The PhINEST study - Pharyngeal ICU Novel Electrical Stimulation Therapy Study protocol of a prospective, multi-site, randomized, sham-controlled, single-blind (outcome assessor-blinded) study

Introduction: Post-extubation dysphagia is commonly observed in ICU patients and associated with increased aspiration rates, delayed resumption of oral intake/ malnutrition, prolonged ICU and hospital length of stay, decreased quality of life, and increased mortality. Conventional therapeutic approaches are limited. Pharyngeal electrical stimulation (PES) was previously shown to improve swallowing function and airway safety in severely dysphagic tracheostomised stroke patients. Methods: In a multi-center, single-blind, 1:1 randomized controlled study, up to 400 (360 evaluable) mixed emergency adult ICU patients with recent extubation following mechanical ventilation and confirmed oropharyngeal dysphagia will be enrolled at investigational academic ICUs. Primary objective is to evaluate the effectiveness of PES in reducing the severity of unsafe swallows. Patients will be randomized to receive PES (or sham) treatment on 3 consecutive days in addition to best supportive care. Primary endpoint is a composite of 2 endpoints with hierarchy based on clinical priorities: 1) Swallowing safety based on worst penetration-aspiration-scale (PAS) score in series of up to 4 boli using thin stimuli approx. From 24 to 60 hours after treatment completion, converted to a trichotomized ordinal response of safe (PAS 1-3), penetration (PAS 4-5), or aspiration (PAS 6-8). 2) Dysphagia Outcome and Severity Scale scores determined by bedside assessment 7 +/- 1 days after treatment completion. Oropharyngeal dysphagia will be assessed by Fiberoptic Endoscopic Evaluation of Swallowing by blinded study staff. Patients will be followed-up for a maximum of 90 days. Discussion: This study will evaluate the effects of PES on swallowing safety in critically ill ICU patients post mechanical ventilation with oropharyngeal dysphagia.Peer reviewe

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 Societ

Clinical determinants and neural correlates of presbyphagia in community-dwelling older adults

Background“Presbyphagia” refers to characteristic age-related changes in the complex neuromuscular swallowing mechanism. It has been hypothesized that cumulative impairments in multiple domains affect functional reserve of swallowing with age, but the multifactorial etiology and postulated compensatory strategies of the brain are incompletely understood. This study investigates presbyphagia and its neural correlates, focusing on the clinical determinants associated with adaptive neuroplasticity.Materials and methods64 subjects over 70 years of age free of typical diseases explaining dysphagia received comprehensive workup including flexible endoscopic evaluation of swallowing (FEES), magnetoencephalography (MEG) during swallowing and pharyngeal stimulation, volumetry of swallowing muscles, laboratory analyzes, and assessment of hand-grip-strength, nutritional status, frailty, olfaction, cognition and mental health. Neural MEG activation was compared between participants with and without presbyphagia in FEES, and associated clinical influencing factors were analyzed. Presbyphagia was defined as the presence of oropharyngeal swallowing alterations e.g., penetration, aspiration, pharyngeal residue pooling or premature bolus spillage into the piriform sinus and/or laryngeal vestibule.Results32 of 64 participants showed swallowing alterations, mainly characterized by pharyngeal residue, whereas the airway was rarely compromised. In the MEG analysis, participants with presbyphagia activated an increased cortical sensorimotor network during swallowing. As major clinical determinant, participants with swallowing alterations exhibited reduced pharyngeal sensation. Presbyphagia was an independent predictor of a reduced nutritional status in a linear regression model.ConclusionsSwallowing alterations frequently occur in otherwise healthy older adults and are associated with decreased nutritional status. Increased sensorimotor cortical activation may constitute a compensation attempt to uphold swallowing function due to sensory decline. Further studies are needed to clarify whether the swallowing alterations observed can be considered physiological per se or whether the concept of presbyphagia may need to be extended to a theory with a continuous transition between presbyphagia and dysphagia

Substance P Saliva Reduction Predicts Pharyngeal Dysphagia in Parkinson's Disease

Introduction: Although patients with Parkinson's disease (PD) often suffer from oropharyngeal dysphagia, knowledge about the underlying pathophysiological mechanisms is limited. Substance P (SP) is a localization-independent neurotransmitter of the entire nervous system. Reduced levels of SP were found in saliva of patients with impaired cough reflex and in advanced stages of PD. The aim of the study was to investigate SP in PD patients in order to gain further insights into the underlying pathophysiology of PD-related dysphagia and to evaluate the potential of SP as a biomarker for early dysphagia.Methods: Flexible endoscopic evaluation of swallowing (FEES) was used to objectively assess pharyngeal swallowing function. From a cohort of 105 consecutive PD patients 20 subjects were recruited: in 10 of them pharyngeal dysphagia was excluded by FEES, the other 10 subjects showed signs of early pharyngeal dysphagia defined as hypopharyngeal sensory deficit with mild to moderate vallecular residues after swallowing solid consistencies. Analysis of the Substance P level in saliva of the 20 included PD patients was performed in the clinical on state condition by ELISA-type immunoassay. Significant differences were calculated by using the Mann-Whitney test.Results: Twenty PD patients with a mean age of 69.5 ± 12.5 years (8 female) were included in the study. No significant differences were found regarding gender, age, UPDRS III, Hoehn and Yahr stage, disease duration, and Levodopa equivalent dose between the non-dysphagic and dysphagic subjects. Dysphagia was mainly characterized by unrecognized residues in the valleculae without any aspiration risk for all of the tested consistencies in FEES and was thereby scored as mild in all cases. Saliva SP concentrations were significantly lower in PD patients with pharyngeal dysphagia compared to those with a normal pharyngeal swallowing function (9,644 vs. 17,591 pg/mL; p = 0.001).Conclusion: Reduced saliva SP concentrations may predict early pharyngeal swallowing dysfunction in PD patients. This finding supports the hypothesis that an impaired SP mediated neurotransmission has a significant impact for the development of dysphagia in PD patients. Larger studies are needed to confirm SP as a clinical useful biomarker for early detection of PD-related dysphagia

Pharyngeal electrical stimulation for neurogenic dysphagia following stroke, traumatic brain injury or other causes: Main results from the PHADER cohort study

BackgroundNeurogenic dysphagia is common and has no definitive treatment. We assessed whether pharyngeal electrical stimulation (PES) is associated with reduced dysphagia.MethodsThe PHAryngeal electrical stimulation for treatment of neurogenic Dysphagia European Registry (PHADER) was a prospective single-arm observational cohort study. Participants were recruited with neurogenic dysphagia (comprising five groups – stroke not needing ventilation; stroke needing ventilation; ventilation acquired; traumatic brain injury; other neurological causes). PES was administered once daily for three days. The primary outcome was the validated dysphagia severity rating scale (DSRS, score best-worst 0–12) at 3 months.FindingsOf 255 enrolled patients from 14 centres in Austria, Germany and UK, 10 failed screening. At baseline, mean (standard deviation) or median [interquartile range]: age 68 (14) years, male 71%, DSRS 11·4 (1·7), time from onset to treatment 32 [44] days; age, time and DSRS differed between diagnostic groups. Insertion of PES catheters was successfully inserted in 239/245 (98%) participants, and was typically easy taking 11·8 min. 9 participants withdrew before the end of treatment. DSRS improved significantly in all dysphagia groups, difference in means (95% confidence intervals, CI) from 0 to 3 months: stroke (n = 79) –6·7 (–7·8, –5·5), ventilated stroke (n = 98) –6·5 (–7·6, –5·5); ventilation acquired (n = 35) –6·6 (–8·4, –4·8); traumatic brain injury (n = 24) -4·5 (–6·6, –2·4). The results for DSRS were mirrored for instrumentally assessed penetration aspiration scale scores. DSRS improved in both supratentorial and infratentorial stroke, with no difference between them (p = 0·32). In previously ventilated participants with tracheotomy, DSRS improved more in participants who could be decannulated (n = 66) –7·5 (–8·6, –6·5) versus not decannulated (n = 33) –2·1 (–3·2, –1·0) (

Effect of Intestinal Levodopa-Carbidopa Infusion on Pharyngeal Dysphagia: Results from a Retrospective Pilot Study in Patients with Parkinson’s Disease

Background. Pharyngeal dysphagia is a common symptom of Parkinson’s disease (PD) leading to severe complications. PD-related pharyngeal dysphagia (PDrPD) may significantly improve in up to half of patients following acute oral levodopa challenge. Objective. The aim of this study was to investigate the effects of levodopa-carbidopa intestinal gel (LCIG) on PDrPD. Methods. Forty-five PD patients under LCIG treatment were available for retrospective analysis. In all patients with PDrPD who underwent flexible endoscopic evaluation of swallowing (FEES) in the clinical “on-state” both before and after implementation of LCIG treatment, FEES videos were systematically reassessed. PDrPD was characterized using a PD-specific FEES score evaluating premature bolus spillage, penetration/aspiration, and pharyngeal residue. Further, the duration of white-out was assessed, as a parameter for pharyngeal bradykinesia. Results. Eleven patients with PDrPD (mean age 74.6 ± 4.4 years; mean Hoehn and Yahr stage 3.8 ± 0.6) received FEES both before and after the onset of LCIG treatment. The mean swallowing score improved from 14.9 ± 7.3 to 13.0 ± 6.9 after implementation of LCIG; however, this difference was not significant (p=0.312). Premature bolus spillage decreased significantly (p=0.002) from 5.4 ± 1.1 to 3.6 ± 1.0, and white-out duration decreased significantly (p=0.002) from 984 ± 228 ms to 699 ± 131 ms after implementation of LCIG. Conclusions. LCIG may affect PDrPD and reduce premature bolus spillage and pharyngeal bradykinesia. Future studies with larger sample sizes are required to follow-up on these pilot results and identify which factors predict a good response of PDrPD to LCIG treatment

Mind the gap: acute bilateral vocal cord palsy in CIDP after extending the IVIG treatment interval?

Cranial nerve involvement is rarely seen in chronic inflammatory demyelinating polyneuropathy (CIDP). We present a patient diagnosed with CIDP who was in a stable medical condition under long-term treatment with intravenous immunoglobulin (IVIG) every five weeks for more than seven years. Following a 12-day delay in the patient’s regular IVIG therapy, he developed acute bilateral vocal cord palsy. The patient had to be intubated and tracheostomized because of acute respiratory distress. Weaning from mechanical ventilation was complicated due to pneumonia. After antibiotic treatment and restarting IVIG therapy vocal cord palsy rapidly improved allowing for subsequent decannulation. Although coincidence between treatment delay and symptom development does not prove definitive causality this case report may serve as a reminder how time critical IVIG therapy can be for sufficient symptom control. Moreover, it provides evidence that IVIG therapy may be effective for the treatment of cranial nerve symptoms in CIDP