Human Herpes Virus 6 Encephalitis Presenting as Fatal Refractory Status Epilepticus: a Case Report and Systematic Review.

PURPOSE: Encephalitis secondary to human herpesvirus 6 (HHV-6) infection is frequently encountered in immunocompromised patients; in contrast, HHV-6 encephalitis in immunocompetent patients is rare. There are only 3 reports of status epilepticus due to HHV-6 encephalitis in immunocompetent adults. In the present study, a case of refractory status epilepticus secondary to HHV-6 encephalitis was reported in an immunocompetent female. CASE REPORT: We report a case of a previously healthy 46-year-old female who presented with a one-week history of back pain, fever and generalized tonic-clonic seizures that progressed to status epilepticus. The video electroencephalography showed epileptiform discharges on both frontotemporal regions. Neuroimaging showed hyperintensities on the bilateral insula and temporal lobes. The cerebrospinal fluid showed elevated pressure and was positive for HHV-6. She was given ganciclovir and a total of eleven antiepileptic drugs. Despite these medications, she developed refractory status epilepticus and eventually succumbed due to multiple medical complications. CONCLUSION: This case highlights HHV-6 encephalitis as an important diagnostic consideration in patients presenting with refractory status epilepticus, regardless of immune status.

Intra- and interrater reliability of the Chicago Classification of achalasia subtypes in pediatric high-resolution esophageal manometry (HRM) recordings.

BACKGROUND: Subtyping achalasia by high-resolution manometry (HRM) is clinically relevant as response to therapy and prognosis have shown to vary accordingly. The aim of this study was to assess inter- and intrarater reliability of diagnosing achalasia and achalasia subtyping in children using the Chicago Classification (CC) V3.0. METHODS: Six observers analyzed 40 pediatric HRM recordings (22 achalasia and 18 non-achalasia) twice by using dedicated analysis software (ManoView 3.0, Given Imaging, Los Angeles, CA, USA). Integrated relaxation pressure (IRP4s), distal contractile integral (DCI), intrabolus pressurization pattern (IBP), and distal latency (DL) were extracted and analyzed hierarchically. Cohen's κ (2 raters) and Fleiss' κ (>2 raters) and the intraclass correlation coefficient (ICC) were used for categorical and ordinal data, respectively. RESULTS: Based on the results of dedicated analysis software only, intra- and interrater reliability was excellent and moderate (κ=0.89 and κ=0.52, respectively) for differentiating achalasia from non-achalasia. For subtyping achalasia, reliability decreased to substantial and fair (κ=0.72 and κ=0.28, respectively). When observers were allowed to change the software-driven diagnosis according to their own interpretation of the manometric patterns, intra- and interrater reliability increased for diagnosing achalasia (κ=0.98 and κ=0.92, respectively) and for subtyping achalasia (κ=0.79 and κ=0.58, respectively). CONCLUSIONS: Intra- and interrater agreement for diagnosing achalasia when using HRM and the CC was very good to excellent when results of automated analysis software were interpreted by experienced observers. More variability was seen when relying solely on the software-driven diagnosis and for subtyping achalasia. Therefore, diagnosing and subtyping achalasia should be performed in pediatric motility centers with significant expertise.

Evaluation of the language profile in children with rolandic epilepsy and developmental dysphasia: Evidence for distinct strengths and weaknesses.

Although benign, rolandic epilepsy (RE) or benign childhood epilepsy with centro-temporal spikes is often associated with language impairment. Recently, fronto-rolandic EEG abnormalities have been described in children with developmental dysphasia (DD), suggesting an interaction between language impairment and interictal epileptiform discharges. To investigate if a behavioral-linguistic continuum between RE and DD exists, a clinical prospective study was carried out to evaluate the language profile of 15 children with RE and 22 children with DD. Language skills were assessed using an extensive, standardized test battery. Language was found to be impaired in both study groups, however RE and DD were associated with distinct language impairment profiles. Children with RE had difficulties with sentence comprehension, semantic verbal fluency and auditory short-term memory, which are unrelated to age of epilepsy onset and laterality of epileptic focus. In children with DD, sentence comprehension and verbal fluency were among their relative strengths, whereas sentence and lexical production constituted relative weaknesses.

Perioperative serum levels of procalcitonin, C-reactive protein, and leukocytes in head and neck free flaps.

Microvascular free flaps are considered to be the gold standard in reconstructive head and neck surgery. However, reduced postoperative transplant perfusion is one of the serious postoperative complications and calls for close and reliable monitoring. Procalcitonin, C-reactive protein, and leukocytes are closely associated with local and systemic inflammatory reactions and might have prognostic capacity concerning tissue necrosis. This study aimed to evaluate perioperative serum levels of these three biomarkers to assess their potential in postoperative flap monitoring. A total of 100 patients with microvascular head and neck reconstructions were included in the study. Perioperative serum levels of parameters were measured and the clinical data were analyzed and correlated. A total of 13% of all flaps developed reduced postoperative perfusion. Analysis of the parameters revealed statistically significant differences in the overall patient collective over time, irrespective of clinically reduced flap perfusion. Co-factors such as sex and history of tobacco and alcohol abuse showed significant differences. The efficacy of the parameters in free flap monitoring has not been verified, although the role of procalcitonin in postoperative monitoring, with special regard to the early detection of infections, is underlined by the present study results.

Effect of methylnaltrexone and naloxone on esophageal motor function in man.

BACKGROUND: Endogenous opioids (EO) acting on µ-opiod receptors in central and enteric nervous system (ENS) control gastrointestinal motility but it is still unclear whether EO in ENS may control esophageal function in man, thus we will study the effects of methylnaltrexone (MNTX), a peripherally selective, and naloxone (NA), a non-selective µ-opiod receptor antagonist, on esophageal motility in healthy subjects. METHODS: Fifteen HV (6 M; 34.1 ± 0.6 years; BMI: 22.1 ± 0.1 kg/m2 ) underwent three esophageal high-resolution manometry impedance (HRiM) studies with 10 saline swallows administered every 30 minutes: drug was administered after 30 minutes (MNTX subcutaneously/NA or saline intravenously), a solid meal after 90 minutes; measurements continued for 120 minutes postprandially. KEY RESULTS: Methylnaltrexone did not significantly decrease the upper esophageal sphincter (UES) percentage of relaxation preprandially (72.5 ± 5 vs 66.9 ± 4.6 and 73 ± 3.8%, ANOVA between placebo, MNTX and NA, P=NS) and postprandially (60 minutes: 68.2 ± 5.6 vs 61 ± 5.5 and 67.1 ± 5.6%; 120 minutes: 68 ± 5.9 vs 59.3 ± 5.2 and 67.7 ± 4.7%; ANOVA between placebo, MNTX and NA, P=NS). MNTX and NA did not significantly alter preprandial and postprandial LES resting pressures and integrated relaxation pressure (ANOVA between placebo, MNTX and NA, all P=NS). Peak front velocity and distal contractile integral were not altered pre- and postprandially by MNTX and NA (ANOVA between placebo, MNTX and NA, P=NS). Transient lower esophageal sphincter relaxations (TLESRs') number was not altered by MNTX and NA (ANOVA between placebo, MNTX and NA, all P=NS). CONCLUSIONS AND INFERENCES: The peripheral selective and non-selective µ-opioid receptor antagonists MNTX and NA, respectively, do not alter TLESRs occurrence and esophageal peristalsis.

High-resolution impedance manometry parameters enhance the esophageal motility evaluation in non-obstructive dysphagia patients without a major Chicago Classification motility disorder.

BACKGROUND: High-resolution impedance manometry (HRIM) allows evaluation of esophageal bolus retention, flow, and pressurization. We aimed to perform a collaborative analysis of HRIM metrics to evaluate patients with non-obstructive dysphagia. METHODS: Fourteen asymptomatic controls (58% female; ages 20-50) and 41 patients (63% female; ages 24-82), 18 evaluated for dysphagia and 23 for reflux (non-dysphagia patients), with esophageal motility diagnoses of normal motility or ineffective esophageal motility, were evaluated with HRIM and a global dysphagia symptom score (Brief Esophageal Dysphagia Questionnaire). HRIM was analyzed to assess Chicago Classification metrics, automated pressure-flow metrics, the esophageal impedance integral (EII) ratio, and the bolus flow time (BFT). KEY RESULTS: Significant symptom-metric correlations were detected only with basal EGJ pressure, EII ratio, and BFT. The EII ratio, BFT, and impedance ratio differed between controls and dysphagia patients, while the EII ratio in the upright position was the only measure that differentiated dysphagia from non-dysphagia patients. CONCLUSIONS & INFERENCES: The EII ratio and BFT appear to offer an improved diagnostic evaluation in patients with non-obstructive dysphagia without a major esophageal motility disorder. Bolus retention as measured with the EII ratio appears to carry the strongest association with dysphagia, and thus may aid in the characterization of symptomatic patients with otherwise normal manometry.

Objective prediction of pharyngeal swallow dysfunction in dysphagia through artificial neural network modeling.

BACKGROUND: Pharyngeal pressure-flow analysis (PFA) of high resolution impedance-manometry (HRIM) with calculation of the swallow risk index (SRI) can quantify swallow dysfunction predisposing to aspiration. We explored the potential use of artificial neural networks (ANN) to model the relationship between PFA swallow metrics and aspiration and to predict swallow dysfunction. METHODS: Two hundred consecutive dysphagia patients referred for videofluoroscopy and HRIM were assessed. Presence of aspiration was scored and PFA software derived 13 metrics and the SRI. An ANN was created and optimized over training cycles to achieve optimal classification accuracy for matching inputs (PFA metrics) to output (presence of aspiration on videofluoroscopy). Application of the ANN returned a value between 0.00 and 1.00 reflecting the degree of swallow dysfunction. KEY RESULTS: Twenty one patients were excluded due to insufficient number of swallows (<4). Of 179, 58 aspirated and 27 had aspiration pneumonia history. The SRI was higher in aspirators (aspiration 24 [9, 41] vs no aspiration 7 [2, 18], p < 0.001) and patients with pneumonia (pneumonia 27 [5, 42] vs no pneumonia 8 [3, 24], p < 0.05). The ANN Predicted Risk was higher in aspirators (aspiration 0.57 [0.38, 0.82] vs no aspiration 0.13 [0.4, 0.25], p < 0.001) and in patients with pneumonia (pneumonia 0.46 [0.18, 0.60] vs no pneumonia 0.18 [0.6, 0.49], p < 0.01). Prognostic value of the ANN was superior to the SRI. CONCLUSIONS & INFERENCES: In a heterogeneous cohort of dysphagia patients, PFA with ANN modeling offers enhanced detection of clinically significant swallowing dysfunction, probably more accurately reflecting the complex interplay of swallow characteristics that causes aspiration.

Correlation of esophageal pressure-flow analysis findings with bolus transit patterns on videofluoroscopy.

Pressure-flow analysis quantifies the interactions between bolus transport and pressure generation. We undertook a pilot study to assess the interrelationships between pressure-flow metrics and fluoroscopically determined bolus clearance and bolus transport across the esophagogastric junction (EGJ). We hypothesized that findings of abnormal pressure-flow metrics would correlate with impaired bolus clearance and reduced flow across the EGJ. Videofluoroscopic images, impedance, and pressure were recorded simultaneously in nine patients with dysphagia (62-82 years, seven male) tested with liquid barium boluses. A 3.6 mm diameter solid-state catheter with 25 × 1 cm pressure/12 × 2 cm impedance was utilized. Swallowed bolus clearance was assessed using a validated 7-point radiological bolus transport scale. The cumulative period of bolus flow across the EGJ was also fluoroscopically measured (EGJ flow time). Pressure only parameters included the length of breaks in the 20 mmHg iso-contour and the 4 second integrated EGJ relaxation pressure (IRP4s). Pressure-flow metrics were calculated for the distal esophagus, these were: time from nadir impedance to peak pressure (TNadImp to PeakP) to quantify bolus flow timing; pressure flow index (PFI) to integrate bolus pressurization and flow timing; and impedance ratio (IR) to assess bolus clearance. When compared with controls, patients had longer peristaltic breaks, higher IRs, and higher residual EGJ relaxation pressures (break length of 8 [2, 13] vs. 2 [0, 2] cm, P = 0.027; IR 0.5 ± 0.1 vs. 0.3 ± 0.0, P = 0.019; IRP4s 11 ± 2 vs. 6 ± 1 mmHg, P = 0.070). There was a significant positive correlation between higher bolus transport scores and longer peristaltic breaks (Spearman correlation r = 0.895, P < 0.001) and with higher IRs (r = 0.661, P < 0.05). Diminished EGJ flow times correlated with a shorter TNadImp to PeakP (r = -0.733, P < 0.05) and a higher IR (r = -0.750, P < 0.05). Longer peristaltic breaks and higher IR correlate with failed bolus clearance on videofluoroscopy. The metric TNadImp to PeakP appears to be a marker of the period of time over which the bolus flows across the EGJ.

Inter-rater reliability and validity of automated impedance manometry analysis and fluoroscopy in dysphagic patients after head and neck cancer radiotherapy.

BACKGROUND: Pharyngeal automated impedance manometry (AIM) analysis is a novel non-radiological method to analyze swallowing function based on impedance-pressure recordings. In dysphagic head and neck cancer patients, we evaluated the reliability and validity of the AIM-derived swallow risk index (SRI) and a novel measure of postswallow residue (iZn/Z) by comparing it against videofluoroscopy as the gold standard. METHODS: Three blinded experts classified 88 videofluoroscopic swallows from 16 patients for aspiration and degree of postswallow residue. Pressure-impedance recordings of the patient and age-matched control swallows were analyzed using AIM by three observers who derived the SRI and iZn/Z. Intra-class correlation coefficients (ICC) were calculated for videofluoroscopic and AIM measures. Patient pressure/impedance measurements were compared with videofluoroscopy scores and control subjects to determine validity for detecting clinically relevant swallowing dysfunction. KEY RESULTS: Agreement among observers assessing presence of penetration and aspiration was modest (ICC 0.57) for videofluoroscopy and good (ICC 0.71, 0.82) for AIM-derived SRI and iZn/Z. When compared with age-matched controls, the SRI was higher in patients with aspiration (mean diff. 28.6, 95% CI [55.85, 1.355], p < 0.05). The iZn/Z had moderate positive correlation with bolus residue on fluoroscopy (BRS score) (rs (86) = 0.4120, p < 0.0001) and was increased in both patients with aspiration (∆244 [419.7, 69.52; p < 0.05]) and penetration (∆240 [394.3, 85.77]; p < 0.05) compared to controls. CONCLUSIONS & INFERENCES: AIM-based measures of swallowing function have better inter-rater reliability than comparable fluoroscopically derived measures. These measures are easily determined and objective markers of clinically relevant features of disordered swallowing following radiotherapy.

Impedance as an adjunct to manometric testing to investigate symptoms of dysphagia: What it has failed to do and what it may tell us in the future.

Dysphagia is a common reason for referral for investigations of oesophageal motility. Impedance measurement has now been incorporated into commercially available diagnostic manometry systems for more than a decade. This innovation, which offered the ability to record patterns of bolus transport without the need for simultaneous radiology, has for the most part failed to live up to expectations, offering few additional diagnostic insights. This review examines the potential pitfalls related to how impedance patterns are currently analysed and introduces and discusses the new concept of pressure-flow analysis integrating pressure and impedance measurements to derive new metrics linked to the pressures occurring within and around the bolus as it is being transported.

Automatische Impedantie Manometrie (AIM): objectieve diagnostiek van oro-faryngale dysfagie.

AUTOMATED IMPEDANCE MANOMETRY (AIM): OBJECTIVE DIAGNOSIS OF OROPHARYNGEAL DYSPHAGIA: This review article aims to demonstrate the clinical potential of Automated Impedance Manometry (AIM) as a new, non-radiological technique for screening and diagnosis of oro-pharyngeal dysphagia. An integrated - rather than separate - analysis of pressure and impedance patterns generated in the pharynx when swallowing a food bolus, can be a useful complement to the radiological investigations considered as gold standard today. Major advantages are the objective nature of this technique and the fully automated calculation of various swallow parameters. A global measure of swallowing function can be derived (a Swallow Risk Index, SRI) and is related to (the severity of) the risk of aspiration and the presence of pharyngeal post-swallow residue. It was shown that aspiration on videofluoroscopy was accurately detected by using AIM with a sensitivity of 0.88 and a specificity of 0.96. AIM analysis can be performed quickly and is reliable in the hands of different end users. Various parameters are sufficiently sensitive to detect changes in bolus consistency and - as was recently found - are influenced by swallowing manoeuvers. Furthermore, different patterns of deviant swallow parameters can be found in different patient populations. Whether this observation can provide specific diagnoses and - as a consequence - more targeted treatments is currently under investigation.

Presbyfagie: de invloed van het primair verouderingsproces op de slikfunctie.

PRESBYPHAGIA: THE INFLUENCE OF PRIMARY AGING ON SWALLOWING FUNCTION: Elderly often get confronted with swallowing difficulties. It is important to differentiate between presbyphagia, which describes the influence of primary aging on swallow function and dysphagia, which is a pathological swallowing disorder caused by age related diseases and their treatment. In this literature overview the focus is on presbyphagia. The influence of primary aging on the oropharyngeal swallowing function and on other body functions that are indirectly related to swallowing will be discussed. From the literature we learn that in primary aging a number of functions stay preserved, a number of functions deteriorate, and some compensatory mechanisms are evident. The swallow safety as such however, stays preserved. To conclude with we discuss some clinical implications concerning both the detection of swallowing disorders in the elderly and the establishment of preventive action for the healthy elderly.

Applying the Chicago Classification criteria of esophageal motility to a pediatric cohort: effects of patient age and size.

BACKGROUND: Applying the 2012 Chicago Classification (CC) of esophageal motility disorders to pediatric patients is problematic as it relies upon adult-derived criteria. As shorter esophageal length and smaller esophago-gastric junction (EGJ) diameter may influence CC metrics, we explored the potential for age- and size-adjustment of diagnostic criteria. METHODS: We evaluated 76 high-resolution solid state impedance-manometry recordings in children referred for manometry (32M; mean age 9 ± 1 years) and 25 recordings from healthy adult subjects (7M; mean age 36 ± 2 years). CC metrics; integrated relaxation pressure (IRP4s, mmHg), contractile front velocity (CFV, cm/s), distal contractile integral (DCI, mmHg cm/s), distal latency (DL, s), and peristaltic break size (BS, cm) were derived for 10 liquid swallows using CC analysis software. Effects of age and size were examined using regression analysis. KEY RESULTS: Younger patient age and shorter size correlated significantly with greater IRP4s (p < 0.05), shorter DL (p < 0.001) and smaller BS (p < 0.05). Standard diagnostic CC criteria were adjusted using the slope of the linear regression equation to define the age/size-related trend. Sixty-six percent of the pediatric cohort showed abnormal motility when applying standard CC criteria. Adjustment for age and size reduced this to 50% and 53% respectively, with the largest reduction being in the IRP4s- and DL-dependent disorders EGJ outflow obstruction and diffuse esophageal spasm (13% to 7% and 5% and 14% to 1 and 5%, respectively). CONCLUSIONS & INFERENCES: CC metrics, particularly IRP4s and DL, are age and size dependent, and therefore, require adjustment to improve accuracy of diagnosis of esophageal motility disorders in children.

Automated impedance manometry analysis as a method to assess esophageal function.

BACKGROUND: Diagnostic evaluation of non-achalasia esophageal dysphagia remains challenging because of a lack of a clear relationship between symptoms, esophageal contraction patterns, and esophageal bolus flow. This study evaluates a novel approach to pressure-impedance analysis called automated impedance manometry (AIM) analysis in relation to bolus characteristics, Chicago classification metrics, bolus perception, and dysphagia. METHODS: AIM analysis was performed on esophageal high resolution manometry-impedance recordings from 12 healthy controls and 15 patients with dysphagia. In each subject, 10 liquid, 10 semisolid, and 10 solid swallows were analyzed using AIMplot software. KEY RESULTS: This study demonstrated that (i) esophageal pressure-flow parameters differ with bolus type (liquid, semisolid, and solids), (ii) impedance at peak pressure parameter can discriminate normal from dysphagic subjects with high accuracy on a cut-off threshold at 2400 Ohms (kappa 0.77, sensitivity 0.83, and specificity 0.93), and (iii) nadir impedance and impedance at peak pressure highly correlate with perception of esophageal bolus flow (r = -0.65, p = 0.02; r = -0.70, p = 0.01 resp). CONCLUSIONS & INFERENCES: This study presents novel esophageal pressure-flow variables in control subjects and in a cohort of patients with dysphagia. These variables are altered in relation to bolus consistency and can discriminate between subjects with and without symptoms of dysphagia. For the first time, we present high resolution esophageal pressure-flow variables that accurately link in with patient perception of esophageal bolus hold up.

Balloon dilation of the esophago-gastric junction affects lower and upper esophageal sphincter function in achalasia.

BACKGROUND: Pneumatic dilation of the lower esophageal sphincter (LES) in achalasia has an unappreciated effect on upper esophageal sphincter (UES) function. We studied UES pressure patterns at baseline and alterations in UES parameters resulting from therapy. METHODS: High-resolution manometry (HRM) tracings from 50 achalasia patients, seen at a tertiary center between January 2009 and July 2011, were reviewed. Manometric parameters studied were (i) LES: resting pressure (restP), 4-second integrated relaxation pressure (IRP4); (ii) UES: resting pressure (restP), minimal relaxation pressure (MRP), peak pressure (PP), relaxation interval (RI), intrabolus pressure (IBP), and deglutitive sphincter resistance (DSR). Mixed models analyses with LES and UES parameters as dependent variables and treatment stage as within-subject independent variable of interest were used. Correlations between treatment-induced changes in LES, UES, and esophageal body (EB) parameters were performed. KEY RESULTS: Pre- and posttreatment HRM tracings were available from 50 patients (mean age 52.7 ± 18.6 years, 29 men). Upper esophageal sphincter parameters MRP (17.9 ± 1.2 vs 15.2 ± 0.9 mmHg; p = 0.02) and IBP (31.5 ± 1.5 vs 27.4 ± 1.2 mmHg; p = 0.009) were significantly reduced after initial balloon dilation and this effect was significant in type II achalasia (p = 0.002 and p = 0.0006). Peak pressure, RI, and DSR were not. The therapeutic effect on LES IRP4 correlated significantly with the change in UES MRP, statistically mediated by the change in EB deglutitive pressure (p = 0.004 and p = 0.0002). CONCLUSIONS & INFERENCES: We present the first HRM study demonstrating that pneumatic dilation of the LES affects intraesophageal and UES pressures in patients with achalasia.

Swallowing dysfunction in healthy older people using pharyngeal pressure-flow analysis.

BACKGROUND: Age-related loss of swallowing efficiency may occur for multiple reasons. Objective assessment of individual dysfunctions is difficult and may not clearly differentiate these from normal. Pharyngeal pressure-flow analysis is a novel technique that allows quantification of swallow dysfunction predisposing to aspiration risk based on a swallow risk index (SRI). In this study, we examined the effect of ageing on swallow function. METHODS: Studies were performed in 68 healthy subjects aged 20-91 years (mean 59 years; 29 male), asymptomatic for oropharyngeal disease. Swallowing of liquid and viscous boluses was recorded with a pressure-impedance catheter. Indices of swallow function including the SRI, postswallow residues, upper esophageal sphincter opening and bolus transit time were derived using purpose designed software. KEY RESULTS: Swallow function worsened with increasing age with a significant decline after 80 years. Higher SRI correlated with increasing age (r = 0.257, p < 0.05 for liquids and r = 0.361, p < 0.005 viscous bolus). Subjects over 80 years were overrepresented amongst those with an SRI considered diagnostically relevant (SRI > 15). In addition, upper esophageal sphincter opening was reduced and postswallow residues increased in older subjects. CONCLUSIONS & INFERENCES: Pharyngeal pressure-flow analysis reveals multiple functional abnormalities in older individuals. The higher SRI levels seen in asymptomatic elders possibly reflect a loss of functional reserve with ageing. Automated impedance manometry analysis of swallow function may allow the risk of developing disordered swallowing to be quantified numerically.

New measures of upper esophageal sphincter distensibility and opening patterns during swallowing in healthy subjects using EndoFLIP®.

BACKGROUND: This paper aims to measure upper esophageal sphincter (UES) distensibility and extent and duration of UES opening during swallowing in healthy subjects using EndoFLIP(®). METHODS: Fourteen healthy subjects (20-50 years) were recruited. An EndoFLIP(®) probe was passed trans-orally and the probe balloon was positioned across the UES. Two 20-mL ramp distensions were completed and UES cross-sectional area (CSA) and intra-balloon pressure (IBP) were evaluated. At 12-mL balloon volume, subjects completed dry, 5- and 10-mL liquid swallows and extent (mm) and duration (s) of UES opening and minimum IBP (mmHg) were analyzed across swallows. KEY RESULTS: Thirteen subjects completed the study protocol. A significant change in UES CSA (P < .001) and IBP (P < .000) was observed during 20-mL distension. UES CSA increased up to 10-mL distension (P < .001), from which point IBP raised significantly (P = 0.004). There were significant changes in UES diameter (mm) (P < .000) and minimum IBP (mmHg) (P < .000) during swallowing events. Resting UES diameter (4.9 mm; IQR 0.02) and minimum IBP (18.8 mmHg; IQR 2.64) changed significantly during dry (9.6 mm; IQR 1.3: P < .001) (3.6 mmHg; IQR 4.1: P = 0.002); 5 mL (8.61 mm; IQR 2.7: P < .001) (4.8 mmHg; IQR 5.7: P < .001) and 10-mL swallows (8.3 mm; IQR 1.6: P < 0.001) (3 mmHg; 4.6: P < .001). Median duration of UES opening was 0.5 s across dry and liquid swallows (P = 0.91). Color contour plots of EndoFLIP(®) data capture novel information regarding pharyngo-esophageal events during swallowing. CONCLUSIONS & INFERENCES: Authors obtained three different types of quantitative data (CSA, IBP, and timing) regarding UES distensibility and UES opening patterns during swallowing in healthy adults using only one device (EndoFLIP(®)). This new measure of swallowing offers fresh information regarding UES dynamics which may ultimately improve patient care.

A new evaluation of the upper esophageal sphincter using the functional lumen imaging probe: a preliminary report.

Objective and reliable evaluation of upper esophageal sphincter (UES) opening during swallowing based on videofluoroscopy and pharyngeal manometry challenges dysphagia clinicians. The functional lumen imaging probe (FLIP) is a portable tool based on impedance planimetry originally designed to measure esophogastric junction compliance. It is hypothesized that FLIP can evaluate UES distensibility, and can provide UES diameter and pressure measurements at rest, during swallowing, and during voluntary maneuvers. Eleven healthy adult subjects consented to FLIP evaluation. The probe was inserted transorally, and the balloon was positioned across the UES. Two 20-mL ramp distensions were completed. Changes in UES diameter and intraballoon pressure were measured during dry and 5-mL liquid swallows, and during voluntary swallow postures and maneuvers employed in clinical practice. The protocol was completed by 10 of 11 healthy subjects. Mean intraballoon pressure increased throughout 5-mL (5.8 mmHg; -4.5-18.6 mmHg), 10-mL (8.7 mmHg; 2.3-28.5 mmHg), 15-mL (17.3 mmHg; 9.5-34.8 mmHg), and 20-mL (31.2 mmHg; 16-46.3 mmHg) balloon volumes. Mean resting UES diameter (4.9 mm) increased during dry swallows (9.2 mm) and 5-mL liquid swallows (7.7 mm). Mean UES diameter increased during 5-mL liquid swallows with head turn to right (8.1 mm) and left (8.3 mm), chin tuck (8.4 mm), effortful swallow (8.5 mm), Mendelsohn maneuver (8.1 mm), and supraglottic swallow (7.8 mm). FLIP was safely inserted and distended in the UES, and provided useful quantitative data regarding UES distensibility and UES diameter changes during swallowing maneuvers. Further research is being conducted to explore the role of FLIP in UES evaluation.

An impedance-manometry based method for non-radiological detection of pharyngeal postswallow residue.

BACKGROUND: Postswallow residue is indicative of impaired pharyngeal bolus clearance. The integrated nadir impedance to impedance ratio (iZn/Z) is a novel functional variable that can be derived using automated impedance manometry (AIM). In this study, the postswallow pharyngeal iZn/Z was evaluated as a potential correlated postswallow residue and therefore predictor of ineffective swallowing. METHODS: Optimal iZn/Z criteria were determine using a database of 50 randomly selected bolus swallows recorded with impedance, manometry, and videofluoroscopy. The iZn/Z was derived for a region of interest (ROI), spanning the mid-point of the pharyngeal stripping wave to the upper esophageal sphincter proximal margin, and from 0.25 to 1.25 s after the peak of the pharyngeal stripping wave. Videofluorscopy was scored by four experts using a six-point bolus residue scale (BRS) score. Optimized criteria for iZn/Z were then applied to a much larger database of 225 swallows scored for residue by one expert observer. KEY RESULTS: Among individual database, swallows iZn/Z was significantly correlated with average expert BRS score (r = 0.748, P < 0.0001). An iZn/Z of ≥ 500 was optimally predictive of swallows with residue defined by a BRS score of 4 or more. Within the larger cohort, iZn/Z was higher in dysphagia patient swallows compared with controls [2 (1, 4) vs 1 (1, 3), P < 0.005] and swallows with an iZn/Z ≥ 500 had higher bolus residue scores [4 (1, 6) vs 2 (1, 4), P < 0.001]. CONCLUSIONS & INFERENCES: The AIM derived iZn/Z is an easily determined objective non-radiological marker of clinically relevant postswallow residue and therefore has potential diagnostic relevance as a predictor of ineffective swallowing.

Effect of buspirone, a 5-HT1A receptor agonist, on esophageal motility in healthy volunteers.

There are limited data concerning the effects of 5-HT(1A) receptor activation on esophageal motility. Sumatriptan, a 5-HT(1A) receptor agonist, was recently reported to enhance esophageal peristalsis after intravenous administration. Buspirone, an orally available 5-HT(1A) receptor agonist, was shown to modulate gastroduodenal motor function. Our aim was to evaluate the effect of buspirone on esophageal motility of healthy volunteers. On two separate visits, 20 healthy volunteers aged 21-29 years (nine women) underwent esophageal manometry before and 10, 30, and 60 minutes after the administration of buspirone 20-mg or placebo capsule, according to a double-blind crossover design. At each time point, we compared buspirone and placebo effects on: resting pressure of the lower esophageal sphincter (LES); residual pressure and duration of LES relaxation; amplitude, duration, and onset velocity of esophageal body contractions, during 10 swallows of 5 mL of water. Significant analysis of variance differences (P < 0.05) are presented as mean ± standard deviation. Buspirone significantly increased mean distal esophageal wave amplitude (151 vs. 87 mmHg, P < 0.05) and duration (6.1 vs. 4.2 seconds, P < 0.05). Similarly, buspirone significantly increased mean LES resting pressure (26 vs. 21 mmHg, P < 0.05) and mean residual LES pressure (7.9 vs. 2 mmHg, P < 0.05), whereas reduced mean LES relaxation duration (7.2 vs. 8.0 seconds, P < 0.05) and mean distal onset velocity (7.6 vs. 14.7 cm/second, P < 0.05). Buspirone enhances esophageal peristalsis and LES function in healthy volunteers. Further study is warranted on the effects of buspirone on esophageal function and symptoms in patients with ineffective esophageal motility.