Gait asymmetry and symptom laterality in Parkinson's disease: two of a kind?

BACKGROUND: The laterality of motor symptoms is considered a key feature of Parkinson's disease (PD). Here, we investigated whether gait and turning asymmetry coincided with symptom laterality as determined by the MDS-UPRDS part III and whether it was increased compared to healthy controls (HC). METHODS: We analyzed the asymmetry of gait and turning with and without a cognitive dual task (DT) using motion capture systems and wearable sensors in 97 PD patients mostly from Hoehn & Yahr stage II and III and 36 age-matched HC. We also assessed motor symptom asymmetry using the bilateral sub-items of the MDS-UPDRS-III. Finally, we examined the strength of the association between gait asymmetry and symptom laterality. RESULTS: Participants with PD had increased gait but not more turning asymmetry compared to HC (p < 0.05). Only 53.7% of patients had a shorter step length on the more affected body side as determined by the MDS-UPDRS-III. Also, 54% took more time and 29% more steps during turns toward the more affected side. The degree of asymmetry in the different domains did not correlate with each other and was not influenced by DT-load. CONCLUSIONS: We found a striking mismatch between the side and the degree of asymmetry in different motor domains, i.e., in gait, turning, and distal symptom severity in individuals with PD. We speculate that motor execution in different body parts relies on different neural control mechanisms. Our findings warrant further investigation to understand the complexity of gait asymmetry in PD.

Towards a better understanding of anticipatory postural adjustments in people with Parkinson's disease.

INTRODUCTION: Previous studies have shown that anticipatory postural adjustments (APAs) are altered in people with Parkinson's disease but its meaning for locomotion is less understood. This study aims to investigate the association between APAs and gait initiation, gait and freezing of gait and how a dynamic postural control challenging training may induce changes in these features. METHODS: Gait initiation was quantified using wearable sensors and subsequent straight walking was assessed via marker-based motion capture. Additionally, turning and FOG-related outcomes were measured with wearable sensors. Assessments were conducted one week before (Pre), one week after (Post) and 4 weeks after (Follow-up) completion of a training intervention (split-belt treadmill training or regular treadmill training), under single task and dual task (DT) conditions. Statistical analysis included a linear mixed model for training effects and correlation analysis between APAs and the other outcomes for Pre and Post-Pre delta. RESULTS: 52 participants with Parkinson's disease (22 freezers) were assessed. We found that APA size in the medio-lateral direction during DT was positively associated with gait speed (p<0.001) and stride length (p<0.001) under DT conditions at Pre. The training effect was largest for first step range of motion and was similar for both training modes. For the associations between changes after the training (pooled sample) medio-lateral APA size showed a significant positive correlation with first step range of motion (p = 0.033) only in the DT condition and for the non-freezers only. CONCLUSIONS: The findings of this work revealed new insights into how APAs were not associated with first step characteristics and freezing and only baseline APAs during DT were related with DT gait characteristics. Training-induced changes in the size of APAs were related to training benefits in the first step ROM only in non-freezers. Based on the presented results increasing APA size through interventions might not be the ideal target for overall improvement of locomotion.

Split-Belt Treadmill Training to Improve Gait Adaptation in Parkinson's Disease.

BACKGROUND: Gait deficits in people with Parkinson's disease (PD) are triggered by circumstances requiring gait adaptation. The effects of gait adaptation training on a split-belt treadmill (SBT) are unknown in PD. OBJECTIVE: We investigated the effects of repeated SBT versus tied-belt treadmill (TBT) training on retention and automaticity of gait adaptation and its transfer to over-ground walking and turning. METHODS: We recruited 52 individuals with PD, of whom 22 were freezers, in a multi-center randomized single-blind controlled study. Training consisted of 4 weeks of supervised treadmill training delivered three times per week. Tests were conducted pre- and post-training and at 4-weeks follow-up. Turning (primary outcome) and gait were assessed over-ground and during a gait adaptation protocol on the treadmill. All tasks were performed with and without a cognitive task. RESULTS: We found that SBT-training improved gait adaptation with moderate to large effects sizes (P < 0.02) compared to TBT, effects that were sustained at follow-up and during dual tasking. However, better gait adaptation did not transfer to over-ground turning speed. In both SBT- and TBT-arms, over-ground walking and Movement Disorder Society-Unified Parkinson's Disease Rating Scale III (MDS-UPDRS-III scores were improved, the latter of which reached clinically meaningful effects in the SBT-group only. No impact was found on freezing of gait. CONCLUSION: People with PD are able to learn and retain the ability to overcome asymmetric gait-speed perturbations on a treadmill remarkably well, but seem unable to generalize these skills to asymmetric gait off-treadmill. Future study is warranted into gait adaptation training to boost the transfer of complex walking skills. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Dual Task Turning in Place: A Reliable, Valid, and Responsive Outcome Measure of Freezing of Gait.

BACKGROUND: Freezing of gait (FOG) is a complex symptom in Parkinson's disease (PD) that is both elusive to elicit and varied in its presentation. These complexities present a challenge to measuring FOG in a sensitive and reliable way, precluding therapeutic advancement. OBJECTIVE: We investigated the reliability, validity, and responsiveness of manual video annotations of the turning-in-place task and compared it to the sensor-based FOG ratio. METHODS: Forty-five optimally medicated people with PD and FOG performed rapid alternating 360° turns without and with an auditory stroop dual task, thrice over two consecutive days. The tasks were video recorded, and inertial sensors were placed on the lower back and shins. Interrater reliability between three raters, criterion validity with self-reported FOG, and responsiveness to single-session split-belt treadmill (SBT) training were investigated and contrasted with the sensor-based FOG ratio. RESULTS: Visual ratings showed excellent agreement between raters for the percentage time frozen (%TF) (ICC [intra-class correlation coefficient] = 0.99), the median duration of a FOG episode (ICC = 0.90), and the number of FOG episodes (ICC = 0.86). Dual tasking improved the sensitivity and validity of visual FOG ratings resulting in increased FOG detection, criterion validity with self-reported FOG ratings, and responsiveness to a short SBT intervention. The sensor-based FOG ratio, on the contrary, showed complex FOG presentation-contingent relationships with visual and self-reported FOG ratings and limited responsiveness to SBT training. CONCLUSIONS: Manual video annotations of FOG during dual task turning in place generate reliable, valid, and sensitive outcomes for investigating therapeutic effects on FOG. © 2021 International Parkinson and Movement Disorder Society.

How many gait initiation trials are necessary to reliably detect anticipatory postural adjustments and first step characteristics in healthy elderly and people with Parkinson's disease?

BACKGROUND: The gait initiation (GI) process can be characterized by anticipatory postural adjustments (APAs) and first step characteristics. However, even within a constrained environment, it is unclear how many trials are necessary to obtain a reliable measurement of the GI process within one assessment. RESEARCH QUESTION: How many gait initiation trials are necessary to reliably detect APAs and first step characteristics in healthy elderly (HC) and people with Parkinson's disease with Freezing of Gait (PD + FOG) under single (ST) and dual task (DT) conditions and are there any potential systematic errors? METHODS: Thirty-eight PD + FOG (ON-medication) and 30 HC performed 5 trials of GI under ST and DT (auditory stroop test). APAs and first-step-outcomes were captured with IMUs placed on the lower back and on each foot. Intraclass correlation coefficients (ICCs) and the standard error of measurement (SEM) were computed to investigate reliability and mixed model analysis to find potential systematic errors. Additionally, we computed an estimation for the number of necessary trials to reach acceptable reliability (ICC = 0.75) for each outcome. RESULTS: ICCs varied from low reliability to excellent reliability across outcomes in PD + FOG and HC. ICCs were comparable under ST and DT for most outcomes. SEM results confirmed the ICC results. A systematic error was found for the first trial in first step ROM. Number of necessary trials varied largely across outcomes. SIGNIFICANCE: Within-session reliability varied across outcomes but was similar for PD + FOG and HC, and ST and DT. ML size of APA and first step ROM were most reliable, whereas APA duration and latency were least reliable. Depending on the outcome of interest, future studies should conduct multiple trials of GI to increase reliability.

Validation of the German Version of the New Freezing of Gait Questionnaire for People with Parkinson's Disease.

Freezing of gait (FOG) in Parkinson's disease (PD) is a highly disabling symptom which impacts quality of life. The New FOG Questionnaire (NFOG-Q) is the most commonly used tool worldwide to characterize FOG severity in PD. This study aims to provide a German translation of the NFOG-Q and to assess its validity in people with PD. The questionnaire was translated using forward-backward translation. Validity was tested in 57 PD patients with FOG via Cronbach's alpha for internal consistency and Spearman correlations with several clinical measures to quantify disease severity, mobility, fall risk, and cognitive state for convergent and divergent validity. The German version of the NFOG-Q shows good internal consistency (Cα = 0.84). Furthermore, the NFOG-Q score was significantly correlated with the MDS-UPDRS III, H&Y stage, Timed Up and Go test, and the subjective fear of falling (FES-I). The lack of correlation with cognition (MoCA) points towards good divergent validity. This study provides a German version of the NFOG-Q which proved to be valid for the assessment of FOG severity in individuals with PD.

Short-Term Effects of Single-Session Split-Belt Treadmill Training on Dual-Task Performance in Parkinson's Disease and Healthy Elderly.

Background: Dual-tasking is challenging for people with Parkinson's disease and freezing of gait (PD+FOG) and can exacerbate freezing episodes and falls. Split-belt treadmill training (SBT) is a novel tool to train complex gait and may improve dual-task (DT) walking and turning. Objective: To investigate the single-session effects of SBT on DT walking and DT turning performance in PD+FOG and older adults (OA), compared to regular treadmill training. Methods: Forty-five PD+FOG and 36 OA participated in a single training session (30 min). They were randomized into one of four training groups: (A) SB75-steady belt speed ratio 0.75:1; (B) SB50-steady belt speed ratio 0.5:1; (C) SBCR-changing belt speed ratios between 0.75:1 and 0.5:1; and (D) Tied-Belt (TBT). Over-ground straight-line gait and an alternating turning in place task combined with a cognitive dual-task (DT) (auditory Stroop) were assessed pre- and post-training, and the following day (retention). Constrained longitudinal data analysis was used to investigate the training effects for all participants and for PD+FOG alone. Results: DT gait speed improved at post-training for all groups (p < 0.001). However, SBT (SB50 and SBCR) led to larger post-training improvements compared to TBT, which were still visible at retention (SB50). For mean DT turning speed and Stroop response time while walking, only SBT groups showed significant improvements at post-training or retention. DT stride length, peak DT turning speed, and Stroop performance index while walking also showed larger gains in SBT compared to TBT. Results for PD+FOG alone showed similar effects although with smaller effect sizes. Conclusions: A single session of SBT in PD+FOG and OA showed larger short-term effects on DT walking and turning compared to TBT. Cognitive DT performance was also improved in SBT, likely due to reduced cortical control of gait. These results illustrate the potential for SBT to improve DT during complex gait and possibly reduce fall risk in clinical and healthy populations.

The Effect of One Session Split-Belt Treadmill Training on Gait Adaptation in People With Parkinson's Disease and Freezing of Gait.

BACKGROUND: Freezing of gait (FOG) in Parkinson's disease (PD) is associated with gait asymmetry and switching difficulty. A split-belt treadmill may potentially address those deficits. OBJECTIVE: To investigate the immediate and retention effects of one-session split-belt treadmill training (SBT) in contrast to regular tied-belt treadmill training (TBT) on gait asymmetry and adaptation in people with PD and FOG (PD + FOG) and healthy controls (HC). Additionally, to investigate differential effects of 3 SBT protocols and compare different gait adaptation outcomes. METHODS: PD + FOG (n = 45) and HC (n = 36) were randomized to 1 of 3 SBT groups (belt speeds' ratio 0.75:1; 0.5:1 or changing ratios) or TBT group. Participants were tested at Pre, Post, and Retention after one treadmill training session. Gait asymmetry was measured during a standardized adaptation test on the split-belt treadmill. RESULTS: SBT proved beneficial for gait adaptation in PD + FOG and HC (P < .0001); however, HC improved more. SBT with changing ratios demonstrated significant effects on gait adaptation from Pre to Post in PD + FOG, supported by strong effect sizes (d = 1.14) and improvements being retained for 24 hours. Mean step length asymmetry during initial exposure was lower in HC compared with PD + FOG (P = .035) and differentiated best between the groups. CONCLUSIONS: PD + FOG improved gait adaptation after a single SBT session although effects were smaller than in HC. SBT with changing ratios was the most effective to ameliorate gait adaptation in PD + FOG. These promising results warrant future study on whether long-term SBT strengthens adaptation in PD + FOG and has potential to induce a better resilience to FOG. Clinical trial ID: NCT03725215.

Split-belt treadmill walking in patients with Parkinson's disease: A systematic review.

BACKGROUND: Walking on a split-belt treadmill (SBT) can help to modulate an asymmetric gait, particularly for people with neurological conditions, such as Parkinson's disease (PD), where asymmetry plays a role due to the laterality of the disease. RESEARCH QUESTION: This systematic review critically evaluates the literature on SBT in PD. First, different SBT paradigms and methodological approaches were evaluated. Second, the review explored how people with PD adapt their gait to different SBT conditions compared to healthy controls (HC). METHODS: We conducted a systematic search of the PubMED, PsychINFO, and Web of Knowledge databases. Original research articles, published in English and investigating SBT walking in people with PD, were included. RESULTS: From the 925 studies originally identified, seven met the inclusion criteria and were selected for evaluation (n = 118 individuals with PD of whom 44 had freezing of gait (FOG)). The SBT paradigms varied across studies regarding the SBT settings, definitions of gait variables, and criteria for determining dominance of body side. Gait variability and bilateral coordination were found to adapt to the SBT condition similarly in people with PD and healthy controls (HC). Inconsistent results were found with respect to the adaptation of gait asymmetry, for the differences between PD and HC participants. The subgroup of people with PD and FOG showed reduced accuracy in detecting belt speed differences and slower adaptation to SBT conditions. CONCLUSION: Individuals with mild to moderately severe PD adapted similarly to HCs to SBT walking for gait variability and bilateral gait coordination. However, those with FOG had impaired perception of belt speed differences and did not adapt their gait so readily. Although SBT can be useful for modulating gait asymmetry in some people with PD, it was not beneficial for all. We recommend standardization of SBT protocols for clinical practice in future studies.

Moderate Frequency Resistance and Balance Training Do Not Improve Freezing of Gait in Parkinson's Disease: A Pilot Study.

Background and Aim: Individuals with Parkinson's disease (PD) and Freezing of Gait (FOG) have impaired postural control, which relate to the severity of FOG. The aim of this study was to analyze whether a moderate frequency resistance (RT) and balance training (BT), respectively, are effective to diminish FOG. Methods: This post-hoc sub-analysis of a randomized controlled training intervention study of PD patients with and without FOG reports about results from FOG patients. Twelve FOG patients performed RT and 8 BT (training 2x/week, 7 weeks). Testing was performed prior and post intervention. FOG was assessed with the FOG Questionnaire (FOGQ) and with the FOG score of a FOG provoking walking course. Balance performance was evaluated with the Fullerton Advanced Balance (FAB) scale. Tests were conducted by raters blinded to group allocation and assessment time point (only FOG score and FAB scale). Results: For the FOGQ and FOG score, no significant differences were found within and between the two training groups (p > 0.05) and effect sizes for the improvements were small (r < 0.1). Groups did not significantly improve in the FAB scale. FOG score changes and FAB scale changes within the RT group showed a trend toward significant negative correlation (Rho = -0.553, p = 0.098). Conclusions: Moderate frequency RT and BT was not effective in reducing FOG in this pilot study. The trend toward negative correlation between changes in FOG score and FAB scale suggests an interaction between balance (improvement) and FOG (improvement). Future studies should include larger samples and high frequency interventions to investigate the role of training balance performance to reduce the severity of FOG.