Effects of overground gait training assisted by a wearable exoskeleton in patients with Parkinson's disease.

BACKGROUND: In the recent past, wearable devices have been used for gait rehabilitation in patients with Parkinson's disease. The objective of this paper is to analyze the outcome of a wearable hip orthosis whose assistance adapts in real time to the patient's gait kinematics via adaptive oscillators. In particular, this study focuses on a metric characterizing natural gait variability, i.e., the level of long-range autocorrelations (LRA) in series of stride durations. METHODS: Eight patients with Parkinson's disease (Hoehn and Yahr stages 1[Formula: see text]2.5) performed overground gait training three times per week for four consecutive weeks, assisted by a wearable hip orthosis. Gait was assessed based on performance metrics such as the hip range of motion, speed, stride length and duration, and the level of LRA in inter-stride time series assessed using the Adaptive Fractal Analysis. These metrics were measured before, directly after, and 1 month after training. RESULTS: After training, patients increased their hip range of motion, their gait speed and stride length, and decreased their stride duration. These improvements were maintained 1 month after training. Regarding long-range autocorrelations, the population's behavior was standardized towards a metric closer to the one of healthy individuals after training, but with no retention after 1 month. CONCLUSION: This study showed that an overground gait training with adaptive robotic assistance has the potential to improve key gait metrics that are typically affected by Parkinson's disease and that lead to higher prevalence of fall. TRIAL REGISTRATION: ClinicalTrials.gov Identifer NCT04314973. Registered on 11 April 2020.

Case report: Motor neuron disease phenotype associated with symptomatic copper deficiency: Challenging diagnosis and treatment.

Copper deficiency is an acquired condition that can lead to neurologic dysfunctions, such as myelopathy, motor neuron impairment, polyneuropathy, cognitive impairment, and optic nerve neuropathy. Associated biological findings are low serum copper and ceruloplasmin levels with low copper urinary excretion. We report the case of a previously healthy 59-year-old man who presented a complex neurological picture starting with symptoms and radiological signs consistent with degenerative myelopathy in the presence of persisting low serum copper and ceruloplasmin despite oral and intravenous copper supplementation. Over time, his symptoms evolved into a motor neuron disease evocating an amyotrophic lateral sclerosis (ALS) phenotype. The potential role of copper deficiency is discussed, together with the difficulties in biomonitoring copper supplementation.

Immersive Virtual Reality to Restore Natural Long-Range Autocorrelations in Parkinson's Disease Patients' Gait During Treadmill Walking.

Effects of treadmill walking on Parkinson's disease (PD) patients' spatiotemporal gait parameters and stride duration variability, in terms of magnitude [coefficient of variation (CV)] and temporal organization [long range autocorrelations (LRA)], are known. Conversely, effects on PD gait of adding an optic flow during treadmill walking using a virtual reality headset, to get closer to an ecological walk, is unknown. This pilot study aimed to compare PD gait during three conditions: Overground Walking (OW), Treadmill Walking (TW), and immersive Virtual Reality on Treadmill Walking (iVRTW). Ten PD patients completed the three conditions at a comfortable speed. iVRTW consisted in walking at the same speed as TW while wearing a virtual reality headset reproducing an optic flow. Gait parameters assessed were: speed, step length, cadence, magnitude (CV) and temporal organization (evenly spaced averaged Detrended Fluctuation Analysis, α exponent) of stride duration variability. Motion sickness was assessed after TW and iVRTW using the Simulator Sickness Questionnaire (SSQ). Step length was greater (p = 0.008) and cadence lower (p = 0.009) during iVRTW compared to TW while CV was similar (p = 0.177). α exponent was similar during OW (0.77 ± 0.07) and iVRTW (0.76 ± 0.09) (p = 0.553). During TW, α exponent (0.85 ± 0.07) was higher than during OW (p = 0.039) and iVRTW (p = 0.016). SSQ was similar between TW and iVRTW (p = 0.809). iVRTW is tolerable, could optimize TW effects on spatiotemporal parameters while not increasing CV in PD. Furthermore, iVRTW could help to capture the natural LRA of PD gait in laboratory settings and could potentially be a challenging second step in PD gait rehabilitation.

Influence of Autocorrelated Rhythmic Auditory Stimulations on Parkinson's Disease Gait Variability: Comparison With Other Auditory Rhythm Variabilities and Perspectives.

Parkinson's Disease patients suffer from gait impairments such as reduced gait speed, shortened step length, and deterioration of the temporal organization of stride duration variability (i.e., breakdown in Long-Range Autocorrelations). The aim of this study was to compare the effects on Parkinson's Disease patients' gait of three Rhythmic Auditory Stimulations (RAS), each structured with a different rhythm variability (isochronous, random, and autocorrelated). Nine Parkinson's Disease patients performed four walking conditions of 10-15 min each: Control Condition (CC), Isochronous RAS (IRAS), Random RAS (RRAS), and Autocorrelated RAS (ARAS). Accelerometers were used to assess gait speed, cadence, step length, temporal organization (i.e., Long-Range Autocorrelations computation), and magnitude (i.e., coefficient of variation) of stride duration variability on 512 gait cycles. Long-Range Autocorrelations were assessed using the evenly spaced averaged Detrended Fluctuation Analysis (α-DFA exponent). Spatiotemporal gait parameters and coefficient of variation were not modified by the RAS. Long-Range Autocorrelations were present in all patients during CC and ARAS although all RAS conditions altered them. The α-DFA exponents were significantly lower during IRAS and RRAS than during CC, exhibiting anti-correlations during IRAS in seven patients. α-DFA during ARAS was the closest to the α-DFA during CC and within normative data of healthy subjects. In conclusion, Isochronous RAS modify patients' Long-Range Autocorrelations and the use of Autocorrelated RAS allows to maintain an acceptable level of Long-Range Autocorrelations for Parkinson's Disease patients' gait.

Effects of Fampridine in People with Multiple Sclerosis: A Systematic Review and Meta-analysis.

BACKGROUND: Prolonged-release (PR) fampridine is a potassium channel blocker used as a symptomatic treatment for walking disability in patients with multiple sclerosis (MS). Its clinical effects in such patients have not been systematically reviewed, and may be more wide-ranging than expected. OBJECTIVES: To summarize the evidence on the effects of PR fampridine in patients with MS. METHODS: A systematic search of Pubmed, Scopus (including EMBASE), and PsycINFO (completed in 01/2019) was carried out to identify randomized controlled trials (RCT) that compared PR fampridine to placebo. When appropriate, data were pooled using a random-effects model, and standardized mean differences (SMD) were computed. Study quality was assessed using the Downs and Black checklist. PRISMA guidelines were followed. All retrieved functional outcomes were categorized according to the International Classification of Functioning, Disability and Health (ICF). RESULTS: A total of 706 articles were screened for inclusion. Twenty RCTs involving 2616 patients met the eligibility criteria. Most studies were of good-to-excellent quality. PR fampridine administration resulted in significant benefits in relation to walking short distances (SMD: 1.23 (95% IC 0.65-1.81)) and perceived walking capacity (0.64 (0.27-1.02)). Its effects on muscle strength and middle-distance walking were not significant (0.53 (- 0.04 to 1.10) and 0.31 (- 0.18 to 0.80), respectively). No effect on higher-level cognitive functions (- 0.07 (- 0.58 to 0.45)) or hand and arm use (0.16 (- 0.33 to 0.64)) was observed. Individual studies reported effects on other outcomes across the ICF domains. CONCLUSIONS: There is strong evidence that PR fampridine exerts strong effects on the ability to walk short distances and on perceived walking capacity. Other effects of PR fampridine according to the ICF are possible but still unclear.

Locus Coeruleus atrophy doesn't relate to fatigue in Parkinson's disease.

Fatigue is a frequent complaint among healthy population and one of the earliest and most debilitating symptoms in Parkinson's disease (PD). Earlier studies have examined the role of dopamine and serotonin in pathogenesis of fatigue, but the plausible role of noradrenalin (NA) remains underexplored. We investigated the relationship between fatigue in Parkinsonian patients and the extent of degeneration of Locus Coeruleus (LC), the main source of NA in the brain. We quantified LC and Substantia Nigra (SN) atrophy using neuromelanin-sensitive imaging, analyzed with a novel, fully automated algorithm. We also assessed patients' fatigue, depression, sleep disturbance and vigilance. We found that LC degeneration correlated with the levels of depression and vigilance but not with fatigue, while fatigue correlated weakly with atrophy of SN. These results indicate that LC degeneration in Parkinson's disease is unlikely to cause fatigue, but may be involved in mood and vigilance alterations.

Gait Complexity and Regularity Are Differently Modulated by Treadmill Walking in Parkinson's Disease and Healthy Population.

Variability raises considerable interest as a promising and sensitive marker of dysfunction in physiology, in particular in neurosciences. Both internally (e.g., pathology) and/or externally (e.g., environment) generated perturbations and the neuro-mechanical responses to them contribute to the fluctuating dynamics of locomotion. Defective internal gait control in Parkinson's disease (PD), resulting in typical timing gait disorders, is characterized by the breakdown of the temporal organization of stride duration variability. Influence of external cue on gait pattern could be detrimental or advantageous depending on situations (healthy or pathological gait pattern, respectively). As well as being an interesting rehabilitative approach in PD, treadmills are usually implemented in laboratory settings to perform instrumented gait analysis including gait variability assessment. However, possibly acting as an external pacemaker, treadmill could modulate the temporal organization of gait variability of PD patients which could invalidate any gait variability assessment. This study aimed to investigate the immediate influence of treadmill walking (TW) on the temporal organization of stride duration variability in PD and healthy population. Here, we analyzed the gait pattern of 20 PD patients and 15 healthy age-matched subjects walking on overground and on a motorized-treadmill (randomized order) at a self-selected speed. The temporal organization and regularity of time series of walking were assessed on 512 consecutive strides and assessed by the application of non-linear mathematical methods (i.e., the detrended fluctuation analysis and power spectral density; and sample entropy, for the temporal organization and regularity of gait variability, respectively). A more temporally organized and regular gait pattern seems to emerge from TW in PD while no influence was observed on healthy gait pattern. Treadmill could afford the necessary framework to regulate gait rhythmicity in PD. Overall, the results support the hypothesis of a greater dependence to regulatory inputs as an explanatory factor of treadmill influence observed in PD. Also, since treadmill misrepresents the gait as more healthy than it is, the present findings underline that gait analysis using treadmill devices should be cautiously considered in PD and especially for gait variability assessment in gait lab.

Does Nordic Walking restore the temporal organization of gait variability in Parkinson's disease?

BACKGROUND: Gait disorders of Parkinson's disease (PD) are characterized by the breakdown of the temporal organization of stride duration variability that was tightly associated to dynamic instability in PD. Activating the upper body during walking, Nordic Walking (NW) may be used as an external cueing to improve spatiotemporal parameters of gait, such as stride length or gait variability, in PD. The aim of this study was to evaluate the beneficial effects of NW on temporal organization of gait variability and spatiotemporal gait variables in PD. METHODS: Fourteen mild to moderate PD participants and ten age-matched healthy subjects performed 2 × 12 min overground walking sessions (with and without pole in a randomized order) at a comfortable speed. Gait speed, cadence, step length and temporal organization (i.e. long-range autocorrelations; LRA) of stride duration variability were studied on 512 consecutive gait cycles using a unidimensional accelerometer placed on the malleola of the most affected side in PD patients and of the dominant side in healthy controls. The presence of LRA was determined using the Rescaled Range Analysis (Hurst exponent) and the Power Spectral Density (α exponent). To assess NW and disease influences on gait, paired t-tests, Z-score and a two-way (pathological condition x walking condition) ANOVA repeated measure were used. RESULTS: Leading to significant improvement of LRA, NW enhances step length and reduces gait cadence without any change in gait speed in PD. Interestingly, LRA and step length collected from the NW session are similar to that of the healthy population. CONCLUSION: This cross-sectional controlled study demonstrates that NW may constitute a powerful way to struggle against the randomness of PD gait and the typical gait hypokinesia. Involving a voluntary intersegmental coordination, such improvement could also be due to the upper body rhythmic movements acting as rhythmical external cue to bypass their defective basal ganglia circuitries. ETHICS COMMITTEE'S REFERENCE NUMBER: B403201318916 TRIAL REGISTRATION: NCT02419768.

Temporal organization of stride duration variability as a marker of gait instability in Parkinson's disease.

OBJECTIVE: Gait instability and fall risk are major concerns in Parkinson's disease. This study shows that the temporal organization of gait variability can represent a marker of gait instability that complements standard assessment of motor deficits in Parkinson's disease. METHODS: Temporal organization (long-range autocorrelation; LRA) of stride duration variability, collected from 20 persons with Parkinson's disease walking overground at a comfortable speed, was studied. The presence of LRA was based on the scaling properties of the series variability and the shape of the power spectral density. Simultaneously, measures of neurological impairment (MDS-UPDRS), balance (BESTest), and balance confidence (ABC-Scale) were collected. To precisely identify the relationship between LRA and functional measures, correlation coefficients were applied. RESULTS: Degradation of LRA was strongly correlated with other clinical scores, in such a way that the temporal organization of gait variability was more random for patients presenting with greater motor impairments. Importantly, these measures were relatively independent of age, and gait speed, thus they can be applied to a wide clinical population.  Conclusion: The findings of this study emphasize that temporal organization of gait variability is related to degree of functional impairment in Parkinson's disease. LRA may thus be regarded as an objective and quantitative measure of gait stability for both clinical practice and research.

Variability of human gait: effect of backward walking and dual-tasking on the presence of long-range autocorrelations.

Information from the central and peripheral nervous systems is continuously integrated to produce a stable gait pattern. However, stride duration fluctuates in a complex manner in healthy subjects, exhibiting long-range autocorrelations that can span over hundreds of consecutive strides. The present study was conducted to explore the mechanisms controlling the long-term fluctuation dynamics of gait. In the first part of the study, stride duration variability was evaluated on a treadmill during forward (FW) and backward walking (BW). Despite the modification of the biomechanical constraints imposed on the locomotor system, the characteristics of the long-range autocorrelations remained unchanged in both modes of locomotion (FW: H = 0.79 ± 0.04 and α = 0.58 ± 0.13; BW: H = 0.79 ± 0.11 and α = 0.53 ± 0.25). In the second part of the study, stride duration variability was assessed while the subjects were performing a dual-task paradigm that combined gait and mental calculation. The long-term variability of stride duration was similar during usual walking (H = 0.80 ± 0.06 and α = 0.57 ± 0.13) and in dual-tasking (H = 0.77 ± 0.06 and α = 0.52 ± 0.16), whereas walking altered the performance of the cognitive task. Hence, the biomechanical and cognitive interferences imposed in the present study were not sufficient to induce a modification of the long-range autocorrelations highlighted in walking variability. These observations underline the robustness of the long-range autocorrelations.

Dynamics of revolution time variability in cycling pattern: voluntary intent can alter the long-range autocorrelations.

Long-range dependency has been found in most rhythmic motor signals. The origin of this property is unknown and largely debated. There is a controversy on the influence of voluntary control induced by requiring a pre-determined pace such as asking subjects to step to a metronome. We studied the cycle duration variability of 15 men pedaling on an ergometer at free pace and at an imposed pace (60 rpm). Revolution time was determined based on accelerometer signals (sample frequency 512 Hz). Revolution time variability was assessed by coefficient of variation (CV). The presence of long-range autocorrelations was based on scaling properties of the series variability (Hurst exponent) and the shape of the power spectral density (α exponent). Mean revolution time was significantly lower at freely chosen cadence, while values of CV were similar between both sessions. Long-range autocorrelations were highlighted in all series of cycling patterns. However, Hurst and α exponents were significantly lower at imposed cadence. This study demonstrates the presence of long-range autocorrelations during cycling and that voluntary intent can modulate the interdependency between consecutive cycles. Therefore, cycling may constitute a powerful paradigm to investigate the influence of central control mechanisms on the long-range interdependency characterizing rhythmic motor tasks.