Pharyngeal Weakness Research Articles

G.P.65: Obstructive sleep apnoea and subclinical impairment of respiratory function are common in sporadic inclusion body myositis

To examine the occurrence of respiratory dysfunction in sporadic inclusion body myositis (IBM) and its relationship to peripheral muscle strength and ventilation during sleep. Anthropometric, muscle strength, dyspnoea, daytime sleepiness and dysphagia data were collected. Spirometry, respiratory muscle strength and arterial blood gas tensions were measured. Ventilation during sleep was assessed by dual channel (oximetry, nasal pressure) home monitoring. Sixteen patients with biopsy-proven IBM were studied (10 males, 6 females; age 68.1±9.9years; disease duration 11.9±5.0years; body mass index 28.5±4.0kg/m²). Four patients reported excessive daytime sleepiness (Epworth Sleepiness Scale ⩾10); 8 had at least mild dysphagia (Dysphagia Outcome Severity Scale ⩽5); forced vital capacity was <80% of the predicted normal in 7; sniff nasal inspiratory pressure was reduced (<60cm H₂O) in 3; daytime hypoxemia (PaO₂<80mmHg) was present in 10 and hypercapnia (PaCO₂>45mmHg) in one. Sleep study was performed in 15 patients and revealed sleep hypoxemia (⩾2% of total sleep time at or below a saturation <90% (TST⩽90)) in 10 and obstructive sleep apnoea (respiratory disturbance index 23.4±12.8 (range 7–50.3) events/h) in all 15. Daytime PaO₂ was related to TST⩽90 (<i>r</i>=−0.55, <i>p</i>=0.04). Asymptomatic impairment of wakeful respiratory function was common and obstructive sleep apnoea was observed in all patients tested, irrespective of daytime respiratory function. This high occurrence probably reflects the combined effects of pharyngeal muscle weakness and sleep-related reduction in muscle activation and ventilatory drive. These findings suggest that tests of respiratory function, including an overnight sleep study, should be performed routinely in IBM patients, irrespective of peripheral muscle function or other non-respiratory disease severity parameters.

Pharyngeal weakness and upper esophageal sphincter opening in patients with unilateral vocal fold immobility.

To evaluate pharyngeal strength and upper esophageal sphincter opening in patients with unilateral vocal fold immobility (UVFI). Case control study. Charts of individuals with UVFI who underwent a videofluoroscopic swallow study were reviewed. To exclude confounding variables associated with pharyngeal weakness, inclusion was limited to patients with iatrogenic and idiopathic UVFI. Data abstracted included patient demographics, etiology of UVFI, pharyngeal constriction ratio (PCR), and upper esophageal sphincter (UES) opening (UESmax). Data were compared to age/gender-matched controls with no history of dysphagia or UVFI. Discrete variables were analyzed using a chi-square test of independence, and an independent samples t test was used to compare the UVFI and control groups (P = 0.05). A one-way analysis of variance (ANOVA) was used to compare iatrogenic and idiopathic UVFI groups. The mean age of the cohort (n = 25) was 61 (±14 SD) years and 52% was female. The etiologies of UVFI were iatrogenic (n = 17) and idiopathic (n = 8). Thirty-eight percent of UVFI patients (n = 25) aspirated compared to 0% of controls (P < 0.05). The mean PCR for the UVFI group was 0.14 (±0.02) compared to 0.06 (±.01) for controls (P < 0.05). The mean UESmax for the UVFI group was 0.82 cm (±0.04) compared to 1.0 cm (±0.05) for controls (P > 0.05). Individuals with UVFI of iatrogenic and idiopathic etiologies with subjective dysphagia demonstrate objective evidence of pharyngeal weakness. The increased prevalence of aspiration in this population may not be solely the result of impaired airway protection.

Speech Pathologist Practice Patterns for Evaluation and Management of Suspected Cricopharyngeal Dysfunction

Speech pathologists are often the first professionals to identify signs of a cricopharyngeal (CP) dysfunction and make recommendations for further care. There are many care options for patients with CP dysfunction, but it is unclear how certain interventions are used in practice. A paper-based survey employing two clinical cases involving suspected CP dysfunction (Case 1 with adequate pharyngeal strength and Case 2 with coexisting pharyngeal weakness) was sent to members of American Speech-Language Hearing Association's Special Interest Group 13. Respondents ranked the order of management approaches (swallowing therapy, further evaluation, and referral to another medical professional) and selected specific interventions under each approach that they would recommend for each case. Completed surveys from 206 respondents were entered into analysis. The majority of the respondents recommended swallowing therapy as a first approach for each case (Case 1: 64 %; Case 2: 88 %). The most prevalent swallowing exercises recommended were the Shaker (73 %), effortful swallow (62 %), and Mendelsohn maneuver (53 %) for Case 1 and effortful swallow (92 %), Shaker (84 %), and tongue-hold swallow (73 %) for Case 2. 76 % of respondents recommended a referral for Case 1, while 38 % recommended the same for Case 2. Respondents with access to more types of evaluative tools were more likely to recommend further evaluation, and those with access to only videofluoroscopy were less likely to recommend further evaluation. However, the high degree of variability in recommendations reflects the need for best practice guidelines for patients with signs of CP dysfunction.

Distal myopathies: from clinical classification to molecular understanding

The distal myopathies are a group of rare diseases that in the past were primarily classified by eponyms. Classification criteria were the beginning of the disease, the distribution of the muscle weakness, the course of the disease, the prognosis, and histological changes in the muscle biopsy. Advances of molecular genetics have identified various genes and mutations in many of the clinical phenotypes. This led to modifications and extensions of the existing clinical classification. Our own study on 42 patients with distal myopathy including 15 patients from six families with matrin-3 mutation suggests that in distal myopathies (1) there seem to be no monogenetic classical phenotypes; (2) there are phenotypes with different genotypes and (3) phenotypes with genotypes that are usually associated with other than distal phenotypes. Some of these phenotypes could not be classified according to the traditional clinical classification. In matrin-3 associated myopathy most but not all patients had predominant distal weakness. Also in the initial families distal weakness myopathy was associated with vocal cord and pharyngeal weakness, this was observed in half of our patients. Three of 15 patients met the criteria of Welander-phenotype. The recent classification by Udd distinguishes major groups of myopathies based on age of onset, mode of inheritance, and morphological changes in muscle biopsy. In many but not all subforms of these major groups the genotype has been established so far.

Dysphagia Characteristics in Zenker’s Diverticulum

To evaluate dysphagia characteristics in patients with Zenker's diverticulum (ZD). Case series with chart review. Outpatient tertiary care dysphagia clinic. All ZD cases surgically treated over a 6-year period were identified and reviewed for dysphagia history and dysphagia characteristics on initial presentation using fiber-optic endoscopic evaluation of swallowing (FEES). Dysphagia symptoms and swallowing abnormalities were compared across groups based on diverticulum size (small <1 cm, medium 1-3 cm, and large >3 cm). Forty-six patients underwent a total of 52 procedures during the study period. ZD size was available in 49 cases (6 small, 26 medium, 17 large). Regurgitation symptoms were less frequent in patients with small (17%) compared with medium (68%) or large diverticula (76%; P = .03). Postswallow hypopharyngeal reflux (PSHR) was less frequent in patients with small (17%) compared with medium (91%) and large diverticula (87%; P < .01). PSHR was present on all FEES available for patients who presented with a recurrent or residual ZD (n = 7). In all cases, PSHR resolved after successful treatment of ZD. Pharyngeal residue indicating possible weakness was present in 24% of all patients at initial presentation. Preoperative assessment of dysphagia characteristics in ZD patients reveals that PSHR is predictive of a ZD larger than 1 cm and may be useful in surgical planning. PSHR is also helpful in identifying patients with recurrent or residual symptomatic ZD following surgical treatment. Pharyngeal weakness is present in a subset of ZD patients.

Dysphagia Characteristics in Zenker’s Diverticulum

Objective: To evaluate the presenting signs and symptoms of dysphagia in patients with Zenker’s diverticulum (ZD). Method: All patients surgically treated for ZD over a 6-year period were identified. Charts were reviewed for dysphagia history and findings on fiberoptic endoscopic evaluation of swallowing (FEES). Dysphagia symptoms and swallowing abnormalities were compared across groups based upon diverticulum size (small &lt;1 cm, medium 1-3 cm, and large &gt;3 cm). Results: Forty-one patients were identified. ZD size was available in 39 cases (6 small, 18 medium, 15 large). Regurgitation symptoms were less frequent in patients with small (17%) compared to medium (70%) or large diverticula (73%) ( P &lt; .01). Similarly, esophagopharyngeal reflux (EPR) on FEES was less frequent in patients with small (17%) compared to medium (88%) and large diverticula (92%) ( P &lt; .01). EPR was present in all patients presenting for revision surgery (N = 9). In all cases, EPR resolved after successful treatment. Eighteen percent of all patients had evidence of pharyngeal weakness on FEES which did not change significantly on initial postoperative exam. Conclusion: Dysphagia with EPR is predictive of a ZD larger than 1 cm, and may be useful in preoperative planning. EPR is also helpful in identifying patients with recurrent or residual symptomatic ZD following surgical treatment. Pharyngeal weakness is present in a subset of ZD patients.

Four-dimensional ultrasound calf muscle imaging in patients with genetic types of distal myopathy

PurposeTo demonstrate the capabilities of 4D ultrasound calf muscle imaging in patients with genetic types of distal myopathies (DMs). MethodsThree patients with DM were studied: a 58-year-old man with Vocal Cord and Pharyngeal Weakness Distal Myopathy (VCPDM), a 36-year-old woman with Tibial Muscular Dystrophy (TMD) and a 27-year-old woman with Hereditary Inclusion Body Myopathy Type 2 (HIBM2). Their calf muscles were evaluated in rest and during maximal plantar flexion using 3D/4D ultrasound imaging. The results were compared to myosonograms of healthy controls. ResultsAll patients had myopathic syndrome due to advanced muscular dystrophy. In comparison to controls abnormal calf muscle architectonics, reduced muscle contractility and a combination of spot-like hypo- and hyperechoic areas were established on 4D ultrasound imaging. The changes were associated with the degree of muscle atrophy, fat and fibrous tissue infiltration. ConclusionsFour-dimensional myosonology gives additional information for muscle architectonics in patients with genetic types of DM. Further studies are needed to evaluate if the described findings are typical for specific genetic types of myopathy.

Treatment guidelines for Guillain-Barré Syndrome

Guillain–Barre syndrome (GBS) is an acute onset, usually monophasic immune-mediated disorder of the peripheral nervous system. The term GBS is often considered to be synonymous with acute inflammatory demyelinating polyradiculoneuropathy (AIDP), but with the increasing recognition of variants over the past few decades, the number of diseases that fall under the rubric GBS have grown to include axonal variants and more restricted variants, such as Miller Fisher syndrome (MFS) [Table 1].[1] Table 1 Guillain–Barre syndrome—clinical variants Epidemiology The reported incidence rates for GBS are 1–2 per 100,000 population.[2–4] The lifetime likelihood of any individual acquiring GBS is 1:1000.[5] The subtypes of GBS have different incidence rates in different parts of the world. In Europe and North America AIDP is dominant contributing to 90% of the cases. In contrast in China and Japan AMAN being the most common subtype.[6,7] The picture is intermediate when we look at other population. In Indian series the incidence of AIDP and AMAN are virtually equal although AMAN is more common in younger patients.[8] There seems to be a slight preponderance of AIDP in studies by Gupta et al[9] and by Meena et al (unpublished data from NIMS, Hyderabad). Available Indian literature indicates a peak incidence between June–July and Sept–October.[10] In western countries, GBS is common in the 5th decade,[11] but in India it occurs more commonly at a younger age.[10,12] GBS is equally common in men and women and can occur at any age. There is a male preponderance among the hospitalized population.[10,12]

PONM04 Myofibrillar myopathy caused by a mutation in the desmin gene: expanding the phenotype

BackgroundMyofibrillar myopathy (MFM) is a group of morphologically distinct muscle disorders, with genetic and phenotypic variability. When a mutation in the desmin gene is found, it is termed a desminopathy....

An anatomical and clinical review of cricopharyngeal achalasia in the dog

Cricopharyngeal achalasia is a rare cause of dysphagia in the dog. However it must be differentiated from other causes of dysphagia as it is treatable with surgery. It is a disruption of the cricopharyngeal phase of the oropharyngeal phase of deglutition. There appears to be an incoordination in the swallowing process between the relaxation of the rostral, middle pharyngeal muscles and the caudal pharyngeal muscles. It is seen as a primary condition in young animals presenting soon after weaning onto solid food. The dogs appear clinically healthy unless there is secondary aspiration pneumonia or emaciation. These dogs may present as respiratory emergencies and require intensive support and treatment prior to corrective surgery. The diagnosis is made on videofluoroscopy. The condition carries a good prognosis for cure with surgical myectomy of the cricopharyngeal muscle and the thyropharyngeal muscle, which make up the upper oesophageal sphincter. Temporary relief prior to surgery can be achieved by injection of the cricopharyngeal muscle with botulism toxin. Surgical treatment for dysphagia secondary to an underlying neurological, neuromuscular or pharyngeal weakness carries a guarded prognosis and will make aspiration pneumonia worse.

Matrin3 myopathy: Distal and axial myopathy with pathology of the nucleus and the perinuclear region

Introduction: Recently it was shown, that a mutation in the MATR3 gene causes vocal cord and pharyngeal weakness with distal myopathy (VCPDM) in a North American and in a Bulgarian pedigree. MATR3 encodes Matrin 3, a component of the nuclear matrix. Vocal cord or swallowing dysfunction occurred in most cases of VCPDM. Detailed clinical descriptions or structural data of muscles were not given. Here we report on the clinical and myopathological data of the worldwide third family in detail. In four individuals of our German family (III3, IV2, IV3, V2, see pedigree. *: index patient, D: Diabetes mellitus) the same S85C mutation in the MATR3 gene was detected. Three of them were symptomatic (III3, IV2, IV3).

Autosomal dominant distal vacuolar myopathy associated with mutation of the nuclear matrix protein matrin 3

Inherited distal myopathies represent a heterogeneous group of skeletal muscle disorders. One type of adult-onset, progressive autosomal dominant distal myopathy, frequently associated with dysphagia and dysphonia, has been mapped to chromosome 5q31 in a North American pedigree (vocal cord and pharyngeal weakness with distal myopathy; VCPDM). We recently identified a second large VCPDM family of Bulgarian descent and performed fine mapping of the critical interval. Sequencing of positional candidate genes revealed precisely the same non-conservative S85C missense mutation affecting an interspecies conserved residue in the MATR3 gene in both families (Senderek et al., Am J Human Genet, in press). MATR3 is expressed in skeletal muscle and encodes matrin 3, a component of the proteinaceous network that extends throughout the nucleus and has been termed the nuclear matrix. Different disease related haplotype signatures in the two families provide evidence that two independent mutational events at the same position in MATR3 cause VCPDM. Histopathological and electron microscopical analysis of two muscle biopsies revealed reduced matrin 3 immunoreactivity of muscle fiber nuclei and myonuclear degeneration as well as autophagic vacuoles in affected muscle fibers.

G.O.5 A new autosomal dominant distal vacuolar myopathy associated with mutation of the nuclear matrix protein, matrin 3

Distal myopathies represent a heterogeneous group of inherited skeletal muscle disorders. One type of adult-onset, progressive autosomal dominant distal myopathy, frequently associated with dysphagia and dysphonia, has been mapped to chromosome 5q31 in a North American pedigree (vocal cord and pharyngeal weakness with distal myopathy; VCPDM). We report the identification of a second large VCPDM family of Bulgarian descent and fine mapping of the critical interval. Sequencing of positional candidate genes revealed precisely the same non-conservative S85C missense mutation affecting an interspecies conserved residue in the MATR3 gene in both families.

Autosomal-Dominant Distal Myopathy Associated with a Recurrent Missense Mutation in the Gene Encoding the Nuclear Matrix Protein, Matrin 3

Distal myopathies represent a heterogeneous group of inherited skeletal muscle disorders. One type of adult-onset, progressive autosomal-dominant distal myopathy, frequently associated with dysphagia and dysphonia (vocal cord and pharyngeal weakness with distal myopathy [VCPDM]), has been mapped to chromosome 5q31 in a North American pedigree. Here, we report the identification of a second large VCPDM family of Bulgarian descent and fine mapping of the critical interval. Sequencing of positional candidate genes revealed precisely the same nonconservative S85C missense mutation affecting an interspecies conserved residue in the MATR3 gene in both families. MATR3 is expressed in skeletal muscle and encodes matrin 3, a component of the nuclear matrix, which is a proteinaceous network that extends throughout the nucleus. Different disease related haplotype signatures in the two families provided evidence that two independent mutational events at the same position in MATR3 cause VCPDM. Our data establish proof of principle that the nuclear matrix is crucial for normal skeletal muscle structure and function and put VCPDM on the growing list of monogenic disorders associated with the nuclear proteome.

Impaired Opening of the Upper Esophageal Sphincter in Patients with Medullary Infarctions

The aim of this study was to report on nine dysphagic patients with medullary infarction and to evaluate swallowing characteristics based on the location of the lesions.We retrospectively reviewed the medical records of these nine patients. The medullary lesions were midlateral (three patients), dorsolateral (one patient), inferodorsolateral (four patients), and paramedian (one patient). The levels of the lesions were upper (four patients), middle (two patients), upper and middle (two patients), and middle and lower medulla (one patient). Dysphagia after medullary infarction was more common in patients with upper or middle medullary level and dorsolateral medullary level lesions. The common findings on videofluoroscopic swallowing studies in patients with lateral medullary infarctions were impaired upper esophageal sphincter opening, aspiration from pyriform sinuses' residue caused by pharyngeal weakness, and multiple swallowing to clear boluses from the pharynx to the esophagus. In patients with medullary infarctions, the lesion levels and loci and their related clinical findings can be useful in predicting dysphagia and aspiration. Because severe dysphagia with serious complication is very common in patients with medullary infarctions, active diagnostic and therapeutic approaches are needed.

Fiberoptic endoscopic evaluation of swallowing with simultaneous tensilon application in diagnosis and therapy of myasthenia gravis

Dysphagia is a common symptom in myasthenia gravis (MG). Clinical examination alone fails to detect and grade myasthenic dysphagia sufficiently. For a more precise examination of swallowing function in myasthenia gravis additional technical tools are necessary. To investigate the diagnostic and therapeutic impact of fiberoptic endoscopic evaluation of swallowing with simultaneous Tensilon application (FEES-Tensilon Test) in myasthenia gravis. FEES-Tensilon Test was performed following a standardized protocol. Four severely affected patients with dysphagia as their leading symptom were examined. Dysphagia was characterized by five salient endoscopic findings: leakage, delayed swallowing reflex, penetration, aspiration and residues. If a normalisation or at least an improvement of swallowing function occurred shortly after Tensilon administration the FEES-Tensilon Test was rated as being positive. In three patients the FEES-Tensilon Test successfully detected MG-related dysphagia. In one patient with dysphagia caused by oculopharyngeal muscular dystrophy the FEES-Tensilon Test was truly negative. Beside an early diagnosis of MG-related dysphagia, the FEES-Tensilon Test was useful in the differentiation between myasthenic and cholinergic crisis and in guiding treatment decisions. In all patients the FEES-Tensilon Test was superior to clinical evaluation of dysphagia. No severe side effect occurred while performing the FEES-Tensilon Test. The FEES-Tensilon Test is a suitable tool in the diagnosis and therapy of myasthenia gravis with pharyngeal muscles weakness.

Videofluoroscopic Findings in Dysphagic Patients with Cricopharyngeal Dysfunction: Before and after Open Cricopharyngeal Myotomy

Functional outcomes after open cricopharyngeal myotomy (CPM) for Zenker's diverticulum (ZD) and cricopharyngeal dysfunction without diverticulum (CPD) have not been uniformly measured by videofluorographic swallow study (VFSS). Here we characterize preoperative VFSS findings in these groups and evaluate the effect of CPM on swallowing via postoperative VFSS. We performed a retrospective review of paired preoperative and postoperative VFSS results from 50 patients (36 with ZD and 14 with CPD) over 6 years. Semiquantitative scales were used to assess 1) degree of stasis in the pharyngeal recesses; 2) degree of narrowing at the pharyngoesophageal sphincter (PES); 3) aspiration; and 4) diverticular size. Findings were compared between the groups and across subjects. Pharyngeal stasis was more severe in subjects with CPD than in subjects with ZD, both before and after CPM (p = .02 and p = .0002, respectively). The CPM improved PES narrowing in both groups (p = .03; p = .06) and reduced diverticular size in the ZD group (p < .001), but it did not significantly reduce the stasis severity or the proportion of patients with aspiration. According to VFSS, CPM opens up the PES and decreases diverticular size. More severe stasis in CPD suggests that diffuse pharyngeal weakness may play a role in this disease, and may partially explain the variable post-CPM outcomes that have been observed in CPD.

Myotilin is not the Causative Gene for Vocal Cord and Pharyngeal Weakness with Distal Myopathy (VCPDM)

Myotilin (MYOT) is a promising candidate gene for Vocal Cord and Pharyngeal Weakness with Distal Myopathy (VCPDM, also known as MPD2). Located within the minimum VCPDM candidate interval, myotilin mutations also cause a similarly progressive and adult-onset muscle disease. We examined myotilin in VCPDM patients by sequence analysis, RT-PCR, Southern blotting, and western blotting. We detected no defects in the myotilin gene, transcript, or protein in VCPDM. We also report several useful SNPs and STRs for the analysis of myotilin in muscle diseases of suspected, yet unknown genetic origin. We conclude that MYOT mutations likely are not a cause of VCPDM.

MuSK antibody-positive, seronegative myasthenia gravis in Korea

Several reports from Western countries suggest differences in the clinical features of patients with muscle specific kinase (MuSK) antibody-positive and -negative seronegative myasthenia gravis (MG). We performed the first survey in Korea of MuSK antibodies, studying 23 patients with acetylcholine receptor (AChR)-antibody seronegative MG. MuSK antibodies were present in 4 (26.7%) of 15 generalized seronegative MG patients and none of 8 ocular seronegative MG patients. All four MuSK positive patients were females, with pharyngeal and respiratory muscle weakness, and required immunosuppressive treatment. However, overall disease severity and age at onset was similar to that of MuSK-negative MG and treatment responses were equally good.

Poster 62: Prevalence of dysphagia in inflammatory myositis

Objective: To determine the prevalence and the phases of dysphagia in inflammatory myositis. Design: Inception cohort study. Setting: Rehabilitation department of a tertiary care hospital. Participants: 64 patients (39 women, 25 men; mean age, 45.1±15.9y) diagnosed as inflammatory myositis by the rheumatologists. Interventions: Not applicable. Main Outcome Measures: We reviewed patient charts, and surveyed patients’ current feeding, underlying disease, and the prevalence and phases of dysphagia using a questionnaire. The questionnaire was composed of 11 different determinants, 7 for the evaluation of the oral phase and 4 for the pharyngeal phase. Results: The mean age when diagnosed was 41.4±14.8 years. The prevalence of dysphagia was 50% (32/64), 34% (22/64) in the oral phase, and 43.8% (28/64) in the pharyngeal phase. There was no significant difference between dermatomyositis and polymyositis regarding the prevalence. The most common cause of dysphagia was pharyngeal muscle weakness (35.9% in the pharyngeal phase) and dry mouth (28.1% in the oral phase). The next most common causes were opening of mouth (12.5%), chewing (12.5%), residual material in mouth (12.5% in the oral phase), and choking sign indicating aspiration (29.7% in the pharyngeal phase). Conclusion: The prevalence of dysphagia in inflammatory myositis is very high. Because we can train these patients to improve dysphagia, we must pay particular attention to dysphagia.