Randomized trial of deep brain stimulation for Parkinson disease: thirty-six-month outcomes.
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ABSTRACT: Objectives
Our 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.Methods
Patients 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.Results
Motor 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.Conclusions
The 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 evidence
This 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.
SUBMITTER: Weaver FM
PROVIDER: S-EPMC3385495 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo report 5-year outcomes from the subthalamic nucleus (STN) deep brain stimulation (DBS) in early-stage Parkinson disease (PD) pilot clinical trial.MethodsThe 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.ResultsEarly 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.ConclusionsThese 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 evidenceThis 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.
| S-EPMC7455319 | biostudies-literature
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:Deep brain stimulation is an accepted treatment for advanced Parkinson disease (PD), although there are few randomized trials comparing treatments, and most studies exclude older patients.To compare 6-month outcomes for patients with PD who received deep brain stimulation or best medical therapy.Randomized controlled trial of patients who received either deep brain stimulation or best medical therapy, stratified by study site and patient age (< 70 years vs > or = 70 years) at 7 Veterans Affairs and 6 university hospitals between May 2002 and October 2005. A total of 255 patients with PD (Hoehn and Yahr stage > or = 2 while not taking medications) were enrolled; 25% were aged 70 years or older. The final 6-month follow-up visit occurred in May 2006.Bilateral deep brain stimulation of the subthalamic nucleus (n = 60) or globus pallidus (n = 61). Patients receiving best medical therapy (n = 134) were actively managed by movement disorder neurologists.The primary outcome was time spent in the "on" state (good motor control with unimpeded motor function) without troubling dyskinesia, using motor diaries. Other outcomes included motor function, quality of life, neurocognitive function, and adverse events.Patients who received deep brain stimulation gained a mean of 4.6 h/d of on time without troubling dyskinesia compared with 0 h/d for patients who received best medical therapy (between group mean difference, 4.5 h/d [95% CI, 3.7-5.4 h/d]; P < .001). Motor function improved significantly (P < .001) with deep brain stimulation vs best medical therapy, such that 71% of deep brain stimulation patients and 32% of best medical therapy patients experienced clinically meaningful motor function improvements (> or = 5 points). Compared with the best medical therapy group, the deep brain stimulation group experienced significant improvements in the summary measure of quality of life and on 7 of 8 PD quality-of-life scores (P < .001). Neurocognitive testing revealed small decrements in some areas of information processing for patients receiving deep brain stimulation vs best medical therapy. At least 1 serious adverse event occurred in 49 deep brain stimulation patients and 15 best medical therapy patients (P < .001), including 39 adverse events related to the surgical procedure and 1 death secondary to cerebral hemorrhage.In this randomized controlled trial of patients with advanced PD, deep brain stimulation was more effective than best medical therapy in improving on time without troubling dyskinesias, motor function, and quality of life at 6 months, but was associated with an increased risk of serious adverse events.clinicaltrials.gov Identifier: NCT00056563.
| S-EPMC2814800 | biostudies-literature
Project description:ImportanceDeep brain stimulation of the nucleus basalis of Meynert (NBM DBS) has been proposed as a treatment option for Parkinson disease dementia.ObjectiveTo evaluate the safety and potential symptomatic effects of NBM DBS in patients with Parkinson disease dementia.Design, setting, and participantsA randomized, double-blind, crossover clinical trial evaluated the results of 6 patients with Parkinson disease dementia who were treated with NBM DBS at a neurosurgical referral center in the United Kingdom from October 26, 2012, to July 31, 2015. Eligible patients met the diagnostic criteria for Parkinson disease dementia, had motor fluctuations, were appropriate surgical candidates aside from the coexistence of dementia, were age 35 to 80 years, were able to give informed consent, had a Mini-Mental State Examination score of 21 to 26, had minimal atrophy seen on results of brain magnetic resonance imaging, and lived at home with a caregiver-informant.InterventionsAfter surgery, patients were assigned to receive either active stimulation (bilateral, low-frequency [20 Hz] NBM DBS) or sham stimulation for 6 weeks, followed by the opposite condition for 6 weeks.Main outcomes and measuresThe primary outcome was the difference in scores on each item of an abbreviated cognitive battery (California Verbal Learning Test-II, Wechsler Adult Intelligence Scale-III digit span, verbal fluency, Posner covert attention test, and simple and choice reaction times) between the 2 conditions. Secondary outcomes were exploratory and included differences in scores on standardized measurements of cognitive, psychiatric, and motor symptoms and resting state functional magnetic resonance imaging.ResultsSurgery and stimulation were well tolerated by all 6 patients (all men; mean [SD] age, 65.2 [10.7] years), with no serious adverse events during the trial. No consistent improvements were observed in the primary cognitive outcomes or in results of resting state functional magnetic resonance imaging. An improvement in scores on the Neuropsychiatric Inventory was observed with NBM DBS (8.5 points [range, 4-26 points]) compared with sham stimulation (12 points [range, 8-38 points]; median difference, 5 points; 95% CI, 2.5-8.5 points; P = .03) and the preoperative baseline (13 points [range, 5-25 points]; median difference, 2 points; 95% CI, -8 to 5.5 points; P = .69).Conclusions and relevanceLow-frequency NBM DBS was safely conducted in patients with Parkinson disease dementia; however, no improvements were observed in the primary cognitive outcomes. Further studies may be warranted to explore its potential to improve troublesome neuropsychiatric symptoms.Trial registrationclinicaltrials.gov Identifier: NCT01701544.
| S-EPMC5838617 | 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) of the thalamic ventral intermediate nucleus (VIM) effectively suppresses arm tremor. Uncontrolled studies suggest the posterior subthalamic area (PSA) may be superior. We compared the intra-individual efficacy of VIM- versus PSA-DBS on tremor suppression and arm function.MethodsWe performed a randomized, double-blind, crossover trial at Oslo University Hospital in patients (18-80 years) with isolated or combined action tremor affecting at least one arm. Four-contact DBS leads were implanted (bi- or unilaterally) with a trajectory to cover the VIM (upper two contacts) and PSA (lower two contacts). Patients were randomized (1:1 ratio) post-surgery to: Group 1, VIM-stimulation months 0-3 (period 1), then PSA-stimulation months 4-6 (period 2); Group 2, PSA-stimulation first, then VIM-stimulation. Primary endpoint was the difference in improvement from baseline to the end of the VIM- versus PSA-period in the sum of the dominant arm tremor scores of the Fahn-Tolosa-Marin Tremor Rating Scale (FTMTRS), items 5/6 + 10-14.ResultsForty-five patients were randomized to Group 1 (n = 23) or 2 (n = 22). In the primary endpoint per-protocol analysis (mixed model, n = 40), mean difference in the sum FTMTRS score improvement for the dominant arm was -2.65 points (95% CI -4.33 to -0.97; p = 0.002). The difference in favour of PSA stimulation was highly significant in period 2, but not period 1.InterpretationOur randomized trial demonstrated that PSA stimulation provided superior tremor suppression compared with VIM stimulation. A period effect reducing tremor for up to three months in both groups was most likely attributed to a post-surgery stun effect. ANN NEUROL 2022;91:585-601.
| S-EPMC9311445 | biostudies-literature
Project description:ObjectiveWe evaluate the 6-month efficacy of Keep Active Minnesota, a phone- and mail-based physical activity maintenance intervention designed for use with adults age 50 to 70 years who have increased their physical activity within the past year.MethodParticipants (N=1049) recruited in 2004 and 2005 from one large managed-care organization in Minnesota were randomly assigned to either treatment (N=523) or usual care (N=526) with physical activity assessed using the Community Healthy Activities Model Program for Seniors questionnaire, and expressed as kcal/week expenditures.ResultsTotal physical activity at baseline was similar for treatment and usual care participants (p<0.44) as was moderate/vigorous physical activity (p<0.21). Maintenance of physical activity was higher among treatment participants whose mean 6-month change in total kcal/week energy expenditure was -91, compared to -683 for usual care participants (p<0.002). Mean 6-month change in kcal/week expenditure in moderate or vigorous activities was -49 for treatment participants, compared to -612 for usual care participants (p<0.001).ConclusionsThis phone- and mail-based physical activity maintenance intervention is efficacious at maintaining physical activity at 6 months.
| S-EPMC2350214 | 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.
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Project description:For over half a century, neurosurgeons have attempted to treat pain from a diversity of causes using acute and chronic intracranial stimulation. Targets of stimulation have included the sensory thalamus, periventricular and periaqueductal gray, the septum, the internal capsule, the motor cortex, posterior hypothalamus, and more recently, the anterior cingulate cortex. The current work focuses on presenting and evaluating the evidence for the efficacy of these targets in a historical context while also highlighting the major challenges to having a double-blind placebo-controlled clinical trial. Considerations for pain research in general and use of intracranial targets specifically are included.
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Project description:Obsessive-compulsive disorder (OCD), a leading cause of disability, affects ~1-2% of the population, and can be distressing and disabling. About 1/3 of individuals demonstrate poor responsiveness to conventional treatments. A small proportion of these individuals may be deep brain stimulation (DBS) candidates. Candidacy is assessed through a multidisciplinary process including assessment of illness severity, chronicity, and functional impact. Optimization failure, despite multiple treatments, is critical during screening. Few patients nationwide are eligible for OCD DBS and thus a multi-center approach was necessary to obtain adequate sample size. The study was conducted over a six-year period and was a NIH-funded, eight-center sham-controlled trial of DBS targeting the ventral capsule/ventral striatum (VC/VS) region. There were 269 individuals who initially contacted the sites, in order to achieve 27 participants enrolled. Study enrollment required extensive review for eligibility, which was overseen by an independent advisory board. Disabling OCD had to be persistent for ≥5 years despite exhaustive medication and behavioral treatment. The final cohort was derived from a detailed consent process that included consent monitoring. Mean illness duration was 27.2 years. OCD symptom subtypes and psychiatric comorbidities varied, but all had severe disability with impaired quality of life and functioning. Participants were randomized to receive sham or active DBS for three months. Following this period, all participants received active DBS. Treatment assignment was masked to participants and raters and assessments were blinded. The final sample was consistent in demographic characteristics and clinical features when compared to other contemporary published prospective studies of OCD DBS. We report the clinical trial design, methods, and general demographics of this OCD DBS sample.
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