Deep brain stimulation in early-stage Parkinson disease: Five-year outcomes.
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ABSTRACT: Objective
To report 5-year outcomes from the subthalamic nucleus (STN) deep brain stimulation (DBS) in early-stage Parkinson disease (PD) pilot clinical trial.Methods
The pilot was a prospective, single-blind clinical trial that randomized patients with early-stage PD (Hoehn & Yahr II off medications) to receive bilateral STN DBS plus optimal drug therapy (ODT) vs ODT alone (IDEG050016, NCT0282152, IRB040797). Participants who completed the 2-year trial participated in this observational follow-up study, which included annual outpatient visits through 5 years. This analysis includes 28 patients who were taking PD medications for 6 months to 4 years at enrollment. Outcomes were analyzed using both proportional odds logistic regression and linear mixed effects models.Results
Early STN DBS + ODT participants required lower levodopa equivalent daily doses (p = 0.04, β = -240 mg, 95% confidence interval [CI] -471 to -8) and had 0.06 times the odds of requiring polypharmacy at 5 years compared to early ODT participants (p = 0.01, odds ratio [OR] 0.06, 95% CI 0.00 to 0.65). The odds of having worse rest tremor for early STN DBS + ODT participants were 0.21 times those of early ODT participants (p < 0.001, OR 0.21, 95% CI 0.09 to 0.45). The safety profile was similar between groups.Conclusions
These results suggest that early DBS reduces the need for and complexity of PD medications while providing long-term motor benefit over standard medical therapy. Further investigation is warranted, and the Food and Drug Administration has approved the conduct of a prospective, multicenter, pivotal clinical trial of DBS in early-stage PD (IDEG050016).Classification of evidence
This study provides Class II evidence that DBS implanted in early-stage PD decreases the risk of disease progression and polypharmacy compared to optimal medical therapy alone.
SUBMITTER: Hacker ML
PROVIDER: S-EPMC7455319 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveThe deep brain stimulation (DBS) in early-stage Parkinson's disease (PD) pilot clinical trial randomized 30 patients (Hoehn & Yahr II off; medication duration 0.5-4 years; without dyskinesia/motor fluctuations) to optimal drug therapy (ODT) (early ODT) or bilateral subthalamic nucleus (STN) DBS plus ODT (early DBS+ODT). This study aims to report the 11-year outcomes of patients who completed the DBS in early-stage PD pilot clinical trial.Materials and methodsAttempts were made to contact all 29 subjects who completed the two-year trial to participate in an 11-year follow-up study. Mixed-effects models compared overall trend in outcomes for randomization groups (fixed-effects: assigned treatment, year, their interaction; random-effect: subject) to account for repeated measures.ResultsTwelve subjects participated in this 11-year follow-up study (n = 8 early ODT, n = 4 early DBS+ODT). Participating subjects were 70.0 ± 4.8 years old with a PD medication duration of 13.7 ± 1.7 years (early DBS duration 11.5 ± 1.3 years, n = 4). Three early ODT subjects received STN-DBS as standard of care (DBS duration 6.5 ± 2.0 years). Early ODT subjects had worse motor complications (Unified Parkinson's Disease Rating Scale [UPDRS]-IV) than early DBS+ODT subjects over the 11-year follow-up period (between-group difference = 3.5 points; pinteraction = 0.03). Early DBS+ODT was well-tolerated after 11 years and showed comparable outcomes to early ODT for other UPDRS domains, Parkinson Disease Questionnaire-39 (PDQ-39), and levodopa equivalent daily dose (LEDD).ConclusionsEleven years after randomization, early DBS+ODT subjects had fewer motor complications than early ODT subjects. These results should be interpreted with caution because only 40% of pilot trial subjects participated in this 11-year follow-up study. The Food and Drug Administration has approved the conduct of a pivotal clinical trial evaluating DBS in early-stage PD (IDEG050016).Clinical trial registrationThe Clinicaltrials.gov registration number for the study is NCT00282152.
| S-EPMC10198566 | biostudies-literature
Project description:ObjectiveTo evaluate whether the progression of individual motor features was influenced by early deep brain stimulation (DBS), a post hoc analysis of Unified Parkinson's Disease Rating Scale-III (UPDRS-III) score (after a 7-day washout) was conducted from the 2-year DBS in early Parkinson disease (PD) pilot trial dataset.MethodsThe prospective pilot trial enrolled patients with PD aged 50-75 years, treated with PD medications for 6 months-4 years, and no history of dyskinesia or other motor fluctuations, who were randomized to receive optimal drug therapy (ODT) or DBS plus ODT (DBS + ODT). At baseline and 6, 12, 18, and 24 months, all patients stopped all PD therapy for 1 week (medication and stimulation, if applicable). UPDRS-III "off" item scores were compared between the ODT and DBS + ODT groups (n = 28); items with significant between-group differences were analyzed further.ResultsUPDRS-III "off" rest tremor score change from baseline to 24 months was worse in patients receiving ODT vs DBS + ODT (p = 0.002). Rest tremor slopes from baseline to 24 months favored DBS + ODT both "off" and "on" therapy (p < 0.001, p = 0.003, respectively). More ODT patients developed new rest tremor in previously unaffected limbs than those receiving DBS + ODT (p = 0.001).ConclusionsThese results suggest the possibility that DBS in early PD may slow rest tremor progression. Future investigation in a larger cohort is needed, and these findings will be tested in the Food and Drug Administration-approved, phase III, pivotal, multicenter clinical trial evaluating DBS in early PD.Classification of evidenceThis study provides Class II evidence that for patients with early PD, DBS may slow the progression of rest tremor.
| S-EPMC6093763 | biostudies-literature
Project description:BackgroundStudies comparing long-term outcomes between general anesthesia (GA) and local anesthesia (LA) for STN-DBS in Parkinson's disease (PD) are lacking. Whether patients who received STN-DBS in GA could get the same benefit without compromising electrophysiological recording is debated.MethodsWe compared five-year outcomes for different anesthetic methods (GA vs LA) during STN-DBS for PD. Thirty-six consecutive PD patients with similar preoperative characteristics, including age, disease duration, and severity, underwent the same surgical procedures except the GA (n=22) group with inhalational anesthesia and LA (n=14) with local anesthesia during microelectrode recording and intraoperative macrostimulation test. Surgical outcome evaluations included Unified Parkinson's Disease Rating Scale (UPDRS), Mini-Mental Status Examinations, and the Beck Depression Inventory. Stimulation parameters and coordinates of STN targeting were also collected.ResultsBoth groups attained similar benefits in UPDRS part III from STN-DBS (GA 43.2 ± 14.1% vs. LA 46.8 ± 13.8% decrease, p=0.45; DBS on/Med off vs. DBS off/Med off) and no difference in reduction of levodopa equivalent doses (GA 47.56 ± 18.98% vs. LA 51.37 ± 31.73%, p=0.51) at the five-year follow-up. In terms of amplitude, frequency, and pulse width, the stimulation parameters used for DBS were comparable, and the coordinates of preoperative targeting and postoperative electrode tip were similar between two groups. There was no difference in STN recording length as well. Significantly less number of MER tracts in GA was found (p=0.04). Adverse effects were similar in both groups.ConclusionsOur study confirmed that STN localization with microelectrode recording and patient comfort could be achieved based on equal effectiveness and safety of STN-DBS under GA compared with LA.
| S-EPMC6360066 | biostudies-literature
Project description:IntroductionThe pilot trial of deep brain stimulation (DBS) in early-stage Parkinson's disease (PD) randomized 30 patients (medication duration 0.5-4 years; without dyskinesia or motor fluctuations) to receive optimal drug therapy alone (early ODT) or subthalamic nucleus (STN) DBS plus ODT (early DBS + ODT). This study reports long-term neuropsychological outcomes from the early DBS pilot trial.MethodsThis is an extension of an earlier study that examined two-year neuropsychological outcomes in the pilot trial. The primary analysis was conducted on the five-year cohort (n = 28), and a secondary analysis was conducted on the 11-year cohort (n = 12). Linear mixed effects models for each analysis compared overall trend in outcomes for randomization groups. All subjects who completed the 11-year assessment were also pooled to evaluate long-term change from baseline.ResultsThere were no significant differences between groups in either the five- or 11-year analyses. Across all PD patients who completed the 11-year visit, there was significant decline in Stroop Color and Color-Word and Purdue Pegboard from baseline to 11 years.ConclusionsPrevious significant differences between the groups in phonemic verbal fluency and cognitive processing speed showing more decline for early DBS + ODT subjects one year after baseline diminished as PD progressed. No cognitive domains were worse for early DBS + ODT subjects compared to standard of care subjects. There were shared declines across all subjects on cognitive processing speed and motor control, likely reflecting disease progression. More study is needed to understand the long-term neuropsychological outcomes associated with early DBS in PD.
| S-EPMC11232874 | biostudies-literature
Project description:BackgroundDeep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson's disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD.MethodsThirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50-75, on medication ≥6 months but ≤4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n = 15) or DBS + ODT (n = 15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months.ResultsAs hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. Medication requirements in the DBS + ODT group were lower at all time points with a maximal difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS + ODT group suffered serious adverse events; remaining adverse events were mild or transient.ConclusionsThis study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD.
| S-EPMC4103427 | biostudies-literature
Project description:ObjectivesOur objective was to compare long-term outcomes of deep brain stimulation (DBS) of the globus pallidus interna (GPi) and subthalamic nucleus (STN) for patients with Parkinson disease (PD) in a multicenter randomized controlled trial.MethodsPatients randomly assigned to GPi (n = 89) or STN DBS (n = 70) were followed for 36 months. The primary outcome was motor function on stimulation/off medication using the Unified Parkinson's Disease Rating Scale motor subscale. Secondary outcomes included quality of life and neurocognitive function.ResultsMotor function improved between baseline and 36 months for GPi (41.1 to 27.1; 95% confidence interval [CI] -16.4 to -10.8; p < 0.001) and STN (42.5 to 29.7; 95% CI -15.8 to -9.4; p < 0.001); improvements were similar between targets and stable over time (p = 0.59). Health-related quality of life improved at 6 months on all subscales (all p values significant), but improvement diminished over time. Mattis Dementia Rating Scale scores declined faster for STN than GPi patients (p = 0.01); other neurocognitive measures showed gradual decline overall.ConclusionsThe beneficial effect of DBS on motor function was stable and comparable by target over 36 months. Slight declines in quality of life following initial gains and gradual decline in neurocognitive function likely reflect underlying disease progression and highlight the importance of nonmotor symptoms in determining quality of life.Classification of evidenceThis study provides Class III evidence that improvement of motor symptoms of PD by DBS remains stable over 3 years and does not differ by surgical target. Neurology® 2012;79:55-65.
| S-EPMC3385495 | biostudies-literature
Project description:OBJECTIVE:To investigate predictors for improvement of disease-specific quality of life (QOL) after deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson disease (PD) with early motor complications. METHODS:We performed a secondary analysis of data from the previously published EARLYSTIM study, a prospective randomized trial comparing STN-DBS (n = 124) to best medical treatment (n = 127) after 2 years follow-up with disease-specific QOL (39-item Parkinson's Disease Questionnaire summary index [PDQ-39-SI]) as the primary endpoint. Linear regression analyses of the baseline characteristics age, disease duration, duration of motor complications, and disease severity measured at baseline with the Unified Parkinson's Disease Rating Scale (UPDRS) (UPDRS-III "off" and "on" medications, UPDRS-IV) were conducted to determine predictors of change in PDQ-39-SI. RESULTS:PDQ-39-SI at baseline was correlated to the change in PDQ-39-SI after 24 months in both treatment groups (p < 0.05). The higher the baseline score (worse QOL) the larger the improvement in QOL after 24 months. No correlation was found for any of the other baseline characteristics analyzed in either treatment group. CONCLUSION:Impaired QOL as subjectively evaluated by the patient is the most important predictor of benefit in patients with PD and early motor complications, fulfilling objective gold standard inclusion criteria for STN-DBS. Our results prompt systematically including evaluation of disease-specific QOL when selecting patients with PD for STN-DBS. CLINICALTRIALSGOV IDENTIFIER:NCT00354133.
| S-EPMC6442017 | biostudies-literature
Project description:Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidum internus (GPi) improves motor functions in patients with Parkinson's disease (PD) but may cause a decline in specific cognitive domains. The aim of this systematic review and meta-analysis was to assess the long-term (1-3 years) effects of STN or GPi DBS on four cognitive functions: (i) memory (delayed recall, working memory, immediate recall), (ii) executive functions including inhibition control (Color-Word Stroop test) and flexibility (phonemic verbal fluency), (iii) language (semantic verbal fluency), and (iv) mood (anxiety and depression). Medline and Web of Science were searched, and studies published before July 2021 investigating long-term changes in PD patients following DBS were included. Random-effects model meta-analyses were performed using the R software to estimate the standardized mean difference (SMD) computed as Hedges' g with 95% CI. 2522 publications were identified, 48 of which satisfied the inclusion criteria. Fourteen meta-analyses were performed including 2039 adults with a clinical diagnosis of PD undergoing DBS surgery and 271 PD controls. Our findings add new information to the existing literature by demonstrating that, at a long follow-up interval (1-3 years), both positive effects, such as a mild improvement in anxiety and depression (STN, Hedges' g = 0,34, p = 0,02), and negative effects, such as a decrease of long-term memory (Hedges' g = -0,40, p = 0,02), verbal fluency such as phonemic fluency (Hedges' g = -0,56, p < 0,0001), and specific subdomains of executive functions such as Color-Word Stroop test (Hedges' g = -0,45, p = 0,003) were observed. The level of evidence as qualified with GRADE varied from low for the pre- verses post-analysis to medium when compared to a control group.
| S-EPMC10148791 | biostudies-literature
Project description:ObjectivesThe oscillation model of Parkinson disease (PD) states that, in the subthalamic nucleus (STN), increased θ (4-10 Hz) and β (11-30 Hz) frequencies were associated with worsening whereas γ frequencies (31-100 Hz) were associated with improvement of motor symptoms. However, the peak STN frequency in each band varied widely from subject to subject. We hypothesized that STN deep brain stimulation (DBS) at individualized γ frequencies would improve whereas θ or β frequencies would worsen PD motor signs.MethodsWe prospectively studied 13 patients with PD. STN local field potential (LFP) was recorded after electrode implantations, in the OFF and then in ON dopaminergic medication states while patients performed wrist movements. Six individual peak frequencies of the STN LFP power spectra were obtained: the greatest decrease in θ and β and greatest increase in γ frequencies in the ON state (MED) and during movements (MOVE). Eight DBS frequencies were applied including 6 MED and MOVE frequencies, high frequency (HF) used for chronic stimulation, and no stimulation. The patients were assessed using the motor Unified Parkinson's Disease Rating Scale (mUPDRS).ResultsSTN DBS at γ frequencies (MED and MOVE) and HF significantly improved mUPDRS scores compared to no stimulation and both γ frequencies were not different from HF. DBS at θ and β frequencies did not worsen mUPDRS scores compared to no stimulation.ConclusionShort-term administration of STN DBS at peak dopamine-dependent or movement-related γ frequencies were as effective as HF for reducing parkinsonian motor signs but DBS at θ and β frequencies did not worsen PD motor signs.Classification of evidenceThis study provides Class III evidence that STN DBS at patient-specific γ frequencies and at usual high frequencies both improved mUPDRS scores compared to no stimulation and did not differ in effect.
| S-EPMC3369506 | biostudies-literature
Project description:ObjectiveDeep brain stimulation (DBS) for Parkinson disease (PD) is traditionally performed with awake intraoperative testing and/or microelectrode recording. Recently, however, the procedure has been increasingly performed under general anesthesia with image-based verification. The authors sought to compare structural and functional networks engaged by awake and asleep PD-DBS of the subthalamic nucleus (STN) and correlate them with clinical outcomes.MethodsLevodopa equivalent daily dose (LEDD), pre- and postoperative motor scores on the Movement Disorders Society-Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III), and total electrical energy delivered (TEED) at 6 months were retroactively assessed in patients with PD who received implants of bilateral DBS leads. In subset analysis, implanted electrodes were reconstructed using the Lead-DBS toolbox. Volumes of tissue activated (VTAs) were used as seed points in group volumetric and connectivity analysis.ResultsThe clinical courses of 122 patients (52 asleep, 70 awake) were reviewed. Operating room and procedure times were significantly shorter in asleep cases. LEDD reduction, MDS-UPDRS III score improvement, and TEED at the 6-month follow-up did not differ between groups. In subset analysis (n = 40), proximity of active contact, VTA overlap, and desired network fiber counts with motor STN correlated with lower DBS energy requirement and improved motor scores. Discriminative structural fiber tracts involving supplementary motor area, thalamus, and brainstem were associated with optimal clinical improvement. Areas of highest structural and functional connectivity with VTAs did not significantly differ between the two groups.ConclusionsCompared to awake STN DBS, asleep procedures can achieve similarly optimal targeting-based on clinical outcomes, electrode placement, and connectivity estimates-in more efficient procedures and shorter operating room times.
| S-EPMC10215008 | biostudies-literature