Technology in Parkinson's disease:challenges and opportunities

The miniaturization, sophistication, proliferation, and accessibility of technologies are enabling the capture of more and previously inaccessible phenomena in Parkinson's disease (PD). However, more information has not translated into a greater understanding of disease complexity to satisfy diagnostic and therapeutic needs. Challenges include noncompatible technology platforms, the need for wide-scale and long-term deployment of sensor technology (among vulnerable elderly patients in particular), and the gap between the "big data" acquired with sensitive measurement technologies and their limited clinical application. Major opportunities could be realized if new technologies are developed as part of open-source and/or open-hardware platforms that enable multichannel data capture sensitive to the broad range of motor and nonmotor problems that characterize PD and are adaptable into self-adjusting, individualized treatment delivery systems. The International Parkinson and Movement Disorders Society Task Force on Technology is entrusted to convene engineers, clinicians, researchers, and patients to promote the development of integrated measurement and closed-loop therapeutic systems with high patient adherence that also serve to (1) encourage the adoption of clinico-pathophysiologic phenotyping and early detection of critical disease milestones, (2) enhance the tailoring of symptomatic therapy, (3) improve subgroup targeting of patients for future testing of disease-modifying treatments, and (4) identify objective biomarkers to improve the longitudinal tracking of impairments in clinical care and research. This article summarizes the work carried out by the task force toward identifying challenges and opportunities in the development of technologies with potential for improving the clinical management and the quality of life of individuals with PD. © 2016 International Parkinson and Movement Disorder Society

Treatment of Essential Tremor with Long-chain Alcohols: Still Experimental or Ready for Prime Time?

Aim:&nbsp;To review current literature on long‐chain alcohols and their derivatives as novel pharmacotherapy for the treatment of essential tremor (ET).&nbsp;Background:&nbsp;Currently available and recommended pharmacotherapies for ET are often limited by suboptimal treatment effects, frequent adverse effects, and drug interactions. While ethanol is reported to profoundly decrease tremor severity in the majority of patients with ET, preclinical experience suggests that long‐chain alcohols such as 1‐octanol might lead to a comparable tremor reduction without ethanol&rsquo;s typical side effects of sedation and intoxication. Here, we review the literature on the first clinical trials on 1‐octanol and its metabolite octanoic acid (OA) for the treatment of ET.Methods:&nbsp;The literature on preclinical and clinical trials on long‐chain alcohols as well as OA was reviewed and summarized, and an outlook given on next phases of development.Discussion:&nbsp;1‐octanol was demonstrated to be safe and effective in a double‐blind, placebo‐controlled low‐dose trial, and open‐label data showed excellent tolerability and dose‐dependent efficacy up to 128 mg/kg. Despite 1‐octanol&rsquo;s efficacy, its future viability as an effective therapy is limited by its pharmacological properties that require large volumes to be orally administered. Pharmacokinetic data indicate that OA is the active metabolite of 1‐octanol. Preclinical efficacy data for OA are positive, and human pilot data demonstrated excellent safety as well as efficacy in secondary outcome measures of tremor amplitudes. OA also has more favorable pharmacological properties for drug delivery; hence, OA may be worth developing as a pharmaceutical.</p

Impaired sense of agency in functional movement disorders: An fMRI study.

The sense of agency (SA) is an established framework that refers to our ability to exert and perceive control over our own actions. Having an intact SA provides the basis for the human perception of voluntariness, while impairments in SA are hypothesized to lead to the perception of movements being involuntary that may be seen many neurological or psychiatric disorders. Individuals with functional movement disorders (FMD) experience a lack of control over their movements, yet these movements appear voluntary by physiology. We used fMRI to explore whether alterations in SA in an FMD population could explain why these patients feel their movements are involuntary. We compared the FMD group to a control group that was previously collected using an ecologically valid, virtual-reality movement paradigm that could modulate SA. We found selective dysfunction of the SA neural network, whereby the dorsolateral prefrontal cortex and pre-supplementary motor area on the right did not respond differentially to the loss of movement control. These findings provide some of the strongest evidence to date for a physiological basis underlying these disabling disorders

Impaired sense of agency in functional movement disorders: An fMRI study.

The sense of agency (SA) is an established framework that refers to our ability to exert and perceive control over our own actions. Having an intact SA provides the basis for the human perception of voluntariness, while impairments in SA are hypothesized to lead to the perception of movements being involuntary that may be seen many neurological or psychiatric disorders. Individuals with functional movement disorders (FMD) experience a lack of control over their movements, yet these movements appear voluntary by physiology. We used fMRI to explore whether alterations in SA in an FMD population could explain why these patients feel their movements are involuntary. We compared the FMD group to a control group that was previously collected using an ecologically valid, virtual-reality movement paradigm that could modulate SA. We found selective dysfunction of the SA neural network, whereby the dorsolateral prefrontal cortex and pre-supplementary motor area on the right did not respond differentially to the loss of movement control. These findings provide some of the strongest evidence to date for a physiological basis underlying these disabling disorders

Dalfampridine in Parkinson's disease related gait dysfunction: A randomized double blind trial.

BackgroundDisease-related gait dysfunction causes extensive disability for persons with Parkinson's disease (PD), with no effective therapies currently available. The potassium channel blocker dalfampridine has been used in multiple neurological conditions and improves walking in persons with multiple sclerosis.ObjectivesWe aimed to evaluate the effect of dalfampridine extended release (D-ER) 10mg tablets twice daily on different domains of walking in participants with PD.MethodsTwenty-two participants with PD and gait dysfunction were randomized to receive D-ER 10mg twice daily or placebo for 4weeks in a crossover design with a 2-week washout period. The primary outcomes were change in the gait velocity and stride length.ResultsAt 4weeks, gait velocity was not significantly different between D-ER (0.89m/s±0.33) and placebo (0.93m/s±0.27) conditions. The stride length was also similar between conditions: 0.96m±0.38 for D-ER versus 1.06m±0.33 for placebo. D-ER was generally well tolerated with the most frequent side effects being dizziness, nausea and balance problems.ConclusionsD-ER is well tolerated in PD patients, however it did not show significant benefit for gait impairment

Dalfampridine in Parkinson's disease related gait dysfunction: A randomized double blind trial.

BackgroundDisease-related gait dysfunction causes extensive disability for persons with Parkinson's disease (PD), with no effective therapies currently available. The potassium channel blocker dalfampridine has been used in multiple neurological conditions and improves walking in persons with multiple sclerosis.ObjectivesWe aimed to evaluate the effect of dalfampridine extended release (D-ER) 10mg tablets twice daily on different domains of walking in participants with PD.MethodsTwenty-two participants with PD and gait dysfunction were randomized to receive D-ER 10mg twice daily or placebo for 4weeks in a crossover design with a 2-week washout period. The primary outcomes were change in the gait velocity and stride length.ResultsAt 4weeks, gait velocity was not significantly different between D-ER (0.89m/s±0.33) and placebo (0.93m/s±0.27) conditions. The stride length was also similar between conditions: 0.96m±0.38 for D-ER versus 1.06m±0.33 for placebo. D-ER was generally well tolerated with the most frequent side effects being dizziness, nausea and balance problems.ConclusionsD-ER is well tolerated in PD patients, however it did not show significant benefit for gait impairment

Group demographics.

<p>Summary of age and gender of the FMD and HV groups.</p

Behavioral data contrasting subjective SA with objective control among FMD subjects and controls.

<p>A) Box plots represent median subjective ratings (central line), upper/lower quartiles (box), min/max (whiskers), and outliers (points) for each group and control condition. B) Shows mean/standard error of group subjective ratings along with tendencies to over (positive) or underestimate (negative) control. Asterisks (*) represent significant differences (<i>p</i> < 0.05) between FMD and HV group responses.</p