Stem cells derived from pluripotent cells offer the hope of new treatments for diseases for which current therapy is inadequate. Clinical trials are essential in developing effective and safe stem cell therapies and fulfilling this promise. However, such clinical trials raise ethical issues that are more complex than those raised in clinical trials using drugs, cord blood stem cells, or adult stem cells. Several clinical trials are now being carried out with stem cells derived from pluripotent cells, and many more (...) can be expected in light of the rapid scientific progress in the field.Degenerative neurological diseases are desirable targets for stem cell clinical trials. The FDA has approved Phase 1 clinical trials of neural stem cell transplantation for Batten Disease, Pelizaeus-Merzbacher Disease, and spinal cord injury. In Parkinson Disease, stem cell transplantation could correct the primary pathophysiological defect — inadequate levels of the neurotransmitter dopamine. Current treatment is unsatisfactory in late-stage PD. (shrink)

PURPOSE: To evaluate the effects of social support on comprehension and recall of consent form information in a study of Parkinson disease patients and their caregivers.DESIGN and METHODS: Comparison of comprehension and recall outcomes among participants who read and signed the consent form accompanied by a family member/friend versus those of participants who read and signed the consent form unaccompanied. Comprehension and recall of consent form information were measured at one week and one month respectively, using Part A (...) of the Quality of Informed Consent Questionnaire .RESULTS: The mean age of the sample of 143 participants was 71 years . Analysis of covariance was used to compare QuIC scores between the intervention group and control group . In the 1-week model, no statistically significant intervention effect was found . However, the intervention status by patient status interaction was statistically significant . In the 1-month model, no statistically significant intervention effect was found . Again, however, the intervention status by patient status interaction was statistically significant . At both time periods, intervention group patients scored higher on the QuIC than did intervention group caregivers, and control group patients scored lower on the QuIC than did control group caregivers.IMPLICATIONS: Social support played a significant role in enhancing comprehension and recall of consent form information among patients. (shrink)

Research with nonhuman primates is essential to medical progress and will still be necessary for the foreseeable future. Almost all research scientists agree that animal research is critical to understanding basic biology, discovering new treatments for human (and animal) diseases, and maximizing the safety of new medicines while minimizing their harm to humans. All but two of the Nobel prizes in medicine awarded over the last one hundred years have depended on animal research, and the list of modern medicines, vaccines, (...) and other treatments, as well as basic science discoveries, is so extensive that it could not be adequately covered in even a huge volume. Increases in average life span in the last century are the result of improved public health measures, and many diseases may be related to lifestyle choices. But animal research has contributed to understanding these factors and to the development of vaccines and lifesaving treatments. The philosophical debate regarding the benefits and moral costs of animal research has also filled many volumes by ethicists and philosophers. The major arguments against the use of animals in medical research have been explicitly refuted by a few brave scientists, as well as implicitly by the vast majority of the working biomedical science community. My contribution to this discussion is to provide a personal perspective on my decision if, when, and how to use monkeys in research experiments on Parkinson disease. As a physician researcher, I have been working for many years to understand and cure Parkinson disease. (shrink)

Clinical trials of stem cell transplantation raise ethical issues that are intertwined with scientific and design issues, including choice of control group and intervention, background interventions, endpoints, and selection of subjects. We recommend that the review and IRB oversight of stem cell clinical trials should be strengthened. Scientific and ethics review should be integrated in order to better assess risks and potential benefits. Informed consent should be enhanced by assuring that participants comprehend key aspects of the trial. For the trial (...) to yield generalizable knowledge, negative findings and serious adverse events must be reported. (shrink)

Parkinson's Disease (PD) is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms generally come on slowly over time. Early in the disease, the most obvious are shaking, rigidity, slowness of movement, and difficulty with walking. Doctors do not know what causes it and finds difficulty in early diagnosing the presence of Parkinson’s disease. An artificial neural network system with back propagation algorithm is presented in this paper (...) for helping doctors in identifying PD. Previous research with regards to predict the presence of the PD has shown accuracy rates up to 93% [1]; however, accuracy of prediction for small classes is reduced. The proposed design of the neural network system causes a significant increase of robustness. It is also has shown that networks recognition rates reached 100%. (shrink)

Parkinson´s disease (PD) is a neurodegenerative disorder characterized by motor symptoms following dopaminergic depletion in the substantia nigra. Besides motor impairments however, several non-motor detriments can have the potential to considerably impact subjectively perceived quality of life in patients. Particularly emotion recognition of facial expressions has been shown to be affected in PD, and especially the perception of negative emotions like fear, anger or disgust is impaired. While emotion processing generally refers to automatic implicit as well as conscious (...) explicit processing, the focus of most previous studies in PD was on explicit recognition of emotions only, while largely ignoring implicit processing deficits. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is widely accepted as therapeutic measure in the treatment of PD and has been shown to advantageously influence motor problems. Among various concomitant non-motor effects of STN-DBS, modulation of facial emotion recognition under subthalamic stimulation has been investigated in previous studies with rather heterogeneous results. While there seems to be consensus regarding the processing of disgust which significantly deteriorates under STN stimulation, findings concerning emotions like fear or happiness report heterogeneous data and seem to depend on various experimental settings and measurements. In the present review, we summarized previous investigations focusing on STN-DBS influence on recognition of facial emotional expressions in patients suffering from PD. In a first step, we provide a synopsis of disturbances and problems in facial emotion processing observed in patients with PD. Secondly, we present findings of STN-DBS influence on facial emotion recognition and especially highlight different impacts of stimulation on implicit and explicit emotional processing. (shrink)

Artificial intelligence (AI) has garnered tremendous attention in health care, and many hope that AI can enhance our health system’s ability to care for people with chronic and degenerative conditions, including Parkinson’s Disease (PD). This paper reports the themes and lessons derived from a qualitative study with people living with PD, family caregivers, and health care providers regarding the ethical dimensions of using AI to monitor, assess, and predict PD symptoms and progression. Thematic analysis identified ethical concerns at (...) four intersecting levels: personal, interpersonal, professional/institutional, and societal levels. Reflecting on potential benefits of predictive algorithms that can continuously collect and process longitudinal data, participants expressed a desire for more timely, ongoing, and accurate information that could enhance management of day-to-day fluctuations and facilitate clinical and personal care as their disease progresses. Nonetheless, they voiced concerns about intersecting ethical questions around evolving illness identities, familial and professional care relationships, privacy, and data ownership/governance. The multi-layer analysis provides a helpful way to understand the ethics of using AI in monitoring and managing PD and other chronic/degenerative conditions. (shrink)

Implanted medical devices—for example, cardiac defibrillators, deep brain stimulators, and insulin pumps—offer users the possibility of regaining some control over an increasingly unruly body, the opportunity to become part “cyborg” in service of addressing pressing health needs. We recognize the value and effectiveness of such devices, but call attention to what may be less clear to potential users—that their vulnerabilities may not entirely disappear but instead shift. We explore the kinds of shifting vulnerabilities experienced by people with Parkinson’s (...) class='Hi'>disease (PD) who receive therapeutic deep brain stimulators to help control their tremors and other symptoms of PD. (shrink)

We investigated family members’ lived experience of Parkinson’s disease aiming to investigate opportunities for well-being. A lifeworld-led approach to healthcare was adopted. Interpretative phenomenological analysis was used to explore in-depth interviews with people living with PD and their partners. The analysis generated four themes: It’s more than just an illness revealed the existential challenge of diagnosis; Like a bird with a broken wing emphasizing the need to adapt to increasing immobility through embodied agency; Being together with PD exploring (...) the kinship within couples and belonging experienced through support groups; and Carpe diem! illuminated the significance of time and fractured future orientation created by diagnosis. Findings were interpreted using an existential-phenomenological theory of well-being. We highlighted how partners shared the impact of PD in their own ontological challenges. Further research with different types of families and in different situations is required to identify services required to facilitate the process of learning to live with PD. Care and support for the family unit needs to provide emotional support to manage threats to identity and agency alongside problem-solving for bodily changes. Adopting a lifeworld-led healthcare approach would increase opportunities for well-being within the PD illness journey. (shrink)

Introduction As deep brain stimulation (DBS) has shifted to being used earlier during Parkinson’s disease (PD), data is lacking regarding patient specific attitudes, preferences, and factors which may influence the timing of and decision to proceed with DBS in the United States. This study aims to identify and compare attitudes and preferences regarding the earlier use of DBS in Parkinson’s patients who have and have not undergone DBS. Methods We developed an online survey concerning attitudes about DBS (...) and its timing in PD. The survey was distributed nationally in the United States via the Michael J. Fox Foundation Trial Finder, the American Parkinson Disease Association flyers, and as a link on the Parkinson Alliance website. Differences in responses between PD DBS and non-DBS patients were assessed. Results A total of 445 patients with PD met eligibility criteria for the survey of which 160 self-identified as having undergone DBS. Fifty-five percent (n = 124) of non-DBS patients believed that DBS for PD should only be considered after all medication options have been tried. Patients favoring early DBS had fewer concerns regarding the surgery than those favoring later DBS. Conclusion Our findings highlight a variety of important considerations and concerns patients have regarding DBS and its timing. These viewpoints are important aspects of shared decision-making, as they help to identify patients’ preferences, values, and goals, which should enable providers to better navigate, with their patients, the decision path for therapeutic options to consider. (shrink)

BackgroundThe cognitive outcomes induced by subthalamic nucleus deep brain stimulation (STN-DBS) remain unclear, especially in PD patients with mild cognitive impairment (MCI). This study explored the cognitive effects of STN-DBS in PD patients with MCI.MethodsThis was a retrospective cohort study that included 126 PD patients who underwent STN-DBS; all patients completed cognitive and motor assessments before and at least 6 months after surgery. Cognitive changes were mainly evaluated by the Montreal cognitive assessment (MoCA) scale and the seven specific MoCA domains, (...) including visuospatial/executive function, naming, attention, language, abstract, delayed recall, and orientation. Motor improvement was evaluated by the UPDRS-III. Cognitive changes and motor improvements were compared between PD-MCI and normal cognitive (NC) patients. Logistic regression analyses were performed to explore predictors of post-operative cognitive change.ResultsAt the time of surgery, 61.90% of the included PD patients had MCI. Compared with the PD-MCI group, the PD-NC group had a significantly higher proportion of cases with post-operative cognitive decline during follow-up of up to 36 months (mean 17.34 ± 10.61 months), mainly including in global cognitive function, visuospatial/executive function and attention. Covariate-adjusted binary logistic regression analyses showed that pre-operative global cognitive status was an independent variable for post-operative cognitive decline. We also found that pre-operative cognitive specific function could predict its own decline after STN-DBS, except for the naming and orientation domains.ConclusionPD-MCI patients are at a lower risk of cognitive decline after STN-DBS compared with PD-NC patients. (shrink)

In April 1999, Dr. Curt Freed of the University of Colorado in Denver and Dr. Stanley Fahn of Columbia Presbyterian Center in New York presented the results of a four-year, $5.7 million government-financed study using tissue from aborted fetuses to treat Parkinson’s disease at a conference of the American Academy of Neurology. The results of the first government-financed, placebo-controlled clinical study using fetal tissue showed that the symptoms of some Parkinson’s patients had been relieved. This research study (...) involved forty subjects, nineteen women and twenty-one men; all suffered from Parkinson’s disease for an average of 13.5 years. In the study, each subject underwent neurosurgery: “four tiny burr holes, drilled through the wrinkle lines above the eyebrows into the skull, to clear a pathway to the brain. But only half received injections of fetal cells into the putamen, the region of the brain that controls movement; the other half received nothing. One year later, three members of the placebo group said their symptoms had improved.” In two-thirds of the transplant recipients, the fetal tissue took hold and seemed to establish a new network to produce the missing neurochemical dopamine. (shrink)

Environmental influences on the experiences of people with Parkinson’s diseaseThis study elucidates environmental influences on lived illness experiences. For two consecutive years, persons with Parkinson’s disease (PD) participated in 1 week of daily walking in the Swedish mountains. Daily, low‐intensive walking that is free of intense effort or time pressures associated with group interaction characterized the week. Participants were interviewed 3 months after the mountain stay regarding experiences in the mountains, daily living, and how their experience in (...) the mountains influenced their daily living after returning home. A phenomenological method was used for data analysis. Results point to the close connection between mind, body, and environment. The connection becomes highlighted when people are afflicted with sickness, such as PD, which causes impaired control of body language, impaired voluntary mobility, and lowered energy levels. The results also show how a social context in an environment with suitable physical challenges led to a change in individuals’ perceptions of the manageability of their experienced sicknesses. These results provide a deepened understanding of how individuals with PD experience illness, its influences on daily life, and how a suitable environment opens opportunities for managing daily issues. (shrink)

Despite intense academic debate in the recent past over the use of ‘sham surgery’ control groups in research, there has been a recent resurgence in their use in the field of neurodegenerative disease. Yet the primacy of ethical arguments in favour of sham surgery controls is not yet established. Preliminary empirical research shows an asymmetry between the views of neurosurgical researchers and patients on the subject, while different ethical guidelines and regulations support conflicting interpretations. Research ethics committees faced with (...) a proposal involving sham surgery should be aware of its ethical complexities. An overview of recent and current placebo-controlled surgical trials in the field of Parkinson's Disease is provided here, followed by an analysis of the key ethical issues which such trials raise. (shrink)

Recently it has been hypothesized that apoptotic cell death is involved in several neuropathological conditions including Parkinson's disease (PD). Initial morphological studies assessing the presence of apoptosis in Parkinsonian brain tissues yielded mixed results. Based on more recent studies in human PD brains as well in animal and cell culture models of the disease, a picture is emerging, however, that strongly suggests that many of the molecular players thought to participate in this type of neuronal cell death (...) are active in the disease. The task of researchers in the field is now to deduce how these players may be interacting with one another to bring about cell death in PD and to design effective therapies to interfere with these processes. BioEssays 23:640–646, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Deep brain stimulation of the subthalamic nucleus or the globus pallidus is an established treatment for Parkinson’s disease that yields a marked and lasting improvement of motor symptoms. Yet, DBS benefit on gait disturbances in PD is still debated and can be a source of dissatisfaction and poor quality of life. Gait disturbances in PD encompass a variety of clinical manifestations and rely on different pathophysiological bases. While gait disturbances arising years after DBS surgery can be related to (...) disease progression, early impairment of gait may be secondary to treatable causes and benefits from DBS reprogramming. In this review, we tackle the issue of gait disturbances in PD patients with DBS by discussing their neurophysiological basis, providing a detailed clinical characterization, and proposing a pragmatic programming approach to support their management. (shrink)

Precise and timely diagnosis of Parkinson’s disease is important to control its progression among subjects. Currently, a neuroimaging technique called dopaminergic imaging that uses single photon emission computed tomography (SPECT) with 123I-Ioflupane is popular among clinicians for detecting Parkinson’s disease in early stages. Unlike other studies, which consider only low-level features like gray matter, white matter, or cerebrospinal fluid, this study explores the non-linear relation between different biomarkers (SPECT + biological) using deep learning and multivariate logistic (...) regression. Striatal binding ratios are obtained using 123I-Ioflupane SPECT scans from four brain regions which are further integrated with five biological biomarkers to increase the diagnostic accuracy. Experimental results indicate that this investigated approach can differentiate subjects with 100% accuracy. The obtained results outperform the ones reported in the literature. Furthermore, logistic regression model has been developed for estimating the Parkinson’s disease onset probability. Such models may aid clinicians in diagnosing this disease. (shrink)

While slowness of movement is an obligatory characteristic of Parkinson’s disease (PD), there are conditions in which patients move uncharacteristically fast, attributed to deficient motor inhibition. Here we investigate deficient inhibition in an optimal sensory-motor integration framework, using a game in which subjects used a paddle to catch a virtual ball. Display of the ball was extinguished as soon as the catching movement started, segregating the task into a sensing and acting phase. We analyzed the behavior of 9 (...) PD patients (ON medication) and 10 age-matched controls (HC). The switching times (between sensing and acting phase) were compared to the predicted optimal switching time, based on the individual estimates of sensory and motor uncertainties. The comparison showed that deviation from predicted optimal switching times were similar between groups. However, PD patients showed a weaker correlation between variability in switching time and sensory-motor uncertainty, indicating a reduced propensity to generate exploratory behavior for optimizing goal-directed movements. Analysis of the movement kinematics revealed that PD patients, compared to controls, used a lower peak velocity of the paddle and intercepted the ball with greater velocity. Adjusting the trial duration to the time for the paddle to stop moving, we found that PD patients spent a smaller proportion of the trial duration for observing the ball. Altogether, the results do not show the premature movement initiation and truncated sensory processing that we predicted to ensue from deficient inhibition in PD. (shrink)

The present study investigated the effect of Parkinson’s disease (PD) on prospective memory (PM) tasks by varying the emotional content of the PM actions. Twenty-one older adults with PD and 25 healthy older adults took part in the present study. Participants performed three virtual days in the Virtual Week task. On each virtual day, participants performed actions with positive, negative or neutral content. Immediately following each virtual day, participants completed a recognition task to assess their retrospective memory for (...) the various prospective memory tasks. PD patients were less accurate than the control group at both PM accuracy and recognition task accuracy. The effect of emotional valence was also evident, indicating that all participants were more accurate on positive PM tasks than both negative and neutral. This study confirmed PM impairment in PD patients and extended previous research showing how positive emotional stimuli can influence PM performance. (shrink)

Parkinson's disease has long been perceived as a pure motor disorder, partly due to its initial description by James Parkinson, who suggested that "senses and intellect remain intact", and partly due to the fact that patients with PD did not survive long, before effective treatment became available. As the survival time of patients with Parkinson's disease has substantially increased due to modern treatment, it has become apparent that cognitive deficits and dementia are also frequent features, (...) especially in elderly patients. With the progression of the disease and age, dementia develops in a substantial number of patients and constitutes a major therapeutic challenge. Dementia has thus increasingly been the focus of research and practice in recent years and a large body of knowledge has been accumulated. Despite these developments there has been no single volume dedicated to this topic. This book provides an extensive overview of the current status of knowledge pertaining to cognitive impairment and dementia associated with Parkinson's disease, intended as a reference book for general neurologists, neurology residents and also those with a special interest in movement disorders. In this edited volume experts in the field describe in detail all aspects of cognitive impairment and dementia in Parkinson's disease, including epidemiology, spectrum of clinical features, pathology, neurochemistry and genetics, findings in auxiliary investigations, relation to other neurodegenerative disorders, diagnostic process and management, and rounded up by discussion of future research directions and expectations. The text is complemented and enriched with tables, figures and heavily referenced to encompass all relevant literature. (shrink)

Disruptions in dopamine transmission within the basal ganglia (BG) produce deficits in voluntary actions, that is, in the interface between cortically-generated goal representation and BG-mediated response selection. Under conditions of dopamine loss in humans and other animals, responses are impaired when they require internal generation, but are relatively intact when elicited by external stimuli.

Why are some patients with Parkinson's disease unhappy about the outcome of deep brain stimulation (DBS)? Meccaci and Haselager (2014) attempt to answer this question by analyzing the seminal case...

Objective: To investigate the correlation between preoperative response to the L-dopa challenge test and efficacy of deep brain stimulation (DBS) on motor function in Parkinson’s disease (PD).Methods: We retrospectively reviewed the data of 38 patients with idiopathic PD who underwent DBS surgery with a median follow-up duration of 7 months. Twenty underwent bilateral globus pallidus interna (GPi) DBS, and 18 underwent bilateral subthalamic nucleus (STN) DBS. The Movement Disorder Society Unified Parkinson Disease Rating Scale-Motor Part (MDS (...) UPDRS-III) was assessed before surgery and at the last follow-up in different medication and stimulation conditions, respectively.Results: Pearson’s correlation analysis revealed a positive correlation between preoperative L-dopa challenge responsiveness and GPi-DBS responsiveness on the total score (R2 = 0.283, p = 0.016) but not on the non-tremor total score (R2 = 0.158, p = 0.083) of MDS UPDRS-III. Such correlation remained significant (R2′ = 0.332, p = 0.010) after controlling for age at the time of surgery as confounding factor by partial correlation analysis. The preoperative L-dopa challenge responsiveness was significantly correlated with the tremor-controlling outcome of GPi-DBS (R2 = 0.390, p = 0.003). In contrast, we found a positive correlation between preoperative L-dopa challenge responsiveness and STN-DBS responsiveness on the non-tremor total score (R2 = 0.290, p = 0.021), but not on the total score (R2 = 0.130, p = 0.141) of MDS UPDRS-III. The partial correlation analysis further demonstrated that the predictive value of preoperative L-dopa challenge responsiveness on the non-tremor motor outcome of STN-DBS was eliminated (R2′ = 0.120, p = 0.174) after controlling for age at the time of surgery as confounding factor.Interpretation: The short-term predictive value of preoperative response to the L-dopa challenge test for the motor outcome of GPi-DBS in PD was systematically described. Our findings suggest: (1) a solid therapeutic effect of GPi-DBS in treating L-dopa-responsive tremors; (2) a negative effect of age at the time of surgery on motor outcomes of STN-DBS, (3) a possible preference of STN- to GPi-DBS in L-dopa-resistant tremor control, and (4) a possible preference of GPi- to STN-DBS in elderly PD patients who have a satisfactory dopamine response. (shrink)

BackgroundNew disease-modifying ways to treat Parkinson’s disease (PD) may soon become a reality with intracerebral transplantation of cell products produced from human embryonic stem cells (hESCs). The aim of this study was to assess what factors influence preferences of patients with PD regarding stem-cell based therapies to treat PD in the future.MethodsPatients with PD were invited to complete a web-based discrete choice experiment to assess the importance of the following attributes: (i) type of treatment, (ii) aim of (...) treatment, (iii) available knowledge of the different types of treatments, (iv) effect on symptoms, and (v) risk for severe side effects. Latent class conditional logistic regression models were used to determine preference estimates and heterogeneity in respondents’ preferences.ResultsA substantial difference in respondents’ preferences was observed in three latent preference patterns (classes). “Effect on symptoms” was the most important attribute in class 1, closely followed by “type of treatment,” with medications as preferred to other treatment alternatives. Effect on symptoms was also the most important attribute in class 2, with treatment with hESCs preferred over other treatment alternatives. Likewise for class 3, that mainly focused on “type of treatment” in the decision-making. Respondents’ class membership was influenced by their experience in treatment, side effects, and advanced treatment therapy as well as religious beliefs.ConclusionsMost of the respondents would accept a treatment with products emanating from hESCs, regardless of views on the moral status of embryos. Preferences of patients with PD may provide guidance in clinical decision-making regarding treatments deriving from stem cells. (shrink)

Parkinson’s disease (PD) is a common neurodegenerative disorder of the nervous system that affects about 1 in 800 people and for which we have symptomatic but not curative therapies. At the core of the disease is the loss of a specific population of dopaminergic neurons within the brain, and replacement of dopamine through drug therapies has provided clinically significant benefit for many patients. However this therapy only ever offers a temporary amelioration of symptoms and with time this symptomatic (...) therapy becomes less efficacious and produces its own unique side-effects. As a result more effective curative therapies have been sought, including the use of cell based therapies to replace the lost dopaminergic neurons. In this review I am going to discuss PD and its possible repair using neural transplants. In particular I am going to discuss which type of cells are best considered as a reparative therapy, where they should be transplanted in the brain, when in the disease course and in which type of patient. By considering these issues, I hope to be able to make some recommendations as to the future use of this approach in PD. (shrink)

BackgroundHuman embryonic stem cells are currently used for developing treatment against Parkinson’s disease (PD). However, the use of ES cells is surrounded with moral concerns. Research regarding the public's attitudes can form an important basis for policymaking. The aim was to explore the perceptions of the public on using donated human embryos for developing treatment of Parkinson’s Disease.MethodsSemi-structured individual qualitative interviews were conducted with 11 members of the general population in Sweden. Interviews were analyzed with thematic (...) content analyses.ResultsFour categories and additional sub-categories; Different views on the embryo requires delicacy, Using embryos to treat Parkinson’s disease, Doing things in the right way, and Communication, media, and public opinion. In general, respondents were positive towards the usage of embryotic stem cells to treat PD, but the usage were conditioned and specific terms were demanded. Informed consent from both donors were required and delicacy and sensitivity when working with embryos were needed.ConclusionsIt was perceived better to use surplus embryos to treat PD increase is than to discard them, also among those who perceived the embryo as “a potential life.” The participants raised several conditions under usage for treatment should be allowed. Even if the embryos otherwise are going to be discarded, usage requires informed consent from the donating couples. (shrink)

Neurodegenerative Parkinson's Disease is one of the common incurable diseases among the elderly. Clinical assessments are characterized as standardized means for PD diagnosis. However, relying on medical evaluation of a patient's status can be subjective to physicians' experience, making the assessment process susceptible to human errors. The use of ICT-based tools for capturing the status of patients with PD can provide more objective and quantitative metrics. In this vein, the Personalized Serious Game Suite and intelligent Motor Assessment Tests, (...) produced within the i-PROGNOSIS European project, are explored in the current study. More specifically, data from 27 patients with PD at Stage 1 and Stage 3 produced from their interaction with PGS/iMAT are analyzed. Five feature vector scenarios are set, including features from PGS or iMAT scores or their combination, after also taking into consideration the age of patients with PD. These FVs are fed into three machine learning classifiers, i.e., K-Nearest Neighbor, Support Vector Machines, and Random Forest, to infer the stage of each patient with PD. A Leave-One-Out Cross-Validation method is adopted for testing the classification performance. The experimental results show that a high classification accuracy is achieved from both data sources, justifying the effectiveness of PGS/iMAT to efficiently reflect the motor skill status of patients with PD and further potentiating PGS/iMAT enhancement with a machine learning a part to infer for the stage of patients with PD. Clearly, this integrated approach provides new opportunities for remote monitoring of the stage of patients with PD, contributing to a more efficient organization and set up of personalized interventions. (shrink)

Parkinson’s Disease can be treated with the use of microelectrode recording and stimulation. This paper presents a data stream classifier that analyses raw data from micro-electrodes and decides whether the measurements were taken from the subthalamic nucleus (STN) or not. The novelty of the proposed approach is based on the fact that distances based on raw data are used. Two distances are investigated in this paper, i.e. Normalized Compression Distance (NCD) and Lempel-Ziv Jaccard Distance (LZJD). No new features (...) needed to be extracted due to the fact that in the case of high-dimensional data the process is extremely time-consuming. The k-nearest neighbour (k-NN) was chosen as the classifier due to its simplicity, which is essential in data stream classification. Results obtained from classifiers based on k-NN: k-NN, k-NN were compared with Probabilistic Approximate Window (k-NN with PAW); k-NN with Probabilistic Approximate Window and Adaptive Windowing (k-NN with PAW and ADWIN); and Self Adjusting Memory k-NN (SAM k-NN), which use the proposed distances, with the performance of the same classifiers but using standard Euclidean distance. Prequential accuracy was chosen as the performance measure. The results of the experiments performed with the described approach are in most cases better, i.e. the performance measures for kNN classifiers that use NCD and LZJD distances are better by up to 8.5 per cent and 14 per cent, respectively. Moreover, the proposed approach performs better when compared with other stream classification algorithms, i.e. Hoeffding Tree, Naive Bayes, and Leveraging Bagging. In the discussed case, an improvement of classification rate of up to 17.9 per cent when using Lempel-Ziv Jaccard Distance instead of the Euclidean was noted. (shrink)

When efficiently used for action, tool becomes part of body, with effect on the spatial temporal movement parameters and body size perception. Until now, no previous investigation was reported about tool embodiment in Parkinson’s disease (PD), that is a neurological disease characterized by several sensory and motor symptoms affecting body and action. We enrolled fourteen individuals affected by PD and eighteen healthy individuals as controls. We studied the spatial-temporal parameters on self-paced free pointing movements task, via an (...) optoelectronic system, before and after a short training in which a 27 cm long rod was used to point toward a far target. Moreover, we investigated changes in estimation of arm length through the Tactile Estimation Task. After the tool use training, controls showed changes in spatial-temporal parameters: they were slower to perform movements and reported higher value of deceleration, respect to the baseline. However, such a difference did not emerged in the PD individuals. In the Tactile Discrimination Task, no difference emerged before and after the tool use training in both groups. Our results were suggestive of possible difficulties of tool embodiment process in PD. We discussed our results in relation to aberrant multisensory integration as well as in terms of the effect of PD sensory and motor symptoms on body schema plasticity. The present study points at a novel way to conceive PD sensory motor signs and symptoms, in terms of their effect on individuals’ body representation. (shrink)

Deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson’s disease can lead to the development of neuropsychiatric symptoms. These can include harmful changes in mood and behaviour that alienate family members and raise ethical questions about personal responsibility for actions committed under stimulation-dependent mental states. Qualitative interviews were conducted with twenty participants following subthalamic DBS at a movement disorders centre, in order to explore the meaning and significance of stimulation-related neuropsychiatric symptoms amongst a purposive sample (...) of persons with PD and their spousal caregivers. Interview transcripts underwent inductive thematic analysis. Clinical and experiential aspects of post-DBS neuropsychiatric symptoms were identified. Caregivers were highly burdened by these symptoms and both patients and caregivers felt unprepared for their consequences, despite having received information prior to DBS, desiring greater family and peer engagement prior to neurosurgery. Participants held conflicting opinions as to whether emergent symptoms were attributable to neurostimulation. Many felt that they reflected aspects of the person’s “real” or “younger” personality. Those participants who perceived a close relationship between stimulation changes and changes in mental state were more likely to view these symptoms as inauthentic and uncontrollable. Unexpected and troublesome neuropsychiatric symptoms occurred despite a pre-operative education programme that was delivered to all participants. This suggests that such symptoms are difficult to predict and manage even if best practice guidelines are followed by experienced centres. Further research aimed at predicting these complications may improve the capacity of clinicians to tailor the consent process. (shrink)

BackgroundPublic health guidelines have recommended that elective medical procedures, including deep brain stimulation surgery for Parkinson’s disease, should not be scheduled during the coronavirus pandemic to prevent further virus spread and overload on health care systems. However, delaying DBS surgery for PD may not be in the best interest of individual patients and is not called for in regions where virus spread is under control and inpatient facilities are not overloaded.MethodsWe administered a newly developed phone questionnaire to 20 (...) consecutive patients with PD who received DBS surgery in Ruijin Hospital in Shanghai during the COVID-19 pandemic. The questionnaire was designed to gather the patients’ experiences and perceptions on the impact of COVID-19 on their everyday activities and access to medical care.ResultsMost of the patients felt confident about the preventive measures taken by the government and hospitals, and they have changed their daily living activities accordingly. Moreover, a large majority of patients felt confident obtaining access to regular and COVID-19-related health care services if needed. Routine clinical referral, sense of security in the hospital during the outbreak, and poor control of PD symptoms were the three main reasons given by patients for seeking DBS surgery during the COVID-19 pandemic.ConclusionThe COVID-19 pandemic has considerably impacted medical care and patients’ lives but elective procedures, such as DBS surgery for PD, do not need to be rescheduled when the health care system is not overloaded and adequate public health regulations are in place. (shrink)

Background and purposeWe previously established a radiological protocol to discriminate multiple system atrophy-parkinsonian subtype from Parkinson’s disease. However, we do not know if it can differentiate early stage disease. This study aimed to investigate whether the morphological and intensity changes in susceptibility weighted imaging of the lentiform nucleus could discriminate MSA-P from PD at early stages.MethodsWe retrospectively enrolled patients with MSA-P, PD and sex- and age-matched controls whose brain MRI included SWI, between January 2015 and July 2020 (...) at the Movement Disorder Center. Two specialists at the center reviewed the medical records and made the final diagnosis, and two experienced neuroradiologists performed MRI analysis, based on a defined and revised protocol for conducting morphological measurements of the LN and signal intensity.ResultsNineteen patients with MSA-P and 19 patients with PD, with less than 2 years of disease duration, and 19 control individuals were enrolled in this study. We found that patients with MSA- P presented significantly decreased size in the short line and corrected short line, ratio of the SL to the long line and corrected SLLr of the LN, increased standard deviation of signal intensity compared to patients with PD and controls. With receiver operating characteristic analysis, this finding had a sensitivity of 89.5% and a specificity of 73.7% to distinguish MSA- P from PD.ConclusionCompared to PD and controls, patients with MSA-P are characterized by a narrowing morphology of the posterior region of the LN. Quantitative morphological changes provide a reference for clinical auxiliary diagnosis. (shrink)

Postural instability in Parkinson’s disease (PD) is characterized by impaired postural responses to transient perturbations, increased postural sway in stance and difficulty transitioning between tasks. In addition, some studies suggest that loss of dopamine in the basal ganglia due to PD results in difficulty using proprioceptive information for motor control. Here, we quantify the ability of subjects with PD and age-matched control subjects to use and re-weight sensory information for postural control during steady-state conditions of continuous rotations of (...) the stance surface or visual surround. We measure the postural sway of subjects in response to a pseudorandom, surface-tilt stimulus with eyes closed, and in response to a pseudorandom, visual-tilt stimulus. We use a feedback control model of the postural control system to interpret our results, focusing on sensory weighting as a function of stimulus amplitude. We find that subjects with PD can re-weight their dependence upon sensory information in response to changes in surface- or visual-stimulus amplitude. Specifically, subjects with PD behaved like age-matched control subjects by decreasing proprioceptive contribution to stance control with increasing surface-tilt amplitude, and decreasing visual contribution with increasing visual-tilt amplitude. However, subjects with PD do not decrease their reliance on proprioception as much as age-matched controls for small increases in surface-stimulus amplitudes. Levodopa medication did not affect sensory re-weighting behaviors for postural control. The impairment in PD subject’s ability to respond differently to small changes in surface rotation amplitudes is consistent with an increased threshold for perceiving proprioceptive signals, which may result from decreased signal-to-noise in the dopaminergic pathways associated with sensory processing and/or sensory integration. (shrink)

ObjectiveFreezing of gait is detrimental to patients with idiopathic Parkinson’s disease. Its pathophysiology represents a multilevel failure of motor processing in the cortical, subcortical, and brainstem circuits, ultimately resulting in ineffective motor output of the spinal pattern generator. Electrophysiological studies pointed to abnormalities of oscillatory activity in freezers that covered a broad frequency range including the theta, alpha, and beta bands. We explored muscular frequency domain activity with respect to freezing, and used deep brain stimulation to modulate these (...) rhythms thereby evaluating the supraspinal contributions to spinal motor neuron activity.MethodsWe analyzed 9 PD freezers and 16 healthy controls. We studied the patients after overnight withdrawal of dopaminergic medication with stimulation off, stimulation of the subthalamic nucleus or the substantia nigra pars reticulate, respectively. Patients performed a walking paradigm passing a narrow obstacle. We analyzed the frequency-domain spectra of the tibialis anterior and gastrocnemius muscles in ‘regular gait’ and during the ‘freezing’ episodes.ResultsIn stimulation off, PD freezers showed increased muscle activity of the alpha and low-beta band compared to HC in both TA and GA. This activity increase was present during straight walking and during the freezes to similar extent. STN- but not SNr-DBS decreased this activity and paralleled the clinical improvement of freezing.ConclusionWe found increased muscle activation of the alpha and lower beta band in PD freezers compared to HC, and this was attenuated with STN-DBS. Future studies may use combined recordings of local field potentials, electroencephalography, and electromyography to interrogate the supraspinal circuit mechanisms of the pathological activation pattern of the spinal pattern generator. (shrink)

IntroductionAlthough the motor signs of Parkinson’s disease are well defined, nonmotor symptoms, including higher-level language deficits, have also been shown to be frequent in patients with PD. In the present study, we used a lexical decision task to find out whether access to the mental lexicon is impaired in patients with PD, and whether task performance is affected by bradykinesia.Materials and MethodsParticipants were 34 nondemented patients with PD, either without medication or under optimum medication. A total of 19 (...) age-matched control volunteers were also recruited. We recorded reaction times to the LDT and a simple RT task. In each task, stimuli were either visual or auditory. Statistical analyses consisted of repeated-measures analyses of variance and Tukey’s HSD post hoc tests.ResultsIn the LDT, participants with PD both off and on medication exhibited intact access to the mental lexicon in both modalities. In the visual modality, patients off medication were just as fast as controls when identifying real words, but slower when identifying pseudowords. In the visual modality of the control task, RTs for pseudowords were significantly longer for PD patients off medication than for controls, revealing an unexpected but significant lexicality effect in patients that was not observed in the auditory modality. Performances of patients on medication did not differ from those of age-matched controls.DiscussionMotor execution was not slowed in patients with PD either off or on medication, in comparison with controls. Regarding lexical access, patients off medication seemed to have difficulty inhibiting a cognitive-linguistic process when it was not required, and exhibit a specific pseudoword processing deficit in the LDT, which may have been related to impaired lateral word inhibition within the mental lexicon. These deficits seemed to be compensated by medication. (shrink)

BackgroundExercise is increasingly recognized as a key component of Parkinson’s disease treatment strategies, but the underlying mechanism of how exercise affects PD is not yet fully understood.ObjectiveThe activation likelihood estimation method is used to study the mechanism of exercise affecting PD, providing a theoretical basis for studying exercise and PD, and promoting the health of patients with PD.MethodsRelevant keywords were searched on the PubMed, Cochrane Library, and Web of Science databases. Seven articles were finally included according to the (...) screening criteria, with a total sample size of 97 individuals. Using the GingerALE 3.0.2 software, an ALE meta-analysis was performed using seven studies that met the requirements, and the probability of the cross-experiment activation of each voxel was calculated.ResultsThe meta-analysis produced seven clusters, and major activations were found in the cerebellum, occipital lobe, parietal lobe, and frontal lobe brain regions.ConclusionExercise for PD mainly results in the enhanced activation of the cerebellum, occipital lobe, parietal lobe, and frontal lobe. Exercise for PD does not cause a change in the activation of a single brain area, and the observed improvement may result from coordinated changes in multiple brain areas. (shrink)

In Parkinson’s disease, the fronto-striatal network is involved in motor and cognitive symptoms. Working memory updating training engages this network in healthy populations, as observed by improved cognitive performance and increased striatal BOLD signal. This two-part study aimed to assess the feasibility of WM updating training in PD and measure change in cognition, movement and functional brain response in one individual with PD after WM updating training. A feasibility and single-subject study were performed in which patients with PD (...) completed computerized WM updating training. The outcome measures were the pre-post changes in criterion and transfer cognitive tests; cognitive complaints; psychological health; movement kinematics; and task-related BOLD signal. Participants in the feasibility study showed improvements on the criterion tests at post-test. FL displayed the largest improvements on the criterion tests and smaller improvements on transfer tests. Furthermore, FL reported improved cognitive performance in everyday life. A shorter onset latency and smoother upper-limb goal-directed movements were measured at post-test, as well as increased activation within the striatum and decreased activation throughout the fronto-parietal WM network. This two-part study demonstrated that WM updating training is feasible to complete for PD patients and that change occurred in FL at post-test in the domains of cognition, movement and functional brain response. (shrink)

Deep Brain Stimulation (DBS) is an effective treatment for advanced Parkinson’s disease. However, identifying stimulation parameters, such as contact and current amplitudes, is time-consuming based on trial and error. Directional leads add more stimulation options and render this process more challenging with a higher workload for neurologists and more discomfort for patients. In this study, a sweet spot-guided algorithm was developed that automatically suggested stimulation parameters. These suggestions were retrospectively compared to clinical monopolar reviews. A cohort of 24 (...) Parkinson’s disease patients underwent bilateral DBS implantation in the subthalamic nucleus at our center. First, the DBS’ leads were reconstructed with the open-source toolbox Lead-DBS. Second, a sweet spot for rigidity reduction was set as the desired stimulation target for programming. This sweet spot and estimations of the volume of tissue activated were used to suggest (i) the best lead level, (ii) the best contact, and (iii) the effect thresholds for full therapeutic effect for each contact. To assess these sweet spot-guided suggestions, the clinical monopolar reviews were considered as ground truth. In addition, the sweet spot-guided suggestions for best lead level and best contact were compared against reconstruction-guided suggestions, which considered the lead location with respect to the subthalamic nucleus. Finally, a graphical user interface was developed as an add-on to Lead-DBS and is publicly available. With the interface, suggestions for all contacts of a lead can be generated in a few seconds. The accuracy for suggesting the best out of four lead levels was 56%. These sweet spot-guided suggestions were not significantly better than reconstruction-guided suggestions (p = 0.3). The accuracy for suggesting the best out of eight contacts was 41%. These sweet spot-guided suggestions were significantly better than reconstruction-guided suggestions (p < 0.001). The sweet spot-guided suggestions of each contact’s effect threshold had a mean error of 1.2 mA. On an individual lead level, the suggestions can vary more with mean errors ranging from 0.3 to 4.8 mA. Further analysis is warranted to improve the sweet spot-guided suggestions and to account for more symptoms and stimulation-induced side effects. (shrink)