Pharmacotherapy in the management of early Parkinson’s disease: cost-effectiveness and patient acceptability

In the absence of a cure, the primary goals in managing Parkinson’s disease (PD) are to preserve functionality and health-related quality of life (HRQoL). Current therapeutic strategies for PD include symptomatic treatment and are primarily focused on replacing dopamine in the brain. Dopamine agonists can be used as an alternative initial levodopa therapy, to delay the onset of motor complications, but at the expense of more dopaminergic adverse effects; poorer control of motor symptoms; and increased cost. In PD, treatment effects and costs accumulate over time; hence the choice of time horizon in cost-effectiveness analysis can be particularly important. Pharmaceutical expenditures have grown rapidly in recent decades and now total nearly 10% of all health care costs. The main approach to treat PD at the present time is to advance knowledge of the efficacy, to reduce long-term complications associated with treatment, and to improve patient HRQoL and society burden. The implementation of cost-effectiveness studies, including the societal perspective, should be considered as an outcome of new therapy strategies, which would be helpful to health care decision makers

Review of Prevalence Studies of Tic Disorders: Methodological Caveats

Introduction: Tic disorders are neurodevelopmental disorders of childhood associated with psychiatric comorbidity and academic problems. Estimating the prevalence and understanding the epidemiology of tic disorders is more complex than was once thought. Until fairly recently, tic disorders were thought to be rare, but today tics are believed to be the most common movement disorder, with 0.2-46.3% of schoolchildren experiencing tics during their lifetime. Tentative explanations for differing prevalence estimates include the multidimensional nature of tics with a varied and heterogeneous presentation, and the use of different epidemiological methods and study designs. Methods: Literature review and analysis of methodological issues pertinent to epidemiological studies of tic disorders. Results: Epidemiological studies of tic disorders were reviewed, and the main elements of epidemiological studies, including sample selection, case ascertainment strategy, definition of tic disorders, and the degree of coverage of the eligible population (i.e., the response rate) were examined. Discussion: In order to improve the quality of epidemiological studies of tic disorders, a number of recommendations were made, including but not limited to a review of the diagnostic criteria for tic disorders, and inclusion of new tic disorder categories for those with tics of secondary etiology

Telemedicine in the Management of Parkinson’s Disease: Achievements, Challenges, and Future Perspectives

As the global population grows, there is an increasing demand for neurologic consultation that prompts new ways to reach more patients. Telemedicine can provide an accessible, cost-effective, and high-quality healthcare services. In this article, we highlight recent developments, achievements, and challenges regarding outcomes, clinical care, tele-education, teletreatment, teleresearch, and cybersecurity for telemedicine applied to Parkinson´s disease (PD) and other neurological conditions

Is Restless Legs Syndrome Associated with an Increased Risk of Mortality? A Meta-Analysis of Cohort Studies

Background: Restless legs syndrome (RLS) is a common sleep disorder,. although controversial, growing evidence relates the presence of RLS to an increased risk of mortality, mainly due to cardiovascular events. The aim of this article was to review the role of RLS as a risk factor of mortality according to independent cohort studies. Methods: We performed a literature review via PubMed database for articles relating RLS and mortality. We used the random-effects model to calculate the pooled effect estimates on mortality. Heterogeneity between studies was assessed using quantitative and qualitative analysis. Results: Out of 100 articles identified, 13 were finally included. Although studies were heterogeneous (p = 0.001), no significant publication bias was found. When all cohort studies were considered, the random-effects model yielded a significantly increased risk of mortality in RLS versus non-RLS patients (13 studies, hazard ratio [HR] = 1.52, 95% confidence interval [CI] 1.28–1.80). However, this association was not statistically significant when only cohort studies using the international RLS diagnostic criteria were considered (5 studies, HR = 1.63, 95% CI 0.94–2.81). Discussion: The results of this meta-analysis suggest that RLS seems to be a risk factor of mortality, although this association is conditioned by the diagnostic criteria used in the studies. Future long-term follow-up standardized mortality studies are needed to address this important question that carries potential impact on population global health

Tremor Control Devices for Essential Tremor: A Systematic Literature Review

Background: There is a growing interest in nonpharmacological approaches for essential tremor (ET), including tremor cancelation devices. However, the true efficacy of such devices in ET remains unclear. Methods: A systematic literature review was conducted using standardized criteria regarding efficacy and comfortability. Devices focused on design or experimental testing in which tremor was simulated in a robot were excluded. Results: Out of 324 articles initially identified, 12 articles were included. Orthoses using biomechanical loading and neuromodulation with electrical stimulation, and external tremor cancelation devices, were the main interventions used to suppress tremor. All devices were designed to control tremor of the upper limbs at different anatomical locations. Overall, an average tremor attenuation of 50–98% was reported (level of evidence III). Interference with voluntary movements and portability was described as the main drawback. Discussion: In conclusion, this review highlights the growing interest in emerging tremor control devices and the importance of assessing comfort without affecting voluntary movements. However, the level of evidence regarding the efficacy of these tremor control devices remains low. An integrated multidisciplinary combination approach of engineering, robotics, physiology, physiotherapy, and clinical assessment is needed to improve the quality of non-pharmacological interventions for ET

Can plasma α-Synuclein help us to differentiate parkinson’s disease from essential tremor?

Background: Studies have revealed controversial results regarding the diagnostic accuracy of plasma α-synuclein levels in patients with Parkinson’s disease (PD). This study was aimed to analyze the diagnostic accuracy of plasma α-synuclein in PD versus healthy controls and patients with essential tremor (ET). Methods: In this cross-sectional study, we included de novo (n = 19) and advanced PD patients [OFF (n = 33), and On (n = 35) states], patients with ET (n = 19), and controls (n = 35). The total plasma α-synuclein levels were determined using an ELISA sandwich method. We performed adjusted multivariate regression analysis to estimate the association of α-synuclein levels with group conditions [controls, ET, and de novo, OFF and ON-PD]. We studied the diagnostic accuracy of plasma α-synuclein using the area under the curve (AUC). Results: The plasma α-synuclein levels were higher in controls compared to PD and ET (p < 0.0001), discriminating de novo PD from controls (AUC = 0.74, 95% CI 0.60–0.89), with a trend towards in advanced PD (OFF state) from ET (AUC = 0.69, 95% CI 0.53–0.84). Conclusions: This is the first study examining and comparing plasma α-synuclein levels in ET vs. PD and controls. Preliminary findings suggest that plasma α-synuclein levels might help to discriminate de novo and advanced PD from controls and ET.Junta de Castilla y León is acknowledged for funding through the Biomedicine open project call (Ref. BIO/BU06/14

Clinical manifestations of intermediate allele carriers in Huntington disease

OBJECTIVE: There is controversy about the clinical consequences of intermediate alleles (IAs) in Huntington disease (HD). The main objective of this study was to establish the clinical manifestations of IA carriers for a prospective, international, European HD registry. METHODS: We assessed a cohort of participants at risk with &lt;36 CAG repeats of the huntingtin (HTT) gene. Outcome measures were the Unified Huntington\u27s Disease Rating Scale (UHDRS) motor, cognitive, and behavior domains, Total Functional Capacity (TFC), and quality of life (Short Form-36 [SF-36]). This cohort was subdivided into IA carriers (27-35 CAG) and controls (&lt;27 CAG) and younger vs older participants. IA carriers and controls were compared for sociodemographic, environmental, and outcome measures. We used regression analysis to estimate the association of age and CAG repeats on the UHDRS scores. RESULTS: Of 12,190 participants, 657 (5.38%) with &lt;36 CAG repeats were identified: 76 IA carriers (11.56%) and 581 controls (88.44%). After correcting for multiple comparisons, at baseline, we found no significant differences between IA carriers and controls for total UHDRS motor, SF-36, behavioral, cognitive, or TFC scores. However, older participants with IAs had higher chorea scores compared to controls (p = 0.001). Linear regression analysis showed that aging was the most contributing factor to increased UHDRS motor scores (p = 0.002). On the other hand, 1-year follow-up data analysis showed IA carriers had greater cognitive decline compared to controls (p = 0.002). CONCLUSIONS: Although aging worsened the UHDRS scores independently of the genetic status, IAs might confer a late-onset abnormal motor and cognitive phenotype. These results might have important implications for genetic counseling. CLINICALTRIALSGOV IDENTIFIER: NCT01590589

Parkinson Symptoms and Health Related Quality of Life as Predictors of Costs: A Longitudinal Observational Study with Linear Mixed Model Analysis

OBJECTIVE: To estimate the magnitude in which Parkinson's disease (PD) symptoms and health- related quality of life (HRQoL) determined PD costs over a 4-year period. MATERIALS AND METHODS: Data collected during 3-month, each year, for 4 years, from the ELEP study, included sociodemographic, clinical and use of resources information. Costs were calculated yearly, as mean 3-month costs/patient and updated to Spanish €, 2012. Mixed linear models were performed to analyze total, direct and indirect costs based on symptoms and HRQoL. RESULTS: One-hundred and seventy four patients were included. Mean (SD) age: 63 (11) years, mean (SD) disease duration: 8 (6) years. Ninety-three percent were HY I, II or III (mild or moderate disease). Forty-nine percent remained in the same stage during the study period. Clinical evaluation and HRQoL scales showed relatively slight changes over time, demonstrating a stable group overall. Mean (SD) PD total costs augmented 92.5%, from € 2,082.17 (€ 2,889.86) in year 1 to € 4,008.6 (€ 7,757.35) in year 4. Total, direct and indirect cost incremented 45.96%, 35.63%, and 69.69% for mild disease, respectively, whereas increased 166.52% for total, 55.68% for direct and 347.85% for indirect cost in patients with moderate PD. For severe patients, cost remained almost the same throughout the study. For each additional point in the SCOPA-Motor scale total costs increased € 75.72 (p = 0.0174); for each additional point on SCOPA-Motor and the SCOPA-COG, direct costs incremented € 49.21 (p = 0.0094) and € 44.81 (p = 0.0404), respectively; and for each extra point on the pain scale, indirect costs increased € 16.31 (p = 0.0228). CONCLUSIONS: PD is an expensive disease in Spain. Disease progression and severity as well as motor and cognitive dysfunctions are major drivers of costs increments. Therapeutic measures aimed at controlling progression and symptoms could help contain disease expenses.Abbvie Pharmaceuticals has solely funded the publication of this study; however, the funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

Functionality and Quality of Life with Parkinson’s Disease after Use of a Dynamic Upper Limb Orthosis: A Pilot Study

Parkinson’s disease (PD) is a chronic, neurodegenerative movement disorder, whose symptoms have a negative impact on quality of life and functionality. Although its main treatment is pharmacological, non-pharmacological aids such as the dynamic elastomeric fabric orthosis (DEFO) merit an evaluation. Our objective is to assess the DEFO in upper limb (UL) functional mobility and in the quality of life of PD patients. A total of 40 patients with PD participated in a randomized controlled crossover study, and were assigned to a control group (CG) and to an experimental group (EG). Both groups used the DEFO for two months, the experimental group the first two months of the study and the control group the last two. Motor variables were measured in the ON and OFF states at the baseline assessment and at two months. Differences from the baseline assessment were observed in some motor items of the Kinesia assessment, such as rest tremor, amplitude, rhythm or alternating movements in the ON and OFF states with and without orthosis. No differences were found in the unified Parkinson’s disease rating scale (UPDRS) or the PD quality-of-life questionnaire. The DEFO improves some motor aspects of the UL in PD patients but this does not translate to the amelioration of the standard of functional and quality-of-life scales