Use of AR/VR for Treatment of Freezing of Gait (FoG) in Parkinson's Disease (PD).

Objective To explore the clinical features of freezing of gait (FOG) in Parkinson's disease (PD) patients. Methods Two hundred and sixty-five PD patients from the Department of Neurology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine were consecutively recruited between March 2012 and August 2014. According to the complaints of FOG and the gait symptoms, PD patients were further divided into two groups: PD with FOG group (n=70) and PD without FOG group (n=195). Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn and Yahr (H-Y) stage were used to evaluate the severity of the motor symptoms. The Non-Motor Symptoms Questionnaire (NMSQuest) was initially used to investigate the occurrence of non-motor symptoms, and odor discrimination was performed with the 16-item odor identification test from extended version of Sniffin' Sticks (SS-16). Simultaneously, all participants were evaluated with rapid eye movement sleep behavior disorder screening questionnaire (RBDSQ) for detecting RBD in PD patients and autonomic dysfunction was assessed with the Scale for Outcomes in PD-Autonomic (SCOPA-AUT). The Mini-Mental State Examination (MMSE) and the 17-item Hamilton Depression Rating Scale (HAMD-17) were also used to evaluate the cognitive function and severity of depressive symptoms, respectively. Results (1) 26.42% (70/265) of PD patients had been experiencing FOG.(2) The duration of the disease (8.00 (5.00, 10.00) years vs 4.00 (2.00, 6.00) years, Z=–6.797, P<0.001) or the age ((65.23±7.79) years vs (61.76±8.39) years, t= 3.018, P=0.003) in PD with FOG group was significantly longer or older than that in non-FOG group.(3) Most of the motor symptoms in FOG group, including H-Y stage (2.50 (2.38, 3.00) vs 1.50 (1.00, 2.50), Z=–7.264, P<0.001), UPDRS-Ⅱscore (14.13±4.59 vs 9.51±3.77, t=7.552, P<0.001), UPDRS-Ⅲ score (27.00 (18.75, 37.25) vs 20.00 (15.00, 26.00), Z=–4.228, P<0.001) and the levodopa equivalent dose (LED; 637.50 (425.00, 800.78) mg vs 262.50 (100.00, 450.00) mg, Z=–7.630, P<0.001) showed significantly higher values than that in non-FOG group.(4) The non-motor symptoms (NMSQuest: 6.50 (5.00, 9.25) vs 5.00 (3.00, 7.00), Z=–3.748, P<0.001) occurred much frequently in FOG group, especially in the depression (HAMD-17: 6.50 (3.00, 10.00) vs 4.00 (1.00, 7.00), Z=–3.739, P<0.001) and autonomic dysfunctions (SCOPA-AUT: 13.39±6.48 vs 9.79±6.17, t= 4.129, P<0.001), but there were no significant differences between the two groups in cognitive function, RBD and odor discrimination.(5) The binary Logistic regression analysis indicated that FOG correlated with H-Y stage (B=1.333, P<0.001), LED (B=0.002, P=0.003) and HAMD-17 score (B=0.127, P=0.041). Conclusions FOG is a common symptom in PD patients. It is mainly related to depression, disease progression and levodopa treatment. Motor dysfunctions and non-motor symptoms were more popular in PD patients with FOG. Key words: Parkinson disease; Gait; Gait disorders, neurologic

Parkinson's disease (PD) is a neurodegenerative disease characterized by motor symptoms and gait impairments. Among them, freezing of gait (FOG) is one of the most disabling manifestations. Backward walking (BW) is an activity of daily life that individuals with PD might find difficult and could cause falls. Recent studies have reported that gait impairments in PD were more pronounced in BW, particularly in people presenting FOG. However, to the best of our knowledge, no systematic review has synthetized the literature which compared BW performance in PD patients with and without FOG. The aim of this study was to evaluate the differences in BW performance between PD patients with FOG and PD patients without FOG. Two databases, PubMed and Web of Science, were systematically searched to identify studies comparing BW performance in PD patients with and without FOG. The National Institutes of Health (NIH) tool was used to assess the quality of the studies included. Seven studies with 431 PD patients (179 PD with FOG and 252 PD without FOG) met the inclusion criteria and were included in this review. Among them, 5 studies reported walking speed, 3 studies step length, stride length and lower limb range of motion, 2 studies functional ambulation profile, toe clearance height, swing, and stance percent and 1 study reported the decomposition index and stepping coordination. Compared to PD patients without FOG, PD patients with FOG showed slower walking speed and reduced step length in 3 studies, shorter stride length, lower functional ambulation profile and decreased ankle range of motion in 2 studies, and smaller swing percent, higher stance percent, worse stepping coordination, greater decomposition between movements, and lower toe clearance height in one study. Despite the small number of included studies, the findings of this review suggested that PD patients with FOG have worse gait performance during the BW task than PD without FOG.

Background: Patients with idiopathic Parkinson’s disease (PD) have a flexed posture and are at an increased risk of falls. In addition, fear of falling (FOF) is among the main complaints of PD patients. To reduce the risk of falling, complex non-drug interventions are required, involving balance-challenging exercises with proper strength, along with posture alignment through corrective exercise interventions (Alexander techniques), which are often utilized to manage patients with PD and thoracic hyperkyphosis. Objectives: To investigate the effects of Alexander-based corrective techniques (ABCT) on forward flexed posture (thoracic hyperkyphosis and forward head posture), risk of falling, and FOF among idiopathic PD patients. Methods: In this interventional study, 26 male and female patients were randomly assigned to the experimental (n, 13) and control groups (n, 13). The subjects participated in a postural realignment program, consisting of 60-minute sessions over 8 weeks (3 sessions per week). Pre- and posttest evaluations were also carried out. Results: The results of paired t test regarding the effects of ABCT on the thoracic kyphosis angle (TKA), craniovertebral angle (CVA), falls efficacy scale-international (FES-I) score, freezing of gait (FOG), and functional reach test (FRT) score revealed a significant difference between the pre- and posttest stages in the control group (P = 0.05). In addition, the t test results showed a significant difference in the mean changes of TKA, FES-I score, FOG, and FRT score between the groups in the pre- and postintervention stages. The Pearson’s correlation test showed that TKA had a significant positive correlation with FES-I and FOG in the groups. On the other hand, the results of Pearson’s correlation test showed a significant negative correlation between TKA and FRT. Finally, the Pearson’s correlation coefficient showed a significant positive correlation between CVA and FES-I, but not FRT in the groups. Conclusions: The findings of this study indicated that 8 weeks (24 sessions) of ABCT in the experimental group caused considerable improvements in TKA, CVA, FOF, FOG, and risk of fall in patients with PD.

Aim: We studied the longitudinal associations between freezing of gait (FoG), fear of falling (FoF) and anxiety, and how these associations are influenced by confounding factors. Materials & methods: We analyzed longitudinal motor and nonmotor measurements from 153 Parkinson's disease patients. Possible confounding factors were divided into three subgroups: demographics, disease characteristics, medication use and adverse effects of medication. Results: All crude associations between FoG, FoF and anxiety were significant and remained so after adjusting for confounders. When analyzing FoF and anxiety together as independent variables, the association between FoG and FoF remained, and the association between FoG and anxiety diminished. Conclusion: We confirm the complex interactions between motor and nonmotor symptoms in Parkinson's disease, and plead for a multidisciplinary approach.

Long-term update of the effect of spinal cord stimulation in advanced Parkinson’s disease patients

GENERAL COMMENTARY article Front. Neurol., 28 April 2015Sec. Movement Disorders Volume 6 - 2015 | https://doi.org/10.3389/fneur.2015.00084

Freezing of gait (FOG) is a complex gait disturbance in Parkinson’s disease (PD), during which the patient is not able to effectively initiate gait or continue walking. The mystery of the FOG phenomenon is still unsolved. Recent studies have revealed abnormalities in cortical activities associated with FOG, which highlights the importance of cortical and cortical-subcortical network dysfunction in PD patients with FOG. In this paper, phase-locking value (PLV) of eight frequency sub-bands between 0.05 Hz and 35 Hz over frontal, motor, and parietal areas [during an ankle dorsiflexion (ADF) task] is used to investigate EEG phase synchronization. PLV was investigated over both superficial and deeper networks by analyzing EEG signals preprocessed with and without Surface Laplacian (SL) spatial filter. Four groups of participants were included: PD patients with severe FOG (N = 5, 5 males), PD patients with mild FOG (N = 7, 6 males), PD patients without FOG (N = 14, 13 males), and healthy age-matched controls (N = 13, 10 males). Fifteen trials were recorded from each participant. At superficial layers, frontoparietal theta phase synchrony was a unique feature present in PD with FOG groups. At deeper networks, significant dominance of interhemispheric frontoparietal alpha phase synchrony in PD with FOG, in contrast to beta phase synchrony in PD without FOG, was identified. Alpha phase synchrony was more distributed in PD with severe FOG, with higher levels of frontoparietal alpha phase synchrony. In addition to FOG-related abnormalities in PLV analysis, phase-amplitude coupling (PAC) analysis was also performed on frequency bands with PLV abnormalities. PAC analysis revealed abnormal coupling between theta and low beta frequency bands in PD with severe FOG at the superficial layers over frontal areas. At deeper networks, theta and alpha frequency bands show high PAC over parietal areas in PD with severe FOG. Alpha and low beta also presented PAC over frontal areas in PD groups with FOG. The results introduced significant phase synchrony differences between PD with and without FOG and provided important insight into a possible unified underlying mechanism for FOG. These results thus suggest that PLV and PAC can potentially be used as EEG-based biomarkers for FOG.

Parkinson's disease (PD) patients are at risk for developing bone health problems, and freezing of gait (FOG) in PD is associated with a high risk of falling and fracture. This study aimed to determine the association between FOG and bone mineral density (BMD) in patients with PD. We included 148 PD patients. FOG was assessed using the FOG Questionnaire (FOG-Q), and BMD was measured by dual-energy X-ray absorptiometry. Of 148 PD patients, 102 (68.9%) had FOG. PD patients with FOG were older and had longer disease duration, higher levodopa equivalent dose, higher modified Hoehn and Yahr stage, higher Unified PD Rating Scale motor score, higher FOG-Q score, higher total Non-Motor Symptom Scale score, and lower BMD scores in the femoral neck area than those without FOG. Pearson correlation analysis revealed that age, sex, body mass index, and age at onset were significantly correlated with areal BMDs in all areas. FOG-Q scores correlated negatively with areal BMDs in the total hip area and femoral neck, but not with areal BMD in the lumbar spine. Multivariate regression analysis showed that FOG-Q score was significantly correlated with areal BMD in the femoral neck, but not with areal BMDs in the lumbar spine or total hip. FOG in PD patients correlates significantly with BMD in the femoral neck area. Therefore, PD patients with FOG should be screened for osteoporosis.

The neural mechanisms underlying freezing of gait (FOG) in Parkinson's disease (PD) have not been completely comprehended. Sensory-motor integration dysfunction was proposed as one of the contributing factors. Here, we investigated short-latency afferent inhibition (SAI) and long-latency afferent inhibition (LAI), and analyzed their association with gait performance in FOG PD patients, to further validate the role of sensorimotor integration in the occurrence of FOG in PD. Twenty-five levodopa responsive-FOG PD patients (LR-FOG), fifteen levodopa unresponsive-FOG PD patients (LUR-FOG), twenty-eight PD patients without FOG (NO-FOG PD) and twenty-two healthy controls (HC) were included in the study. Clinical features such as PD motor symptoms, FOG severity and cognitive abilities were evaluated using clinical scales in subjects with PD. All participants underwent paired associative stimulation (PAS) to evaluate SAI and LAI in addition to regular input-output curve by transcranial magnetic stimulation. The performances of gait were assessed using a portable gait analyzing system in 10-meter timed Up and Go task. The correlations between the gait spatiotemporal parameters or the scores of FOG scale and the magnitudes of SAI or LAI were analyzed. Compared to HC and NO-FOG PD patients, SAI was decreased in FOG PD subgroups. LAI was also reduced in both LR-FOG PD and LUR-FOG PD in relative to HC; however, only LUR-FOG PD showed significant reduction of LAI in comparison to NO-FOG PD group. FOG PD patients showed poorer gait performance compared to HC and NO-FOG PD group. The reduction of SAI and LAI were correlated with the impaired gait spatiotemporal parameters or scores of FOG scale in PD with FOG. The SAI and LAI were attenuated in PD patients with FOG, and the reduction of SAI or LAI were correlated to disturbed gait performance, indicating that sensory-motor integration dysfunction played a role in the development of FOG in PD.

Parkinson's disease (PD) patients with freezing of gait (FOG) may present with complex and heterogeneous cognitive profiles. Owing to limited access to comprehensive neuropsychological battery in ordinary clinical practice, the Montreal Cognitive Assessment (MoCA) is likely to be easily available cognitive data for comparisons among studies. This study aims to explore the cognitive profiles stratified by education using MoCA in PD patients with FOG. PD patients with FOG (FOG+, n = 52) and without FOG (FOG-, n = 71) were included in our study. MoCA items were categorized into five subsections (attention/working memory, executive function, episodic memory, language, and visuospatial function) referring to previously published criteria. Cognitive assessments were compared based on five subsections between groups stratified by three education levels (0-6 years, 7-12 years, and >12 years). The association of cognitive measurements with FOG were analyzed using binary logistic regression models with adjustment for variables. The total scores and subscores of each subsection of MoCA were similar between two groups of each education level. Further detailed analysis showed that a composite measure labeled "Attention/working memory-Composite" (abbreviated to Attention-C), consisting of the scores of four items (target detection task, serial sevens, digit forward and backward, and sentence repetition), were lower significantly in FOG+ group compared with FOG- group in patients with education year ≤6 years. The significant association of Attention-C with FOG held true when controlling for disease duration, but not for H-Y stage, MDS-UPDRS III, HAMA, and HAMD. Overall, our findings gave a hint that Attention-C derived from MoCA might be a potential factor associated with FOG in PD patients with lower education level (education year ≤ 6 years), which will need to be validated in future studies.

Multifaceted Sensory Electrical Stimulation cueing for Freezing of Gait in Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative disorder characterized by a range of motor and non-motor symptoms. Among the motor complaints, freezing of gait (FOG) is a common and disabling phenomenon that episodically hinders patients' ability to produce efficient steps. Concurrently, sleep disorders are prevalent in PD and significantly impact the quality of life of affected individuals. Numerous studies have suggested a bidirectional relationship between FOG and sleep disorders. Therefore, our objective was to systematically review the literature and compare sleep outcomes in PD patients with FOG (PD + FOG) and those without FOG (PD-FOG). By conducting a comprehensive search of the PubMed and Web of Science databases, we identified 20 eligible studies for inclusion in our analysis. Our review revealed that compared to PD-FOG, PD + FOG patients exhibited more severe symptoms of rapid eye movement sleep behavior disorder in nine studies, increased daytime sleepiness in eight studies, decreased sleep quality in four studies, and more frequent and severe sleep disturbances in four studies. These findings indicate that PD + FOG patients generally experience worse sleep quality, higher levels of daytime sleepiness, and more disruptive sleep disturbances compared to those without FOG (PD-FOG). The association between sleep disturbances and FOG highlights the importance of evaluating and monitoring these symptoms in PD patients and open the possibility for future studies to assess the impact of managing sleep disturbances on the severity and occurrence of FOG, and vice versa.

Background: Freezing of gait (FoG) is a disabling gait disorder that commonly occurs in advanced stages of Parkinson's disease (PD). The neuroanatomical mechanisms underlying FoG in PD are still unclear. The present study aims to explore alterations of structural gray matter (GM) in PD patients with FoG. Method: Twenty-four PD patients with FoG (FoG+), 37 PD patients without FoG (FoG-) and 24 healthy controls (HC) were included. All subjects underwent a standardized MRI protocol. The cortical thickness (CTh), segmentation volume without ventricles (BrainSegVolNotVent) and estimated total intracranial volume (eTIV) were analysed using the FreeSurfer pipeline. Results: CTh differences were found in the right middle temporal gyrus (rMTG) generally. Compared to that in HCs, the CTh of the rMTG in both the FoG+ and FoG- groups was smaller, while no significant difference between the FoG+ and FoG- groups. Correlation analyses demonstrated a negative correlation between the CTh of the rMTG and the UPDRS part II score in PD subjects, and a borderline significant correlation between the score of Freezing of Gait Questionnaire (FoGQ) and rMTG CTh. Additionally, receiver operating characteristic curve (ROC) analysis revealed a cut-off point of CTh =3.08 mm in the rMTG that could be used to differentiate PD patients and HCs (AUC =0.79, P <0.01). There were no differences in the BrainSegVolNotVent or eTIV among the 3 groups. Conclusions: Our findings currently suggest no significant difference between FoG+ and FoG- patients in terms of structural gray matter changes. However, decreased CTh in the rMTG related to semantic control may be used as a biomarker to differentiate PD patients and HCs.

T50. Freezing of gait does not modulate neural oscillations in motor cortices

Deep brain stimulation and refractory freezing of gait in Parkinson’s disease: Improvement with high-frequency current steering co-stimulation of subthalamic nucleus and substantia Nigra