An intestinal zinc sensor regulates food intake and developmental growth.

In cells, organs and whole organisms, nutrient sensing is key to maintaining homeostasis and adapting to a fluctuating environment1. In many animals, nutrient sensors are found within the enteroendocrine cells of the digestive system; however, less is known about nutrient sensing in their cellular siblings, the absorptive enterocytes1. Here we use a genetic screen in Drosophila melanogaster to identify Hodor, an ionotropic receptor in enterocytes that sustains larval development, particularly in nutrient-scarce conditions. Experiments in Xenopus oocytes and flies indicate that Hodor is a pH-sensitive, zinc-gated chloride channel that mediates a previously unrecognized dietary preference for zinc. Hodor controls systemic growth from a subset of enterocytes-interstitial cells-by promoting food intake and insulin/IGF signalling. Although Hodor sustains gut luminal acidity and restrains microbial loads, its effect on systemic growth results from the modulation of Tor signalling and lysosomal homeostasis within interstitial cells. Hodor-like genes are insect-specific, and may represent targets for the control of disease vectors. Indeed, CRISPR-Cas9 genome editing revealed that the single hodor orthologue in Anopheles gambiae is an essential gene. Our findings highlight the need to consider the instructive contributions of metals-and, more generally, micronutrients-to energy homeostasis.

Histone variants in archaea - An undiscovered country.

Exchanging core histones in the nucleosome for paralogous variants can have important functional ramifications. Many of these variants, and their physiological roles, have been characterized in exquisite detail in model eukaryotes, including humans. In comparison, our knowledge of histone biology in archaea remains rudimentary. This is true in particular for our knowledge of histone variants. Many archaea encode several histone genes that differ in sequence, but do these paralogs make distinct, adaptive contributions to genome organization and regulation in a manner comparable to eukaryotes? Below, we review what we know about histone variants in archaea at the level of structure, regulation, and evolution. In all areas, our knowledge pales when compared to the wealth of insight that has been gathered for eukaryotes. Recent findings, however, provide tantalizing glimpses into a rich and largely undiscovered country that is at times familiar and eukaryote-like and at times strange and uniquely archaeal. We sketch a preliminary roadmap for further exploration of this country; an undertaking that may ultimately shed light not only on chromatin biology in archaea but also on the origin of histone-based chromatin in eukaryotes.

A Short Progressive Supranuclear Palsy Quality of Life Scale.

OBJECTIVE: The Progressive Supranuclear Palsy quality of life scale (PSP-QoL) has been shown to be a useful tool for capturing health-related quality of life of patients in "everyday life" and in progressive supranuclear palsy (PSP) research. However, at 45 items in length, the questionnaire can take a long time, exhausting PSP patients, in particular if cognitive impaired, which can have a negative impact on the assessment. The aim of this study was to establish a condensed version of the PSP-QoL for research and routine clinical care. METHODS: In this retrospective study, data originating from a German cohort of PSP patients was analyzed. Data from 245 PSP patients were included in this study. The short PSP-QoL questionnaire was created using a two-factor solution and item-total and inter-item correlations for mental and physical aspects of daily living of the PSP-QoL followed by confirmatory factor analysis. RESULTS: The final scale included 12 items representing mental (five items) and physical symptoms (seven items). The specified two-factor model displayed an excellent fit in the confirmatory factor analysis. The short Progressive Supranuclear Palsy Quality of Life scale (PSP-ShoQoL) correlated moderately with the PSP Rating Scale (r [243] = 0.514, P < 0.001) and Geriatric depression scale (r [231] = 0.548, P < 0.001). Sensitivity to change confirmed a significant decrease in QoL after 12 months. DISCUSSION: In this study, we created a 12-item PSP-ShoQoL designed to "facilitate" daily clinical work that correlated strongly with the PSP-QoL and was sensitive to change. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Exploring the lived experiences of individuals with Parkinson's disease and their relatives: insights into care provision experiences, disease management support, self-management strategies, and future needs in Germany (qualitative study).

BACKGROUND: Parkinson's disease (PD) significantly impacts the health-related quality of life of affected individuals and their relatives. In order to support the affected individuals and their families in coping with PD, it is essential to offer comprehensive information about their experiences. A comprehensive understanding of their lived experiences with the disease, the healthcare system, applied self-management strategies and their needs is considered crucial for developing a PD support program. Therefore, we aimed to explore the lived experiences and support needs of individuals with PD and their relatives in Germany. METHODS: This non-interventional, qualitative study conducted an explorative status quo and needs assessment. It generated knowledge through semi-structured focus groups and interviews with individuals with PD at various disease stages and their relatives. The interviews were digitally recorded, transcribed verbatim, and analysed using content analysis. RESULTS: Fifty-two individuals with PD and 29 relatives participated in eight focus groups and 13 paired and 13 individual interviews. Four themes with corresponding subthemes emerged: (1) experiences, revealing individuals' experiences around their diagnosis and with disease-specific care provision; (2) management support offers, clarifying who provides support and the type of support offered; (3) self-management, including comprehensibility, meaningfulness and manageability; and (4) future needs, differentiating between deficits and needs. Most participants expressed a sense of abandonment when obtaining self-management strategies and mastering their lives with PD, often referred to as 'life 2.0'. They identified the lack of structured and adequate provision of information, system orientation and social awareness. CONCLUSIONS: In Germany, there is an urgent need for a comprehensive PD care program that addresses the needs of individuals with PD and their relatives from the start of their care trajectory. It could assist individuals in gaining a comprehensive understanding of the disease, obtaining self-management strategies, building a support network, and becoming experts in self-managing their disease. Moreover, it may positively influence their care trajectory and reduce burdens, such as overburdening, fear of progression, and health anxiety. TRIAL REGISTRATION: German Clinical Studies Register ( https://www.drks.de/DRKS00030090 , No. DRKS00030090, Date of registration: 15.12.2022).

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.

Fitness landscape of a dynamic RNA structure.

RNA structures are dynamic. As a consequence, mutational effects can be hard to rationalize with reference to a single static native structure. We reasoned that deep mutational scanning experiments, which couple molecular function to fitness, should capture mutational effects across multiple conformational states simultaneously. Here, we provide a proof-of-principle that this is indeed the case, using the self-splicing group I intron from Tetrahymena thermophila as a model system. We comprehensively mutagenized two 4-bp segments of the intron. These segments first come together to form the P1 extension (P1ex) helix at the 5' splice site. Following cleavage at the 5' splice site, the two halves of the helix dissociate to allow formation of an alternative helix (P10) at the 3' splice site. Using an in vivo reporter system that couples splicing activity to fitness in E. coli, we demonstrate that fitness is driven jointly by constraints on P1ex and P10 formation. We further show that patterns of epistasis can be used to infer the presence of intramolecular pleiotropy. Using a machine learning approach that allows quantification of mutational effects in a genotype-specific manner, we demonstrate that the fitness landscape can be deconvoluted to implicate P1ex or P10 as the effective genetic background in which molecular fitness is compromised or enhanced. Our results highlight deep mutational scanning as a tool to study alternative conformational states, with the capacity to provide critical insights into the structure, evolution and evolvability of RNAs as dynamic ensembles. Our findings also suggest that, in the future, deep mutational scanning approaches might help reverse-engineer multiple alternative or successive conformations from a single fitness landscape.

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.

[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.

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.

Histone variants in archaea and the evolution of combinatorial chromatin complexity.

Nucleosomes in eukaryotes act as platforms for the dynamic integration of epigenetic information. Posttranslational modifications are reversibly added or removed and core histones exchanged for paralogous variants, in concert with changing demands on transcription and genome accessibility. Histones are also common in archaea. Their role in genome regulation, however, and the capacity of individual paralogs to assemble into histone-DNA complexes with distinct properties remain poorly understood. Here, we combine structural modeling with phylogenetic analysis to shed light on archaeal histone paralogs, their evolutionary history, and capacity to generate combinatorial chromatin states through hetero-oligomeric assembly. Focusing on the human commensal Methanosphaera stadtmanae as a model archaeal system, we show that the heteromeric complexes that can be assembled from its seven histone paralogs vary substantially in DNA binding affinity and tetramer stability. Using molecular dynamics simulations, we go on to identify unique paralogs in M. stadtmanae and Methanobrevibacter smithii that are characterized by unstable interfaces between dimers. We propose that these paralogs act as capstones that prevent stable tetramer formation and extension into longer oligomers characteristic of model archaeal histones. Importantly, we provide evidence from phylogeny and genome architecture that these capstones, as well as other paralogs in the Methanobacteriales, have been maintained for hundreds of millions of years following ancient duplication events. Taken together, our findings indicate that at least some archaeal histone paralogs have evolved to play distinct and conserved functional roles, reminiscent of eukaryotic histone variants. We conclude that combinatorially complex histone-based chromatin is not restricted to eukaryotes and likely predates their emergence.

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.

Conserved Cdk inhibitors show unique structural responses to tyrosine phosphorylation.

Balanced proliferation-quiescence decisions are vital during normal development and in tissue homeostasis, and their dysregulation underlies tumorigenesis. Entry into proliferative cycles is driven by Cyclin/Cyclin-dependent kinases (Cdks). Conserved Cdk inhibitors (CKIs) p21Cip1/Waf1, p27Kip1, and p57Kip2 bind to Cyclin/Cdks and inhibit Cdk activity. p27 tyrosine phosphorylation, in response to mitogenic signaling, promotes activation of CyclinD/Cdk4 and CyclinA/Cdk2. Tyrosine phosphorylation is conserved in p21 and p57, although the number of sites differs. We use molecular-dynamics simulations to compare the structural changes in Cyclin/Cdk/CKI trimers induced by single and multiple tyrosine phosphorylation in CKIs and their impact on CyclinD/Cdk4 and CyclinA/Cdk2 activity. Despite shared structural features, CKI binding induces distinct structural responses in Cyclin/Cdks and the predicted effects of CKI tyrosine phosphorylation on Cdk activity are not conserved across CKIs. Our analyses suggest how CKIs may have evolved to be sensitive to different inputs to give context-dependent control of Cdk activity.

EvoChromo: towards a synthesis of chromatin biology and evolution.

Over the past few years, interest in chromatin and its evolution has grown. To further advance these interests, we organized a workshop with the support of The Company of Biologists to debate the current state of knowledge regarding the origin and evolution of chromatin. This workshop led to prospective views on the development of a new field of research that we term 'EvoChromo'. In this short Spotlight article, we define the breadth and expected impact of this new area of scientific inquiry on our understanding of both chromatin and evolution.

Endoscopic Characteristics of Dysphagia in Multiple System Atrophy Compared to Parkinson's Disease.

BACKGROUND: Dysphagia is a major clinical concern in multiple system atrophy (MSA). A detailed evaluation of its major endoscopic features compared with Parkinson's disease (PD) is lacking. OBJECTIVE: This study systematically assessed dysphagia in MSA compared with PD and correlated subjective dysphagia to objective endoscopic findings. METHODS: Fifty-seven patients with MSA (median, 64 [interquartile range (IQR): 59-71] years; 35 women) underwent flexible endoscopic evaluation of swallowing using a specific MSA-flexible endoscopic evaluation of swallowing task protocol. Findings were compared with an age-matched cohort of 57 patients with PD (median, 67 [interquartile range: 60-73] years; 28 women). In a subcohort, subjective dysphagia was assessed using the Swallowing Disturbance Questionnaire and correlated to endoscopy findings. RESULTS: Patients with MSA predominantly showed symptoms suggestive of oral-phase disturbance (premature spillage, 75.4%, piecemeal deglutition, 75.4%). Pharyngeal-phase symptoms occurred less often (pharyngeal residues, 50.9%; penetration/aspiration, 28.1%). In contrast, pharyngeal symptoms were the most common finding in PD (pharyngeal residues, 47.4%). Oral symptoms occurred less frequently in PD (premature spillage, 15.8%, P < 0.001; piecemeal deglutition, 1.8%, P < 0.01). Patients with MSA had a greater risk for oral-phase disturbances with increased disease severity (P < 0.05; odds ratio, 3.15). Patients with MSA showed a significantly higher intraindividual interswallow variability compared with PD. When correlating Swallowing Disturbance Questionnaire scores with endoscopy results, its cutoff, validated for PD, was not sensitive enough to identify patients with MSA with dysphagia. We developed a subscore for identifying dysphagia in MSA and calculated a new cutoff (sensitivity 85%, specificity 100%). CONCLUSIONS: In contrast with patients with PD, patients with dysphagic MSA more frequently present with oral-phase symptoms and a significantly higher intraindividual interswallow variability. A novel Swallowing Disturbance Questionnaire MSA subscore may be a valuable tool to identify patients with MSA with early oropharyngeal dysphagia. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Detecting myositis as a cause of unexplained dysphagia: Proposal for a diagnostic algorithm.

BACKGROUND AND PURPOSE: Idiopathic inflammatory myopathy (IIM) can present with dysphagia as a leading or only symptom. In such cases, diagnostic evaluation may be difficult, especially if serological and electromyographical findings are unsuspicious. In this observational study we propose and evaluate a diagnostic algorithm to identify IIM as a cause of unexplained dysphagia. METHODS: Over a period of 4 years, patients with unexplained dysphagia were offered diagnostic evaluation according to a specific algorithm: The pattern of dysphagia was characterized by instrumental assessment (swallowing endoscopy, videofluoroscopy, high-resolution manometry). Patients with an IIM-compatible dysphagia pattern were subjected to further IIM-focused diagnostic procedures, including whole-body muscle magnetic resonance imaging, electromyography, creatine kinase blood level, IIM antibody panel and, as a final diagnostic step, muscle biopsy. Muscle biopsies were taken from affected muscles. In cases where no other muscles showed abnormalities, the cricopharyngeal muscle was targeted. RESULTS: Seventy-two patients presented with IIM-compatible dysphagia as a leading or only symptom. As a result of the specific diagnostic approach, 19 of these patients were diagnosed with IIM according to the European League Against Rheumatism (EULAR) criteria. Eighteen patients received immunomodulatory therapy as a result of the diagnosis. Of 10 patients with follow-up swallowing examination, dysphagia improved in three patients after therapy, while it remained at least stable in six patients. CONCLUSIONS: Idiopathic inflammatory myopathy constitutes a potentially treatable etiology in patients with unexplained dysphagia. The diagnostic algorithm presented in this study helps to identify patients with an IIM-compatible dysphagia pattern and to assign those patients for further IIM-focused diagnostic and therapeutic procedures.

Opicapone Use in Clinical Practice across Germany: A Sub-Analysis of the OPTIPARK Study in Parkinson's Disease Patients with Motor Fluctuations.

INTRODUCTION: The OPTIPARK study confirmed the effectiveness and safety of opicapone as adjunct therapy to levodopa in patients with Parkinson's disease (PD) and motor fluctuations under real-world conditions. The aim of this sub-analysis was to evaluate opicapone in the German patient cohort of OPTIPARK in order to provide country-specific data. METHODS: OPTIPARK was an open-label, single-arm study conducted in routine clinical practice across Germany and the UK. Patients with PD and motor fluctuations received once-daily opicapone 50 mg for 3 months in addition to levodopa. The primary endpoint was Clinicians' Global Impression of Change (CGI-C). Secondary assessments included Patients' Global Impressions of Change (PGI-C), Unified Parkinson's Disease Rating Scale (UPDRS) I-IV, Parkinson's Disease Questionnaire (PDQ-8), and Non-Motor Symptoms Scale (NMSS). This sub-analysis reports outcomes from the German patients only. RESULTS: Overall, 363 (97.6%) of the 372 patients included in the German cohort received ≥1 dose of opicapone and 291 (80.2%) completed the study. Improvements on CGI-C and PGI-C were reported by 70.8% and 76.3% of patients, respectively. UPDRS scores improved for activities of daily living during OFF time by -3.3 ± 4.5 points and motor scores during ON time by -5.3 ± 7.9 points. PDQ-8 and NMSS scores also demonstrated improvements. Treatment emergent adverse events considered at least possibly related to opicapone occurred in 37.7% of patients, with most being of mild or moderate intensity. CONCLUSION: Opicapone added to levodopa in patients with PD and motor fluctuations was effective and generally well tolerated in routine clinical practice across Germany.

Targeting the sensory feedback within the swallowing network-Reversing artificially induced pharyngolaryngeal hypesthesia by central and peripheral stimulation strategies.

Pharyngolaryngeal hypesthesia is a major reason for dysphagia in various neurological diseases. Emerging neuromodulation devices have shown potential to foster dysphagia rehabilitation, but the optimal treatment strategy is unknown. Because functional imaging studies are difficult to conduct in severely ill patients, we induced a virtual sensory lesion in healthy volunteers and evaluated the effects of central and peripheral neurostimulation techniques. In a sham-controlled intervention study with crossover design on 10 participants, we tested the potential of (peripheral) pharyngeal electrical stimulation (PES) and (central) transcranial direct current stimulation (tDCS) to revert the effects of lidocaine-induced pharyngolaryngeal hypesthesia on central sensorimotor processing. Changes were observed during pharyngeal air-pulse stimulation and voluntary swallowing applying magnetoencephalography before and after the interventions. PES induced a significant (p < .05) increase of activation during swallowing in the bihemispheric sensorimotor network in alpha and low gamma frequency ranges, peaking in the right premotor and left primary sensory area, respectively. With pneumatic stimulation, significant activation increase was found after PES in high gamma peaking in the left premotor area. Significant changes of brain activation after tDCS could neither be detected for pneumatic stimulation nor for swallowing. Due to the peripheral cause of dysphagia in this model, PES was able to revert the detrimental effects of reduced sensory input on central processing, whereas tDCS was not. Results may have implications for therapeutic decisions in the clinical context.

Expiratory Muscle Strength Training for Therapy of Pharyngeal Dysphagia in Parkinson's Disease.

BACKGROUND: Pharyngeal dysphagia in Parkinson's disease (PD) is a common and clinically relevant symptom associated with poor nutrition intake, reduced quality of life, and aspiration pneumonia. Despite this, effective behavioral treatment approaches are rare. OBJECTIVE: The objective of this study was to verify if 4 week of expiratory muscle strength training can improve pharyngeal dysphagia in the short and long term and is able to induce neuroplastic changes in cortical swallowing processing. METHODS: In this double-blind, randomized, controlled trial, 50 patients with hypokinetic pharyngeal dysphagia, as confirmed by flexible endoscopic evaluation of swallowing, performed a 4-week expiratory muscle strength training. Twenty-five participants used a calibrated ("active") device, 25 used a sham handheld device. Swallowing function was evaluated directly before and after the training period, as well as after a period of 3 month using flexible endoscopic evaluation of swallowing. Swallowing-related cortical activation was measured in 22 participants (active:sham; 11:11) using whole-head magnetencephalography. RESULTS: The active group showed significant improvement in the flexible endoscopic evaluation of swallowing-based dysphagia score after 4 weeks and after 3 months, whereas in the sham group no significant changes from baseline were observed. Especially, clear reduction in pharyngeal residues was found. Regarding the cortical swallowing network before and after training, no statistically significant differences were found by magnetencephalography examination. CONCLUSIONS: Four-week expiratory muscle strength training significantly reduces overall dysphagia severity in PD patients, with a sustained effect after 3 months compared with sham training. This was mainly achieved by improving swallowing efficiency. The treatment effect is probably caused by peripheral mechanisms, as no changes in the cortical swallowing network were identified. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Predictors, outcome and characteristics of oropharyngeal dysphagia in idiopathic inflammatory myopathy.

INTRODUCTION: Oropharyngeal dysphagia is a clinical hallmark of idiopathic inflammatory myopathy (IIM). This study investigated predictors, outcome, and characteristics of oropharyngeal dysphagia in patients with different types of IIM. METHODS: Flexible endoscopic evaluation of swallowing (FEES) videos of 71 IIM patients were retrospectively analyzed for bolus spillage, penetration, aspiration, and pharyngeal residue. Based on these findings, dysphagia severity was rated. Regression analyses were performed to investigate demographic and disease-specific predictors of dysphagia severity and pneumonia as outcome-relevant complications of dysphagia. A score was developed to rate the quality of the endoscopic white-out as a surrogate marker for pharyngeal muscle weakness with consecutive residue. RESULTS: Our analysis revealed no independent predictors of dysphagia severity. Dysphagia severity, however, was an independent predictor for pneumonia, which occurred in 24% of patients. Pharyngeal residue with risk of postdeglutitive aspiration was the most common dysphagia pattern. Attenuation of the endoscopic white-out was related to residue severity. DISCUSSION: Dysphagia in IIM assessed with FEES is associated with relevant complications, such as aspiration pneumonia, and must be considered independently of peripheral muscle weakness and disease duration. Swallowing impairment mainly presents with pharyngeal residue. The quality of the white-out may serve as a semi-quantitative surrogate marker for pharyngeal contractility.

Effect of cognitive and motor dual-task on oropharyngeal swallowing in Parkinson's disease.

BACKGROUND: Dysphagia frequently occurs in patients with Parkinson's disease (PD) and is associated with severe complications. However, the underlying pathology is poorly understood at present. This study investigated the effect of cognitive and motor dual-task interference on oropharyngeal swallowing in PD. METHODS: Thirty PD patients (23 men, mean age 65.90 ± 9.32 years, mean Hoehn and Yahr stage 2.62 ± 0.81, mean UPDRS 18.00 ± 7.18) were examined using flexible endoscopic evaluation of swallowing (FEES). FEES was performed during three paradigms: at baseline without interference, during a cognitive dual-task, and during a motor dual-task. Oropharyngeal swallowing function was rated using a score which was validated to detect changes in PD related dysphagia. The three paradigms were compared using a two-way-repetitive-measures-ANOVA and a post-hoc-analysis. RESULTS: Mean swallowing score in baseline FEES was 10.67 ± 5.89. It significantly increased (worsened) to 15.97 ± 7.62 (p < 0.001) in the motor dual-task and to 14.55 ± 7.49 (p < 0.001) in the cognitive dual-task. Premature bolus spillage and pharyngeal residue both significantly increased during both of the dual-task conditions whereas penetration/aspiration events did not change. CONCLUSION: Oropharyngeal swallowing in patients with PD is not purely reflexive but requires mental capacity. Additional allocation of attentional resources in the central control of swallowing seems to be an effective compensatory mechanism in PD-related dysphagia: The proposed dual-task protocol may be useful to challenge swallowing functional reserve. Conversely, as a therapeutic strategy, it could be beneficial to focus attention on swallowing and to avoid dual-task situations.