Dystonia Associated with Idiopathic Slow Orthostatic Tremor

Background: We aimed to characterize the clinical and electrophysiological features of patients with slow orthostatic tremor. Case Report: The clinical and neurophysiological data of patients referred for lower limb tremor on standing were reviewed. Patients with symptomatic or primary orthostatic tremor were excluded. Eight patients were identified with idiopathic slow 4–8 Hz orthostatic tremor, which was associated with tremor and dystonia in cervical and upper limb musculature. Coherence analysis in two patients showed findings different to those seen in primary orthostatic tremor. Discussion: Slow orthostatic tremor may be associated with dystonia and dystonic tremor

Objective analysis of neck muscle boundaries for cervical dystonia using ultrasound imaging and deep learning

Objective: To provide objective visualization and pattern analysis of neck muscle boundaries to inform and monitor treatment of cervical dystonia. Methods: We recorded transverse cervical ultrasound (US) images and whole-body motion analysis of sixty-one standing participants (35 cervical dystonia, 26 age matched controls). We manually annotated 3,272 US images sampling posture and the functional range of pitch, yaw, and roll head movements. Using previously validated methods, we used 60-fold cross validation to train, validate and test a deep neural network (U-net) to classify pixels to 13 categories (five paired neck muscles, skin, ligamentum nuchae, vertebra). For all participants for their normal standing posture, we segmented US images and classified condition (Dystonia/Control), sex and age (higher/lower) from segment boundaries. We performed an explanatory, visualization analysis of dystonia muscle-boundaries. Results: For all segments, agreement with manual labels was Dice Coefficient (64±21%) and Hausdorff Distance (5.7±4 mm). For deep muscle layers, boundaries predicted central injection sites with average precision 94±3%. Using leave-one-out cross-validation, a support-vector-machine classified condition, sex, and age from predicted muscle boundaries at accuracy 70.5%, 67.2%, 52.4% respectively, exceeding classification by manual labels. From muscle boundaries, Dystonia clustered optimally into three sub-groups. These sub-groups are visualized and explained by three eigen-patterns which correlate significantly with truncal and head posture. Conclusion: Using US, neck muscle shape alone discriminates dystonia from healthy controls. Significance: Using deep learning, US imaging allows online, automated visualization, and diagnostic analysis of cervical dystonia and segmentation of individual muscles for targeted injection. The dataset is available (DOI: 10.23634/MMUDR.00624643)

Increased Intraepidermal Nerve Fiber Degeneration and Impaired Regeneration Relate to Symptoms and Deficits in Parkinson's Disease

Background: Previous studies have shown cutaneous small fiber pathology in patients with Parkinson's disease (PD). These studies have focused on nerve degeneration, but recent reports suggest that nerve regeneration may also be important in PD pathology.Objective: To establish the extent of intraepidermal nerve fiber (IENF) degeneration and regeneration and its relationship to clinical and neurological deficits in Parkinson's disease (PD).Methods: Twenty-three PD patients and 10 age-matched controls underwent skin biopsy and assessment of somatic and autonomic symptoms and deficits. We have assessed Intraepidermal Nerve Fiber Density (IENFD) using standard PGP9.5 staining and GAP-43 to assess Mean Axonal Length (MAL) and Intraepidermal Total Nerve Fiber Length (IETNFL).Results: IENFD (p < 0.0001), MAL (p < 0.0001), IETNFL/Area (p = 0.009), and IETNFL/Length (p = 0.04) were significantly reduced in patients with PD compared to controls. IENFD correlated significantly with disease duration (p = 0.03), cumulative levodopa dose (p = 0.02), Unified Parkinson's Disease Rating Scale, Part III (UPDRS-III) (p = 0.01), Schwab and England Activities of Daily Living (ADL) (p = 0.03), NSP (p = 0.03), and 30:15 ratio (p = 0.03). IETNFL/Area correlated with the Autonomic Scale for Outcomes in Parkinson's Disease (SCOPA-AUT) (p = 0.03) and Diabetic Neuropathy Symptom score (DNS) (p = 0.04) and IETNFL/Length correlated with DNS (p = 0.03). MAL correlated with SCOPA-AUT (p = 0.01), DNS (p = 0.02), and DB-HRV (p = 0.02).Conclusion: Increased IENF degeneration and impaired regeneration correlates with somatic and autonomic symptoms and deficits in patients with PD

A neurophysiological investigation of anticipation to pain in Parkinson's disease

Chronic pain is common in people with Parkinson's disease and is often considered to be caused by the motor impairments associated with the disease. Altered top‐down processing of pain characterises several chronic pain conditions and occurs when the cortex modifies nociceptive processing in the brain and spinal cord. This contrasts with bottom‐up modulation of pain whereby nociceptive processing is modified on its way up to the brain. Although several studies have demonstrated altered bottom‐up pain processing in Parkinson's, the contribution of enhanced anticipation to pain and atypical top‐down processing of pain has not been fully explored. During the anticipation to noxious stimuli, EEG source localisation reported an increased activation in the midcingulate cortex and supplementary motor area in the Parkinson's disease group compared to the healthy control group during mid [−1,500 –1,000]‐and late anticipation [−500 0], indicating enhanced cortical activity before noxious stimulation. The Parkinson's disease group was also more sensitive to the laser and required a lower voltage level to induce pain. This study provides evidence supporting the hypothesis that enhanced top‐down processing of pain may contribute to the development of chronic pain in Parkinson's. Additional research to establish whether the altered anticipatory response is unique to noxious stimuli is required as no control stimulus was used within the current study. With further research to confirm these findings, our results inform a scientific rationale for novel treatment strategies of pain in Parkinson's disease, including mindfulness, cognitive therapies and other approaches targeted at improving top‐down processing of pain

Structural connectivity and brain network analyses in Parkinson's disease: A cross-sectional and longitudinal study.

IntroductionParkinson's disease (PD) is an idiopathic disease of the central nervous system characterized by both motor and non-motor symptoms. It is the second most common neurodegenerative disease. Magnetic resonance imaging (MRI) can reveal underlying brain changes associated with PD.ObjectiveIn this study, structural connectivity and white matter networks were analyzed by diffusion MRI and graph theory in a cohort of patients with PD and a cohort of healthy controls (HC) obtained from the Parkinson's Progression Markers Initiative (PPMI) database in a cross-sectional analysis. Furthermore, we investigated longitudinal changes in the PD cohort over 36 months.ResultCompared with the control group, participants with PD showed lower structural connectivity in several brain areas, including the corpus callosum, fornix, and uncinate fasciculus, which were also confirmed by a large effect-size. Additionally, altered connectivity between baseline and after 36 months was found in different network paths inside the white matter with a medium effect-size. Network analysis showed trends toward lower network density in PD compared with HC at baseline and after 36 months, though not significant after correction. Significant differences were observed in nodal degree and strength in several nodes.ConclusionIn conclusion, altered structural and network metrics in several brain regions, such as corpus callosum, fornix, and cingulum were found in PD, compared to HC. We also report altered connectivity in the PD group after 36 months, reflecting the impact of both PD pathology and aging processes. These results indicate that structural and network metrics might yield insight into network reorganization that occurs in PD

Changes in Parkinson's disease sleep symptoms and daytime somnolence after bilateral subthalamic deep brain stimulation in Parkinson's disease

AbstractIntroduction: Deep brain stimulation (DBS) markedly improves motor function in advanced Parkinson’s disease (PD), but its effect on sleep is less clear. Patients and methods: Forty PD patients who had subthalamic DBS (STN-DBS) were identified from an on-going non-motor naturalistic longitudinal study (NILS). All patients were followed up for at least 6 months, 26 patients had a 1 year follow-up. A total PDSS score of 100 or less, a score in any PDSS-item of 6 or less, and a Epworth score of 10 or more were classified as being significant. Results: Forty-five percent of patients reported significant improvement in the total PDSS score at 6 months, and 35% at 12 months. In terms of magnitude, the total PDSS score at 6 months was significantly improved from baseline while the improvement at 12 months was not statistically significant. The most frequently reported improvements were overall sleep quality and maintenance of sleep. Some patients reported worsening of the total PDSS score. More than half of the patients reporting daytime sleepiness at baseline had persistent sleepiness at 6 and 12 months. The mean Epworth Score did not improve because a significant number of patients without sleepiness at baseline reported new-onset sleepiness at 6 and 12 months. Neither medication changes nor motor improvement were consistently related to sleep changes after DBS. Conclusion: Subthalamic DBS is associated with a statistically and clinically significant, but variable, improvement in sleep as measured by the PDSS. The most frequent improvements were better overall sleep quality and better sleep maintenance.</jats:p

What is available to support pain management in Parkinson’s: a scoping review protocol

Objective: A scoping review will be undertaken to examine and map the available evidence that has been produced in relation to pain management in Parkinson’s, with a focus on behavioural interventions, resources and/or how professionals support people with Parkinson’s self-management of pain. Methods: This review will be based on the methodological framework given by Arksey and O’Malley’s (2005), including enhancements by Levac et al., Peters et al. and the Joanna Briggs Institute. We will include studies from PubMed, SCOPUS, CINAHL, MEDLINE Web of Science, APA PsycINFO and ASSIA from January, 2010 onwards. Both quantitative and qualitative data will be analysed separately to identify the characteristics of support for pain management available, orientation of the approach and any identifiable behaviour change components and their outcomes. The COM-B behaviour change model and Theoretical Domains Framework will provide a theoretical framework for synthesising evidence in this review. Conclusion: This scoping review will help to explore studies focusing on the evidence supporting a range of interventions relating to the management of pain experienced by people living with Parkinson’s. The focus will be on describing what is available to support self-management, identify what behaviour change components have been used and their effectiveness, identify barriers and enablers to pain management and explore gaps in current provision of pain management. This review will identify implications and priorities for the follow-up phases to the larger ‘Pain in Parkinson’s’ Project which is designed to support clinicians and individuals living with Parkinson’s

Corneal Confocal Microscopy Identifies Parkinson's Disease with More Rapid Motor Progression

From Wiley via Jisc Publications RouterHistory: received 2020-12-15, rev-recd 2021-03-11, accepted 2021-03-12, pub-electronic 2021-04-07, pub-print 2021-08Article version: VoRPublication status: PublishedFunder: Michael J Fox Foundation Trust (Grant ID 12059); Id: http://dx.doi.org/10.13039/100010269ABSTRACT: Background: Corneal confocal microscopy (CCM) is a noninvasive, reproducible ophthalmic technique to quantify corneal small nerve fiber degeneration. CCM demonstrates small nerve fiber damage in Parkinson's disease (PD), but its role as a longitudinal biomarker of PD progression has not been explored. Objective: The aim of this study was to assess corneal nerve morphology using CCM in relation to disease progression in PD. Methods: Sixty‐four participants with PD were assessed at baseline and at 12‐month follow‐up. Participants underwent CCM with automated corneal nerve quantification and assessment of Movement Disorder Society Unified Parkinson's Disease Rating Scale, Hoehn and Yahr stage, and Montreal Cognitive Assessment. Results: Corneal nerve fiber density (CNFD), corneal nerve branch density, corneal nerve fiber length, corneal total branch density, and corneal nerve fiber area were significantly lower in participants with PD compared with healthy control subjects. Worsening of Movement Disorder Society Unified Parkinson's Disease Rating Scale part III score over 12 months was significantly greater in participants with a CNFD in the lowest compared with the highest quartile at baseline (mean difference: 6.0; 95% CI: 1.0–10.9; P = 0.019). There were no significant changes in CNFD, corneal nerve branch density, corneal nerve fiber length, corneal total branch density, corneal nerve fiber area, or corneal nerve fiber width between baseline and 12‐month follow‐up. Conclusions: CCM identifies neurodegeneration in patients with PD, especially those who show the greatest progression in neurological disability. CCM may be a useful tool to help enrich clinical trials with those likely to exhibit more rapid progression and reduce required sample size and cost of studies. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Societ

Validating differential volatilome profiles in Parkinson’s disease

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A detailed clinical study of pain in 1957 participants with early/moderate Parkinson's disease

Introduction The causes of pain in early/moderate Parkinson's disease (PD) are not well understood. Although peripheral factors such as rigidity, reduced joint movements and poor posture may contribute towards the development of pain, central mechanisms including altered nociceptive processing may also be involved. Methods We performed a large clinical study to investigate potential factors contributing towards pain in early/moderate PD. We recruited 1957 PD participants who had detailed assessments of pain, motor and non-motor symptoms. The King's Parkinson's Pain scale was used to quantify different subtypes of pain. Results 85% of participants reported pain (42% with moderate to severe pain). Pain influenced quality of life more than motor symptoms in a multiple regression model. Factors predicting overall pain severity included affective symptoms, autonomic symptoms, motor complications, female gender and younger age, but not motor impairment or disease duration. There was negligible correlation between the severity of motor impairment and the severity of musculoskeletal or dystonic pain as well as between the severity of OFF period motor problems and the severity of OFF period pain or OFF period dystonic pain. Features of central sensitization, including allodynia and altered pain sensation were common in this population. The use of drugs targeting central pain was very low. Conclusions Pain in early/moderate PD cannot be explained by peripheral factors. Central causes may play a much more important role than previously considered. These results should lead to a major shift in the investigation and management of this common and disabling symptom