The Impact of Periventricular Leukoaraiosis in Post-stroke Oropharyngeal Dysphagia: A Swallowing Biomechanics and MRI-Based Study.

Oropharyngeal dysphagia is a highly prevalent post-stroke complication commonly associated with topographically specific gray-matter damage. In contrast, the role of damage to the extensive white matter brain network (leukoaraiosis) in post-stroke oropharyngeal dysphagia has not yet been clarified. We aim to assess the role of leukoaraiosis in post-stroke oropharyngeal dysphagia. We designed a cross-sectional study and retrospectively collected from our database patients with dysphagia affected by a recent stroke and on whom both a brain 1.5 T-MRI and a videofluoroscopy had been performed. Leukoaraiosis was assessed in brainstem and in cerebral regions (periventricular or deep) with Fazekas scale. Penetration-Aspiration-Scale and time to laryngeal vestibule closure and to upper esophageal sphincter opening were analyzed. Study population (n = 121; 57% men, 75.5 ± 9.4y) presented mostly supratentorial ischemic PACI-type strokes. Of the patients, 86% had unsafe swallows (PAS = 3.97 ± 2.04); 94.2% had cerebral leukoaraiosis (Fazekas = 3.36 ± 1.7) and 42.1% had brainstem-leukoaraiosis, hypertension being the main risk factor. We found both significant positive associations between degree of periventricular-leukoaraiosis and total-leukoaraiosis and presence of risk of aspirations (p = 0.016 and p = 0.023, respectively); and a correlation between periventricular-leukoaraiosis and PAS scale severity (r = 0.179, p = 0.049). No correlations/associations were found between stroke volume and dysphagia in this study. Our study supports a role for leukoaraiosis in the pathophysiology of dysphagia. Stroke is associated with chronic short-connection/circuit injury and damage to periventricular white matter long connections is a relevant neuro-pathophysiological mechanism contributing to impaired safety of swallow in post-stroke oropharyngeal dysphagia patients.

A Comparative Study Between Two Sensory Stimulation Strategies After Two Weeks Treatment on Older Patients with Oropharyngeal Dysphagia.

Oropharyngeal dysphagia (OD) is a prevalent geriatric syndrome. Treatment is based on compensatory strategies to avoid complications. New treatments based on sensory stimulation to promote the recovery of the swallowing function have proved effective in acute studies but prolonged treatment needs further research. Our aim was to evaluate and compare the effect of two, longer-term sensory treatment strategies on older patients with OD. 38 older patients (≥70 years) were studied with videofluoroscopy (pre/posttreatment) and randomized into two 10-day treatment groups: Group A-transient receptor potential vanilloid 1 (TRPV1) agonist (capsaicin 1 × 10(-5) M) and Group B-transcutaneous sensory electrical stimulation (TSES) (Intelect VitalStim, biphasic pulses, 300 µs, 80 Hz). Patients were analyzed for treatment response. Patients were old (80.47 ± 5.2 years), with comorbidities (3.11 ± 1.59 Charlson Index), polymedication (8.92 ± 3.31 drugs/patient), and mild functional impairment (86.84 ± 17.84 Barthel Index), and 28.9 % were at risk of malnutrition (MNA-sf). Overall, all patients had videofluoroscopic signs of impaired safety of swallow (ISS) with delayed oropharyngeal swallow response (OSR). After sensory stimulation, prevalence of ISS decreased to 68.42 % in both groups (P = 0.019). There were 68.42 % responders in Group A (TRPV1) and 42.11 % in Group B (TSES). Group A responders showed an improvement in the penetration-aspiration scale (PAS, 5.23 ± 2.04 to 3 ± 1.47; P = 0.002), and the same was true for those of Group B (4.63 ± 1.41 to 2.13 ± 0.64; P = 0.007). 10-day sensory stimulation with either therapy improved safety of swallow and OSR in older patients with OD, reducing the severity of OD in a significant subgroup of these patients.

Natural capsaicinoids improve swallow response in older patients with oropharyngeal dysphagia.

OBJECTIVE: There is no pharmacological treatment for oropharyngeal dysphagia (OD). The aim of this study was to compare the therapeutic effect of stimulation of oropharyngeal transient receptor potential vanilloid type 1 (TRPV1) with that of thickeners in older patients with OD. DESIGN: A clinical videofluoroscopic non-randomised study was performed to assess the signs of safety and efficacy of swallow and the swallow response in (1) 33 patients with OD (75.94 ± 1.88 years) while swallowing 5, 10 and 20 ml of liquid (20.4 mPa.s), nectar (274.4 mPa.s), and pudding (3930 mPa.s) boluses; (2) 33 patients with OD (73.94 ± 2.23 years) while swallowing 5, 10 and 20 ml nectar boluses, and two series of nectar boluses with 150 µM capsaicinoids and (3) 8 older controls (76.88 ± 1.51 years) while swallowing 5, 10 and 20 ml nectar boluses. RESULTS: Increasing bolus viscosity reduced the prevalence of laryngeal penetrations by 72.03% (p < 0.05), increased pharyngeal residue by 41.37% (p < 0.05), delayed the upper esophageal sphincter opening time and the larynx movement and did not affect the laryngeal vestibule closure time and maximal hyoid displacement. Treatment with capsaicinoids reduced both, penetrations by 50.% (p < 0.05) and pharyngeal residue by 50.% (p < 0.05), and shortened the time of laryngeal vestibule closure (p < 0.001), upper esophageal sphincter opening (p < 0.05) and maximal hyoid and laryngeal displacement. CONCLUSION: Stimulation of TRPV1 by capsaicinoids strongly improved safety and efficacy of swallow and shortened the swallow response in older patients with OD. Stimulation of TRPV1 might become a pharmacologic strategy to treat OD.

Oropharyngeal dysphagia is a risk factor for community-acquired pneumonia in the elderly.

The aim of this study was to explore whether oropharyngeal dysphagia is a risk factor for community-acquired pneumonia (CAP) in the elderly and to assess the physiology of deglutition of patients with pneumonia. In the case-control study, 36 elderly patients (aged ≥ 70 years) hospitalised with pneumonia were matched by age and sex with two independently living controls. All subjects were given the volume-viscosity swallow test to identify signs of oropharyngeal dysphagia. In the pathophysiological study, all cases and 10 healthy elderly subjects were examined using videofluoroscopy. Prevalence of oropharyngeal dysphagia in the case-control study was 91.7% in cases and 40.3% in controls (p<0.001). Adjusting for functionality and comorbidities, dysphagia showed an independent effect on pneumonia (OR 11.9, 95% CI 3.03-46.9). Among cases in the pathophysiological study, 16.7% showed safe swallow, 30.6% high penetrations, 36.1% severe penetrations and 16.7% silent aspirations during videofluoroscopy, while in the healthy elderly subjects these percentages were 80%, 20%, 0% and 0%, respectively (p<0.001). A delay in closure of the laryngeal vestibule (0.414 ± 0.029 s versus 0.200 ± 0.059 s, p<0.01) was the main mechanism of impaired airway protection. In elderly subjects, oropharyngeal dysphagia is strongly associated with CAP, independently of functionality and comorbidities. Elderly patients with pneumonia presented a severe impairment of swallow and airway protection mechanisms. We recommend universal screening of dysphagia in older persons with pneumonia.

Shear-Viscosity-Dependent Effect of a Gum-Based Thickening Product on the Safety of Swallowing in Older Patients with Severe Oropharyngeal Dysphagia.

Fluid thickening is a valid therapeutic strategy for patients with oropharyngeal dysphagia (OD). The main aim of this study was to determine the therapeutic effect of the xanthan-gum-based thickener Tsururinko Quickly (TQ, Morinaga Milk Co., Tokyo, Japan) in older patients with severe OD. A total of 85 patients (83.32 ± 6.75 y) with OD and a penetration-aspiration score (PAS) of n ≥ 3 were studied by videofluoroscopy while swallowing duplicate 10 mL boluses at <50 mPa·s, 100, 200, 400, 800, and 1600 mPa·s, to assess the safety and efficacy of swallowing and the biomechanics of a swallowing response at each viscosity level. At <50 mPa·s, only 16.25% patients swallowed safely, 45% had penetrations (PAS 3-5), and 38.75% had aspirations (PAS 6-8). Fluid thickening with TQ greatly increased the prevalence of patients with safe swallowing from 62.90% at 100 mPa·s to 95.24% at 1600 mPa·s in a shear-viscosity-dependent manner. The penetrations and aspirations were significantly reduced to 3.60% and 1.19%, respectively, at 1600 mPa·s. The threshold viscosity was 100 mPa·s and the increasing viscosity above 800 mPa·s did not further improve the therapeutic effect significantly. Increasing the shear viscosity significantly reduced the time to laryngeal vestibule closure (-16.70%), increased the time to upper oesophageal sphincter opening (+26.88%), and reduced the pharyngeal bolus velocity (-31.62%) without affecting the pharyngeal residue. TQ has a strong shear-viscosity-dependent effect on the safety of swallowing in older patients with severe OD without increasing the pharyngeal residue. The therapeutic range for TQ is 100-800 mPa·s, with 200 and 800 mPa·s being the optimal doses to cover the needs of older patients with OD.

COVID-19 is associated with oropharyngeal dysphagia and malnutrition in hospitalized patients during the spring 2020 wave of the pandemic.

BACKGROUND & AIMS: Prevalence and complications of oropharyngeal dysphagia (OD) and malnutrition (MN) in COVID-19 patients is unknown. Our aim was to assess the prevalence, risk factors and clinical outcomes of OD and MN in a general hospital during the first wave of the COVID-19 pandemic. METHODS: This was a prospective, observational study involving clinical assessment of OD (Volume-Viscosity Swallowing Test), and nutritional screening (NRS2002) and assessment (GLIM criteria) in COVID-19 patients hospitalized in general wards at the Consorci Sanitari del Maresme, Catalonia, Spain. The clinical characteristics and outcomes of patients were assessed at pre-admission, admission and discharge, and after 3 and 6-months follow-up. RESULTS: We included 205 consecutive patients (69.28 ± 17.52 years, Charlson 3.74 ± 2.62, mean hospital stay 16.8 ± 13.0 days). At admission, Barthel Index was 81.3 ± 30.3; BMI 28.5 ± 5.4 kg/m2; OD prevalence 51.7% (44.1% impaired safety of swallow); and 45.5% developed MN with a mean weight loss of 10.1 ± 5.0 kg during hospitalization. OD was an independent risk factor for MN during hospitalization (OR 3.96 [1.45-10.75]), and hospitalization was prolonged in patients with MN compared with those without (21.9 ± 14.8 vs 11.9 ± 8.9 days, respectively; p < 0.0001). OD was independently associated with comorbidities, neurological symptoms, and low functionality. At 6-month follow-up, prevalence of OD was still 23.3% and that of MN only 7.1%. Patients with OD at discharge showed reduced 6-month survival than those without OD at discharge (71.6% vs 92.9%, p < 0.001); in contrast, those with MN at discharge did not show 6-month survival differences compared to those without (85.4% vs 83.8%, p = 0.8). CONCLUSIONS: Prevalence and burden of OD and MN in patients hospitalized in COVID-19 wards is very high. Our results suggest that optimizing the management of MN might shorten the hospitalization period but optimizing the management of OD will likely impact the nutritional status of COVID-19 patients and improve their clinical outcomes and survival after hospital discharge. CLINICALTRIALS: gov Identifier: NCT04346212.

Effect of Transcutaneous Electrical Stimulation in Chronic Poststroke Patients with Oropharyngeal Dysphagia: 1-Year Results of a Randomized Controlled Trial.

Background. Chronic poststroke oropharyngeal dysphagia (CPSOD) is associated with impaired oropharyngeal sensory/motor function. We aimed to assess effect of sensory (SES) and motor (NMES) transcutaneous electrical stimulation (TES) on safety of swallow and clinical outcomes in patients with CPSOD in a one-year follow-up randomized controlled trial. Methods. Ninety patients (74.1 ± 11.5 y, modified Rankin score 2.6 ± 1.7) with CPSOD and impaired safety of swallow were randomized to (a) compensatory treatment (CT), (b) CT + SES, and (c) CT + NMES. Patients were treated with up to two cycles (6 months apart) of 15 × 1 hour TES sessions over two weeks and followed up with 4-5 clinical and videofluoroscopic assessments during one year. Key results. Baseline penetration-aspiration scale (PAS) was 4.61 ± 1.75, delayed time to laryngeal vestibule closure (LVC) 396.4 ± 108.7 ms, and impaired efficacy signs 94.25%. Swallowing parameters significantly improved between baseline and 1-year follow-up in SES and NMES groups for prevalence of patients with a safe swallow (P < .001), mean PAS (P < .001), time to LVC (P < .01), and need for thickening agents (P < .001). Patients in the CT presented a less intense improvement of signs of impaired safety of swallow without significant changes in time to LVC. No differences between groups were observed for 1-year mortality (6.1%), respiratory infections (9.6%), nutritional and functional status, QoL, and hospital readmission rates (27.6%). No significant adverse events related to TES were observed. Conclusions and inferences. Transcutaneous electrical stimulation is a safe and effective therapy for older patients with CPSOD. After 1-year follow-up, TES greatly improved the safety of swallow and reduced the need for fluid thickening in these patients.

Assessment of Swallowing Disorders, Nutritional and Hydration Status, and Oral Hygiene in Students with Severe Neurological Disabilities Including Cerebral Palsy.

BACKGROUND: Special needs schools (SNS) educate children and young people with major neurological disabilities who are at high risk of oropharyngeal dysphagia (OD) and malnutrition (MN). We aimed to assess the prevalence of OD, MN, dehydration (DH), and oral health (OH) in students at an SNS. METHODS: A cross-sectional observational study was conducted at SNS L'Arboç, Catalonia, Spain. We assessed (a) demographics, health status, comorbidities, and gross motor function classification system (GMFCS), (b) swallowing function, oral-motor evaluation, masticatory capacity, and EDACS classification for eating and drinking abilities, (c) nutritional and DH status (anthropometry, bioimpedance and dietary records), and (d) OH (Oral Hygiene Index Simplified). RESULTS: A total of 33 students (mean age 13.3 years; 39.4% level V of GMFCS) were included. Main diagnosis was cerebral palsy at 57.6%. All students presented OD, 90.6% had impaired safety, 68.7% were at levels II-III of EDACS, and 31.3% required PEG; furthermore, 89.3% had chronic MN, 21.4% had acute MN, 70% presented intracellular DH, and 83.9% presented impaired OH. CONCLUSION: MN, DH, OD, and poor OH are highly prevalent conditions in students with cerebral palsy and other neurological disabilities and must be specifically managed through nutritional and educational strategies. The multidisciplinary team at SNS should include healthcare professionals specifically trained in these conditions.

A Systematic and a Scoping Review on the Psychometrics and Clinical Utility of the Volume-Viscosity Swallow Test (V-VST) in the Clinical Screening and Assessment of Oropharyngeal Dysphagia.

(1) Background: The volume-viscosity swallow test (V-VST) is a clinical tool for screening and diagnosis of oropharyngeal dysphagia (OD). Our aims were to examine the clinical utility of the V-VST against videofluoroscopy (VFS) or fiberoptic endoscopic evaluation of swallow (FEES) and to map the V-VST usage with patients at risk of OD across the years since it was described for the first time, carrying a systematic and a scoping review. (2) Methods: We performed both a systematic review (SR) including studies that look at the diagnostic test accuracy, and a scoping review (ScR) with articles published from September 2008 to May 2020. Searches were done in different databases, including PubMed and EMBASE from September 2008 until May 2020, and no language restrictions were applied. A meta-analysis was done in the SR to assess the psychometric properties of the V-VST. Quality of studies was assessed by Dutch Cochrane, QUADAS, GRADE (SR), and STROBE (ScR) criteria. The SR protocol was registered on PROSPERO (registration: CRD42020136252). (3) Results: For the diagnostic accuracy SR: four studies were included. V-VST had a diagnostic sensitivity for OD of 93.17%, 81.39% specificity, and an inter-rater reliability Kappa = 0.77. Likelihood ratios (LHR) for OD were 0.08 (LHR-) and 5.01 (LHR+), and the diagnostic odds ratio for OD was 51.18. Quality of studies in SR was graded as high with low risk of bias. In the ScR: 34 studies were retrieved. They indicated that V-VST has been used internationally to assess OD's prevalence and complications. (4) Conclusions: The V-VST has strong psychometric properties and valid endpoints for OD in different phenotypes of patients. Our results support its utility in the screening and clinical diagnosis and management of OD.

Pathophysiology of Swallowing Dysfunction in Parkinson Disease and Lack of Dopaminergic Impact on the Swallow Function and on the Effect of Thickening Agents.

(1) Background: The effect of dopaminergic treatment on swallowing response in patients with Parkinson's disease (PD) suffering oropharyngeal dysphagia (OD) is not understood. Aim: To characterize OD pathophysiology in PD and to assess whether dopaminergic states affect swallow function and the effect of thickeners. (2) Methods: Fifty patients with PD (40 evaluated in OFF/ON states) and 12 healthy volunteers (HVs) were evaluated with videofluoroscopy (VFS) to assess the swallowing biomechanics and kinematics of the swallowing response at three different shear-viscosities (<50, 120, and 4000 mPa·s); (3) Results: Patients presented a mean age of 70.46 ± 10.03 years. Disease evolution was 5.09 ± 3.86 year and Hoehn-Yahr stage was 2.32 ± 0.81. For HVs, mean age was 40.20 ± 2.50 year. Penetrations were present in 37.50% of PD patients and were associated with delayed laryngeal vestibule closure (LVC = 293.33 ± 90.07 ms). In contrast, HVs presented a LVC = 164.00 ± 39.78 ms (p < 0.05). An LVC ≥ 260 ms cutoff predicted unsafe swallow (sensitivity ≥ 0.83, specificity ≥ 0.57, AUC = 0.80) in PD. Increasing bolus viscosity improved deglutition safety but increased oropharyngeal residue. There were no differences in swallowing between the OFF/ON states. (4) Conclusions: In initial PD stages, oropharyngeal swallow response is severely delayed, while mildly impaired swallow safety improves with increasing bolus viscosity, which increases residue. Dopaminergic treatment does not affect swallowing or the therapeutic effect of thickeners.

Short-term neurophysiological effects of sensory pathway neurorehabilitation strategies on chronic poststroke oropharyngeal dysphagia.

BACKGROUND: Neurorehabilitation strategies for chronic poststroke (PS) oropharyngeal dysphagia (OD) have been mainly focused on the neurostimulation of the pharyngeal motor cortex with only marginal effects. In contrast, treatments targeting the PS oropharyngeal sensory pathway dysfunction offer very promising results, but there is little knowledge on the underlying mechanisms. We aimed to explore the neurophysiological mechanisms behind the effect of three sensory neurostimulation strategies. METHODS: We carried out a randomized two-blinded parallel group's crossover sham-controlled clinical trial in 36 patients with unilateral stroke and chronic unsafe swallow to investigate the effect of repetitive transcranial magnetic stimulation (rTMS) of the primary sensory cortex (A), oral capsaicin (B) and intra-pharyngeal electrical stimulation (IPES; C). The effect was evaluated immediately after the interventions with videofluoroscopy (VFS) and motor/sensory evoked potentials (MEP/SEP). KEY RESULTS: Interventions induced no changes in the biomechanics of the swallow response during VFS. However, an enhancement of motor cortex excitability (latency shortening and increased size of thenar MEP) was found with active interventions (A + B + C, and B/C alone; P < .05 for all) but not with sham. Active but not sham interventions shortened pharyngeal SEP latency in the ipsilesional hemisphere (A + B + C: P2-peak, P = .039; A: N2-peak, P = .034) and antagonized the physiological habituation in pharyngeal MEP (A + B + C and A alone, P < .05 for both). CONCLUSIONS AND INFERENCES: Sensory pathway neurostimulation strategies caused immediate enhancement of motor cortex excitability with peripheral strategies (capsaicin and IPES) and of pharyngeal sensory conduction with rTMS. These changes support the use of sensory neurorehabilitation strategies in promoting swallow recovery in chronic PS-OD.

Therapeutic Effect, Rheological Properties and α-Amylase Resistance of a New Mixed Starch and Xanthan Gum Thickener on Four Different Phenotypes of Patients with Oropharyngeal Dysphagia.

Thickened fluids are a therapeutic strategy for oropharyngeal dysphagia (OD). However, its therapeutic effect among different phenotypes of OD patients has not yet been compared. We aimed to assess the therapeutic effect and α-amylase resistance of a mixed gum/starch thickener [Fresubin Clear Thickener® (FCT)] on four phenotypes of OD patients: G1) 36 older; G2) 31 head/neck cancer (HNC); G3) 30 Parkinson's disease; and G4) 31 chronic post-stroke. Therapeutic effect of FCT was assessed during videofluoroscopy using the Penetration-Aspiration Scale (PAS), for 5/20 mL boluses, at four levels of shear-viscosity (<50, 250, 1000 and 2000 mPa·s). The effect of α-amylase was assessed after 30 s of oral incubation. Patients had high prevalence of VFS signs of impaired efficacy (98.44%) and safety (70.31%) of swallow with a severe PAS score (4.44 ± 0.20). Most severe OD was in HNC (80.6% unsafe swallows). FCT showed a strong therapeutic effect on the safety of swallow at a range between 250-1000 mPa·s (74.19-96.67%, safe swallows in G1, G3, G4, and 58.06% in G2), without increasing pharyngeal residue. Viscosity was unaffected by α-amylase. Increasing shear-viscosity with FCT causes a strong viscosity-dependent therapeutic effect on the safety of swallow. This effect depends on the phenotype and is similar among older, Parkinson's and post-stroke patients.

Neurophysiological and Biomechanical Evaluation of the Mechanisms Which Impair Safety of Swallow in Chronic Post-stroke Patients.

Oropharyngeal dysphagia (OD) is a common post-stroke complication and is associated with respiratory infections. The aim was to assess the biomechanical impairments in swallow function and the afferent and efferent swallowing pathways impairing swallow safety in chronic post-stroke patients. We studied 30 patients with unilateral stroke and chronic OD (> 3 months from stroke onset) with impaired safety of swallow (Penetration-Aspiration Scale [PAS] ≥ 2). We evaluated the efficacy, safety, and kinematics of the swallow response (residue, PAS, laryngeal vestibule closure time [LVCT]) with videofluoroscopy, sensory evoked potentials to pharyngeal electrical stimulation (pSEP), and pharyngeal motor evoked potentials (pMEP) to transcranial magnetic stimulation of both hemispheres. Mean age of patients was 70.1 ± 10.9 years (7 women). Stroke severity at onset was moderate (NIHSS median 10 [IQ range 3-11.5]), and modified Rankin Scale 2.8 ± 1.3. Mean PAS was 5.1 ± 1.9; prevalence of delayed LVCT was 86.7% and 30% presented aspirations. Pharyngeal hypoesthesia was present in 46.7% of patients and 92.3% showed abnormally asymmetrical pSEPs when comparing the ipsilesional with the contralesional hemisphere. Increased duration of swallow was associated with lower pSEP amplitude (P1-N2) in the contralesional hemisphere (p = 0.033). Patients with right hemispheric strokes showed greater reduction of pSEPs amplitude (N1-P1, p = 0.049). In contrast, pharyngeal resting motor threshold and pMEPs were symmetric in 73.3% patients without the physiologic hemispheric dominance. Mild-to-moderate disabled chronic post-stroke patients with OD presented severe impaired biomechanics of swallow response and high prevalence of aspirations. Initial results from the neurophysiological evaluation demonstrated prevalent impairments with disrupted integration of pharyngeal sensory inputs and reduced cortical excitability of efferent pathways. Patients with right hemispheric strokes showed poorer neurophysiological responses.

A randomized clinical trial on the acute therapeutic effect of TRPA1 and TRPM8 agonists in patients with oropharyngeal dysphagia.

BACKGROUND: Oropharyngeal dysphagia (OD) treatment is moving away from compensatory strategies toward active treatments that improve swallowing function. The aim of this study was to assess the acute therapeutic effect of TRPA1/M8 agonists in improving swallowing function in OD patients. METHODS: Fifty-eight patients with OD caused by aging, stroke, or neurodegenerative disease were included in a three-arm, quadruple-blind, randomized clinical trial (NCT02193438). Swallowing safety and efficacy and the kinematics of the swallow response were assessed by videofluoroscopy (VFS) during the swallow of 182 ± 2 mPa·s viscosity (nectar) boluses of a xanthan gum thickener supplemented with (a) 756.6 µmol/L cinnamaldehyde and 70 µmol/L zinc (CIN-Zn) (TRPA1 agonists), (b) 1.6 mmol/L citral (CIT) (TRPA1 agonist), or (c) 1.6 mmol/L citral and 1.3 mmol/L isopulegol (CIT-ISO) (TRPA1 and TRPM8 agonists). The effects on pharyngeal event-related potentials (ERP) were assessed by electroencephalography. KEY RESULTS: TRPA1 stimulation with either CIN-Zn or CIT reduced time to laryngeal vestibule closure (CIN-Zn P = .002, CIT P = .023) and upper esophageal sphincter opening (CIN-Zn P = .007, CIT P = .035). In addition, CIN-Zn reduced the penetration-aspiration scale score (P = .009), increased the prevalence of safe swallows (P = .041), and reduced the latency of the P2 peak of the ERP. CIT-ISO had no positive effect on biomechanics or neurophysiology. No significant adverse events were observed. CONCLUSIONS AND INFERENCES: TRPA1 stimulation with CIN-Zn or CIT improves the swallow response which, in the case of CIN-Zn, is associated with a significant improvement in cortical activation and safety of swallow. These results provide the basis for the development of new active treatments for OD using TRPA1 agonists.

Acute and subacute effects of oropharyngeal sensory stimulation with TRPV1 agonists in older patients with oropharyngeal dysphagia: a biomechanical and neurophysiological randomized pilot study.

BACKGROUND: Older people with oropharyngeal dysphagia (OD) present a decline in pharyngeal sensory function. The aim of this proof-of-concept study was to assess the biomechanical and neurophysiological effects of acute and subacute oropharyngeal sensory stimulation with transient receptor potential vanilloid 1 (TRPV1) agonists (capsaicinoids) in older patients with OD. METHODS: We studied the effect of a single dose versus multiple doses (2 weeks) of oral capsaicin treatment (10-5 M) or placebo in 28 older patients with OD (81.2 ± 4.6 years) using videofluoroscopy (penetration-aspiration scale [PAS], timing of swallow response) and electroencephalography (EEG) (latency and amplitude of pharyngeal event-related potential [ERP]). RESULTS: Acute stimulation by capsaicinoids 10-5 M did not improve swallow function and did not produce significant changes in pharyngeal ERP. In contrast, after 10 days of treatment, patients presented a clinically relevant and statistically significant reduction in the laryngeal vestibule closure (LVC) time (22.5%, p = 0.042), and in the PAS (24.2%, p = 0.038), compared with the placebo group. EEG results showed a reduction in the latency of the N1 peak (28.6%, p = 0.007) and an increase of the amplitude of the P1-N2 (59.4%, p = 0.038) and the N2-P2 (43.6%, p = 0.050) peaks. We observed a strong and significant correlation between the reduction in the latency of the N1 peak and change in LVC time after subacute treatment (r = 0.750, p = 0.003). CONCLUSIONS: After 2 weeks of treatment, oropharyngeal sensory stimulation with capsaicinoids induced cortical changes that were correlated with improvements in swallowing biomechanics in older patients with OD. These results further show that sensory stimulation by TRPV1 agonists can become a useful pharmacological treatment for older patients with OD.

Natural History of Swallow Function during the Three-Month Period after Stroke.

Oropharyngeal dysphagia is a prevalent complication following stroke (PS-OD), and one that is sometimes spontaneously recovered. This study describes the natural history of PS-OD between admission and three months post-stroke, and the factors associated with its prevalence and development. PS-OD was assessed with the volume-viscosity swallow test (V-VST) in all stroke patients on admission and at the three-month follow-up. We analyzed clinical, demographic, and neuroanatomical factors of 247 older post-stroke patients (National Institute of Health Stroke Scale (NIHSS) = 3.5 ± 3.8), comparing among those with PS-OD the ones with and without spontaneous recovery. PS-OD prevalence on admission was 39.7% (34.0% impaired safety; 30.8%, efficacy) and 41.7% (19.4% impaired safety; 39.3%, efficacy) at three months. Spontaneous swallow recovery occurred in 42.4% of patients with unsafe and in 29.9% with ineffective swallow, associated with younger age and optimal functional status. However, 26% of post-stroke patients developed new signs/symptoms of ineffective swallow related to poor functional, nutritional and health status, and institutionalization. PS-OD prevalence on admission and at the three-month follow-up was very high in the study population. PS-OD is a dynamic condition with some spontaneous recovery in patients with optimal functional status, but also new signs/symptoms can appear due to poor functionality. Regular PS-OD monitoring is needed to identify patients at risk of nutritional and respiratory complications.

Effect of a gum-based thickener on the safety of swallowing in patients with poststroke oropharyngeal dysphagia.

BACKGROUND: Increasing viscosity with thickening agents is a valid therapeutic strategy for oropharyngeal dysphagia (OD). To assess the therapeutic effect of a xanthan gum-based thickener (Nutilis Clear® ) at six viscosities compared with thin liquid in poststroke OD (PSOD) patients. METHODS: A total of 120 patients with PSOD were studied in this controlled, multiple-dose, fixed-order, and single-blind study using videofluoroscopy (VFSS). A series of boluses of 10 mL thin liquid and 2000, 1400, 800, 450, 250, and 150 mPa s viscosities were given in duplicate, interrupted in case of aspiration. We assessed the safety and efficacy of swallow and the kinematics of the swallow response. KEY RESULTS: A total of 41.2% patients had safe swallow at thin liquid which significantly increased for all viscosities from 71.9% at 150 mPa s to 95.6% at 1400 mPa s (P < .001). PAS score (3.7 ± 2.3) at thin liquid was also reduced by increasing bolus viscosity (P < .001). The prevalence of patients with aspiration at thin liquid was 17.5% and decreased at all viscosities (P < .01), except at 150 mPa s. Increasing viscosity shortened time to laryngeal vestibule closure (LVC) at all viscosities (P < .01) and reduced bolus velocity at ≥450 mPa s (P < .05). The prevalence of patients with pharyngeal residue at each viscosity 37.7%-44.7% was similar to that at thin liquid (41.2%). CONCLUSIONS AND INFERENCES: The prevalence of unsafe swallow with thin liquids is very high in PSOD. Increasing shear bolus viscosity with this xanthan gum-based thickener significantly increased the safety of swallow in patients with PSOD in a viscosity-dependent manner without increasing the prevalence of pharyngeal residue.

Pathophysiology of Oropharyngeal Dysphagia Assessed by Videofluoroscopy in Patients with Dementia Taking Antipsychotics.

OBJECTIVES: The objective of this study was to assess the pathophysiology of oropharyngeal dysphagia (OD) in patients with dementia, specifically in those taking antipsychotics (APs). DESIGN: A cross-sectional study was performed from January 2011 to May 2017 in a general hospital. SETTING AND PARTICIPANTS: We included 114 patients with dementia, of which 39 (34.2%) were taking APs (82.5 ± 7.8 years, Barthel Index 52.28 ± 30.42) and 29 patients without dementia (82.4 ± 6.7 years, Barthel Index 77.71 ± 24.7) and OD confirmed by a videofluoroscopy. MEASURES: Demographical and clinical factors as well as swallowing function of patients with dementia with OD were compared with older patients without dementia with OD. We also compared patients with dementia taking and not taking APs. Impaired efficacy during videofluoroscopy was defined as the presence of oral and/or pharyngeal residue, and impaired safety (unsafe swallow) was defined as aspiration or penetration. Receiver operating characteristic curves were drawn for laryngeal vestibule closure (LVC) time to predict unsafe swallow. RESULTS: 87.7% of patients with dementia presented impaired efficacy of swallow and 74.6% impaired safety [penetration-aspiration scale (PAS) 3.94 ± 1.94]. 86.2% of patients without dementia presented impaired efficacy and 44.8% impaired safety (PAS 2.21 ± 1.92). Time to LVC was significantly delayed in patients with dementia taking APs in comparison with patients without dementia (LVC 0.377 ± 0.093 vs 0.305 ± 0.026, P = .003). In contrast, there were no differences in the PAS and LVC time in patients with dementia taking and not taking APs (PAS 3.96 ± 0.26 vs 3.88 ± 0.22, LVC 0.398 ± 0.117 vs 0.376 ± 0.115, NS). LVC time ≥0.340 seconds predicted unsafe swallow in patients with dementia with an accuracy of 0.71. CONCLUSIONS/IMPLICATIONS: Patients with dementia presented high prevalence and severity of videofluoroscopy signs of impaired efficacy and safety of swallow and a more severe impairment in airway protection mechanisms (higher PAS and LVC delay). Clinical practice should implement specific protocols to prevent OD and its complications in these patients. AP treatment did not significantly worsen swallowing impairments.

Nutritional status of older patients with oropharyngeal dysphagia in a chronic versus an acute clinical situation.

BACKGROUND: Oropharyngeal dysphagia (OD) is a prevalent risk factor for malnutrition (MN) in older patients and both conditions are related to poor outcome. OBJECTIVE: To explore the nutritional status in older patients with OD in a chronic and an acute clinical situation. DESIGN: We examined 95 older (≥70 years) patients with OD associated to chronic neurological diseases or aging, and 23 older patients with OD and acute community-acquired pneumonia (CAP) with videofluoroscopy; and 15 older people without OD. We collected nutritional status, measured with the Mini Nutritional Assessment (MNA®), anthropometric measurements, and biochemistry and bioimpedance for body composition. Functional status was assessed with the Barthel index. RESULTS: 1) Taking into consideration patients with OD with chronic conditions, 51.1% presented a MNA® ≤23.5; 16.7%, sarcopenia and a) reduced visceral and muscular protein compartments and fat compartment; b) muscular weakness c) intracellular water depletion, and d) reduced body weight. Patients with OD and MNA® ≤23 needed higher levels of nectar viscosity for a safe swallow and had increased oropharyngeal residue at spoon-thick viscosity. 2) Patients with OD and CAP, 69.5%, presented an MNA® ≤23.5 and 29.4% sarcopenia, the inflammatory response of the pneumonia adding to the more severe depletion in visceral protein and muscular mass. CONCLUSIONS: Prevalence of impaired nutritional status (malnutrition risk, and sarcopenia) among older patients with OD associated with either chronic or acute conditions is very high. In patients with OD and chronic diseases, poor nutritional status further impairs OD with an increase in oropharyngeal residue at spoon-thick viscosity. In the acute setting there is inflammation and an additional protein deficiency. These findings will help develop specific products both for OD and nutritional status in each specific clinical situation.

Effect of oral piperine on the swallow response of patients with oropharyngeal dysphagia.

BACKGROUND: Oropharyngeal dysphagia (OD) is a major gastrointestinal motility disorder that causes severe nutritional and respiratory complications in elderly and neurological patients. In an earlier study, we found that stimulation of pharyngeal sensory neurons by capsaicinoids acting on transient receptor potential vanilloid 1 (TRPV1) improved the swallow response of dysphagic patients. The aim of this study was to explore the effect of piperine, a dual TRPV1/TRPA1 agonist, on the swallow response of dysphagic patients. METHODS: A videofluoroscopic study was performed to assess the signs of impaired safety and efficacy of swallow and the swallow response of 40 dysphagic patients while swallowing one series of nectar control boluses and two series of nectar boluses supplemented with piperine. Patients were randomized into two groups: one group received 150 µM piperine and the other group received 1 mM. RESULTS: Piperine improved the safety of swallow by: (a) reducing the prevalence of unsafe swallows by -34.48% (P = 0.004) at 150 µM and -57.19% (P < 0.001) at 1 mM, and the severity score of the penetration-aspiration scale from 3.25 ± 0.51 to 1.85 ± 0.27 (P = 0.003, 1 mM); and (b) shortening the time to laryngeal vestibule closure from 0.366 ± 0.024 to 0.270 ± 0.022 s with 150 µM piperine (P < 0.001) and from 0.380 ± 0.032 to 0.306 ± 0.028 s with 1 mM piperine (P < 0.05). CONCLUSIONS: Supplementing the alimentary bolus with piperine speeds swallow response and strongly improves safety of swallow in patients with OD, with a maximal therapeutic effect at 1 mM. Our results suggest that activation of TRPV1/A1 in oropharyngeal sensory neurons is a very promising neurostimulation strategy for dysphagic patients.