Chronic post-stroke oropharyngeal dysphagia is associated with impaired cortical activation to pharyngeal sensory inputs.

BACKGROUND AND PURPOSE: The role of afferent sensory pathways in the pathophysiology of post-stroke oropharyngeal dysphagia is not known. We hypothesized that patients with chronic post-stroke dysphagia (PSD) would show impaired sensory cortical activation in the ipsilesional hemisphere. METHODS: We studied 28 chronic unilateral post-stroke patients [17 PSD and 11 post-stroke non-dysphagic patients (PSnD)] and 11 age-matched healthy volunteers. Event-related sensory-evoked potentials to pharyngeal stimulation (pSEP) and sensory thresholds were assessed. We analyzed pSEP peak latency and amplitude (N1, P1, N2 and P2), and neurotopographic stroke characteristics from brain magnetic resonance imaging. RESULTS: Healthy volunteers presented a highly symmetric bihemispheric cortical pattern of brain activation at centroparietal areas (N1-P1 and N2-P2) to pharyngeal stimuli. In contrast, an asymmetric pattern of reduced ipsilesional activation was found in PSD (N2-P2; P = 0.026) but not in PSnD. PSD presented impaired safety of swallow (penetration-aspiration score: 4.3 ± 1.6), delayed laryngeal vestibule closure (360.0 ± 70.0 ms) and higher National Institute of Health Stroke Scale (7.0 ± 6.2 vs. 1.9 ± 1.4, P = 0.001) and Fazekas scores (3.0 ± 1.4 vs. 2.0 ± 1.1; P < 0.05) than PSnD. pSEP showed a unilateral delay at stroke site exclusively for PSD (peak-latency interhemispheric difference vs. PSnD: N1, 6.5 ± 6.7 vs. 1.1 ± 1.0 ms; N2, 32.0 ± 15.8 vs. 4.5 ± 4.9 ms; P < 0.05). CONCLUSIONS: Chronic post-stroke oropharyngeal dysphagia is associated with stroke severity and degree of leukoaraoisis. Impaired conduction and cortical integration of pharyngeal sensory inputs at stroke site are key features of chronic PSD. These findings highlight the role of sensory pathways in the pathophysiology of post-stroke oropharyngeal dysphagia and offer a potential target for future treatments.

Evaluating the Psychometric Properties of the Eating Assessment Tool (EAT-10) Using Rasch Analysis.

Early and reliable screening for oropharyngeal dysphagia (OD) symptoms in at-risk populations is important and a crucial first stage in effective OD management. The Eating Assessment Tool (EAT-10) is a commonly utilized screening and outcome measure. To date, studies using classic test theory methodologies report good psychometric properties, but the EAT-10 has not been evaluated using item response theory (e.g., Rasch analysis). The aim of this multisite study was to evaluate the internal consistency and structural validity and conduct a preliminary investigation of the cross-cultural validity of the EAT-10; floor and ceiling effects were also checked. Participants involved 636 patients deemed at risk of OD, from outpatient clinics in Spain, Turkey, Sweden, and Italy. The EAT-10 and videofluoroscopic and/or fiberoptic endoscopic evaluation of swallowing were used to confirm OD diagnosis. Patients with esophageal dysphagia were excluded to ensure a homogenous sample. Rasch analysis was used to investigate person and item fit statistics, response scale, dimensionality of the scale, differential item functioning (DIF), and floor and ceiling effect. The results indicate that the EAT-10 has significant weaknesses in structural validity and internal consistency. There are both item redundancy and lack of easy and difficult items. The thresholds of the rating scale categories were disordered and gender, confirmed OD, and language, and comorbid diagnosis showed DIF on a number of items. DIF analysis of language showed preliminary evidence of problems with cross-cultural validation, and the measure showed a clear floor effect. The authors recommend redevelopment of the EAT-10 using Rasch analysis.

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.

Potential role of the gaseous mediator hydrogen sulphide (H2S) in inhibition of human colonic contractility.

BACKGROUND: Hydrogen sulphide (H2S) is an endogenous signalling molecule that might play a physiologically relevant role in gastrointestinal motility. Cystathionine ß-synthase (CBS) and cystathionine γ-lyase (CSE) are two enzymes responsible for H2S production. d,l-Propargylglycine (PAG) is a CSE inhibitor whereas both aminooxyacetic acid (AOAA) and hydroxylamine (HA) are CBS inhibitors. The characterization of H2S responses and its mechanism of action are crucial to define H2S function. METHODS: Human colonic strips were used to investigate the role of H2S on contractility (muscle bath) and smooth muscle electrophysiology (microelectrodes). NaHS was used as a H2S donor. RESULTS: Combination of PAG and AOAA depolarized the smooth muscle (5-6mV, n=4) and elicited a transient increase in tone (260.5±92.8mg, n=12). No effect was observed on neural mediated inhibitory junction potential or relaxation. In the presence of tetrodotoxin 1µM, NaHS concentration-dependently inhibited spontaneous contractions (EC50=329.2µM, n=18). This effect was partially reduced by the guanylyl cyclase inhibitor ODQ 10µM (EC50=2.6µM, n=12) and by l-NNA 1mM (EC50=1.4mM, n=8). NaHS reversibly blocked neural mediated cholinergic (EC50=2mM) and tachykinergic (EC50=5.7mM) contractions. NaHS concentration-dependently reduced the increase in spontaneous mechanical activity (AUC) induced by carbachol (EC50=1.9mM) and NKA (EC50=1.7mM AUC). CONCLUSIONS: H2S might be an endogenous gasomediator regulating human colonic contractility. Its inhibitory effect is observed at high concentrations and could be mediated by a direct effect on smooth muscle with a possible synergistic effect with NO, as well as by an interaction with the cholinergic and tachykinergic neural mediated pathways.

Patterns of impaired internal anal sphincter activity in patients with anal fissure.

AIM: The patterns of impaired internal anal sphincter activity were studied in patients with anal fissure (AF). METHOD: Twenty healthy controls and 61 patients with acute AF were studied, using anorectal manometry with electromyography (EMG), and 53 patients with chronic AF using high-resolution manometry and ultrasonography. Mean and maximal resting anal pressure (MRAP), spontaneous rhythmic slow and ultraslow waves (USW) and relaxation induced by rectal distension were measured. RESULTS: Patients with acute AF had higher mean (106.4 ± 28.1 mmHg) and maximal resting anal pressure (161.5 ± 43.7 mmHg) than those with chronic AF (P < 0.05); 95% of patients had slow waves (SW) and 67% ultraslow waves. Patients with chronic AF had higher mean (92.4 ± 22.6 mmHg) and maximal resting anal pressure (117.5 ± 32.0 mmHg) than controls and 94% of patients had slow waves and 69% ultraslow waves. Patients with ultraslow waves (with either acute or chronic AF) had increased internal sphincter hypertonicity (mean and maximal resting pressure), decreased internal sphincter relaxation and increased after-contraction following rectal distension. CONCLUSIONS: Patients with acute AF had higher hypertonicity than those with chronic AF and both had increased spontaneous rhythmic activity (waves). Patients with AF and ultraslow waves had higher internal anal sphincter hypertonicity and reduced internal sphincter relaxation and enhanced after-contraction following rectal distension.

History and Science behind the Eating Assessment Tool-10 (Eat-10): Lessons Learned.

INTRODUCTION: Oropharyngeal dysphagia (OD) is an underdiagnosed medical condition with a high prevalence in populations such as patients with frailty, neurological disease, or head and neck pathology. Potential barriers to its diagnosis include lack of (or low) awareness of the existence and severity of the condition, the hidden nature of the condition within the 'normal ageing' process, clinical limitations, and socioeconomic reasons. Consequently, an effective treatment is not systematically offered in a timely manner, and complications, such as dehydration and respiratory infections or aspiration pneumonia, can arise. To overcome this issue, the early use of screening questionnaires to identify people at risk of swallowing disorders represents the cornerstone of preventive medicine. Several screening tools have been created but few are widely used in clinical practice. The Eating Assessment Tool-10 (EAT-10) was developed as a quick, easy-to-understand, and self-administered screening tool for OD. METHODS: A literature review was conducted in five databases with no restrictions on the language, date of publication, or design of the study to identify aspects of the validation, applicability, and usefulness of EAT-10. RESULTS AND CONCLUSIONS: Transcultural adaptation and translation studies, as well as studies involving various types of patients with dysphagia in different settings have shown the validity and reliability of EAT-10 in relation to the gold standard and other validation tools. The use of this standardised screening tool could be used as a primary screening instrument of dysphagia in routine clinical practice across a wide range of diseases and settings and thereby increase the likelihood of early diagnosis and management of a condition that lead to serious complications and impaired quality of life.

Characteristics and Therapeutic Needs of Older Patients with Oropharyngeal Dysphagia Admitted to a General Hospital.

BACKGROUND: Oropharyngeal dysphagia (OD) is a prevalent geriatric syndrome causing severe nutritional and respiratory complications. OBJECTIVE: We aimed to describe the characteristics and therapeutic needs of older patients with OD admitted to a general hospital. DESIGN, PARTICIPANTS AND MEASUREMENTS: Prospective cohort study with patients (≥70 years) with OD consecutively admitted to a general hospital. OD was clinically assessed with the Volume-Viscosity Swallowing Test and nutritional status with the Mini Nutritional Assessment-short form. Oral health (OH) and periodontal diseases were evaluated by dentists. Functionality, frailty, sarcopenia, comorbidities, dehydration, quality of life (QoL) and mortality were also assessed. RESULTS: We included 235 patients (87.3±5.5 years) with OD hospitalized for acute diseases (9.6±7.6 days). On admission, they had low functionality (Barthel: 51.3±25.1), frailty (Fried: 3.9±0.9; Edmonton: 10.3±2.7, 87.2-91.1% frail) and high comorbidities (Charlson: 3.7±2.0). Moreover, 85.1% presented signs of impaired safety and 84.7% efficacy of swallow. Up to 48% required fluid adaptation with a xanthan gum-based thickener (89.4% at 250 mPa·s; 10.6% at 800 mPa·s) and 93.2% a texture-modified diet (TMD) (74.4%, fork-mashable; 25.6%, pureed). A total of 98.7% had nutritional risk, 32.3% sarcopenia and 75.3% dehydration. OH was moderate (Oral Hygiene Index-simplified: 2.0±1.3) and 67.4% had periodontitis. QoL self-perception was 62.2% and 5.5% of patients died during hospitalization. CONCLUSION: Hospitalized older OD patients have impaired safety of swallow, frailty, malnutrition, dehydration, low functional capacity and poor OH and high risk of respiratory infections. They need a multimodal intervention including fluid thickening, TMD, thickened oral nutritional supplementation and OH care to improve health status and reduce OD-associated complications.

Regional functional specialization and inhibitory nitrergic and nonnitrergic coneurotransmission in the human esophagus.

The aim of this study was to explore the myenteric mechanisms of control of human esophageal motility and the effect of nitrergic and nonnitrergic neurotransmitters. Human circular esophageal strips were studied in organ baths and with microelectrodes. Responses following electrical field stimulation (EFS) of enteric motoneurons (EMNs) or through nicotinic acetylcholine receptors were compared in the esophageal body (EB) and in clasp and sling regions in the lower esophageal sphincter (LES). In clasp LES strips: 1) sodium nitroprusside (1 nM to 100 µM), adenosine-5'-[ß-thio]diphosphate trilithium salt (1-100 µM), and vasoactive intestinal peptide (1 nM to 1 µM) caused a relaxation; 2) 1 mM N(ω)-nitro-L-arginine (L-NNA) shifted the EFS "on"-relaxation to an "off"-relaxation, partly antagonized by 10 µM 2'-deoxy-N(6)-methyladenosine 3',5'-bisphosphate tetrasodium salt (MRS2179) or 10 U/ml α-chymotrypsin; and 3) nicotine-relaxation (100 µM) was mainly antagonized by L-NNA, and only partly by MRS2179 or α-chymotrypsin. In sling LES fibers, EFS and nicotine relaxation was abolished by L-NNA. In the EB, L-NNA blocked the latency period, and MRS2179 reduced "off"-contraction. The amplitude of cholinergic contraction decreased from the EB to both LES sides. EFS induced a monophasic inhibitory junction potential in clasp, sling, and EB fibers abolished by L-NNA. Our study shows a regional specialization to stimulation of EMNs in the human esophagus, with stronger inhibitory responses in clasp LES fibers and stronger cholinergic excitatory responses in the EB. Inhibitory responses are mainly triggered by nitrergic EMNs mediating the inhibitory junction potentials in the LES and EB, EFS on-relaxation in clasp and sling LES sides, and latency in the EB. We also found a minor role for purines (through P2Y(1) receptors) and vasoactive intestinal peptide-mediating part of nonnitrergic clasp LES relaxation.

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.

Effect of A Minimal-Massive Intervention in Hospitalized Older Patients with Oropharyngeal Dysphagia: A Proof of Concept Study.

BACKGROUND: Oropharyngeal dysphagia (OD) is a newly defined geriatric syndrome that causes nutritional and respiratory complications in older hospitalized patients. Following hospital discharge, OD also causes hospital readmission and mortality in this population. OBJECTIVE: Our aim was to assess the effect of a minimal-massive intervention (MMI) in reducing nutritional and respiratory complications in older hospitalized patients with OD. DESIGN AND PARTICIPANTS: An open label trial was performed on 186 hospitalized older patients (>70y) with OD; 62 of these patients with OD were treated with the MMI and paired by sex, age, functionality, comorbidities and body mass index with two controls. INTERVENTION: The MMI consisted of: a) fluid thickening and texture-modified foods, b) caloric and protein supplementation; and c) oral health and hygiene recommendations during hospitalization and following discharge. The control group followed the standard clinical practice without MMI. MEASUREMENTS: Main study outcomes were hospital readmissions, respiratory infections, nutritional status and survival after 6 months follow up. RESULTS: Both groups had similar advanced age (84.87±6.02MMI and 84.42±5.31 years), poor functionality (Barthel 59.51±26.76 MMI and 58.84±26.87), and high comorbidities (Charlson 3.00±1.60 MMI and 3.06±1.45). Main results showed that MMI improved nutritional status (MNA 9.84±2.05 pre-MMI vs. 11.31±2.21 post-MMI; p=0.0038) and functionality (Barthel 62.34±25.43 pre-MMI vs. 73.44±25.19 post-MMI; p=0.007). In addition MMI decreased hospital readmissions (68.8 readmissions/100 persons-year (28.1-109.38) MMI vs. 190.8 (156.0-225.7); p=0.001), respiratory infections (12.50 readmissions/100 persons-year (0-29.82) MMI vs. 74.68 (52.86-96.50); p=0.002), and increased 6-month survival (84.13% MMI vs. 70.96%; p=0.044). CONCLUSIONS: Our results suggest that a MMI in hospitalized older patients with OD improves nutritional status and functionality and reduces hospital readmissions, respiratory infections and mortality. MMI might become a new simple and cost-effective strategy to avoid OD complications in the geriatric population admitted with an acute disease to a general hospital.

Increased levels of substance P in patients taking beta-blockers are linked with a protective effect on oropharyngeal dysphagia.

BACKGROUND: We have recently found a potential protective effect of beta-blockers on oropharyngeal dysphagia (OD). The action mechanism by which beta-blockers could wield this protective effect is unknown, but the neurotransmitter substance P (SP) could play a key role. The aim of this study was to analyze serum and saliva SP levels in patients taking beta-blockers (TBB), and to explore its relationship with OD. METHODS: Adult (>50 year) patients TBB were randomly recruited from the primary care setting and 1:1 matched by age, sex, and Barthel Index (BI) with patients not taking beta-blockers (NTBB). Serum and saliva samples were taken and analyzed for their SP levels using an enzyme-linked immunosorbent assay (ELISA). Socio-demographic and clinical variables were collected. Dysphagia was evaluated in all patients using the clinical volume-viscosity swallow test (V-VST). KEY RESULTS: We studied 28 patients TBB (64.96 ± 7.31 years, 57.1% women, BI 99.6 ± 1.31, carvedilol-equivalent dose 24.11 ± 18.12 mg) and 28 patients NTBB (65.61 ± 6.43 years, 57.1% women, BI 99.6 ± 1.31). SP serum levels were significantly higher in patients TBB (260.68 ± 144.27 vs 175.46 ± 108.36 pg/mL, P = .009) as were SP saliva levels (170.34 ± 146.48 vs 102.73 ± 52.28 pg/mL, P < .001) compared with patients NTBB. The prevalence of OD was 32.1% in patients TBB and 67.9% in patients NTBB (P = .015). Moreover, patients with OD had significantly lower SP saliva levels in comparison with patients without clinical signs of OD (98.39 ± 43.25 vs 174.69 ± 147.21 pg/mL) P < .001. CONCLUSIONS & INFERENCES: We have found that serum and saliva SP levels are greater in patients TBB. This increase in SP levels could be the action mechanism by which beta-blockers protect patients from OD.

Prevalence, risk factors and complications of oropharyngeal dysphagia in stroke patients: A cohort study.

BACKGROUND: Oropharyngeal dysphagia (OD) is a prevalent poststroke condition with severe complications and increased mortality. Poststroke OD prevalence varies among studies and there is little evidence of its related risk factors and associated complications. OBJECTIVE: to evaluate the prevalence of OD after stroke and the risk factors and associated complications. METHODS: We performed a prospective longitudinal study of stroke patients consecutively admitted to a general hospital. OD was diagnosed with the volume-viscosity swallow test (V-VST). Demographic, functional status and topographical and clinical variables of stroke were collected to assess risk factors for OD. We evaluated functional status, mortality, respiratory infections, and readmissions 3 and 12 months after stroke. A multivariate regression analysis determined associated risk factors for OD and for each outcome variable. KEY RESULTS: We included 395 stroke patients with a 45.06% prevalence of OD on admission. OD was independently associated with age (OR = 1.05; CI = 1.02-1.08), previous stroke (OR = 2.40; CI = 1.00-5.79), severity using the National Institute of Health Stroke Scale (OR = 3.52; CI = 1.57-7.87) and volume of the lesion (OR = 1.02; CI = 1.01-1.03). OD after stroke was an independent risk factor for prolonged hospital stay (P = .049; ß = 0.938) and institutionalization after discharge (OR = 0.47; CI = 0.24-0.92); OD was an independent risk factor for poorer functional capacity (OR = 3.00; CI = 1.58-5.68) and increased mortality (HR = 6.90; CI = 1.57-30.34) 3 months after stroke. CONCLUSIONS & INFERENCES: Poststroke OD is prevalent and associated with poor short and long term prognosis. Stroke severity and patient status before stroke were more relevant to OD than lesion location. Systematic screening programs and early OD management could significantly improve poststroke patient outcome.

TRPM8, ASIC1, and ASIC3 localization and expression in the human oropharynx.

BACKGROUND: Oropharyngeal dysphagia (OD) is a prevalent disease with poor prognosis among older people and has no pharmacological treatment. Polymodal sensory receptors like the TRP or ASIC family receptors are potential targets to treat OD. TRPM8 agonists and acidic solutions can improve the swallow response in patients with OD, but little is known about the expression of TRPM8, ASIC1, and ASIC3 in the human oropharynx. The aim of this study was to assess the expression and localization of TRPM8, ASIC1, and ASIC3 in human samples of the oropharynx to lay the basis for new pharmacological treatments for OD. METHODS: Pathology-free samples from oropharyngeal regions innervated by cranial nerves V, IX, and X were obtained during major ENT surgery and processed to obtain mRNA (20 patients) or to be used in immunohistochemical assays (12 patients). TRPM8, ASIC1, and ASIC3 expression and localization were studied with RT-qPCR and fluorescent immunohistochemistry. KEY RESULTS: ASIC3 was expressed in the 3 regions studied with similar levels and was localized on sensory fibers innervating the mucosa below the basal lamina of all studied regions. TRPM8 was also co-localized on the sensory fibers innervating the mucosa below the basal lamina of all studied regions. In contrast, ASIC1 was only found in the nerves innervating the tongue muscular fibers. CONCLUSIONS & INFERENCES: TRPM8 and ASIC3 are found on submucosal sensory nerves in the human oropharynx. Our study lays the basis to use oropharyngeal TRPM8 and ASIC3 receptors as therapeutic targets to develop new active pharmacological treatments for OD patients.

Mechanisms controlling function in the clasp and sling regions of porcine lower oesophageal sphincter.

BACKGROUND: Characterization of functional differences between lower oesophageal sphincter (LOS) clasp and sling muscles might aid the development of more specific pharmacological and surgical approaches for the treatment of motility disorders. METHODS: Circular LOS strips from 25 adult pigs were studied in organ baths to compare the physiology of clasp and sling fibres. RESULTS: Sling strips developed greater tone than clasp fibres (mean(s.e.m.) 7.59(0.89) versus 4.72(0.67) g; P = 0.017). LOS tone was more dependent on extracellular calcium in clasp strips and on the activity of cholinergic enteric motor neurones (EMNs) in sling strips. The amplitude of maximal relaxation caused by electrical field stimulation (EFS, 3Hz) of EMNs was greater in clasp strips (mean(s.e.m.) 74.5(2.3) versus 58.1(2.2) per cent of tone; P < 0.001). EFS-induced relaxation was reduced in clasp fibres and fully blocked in sling fibres by nitrergic blockade with 10 micromol/l 1H-[1,2,4]oxadiazole-[4,3-alpha]quinoxalin-1-one (ODQ). The amplitude of EFS cholinergic responses was significantly greater in sling fibres. In the clasp region, relaxation caused by stimulation of EMNs with 100 micromol/l nicotine was reduced by ODQ. In sling fibres, nicotine induced relaxation at rest and cholinergic contraction following ODQ. CONCLUSION: Clasp and sling fibres of the porcine LOS show marked intrinsic functional differences. This should be considered when developing more specific approaches to human LOS motility disorders.

Interstitial cells of Cajal and neuromuscular transmission in the rat lower oesophageal sphincter.

The distribution of interstitial cells of Cajal (ICC) and neurotransmission were investigated in lower oesophageal sphincter (LES) circular muscle strips from Sprague-Dawley (SD) rats, Ws/Ws mutant rats and their wild-type (+/+) siblings. Intramuscular c-Kit-positive cells, confirmed to be ICC-IM by electron microscopy, were observed throughout both muscle layers from SD and +/+ rats. In contrast, c-Kit-positive, ultrastructurally typical ICC-IM were absent in Ws/Ws. LES strips from Ws/Ws rats showed increased spontaneous contractile activity. Strips from SD and +/+ rats, responded to electrical neuronal stimulation with a relaxation that was in part L-NNA and in part apamin sensitive, followed by a contraction which was decreased by atropine. In Ws/Ws rats, similar to +/+ rats, neurally mediated relaxation was L-NNA and apamin sensitive and the contraction was decreased by atropine. We conclude that in the rat LES, relaxation is mediated by NO and an apamin-sensitive mediator, and contraction primarily by acetylcholine. Despite the absence of c-Kit-positive ICC, nerve-muscle interaction can be accomplished likely by diffusion of neurotransmitters to the smooth muscle cells. The lack of c-Kit-positive ICC is related to an increase in the basal tone and spontaneous contractile activity. The presence of fibroblast-like ICC in Ws/Ws rats might represent immature ICC whose possible functions need further investigation.

Spatiotemporal characteristics of the pharyngeal event-related potential in healthy subjects and older patients with oropharyngeal dysfunction.

BACKGROUND: Oropharyngeal dysphagia (OD) is a highly prevalent symptom in older people. Appropriate oropharyngeal sensory feedback is essential for safe and efficient swallowing. However, pharyngeal sensitivity decreases with advancing age and could play a fundamental role in the physiopathology of swallowing dysfunction associated with aging. We aimed to characterize pharyngeal sensitivity and cortical response to a pharyngeal electrical stimulus in healthy volunteers (HV) and older patients with and without OD. METHODS: Eight young HV, eight older HV without OD, and 14 older patients with OD were studied by electroencephalography through 32 scalp electrodes. Pharyngeal event-related potentials (ERP) were assessed following electrical stimulation of the pharynx. Sensory and tolerance thresholds to the electrical stimulus and latency, amplitude, and scalp current density of each ERP component were analyzed and compared. An ERP source localization study was also performed using the sLORETA software. KEY RESULTS: Older participants (with and without OD) presented an increased sensory threshold to pharyngeal electrical stimulation (10.2 ± 1.7 mA and 11.5 ± 1.9 mA respectively), compared with young HV (6.0 ± 1.2 mA). The cortical activation of older HV in response to pharyngeal electrical stimulus was reduced compared with young HV (N2 amplitude: 0.22 ± 0.79 vs -3.10 ± 0.59, P<.05). Older patients with OD also presented disturbances to the pharyngo-cortical connection together with disrupted pattern of cortical activation. CONCLUSIONS AND INFERENCES: Older people present a decline in pharyngeal sensory function, more severe in older patients with OD. This sensory impairment might be a critical pathophysiological element and a potential target for treatment of swallowing dysfunction in older patients.

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.

Cough reflex attenuation and swallowing dysfunction in sub-acute post-stroke patients: prevalence, risk factors, and clinical outcome.

BACKGROUND: Cough and swallowing impairments in post-stroke patients (PSP) have been associated with increased risk for respiratory complications. AIMS: To assess the prevalence of alterations in protective cough responses in subacute PSP and its association with oropharyngeal dysphagia (OD), clinical, and neurotopographic stroke factors and clinical outcomes. METHODS: Three months after stroke, the cough reflex test (CRT) was performed by nebulizing incremental citric acid concentrations (7.8-1000 mmol L-1 ) to determine the concentration that elicited two and five coughs; OD was assessed by the volume-viscosity swallow test. Clinical and neurotopographic stroke risk factors and complications (readmissions, respiratory infections, institutionalization, and mortality) were recorded from 3 to 12 months post-stroke. RESULTS: We included 225 PSP. Prevalence of impaired CRT was 5.8%, that of OD was 40.4% (20.4% with impaired safety of swallow), and of both impairments was, 1.8%. No specific risk factors associated with impaired CRT were found; however, hemorrhagic, wide circulation infarction (TACI), and brainstem strokes delayed the cough response. OD was associated with age, TACI and poor functional and nutritional status. Outcome of PSPs was unaffected by impaired CRT but OD and impaired safety of swallow increased institutionalization, respiratory infections, and mortality with the poorest outcome for those with both impairments. CONCLUSIONS: Prevalence of subacute post-stroke OD and swallow safety impairments was much higher than CRT attenuation, and risk factors strongly differed suggesting that the swallow response receives a stronger cortical control than the cough reflex. OD has a greater impact on PSP clinical outcome than impaired cough, the poorest prognosis being for patients with both airway protective dysfunctions.