Progressive gait dysfunction is one of the primary motor symptoms in people with Parkinson's disease (PD). It is generally expressed as reduced step length and gait speed and as increased variability ...in step time and step length. People with PD also exhibit stooped posture which disrupts gait and impedes social interaction. The gait and posture impairments are usually resistant to the pharmacological treatment, worsen as the disease progresses, increase the likelihood of falls, and result in higher rates of hospitalization and mortality. These impairments may be caused by perceptual deficiencies (poor spatial awareness and loss of temporal rhythmicity) due to the disruptions in processing intrinsic information related to movement initiation and execution which can result in misperceptions of the actual effort required to perform a desired movement and maintain a stable posture. Consequently, people with PD often depend on external cues during execution of motor tasks. Numerous studies involving open-loop cues have shown improvements in gait and freezing of gait (FoG) in people with PD. However, the benefits of cueing may be limited, since cues are provided in a consistent/rhythmic manner irrespective of how well a person follows them. This limitation can be addressed by providing feedback in real-time to the user about performance (closed-loop cueing) which may help to improve movement patterns. Some studies that used closed-loop cueing observed improvements in gait and posture in PD, but the treadmill-based setup in a laboratory would not be accessible outside of a research setting, and the skills learned may not readily and completely transfer to overground locomotion in the community. Technologies suitable for cueing outside of laboratory environments could facilitate movement practice during daily activities at home or in the community and could strongly reinforce movement patterns and improve clinical outcomes. This narrative review presents an overview of cueing paradigms that have been utilized to improve gait and posture in people with PD and recommends development of closed-loop wearable systems that can be used at home or in the community to improve gait and posture in PD.
Human activity recognition (HAR) is growing in popularity due to its wide-ranging applications in patient rehabilitation and movement disorders. HAR approaches typically start with collecting sensor ...data for the activities under consideration and then develop algorithms using the dataset. As such, the success of algorithms for HAR depends on the availability and quality of datasets. Most of the existing work on HAR uses data from inertial sensors on wearable devices or smartphones to design HAR algorithms. However, inertial sensors exhibit high noise that makes it difficult to segment the data and classify the activities. Furthermore, existing approaches typically do not make their data available publicly, which makes it difficult or impossible to obtain comparisons of HAR approaches. To address these issues, we present wearable HAR (w-HAR) which contains labeled data of seven activities from 22 users. Our dataset's unique aspect is the integration of data from inertial and wearable stretch sensors, thus providing two modalities of activity information. The wearable stretch sensor data allows us to create variable-length segment data and ensure that each segment contains a single activity. We also provide a HAR framework to use w-HAR to classify the activities. To this end, we first perform a design space exploration to choose a neural network architecture for activity classification. Then, we use two online learning algorithms to adapt the classifier to users whose data are not included at design time. Experiments on the w-HAR dataset show that our framework achieves 95% accuracy while the online learning algorithms improve the accuracy by as much as 40%.
OBJECTIVES:Determine diagnostic accuracy of a clinical diagnosis of Parkinson disease (PD) using neuropathologic diagnosis as the gold standard.
METHODS:Data from the Arizona Study of Aging and ...Neurodegenerative Disorders were used to determine the predictive value of a clinical PD diagnosis, using 2 clinical diagnostic confidence levels, PossPD (never treated or not clearly responsive) and ProbPD (responsive to medications). Neuropathologic diagnosis was the gold standard.
RESULTS:Based on first visit, 9 of 34 (26%) PossPD cases had neuropathologically confirmed PD while 80 of 97 (82%) ProbPD cases had confirmed PD. PD was confirmed in 8 of 15 (53%) ProbPD cases with <5 years of disease duration and 72 of 82 (88%) with ≥5 years of disease duration. Using final diagnosis at time of death, 91 of 107 (85%) ProbPD cases had confirmed PD. Clinical variables that improved diagnostic accuracy were medication response, motor fluctuations, dyskinesias, and hyposmia.
CONCLUSIONS:Using neuropathologic findings of PD as the gold standard, this study establishes the novel findings of only 26% accuracy for a clinical diagnosis of PD in untreated or not clearly responsive subjects, 53% accuracy in early PD responsive to medication (<5 yearsʼ duration), and >85% diagnostic accuracy of longer duration, medication-responsive PD. Caution is needed when interpreting clinical studies of PD, especially studies of early disease that do not have autopsy confirmation. The need for a tissue or other diagnostic biomarker is reinforced.
CLASSIFICATION OF EVIDENCE:This study provides Class II evidence that a clinical diagnosis of PD identifies patients who will have pathologically confirmed PD with a sensitivity of 88% and specificity of 68%.
Many patients with Parkinson's disease have potentially disabling off episodes that are not predictably responsive to levodopa. In this study, we assessed the safety and efficacy of apomorphine ...sublingual film as an on-demand therapy for off episodes in patients with Parkinson's disease.
This randomised, double-blind, placebo-controlled study was done by movement disorder specialists at 32 sites in the USA and one in Canada. Patients with Parkinson's disease who had 2 h or more of off time per day with predictable morning off periods, were responsive to levodopa, and were on stable doses of anti-parkinsonian medication were eligible. In an open-label titration phase, increasing doses of apomorphine sublingual film (10–35 mg) were administered until a tolerable full on response was achieved. Patients were then randomly assigned (1:1) with an interactive web-response system to receive the effective dose of apomorphine sublingual film or matching placebo in a 12-week, double-blind maintenance phase. Randomisation was not stratified, and the block size was four. All patients and study personnel were masked to treatment assignments. The primary endpoint was the in-clinic change from predose to 30 min post-dose in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part 3 (motor) score at week 12, analysed on a modified intention-to-treat population by use of a mixed-effect model for repeated measures. Safety analyses were done on all enrolled patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov, NCT02469090.
Between June 18, 2015, and Dec 11, 2017, 109 patients were enrolled and randomly assigned to receive apomorphine sublingual film (n=54) or placebo (n=55). All patients received the assigned study treatment, and 34 (63%) of 54 patients receiving apomorphine sublingual film and 46 (84%) of 55 receiving placebo completed the study. Least squares mean (SE) change from predose to 30 min post-dose in MDS-UPDRS part 3 score at week 12 was −11·1 (SE 1·46, 95% CI −14·0 to −8·2) with apomorphine sublingual film and −3·5 (1·29, −6·1 to −0·9) with placebo (difference −7·6, SE 1·96, 95% CI −11·5 to −3·7; p=0·0002). Mild-to-moderate oropharyngeal events were the most common side-effect, reported in 17 (31%) of 54 patients receiving apomorphine sublingual film and in four (7%) of 55 patients receiving placebo, leading to treatment discontinuation in nine (17%) patients treated with apomorphine and in one (2%) patient treated with placebo. Other treatment-emergent adverse events were transient nausea (in 15 28% patients receiving apomorphine sublingual film), somnolence (seven 13%), and dizziness (five 9%). Orthostatic hypotension, syncope, dyskinesia, hallucinations, prolongation of the QT interval, and impulse control disorders were infrequent (prevalence ≤2% of all patients) or did not occur. One patient treated with apomorphine sublingual film (with known cardiac risk factors) had a fatal cardiac arrest.
Although nearly a third of patients discontinued treatment primarily because of oropharyngeal side-effects, apomorphine sublingual film provided an efficacious, on-demand treatment for off episodes for most patients with Parkinson's disease in this trial. The long-term safety and efficacy of apomorphine sublingual film are currently being investigated.
Cynapsus Therapeutics and Sunovion.
In BriefTraditionally, deep brain stimulation (DBS) surgery for Parkinson's disease is performed with the patient awake, which allows for test stimulation of therapeutic effects. The feasibility of ..."asleep" DBS-performing DBS surgery without test stimulation-presumes that 1) the appropriate target can be selected using MR imaging, and therefore 2) intraoperative assessment of lead placement is sufficiently predictive of functional outcomes. This study prospectively compares functional outcomes of patients treated using the awake and the asleep techniques.
The discovery and reliable detection of markers for neurodegenerative diseases have been complicated by the inaccessibility of the diseased tissue--such as the inability to biopsy or test tissue from ...the central nervous system directly. RNAs originating from hard to access tissues, such as neurons within the brain and spinal cord, have the potential to get to the periphery where they can be detected non-invasively. The formation and extracellular release of microvesicles and RNA binding proteins have been found to carry RNA from cells of the central nervous system to the periphery and protect the RNA from degradation. Extracellular miRNAs detectable in peripheral circulation can provide information about cellular changes associated with human health and disease. In order to associate miRNA signals present in cell-free peripheral biofluids with neurodegenerative disease status of patients with Alzheimer's and Parkinson's diseases, we assessed the miRNA content in cerebrospinal fluid and serum from postmortem subjects with full neuropathology evaluations. We profiled the miRNA content from 69 patients with Alzheimer's disease, 67 with Parkinson's disease and 78 neurologically normal controls using next generation small RNA sequencing (NGS). We report the average abundance of each detected miRNA in cerebrospinal fluid and in serum and describe 13 novel miRNAs that were identified. We correlated changes in miRNA expression with aspects of disease severity such as Braak stage, dementia status, plaque and tangle densities, and the presence and severity of Lewy body pathology. Many of the differentially expressed miRNAs detected in peripheral cell-free cerebrospinal fluid and serum were previously reported in the literature to be deregulated in brain tissue from patients with neurodegenerative disease. These data indicate that extracellular miRNAs detectable in the cerebrospinal fluid and serum are reflective of cell-based changes in pathology and can be used to assess disease progression and therapeutic efficacy.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Parkinson’s disease (PD) is a neurological disorder with complicated and disabling motor and non-motor symptoms. The complexity of PD pathology is amplified due to its dependency on patient diaries ...and the neurologist’s subjective assessment of clinical scales. A significant amount of recent research has explored new cost-effective and subjective assessment methods pertaining to PD symptoms to address this challenge. This article analyzes the application areas and use of mobile and wearable technology in PD research using the PRISMA methodology. Based on the published papers, we identify four significant fields of research: diagnosis, prognosis and monitoring, predicting response to treatment, and rehabilitation. Between January 2008 and December 2021, 31,718 articles were published in four databases: PubMed Central, Science Direct, IEEE Xplore, and MDPI. After removing unrelated articles, duplicate entries, non-English publications, and other articles that did not fulfill the selection criteria, we manually investigated 1559 articles in this review. Most of the articles (45%) were published during a recent four-year stretch (2018–2021), and 19% of the articles were published in 2021 alone. This trend reflects the research community’s growing interest in assessing PD with wearable devices, particularly in the last four years of the period under study. We conclude that there is a substantial and steady growth in the use of mobile technology in the PD contexts. We share our automated script and the detailed results with the public, making the review reproducible for future publications.
Neuropathology has demonstrated a high rate of comorbid pathology in dementia due to Alzheimer's disease (ADD). The most common major comorbidity is Lewy body disease (LBD), either as dementia with ...Lewy bodies (AD-DLB) or Alzheimer's disease with Lewy bodies (AD-LB), the latter representing subjects with ADD and LBD not meeting neuropathological distribution and density thresholds for DLB. Although it has been established that ADD subjects with undifferentiated LBD have a more rapid cognitive decline than those with ADD alone, it is still unknown whether AD-LB subjects, who represent the majority of LBD and approximately one-third of all those with ADD, have a different clinical course.
Subjects with dementia included those with "pure" ADD (n = 137), AD-DLB (n = 64) and AD-LB (n = 114), all with two or more complete Mini Mental State Examinations (MMSE) and a full neuropathological examination.
Linear mixed models assessing MMSE change showed that the AD-LB group had significantly greater decline compared to the ADD group (β = -0.69, 95% CI: -1.05, -0.33, p<0.001) while the AD-DLB group did not (β = -0.30, 95% CI: -0.73, 0.14, p = 0.18). Of those with AD-DLB and AD-LB, only 66% and 2.1%, respectively, had been diagnosed with LBD at any point during their clinical course. Compared with clinically-diagnosed AD-DLB subjects, those that were clinically undetected had significantly lower prevalences of parkinsonism (p = 0.046), visual hallucinations (p = 0.0008) and dream enactment behavior (0.013).
The probable cause of LBD clinical detection failure is the lack of a sufficient set of characteristic core clinical features. Core DLB clinical features were not more common in AD-LB as compared to ADD. Clinical identification of ADD with LBD would allow stratified analyses of ADD clinical trials, potentially improving the probability of trial success.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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