoperatively, at 1 year, and beyond 10 years after subthalamic stimulation with an established protocol including motor, non‐motor, and neuropsychological assessments. Results Eighty‐five people with PD were included. Independence scores in the off‐medication condition (measured with the Schwab & England Activities of Daily Living Scale) as well as quality of life (measured with the Parkinson's Disease Questionnaire [PDQ]‐37) remained improved at longest follow‐up compared to preoperatively (respectively, p < 0.001, p = 0.015). Cognitive scores, measured with the Mattis Dementia Rating Scale, significantly worsened compared to before and 1 year after surgery (p < 0.001), without significant change in depression, measured with the Beck Depression Inventory. Motor fluctuations, dyskinesias, and off dystonia remained improved at longest follow‐up (p < 0.001), with a significant reduction in dopaminergic treatment (45%, p < 0.001). Conclusions This study highlights the long‐term improvement of subthalamic stimulation on independence and quality of life, despite the progression of disease and the occurrence of levodopa‐resistant symptoms.

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Subthalamic Nucleus Stimulation in Parkinson's Disease: 5‐Year Extension Study of a Randomized Trial

Cited by 7 publications

References 58 publications

Bidirectional Optogenetic Modulation of the Subthalamic Nucleus in a Rodent Model of Parkinson’s Disease

Bidirectional Optogenetic Modulation of the Subthalamic Nucleus in a Rodent Model of Parkinson’s Disease

Neurostimulation for Advanced Parkinson Disease and Quality of Life at 5 Years

Long‐term independence and quality of life after subthalamic stimulation in Parkinson disease

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