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Although components of possible Parkinson's disease can be found in earlier documents, the first clear medical description was written in 1817 by James Parkinson. In the mid-1800s, Jean-Martin Charcot was particularly influential in refining and expanding this early description and in disseminating information internationally about Parkinson's disease. He separated the clinical spectrum of Parkinson's disease from multiple sclerosis and other disorders characterized by tremor, and he recognized cases that later would likely be classified among the parkinsonism-plus syndromes. Early treatments of Parkinson's disease were based on empirical observation, and anticholinergic drugs were used as early as the nineteenth century. The discovery of dopaminergic deficits in Parkinson's disease and the synthetic pathway of dopamine led to the first human trials of levodopa. Further historically important anatomical, biochemical, and physiological studies identified additional pharmacological and neurosurgical targets for Parkinson's disease and allow modern clinicians to offer an array of therapies aimed at improving function in this still incurable disease.
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OBJECTIVE: Mutations in the glucocerebrosidase (GBA1) gene and subthalamic nucleus deep brain stimulation (STN-DBS) are independently associated with cognitive dysfunction in persons with Parkinson's disease (PwP). We hypothesized that PwP with both GBA1 mutations and STN-DBS are at greater risk of cognitive dysfunction than PwP with only GBA1 mutations or STN-DBS, or neither. In this study, we determined the pattern of cognitive dysfunction in PwP based on GBA1 mutation status and STN-DBS treatment. METHODS: PwP who are GBA1 mutation carriers with or without DBS (GBA1+DBS+, GBA1+DBS-), and noncarriers with or without DBS (GBA1-DBS+, GBA1-DBS-) were included. Using the NIH Toolbox, cross-sectional differences in response inhibition, processing speed, and episodic memory were compared using analysis of variance with adjustment for relevant covariates. RESULTS: Data were available for 9 GBA1+DBS+, 14 GBA1+DBS-, 17 GBA1-DBS+, and 26 GBA1-DBS- PwP. In this cross-sectional study, after adjusting for covariates, we found that performance on the Flanker test (measure of response inhibition) was lower in GBA1+DBS+ PwP compared with GBA1-DBS+ PwP (P = 0.030). INTERPRETATION: PwP who carry GBA1 mutations and have STN-DBS have greater impaired response inhibition compared with PwP with STN-DBS but without GBA1 mutations. Longitudinal data, including preoperative scores, are required to definitively determine whether GBA1 mutation carriers respond differently to STN-DBS, particularly in the domain of response inhibition.
Subject(s)
Deep Brain Stimulation , Parkinson Disease , Subthalamic Nucleus , Humans , Parkinson Disease/complications , Parkinson Disease/genetics , Parkinson Disease/therapy , Cross-Sectional Studies , Glucosylceramidase/geneticsABSTRACT
BACKGROUND: Parkinson's disease psychosis (PDP) is a multidimensional construct that is challenging to measure. Accurate assessment of PDP requires comprehensive and reliable clinical outcome assessment (COA) measures. OBJECTIVE: To identify PDP measurement gaps in available COAs currently used in clinical and research settings. METHODS: We conducted a scoping review using Preferred Reporting Items for Systematic Review and Meta-Analysis Extension for Scoping Reviews (PRISMA-ScR) guidelines. We implemented a three-step search strategy in international databases with keywords related to Parkinson's disease (PD), psychosis, and COA. We analyzed studies using COA to assess PDP, classifying their items according to domains and subdomains. RESULTS: From 5673 identified studies, we included 628 containing 432 PDP core items from 32 COAs. Among the 32 COAs, 19 were PD-specific, containing 266 items, constructed as clinician-reported outcomes (ClinRO) (148 items), patient-reported outcomes (PRO) (112 items), and observer-reported outcomes (ObsRO) (six items). Across all PD-specific COAs, regardless of structure, 89.4% of the items from 27 COAs focused primarily on assessing PDP symptoms' severity, and only 9.7% of items probed the impact of PDP on a person's daily functioning. CONCLUSIONS: Symptom-based domains are currently prioritized for measuring the severity of PDP, with limited coverage of the functional impact of PDP on patients' lives. Whereas the International Parkinson and Movement Disorder Society has traditionally developed a "Unified" COA that culls items from prior COAs to form a new one, a new COA will largely need newly developed items if the functional impact of PDP is prioritized. © 2024 International Parkinson and Movement Disorder Society.
Subject(s)
Parkinson Disease , Psychotic Disorders , Humans , Parkinson Disease/diagnosis , Psychotic Disorders/diagnosis , Psychotic Disorders/etiologyABSTRACT
Background and Objectives: Falls in a person with Parkinson disease (PwP) are frequent, consequential, and only partially prevented by current therapeutic options. Notably, most falls in PwPs occur in the home or its immediate surroundings; however, our current strategies for fall prevention are clinic-centered. The primary objective of this nonrandomized pilot trial was to investigate the feasibility and preliminary efficacy of the novel implementation of home-based PD telerehabilitation (tele-physical/occupational therapy) focusing on fall risk reduction and home-safety modification. Methods: Persons with mild-to-moderate PD who were identified as being at risk of falls by their movement disorders neurologist were recruited from a tertiary movement disorders clinic. After an initial in-person evaluation by the study physical and occupational therapists, 15 patients with PD (Hoehn and Yahr Stage 2 (n = 8) and Stage 3 (n = 7)) participated in 4 biweekly PT/OT televisits with care partner supervision over the course of 10 weeks. The Goal Attainment Scale (GAS) was implemented to assess progress toward individualized PT/OT goals established at baseline. Outcomes were assessed at the end of the intervention at 10 weeks and at a six-month follow-up. Results: Participants completed all 120 protocol-defined televisits without dropouts and adverse events. At 10 weeks, mean composite PT and OT-GAS scores showed significant improvement from baseline (PT: p < 0.001, OT: p < 0.008), which continued at 6 months (PT: p < 0.0005, OT: p < 0.0005). Home-modification recommendations made through novel virtual home-safety tours were cumulatively met by participants at 87% at 10 weeks and 91% at 6 months. Discussion: Home-based telerehabilitation is a promising new strategy toward fall prevention in PD. The GAS has the potential to serve as an effective and patient-driven primary outcome variable for rehabilitation interventions for heterogeneous PwPs to assess progress toward personalized goals. Trial Registration Information: ClinicalTrial.gov identifier: NCT04600011.
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Background and Purpose: The International Movement Disorder Society revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is widely used in the assessment of the severity of Parkinson's disease (PD). This study aimed to validate the Kazakh version of the MDS-UPDRS, explore its dimensionality, and compare it to the original English version. Methods: The validation was conducted in three phases: first, the English version of the MDS-UPDRS was translated into Kazakh and thereafter back-translated into English by two independent teams; second, the Kazakh version underwent a cognitive pretesting; third, the Kazakh version was tested in 360 native Kazakh-speaking PD patients. Both confirmatory and exploratory factor analyses were performed to validate the scale. We calculated the comparative fit index (CFI) for confirmatory factor analysis and used unweighted least squares for exploratory factor analysis. Results: The CFI was higher than 0.90 for all parts of the scale, thereby meeting the pre-set threshold for the official designation of a validated translation. Exploratory factor analysis also showed that the Kazakh MDS-UPDRS has the analogous factors structure in each part as the English version. Conclusions: The Kazakh MDS-UPDRS had a consistent overall structure as the English MDS-UPDRS, and it was designated as the official Kazakh MDS-UPDRS, which can reliably be used in the Kazakh-speaking populations. Presently, Kazakhstan stands as the sole country in both Central Asia and Transcaucasia with an MDS-approved translated version of the MDS-UPDRS. We expect that other Central Asian and Transcaucasian countries will embark on the MDS Translation Program for MDS-UPDRS in the near future.
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BACKGROUND AND OBJECTIVES: To effectively customize Parkinson disease (PD) programs, it is important to incorporate the "individual's voice" and have a thorough understanding of the symptom priorities of people with PD (PwP) and care partners (CP). In this convergent integrated mixed-method systematic review, we aimed to analyze qualitative and quantitative evidence of PD motor and nonmotor symptoms affecting health-related quality of life (HRQOL) in PwP and CP, comparing priorities across different levels of disease severity. METHODS: We searched MEDLINE, PsycINFO, Web of Science, Embase, and Scopus; ProQuest Dissertations and Theses Global; and the Michael J. Fox Foundation Data Resources for studies published up to June 29, 2022. We included qualitative, quantitative, and mixed-method studies investigating PD symptom priorities among PwP and CP. We critically appraised eligible studies for methodological quality using the Mixed-Methods Appraisal Tool. Derived terms were mapped and coded according to thematic attribution. Independent syntheses of qualitative and quantitative evidence and transformation of quantitative data into qualitative formats were performed. RESULTS: Of the 7,716 identified studies, we included 70 that provided qualitative (n = 13), quantitative (n = 53), and mixed (n = 4) evidence. We included 604 mapped terms representing 11 PwP-identified and CP-identified motor and nonmotor symptom categories. Across all PD stages, both PwP and CP considered 5 domains more affecting their HRQOL, namely: "motor functionality," "mood," "cognition," "gait, balance, posture, and falls," and "nighttime sleep disorders." In early disease, PwP and CP considered "mood" the domain that most affected their HRQOL. In advanced PD, PwP considered "pain" the domain that most affects their HRQOL, while CP considered "psychiatric symptoms." The domain "gait, balance, posture, and falls" was equally considered by both PwP and CP as the second domain that most affects their HRQOL in the advanced stage of PD. DISCUSSION: The ranking of the priority of symptoms is largely shared by PwP and CP, and motor symptom priorities dominate the full disease spectrum. However, the nonmotor symptom priorities shift according to the disease severity stage. Tailored care and research require that providers consider these shifting priorities and incorporate the "individual's voice" into treatment decisions.
Subject(s)
Parkinson Disease , Humans , Caregivers/psychology , Parkinson Disease/therapy , Parkinson Disease/psychology , Quality of Life/psychologyABSTRACT
Background: Assessing disease severity can be performed using either clinician-rated scales (CRS) or patient-rated outcome (PRO) tools. These two measures frequently demonstrate poor correlations. Objectives: To determine if the correlation between a CRS and PRO for motor features of cervical dystonia (CD) improves by accounting for non-motor features. Methods: Subjects with CD (N = 209) were evaluated using a CRS (Toronto Western Spasmodic Torticollis Rating Scale, TWSTRS) and a PRO (Cervical Dystonia Impact Profile, CDIP-58). Results: Linear regression revealed a weak correlation between the two measures, even when considering only the motor subscales of each. The strength of this relationship improved with a regression model that included non-motor symptoms of pain, depression, and disability. Conclusions: These results argue that the results of motor assessments in a PRO for CD cannot be fully appreciated without simultaneous assessment of non-motor co-morbidities. This conclusion might apply to other disorders, especially those with frequent non-motor co-morbidities.
Subject(s)
Parkinson Disease , Humans , Mental Status and Dementia Tests , Severity of Illness IndexABSTRACT
Background: The Modified Rush Video-Based Tic Rating Scale (MRVS) is the most widely used video-based scale for assessing tic severity in patients with Tourette syndrome (TS). However, shortcomings of the MRVS, including a lack of clear instructions, a time-consuming recording procedure, and weak correlations with the gold standard for tic assessment, the Yale Global Tic Severity Scale-Total Tic Score (YGTSS-TTS), limits its use in research settings, although video assessments are generally considered objective, reliable, and time-saving measurements. Objectives: We aimed to revise the MRVS (MRVS-R) to simplify and standardize the assessment procedure and improve the correlation with the YGTSS-TTS. Methods: We used 102 videos of patients with TS or persistent motor tic disorder filmed according to the MRVS. We compared the tic frequency assessed by MRVS with frequencies according to MRVS-R based on a 5-min (instead of a 10-min) video to investigate whether reducing the recording time leads to significant changes. In addition, we adapted the MRVS to the YGTSS and defined new anchor values for motor and phonic tic frequency based on frequency distributions as assessed in our sample. Finally, we compared the MRVS-R and MRVS regarding psychometric properties and correlation with the YGTSS-TTS. Results: Cutting video recording time in half did not significantly affect assessments of motor and phonic tic frequencies. Psychometric properties were acceptable. Most important, proposed revisions of the MRVS improved correlation with the YGTSS-TTS. Conclusions: The MRVS-R is a simplified version of the MRVS with comparable psychometric qualities, but higher correlations with the YGTSS-TTS.
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Despite decades of research, we do not definitively know how people sometimes see things that are not there. Eight models of complex visual hallucinations have been published since 2000, including Deafferentation, Reality Monitoring, Perception and Attention Deficit, Activation, Input, and Modulation, Hodological, Attentional Networks, Active Inference, and Thalamocortical Dysrhythmia Default Mode Network Decoupling. Each was derived from different understandings of brain organisation. To reduce this variability, representatives from each research group agreed an integrated Visual Hallucination Framework that is consistent with current theories of veridical and hallucinatory vision. The Framework delineates cognitive systems relevant to hallucinations. It allows a systematic, consistent, investigation of relationships between the phenomenology of visual hallucinations and changes in underpinning cognitive structures. The episodic nature of hallucinations highlights separate factors associated with the onset, persistence, and end of specific hallucinations suggesting a complex relationship between state and trait markers of hallucination risk. In addition to a harmonised interpretation of existing evidence, the Framework highlights new avenues of research, and potentially, new approaches to treating distressing hallucinations.
Subject(s)
Attention Deficit Disorder with Hyperactivity , Hallucinations , Humans , Hallucinations/psychology , BrainSubject(s)
Parkinson Disease , Humans , Mental Status and Dementia Tests , Severity of Illness IndexABSTRACT
The genetic basis of Neurogenic Orthostatic Hypotension (NOH) in Parkinson's disease (PD) has been inadequately explored. In a cross-sectional study, we examined the association between NOH and PD-related single-nucleotide polymorphisms (SNPs) and mapped their effects on gene expression and metabolic and signaling pathways. Patients with PD, free from pathological conditions associated with OH, and not taking OH-associated medications were included. NOH was defined as per international guidelines. Logistic regression was used to relate SNPs to NOH. Linkage-disequilibrium analysis, expression quantitative trait loci, and enrichment analysis were used to assess the effects on gene expression and metabolic/signaling pathways. We included 304 PD patients in the study, 35 of whom had NOH (11.5%). NOH was more frequent in patients with SNPs in SNCA, TMEM175, FAM47E-STBD1, CCDC62, SCN3A, MIR4696, SH3GL2, and LZTS3/DDRGK1 and less frequent in those with SNPs in ITGA8, IP6K2, SIPA1L2, NDUFAF2. These SNPs affected gene expression associated with the significant hierarchical central structures of the autonomic nervous system. They influenced several metabolic/signaling pathways, most notably IP3/Ca++ signaling, the PKA-CREB pathway, and the metabolism of fatty acids. These findings provide new insights into the pathophysiology of NOH in PD and may provide targets for future therapies.
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Background: Behaviors interfering with medication adherence (MA) are common and often complex in Parkinson's disease (PD), negatively affecting quality of life and undermining the value of clinical trials. The Clinical Outcome Assessments (COA) Scientific Evaluation Committee of the International Parkinson and Movement Disorder Society (MDS) commissioned the assessment of MA rating scales to recommend the use in PD. Objective: Critically review the measurement properties of rating scales used to assess MA in PD and to issue recommendations. Methods: We conducted systematic review across seven databases to identify structured scales to assess MA in PD. Eligible studies were critically appraised for methodological quality using the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) Risk of Bias checklist. Standards for good measurement properties of the selected scales were summarized narratively using the COSMIN, the MDS-COA Committee methodology, the World Health Organization concepts, and the Ascertaining Barriers to Compliance taxonomy. The certainty of the evidence was determined using the modified Grades of Recommendation, Assessment, Development and Evaluation approach with final assessments (highest to lowest) of "Recommended," "Suggested" and "Listed". Results: Of the nine reviewed scales, none met the designation "Recommended". The Morisky Medication Adherence Scale (MMAS-8); Beliefs Related to Medications Adherence questionnaire, Beliefs about Medication Questionnaire, Medication Adherence Rating Scale, and Satisfaction with Information on Medicines Scale were rated "Suggested". Conclusions: We suggest further work focusing on resolving the problems of the suggested scales or developing a new scale meeting all required criteria.
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A pro-inflammatory intestinal microbiome is characteristic of Parkinson's disease (PD). Prebiotic fibers change the microbiome and this study sought to understand the utility of prebiotic fibers for use in PD patients. The first experiments demonstrate that fermentation of PD patient stool with prebiotic fibers increased the production of beneficial metabolites (short chain fatty acids, SCFA) and changed the microbiota demonstrating the capacity of PD microbiota to respond favorably to prebiotics. Subsequently, an open-label, non-randomized study was conducted in newly diagnosed, non-medicated (n = 10) and treated PD participants (n = 10) wherein the impact of 10 days of prebiotic intervention was evaluated. Outcomes demonstrate that the prebiotic intervention was well tolerated (primary outcome) and safe (secondary outcome) in PD participants and was associated with beneficial biological changes in the microbiota, SCFA, inflammation, and neurofilament light chain. Exploratory analyses indicate effects on clinically relevant outcomes. This proof-of-concept study offers the scientific rationale for placebo-controlled trials using prebiotic fibers in PD patients. ClinicalTrials.gov Identifier: NCT04512599.
Subject(s)
Gastrointestinal Microbiome , Parkinson Disease , Humans , Prebiotics , Feces , Fatty Acids, Volatile/metabolismABSTRACT
BACKGROUND: The prevalence of levodopa-induced dyskinesia (LID) in Parkinson's disease (PD) varies among geographical regions. Cultural differences in patient-based perceptions of LID have not been studied. OBJECTIVE: We compared patient and clinician evaluations of LID severity across multiple cultures in patients with PD. METHODS: The data set included the Unified Dyskinesia Rating (UDysRS) scores from 16 language translation programs (3566 patients). We defined the Perception Severity Index (PSI) as the ratio between normalized patient-based subjective ratings (UDysRS Part 1B) and normalized clinician examination (Parts 3 and 4) scores (Part 1B/Parts 3 + 4) and compared the PSI across languages. RESULTS: The mean PSI for the Chinese language (2.16) was higher than those of all other languages, whereas the ratio for the Korean language (0.73) was lower than those for Japanese, German, Turkish, Greek, Polish, and Finnish languages (corrected P values <0.05). CONCLUSIONS: Culture, as represented by language, affects the subjective perception of LID and needs to be considered in multinational clinical PD trials on dyskinesia. © 2023 International Parkinson and Movement Disorder Society.