Search

The use of ultrasound as an adjunct to clinical swallowing evaluation provides quantitative physiological and morphological data. As a low-risk procedure, ultrasound imaging can be performed outside of a medical setting. This is particularly important for patients living in rural areas with restricted access to a hospital. Technical advances have produced pocket-sized ultrasound technology that is more affordable, and therefore within the fiscal reach of most allied health services.To explore the validity and reliability of pocket-sized ultrasound technology in dysphagia assessment.Data were acquired from 43 patients with dysphagia using the Clarius ultrasound device. Ultrasound and videofluoroscopic measures of hyoid and laryngeal displacement during liquid and puree swallowing were collected concurrently to quantify correlation and agreement between identical measures derived from the two instruments. Reliability of ultrasound was assessed for measures of hyoid and laryngeal displacement, tongue thickness, and size of the submental muscles in eight patients. Reliability was evaluated for the entire process of data acquisition including scanning and online measurement using an iPad in a clinical setting and for offline measurement on a computer screen to explore environmental influences on reliability.Results revealed poor correlation between the measures of interest across instruments. Reliability of the entire process of data acquisition in a clinical setting was insufficient while reliability was more promising for offline measurements.The clinical use of pocket-sized ultrasound devices, such as the Clarius system, for swallowing evaluation is not indicated at this time. Enhanced validity and reliability of the entire process of data acquisition are needed prior to clinical translation of such technology.What is already known on the subject The use of ultrasound allows for radiation-free, non-invasive swallowing assessment. Some data suggest that ultrasound is valid and reliable in the evaluation of swallowing using standard-sized equipment. Insufficient validity and reliability have been reported for pocket-sized ultrasound technology in the assessment of healthy swallowing. What this paper adds to existing knowledge This research is the first to provide validity and reliability data of the pocket-sized Clarius technology in the evaluation of swallowing in patients with dysphagia. Insufficient validity and reliability of online data acquisition in a clinical environment were found. Reliability for offline measurement was more promising. What are the potential or actual clinical implications of this work? The clinical use of pocket-sized ultrasound devices, such as the Clarius system, for swallowing assessment is not indicated at this time.

Use of topical nasal anesthetic (TNA) is common in high-resolution impedance manometry (HRIM). This study investigated the effect of TNA on swallowing and procedure tolerability during HRIM with a 4.2-mm catheter, a more commonly used catheter size with impedance capabilities.Randomised experimental study with blinding of participants.Twenty healthy participants (mean age = 33 years, 16 female) were randomized to undergo HRIM using the ManoScan™ ESO Z 4.2-mm catheter twice, 1 week apart, under two conditions: with TNA (viscous lidocaine) and with placebo. Analyses included esophageal data of three saliva, three saline (5 mL), and three bread swallows (2 cm × 2 cm) performed while reclined 45°, and pharyngeal data under the same conditions while seated upright. Pharyngeal and upper esophageal sphincter (UES) HRIM parameters were analyzed using the Swallow Gateway analysis platform. Visual analogue scale (VAS) scores rating procedural comfort were analyzed.There were no significant physiological differences in pharyngeal and UES parameters between conditions. There were also no significant differences in VAS scores under placebo (mean = 54.8, standard deviation (SD) = 19.3) and TNA (mean = 60.0, SD = 21.9) (t[19] = -0.9, P = .4) conditions; however, there was a significant difference in the first versus second session (t[19]) = 5.1, P .05).TNA did not improve comfort, but it also did not significantly affect swallowing behavior. There was, however, a practice effect regardless of TNA use with improved tolerance of the 4.2-mm catheter and likely more natural swallowing behavior during the second session of HRIM.3 Laryngoscope, 132:2124-2131, 2022.

Chronic traumatic encephalopathy (CTE) is a neuropathological diagnosis defined by a unique pattern of hyperphosphorylated tau (p-tau) accumulation that begins in neocortical regions of the brain. It is associated with a range of neuropsychological symptoms, but a definitive diagnosis can only be made by postmortem brain examination. In 2018, we instituted CTE screening for all autopsy brains as part of our routine departmental protocol by performing p-tau immunohistochemistry on a restricted set of 3 neocortical blocks (frontal, temporal, and parietal). This strategy allowed us to identify 4 cases of low-stage CTE from 180 consecutive autopsies. Two of the 4 cases had a documented history of brain injury; for the remaining 2 cases, there was a long history of treatment-resistant tonic/clonic epilepsy suggesting that undocumented brain injuries may have occurred. Our experience indicates that 3-block CTE screening is useful in identifying CTE in routine practice. The results of this study further support the association between prior head injuries and CTE and demonstrate that, albeit uncommon, CTE does occur in the general population. Our findings suggest that p-tau screening should be routinely pursued in brain autopsy, particularly where there is a documented or likely history of traumatic brain injury.

Swallowing is a vital function that serves to safely transport food and fluid to the stomach, while simultaneously protecting our airways. Evaluation of swallowing is important for the diagnosis and rehabilitation of individuals with dysphagia, a disorder of swallowing. Flexible high-density surface electromyography (HD sEMG) arrays were designed and fabricated to span the floor of mouth and neck muscles. These arrays were applied on 6 healthy participants over duplicate recording sessions. During each recording session, participants performed three different swallowing motor tasks. The HD sEMG signals were filtered and tasks extracted. For each task, the RMS amplitude was computed, visualized, and compared. Dynamic motor coordination was evident in the filtered signals traces, with different electrode locations showing unique temporal activations. The 2D topographical maps allowed the location of different RMS intensities to be visualized, revealing qualitatively similar patterns across participants and tasks. These motor task trends were also seen within RMS quantifications. The RMS metric across all participants identified significant differences between non-effortful 3 ml and effortful 3 ml swallow tasks ( p=0.006) and there was a minimal variation of 3.1±1.9 μV RMS for repeated recording sessions by each participant. The HD-sEMG array successfully recorded differences in muscle activations during swallowing and was able to discern between two different motor tasks. The arrays offers a spatially detailed non-invasive assessment of the neuromuscular performance of swallowing. Clinical Relevance- The utility of HD-sEMG arrays for evaluation of the muscles involved in swallowing could enable diagnosis and rehabilitation of individuals with dysphagia.

To identify and characterize subgroups of stroke patients with clinical signs of dysphagia, based on swallowing-related strength and skill impairments of the submental muscle group.Prospective observational study.Inpatient rehabilitation centers and community dwellings.Individuals (N=114), including stroke patients with dysphagia (n=55) and 2 control groups including myopathic patients with dysphagia (n=19) and healthy volunteers (n=40) were included in this study.Not applicable.Novel clinical assessment of strength (force generation) and skill (spatial and temporal precision of muscle activation) of the submental muscle group during swallowing and nonswallowing behaviors, using surface electromyography and dynamometry.Hierarchical cluster analysis revealed 4 clusters, which could be broadly characterized as cluster 1: intact strength and skill, cluster 2: poor strength and poor nonswallowing skill, cluster 3: poor strength, and cluster 4: poor strength and poor swallowing skill. Membership in cluster was significantly associated with medical diagnosis (P.001). The majority of healthy and myopathic participants were assigned to clusters 1 and 3, respectively, whereas stroke patients were found in all 4 clusters. Skill outcome measures were more predictive of cluster assignment than strength measures.Although healthy and myopathic participants demonstrated predominantly homogeneous swallowing patterns of submental muscle function within their etiology, several subgroups were identified within stroke, possibly reflecting different subtypes of swallowing function. Future research should focus on the nature and rehabilitation needs of these subtypes. Assessment of skill in swallowing may be an important but overlooked aspect of rehabilitation.

The development of highly productive, genetically stable manufacturing cell lines is on the critical path to IND filing for protein‐based biologic drugs. Here, we describe the Leap‐In Transposase® platform, a novel transposon‐based mammalian (e.g., Chinese hamster ovary) cell line development system that produces high‐titer stable pools with productivity and product quality attributes that are highly comparable to clones that are subsequently derived therefrom. The productivity distributions of clones are strongly biased toward high producers, and genetic and expression stability is consistently high. By avoiding the poor integration rates, concatemer formation, detrimental transgene recombination, low average expression level, unpredictable product quality, and inconsistent genetic stability characteristic of nonhomologous recombination methods, Leap‐In provides several opportunities to de‐risk programs early and reduce timelines and resources., Assessment of integrated copy numbers by ddPCR and productivity assessments from representative production cultures demonstrate that >90% of the clones established by Leap–In transposons maintain the To productivity and copy number levels

Background The Test of Masticating and Swallowing Solids (TOMASS) is an international standardized swallowing assessment tool. However, its psychometric characteristics have not been analysed in patients with dysphagia. Aims To analyse TOMASS's (1) inter- and intra-rater reliability in a clinical population of patients with dysphagia, (2) known-group validity, (3) concurrent validity and (4) correlation with meal duration. Methods & procedures Two age- and gender-matched groups of 39 participants each were recruited: A group of patients with dysphagia and a control group with no history of dysphagia. The TOMASS was carried out in both populations, video-recorded and scored offline by two speech and language therapists (SLT 1 and SLT 2) (inter-rater reliability) and twice by the same SLT (intra-rater reliability). In the clinical group, the TOMASS was carried out three times: (1) to verify understanding of the required tasks, (2) performed concurrently during fibreoptic endoscopic evaluation of swallowing (FEES) to assess validity and (3) during clinical assessment to assess reliability. TOMASS under endoscopic control was recorded and the number of white-out events was counted to compare with the number of observed swallows per cracker during standard TOMASS as a measure of concurrent validity. As additional measures of TOMASS validity, oral dental status, classified as 'functional' or 'partially functional', and duration of a standard meal were assessed by an SLT (SLT 1 or SLT 2), and then correlated with TOMASS. Outcome & results TOMASS's inter- and intra-rater reliability were high (intraclass correlation coefficient (ICC) > 0.95) in both the clinical and the control groups. The number of masticatory cycles (p = 0.020), swallows (p = 0.013) and total time (p = 0.003) of TOMASS were significantly lower in the control group than in the clinical group. Patients with 'partially functional' oral dental status showed a significantly higher number of masticatory cycles per cracker and a longer duration of ingestion than patients with a 'functional' one. Concurrent validity suggested a substantial agreement between TOMASS and FEES in defining the number of swallows per cracker. The mean difference of the two measures was -0.02 (95% confidence interval (CI) = -1.7 to 1.2). Meal duration significantly correlated with the 'number of swallows per cracker' (r = 0.49; p = 0.002) and 'total time' (r = 0.41; p = 0.011). Conclusions & implications Preliminary psychometric analysis of TOMASS in a clinical sample of outpatients with dysphagia suggests that it is a reliable and valid (specifically related to the number of swallows per cracker) tool. TOMASS's application in clinical practice to quantitatively measure solid bolus ingestion is recommended. What this paper adds What is already known on the subject The Test of Masticating and Swallowing Solids (TOMASS) is an international standardized swallowing assessment tool to evaluate oral preparation and oral phase of solids. The TOMASS' reliability and validity were tested on healthy subjects and normative data were gained. What this paper adds to existing knowledge The study provides the first data on the validity and reliability of the TOMASS in a clinical population. The TOMASS was proved to be a reliable and valid tool also in patients with dysphagia and to distinguish between patients with dysphagia and healthy subjects. What are the potential or actual clinical implications of this work? The use of the TOMASS in clinical practice is recommended as a valid and reliable tool to quantitatively measure the ingestion of solid in patients with dysphagia.

Adequate hyoid and laryngeal displacement facilitate safe and efficient swallowing. Although videofluoroscopy is commonly used for assessment of this biomechanical event, ultrasound provides benefits as a radiation-free modality for this purpose. This study investigated validity of a pocket-sized ultrasound system (Clarius™) in the assessment of hyoid and laryngeal excursion. Hyoid excursion and thyrohyoid approximation were concurrently assessed in 20 healthy adults using ultrasound and videofluoroscopy during saliva, liquid, and puree swallowing. Correlation analyses were performed to evaluate validity. There was a strong and moderate positive association between ultrasound and videofluoroscopic measurements of hyoid excursion during dry and liquid swallowing, respectively. No evidence for a significant association was found for ultrasound and videofluoroscopic measurements of hyoid excursion for puree swallowing and of thyrohyoid approximation for any bolus type. Further work towards improved validity is necessary prior to clinical transfer of the pocket-sized Clarius™ system in clinical swallowing assessment.

Background Parkinson’s disease (PD) is a neurodegenerative disorder characterized by a combination of motor and non-motor dysfunction. Dysphagia is a common symptom in PD, though it is still too frequently underdiagnosed. Consensus is lacking on screening, diagnosis, and prognosis of dysphagia in PD. Objective To systematically review the literature and to define consensus statements on the screening and the diagnosis of dysphagia in PD, as well as on the impact of dysphagia on the prognosis and quality of life (QoL) of PD patients. Methods A multinational group of experts in the field of neurogenic dysphagia and/or PD conducted a systematic revision of the literature published since January 1990 to February 2021 and reported the results according to PRISMA guidelines. The output of the research was then analyzed and discussed in a consensus conference convened in Pavia, Italy, where the consensus statements were drafted. The final version of statements was subsequently achieved by e-mail consensus. Results Eighty-five papers were used to inform the Panel’s statements even though most of them were of Class IV quality. The statements tackled four main areas: (1) screening of dysphagia: timing and tools; (2) diagnosis of dysphagia: clinical and instrumental detection, severity assessment; (3) dysphagia and QoL: impact and assessment; (4) prognostic value of dysphagia; impact on the outcome and role of associated conditions. Conclusions The statements elaborated by the Consensus Panel provide a framework to guide the neurologist in the timely detection and accurate diagnosis of dysphagia in PD.

Sleep is associated with stages of relative cortical quiescence, enabling evaluation of swallowing under periods of reduced consciousness and, hence, absent volition. The aim of this study was to measure and characterize changes in the characteristics of pharyngeal swallows during sleep and wake using high-resolution manometry (HRM). Pharyngeal swallows were recorded with a ManoScan™ HRM in wake-upright, wake-supine, and sleep conditions in 20 healthy participants (mean 27 years; range 21–52). Velopharyngeal and hypopharyngeal segments were analysed separately. Contractile integral, mean peak pressure, inverse velocity of superior-to-inferior pharyngeal pressure, and time to first maximum pressure were analysed with custom-designed software. The supine-wake condition was compared to both upright-wake and sleep conditions using linear mixed effects models. No significant differences were found between supine-wake and upright-wake conditions on any measures. The mean peak pharyngeal pressure was lower during sleep than during the supine-wake condition for both the velopharynx (− 60 mmHg, standard error [SE] = 11, p

This study evaluated the effects of cerebellar tDCS on motor learning for swallowing.In a double-blind RCT, 39 healthy adults received either sham, anodal tDCS, or cathodal tDCS in two sessions on two consecutive days. Following 20 min cerebellar tDCS (2 mA) or sham, they underwent swallowing skill training that targeted control of timing and magnitude of submental muscle activation during swallowing. Linear mixed models were used to identify the effects of stimulation on timing and magnitude accuracy as measured by the change in task performance for each training session, and for skill retention on days 3 and 10 post-intervention.Only the sham group had a reduced temporal error from baseline to all following timepoints. When compared to error changes in the sham group, changes from baseline in temporal errors were higher at all timepoints post-intervention for the anodal group, and higher at both retention assessments for the cathodal group. Amplitude errors were smaller for all conditions at all timepoints post-intervention compared to baseline.Cerebellar tDCS was found to inhibit temporal aspects of motor skill learning in swallowing. For the tDCS parameters used in this study, there is no support for use of tDCS to facilitate swallowing rehabilitation.

Supratentorial structures are known to be involved in the neural control of swallowing, thus the potential for volitional manipulation of pharyngeal swallowing is of rehabilitative interest. The extent of volitional control of the upper oesophageal sphincter (UOS) during swallowing remains unclear. Prior research has shown that the UOS opening duration can be volitionally prolonged during execution of the Mendelsohn manoeuvre, which does not change the UOS opening time in isolation but the swallowing response in its entirety. This study explored the capacity of healthy adults to increase the period of pressure drop in the region of the UOS (UOS-Pdrop) during swallowing, through volitional UOS pressure modulation in the absence of altered pharyngeal pressure. The period of UOS-Pdrop was used as a proxy of UOS opening duration that is associated with a pressure decrease at the region of the UOS. Six healthy adults were seen 45 min daily for 2 weeks and for one follow-up session. During training, high-resolution manometry contour plots were provided for visual biofeedback. Participants were asked to maximally prolong the blue period on the monitor (period of UOS-Pdrop) without altering swallowing biomechanics. Performance was assessed prior to training start and following training. There was evidence within the first session for task-specific volitional prolongation of the period of UOS-Pdrop during swallowing with biofeedback; however, performance was not enhanced with further training. This may suggest that the amount to which the period of UOS-Pdrop may be prolonged is restricted in healthy individuals. The findings of this study indicate a potential of healthy adults to volitionally prolong UOS opening duration as measured by the period of pressure drop at the region of the UOS. Further research is indicated to evaluate purposeful pressure modulation intra-swallow in patient populations with UOS dysfunction to clarify if the specificity of behavioural treatment may be increased.

This preliminary, exploratory study evaluated the acoustic intensity of effective and ineffective clearance of penetrated and aspirated material from the laryngeal vestibule in patients with dysphagia.A lapel microphone was attached anterior to participants' tragus and recorded coughing in decibels during their videofluoroscopic swallowing studies (VFSS).Eighty-eight patients were recruited. Thirteen patients, with visible airway invasion and coughing were included in the final analysis. No coughs were effective at expelling aspirated material from the airway (No coughs were effective at expelling aspirated material from the airway. Some coughs effectively expelled penetrated material from the airway. However, the relationship between acoustic intensity and cough effectiveness is unclear due to the limited number of observations. Given that perceptual evaluation of coughing is widely used in dysphagia clinical practice to determine cough effectiveness, this is an important area for future research.

Extracellular vesicles (EVs) play key roles in glioblastoma (GBM, astrocytoma grade IV) biology and are novel sources of biomarkers. EVs released from GBM tumors can cross the blood-brain-barrier into the periphery carrying GBM molecules, including small non-coding RNA (sncRNA). Biomarkers cargoed in circulating EVs have shown great promise for assessing the molecular state of brain tumors in situ. Neurosurgical aspirate fluids captured during tumor resections are a rich source of GBM-EVs isolated directly from tumor microenvironments. Using density gradient ultracentrifugation, EVs were purified from cavitron ultrasonic surgical aspirate (CUSA) washings from GBM (n = 12) and astrocytoma II-III (GII-III, n = 5) surgeries. The sncRNA contents of surgically captured EVs were profiled using the Illumina&reg, NextSeqTM 500 NGS System. Differential expression analysis identified 27 miRNA and 10 piRNA species in GBM relative to GII-III CUSA-EVs. Resolved CUSA-EV sncRNAs could discriminate serum-EV sncRNA profiles from GBM and GII-III patients and healthy controls and 14 miRNAs (including miR-486-3p and miR-106b-3p) and cancer-associated piRNAs (piR_016658, _016659, _020829 and _204090) were also significantly expressed in serum-EVs. Circulating EV markers that correlate with histological, neuroradiographic and clinical parameters will provide objective measures of tumor activity and improve the accuracy of GBM tumor surveillance.

Improving outcomes for diffuse glioma patients requires methods that can accurately and sensitively monitor tumour activity and treatment response. Extracellular vesicles (EV) are membranous nanoparticles that can traverse the blood&ndash, brain-barrier, carrying oncogenic molecules into the circulation. Measuring clinically relevant glioma biomarkers cargoed in circulating EVs could revolutionise how glioma patients are managed. Despite their suitability for biomarker discovery, the co-isolation of highly abundant complex blood proteins has hindered comprehensive proteomic studies of circulating-EVs. Plasma-EVs isolated from pre-operative glioma grade II&ndash, IV patients (n = 41) and controls (n = 11) were sequenced by Sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) and data extraction was performed by aligning against a custom 8662-protein library. Overall, 4054 proteins were measured in plasma-EVs. Differentially expressed proteins and putative circulating-EV markers were identified (adj. p-value &lt, 0.05), including those reported in previous in-vitro and ex-vivo glioma-EV studies. Principal component analysis showed that plasma-EV protein profiles clustered according to glioma histological-subtype and grade, and plasma-EVs resampled from patients with recurrent tumour progression grouped with more aggressive glioma samples. The extensive plasma-EV proteome profiles achieved here highlight the potential for SWATH-MS to define circulating-EV biomarkers for objective blood-based measurements of glioma activity that could serve as ideal surrogate endpoints to assess tumour progression and allow more dynamic, patient-centred treatment protocols.

The effortful swallowing technique aims to compensate for or rehabilitate impaired swallowing by using maximal volitional effort to behaviorally modify aspects of swallowing physiology. Given that swallowing is a submaximal task, swallowing at submaximal levels has recently been suggested as a more task-specific therapeutic technique. The aim of this study was to investigate differences in muscle activity during minimum, regular, and maximum effort swallowing of different boluses and across different ages, with the goal of characterizing the task specificity of minimum effort and maximum effort swallowing. Forty-three healthy adults (22 female) representing four age groups (20–39, 40–59, 60–79, and 80 + years) participated in the study. They were verbally cued to swallow saliva and 5 mL water boluses using participant-determined minimum, regular, and maximum levels of effort, in randomized order. sEMG peak amplitude and duration of each swallow were measured. Linear mixed effects analyses demonstrated that compared to regular effort swallowing, maximum effort swallowing resulted in increased sEMG amplitude (p

Purpose This study evaluated the safety and efficacy of a sensory stimulation protocol that was designed to modulate citric acid cough thresholds as a potential treatment for silent aspiration. Method Healthy adults ( n = 24) were randomly assigned to one of three sensory stimulation groups: (a) high-intensity ultrasonically nebulized distilled water (UNDW) inhalations (1.6 ml/min); (b) low-intensity UNDW inhalations (0.5 ml/min); and (3) control, 0.9% saline inhalations (1.6 ml/min). Sensory stimulation was delivered once a day, for 4 consecutive days. Citric acid cough thresholds were determined at baseline, Day 3, and Day 5 to evaluate changes in cough sensitivity. Spirometry was undertaken before, during, and after each sensory stimulation session to monitor for bronchoconstriction. Results No participant showed evidence of bronchoconstriction during the sensory stimulation protocol. There was an interaction effect between day and group on suppressed cough thresholds, χ 2 (4) = 11.32, p = .02. When compared to the control group, there was a decrease in citric acid cough thresholds across Days 1–5 in the high-intensity (−1.8 doubling concentrations, 95% confidence interval [−2.88, −0.72], p = .01) and low-intensity (−1.3 doubling concentrations, 95% confidence interval [−2.4, −0.2], p = .03) UNDW inhalation groups, representing a sensitization effect of UNDW inhalations on cough sensitivity. Conclusions The UNDW sensory stimulation protocol was safe in healthy adults. The findings provide preliminary evidence that UNDW inhalations sensitize laryngeal afferents related to citric acid–induced cough induction. The therapeutic potential of the UNDW sensory stimulation protocol will be explored in patients with reduced cough sensitivity who are at risk of silent aspiration and aspiration pneumonia. Plain Language Summary This study explored the safety and efficacy of a sensory stimulation protocol that was designed to modulate cough sensitivity as a potential treatment for silent aspiration. The study revealed that inhalations of nebulized distilled water were safe and increased cough sensitivity, when compared to control saline inhalations.

Resting pressure at the upper oesophageal sphincter (UOS) has been reported to be susceptible to factors such as emotional stress or respiration. This exploratory study investigated the potential for behavioural modulation of UOS resting pressure in healthy adults to increase our understanding of volitional control of UOS pressure, and the potential development of rehabilitation approaches. Six healthy adults were seen one hour daily for two weeks (10 days) and for one post-training session after a training break of two weeks. Manipulation of UOS resting pressure was practised during a protocol of alternating increased and decreased pressure. A high-resolution manometry contour plot was used as a biofeedback modality. Participants were asked to explore how to achieve warmer and cooler colours (pressure increase and decrease, respectively) at the UOS resting pressure band, without changing head position or manipulating activity of other muscles. Performance was analysed prior to training start and following daily training. Participants were able to increase resting pressure following one week of practice; however, there was no evidence for purposeful pressure decrease. The increased resting pressure achieved by participants indicates a capacity for purposeful pressure modulation given intensive biofeedback training. The lack of volitional reduction in pressure may be explained by sustained pressure generation due to the intrinsic muscular characteristics of the UOS and a flooring effect in healthy subjects, in whom physiology mandates a minimum degree of resting pressure to fulfil the barrier function. Distention caused by the presence of the intraluminal catheter cannot be ruled out.

The Test of Masticating and Swallowing Solids (TOMASS) is a validated assessment tool measuring the efficiency of solid bolus intake by four quantitative parameters: discrete bites, masticatory cycles, swallows and time to ingest a single cracker. A normative database for adults (20-80+ years) has previously been established. The objective of this study was to investigate the applicability and reliability of the TOMASS in children and adolescents (TOMASS-C) and to establish the normative database for this younger population. We collected data from 638 participants (male: 311, female: 327) in five age groups (4-18 years) with five different but very similar test crackers in four countries. Significant effects of bolus type (cracker), age group and gender on the TOMASS parameters were identified, requiring stratification of the TOMASS-C database by these variables. Intra-rater reliability was excellent (ICC > 0.94) for all parameters; inter-rater reliability was moderate for "number of swallows" (ICC = 0.54), good for "bites" (ICC = 0.78) and "time" (ICC = 0.82), and excellent for "masticatory cycles" (ICC = 0.96). The "Test of Masticating and Swallowing Solids in Children (TOMASS-C)" was identified to be a reliable diagnostic tool for the comprehensive measurement of discrete oral stage components of solid bolus ingestion, standardised by a large normative database that covers age groups from preschoolers to young adults. While differences between gender groups were less pronounced than in the adult population, previous results relating to changes in masticatory and swallowing as a function of age are confirmed by our data.

Notable differences have been identified between low-resolution manometry (LRM) and high-resolution manometry (HRM) in normative data. This study aimed to investigate within-subject differences between unidirectional LRM and circumferential HRM solid-state measurement sensors in the pharyngoesophageal segment during swallowing. Ten healthy subjects (mean 26.9 years) were evaluated with both a 2.10 mm unidirectional catheter and a 2.75 mm circumferential catheter, with randomized order of catheter placement. Unidirectional measurements were made in four directions (posterior, anterior, right-lateral, left-lateral). Pressures and durations were analyzed to compare (1) posterior to anterior and lateral recordings and (2) posterior and average-LRM measures (C-LRM) to HRM measures at same anatomical location. No significant differences were found in any of the measures across the four radial directions. A lower amplitude was measured in C-LRM compared to HRM for pharyngeal sensors (LRM Sensor 1: − 39.7 mmHg; Sensor 2: − 61.4 mmHg). Compared with posterior-LRM, HRM recorded higher UES pressures (− 12.8 mmHg) and longer UES relaxation durations (− 0.31 s). This exploratory study is the first to compare within-subject pressures between unidirectional LRM and circumferential HRM. Substantial differences in pharyngeal manometric measures were found, particularly with regard to UES function. This is clinically important as manometry is uniquely able to evaluate UES function and clarify differential diagnoses in patients with dysphagia.

Background Clinical swallowing assessment is largely limited to qualitative assessment of behavioural observations. There are limited quantitative data that can be compared with a healthy population for identification of impairment. The Test of Masticating and Swallowing Solids (TOMASS) was developed as a quantitative assessment of solid bolus ingestion. Aims This research programme investigated test development indices and established normative data for the TOMASS to support translation to clinical dysphagia assessment. Methods & Procedures A total of 228 healthy adults (ages 20–80+ years) stratified by age and sex participated in one or more of four consecutive studies evaluating test–retest and interrater reliability and validity to instrumental assessment. For each study the test required participants to ingest a commercially available cracker with instructions to ‘eat this as quickly as is comfortably possible’. Further averaged measures were derived including the number of masticatory cycles and swallows per bite, and time per bite, masticatory cycle and swallow. Initial analyses identified significant differences on salient measures between two commercially available crackers that are nearly identical in shape, size and ingredients, suggesting the need for separate normative samples for specific regional products. Additional analyses on a single cracker identified that the TOMASS was sensitive at detecting changes in performance based on age and sex. Test–retest reliability across days and interrater reliability between clinicians was high, as was validation of observational measures to instrumental correlates of the same behaviours. Therefore, normative data are provided for the TOMASS from a minimum of 80 healthy controls, stratified by age and sex, for each of seven commercially available crackers from broad regions worldwide. Outcomes & Results Analyses on a single cracker identified Arnott's Salada, and that TOMASS measures were sensitive for detecting changes in performance based on age and sex. Interrater and test–retest reliability across days were high, as was validation of observational measures to instrumental correlates of the same behaviours. Significant differences were identified between two commercially available crackers, nearly identical in shape, size and ingredients, thus normative samples for specific regional products were required. Normative data were then acquired for the TOMASS from a minimum of 80 healthy controls, stratified by age and sex, for each of seven commercially available crackers from broad regions worldwide. Conclusions & Implications The TOMASS is presented as a valid, reliable and broadly normed clinical assessment of solid bolus ingestion. Clinical application may help identify dysphagic patients at bedside and provide a non-invasive, but sensitive, measure of functional change in swallowing.

The aim of this study was to investigate whether diurnal variation in cough reflex sensitivity exists in healthy young adults when a tidal-breathing method is used. Fifty-three participants (19-37 years) underwent cough reflex testing on two occasions: once in the morning (between 9 am - midday) and once in the afternoon (between 2-5 pm). The order of testing was counter-balanced. Within each assessment, participants inhaled successively higher citric acid concentrations via a facemask, with saline solution randomly interspersed to control for a placebo response. The lowest concentration that elicited a reflexive cough response was recorded. Morning cough thresholds (mean=0.6mol/L) were not different from afternoon cough thresholds (mean=0.6mol/L), p=0.16, T=101, r=-0.14. We found no evidence of diurnal variability in cough reflex testing. There was, however, an order effect irrespective of time of day, confirming that healthy participants are able to volitionally modulate their cough response.

Background Corticobulbar symptoms have been reported in all stages of Huntington's disease (HD); aspiration pneumonia associated with swallowing impairment has been identified as the most common cause of death. Whilst recent research has described positive effects of corticobulbar rehabilitation in other neurodegenerative conditions, it is unclear if this is similarly effective in HD. Preliminary evidence in corticospinal rehabilitation has revealed physical therapy and exercise could be beneficial for individuals with HD. Objective This systematic review will explore the literature relative to rehabilitation of corticobulbar symptoms in adults with HD. Methods Two investigators independently searched relevant electronic databases for literature related to corticobulbar rehabilitation in HD, published in English until October 2019. Included studies were critically appraised using the Oxford Centre for Evidence-based Medicine Levels of Evidence, Cochrane Risk of Bias Tool and Scottish Intercollegiate Guidelines Network checklists. Study outcomes included measurements of function, quality of life or neuromuscular physiology. Results Seventy-seven publications were screened with eight studies meeting the inclusion criteria - two randomised control trials and six intervention studies. Validated and objective outcome measures of corticobulbar symptoms were infrequently used. There was a high risk of bias identified in 7/8 studies. The data suggested positive clinical outcomes, no adverse effects and no deterioration observed across longitudinal studies. Conclusions This systematic review documented a lack of high-quality evidence to support the use of rehabilitation to treat corticobulbar symptoms in HD. However, the suggestion of potential positive effects based on available, albeit limited, studies provides justification for further research in this area.

Background: Regular moderate-to-vigorous-intensity physical activity results in health benefits in people with diabetes. No study has observed the moderate-to-vigorous-intensity physical activity typically performed by people with diabetes-related foot ulcers (DFU) in their everyday free-living environments. We observed the bouts, and accumulated time, spent doing moderate-to-vigorous-intensity physical activity in cases with DFU compared with diabetes-related peripheral neuropathy (DPN) and diabetes (DM) controls over a one-week period. Methods: This was a secondary analysis of a cross-sectional case-control study. Participants wore a multisensor device for >5 days (>22 hours per day). Primary outcomes included the number, duration (minutes) and intensity (metabolic equivalent tasks [METs]) of bouts of moderate-to-vigorous-intensity physical activity (defined as at least >3 METs for >10 consecutive minutes). Secondary outcomes included the total accumulated times spent doing moderate-to-vigorous-intensity physical activity (>3 METs) and doing sedentary-intensity activity (Results: Overall, 15 DM, 23 DPN, and 27 DFU participants were included. All groups recorded similar low median daily numbers (0.33, 0.29, 0.25 numbers, respectively), duration (15, 17, 14 minutes), and intensity of daily bouts of moderate-to-vigorous-intensity physical activity (4.1, 4.3, 3.9 METs) (all, P > .1). Median accumulated daily time spent doing moderate-to-vigorous-intensity physical activity was also similar (40, 37, 36 minutes; P > .8). Those with DFU had more mean accumulated daily time spent doing sedentary-intensity activity (796 minutes) compared to DPN (720 minutes; P < .05), but not compared to DM (728 minutes; P < .08). DFU subgroups with minor amputations had more median accumulated daily time spent doing moderate-to-vigorous-intensity physical activity (66, 28 minutes; P < .05) and less mean time doing sedentary-intensity activity (745, 837; P < .05) than those without amputations. Conclusions: People with DFU performed similar low numbers of daily bouts of moderate-to-vigorous-intensity physical activity to controls, but spend more time doing sedentary-intensity activities. Interventions that gradually increase the moderate-to-vigorous-intensity physical activity in people with DFU should be investigated.

OBJECTIVE To establish how oral bacteria are related to cough sensitivity and pneumonia in a clinical stroke population. BACKGROUND Stroke patients are at risk of colonisation by respiratory pathogens due, in part, to sudden discontinuation of effective oral hygiene. When combined with reduced cough reflex sensitivity, aspiration of contaminated oropharyngeal contents and can lead to pneumonia. Relationships between oral bacteria, cough sensitivity and pneumonia have not been established. MATERIALS AND METHODS A total of 102 patients with acute stroke underwent saliva sampling and cough reflex testing at admission to hospital, discharge and one month. A qPCR assay compared levels of bacteria in saliva. Pneumonia events were recorded. RESULTS Relative levels of bacteria were lowest at admission to hospital (6.04 × 10-6 ). There was a slight (non-significant) increase in bacterial levels at discharge (1.69 × 10-2 , P = .73). By one month, bacterial levels had significantly increased (9.17 × 10-2 ) relative to admission [P

Primary motor networks are known to be involved in the control of voluntary oral movements as well as the modulation of pharyngeal movements during experimentally controlled single swallows performed on command. The role of these networks in the more typical task of sequential swallowing remains unexplored. This study evaluated the hypothesis that experimental disruption of motor cortical activation would reduce the rate and regularity of repeatedly performed volitional or volitionally initiated motor tasks controlled by corticospinal (finger tapping) and corticobulbar (eyebrow movement, jaw opening, volitional sequential swallowing) motor systems, but would not influence a more reflexive corticobulbar task (reflexive sequential swallowing to pharyngeal water infusion). This premise was investigated in 24 healthy participants using two techniques: a dual task paradigm and a transcranial magnetic stimulation paradigm. Disruption effects were quantified by changes in rate and regularity of performance for each tested motor task. In summary, volitional motor tasks controlled by corticospinal motor networks (finger tapping) are more susceptible to behavioural and neurophysiological disruption than tasks controlled by cortiobulbar motor networks containing a reflexive component (both volitional and experimentally initiated consecutive swallowing). Purely volitional motor tasks controlled by the corticobulbar motor system (eyebrow raising or jaw opening) were affected in similar ways as the volitional corticospinal motor tasks. In summary, tasks involving sequential pharyngeal swallowing - whether volitionally or experimentally initiated - are largely robust against disruption of primary cortical motor networks, supporting a key role of medullary CPGs in the motor control of sequential pharyngeal swallowing.

Cough suppression is part of the pharmacodynamic profile of opioids. We investigated the impact of clinical doses of fentanyl on suppressing the cough reflex. Thirteen volunteers received 2 μg.kg(-1) of fentanyl in a divided administration protocol. Three minutes after each administration and at 10 min intervals during washout, suppressed cough reflex testing with nebulised citric acid was performed and compared with fentanyl effect-site concentration. Mean (SD) citric acid concentration provoking cough increased from 0.5 (0.28) mol.l(-1) at baseline to 1.2 (0.50) mol.l(-1) after 2 μg.kg(-1) of fentanyl (p = 0.01). Mean (SD) fentanyl effect-site concentration after the final dose of fentanyl was 1.89 (0.05) ng.ml(-1) . A strong positive correlation was found between suppressed cough reflex thresholds and fentanyl effect-site concentrations during both fentanyl administration and washout phases of the study (r(2) = 0.79, p = 0.01). The mean (SD) length of time for return of suppressed cough response was 44.6 (18.8) min. Clinically relevant doses of fentanyl produced cough reflex suppression in healthy volunteers.

A substantial pressure drift in high-resolution manometry (HRM) has been reported; however, fundamental questions remain regarding the origin and management of this drift. The aim of this study was to provide critical in-depth analyses of ManoScan(™) HRM drift in vitro and in vivo.A total of sixteen 15-min studies and twelve 5-h studies were performed in a water bath at 37 °C at 4.0 cm depth (2.9 mmHg) with ESO and ESO Z catheters. Six 5-h in vitro studies were performed similarly at a depth of 9.0 cm (6.6 mmHg). Eight 15-min studies and nine 8-h in vivo studies were performed with healthy participants. Two correction methods - thermal compensation (TC) and interpolated thermal compensation (ITC) - were tested.Overall pressure drift varied both between studies (p 0.01) and within sensors (p 0.01). Drift resulted from thermal shock, an initial pressure change at intubation, and baseline drift, a linear drift over time (R(2) 0.96). Contrary to previous reports, there was no correlation between drift and average (r = -0.02) or maximum pressure exposure (r = -0.05). Following data correction, ITC had the lowest median error but persisted with a maximum error of 2.5 mmHg (IQR = 3.0).The substantial drift in the ManoScan(™) HRM system is highly variable and not corrected via the standard operating instructions. ITC has superior performance but requires communication with the manufacturer to enable this option. This has a substantial impact on clinical diagnosis, utility of existing normative data, and future research of HRM.

This systematic review appraises and summaries methodology documented in studies using high resolution pharyngeal manometry (HRM) with and without impedance technology (HRIM) in adult populations. Four electronic databases CINAHL, EMBASE, MEDLINE, and Cochrane Library were searched up to, and including March 2017. Studies reporting pharyngeal HRM/HRIM for swallowing and/or phonatory assessment, published in peer-reviewed journals in English, German, or Spanish were assessed for the inclusion criteria. Of the selected studies, methodological aspects of data acquisition and analysis were extracted. Publications were graded based on their level of evidence and quality of methodological aspects was assessed. Sixty-two articles were identified eligible, from which 50 studies reported the use of HRM and 12 studies used HRIM. Of all included manuscripts, the majority utilized the ManoScan™ system (64.5%), a catheter diameter of 4.2 mm was most prevalently documented (30.6%). Most publications reported the application of topical anesthesia (53.2%). For data analysis in studies using HRM, software intrinsic to the recording system was reported most frequently (56%). A minority of the studies using HRM provided data about measurement reliability (10%). This is higher for studies using HRIM (50%). Considerable methodological variability exists regarding data acquisition and analysis in published studies using HRM/HRIM. Lacking reports of methodology make study replications difficult and reduce the comparability across studies. More data regarding the impact of individual methodological aspects on study outcomes are further required for the development of methodological recommendations.

Background The Test of Masticating and Swallowing Solids (TOMASS) has been developed to provide clinicians with objective data regarding the efficiency of oral phase function and solid bolus ingestion. Aims To determine if the TOMASS will detect changes in the oral phase of swallowing imposed by topical anaesthesia, thus providing validation of its clinical utility. Methods & procedures Per the standard protocol, 10 healthy participants ate one-quarter of an Arnotts SaladaTM biscuit. The number of bites per cracker, number of masticatory cycles, number of swallows and total time taken were recorded at baseline, following application of topical oral anaesthetic; this was additionally compared with a post-anaesthetic condition. Median and interquartile range (IQR) were calculated. Wilcoxon signed-rank tests were conducted to evaluate trial effect, and Friedman's tests were used to detect differences in the number of bites, number of swallows, number of chews and time taken to eat the crackers. Outcomes & results Results indicated that the number of both bites and swallows did not significantly change across conditions (χ²(2) = 0.105, p = 0.949, χ²(2) = 1.357, p = 0.507); however, the number of chews for the anaesthetic condition was significantly higher when compared with the baseline (p = 0.02) and post-anaesthesia conditions (p = 0.02). Further, the durations of ingestion in the anaesthetic condition were significantly longer than the baseline (p = 0.01) and post-anaesthesia (p = 0.01) conditions. Across all measures, there were no differences between baseline and post-anaesthesia conditions. Conclusions & implications Although further exploration is required, these early data suggest the TOMASS is a sensitive measure in the evaluation of the oral-phase preparation of solid textures.

Glioblastoma, WHO-grade IV glioma, carries a dismal prognosis owing to its infiltrative growth and limited treatment options. Glioblastoma-derived extracellular vesicles (EVs; 30-1000 nm membranous particles) influence the microenvironment to mediate tumor aggressiveness and carry oncogenic cargo across the blood-brain barrier into the circulation. As such, EVs are biomarker reservoirs with enormous potential for assessing glioblastoma tumors in situ. Neurosurgical aspirates are rich sources of EVs, isolated directly from glioma microenvironments. EV proteomes enriched from glioblastoma (n = 15) and glioma grade II-III (n = 7) aspirates are compared and 298 differentially-abundant proteins (p-value < 0.00496) are identified using quantitative LC-MS/MS. Along with previously reported glioblastoma-associated biomarkers, levels of all eight subunits of the key molecular chaperone, T-complex protein 1 Ring complex (TRiC), are higher in glioblastoma-EVs, including CCT2, CCT3, CCT5, CCT6A, CCT7, and TCP1 (p < 0.00496). Analogous increases in TRiC transcript levels and DNA copy numbers are detected in silico; CCT6A has the greatest induction of expression and amplification in glioblastoma and shows a negative association with survival (p = 0.006). CCT6A is co-localized with EGFR at 7p11.2, with a strong tendency for co-amplification (p < 0.001). Immunohistochemistry corroborates the CCT6A proteomics measurements and indicated a potential link between EGFR and CCT6A tissue expression. Putative EV-biomarkers described here should be further assessed in peripheral blood.

Cough reflex testing has been evaluated as a component of the clinical swallowing assessment as a means of identifying patients at risk of aspiration during swallowing. A previous study by our research group found good sensitivity and specificity of the cough reflex test for identifying patients at risk of aspiration post-stroke, yet its use did not decrease pneumonia rates, contrary to previous reports. The aim of this study was to expand on our earlier work by implementing a clinical management protocol incorporating cough reflex testing within the same healthcare setting and compare patient outcomes to those from the original study and to evaluate clinical outcomes in patients with acute stroke who were managed using the Dysphagia in Stroke Protocol (DiSP). Secondarily, to compare those outcomes to historical data prior to implementation of the DiSP. This clinical audit measured outcomes from 284 patients with acute stroke managed per the DiSP, which guides use of videofluoroscopic swallowing study and patient management based on clinical exam with cough reflex testing. Data from our previous trial were included for comparison of pre- and post-DiSP patient outcomes. Data collection took place between November 2012 and April 2016 at four urban hospitals within New Zealand. Following implementation of the DiSP, the rate of aspiration pneumonia (10%) was substantially lower than the pre-DiSP rate (28%), with no pneumonia readmissions within 3 months. Pneumonia-related mortality was unchanged. By 3 months, 81% of the patients were on a normal diet and 67% had returned home, compared to pre-DiSP outcomes of 55% and 55% respectively. Previous work has suggested that simply implementing cough reflex testing in dysphagia management may not be sufficient to improve patient outcomes. The present study adds to this picture by suggesting that the true variable of influence may be the way in which the results of the test are applied to patient care. There is a strong case to support the use of a structured protocol if cough reflex testing is to be implemented in clinical practice.

Diagnostic assessment of swallowing in routine clinical practice relies heavily on the long-standing techniques of videofluoroscopic swallowing study (VFSS) and videoendoscopic evaluation of swallowing (VEES). These complementary and sophisticated techniques provide a real-time visualization of biomechanical movements of the structures involved in swallowing and consequent effects on bolus flow. Despite the sophistication of this instrumentation, interpretation relies heavily on subjective clinical judgement and temporal resolution is limited, limitations that may influence patient management. Adjunctive diagnostic assessments may be utilized to compensate for the limitations posed by VFSS and VEES. Ultrasound and pharyngeal manometry do not represent the latest in technological advances, with both emerging in swallowing research over 20 years ago. However, both have resisted integration into routine clinical practice, despite the fact that they offer quantitative metrics of swallowing that are not available using standard techniques. The aim of this review is to present recent research on these two less frequently used modalities in clinical swallowing assessment, discuss potential applications in clinical practice and review supportive data on test-retest reliability, rater reliability and validity. The paper will conclude with a case report that exemplifies the unique contribution of these modalities in executing and revising therapeutic approaches for a patient with neurogenic dysphagia.

Objective Topical nasal anesthetic (TNA) is used when evaluating pharyngeal swallowing with high-resolution manometry (HRM). It is unclear if desensitizing the nasal mucosa improves procedure tolerability or affects pharyngeal pressure. This study evaluated the effects of TNA on comfort and pharyngeal pressure using HRM. Methods A double-blinded study was conducted with 20 healthy participants ( x¯ = 27 years). Participants performed five saliva and five 10-mL swallows during two exams with ManoScan HRM ESO catheter (Medtronic, Minneapolis, MN) randomized under placebo (nonanesthetic lubricant) and anesthetized (0.4 mL of 2% viscous lidocaine hydrochloride) conditions. Comfort was rated using a 100-mm visual analog scale (VAS). Pharyngeal HRM amplitude and timing were analyzed. Results VAS ratings were similar under placebo (mean = 38.4, standard deviation [SD] = 19.92) and TNA conditions (mean = 33.78, SD = 18.9), with no significant differences between placebo and anesthetized conditions (t[19] = 1.23, P = 0.23) or tolerability at first and second procedure (t[19] = 1.38, P = 0.18). Lower maximum and mean pharyngeal pressure were found for the TNA condition when compared to placebo (dry: maximum [-15.45 mmHg, standard error (SE) = 5.06 mmHg, P = 0.021]; mean [-5.22 mmHg, SE = 1.58 mmHg, P = 0.005]), and (liquid: maximum [-14.79 mmHg, SE = 5.01 mmHg, P = 0.010]; mean [-2.79 mmHg, SE = 1.99 mmHg, P = 0.008]). Conclusion This double-blind, randomized study is the first to investigate effects of TNA on tolerability and pharyngeal pressure using HRM. Results indicate TNA offered no significant difference in procedure comfort while affecting the magnitude of pharyngeal swallowing. Level of evidence 4. Laryngoscope, 128:1335-1339, 2018.

Summary Researchers have recently developed a novel oily formulation for potential use as a saliva substitute for the treatment of dry mouth. The aim of this randomised, crossover study was to compare this new formulation to a currently available saliva substitute and a control of water on measures of mastication, subjective feeling of oral dryness and product acceptability. Forty participants treated with radiotherapy to the head and neck and experiencing xerostomia were invited to participate in the trial. Each participant trialled all three products in a randomised order. The effect of each product was measured using the Test of Masticating and Swallowing Solids (TOMASS), the Shortened Xerostomia Inventory (SXI) and a questionnaire designed to test patient acceptability of each product. Outcome data were gathered in a single session after the first administration of each product to evaluate immediate effects and after 7 days of use to evaluate longer-term effects. Statistical analyses consisted of repeated-measures analysis of variance and mixed models. There was no evidence that application of the three formulations had an effect on any of the TOMASS measures, either immediately or after one week of use (P > 0·05). There was a significant main effect of formulation on the SXI score (P = 0·02). Application of the novel emulsion resulted in a clinically small but significant improvement in SXI score (P

To examine the effects of skill training on swallowing in individuals with dysphagia secondary to Parkinson's disease (PD) and to explore skill retention after treatment termination.Within-subject pilot study with follow-up after 2 weeks of treatment and after a 2-week nontreatment period.Clinic in a research institute.Patients (N=10; mean age, 67.4y) included 3 women (mean Hoehn and Yahr score, 2.6) and 7 men (mean Hoehn and Yahr score, 2.4).Patients underwent 10 daily sessions of skill training therapy focused on increasing precision in muscle contraction during swallowing using visual feedback.Data from the timed water swallow test, Test of Mastication and Swallowing Solids, surface electromyography (sEMG) of submental muscles, and swallowing-related quality of life questionnaire were collected at 2 baseline sessions (conducted 2wk apart) at the end of treatment and after 2 nontreatment weeks to assess skill retention.Immediately after posttreatment, the swallowing rate for liquids (P=.034), sEMG durational parameters of premotor time (P=.003), and preswallow time (P.001) improved. A functional carryover effect was seen from dry to water swallows (P=.009). Additionally, swallowing-related quality of life improved (P=.018). Reassessment at 2 weeks after treatment termination revealed short-term retention of treatment effects.A skill-based training approach produced functional, biomechanical, and swallowing-related quality of life improvements in this cohort indicating compelling evidence for the effectiveness of this novel approach for dysphagia rehabilitation in PD.

Silent aspiration is associated with pneumonia and mortality, and is poorly identified by traditional clinical swallowing evaluation (CSE). The aim of this study was to validate cough reflex testing (CRT) for identification of silent aspiration against aspiration confirmed by instrumental assessment.Cough reflex threshold testing was completed on all patients using inhaled, nebulised citric acid. Within an hour, 80 patients underwent videofluoroscopic study of swallowing (VFSS) and 101 patients underwent fibreoptic endoscopic evaluation of swallowing (FEES). All tests were recorded and analysed by two researchers blinded to the result of the alternate test.Significant associations between CRT result and cough response to aspiration on VFSS (X(2) (2)=11.046, p=.003) and FEES (X(2) (2)=34.079, p.001) were identified. Sensitivity and specificity were optimised at 0.6mol/L in patients undergoing VFSS (71%, 60% respectively) and at 0.4mol/L in patients undergoing FEES (69%, 71% respectively). A concentration of 0.8mol/L had the highest odds ratio (OR) for detecting silent aspiration (8 based on VFSS; 7 based on FEES).CRT results are significantly associated with aspiration response on instrumental assessment. Lower concentrations of citric acid provide a better predictive measure of silent aspiration.

Mutations in isocitrate dehydrogenase -1 or -2 (IDH1 or IDH2) are found in the majority of WHO grade II and III diffuse gliomas and secondary glioblastomas. IDH mutation screening is rapidly becoming part of the routine pathological work up of human brain tumors, providing both diagnostic and prognostic information. Here, we characterize four rare and novel IDH1 mutations identified in surgical human glioma samples: two instances of an IDH1 p.R132S mutation caused by a previously undescribed dinucleotide deletion/insertion mutation, a novel homozygous somatic IDH1 p.R132L mutation, and an IDH1 p.R100Q mutation. Characterization of novel and rare IDH mutations may provide additional insight into the mechanisms of mutant IDH in neoplasia. Furthermore, given the clinical import of IDH status, these results highlight the need for comprehensive mutation screening, beyond the targeted identification of common pathogenic variants.

Changes in morphometry of head and neck muscles have received little attention in research relative to limb muscles. While recent literature suggests that high-frequency ultrasound transducers can provide superior spatial resolution compared to that of magnetic resonance imaging (MRI), no studies have compared these imaging methods for investigating the submental muscle group. This preliminary study sought to compare ultrasound and MRI as a method of quantifying the cross-sectional area (CSA) of the submental muscle group. Measurements were taken from coronal ultrasound and MRI images in 11 healthy participants. Comparisons were limited to the anterior belly of the digastric muscle because of differences in imaging resolution. Ultrasound CSA measurements were smaller than MRI measurements (p = 0.01) by 10 % (95% CI = -18 to -2). Correlations were significant and relatively high (left: r = 0.909, p < 0.001; right: r = 0.776, p = 0.005). Ultrasound imaging has the advantages of natural participant positioning, superior clarity of muscle borders of the submental muscles, requires less acquisition time, and is a less expensive method of imaging compared to MRI. This preliminary study has shown that ultrasound is a viable imaging modality for quantitative measurements of the anterior belly of the digastric muscle and has advantages over MRI beyond cost and accessibility.

Heck FM, Doeltgen SH, Huckabee M-L. Effects of submental neuromuscular electrical stimulation on pharyngeal pressure generation. Objective To investigate the immediate and late effects of submental event-related neuromuscular electrical stimulation (NMES) on pharyngeal pressure generation during noneffortful and effortful saliva swallows. Design Before-after trial. Setting Swallowing rehabilitation research laboratory. Participants Sex-matched (N=20) healthy research volunteers. Interventions Participants received 80Hz NMES of 4-second duration to floor of mouth muscles that was time-locked to 60 volitional saliva swallows. Main Outcome Measures Manometry measures of peak pressures and duration of pressure events in the oropharynx, hypopharynx, and the upper esophageal sphincter (UES) were derived during execution of noneffortful and effortful saliva swallows. Measures were taken at baseline, during stimulation, and at 5-, 30-, and 60-minutes poststimulation. Results Baseline pharyngeal and UES pressures did not differ between stimulated and nonstimulated swallows. At 5- and 30-minutes poststimulation, peak pressure decreased at the hypopharyngeal and at the UES sensor during noneffortful swallows. The effect lasted up to an hour only in the hypopharynx. No changes in duration of pressure events were observed. Conclusions Using this treatment paradigm, decreased peak amplitude in the hypopharynx up to an hour after treatment indicates a potential risk of decreased bolus flow associated with NMES. On the other hand, decreased UES relaxation pressure may facilitate bolus transit into the esophagus.

The recent application of neurostimulation techniques to enhance the understanding of swallowing neural plasticity has expanded the focus of rehabilitation research from manipulation of swallowing biomechanics to manipulation of underlying neural systems. Neuromodulatory strategies that promote the brain's ability to reorganize its neural connections have been shown to hold promising potential to aid the recovery of impaired swallowing function. These techniques include those applied to the brain through the intact skull, such as transcranial magnetic stimulation or transcranial direct current stimulation, or those applied to the sensorimotor system in the periphery, such as neuromuscular electrical stimulation. Recent research has demonstrated that each of these techniques, either by themselves or in combination with these and other treatments, can, under certain circumstances, modify the excitability of motor representations of muscles involved in swallowing. In some studies, experimentally induced plastic changes have been shown to have functional relevance for swallowing biomechanics. However, the transition of novel, neuromodulatory brain stimulation techniques from the research laboratory to routine clinical practice is accompanied by a number of ethical, organizational, and clinical implications that impact professions concerned with the treatment of swallowing rehabilitation. In this article, we provide a brief overview of the neuromodulatory strategies that may hold potential to aid the recovery of swallowing function, and raise a number of issues that we believe the clinical professions involved in the rehabilitation of swallowing disorders must confront as these novel brain stimulation techniques emerge into clinical practice.

Purpose. Anterior hyoid displacement is essential for efficient swallowing and is usually investigated with videofluoroscopy. Ultrasound offers a less expensive and noninvasive method of investigation. The present study investigated the viability of a novel method of quantifying hyoid displacement from sonograms using an anatomic reference point, through an evaluation of inter- and intra-rater reliability. Methods. Three raters reviewed the sonographic video sweeps of five discrete swallows from each of five participants for inter-rater reliability. The primary investigator measured each swallow on two occasions for intra-rater reliability. Electronic calipers were used to measure distances from a “rest” frame prior to the swallow of interest and a “maximal displacement” frame, at which the hyoid bone was at maximal anterior displacement during each swallow. Results. Single-measure intraclass correlation coefficient was high for inter-rater agreement at 0.86 for rest measures and 0.86 for maximal displacement. Intra-rater reliability was even higher at 0.95 for rest and 0.98 for maximal displacement. Conclusions. These preliminary results suggest that by using a novel analysis approach involving an anatomic reference point, raters can achieve high agreement on measurement of position of hyoid at maximal displacement relative to rest. © 2011 Wiley Periodicals, Inc. J Clin Ultrasound 40:74–78, 2012

The risk of aspiration pneumonia in Parkinson's disease (PD) may be increased by sensory loss in the laryngopharynx and a reduced cough reflex. This study investigated changes in chemo- and mechanosensation with age and in PD and documented cough thresholds and cortical influences over cough. Single-breath citric acid inhalation cough challenge and flexible nasendoscopy were performed in 32 participants with idiopathic PD (mean age = 68.5 years, range = 45.8-82.5) and 16 healthy young adults (8 males, mean age = 25.1 years, range = 21.3-32.4), and 16 healthy elders (8 males, mean age = 72.8 years, range = 61.5-84.7) as controls. Individuals with PD had reduced sensation at the base of the tongue compared to age- and gender-matched counterparts (p

This project evaluated the effects of olfactory and gustatory stimuli on the amplitude and latency of motor-evoked potentials (MEPs) from the submental muscles when evoked by transcranial magnetic stimulation (TMS). Sixteen healthy volunteers (8 males; age range 19-43) participated in the study. Lemon concentrate at 100% and diluted in water to 25% were presented separately as odor and tastant stimuli. Tap water was used as control. 15 trials of TMS-evoked MEPs triggered by volitional contraction of the submental muscles and volitional swallowing were measured at baseline, during control condition, during stimulus presentation, and immediately, 30-, 60-, and 90-min poststimulation for each of the four stimulus presentations. Experiments were repeated using the combined odor and tastant concentrations that most influenced the MEP independently. Differences in MEP amplitude measured during swallowing were seen at 30-, 60-, and 90-min poststimulation for simultaneous olfactory and gustatory stimulation as opposed to no differences seen at any point for stimuli presented separately. This study has shown that combined odor and tastant stimulation (i.e., flavor) can increase MEP amplitude during swallowing and that this enhancement of MEP can persist for at least 90min following stimulation. As increased MEP amplitude has been associated with improved swallowing performance, a follow-up study is underway to determine the biomechanical changes produced by altered MEPs to facilitate translation of these data to clinical dysphagia management.

In the past, iron-deficiency anemia in children has had a widespread presence in rural China. Given the recent economic growth in China, it is unclear if anemia among infants/toddlers remains a problem. The objective of this study is to measure the anemia rate in rural Chinese infants/toddlers across four major subpopulations and attempt to discover the sources of anemia. We use a mixed-methods approach combining quantitative data on 2909 rural Chinese infants/toddlers and their families with qualitative interviews with 84 caregivers of infants aged 6 to 30 months. Quantitative analysis indicates that the overall prevalence of anemia (43%) within sampled infants/toddlers was high, especially in comparison to the low rates of stunting (2&ndash, 5%), being underweight (2%), and wasting (2&ndash, 4%). These findings suggest that in rural China, anemia stems from the poor quality of the diets of infants/toddlers, rather than insufficient quantities of food being consumed. Qualitative analysis illustrates the factors that are contributing to anemia. Caregivers do not understand the causes of this condition, the symptoms that would lead one to recognize this condition, or the steps needed to treat their child with this condition. The findings offer a comprehensive understanding of the limited awareness of anemia among rural Chinese caregivers.

Background. Neuromuscular electrical stimulation (NMES) of the muscles underlying the pharynx and faucial pillars affects the excitability of corticobulbar projections in a frequency- and duration-specific manner. The anterior hyomandibular (submental) muscles are primary targets for the clinical application of NMES to improve disordered swallowing, but the optimal NMES parameters for this application are unknown. Objective. To determine the influence of NMES parameters on the excitability of corticobulbar projections to the submental musculature. Methods. Transcranial magnetic stimulation (TMS) was used in event-related protocols, triggered by either volitional contraction of the submental muscles or pharyngeal swallowing, to assess corticobulbar excitability prior to, immediately following, and 30, 60, and 90 minutes post-NMES in 25 healthy volunteers. In the first 2 experiments, 4 stimulus frequencies (5, 20, 40, and 80 Hz) and 3 NMES dosages, manipulated through stimulus train durations or number of repetitions, were evaluated. The optimal excitatory NMES triggered by volitional swallowing (event-related NMES) was then replicated in a new sample and contrasted with non-event-related NMES (either discrete events or continuously for 1 hour). Results. It was found that 80Hz NMES increased motor-evoked potential (MEP) amplitude at 30 minutes and 60 minutes poststimulation only after 60 repetitions of 4-s event-related NMES trains. Non-event-related and continuous NMES did not affect MEP amplitudes. No changes in MEP onset latencies were observed. Conclusions. Changes in corticobulbar excitability induced by NMES of the submental muscle group are frequency and dose dependent and only occur after NMES triggered by volitional swallowing. Underlying neural mechanisms are discussed.

The present study examined whether abnormal cerebral control was evident in the lip movements of adult stutterers (AS) compared to non-stutterers (ANS), as demonstrated during speech and non-speech tasks. Electromyographic (EMG) activity during production of words with initial /f/ and /p/ phonemes, single-sentence production and lip pursing were measured. Differences between AS and ANS were evident in all tasks. For AS, the highest EMG amplitude was in the region of the left lower lip, which is indicative of greater right hemisphere participation. However, in ANS the right lower lip displayed the highest EMG amplitude, suggesting greater left hemisphere participation. Further, AS showed greater asynchronous lip activity than ANS for all tasks. These results support the hypotheses of reversed lateralization for speech and non-speech processing and reduced coordination of speech musculature in AS.