Vertical locomotion improves horizontal locomotion: effects of climbing on gait and other mobility aspects in Parkinson's disease. A secondary analysis from a randomized controlled trial.

BACKGROUND: In the Climb Up! Head Up! trial, we showed that sport climbing reduces bradykinesia, tremor, and rigidity in mildly to moderately affected participants with Parkinson's disease. This secondary analysis aimed to evaluate the effects of sport climbing on gait and functional mobility in this cohort. METHODS: Climb Up! Head Up! was a 1:1 randomized controlled trial. Forty-eight PD participants (Hoehn and Yahr stage 2-3) either participated in a 12-week, 90-min-per-week sport climbing course (intervention group) or were engaged in regular unsupervised physical activity (control group). Relevant outcome measures for this analysis were extracted from six inertial measurement units placed on the extremities, chest, and lower back, that were worn during supervised gait and functional mobility assessments before and after the intervention. Assessments included normal and fast walking, dual-tasking walking, Timed Up and Go test, Instrumented Stand and Walk test, and Five Times Sit to Stand test. RESULTS: Compared to baseline, climbing improved gait speed during normal walking by 0.09 m/s (p = 0.005) and during fast walking by 0.1 m/s. Climbing also reduced the time spent in the stance phase during fast walking by 0.03 s. Climbing improved the walking speed in the 7-m- Timed Up and Go test by 0.1 m/s (p < 0.001) and the turning speed by 0.39 s (p = 0.052), the speed in the Instrumented Stand and Walk test by 0.1 m/s (p < 0.001), and the speed in the Five Times Sit to Stand test by 2.5 s (p = 0.014). There was no effect of sport climbing on gait speed or gait variables during dual-task walking. CONCLUSIONS: Sport climbing improves gait speed during normal and fast walking, as well as functional mobility in people with Parkinson's disease. Trial registration This study was registered within the U.S. National Library of Medicine (No: NCT04569981, date of registration September 30th, 2020).

Next-generation sequencing and comprehensive data reassessment in 263 adult patients with neuromuscular disorders: insights into the gray zone of molecular diagnoses.

BACKGROUND: Neuromuscular disorders (NMDs) are heterogeneous conditions with a considerable fraction attributed to monogenic defects. Despite the advancements in genomic medicine, many patients remain without a diagnosis. Here, we investigate whether a comprehensive reassessment strategy improves the diagnostic outcomes. METHODS: We analyzed 263 patients with NMD phenotypes that underwent diagnostic exome or genome sequencing at our tertiary referral center between 2015 and 2023. We applied a comprehensive reassessment encompassing variant reclassification, re-phenotyping and NGS data reanalysis. Multivariable logistic regression was performed to identify predictive factors associated with a molecular diagnosis. RESULTS: Initially, a molecular diagnosis was identified in 53 cases (20%), while an additional 23 (9%) had findings of uncertain significance. Following comprehensive reassessment, the diagnostic yield increased to 23%, revealing 44 distinct monogenic etiologies. Reasons for newly obtained molecular diagnoses were variant reclassifications in 7 and NGS data reanalysis in 3 cases including one recently described disease-gene association (DNAJB4). Male sex reduced the odds of receiving a molecular diagnosis (OR 0.42; 95%CI 0.21-0.82), while a positive family history (OR 5.46; 95%CI 2.60-11.76) and a myopathy phenotype (OR 2.72; 95%CI 1.11-7.14) increased the likelihood. 7% were resolved through targeted genetic testing or classified as acquired etiologies. CONCLUSION: Our findings reinforce the use of NGS in NMDs of suspected monogenic origin. We show that a comprehensive reassessment enhances diagnostic accuracy. However, one needs to be aware that genetic diagnoses are often made with uncertainty and can even be downgraded based on new evidence.

Climb up! Head up! Climbing improves posture in Parkinson's disease. A secondary analysis from a randomized controlled trial.

OBJECTIVE: To investigate the effect of sport climbing on a biomechanical marker of axial posture in patients with Parkinson's disease, as well as its association with age, body mass index and health-related quality-of-life outcome measures. DESIGN: Pre-planned secondary analysis of our randomized controlled, semi-blind trial (unblinded patients, blinded assessors) comparing sport climbing to unsupervised exercise. SETTING: Single-centre study conducted at the Department of Neurology of the Medical University of Vienna, Austria. PARTICIPANTS: Forty-eight Parkinson's disease patients (aged 64 ± 8 years, Hoehn & Yahr stage 2-3) were included. INTERVENTION: Sport climbers (n = 24) followed a 12-week, 90 min/week supervised top-rope sport climbing course in an indoor climbing gym. The unsupervised training group (n = 24) independently followed the 'European Physiotherapy Guidelines for Parkinson's Disease' and World Health Organization recommendations for an active lifestyle for 12 weeks. MAIN MEASURES: Posture was assessed with the horizontal distance of the seventh cervical vertebra to the wall at baseline and after the intervention. RESULTS: Participating in the sport climbing group significantly predicted the biomechanical marker of axial posture (P = 0.044). The improvement in the biomechanical marker did not affect the quality of life, depression, fatigue, physical activity or fear of falling. Participants in the sport climbing group showed a significantly decreased horizontal distance of the seventh cervical vertebra to the wall after the intervention (-1.7 cm (95%CI [-2.6, -0.8]). In the unsupervised training group, no difference was found (-0.5 cm; 95%CI -1.3, 0.2]). CONCLUSIONS: We conclude that sport climbing improves a biomechanical marker of axial posture in Parkinson's disease.

Additive Effect of Dopaminergic Medication on Gait Under Single and Dual-Tasking Is Greater Than of Deep Brain Stimulation in Advanced Parkinson Disease With Long-Duration Deep Brain Stimulation.

INTRODUCTION: Patients with advanced Parkinson disease (PD) often experience problems with mobility, including walking under single- (ST) and dual-tasking (DT) conditions. The effects of deep brain stimulation in the subthalamic nucleus (DBS) versus dopaminergic medication (Med) on these conditions are not well investigated. MATERIALS AND METHODS: We used two ST and two DT-gait paradigms to evaluate the effect of DBS and dopaminergic medication on gait parameters in 14 PD patients (mean age 66 ± 8 years) under DBSOFF/MedON, DBSON/MedOFF, and DBSON/MedON conditions. They performed standardized 20-meter walks with convenient and fast speed. To test DT capabilities, they performed a checking-boxes and a subtraction task during fast-paced walking. Quantitative gait analysis was performed using a tri-axial accelerometer (Dynaport, McRoberts, The Netherlands). Dual-task costs (DTC) of gait parameters and secondary task performance were compared intraindividually between DBSOFF/MedON vs DBSON/MedON, and DBSON/MedOFF vs DBSON/MedON to estimate responsiveness. RESULTS: Dopaminergic medication increased gait speed and cadence at convenient speed. It increased cadence and decreased number of steps at fast speed, and improved DTC of cadence during the checking boxes and DTC of cadence and number of steps during the subtraction tasks. DBS only improved DTC of cadence during the checking boxes and DTC of gait speed during the subtraction task. CONCLUSION: Dopaminergic medication showed larger additional effects on temporal gait parameters under ST and DT conditions in advanced PD than DBS. These results, after confirmation in independent studies, should be considered in the medical management of advanced PD patients with gait and DT deficits.

The therapeutic effects of climbing: A systematic review and meta-analysis.

OBJECTIVE: Several recent studies show a growing popularity of therapeutic climbing (TC) for patients with various conditions. This could be an attempt to fill the gap left by traditional exercises that do not always address physical, mental, and social well-being. This review provides an overview of the physical, mental, and social effects and safety aspects of climbing for different indications. LITERATURE SURVEY: A literature search was conducted on July 8, 2020 (update search August 26, 2021). We searched MEDLINE via Ovid, Embase, and PubMed and bibliographies of included studies, and we conducted a manual search. METHODOLOGY: Two independent reviewers evaluated the quality of the studies using appropriate Risk of Bias (RoB) tools, and the level of evidence for each domain was graded. Study characteristics and effectiveness data for TC were extracted and synthesized. Meta-analyses were conducted for the three dimensions (physical/mental/social health), using a random-effects model. SYNTHESIS: A total of 112 publications were reviewed, and 22 full-text articles were assessed regarding the eligibility criteria, of which 18 trials involving 568 patients were included. TC is safe and positively affects physical (e.g., fitness, motor control, movement velocity, dexterity, strength), mental (e.g., depressiveness, somatisation, psychoticism, emotion regulation, body perception, self-esteem, fatigue), and social (e.g., social functioning, trust, communication, sense of responsibility) health for individuals with neurological, orthopedic, psychiatric, and pediatric ailments. The meta-analysis showed a statistically significant improvement in the physical dimension favoring the climbing group. Improvements that were not statistically significant were found for the mental/social dimensions in the climbing group. The heterogeneity of data was moderate/high (social/mental dimension), and for the physical dimension, data were homogenous. CONCLUSIONS: The studies investigating TC outline its positive effects in various patient groups. TC is a safe and effective treatment for improving physical/mental/social well-being. This review is based on the best available evidence; however, significant gaps remain in providing sufficiently strong evidence.

Thrombectomy in basilar artery occlusion.

BACKGROUND AND PURPOSE: The benefit of thrombectomy (TE) for acute ischemic stroke (AIS) in patients suffering basilar artery occlusion (BAO) is still unclear. Our aim was to analyze functional outcome after 3 months in BAO compared to anterior circulation large vessel occlusion (ACLVO) in a nationwide registry. METHODS: Patients enrolled into the Austrian Endostroke Registry from 2013 to 2018 were analyzed. We used propensity score matching to control for imbalances and to compare patients with BAO and ACLVO. The primary outcome was favorable functional outcome after 3 months measured by the modified Rankin Scale (mRS) (0-2). Multivariate models were applied to estimate the effect of localization (BAO vs ACLVO). RESULTS: In total, 2288 patients underwent TE for AIS with proximal vessel occlusion, of these 267 with BAO. Two hundred and sixty-four patients with BAO were matched to 264 patients with ACLVO. Baseline characteristics were well-balanced. The 90-day mortality did not significantly differ between patients with BAO and ACLVO. In a multivariate logistic regression model, we did not detect a significant difference in functional outcome between BAO and ACLVO (odds ratio for favorable outcome defined as mRS = 0-2: 1.19; 95% confidence interval (CI) = 0.78-1.81; p = 0.42). In patients with an onset-to-door-time ⩾270 min, TE of BAO was associated with poor functional outcome defined as mRS 3-6 (odds ratio (OR) = 3.97; 95% CI = 1.32-11.94; p = 0.01) as compared to ACLVO. CONCLUSION: In this study, functional outcome did not differ after TE in patients with BAO and ACLVO overall; however, we detected an association of BAO with poor outcome in patients arriving late.

A randomised controlled trial on effectiveness and feasibility of sport climbing in Parkinson's disease.

Physical activity is of prime importance in non-pharmacological Parkinson's disease (PD) treatment. The current study examines the effectiveness and feasibility of sport climbing in PD patients in a single-centre, randomised controlled, semi-blind trial. A total of 48 PD patients without experience in climbing (average age 64 ± 8 years, Hoehn & Yahr stage 2-3) were assigned either to participate in a 12-week sport climbing course (SC) or to attend an unsupervised physical training group (UT). The primary outcome was the improvement of symptoms on the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS-III). Sport climbing was associated with a significant reduction of the MDS-UPDRS-III (-12.9 points; 95% CI -15.9 to -9.8), while no significant improvement was to be found in the UT (-3.0 points; 95% CI -6.0 to 0.1). Bradykinesia, rigidity and tremor subscales significantly improved in SC, but not in the unsupervised control group. In terms of feasibility, the study showed a 99% adherence of participants to climbing sessions and a drop-out rate of only 8%. No adverse events occurred. This trial provides class III evidence that sport climbing is highly effective and feasible in mildly to moderately affected PD patients.

How COVID-19 will boost remote exercise-based treatment in Parkinson's disease: a narrative review.

The lack of physical exercise during the COVID-19 pandemic-related quarantine measures is challenging, especially for patients with Parkinson's disease (PD). Without regular exercise not only patients, but also nursing staff and physicians soon noticed a deterioration of motor and non-motor symptoms. Reduced functional mobility, increased falls, increased frailty, and decreased quality of life were identified as consequences of increased sedentary behavior. This work overviews the current literature on problems of supplying conventional physiotherapy and the potential of telerehabilitation, allied health services, and patient-initiated exercise for PD patients during the COVID-19 period. We discuss recent studies on approaches that can improve remote provision of exercise to patients, including telerehabilitation, motivational tools, apps, exergaming, and virtual reality (VR) exercise. Additionally, we provide a case report about a 69-year-old PD patient who took part in a 12-week guided climbing course for PD patients prior to the pandemic and found a solution to continue her climbing training independently with an outdoor rope ladder. This case can serve as a best practice example for non-instructed, creative, and patient-initiated exercise in the domestic environment in difficult times, as are the current. Overall, many recent studies on telemedicine, telerehabilitation, and patient-initiated exercises have been published, giving rise to optimism that facilitating remote exercise can help PD patients maintain physical mobility and emotional well-being, even in phases such as the COVID-19 pandemic. The pandemic itself may even boost the need to establish comprehensive and easy-to-do telerehabilitation programs.

The aptamer BT200 blocks von Willebrand factor and platelet function in blood of stroke patients.

The effect of conventional anti-platelet agents is limited in secondary stroke prevention, and their effects are blunted under high shear stress in the presence of increased levels of circulating von Willebrand factor (VWF). VWF is critically involved in thrombus formation at sites of stenotic extracranial/intracranial arteries. A third generation anti-VWF aptamer (BT200) has been generated which could be useful for secondary stroke prevention. To characterize the effects of BT200 in blood of patients with large artery atherosclerosis stroke (LAA). Blood samples were obtained from 33 patients with acute stroke or transient ischemic attack to measure inhibition of VWF activity and VWF-dependent platelet function. Patients who received clopidogrel or dual antiplatelet therapy did not differ in VWF dependent platelet function tests from aspirin treated patients. Of 18 patients receiving clopidogrel with or without aspirin, only 3 had a prolonged collagen adenosine diphosphate closure time, and none of the patients had ristocetin induced aggregation in the target range. BT200 concentration-dependently reduced median VWF activity from 178 to < 3%, ristocetin induced platelet aggregation from 40U to < 10U and prolonged collagen adenosine diphosphate closure times from 93 s to > 300 s. Baseline VWF activity correlated (r = 0.86, p < 0.001) with concentrations needed to reduce VWF activity to < 20% of normal, indicating that BT200 acts in a target concentration-dependent manner. Together with a long half-life supporting once weekly administration, the safety and tolerability observed in an ongoing phase I trial, and the existence of a reversal agent, BT200 is an interesting drug candidate.