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Background: A randomized trial suggested that reducing left-sided subthalamic stimulation amplitude could improve axial dysfunction., Objectives: To explore open-label tolerability and associations between trial outcomes and asymmetry data., Methods: We collected adverse events in trial participants treated with open-label lateralized settings for ≥3 months. We explored associations between trial outcomes, location of stimulation and motor asymmetry., Results: 14/17 participants tolerated unilateral amplitude reduction (left-sided = 10, right-sided = 4). Two hundred eighty-four left-sided and 1113 right-sided stimulated voxels were associated with faster gait velocity, 81 left-sided and 22 right-sided stimulated voxels were associated with slower gait velocity. Amplitude reduction contralateral to shorter step length was associated with 2.4-point reduction in axial MDS-UPDRS. Reduction contralateral to longer step length was associated with 10-point increase in MDS-UPDRS., Conclusions: Left-sided amplitude reduction is potentially more tolerable than right-sided amplitude reduction. Right-sided more than left-sided stimulation could be associated with faster gait velocity. Shortened step length might reflect contralateral overstimulation., (© 2024 The Author(s). Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Clinical Vignette: A 23-year-old woman with pantothenate kinase-associated neurodegeneration (PKAN) presented with medication-refractory generalized dystonia and an associated gait impairment., Clinical Dilemma: Bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) can be an effective treatment for dystonia. However, outcomes for PKAN DBS have been variable and there are no standardized criteria for patient selection., Clinical Solution: Bilateral GPi DBS implantation resulted in improvement in dystonia and gait. The benefit has persisted over one year after implantation., Gap in Knowledge: PKAN is a rare neurodegenerative disorder and evidence supporting the use of PKAN DBS has been largely limited to case reports and case series. Consequently, there is a paucity of long-term data, especially on gait-related outcomes., Expert Commentary: The clinical characteristics of dystonia that respond to DBS tend to respond in PKAN. Clinicians counselling patients about the effects of DBS for PKAN should thoughtfully discuss gait and postural instability as important aspects to consider, especially as the disease will progress post-DBS., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Background: Vibrotactile stimulation has been studied in its efficacy of reducing freezing of gait (FOG) in patients with Parkinson's disease (PD). However, the results are still controversial. We evaluated the efficacy of a newly developed vibrotactile foot device on freezing severity and gait measures in PD patients with FOG., Objective: To evaluate the efficacy of vibrotactile foot device on PD patients with FOG., Methods: Thirty-three PD patients with FOG were examined during their "off" medication state. The efficacy of the vibrotactile foot device was evaluated using a gait protocol comprising walking trials with vibrotactile stimulation "off" and "on." Walking trials were videotaped for the offline rating by two movement disorder specialists. The Opal inertial sensor unit (128 Hz; Mobility Lab; APDM Inc., Portland, OR, USA) was used for quantitative gait analysis., Results: The results demonstrated 33.1% reduction in number of FOG episodes (P < 0.001) and 32.6% reduction of freezing episodes (P < 0.001). Quantitative gait analysis showed a significant increase in step length (P = 0.033). A moderate negative correlation was observed between the change of percent time frozen and age (r = -0.415, P = 0.016). 73% of participants reported minimal to substantial improvement in walking with this vibrating stimulation delivered by the vibrotactile foot device., Conclusions: The vibrotactile foot device is an efficient device that could significantly reduce freezing severity and provide gait regulation to patients with PD experiencing frequent freezing. It could potentially be used in the home environment for improving the quality of life., (© 2024 International Parkinson and Movement Disorder Society.)

Patients with advanced Parkinson's disease often suffer from severe gait and balance problems, impacting quality of live and persisting despite optimization of standard therapies. The aim of this review was to systematically review the efficacy of STN-DBS programming techniques in alleviating gait disturbances in patients with advanced PD. Searches were conducted in PubMed, Embase, and Lilacs databases, covering studies published until May 2024. The review identified 36 articles that explored five distinct STN-DBS techniques aimed at addressing gait and postural instability in Parkinson's patients: low-frequency stimulation, ventral STN stimulation for simultaneous substantia nigra activation, interleaving, asymmetric stimulation and a short pulse width study. Among these, 21 articles were included in the meta-analysis, which revealed significant heterogeneity among studies. Notably, low-frequency STN-DBS demonstrated positive outcomes in total UPDRS-III score and FOG-Q, especially when combined with dopaminergic therapy. The most favorable results were found for low-frequency STN stimulation. The descriptive analysis suggests that unconventional stimulation approaches may be viable for gait problems in patients who do not respond to standard therapies., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Persistent lower limb dysfunction is a major challenge in post-stroke recovery. Repetitive transcranial magnetic stimulation is recognized for addressing post-stroke motor deficits. Our study explores the efficacy of combining rTMS with gait-adaptive training to enhance lower limb function and regulatory mechanisms in subacute stroke., Materials and Methods: This randomized controlled trial enrolled 27 patients with subacute hemiparesis, dividing them into experimental and control groups. Both groups underwent gait-adaptability training 5 times/week for 4 weeks, with the experimental group receiving daily low-frequency transcranial magnetic stimulation before training. Primary outcomes included the pairwise derived brain symmetry index, lower-extremity Fugl-Meyer Assessment, 10-meter walk test, and Berg Balance Scale. Assessments occurred before and after the four-week intervention., Results: The experimental and control groups showed significant improvements in the Fugl-Meyer Assessment, 10-meter walk test, and Berg Balance Scale after the 4-week intervention compared to baseline (all p<0.05). However, the experimental group demonstrated significantly greater improvements compared to the control group in the Fugl-Meyer Assessment (p=0.024) and the 10-meter walk test (p=0.033). Additionally, the experimental group exhibited a more pronounced decrease in the pairwise derived brain symmetry index (p=0.026) compared to the control group. Within the experimental group, the cortical subgroup's pairwise derived brain symmetry index was significantly lower than that of the control group (p=0.006)., Conclusions: Combining low-frequency transcranial magnetic stimulation with Gait-Adaptive Training effectively enhances lower limb function and Regulatory mechanisms of the cerebral hemisphere in subacute stroke recovery, and it can provide rapid and effective rehabilitation effect compared with gait adaptation training alone., Competing Interests: Declaration of competing interest The Authors declare that there is no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Background: Hinged ankle foot orthoses (HAFO) are commonly prescribed for children with cerebral palsy (CP) to improve their ambulatory function., Objectives: The aim of this study was to compare the effect of vibration-HAFO with that of the same orthosis without vibration on gait, function, and spasticity in hemiplegic CP children., Study Design: Randomized Control Trial Design (a pilot study)., Methods: Twenty-three children with hemiplegic CP participated in this study. The control group (n = 12) used HAFO, and the intervention group (n = 11) used vibration-HAFO for four weeks. Pre-post three-dimensional gait analysis was done. Calf muscle spasticity and function were also measured., Results: Results showed significant differences between the two groups in the one-minute walking test (p = 0.023) and spasticity (after intervention [p = 0.022], after follow-up [p = 0.020]). Also, significant differences were detected between the two groups in the step width (p = 0.042), maximum hip abduction (p = 0.008), stance maximum dorsiflexion (p = 0.036) and mean pelvic tilt (p = 0.004) in the barefoot condition. Gait cycle time (p = 0.005), maximum hip abduction (p = 0.042), and cadence (p = 0.001) were different between groups in the braced condition. We couldn't find any significant within and between groups differences in knee kinematic parameters. The mean time of using vibration was 16.83 minutes per day., Conclusions: The vibration-hinged AFO is feasible, safe, and acceptable for children with hemiplegic CP to be integrated into practice. Temporospatial and clinical parameters, especially spasticity, were improved. There were slight trends toward improvement in pelvic and knee kinematics. Vibration-HAFO is of benefit to ambulatory CP children with mild and moderate spasticity. It improved the walking capacity of the children., (Copyright © 2023 International Society for Prosthetics and Orthotics.)

With disease-modifying drugs on the horizon for degenerative ataxias, ecologically valid, finely granulated, digital health measures are highly warranted to augment clinical and patient-reported outcome measures. Gait and balance disturbances most often present as the first signs of degenerative cerebellar ataxia and are the most reported disabling features in disease progression. Thus, digital gait and balance measures constitute promising and relevant performance outcomes for clinical trials.This narrative review with embedded consensus will describe evidence for the sensitivity of digital gait and balance measures for evaluating ataxia severity and progression, propose a consensus protocol for establishing gait and balance metrics in natural history studies and clinical trials, and discuss relevant issues for their use as performance outcomes., (© 2023. The Author(s).)

Background: Gait impairment is a key feature in later stages of Parkinson's disease (PD), which often responds poorly to pharmacological therapies. Neuromodulatory treatment by low-intensity noisy galvanic vestibular stimulation (nGVS) has indicated positive effects on postural instability in PD, which may possibly be conveyed to improvement of dynamic gait dysfunction., Objective: To investigate the effects of individually tuned nGVS on normal and cognitively challenged walking in PD patients with mild-to-moderate gait dysfunction., Methods: Effects of nGVS of varying intensities (0-0.7 mA) on body sway were examined in 32 patients with PD (ON medication state, Hoehn and Yahr: 2.3 ± 0.5), who were standing with eyes closed on a posturographic force plate. Treatment response and optimal nGVS stimulation intensity were determined on an individual patient level. In a second step, the effects of optimal nGVS vs. sham treatment on walking with preferred speed and with a cognitive dual task were investigated by assessment of spatiotemporal gait parameters on a pressure-sensitive gait carpet., Results: Evaluation of individual balance responses yielded that 59% of patients displayed a beneficial balance response to nGVS treatment with an average optimal improvement of 23%. However, optimal nGVS had no effects on gait parameters neither for the normal nor the cognitively challenged walking condition compared to sham stimulation irrespective of the nGVS responder status., Conclusions: Low-intensity nGVS seems to have differential treatment effects on static postural imbalance and continuous gait dysfunction in PD, which could be explained by a selective modulation of midbrain-thalamic circuits of balance control., (© 2024. The Author(s).)

Background: Parkinson's Disease (PD) is a progressive neurological disorder that results in potentially debilitating mobility deficits. Recently, spinal cord stimulation (SCS) has been proposed as a novel therapy for PD gait disorders. The highest levels of evidence remain limited for SCS., Objectives: In this systematic review and narrative synthesis, the literature was searched using combinations of key phrases indicating spinal cord stimulation and PD., Methods: We included pre-clinical studies and all published clinical trials, case reports, conference abstracts as well as protocols for ongoing clinical trials. Additionally, we included trials of SCS applied to atypical parkinsonism., Results: A total of 45 human studies and trials met the inclusion criteria. Based on the narrative synthesis, a number of knowledge gaps and future avenues of potential research were identified. This review demonstrated that evidence for SCS is currently not sufficient to recommend it as an evidence-based therapy for PD related gait disorders. There remain challenges and significant barriers to widespread implementation, including issues regarding patient selection, effective outcome selection, stimulation location and mode, and in programming parameter optimization. Results of early randomized controlled trials are currently pending. SCS is prone to placebo, lessebo and nocebo as well as blinding effects which may impact interpretation of outcomes, particularly when studies are underpowered., Conclusion: Therapies such as SCS may build on current evidence and be shown to improve specific gait features in PD. Early negative trials should be interpreted with caution, as more evidence will be required to develop effective methodologies in order to drive clinical outcomes., (© 2024 International Parkinson and Movement Disorder Society.)

Background: In children with unilateral spastic cerebral palsy (USCP), ankle-foot orthoses (AFOs) are widely used to correct common gait deviations such as a drop-foot pattern. Most studies on this topic have investigated specific time points while omitting other parts of the gait cycle., Objectives: This study investigated the separate effects of prefabricated carbon fiber AFOs and custom-made hinged AFOs compared with barefoot walking in children with USCP with a drop-foot gait pattern using statistical parametric mapping., Study Design: Retrospective, cross-sectional, repeated measures study., Methods: Twenty ambulatory children (9.9 ± 2.5 years) with USCP and a drop-foot gait pattern were included. Kinematics, kinetics, and spatiotemporal parameters assessed during 3-dimensional gait analysis were compared between barefoot and AFO walking. Statistical parametric mapping was used to compare joint angles and moment waveforms. Kinematics, kinetics and spatiotemporal parameters assessed during 3-dimensional gait analysis were compared between barefoot and AFO walking for each AFO type but not between the 2 AFO types., Results: Compared with barefoot walking, there was a steeper sole angle at initial contact, corresponding to a heel strike pattern, and an increased ankle dorsiflexion in swing with the use of both AFOs. The ankle plantar flexion moment during loading response increased. Ankle power generation during pre-swing decreased in the carbon fiber AFO group when walking with AFOs., Conclusions: Both AFOs were beneficial for improving a drop-foot gait pattern in these small patient groups and can, therefore, be recommended to treat this gait deviation in patients with unilateral cerebral palsy. However, the reduction in ankle power generation during push-off and additional goals targeted by AFOs, such as correction of structural or flexible foot deformities, should be considered for prescription., (Copyright © 2024 International Society for Prosthetics and Orthotics.)

Background: Repetitive transcranial magnetic stimulation (rTMS) is a nonpharmacological and noninvasive brain stimulation technique that has been proven to be effective in Parkinson's disease (PD). The combination of rTMS and treadmill training improved gait function in PD greater than treadmill training alone., Objective: The aim of our study was to evaluate the combination of a novel high-intensity, short intervention rTMS treatment and a multimodal treatment protocol including of physiotherapy, occupational therapy and language therapy, the so-called Parkinson's Disease Multimodal Complex Treatment (PD-MCT), to improve motor function., Methods: In this randomized double-blind sham-controlled trial rTMS with 48 Hz or sham was applied over the cerebellum 3 times a day for 5 consecutive days. Patients were assessed at baseline (V0), after 5 days of treatment (V1), and 4 weeks later (V2). The primary clinical outcome measure was the motor sum-score of the Unified PD Rating Scale (UPDRS III ), secondary clinical outcomes were quantitative motor tasks., Results: A total of 36 PD patients were randomly allocated either to rTMS (n = 20) or sham (n = 16), both combined with PD-MCT. rTMS improved the UDPRSIII score comparing baseline and V1 in the treatment group by -8.2 points ( P  = .004). The 8MW and dynamic posturography remained unchanged in both groups after intervention. Conclusion. Compressing weeks of canonical rTMS protocols into 5 days was effective and well tolerated. rTMS may serve as an add-on therapy for augmenting the multimodal complex treatment of motor symptoms, but seems to be ineffective to treat postural instability., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MGE receives research support from the German Ministry of Education and Research (BMBF) within the European Joint Program for Rare Diseases (EJP-RD) 2021 Transnational Call for Rare Disease Research Projects, from the National Ataxia Foundarion (NAF), and from Ataxia UK, and received consulting fees from Healthcare Manufaktur, Germany, all unrelated to this study. MGE is member of the European Reference Network Rare Neurological Diseases (ERN-RND). All other authors declare no potential conflict of interest with respect to the research, the authorship, and publication of this article.

Objective: To investigate the involvement of the visual cortex in improving freezing of gait (FoG) after subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) patients using whole-brain seed-based functional connectivity., Methods: A total of 66 PD patients with FoG who underwent bilateral STN-DBS were included in our study. Patients were divided into a FoG responder group and an FoG nonresponder group according to whether FoG improved 1 year after DBS. We compared the differences in clinical characteristics, brain structural imaging, and seed-based functional connectivity between the 2 groups. The locations of active contacts were further analyzed., Results: All PD patients benefited from STN-DBS. No significant differences in the baseline characteristics or brain structures were found between the 2 groups. Seed-based functional connectivity analysis revealed that better connectivity in bilateral primary visual areas was associated with better clinical improvement in FoG (P < 0.05 familywise error corrected). Further analysis revealed that this disparity was associated with the location of the active contacts within the rostral region of the sensorimotor subregion in the FoG responder group, in contrast to the findings in the FoG nonresponder group., Conclusions: This study suggested that DBS in the rostral region of the STN sensorimotor subregion may alleviate FoG by strengthening functional connectivity in primary visual areas, which has significant implications for guiding surgical strategies for FoG in the future., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Gait disorders in patients with Parkinson's disease (PD) can become disabling with disease progression without effective treatment., Objectives: To investigate the efficacy of intermittent θ burst trans-spinal magnetic stimulation (TsMS) in PD patients with gait and balance disorders., Methods: This was a randomized, parallel, double-blind, controlled trial. Active or sham TsMS was applied at third thoracic vertebra with 100% of the trans-spinal motor threshold, during 5 consecutive days. Participants were evaluated at baseline, immediately after last session, 1 and 4 weeks after last session. Primary outcome was Total Timed Up and Go (TUG) values comparing active versus sham phases 1 week after intervention. The secondary outcome measurements consisted of motor, gait and balance scales, and questionnaires for quality of life and cognition., Results: Thirty-three patients were included, average age 68.5 (6.4) years in active group and 70.3 (6.3) years in sham group. In active group, Total TUG mean baseline was 107.18 (95% CI, 52.1-116.1), and 1 week after stimulation was 93.0 (95% CI, 50.7-135.3); sham group, Total TUG mean baseline was 101.2 (95% CI, 47.1-155.3) and 1 week after stimulation 75.2 (95% CI 34.0-116.4), P = 0.54. Similarly, intervention had no significant effects on secondary outcome measurements. During stimulation period, five patients presented with mild side effects (three in active group and two in sham group)., Discussion: TsMS did not significantly improve gait or balance analysis in patients with PD and gait disorders. The protocol was safe and well tolerated. © 2024 International Parkinson and Movement Disorder Society., (© 2024 International Parkinson and Movement Disorder Society.)

Background: Gait impairment has a major impact on quality of life in patients with Parkinson's disease (PD). It is believed that basal ganglia oscillatory activity at β frequencies (15-30 Hz) may contribute to gait impairment, but the precise dynamics of this oscillatory activity during gait remain unclear. Additionally, auditory cues are known to lead to improvements in gait kinematics in PD. If the neurophysiological mechanisms of this cueing effect were better understood they could be leveraged to treat gait impairments using adaptive Deep Brain Stimulation (aDBS) technologies., Objective: We aimed to characterize the dynamics of subthalamic nucleus (STN) oscillatory activity during stepping movements in PD and to establish the neurophysiological mechanisms by which auditory cues modulate gait., Methods: We studied STN local field potentials (LFPs) in eight PD patients while they performed stepping movements. Hidden Markov Models (HMMs) were used to discover transient states of spectral activity that occurred during stepping with and without auditory cues., Results: The occurrence of low and high β bursts was suppressed during and after auditory cues. This manifested as a decrease in their fractional occupancy and state lifetimes. Interestingly, α transients showed the opposite effect, with fractional occupancy and state lifetimes increasing during and after auditory cues., Conclusions: We show that STN oscillatory activity in the α and β frequency bands are differentially modulated by gait-promoting oscillatory cues. These findings suggest that the enhancement of α rhythms may be an approach for ameliorating gait impairments in PD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: To study if functional electrical stimulation (FES) of the peroneal nerve, which activates dorsiflexion, can improve body functions, activities, and participation and could be an effective alternative treatment in individuals with unilateral spastic cerebral palsy (CP)., Method: A randomized cross-over trial was performed in 25 children with unilateral spastic CP (classified in Gross Motor Function Classification System levels I and II) aged 4 to 18 years (median age at inclusion 9 years 8 months, interquartile range = 7 years-13 years 8 months), 15 patients were male. The study consisted of two 12-week blocks of treatment, that is, conventional treatment (ankle foot orthosis [AFO] or adapted shoes) and FES, separated by a 6-week washout period. Outcome measures included the Goal Attainment Scale (GAS), the Cerebral Palsy Quality of Life questionnaire, and a three-dimensional gait analysis., Results: Eighteen patients completed the trial. The proportion of GAS goals achieved was not significantly higher in the FES versus the conventional treatment phase (goal 1 p = 0.065; goal 2 p = 1.00). When walking while stimulated with FES, ankle dorsiflexion during mid-swing decreased over time (p = 0.006, average decrease of 4.8° with FES), with a preserved increased ankle range of motion compared to conventional treatment (p < 0.001, mean range of motion with FES +10.1° compared to AFO). No changes were found in the standard physical examination or regarding satisfaction with orthoses and feelings about the ability to dress yourself. In four patients, FES therapy failed; in 12 patients FES therapy continued after the trial., Interpretation: FES is not significantly worse than AFO; however, patient selection is critical, and a testing period and thorough follow-up are needed., (© 2023 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

Background: Instrumented gait analysis (IGA) has been around for a long time but has never been shown to be useful for improving patient outcomes. In this study we demonstrate the potential utility of IGA by showing that machine learning models are better able to estimate treatment outcomes when they include both IGA and clinical (CLI) features compared to when they include CLI features alone., Design: We carried out a retrospective analysis of data from ambulatory children diagnosed with cerebral palsy who were seen at least twice at our gait analysis center. Individuals underwent a variety of treatments (including no treatment) between sequential gait analyses. We fit Bayesian Additive Regression Tree (BART) models that estimated outcomes for mean stance foot progression to demonstrate the approach. We built two models: one using CLI features only, and one using CLI and IGA features. We then compared the models' performance in detail. We performed similar, but less detailed, analyses for a number of other outcomes. All results were based on independent test data from a 70%/30% training/testing split., Results: The IGA model was more accurate than the CLI model for mean stance-phase foot progression outcomes (RMSEIGA = 11∘, RMSECLI = 13∘) and explained more than 1.5 × as much of the variance (R2IGA = .45, R2CLI = .28). The IGA model outperformed the CLI model for every level of treatment complexity, as measured by number of simultaneous surgeries. The IGA model also exhibited superior performance for estimating outcomes of mean stance-phase knee flexion, mean stance-phase ankle dorsiflexion, maximum swing-phase knee flexion, gait deviation index (GDI), and dimensionless speed., Interpretation: The results show that IGA has the potential to be useful in the treatment planning process for ambulatory children diagnosed with cerebral palsy. We propose that the results of machine learning outcome estimators-including estimates of uncertainty-become the primary IGA tool utilized in the clinical process, complementing the standard medical practice of conducting a through patient history and physical exam, eliciting patient goals, reviewing relevant imaging data, and so on., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Schwartz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: In this research, paying particular attention to freezıng of gait (FOG), we aimed to investigate the associations between the clinical features and quality of lilfe (QOL) indexes comparatively in our PD subjects with and without STN-DBS therapy., Methods: All consecutive PD subjects with and without STN-DBS who applied to our movement disorders outpatient clinics between January/2022 and September/2022; and accepted to participate in the study were enrolled. The demographic data and clinical features were noted. Besides, the MDS-UPDRS, the FOG Questionnaire (FOGQ) and the Parkinson's Disease Questionnaire (PDQ-39) have also been performed on all individuals., Results: Overall, 105 patients with PD participated in this study (34 patients with STN-DBS, 71 patients without STN-DBS). No difference was found in the PDQ-39 scores between patients with and without STN-DBS. The correlation analyses between the PQQ-39 scores and the clinical parameters revealed significant moderate correlations with the FOGQ score and low correlations with MDS-UPDRS scores. The analyses repeated in either patient group showed that there were no correlations between the MDS-UPDRS scores and PDQ-39 indexes in the DBS group. Besides, the correlations between the PDQ-39 scores and the FOG scores were more prominent in patients without DBS therapy., Conclusion: FOG was found to be associated with worse QOL status in both patients with and without STN-DBS therapy. However, the correlations analyses in either group showed that FOG was a more significant determinant in the QOL indexes in patients without DBS. Future studies evaluating the impact of other clinical features such as falls and gait impairment in QOL of patients with STN-DBS may provide contributions to the current evidence.

Background: Asymmetric gait patterns are mostly observed in hemiplegic stroke patients. These abnormal gait patterns resulting in abnormal speed, and decreased ability in daily of activity living., Objective: This study aimed to determine the immediate changes in gait parameters and plantar pressure during elevation by wearing an insole on the sound side lower extremity of patients with hemiplegia., Methods: Thirty-six participants were recruited, comprising those with a post-stroke follow-up of ≥3 months and a functional ambulation category score of ≥2. The participants were asked to walk with and without a 1 cm insole in the shoe of their sound side, and the order of wearing or not wearing the insole was randomized. Gait parameters, bilateral gait parameters, and dynamic plantar pressure were measured using the GAITRite Walkway System., Results: Paired t-test was used to examine immediate changes in gait parameters and plantar pressure with and without insoles during walking in the same group. Overall, gait velocity and step length significantly decreased (p < 0.05), whereas step time significantly increased (p < 0.05). The swing phase of the affected sidelower extremities significantly increased (p < 0.05), and the stance phase significantly decreased (p < 0.05). Double-support unloading phase (pre-swing phase) significantly increased (p < 0.05). The changes in plantar pressure were significantly increased in some lateral zones and significantly decreased in the medial zone of the mid-hindfoot, both in terms of pressure per time and peak pressure (p < 0.05)., Conclusion: Although this study did not show immediate positive effects on gait parameters and gait cycle, it is expected that sensory input from the sole of the foot through changes in plantar pressure may help improve gait asymmetry and regulate postural symmetry.

Background: A reduction in stride length is considered a key characteristic of gait kinematics in Parkinson's disease (PD) and has been identified as a predictor of falls. Although low-frequency stimulation (LFS) has been suggested as a method to improve gait characteristics, the underlying structural network is not well understood., Objective: This study aims to investigate the structural correlates of changes in stride length during LFS (85 Hz)., Methods: Objective gait performance was retrospectively evaluated in 19 PD patients who underwent deep brain stimulation (DBS) at 85 Hz and 130 Hz. Individual DBS contacts and volumes of activated tissue (VAT) were computed using preoperative magnetic resonance imaging (MRI) and postoperative computed tomography (CT) scans. Structural connectivity profiles to predetermined cortical and mesencephalic areas were estimated using a normative connectome., Results: LFS led to a significant improvement in stride length compared to 130 Hz stimulation. The intersection between VAT and the associative subregion of the subthalamic nucleus (STN) was associated with an improvement in stride length and had structural connections to the supplementary motor area, prefrontal cortex, and pedunculopontine nucleus. Conversely, we found that a lack of improvement was linked to stimulation volumes connected to cortico-diencephalic fibers bypassing the STN dorsolaterally. The robustness of the connectivity model was verified through leave-one-patient-out, 5-, and 10-fold cross cross-validation paradigms., Conclusion: These findings offer new insights into the structural connectivity that underlies gait changes following LFS. Targeting the non-motor subregion of the STN with LFS on an individual level may present a potential therapeutic approach for PD patients with gait disorders., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The study "A spinal cord neuroprosthesis for locomotor deficits due to Parkinson's disease" by Milekovic et al. introduces a novel neuroprosthesis for treating locomotor deficits in late-stage Parkinson's disease (PD). This approach employs an epidural spinal array targeting dorsal roots and electromyography to create a spatiotemporal map of muscle activation, aiming to restore natural gait patterns. Significant improvements in gait freezing and balance were observed in both non-human primate models and a human patient, resulting in improved mobility and quality of life. This innovative method, integrating real-time feedback and non-invasive motor intention decoding, marks a significant advancement in PD treatment.

Freezing of gait (FoG) is a profoundly disruptive gait disturbance in Parkinson's disease, causing unintended stops while walking. Therapies for FoG reveal modest and transient effects, resulting in a lack of effective treatments. Here we show proof of concept that FoG can be averted using soft robotic apparel that augments hip flexion. The wearable garment uses cable-driven actuators and sensors, generating assistive moments in concert with biological muscles. In this n-of-1 trial with five repeated measurements spanning 6 months, a 73-year-old male with Parkinson's disease and substantial FoG demonstrated a robust response to robotic apparel. With assistance, FoG was instantaneously eliminated during indoor walking (0% versus 39 ± 16% time spent freezing when unassisted), accompanied by 49 ± 11 m (+55%) farther walking compared to unassisted walking, faster speeds (+0.18 m s -1 ) and improved gait quality (-25% in gait variability). FoG-targeting effects were repeatable across multiple days, provoking conditions and environment contexts, demonstrating potential for community use. This study demonstrated that FoG was averted using soft robotic apparel in an individual with Parkinson's disease, serving as an impetus for technological advancements in response to this serious yet unmet need., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

People with late-stage Parkinson's disease (PD) often suffer from debilitating locomotor deficits that are resistant to currently available therapies. To alleviate these deficits, we developed a neuroprosthesis operating in closed loop that targets the dorsal root entry zones innervating lumbosacral segments to reproduce the natural spatiotemporal activation of the lumbosacral spinal cord during walking. We first developed this neuroprosthesis in a non-human primate model that replicates locomotor deficits due to PD. This neuroprosthesis not only alleviated locomotor deficits but also restored skilled walking in this model. We then implanted the neuroprosthesis in a 62-year-old male with a 30-year history of PD who presented with severe gait impairments and frequent falls that were medically refractory to currently available therapies. We found that the neuroprosthesis interacted synergistically with deep brain stimulation of the subthalamic nucleus and dopaminergic replacement therapies to alleviate asymmetry and promote longer steps, improve balance and reduce freezing of gait. This neuroprosthesis opens new perspectives to reduce the severity of locomotor deficits in people with PD., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Dysfunction of the primary motor cortex, participating in regulation of posture and gait, is implicated in freezing of gait (FOG) in Parkinson's disease (PD)., Objective: The aim was to reveal the mechanisms of "OFF-period" FOG (OFF-FOG) and "levodopa-unresponsive" FOG (ONOFF-FOG) in PD., Methods: We measured the transcranial magnetic stimulation (TMS) indicators and gait parameters in 21 healthy controls (HCs), 15 PD patients with ONOFF-FOG, 15 PD patients with OFF-FOG, and 15 PD patients without FOG (Non-FOG) in "ON" and "OFF" medication conditions. Difference of TMS indicators in the four groups and two conditions and its correlations with gait parameters were explored. Additionally, we explored the effect of 10 Hz repetitive TMS on gait and TMS indicators in ONOFF-FOG patients., Results: In "OFF" condition, short interval intracortical inhibition (SICI) exhibited remarkable attenuation in FOG patients (both ONOFF-FOG and OFF-FOG) compared to Non-FOG patients and HCs. The weakening of SICI correlated with impaired gait characteristics in FOG. However, in "ON" condition, SICI in ONOFF-FOG patients reduced compared to OFF-FOG patients. Pharmacological treatment significantly improved SICI and gait in OFF-FOG patients, and high-frequency repetitive TMS distinctly improved gait in ONOFF-FOG patients, accompanied by enhanced SICI., Conclusions: Motor cortex disinhibition, represented by decreased SICI, is related to FOG in PD. Refractory freezing in ONOFF-FOG patients correlated with the their reduced SICI insensitive to dopaminergic medication. SICI can serve as an indicator of the severity of impaired gait characteristics in FOG and reflect treatments efficacy for FOG in PD patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

BACKGROUND The posterior parietal cortex (PPC) is a key brain area for visuospatial processing and locomotion. It has been repetitively shown to be involved in the neural correlates of freezing of gait (FOG), a common symptom of Parkinson's disease (PD). However, current neuroimaging modalities do not allow to precisely determine the role of the PPC during real FOG episodes. OBJECTIVES The purpose of this study was to modulate the PPC cortical excitability using repetitive transcranial magnetic stimulation (rTMS) to determine whether the PPC contributes to FOG or compensates for dysfunctional neural networks to reduce FOG. METHODS Fourteen participants with PD who experience freezing took part in a proof of principle study consisting of three experimental sessions targeting the PPC with inhibitory, excitatory, and sham rTMS. Objective FOG outcomes and cortical excitability measurements were acquired before and after each stimulation protocol. RESULTS Increasing PPC excitability resulted in significantly fewer freezing episodes and percent time frozen during a FOG-provoking task. This reduction in FOG most likely emerged from the trend in PPC inhibiting the lower leg motor cortex excitability. CONCLUSION Our results suggest that the recruitment of the PPC is linked to less FOG, providing support for the beneficial role of the PPC upregulation in preventing FOG. This could potentially be linked to a reduction of the cortical input burden on the basal ganglia prior to FOG. Excitatory rTMS interventions targeting the PPC may have the potential to reduce FOG., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Freezing of gait (FOG) is one of the most disabling symptoms of Parkinsonism. Moreover, it does not respond well to medication. Visual cues have been shown to alleviate FOG in Parkinsonism; however, their efficacy is inconsistent. Currently, most mobile cueing devices are used as an open-loop cueing system, which requires manual control to enable constant visual cues. Thus, such devices may not be suitable for some people, especially those who have attention deficits. In addition, objective measurements of FOG in real-life situations remain challenging. Therefore, we developed a smart-ankle laser as a closed-loop cueing system that can detect the patient's walking pattern and automatically project a laser line that follows each walking step, thus requires less attention. Real-time motion was also recorded within the device for FOG measurement. We studied the efficacy of the device in three Parkinsonism patients with FOG (one man and two women, aged 58-76 years) immediately after use and two patients at 1-week follow-up. Gait speed, Timed Up and Go test performance, stride length, and % FOG improved with the use of the laser, without adverse effects.

Introduction: Deep Brain Stimulation (DBS) is an option to treat advanced Parkinson's Disease (PD), but can cause gait disturbance due to stimulation side efffects. This study aims to evaluate the objective effect of directional current steering by DBS on gait performance in PD, utilizing a three-dimensional gait analysis system., Methods: Eleven patients diagnosed with PD and were implanted with directional lead were recruited. The direction of the pyramidal tract (identified by the directional mode screening) was set as 0°. Patients performed the six-meter-walk test and the time up-and-go (TUG) test while an analysis system recorded gait parameters utilizing a three-dimensional motion capture camera. The gait parameters were measured for the baseline, the directional steering at eight angles (0°, 45°, 90°, 135°, 180°, 225°, 270°, and 315°), and the conventional ring mode with 1, 2, and 3 mA. Pulse width and frequency were fixed. Placebo stimulation (0 mA) was used for a control., Results: Eleven patients completed the study. No significant difference were observed between gait parameters during the directional, baseline, placebo, or ring modes during the six-meter-walk test (p > 0.05). During the TUG test, stride length was significantly different between 0° and other directions (p < 0.001), but no significant differences were observed for the other gait parameters. Stride width was non-significantly narrower in the direction of 0°., Conclusion: Controlling stimulation using directional steering may improve gait in patients with PD, while avoiding pyramidal side effects., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: GO reports a relationship with Medtronic, Boston Scientific, Otsuka Pharmaceutical, Sumitomo Dainippon Pharma, Novartis Pharma, FP Pharmaceutical Corporation, Kyowa Hakko Kirin, Takeda Pharmaceutical Company Ltd, Eisai Co., Ltd, Mylan EPD, and Abbvie. that includes: speaking and lecture fees. SS, JB, MN, FS, RN, MI have no financial relationship to disclose. NH has received speaker honoraria from Dai-Nippon Sumitomo, Otsuka, Takeda, Kyowa Hakko-Kirin, Boehringer Ingelheim, FP, Eisai, Kissei, Nihon Medi-physics, Novartis, Biogen Idec Japan, AbbVie, Boston Scientific Japan, Sanofi, Alexion, Mylan N. V., and Daiichi Sankyo. NH has received consultancies and subcontracting from Dai-Nippon Sumitomo, Biogen Idec, Otsuka, Takeda, Kyowa Hakko- Kirin, Meiji Seika, Hisamitsu, Kao, and Ono. KB, MT, SK, BT, and TI are employees of Kao Corporation., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: We aimed to investigate the gait parameters in patients with subthalamic nucleus deep brain stimulation (STN-DBS) therapy using quantitative gait analyses and reveal the associated clinical features., Methods: Parkinson's disease (PD) subjects with STN-DBS who applied to our movement disorders outpatient clinics between December/2021 and March/2022 were enrolled. In addition to the evaluation of the demographic data and the clinical features; clinical scales measuring the freezing of gait (FOG), falls and quality of life were performed. A gait analyzer program was used to perform gait analysis., Results: Thirty patients with a mean age of 59.4 ± 8.3 (F/M = 7/23) were enrolled. The comparative analyses between the tremor-dominant and akinetic-rigid (AR) subtype patients showed that the step time asymmetry measures were higher in the AR group. The comparative analyses according to the symptom onset side showed that the step length was smaller in those with left-side symptom onset. The correlation analyses showed that there were correlations between the quality-of-life indexes and FOG questionnaire and falls efficacy scale (FES) scores. Finally, the correlation analyses between clinical scales and gait parameters revealed that there were significant correlations between the FES scores and the step length asymmetry (SLA)., Conclusion: We found a strong relationship between falls and quality of life indexes of our patients under STN-DBS therapy. In this patient group, particular evaluation of fallings and the follow-up of SLA in gait analysis may constitute important points during the evaluation of patients in routine clinical practice.

Background: Gait freezing is a common, disabling symptom of Parkinson's disease characterized by sudden motor arrest during walking. Adaptive deep brain stimulation devices that detect freezing and deliver real-time, symptom-specific stimulation are a potential treatment strategy. Real-time alterations in subthalamic nucleus firing patterns have been demonstrated with lower limb freezing, however, whether similar abnormal signatures occur with freezing provoked by cognitive load, is unknown., Methods: We obtained subthalamic nucleus microelectrode recordings from eight Parkinson's disease patients performing a validated virtual reality gait task, requiring responses to on-screen cognitive cues while maintaining motor output., Results: Signal analysis during 15 trials containing freezing or significant motor output slowing precipitated by dual-tasking demonstrated reduced θ frequency (3-8 Hz) firing compared to 18 unaffected trials., Conclusions: These preliminary results reveal a potential neurobiological basis for the interplay between cognitive factors and gait disturbances including freezing in Parkinson's disease, informing development of adaptive deep brain stimulation protocols. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Foot-drop is one of the most diagnosed and physically limiting symptoms persons with multiple sclerosis (pwMS) experience. Clinicians prescribe ankle-foot orthosis (AFO) and functional electrical stimulation (FES) devices to help alleviate the effects of foot drop, but it is unclear how their clinical and functional gait improvements compare given the user's level of disability, type of multiple sclerosis, walking environment, or desired physical activity. The research questions explored were what is the current state of AFO and FES research for pwMS? What are the prevailing research trends? What definitive clinical and functional device comparisons exist for pwMS? eight databases were systematically searched for relevant literature published between 2009 and 2021. The American Association of Orthotists and Prosthetists and Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines for systematic literature reviews were followed. A team of 3 researchers critically evaluated 17 articles that passed eligibility criteria. This review discusses the current state and trends of research, provides evidence statements on device effects, and recommends improvements for future studies. A meta-analysis would be informative, but study variability across the literature makes directly comparing AFO and FES device effects unreliable. This review contributes new and useful information to multiple sclerosis literature that can be used by both clinicians and researchers. Clinicians can use the provided insights to prescribe more effective, customized treatments, and other researchers can use them to evaluate and design future studies., (Copyright © 2022 International Society for Prosthetics and Orthotics.)

An ankle foot orthosis (AFO) is a standard type of orthosis applied to immediately treat foot drop symptoms. Kinesiology taping (KT) is a therapeutic method used in patients with neurological diseases, such as stroke, as well as in patients after orthopedic and sports injuries. This study aimed to compare outcomes of AFO treatment with those of KT to investigate the effect on gait ability in patients with foot drop after stroke. We recruited 18 patients exhibiting foot drop from stroke. Gait ability was assessed under 2 conditions: treatment with KT and that with AFO using the GAITRite system according to the following parameters: cadence, velocity, swing time, stance time, step length, and stride length. As a result, gait ability after treatment with KT and that after treatment with AFO showed no significant differences in cadence (P = .851), velocity (P = .865), swing time (P = .289 and .123), stance time (P = .255 and .711), step length (P = .955 and .975), and stride length (P = .711 and .690) of the affected and less-affected limbs. This study demonstrated that KT and AFO use have similar effects on gait function in patients with foot drop after stroke. Thus, treatment of foot drop with KT may be an alternative in patients for whom AFO use is contraindicated., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Cueing strategies can alleviate freezing of gait (FOG) in people with Parkinson's disease (PD). We evaluated tactile cueing delivered via vibrating socks, which has the benefit of not being noticeable to bystanders., Objective: To evaluate the effect of tactile cueing compared to auditory cueing on FOG., Methods: Thirty-one persons with PD with FOG performed gait tasks during both ON and OFF state. The effect of open loop and closed loop tactile cueing, as delivered by vibrating socks, was compared to an active control group (auditory cueing) and to a baseline condition (uncued gait). These four conditions were balanced between subjects. Gait tasks were videotaped and annotated for FOG by two experienced raters. Motion data were collected to analyze spatiotemporal gait parameters. Responders were defined as manifesting a relative reduction of > 10% in the percent time frozen compared to uncued gait., Results: The average percent time frozen during uncued gait was 11.2% in ON and 21.5% in OFF state. None of the three tested cueing modalities affected the percentage of time frozen in either the ON (p = 0.20) or OFF state (p = 0.12). The number of FOG episodes and spatiotemporal gait parameters were also not affected. We found that 22 out of 31 subjects responded to cueing, the response to the three types of cueing was highly individual., Conclusions: Cueing did not improve FOG at the group level; however, tactile as well as auditory cueing improved FOG in many individuals. This highlights the need for a personalized approach when using cueing to treat FOG., (© 2023. The Author(s).)

Introduction: Gait disturbances are a major contributor to the disability associated with Parkinson's disease. Although pharmacologic therapies and deep brain stimulation improve most motor parkinsonian features, their effects on gait are highly variable. Spinal cord stimulation, typically used for the treatment of chronic pain, has emerged as a potential therapeutic approach to improve gait disturbances in Parkinson's disease., Areas Covered: The authors review the available evidence on the effects of spinal cord stimulation in patients with Parkinson's disease, targeting primarily gait abnormalities. They also discuss possible mechanisms, safety, and methodological implications for future clinical trials. This systematic review of originally published articles in English language was performed using The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA).

The study was conducted at University of Lahore Teaching Hospital and Sir Ganga Ram Hospital, Lahore, using non-probability convenience sampling. Thirty-eight patients of Parkinson's disease were allocated by randomisation into two groups. PNF Group (group A) performed proprioceptive neuromuscular facilitation incorporated with conservative treatment, while for the conventional therapy group (group B) only conservative treatment was followed. Berg Balance Scale, Freezing of Gait questionnaire, and Functional Independence measure were used as outcome measuring tool. Berg balance scale values were significantly improved in group A at 12th week as compared to group B. Freezing of gait and functional independence was more significantly reduced in group A at sixth and 12th week as compared to group B. Hence, it is concluded that Proprioceptive neuromuscular facilitation combined with routine treatment regime improves balance, gait, and function of Parkinson's patients more effectively as compared with routine treatment protocol only.

Perturbation-based balance training (PBT) exposes individuals to a series of sudden upright balance perturbations to improve their reactive postural responses. In this study, we aimed to evaluate the effect of a short PBT program on body balance recovery following a perturbation in individuals with freezing of gait due to Parkinson's disease. Volunteers (mean age = 64 years, SD = 10.6) were pseudorandomly assigned either to a PBT (n = 9) or to a resistance training (RT, n = 10) group. PBT was implemented through balance perturbations varying in the kind, direction, side and magnitude of support base displacements. Both groups exercised with progressive difficulty/load activities twice a week for 4 weeks. Specific gains and generalization to dual-tasking and faster-than-trained support base displacements were evaluated 24 h after the end of the training, and retention was evaluated after 30 days of no training. Results showed that, compared with RT, PBT led to more stable postural responses in the 30-day retention evaluation, as indicated by decreased CoP displacement, velocity and time to direction reversal and reduced numbers of near-falls. We found no transfer either to a dual task or to a higher perturbation velocity. In conclusion, a training program based on diverse unpredictable balance perturbations improved the stability of reactive postural responses to those perturbations suffered during the training, without generalization to more challenging tasks., (© 2023 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

(1) Background: Stroke is one of the leading causes of disability. To identify the best treatment strategies for people with stroke (PwS), the aim of the current study was to compare the effects of training on a treadmill with functional electrical stimulation (TT-FES) with training on a treadmill (TT), and to analyze the effects of sequence of training on mobility and the parameters of walking ability. (2) Methods: Prospective, longitudinal, randomized and crossover study, in which 28 PwS were distributed into groups, namely the A-B Group (TT-FES followed by TT) and B-A Group (TT followed by TT-FES), using the foot drop stimulator, and were measured with functional tests. (3) Results: We found improved mobility, balance, non-paretic limb coordination, and endurance only in the group that started with TT-FES. However, sensorimotor function improved regardless of the order of training, and paretic limb coordination only improved in the B-A Group, but after TT-FES. These data indicate that the order of the protocols changed the results. (4) Conclusions: Although biomechanical evaluation methods were not used, which can be considered a limitation, our results showed that TT-FES was superior to isolated training on a treadmill with regard to balance, endurance capacity, and coordination of the non-paretic limb.

Background: Music Therapy (MT) is a unique treatment method for Persons with Multiple Sclerosis (PwMS) that can accelerate their functional recovery. MT has been proven to adjust the gait performance of PwMS in a short period. Its therapeutic effects in gait disorders of PwMS for long-term intervention are also starting to draw interest, but it has yet to be investigated., Aim: This review aimed to systematically examine the outcomes of PwMS with gait disorders after receiving MT intervention., Methods: A systematic review has been performed using several academic databases with keywords such as music therapy, multiple sclerosis, and gait. The study protocol was registered on PROSPERO (CRD42022365668)., Results: A total of 405 studies were initially identified. After applying the inclusion and exclusion criteria, twelve studies were finally included. The results showed that all PwMS received MT intervention with different strategies, and ten studies confirmed that gait disorders of PwMS were effectively improved by MT intervention., Conclusion: Most previous studies focused on the transient effects of MT on the gait performance of PwMS. This review bridges gaps in the long-term intervention of MT on gait disorders of PwMS and offers references for therapists to design treatment plans. According to this review, MT intervention has positive therapeutic effects on gait disorders in PwMS., Competing Interests: Declaration of Competing Interest All authors (Lingyu Kong, Xinwen Zhang, Lingyue Meng, Hao Xue, Wenlong Zhou, Xin Meng, Qiuxia Zhang, and Jianzhong Shen) declare no conflict of interest. All authors have read and approved the final version of the manuscript (Title: Effects of Music Therapy Intervention on Gait Disorder in Persons with Multiple Sclerosis: A Systematic Review of Clinical Trials)., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Deep brain stimulation (DBS) is a common treatment for Parkinson's disease. However, the clinical efficacy of short pulse width DBS (spDBS) compared with conventional DBS (cDBS) is still unknown., Objective: This meta-analysis investigated the effectiveness of spDBS versus cDBS in patients with PD., Methods: Four databases (PubMed, Cochrane, Web of Science, and Embase) were independently searched until October 2021 by two reviewers. We utilized the following scales and items: therapeutic windows (TW), efficacy threshold, side effect threshold, Movement Disorder Society-Sponsored Revision Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III off-medication score, Speech Intelligence Test (SIT), and Freezing of Gait Questionnaire (FOG-Q)., Results: The analysis included seven studies with a total of 87 patients. The results indicated that spDBS significantly widened the therapeutic windows (0.99, 95% CI = 0.61 to 1.38) while increasing the threshold amplitudes of side effects (2.25, 95% CI = 1.69 to 2.81) and threshold amplitudes of effects (1.60, 95% CI = 0.84 to 2.36). There was no statistically significant difference in UPDRS part III, SIT, and FOG-Q scores between spDBS and cDBS groups, suggesting that treatment with both cDBS and spDBS may result in similar effects of improved dysarthria and gait disorders., Conclusions: Compared with cDBS, spDBS is effective in expanding TW. Both types of deep brain stimulation resulted in improved gait disorders and speech intelligibility., (© 2022. Fondazione Società Italiana di Neurologia.)

Background: Wearable sensors-based systems have emerged as a potential tool to continuously monitor Parkinson's Disease (PD) motor features in free-living environments., Objectives: To analyse the responsivity of wearable inertial sensor (WIS) measures (On/Off-Time, dyskinesia, freezing of gait (FoG) and gait parameters) after treatment adjustments. We also aim to study the ability of the sensor in the detection of MF, dyskinesia, FoG and the percentage of Off-Time, under ambulatory conditions of use., Methods: We conducted an observational, open-label study. PD patients wore a validated WIS (STAT-ONTM) for one week (before treatment), and one week, three months after therapeutic changes. The patients were analyzed into two groups according to whether treatment changes had been indicated or not., Results: Thirty-nine PD patients were included in the study (PD duration 8 ± 3.5 years). Treatment changes were made in 29 patients (85%). When comparing the two groups (treatment intervention vs no intervention), the WIS detected significant changes in the mean percentage of Off-Time (p = 0.007), the mean percentage of On-Time (p = 0.002), the number of steps (p = 0.008) and the gait fluidity (p = 0.004). The mean percentage of Off-Time among the patients who decreased their Off-Time (79% of patients) was -7.54 ± 5.26. The mean percentage of On-Time among the patients that increased their On-Time (59% of patients) was 8.9 ± 6.46. The Spearman correlation between the mean fluidity of the stride and the UPDRS-III- Factor I was 0.6 (p = <0.001). The system detected motor fluctuations (MF) in thirty-seven patients (95%), whilst dyskinesia and FoG were detected in fifteen (41%), and nine PD patients (23%), respectively. However, the kappa agreement analysis between the UPDRS-IV/clinical interview and the sensor was 0.089 for MF, 0.318 for dyskinesia and 0.481 for FoG., Conclusions: It's feasible to use this sensor for monitoring PD treatment under ambulatory conditions. This system could serve as a complementary tool to assess PD motor complications and treatment adjustments, although more studies are required., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: AB is shareholder of Sense4Care. This does not alter our adherence to PLOS ONE policies on sharing data and materials. AB reports receiving honoraria from Bial and Zambon. NC reports receiving consultancy fees as member of the advisory board from Italfármaco, Abbvie and Zambon, speaking fees from Lundbeck and Zambon, and honoraria from Bial, Zambon and UCB. AP declares no conflict of interest. PQ declares no conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Caballol et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Objectives: Freezing of gait (FOG) is a disabling gait disorder in patients with Parkinson's disease (PD), characterized by recurrent episodes of halting steps. Dopaminergic drugs are common treatments for PD and FOG; however, these drugs may worsen FOG. Deep brain stimulation (DBS) is another option used to treat selected patients. The device needs to be programmed at a specific frequency, amplitude, and pulse width to achieve optimum effects for each patient. This systematic review aimed to evaluate the efficacy of DBS for FOG and its correlation with programmed parameters and the location of the electrodes in the brain., Materials and Methods: Data for this systematic review were gathered from five online databases: Medline ( via PubMed), Scopus, Embase, Web of Science, and Cochrane Library (including both Cochrane Reviews and Cochrane Trials) with a broad search strategy. We included those articles that reported clinical trials and a specific measurement for FOG., Results: This review included 13 studies of DBS that targeted the subthalamic nucleus (STN), substantia nigra (SNr), or pedunculopontine nucleus (PPN). Our analysis showed that low-frequency stimulation (LFS) was superior to high-frequency stimulation (HFS) for improving FOG. In the long term, the efficacy of both LFS and HFS decreased. The effect of amplitude was variable, and this parameter needed to be adjusted for each patient. Bilateral stimulation was better than unilateral stimulation., Conclusion: DBS is a promising choice for the treatment of severe FOG in patients with PD. Bilateral, low-frequency stimulation combined with medical therapy is associated with better responses, especially in the first 2 years of treatment. However, individualizing the DBS parameters should be considered to optimize treatment response.

Background: The sequence effect is the progressive deterioration in speech, limb movement, and gait that leads to an inability to communicate, manipulate objects, or walk without freezing of gait. Many studies have demonstrated a lack of improvement of the sequence effect from dopaminergic medication, however few studies have studied the metric over time or investigated the effect of open-loop deep brain stimulation in people with Parkinson's disease (PD)., Objective: To investigate whether the sequence effect worsens over time and/or is improved on clinical (open-loop) deep brain stimulation (DBS)., Methods: Twenty-one people with PD with bilateral subthalamic nucleus (STN) DBS performed thirty seconds of instrumented repetitive wrist flexion extension and the MDS-UPDRS III off therapy, prior to activation of DBS and every six months for up to three years. A sub-cohort of ten people performed the task during randomized presentations of different intensities of STN DBS., Results: The sequence effect was highly correlated with the overall MDS-UPDRS III score and the bradykinesia sub-score and worsened over three years. Increasing intensities of STN open-loop DBS improved the sequence effect and one subject demonstrated improvement on both open-loop and closed-loop DBS., Conclusion: Sequence effect in limb bradykinesia worsened over time off therapy due to disease progression but improved on open-loop DBS. These results demonstrate that DBS is a useful treatment of the debilitating effects of the sequence effect in limb bradykinesia and upon further investigation closed-loop DBS may offer added improvement.

Deep brain stimulation (DBS) conventionally target at basal ganglia or thalamic structures, modulating nodal points in the cortico-basal ganglia circuit, in order to effectively treat various movement disorders, including Parkinson's disease, tremor and dystonia (especially mobile type dystonia). However, there are still some other movement disorders, such as dystonia (especially fixed type dystonia), ataxia and freezing of gait, which are not responding well to the current DBS therapy. Cerebellum, similar to basal ganglia, also plays a critical role in the pathophysiology of movement disorders. Deep cerebellar structures, such as dentate nucleus or superior cerebellar peduncle, are noticed for their potential role as treatment targets in movement disorders in recent years. With increasing evidences of animal DBS experiments, recent clinical human subject studies reported that some movement disorders patients not responding to DBS with conventional targets, may benefit significantly from cerebellar DBS. These pioneer study results are invaluable for understanding the clinical use of cerebellar DBS for treatment of movement disorders. We review the recent data of cerebellar DBS performed by different groups and summarize the indications, surgical targets, programming details and outcomes in these clinical reports. We then synthesize the current pathophysiological study of cerebellum on different movement disorders and discuss the potential mechanism of action of cerebellar DBS. In addition to basal ganglia, it is important to study new DBS targets in the cerebellum for more comprehensive treatment of movement disorders., Competing Interests: Declaration of Competing Interest The authors report no declaration of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Freezing of gait (FOG) is a devastating symptom that develops in patients with advanced Parkinson's disease (PD) and is often unresponsive to pharmacological treatment. Recent research suggests that FOG may result from dysfunctional plantar peripheral sensory systems. The impact of combined plantar pressure and vibratory stimulation over vibratory or pressure alone on FOG remains unexplored., Methods: PD patients with FOG were randomised into four groups and treated with combined vibratory and pressure stimulation, vibratory stimulation alone, pressure stimulation alone, or controls (no stimulation). Vibratory stimulation targeted both Achilles' tendons. Simultaneous bilateral pressure stimulation was applied to the first hallux, first metatarsal bone, and the sole. The primary outcome included normalized percent changes in percent FOG measured both pre- and immediately post-stimulation. Other outcomes including clinical rating scale, response to questionnaires, number and duration of freezing episodes, and spatiotemporal gait parameters at pre- and freezing episodes were also explored., Results: Sixty PD patients participated in the study. Patients who were treated with combined vibratory and pressure stimulation responded with significant decreases in normalized percent changes of percent FOG (62.75 ± 25.54%, p < 0.001) compared with those treated with vibration alone (11.38 ± 8.29%, p < 0.001), pressure alone (15.15 ± 16.18%, p < 0.001), or controls (8.59 ± 16.85%, p < 0.001)., Conclusion: Our study demonstrated the benefit of combined vibratory and pressure stimulation on FOG suggesting that this strategy might be developed as a novel treatment modality for PD patients with FOG., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The effect of robot-assisted gait training has been demonstrated to improve gait recovery in patients with stroke. The aim of this study was to determine effects of robot-assisted gait training with various training modes in patients post stroke., Methods: Forty-seven patients post stroke were randomly assigned to one of 4 groups: Healbot T with pelvic off mode (pelvic off group; n = 11); Healbot T with pelvic control mode (pelvic on group; n = 12); Healbot T with constraint-induced movement therapy (CIMT) mode (CIMT group; n = 10); and conventional physiotherapy (control group; n = 10). All patients received a 30-minute session 10 times for 4 weeks. The primary outcomes were the 10-meter walk test (10MWT) and Berg Balance Scale (BBS). The secondary outcomes were functional ambulation category, timed up and go (TUG), and motricity index of the lower extremities (MI-Lower)., Results: The pelvic off group showed significant improvements in BBS, TUG, and MI-Lower (P < .05). The pelvic on and CIMT groups showed significant improvement in 10MWT, BBS, TUG, and MI-Lower (P < .05). Compared with control group, the pelvic on group showed greater improvement in the TUG and BBS scores; the CIMT group showed greater improvement in 10MWT and MI-Lower (P < .05)., Conclusion: This study suggested that Healbot T-assisted gait training benefited patients with stroke. The Healbot T with pelvic motion and CIMT modes were more helpful in improving balance and walking ability and lower limb strength, respectively, compared with conventional physiotherapy., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Subthalamic deep-brain-stimulation (STN-DBS) is an effective means to treat Parkinson's disease (PD) symptoms. Its benefit on gait disorders is variable, with freezing of gait (FOG) worsening in about 30% of cases. Here, we investigate the clinical and anatomical features that could explain post-operative FOG., Methods: Gait and balance disorders were assessed in 19 patients, before and after STN-DBS using clinical scales and gait recordings. The location of active stimulation contacts were evaluated individually and the volumes of activated tissue (VAT) modelled for each hemisphere. We used a whole brain tractography template constructed from another PD cohort to assess the connectivity of each VAT within the 39 Brodmann cortical areas (BA) to search for correlations between postoperative PD disability and cortico-subthalamic connectivity., Results: STN-DBS induced a 100% improvement to a 166% worsening in gait disorders, with a mean FOG decrease of 36%. We found two large cortical clusters for VAT connectivity: one "prefrontal", mainly connected with BA 8,9,10,11 and 32, and one "sensorimotor", mainly connected with BA 1-2-3,4 and 6. After surgery, FOG severity positively correlated with the right prefrontal VAT connectivity, and negatively with the right sensorimotor VAT connectivity. The right prefrontal VAT connectivity also tended to be positively correlated with the UPDRS-III score, and negatively with step length. The MDRS score positively correlated with the right sensorimotor VAT connectivity., Conclusion: Recruiting right sensorimotor and avoiding right prefrontal cortico-subthalamic fibres with STN-DBS could explain reduced post-operative FOG, since gait is a complex locomotor program that necessitates accurate cognitive control., Competing Interests: Declaration of competing interest The Authors declare to have no conflict of interest relative to this research., (Copyright © 2022 Elsevier Ltd. All rights reserved.)