A comparative study on the therapeutic effect of TRPV1, TRPA1, and TRPM8 agonists on swallowing dysfunction associated with aging and neurological diseases.

BACKGROUND: Oropharyngeal sensory impairment is a potential target to treat swallowing dysfunction in patients with oropharyngeal dysphagia (OD). AIM: To assess the therapeutic effect of stimulating oropharyngeal sensory afferents with TRPV1, TRPA1, or TRPM8 agonists vs increasing bolus viscosity in older and neurologic patients with OD by comparing four studies of similar experimental design. METHODS: Swallow function of 142 older patients with impaired safety of swallow at nectar ([50-350] mPa·s) viscosity was evaluated with videofluoroscopy (VFS) while treated with TRPV1 (150 µmol/L), TRPV1/A1 (150 µmol/L and 1 mmol/L), or TRPM8 (1 mmol/L or 10 mmol/L) agonists or modified starch (MS) at spoon thick viscosity (>1750 mPa·s). RESULTS: TRPV1 stimulation with capsaicinoids reduced penetrations by 50%, pharyngeal residue by 80%, and LVC time by 24.38% and increased bolus velocity by 36.51%. TRPV1/A1 stimulation with piperine reduced penetrations by 56.32%, LVC time by 25.55% and increased bolus velocity by 23.63%. TRPM8 stimulation with menthol 1 mmol/L reduced penetrations by 37.5% while 10 mmol/L reduced LVC time by 18.44%. Thickeners reduced penetrations by 77.11%, but increased pharyngeal residue by 19.89%, delayed LVC by 41.73%, and reduced bolus velocity by 13.44%. CONCLUSION: Natural capsaicinoids have a stronger therapeutic effect on VFS signs and swallow response by stimulating TRPV1 than TRPV1/A1 or TRPM8 agonists. While TRP stimulants increased bolus velocity and reduced swallow response times, thickeners reduced bolus velocity and further delayed the swallow response. This study sets the bases to develop new pharmacologic strategies for older patients with OD, moving away from compensation toward the recovery of swallow function.

Videofluoroscopic assessment of the pathophysiology of chronic poststroke oropharyngeal dysphagia.

BACKGROUND AND PURPOSE: Oropharyngeal dysphagia (OD) is a major complaint following stroke, associated with poor clinical outcome and high mortality rates. We aimed at characterizing the kinematics of swallow response associated with unsafe swallowing in chronic poststroke patients with OD. PATIENTS AND METHODS: Consecutive poststroke patients with a positive volume-viscosity swallow test for OD 3 months following stroke were studied by videofluoroscopy (VFS). Demographical and clinical factors and kinematics of swallow response were compared between those poststroke patients with safe swallow (penetration-aspiration scale, PAS≤2) and those with unsafe swallow (PAS≥3). Receiver operating characteristic (ROC) curves were drawn for laryngeal vestibule closure (LVC) time which predicts unsafe swallow. RESULTS: We studied 73 poststroke patients (76.7±9.3 years, 53.4% male) by VFS (60.4% with impaired safety, PAS=4.47±1.44, and 95.9% with impaired efficacy of swallow). Poststroke patients with unsafe swallow presented a poorer functional (Rankin 2.2±1.6 vs 1.2±1.0, P<.012) and nutritional status (MNA-sf≤11, 34.2% vs 7.4%, P<.05) than poststroke patients with safe swallow. Poststroke patients with unsafe swallow presented a significant delay in LVC time (406.4±99.5 ms vs 318.9±80.4 ms; P<.05) and weaker tongue bolus propulsion forces (0.771±0.450 mJ vs 1.638±3.212 mJ; P=.043). LVC time ≥340 ms predicts unsafe swallow in chronic poststroke patients with a diagnostic accuracy of 0.78. CONCLUSIONS: Impaired safety of swallow in chronic poststroke patients is caused by specific impairments in swallow response including delayed timing of airway protection mechanisms and weak tongue propulsion forces. Treatments aiming to restore swallowing function in poststroke patients with OD should be targeted to improve these critical biomechanical events.

A Comparative Study Between Modified Starch and Xanthan Gum Thickeners in Post-Stroke Oropharyngeal Dysphagia.

Thickeners are used in post-stroke oropharyngeal dysphagia (OD) as a compensatory therapeutic strategy against aspirations. To compare the therapeutic effects of modified starch (MS) and xanthan gum (XG) thickeners on swallow safety and efficacy in chronic post-stroke OD patients using clinical and videofluoroscopic (VFS) assessment. Patients were studied by clinical assessment (volume-viscosity swallow test, V-VST) and VFS using 3 volumes (5, 10, 20 mL) and 3 viscosities (liquid, nectar and spoon thick), comparing MS and XG. We studied 122 patients (46MS, 76XG). (A) V-VST showed that both thickeners similarly improved safety of swallow. Prevalence of safe swallowing significantly increased with enhanced viscosity (P < 0.001 vs liquid), MS: 47.83 % at liquid, 84.93 % at nectar and 92.96 % at spoon thick; XG: 55.31 % at liquid, 77.78 % at nectar and 97.84 % at spoon thick. Patients on MS reported higher prevalence of pharyngeal residue at spoon-thick viscosities. (B) VFS: increasing bolus viscosity with either thickener increased prevalence of safe swallows (P < 0.001 vs liquid), MS: 30.25 % liquid, 61.07 % nectar and 92.64 % spoon thick; XG: 29.12 % liquid, 71.30 % nectar and 89.91 % spoon thick. Penetration-aspiration scale score was significantly reduced with increased viscosity with both thickeners. MS increased oral and pharyngeal residues at nectar and spoon-thick viscosities but XG did not. Timing of airway protection mechanisms and bolus velocity were not affected by either thickener. Increasing bolus viscosity with MS and XG thickeners strongly and similarly improved safety of swallow in chronic post-stroke OD by a compensatory mechanism; in contrast only MS thickeners increased oropharyngeal residue.

Sensitivity and specificity of the Eating Assessment Tool and the Volume-Viscosity Swallow Test for clinical evaluation of oropharyngeal dysphagia.

BACKGROUND: Oropharyngeal dysphagia (OD) is an underdiagnosed digestive disorder that causes severe nutritional and respiratory complications. Our aim was to determine the accuracy of the Eating Assessment Tool (EAT-10) and the Volume-Viscosity Swallow Test (V-VST) for clinical evaluation of OD. METHODS: We studied 120 patients with swallowing difficulties and 14 healthy subjects. OD was evaluated by the 10-item screening questionnaire EAT-10 and the bedside method V-VST, videofluoroscopy (VFS) being the reference standard. The V-VST is an effort test that uses boluses of different volumes and viscosities to identify clinical signs of impaired efficacy (impaired labial seal, piecemeal deglutition, and residue) and impaired safety of swallow (cough, voice changes, and oxygen desaturation ≥3%). Discriminating ability was assessed by the AUC of the ROC curve and sensitivity and specificity values. KEY RESULTS: According to VFS, prevalence of OD was 87%, 75.6% with impaired efficacy and 80.9% with impaired safety of swallow including 17.6% aspirations. The EAT-10 showed a ROC AUC of 0.89 for OD with an optimal cut-off at 2 (0.89 sensitivity and 0.82 specificity). The V-VST showed 0.94 sensitivity and 0.88 specificity for OD, 0.79 sensitivity and 0.75 specificity for impaired efficacy, 0.87 sensitivity and 0.81 specificity for impaired safety, and 0.91 sensitivity and 0.28 specificity for aspirations. CONCLUSIONS & INFERENCES: Clinical methods for screening (EAT-10) and assessment (V-VST) of OD offer excellent psychometric proprieties that allow adequate management of OD. Their universal application among at-risk populations will improve the identification of patients with OD at risk for malnutrition and aspiration pneumonia.

The effects of a xanthan gum-based thickener on the swallowing function of patients with dysphagia.

BACKGROUND: Increasing bolus viscosity of thin liquids is a basic therapeutic strategy to protect patients with oropharyngeal dysphagia (OD) from aspiration. However, conventional starch thickeners increase post-deglutitive residue. AIM: To assess the therapeutic effect of a new xanthan gum-based thickener, Resource ThickenUp Clear (Nestlé Health Science, Vevey, Switzerland) on patients with oropharyngeal dysphagia. METHODS: We studied the effect of Resource ThickenUp Clear using a clinical method and videofluoroscopy on 120 patients with oropharyngeal dysphagia (66 with stroke, 41 older and 13 with neurodegenerative diseases) and 14 healthy volunteers while swallowing thin-liquid, nectar-like and spoon-thick boluses. We assessed the prevalence of signs of impaired safety and efficacy of swallow and the physiology of the swallow response. RESULTS: Increasing bolus viscosity with Resource ThickenUp Clear: (i) improved safety of swallow demonstrated by a reduction in the prevalence of cough and voice changes in the clinical study and penetrations and aspirations during video fluoroscopy. Prevalence of aspirations was 12.7% with thin liquid, 7.7% with nectar-like (P < 0.01) and 3.4% with spoon-thick (P < 0.01) viscosities. Penetration-Aspiration Scale was reduced from 3.24 ± 0.18 at thin liquid to 2.20 ± 0.18 at nectar-like (P < 0.001) and to 1.53 ± 0.13 at spoon-thick (P < 0.001) viscosities; (ii) did not enhance pharyngeal residue; (iii) nectar-like viscosity did not affect bolus velocity nor timing of swallow response and (iv) spoon-thick viscosity reduced bolus velocity. CONCLUSIONS: Resource ThickenUp Clear improves the safety of swallow without increasing residue providing a viscosity-dependent therapeutic effect for patients with oropharyngeal dysphagia. At nectar viscosity, the effect is due to intrinsic texture properties, spoon-thick viscosity adding changes in swallow physiology. NCT01158313.

Effect of surface sensory and motor electrical stimulation on chronic poststroke oropharyngeal dysfunction.

BACKGROUND: Chronic poststroke oropharyngeal dysfunction (OD) is a common condition, leading to severe complications, including death. Treatments for chronic poststroke OD are scarce. The aim of our study was to assess and compare the efficacy and safety of treatment with surface electrical stimulation (e-stim) at sensory and motor intensities in patients with chronic poststroke OD. METHODS: Twenty chronic poststroke patients with OD were randomly assigned to (i) sensory e-stim (treatment intensity: 75% of motor threshold) or (ii) motor e-stim (treatment intensity: motor threshold). Patients were treated during 10 days, 1 h/day. Videofluoroscopy was performed at the beginning and end of the study to assess signs of impaired efficacy and safety of swallow and timing of swallow response. KEY RESULTS: Patients presented advanced age (74.95 ± 2.18), 75% were men. The mean days poststroke was 336.26 ± 89.6. After sensory stimulation, the number of unsafe swallows was reduced by 66.7% (p < 0.001), the laryngeal vestibule closure time by 22.94% (p = 0.027) and maximal vertical hyoid extension time by 18.6% (p = 0.036). After motor stimulation, the number of unsafe swallows was reduced by 62.5% (p = 0.002), the laryngeal vestibule closure time by 38.26% (p = 0.009) and maximal vertical hyoid extension time by 24.8% (p = 0.008). Moreover, the motor stimulus reduced the pharyngeal residue by 66.7% (p = 0.002), the upper esophageal sphincter opening time by 39.39% (p = 0.009), and increased bolus propulsion force by 211.1% (p = 0.008). No serious adverse events were detected during the treatment. CONCLUSIONS & INFERENCES: Surface e-stim is a safe and effective treatment for chronic poststroke dysphagic patients.

Pathophysiology of oropharyngeal dysphagia in the frail elderly.

BACKGROUND: Oropharyngeal dysphagia is a major complaint among the elderly. Our aim was to assess the pathophysiology of oropharyngeal dysphagia in frail elderly patients (FEP). METHODS: A total of 45 FEP (81.5 +/- 1.1 years) with oropharyngeal dysphagia and 12 healthy volunteers (HV, 40 +/- 2.4 years) were studied using videofluoroscopy. Each subject's clinical records, signs of safety and efficacy of swallow, timing of swallow response, hyoid motion and tongue bolus propulsion forces were assessed. KEY RESULTS: Healthy volunteers presented a safe and efficacious swallow, faster laryngeal closure (0.157 +/- 0.013 s) upper esophageal sphincter opening (0.200 +/- 0.011 s), and maximal vertical hyoid motion (0.310 +/- 0.048 s), and stronger tongue propulsion forces (22.16 +/- 2.54 mN) than FEP. By contrast, 63.63% of FEP presented oropharyngeal residue, 57.10%, laryngeal penetration and 17.14%, tracheobronchial aspiration. Frail elderly patients with impaired swallow safety showed delayed laryngeal vestibule (LV) closure (0.476 +/- 0.047 s), similar bolus propulsion forces, poor functional capacity and higher 1-year mortality rates (51.7%vs 13.3%, P = 0.021) than FEP with safe swallow. Frail elderly patients with oropharyngeal residue showed impaired tongue propulsion (9.00 +/- 0.10 mN), delayed maximal vertical hyoid motion (0.612 +/- 0.071 s) and higher (56.0%vs 15.8%, P = 0.012) 1-year mortality rates than those with efficient swallow. CONCLUSION & INFERENCES: Frail elderly patients with oropharyngeal dysphagia presented poor outcome and high mortality rates. Impaired safety of deglutition and aspirations are mainly caused by delayed LV closure. Impaired efficacy and residue are mainly related to weak tongue bolus propulsion forces and slow hyoid motion. Treatment of dysphagia in FEP should be targeted to improve these critical events.

The effect of bolus viscosity on swallowing function in neurogenic dysphagia.

AIM: To assess the pathophysiology and treatment of neurogenic dysphagia. METHODS: 46 patients with brain damage, 46 with neurodegenerative diseases and eight healthy volunteers were studied by videofluoroscopy while swallowing 3-20 mL liquid (20.4 mPa s), nectar (274.4 mPa s) and pudding (3931.2 mPa s) boluses. RESULTS: Volunteers presented a safe and efficacious swallow, short swallow response (< or =740 ms), fast laryngeal closure (< or =160 ms) and strong bolus propulsion (> or =0.33 mJ). Brain damage patients presented: (i) 21.6% aspiration of liquids, reduced by nectar (10.5%) and pudding (5.3%) viscosity (P < 0.05) and (ii) 39.5% oropharyngeal residue. Neurodegenerative patients presented: (i) 16.2% aspiration of liquids, reduced by nectar (8.3%) and pudding (2.9%) viscosity (P < 0.05) and (ii) 44.4% oropharyngeal residue. Both group of patients presented prolonged swallow response (> or =806 ms) with a delay in laryngeal closure (> or =245 ms), and weak bolus propulsion forces (< or =0.20 mJ). Increasing viscosity did not affect timing of swallow response or bolus kinetic energy. CONCLUSIONS: Patients with neurogenic dysphagia presented high prevalence of videofluoroscopic signs of impaired safety and efficacy of swallow, and were at high risk of respiratory and nutritional complications. Impaired safety is associated with slow oropharyngeal reconfiguration and impaired efficacy with low bolus propulsion. Increasing bolus viscosity greatly improves swallowing function in neurological patients.