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In patients with idiopathic normal-pressure hydrocephalus responsive to CSF drainage, shunting improved gait and balance at 3 months, but not cognition or incontinence, and was associated with some procedure-related risks.

Gait disorders represent a therapeutic challenge in Parkinson’s disease (PD). This study investigated the efficacy of 4-week action observation training (AOT) on disease severity, freezing of gait and motor abilities in PD, and evaluated treatment-related brain functional changes. 25 PD patients with freezing of gait were randomized into two groups: AOT (action observation combined with practicing the observed actions) and “Landscape” (same physical training combined with landscape-videos observation). At baseline and 4-week, patients underwent clinical evaluation and fMRI. Clinical assessment was repeated at 8-week. At 4-week, both groups showed reduced freezing of gait severity, improved walking speed and quality of life. Moreover, AOT was associated with reduced motor disability and improved balance. AOT group showed a sustained positive effect on motor disability, walking speed, balance and quality of life at 8-week, with a trend toward a persisting reduced freezing of gait severity. At 4-week vs. baseline, AOT group showed increased recruitment of fronto-parietal areas during fMRI tasks, while the Landscape group showed a reduced fMRI activity of the left postcentral and inferior parietal gyri and right rolandic operculum and supramarginal gyrus. In AOT group, functional brain changes were associated with clinical improvements at 4-week and predicted clinical evolution at 8-week. AOT has a more lasting effect in improving motor function, gait and quality of life in PD patients relative to physical therapy alone. AOT-related performance gains are associated with an increased recruitment of motor regions and fronto-parietal mirror neuron and attentional control areas.

Background The loss of gait automaticity is a key cause of motor deficits in Parkinson’s disease (PD) patients, even at the early stage of the disease. Action observation training (AOT) shows promise in enhancing gait automaticity. However, effective assessment methods are lacking. We aimed to propose a novel gait normalcy index based on dual task cost (NIDTC) and evaluate its validity and responsiveness for early-stage PD rehabilitation. Methods Thirty early-stage PD patients were recruited and randomly assigned to the AOT or active control (CON) group. The proposed NIDTC during straight walking and turning tasks and clinical scale scores were measured before and after 12 weeks of rehabilitation. The correlations between the NIDTCs and clinical scores were analyzed with Pearson correlation coefficient analysis to evaluate the construct validity. The rehabilitative changes were assessed using repeated-measures ANOVA, while the responsiveness of NIDTC was further compared by t tests. Results The turning-based NIDTC was significantly correlated with multiple clinical scales. Significant group-time interactions were observed for the turning-based NIDTC (F = 4.669, p = 0.042), BBS (F = 6.050, p = 0.022) and PDQ-39 (F = 7.772, p = 0.011) tests. The turning-based NIDTC reflected different rehabilitation effects between the AOT and CON groups, with the largest effect size (p = 0.020, Cohen’s d = 0.933). Conclusion The turning-based NIDTC exhibited the highest responsiveness for identifying gait automaticity improvement by providing a comprehensive representation of motor ability during dual tasks. It has great potential as a valid measure for early-stage PD diagnosis and rehabilitation assessment. Trial registration Chinese Clinical Trial Registry: ChiCTR2300067657

Hereditary transthyretin amyloidosis is caused by the deposition of misfolded transthyretin proteins in peripheral nerves and other tissues. This phase 3 trial tested patisiran, a small interfering RNA targeting transthyretin messenger RNA, to treat the disease.

Introduction People with Parkinson’s Disease (PD) show abnormal gait patterns compromising their independence and quality of life. Among all gait alterations due to PD, reduced step length, increased cadence, and decreased ground-reaction force during the loading response and push-off phases are the most common. Wearable biofeedback technologies offer the possibility to provide correlated single or multi-modal stimuli associated with specific gait events or gait performance, hence promoting subjects’ awareness of their gait disturbances. Moreover, the portability and applicability in clinical and home settings for gait rehabilitation increase the efficiency in the management of PD. The Wearable Vibrotactile Bidirectional Interface (BI) is a biofeedback device designed to extract gait features in real-time and deliver a customized vibrotactile stimulus at the waist of PD subjects synchronously with specific gait phases. The aims of this study were to measure the effect of the BI on gait parameters usually compromised by the typical bradykinetic gait and to assess its usability and safety in clinical practice. Methods In this case series, seven subjects (age: 70.4 ± 8.1 years; H&Y: 2.7 ± 0.3) used the BI and performed a test on a 10-meter walkway (10mWT) and a two-minute walk test (2MWT) as pre-training (Pre-trn) and post-training (Post-trn) assessments. Gait tests were executed in random order with (Bf) and without (No-Bf) the activation of the biofeedback stimulus. All subjects performed three training sessions of 40 min to familiarize themselves with the BI during walking activities. A descriptive analysis of gait parameters (i.e., gait speed, step length, cadence, walking distance, double-support phase) was carried out. The 2-sided Wilcoxon sign-test was used to assess differences between Bf and No-Bf assessments ( p  < 0.05). Results After training subjects improved gait speed (Pre-trn_No-Bf: 0.72(0.59,0.72) m/sec; Post-trn_Bf: 0.95(0.69,0.98) m/sec; p  = 0.043) and step length (Pre-trn_No-Bf: 0.87(0.81,0.96) meters; Post-trn_Bf: 1.05(0.96,1.14) meters; p  = 0.023) using the biofeedback during the 10mWT. Similarly, subjects’ walking distance improved (Pre-trn_No-Bf: 97.5 (80.3,110.8) meters; Post-trn_Bf: 118.5(99.3,129.3) meters; p  = 0.028) and the duration of the double-support phase decreased (Pre-trn_No-Bf: 29.7(26.8,31.7) %; Post-trn_Bf: 27.2(24.6,28.7) %; p  = 0.018) during the 2MWT. An immediate effect of the BI was detected in cadence (Pre-trn_No-Bf: 108(103.8,116.7) step/min; Pre-trn_Bf: 101.4(96.3,111.4) step/min; p  = 0.028) at Pre-trn, and in walking distance at Post-trn (Post-trn_No-Bf: 112.5(97.5,124.5) meters; Post-trn_Bf: 118.5(99.3,129.3) meters; p  = 0.043). SUS scores were 77.5 in five subjects and 80.3 in two subjects. In terms of safety, all subjects completed the protocol without any adverse events. Conclusion The BI seems to be usable and safe for PD users. Temporal gait parameters have been measured during clinical walking tests providing detailed outcomes. A short period of training with the BI suggests improvements in the gait patterns of people with PD. This research serves as preliminary support for future integration of the BI as an instrument for clinical assessment and rehabilitation in people with PD, both in hospital and remote environments. Trial registration The study protocol was registered (DGDMF.VI/P/I.5.i.m.2/2019/1297) and approved by the General Directorate of Medical Devices and Pharmaceutical Service of the Italian Ministry of Health and by the ethics committee of the Lombardy region (Milan, Italy).

Many people with chronic stroke (PwCS) exhibit deficits in step width modulation, an important strategy for walking balance. A single exposure to swing leg perturbations can temporarily strengthen this modulation. The objective of this parallel, double-blinded, randomized controlled trial was to investigate whether repeated perturbations cause sustained increases in step modulation (NCT02964039; funded by the VA). 54 PwCS at the Medical University of South Carolina were randomly assigned to one of three intervention groups: Control (n = 18), with minimal forces; Assistive (n = 18), pushing the swing leg toward a mechanically appropriate location; Perturbing (n = 18), pushing the swing leg away from a mechanically appropriate location. All intervention groups included 24 training sessions over 12-weeks with up to 30-minutes of treadmill walking while interfaced with a novel force-field and a 12-week follow-up period, with five interspersed assessment sessions. Our primary outcome measure was paretic step width modulation, the partial correlation between step width and pelvis displacement (ρ SW ). Secondarily, we quantified swing and stance leg contributions to step modulation, clinical assessments of walking balance and confidence, and real-world falls. Outcomes were analyzed for participants who completed all assessment sessions (n = 44). Only the Perturbing group exhibited significant increases in paretic ρ SW , which were present after 4-weeks of training and sustained through follow-up (t = 2.42–3.17). These changes were due to improved control of paretic swing leg positioning. However, perturbation-induced changes in step modulation were not always significantly greater than those in the Control group, and clinical assessments were similar across intervention groups. Participants in the Perturbing group experienced a lower fall rate than those in the Control group (incidence rate ratio = 0.53), although our small sample size warrants caution. The present results indicate that perturbations can cause sustained modifications of targeted biomechanical characteristics of post-stroke gait, although such changes alone may be insufficient to change more complex clinical assessments.

Background Robots offer an alternative, potentially advantageous method of providing repetitive, high-dosage, and high-intensity training to address the gait impairments caused by stroke. In this study, we compared the effects of the Stride Management Assist (SMA®) System, a new wearable robotic device developed by Honda R&D Corporation, Japan, with functional task specific training (FTST) on spatiotemporal gait parameters in stroke survivors. Methods A single blinded randomized control trial was performed to assess the effect of FTST and task-specific walking training with the SMA® device on spatiotemporal gait parameters. Participants ( n  = 50) were randomly assigned to FTST or SMA. Subjects in both groups received training 3 times per week for 6–8 weeks for a maximum of 18 training sessions. The GAITRite® system was used to collect data on subjects’ spatiotemporal gait characteristics before training (baseline), at mid-training, post-training, and at a 3-month follow-up. Results After training, significant improvements in gait parameters were observed in both training groups compared to baseline, including an increase in velocity and cadence, a decrease in swing time on the impaired side, a decrease in double support time, an increase in stride length on impaired and non-impaired sides, and an increase in step length on impaired and non-impaired sides. No significant differences were observed between training groups; except for SMA group, step length on the impaired side increased significantly during self-selected walking speed trials and spatial asymmetry decreased significantly during fast-velocity walking trials. Conclusions SMA and FTST interventions provided similar, significant improvements in spatiotemporal gait parameters; however, the SMA group showed additional improvements across more parameters at various time points. These results indicate that the SMA® device could be a useful therapeutic tool to improve spatiotemporal parameters and contribute to improved functional mobility in stroke survivors. Further research is needed to determine the feasibility of using this device in a home setting vs a clinic setting, and whether such home use provides continued benefits. Trial registration This study is registered under the title “Development of walk assist device to improve community ambulation” and can be located in clinicaltrials.gov with the study identifier: NCT01994395 .

Freezing of Gait (FOG) is one of the most debilitating gait impairments in Parkinson’s disease (PD), leading to increased fall risk and reduced health-related quality of life. The utility of parkinsonian medications is often limited in the case of FOG and it frequently becomes dopamine resistant. Recent studies have suggested that pre-frontal cortex (PFC) dysfunction contributes to FOG; however, most previous findings provide only indirect evidence. To better understand the role of the PFC, we aimed to investigate the impact of high frequency, deep, repetitive transcranial magnetic stimulation (drTMS) of the medial PFC on FOG and its mediators. Nine patients with advanced PD participated in a randomized, cross-over exploratory study. We applied drTMS over the medial PFC for 16 weeks, with real and sham conditions; each condition included an intensive (i.e., 3 times a week) phase and a maintenance (once a week) phase. Scores on a FOG-provoking test, the motor part of the Unified Parkinson’s Disease Rating Scale, and gait variability significantly improved after real drTMS, but not after the sham condition. Self-report of FOG severity and cognitive scores did not improve. Due to discomfort and pain during treatment, two patients dropped out and the study was halted. These initial findings support the cause-and-effect role of the pre-frontal cortex in FOG among patients with PD. Due to the small sample size, findings should be interpreted cautiously. Further studies are needed to more fully assess the role of the medial PFC in the underlying mechanism of FOG and the possibility of using non-invasive brain stimulation to modify FOG.

Background Stroke is a leading cause of long-term disability, with lower limb dysfunction being a common sequela that significantly impacts patients' mobility and quality of life. Robotic-assisted training has emerged as a promising intervention for gait rehabilitation post-stroke. This study aims to compare the effects of active and passive lower limb robotic training on gait recovery in stroke patients. Methods This randomized controlled trial included 45 stroke patients who were divided into three groups: active mode group, passive mode group, and control group. All participants received standard rehabilitation therapy, while the intervention groups additionally received 20 min of robotic training (active or passive mode) daily for 10 sessions over two weeks. Outcome measures included the Fugl-Meyer Assessment (FMA) for motor function, motor evoked potentials (MEP) for neurophysiological assessment, and functional near-infrared spectroscopy (fNIRS) for brain imaging. Results Both active and passive groups showed significant improvements in FMA scores and MEP measures compared to pre-treatment baselines ( P  < 0.01). The active group exhibited significantly greater FMA score improvements ( P  = 0.02) and MEP amplitudes ( P  < 0.01) than the passive group. Additionally, fNIRS results indicated significantly enhanced brain activation in the affected motor cortex in the active group post-treatment ( F  = 5.82, P  = 0.026), a change not observed in the passive group. These findings underscore the clinical superiority of active robotic training in enhancing motor recovery post-stroke. Conclusion Active mode robotic training is more effective than passive mode training in improving motor function and neurophysiological outcomes in stroke patients. These findings support the preferential use of active mode robotic training in clinical rehabilitation settings for enhancing gait recovery post-stroke. Further research with larger sample sizes and longer follow-up periods is warranted to confirm these results and explore long-term benefits.

Objective: To improve gait and balance in patients with Parkinson’s disease by combining anodal transcranial direct current stimulation with physical training. Design: In a double-blind design, one group (physical training; n = 8) underwent gait and balance training during transcranial direct current stimulation (tDCS; real/sham). Real stimulation consisted of 15 minutes of 2 mA transcranial direct current stimulation over primary motor and premotor cortex. For sham, the current was switched off after 30 seconds. Patients received the opposite stimulation (sham/real) with physical training one week later; the second group (No physical training; n = 8) received stimulation (real/sham) but no training, and also repeated a sequential transcranial direct current stimulation session one week later (sham/real). Setting: Hospital Srio Libanes, Buenos Aires, Argentina. Subjects: Sixteen community-dwelling patients with Parkinson’s disease. Interventions: Transcranial direct current stimulation with and without concomitant physical training. Main measures: Gait velocity (primary gait outcome), stride length, timed 6-minute walk test, Timed Up and Go Test (secondary outcomes), and performance on the pull test (primary balance outcome). Results: Transcranial direct current stimulation with physical training increased gait velocity (mean = 29.5%, SD = 13; p < 0.01) and improved balance (pull test: mean = 50.9%, SD = 37; p = 0.01) compared with transcranial direct current stimulation alone. There was no isolated benefit of transcranial direct current stimulation alone. Although physical training improved gait velocity (mean = 15.5%, SD = 12.3; p = 0.03), these effects were comparatively less than with combined tDCS + physical therapy (p < 0.025). Greater stimulation-related improvements were seen in patients with more advanced disease. Conclusions: Anodal transcranial direct current stimulation during physical training improves gait and balance in patients with Parkinson’s disease. Power calculations revealed that 14 patients per treatment arm (α = 0.05; power = 0.8) are required for a definitive trial.