A Double-Blind, Randomized, Placebo-Controlled Trial of Ursodeoxycholic Acid (UDCA) in Parkinson's Disease.

BACKGROUND: Rescue of mitochondrial function is a promising neuroprotective strategy for Parkinson's disease (PD). Ursodeoxycholic acid (UDCA) has shown considerable promise as a mitochondrial rescue agent across a range of preclinical in vitro and in vivo models of PD. OBJECTIVES: To investigate the safety and tolerability of high-dose UDCA in PD and determine midbrain target engagement. METHODS: The UP (UDCA in PD) study was a phase II, randomized, double-blind, placebo-controlled trial of UDCA (30 mg/kg daily, 2:1 randomization UDCA vs. placebo) in 30 participants with PD for 48 weeks. The primary outcome was safety and tolerability. Secondary outcomes included 31-phosphorus magnetic resonance spectroscopy (31 P-MRS) to explore target engagement of UDCA in PD midbrain and assessment of motor progression, applying both the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) and objective, motion sensor-based quantification of gait impairment. RESULTS: UDCA was safe and well tolerated, and only mild transient gastrointestinal adverse events were more frequent in the UDCA treatment group. Midbrain 31 P-MRS demonstrated an increase in both Gibbs free energy and inorganic phosphate levels in the UDCA treatment group compared to placebo, reflecting improved ATP hydrolysis. Sensor-based gait analysis indicated a possible improvement of cadence (steps per minute) and other gait parameters in the UDCA group compared to placebo. In contrast, subjective assessment applying the MDS-UPDRS-III failed to detect a difference between treatment groups. CONCLUSIONS: High-dose UDCA is safe and well tolerated in early PD. Larger trials are needed to further evaluate the disease-modifying effect of UDCA in PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

A Single-Sensor Approach to Quantify Gait in Patients with Hereditary Spastic Paraplegia.

Hereditary spastic paraplegia (HSP) is characterised by progressive lower-limb spasticity and weakness resulting in ambulation difficulties. During clinical practice, walking is observed and/or assessed by timed 10-metre walk tests; time, feasibility, and methodological reliability are barriers to detailed characterisation of patients' walking abilities when instrumenting this test. Wearable sensors have the potential to overcome such drawbacks once a validated approach is available for patients with HSP. Therefore, while limiting patients' and assessors' burdens, this study aims to validate the adoption of a single lower-back wearable inertial sensor approach for step detection in HSP patients; this is the first essential algorithmic step in quantifying most gait temporal metrics. After filtering the 3D acceleration signal based on its smoothness and enhancing the step-related peaks, initial contacts (ICs) were identified as positive zero-crossings of the processed signal. The proposed approach was validated on thirteen individuals with HSP while they performed three 10-metre tests and wore pressure insoles used as a gold standard. Overall, the single-sensor approach detected 794 ICs (87% correctly identified) with high accuracy (median absolute errors (mae): 0.05 s) and excellent reliability (ICC = 1.00). Although about 12% of the ICs were missed and the use of walking aids introduced extra ICs, a minor impact was observed on the step time quantifications (mae 0.03 s (5.1%), ICC = 0.89); the use of walking aids caused no significant differences in the average step time quantifications. Therefore, the proposed single-sensor approach provides a reliable methodology for step identification in HSP, augmenting the gait information that can be accurately and objectively extracted from patients with HSP during their clinical assessment.

Runners' responses to a biofeedback intervention aimed to reduce tibial acceleration differ within and between individuals.

An increment in peak tibial acceleration (PTA) may be related to an increased risk of running-rated injury. Many authors believe that reducing PTA through improved shock-absorption could, therefore, help prevent injury. The aim of the current study was, therefore, to investigate the individual responses of participants to a biofeedback intervention aimed at reducing PTA.11 participants (two females, nine males; 43 ±â€¯10 years; stature: 1.74 ±â€¯0.07 m; body mass: 74 ±â€¯11 kg; distance running a week: 19 ±â€¯14 km; 5 km time: 24 ±â€¯3 min) received an intervention of six sessions of multisensory biofeedback aimed at reducing PTA. Mean PTA and kinematic patterns were measured at baseline, directly after the feedback intervention and a month after the end of the intervention. Group as well as single-subject analyses were performed to quantify differences between the sessions. A significant decrease of 26 per cent (effect size: Hedges' g = 0.94) in mean PTA was found a month after the intervention. No significant changes or large effect sizes were found for any group differences in the kinematic variables. However, on an individual level, shock-absorbing solutions differed both within and between participants. The data suggest participants did not learn a specific solution to reduce PTA but rather learned the concept of reducing PTA. These results suggest future research in gait retraining should investigate individual learning responses and focus on the different strategies participants use both between and within sessions. For training purposes, participants should not focus on learning one running strategy, but they should explore several strategies.

The use of biofeedback for gait retraining: A mapping review.

BACKGROUND: Biofeedback seems to be a promising tool to improve gait outcomes for both healthy individuals and patient groups. However, due to differences in study designs and outcome measurements, it remains uncertain how different forms of feedback affect gait outcomes. Therefore, the aim of this study is to review primary biomechanical literature which has used biofeedback to alter gait-related outcomes in human participants. METHODS: Medline, Cinahl, Cochrane, SPORTDiscus and Pubmed were searched from inception to December 2017 using various keywords and the following MeSHterms: biofeedback, feedback, gait, walking and running. From the included studies, sixteen different study characteristics were extracted. FINDINGS: In this mapping review 173 studies were included. The most common feedback mode used was visual feedback (42%, n = 73) and the majority fed-back kinematic parameters (36%, n = 62). The design of the studies was poor: only 8% (n = 13) of the studies had both a control group and a retention test; 69% (n = 120) of the studies had neither. A retention test after 6 months was performed in 3% (n = 5) of the studies, feedback was faded in 9% (n = 15) and feedback was given in the field rather than the laboratory in 4% (n = 8) of the studies. INTERPRETATION: Further work on biofeedback and gait should focus on the direct comparison between different modes of feedback or feedback parameters, along with better designed and field based studies.

Biomechanical organization of gait initiation depends on the timing of affective processing.

Gait initiation (GI) from a quiet bipedal posture has been shown to be influenced by the emotional state of the actor. The literature suggests that the biomechanical organization of forward GI is facilitated when pleasant pictures are shown, as compared to unpleasant pictures. However, there are inconsistencies in the literature, which could be due to the neural dynamics of affective processing. This study aimed to test this hypothesis, using a paradigm whereby participants initiated a step as soon as they saw an affective picture (i.e., onset), or as soon as the picture disappeared from the screen (i.e., offset). Pictures were a priori categorized as pleasant or unpleasant, and could also vary in their arousing properties. We analyzed center-of-pressure and center-of-gravity dynamics as a function of emotional content. We found that gait was initiated faster with pleasant images at onset, and faster with unpleasant images at offset. Also, with offset GI the peak velocity of the COG was reduced, and subjects took smaller steps, with unpleasant images relative to pleasant images. The results are discussed in terms of current knowledge regarding temporal processing of emotions, and its effects on GI.