[Gastrointestinal disorders in hyperkinetic movement disorders and ataxia]. / Gastrointestinale Störungen bei hyperkinetischen Bewegungsstörungen und Ataxien.

Disorders of the gastrointestinal tract in patients suffering from hypokinetic movement disorders, and in particular Parkinson's disease, have increasingly been the subject of more intensive neuromedical research. So far, few data are available for patients with hyperkinetic movement disorders and ataxias. This review article summarizes the currently available and relevant publications on this topic. The particular focus is on essential tremor, restless legs syndrome, Huntington's disease and the group of hereditary ataxias. Further intensive research will be necessary in the future to collect detailed information also for these disease symptoms about specific disturbance patterns, in order to understand the underlying pathological pathways and to derive specific treatment approaches.

Pharyngeal Electrical Stimulation prior to extubation - Reduction of extubation failure rate in acute stroke patients?

PURPOSE: The aim of our study was to assess if PES before extubation can minimize the extubation failure risk in orally intubated, mechanically ventilated stroke patients at high risk of severe dysphagia. MATERIALS AND METHODS: Thirty-two ICU patients were prospectively enrolled in this study presenting with a high risk for dysphagia as defined by a DEFISS (Determine Extubation Failure In Severe Stroke) risk score and compared 1:1 to a retrospective matched patient control group. The prospective patient group received PES prior to extubation. Endpoints were need for reintubation, swallowing function as assessed with FEES, pneumonia incidence and length of stay after extubation. RESULTS: Post-extubation, the Fiberoptic Endoscopic Dysphagia Severity Score (FEDSS, 4.31 ± 1.53vs.5.03 ± 1.28;p = 0.047) and reintubation rate within 72 h (9.4vs.34.4%;p = 0.032) were significantly lower in the PES group than in the historical control group. Pulmonary infections after extubation were less common in PES-treated patients although this difference was not significant (37.5vs.59.4%;p = 0.133). Time from extubation to discharge was significantly shorter after PES compared with the control group (14.09 ± 11.58vs.26.59 ± 20.49 days;p = 0.003). CONCLUSIONS: In orally intubated and mechanically ventilated stroke patients at high risk of severe dysphagia, PES may improve swallowing function, reduce extubation failure risk and decrease time from extubation to discharge. Further research is required.

Which Comprehensive Geriatric Assessment (CGA) instruments are currently used in Germany: a survey.

BACKGROUND: The Comprehensive Geriatric Assessment (CGA) records geriatric syndromes in a standardized manner, allowing individualized treatment tailored to the patient's needs and resources. Its use has shown a beneficial effect on the functional outcome and survival of geriatric patients. A recently published German S1 guideline for level 2 CGA provides recommendations for the use of a broad variety of different assessment instruments for each geriatric syndrome. However, the actual use of assessment instruments in routine geriatric clinical practice and its consistency with the guideline and the current state of literature has not been investigated to date. METHODS: An online survey was developed by an expert group of geriatricians and sent to all licenced geriatricians (n = 569) within Germany. The survey included the following geriatric syndromes: motor function and self-help capability, cognition, depression, pain, dysphagia and nutrition, social status and comorbidity, pressure ulcers, language and speech, delirium, and frailty. Respondents were asked to report which geriatric assessment instruments are used to assess the respective syndromes. RESULTS: A total of 122 clinicians participated in the survey (response rate: 21%); after data cleaning, 76 data sets remained for analysis. All participants regularly used assessment instruments in the following categories: motor function, self-help capability, cognition, depression, and pain. The most frequently used instruments in these categories were the Timed Up and Go (TUG), the Barthel Index (BI), the Mini Mental State Examination (MMSE), the Geriatric Depression Scale (GDS), and the Visual Analogue Scale (VAS). Limited or heterogenous assessments are used in the following categories: delirium, frailty and social status. CONCLUSIONS: Our results show that the assessment of motor function, self-help capability, cognition, depression, pain, and dysphagia and nutrition is consistent with the recommendations of the S1 guideline for level 2 CGA. Instruments recommended for more frequent use include the Short Physical Performance Battery (SPPB), the Montreal Cognitive Assessment (MoCA), and the WHO-5 (depression). There is a particular need for standardized assessment of delirium, frailty and social status. The harmonization of assessment instruments throughout geriatric departments shall enable more effective treatment and prevention of age-related diseases and syndromes.

Smartwatch Versus Routine Tremor Documentation: Descriptive Comparison.

We addressed the limitations of subjective clinical tremor assessment by comparing routine neurological evaluation with a Tremor Occurrence Score derived from smartwatch sensor data, among 142 participants with Parkinson disease and 77 healthy controls. Our findings highlight the potential of smartwatches for automated tremor detection as a valuable addition to conventional assessments, applicable in both clinical and home settings.

Nucleosomes at the Dawn of Eukaryotes.

Genome regulation in eukaryotes revolves around the nucleosome, the fundamental building block of eukaryotic chromatin. Its constituent parts, the four core histones (H3, H4, H2A, H2B), are universal to eukaryotes. Yet despite its exceptional conservation and central role in orchestrating transcription, repair, and other DNA-templated processes, the origins and early evolution of the nucleosome remain opaque. Histone-fold proteins are also found in archaea, but the nucleosome we know-a hetero-octameric complex composed of histones with long, disordered tails-is a hallmark of eukaryotes. What were the properties of the earliest nucleosomes? Did ancestral histones inevitably assemble into nucleosomes? When and why did the four core histones evolve? This review will look at the evolution of the eukaryotic nucleosome from the vantage point of archaea, focusing on the key evolutionary transitions required to build a modern nucleosome. We will highlight recent work on the closest archaeal relatives of eukaryotes, the Asgardarchaea, and discuss what their histones can and cannot tell us about the early evolution of eukaryotic chromatin. We will also discuss how viruses have become an unexpected source of information about the evolutionary path toward the nucleosome. Finally, we highlight the properties of early nucleosomes as an area where new tools and data promise tangible progress in the not-too-distant future.

Development of a Core Outcome Set for Dysphagia Interventions in Parkinson's disease (COS-DIP): study protocol.

INTRODUCTION: Current clinical trials on swallowing disorders (dysphagia) in Parkinson's disease (PD) apply a high variety of outcomes and different outcome measures making comparative effectiveness research challenging. Furthermore, views of patients and dysphagia clinicians when selecting trial outcomes have not been considered in the past, thus study results may have little importance to them. This study aims to develop an agreed standardised Core Outcome Set for Dysphagia Interventions in Parkinson's disease (COS-DIP), systematically measured and reported as a minimum for all clinical trials. It will also comprise guidance on outcome definitions, outcome measures and time points of measurement. METHODS AND ANALYSIS: The COS-DIP development will comprise five stages following established methodology: (1) a recent scoping review on all applied outcomes, their definitions, methods and time points of measurement in clinical trials in dysphagia in PD, (2) online surveys and focus groups with clinicians, patients, caregivers and family members to identify outcomes that are important to them, (3) an identified list of outcomes based on results of stage 1 and 2, (4) three round online Delphi survey with up to 200 key stakeholders to determine core outcomes and (5) two online consensus meetings with up to 40 representative key stakeholders to agree on all outcomes, definitions, methods and time points of measurement in the final COS-DIP. ETHICS AND DISSEMINATION: Full ethical approval was obtained from the Research Ethics Committee, School of Linguistic, Speech and Communication Sciences, Trinity College Dublin, on 15 May 2023 (HT27). Dissemination of the COS-DIP will be enhanced through presentations at (inter-) national conferences and through peer-reviewed, open access publications of related manuscripts. Lay and professional information sheets and infographics will be circulated through relevant patient and professional organisations and networks. TRIAL REGISTRATION NUMBER: The COS-DIP study was registered prospectively with the Core Outcome Measures in Effectiveness Trials (COMET) database on 24 September 2021 (www.comet-initiative.org/Studies/Details/1942).

Interdisciplinary network care collaboration in Parkinson's disease: a baseline evaluation in Germany.

BACKGROUND: The strengthening of interdisciplinary care collaboration in Parkinson's disease is taking on increasing importance in daily medical routine. Therefore, care providers worldwide are organizing themselves in disease-specific regional network structures. However, the existing networks are heterogeneous, and the driving key players are yet unidentified. OBJECTIVES: To systematically identify key factors of the composition of health care professionals, who are initially interested in the development of a Parkinson network for interdisciplinary care collaboration, their motivation, and expectations, we conducted a basic evaluation in three different German regions covering a total number of 23,405 people with Parkinson's. METHODS: A specially developed semi-open questionnaire focusing on socio-demographic information, ways of contact, interdisciplinary collaboration, and connectedness was used. Statistical analyses were performed based on a predesigned codebook. RESULTS: The most crucial professions were outpatient therapists (physio-, occupational-, speech therapists) (36.7%), average case load of 10.1 patients/3 months and inpatient movement disorder specialists (21.1%), average case load of 197.4 patients/3 months. Before implementation of PD networks, 48.9% of outpatient therapists did not have any contact with neurologists. 58.9% of caregivers considered the current frequency of collaboration to be insufficient. The lack of political support as well as a lack of time were identified as main hurdles to increased collaboration. CONCLUSION: The identified driving forces in strengthened care collaboration are assigned to different healthcare sectors. This makes networks which provide tools for specialized education and interdisciplinary, cross-sectoral communication indispensable. For an areawide rollout, a rethinking of political frameworks towards network care is strongly necessary.

Machine Learning in the Parkinson's disease smartwatch (PADS) dataset.

The utilisation of smart devices, such as smartwatches and smartphones, in the field of movement disorders research has gained significant attention. However, the absence of a comprehensive dataset with movement data and clinical annotations, encompassing a wide range of movement disorders including Parkinson's disease (PD) and its differential diagnoses (DD), presents a significant gap. The availability of such a dataset is crucial for the development of reliable machine learning (ML) models on smart devices, enabling the detection of diseases and monitoring of treatment efficacy in a home-based setting. We conducted a three-year cross-sectional study at a large tertiary care hospital. A multi-modal smartphone app integrated electronic questionnaires and smartwatch measures during an interactive assessment designed by neurologists to provoke subtle changes in movement pathologies. We captured over 5000 clinical assessment steps from 504 participants, including PD, DD, and healthy controls (HC). After age-matching, an integrative ML approach combining classical signal processing and advanced deep learning techniques was implemented and cross-validated. The models achieved an average balanced accuracy of 91.16% in the classification PD vs. HC, while PD vs. DD scored 72.42%. The numbers suggest promising performance while distinguishing similar disorders remains challenging. The extensive annotations, including details on demographics, medical history, symptoms, and movement steps, provide a comprehensive database to ML techniques and encourage further investigations into phenotypical biomarkers related to movement disorders.

The comorbidity and co-medication profile of patients with progressive supranuclear palsy.

BACKGROUND: Progressive supranuclear palsy (PSP) is usually diagnosed in elderly. Currently, little is known about comorbidities and the co-medication in these patients. OBJECTIVES: To explore the pattern of comorbidities and co-medication in PSP patients according to the known different phenotypes and in comparison with patients without neurodegenerative disease. METHODS: Cross-sectional data of PSP and patients without neurodegenerative diseases (non-ND) were collected from three German multicenter observational studies (DescribePSP, ProPSP and DANCER). The prevalence of comorbidities according to WHO ICD-10 classification and the prevalence of drugs administered according to WHO ATC system were analyzed. Potential drug-drug interactions were evaluated using AiDKlinik®. RESULTS: In total, 335 PSP and 275 non-ND patients were included in this analysis. The prevalence of diseases of the circulatory and the nervous system was higher in PSP at first level of ICD-10. Dorsopathies, diabetes mellitus, other nutritional deficiencies and polyneuropathies were more frequent in PSP at second level of ICD-10. In particular, the summed prevalence of cardiovascular and cerebrovascular diseases was higher in PSP patients. More drugs were administered in the PSP group leading to a greater percentage of patients with polypharmacy. Accordingly, the prevalence of potential drug-drug interactions was higher in PSP patients, especially severe and moderate interactions. CONCLUSIONS: PSP patients possess a characteristic profile of comorbidities, particularly diabetes and cardiovascular diseases. The eminent burden of comorbidities and resulting polypharmacy should be carefully considered when treating PSP patients.

Validation of the DIGEST-FEES as a Global Outcome Measure for Pharyngeal Dysphagia in Parkinson's Disease.

Flexible Endoscopic Evaluation of Swallowing (FEES) is one of two diagnostic gold standards for pharyngeal dysphagia in Parkinson's disease (PD), however, validated global outcome measures at the patient level are widely lacking. The Dynamic Imaging Grade of Swallowing Toxicity for Flexible Endoscopic Evaluation of Swallowing (DIGEST-FEES) represents such an outcome measure but has been validated primarily for head and neck cancer collectives. The objective of this study was, therefore, to investigate the validity of the DIGEST-FEES in patients with PD. Content validity was evaluated with a modified Delphi expert survey. Subsequently, 66 FEES videos in PD patients were scored with the DIGEST-FEES. Criterion validity was determined using Spearman's correlation coefficient between the DIGEST-FEES and the Penetration-Aspiration Scale (PAS), the Yale-Residue-Rating-Scale, the Functional-Oral-Intake-Scale (FOIS), and the swallowing-related Unified-Parkinson-Disease-Rating-Scale (UPDRS) items. Inter-rater reliability was determined using 10 randomly selected FEES-videos examined by a second rater. As a result, the overall DIGEST-FEES-rating exhibited significant correlations with the Yale-Valleculae-Residue-Scale (r = 0.84; p < 0.001), the Yale-Pyriform-Sinus-Residue-Scale (r = 0.70; p < 0.001), the FOIS (r = - 0.55, p < 0.001), and the UPDRS-Swallowing-Item-Score (r = 0.42, p < 0.001). Further, the DIGEST-FEES-safety subscore correlated with the PAS (r = 0.63, p < 0.001). Inter-rater reliability was high for the overall DIGEST-FEES rating (quadratic weighted kappa of 0.82). Therefore, DIGEST-FEES is a valid and reliable score to evaluate overall pharyngeal dysphagia severity in PD. Nevertheless, the modified Delphi survey identified domains where DIGEST-FEES may need to be specifically adapted to PD or neurological collectives in the future.

Histones with an unconventional DNA-binding mode in vitro are major chromatin constituents in the bacterium Bdellovibrio bacteriovorus.

Histone proteins bind DNA and organize the genomes of eukaryotes and most archaea, whereas bacteria rely on different nucleoid-associated proteins. Homology searches have detected putative histone-fold domains in a few bacteria, but whether these function like archaeal/eukaryotic histones is unknown. Here we report that histones are major chromatin components in the bacteria Bdellovibrio bacteriovorus and Leptospira interrogans. Patterns of sequence evolution suggest important roles for histones in additional bacterial clades. Crystal structures (<2.0 Å) of the B. bacteriovorus histone (Bd0055) dimer and the histone-DNA complex confirm conserved histone-fold topology but indicate a distinct DNA-binding mode. Unlike known histones in eukaryotes, archaea and viruses, Bd0055 binds DNA end-on, forming a sheath of dimers encasing straight DNA rather than wrapping DNA around their outer surface. Our results demonstrate that histones are present across the tree of life and highlight potential evolutionary innovation in how they associate with DNA.

Evaluation of free-floating tracheal intubation in weightlessness via ice-pick position with a direct laryngoscopy and classic approach with indirect videolaryngoscopy.

Long duration spaceflights to the Moon or Mars are at risk for emergency medical events. Managing a hypoxemic distress and performing an advanced airway procedure such as oro-tracheal intubation may be complicated under weightlessness due to ergonomic constraints. An emergency free-floating intubation would be dangerous because of high failure rates due to stabilization issues that prohibits its implementation in a space environment. Nevertheless, we hypothesized that two configurations could lead to a high first-pass success score for intubation performed by a free-floating operator. In a non-randomized, controlled, cross-over simulation study during a parabolic flight campaign, we evaluated and compared the intubation performance of free-floating trained operators, using either a conventional direct laryngoscope in an ice-pick position or an indirect laryngoscopy with a video-laryngoscope in a classic position at the head of a high-fidelity simulation manikin, in weightlessness and in normogravity. Neither of the two tested conditions reached the minimal terrestrial ILCOR recommendations (95% first-pass success) and therefore could not be recommended for general implementation under weightlessness conditions. Free-floating video laryngoscopy at the head of the manikin had a significant better success score than conventional direct laryngoscopy in an ice-pick position. Our results, combined with the preexisting literature, emphasis the difficulties of performing oro-tracheal intubation, even for experts using modern airway devices, under postural instability in weightlessness. ClinicalTrials registration number NCT05303948.

Swallowing Characteristics in Patients with Multiple System Atrophy Analyzed Using FEES Examination.

Patients with multiple system atrophy (MSA) frequently experience dysphagia but only few studies analyzed its characteristics. The aim of this study was to describe the swallowing characteristics in these patients using fiberoptic endoscopic evaluation of swallowing (FEES). In addition, the swallowing abilities in patients with predominantly cerebellar MSA (MSA-C) and predominantly parkinsonian MSA (MSA-P) were compared. Twenty-five patients with MSA (16 MSA-P and 9 MSA-C) were enrolled. Clinical data including age, sex, functional oral intake scale (FOIS) score, body mass index (BMI) and the results of the global disability-unified MSA rating scale (GD-UMSARS) were collected. Three different textures of food (liquid, semisolid, solid) were provided during FEES examination. The characteristics of dysphagia (safety, efficiency, phenotype) and laryngeal movement alterations were analyzed. Delayed pharyngeal phase (92%) and posterior oral incontinence (52%) were the phenotypes more frequently seen. Penetration was more frequent with Liquid (68%), while aspiration occurred only with Liquid (20%). Residues of ingested food were demonstrated both in the pyriform sinus and in the vallecula with all the consistencies. Vocal fold motion impairment was the laryngeal movement alteration most frequently encountered (56%). No significant differences between patients with MSA-P and MSA-C in the dysphagia characteristics and laryngeal movement alterations were found. Patients with MSA frequently experience swallowing impairment and altered laryngeal mobility. Dysphagia characteristics and laryngeal movements alterations seems to be similar in MSA-C and MSA-P.

Utilizing a tablet-based artificial intelligence system to assess movement disorders in a prospective study.

Spiral drawings on paper are used as routine measures in hospitals to assess Parkinson's Disease motor deficiencies. In the age of emerging mobile health tools and Artificial Intelligence a comprehensive digital setup enables granular biomarker analyses and improved differential diagnoses in movement disorders. This study aims to evaluate on discriminatory features among Parkison's Disease patients, healthy subjects and diverse movement disorders. Overall, 24 Parkinson's Disease patients, 27 healthy controls and 26 patients with similar differential diagnoses were assessed with a novel tablet-based system. It utilizes an integrative assessment by combining a structured symptoms questionnaire-the Parkinson's Disease Non-Motor Scale-and 2-handed spiral drawing captured on a tablet device. Three different classification tasks were evaluated: Parkinson's Disease patients versus healthy control group (Task 1), all Movement disorders versus healthy control group (Task 2) and Parkinson's Disease patients versus diverse other movement disorder patients (Task 3). To systematically study feature importances of digital biomarkers a Machine Learning classifier is cross-validated and interpreted with SHapley Additive exPlanations (SHAP) values. The number of non-motor symptoms differed significantly for Tasks 1 and 2 but not for Task 3. The proposed drawing features partially differed significantly for all three tasks. The diagnostic accuracy was on average 94.0% in Task 1, 89.4% in Task 2, and 72% in Task 3. While the accuracy in Task 3 only using the symptom questionnaire was close to the baseline, it greatly improved when including the tablet-based features from 60 to 72%. The accuracies for all three tasks were significantly improved by integrating the two modalities. These results show that tablet-based drawing features can not only be captured by consumer grade devices, but also capture specific features to Parkinson's Disease that significantly improve the diagnostic accuracy compared to the symptom questionnaire. Therefore, the proposed system provides an objective type of disease characterization of movement disorders, which could be utilized for home-based assessments as well.Clinicaltrials.gov Study-ID: NCT03638479.

Design and implementation of ParkinsonAKTIV: an interventional study to evaluate the effectiveness of a novel online platform to guide quickcard-based treatment decisions.

INTRODUCTION: Patients with Parkinson's Disease (PD) require an all-encompassing and individualized care including pharmacological as well as non-pharmacological treatment approaches, such as physical therapy, occupational therapy and speech and swallowing therapy. ParkinsonAKTIV is an innovative, multidisciplinary, and comprehensive approach to guide this non-pharmacological PD treatment in northwestern Germany. Its online communication platform called JamesAKTIV has been developed to enhance and standardize PD healthcare professionals' communication. The implementation of ParkinsonAKTIV and JamesAKTIV is accompanied through a detailed process evaluation and to gather evidence on the impact on patient-related outcomes, such as health-related quality of life and healthcare costs for people with PD through an effectiveness evaluation. METHODS: The study design contains two parts: (1) first, a quantitative effectiveness evaluation is conducted utilizing a prospective quasi-experimental approach with a control group which examines PD patient's health-related quality of life and physician-assessed PD patient's health status (Unified Parkinson Disease Rating Scale). Moreover, a health economic evaluation of the ParkinsonAKTIV intervention is conducted using patient-reported outcomes and cost data as well as routine data from a statutory health insurance. (2) Second, a mixed-methods process evaluation among healthcare professionals, which examines the feasibility and potential barriers and facilitators of ParkinsonAKTIV for routine care, is performed. Quantitative results from a social network analysis and a survey among healthcare professionals will be triangulated with data from qualitative stakeholder interviews and focus group discussions. PERSPECTIVE: Findings are expected to provide evidence of an increase in quality of life of patients with PD, less severe PD symptoms, and a better ability to participate in activities of daily living. ParkinsonAKTIV has the potential of increasing PD patients' quality of care through sufficient and more tailored prescription of non-pharmacological therapies. It is anticipated that ParkinsonAKTIV will improve communication among health professionals. Results from the ParkinsonAKTIV study will provide first practice-oriented evidence and a roadmap for implementation of an online tool for a comprehensive, multidisciplinary care PD network for patients and their caregivers in routine care in Germany. Trial registration ClinicalTrials.gov: registration number NCT05251298 (retrospectively registered: https://clinicaltrials.gov/ct2/show/record/NCT05251298 ).

Costs of post-stroke dysphagia during acute hospitalization from a health-insurance perspective.

Purpose: Oropharyngeal dysphagia is a common and complication-prone symptom after stroke and is assumed to increase medical expenses. The purpose of this study was therefore to examine acute hospitalization costs associated with post-stroke dysphagia. Method: This retrospective study included patients with acute stroke who had been examined by Flexible Endoscopic Evaluation of Swallowing (FEES). Health insurance expenditures were determined for the patient cases according to the 2021 revenue criteria. Multiple linear regression was used to examine predictors of health insurance spending including age, sex, stroke severity, stroke characteristics, comorbidity, therapeutic interventions, duration of artificial ventilation, length of hospital stay, and severity of dysphagia, as assessed by the Fiberoptic Endoscopic Dysphagia Severity Scale (FEDSS), ranging from 1 (best) to 6 (worst). Findings: Six hundred seventy four patients (men/women: 367/307; mean age: 71.1 ± 12.8 years; mean National Institute of Health Stroke Scale: 11.2 ± 6.2; FEDSS 1/2/3/4/5/6: 113/73/144/119/124/101; mean health-insurance costs 11,521.5 ± 12,950.5€) were included in the analysis. Advanced age (p = 0.007; B = 57.6), catheter interventions (p < 0.001; B = 4105.6), tracheotomy (p = 0.006; B = 5195.2), duration of artificial ventilation (p < 0.001; B = 388.6), length of hospital stay (p < 0.001; B = 441.9), and severe dysphagia with an FEDSS of 6 (p = 0.004, B = 2554.3) were independent predictors of increased health insurance expenditures (p < 0.001, R-squared = adjusted-R-squared = 0.83). Discussion and conclusion: The results of this study show an association between severe dysphagia and health care costs for acute hospitalization from a health-insurance perspective. Therefore, therapies that target severe dysphagia with impaired secretion management may have the potential to reduce costs.

Relationship between post-stroke dysphagia and pharyngeal sensory impairment.

BACKGROUND: Post-stroke dysphagia (PSD) is common and can lead to serious complications. Pharyngeal sensory impairment is assumed to contribute to PSD. The aim of this study was to investigate the relationship between PSD and pharyngeal hypesthesia and to compare different assessment methods for pharyngeal sensation. METHODS: In this prospective observational study, fifty-seven stroke patients were examined in the acute stage of the disease using Flexible Endoscopic Evaluation of Swallowing (FEES). The Fiberoptic Endoscopic Dysphagia Severity Scale (FEDSS) and impaired secretion management according to the Murray-Secretion Scale were determined, as well as premature bolus spillage, pharyngeal residue and delayed or absent swallowing reflex. A multimodal sensory assessment was performed, including touch-technique and a previously established FEES-based swallowing provocation test with different volumes of liquid to determine the latency of swallowing response (FEES-LSR-Test). Predictors of FEDSS, Murray-Secretion Scale, premature bolus spillage, pharyngeal residue, and delayed or absent swallowing reflex were examined with ordinal logistic regression analyses. RESULTS: Sensory impairment using the touch-technique and the FEES-LSR-Test were independent predictors of higher FEDSS, Murray-Secretion Scale, and delayed or absent swallowing reflex. Decreased sensitivity according to the touch-technique correlated with the FEES-LSR-Test at 0.3 ml and 0.4 ml, but not at 0.2 ml and 0.5 ml trigger volumes. CONCLUSIONS: Pharyngeal hypesthesia is a crucial factor in the development of PSD, leading to impaired secretion management and delayed or absent swallowing reflex. It can be investigated using both the touch-technique and the FEES-LSR-Test. In the latter procedure, trigger volumes of 0.4 ml are particularly suitable.

Gastrointestinal barriers to levodopa transport and absorption in Parkinson's disease.

Levodopa is the gold standard for the symptomatic treatment of Parkinson's disease (PD). There are well documented motor and non-motor fluctuations, however, that occur almost inevitably once levodopa is started after a variable period in people with PD. Whilst brain neurodegenerative processes play a part in the pathogenesis of these fluctuations, a range of barriers across the gastrointestinal (GI) tract can alter levodopa pharmacokinetics, ultimately contributing to non-optimal levodopa response and symptoms fluctuations. GI barriers to levodopa transport and absorption include dysphagia, delayed gastric emptying, constipation, Helicobacter pylori infection, small intestinal bacterial overgrowth and gut dysbiosis. In addition, a protein-rich diet and concomitant medication intake can further alter levodopa pharmacokinetics. This can result in unpredictable or sub-optimal levodopa response, 'delayed on' or 'no on' phenomena. In this narrative review, we provided an overview on the plethora of GI obstacles to levodopa transport and absorption in PD and their implications on levodopa pharmacokinetics and development of motor fluctuations. In addition, management strategies to address GI dysfunction in PD are highlighted, including use of non-oral therapies to bypass the GI tract.