Freezing Of Gait In Parkinson's Disease Research Articles

Alprazolam Reduces Freezing of Gait (FOG) and Improves FOG-Related Gait Deficiencies.

Freezing of gait (FOG) is an intractable motor symptom in Parkinson's disease (PD) that increases fall risk and impairs the quality of life. FOG has been associated with anxiety, with experimental support for the notion that anxiety itself provokes FOG. We investigated the effect of acute anxiety reduction via alprazolam on FOG in PD. In ten patients with PD, FOG, and normal cognition, we administered 0.25 mg alprazolam in one session and placebo in another, in counterbalanced order. At each session, on separate days, patients walked on a pressure-sensitive walkway. Using Oculus Rift virtual-reality goggles, patients walked along a plank that appeared to be (a) level with the floor, in the low-anxiety condition or (b) raised high above the ground, in the high-anxiety conditions. In this way, we assessed the impacts of anxiety and alprazolam (i.e., anxiety reduction) on FOG frequency and other gait parameters. FOG events appeared only in the high-anxiety conditions. Alprazolam significantly reduced subjective and objective measures of anxiety, as well as the prevalence of FOG (p = 0.05). Furthermore, alprazolam improved swing time (p < 0.05) and gait variability in all conditions, particularly during the elevated plank trials. Interpretation. Our results suggest that (1) anxiety induces FOG, and (2) alprazolam concomitantly reduces anxiety and FOG. Alprazolam further improved gait stability (i.e., swing time and gait variability). These findings reveal that anxiety triggers FOG in PD. Treating anxiety can reduce FOG and improve gait stability, potentially offering new therapeutic avenues for this intractable and disabling symptom in PD.

Residual effects of combined vibratory and plantar stimulation while seated influences plantar pressure and spatiotemporal gait measures in individuals with Parkinson's disease exhibiting freezing of gait.

Combined plantar pressure and vibratory stimulation has been shown to decrease freezing of gait (FOG) episodes and improve spatiotemporal gait parameters compared to single stimulation in Parkinson's disease (PD) patients with FOG. However, the effect of combined plantar stimulations on plantar pressure analysis has never been explored. Forty PD patients with frequent FOG were allocated to either FOG shoes embedded with a 100 Hz vibratory stimulation at the Achilles tendons and a soft thickened silicone pad at the hallux and sole, or sham shoes with a non-working vibratory motor and a flat non-pressure silicone pad (20 patients per arm) while seated for 96 s. The objective gait and plantar pressure analysis were measured immediately after the stimulation. Outcomes included the normalized percentage of changes in percent FOG (%FOG) and plantar pressure in the heel-strike and push-off phase that were compared between pre- and post-stimulations. The FOG shoes group showed significantly decreased %FOG (81.5 ± 28.9% vs. 6.8 ± 22.1%, p < 0.001), plantar pressure in the heel-strike (47.8 ± 43.7% vs. 4.3 ± 9.8%, p < 0.001), plantar pressure in the push-off (57.7 ± 59.6% vs. 6.2 ± 11.6%, p < 0.001), force time integral (FTI) (40.9 ± 32.5% vs. 6.6 ± 17.3%, p < 0.001), and decreased heel contact time (19.3 ± 12.3% vs. 22.7 ± 32.5%, p < 0.001) when compared to the sham group. There was a strong negative correlation between %FOG and peak plantar pressure (r = -0.440, p = 0.005), plantar pressure in the heel-strike (r = -0.847, p < 0.001). Our study demonstrated that the FOG shoe could decrease FOG episodes by improving the heel-strike pressure, toe push-off and normalized heel-to-toe plantar pressure, suggesting that modification inputs from the peripheral sensory systems might significant improvement in FOG in PD.

Cortical Disinhibition Drives Freezing of Gait in Parkinson's Disease and an Exploratory Repetitive Transcranial Magnetic Stimulation Study.

Dysfunction of the primary motor cortex, participating in regulation of posture and gait, is implicated in freezing of gait (FOG) in Parkinson's disease (PD). The aim was to reveal the mechanisms of "OFF-period" FOG (OFF-FOG) and "levodopa-unresponsive" FOG (ONOFF-FOG) in PD. We measured the transcranial magnetic stimulation (TMS) indicators and gait parameters in 21 healthy controls (HCs), 15 PD patients with ONOFF-FOG, 15 PD patients with OFF-FOG, and 15 PD patients without FOG (Non-FOG) in "ON" and "OFF" medication conditions. Difference of TMS indicators in the four groups and two conditions and its correlations with gait parameters were explored. Additionally, we explored the effect of 10 Hz repetitive TMS on gait and TMS indicators in ONOFF-FOG patients. In "OFF" condition, short interval intracortical inhibition (SICI) exhibited remarkable attenuation in FOG patients (both ONOFF-FOG and OFF-FOG) compared to Non-FOG patients and HCs. The weakening of SICI correlated with impaired gait characteristics in FOG. However, in "ON" condition, SICI in ONOFF-FOG patients reduced compared to OFF-FOG patients. Pharmacological treatment significantly improved SICI and gait in OFF-FOG patients, and high-frequency repetitive TMS distinctly improved gait in ONOFF-FOG patients, accompanied by enhanced SICI. Motor cortex disinhibition, represented by decreased SICI, is related to FOG in PD. Refractory freezing in ONOFF-FOG patients correlated with the their reduced SICI insensitive to dopaminergic medication. SICI can serve as an indicator of the severity of impaired gait characteristics in FOG and reflect treatments efficacy for FOG in PD patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Fuzzy Intelligence Learning Based on Bounded Rationality in IoMT Systems: A Case Study in Parkinson’s Disease

As a cause of interfering with routine activities, freezing of gait (FOG) is a severe syndrome of Parkinson’s disease (PD) and usually performs as an abrupt and momentary inability to effective stepping forward. Advanced wearable acceleration sensors based on socially implemented Internet of medical things (IoMT) devices can remotely provide a platform for recognizing FOG. However, due to the diverse data acquisition modes that appear in classic IoMT devices, the obtained data may contain imprecise, hesitant, and incomplete ones. Meanwhile, the bounded rationality owned by neurologists usually has a big impact on using wearable acceleration sensors to predict illnesses. Therefore, the objective of this article lies in exploring a fuzzy intelligence learning approach based on bounded rationality in IoMT systems and providing a valid scheme for biomedical data analysis. Specifically, a brand-new three-way group decision-making approach by means of TODIM (an acronym in Portuguese for interactive multicriteria decision-making) with incomplete dual hesitant fuzzy (DHF) information and its applications in detecting FOG in PD using IoMT devices are systematically explored. First, taking advantage of DHF sets (DHFSs) when depicting realistic group decision information, the concept of multigranulation (MG) incomplete DHF information systems is built. Second, adjustable MG DHF probabilistic rough sets (PRSs) are further put forward via DHF similarity relations. Third, a three-way group decision-making approach is constructed by virtue of adjustable MG DHF PRSs and TODIM. Finally, the validity, effectiveness, and practicality of the constructed three-way group decision-making approach are investigated by a University of California, Irvine (UCI) dataset with several experimental analyses in the background of FOG detection in PD using IoMT devices. The experimental result indicates that the developed fuzzy intelligence learning approach achieves reasonable diagnostic conclusions for FOG detection in PD from the perspective of uncertain information processing abilities, decision risks, and bounded rationality.

Multi-muscle synergies in preparation for gait initiation in Parkinson’s disease

ObjectiveWe investigated changes in indices of muscle synergies prior to gait initiation and the effects of gaze shift in patients with Parkinson’s disease (PD). A long-term objective of the study is to develop a method for quantitative assessment of gait-initiation problems in PD. MethodsPD patients without clinical signs of postural instability and two control groups (age-matched and young) performed a gait initiation task in a self-paced manner, with and without a quick prior gaze shift produced by turning the head. Muscle groups with parallel scaling of activation levels (muscle modes) were identified as factors in the muscle activation space. Synergy index stabilizing center of pressure trajectory in the anterior-posterior and medio-lateral directions (indices of stability) was quantified in the muscle mode space. A drop in the synergy index in preparation to gait initiation (anticipatory synergy adjustment, ASA) was quantified. ResultsCompared to the control groups, PD patients showed significantly smaller synergy indices and ASA for both directions of the center of pressure shift. Both PD and age-matched controls, but not younger controls, showed detrimental effects of the prior gaze shift on the ASA indices. ConclusionsPD patients without clinically significant posture or gait disorders show impaired stability of the center of pressure and its diminished adjustment during gait initiation. SignificanceThe indices of stability and ASA may be useful to monitor pre-clinical gait disorders, and lower ASA may be relevant to emergence of freezing of gait in PD.

The Impact of Motor-Cognitive Dual-Task Training on Physical and Cognitive Functions in Parkinson's Disease.

Rehabilitation is a high-potential approach to improving physical and cognitive functions in Parkinson's disease (PD). Dual-task training innovatively combines motor and cognitive rehabilitation in a comprehensive module. Patients perform motor and cognitive tasks at the same time in dual-task training. The previous studies of dual-task training in PD had high heterogeneity and achieved controversial results. In the current review, we aim to summarize the current evidence of the effect of dual-task training on motor and cognitive functions in PD patients to support the clinical practice of dual-task training. In addition, we also discuss the current opinions regarding the mechanism underlying the interaction between motor and cognitive training. In conclusion, dual-task training is suitable for PD patients with varied disease duration to improve their motor function. Dual-task training can improve motor symptoms, single-task gait speed, single-task steep length, balance, and objective experience of freezing of gait in PD. The improvement in cognitive function after dual-task training is mild.

Techniques for the detection and management of freezing of gait in Parkinson's disease – A systematic review and future perspectives

Freezing of Gait (FoG) is one of the most critical debilitating motor symptoms of advanced Parkinson's disease (PD) with a higher rate of occurrence in aged people. PD affects the cardinal motor functioning and leads to non-motor symptoms, including cognitive and neurobehavioral abnormalities, autonomic dysfunctions and sleep disorders. Since its pathogenesis is complex and unclear yet, this paper targets the studies done on the pathophysiology and epidemiology of FoG in PD. Gait disorder and cardinal features vary from festination (involuntary hurrying in walking) to freezing of gait (breakdown of repetitive movement of steps despite the intention to walk) in patients. Hence, it is difficult to assess the FoG in clinical trials. Therefore, the current research emphasizes wearable sensor-based systems over pharmacology and surgical methods.•This paper presents a technological review of various techniques used for the assessment of FoG with a comprehensive comparison.•Researchers are aiming at the development of wireless sensor-based assistive devices to (a) predict the FoG episode in a different environment, (b) acquire the long-term data for real-time analysis, and (c) cue the FoG patients.•We summarize the work done till now and future research directions needed for a suitable cueing mechanism to overcome FoG.

Baseline cerebral structural morphology predict freezing of gait in early drug-naïve Parkinson’s disease

Freezing of gait (FOG) greatly impacts the daily life of patients with Parkinson’s disease (PD). However, predictors of FOG in early PD are limited. Moreover, recent neuroimaging evidence of cerebral morphological alterations in PD is heterogeneous. We aimed to develop a model that could predict the occurrence of FOG using machine learning, collaborating with clinical, laboratory, and cerebral structural imaging information of early drug-naïve PD and investigate alterations in cerebral morphology in early PD. Data from 73 healthy controls (HCs) and 158 early drug-naïve PD patients at baseline were obtained from the Parkinson’s Progression Markers Initiative cohort. The CIVET pipeline was used to generate structural morphological features with T1-weighted imaging (T1WI). Five machine learning algorithms were calculated to assess the predictive performance of future FOG in early PD during a 5-year follow-up period. We found that models trained with structural morphological features showed fair to good performance (accuracy range, 0.67–0.73). Performance improved when clinical and laboratory data was added (accuracy range, 0.71–0.78). For machine learning algorithms, elastic net-support vector machine models (accuracy range, 0.69–0.78) performed the best. The main features used to predict FOG based on elastic net-support vector machine models were the structural morphological features that were mainly distributed in the left cerebrum. Moreover, the bilateral olfactory cortex (OLF) showed a significantly higher surface area in PD patients than in HCs. Overall, we found that T1WI morphometric markers helped predict future FOG occurrence in patients with early drug-naïve PD at the individual level. The OLF exhibits predominantly cortical expansion in early PD.

Spinal cord stimulation for freezing of gait in Parkinson's disease and progressive supranuclear palsy: a case series

Background: Freezing of gait (FOG) in Parkinson's disease (PD) and progressive supranuclear palsy (PSP) exert a significant adverse impact on the patients quality of life, the degree of their disability, and the risk of falls. A specific characteristic of FOG is a poor response to medical treatment. According to the data of open-label clinical trials and clinical case series published in the last decade, spinal cord stimulation (SCS) can be considered as one of the methods to improve this type of movement disorders.&#x0D; Materials and methods: We present a clinical series of patients with PD and PSP, who underwent implantation of a chronic epidural SCS system at the mid-thoracic level to correct FOG. The efficacy of surgical treatment was assessed at 2 and 5 months with the following scales and questionnaires: part III Unified Parkinson's Disease Rating Scale of Movement Disorder Society (MDS-UPDRS), Freezing of Gait Questionnaire (FOG-Q), Activity-Specific Balance Confidence Scale (ABC), Parkinson's Disease Quality of Life Questionnaire-8 (PDQ-8), Time up and Go Test (TUG), 10 Meter Walk Test. The patients were asked to report possible adverse reactions after the procedure.&#x0D; Results: The results of a 5-month follow-up were obtained from 4 patients (2 with PD and 2 with PSP). There were no adverse events associated with SCS. Оnly one patient with PD experienced a decrease in the severity of motor symptoms according to the MDS-UPDRS part III scale. An increase in the speed of 10 meters' walking distance and TUG test performance was observed in 3 patients. All patients reported an improvement in the quality of life (according to the PDQ-8 questionnaire) and confidence in maintaining balance (according to the ABC questionnaire) by month 2 after surgery. However, at month 5, a negative trend was noted again.&#x0D; Conclusion: The SCS method was safe in all 4 clinical cases described. There was a positive effect of SCS on the improvement of FOG and postural balance in PD and PSP. However, the duration of the therapeutic effect may vary.

Quantitative Susceptibility Mapping Changes Relate to Gait Issues in Parkinson's Disease.

Quantitative susceptibility mapping (QSM) demonstrates elevated iron content in Parkinson's disease (PD) patients within the basal ganglia, though it has infrequently been studied in relation to gait difficulties including freezing of gait (FOG). Our purpose was to relate QSM of basal ganglia and extra-basal ganglia structures with qualitative and quantitative gait measures in PD. This case-control study included PD and cognitively unimpaired (CU) participants from the Comprehensive Assessment of Neurodegeneration and Dementia study. Whole brain QSM was acquired at 3T. Region of interests (ROIs) were drawn blinded manually in the caudate nucleus, putamen, globus pallidus, pulvinar nucleus of the thalamus, red nucleus, substantia nigra, and dentate nucleus. Susceptibilities of ROIs were compared between PD and CU. Items from the FOG questionnaire and quantitative gait measures from PD participants were compared to susceptibilities. Twenty-nine participants with PD and 27 CU participants were included. There was no difference in susceptibility values in any ROI when comparing CU versus PD (p > 0.05 for all). PD participants with gait impairment (n = 23) had significantly higher susceptibility in the putamen (p = 0.008), red nucleus (p = 0.01), and caudate nucleus (p = 0.03) compared to those without gait impairment (n = 6). PD participants with FOG (n = 12) had significantly higher susceptibility in the globus pallidus (p = 0.03) compared to those without FOG (n = 17). Among quantitative gait measures, only stride time variability was significantly different between those with and without FOG (p = 0.04). Susceptibilities in basal ganglia and extra-basal ganglia structures are related to qualitative measures of gait impairment and FOG in PD.

Smart ankle bracelet-laser device to improve gait and detect freezing of gait in Parkinsonism patients: a case series

ABSTRACT Freezing of gait (FOG) is one of the most disabling symptoms of Parkinsonism. Moreover, it does not respond well to medication. Visual cues have been shown to alleviate FOG in Parkinsonism; however, their efficacy is inconsistent. Currently, most mobile cueing devices are used as an open-loop cueing system, which requires manual control to enable constant visual cues. Thus, such devices may not be suitable for some people, especially those who have attention deficits. In addition, objective measurements of FOG in real-life situations remain challenging. Therefore, we developed a smart-ankle laser as a closed-loop cueing system that can detect the patient’s walking pattern and automatically project a laser line that follows each walking step, thus requires less attention. Real-time motion was also recorded within the device for FOG measurement. We studied the efficacy of the device in three Parkinsonism patients with FOG (one man and two women, aged 58–76 years) immediately after use and two patients at 1-week follow-up. Gait speed, Timed Up and Go test performance, stride length, and % FOG improved with the use of the laser, without adverse effects.

Alterations of structure and functional connectivity of visual brain network in patients with freezing of gait in Parkinson's disease.

Freezing of gait (FOG) is a disabling gait disorder common in advanced stage of Parkinson’s disease (PD). The gait performance of PD-FOG patients is closely linked with visual processing. Here, we aimed to investigate the structural and functional change of visual network in PD-FOG patients. Seventy-eight PD patients (25 with FOG, 53 without FOG) and 29 healthy controls (HCs) were included. All the participants underwent structural 3D T1-weighted magnetic resonance imaging (MRI) and resting state functional MRI scan. Our results demonstrated a significant decrease of right superior occipital gyrus gray matter density in PD-FOG relative to non-FOG (NFOG) patients and healthy controls (PD-FOG vs. PD-NFOG: 0.33 ± 0.04 vs. 0.37 ± 0.05, p = 0.005; PD-FOG vs. HC: 0.37 ± 0.05 vs. 0.39 ± 0.06, p = 0.002). Functional MRI revealed a significant decrease of connectivity between right superior occipital gyrus and right paracentral lobule in PD-FOG compared to PD-NFOG (p = 0.045). In addition, the connectivity strength was positively correlated with gray matter density of right superior occipital gyrus (r = 0.471, p = 0.027) and negatively associated with freezing of gait questionnaire (FOGQ) score (r = -0.562, p = 0.004). Our study suggests that the structural and functional impairment of visual-motor network might underlie the neural mechanism of FOG in PD.

Association between levels of high-sensitivity C-reactive protein in plasma and freezing of gait in Parkinson's disease.

This study explored the potential relationship between levels of high-sensitivity C-reactive protein (hs-CRP) in plasma and freezing of gait (FOG) in Parkinson's disease (PD) in China. A total of 72 healthy subjects, 62 PD patients with FOG, and 83 PD patients without FOG from our center were enrolled in this prospective study. Patients with FOG showed significantly higher hs-CRP levels than controls, but patients without FOG did not. Binary logistic regression analysis identified levels of hs-CRP in plasma to be an independent risk factor for FOG among the patients in our cohort (OR 6.371, 95% CI 2.589-15.678, p < 0.001). In fact, a cut-off level of 0.935mg/L distinguished patients with or without FOG [area under the ROC curve (AUC) = 0.908, sensitivity 87.1%, specificity 89.2%]. Our study suggests that high levels of hs-CRP in plasma are associated with the occurrence of FOG in PD. The pooled data combined with a previous study carried out in Spain also indicate a positive association between plasma hs-CRP levels and FOG in PD. However, more research is still needed to verify the plasma hs-CRP as a potential biomarker of FOG.

Functional networks underlying freezing of gait: a resting-state electroencephalographic study

IntroductionThe pathophysiology of freezing of gait in people with Parkinson's disease (PD) remains unclear, despite its association with motor, cognitive, limbic and sensory-perceptual impairments. Resting-state electroencephalography (EEG) may provide functional information for a better understanding of freezing of gait by studying spectral power and connectivity between brain regions in different frequency bands. MethodsHigh-resolution EEG was recorded in 36 patients with PD (18 freezers, 18 non-freezers), and 18 healthy controls during a 5-min resting-state protocol with eyes open, followed by a basic spectral analysis in the sensor space and a more advanced analysis of functional connectivity at the source level. ResultsFreezers showed a diffusely higher theta-band relative spectral power than controls. This increased power was correlated with a deficit in executive control. Concerning resting-state functional connectivity, connectivity strength within a left fronto-parietal network appeared to be higher in freezers than in controls in the theta band, and to be correlated with freezing severity and a history of falls. ConclusionWe have shown that spectral power and connectivity analyses of resting-state EEG provide useful and complementary information to better understand freezing of gait in PD. The higher connectivity strength seen within the left ventral attention network in freezers is in keeping with an excessive guidance of behavior by external cues, due to executive dysfunction, and spectral analysis also found changes in freezers that was closely correlated with executive control deficits. This exaggerated influence of the external environment might result in behavioral consequences that contribute to freezing of gait episodes. These findings should be further investigated with a longitudinal study.

Turning reveals the characteristics of gait freezing better than walking forward and backward in Parkinson’s disease

BackgroundsPeople with Parkinson’s disease (PD) experiences walking disturbances and freezing of gait (FoG) is one of the most distressing symptoms. Research questionThis study aimed to comprehensively analyze the walking characteristics of patients with PD, including forward and backward walking and turning, in order to define the characteristics of FoG. MethodsA total of 68 patients with PD and 14 control subjects were enrolled in this study. Forward and backward walking and 360-degree turning were recorded at preferred speed in “off” state using three-dimensional motion analysis system. ResultsPD patients showed a narrower step length, slower walking speed, and higher asymmetry index (AI) of step length during forward and backward walking. During turning, the PD patients had more turning steps, longer turning time, and shorter step length than the control subjects. No difference was observed in the characteristics of forward walking according to the FoG status, but the freezer group showed a narrower step length and decreased range of motion in the ankle joints during backward walking. Freezer group showed longer step time and higher AI of step length at turning. The severity of FoG was correlated with step length and walking speed during forward and backward walking, total step count, total step time, and walking speed during turning. SignificanceThe characteristics and impacts of FoG in PD were most prominent during turning, followed by backward and forward walking. Further comprehensive analyses of walking including turning might contribute to the understanding of the pathophysiology of walking disturbances in PD.

Relationship Between Brain Volumes and Objective Balance and Gait Measures in Parkinson's Disease.

Instrumented measures of balance and gait measure more specific balance and gait impairments than clinical rating scales. No prior studies have used objective balance/gait measures to examine associations with ventricular and brain volumes in people with Parkinson's disease (PD). To test the hypothesis that larger ventricular and smaller cortical and subcortical volumes are associated with impaired balance and gait in people with PD. Regional volumes from structural brain images were included from 96 PD and 50 control subjects. Wearable inertial sensors quantified gait, anticipatory postural adjustments prior to step initiation (APAs), postural responses to a manual push, and standing postural sway on a foam surface. Multiple linear regression models assessed the relationship between brain volumes and balance/gait and their interactions in PD and controls, controlling for sex, age and corrected for multiple comparisons. Smaller brainstem and subcortical gray matter volumes were associated with larger sway area in people with PD, but not healthy controls. In contrast, larger ventricle volume was associated with smaller APAs in healthy controls, but not in people with PD. A sub-analysis in PD showed significant interactions between freezers and non-freezers, in several subcortical areas with stride time variability, gait speed and step initiation. Our models indicate that smaller subcortical and brainstem volumes may be indicators of standing balance dysfunction in people with PD whereas enlarged ventricles may be related to step initiation difficulties in healthy aging. Also, multiple subcortical region atrophy may be associated with freezing of gait in PD.

Executive function and dopamine response in Parkinson's disease freezing of gait

BackgroundThis investigation examined whether aspects of attention and executive functioning differed between Parkinson's Disease (PD) patients with freezing of gait (FOG) based on responsiveness to dopamine. We also explored association of cognition with FOG severity and gait metrics. MethodsFifty-four individuals with PD completed the study protocol: 17 without freezing (PDC), 23 with dopa-responsive FOG (RFOG), and 14 with dopa-unresponsive (URFOG). Standardized neuropsychological tests assessed attention (focused and sustained), psychomotor speed, and set-switching (time and errors). FOG severity was measured using the new FOG Questionnaire (nFOG-Q). Metrics from timed up and go (TUG) tasks were obtained while “on” and “off” dopamine, with and without dual cognitive tasks. ResultsAfter controlling for clinical and demographic factors, analysis of covariance revealed a significant between-group difference for set-switching errors; planned contrasts revealed increased set-switching errors in URFOG relative to RFOG and PD control groups. Groups were not different in other cognitive domains. FOG severity was modestly associated with set-switching errors in RFOG but not URFOG. TUG performances while “on” were associated with set-switching errors in PD controls, and with focused attention in RFOG. ConclusionPD patients with dopa-unresponsive FOG are more prone to set-switching errors than those who respond to treatment. Furthermore, executive function appears relevant to FOG severity only in patients who show dopamine response. Together, these findings suggest disruption of a common dopamine-mediated pathway for FOG and ability to monitor rules while alternating cognitive processes. Consideration of dopa-response could be useful in characterizing cohorts and treating FOG in PD.

Gait and Balance Assessments using Smartphone Applications in Parkinson's Disease: A Systematic Review.

Gait dysfunctions and balance impairments are key fall risk factors and associated with reduced quality of life in individuals with Parkinson’s Disease (PD). Smartphone-based assessments show potential to increase remote monitoring of the disease. This review aimed to summarize the validity, reliability, and discriminative abilities of smartphone applications to assess gait, balance, and falls in PD. Two independent reviewers screened articles systematically identified through PubMed, Web of Science, Scopus, CINAHL, and SportDiscuss. Studies that used smartphone-based gait, balance, or fall applications in PD were retrieved. The validity, reliability, and discriminative abilities of the smartphone applications were summarized and qualitatively discussed. Methodological quality appraisal of the studies was performed using the quality assessment tool for observational cohort and cross-sectional studies. Thirty-one articles were included in this review. The studies present mostly with low risk of bias. In total, 52% of the studies reported validity, 22% reported reliability, and 55% reported discriminative abilities of smartphone applications to evaluate gait, balance, and falls in PD. Those studies reported strong validity, good to excellent reliability, and good discriminative properties of smartphone applications. Only 19% of the studies formally evaluated the usability of their smartphone applications. The current evidence supports the use of smartphone to assess gait and balance, and detect freezing of gait in PD. More studies are needed to explore the use of smartphone to predict falls in this population. Further studies are also warranted to evaluate the usability of smartphone applications to improve remote monitoring in this population.Registration: PROSPERO CRD 42020198510 Supplementary InformationThe online version contains supplementary material available at 10.1007/s10916-021-01760-5.

Normal-sized basal ganglia perivascular space related to motor phenotype in Parkinson freezers.

Changes in basal ganglia (BG) perivascular spaces (PVSs) are related to motor and cognitive behaviors in Parkinson’s disease (PD). However, the correlation between the initial motor phenotype and PVSs distribution/burden in PD freezing of gait (FOG) remains unclear. In addition, the normal-sized PVSs (nPVSs) have not been well-studied. With high-resolution 7T-MRI, we studied nPVSs burden in BG, thalamus, midbrain and centrum semiovale. The numbers and volume of nPVSs were assessed in 10 healthy controls, 10 PD patients without FOG, 20 with FOG [10 tremor dominant (TD), 10 non-TD subtype]. Correlation analyses were further performed in relation to clinical parameters. In this proof of concept study, we found that the nPVS burden of bilateral and right BG were significantly higher in freezers. A negative correlation existed between the tremor score and BG-nPVSs count. A positive correlation existed between the levodopa equivalent daily dose and BG-nPVSs count. The nPVS burden correlated with the progression to FOG in PD, but the distribution and burden of nPVS differ in TD vs. non-TD subtypes. High resolution 7T-MRI is a sensitive and reliable tool to evaluate BG-nPVS, and may be a useful imaging marker for predicting gait impairment that may evolve into FOG in PD.

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

Freezing of gait (FOG) is considered one of the most disturbing and least understood symptoms in Parkinson's disease (PD). The reported prevalence rates of FOG in PD vary widely, ranging from 5 to 85.9%. We conducted a systematic review and meta-analysis to provide a reliable estimate of the average point prevalence of FOG in PD, and we further investigated the study characteristics that might have influenced the estimate. We searched different databases to identify studies that report the prevalence of FOG in PD or include relevant raw data for further calculation. The last inclusion date was February 20, 2020. The modified Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool was used for the quality assessment, and articles that met the predefined criteria were included in the quantitative analysis. Sixty-six studies were selected from 3392 references. A weighted prevalence of 50.6% in 9072 PD patients experienced FOG based on the special questionnaires (the FOG-Q and NFOG-Q), which was about twice as high as that assessed by the specific items of the clinical rating scales (UPDRS item2.14 and MDS-UPDRS item3.11) (23.2%) or simple clinical questions (25.4%). The weighted prevalence was 37.9% for early stage (≤ 5years) and 64.6% for advanced stage (≥ 9years). Moreover, a higher prevalence was calculated from the population-based studies than that in multicenter and single-center studies (47.3% vs. 33.5% and 37.1%, respectively). The result from this systematic review confirms that FOG is very common in PD and its prevalence is usually underestimated in hospital settings. Importantly, a more accurate assessment of FOG in future clinical researches would involve the use of special FOG scale rather than a single item on a scale or a general clinical inquiry.