Non-Motor Fluctuations in Parkinson's Disease: Validation of the Non-Motor Fluctuation Assessment Questionnaire.

BACKGROUND: In patients with Parkinson's disease (PD), sleep, mood, cognitive, autonomic, and other non-motor symptoms may fluctuate in a manner similar to motor symptoms. OBJECTIVES: To validate a final version of a patient-rated questionnaire that captures the presence and severity of non-motor fluctuations in levodopa-treated PD patients (NoMoFA). METHODS: We recruited PD subjects from five movement disorders centers across the US and Canada. We assessed the internal consistency, floor and ceiling effects, test-retest reliability, and concurrent validity of NoMoFA. Classical test theory and item response theory methods informed item reduction and Delphi process yielded a final questionnaire. RESULTS: Two hundred subjects and their care-partners participated in the study (age: 66.4 ± 9.6 years; disease duration: 9 ± 5.5 years; median Hoehn and Yahr [H&Y] OFF: 3 [range 1-5]; mean Unified Parkinson's Disease Rating Scale (UPDRS) III ON score: 27.4 ± 14.9). Acceptability of the scale was adequate. There were floor effects in 8/28 items. Cronbach's alpha was 0.894. While eight items had "item-to-total" correlations below the cutoff of 0.4, removing these items did not improve Cronbach's alpha. Test-retest reliability was acceptable (intraclass correlation coefficient [ICC] 0.73; 95% confidence interval, 0.64-0.80). Concurrent validity was adequate with all Spearman's rho values comparing NoMoFA score to other measures of parkinsonian severity showing significance and in the expected direction. A final Delphi panel eliminated one item to avoid redundancy. CONCLUSIONS: The final 27-item self-administered NoMoFA is a valid and reliable questionnaire, capturing both static and fluctuating non-motor symptoms in PD. © 2021 International Parkinson and Movement Disorder Society.

Modernizing Daily Function Assessment in Parkinson's Disease Using Capacity, Perception, and Performance Measures.

Many disease symptoms restrict the quality of life of the affected. This usually occurs indirectly, at least in most neurological diseases. Here, impaired daily function is interposed between the symptoms and the reduced quality of life. This is reflected in the International Classification of Function, Disability and Health model published by the World Health Organization in 2001. This correlation between symptom, daily function, and quality of life makes it clear that to evaluate the success of a therapy and develop new therapies, daily function must also be evaluated as accurately as possible. However, daily function is a complex construct and therefore difficult to quantify. To date, daily function has been measured primarily by capacity (clinical assessments) and perception (surveys and patient-reported outcomes) assessment approaches. Now, daily function can be captured in a new dimension, that is, performance, through new digital technologies that can be used in the home environment of patients. This viewpoint discusses the differences and interdependencies of capacity, perception, and performance assessment types using the example of Parkinson's disease. Options regarding how future study protocols should be designed to get the most comprehensive and validated picture of daily function in patients are presented. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Assessment of Emergency Department and Inpatient Use and Costs in Adult and Pediatric Functional Neurological Disorders.

Importance: There is limited information about health care use and costs in patients with functional neurological disorders (FNDs). Objective: To assess US emergency department (ED) and inpatient use and charges for FNDs. Design, Setting, and Participants: This economic evaluation used Healthcare Cost and Utilization Project data to assess all-payer (1) adult (age, ≥18 years) hospitalizations (2008-2017), (2) pediatric (age, 5-17 years) hospitalizations (2003, 2006, 2009, 2012, and 2016), and (3) adult and pediatric ED evaluations (2008-2017). International Classification of Diseases, Ninth Revision, Clinical Modification code 300.11 (conversion disorder) or 306.0 (musculoskeletal malfunction arising from mental factors) and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Clinical Modification codes for conversion disorder/functional neurological symptom disorder (F44.4 to F44.7) were used to conservatively define FNDs and to compare them with other neurological disorders that are associated with high levels of health care use. Analysis was performed between January 2019 and July 2020. Main Outcomes and Measures: Admission traits (eg, demographic characteristics of patients, length of stay, and discharge disposition) and hospital charges. Results: Compared with other neurological disorders in 2017, emergency FND evaluations of 36 359 adults (25 807 women [71.0%] and 3800 children (2733 girls [71.9%]) more frequently resulted in inpatient admissions (22 895 adult admissions [69.2% female] and 1264 pediatric admissions [73.4% ]). These FND admissions had a shorter mean (SEM) hospital length of stay (5.21 [0.15] days vs 6.03 [0.03] days, P < .001) but higher workup rates than admissions for comparable neurological diagnoses. Admissions for FNDs had low rates of inpatient physical therapy, occupational therapy, speech and language pathology, and psychiatric consultation. The total annual costs (a proxy for total costs in 2017 US dollars) were $1066 million (95% CI, $971-$1160 million) for adult FND inpatient charges in 2017 compared with $1241 million (95% CI, $1132-$1351 million) for anterior horn cell disease; $75 million (95% CI, $57-$92 million) for pediatric FND inpatient charges in 2012 compared with $86 million (95% CI, $63-$108 million) for demyelinating diseases; and $163 million (95% CI, $144-$182 million) for adult and pediatric ED visits in 2017 compared with $135 million (95% CI $111-$159 million) for refractory epilepsy. Total charges per admission for ED care of FNDs were higher than the other comparison groups in adults. Total costs and costs per admission for FNDs increased from 2008 to 2017 at a higher rate than that of other neurological disorders. Conclusions and Relevance: This economic evaluation found that the more than $1.2 billion and increasing annual costs for ED and inpatient care of FNDs were similar to other investigation-intensive and pharmacologically demanding neurological disorders. Unnecessary investigations and iatrogenic harm inflate costs at the expense of necessary but neglected psychiatric and rehabilitative treatments.

Long-term unsupervised mobility assessment in movement disorders.

Mobile health technologies (wearable, portable, body-fixed sensors, or domestic-integrated devices) that quantify mobility in unsupervised, daily living environments are emerging as complementary clinical assessments. Data collected in these ecologically valid, patient-relevant settings can overcome limitations of conventional clinical assessments, as they capture fluctuating and rare events. These data could support clinical decision making and could also serve as outcomes in clinical trials. However, studies that directly compared assessments made in unsupervised and supervised (eg, in the laboratory or hospital) settings point to large disparities, even in the same parameters of mobility. These differences appear to be affected by psychological, physiological, cognitive, environmental, and technical factors, and by the types of mobilities and diagnoses assessed. To facilitate the successful adaptation of the unsupervised assessment of mobility into clinical practice and clinical trials, clinicians and researchers should consider these disparities and the multiple factors that contribute to them.

A roadmap for implementation of patient-centered digital outcome measures in Parkinson's disease obtained using mobile health technologies.

Obtaining reliable longitudinal information about everyday functioning from individuals with Parkinson's disease (PD) in natural environments is critical for clinical care and research. Despite advances in mobile health technologies, the implementation of digital outcome measures is hindered by a lack of consensus on the type and scope of measures, the most appropriate approach for data capture (eg, in clinic or at home), and the extraction of timely information that meets the needs of patients, clinicians, caregivers, and health care regulators. The Movement Disorder Society Task Force on Technology proposes the following objectives to facilitate the adoption of mobile health technologies: (1) identification of patient-centered and clinically relevant digital outcomes; (2) selection criteria for device combinations that offer an acceptable benefit-to-burden ratio to patients and that deliver reliable, clinically relevant insights; (3) development of an accessible, scalable, and secure platform for data integration and data analytics; and (4) agreement on a pathway for approval by regulators, adoption into e-health systems and implementation by health care organizations. We have developed a tentative roadmap that addresses these needs by providing the following deliverables: (1) results and interpretation of an online survey to define patient-relevant endpoints, (2) agreement on the selection criteria for use of device combinations, (3) an example of an open-source platform for integrating mobile health technology output, and (4) recommendations for assessing readiness for deployment of promising devices and algorithms suitable for regulatory approval. This concrete implementation guidance, harmonizing the collaborative endeavor among stakeholders, can improve assessments of individuals with PD, tailor symptomatic therapy, and enhance health care outcomes. © 2019 International Parkinson and Movement Disorder Society.

Telemedicine in Neurological Disorders: Opportunities and Challenges.

Introduction: Telemedicine represents an emerging model for the assessment and management of various neurological disorders. Methods: We sought to discuss opportunities and challenges for the integration of telemedicine in the management of common and uncommon neurological disorders by reviewing and appraising studies that evaluate telemedicine as a means to facilitate the access to care, deliver highly specialized visits, diagnostic consultations, rehabilitation, and remote monitoring of neurological disorders. Results: Opportunities for telemedicine in neurological disorders include the replacement of or complement to in-office evaluations, decreased time between follow-up visits, reduction in disparities in access to healthcare, and promotion of education and training through interactions between primary care physicians and tertiary referral centers. Critical challenges include the integration of the systems for data monitoring with an easy-to-use, secure, and cost-effective platform that is both widely adopted by patients and healthcare systems and embraced by international scientific societies. Conclusions: Multiple applications may spawn from a model based on digitalized healthcare services. Integrated efforts from multiple stakeholders will be required to develop an interoperable software platform capable of providing not only a holistic approach to care but also one that reduces disparities in the access to care.

Technology-based assessment of motor and nonmotor phenomena in Parkinson disease.

INTRODUCTION: The increasing development and availability of portable and wearable technologies is rapidly expanding the field of technology-based objective measures (TOMs) in neurological disorders, including Parkinson disease (PD). Substantial challenges remain in the recognition of disease phenomena relevant to patients and clinicians, as well as in the identification of the most appropriate devices to carry out these measurements. Areas covered: The authors systematically reviewed PubMed for studies employing technology as outcome measures in the assessment of PD-associated motor and nonmotor abnormalities. Expert commentary: TOMs minimize intra- and inter-rater variability in clinical assessments of motor and nonmotor phenomena in PD, improving the accuracy of clinical endpoints. Critical unmet needs for the integration of TOMs into clinical and research practice are the identification and validation of relevant endpoints for individual patients, the capture of motor and nonmotor activities from an ecologically valid environment, the integration of various sensor data into an open-access, common-language platforms, and the definition of a regulatory pathway for approval of TOMs. The current lack of multidomain, multisensor, smart technologies to measure in real time a wide scope of relevant changes remain a significant limitation for the integration of technology into the assessment of PD motor and nonmotor functional disability.

App-Based Bradykinesia Tasks for Clinic and Home Assessment in Parkinson's Disease: Reliability and Responsiveness.

BACKGROUND: Clinical rating of bradykinesia in Parkinson disease (PD) is challenging as it must combine several movement features into a single score. Additionally, in-clinic assessment cannot capture fluctuations throughout the day. OBJECTIVE: To evaluate the reliability and responsiveness of a motion sensor-based tablet app for objective bradykinesia assessment in clinic and at home as compared to clinical ratings. METHODS: Thirty-two PD patients treated with subthalamic deep brain stimulation (DBS) were outfitted with a motion sensor on the index finger of the more affected hand to perform two repetitions of finger-tapping, hand opening-closing, and arm pronation-supination tasks with DBS on and 10, 20, and 30 minutes after turning DBS off. Tasks were videotaped for blinded clinician rating using the Modified Bradykinesia Rating Scale (MBRS). Participants were then sent home with an app-based system to perform two repetitions of the same tasks six times per day spaced two hours apart, three days per week, for two weeks. Intraclass correlation (ICC) and minimal detectable change (MDC) were calculated. RESULTS: As the effects of DBS wore off, motion sensors detected worsening of amplitude sooner than did clinician-rated MBRS for all three tasks. ICCs were significantly higher and MDCs were significantly lower for motion sensors in the clinic and at home than for clinician ratings (p < 0.01). CONCLUSIONS: The tablet-based app demonstrated higher reliability and responsiveness in capturing bradykinesia-related tasks in the clinic and at home than did clinician ratings. This tool may enhance the assessment of novel therapies.

Placebo effect of medication cost in Parkinson disease: a randomized double-blind study.

OBJECTIVE: To examine the effect of cost, a traditionally "inactive" trait of intervention, as contributor to the response to therapeutic interventions. METHODS: We conducted a prospective double-blind study in 12 patients with moderate to severe Parkinson disease and motor fluctuations (mean age 62.4 ± 7.9 years; mean disease duration 11 ± 6 years) who were randomized to a "cheap" or "expensive" subcutaneous "novel injectable dopamine agonist" placebo (normal saline). Patients were crossed over to the alternate arm approximately 4 hours later. Blinded motor assessments in the "practically defined off" state, before and after each intervention, included the Unified Parkinson's Disease Rating Scale motor subscale, the Purdue Pegboard Test, and a tapping task. Measurements of brain activity were performed using a feedback-based visual-motor associative learning functional MRI task. Order effect was examined using stratified analysis. RESULTS: Although both placebos improved motor function, benefit was greater when patients were randomized first to expensive placebo, with a magnitude halfway between that of cheap placebo and levodopa. Brain activation was greater upon first-given cheap but not upon first-given expensive placebo or by levodopa. Regardless of order of administration, only cheap placebo increased activation in the left lateral sensorimotor cortex and other regions. CONCLUSION: Expensive placebo significantly improved motor function and decreased brain activation in a direction and magnitude comparable to, albeit less than, levodopa. Perceptions of cost are capable of altering the placebo response in clinical studies. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that perception of cost is capable of influencing motor function and brain activation in Parkinson disease.

Feasibility of home-based automated Parkinson's disease motor assessment.

Patients with Parkinson's disease (PD) receive therapies aimed at addressing a diverse range of motor symptoms. Motor complications in the form of symptom fluctuations and dyskinesias that commonly occur with chronic PD medication use may not be effectively captured by Unified Parkinson's Disease Rating Scale (UPDRS) assessments performed in the clinic. Therefore, home monitoring may be a viable adjunct tool to provide insight into PD motor symptom response to treatment. In this pilot study, we sought to evaluate the feasibility of capturing PD motor symptoms at home using a computer-based assessment system. Ten subjects diagnosed with idiopathic PD used the system at home and ten non-PD control subjects used the system in a laboratory. The Kinesia system consists of a wireless finger-worn motion sensor and a laptop computer with software for automated tremor and bradykinesia severity score assessments. Data from control subjects were used to develop compliance algorithms for rejecting motor tasks performed incorrectly. These algorithms were then applied to data collected from the PD subjects who used the Kinesia system at home to complete motor exams 3-6 times per day over 3-6 days. Motor tasks not rejected by the compliance algorithms were further processed for symptom severity. PD subjects successfully completed motor assessments at home, with approximately 97% of all motor task data files (1222/1260) accepted. These findings suggest that objective home monitoring of PD motor fluctuations is feasible.

Early versus delayed bilateral subthalamic deep brain stimulation for parkinson's disease: a decision analysis.

The long-term benefits of subthalamic nucleus deep brain stimulation (STN DBS) applied earlier in the disease course, before significant disability accumulates, remain to be determined. We developed a Markov state transition decision analytic model to compare effectiveness in quality-adjusted life years (QALYs) of STN DBS applied to patients with PD at an "early" ("off time" 10-20%) versus "delayed" stage ("off time" >40%). A lifelong time horizon and societal perspective were assumed. Probabilities and rates were obtained from literature review; utilities were derived using the time trade-off technique and a computer-assisted utility assessment software tool applied to a cohort of 22 STN-DBS and 21 non-STN-DBS PD patients. Uncertainty was assessed through one- and two-way sensitivity analyses and probabilistic sensitivity analysis using second-order Monte Carlo simulations. Early STN DBS was preferred with a quality-adjusted life expectancy of 22.3 QALYs, a gain of 2.5 QALYs over those with delayed surgery (19.8 QALYs). Early STN DBS was preferred in 69% of 5,000 Monte Carlo simulations. Early surgery was robustly favored through most sensitivity analyses. Delayed STN DBS afforded greater QALYs when using utility estimates exclusively from non-STN-DBS patients and, for the entire group, if the rate of motor progression were to exceed 25% per year. Although decision modeling requires assumptions and simplifications, our exploratory analysis suggests that STN DBS performed in early PD may convey greater quality-adjusted life expectancy when compared to a delayed procedure. These findings support further evaluation of early STN DBS in a controlled clinical trial.