ABSTRACT
The etiopathogenesis of Zenker's diverticulum (ZD) remains uncertain. Increased hypopharyngeal pressure due to a hypertonic upper esophageal sphincter results in herniation proximal to the sphincter producing a pulsion diverticulum. Gastroesophageal reflux, which is known to induce shortening of the injured esophagus, likely plays a prominent role in ZD formation by pulling the cricopharyngeus muscle (CPM) away from the anchored inferior constrictor muscle. This creates a "weak zone" encouraging herniation. A bilobed diverticulum may originate from continuation of the fibrous midline raphe inferiorly to developmentally include part of the CPM. We report using laser endoscopy to divide the inter-diverticular septum followed by transmucosal cricopharyngeus myotomy. Presentation of a rare, bilobed diverticulum emphasizes the importance of the midline prevertebral raphe in anchoring the pharyngeal constrictor muscles with respect to the CPM. This lends support to the hypothesis that the etiopathogenesis of ZD is multifactorial while guiding us to a unified understanding of ZD.
Subject(s)
Diverticulum/pathology , Pharyngeal Diseases/pathology , Zenker Diverticulum/pathology , Diverticulum/etiology , Esophageal Sphincter, Upper/pathology , Gastroesophageal Reflux/complications , Humans , Hypopharynx/pathology , Muscle Hypertonia/complications , Muscle Hypertonia/pathology , Pharyngeal Diseases/etiology , Pharyngeal Muscles/pathology , Pressure , Zenker Diverticulum/etiologyABSTRACT
Achalasia may present in a non-advanced or an advanced (end stage) stage based on the degree of esophageal dilatation. Manometric parameters and esophageal caliber may be prognostic for the outcome of treatment. The correlation between manometry and disease stage has not been yet fully studied. This study aims to describe high-resolution manometry findings in patients with achalasia and massive dilated megaesophagus. Eighteen patients (mean age 61 years, 55% females) with achalasia and massive dilated megaesophagus, as defined by a maximum esophageal dilatation >10 cm at the barium esophagram, were studied. Achalasia was considered secondary to Chagas' disease in 14 (78%) of the patients and idiopathic in the remaining. All patients underwent high-resolution manometry. Upper esophageal sphincter was hypotonic and had impaired relaxation in the majority of patients. Aperistalsis was seen in all patients with an equal distribution of Chicago type I and type II. No type III was noticed. Lower esophageal sphincter did not have a characteristic manometric pattern. In 50% of the cases, the manometry catheter was not able to reach the stomach. Our results did not show a manometric pattern in patients with achalasia and massive dilated esophagus.
Subject(s)
Esophageal Achalasia/pathology , Esophagus/pathology , Manometry/methods , Chagas Disease/complications , Dilatation, Pathologic/diagnostic imaging , Dilatation, Pathologic/etiology , Esophageal Achalasia/diagnostic imaging , Esophageal Achalasia/etiology , Esophageal Sphincter, Lower/diagnostic imaging , Esophageal Sphincter, Lower/pathology , Esophageal Sphincter, Upper/diagnostic imaging , Esophageal Sphincter, Upper/pathology , Esophagus/diagnostic imaging , Female , Humans , Male , Middle Aged , Prognosis , Radiography/methods , Retrospective StudiesABSTRACT
A 43-year-old man with complaints of increased difficulty swallowing and weight loss underwent videofluorographic examination of swallowing, which revealed severely reduced cricopharyngeal opening. Endoscopic cricopharyngeal myotomy was carried out using a modified technique (mECPM). A benign fibrotic stricture of the upper esophageal sphincter (UES) was identified under visualization of a distending operating laryngoscope. A vertical midline incision in the strictured mucosa and submucosal resection of the cricopharyngeal muscle were done using a CO2 laser. The initial vertical mucosal incision was tightly sutured in the horizontal direction with absorbable surgical sutures. Histopathological examination of the cricopharyngeal muscle revealed infiltration of inflammatory cells. The patient started oral intake on postoperative day 7. He has been symptom free for 2 years with an improved body mass index, and postoperative laryngoscopy revealed no salivary retention in the piriform sinuses. The technique presented here provides sufficient opening of the UES by eliminating the problem of restenosis. mECPM will be useful for treating benign fibrotic strictures of the UES.
Subject(s)
Endoscopy/methods , Esophageal Sphincter, Upper/diagnostic imaging , Esophageal Sphincter, Upper/surgery , Laser Therapy/methods , Adult , Constriction, Pathologic/diagnostic imaging , Constriction, Pathologic/surgery , Deglutition Disorders/diagnosis , Deglutition Disorders/etiology , Esophageal Sphincter, Upper/pathology , Esophagoscopy/methods , Fibrosis/parasitology , Fibrosis/surgery , Fluoroscopy/methods , Humans , Intraoperative Care/methods , Lasers, Gas/therapeutic use , Male , Recovery of Function , Risk Assessment , Treatment Outcome , Video RecordingSubject(s)
Deglutition Disorders/diagnosis , Suicide, Attempted , Adult , Angioplasty, Balloon, Coronary , Carotid Arteries/surgery , Constriction, Pathologic/diagnosis , Deglutition Disorders/therapy , Endoscopy, Digestive System , Esophageal Sphincter, Upper/pathology , Esophageal Sphincter, Upper/surgery , Female , Humans , Laryngoscopy , Lasers, Gas , Middle Aged , Stents , Vagus Nerve Injuries/diagnosisABSTRACT
Gastroesophageal reflux disease (GERD) is a frequent consideration in intensive care unit neonates. We tested the hypothesis that symptoms in GERD are dependent on the spatiotemporal and physicochemical characteristics of reflux events by evaluating the symptom sensitivity index (SSI) and symptom index (SI) in relation to the refluxate characteristics. Thirty symptomatic neonates (30.7 ± 0.8 wk gestation) were evaluated using manometry and pH-impedance methods. During 704.3 h of recordings, 2063 gastroesophageal reflux (GER) were observed; 54% of the GER were associated with symptoms. Defined by physical characteristics, there were 51.3% liquid, 29.1% gas, and 19.6% mixed GER. Defined by chemical characteristics, there were 48.5% acid and 51.5% nonacid GER. Defined by most proximal extent, 79.2% were supra-UES (upper esophageal sphincter) and 20.8% were infra-UES. Higher SSI was noted with pH-only events (p < 0.0001 versus pH-impedance events). Higher SI was noted with movement symptoms (versus sensory, p = 0.04). In a subset analysis, the frequencies of GER events, acid clearance time, and SSI were all greater in chronic lung disease versus none (p < 0.001). In conclusion, clinical significance of symptoms as measured by SSI and SI and characterization of spatial-temporal-physical-chemical nature of GER events as defined by pH-impedance methods clarifies the definition of GERD.
Subject(s)
Gastroesophageal Reflux/complications , Gastroesophageal Reflux/metabolism , Gastroesophageal Reflux/pathology , Lung Diseases/complications , Esophageal Sphincter, Upper/metabolism , Esophageal Sphincter, Upper/pathology , Humans , Hydrogen-Ion Concentration , Infant, Newborn , Intensive Care, Neonatal , Manometry , Models, Statistical , Time FactorsABSTRACT
Chagas' disease and idiopathic achalasia patients have similar impairment of distal esophageal motility. In Chagas' disease, the contractions occurring in the distal esophageal body are similar after wet or dry swallows. Our aim in this investigation was to evaluate the effect of wet swallows and dry swallows on proximal esophageal contractions of patients with Chagas' disease and with idiopathic achalasia. We studied 49 patients with Chagas' disease, 25 patients with idiopathic achalasia, and 33 normal volunteers. We recorded by the manometric method with continuous water perfusion the pharyngeal contractions 1 cm above the upper esophageal sphincter and the proximal esophageal contractions 5 cm from the pharyngeal recording point. Each subject performed in duplicate swallows of 3-mL and 6-mL boluses of water and dry swallows. We measured the time between the onset of pharyngeal contractions and the onset of proximal esophageal contractions (pharyngeal-esophageal time [PET]), and the amplitude, duration, and area under the curve (AUC) of proximal esophageal contractions. Patients with Chagas' disease and with achalasia had longer PET, lower esophageal proximal contraction amplitude, and lower AUC than controls (P≤ 0.02). In Chagas' disease, wet swallows caused shorter PET, higher amplitude, and higher AUC than dry swallows (P≤ 0.03).There was no difference between swallows of 3- or 6-mL boluses. There was no difference between patients with Chagas' disease and with idiopathic achalasia. We conclude that patients with Chagas' disease and with idiopathic achalasia have a delay in the proximal esophageal response and lower amplitude of the proximal esophageal contractions.
Subject(s)
Chagas Disease , Deglutition , Esophageal Achalasia , Manometry , Myenteric Plexus/pathology , Adult , Aged , Chagas Disease/diagnosis , Chagas Disease/physiopathology , Comparative Effectiveness Research , Esophageal Achalasia/diagnosis , Esophageal Achalasia/physiopathology , Esophageal Sphincter, Upper/pathology , Esophageal Sphincter, Upper/physiopathology , Female , Gastrointestinal Motility , Humans , Male , Middle AgedABSTRACT
The aim of this work was to assess the efficacy of external myotomy of the upper esophageal sphincter (UES) for oropharyngeal dysphagia. In the period 1991-2006, 28 patients with longstanding dysphagia and/or aspiration problems of different etiologies underwent UES myotomy as a single surgical treatment. The main symptoms were difficulties in swallowing of a solid-food bolus, aspiration, and recurrent incidents of solid-food blockages. Pre- and postoperative manometry and videofluoroscopy were used to assess deglutition and aspiration. Outcome was defined as success in the case of complete relief or marked improvement of dysphagia and aspiration and as failure in the case of partial improvement or no improvement. Initial results showed success in 21 and failure in 7 patients. The best outcomes were observed in patients with dysphagia of unknown origin, noncancer-related iatrogenic etiology, and neuromuscular disease. No correlation was found between preoperative constrictor pharyngeal muscle activity and success rate. After follow-up of more than 1 year, 20 patients were marked as success and 3 as failure. All successful patients had full oral intake with a normal bolus consistency without clinically significant aspiration. We conclude that in select cases of oropharyngeal dysphagia success may be achieved by UES myotomy with restoration of oral intake of normal bolus consistency.
Subject(s)
Esophageal Sphincter, Upper/surgery , Gastroesophageal Reflux/surgery , Adult , Aged , Aged, 80 and over , Confidence Intervals , Esophageal Sphincter, Upper/pathology , Female , Fluoroscopy/instrumentation , Fluoroscopy/methods , Gastroesophageal Reflux/diagnosis , Gastroesophageal Reflux/pathology , Humans , Male , Manometry , Middle Aged , Prognosis , Retrospective Studies , Statistics as Topic , Statistics, Nonparametric , Time Factors , Video RecordingABSTRACT
Laryngopharyngeal reflux (LPR) is common in clinical practice. Heterotopic gastric mucosal patch of the proximal esophagus (HGMP) is reported to cause LPR symptoms. This study assessed the prevalence of LPR symptoms and correlation with the size of HGMP. Four hundred and sixty-two patients undergoing endoscopy were carefully questioned regarding LPR symptoms experienced in the previous 12 weeks. The size of the HGMP was assessed and documented during endoscopy. Clinicopathological classifications were assigned (types I-V) accordingly. HGMP [median one patch (range 1-3), median size 15 mm [3-35] was detected in 26 (19 HGM type I and 7 HGM type II] patients giving a prevalence of 5.6%. Among the indications, there were significantly more LPR symptoms as referral indications among patients with HGMP. There were no significant differences in the endoscopic findings. On specific enquiries, significantly more HGMP patients had experienced any LPR symptoms (73.1 vs. 25.9%, p < 0.001) specifically chronic cough (p = 0.002), throat discomfort/hoarseness (p < 0.001), globus sensation (p = 0.004), regurgitation (p < 0.001). HGMP patients also had more heartburn (p = 0.001). Larger HGMP (≥ 15 mm) was only associated with more chronic cough (p = 0.022). In conclusion, patients with HGMP have significantly more LPR symptoms. However, most were mild and detected through specific enquiries. Interestingly, the size of HGMP did not significantly affect the prevalence of LPR symptoms.
Subject(s)
Choristoma/pathology , Esophageal Sphincter, Upper/pathology , Gastric Mucosa , Laryngopharyngeal Reflux/etiology , Biopsy , Chi-Square Distribution , Esophagoscopy , Female , Humans , Laryngopharyngeal Reflux/pathology , Male , Middle Aged , Statistics, NonparametricABSTRACT
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.
Subject(s)
Brain Infarction/complications , Deglutition Disorders , Deglutition , Esophageal Sphincter, Upper/pathology , Medulla Oblongata/pathology , Stroke/complications , Adult , Aged , Aged, 80 and over , Brain Infarction/pathology , Female , Humans , Male , Middle Aged , Retrospective Studies , Stroke/pathology , Time FactorsABSTRACT
As more than 40% of adults experience symptoms of the gastroesophageal reflux (GER) and 26% are affected by the extraesophageal reflux (EER), the aim of this article was to review the literature concerning pathophysiological mechanisms contributing to these common diseases. Reflux symptoms are ascribable for nearly one-third of otolaryngeal disorders. In contrast to patients solely affected by GERD, patients with otolaryngeal disorders attributable to extraesophageal reflux have a relatively good esophageal acid clearance but for unknown reasons increased amounts of laryngeal reflux. Transient upper esophageal sphincter relaxations are discussed as the pathophysiological mechanism, as the resting tone of the upper esophageal sphincter is not affected. When exposed to gastroduodenal contents, the ciliated epithelium of otolaryngeal structures is more susceptible to damage, and thereby even a few reflux episodes are suggested to cause extraesophageal reflux disease (EERD). Particularly active pepsin contributes to laryngeal lesions and eustachian tube dysfunction. Despite the importance of EER in laryngeal diseases, the causative role in other otolaryngeal disorders like sinusitis and otitis media with effusion remains unresolved.
Subject(s)
Esophageal Sphincter, Upper/physiopathology , Gastroesophageal Reflux/physiopathology , Hypopharynx/physiopathology , Otitis Media with Effusion/physiopathology , Otorhinolaryngologic Diseases/physiopathology , Adult , Age Factors , Esophageal Sphincter, Upper/pathology , Esophageal pH Monitoring , Female , Gastroesophageal Reflux/epidemiology , Humans , Incidence , Laryngeal Diseases/epidemiology , Laryngeal Diseases/physiopathology , Male , Middle Aged , Otitis Media with Effusion/epidemiology , Otorhinolaryngologic Diseases/epidemiology , Prognosis , Risk Assessment , Severity of Illness Index , Sex FactorsABSTRACT
RATIONALE: Botulinum toxin injection is a widely used procedure for the treatment of the dysfunction of the upper esophageal sphincter (UES). Although the injection can be guided by ultrasound, electromyography, or computed tomography, such techniques cannot determine the exact extent of narrowed UES and ensure that the narrowed extent is fully covered by the treatment. This report describes a dual guiding technique with ultrasound and the balloon catheter in a patient with poststroke dysphagia to improve these weaknesses. PATIENT CONCERNS: The patient was admitted to a rehabilitation hospital 2 weeks postcerebral infarction. DIAGNOSES: Clinical presentation of the patient included severe hemiplegia and dysphagia. The fiberoptic endoscopic evaluation of swallowing (FEES) revealed penetration/aspiration when swallowing 1 ml water and 1 ml yogurt and pooling in the postcricoid region. INTERVENTIONS: Balloon catheter dilatation procedures and Botulinum toxin injection were performed. We used a dual guiding technique with ultrasound and the balloon catheter to determine the whole segment of UES dysfunction by locating the lowest level of the impaired UES opening and to reduce difficulty in differentiating UES from adjacent tissues during Botulinum toxin injection. OUTCOMES: No persistent progress was observed on the symptoms and volume of the balloon during dilatation. The patient showed quick responses after Botulinum toxin injection. The postinjection balloon catheter dilatation showed an increased maximum volume (preinjection, 5.5 ml vs. postinjection, 14 ml), and the patient was able to eat yogurt, congee, or semi-solid food 100-150 ml 4 weeks after the injection. LESSONS: The dual guiding method holds several advantages, suggesting that it may be considered as a promising choice in dealing with UES dysfunction.
Subject(s)
Botulinum Toxins, Type A/administration & dosage , Catheterization/methods , Deglutition Disorders/drug therapy , Esophageal Sphincter, Upper/pathology , Ultrasonography, Interventional/methods , Botulinum Toxins, Type A/therapeutic use , Deglutition Disorders/etiology , Humans , Male , Middle Aged , Stroke/complicationsABSTRACT
PURPOSE OF REVIEW: Laryngopharyngeal reflux is a well-recognized and widely used term in ear, nose and throat practice. However, the symptoms and signs attributed to laryngopharyngeal reflux are non-specific and treatment is usually empirical. This review discusses current knowledge on diagnosis and treatment of laryngopharyngeal reflux. RECENT FINDINGS: Information is evolving regarding the implications of laryngopharyngeal reflux in the development of pathological conditions affecting the upper aerodigestive tract epithelium such as chronic laryngitis, otitis media with effusion and chronic sinusitis. However, there is still much to learn about the pathophysiologic mechanisms of laryngopharyngeal reflux and their role in its related disease conditions and there is still considerable controversy on diagnostic as well as therapeutic parameters for this condition. There is no consensus on the diagnosis and treatment of laryngopharyngeal reflux and the majority of clinicians depend mainly on clinical findings and empirical therapeutic tests rather than more specific investigations. SUMMARY: The concept of laryngopharyngeal reflux is still controversial. The current practice of empirical treatment with proton-pump inhibitors is based on weak evidence. However, this practice seems to be widely accepted and will not change until further clinical and laboratory studies improve our understanding of this common and well-recognized condition.
Subject(s)
Hypopharynx/pathology , Laryngeal Diseases/diagnosis , Laryngeal Diseases/pathology , Laryngeal Diseases/therapy , Chronic Disease , Esophageal Sphincter, Lower/pathology , Esophageal Sphincter, Upper/pathology , Esophageal pH Monitoring , Feeding Behavior , Gastric Acid/metabolism , Gastroesophageal Reflux/diagnosis , Gastroesophageal Reflux/pathology , Gastroesophageal Reflux/physiopathology , Gastroesophageal Reflux/therapy , Histamine H2 Antagonists/therapeutic use , Humans , Hypopharynx/immunology , Laryngeal Diseases/immunology , Laryngeal Diseases/physiopathology , Laryngoscopy , Life Style , Pharyngeal Diseases/diagnosis , Pharyngeal Diseases/immunology , Pharyngeal Diseases/pathology , Pharyngeal Diseases/therapy , Proton Pump Inhibitors/therapeutic useABSTRACT
PURPOSE OF REVIEW: Esophageal motor disorders, often leading to dysphagia and chest pain, continue to pose diagnostic and therapeutic problems. In the past 12 months important new information regarding esophageal motor disorders was published. This information will be reviewed in this paper. RECENT FINDINGS: A number of studies have addressed the issue of heterogeneity in achalasia, the best defined esophageal motility disorder. The spastic esophageal motility disorders nutcracker esophagus and diffuse esophageal spasm may coexist with gastroesophageal reflux disease, which has consequences for the management of patients with these disorders. The entity labelled ineffective esophageal motility is associated with reflux esophagitis, but also with morbid obesity. For the detection of disordered transit caused by ineffective esophageal motility, application of intraluminal impedance monitoring in conjunction with manometry leads to improved diagnosis. New data on the effect of Nissen fundoplication on esophageal motility were published during the last year. SUMMARY: Recent knowledge on the heterogeneity of achalasia and the association of spastic esophageal motor disorders and ineffective motility with reflux disease will help the clinician in the management of patients with these disorders.
Subject(s)
Esophageal Motility Disorders/diagnosis , Esophageal Motility Disorders/therapy , Esophageal Motility Disorders/etiology , Esophageal Sphincter, Lower/pathology , Esophageal Sphincter, Lower/physiopathology , Esophageal Sphincter, Upper/pathology , Esophageal Sphincter, Upper/physiopathology , Fundoplication , Humans , LaparoscopyABSTRACT
Cervical vagal schwannomas are rare pediatric head and neck neoplasms that present a surgical challenge if the nerve is intimately involved with the mass. In some instances, resection of the vagus nerve with the mass is required. This will usually result in vocal cord paralysis and uncommonly dysphagia due to unilateral cricopharyngeal spasm. We present a case in which these two complications resulted in significant dysphagia and aspiration, which improved with expectant management.
Subject(s)
Cervical Plexus/surgery , Cranial Nerve Neoplasms/surgery , Esophageal Diseases/etiology , Esophageal Sphincter, Upper/surgery , Neurilemmoma/surgery , Postoperative Complications/diagnosis , Vagus Nerve/surgery , Adolescent , Cervical Plexus/pathology , Cranial Nerve Neoplasms/diagnosis , Esophageal Diseases/diagnosis , Esophageal Diseases/therapy , Esophageal Sphincter, Upper/pathology , Female , Humans , Neoplasm Recurrence, Local , Neurilemmoma/diagnosis , Postoperative Complications/therapy , Vagus Nerve/pathology , Vocal Cord Paralysis/diagnosis , Vocal Cord Paralysis/etiology , Vocal Cord Paralysis/therapyABSTRACT
OBJECTIVES: Botulinum toxin injection (BTX) and cricopharyngeal (CP) myotomy are performed in the treatment of CP achalasia (CA). The objective of this study was to examine the effects of BTX on neuromuscular histopathologic findings and to make direct comparisons between specimens of muscle from CA patients who had received BTX to the upper esophageal sphincter and from CA patients who had no previous exposure to BTX. METHODS: We performed a retrospective review (2001 to 2005) of CP muscle specimens from all patients who underwent myotomy for CA. Cases of Zenker's diverticulum were excluded. Patient demographics, clinical course, and neuromuscular pathology findings were noted from the chart. RESULTS: Nineteen patients with CA were identified: 10 male and 9 female, with a mean age of 57 years. Eleven had no prior BTX (6 male and 5 female; mean age, 62 years); 8 had previous treatment with BTX (4 male and 4 female; mean age, 51 years). Eight of the 11 BTX-naive patients revealed predominantly myopathic changes on histology. Those with previous BTX tended to be younger; 6 of the 8 had a clinical benefit from their BTX and ultimately went on to myotomy. The CP muscle specimens featured both mixed and neurogenic pathologic changes in 5 of the 8 patients with BTX. Although these findings suggest some impact of BTX on the CP muscle, the difference between the groups was not statistically significant (p < .20, chi2 test). CONCLUSIONS: Treatment with BTX may have some clinical and histopathologic impact on the upper esophageal sphincter of patients with CA. Although neuropathic changes were noted in the CP muscle of previously injected patients at the time of their CP myotomy, the neuromuscular pathologic findings overall were not significantly different from those of BTX-naive patients.
Subject(s)
Botulinum Toxins, Type A/therapeutic use , Esophageal Achalasia/pathology , Esophageal Sphincter, Upper/pathology , Neuromuscular Agents/therapeutic use , Biopsy , Deglutition Disorders/etiology , Esophageal Achalasia/therapy , Female , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
OBJECTIVES: Cricopharyngeal achalasia (CA) can be defined as inadequate opening of the cricopharyngeus muscle (CPM) resulting in dysphagia. Myosin heavy chain (MHC) isoform fiber type composition and size are key determinants of muscle function. These parameters have not been described in CA. It is hypothesized that there is a difference between the MHC isoform composition of the CPM in patients with the clinical diagnosis of CA and that in normal subjects. METHODS: Patients who had received prior botulinum were excluded. The MHC fiber type composition and size in patients and cadaveric controls were determined by adenosine triphosphatase staining and image analysis. RESULTS: The CPMs of 12 CA patients (6 male, 6 female; mean age, 61 years) and 5 control cadaveric subjects (3 male, 2 female; mean age, 67 years) were analyzed. There were relatively fewer type I fibers (67%) in patients with CA than in controls (81%), but the difference was not significant (p = .18). Type I fibers were slightly smaller in CA patients (38.7 microm) than in controls (47.2 microm), but this was not significantly different (p > .05). Of the 12 CA patients, 3 had type II predominance, a feature not seen in normal subjects. CONCLUSIONS: Patients with CA had relatively fewer type I fibers, although the difference was not statistically significant. The MHC isoform composition and fiber size were not different between CA patients and normal subjects. This is the first report to characterize the CPM in patients with CA.
Subject(s)
Esophageal Achalasia/metabolism , Esophageal Sphincter, Upper/metabolism , Muscle Fibers, Skeletal/pathology , Myosin Heavy Chains/metabolism , Adult , Aged , Aged, 80 and over , Biopsy , Esophageal Achalasia/pathology , Esophageal Achalasia/physiopathology , Esophageal Sphincter, Upper/pathology , Esophageal Sphincter, Upper/physiopathology , Female , Humans , Male , Middle Aged , Muscle Contraction/physiology , Muscle Fibers, Skeletal/metabolism , Retrospective StudiesABSTRACT
OBJECTIVES: At present it is believed that the pharyngeal constrictor (PC) muscles are innervated by the vagus (X) nerve and are homogeneous in muscle fiber content. This study tested the hypothesis that adult human PCs are divided into 2 distinct and specialized layers: a slow inner layer (SIL), innervated by the glossopharyngeal (IX) nerve, and a fast outer layer (FOL), innervated by nerve X. METHODS: Eight normal adult human pharynges (16 sides) obtained from autopsies were studied to determine 1) their gross motor innervation by use of Sihler's stain; 2) their terminal axonal branching by use of acetylcholinesterase (AChE) and silver stain; and 3) their myosin heavy chain (MHC) expression in PC muscle fibers by use of immunocytochemical and immunoblotting techniques. In addition, the specialized nature of the 2 PC layers was also studied in developmental (newborn, neonate, and senescent humans), pathological (adult humans with idiopathic Parkinson's disease [IPD]), and comparative (nonhuman primate [adult macaque monkey]) specimens. RESULTS: When nerves IX and X were traced from their cranial roots to their intramuscular termination in Sihler's-stained specimens, it was seen that nerve IX supplied the SIL, whereas branches of nerve X innervated the FOL in the adult human PCs. Use of AChE and silver stain confirmed that nerve IX branches supplying the SIL contained motor axons and innervated motor end plates. In addition to distinct motor innervation, the SIL contained muscle fibers expressing slow-tonic and alpha-cardiac MHC isoforms, whereas the FOL contained muscle fibers expressing developmental MHC isoforms. In contrast, the FOL became obscured in the elderly and in the adult humans with IPD because of an increased proportion of slow muscle fibers. Notably, distinct muscle fiber layers were not found in the human newborn and nonhuman primate (monkey), but were identified in the 2-year-old human. CONCLUSIONS: Human PCs appear to be organized into functional fiber layers, as indicated by distinct motor innervation and specialized muscle fibers. The SIL appears to be a specialized layer unique to normal humans. The presence of the highly specialized slow-tonic and alpha-cardiac MHC isoforms, together with their absence in human newborns and nonhuman primates, suggests that the specialization of the SIL maybe related to speech and respiration. This specialization may reflect the sustained contraction needed in humans to maintain stiffness of the pharyngeal walls during respiration and to shape the walls for speech articulation. In contrast, the FOL is adapted for rapid movement as seen during swallowing. Senescent humans and patients with IPD are known to be susceptible to dysphagia; and this susceptibility may be related to the observed shift in muscle fiber content.
Subject(s)
Esophageal Sphincter, Upper/innervation , Glossopharyngeal Nerve/pathology , Motor Neurons/pathology , Pharyngeal Muscles/innervation , Vagus Nerve/pathology , Adult , Age Factors , Aged , Animals , Axons/pathology , Child, Preschool , Esophageal Sphincter, Upper/pathology , Humans , Immunoenzyme Techniques , Infant , Laryngeal Nerves/pathology , Macaca mulatta , Motor Endplate/diagnostic imaging , Muscle Fibers, Fast-Twitch/pathology , Muscle Fibers, Slow-Twitch/pathology , Myosin Heavy Chains/analysis , Nerve Degeneration/pathology , Nodose Ganglion/pathology , Parkinson Disease/pathology , Pharyngeal Muscles/pathology , Protein Isoforms/analysis , Reference Values , Species Specificity , Superior Cervical Ganglion/pathology , UltrasonographyABSTRACT
Cultures of myoblasts isolated from cricopharyngeal muscles from patients with oculopharyngeal muscular dystrophy (OPMD) have been performed to study the effect of the expanded (GCG)8-13 repeat, located on the poly(A) binding protein nuclear-1 (PABPN1), on satellite cell phenotype. Cell cultures exhibited a reduced myogenicity, as well as a rapid decrease in proliferative lifespan, as compared to controls. The incorporation of BrdU decreased during the proliferative lifespan, due to a progressive accumulation of non-dividing cells. A lower fusion index was also observed, but myoblasts were able to form large myotubes when OPMD cultures were purified, although a rapid loss of myogenicity during successive passages was also observed. Myoblasts isolated from unaffected muscles did not show the defects observed in cricopharyngeal muscle cultures. The PABPN1 was predominantly located in nuclei of myoblasts and in both the nuclei and cytoplasm of myotubes in OPMD cultures. In vivo analysis of OPMD muscles showed that the number of satellite cells was slightly higher than that observed in age matched controls. Mutation of the PABPN1 in OPMD provokes premature senescence in dividing myoblasts, that may be due to intranuclear toxic aggregates. These results suggest that myoblast autografts, isolated from unaffected muscles, and injected into the dystrophic pharyngeal muscles, may be a useful therapeutic strategy to restore muscular function. Its tolerance and feasibility has been preclinically demonstrated in the dog.
Subject(s)
Cell Proliferation , Esophageal Sphincter, Upper/pathology , Muscular Dystrophy, Oculopharyngeal/pathology , Muscular Dystrophy, Oculopharyngeal/therapy , Myoblasts/transplantation , Poly(A)-Binding Protein II/genetics , Adult , Aged , Aged, 80 and over , Animals , Biopsy , Cell Transplantation/methods , Cells, Cultured , Cellular Senescence , DNA/metabolism , Dogs , Gene Expression Regulation/genetics , Humans , Middle Aged , Muscular Dystrophy, Oculopharyngeal/genetics , Muscular Dystrophy, Oculopharyngeal/metabolism , Myoblasts/metabolism , Myoblasts/pathology , Phenotype , Poly(A)-Binding Protein II/metabolism , Satellite Cells, Skeletal Muscle/pathology , Transplantation, Autologous , Trinucleotide RepeatsABSTRACT
Gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux (LPR) are sibling diseases that are a modern-day plague. Millions of Americans suffer from their sequelae, ranging from subtle annoyances to life-threatening illnesses such as asthma, sleep apnea, and cancer. Indeed, the recognized prevalence of GERD alone has increased threefold throughout the 1990s. Knowledge of the precise etiologies for GERD and LPR is becoming essential for proper treatment. This review focuses on the anatomical, physiological, neurobiological, and cellular aspects of these diseases. By definition, gastroesophageal reflux (GER) is the passage of gastric contents into the esophagus; when excessive and damaging to the esophageal mucosa, GERD results. Reflux that advances to the laryngopharynx and, subsequently, to other regions of the head and neck such as the larynx, oral cavity, nasopharynx, nasal cavity, paranasal sinuses, and even middle ear results in LPR. While GERD has long been identified as a source of esophageal disease, LPR has only recently been implicated in causing head and neck problems. Recent research has identified four anatomical/physiological "barriers" that serve as guardians to prevent the cranial incursion of reflux: the gastroesophageal junction, esophageal motor function and acid clearance, the upper esophageal sphincter, and pharyngeal and laryngeal mucosal resistance. Sequential failure of all four barriers is necessary to produce LPR. While it has become apparent that GER must precede both GERD and LPR, the head and neck distribution of the latter clearly separates these diseases as distinct entities warranting specialized focus and treatment.