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.

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.

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.

Evaluation of Compensation Strategies for Gait Impairment in Patients With Parkinson Disease.

BACKGROUND AND OBJECTIVES: Compensation strategies are essential in Parkinson's disease (PD) gait rehabilitation. However, besides external cueing, these strategies have rarely been investigated systematically. We aimed to: (1) establish the patients' perspective on the efficacy and usability of five different compensation strategies; (2) quantify the efficacy of these strategies on spatiotemporal gait parameters; and (3) explore associations between the effects of specific strategies and patient characteristics. METHODS: We recruited persons with PD and self-reported disabling gait impairments for this lab-based, within-subject study. Clinimetrics included: questionnaires (NFOG-Q, VMIQ-2, GMSI), cognitive assessments (ANT, MoCA, Brixton), and physical examinations (MDS-UPDRS III, Mini-BEST, tandem gait, rapid turns test). Gait assessment consisted of six 3-minute trials of continuous walking around a 6-meter walkway. Trials comprised: 1) baseline gait; 2) external cueing; 3) internal cueing; 4) action observation; 5) motor imagery; and 6) adopting a new walking pattern. Spatiotemporal gait parameters were acquired using 3D motion capture analysis. Strategy efficacy was determined by the change in gait variability compared to baseline gait. Associated patient characteristics were explored using regression analyses. RESULTS: 101 participants (50 men; median[range] age: 66[47-91] years) were included. The effects of the different strategies varied greatly among participants. While participants with higher baseline variability showed larger improvements using compensation strategies, participants without freezing of gait, with lower MDS-UPDRS III scores, higher balance capacity and better performance in orienting attention, also showed greater improvements in gait variability. Higher MoCA scores were associated with greater efficacy of external cueing. DISCUSSION: Our findings support the use of compensation strategies in gait rehabilitation for PD, but highlight the importance of a personalized approach. Even patients with high gait variability are able to improve through the application of compensation strategies, but certain levels of cognitive and functional reserve seem necessary to optimally benefit from them. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that gait compensation strategies can be effective in persons with PD.

A Practical Guide to the Evaluation of Compensation Strategies for Gait Impairment in Parkinson's Disease.

The application of compensation strategies is an important element of gait rehabilitation in persons with Parkinson's disease. While the efficacy of these strategies is generally very high, a tailored, personalized approach is necessary to determine the optimal strategies for every patient. We propose a straightforward, practical guide to the evaluation of compensation strategies in clinical practice: considering the primary gait target(s) to optimize functional mobility, the context in which the strategies will be employed in daily life, and patient-specific personal preferences. Furthermore, we introduce www.walkingwithparkinson.com as a resource on the available compensation strategies, developed specifically for persons with Parkinson's disease, their carers, and (allied) healthcare professionals.

Cortical Correlates of Gait Compensation Strategies in Parkinson Disease.

OBJECTIVE: Gait impairment in persons with Parkinson disease is common and debilitating. Compensation strategies (eg, external cues) are an essential part of rehabilitation, but their underlying mechanisms remain unclear. Using electroencephalography (EEG), we explored the cortical correlates of 3 categories of strategies: external cueing, internal cueing, and action observation. METHODS: Eighteen participants with Parkinson disease and gait impairment were included. We recorded 126-channel EEG during both stance and gait on a treadmill under 4 conditions: (1) uncued, (2) external cueing (listening to a metronome), (3) internal cueing (silent rhythmic counting), and (4) action observation (observing another person walking). To control for the effects of sensory processing of the cues, we computed relative power changes as the difference in power spectral density between walking and standing for each condition. RESULTS: Relative to uncued gait, the use of all 3 compensation strategies induced a decrease of beta band activity in sensorimotor areas, indicative of increased cortical activation. Parieto-occipital alpha band activity decreased with external and internal cueing, and increased with action observation. Only internal cueing induced a change in frontal cortical activation, showing a decrease of beta band activity compared to uncued gait. INTERPRETATION: The application of compensation strategies resulted in changed cortical activity compared to uncued gait, which could not be solely attributed to sensory processing of the cueing modality. Our findings suggest there are multiple routes to control gait, and different compensation strategies seem to rely on different cortical mechanisms to achieve enhanced central motor activation in persons with Parkinson disease. ANN NEUROL 2022;91:329-341.

Perception and Use of Compensation Strategies for Gait Impairment by Persons With Parkinson Disease.

BACKGROUND: Gait impairments are common and disabling in Parkinson's disease (PD). Applying compensation strategies helps to overcome these gait deficits. Clinical observations suggest that the efficacy of different compensation strategies varies depending on both individual patient characteristics and the context in which the strategies are applied. This has never been investigated systematically, hampering the ability of clinicians to provide a more personalized approach to gait rehabilitation. OBJECTIVE: We had three aims: (1) to evaluate patients' awareness and actual use of compensation categories for gait impairments in PD; (2) to investigate the patient-rated efficacy of the various compensation strategies, and whether this efficacy depends on the context in which the strategies are applied; and (3) to explore differences in the efficacy between subgroups based on sex, age, disease duration, freezing status, and ability to perform a dual task. METHODS: A survey was conducted among 4,324 adults with PD and self-reported disabling gait impairments. RESULTS: The main findings are: (1) compensation strategies for gait impairments are commonly used by persons with PD, but their awareness of the full spectrum of available strategies is limited; (2) the patient-rated efficacy of compensation strategies is high, but varies depending on the context in which they are applied; and (3) compensation strategies are useful for all types of PD patients, but the efficacy of the different strategies varies per person. CONCLUSIONS: The choice of compensation strategies for gait impairment in PD should be tailored to the individual patient, as well as to the context in which the strategy needs to be applied. CLASSIFICATION OF EVIDENCE: This data provides Class IV evidence that compensation strategies are an effective treatment for gait impairment in Parkinson's disease patients with gait impairment.

Towards subgroup-specific risk estimates: A meta-analysis of longitudinal studies on olfactory dysfunction and risk of Parkinson's disease.

BACKGROUND: Interest has risen in identifying individuals at high risk of incident Parkinson's disease (PD) to facilitate inclusion in neuroprotective treatment trials. Current risk estimates of prodromal markers are based on aggregated data of an entire population, but this approach disregards differences in risk estimates by subgroups of a population. In this proof of concept, we determine subgroup-specific risk estimates of olfactory dysfunction for incident PD. METHODS: PubMed, EMBASE and Cochrane were searched for prospective studies investigating the association between olfactory dysfunction and incident PD. Random-effects meta-analysis, subgroup analyses and meta-regression were performed to investigate general and subgroup risk estimates. RESULTS: Individuals with odor identification dysfunction seemed to be at greater risk of incident PD compared to controls without olfactory dysfunction (OR = 4.18; 95%CI [2.47-7.07]). Risk estimates were higher in studies that included higher percentages of women (regression slope ß = 0.053 increase in log odds ratio per 1% increase 1%, p = 0.0006), increased with mean study age (ß = 0.21 per one year increase; p = 0.005) and in REM-sleep behavior disorder cohorts (ß = 1.95; p = 0.03). Furthermore, the association between olfactory dysfunction and incident PD was most distinct in studies with shorter follow-up duration (ß = -0.56; p = 0.0047). CONCLUSION: The presence of olfactory dysfunction conveys a considerably elevated risk of incident PD, likely more in studies with a higher proportion of women, older individuals or short follow-up duration. Individual patient data are warranted to confirm these findings and to yield subgroup-specific risk estimates of other common markers to refine prodromal PD criteria.

Sex and freezing of gait in Parkinson's disease: a systematic review and meta-analysis.

OBJECTIVE: It is unknown how sex affects the prevalence of freezing of gait (FOG). We conducted a systematic review and meta-analysis to establish the sex-specific prevalence of FOG in persons with Parkinson's disease (PD). In addition, we investigated whether men and women were represented accurately in intervention trials targeting FOG. METHODS: We queried the EMBASE and PubMed databases and identified 2637 articles. Of these, 16 epidemiological studies were included in the meta-analysis, and 51 intervention studies were included in the comparative analysis. RESULTS: In total, 5702 persons were included in the final meta-analysis of epidemiological studies. The pooled estimate of overall FOG prevalence was 43% [95% CI 33-53%]. We found no difference in FOG prevalence between men [44% (34-54%)] and women [42% (31-52%)] with PD. However, women were markedly underrepresented in intervention trials targeting FOG, with an average proportion of only 29.6% of women in trial populations. The percentage of women included in trials was similar across intervention types but differed greatly across geographical regions. CONCLUSION: Sex is not a predictor of FOG. This could aid clinicians in counseling persons with PD about FOG. Importantly, a global effort is needed to include more women into clinical trials. Given the skewed distribution of men and women included in intervention trials targeting FOG, caution might be warranted when extrapolating results from FOG trials to women.

Perceptions of Compensation Strategies for Gait Impairments in Parkinson's Disease: A Survey Among 320 Healthcare Professionals.

Compensation strategies are an essential part of managing gait impairments in people with Parkinson's disease (PD). We conducted an online survey among 320 healthcare professionals with specific expertise in PD management, to evaluate their knowledge of compensation strategies for gait impairments in people with PD, and whether they applied these in daily practice. Only 35% of professionals was aware of all categories of compensation strategies. Importantly, just 23% actually applied all seven available categories of strategies when treating people with PD in clinical practice. We discuss the clinical implications, and provide recommendations to overcome this knowledge gap.

Why People With Parkinson's Disease Experience Near-Drowning-and How to Prevent It.

View Supplementary Video S1 View Supplementary Video S2 View Supplementary Video S3.

Multidisciplinary Care to Optimize Functional Mobility in Parkinson Disease.

This review elaborates on multidisciplinary care for persons living with Parkinson disease by using gait and balance impairments as an example of a treatable target that typically necessitates an integrated approach by a range of different and complementary professional disciplines. Using the International Classification of Functioning, Disability, and Health model as a framework, the authors discuss the assessment and multidisciplinary management of reduced functional mobility due to gait and balance impairments. By doing so, they highlight the complex interplay between motor and nonmotor symptoms, and their influence on rehabilitation. They outline how multidisciplinary care for Parkinson disease can be organized.

Two new cases of mitochondrial myopathy with exercise intolerance, hyperlactatemia and cardiomyopathy, caused by recessive SLC25A4 mutations.

We report the clinical, morphological and molecular features of two patients with autosomal recessive SLC25A4 (ANT1) gene mutations. Furthermore, all previously published cases are reviewed to identify valuable features for future diagnosis. Patients present a common phenotype with exercise intolerance, hyperlactatemia, and hypertrophic cardiomyopathy. Muscle biopsies show wide sub-sarcolemmal mitochondrial aggregates, and increased activities of all respiratory chain complexes. The phenotype of recessive SLC25A4 (ANT1) mutations although rare, is homogenous and easily recognizable and could help orientate the molecular analysis in adults with exercise intolerance associated with hyperlactatemia.