Beneficial Effects of External Cueing on Freezing of Gait in a Subject With Polymerase-γ Gene Mutations.
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ABSTRACT:
SUBMITTER: Nonnekes J
PROVIDER: S-EPMC6749807 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Walking can be challenging for aging individuals and people with neurological disorders such as Parkinson disease (PD). Gait impairment characterized by reduced speed and higher variability destabilizes gait and increases the risk of falls. External auditory cueing provides an effective strategy to improve gait, as matching footfalls to rhythms typically increases gait speed and elicits larger steps, but the need to synchronize to an outside source often has a detrimental effect on gait variability. Internal cueing in the form of singing may provide an alternative to conventional gait therapy. In the present study, we compare the effects of internal and external cueing techniques on forward and backward walking for both people with PD and healthy controls. Results indicate that internal cueing was associated with improvements in gait velocity, cadence, and stride length in the backward direction, and reduced variability in both forward and backward walking. In comparison, external cueing was associated with minimal improvement in gait characteristics and a decline in gait stability. People with gait impairment due to aging or neurological decline may benefit more from internal cueing techniques such as singing as compared to external cueing techniques.
| S-EPMC6195608 | biostudies-literature
Project description:External visual cueing is a well-known means to target freezing of gait (FOG) in Parkinson's disease patients. Holocue is a wearable visual cueing application that allows the HoloLens 1 mixed-reality headset to present on-demand patient-tailored action-relevant 2D and 3D holographic visual cues in free-living environments. The aim of this study involving 24 Parkinson's disease patients with dopaminergic "ON state" FOG was two-fold. First, to explore unfamiliarity and habituation effects associated with wearing the HoloLens on FOG. Second, to evaluate the potential immediate effect of Holocue on alleviating FOG in the home environment. Three sessions were conducted to examine (1) the effect of wearing the unfamiliar HoloLens on FOG by comparing walking with and without the HoloLens, (2) habituation effects to wearing the HoloLens by comparing FOG while walking with HoloLens over sessions, and (3) the potential immediate effect of Holocue on FOG by comparing walking with HoloLens with and without Holocue. Wearing the HoloLens (without Holocue) did significantly increase the number and duration of FOG episodes, but this unfamiliarity effect disappeared with habituation over sessions. This not only emphasizes the need for sufficient habituation to unfamiliar devices, but also testifies to the need for research designs with appropriate control conditions when examining effects of unfamiliar wearable cueing devices. Holocue had overall no immediate effect on FOG, although objective and subjective benefits were observed for some individuals, most notably those with long and/or many FOG episodes. Our participants raised valuable opportunities to improve Holocue and confirmed our assumptions about current and anticipated future design choices, which supports ongoing Holocue development for and with end users.
| S-EPMC8784874 | biostudies-literature
Project description:Parkinson's disease is the second most common neurodegenerative disease worldwide reducing cognitive and motoric abilities of affected persons. Freezing of Gait (FoG) is one of the severe symptoms that is observed in the late stages of the disease and considerably impairs the mobility of the person and raises the risk of falls. Due to the pathology and heterogeneity of the Parkinsonian gait cycle, especially in the case of freezing episodes, the detection of the gait phases with wearables is challenging in Parkinson's disease. This is addressed by introducing a state-automaton-based algorithm for the detection of the foot's motion phases using a shoe-placed inertial sensor. Machine-learning-based methods are investigated to classify the actual motion phase as normal or FoG-affected and to predict the outcome for the next motion phase. For this purpose, spatio-temporal gait and signal parameters are determined from the segmented movement phases. In this context, inertial sensor fusion is applied to the foot's 3D acceleration and rate of turn. Support Vector Machine (SVM) and AdaBoost classifiers have been trained on the data of 16 Parkinson's patients who had shown FoG episodes during a clinical freezing-provoking assessment course. Two clinical experts rated the video-recorded trials and marked episodes with festination, shank trembling, shuffling, or akinesia. Motion phases inside such episodes were labeled as FoG-affected. The classifiers were evaluated using leave-one-patient-out cross-validation. No statistically significant differences could be observed between the different classifiers for FoG detection (p>0.05). An SVM model with 10 features of the actual and two preceding motion phases achieved the highest average performance with 88.5 ± 5.8% sensitivity, 83.3 ± 17.1% specificity, and 92.8 ± 5.9% Area Under the Curve (AUC). The performance of predicting the behavior of the next motion phase was significantly lower compared to the detection classifiers. No statistically significant differences were found between all prediction models. An SVM-predictor with features from the two preceding motion phases had with 81.6 ± 7.7% sensitivity, 70.3 ± 18.4% specificity, and 82.8 ± 7.1% AUC the best average performance. The developed methods enable motion-phase-based FoG detection and prediction and can be utilized for closed-loop systems that provide on-demand gait-phase-synchronous cueing to mitigate FoG symptoms and to prevent complete motoric blockades.
| S-EPMC8685223 | biostudies-literature
Project description:Freezing of gait (FOG) is a common occurrence in patients with Parkinson's disease (PD) that leads to significant limitations in mobility and increases risk of falls. Focused vibrotactile stimulation and cueing are two methods used to alleviate motor symptoms, including FOG, in patients with PD. While effective on their own, the effect of combining both focused vibrotactile stimulation and cueing has yet to be investigated. Two patients, both with a history of PD, suffered from frequent FOG episodes that failed to respond adequately to medication. A novel vibrotactile stimulation device that delivered rhythmic kinesthetic stimuli onto the sternum successfully reduced FOG episodes in both patients and drastically improved their mobility as measured by the Timed Up and Go test. We found that a combination of focused vibrotactile stimulation and cueing was effective in reducing FOG episodes in two patients with PD. Further well-designed prospective studies are needed to confirm our observations.
| S-EPMC8490196 | biostudies-literature
Project description:BackgroundFreezing of gait (FOG) is a highly incapacitating symptom that affects many people with Parkinson's disease (PD). Cueing triggered upon real-time FOG detection (on-demand cueing) shows promise for FOG treatment. Yet, the feasibility of implementation and efficacy in daily life is still unknown. Therefore, this study aims to investigate the effectiveness of DeFOG: a smartphone and sensor-based on-demand cueing solution for FOG.MethodsSixty-two PD patients with FOG will be recruited for this single-blind, multi-center, randomized controlled phase II trial. Patients will be randomized into either the intervention group or the active control group. For four weeks, both groups will receive feedback about their physical activity using the wearable DeFOG system in daily life. In addition, the intervention group will also receive on-demand auditory cueing and instructions. Before and after the intervention, home-based assessments will be performed to evaluate the primary outcome, i.e., "percentage time frozen" during a FOG-provoking protocol. Secondary outcomes include the training effects on physical activity monitored over 7 days and the user-friendliness of the technology.DiscussionThe DeFOG trial will investigate the effectiveness of personalized on-demand cueing in a controlled design, delivered for 4 weeks in the patient's home environment. We anticipate that DeFOG will reduce FOG to a greater degree than in the control group and we will explore the impact of the intervention on physical activity levels. We expect to gain in-depth insight into whether and how patients control FOG using cueing methods in their daily lives.Trial registrationClinicaltrials.gov NCT03978507.
| S-EPMC8591418 | biostudies-literature
Project description: Not available
| S-EPMC6353482 | biostudies-literature
Project description:BackgroundParkinson's disease is a progressive neurological disorder resulting from a degeneration of dopamine producing cells in the substantia nigra. Clinical symptoms typically affect gait pattern and motor performance. Evidence suggests that the use of individual auditory cueing devices may be used effectively for the management of gait and freezing in people with Parkinson's disease. The primary aim of the randomised controlled trial is to evaluate the effect of an individual auditory cueing device on freezing and gait speed in people with Parkinson's disease.MethodsA prospective multi-centre randomised cross over design trial will be conducted. Forty-seven subjects will be randomised into either Group A or Group B, each with a control and intervention phase. Baseline measurements will be recorded using the Freezing of Gait Questionnaire as the primary outcome measure and 3 secondary outcome measures, the 10 m Walk Test, Timed "Up & Go" Test and the Modified Falls Efficacy Scale. Assessments are taken 3-times over a 3-week period. A follow-up assessment will be completed after three months. A secondary aim of the study is to evaluate the impact of such a device on the quality of life of people with Parkinson's disease using a qualitative methodology.ConclusionThe Apple iPod-Shuffle and similar devices provide a cost effective and an innovative platform for integration of individual auditory cueing devices into clinical, social and home environments and are shown to have immediate effect on gait, with improvements in walking speed, stride length and freezing. It is evident that individual auditory cueing devices are of benefit to people with Parkinson's disease and the aim of this randomised controlled trial is to maximise the benefits by allowing the individual to use devices in both a clinical and social setting, with minimal disruption to their daily routine.
| S-EPMC2630976 | biostudies-literature
Project description:IntroductionExercise improves gait in Parkinson disease (PD), but whether exercise differentially affects people with PD with (freezers) and without freezing of gait (non-freezers) remains unclear. This study examines exercise's effects on gait performance, neural correlates related to these effects, and potential neural activation differences between freezers and non-freezers during motor imagery (MI) of gait.MethodsThirty-seven participants from a larger exercise intervention completed behavioral assessments and functional magnetic resonance imaging (fMRI) scans before and after a 12-week exercise intervention. Gait performance was characterized using gait velocity and stride length, and a region of interest (ROI) fMRI analysis examined task-based blood oxygen-level dependent (BOLD) signal changes of the somatomotor network (SMN) during MI of forward (IMG-FWD) and backward (IMG-BWD) gait.ResultsVelocity (F(1,34) = 55.04, p < 0.001) and stride length (F(1,34) = 77.58, p < 0.001) were significantly lower for backward versus forward walking in all participants. The ROI analysis showed freezers had lower BOLD signal compared to non-freezers in the cerebellum (F(1,32) = 7.01, p = 0.01), primary motor (left: F(1,32) = 7.09, p = 0.01; right: F(1,32) = 7.45, p = 0.01), and primary sensory (left: F(1,32) = 9.59, p = 0.004; right: F(1,32) = 8.18, p = 0.007) cortices during IMG-BWD only. The evidence suggests the exercise intervention did not affect gait or BOLD signal during MI.ConclusionWhile all participants had significantly slower and shorter backward velocity and stride length, respectively, the exercise intervention had no effect. Similarly, BOLD signal during MI did not change with exercise; however, freezers had significantly lower BOLD signal during IMG-BWD compared to non-freezers. This suggests potential decreased recruitment of the SMN during MI of gait in freezers.
| S-EPMC6120800 | biostudies-literature
Project description:DNA polymerase gamma (pol gamma ) is required to maintain the genetic integrity of the 16,569-bp human mitochondrial genome (mtDNA). Mutation of the nuclear gene for the catalytic subunit of pol gamma (POLG) has been linked to a wide range of mitochondrial diseases involving mutation, deletion, and depletion of mtDNA. We describe a heterozygous dominant mutation (c.1352G-->A/p.G451E) in POLG2, the gene encoding the p55 accessory subunit of pol gamma , that causes progressive external ophthalmoplegia with multiple mtDNA deletions and cytochrome c oxidase (COX)-deficient muscle fibers. Biochemical characterization of purified, recombinant G451E-substituted p55 protein in vitro revealed incomplete stimulation of the catalytic subunit due to compromised subunit interaction. Although G451E p55 retains a wild-type ability to bind DNA, it fails to enhance the DNA-binding strength of the p140-p55 complex. In vivo, the disease most likely arises through haplotype insufficiency or heterodimerization of the mutated and wild-type proteins, which promote mtDNA deletions by stalling the DNA replication fork. The progressive accumulation of mtDNA deletions causes COX deficiency in muscle fibers and results in the clinical phenotype.
| S-EPMC1474082 | biostudies-literature
Project description:Decreased mitochondrial oxidative phosphorylation (OXPHOS) is one of the hallmarks of cancer. To date, the identity of nuclear gene(s) responsible for decreased OXPHOS in tumors remains unknown. It is also unclear whether mutations in nuclear gene(s) responsible for decreased OXPHOS affect tumorigenesis. Polymerase-gamma (POLG) is the only DNA polymerase known to function in human mitochondria. Mutations in POLG are known to cause mitochondrial DNA (mtDNA) depletion and decreased OXPHOS, resulting in mtDNA depletion syndrome in humans. We therefore sequenced all coding exons (2-23) and flanking intron/splice junctions of POLG in breast tumors. We found that the POLG gene was mutated in 63% of breast tumors. We identified a total of 17 mutations across the POLG gene. Mutations were found in all three domains of the POLG protein, including T251I (the exonuclease domain), P587L (the linker region) and E1143G (the polymerase domain). We identified two novel mutations that include one silent (A703A) and one missense (R628Q) mutation in the evolutionarily conserved POLG linker region. In addition, we identified three novel mutations in the intronic region. Our study also revealed that mtDNA was depleted in breast tumors. Consistently, mutant POLG, when expressed in breast cancer cells, induced a depletion of mtDNA, decreased mitochondrial activity, decreased mitochondrial membrane potential, increased levels of reactive oxygen species and increased Matrigel invasion. Together, our study provides the first comprehensive analysis of the POLG gene mutation in human cancer and suggests a function for POLG (1) in decreased OXPHOS in cancers and (2) in promoting tumorigenicity.
| S-EPMC2782392 | biostudies-literature