Movement Disorder Society-Unified Parkinson's Disease Rating Scale Research Articles

Phase 1 study of safety and preliminary efficacy of intranasal transplantation of human neural stem cells (ANGE-S003) in Parkinson’s disease

BackgroundIntranasal transplantation of ANGE-S003 human neural stem cells showed therapeutic effects and were safe in preclinical models of Parkinson’s disease (PD). We investigated the safety and tolerability of this treatment...

Safety and efficacy of faecal microbiota transplantation in patients with mild to moderate Parkinson's disease (GUT-PARFECT): a double-blind, placebo-controlled, randomised, phase 2 trial

Dysregulation of the gut microbiome has been implicated in Parkinson's disease (PD). This study aimed to evaluate the clinical effects and safety of a single faecal microbiota transplantation (FMT) in patients with early-stage PD. The GUT-PARFECT trial, a single-centre randomised, double-blind, placebo-controlled trial was conducted at Ghent University Hospital between December 01, 2020 and December 12, 2022. Participants (aged 50-65 years, Hoehn and Yahr stage 2) were randomly assigned to receive nasojejunal FMT with either healthy donor stool or their own stool. Computer-generated randomisation was done in a 1:1 ratio through permutated-block scheduling. Treatment allocation was concealed for participants and investigators. The primary outcome measure at 12 months was the change in the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor score obtained during off-medication evaluations. Intention-to-treat analysis was performed using a mixed model for repeated measures analysis. This completed trial is registered on ClinicalTrials.gov (NCT03808389). Between December 2020 and December 2021, FMT procedures were conducted on 46 patients with PD: 22 in the healthy donor group and 24 in the placebo group. Clinical evaluations were performed at baseline, 3, 6, and 12 months post-FMT. Full data analysis was possible for 21 participants in the healthy donor group and 22 in the placebo group. After 12 months, the MDS-UPDRS motor score significantly improved by a mean of 5.8 points (95% CI-11.4 to-0.2) in the healthy donor group and by 2.7 points (-8.3 to 2.9) in the placebo group (p=0.0235). Adverse events were limited to temporary abdominal discomfort. Our findings suggested a single FMT induced mild, but long-lasting beneficial effects on motor symptoms in patients with early-stage PD. These findings highlight the potential of modulating the gut microbiome as a therapeutic approach and warrant a further exploration of FMT in larger cohorts of patients with PD in various disease stages. Flemish PD patient organizations (VPL and Parkili), Research Foundation Flanders (FWO), Biocodex Microbiota Foundation.

Prasinezumab slows motor progression in rapidly progressing early-stage Parkinson’s disease

Prasinezumab, a monoclonal antibody that binds aggregated α-synuclein, is being investigated as a potential disease-modifying therapy in early-stage Parkinson’s disease. Although in the PASADENA phase 2 study, the primary endpoint (Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) sum of Parts I + II + III) was not met, prasinezumab-treated individuals exhibited slower progression of motor signs than placebo-treated participants (MDS-UPDRS Part III). We report here an exploratory analysis assessing whether prasinezumab showed greater benefits on motor signs progression in prespecified subgroups with faster motor progression. Prasinezumab’s potential effects on disease progression were assessed in four prespecified and six exploratory subpopulations of PASADENA: use of monoamine oxidase B inhibitors at baseline (yes versus no); Hoehn and Yahr stage (2 versus 1); rapid eye movement sleep behavior disorder (yes versus no); data-driven subphenotypes (diffuse malignant versus nondiffuse malignant); age at baseline (≥60 years versus <60 years); sex (male versus female); disease duration (>12 months versus <12 months); age at diagnosis (≥60 years versus <60 years); motor subphenotypes (akinetic–rigid versus tremor-dominant); and motor subphenotypes (postural instability gait dysfunction versus tremor-dominant). In these subpopulations, the effect of prasinezumab on slowing motor signs progression (MDS-UPDRS Part III) was greater in the rapidly progressing subpopulations (for example, participants who were diffuse malignant or taking monoamine oxidase B inhibitors at baseline). This exploratory analysis suggests that, in a trial of 1-year duration, prasinezumab might reduce motor progression to a greater extent in individuals with more rapidly progressing Parkinson’s disease. However, because this was a post hoc analysis, additional randomized clinical trials are needed to validate these findings.

Long-term safety, tolerability and efficacy of apomorphine sublingual film in patients with Parkinson's disease complicated by OFF episodes: a phase 3, open-label study.

Apomorphine sublingual film (SL-APO) is an on-demand treatment for OFF episodes in patients with Parkinson's disease (PD). To assess the long-term (≥ 3years) safety/tolerability and efficacy of SL-APO. Study CTH-301 ( http://www. gov NCT02542696; registered 2015-09-03) was a phase 3, multicentre, open-label study of SL-APO in PD patients with motor fluctuations, comprised of a dose-titration and long-term safety phase. All participants received SL-APO. The primary endpoint was safety/tolerability (treatment-emergent adverse events [TEAEs]) during the long-term safety phase. Efficacy assessments included the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III (motor examination), assessed at weeks 24, 36 and 48 during the first year of the long-term safety phase. 496 patients were included and 120 (24.2%) completed the long-term safety phase. Mean duration of SL-APO exposure was 294.3days. TEAEs related to study drug were experienced by 65.3% of patients (most common: nausea [6.0%], stomatitis [1.8%], lip swelling [1.8%], dizziness [1.6%], oral mucosal erythema [1.6%], mouth ulceration [1.6%]). TEAEs leading to study drug withdrawal were experienced by 34.0% of patients (most common: nausea [5.4%], lip swelling [4.5%], mouth ulceration [2.6%], stomatitis [2.3%]). A clinically meaningful reduction in MDS-UPDRS part III score was observed as soon as 15min following administration of SL-APO, with peak effects observed approximately 30min post-dose and sustained up to 90min post-dose; results were consistent over 48weeks. SL-APO was generally well tolerated and efficacious over the long term as an on-demand treatment for OFF episodes in patients with PD.

Association between fatigue and MDS-UPDRS in individuals with Parkinson's disease: cross-sectional study.

Fatigue is significant in the context of Parkinson's disease (PD), considering that one-third of patients classify it as the most restricting symptom in their daily life activities (DLAs). The objective was to verify the relationship (association) between fatigue and non-motor and motor symptoms of PD. A cross-sectional study which included 100 individuals with PD. Initially, demographic and clinical data (modified Hoehn and Yahr scale-HY, anxiety, and depression) were collected. To assess the non-motor and motor symptoms of PD, the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) was applied. Fatigue was evaluated using the Parkinson Fatigue Scale. A higher HY score, greater severity of non-motor aspects of DLAs and motor aspects of DLAs, more motor complications, and higher levels of anxiety as well as depression were observed in the "fatigue" group. Fatigue was associated with a lower daily equivalent levodopa dose (LEDD), a higher body mass index (BMI), anxiety, depression, and the presence of non-motor symptoms. Non-motor symptoms are more determining factors for fatigue than the motor condition itself, with an association between fatigue and higher BMI scores, increased anxiety and depression, lower LEDD, and greater severity of non-motor aspects of DLAs. Individuals in the "fatigue" group had higher HY scores, anxiety, and depression, worse non-motor and motor symptoms related to experiences of daily life, as well as motor complications.

Longitudinal Free-Water Changes in Dementia with Lewy Bodies.

Diffusion-weighted magnetic resonance imaging (dMRI) examines tissue microstructure integrity in vivo. Prior dementia with Lewy bodies (DLB) diffusion tensor imaging studies yielded mixed results. We employed free-water (FW) imaging to assess DLB progression and correlate with clinical decline in DLB. Baseline and follow-up MRIs were obtained at 12 and/or 24 months for 27 individuals with DLB or mild cognitive impairment with Lewy bodies (MCI-LB). FW was analyzed using the Mayo Clinic Adult Lifespan Template. Primary outcomes were FW differences between baseline and 12 or 24 months. To compare FW change longitudinally, we included 20 cognitively unimpaired individuals from the Alzheimer's Disease Neuroimaging Initiative. We followed 23 participants to 12 months and 16 participants to 24 months. Both groups had worsening in Montreal Cognitive Assessment (MoCA) and Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scores. We found significant FW increases at both time points compared to baseline in the insula, amygdala, posterior cingulum, parahippocampal, entorhinal, supramarginal, fusiform, retrosplenial, and Rolandic operculum regions. At 24 months, we found more widespread microstructural changes in regions implicated in visuospatial processing, motor, and cholinergic functions. Between-group analyses (DLB vs. controls) confirmed significant FW changes over 24 months in most of these regions. FW changes were associated with longitudinal worsening of MDS-UPDRS and MoCA scores. FW increased in gray and white matter regions in DLB, likely due to neurodegenerative pathology associated with disease progression. FW change was associated with clinical decline. The findings support dMRI as a promising tool to track disease progression in DLB. © 2024 International Parkinson and Movement Disorder Society.

Impact of subthalamic nucleus stimulation on urinary dysfunction and constipation in Parkinson's disease.

The effect of subthalamic nucleus (STN) deep brain stimulation (DBS) on urinary dysfunction and constipation in Parkinson's disease (PD) is variable. This study aimed to identify potential surgical and nonsurgical variables predictive of these outcomes. The authors used the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I to assess urinary dysfunction (item 10) and constipation (item 11) preoperatively and at 6-12 months postoperatively. A multiple linear regression model was used to investigate the impact of global cerebral atrophy (GCA) and active electrode contact location on the urinary dysfunction and constipation follow-up scores, controlling for age, disease duration, baseline score, motor improvement, and levodopa-equivalent dose changes. An electric field model was applied to localize the maximal-effect sites for constipation and urinary dysfunction compared with those for motor improvement. Among 74 patients, 23 improved, 28 deteriorated, and 23 remained unchanged for urinary dysfunction; 25 improved, 15 deteriorated, and 34 remained unchanged for constipation. GCA score and age significantly predicted urinary dysfunction follow-up score (R2 = 0.36, p < 0.001). Increased GCA and age were independently associated with worsening urinary symptoms. Disease duration, baseline constipation score, and anterior active electrode contacts in both hemispheres were significant predictors of constipation follow-up score (R2 = 0.31, p < 0.001). Higher baseline constipation score and disease duration were associated with worsening constipation; anterior active contact location was associated with improvement in constipation. Anterior active contact location was associated with improvement in constipation in PD patients after STN DBS. PD patients with greater GCA scores before surgery were more likely to experience urinary deterioration after DBS.

Parkinson’s Disease Progression: Exploring the Relationship between Motor Performance and Cognitive Function

Background/Objective: Numerous studies have examined motor and cognitive decline in neurodegenerative diseases such as Parkinson’s Disease (PD) and results vary considerably. Studies also show that decline does not occur synchronously across all aspects of cognition or motor functions in PD. The goal was to examine if correlations exist between decline in specific motor and cognitive functions.&#x0D; Experimental Design: A cohort of 15 PD patients (age 49-81;6 female) and 9 healthy controls (age 53-75;4 female) were enrolled and their motor and cognitive functions were assessed. Decline in motor function, covering tremor, rigidity and bradykinesia was evaluated using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MS-UPDRS) scores. Cognition, covering attention, memory, language, and visuospatial functions, was assessed using the Montreal Cognitive Assessment (MoCA) test. Inertial measurement units (recording at 100 Hz), placed on both wrists, recorded linear acceleration and angular velocity while subjects performed the pronation/supination and kinetic tremor tasks of the MS-UPDRS. Using angular velocity, response time (RT) to initiate movement in each task was computed. Data analysis correlated MS-UPDRS scores with MoCA scores, and RTs.&#x0D; Results: There were no significant correlations between MS-UPDRS and cognitive MoCA scores. There was a significant relationship between deficits in visuospatial function (MoCA) and increased RT in the pronation/supination task.&#x0D; Conclusion/Potential Impact: Using correlation analyses, no correlation was found between MS-UPDRS and MoCA scores. However, RT on the pronation/supination task correlated positively with visuospatial deficits, suggesting a common voluntary attentional deficit. Although no relationship was found between a clinical score of bradykinesia and RT, measures of movement velocities (measured but not analyzed) may correlate better. Identification of interrelating factors between hard-to-measure cognitive and easy-to-measure motor changes in PD patients may aid clinicians in implementing simple and timely interventions to more easily track and ameliorate cognitive deficits and improve patients' overall functional status.

Cross-Spatiotemporal Graph Convolution Networks for Skeleton-Based Parkinsonian Gait MDS-UPDRS Score Estimation.

Gait impairment in Parkinson's Disease (PD) is quantitatively assessed using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), a well-established clinical tool. Objective and efficient PD gait assessment is crucial for developing interventions to slow or halt its advancement. Skeleton-based PD gait MDS-UPDRS score estimation has attracted increasing interest in improving diagnostic efficiency and objectivity. However, previous works ignore the important cross-spacetime dependencies between joints in PD gait. Moreover, existing PD gait skeleton datasets are very small, which is a big issue in deep learning-based gait studies. In this work, we collect a sizable PD gait skeleton dataset by multi-view Azure Kinect sensors. The collected dataset contains 102 PD patients and 30 healthy older adults. In addition, gait data from 16 young adults (aged 24-50 years) are collected to further examine the effect of age on PD gait assessment. For skeleton-based automatic PD gait analysis, we propose a novel cross-spatiotemporal graph convolution network (CST-GCN) to learn complex features of gait patterns. Specifically, a gait graph labeling strategy is designed to assemble and group cross-spacetime neighbors of the root node according to the spatiotemporal semantics of the gait skeleton. Based on this strategy, the CST-GCN module explicitly models the cross-spacetime dependencies among joints. Finally, a dual-path model is presented to realize the modeling and fusion of spatial, temporal, and cross-spacetime gait features. Extensive experiments validate the effectiveness of our method on the collected dataset.

Effect of Lycium ruthenicum and Lycium barbarum intake on Parkinson based on microbiology and metabonomics: A randomized pilot trial

This study aimed to explore the clinical effects of intervention with Lycium ruthenicum Murr. (LR) and Lycium barbarum L. (LB) on PD patients, reveal the mechanism by which gut microbiota is involved in the overall metabolism of PD patients. The study examined the effects of LR and LB intake on intestinal microflora, serum/urine metabolites, and the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) in 30 PD patients enrolled and randomized into 3 groups. Each received 16 g LR daily or 16 g LB daily or blank control for 6 months. The study found that LR and LB intervention reduced the MDS-UPDRS Ⅰ score and MDS-UPDRS Ⅳ score, although not statistically significant. The abundance of Bacteroides increased and the abundance of Flavobacteriaceae in the LR group decreased compared to the control group. LR may regulate the glycerophospholipid metabolism pathway, and α-linolenic acid metabolism pathway to slow down the progress of PD. After LB intervention, the abundance of Lachnoclostridium increased, the abundance of Blautia, norank_f__Eubacterium_coprostanoligenes_group, Bifidobacterium, Coprococcus and norank_f__Lachnospiraceae decreased in the LB group, and compared to the control group, the abundance of Agathobacter increased, the abundance of Lachnospiraceae and Flavobacteriaceae decreased. The results showed that LB may improve PD symptoms by regulating glycine, serine and threonine metabolism pathways, sphingolipid metabolism pathways, and starch and sucrose metabolism pathways. This study provides evidence support for LR and LB as medicinal and food homologous functional foods to improve PD disorders.

Different impulse control disorder evolution patterns and white matter microstructural damage in the progression of Parkinson's disease.

The course of impulse control disorders (ICD) varies in the early stage of Parkinson's disease (PD). We aimed to delineate the association between the evolution pattern of ICD and the progression of PD. A total of 321 de novo PD patients from the Parkinson's Progression Markers Initiative database were included. Patients were followed up for a mean of 6.8 years and were classified into different groups according to the evolution patterns of ICD. Disease progression was compared among groups using survival analysis, in which the endpoint was defined as progression to Hoehn and Yahr stage 3 or higher for motor progression and progression to mild cognitive impairment for cognitive decline. In the fourth year of follow-up, four types of ICD evolution patterns were identified: (1) non-ICD-stable (68.2%), a patient who is consistently free of ICD; (2) late-ICD (14.6%), ICD developed during the follow-up of patients; (3) ICD-stable (11.5%), patients showed persistent ICD; and (4) ICD-reversion (5.6%), baseline ICD disappeared during the follow-up of patients with ICD. The ICD-reversion type shows daily life non-motor symptoms [Movement Disorder Society-Unified Parkinson Disease Rating Scale (MDS-UPDRS) part I], daily life motor symptoms (MDS-UPDRS part II), rapid eye movement sleep behavior disorder, and anxiety symptoms has a greater impact. PD patients with different ICD evolution patterns had different changes in white matter microstructure at the onset of the disease. Those relevant brain regions are involved in ICD and non-motor functions. Four early ICD evolution patterns are identified in de novo PD, with different prognoses and brain white matter microstructural damage patterns, and they may predict motor progression and cognitive decline in PD patients.

Influential factors of non-motor symptoms prognosis in Parkinson's disease patients undergoing deep brain stimulation

Objective: To investigate the effects of electrode activated contact location, volume of tissue activated (VTA) and age on non-motor symptoms, such as emotional symptoms and cognitive function, in Parkinson's disease (PD) patients with deep brain stimulation (DBS). Methods: PD patients who underwent DBS of subthalamic nucleus (STN) at the Department of Functional Neurosurgery of Beijing Tiantan Hospital from September 1, 2020 to August 31, 2022 were retrospectively enrolled. The International Parkinson and Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Montreal Cognitive Assessment (MoCA), and Mini-Mental State Examination Scales (MMSE) were used at the preoperative, 1-month and 12-month postoperative time points. In this study, patients were divided into middle-aged (age<60 years,n=39) and elderly (age≥60 years,n=62) groups to investigate the effect of age factor on the clinical outcome of surgery. Lead-DBS software was used to convert the patients' electrode reconstruction results into Montreal standard space, and the patients were divided into sensorimotor(n=43) and combined groups(n=53) according to the distribution of activation contact locations in the subzones of the STN. In addition, the patients were divided into a cognitive improvement group(n=57)and a cognitive deterioration group(n=44) based on the results of MoCA at 12 months. The positional information of the electrode activation contacts was collected and the VTA was calculated to analyze the effects on electrode activation electroshock location and activated tissue volume on patients' non-motor symptoms. Results: A total of 101 patients with PD were enrolled, including 46 males and 55 females, aged (62.6±8.4) years. Middle-aged patients had significantly higher MoCA scores, delayed recall scores, attention scores, and naming scores than older patients at 12 months postoperatively (all P<0.05). At 12-month follow-up, the improvement rate of MoCA score, HAMA score and HAMD score were -1.77%±20.36%, 39.65%±42.91% and 36.23%±45.45% respectively in sensorimotor group. At 12-month follow-up, the improvement rate of MoCA score, HAMA score and HAMD score was 11.69%±22.24%, 16.62%±68.10% and 2.30%±95.04% respectively in the combined group, and the difference between the two groups was statistically significant (MoCA: P=0.002; HAMA: P=0.040; HAMD: P=0.033) The distribution of VTA in the sensory motor area and marginal area of the left hemisphere STN in patients with improved cognitive function was significantly smaller than that in the deterioration group [(60.53±52.04)mm³vs (84.55±61.00)mm³, P=0.035; (41.81±33.36)mm³vs (59.05±45.46)mm³, P=0.030]. Conclusion: The effect of STN-DBS on emotional symptoms and cognitive function in PD patients is influenced by various factors and is closely related to the patient's age, electrode activation contact location and VTA.

Quantifying Parkinson’s disease severity using mobile wearable devices and machine learning: the ParkApp pilot study protocol

IntroductionThe clinical assessment of Parkinson’s disease (PD) symptoms can present reliability issues and, with visits typically spaced apart 6 months, can hardly capture their frequent variability. Smartphones and smartwatches along...

A Longitudinal Two-Armed Randomized Controlled Trial Protocol to Evaluate the Efficacy of Yoga on Progression of Disease in Early Parkinson’s Disease

Background Numerous studies have shown that yoga can aid patients with Parkinson’s disease (PD) in managing their motor function, functional mobility, balance, anxiety, and overall quality of life. However, most of the reported research either needed more power or evaluated the results during or after the intervention. Due to the long-standing nature of PD, there are still few longitudinal studies investigating the potential of yoga to decrease the progression of the disease. Purpose We study whether sustained adjunct yoga intervention slows PD progression. Methods Over 18 months, this study will investigate the long-term benefits of yoga-based intervention in Parkinson’s patients. The concept of “intention-to-treat (ITT)” will be employed. From the outpatient clinic of the Swami Vivekananda Yoga Anusandhana Samsthana in India, 160 patients with PD will be chosen. They will then be randomly assigned to either the interventional or control groups (1:1). The adjunct intervention group will participate in 21 daily contact yoga sessions (60 min) at the University Medical Center, followed by continued tele-supervised home practice and at-home self-practice. The effectiveness of the adjunct intervention will be evaluated at four different time points (baseline, 3-, 9-, 12-, and 18-month post-randomization). The primary endpoint will be the difference in the Movement Disorder Society-Unified Parkinson Disease Rating Scale (MDS-UPDRS) Part III score at baseline and after 18 months of intervention. Secondary outcomes will include subscores of MDS-UPDRS I, II, and IV, Parkinson’s Disease Questionnaire (PDQ)-39 scores, treatment adherence, the PDQ-39, the Depression, Anxiety, and Stress Scale-21, and the Scales for Outcomes in PD-Sleep Scale (SCOPA-S). The primary outcome will be analyzed using mixed-effect models for repeated measures, adjusted for covariates as fixed effects. Results The protocol was conceptualized in October 2021 and approved by the Institutional Ethics Committee of SVYASA. Recruitment began in February 2022 and is underway with patient enrollment. Conclusion To our knowledge, this is the first controlled study to examine the long-term effects of yoga as an adjuvant therapy on the progression of PD. Key message This would be the first long-term trial to assess the potential of an adjunct yoga intervention to modulate disease progression in early Parkinson’s patients.

Motor subtypes and clinical characteristics in sporadic and genetic Parkinson's disease groups: analysis of the PPMI cohort.

The extensive clinical variations observed in Parkinson's disease (PD) pose challenges in early diagnosis and treatment initiation. However, genetic research in PD has significantly transformed the clinical approach to its treatment. Moreover, researchers have adopted a subtyping strategy based on homogeneous clinical symptoms to improve clinical diagnosis and treatment approaches. We conducted a study to explore clinical characteristics in genetic PD groups with motor symptom subtyping. Data was driven from the Parkinson's Progression Markers Initiative (PPMI) database. The sporadic PD (sPD) group and the genetic PD group including patients with leucine-rich kinase 2 (LRRK2) or glucosylceramidase β (GBA) mutations were analyzed. Motor subtyping was performed using Movement Disorder Society-Unified Parkinson's disease rating scale (MDS-UPDRS) scores. I-123 FP-CIT SPECT scans were used to calculate specific binding ratios (SBRs) in the caudate and putamen. Clinical symptoms of each group were also compared. MDS-UPDRS III scores were lower in the LRRK2 group, compared with the GBA and sPD group (P < 0.001), but no significant differences in striatal SBRs. The putaminal SBR value of the LRRK2 group was higher than the sPD group (P < 0.05). Within the GBA group, we observed lower SBR values in the postural instability/gait difficulty (PIGD) subtype GBA group compared to the tremor-dominant (TD) subtype GBA group (P < 0.05). The TD subtype GBA group exhibited superior putaminal SBRs compared to the TD subtype sPD group (P < 0.05). The TD subtype LRRK2 group had better putaminal SBR values (P < 0.001) and MDS-UPDRS Part III scores (P < 0.05) compared to the TD sPD group. Our subtyping approach offers valuable insights into the clinical characteristics and progression of different genetic PD subtypes. To further validate and expand these findings, future research with larger groups and long-term follow-up data is needed. The subtyping strategy based on motor symptoms holds promise in enhancing the diagnosis and treatment of genetic PD.

Monoaminergic Degeneration and Ocular Motor Abnormalities in De Novo Parkinson's Disease.

Evaluating eye movements in Parkinson's disease (PD) provides valuable insights into the underlying pathophysiological changes. The aim was to investigate the relationship between monoaminergic degeneration and ocular motor abnormalities in de novo PD. Drug-naive PD patients who underwent N-(3-[18 F]fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl) nortropane positron emission tomography scans and video-oculography at diagnosis were eligible. Measurements of saccadic accuracy, latency, and smooth pursuit gain and square wave jerk frequency were collected. Patients underwent Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and detailed cognitive tests. We investigated the associations between ocular motor measurements and specific tracer uptake ratios (SUR) in the caudate nucleus, anterior and posterior putamen, thalamus, and dorsal raphe nuclei, along with motor and cognitive symptoms. One-hundred twenty-four subjects were included in this study. Saccadic accuracy was positively associated with parkinsonian motor severity expressed as Hoehn and Yahr stages, MDS-UPDRS Part III scores, and subscores for bradykinesia and rigidity but not with tremor scores (PFDR < 0.05). Saccadic accuracy correlated with poor performances in the Rey-Complex-Figure copy, and latency with the Digit Symbol Coding and the Montreal Cognitive Assessment scores (PFDR < 0.05). Prolonged saccadic latency correlated with reduced thalamic SUR, whereas decreased saccadic accuracy correlated with reduced SUR in the anterior and posterior putamen (PFDR < 0.05). Reduced smooth pursuit gain showed associations with reduced SUR in the dorsal raphe, a serotonin-predominant region, but did not correlate with parkinsonism severity scores. Defective dopaminergic and nondopaminergic neural systems may discretely influence ocular motor function in de novo PD patients. © 2023 International Parkinson and Movement Disorder Society.

Deterioration of Cough, Respiratory, and Vocal Cord Functions in Patients with Multiple System Atrophy.

The purpose of this study was to clarify changes in cough function in patients with multiple system atrophy (MSA). Seventeen probable patients with MSA were studied. Peak cough flow (PCF), respiratory function (percentage of vital capacity, percentage of forced vital capacity, and percentage of predicted forced expiratory volume in one second), respiratory muscle strength (percentage of maximal inspiratory mouth pressure and percentage of maximal expiratory mouth pressure), and maximum phonation time (MPT) were assessed. Walking ability, disease duration, possibility of air stacking, Unified MSA Rating Scale (UMSARS), and Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III were also assessed. Data were separately analyzed for ambulatory and non-ambulatory groups categorized by Functional Ambulation Categories. PCF, respiratory function, respiratory muscle strength, and MPT were significantly lower in the non-ambulatory group than in the ambulatory group. On the other hand, no correlation between PCF and disease duration was observed. A significant number of patients in the non-ambulatory group were unable to hold their breath. The UMSARS and MDS-UPDRS Part III in the non-ambulatory group were significantly higher than in the ambulatory group. It was concluded that ambulatory dysfunction is associated with the decline of cough function and respiratory-related function in patients with MSA.

Automatic labeling of Parkinson's Disease gait videos with weak supervision.

Motor dysfunction in Parkinson's Disease (PD) patients is typically assessed by clinicians employing the Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Such comprehensive clinical assessments are time-consuming, expensive, semi-subjective, and may potentially result in conflicting labels across different raters. To address this problem, we propose an automatic, objective, and weakly-supervised method for labeling PD patients' gait videos. The proposed method accepts videos of patients and classifies their gait scores as normal (Gait score in MDS-UPDRS = 0) or PD (MDS-UPDRS ≥ 1). Unlike previous work, the proposed method does not require a priori MDS-UPDRS ratings for training, utilizing only domain-specific knowledge obtained from neurologists. We propose several labeling functions that classify patients' gait and use a generative model to learn the accuracy of each labeling function in a self-supervised manner. Since results depended upon the estimated values of the patients' 3D poses, and existing pre-trained 3D pose estimators did not yield accurate results, we propose a weakly-supervised 3D human pose estimation method for fine-tuning pre-trained models in a clinical setting. Using leave-one-out evaluations, the proposed method obtains an accuracy of 89% on a dataset of 29 PD subjects - a significant improvement compared to previous work by 7%-10% depending upon the dataset. The method obtained state-of-the-art results on the Human3.6M dataset. Our results suggest that the use of labeling functions may provide a robust means to interpret and classify patient-oriented videos involving motor tasks.

Validation of the Arabic version of Parkinson's Disease Sleep Scale-Revised Version (PDSS-2)

ObjectivesParkinson's disease sleep scale (PDSS) was recommended by the Movement Disorder Society task force for screening and grading the severity of sleep problems in Parkinson's disease (PD). This work aimed to examine the validity and reliability of an Arabic version of PDSS-2. MethodsThis cross-sectional study was carried out on 133 patients fulfilling diagnostic criteria for PD. The patients were clinically assessed using the following scales: Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), modified Hoehn and Yahr Scale (H&Y), non-motor symptoms scale (NMSS), Beck Depression Inventory (BDI), and Pittsburgh Sleep Quality Index (PSQI). PDSS-2 scale was translated according to approved translation standards into Arabic and back-translated into English. Patients were asked to respond based on their experience in the last week. ResultsThe mean PDSS2 score for the included PD patients was 17±10. Cronbach's α coefficient value was 0.89, indicating good internal consistency. Most items showed high item-total correlation; the lowest was 0.375, considered higher than the conventional cut-off of 0.3. Test-retest reliability showed good agreement (ICC: 0.848). The exploratory factor analysis showed that items had been loaded over four factors. Total PDSS-2 score was positively correlated to age, disease duration, modified H&Y scale, MDS-UPDRS, NMSS, BDI, and global PSQI score. A cut-off point of 13 could differentiate poor sleepers from good sleepers with 91% sensitivity and 70% specificity (AUC 0.893, P<0.001). ConclusionThe Arabic version of PDSS-2 has appropriate validity and can be reliably used for assessing sleep-related problems in Arabic-speaking patients with PD.

Video-Based Activity Recognition for Automated Motor Assessment of Parkinson's Disease.

Over the last decade, video-enabled mobile devices have become ubiquitous, while advances in markerless pose estimation allow an individual's body position to be tracked accurately and efficiently across the frames of a video. Previous work by this and other groups has shown that pose-extracted kinematic features can be used to reliably measure motor impairment in Parkinson's disease (PD). This presents the prospect of developing an asynchronous and scalable, video-based assessment of motor dysfunction. Crucial to this endeavour is the ability to automatically recognise the class of an action being performed, without which manual labelling is required. Representing the evolution of body joint locations as a spatio-temporal graph, we implement a deep-learning model for video and frame-level classification of activities performed according to part 3 of the Movement Disorder Society Unified PD Rating Scale (MDS-UPDRS). We train and validate this system using a dataset of n = 7310 video clips, recorded at 5 independent sites. This approach reaches human-level performance in detecting and classifying periods of activity within monocular video clips. Our framework could support clinical workflows and patient care at scale through applications such as quality monitoring of clinical data collection, automated labelling of video streams, or a module within a remote self-assessment system.