Measuring Physical Functioning Using Wearable Sensors in Parkinson Disease and Chronic Obstructive Pulmonary Disease (the Accuracy of Digital Assessment of Performance Trial Study): Protocol for a Prospective Observational Study.

BACKGROUND: Physical capacity and physical activity are important aspects of physical functioning and quality of life in people with a chronic disease such as Parkinson disease (PD) or chronic obstructive pulmonary disease (COPD). Both physical capacity and physical activity are currently measured in the clinic using standardized questionnaires and tests, such as the 6-minute walk test (6MWT) and the Timed Up and Go test (TUG). However, relying only on in-clinic tests is suboptimal since they offer limited information on how a person functions in daily life and how functioning fluctuates throughout the day. Wearable sensor technology may offer a solution that enables us to better understand true physical functioning in daily life. OBJECTIVE: We aim to study whether device-assisted versions of 6MWT and TUG, such that the tests can be performed independently at home using a smartwatch, is a valid and reliable way to measure the performance compared to a supervised, in-clinic test. METHODS: This is a decentralized, prospective, observational study including 100 people with PD and 100 with COPD. The inclusion criteria are broad: age ≥18 years, able to walk independently, and no co-occurrence of PD and COPD. Participants are followed for 15 weeks with 4 in-clinic visits, once every 5 weeks. Outcomes include several walking tests, cognitive tests, and disease-specific questionnaires accompanied by data collection using wearable devices (the Verily Study Watch and Modus StepWatch). Additionally, during the last 10 weeks of this study, participants will follow an aerobic exercise training program aiming to increase physical capacity, creating the opportunity to study the responsiveness of the remote 6MWT. RESULTS: In total, 89 people with PD and 65 people with COPD were included in this study. Data analysis will start in April 2024. CONCLUSIONS: The results of this study will provide information on the measurement properties of the device-assisted 6MWT and TUG in the clinic and at home. When reliable and valid, this can contribute to a better understanding of a person's physical capacity in real life, which makes it possible to personalize treatment options. TRIAL REGISTRATION: ClinicalTrials.gov NCT05756075; https://clinicaltrials.gov/study/NCT05756075. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55452.

Wrist-worn sensor-based measurements for drug effect detection with small samples in people with Lewy Body Dementia.

INTRODUCTION: Few late-stage clinical trials in Parkinson's disease (PD) have produced evidence on the clinical validity of sensor-based digital measurements of daily life activities to detect responses to treatment. The objective of this study was to assess whether digital measures from patients with mild-to-moderate Lewy Body Dementia demonstrate treatment effects during a randomized Phase 2 trial. METHODS: Substudy within a 12-week trial of mevidalen (placebo vs 10, 30, or 75 mg), where 70/344 patients (comparable to the overall population) wore a wrist-worn multi-sensor device. RESULTS: Treatment effects were statistically significant by conventional clinical assessments (Movement Disorder Society-Unified Parkinson's Disease Rating Scale [MDS-UPDRS] sum of Parts I-III and Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change [ADCS-CGIC] scores) in the full study cohort at Week 12, but not in the substudy. However, digital measurements detected significant effects in the substudy cohort at week 6, persisting to week 12. CONCLUSIONS: Digital measurements detected treatment effects in a smaller cohort over a shorter period than conventional clinical assessments. TRIAL REGISTRATION: clinicaltrials.gov, NCT03305809.

Analytical and clinical validity of wearable, multi-sensor technology for assessment of motor function in patients with Parkinson's disease in Japan.

Continuous, objective monitoring of motor signs and symptoms may help improve tracking of disease progression and treatment response in Parkinson's disease (PD). This study assessed the analytical and clinical validity of multi-sensor smartwatch measurements in hospitalized and home-based settings (96 patients with PD; mean wear time 19 h/day) using a twice-daily virtual motor examination (VME) at times representing medication OFF/ON states. Digital measurement performance was better during inpatient clinical assessments for composite V-scores than single-sensor-derived features for bradykinesia (Spearman |r|= 0.63, reliability = 0.72), tremor (|r|= 0.41, reliability = 0.65), and overall motor features (|r|= 0.70, reliability = 0.67). Composite levodopa effect sizes during hospitalization were 0.51-1.44 for clinical assessments and 0.56-1.37 for VMEs. Reliability of digital measurements during home-based VMEs was 0.62-0.80 for scores derived from weekly averages and 0.24-0.66 for daily measurements. These results show that unsupervised digital measurements of motor features with wrist-worn sensors are sensitive to medication state and are reliable in naturalistic settings.Trial Registration: Japan Pharmaceutical Information Center Clinical Trials Information (JAPIC-CTI): JapicCTI-194825; Registered June 25, 2019.

Virtual exam for Parkinson's disease enables frequent and reliable remote measurements of motor function.

Sensor-based remote monitoring could help better track Parkinson's disease (PD) progression, and measure patients' response to putative disease-modifying therapeutic interventions. To be useful, the remotely-collected measurements should be valid, reliable, and sensitive to change, and people with PD must engage with the technology. We developed a smartwatch-based active assessment that enables unsupervised measurement of motor signs of PD. Participants with early-stage PD (N = 388, 64% men, average age 63) wore a smartwatch for a median of 390 days. Participants performed unsupervised motor tasks both in-clinic (once) and remotely (twice weekly for one year). Dropout rate was 5.4%. Median wear-time was 21.1 h/day, and 59% of per-protocol remote assessments were completed. Analytical validation was established for in-clinic measurements, which showed moderate-to-strong correlations with consensus MDS-UPDRS Part III ratings for rest tremor (⍴ = 0.70), bradykinesia (⍴ = -0.62), and gait (⍴ = -0.46). Test-retest reliability of remote measurements, aggregated monthly, was good-to-excellent (ICC = 0.75-0.96). Remote measurements were sensitive to the known effects of dopaminergic medication (on vs off Cohen's d = 0.19-0.54). Of note, in-clinic assessments often did not reflect the patients' typical status at home. This demonstrates the feasibility of smartwatch-based unsupervised active tests, and establishes the analytical validity of associated digital measurements. Weekly measurements provide a real-life distribution of disease severity, as it fluctuates longitudinally. Sensitivity to medication-induced change and improved reliability imply that these methods could help reduce sample sizes needed to demonstrate a response to therapeutic interventions or disease progression.

Predictors of multi-domain cognitive decline following DBS for treatment of Parkinson's disease.

BACKGROUND: Statistically and clinically significant cognitive declines are observed in a small subset of individuals with Parkinson's Disease (PD) following treatment with Deep Brain Stimulation (DBS). OBJECTIVES: We examine the association between multi-domain cognitive decline (MCD) and demographic and baseline clinical variables and the incidence of serious adverse events (SAE) arising within a six-month interval following DBS for PD. METHOD: Study participants with PD who displayed MCD at 6-month follow-up evaluation after DBS (n = 18) were contrasted with individuals with PD from the same study who did not show cognitive decline after DBS (n = 146). Logistic regression analyses were employed to assess relationship between predictors, including age (>70 years old), pre-DBS cognitive screening test performance, SAE, and MCD. MCD+ and MCD-groups were also compared on other baseline clinical and demographic variables. RESULTS: MCD showed modest association with older age and lower baseline neurocognitive screening performance, whereas the groups did not differ on most other baseline clinical and demographic variables. SAEs during the study interval were the most robust predictor of MCD in the DBS group. A variety of SAEs were documented in study participants experiencing MCD after DBS surgery, including, but not limited to, infections and small intracranial hemorrhages. CONCLUSIONS: Older age and lower baseline cognition measured prior to treatment are associated with MCD measured at six-months after DBS. SAE occurring following DBS surgery are also predictive of MCD. These predictors may reflect aspects of "frailty" in advanced PD. Risk factors for SAE warrant careful consideration in clinical trials.

Toward a Mobile Platform for Real-world Digital Measurement of Depression: User-Centered Design, Data Quality, and Behavioral and Clinical Modeling.

BACKGROUND: Although effective mental health treatments exist, the ability to match individuals to optimal treatments is poor, and timely assessment of response is difficult. One reason for these challenges is the lack of objective measurement of psychiatric symptoms. Sensors and active tasks recorded by smartphones provide a low-burden, low-cost, and scalable way to capture real-world data from patients that could augment clinical decision-making and move the field of mental health closer to measurement-based care. OBJECTIVE: This study tests the feasibility of a fully remote study on individuals with self-reported depression using an Android-based smartphone app to collect subjective and objective measures associated with depression severity. The goals of this pilot study are to develop an engaging user interface for high task adherence through user-centered design; test the quality of collected data from passive sensors; start building clinically relevant behavioral measures (features) from passive sensors and active inputs; and preliminarily explore connections between these features and depression severity. METHODS: A total of 600 participants were asked to download the study app to join this fully remote, observational 12-week study. The app passively collected 20 sensor data streams (eg, ambient audio level, location, and inertial measurement units), and participants were asked to complete daily survey tasks, weekly voice diaries, and the clinically validated Patient Health Questionnaire (PHQ-9) self-survey. Pairwise correlations between derived behavioral features (eg, weekly minutes spent at home) and PHQ-9 were computed. Using these behavioral features, we also constructed an elastic net penalized multivariate logistic regression model predicting depressed versus nondepressed PHQ-9 scores (ie, dichotomized PHQ-9). RESULTS: A total of 415 individuals logged into the app. Over the course of the 12-week study, these participants completed 83.35% (4151/4980) of the PHQ-9s. Applying data sufficiency rules for minimally necessary daily and weekly data resulted in 3779 participant-weeks of data across 384 participants. Using a subset of 34 behavioral features, we found that 11 features showed a significant (P<.001 Benjamini-Hochberg adjusted) Spearman correlation with weekly PHQ-9, including voice diary-derived word sentiment and ambient audio levels. Restricting the data to those cases in which all 34 behavioral features were present, we had available 1013 participant-weeks from 186 participants. The logistic regression model predicting depression status resulted in a 10-fold cross-validated mean area under the curve of 0.656 (SD 0.079). CONCLUSIONS: This study finds a strong proof of concept for the use of a smartphone-based assessment of depression outcomes. Behavioral features derived from passive sensors and active tasks show promising correlations with a validated clinical measure of depression (PHQ-9). Future work is needed to increase scale that may permit the construction of more complex (eg, nonlinear) predictive models and better handle data missingness.

The Project Baseline Health Study: a step towards a broader mission to map human health.

The Project Baseline Health Study (PBHS) was launched to map human health through a comprehensive understanding of both the health of an individual and how it relates to the broader population. The study will contribute to the creation of a biomedical information system that accounts for the highly complex interplay of biological, behavioral, environmental, and social systems. The PBHS is a prospective, multicenter, longitudinal cohort study that aims to enroll thousands of participants with diverse backgrounds who are representative of the entire health spectrum. Enrolled participants will be evaluated serially using clinical, molecular, imaging, sensor, self-reported, behavioral, psychological, environmental, and other health-related measurements. An initial deeply phenotyped cohort will inform the development of a large, expanded virtual cohort. The PBHS will contribute to precision health and medicine by integrating state of the art testing, longitudinal monitoring and participant engagement, and by contributing to the development of an improved platform for data sharing and analysis.

New directions in clinical trials for frontotemporal lobar degeneration: Methods and outcome measures.

INTRODUCTION: Frontotemporal lobar degeneration (FTLD) is the most common form of dementia for those under 60 years of age. Increasing numbers of therapeutics targeting FTLD syndromes are being developed. METHODS: In March 2018, the Association for Frontotemporal Degeneration convened the Frontotemporal Degeneration Study Group meeting in Washington, DC, to discuss advances in the clinical science of FTLD. RESULTS: Challenges exist for conducting clinical trials in FTLD. Two of the greatest challenges are (1) the heterogeneity of FTLD syndromes leading to difficulties in efficiently measuring treatment effects and (2) the rarity of FTLD disorders leading to recruitment challenges. DISCUSSION: New personalized endpoints that are clinically meaningful to individuals and their families should be developed. Personalized approaches to analyzing MRI data, development of new fluid biomarkers and wearable technologies will help to improve the power to detect treatment effects in FTLD clinical trials and enable new, clinical trial designs, possibly leveraged from the experience of oncology trials. A computational visualization and analysis platform that can support novel analyses of combined clinical, genetic, imaging, biomarker data with other novel modalities will be critical to the success of these endeavors.

Quantifying neurologic disease using biosensor measurements in-clinic and in free-living settings in multiple sclerosis.

Technological advances in passive digital phenotyping present the opportunity to quantify neurological diseases using new approaches that may complement clinical assessments. Here, we studied multiple sclerosis (MS) as a model neurological disease for investigating physiometric and environmental signals. The objective of this study was to assess the feasibility and correlation of wearable biosensors with traditional clinical measures of disability both in clinic and in free-living in MS patients. This is a single site observational cohort study conducted at an academic neurological center specializing in MS. A cohort of 25 MS patients with varying disability scores were recruited. Patients were monitored in clinic while wearing biosensors at nine body locations at three separate visits. Biosensor-derived features including aspects of gait (stance time, turn angle, mean turn velocity) and balance were collected, along with standardized disability scores assessed by a neurologist. Participants also wore up to three sensors on the wrist, ankle, and sternum for 8 weeks as they went about their daily lives. The primary outcomes were feasibility, adherence, as well as correlation of biosensor-derived metrics with traditional neurologist-assessed clinical measures of disability. We used machine-learning algorithms to extract multiple features of motion and dexterity and correlated these measures with more traditional measures of neurological disability, including the expanded disability status scale (EDSS) and the MS functional composite-4 (MSFC-4). In free-living, sleep measures were additionally collected. Twenty-three subjects completed the first two of three in-clinic study visits and the 8-week free-living biosensor period. Several biosensor-derived features significantly correlated with EDSS and MSFC-4 scores derived at visit two, including mobility stance time with MSFC-4 z-score (Spearman correlation -0.546; p = 0.0070), several aspects of turning including turn angle (0.437; p = 0.0372), and maximum angular velocity (0.653; p = 0.0007). Similar correlations were observed at subsequent clinic visits, and in the free-living setting. We also found other passively collected signals, including measures of sleep, that correlated with disease severity. These findings demonstrate the feasibility of applying passive biosensor measurement techniques to monitor disability in MS patients both in clinic and in the free-living setting.

Cost-Effectiveness of Deep Brain Stimulation for Advanced Parkinson's Disease in the United States.

OBJECTIVES: Deep brain stimulation (DBS), which uses an implantable device to modulate brain activity, is clinically superior to medical therapy for treating advanced Parkinson's disease (PD). We studied the cost-effectiveness of DBS in conjunction with medical therapy compared to best medical therapy (BMT) alone, using the latest clinical and cost data for the U.S. healthcare system. MATERIALS AND METHODS: We used a decision-analytic state-transition (Markov) model to project PD progression and associated costs for the two treatment strategies. We estimated the discounted incremental cost-effectiveness ratio (ICER) in U.S. dollars per quality-adjusted life-year (QALY) from the Medicare payer perspective, considering a ten-year horizon, and evaluated the robustness of our projections through extensive deterministic sensitivity analyses. RESULTS: Over ten years, DBS treatment led to discounted total costs of $130,510 compared to $91,026 for BMT and added 1.69 QALYs more than BMT, resulting in an ICER of $23,404 per QALY. This ICER was relatively insensitive to variations in input parameters, with neurostimulator replacement, costs for DBS implantation, and costs for treatment of disease-related falls having the greatest effects. Across all investigated scenarios, including a five-year horizon, ICERs remained under $50,000 per QALY. Longer follow-up periods and younger treatment age were associated with greater cost-effectiveness. CONCLUSIONS: DBS is a cost-effective treatment strategy for advanced PD in the U.S. healthcare system across a wide range of assumptions. DBS yields substantial improvements in health-related quality of life at a value profile that compares favorably to other well-accepted therapies.

Pregnancy in a Series of Dystonia Patients Treated with Deep Brain Stimulation: Outcomes and Management Recommendations.

BACKGROUND: Medically refractory dystonia affects children and young adults, and deep brain stimulation (DBS) can allow some patients to regain functional independence. Women with dystonia treated with DBS may wish to conceive a child, but there is limited published information on pregnancy and DBS. OBJECTIVE: To describe a series of dystonia patients treated with DBS who later became pregnant and provide guidelines for women treated with DBS considering conception. METHODS: We reviewed all dystonia DBS cases implanted at the University of California, San Francisco, and University of Alabama at Birmingham from 1998 to 2015 and identified patients who became pregnant. Patient records were reviewed and structured interviews were conducted. RESULTS: Six dystonia patients were identified [1 currently pregnant and 7 live births (including 1 twin pair)]. Patients (n = 5) with pre- and postoperative BFMDRS (Burke-Fahn-Marsden Dystonia Rating Scale) scores improved by 65.9% after DBS. All pregnancies and deliveries were uncomplicated (the delivery mode was not influenced by the presence of DBS), except for 1 child, who was born premature at 35 weeks' gestation. Stimulation remained on (n = 3) or off (n = 4) during deliveries. DBS neurostimulators did not hinder breastfeeding. CONCLUSIONS: In this small sample, pregnancy, delivery, and breastfeeding were safe in dystonia patients treated with DBS. The presence of DBS should not be a contraindication to pregnancy.

Long-Term Safety of Patients with Parkinson's Disease Receiving rAAV2-Neurturin (CERE-120) Gene Transfer.

The objective of this study was to assess the long-term safety of surgically administered recombinant adeno-associated virus serotype-2 (rAAV2)-neurturin (NRTN) to patients with advanced Parkinson's disease. Publications from prior trials reported no unexpected or troubling adverse events related to the vector or transgene comprising rAAV2-NRTN. Because rAAV2-NRTN produces long-term NRTN expression, subjects were enrolled in a long-term safety assessment protocol of rAAV2-NRTN. This article presents safety data for up to 5 years, well beyond that reported in the initial publications. Data from 53 patients are included; 47 received rAAV2-NRTN bilaterally to the putamen, whereas 6 subjects received rAAV2-NRTN bilaterally into putamen-plus-substantia nigra. Patients underwent in-person safety assessments on a quarterly to bi-annual basis, including adverse event monitoring, physical and neurological examinations, brain MRI, and laboratory testing. Parkinsonian status was assessed in an unblinded fashion. Fifty-three subjects completed the long-term safety protocol. Nine nonserious adverse events (non-SAEs) in 6 subjects were deemed "possibly related" to rAAV2-NRTN by the principal investigator, whereas none were deemed "related" to rAAV2-NRTN. Over the course of long-term observation, 33 SAEs were reported in 18 subjects, all of who received rAAV2-NRTN into putamen-only; 31 SAEs were deemed not related to rAAV2-NRTN, and 2 were deemed unlikely related. Safety assessments showed no clinically relevant changes in examination, imaging, or laboratory studies. Motor status, on average, was stable or apparently modestly improved (relative to baseline) over the course of the open-label, long-term follow-up. These findings provide evidence for the long-term safety of neurturin when delivered to the putamen or the putamen-plus-substantia nigra via stereotactic surgery and rAAV2 gene transfer. They therefore supplement the safety results reported in four prior publications from the same subjects, significantly extending the safety data for gene therapy and neurotrophic factor expression targeting the brain and adding to growing evidence that rAAV vector-mediated gene therapy to the CNS can be administered safely.

Differential effects of deep brain stimulation target on motor subtypes in Parkinson's disease.

OBJECTIVE: The Veterans Administration Cooperative Studies Program #468, a multicenter study that randomized Parkinson's disease (PD) patients to either subthalamic nucleus (STN) or globus pallidus internus (GPi) deep brain stimulation (DBS), found that stimulation at either target provided similar overall motoric benefits. We conducted an additional analysis of this data set to evaluate whether PD motor subtypes responded differently to the 2 stimulation targets. METHODS: We classified 235 subjects by motor subtype: tremor dominant (TD), intermediate (I), or postural instability gait difficulty (PIGD), based on pre-DBS baseline Unified Parkinson's Disease Rating Scale (UPDRS) scores off-medication. The primary outcome was change in UPDRS part III (UPDRS-III) off-medication scores from baseline to 24 months post-DBS, compared among subjects with particular PD motor subtypes and by DBS target (STN vs GPi). Changes in tremor, rigidity, akinesia, and gait scores were also assessed using the UPDRS. RESULTS: TD patients had greater mean overall motor improvement, measured by UPDRS-III, after GPi DBS, compared to STN DBS (17.5 ± 13.0 vs 14.6 ± 14.9, p = 0.02), with improvement in gait accounting for this difference. Regardless of stimulation target, PIGD subjects had lower mean overall improvement in UPDRS-III scores compared with I or TD subjects (8.7 ± 12.2 vs 21.7 ± 11.2 vs 16.3 ± 13.8, p = 0.001). INTERPRETATION: Our results suggest that responsiveness to both GPi and STN DBS is similar among different PD motor subtypes, although the TD motor subtype may have a greater response to GPi DBS with respect to gait. PIGD patients obtained less overall benefit from stimulation.

Neuropsychological changes following deep brain stimulation surgery for Parkinson's disease: comparisons of treatment at pallidal and subthalamic targets versus best medical therapy.

BACKGROUND: Deep brain stimulation (DBS) improves motor symptoms in Parkinson's disease (PD), but questions remain regarding neuropsychological decrements sometimes associated with this treatment, including rates of statistically and clinically meaningful change, and whether there are differences in outcome related to surgical target. METHODS: Neuropsychological functioning was assessed in patients with Parkinson's disease (PD) at baseline and after 6 months in a prospective, randomised, controlled study comparing best medical therapy (BMT, n=116) and bilateral deep brain stimulation (DBS, n=164) at either the subthalamic nucleus (STN, n=84) or globus pallidus interna (GPi, n=80), using standardised neuropsychological tests. Measures of functional outcomes were also administered. RESULTS: Comparison of the two DBS targets revealed few significant group differences. STN DBS was associated with greater mean reductions on some measures of processing speed, only one of which was statistically significant in comparison with stimulation of GPi. GPi DBS was associated with lower mean performance on one measure of learning and memory that requires mental control and cognitive flexibility. Compared to the group receiving BMT, the combined DBS group had significantly greater mean reductions at 6-month follow-up in performance on multiple measures of processing speed and working memory. After calculating thresholds for statistically reliable change from data obtained from the BMT group, the combined DBS group also displayed higher rates of decline in neuropsychological test performance. Among study completers, 18 (11%) study participants receiving DBS displayed reliable decline by multiple indicators in two or more cognitive domains, a significantly higher rate than in the BMT group (3%). This multi-domain cognitive decline was associated with less beneficial change in subjective ratings of everyday functioning and quality of life (QOL). The multi-domain cognitive decline group continued to function at a lower level at 24-month follow-up. CONCLUSIONS: In those with PD, the likelihood of significant decline in neuropsychological functioning increases with DBS, affecting a small minority of patients who also appear to respond less optimally to DBS by other indicators of QOL. TRIAL REGISTRATION NUMBER: NCT00056563 and NCT01076452.

Combining cell transplants or gene therapy with deep brain stimulation for Parkinson's disease.

Cell transplantation and gene therapy each show promise to enhance the treatment of Parkinson's disease (PD). However, because cell transplantation and gene therapy generally require direct delivery to the central nervous system, clinical trial design involves unique scientific, ethical, and financial concerns related to the invasive nature of the procedure. Typically, such biologics have been tested in PD patients who have not received any neurosurgical intervention. Here, we suggest that PD patients undergoing deep brain stimulation (DBS) device implantation are an ideal patient population for the clinical evaluation of cell transplantation and gene therapy. Randomizing subjects to an experimental group that receives the biologic concurrently with the DBS implantation-or to a control group that receives the DBS treatment alone-has several compelling advantages. First, this study design enables the participation of patients likely to benefit from DBS, many of whom simultaneously meet the inclusion criteria of biologic studies. Second, the need for a sham neurosurgical procedure is eliminated, which may reduce ethical concerns, promote patient recruitment, and enhance the blinding of surgical trials. Third, testing the biologic by "piggybacking" onto an established, reimbursable procedure should reduce the cost of clinical trials, which may allow a greater number of biologics to reach this critical stage of research translation. Finally, this clinical trial design may lead to combinatorial treatment strategies that provide PD patients with more durable control over disabling motor symptoms. By combining neuromodulation with biologics, we may also reveal important treatment paradigms relevant to other diseases of the brain.

Shorter disease duration correlates with improved long-term deep brain stimulation outcomes in young-onset DYT1 dystonia.

BACKGROUND: Treatment with deep brain stimulation (DBS) of the globus pallidus internus in children with DYT1 primary torsion dystonia is highly effective; however, individual response to stimulation is variable, and a greater understanding of predictors of long-term outcome is needed. OBJECTIVE: To report the long-term outcomes of subjects with young-onset DYT1 primary torsion dystonia treated with bilateral globus pallidus DBS. METHODS: Fourteen subjects (7 male, 7 female) treated consecutively from 2000 to 2010 at our center were included in this retrospective study. The Burke-Fahn-Marsden Dystonia Rating Scale was performed at baseline and at 1, 2, and up to 6 years postoperatively. RESULTS: Pallidal DBS was well tolerated and highly effective, with mean Burke-Fahn-Marsden Dystonia Rating Scale movement scores improving from baseline by 61.5% (P < .001) at 1 year, 64.4% (P < .001) at 2 years, and 70.3% (P < .001) at the final follow-up visit (mean, 32 months; range, 7-77 months). Disability scores also improved significantly. Multiple linear regression analysis revealed a significant influence of duration of disease as a predictor of percent improvement in Burke-Fahn-Marsden Dystonia Rating Scale movement score at long-term follow-up (duration of disease, P < .05). Subjects with fixed orthopedic deformities (4) had less improvement in these regions. Location of the active DBS electrode used at final follow-up visit was not predictive of clinical outcome. CONCLUSION: Our findings highlight the sustained benefit from DBS and the importance of early referral for DBS in children with medically refractory DYT1 primary torsion dystonia, which can lead to improved long-term benefits.

Randomized trial of deep brain stimulation for Parkinson disease: thirty-six-month outcomes.

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.