Quantitative Oculomotor Assessment in Hereditary Ataxia: Discriminatory Power, Correlation with Severity Measures, and Recommended Parameters for Specific Genotypes.

Characterizing bedside oculomotor deficits is a critical factor in defining the clinical presentation of hereditary ataxias. Quantitative assessments are increasingly available and have significant advantages, including comparability over time, reduced examiner dependency, and sensitivity to subtle changes. To delineate the potential of quantitative oculomotor assessments as digital-motor outcome measures for clinical trials in ataxia, we searched MEDLINE for articles reporting on quantitative eye movement recordings in genetically confirmed or suspected hereditary ataxias, asking which paradigms are most promising for capturing disease progression and treatment response. Eighty-nine manuscripts identified reported on 1541 patients, including spinocerebellar ataxias (SCA2, n = 421), SCA3 (n = 268), SCA6 (n = 117), other SCAs (n = 97), Friedreich ataxia (FRDA, n = 178), Niemann-Pick disease type C (NPC, n = 57), and ataxia-telangiectasia (n = 85) as largest cohorts. Whereas most studies reported discriminatory power of oculomotor assessments in diagnostics, few explored their value for monitoring genotype-specific disease progression (n = 2; SCA2) or treatment response (n = 8; SCA2, FRDA, NPC, ataxia-telangiectasia, episodic-ataxia 4). Oculomotor parameters correlated with disease severity measures including clinical scores (n = 18 studies (SARA: n = 9)), chronological measures (e.g., age, disease duration, time-to-symptom onset; n = 17), genetic stratification (n = 9), and imaging measures of atrophy (n = 5). Recurrent correlations across many ataxias (SCA2/3/17, FRDA, NPC) suggest saccadic eye movements as potentially generic quantitative oculomotor outcome. Recommendation of other paradigms was limited by the scarcity of cross-validating correlations, except saccadic intrusions (FRDA), pursuit eye movements (SCA17), and quantitative head-impulse testing (SCA3/6). This work aids in understanding the current knowledge of quantitative oculomotor parameters in hereditary ataxias, and identifies gaps for validation as potential trial outcome measures in specific ataxia genotypes.

Hyaluronate Acid Plus Platelet-Rich Plasma Is Superior to Steroids for Pain Relief Less Than 6 Months Using Injection Therapy of Partial Rotator Cuff Tears: A Systematic Review and Network Meta-analysis.

PURPOSE: To compare the efficacy of steroid injections to other injectable therapies in partial-thickness rotator cuff (RC) tears. METHODS: A systematic literature search was performed until October 25, 2021, in 3 databases (Cochrane Central Register of Controlled Trials, Embase, MEDLINE). Eligible studies compared the efficacy of steroid, hyaluronic acid (HA), platelet-rich plasma (PRP), the combination of HA and PRP (HA + PRP), and adipose-derived regenerative cells in RC tears. The primary outcomes were the visual analog scale (VAS), Constant-Murley Shoulder Outcome Score (CMS) and American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form. Using paired and network meta-analysis, we calculated pooled mean differences (MDs) with 95% confidence intervals (CIs). RESULTS: We included a total of 7 articles in the quantitative synthesis. In shorter periods, the HA + PRP combination was superior to the other substances we investigated (HA + PRP: VAS [0-4 weeks]: MD: -0.99 [95% CI, -1.62 to -0.36]; CMS [0-3 months]: 20.56 [95% CI, 16.18 to 24.94]. This combination was followed by the use of HA or PRP alone, depending on the duration of follow-up and the outcome being studied. In our study, short-term results suggest that saline is superior to steroids for partial tears, but this trend is reversed at 6-month follow-up. CONCLUSIONS: The HA and PRP combination is currently the most effective in partial RC tear treatment in the short term. After 6 months, there is no meaningful difference, so the benefits of the combination are short term. LEVEL OF EVIDENCE: Level II, including Level I to II studies.

No Evidence for the Superiority of 3-T Magnetic Resonance Imaging Over 1.5-T Magnetic Resonance Imaging for Diagnosing Wrist Ligamentous Lesions: A Systematic Review and Meta-analysis.

PURPOSE: To determine the diagnostic accuracy of native magnetic resonance imaging (MRI) regarding different ligamentous lesions of the wrist and to analyze the influence of technical characteristics, such as field strength, application of fat saturation, 3-dimensional sequences, and wrist coils. METHODS: A systematic search was performed using MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases. Studies that were published before February 12, 2024, were included. All studies comparing the diagnostic accuracy of native wrist MRI with that of wrist arthroscopy for suspected ligamentous lesions were included. Results were analyzed by anatomic localization and technical aspects of the MRI. To assess the quality of included studies, we used the revised Quality Assessment of Diagnostic Accuracy Studies tool. RESULTS: The systematic search revealed 5,181 articles. Thirty-seven studies, reporting 3,893 ligamentous lesions, were eligible for inclusion. The studies displayed heterogeneity in terms of technical conditions, such as field strength, the use of wrist coils, the application of 3-dimensional sequences, and fat saturation. Research methods also varied. Overall sensitivity and specificity were 0.78 (0.66-0.86) and 0.81 (0.70-0.89) for 1.5-T MRI, whereas sensitivity was 0.73 (0.68-0.78) and specificity was 0.90 (0.59-0.98) for 3-T MRI. There was no significant difference between the 2 subgroups (P = .3807 and P = .4248). Sensitivity was 0.82 (0.75-0.87) for triangular fibrocartilage complex lesions, 0.63 (0.50-0.74) for scapholunate ligament tears, and 0.41 (0.25-0.60) for lunotriquetral ligament lesions. Specificity for triangular fibrocartilage complex lesions was 0.82 (0.73-0.89), for scapholunate ligament tears was 0.86 (0.73-0.93), and for lunotriquetral ligament lesions was 0.93 (0.81-0.98). CONCLUSIONS: The sensitivity and specificity of MRI are influenced by the anatomic location of the lesion and technical conditions. In terms of diagnostic accuracy, no significant difference was found between 1.5-T and 3-T MRI. LEVEL OF EVIDENCE: Level III, systematic review of Level II-III studies.

Specific features of epitope-MIPs and whole-protein MIPs as illustrated for AFP and RBD of SARS-CoV-2.

Molecularly imprinted polymer (MIP) nanofilms for alpha-fetoprotein (AFP) and the receptor binding domain (RBD) of the spike protein of SARS-CoV-2 using either a peptide (epitope-MIP) or the whole protein (protein-MIP) as the template were prepared by electropolymerization of scopoletin. Conducting atomic force microscopy revealed after template removal and electrochemical deposition of gold a larger surface density of imprinted cavities for the epitope-imprinted polymers than when using the whole protein as template. However, comparable affinities towards the respective target protein (AFP and RBD) were obtained for both types of MIPs as expressed by the KD values in the lower nanomolar range. On the other hand, while the cross reactivity of both protein-MIPs towards human serum albumin (HSA) amounts to around 50% in the saturation region, the nonspecific binding to the respective epitope-MIPs is as low as that for the non-imprinted polymer (NIP). This effect might be caused by the different sizes of the imprinted cavities. Thus, in addition to the lower costs the reduced nonspecific binding is an advantage of epitope-imprinted polymers for the recognition of proteins.

A Strep-Tag Imprinted Polymer Platform for Heterogenous Bio(electro)catalysis.

Molecularly imprinted polymers (MIPs) are artificial receptors equipped with selective recognition sites for target molecules. One of the most promising strategies for protein MIPs relies on the exploitation of short surface-exposed protein fragments, termed epitopes, as templates to imprint binding sites in a polymer scaffold for a desired protein. However, the lack of high-resolution structural data of flexible surface-exposed regions challenges the selection of suitable epitopes. Here, we addressed this drawback by developing a polyscopoletin-based MIP that recognizes recombinant proteins via imprinting of the widely used Strep-tag II affinity peptide (Strep-MIP). Electrochemistry, surface-sensitive IR spectroscopy, and molecular dynamics simulations were employed to ensure an utmost control of the Strep-MIP electrosynthesis. The functionality of this novel platform was verified with two Strep-tagged enzymes: an O2-tolerant [NiFe]-hydrogenase, and an alkaline phosphatase. The enzymes preserved their biocatalytic activities after multiple utilization confirming the efficiency of Strep-MIP as a general biocompatible platform to confine recombinant proteins for exploitation in biotechnology.

Validation of the Rainbow Model of Integrated Care Measurement Tool in Parkinson's Disease.

BACKGROUND: Integrated care is essential for improving the management and health outcomes for people with Parkinson's disease (PD); reliable and objective measures of care integration are few. OBJECTIVE: The aim of this study was to test the psychometric properties of the Rainbow Model of Integrated Care Measurement Tool (RMIC-MT, provider version) for healthcare professionals involved in PD care. METHODS: A cross-sectional survey was administered online to an international network representing 95 neurology centers across 41 countries and 588 healthcare providers. Exploratory factor analysis with principal axis extraction method was used to assess construct validity. Confirmatory factor analysis was used to evaluate model fit of the RMIC-MT provider version. Cronbach's alpha was used to assess the internal consistency reliability. RESULTS: Overall, 371 care providers (62% response rate) participated in this study. No item had psychometric sensitivity problems. Nine factors (professional coordination, cultural competence, triple aims outcome, system coordination, clinical coordination, technical competence, community-centeredness, person-centeredness, and organizational coordination) with 42 items were determined by exploratory factor analysis. Cronbach's alpha ranged from 0.76 (clinical coordination) to 0.94 (system coordination) and showed significant correlation among all items in the scale (>0.4), indicating good internal consistency reliability. The confirmatory factor analysis model passed most goodness-of-fit tests, thereby confirming the factor structure of nine categories with a total of 40 items. CONCLUSIONS: The results provide evidence for the construct validity and other psychometric properties of the provider version of the RMIC-MT to measure integrated care in PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Gray Matter Changes Following Mild COVID-19: An MR Morphometric Study in Healthy Young People.

BACKGROUND: Although COVID-19 is primarily an acute respiratory infection, 5%-40% of patients develop late and prolonged symptoms with frequent neurological complaints, known as long COVID syndrome. The presentation of the disease suggests that COVID infection may cause functional and/or morphological central nervous system alterations, but studies published in the literature report contradictory findings. PURPOSE: To investigate the chronic effects of COVID-19 on cerebral grey matter in a group of young patients without comorbidities, with mild course of COVID infection and no medical complaints at the time of examination. STUDY TYPE: Prospective. POPULATION: Thirty-eight young (age = 26.6 ± 5.0 years; male/female = 14/24), adult participants who recovered from mild COVID infection without a history of clinical long COVID and 37 healthy control subjects (age = 25.9 ± 2.8 years; male/female = 14/23). FIELD STRENGTH/SEQUENCE: Three Tesla, 3D T1-weighted magnetization-prepared rapid gradient-echo, 2D T2-weighted turbo spin-echo. ASSESSMENT: MRI-based morphometry and volumetry along with neuropsychological testing and self-assessed questionnaire. STATISTICAL TESTS: Fisher's exact test, Mann-Whitney U-test, and multiple linear regression analyses were used to assess differences between COVID and healthy control groups. P < 0.05 was used as cutoff for significance. RESULTS: In the COVID group, significantly lower bilateral mean cortical thickness (left/right-hemisphere: 2.51 ± 0.06 mm vs. 2.56 ± 0.07 mm, η2 p = 0.102/2.50 ± 0.06 mm vs. 2.54 ± 0.07 mm, η2 p = 0.101), lower subcortical gray matter (57881 ± 3998 mm3 vs. 60470 ± 5211 mm3 , η2 p = 0.100) and lower right olfactory bulb volume (52.28 ± 13.55 mm3 vs. 60.98 ± 15.8 mm3 , η2 p = 0.078) were found. In patients with moderate to severe anosmia, cortical thickness was significantly lower bilaterally, as compared to patients without olfactory function loss (left/right-hemisphere: 2.50 ± 0.06 mm vs. 2.56 ± 0.05 mm, η2 = 0.173/2.49 ± 0.06 mm vs. 2.55 ± 0.05 mm, η2 = 0.189). Using further exploratory analysis, significantly reduced cortical thickness was detected locally in the right lateral orbitofrontal cortex in the COVID group (2.53 ± 0.10 mm vs. 2.60 ± 0.09 mm, η2 p = 0.112). DATA CONCLUSION: Even without any subjective or objective neurological complaints at the time of the MR scan, subjects in the COVID group showed gray matter alterations in cortical thickness and subcortical gray matter volume. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

Quantitative Oculomotor Assessment in Hereditary Ataxia: Systematic Review and Consensus by the Ataxia Global Initiative Working Group on Digital-motor Biomarkers.

Oculomotor deficits are common in hereditary ataxia, but disproportionally neglected in clinical ataxia scales and as outcome measures for interventional trials. Quantitative assessment of oculomotor function has become increasingly available and thus applicable in multicenter trials and offers the opportunity to capture severity and progression of oculomotor impairment in a sensitive and reliable manner. In this consensus paper of the Ataxia Global Initiative Working Group On Digital Oculomotor Biomarkers, based on a systematic literature review, we propose harmonized methodology and measurement parameters for the quantitative assessment of oculomotor function in natural-history studies and clinical trials in hereditary ataxia. MEDLINE was searched for articles reporting on oculomotor/vestibular properties in ataxia patients and a study-tailored quality-assessment was performed. One-hundred-and-seventeen articles reporting on subjects with genetically confirmed (n=1134) or suspected hereditary ataxia (n=198), and degenerative ataxias with sporadic presentation (n=480) were included and subject to data extraction. Based on robust discrimination from controls, correlation with disease-severity, sensitivity to change, and feasibility in international multicenter settings as prerequisite for clinical trials, we prioritize a core-set of five eye-movement types: (i) pursuit eye movements, (ii) saccadic eye movements, (iii) fixation, (iv) eccentric gaze holding, and (v) rotational vestibulo-ocular reflex. We provide detailed guidelines for their acquisition, and recommendations on the quantitative parameters to extract. Limitations include low study quality, heterogeneity in patient populations, and lack of longitudinal studies. Standardization of quantitative oculomotor assessments will facilitate their implementation, interpretation, and validation in clinical trials, and ultimately advance our understanding of the evolution of oculomotor network dysfunction in hereditary ataxias.

Are Parkinson's disease patients referred too late for device-aided therapies and how can better informed and earlier referrals be encouraged?

In the advanced Parkinson's disease, motor and non-motor symptoms become more severe and more difficult to treat. Oral therapy may become insufficient in controlling a patient´s motor complications, which results in a substantial deterioration of the patient's quality of life, ability to work and self-reliance. This is when device-aided treatments should be considered and offered, if suitable for a given patient. They include subcutaneous and intestinal infusion therapies, deep brain stimulation and, more recently, MRI-guided focussed ultrasound. Device-aided treatments should be offered in accordance with guidelines and treatment standardization. Also there is a need to ensure availability of treatment and education of patients and physicians.

Antiparkinsonian Drug Reduction After Directional Versus Omnidirectional Bilateral Subthalamic Deep Brain Stimulation.

BACKGROUND: Several pilot trials and the Clinical Evaluation of the Infinity Deep Brain Stimulation System (PROGRESS) study have found that directional stimulation can provide a wider therapeutic window and lower therapeutic current strength than omnidirectional stimulation. OBJECTIVE: We conducted a single-center, open-label, registry-based, comparative trial to test the hypothesis that directional stimulation can be associated with a greater reduction in the total daily dose of antiparkinsonian medications (ApMeds) than omnidirectional stimulation. MATERIALS AND METHODS: A total of 52 patients with directional and 57 subjects with omnidirectional bilateral subthalamic deep brain stimulation (STN-DBS) were enrolled. Preoperatively and 12 months postoperatively, the dose of different ApMeds, the number of tablets used daily, the severity of motor and nonmotor symptoms using the Movement Disorder Society-sponsored Unified Parkinson Disease Rating Scale, and the health-related quality of life (HRQoL) using the 39-item Parkinson's Disease Questionnaire (PDQ-39) were assessed. RESULTS: According to the changes in the levodopa equivalent daily dose, directional STN-DBS led to a 13% greater reduction in the total daily dose of ApMed. The 10.3% greater reduction in the dose of levodopa was the main contributor to this difference. The number of different ApMed types also could be decreased in a greater manner with directional stimulation. The improvement in the severity of motor and nonmotor symptoms was comparable; however, we detected a 15.8% greater improvement in the global HRQoL among patients with directional stimulation according to the changes in the summary index of the PDQ-39. The total electrical energy delivered per second was comparable between the groups at 12-month postoperative visit, whereas the amplitude of stimulation was significantly lower and the impedance was significantly higher with directional leads. CONCLUSIONS: Directional programming can further increase the reduction in the total daily dose of ApMed after STN-DBS. In addition, directional stimulation can have additional beneficial effects on the global HRQoL. The greater reduction of ApMed doses did not require more energy-consuming stimulation with directional stimulation.

THN 102 for Excessive Daytime Sleepiness Associated with Parkinson's Disease: A Phase 2a Trial.

BACKGROUND: Excessive daytime sleepiness (EDS) is a frequent and disabling symptom of Parkinson's disease (PD) without approved treatment. THN102 is a novel combination drug of modafinil and low-dose flecainide. OBJECTIVE: The aim of this study is to evaluate the safety and efficacy of THN102 in PD patients with EDS. METHODS: The method involved a randomized, double-blind, placebo-controlled, crossover trial testing two doses of THN102 (200 mg/d modafinil with 2 mg/d [200/2] or 18 mg/d flecainide [200/18]) versus placebo; 75 patients were exposed to treatment. The primary endpoint was safety. The primary efficacy outcome was the change in Epworth Sleepiness Scale (ESS) score. RESULTS: Both doses of THN102 were well tolerated. ESS significantly improved with THN102 200/2 (least square means vs. placebo [95% confidence interval, CI]: -1.4 [-2.49; -0.31], P = 0.012) but did not change significantly with the 200/18 dosage. CONCLUSIONS: THN102 was well tolerated and showed a signal of efficacy at the 200/2 dose, supporting further development for the treatment of EDS in PD. © 2021 International Parkinson and Movement Disorder Society.

European Academy of Neurology guidance for developing and reporting clinical practice guidelines on rare neurological diseases.

BACKGROUND AND PURPOSE: Rare diseases affect up to 29 million people in the European Union, and almost 50% of them affect the nervous system or muscles. Delays in diagnosis and treatment onset and insufficient treatment choices are common. Clinical practice guidelines (CPGs) may improve the diagnosis and treatment of patients and optimize care pathways, delivering the best scientific evidence to all clinicians treating these patients. Recommendations are set for developing and reporting high-quality CPGs on rare neurological diseases (RNDs) within the European Academy of Neurology (EAN), through a consensus procedure. METHODS: A group of 27 experts generated an initial list of items that were evaluated through a two-step Delphi consensus procedure and a face-to-face meeting. The final list of items was reviewed by an external review group of 58 members. RESULTS: The consensus procedure yielded 63 final items. Items are listed according to the domains of the AGREE instruments and concern scope and purpose, stakeholder involvement, rigour of development, and applicability. Additional items consider reporting and ethical issues. Recommendations are supported by practical examples derived from published guidelines and are presented in two tables: (1) items specific to RND CPGs, and general guideline items of special importance for RNDs, or often neglected; (2) items for guideline development within the EAN. CONCLUSIONS: This guidance aims to provide solutions to the issues specific to RNDs. This consensus document, produced by many experts in various fields, is considered to serve as a starting point for further harmonization and for increasing the quality of CPGs in the field of RNDs.

Selective intraoperative cholangiography should be considered over routine intraoperative cholangiography during cholecystectomy: a systematic review and meta-analysis.

BACKGROUND: Decades of debate surround the use of intraoperative cholangiography (IOC) during cholecystectomy. To the present day, the role of IOC is controversial as regards decreasing the rate of bile duct injury (BDI). We aimed to review and analyse the available literature on the benefits of IOC during cholecystectomy. METHODS: A systematic literature search was performed until 19 October 2020 in five databases using the following search keys: cholangiogra* and cholecystectomy. The primary outcomes were BDI and retained stone rate. To investigate the differences between the groups (routine IOC vs selective IOC and IOC vs no IOC), we calculated weighted mean differences (WMD) for continuous outcomes and relative risks (RR) for dichotomous outcomes, with 95% confidence intervals (CI). RESULTS: Of the 19,863 articles, 38 were selected and 32 were included in the quantitative synthesis. Routine IOC showed no superiority compared to selective IOC in decreasing BDI (RR = 0.91, 95% CI 0.66; 1.24). Comparing IOC and no IOC, no statistically significant differences were found in the case of BDI, retained stone rate, readmission rate, and length of hospital stay. We found an increased risk of conversion rate to open surgery in the no IOC group (RR = 0.64, CI 0.51; 0.78). The operation time was significantly longer in the IOC group compared to the no IOC group (WMD = 11.25 min, 95% CI 6.57; 15.93). CONCLUSION: Our findings suggest that IOC may not be indicated in every case, however, the evidence is very uncertain. Further good quality research is required to address this question.

Sudden gamer death: non-violent death cases linked to playing video games.

BACKGROUND AND AIMS: Internet gaming disorder (IGD) is an emerging problem. Rarely, media reports about people, who have died during playing video games, but thus far no systematic, scientific study is available about the topic. We investigated such cases, looking for common characteristics, connection between gaming and death, and the possible reasons leading to death. METHODS: Cases were collected through internet search with general keywords, with ones specific to identified cases, and by working along cross references. RESULTS: 24 cases were found: one from 1982, the others between 2002 and 2021. Twenty-three of the victims were male, age ranged from 11 to 40 years. More than half of the cases originated from Southeast Asia, and 12 deaths happened in internet cafes. Gamers played action-rich multiplayer games. In 18 cases the gaming session before death was extremely long (around a day or even several days) with minimal rest. The cause of death was pulmonary embolism in 5 cases, cerebral hemorrhage in 2 cases, most of the rest was presumably due to fatal cardiac arrhythmia. DISCUSSION: Long sedentary position and dehydration may precipitate thromboembolism, acute blood pressure elevation during gaming may promote cerebral hemorrhage, and several factors (including acute and chronic sleep deprivation, exhaustion, stress) can lead to acute autonomic dysfunction and fatal arrhythmia. CONCLUSION: Incidence of non-violent death cases linked to playing video games is presumably very low. It mostly occurs in young males and it is often characterized by extremely long gaming time.

[Telecare in Parkinson's disease: A nationwide survey among Hungarian neurologists]. / Távellátás Parkinson-kórban: országos felmérés a magyar neurológusok körében.

Background and purpose: COVID-19 has made providing in-person care difficult. In most countries, including Hungary, telemedicine has partly served as a resolution for this issue. Our purpose was to explore the effects of COVID-19 on neurological care, the knowledge of neurology specialists on telemedicine, and the present state of telecare in Hungary, with a special focus on Parkinson's disease (PD). Methods: Between July and October 2021, a nationwide online survey was conducted among actively practicing Hungarian neurology specialists who were managing patients with PD. Results: A total of 104 neurologists were surveyed. All levels of care were evaluated in both publicly funded and private healthcare. Both time weekly spent on outpatient specialty consultation and the number of patients with PD seen weekly significantly decreased in public healthcare, while remained almost unchanged in private care (p<0.001); higher portion of patients were able to receive in-person care in private care (78.8% vs. 90.8%, p<0.001). In telecare, prescribing medicines has already been performed by the most (n=103, 99%). Electronic messages were the most widely known telemedicine tools (n=98, 94.2%), while phone call has already been used by most neurologists (n=95, 91.3%). Video-based consultation has been more widely used in private than public care (30.1% vs. 15.5%, p=0.001). Teleprocedures were considered most suitable for monitoring progression and symptoms of Parkinson's disease and evaluating the need for adjustments to antiparkinsonian pharmacotherapy. Conclusion: COVID-19 has had a major impact on the care of patients with PD in Hungary. Telemedicine has mitigated these detrimental effects; however, further developments could make it an even more reliable component of care.

Concomitant Medication Usage with Levodopa-Carbidopa Intestinal Gel: Results from the COSMOS Study.

BACKGROUND: Levodopa-carbidopa intestinal gel (LCIG) is administered directly to the small intestine of patients with advanced Parkinson's disease (APD) to help maintain stable plasma levodopa levels. OBJECTIVE: The objective of this study was to investigate the effect of LCIG in reducing polypharmacy for the treatment of APD. METHODS: The COmedication Study assessing Mono- and cOmbination therapy with levodopa-carbidopa inteStinal gel (COSMOS) is a large, real-world, multinational observational study investigating comedication use with LCIG. All enrolled patients had used LCIG for ≥12 months and data were collected cross-sectionally (study visit) and retrospectively. The primary endpoint was the percentage of patients using LCIG as monotherapy (without add-on PD medications) at initiation and at 3, 6, 9, and 12 months thereafter. RESULTS: Overall, 409 patients were enrolled from 14 countries and were treated with LCIG for a mean of 35.8 ± 23.2 months. A total of 15.2% of patients initiated LCIG as monotherapy and 31.7% were receiving monotherapy at 12 months after initiation. The mean duration of LCIG monotherapy was 39.3 ± 25.6 months. Use of add-on medications decreased over time with all LCIG regimens. From LCIG initiation to the patient visit, mean off time decreased by 3.8, 4.6, and 3.9 hours/day for LCIG monotherapy, LCIG daytime monotherapy, and LCIG polytherapy groups, respectively, while duration of dyskinesia decreased by 1.7, 2.0, and 1.9 hours/day, respectively. Adverse events likely related to study treatment occurred in 112 patients (27.4%) during LCIG treatment. CONCLUSIONS: LCIG is an effective long-term monotherapy option with a positive risk-benefit profile and contributes to reduced polypharmacy for patients with APD. © 2021 The AbbVie Inc. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Low test-retest reliability of the Epworth Sleepiness Scale within a substantial short time frame.

The Epworth Sleepiness Scale (ESS) is a widely used, validated questionnaire for effectively examining patients' sleepiness in a range of different situations. Test-retest reliability is an important aspect of a questionnaire, which, according to only a few studies, was found to be low in the case of the ESS. All these studies applied long intervals between the tests, thereby increasing the possibility of fundamental change in circumstances, which in turn affect the reliability of the test. The aim of the present study was to investigate the test-retest reliability of the ESS in a short time frame to provide stability of the test circumstances. We also compared the originally used and current accepted statistical methods of test-retest evaluation. We examined 100 unselected patients consecutively referred to the sleep laboratory with the ESS questionnaire, using a test-retest paradigm with an interval of 1 h between two ESS tests. The Lin's concordance coefficient was found to be low, whereas the Pearson's correlation revealed good reliability. Our result provides evidence on the poor test-retest reliability of the ESS, despite the examination protocol excluding changes in test circumstances.

Minimal Clinically Important Differences for Burke-Fahn-Marsden Dystonia Rating Scale and 36-Item Short-Form Health Survey.

BACKGROUND: Although an increasing number of trials are reported on the treatment of generalized or segmental isolated dystonia, the minimal clinically important difference thresholds for the most frequently reported outcome measures are still undetermined. OBJECTIVES: To estimate the minimal clinically important difference for the Burke-Fahn-Marsden Dystonia Rating Scale and the 36-Item Short-Form Health Survey in generalized or segmental dystonia. METHODS: A total of 898 paired examinations of 198 consecutive patients, aged >18 years, with idiopathic and inherited (torsin family 1 member A positive) segmental and generalized isolated dystonia were analyzed. To calculate the minimal clinically important difference thresholds, both anchor- and distribution-based methods were used simultaneously. RESULTS: Any improvement >16.6% or worsening larger than 21.5% on the Burke-Fahn-Marsden Dystonia Rating Scale indicates a minimal, yet clinically relevant, change. Threshold values for the Burke-Fahn-Marsden Dystonia Disability Scale were 0.5 points for both decline and improvement. Cut-off scores for the Physical Component Summary, the Mental Component Summary, and the Global (Total or Overall) Score of the 36-Item Short-Form Health Survey were 5.5 and 5.5, 6.5 and 7.5, and 7.5 and 8.5 points for clinically meaningful improvement and deterioration, respectively. CONCLUSIONS: The minimal clinically important difference represents the smallest change in an outcome measure that is meaningful to patients. Our estimates for the Burke-Fahn-Marsden Dystonia Rating Scale and the 36-Item Short-Form Health Survey may allow more reliable judgment of the clinical relevance of different treatments for segmental and generalized isolated dystonia. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Integrated Care in Parkinson's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Quality of life in Parkinson's disease (PD) is affected by motor and nonmotor symptoms, necessitating an integrated care approach. Existing care models vary considerably in numerous domains. The objectives of this study were to perform a systematic review and meta-analysis of PD integrated care models and develop recommendations for a representative model. METHODS: We conducted a systematic review of published integrated care models and a meta-analysis of randomized, controlled trials examining integrated care versus standard care. The primary outcome was health-related quality of life using a validated PD scale. We evaluated levels of care integration using the Rainbow Model of Integrated Care. RESULTS: Forty-eight publications were identified, including 8 randomized, controlled trials with health-related quality of life data (n = 1,149 total PD patients). Qualitative evaluation of individual care model integration guided by the Rainbow Model of Integrated Care revealed frequent clinical and professional integration, but infrequent organizational and population-based integration elements. Meta-analysis of randomized, controlled trials revealed significant heterogeneity (I2 = 90%, P < 0.0001). Subgroup analysis including only outpatient care models (n = 5) indicated homogeneity of effects (I2 = 0%, P = 0.52) and improved health-related quality of life favoring integrated care, with a small effect size (standardized mean difference [SMD], -0.17; 95% CI, -0.31 to -0.03; P = 0.02). CONCLUSIONS: Outpatient integrated PD care models may improve patient-reported health-related quality of life compared with standard care; however, because of variable methodological approaches and a high risk of bias related to inherent difficulties in study design (eg, blinding of participants and interventionists), generalizability of these results are difficult to establish. The Rainbow Model of Integrated Care is a promising method of evaluating elements and levels of integration from individual patient care to population health in a PD context. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, LLC. on behalf of International Parkinson and Movement Disorder Society.

[Advanced Parkinson's disease characteristics in clinical practice: Results from the OBSERVE-PD study and sub-analysis of the Hungarian data]. / Az elôrehaladott Parkinson-kór jellemzôi a klinikai gyakorlatban: az OBSERVE-PD vizsgálat eredményei és a magyarországi alcsoport elemzése.

BACKGROUND AND PURPOSE: The majority of patients with advanced Parkinson's disease are treated at specialized movement disorder centers. Currently, there is no clear consensus on how to define the stages of Parkinson's disease; the proportion of Parkinson's patients with advanced Parkinson's disease, the referral process, and the clinical features used to characterize advanced Parkinson's disease are not well delineated. The primary objective of this observational study was to evaluate the proportion of Parkinson's patients identified as advanced patients according to physician's judgment in all participating movement disorder centers across the study. Here we evaluate the Hungarian subset of the participating patients. METHODS: The study was conducted in a cross-sectional, non-interventional, multi-country, multi-center format in 18 countries. Data were collected during a single patient visit. Current Parkinson's disease status was assessed with Unified Parkinson's Disease Rating Scale (UPDRS) parts II, III, IV, and V (modified Hoehn and Yahr staging). Non-motor symptoms were assessed using the PD Non-motor Symptoms Scale (NMSS); quality of life was assessed with the PD 8-item Quality-of-Life Questionnaire (PDQ-8). Parkinson's disease was classified as advanced versus non-advanced based on physician assessment and on questions developed by the Delphi method. RESULTS: Overall, 2627 patients with Parkinson's disease from 126 sites were documented. In Hungary, 100 patients with Parkinson's disease were documented in four movement disorder centers, and, according to the physician assessment, 50% of these patients had advanced Parkinson's disease. Their mean scores showed significantly higher impairment in those with, versus without advanced Parkinson's disease: UPDRS II (14.1 vs. 9.2), UPDRS IV Q32 (1.1 vs. 0.0) and Q39 (1.1 vs. 0.5), UPDRS V (2.8 vs. 2.0) and PDQ-8 (29.1 vs. 18.9). CONCLUSION: Physicians in Hungarian movement disorder centers assessed that half of the Parkinson's patients had advanced disease, with worse motor and non-motor symptom severity and worse QoL than those without advanced Parkinson's disease. Despite being classified as eligible for invasive/device-aided treatment, that treatment had not been initiated in 25% of these patients.