Dataset Information

Acute and Chronic Mood and Apathy Outcomes from a randomized study of unilateral STN and GPi DBS.

ABSTRACT:

Objective

To study mood and behavioral effects of unilateral and staged bilateral subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) for Parkinson's disease (PD).

Background

There are numerous reports of mood changes following DBS, however, most have focused on bilateral simultaneous STN implants with rapid and aggressive post-operative medication reduction.

Methods

A standardized evaluation was applied to a subset of patients undergoing STN and GPi DBS and who were also enrolled in the NIH COMPARE study. The Unified Parkinson Disease Rating Scale (UPDRS III), the Hamilton depression (HAM-D) and anxiety rating scales (HAM-A), the Yale-Brown obsessive-compulsive rating scale (YBOCS), the Apathy Scale (AS), and the Young mania rating scale (YMRS) were used. The scales were repeated at acute and chronic intervals. A post-operative strategy of non-aggressive medication reduction was employed.

Results

Thirty patients were randomized and underwent unilateral DBS (16 STN, 14 GPi). There were no baseline differences. The GPi group had a higher mean dopaminergic dosage at 1-year, however the between group difference in changes from baseline to 1-year was not significant. There were no differences between groups in mood and motor outcomes. When combining STN and GPi groups, the HAM-A scores worsened at 2-months, 4-months, 6-months and 1-year when compared with baseline; the HAM-D and YMRS scores worsened at 4-months, 6-months and 1-year; and the UPDRS Motor scores improved at 4-months and 1-year. Psychiatric diagnoses (DSM-IV) did not change. No between group differences were observed in the cohort of bilateral cases.

Conclusions

There were few changes in mood and behavior with STN or GPi DBS. The approach of staging STN or GPi DBS without aggressive medication reduction could be a viable option for managing PD surgical candidates. A study of bilateral DBS and of medication reduction will be required to better understand risks and benefits of a bilateral approach.

SUBMITTER: Okun MS

PROVIDER: S-EPMC4254912 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Acute and Chronic Mood and Apathy Outcomes from a randomized study of unilateral STN and GPi DBS.

Okun Michael S MS Wu Samuel S SS Fayad Sarah S Ward Herbert H Bowers Dawn D Rosado Christian C Bowen Lauren L Jacobson Charles C Butson Christopher C Foote Kelly D KD

PloS one 20141203 12

<h4>Objective</h4>To study mood and behavioral effects of unilateral and staged bilateral subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) for Parkinson's disease (PD).<h4>Background</h4>There are numerous reports of mood changes following DBS, however, most have focused on bilateral simultaneous STN implants with rapid and aggressive post-operative medication reduction.<h4>Methods</h4>A standardized evaluation was applied to a subset of patients undergoi ...[more]

PMID: 25469706

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Project description:Background: The efficacy of deep brain stimulation (DBS) therapy in Parkinson's disease (PD) patients is highly dependent on the precise localization of the target structures such as subthalamic nucleus (STN). Most commonly, microelectrode single unit activity (SUA) recordings are performed to refine the target. This process is heavily experience based and can be technically challenging. Local field potentials (LFPs), representing the activity of a population of neurons, can be obtained from the same microelectrodes used for SUA recordings and allow flexible online processing with less computational complexity due to lower sampling rate requirements. Although LFPs have been shown to contain biomarkers capable of predicting patients' symptoms and differentiating various structures, their use in the localization of the STN in the clinical practice is not prevalent. Methods: Here we present, for the first time, a randomized and double-blinded pilot study with intraoperative online LFP processing in which we compare the clinical benefit from SUA- versus LFP-based implantation. Ten PD patients referred for bilateral STN-DBS were randomly implanted using either SUA or LFP guided targeting in each hemisphere. Although both SUA and LFP were recorded for each STN, the electrophysiologist was blinded to one at a time. Three months postoperatively, the patients were evaluated by a neurologist blinded to the intraoperative recordings to assess the performance of each modality. While SUA-based decisions relied on the visual and auditory inspection of the raw traces, LFP-based decisions were given through an online signal processing and machine learning pipeline. Results: We found a dramatic agreement between LFP- and SUA-based localization (16/20 STNs) providing adequate clinical improvement (51.8% decrease in 3-month contralateral motor assessment scores), with LFP-guided implantation resulting in greater average improvement in the discordant cases (74.9%, n = 3 STNs). The selected tracks were characterized by higher activity in beta (11-32 Hz) and high-frequency (200-400 Hz) bands (p < 0.01) of LFPs and stronger non-linear coupling between these bands (p < 0.05). Conclusion: Our pilot study shows equal or better clinical benefit with LFP-based targeting. Given the robustness of the electrode interface and lower computational cost, more centers can utilize LFP as a strategic feedback modality intraoperatively, in conjunction to the SUA-guided targeting.

Project description:BackgroundSome people with Parkinson's disease (PD) report poorer dynamic postural stability following high-frequency deep brain stimulation of the subthalamic nucleus (STN-DBS), which may contribute to an increased falls risk. However, some studies have shown low-frequency (60 Hz) STN-DBS improves clinical measures of postural stability, potentially providing support for this treatment. This double-blind randomised crossover study aimed to investigate the effects of low-frequency STN-DBS compared to high-frequency stimulation on objective measures of gait rhythmicity in people with PD.MethodsDuring high- and low-frequency STN-DBS and while off-medication, participants completed assessments of symptom severity and walking (e.g., Timed Up-and-Go). During comfortable walking, the harmonic ratio, an objective measures of gait rhythmicity, was derived from head- and trunk-mounted accelerometers to provide insight in dynamic postural stability. Lower harmonic ratios represent less rhythmic walking and have discriminated people with PD who experience falls. Linear mixed model analyses were performed on fourteen participants.ResultsLow-frequency STN-DBS significantly improved medial-lateral and vertical trunk rhythmicity compared to high-frequency. Improvements were independent of electrode location and total electrical energy delivered. No differences were noted between stimulation conditions for temporal gait measures, clinical mobility measures, motor symptom severity or the presence of gait retropulsion.ConclusionsThis study provides evidence for the acute benefits of low-frequency stimulation for gait outcomes in STN-DBS PD patients, independent of electrode location. However, the perceived benefits of this therapy may be diminished for people who experienced significant tremor pre-operatively, as lower frequencies may cause these symptoms to re-emerge.Trial registrationThis study was prospectively registered with the Australian and New Zealand Clinical Trials Registry on 5 June 2018 (ACTRN12618000944235).

Project description:Severe gait disturbances in idiopathic Parkinson's disease (PD) are observed in up to 80% of all patients in advanced disease stages with important impact on quality of life. There is an unmet need for further symptomatic therapeutic strategies, particularly as gait disturbances generally respond unfavourably to dopaminergic medication and conventional deep brain stimulation of the subthalamic nucleus in advanced disease stages. Recent pathophysiological research pointed to nigro-pontine networks entrained to locomotor integration. Stimulation of the pedunculopontine nucleus is currently under investigation, however, hitherto remains controversial. The substantia nigra pars reticulata (SNr)--entrained into integrative locomotor networks--is pathologically overactive in PD. High-frequent stimulation of the substantia nigra pars reticulata preferentially modulated axial symptoms and therefore is suggested as a novel therapeutic candidate target for neuromodulation of refractory gait disturbances in PD.12 patients with idiopathic Parkinson's disease and refractory gait disturbances under best individual subthalamic nucleus stimulation and dopaminergic medication will be enroled into this double-blind 2 × 2 cross-over clinical trial. The treatment consists of two different stimulation settings using (i) conventional stimulation of the subthalamic nucleus [STNmono] and (ii) combined stimulation of distant electrode contacts located in the subthalamic nucleus and caudal border zone of STN and substantia nigra pars reticulata [STN+SNr]. The primary outcome measure is the change of the cumulative 'axial score' (UPDRS II items '13-15' and UPRDS III items '27-31') at three weeks of constant stimulation in either condition. Secondary outcome measures include specific scores on freezing of gait, balance function, quality of life, non-motor symptoms, and neuropsychiatric symptoms. The aim of the present trial is to investigate the efficacy and safety of a three week constant combined stimulation on [STN+SNr] compared to [STNmono]. The results will clarify, whether stimulation on nigral contacts additional to subthalamic stimulation will improve therapeutic response of otherwise refractory gait disturbances in PD.The trial was registered with the clinical trials register of http://www.clinicaltrials.gov (NCT01355835).

Dataset Information

Acute and Chronic Mood and Apathy Outcomes from a randomized study of unilateral STN and GPi DBS.

Objective

Background

Methods

Results

Conclusions

Publications

Acute and Chronic Mood and Apathy Outcomes from a randomized study of unilateral STN and GPi DBS.

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