Arm Swing while Walking and Running: A New Clinical Feature to Separate Parkinson's Disease from Functional Parkinsonism.

BACKGROUND: Functional parkinsonism is an important differential diagnosis of Parkinson's disease (PD). Based on anecdotal experience, we hypothesized that arm swing while walking and running could differentiate these two conditions, but this assumption has not been previously explored systematically. OBJECTIVES: To examine differences in arm swing while walking and running between patients with PD and functional parkinsonism. METHODS: We analyzed blinded video assessments of arm swing and other gait parameters in patients with asymmetrical PD (n = 81) and functional parkinsonism (n = 8) while walking and running. The groups were matched for age, sex and disease duration. RESULTS: In contrast to those with PD, patients with functional parkinsonism (i) were more likely to have a marked asymmetry in arm swing while walking (5/8 vs. 25/81; P = 0.06), (ii) were less likely to improve arm swing while running with full effort (3/8 vs. 72/81; P < 0.001) and (iii) demonstrated normal passive arm swing even when asymmetry of arm swing was marked during running/walking (6/6 vs. 9/33; P = 0.002). CONCLUSIONS: Assessment of arm swing while walking and running and passive arm swing could be important differentiating clinical features between functional parkinsonism and PD.

Smartphone applications for Movement Disorders: Towards collaboration and re-use.

BACKGROUND: Numerous smartphone and tablet applications (apps) are available to monitor movement disorders, but an overview of their purpose and stage of development is missing. OBJECTIVES: To systematically review published literature and classify smartphone and tablet apps with objective measurement capabilities for the diagnosis, monitoring, assessment, or treatment of movement disorders. METHODS: We systematically searched for publications covering smartphone or tablet apps to monitor movement disorders until November 22nd, 2023. We reviewed the target population, measured domains, purpose, and technology readiness level (TRL) of the proposed app and checked their availability in common app stores. RESULTS: We identified 113 apps. Most apps were developed for Parkinson's disease specifically (n = 82; 73%) or for movement disorders in general (n = 17; 15%). Apps were either designed to momentarily assess symptoms (n = 65; 58%), support treatment (n = 22; 19%), aid in diagnosis (n = 16; 14%), or passively track symptoms (n = 11; 10%). Commonly assessed domains across movement disorders included fine motor skills (n = 34; 30%), gait (n = 36; 32%), and tremor (n = 32; 28%) for the motor domain and cognition (n = 16; 14%) for the non-motor domain. Twenty-six (23%) apps were proof-of-concepts (TRL 1-3), while most apps were tested in a controlled setting (TRL 4-6; n = 63; 56%). Twenty-four apps were tested in their target setting (TRL 7-9) of which 10 were accessible in common app stores or as Android Package. CONCLUSIONS: The development of apps strongly gravitates towards Parkinson's disease and a selection of motor symptoms. Collaboration, re-use and further development of existing apps is encouraged to avoid reinventions of the wheel.

Functional freezing of gait: lessons from compensation.

We highlight a specific and hitherto poorly characterised phenotype of functional gait impairments: functional freezing of gait. Unique to the presented case is the use of compensation strategies, many of which at first sight might appear to hint towards the presence of freezing of gait typical of Parkinson's disease or another form of Parkinsonism. Importantly, however, this patient's compensation strategies involved various inconsistent and incongruent elements, supporting the diagnosis of a functional neurological disorder. Recognising the features of functional freezing also helps to appreciate better the classical manifestations of freezing of gait in Parkinson's disease.

The 'Pants-Sign': A Predictor for Falling in People with Parkinson's Disease?

BACKGROUND: A history of falls is the most established predictor of future falls in people with Parkinson's disease (PD). However, predicting a first fall remains challenging. OBJECTIVE: To assess whether experiencing difficulties putting on pants while standing is a viable predictor of future falling, and specifically a first fall, in persons with PD. We define this 'Pants-sign' as people who resort to putting on their pants only while seated. METHODS: 264 persons with PD were included. Information on the Pants-sign, history of falls, disease severity (MDS-UPDRS part III), freezing of gait (N-FOGQ > 0), cognitive function (MoCA), self-reported disability (Schwab & England scale), health-related quality of life (SF-12), Timed-Up-and-Go, and one-legged stance were determined at baseline and after one-year follow-up. The association between the Pants-sign and future falling was examined by univariate logistic regression analysis. A multivariate step-wise logistic regression with forward selection was employed to identify the strongest associations in the entire cohort and a sub-cohort of people without falls in the year prior to baseline. RESULTS: The Pants-sign was univariably associated with a future fall (OR = 2.406, 95% CI [1.313-4.409], p = 0.004]), but was not an independent predictor in the multivariate logistic regression; predictors were higher MDS-UPDRS part III scores (OR = 1.088, 95% CI [1.056-1.121], p < 0.001] and history of falls (OR = 5.696, 95% CI [2.650-12.243], p≤0.001]. For the sub-cohort of people without falls in the previous year (n = 189), the Pants-sign was not associated with future falls. CONCLUSIONS: The Pants-sign is simple to assess and is associated with future falling in PD but is not an independent predictor.

Predictors and Pathophysiology of Axial Postural Abnormalities in Parkinsonism: A Scoping Review.

Background: Postural abnormalities involving the trunk are referred to as axial postural abnormalities and can be observed in over 20% of patients with Parkinson's disease (PD) and in atypical parkinsonism. These symptoms are highly disabling and frequently associated with back pain and a worse quality of life in PD. Despite their frequency, little is known about the pathophysiology of these symptoms and scant data are reported about their clinical predictors, making it difficult to prompt prevention strategies. Objectives: We conducted a scoping literature review of clinical predictors and pathophysiology of axial postural abnormalities in patients with parkinsonism to identify key concepts, theories and evidence on this topic. Methods: We applied a systematic approach to identify studies, appraise quality of evidence, summarize main findings, and highlight knowledge gaps. Results: Ninety-two articles were reviewed: 25% reported on clinical predictors and 75% on pathophysiology. Most studies identified advanced disease stage and greater motor symptoms severity as independent clinical predictors in both PD and multiple system atrophy. Discrepant pathophysiology data suggested different potential central and peripheral pathogenic mechanisms. Conclusions: The recognition of clinical predictors and pathophysiology of axial postural abnormalities in parkinsonism is far from being elucidated due to literature bias, encompassing different inclusion criteria and measurement tools and heterogeneity of patient samples. Most studies identified advanced disease stage and higher burden of motor symptoms as possible clinical predictors. Pathophysiology data point toward many different (possibly non-mutually exclusive) mechanisms, including dystonia, rigidity, proprioceptive and vestibular impairment, and higher cognitive deficits.

Exploring the levodopa-paradox of freezing of gait in dopaminergic medication-naïve Parkinson's disease populations.

The relationship between dopaminergic treatment and freezing of gait (FOG) in Parkinson's disease (PD) is complex: levodopa is the most effective symptomatic treatment for FOG, but long-term pulsatile levodopa treatment has also been linked to an increase in the occurrence of FOG. This concept, however, continues to be debated. Here, we compared the occurrence of FOG between a levodopa-naive PD cohort and a levodopa-treated cohort. Forty-nine treatment-naive patients and 150 levodopa-treated patients were included. The time since first motor symptoms was at least 5 years. Disease severity was assessed using the MDS-UPDRS part III. Occurrence of FOG was assessed subjectively (new freezing-of-gait-questionnaire) and objectively (rapid turns test and Timed Up-and-Go test). The presence of FOG was compared between the levodopa-treated and levodopa-naive groups using a chi-square test of homogeneity. We also performed a binomial Firth logistic regression with disease duration, disease severity, country of inclusion, location of measurement, and executive function as covariates. Subjective FOG was more common in the levodopa-treated cohort (n = 41, 27%) compared to the levodopa-naive cohort (n = 2, 4%, p < 0.001). The association between FOG and levodopa treatment remained after adjustment for covariates (OR = 6.04, 95%Cl [1.60, 33.44], p = 0.006). Objectively verified FOG was more common in the levodopa-treated cohort (n = 21, 14%) compared to the levodopa-naive cohort (n = 1, 2%, p = 0.02). We found an association between long-term pulsatile levodopa treatment and an increased occurrence of FOG. Future studies should further explore the role of nonphysiological stimulation of dopamine receptors in generating FOG, as a basis for possible prevention studies.

Improved walking capacity after complementary ankle-foot surgery and gait training in a person with an incomplete tetraplegia; a case report.

INTRODUCTION: The population of people with a spinal cord injury (SCI) is changing to a diverse population with an increasing number of incomplete lesions. Often, these individuals have the capacity to walk, but experience disabling gait impairments. CASE PRESENTATION: The course of a 34-year-old male with a chronic incomplete traumatic cervical SCI who initially could walk no more than a few steps with supervision or a wheeled walker is described. He participated in a clinical trial with Targeted Epidural Spinal Stimulation (TESS). After this trial, he was able to walk with a wheeled walker and bilateral orthosis over a distance of 100 meters. Despite these improvements, his main complaints were (1) difficulty to correctly preposition the feet, and (2) pain in his toe and calf muscles. An interdisciplinary approach and the use of structured gait analysis formed the basis for shared decision-making with the team and the patient to perform ankle-foot surgery followed by 2-month gait training with a body weight support system. After this trajectory his walking distance increased to 250 meters, with a wheeled walker; but now without orthosis and with an increased walking speed compared to pre-surgery. Additionally, there was reduction of pain and he experienced no disturbances during sleeping, washing and clothing anymore. DISCUSSION: This case shows that surgical interventions can improve the gait capacity even in case of chronic incomplete SCI. Furthermore, training with a body weight support system after medical-technical interventions is useful to utilize the full potential of these interventions.

The effect of walking with reduced trunk motion on dynamic stability in healthy adults.

BACKGROUND: Most people with Parkinson's disease (PD) walk with a smaller mediolateral base of support (BoS) compared to healthy people, but the underlying mechanisms remain unknown. Reduced trunk motion in people with PD might be related to this narrow-based gait. Here, we study the relationship between trunk motion and narrow-based gait in healthy adults. According to the extrapolated center of mass (XCoM) concept, a decrease in mediolateral XCoM excursion would require a smaller mediolateral BoS to maintain a constant margin of stability (MoS) and remain stable. RESEARCH QUESTION: As proof of principle, we assessed whether walking with reduced trunk motion results in a smaller step width in healthy adults, without altering the mediolateral MoS. METHODS: Fifteen healthy adults walked on a treadmill at preferred comfortable walking speed in two conditions. First, the 'regular walking' condition without any instructions, and second, the 'reduced trunk motion' condition with the instruction: 'Keep your trunk as still as possible'. Treadmill speed was kept the same in the two conditions. Trunk kinematics, step width, mediolateral XCoM excursion and mediolateral MoS were calculated and compared between the two conditions. RESULTS: Walking with the instruction to keep the trunk still significantly reduced trunk kinematics. Walking with reduced trunk motion resulted in significant decreases in step width and mediolateral XCoM excursion, but not in the mediolateral MoS. Furthermore, step width and mediolateral XCoM excursion were strongly correlated during both conditions (r = 0.887 and r = 0.934). SIGNIFICANCE: This study shows that walking with reduced trunk motion leads to a gait pattern with a smaller BoS in healthy adults, without altering the mediolateral MoS. Our findings indicate a strong coupling between CoM motion state and the mediolateral BoS. We expect that people with PD who walk narrow-based, have a similar mediolateral MoS as healthy people, which will be further investigated.

Quantitative assessment of plantar pressure patterns in relation to foot deformities in people with hereditary motor and sensory neuropathies.

BACKGROUND: Hereditary motor and sensory neuropathies (HMSN), also known as Charcot-Marie-Tooth disease, are characterized by affected peripheral nerves. This often results in foot deformities that can be classified into four categories: (1) plantar flexed first metatarsal, neutral hindfoot, (2) plantar flexed first metatarsal, correctable hindfoot varus, (3) plantar flexed first metatarsal, uncorrectable hindfoot varus, and (4) hindfoot valgus. To improve management and for the evaluation of surgical interventions, a quantitative evaluation of foot function is required. The first aim of this study was to provide insight into plantar pressure of people with HMSN in relation to foot deformities. The second aim was to propose a quantitative outcome measure for the evaluation of surgical interventions based on plantar pressure. METHODS: In this historic cohort study, plantar pressure measurements of 52 people with HMSN and 586 healthy controls were evaluated. In addition to the evaluation of complete plantar pressure patterns, root mean square deviations (RMSD) of plantar pressure patterns from the mean plantar pressure pattern of healthy controls were calculated as a measure of abnormality. Furthermore, center of pressure trajectories were calculated to investigate temporal characteristics. Additionally, plantar pressure ratios of the lateral foot, toes, first metatarsal head, second/third metatarsal heads, fifth metatarsal head, and midfoot were calculated to measure overloading of foot areas. RESULTS: Larger RMSD values were found for all foot deformity categories compared to healthy controls (p < 0.001). Evaluation of the complete plantar pressure patterns revealed differences in plantar pressure between people with HMSN and healthy controls underneath the rearfoot, lateral foot, and second/third metatarsal heads. Center of pressure trajectories differed between people with HMSN and healthy controls in the medio-lateral and anterior-posterior direction. The plantar pressure ratios, and especially the fifth metatarsal head pressure ratio, differed between healthy controls and people with HMSN (p < 0.05) and between the four foot deformity categories (p < 0.05). CONCLUSIONS: Spatially and temporally distinct plantar pressure patterns were found for the four foot deformity categories in people with HMSN. We suggest to consider the RMSD in combination with the fifth metatarsal head pressure ratio as outcome measures for the evaluation of surgical interventions in people with HMSN.

Dealing with the heterogeneous presentations of freezing of gait: how reliable are the freezing index and heart rate for freezing detection?

BACKGROUND: Freezing of gait (FOG) is an unpredictable gait arrest that hampers the lives of 40% of people with Parkinson's disease. Because the symptom is heterogeneous in phenotypical presentation (it can present as trembling/shuffling, or akinesia) and manifests during various circumstances (it can be triggered by e.g. turning, passing doors, and dual-tasking), it is particularly difficult to detect with motion sensors. The freezing index (FI) is one of the most frequently used accelerometer-based methods for FOG detection. However, it might not adequately distinguish FOG from voluntary stops, certainly for the akinetic type of FOG. Interestingly, a previous study showed that heart rate signals could distinguish FOG from stopping and turning movements. This study aimed to investigate for which phenotypes and evoking circumstances the FI and heart rate might provide reliable signals for FOG detection. METHODS: Sixteen people with Parkinson's disease and daily freezing completed a gait trajectory designed to provoke FOG including turns, narrow passages, starting, and stopping, with and without a cognitive or motor dual-task. We compared the FI and heart rate of 378 FOG events to baseline levels, and to stopping and normal gait events (i.e. turns and narrow passages without FOG) using mixed-effects models. We specifically evaluated the influence of different types of FOG (trembling vs akinesia) and triggering situations (turning vs narrow passages; no dual-task vs cognitive dual-task vs motor dual-task) on both outcome measures. RESULTS: The FI increased significantly during trembling and akinetic FOG, but increased similarly during stopping and was therefore not significantly different from FOG. In contrast, heart rate change during FOG was for all types and during all triggering situations statistically different from stopping, but not from normal gait events. CONCLUSION: When the power in the locomotion band (0.5-3 Hz) decreases, the FI increases and is unable to specify whether a stop is voluntary or involuntary (i.e. trembling or akinetic FOG). In contrast, the heart rate can reveal whether there is the intention to move, thus distinguishing FOG from stopping. We suggest that the combination of a motion sensor and a heart rate monitor may be promising for future FOG detection.

Modulating arousal to overcome gait impairments in Parkinson's disease: how the noradrenergic system may act as a double-edged sword.

In stressful or anxiety-provoking situations, most people with Parkinson's disease (PD) experience a general worsening of motor symptoms, including their gait impairments. However, a proportion of patients actually report benefits from experiencing-or even purposely inducing-stressful or high-arousal situations. Using data from a large-scale international survey study among 4324 people with PD and gait impairments within the online Fox Insight (USA) and ParkinsonNEXT (NL) cohorts, we demonstrate that individuals with PD deploy an array of mental state alteration strategies to cope with their gait impairment. Crucially, these strategies differ along an axis of arousal-some act to heighten, whereas others diminish, overall sympathetic tone. Together, our observations suggest that arousal may act as a double-edged sword for gait control in PD. We propose a theoretical, neurobiological framework to explain why heightened arousal can have detrimental effects on the occurrence and severity of gait impairments in some individuals, while alleviating them in others. Specifically, we postulate that this seemingly contradictory phenomenon is explained by the inherent features of the ascending arousal system: namely, that arousal is related to task performance by an inverted u-shaped curve (the so-called Yerkes and Dodson relationship). We propose that the noradrenergic locus coeruleus plays an important role in modulating PD symptom severity and expression, by regulating arousal and by mediating network-level functional integration across the brain. The ability of the locus coeruleus to facilitate dynamic 'cross-talk' between distinct, otherwise largely segregated brain regions may facilitate the necessary cerebral compensation for gait impairments in PD. In the presence of suboptimal arousal, compensatory networks may be too segregated to allow for adequate compensation. Conversely, with supraoptimal arousal, increased cross-talk between competing inputs of these complementary networks may emerge and become dysfunctional. Because the locus coeruleus degenerates with disease progression, finetuning of this delicate balance becomes increasingly difficult, heightening the need for mental strategies to self-modulate arousal and facilitate shifting from a sub- or supraoptimal state of arousal to improve gait performance. Recognition of this underlying mechanism emphasises the importance of PD-specific rehabilitation strategies to alleviate gait disability.

Time trends in demographic characteristics of participants and outcome measures in Parkinson's disease research: A 19-year single-center experience.

Background: Females, people with young-onset PD and older individuals, and non-white populations are historically underrepresented in clinical Parkinson's disease (PD) research. Furthermore, research traditionally focused predominantly on motor symptoms of PD. Including a representative and diverse group of people with PD and also studying non-motor symptoms is warranted to better understand heterogeneity in PD and to generalize research findings. Objective: This project aimed to determine whether, within a consecutive series of PD studies performed within a single center in the Netherlands: (1) the proportion of included females, mean age and proportion of native Dutch people changed over time; and 2) reports of the ethnicity of participants and the proportion of studies with non-motor outcomes changed over time. Methods: Characteristics of participants and non-motor outcomes were analyzed using a unique dataset of summary statistics of studies with a large number of participants conducted at a single center during a 19-year period (2003-2021). Results: Results indicate no relationship between calendar time and proportion of females (mean 39 %), mean age (66 years), proportion of studies that reported ethnicity, and proportion of native Dutch people in studies (range 97-100 %). The proportion of participants in whom non-motor symptoms were assessed increased, but this difference was consistent with chance. Conclusion: Study participants in this center reflect the PD population in the Netherlands in terms of sex, but older individuals and non-native Dutch individuals are under-represented. We have still a lot to do in ensuring adequate representation and diversity in PD patients within our research.

Gait-Adaptability Training in People With Hereditary Spastic Paraplegia: A Randomized Clinical Trial.

BACKGROUND AND OBJECTIVES: In people with hereditary spastic paraplegia (HSP), reduced gait adaptability is common and disabling. Gait impairments result from lower extremity spasticity, muscle weakness, and impaired proprioception. The aim of this study was to assess the efficacy of a 5-week gait-adaptability training in people with pure HSP. METHOD: We conducted a randomized clinical trial with a cross-over design for the control group, and a 15-week follow-up period after training. Thirty-six people with pure HSP were randomized to 5 weeks of (i) gait-adaptability training (10 hours of C-Mill training-a treadmill equipped with augmented reality) or (ii) a waiting-list control period followed by 5 weeks gait-adaptability training. Both groups continued to receive usual care. The primary outcome was the obstacle subtask of the Emory Functional Ambulation Profile. Secondary outcome measures consisted of clinical balance and gait assessments, fall rates, and spatiotemporal gait parameters assessed via 3D motion analysis. RESULTS: The gait-adaptability training group (n = 18) did not significantly decrease the time required to perform the obstacle subtask compared to the waiting-list control group (n = 18) after adjusting for baseline differences (mean: -0.33 seconds, 95% CI: -1.3, 0.6). Similar, non-significant results were found for most secondary outcomes. After merging both groups (n = 36), the required time to perform the obstacle subtask significantly decreased by 1.3 seconds (95% CI: -2.1, -0.4) directly following 5 weeks of gait-adaptability training, and this effect was retained at the 15-week follow-up. CONCLUSIONS: We found insufficient evidence to conclude that 5 weeks of gait-adaptability training leads to greater improvement of gait adaptability in people with pure HSP.

Comparison of ground reaction force and marker-based methods to estimate mediolateral center of mass displacement and margins of stability during walking.

Dynamic balance control during human walking can be described by the distance between the mediolateral (ML) extrapolated center of mass (XCoM) position and the base of support, the margin of stability (MoS). The ML center of mass (CoM) position during treadmill walking can be estimated based on kinematic data (marker-based method) and a combination of ground reaction forces and center of pressure positions (GRF-based method). Here, we compare a GRF-based method with a full-body marker-based method for estimating the ML CoM, ML XCoM and ML MoS. Fifteen healthy adults walked on a dual-belt treadmill at comfortable walking speed for three minutes. Kinetic and kinematic data were collected and analyzed using a GRF-based and marker-based method to compare the ML CoM, ML XCoM and ML MoS. High correlation coefficients (r > 0.98) and small differences (Root Mean Square Difference < 0.0072 m) in ML CoM and ML XCoM were found between the GRF-based and marker-based methods. The GRF-based method resulted in larger ML XCoM excursion (0.0118 ± 0.0074 m) and smaller ML MoS values (0.0062 ± 0.0028 m) than the marker-based method, but these differences were consistent across participants. In conclusion, the GRF-based method is a valid method to determine the ML CoM, XCoM and MoS. One should be aware of higher ML XCoM and smaller ML MoS values in the GRF-based method when comparing absolute values between studies. The GRF-based method strongly reduces measurement times and can be used to provide real-time CoM-CoP feedback during treadmill gait training.