Effects and Mechanisms of Exercise on Brain-Derived Neurotrophic Factor (BDNF) Levels and Clinical Outcomes in People with Parkinson's Disease: A Systematic Review and Meta-Analysis.

INTRODUCTION: Exercise therapy may increase brain-derived neurotrophic factor (BDNF) levels and improve clinical outcomes in people living with Parkinson's disease (PD). This systematic review was performed to investigate the effect of exercise therapy on BDNF levels and clinical outcomes in human PD and to discuss mechanisms proposed by authors. METHOD: A search on the literature was performed on PubMed up to December 2023 using the following key words: Parkinson's disease AND exercise, exercise therapy, neurological rehabilitation AND brain-derived neurotrophic factor, brain-derived neurotrophic factor/blood, brain-derived neurotrophic factor/cerebrospinal fluid AND randomized clinical trial, intervention study. Only randomized clinical trials comparing an exercise intervention to treatment as usual, usual care (UC), sham intervention, or no intervention were included. RESULTS: A meta-analysis of BDNF outcomes with pooled data from five trials (N = 216 participants) resulted in a significant standardized mean difference (SMD) of 1.20 [95% CI 0.53 to 1.87; Z = 3.52, p = 0.0004, I2 = 77%], favoring exercise using motorized treadmill, Speedflex machine, rowing machine, and non-specified exercise. Significant improvements were found in Unified Parkinson's Disease Rating Scale (UPDRS), UPDRS-III, 6 Minute Walk Test (6MWT), and Berg Balance Scale (BBS). Methodological quality of trials was categorized as "good" in three trials, "fair" in one trial, and "poor" in one trial. CONCLUSION: Key results of this systematic review are that exercise therapy is effective in raising serum BDNF levels and seems effective in alleviating PD motor symptoms. Exercise therapy confers neuroplastic effects on Parkinson brain, mediated, in part, by BDNF.

(HIIT-The Track) High-Intensity Interval Training for People with Parkinson's Disease: Individual Response Patterns of (Non-)Motor Symptoms and Blood-Based Biomarkers-A Crossover Single-Case Experimental Design.

INTRODUCTION: Physical exercise is receiving increasing interest as an augmentative non-pharmacological intervention in Parkinson's disease (PD). This pilot study primarily aimed to quantify individual response patterns of motor symptoms to alternating exercise modalities, along with non-motor functioning and blood biomarkers of neuroplasticity and neurodegeneration. MATERIALS & METHODS: People with PD performed high-intensity interval training (HIIT) and continuous aerobic exercise (CAE) using a crossover single-case experimental design. A repeated assessment of outcome measures was conducted. The trajectories of outcome measures were visualized in time series plots and interpreted relative to the minimal clinically important difference (MCID) and smallest detectable change (SDC) or as a change in the positive or negative direction using trend lines. RESULTS: Data of three participants were analyzed and engaging in physical exercise seemed beneficial for reducing motor symptoms. Participant 1 demonstrated improvement in motor function, independent of exercise modality; while for participant 2, such a clinically relevant (positive) change in motor function was only observed in response to CAE. Participant 3 showed improved motor function after HIIT, but no comparison could be made with CAE because of drop-out. Heterogeneous responses on secondary outcome measures were found, not only between exercise modalities but also among participants. CONCLUSION: Though this study underpins the positive impact of physical exercise in the management of PD, large variability in individual response patterns to the interventions among participants makes it difficult to identify clear exercise-induced adaptations in functioning and blood biomarkers. Further research is needed to overcome methodological challenges in measuring individual response patterns.

Is Cardiorespiratory Fitness Independently Associated with Fatigue in Patients with Transient Ischemic Attack or Minor Stroke?

Fatigue is a common complaint and a disabling symptom among patients following transient ischemic attack (TIA) or minor stroke. In patients with stroke, decreased cardiorespiratory fitness (CRF) is believed to be related to increased severity of post-stroke fatigue (PSF). However, this association between PSF and CRF in patients with TIA or minor stroke has been less investigated, and currently there is no proven treatment for PSF. We aimed to determine the association between PSF and CRF in patients with TIA or minor stroke and to find out whether this association was distorted by confounders. A cross-sectional association study was conducted among a total of 119 patients with TIA or minor stroke. PSF was measured by the Fatigue Severity Scale (FSS) and CRF was quantified by maximal exercise capacity (V̇O2max). The FSS showed a significant association with V̇O2max (ß = -0.061, SE: 0.022; p = 0.007). This association was confounded by anxiety (ß = -0.044, SE: 0.020; p = 0.028) and depression (ß = -0.030, SE: 0.022; p = 0.177) as measured by the subscales of the Hospital Anxiety and Depression Scale (HADS). After controlling for HADS scores on depression and anxiety, the univariate relationship between V̇O2max and FSS was no longer significant. These results suggest that the association between PSF and CRF in patients with TIA or minor stroke is weak and significantly confounded by the factors of depression and anxiety.

An Overview of Wearable Haptic Technologies and Their Performance in Virtual Object Exploration.

We often interact with our environment through manual handling of objects and exploration of their properties. Object properties (OP), such as texture, stiffness, size, shape, temperature, weight, and orientation provide necessary information to successfully perform interactions. The human haptic perception system plays a key role in this. As virtual reality (VR) has been a growing field of interest with many applications, adding haptic feedback to virtual experiences is another step towards more realistic virtual interactions. However, integrating haptics in a realistic manner, requires complex technological solutions and actual user-testing in virtual environments (VEs) for verification. This review provides a comprehensive overview of recent wearable haptic devices (HDs) categorized by the OP exploration for which they have been verified in a VE. We found 13 studies which specifically addressed user-testing of wearable HDs in healthy subjects. We map and discuss the different technological solutions for different OP exploration which are useful for the design of future haptic object interactions in VR, and provide future recommendations.

Graded peak cycle ergometer test for cognitively impaired patients with Parkinson's disease: a pilot study.

BACKGROUND: Cognitive decline affects up to 50% of patients with Parkinson's disease (PD) in the course of the disease and may be amenable to exercise interventions. To accurately set adequate training intensities, standardized exercise testing is required but such testing takes considerable time and effort. The aim of this pilot study was to investigate the feasibility of a graded peak cycle ergometer exercise test in cognitively impaired patients with Parkinson's Disease (PD), and to define whether age-predicted maximal heart rate (HRmax) matched measured HRmax. METHODS: A convenience sample of seven patients with PD (Hoehn and Yahr: 2-4, and cognitive impairment (Montreal Cognitive Assessment (MoCA) ≤ 26) completed a graded peak cycle ergometer test to voluntary exhaustion. Borg Rating of Perceived Exertion was used to record the individual's perception of exertion. Pre-defined age-predicted HRmax (calculated as 208-(0.7 × age) was compared with the measured HRmax using Bland-Altman plot and a two-one-sided test. RESULTS: All PD patients completed the graded exercise test between 8-12 minutes, showing therefore 100% compliance to the test protocol. No adverse events occurred. Predicted HRmax and measured HRmax did not differ. CONCLUSION: We demonstrate feasibility of graded peak cycle ergometer testing in PD patients with cognitive impairment. The good correspondence of age-predicted HRmax equation with measured HRmax, in this small sample, may in the future provide clinicians with a tool to define training intensities in cognitively impaired PD, without cardiac disease. However, further research is needed to confirm these results.

Effect of an exercise intervention on global cognition after transient ischemic attack or minor stroke: the MoveIT randomized controlled trial.

BACKGROUND: Patients with a transient ischemic attack (TIA) or ischemic stroke are at increased risk of developing cognitive impairment in the subacute phase. At present, the effects of exercise on cognitive functioning following a TIA or stroke are not fully known. The purpose of this trial was to investigate the effect of exercise on global cognition. METHODS: The MoveIT trial is a single-centre, observer-blinded, randomized controlled trial involving a 1-year exercise intervention consisting of a 12-week group exercise program, combined with three counselling visits to the physiotherapists over a 9-month period. The control group received standard care. The primary outcome was global cognitive functioning, assessed at one year, using the Montreal Cognitive Assessment (MoCA). Secondary outcomes included cardiorespiratory fitness, the cardiovascular profile, and attainment of secondary prevention targets, anxiety, depression and fatigue at one and two years. RESULTS: The experimental group consisted of 60 patients, while the control group consisted of 59 patients. The mean age was 64.3 years and 41% were female. No between-group differences were found on global cognitive functioning (MD, 0.7 out of 30, 95% CI, - 0.2 to 1.6) or on secondary outcome measures at 12 months. The only significant between-group difference was found for fatigue, in favour of the experimental group at 12 months (MD, 0.6 out of 63, 95% CI, 0.1 to 1.1). CONCLUSIONS: No benefit of this exercise intervention was found regarding global cognition. Future studies need to focus on optimizing rehabilitation strategies for this vulnerable group of patients. TRIAL REGISTRATION: http://www.trialregister.nl . Unique identifier: NL3721 . Date first registration: 06-03-2013.

Self-monitoring of Physical Activity After Hospital Discharge in Patients Who Have Undergone Gastrointestinal or Lung Cancer Surgery: Mixed Methods Feasibility Study.

BACKGROUND: Self-monitoring of physical activity (PA) using an accelerometer is a promising intervention to stimulate PA after hospital discharge. OBJECTIVE: This study aimed to evaluate the feasibility of PA self-monitoring after discharge in patients who have undergone gastrointestinal or lung cancer surgery. METHODS: A mixed methods study was conducted in which 41 patients with cancer scheduled for lobectomy, esophageal resection, or hyperthermic intraperitoneal chemotherapy were included. Preoperatively, patients received an ankle-worn accelerometer and the corresponding mobile health app to familiarize themselves with its use. The use was continued for up to 6 weeks after surgery. Feasibility criteria related to the study procedures, the System Usability Scale, and user experiences were established. In addition, 6 patients were selected to participate in semistructured interviews. RESULTS: The percentage of patients willing to participate in the study (68/90, 76%) and the final participation rate (57/90, 63%) were considered good. The retention rate was acceptable (41/57, 72%), whereas the rate of missing accelerometer data was relatively high (31%). The mean System Usability Scale score was good (77.3). Interviewed patients mentioned that the accelerometer and app were easy to use, motivated them to be more physically active, and provided postdischarge support. The technical shortcomings and comfort of the ankle straps should be improved. CONCLUSIONS: Self-monitoring of PA after discharge appears to be feasible based on good system usability and predominantly positive user experiences in patients with cancer after lobectomy, esophageal resection, or hyperthermic intraperitoneal chemotherapy. Solving technical problems and improving the comfort of the ankle strap may reduce the number of dropouts and missing data in clinical use and follow-up studies.

Exercise-induced increase in blood-based brain-derived neurotrophic factor (BDNF) in people with multiple sclerosis: A systematic review and meta-analysis of exercise intervention trials.

BACKGROUND: Exercise training may affect the blood levels of brain-derived neurotrophic factor (BDNF), but meta-analyses have not yet been performed comparing pre- and post-intervention BDNF concentrations in patients with multiple sclerosis (PwMS). OBJECTIVE: To perform a meta-analysis to study the influence of exercise on BDNF levels and define components that modulate them across clinical trials of exercise training in adults living with multiple sclerosis (MS). METHOD: Five databases (PubMed, EMBASE, Cochrane Library, PEDro database, CINAHL) were searched up to June 2021. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we included 13 articles in the meta-analysis, including 271 subjects. To investigate sources of heterogeneity, subgroup analysis, meta-regression, and sensitivity analysis were conducted. We performed the meta-analysis to compare pre- and post-exercise peripheral levels of BDNF in PwMS. RESULTS: Post-exercise concentrations of serum BDNF were significantly higher than pre-intervention levels (Standardized Mean Difference (SMD): 0.33, 95% CI: [0.04; 0.61], p-value = 0.02). Meta-regression indicated that the quality of the included studies based on the PEDro assessment tool might be a source of heterogeneity, while no significant effect was found for chronological age and disease severity according to the expanded disability status scale. CONCLUSION: This systematic review and meta-analysis shows that physical activity increases peripheral levels of BDNF in PwMS. More research on the effect of different modes of exercise on BDNF levels in PwMS is warranted.

Comparing two identically protocolized, multicentre, randomized controlled trials on caregiver-mediated exercises poststroke: Any differences across countries?

BACKGROUND: The evidence for rehabilitation interventions poststroke lack sufficient robustness. However, variation in treatment effects across countries have been given little attention. OBJECTIVE: To compare two identically protocolized trials conducted in different western countries in order to identify factors that may have caused variation in secondary trial outcomes. METHODS: Comparative study based on individual patient data (N = 129) from two randomized controlled trials, conducted in hospitals and rehabilitation facilities in the Netherlands (N = 66) and Australia (N = 63). Patients with stroke and their caregivers were randomly allocated to an 8-week caregiver-mediated exercises intervention (N = 63; 31 Australian and 32 Dutch) or to a control group (N = 66; 32 Australian and 34 Dutch). Patient characteristics, compliance, usual care and process measures were compared across countries. We examined if study setting significantly moderated the trial outcomes: Hospital Anxiety and Depression Scale, Fatigue Severity Scale and General Self-Efficacy Scale, measured at 8- and 12 weeks follow-up. In addition, we explored if factors that were significantly different across countries caused variation in these trial outcomes. RESULTS: Most patients suffered an ischemic stroke, were in the subacute phase and participated with their partner. Dutch patients were younger (P = 0.005) and had a lower functional status (P = 0.001). Australian patients were recruited earlier poststroke (P<0.001), spent less time in exercise therapy (P<0.001) and had a shorter length of stay (P<0.001). The level of contamination was higher (P = 0.040) among Dutch controls. No effect modification was observed and trial outcomes did not change after controlling for cross-country differences. CONCLUSIONS: The present study highlighted important clinical differences across countries whilst using an identical study protocol. The observed differences could result in a different potential for recovery and variation in treatment effects across trials. We argue that we can proceed faster to evaluating interventions within international pragmatic trials.

Can telerehabilitation services combined with caregiver-mediated exercises improve early supported discharge services poststroke? A study protocol for a multicentre, observer-blinded, randomized controlled trial.

BACKGROUND: Recovery of walking ability is an important goal for patients poststroke, and a basic level of mobility is critical for an early discharge home. Caregiver-mediated exercises could be a resource-efficient strategy to augment exercise therapy and improve mobility in the first months poststroke. A combination of telerehabilitation and face-to-face support, blended care, may empower patient-caregiver dyads and smoothen the transition from professional support to self-management. The Armed4Stroke study aims to investigate the effects of a caregiver-mediated exercise program using a blended care approach in addition to usual care, on recovery of mobility in the first 6 months poststroke. METHODS: A multicentre, observer-blinded randomized clinical trial in which 74 patient-caregiver dyads will be enrolled in the first 3 months poststroke. Dyads are randomly allocated to a caregiver-mediated exercises intervention or to a control group. The primary endpoint is the self-reported mobility domain of the Stroke Impact Scale. Secondary endpoints include care transition preparedness and psychological functioning of dyads, length of inpatient stay, gait-related measures and extended ADL of patients, and caregiver burden. Outcomes are assessed at enrolment, end of treatment and 6 months follow-up. RESULTS: During 8 weeks, caregivers are trained to become an exercise coach using a blended care approach. Dyads will receive a tailor-made, progressive training program containing task-specific exercises focusing on gait, balance, physical activity and outdoor activities. Dyads are asked to perform the training program a minimum of 5 times a week for 30 min per session, supported by a web-based telerehabilitation system with instruction videos and a messaging environment to communicate with their physiotherapist. CONCLUSIONS: We hypothesize that the Armed4Stroke program will increase self-reported mobility and independence in ADL, facilitating an early discharge poststroke. In addition, we hypothesize that active involvement of caregivers and providing support using blended care, will improve the care transition when professional support tapers off. Therefore, the Armed4Stroke program may complement early supported discharge services. TRIAL REGISTRATION: Netherlands Trial Register, NL7422 . Registered 11 December 2018.

The effect of botulinum toxin-A on neural and non-neural components of wrist hyper-resistance in adults with stroke or cerebral palsy.

BACKGROUND: Botulinum toxin-A (BoNT) is widely used to manage focal upper limb spasticity and is effective in reducing resistance to passive movement, as measured with the modified Ashworth scale. Discrimination and quantification of the underlying neural and non-neural components of hyper-resistance may further improve understanding of the effect of BoNT. OBJECTIVE: To explore the effects of BoNT on neural (NC), non-neural elastic (EC), and viscous (VC) components of resistance to passive wrist extension in adults with stroke or cerebral palsy and the association between the effects on wrist hyper-resistance components and clinical spasticity, pain and motor function scales. DESIGN: Pre-experimental study with pre- and post-intervention measurements at 6 and 12 weeks. SETTING: An outpatient clinic of a hospital. PARTICIPANTS: Adults with chronic stroke or cerebral palsy indicated for BoNT treatment for hyper-resistance in the wrist (N = 18). INTERVENTIONS: BoNT injections in the wrist and/or finger flexor muscles. MAIN OUTCOME MEASURES: Wrist hyper-resistance components, using the NeuroFlexor, and clinical scales (modified Ashworth scale, Tardieu scale, passive wrist extension, pain, Fugl-Meyer motor assessment of the upper extremity, and action research arm test). RESULTS: NC was significantly reduced 6 and 12 weeks post-intervention (median -11.96 Newton, P < .001 and median -9.34 Newton, P = .001, respectively); non-neural EC and VC showed no change. NC reduction 6 weeks post-intervention correlated significantly with BoNT dose (Pearson correlation coefficient rp = -0.56). No significant correlations were found between change scores in wrist hyper-resistance components and clinical scales. CONCLUSIONS: BoNT affected the neural component of resistance to passive wrist extension, while leaving the non-neural elastic and viscous components unaffected. This instrumented approach to quantify the effects of BoNT in the wrist and finger flexor muscles on the components of wrist hyper-resistance may have an added value for BoNT treatment evaluation in clinical practice.

The Cortical Response Evoked by Robotic Wrist Perturbations Reflects Level of Proprioceptive Impairment After Stroke.

Background: Proprioception is important for regaining motor function in the paretic upper extremity after stroke. However, clinical assessments of proprioception are subjective and require verbal responses from the patient to applied proprioceptive stimuli. Cortical responses evoked by robotic wrist perturbations and measured by electroencephalography (EEG) may be an objective method to support current clinical assessments of proprioception. Objective: To establish whether evoked cortical responses reflect proprioceptive deficits as assessed by clinical scales and whether they predict upper extremity motor function at 26 weeks after stroke. Methods: Thirty-one patients with stroke were included. In week 1, 3, 5, 12, and 26 after stroke, the upper extremity sections of the Erasmus modified Nottingham Sensory Assessment (EmNSA-UE) and the Fugl-Meyer Motor Assessment (FM-UE) and the EEG responses (64 channels) to robotic wrist perturbations were measured. The extent to which proprioceptive input was conveyed to the affected hemisphere was estimated by the signal-to-noise ratio (SNR) of the evoked response. The relationships between SNR and EmNSA-UE as well as SNR and time after stroke were investigated using linear regression. Receiver-operating-characteristic curves were used to compare the predictive values of SNR and EmNSA-UE for predicting whether patients regained some selective motor control (FM-UE > 22) or whether they could only move their paretic upper extremity within basic limb synergies (FM-UE ≤ 22) at 26 weeks after stroke. Results: Patients (N = 7) with impaired proprioception (EmNSA-UE proprioception score < 8) had significantly smaller SNR than patients with unimpaired proprioception (N = 24) [EmNSA-UE proprioception score = 8, t(29) = 2.36, p = 0.03]. No significant effect of time after stroke on SNR was observed. Furthermore, there was no significant difference in the predictive value between EmNSA-UE and SNR for predicting motor function at 26 weeks after stroke. Conclusion: The SNR of the evoked cortical response does not significantly change as a function of time after stroke and differs between patients with clinically assessed impaired and unimpaired proprioception, suggesting that SNR reflects persistent damage to proprioceptive pathways. A similar predictive value with respect to EmNSA-UE suggests that SNR may be used as an objective predictor next to clinical sensory assessments for predicting motor function at 26 weeks after stroke.

Physical activity dimensions after stroke: patterns and relation with lower limb motor function.

BACKGROUND: Stroke survivors show deteriorated physical functioning and physical activity levels. Physical activity levels of stroke survivors are generally low. It is increasingly recognized that physical activity is a multidimensional construct that cannot be captured in a single outcome. In-depth insight into multidimensional physical activity patterns may guide the development and timing of targeted rehabilitation interventions. This longitudinal cohort study explored how multidimensional physical activity outcomes develop during recovery in the subacute phase after stroke and if changes in physical activity were correlated to recovery of lower limb motor function. METHODS: Patients were recruited during inpatient rehabilitation. At 3, 12, and 26 weeks post-onset, motor function was measured by the Fugl-Meyer Lower Extremity Assessment (FMA-LE). Physical activity was measured with the Activ8 accelerometer in multiple outcomes: counts per minute during walking (CPMwalking; a measure of Intensity), number of active bouts (Frequency), mean length of active bouts (Distribution) and % of waking time in upright positions (Duration). Generalized estimating equations (GEE) were used to study changes in physical activity over time and the relation with the change in lower limb motor recovery. RESULTS: Thirty-nine patients (age 56 ± 9, 77% male, 89% ischemic stroke) were included. GEE models showed a significant main effect of time for PA Intensity (+ 13%, p = 0.007) and Duration (+ 64%, p = 0.012) between 3 and 12 weeks. Motor function did not show a significant effect in all PA models across the 3 timepoints (p > 0.020). A significant interaction effect of time × motor function was observed (p < 0.001). CONCLUSIONS: Patterns of PA recovery depend on the PA dimensions: PA Intensity and Duration increased mostly between 3 and 12 weeks post-stroke, whereas Frequency and Distribution did not show substantial changes. Further, no strong associations with motor recovery and high inter-individual variability were documented, which underlies the need to consider factors specific to the disease, the individual patient and the context.

Quantifying neural and non-neural components of wrist hyper-resistance after stroke: Comparing two instrumented assessment methods.

Patients with poor upper limb motor recovery after stroke are likely to develop increased resistance to passive wrist extension, i.e., wrist hyper-resistance. Quantification of the underlying neural and non-neural elastic components is of clinical interest. This cross-sectional study compared two methods: a commercially available device (NeuroFlexor®) with an experimental EMG-based device (Wristalyzer) in 43 patients with chronic stroke. Spearman's rank correlation coefficients (r) between components, modified Ashworth scale (MAS) and range of passive wrist extension (PRoM) were calculated with 95% confidence intervals. Neural as well as elastic components assessed by both devices were associated (r = 0.61, 95%CI: 0.38-0.77 and r = 0.53, 95%CI: 0.28-0.72, respectively). The neural component assessed by the NeuroFlexor® associated significantly with the elastic components of NeuroFlexor® (r = 0.46, 95%CI: 0.18-0.67) and Wristalyzer (r = 0.36, 95%CI: 0.06-0.59). The neural component assessed by the Wristalyzer was not associated with the elastic components of both devices. Neural and elastic components of both devices associated similarly with the MAS (r = 0.58, 95%CI: 0.34-0.75 vs. 0.49, 95%CI: 0.22-0.69 and r = 0.51, 95%CI: 0.25-0.70 vs. 0.30, 95%CI: 0.00-0.55); elastic components associated with PRoM (r = -0.44, 95%CI: -0.65- -0.16 vs. -0.74, 95%CI: -0.85- -0.57 for NeuroFlexor® and Wristalyzer respectively). Results demonstrate that both methods perform similarly regarding the quantification of neural and elastic wrist hyper-resistance components and have an added value when compared to clinical assessment with the MAS alone. The added value of EMG in the discrimination between neural and non-neural components requires further investigation.

Symptom dimensions of anxiety in Parkinson's disease: Replication study in a neuropsychiatric patient population.

INTRODUCTION: Anxiety disorders occur in approximately one third of people with Parkinson's disease (PD), and have a major impact on patient and caregiver wellbeing. In order to better understand and diagnose anxiety in PD patients, we investigated the generalizability of the results of a previous factor analysis on anxiety symptoms to a sample of PD patients with neuropsychiatric symptoms. METHODS: In this cross-sectional study, anxiety symptoms were measured with the Beck Anxiety Inventory (BAI) in 123 PD patients who were referred for neuropsychiatric diagnostics and treatment. Subscales of anxiety were analyzed through principal component analysis of BAI items. The associations between BAI subscales and symptoms of motor and cognitive function and depression were assessed through regression analyses. RESULTS: Similar to the previous factor analysis, we found one psychological (affective) and four somatic subscales of anxiety in the BAI. The affective subscale was the principal component explaining 35.9% of the variance. The scores on the total BAI and the affective subscale were significantly associated with depressive symptoms. In a post-hoc analysis, the affective subscale had equal power as compared to the total BAI in predicting whether or not participants were diagnosed with an anxiety disorder after psychiatric evaluation. CONCLUSION: In this study, we replicated our previous findings of one affective and multiple somatic subscales of the BAI. The 7-item affective subscale of the BAI shows potential as a screening tool for non-episodic anxiety in PD. However, in clinical practice, we recommend evaluating anxiety symptoms in the context of other PD symptoms, including motor, autonomic, and other (neuro)psychiatric symptoms.

Smoothness metrics for reaching performance after stroke. Part 1: which one to choose?

BACKGROUND: Smoothness is commonly used for measuring movement quality of the upper paretic limb during reaching tasks after stroke. Many different smoothness metrics have been used in stroke research, but a 'valid' metric has not been identified. A systematic review and subsequent rigorous analysis of smoothness metrics used in stroke research, in terms of their mathematical definitions and response to simulated perturbations, is needed to conclude whether they are valid for measuring smoothness. Our objective was to provide a recommendation for metrics that reflect smoothness after stroke based on: (1) a systematic review of smoothness metrics for reaching used in stroke research, (2) the mathematical description of the metrics, and (3) the response of metrics to simulated changes associated with smoothness deficits in the reaching profile. METHODS: The systematic review was performed by screening electronic databases using combined keyword groups Stroke, Reaching and Smoothness. Subsequently, each metric identified was assessed with mathematical criteria regarding smoothness: (a) being dimensionless, (b) being reproducible, (c) being based on rate of change of position, and (d) not being a linear transform of other smoothness metrics. The resulting metrics were tested for their response to simulated changes in reaching using models of velocity profiles with varying reaching distances and durations, harmonic disturbances, noise, and sub-movements. Two reaching tasks were simulated; reach-to-point and reach-to-grasp. The metrics that responded as expected in all simulation analyses were considered to be valid. RESULTS: The systematic review identified 32 different smoothness metrics, 17 of which were excluded based on mathematical criteria, and 13 more as they did not respond as expected in all simulation analyses. Eventually, we found that, for reach-to-point and reach-to-grasp movements, only Spectral Arc Length (SPARC) was found to be a valid metric. CONCLUSIONS: Based on this systematic review and simulation analyses, we recommend the use of SPARC as a valid smoothness metric in both reach-to-point and reach-to-grasp tasks of the upper limb after stroke. However, further research is needed to understand the time course of smoothness measured with SPARC for the upper limb early post stroke, preferably in longitudinal studies.

Smoothness metric during reach-to-grasp after stroke: part 2. longitudinal association with motor impairment.

BACKGROUND: The cause of smoothness deficits as a proxy for quality of movement post stroke is currently unclear. Previous simulation analyses showed that spectral arc length (SPARC) is a valid metric for investigating smoothness during a multi-joint goal-directed reaching task. The goal of this observational study was to investigate how SPARC values change over time, and whether SPARC is longitudinally associated with the recovery from motor impairments reflected by the Fugl-Meyer motor assessment of the upper extremity (FM-UE) in the first 6 months after stroke. METHODS: Forty patients who suffered a first-ever unilateral ischemic stroke (22 males, aged 58.6 ± 12.5 years) with upper extremity paresis underwent kinematic and clinical measurements in weeks 1, 2, 3, 4, 5, 8, 12, and 26 post stroke. Clinical measures included amongst others FM-UE. SPARC was obtained by three-dimensional kinematic measurements using an electromagnetic motion tracking system during a reach-to-grasp movement. Kinematic assessments of 12 healthy, age-matched individuals served as reference. Longitudinal linear mixed model analyses were performed to determine SPARC change over time, compare smoothness in patients with reference values of healthy individuals, and establish the longitudinal association between SPARC and FM-UE scores. RESULTS: SPARC showed a significant positive longitudinal association with FM-UE (B: 31.73, 95%-CI: [27.27 36.20], P < 0.001), which encompassed significant within- and between-subject effects (B: 30.85, 95%-CI: [26.28 35.41], P < 0.001 and B: 50.59, 95%-CI: [29.97 71.21], P < 0.001, respectively). Until 5 weeks post stroke, progress of time contributed significantly to the increase in SPARC and FM-UE scores (P < 0.05), whereafter they levelled off. At group level, smoothness was lower in patients who suffered a stroke compared to healthy subjects at all time points (P < 0.05). CONCLUSIONS: The present findings show that, after stroke, recovery of smoothness in a multi-joint reaching task and recovery from motor impairments are longitudinally associated and follow a similar time course. This suggests that the reduction of smoothness deficits quantified by SPARC is a proper objective reflection of recovery from motor impairment, as reflected by FM-UE, probably driven by a common underlying process of spontaneous neurological recovery early post stroke.